Association of renal function with mortality among hospitalized patients treated with remdesivir for COVID-19.

BACKGROUND AND AIM: Renal dysfunction is associated with poor outcomes in patients with coronavirus disease 2019 (COVID-19). In an effort to improve outcomes, intravenous remdesivir has been broadly used for the treatment of COVID-19 even in patients with low estimated glomerular filtration rate (eGFR). Our study assessed the residual risk of outcomes of patients with low eGFR despite treatment with remdesivir for COVID-19, during a timeframe prior to the expanded label across all levels of renal function. METHODS: We conducted an observational, retrospective, multi-site cohort study of adults hospitalized with COVID-19 treated with at least one dose of remdesivir between November 6, 2020, and November 5, 2021. Electronic medical records were reviewed to obtain patient characteristics, related laboratory data, and outcomes. The primary endpoint was all-cause mortality by day 28. Multivariable logistic regression was used to evaluate association between groups. RESULTS: The study population consisted of 3024 patients hospitalized with COVID-19 and treated with remdesivir. The median age was 67 [IQR 55, 77] years; 42.7% were women, and 88.6% were white. The median eGFR was 76.6 mL/min/1.73 m2 [IQR 52.5, 95.2]; the majority (67.2%) of patients had an eGFR ≥ 60, while 9% had an eGFR <30. All-cause mortality by day 28 was 8.7%. All-cause mortality rates were significantly higher among patients with impaired renal function (Odds Ratio [OR] 1.63 for patients with eGFR 30-59; OR 1.46 for eGFR 15-29; OR 2.42 for eGFR <15 and OR 5.44 for patients on dialysis) compared to patients with eGFR ≥60 mL/min/1.73m2. CONCLUSIONS: Lower eGFR remains an independent risk factor for mortality in COVID-19 even in patients treated with remdesivir.

Impact of hypoalbuminemia on clinical outcomes among patients with obesity treated with ceftriaxone.

The use of ceftriaxone, a highly protein-bound drug, in the setting of hypoalbuminemia may result in suboptimal drug exposure. Patients with obesity also exhibit higher absolute drug clearance. We aimed to evaluate the impact of hypoalbuminemia on clinical success among hospitalized adults with obesity who were treated with ceftriaxone. This retrospective review included adult inpatients with weight >100 kg or body mass index >40 kg/m2 who received ceftriaxone 2 g intravenously every 12 hours for at least 72 hours. The primary outcome was clinical success, a composite of clinical cure and microbiologic cure. Secondary outcomes included clinical cure, microbiologic cure, length of stay, ICU length of stay, mortality, 30-day readmission, and adverse events. In all, 137 patients were included, 34 of whom had a serum albumin of ≤2.5 g/dL. In a propensity-score-weighted analysis, clinical success was significantly more common among those without hypoalbuminemia (91.2%) as compared to those with hypoalbuminemia (77.8%) (P = 0.038). Death within 30 days (13.7% vs 0%, P < 0.001) and 30-day readmission (31.6% vs 12.0%, P = 0.008) were more common in the hypoalbuminemia group. In a univariate analysis, serum albumin and indication for ceftriaxone use were found to be predictors of clinical success. Hypoalbuminemia was associated with a lower rate of clinical success among patients with obesity who were treated with ceftriaxone 2 g every 12 hours.

Design and evaluation of an electronic prospective medication order review system for medication orders in the inpatient setting.

Objectives: Since the 1970s, a plethora of tools have been introduced to support the medication use process. However, automation initiatives to assist pharmacists in prospectively reviewing medication orders are lacking. The review of many medications may be protocolized and implemented in an algorithmic fashion utilizing discrete data from the electronic health record (EHR). This research serves as a proof of concept to evaluate the capability and effectiveness of an electronic prospective medication order review (EPMOR) system compared to pharmacists' review. Materials and methods: A subset of the most frequently verified medication orders were identified for inclusion. A team of clinical pharmacist experts developed best-practice EPMOR criteria. The established criteria were incorporated into conditional logic built within the EHR. Verification outcomes from the pharmacist (human) and EPMOR (automation) were compared. Results: Overall, 13 404 medication orders were included. Of those orders, 13 133 passed pharmacist review, 7388 of which passed EPMOR. A total of 271 medication orders failed pharmacist review due to order modification or discontinuation, 105 of which passed EPMOR. Of the 105 orders, 19 were duplicate orders correctly caught by both EPMOR and pharmacists, but the opposite duplicate order was rejected, 51 orders failed due to scheduling changes. Discussion: This simulation was capable of effectively discriminating and triaging orders. Protocolization and automation of the prospective medication order review process in the EHR appear possible using clinically driven algorithms. Conclusion: Further research is necessary to refine such algorithms to maximize value, improve efficiency, and minimize safety risks in preparation for the implementation of fully automated systems.

Evaluation of Multisite Programmatic Bundle to Reduce Unnecessary Antibiotic Prescribing for Respiratory Infections: A Retrospective Cohort Study.

Background: The aim of this study was to evaluate the frequency of unnecessary antibiotic prescribing for Tier 3 upper respiratory infection (URI) syndromes across the Mayo Clinic Enterprise before and after a multifaceted antimicrobial stewardship intervention, and to determine ongoing factors associated with antibiotic prescribing and repeat respiratory healthcare contact in the postintervention period. Methods: This was a quasi-experimental, pre/post, retrospective cohort study from 1 January 2019 through 31 December 2022, with 12-month washout during implementation from 1 July 2020 through 30 June 2021. All outpatient encounters, adult and pediatric, from primary care, urgent care, and emergency medicine specialties with a Tier 3 URI diagnosis were included. The intervention was a multifaceted outpatient antibiotic stewardship bundle. The primary outcome was the rate of antibiotic prescribing in Tier 3 encounters. Secondary outcomes included 14-day repeat healthcare contact for respiratory indications and factors associated with persistent unnecessary prescribing. Results: A total of 165 658 Tier 3 encounters, 96 125 in the preintervention and 69 533 in the postintervention period, were included. Following intervention, the prescribing rate for Tier 3 encounters decreased from 21.7% to 11.2% (P < .001). Repeat 14-day respiratory healthcare contact in the no antibiotic group was lower postintervention (9.9.% vs 9.4%; P = .004). Multivariable models indicated that increasing patient age, Charlson comorbidity index, and primary diagnosis selected were the most important factors associated with persistent unnecessary antibiotic prescribing. Conclusions: Outpatient antibiotic stewardship initiatives can reduce unnecessary antibiotic prescribing for Tier 3 URIs without increasing repeat respiratory healthcare contact. Advancing age and number of comorbidities remain risk factors for persistent unnecessary antibiotic prescribing.

Evaluating the Impact of Pharmacist Dual Verification of Anticancer Therapy in the Modern Era.

Background: Pharmacist order verification is a critical step in ensuring medication safety for patients. While the second pharmacist verification (SPV) before dispensing anticancer therapies has been a longstanding practice, its continued necessity in the context of modern electronic health systems lacks robust evidence. Objective: This study aimed to assess the frequency of interventions performed by a second pharmacist to determine the ongoing effectiveness of the SPV process. Methods: This retrospective chart review was conducted at the Mayo Clinic, encompassing all anticancer therapy orders that necessitated an SPV. The study period extended from January 1, 2019, to June 30, 2021, and included inpatient and outpatient anticancer orders. The quantification and reporting of alterations made to discrete order fields subsequent to initial pharmacist verification of clinical significance were performed, utilizing the total number of anticancer therapy orders as the denominator. Results: Approximately 300 000 anticancer therapy orders were screened for inclusion criteria and 2.6% (N = 7634) of orders were modified on the SPV. Most changes were in the categories of rate (N = 1962), order start time (N = 1219), and pharmacy communication note (N = 777). Dosing changes greater than 10% accounted for 0.03% (N = 99) of the orders, with 10 anticancer therapies responsible for more than 50% of these changes. Conclusion and relevance: This study represents the largest report on the impact of SPV in a modern era. Our results suggest the SPV may be valuable for a small proportion of chemotherapy orders but raises questions about the necessity for broad application of this practice.

Clinical outcomes of COVID-19 treated with remdesivir across the continuum of care.

Introduction: During the early phase of the coronavirus disease 2019 (COVID-19), remdesivir was only approved for hospitalized patients. Our institution developed hospital-based, outpatient infusion centers for selected hospitalized patients with COVID-19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined. Methods: Retrospective study of all hospitalized adult patients with COVID-19 who received at least one dose of remdesivir from November 6, 2020, to November 5, 2021, at one of the Mayo Clinic hospitals. Results: Among 3029 hospitalized patients who received treatment with remdesivir for COVID-19, the majority (89.5%) completed the recommended 5-day course. Among them, 2169 (80%) patients completed treatment during hospitalization, whereas 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06-0.32, p < 0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27-2.79, p = 0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5-day course of remdesivir (aOR 2.07, 95% CI 1.45-2.95, p < 0.001). Conclusions: This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5-day course of remdesivir.

An evaluation of intravenous medication preparation times before and after implementation of first-party digital image capture functionality.

PURPOSE: The intravenous (IV) medication compounding workflow has long been associated with preventable medication errors. This has led to the development of technologies designed to enhance the safety of IV compounding workflows. Digital image capture is a component of this technology about which there is relatively limited published literature. This study evaluates image capture implemented within an electronic health record's existing first-party IV workflow solution. METHODS: A retrospective case-control study was conducted to measure IV preparation times before and after digital imaging implementation. Preparations during 3 periods (preimplementation, ≤1 month post implementation, and >1 month post implementation) were matched for 5 variables. A less stringent analysis with matching for 2 variables, as well as an unmatched analysis, were performed post hoc. An employee survey assessed satisfaction with the digital imaging workflow, and revised orders were reviewed to identify new problems introduced by image capture. RESULTS: A total of 134,969 IV dispenses were available for analysis. Median preparation time in the preimplementation and >1 month post implementation cohorts was unchanged in the 5-variable matched analysis (6.87 minutes vs 6.58 minutes, P = 0.14) and increased in the 2-variable matched analysis (6.98 minutes vs 7.35 minutes, P < 0.001) and unmatched analysis (6.55 minutes vs 8.02 minutes, P < 0.001). A large majority of survey respondents (92%) felt that image capture improved patient safety. Of the 105 postimplementation preparations identified as requiring revisions by the checking pharmacist, 24 (22.9%) required revisions directly related to camera functionality. CONCLUSION: Implementation of digital image capture likely increased preparation times. Most IV room staff felt that image capture increased preparation times and were satisfied with how the technology improved patient safety. Image capture introduced camera-specific issues that led to preparations requiring revisions.

Identification of priority targets for intervention in outpatient antimicrobial stewardship.

A multimodal antimicrobial stewardship intervention was associated with a decrease in antibiotic prescribing for targeted non-coronavirus disease 2019 (COVID-19) upper respiratory infections from 27.6% in 2019 to 7.6% in 2021. We describe our approach to prioritizing departments for 3 levels of interventions in the setting of limited stewardship personnel.

A Minimal Information Model for Potential Drug-Drug Interactions.

Despite the significant health impacts of adverse events associated with drug-drug interactions, no standard models exist for managing and sharing evidence describing potential interactions between medications. Minimal information models have been used in other communities to establish community consensus around simple models capable of communicating useful information. This paper reports on a new minimal information model for describing potential drug-drug interactions. A task force of the Semantic Web in Health Care and Life Sciences Community Group of the World-Wide Web consortium engaged informaticians and drug-drug interaction experts in in-depth examination of recent literature and specific potential interactions. A consensus set of information items was identified, along with example descriptions of selected potential drug-drug interactions (PDDIs). User profiles and use cases were developed to demonstrate the applicability of the model. Ten core information items were identified: drugs involved, clinical consequences, seriousness, operational classification statement, recommended action, mechanism of interaction, contextual information/modifying factors, evidence about a suspected drug-drug interaction, frequency of exposure, and frequency of harm to exposed persons. Eight best practice recommendations suggest how PDDI knowledge artifact creators can best use the 10 information items when synthesizing drug interaction evidence into artifacts intended to aid clinicians. This model has been included in a proposed implementation guide developed by the HL7 Clinical Decision Support Workgroup and in PDDIs published in the CDS Connect repository. The complete description of the model can be found at https://w3id.org/hclscg/pddi.

Comparison of Prescribing Practices with Direct Acting Oral Anticoagulant Protocols.

BACKGROUND: The goal of anticoagulation management programs is to prevent thrombosis while minimizing the risks of hemorrhage. Direct acting oral anticoagulants (DOACs) selectively inhibit coagulation proteins to inhibit thrombosis. Previous studies suggest patient monitoring and education provided through anticoagulation services enhance adherence and decrease adverse outcomes in patients receiving DOAC therapy. OBJECTIVE: The objectives of this study were to describe DOAC prescribing adherence to anticoagulation service protocols and to observe whether enrollment in an anticoagulation service resulted in greater prescribing adherence to DOAC protocols. METHODS: A retrospective cohort study evaluated all initial prescriptions of apixaban, dabigatran, and rivaroxaban at Marshfield Clinic from 19 October 2010 to 21 August 2014. Three algorithms analyzed patient and prescription data extracted from the organization's electronic health record and classified prescriptions as per protocol or not per protocol. The algorithms classified not per protocol prescriptions as off-label indication, renal impairment [estimated glomerular filtration rate (eGFR) <30 ml/min], hepatic impairment (rivaroxaban and apixaban), advanced age >74 years (dabigatran), dose too low, or dose too high. The analysis assessed whether enrollment in the Marshfield Clinic Anticoagulation Service DOAC monitoring process was associated with increased adherence to protocols. RESULTS: In aggregate, 72% of apixaban prescriptions, 52% of dabigatran prescriptions, and 70% of rivaroxaban prescriptions were per protocol. Off-label indications and dosage too low were the most common not per protocol reasons for apixaban and rivaroxaban prescriptions. Age ≥75 years and off-label indication were the most common not per protocol reasons for dabigatran prescriptions. Enrollment in the anticoagulation service process was not associated with increased adherence to protocols. CONCLUSION: A significant proportion of DOAC prescriptions did not adhere to protocol expectations. While enrollment in DOAC management through the Marshfield Clinic Anticoagulation Service was not associated with increased adherence to protocols, opportunities exist to optimize DOAC prescribing. Defining ideal DOAC management requires additional research.