Impact of clinical decision support therapeutic interchanges on hospital discharge medication omissions and duplications.

PURPOSE: Automatic therapeutic substitution (ATS) protocols are formulary tools that allow for provider-selected interchange from a nonformulary preadmission medication to a formulary equivalent. Previous studies have demonstrated that the application of clinical decision support (CDS) tools to ATS can decrease ATS errors at admission, but there are limited data describing the impact of CDS on discharge errors. The objective of this study was to describe the impact of CDS-supported interchanges on discharge prescription duplications or omissions. METHODS: This was a single-center, retrospective cohort study conducted at an academic medical center. Patients admitted between June 2017 and August 2019 were included if they were 18 years or older at admission, underwent an ATS protocol-approved interchange for 1 of the 9 included medication classes, and had a completed discharge medication reconciliation. The primary outcome was difference in incidence of therapeutic duplication or omission at discharge between the periods before and after CDS implementation. RESULTS: A total of 737 preimplementation encounters and 733 postimplementation encounters were included. CDS did not significantly decrease the incidence of discharge duplications or omissions (12.1% vs 11.2%; 95% confidence interval [CI], -2.3% to 4.2%) nor the incidence of admission duplication or inappropriate reconciliation (21.4% vs 20.7%; 95% CI, -3.4% to 4.8%) when comparing the pre- and postimplementation periods. Inappropriate reconciliation was the primary cause of discharge medication errors for both groups. CONCLUSION: CDS implementation was not associated with a decrease in discharge omissions, duplications, or inappropriate reconciliation. Findings highlight the need for thoughtful medication reconciliation at the point of discharge.

The Biosimilar Nocebo Effect? A Systematic Review of Double-Blinded Versus Open-Label Studies.

BACKGROUND: Several authors have hypothesized that adverse drug events (ADEs) upon switching from reference biologics to biosimilar products are related to the nocebo effect. However, a thorough and current review of the existing literature has not been conducted. OBJECTIVE: To evaluate if patient and/or physician knowledge of a switch from a reference biologic product to a biosimilar product was associated with an increase in ADEs likely to be susceptible to the nocebo effect. METHODS: Studies reporting efficacy and safety outcomes of a switch from a reference product to a biosimilar product were reviewed. Biologics with FDA-approved biosimilars in the United States were considered for review, including adalimumab, bevacizumab, etanercept, and infliximab. Studies were identified by searching controlled vocabulary (e.g., MeSH terms) and keywords within MEDLINE (via PubMed) and Embase. Descriptive statistics were used to quantify subjective and objective complications in double-blinded and single-blinded or open-label studies. RESULTS: Thirty-one trials including 3,271 patients were reviewed in the full analysis. Median discontinuation rates for any reason were 14.3% (range = 0.0-33.3) in open-label studies compared with 6.95% (range = 5.2-11.0) in double-blinded studies. Discontinuation rates for ADEs were 5.6% (range = 0.0-24.2) in open-label studies versus 3.1% (range = 2.0-5.2) in double-blinded studies, suggesting the nocebo effect does affect biosimilar adoption. Subgroup analyses of antidrug antibody (ADA) development and infusion reactions were similar between infliximab open-label and double-blinded studies. Discontinuation rates for any reason, for ADEs, and for lack of efficacy were generally higher in infliximab open-label trials compared with double-blinded trials. Etanercept biosimilar discontinuation rates for any reason were similar between study designs; however, incidences of injection site reactions and discontinuation rates for ADEs were higher in double-blinded compared with open-label study designs. CONCLUSIONS: Current evidence is insufficient to confirm a biosimilar nocebo effect, although higher discontinuation rates in infliximab biosimilar open-label studies support this theory. Further studies are needed to evaluate the existence of a biosimilar nocebo effect. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest to disclose.

Rising cost of antidotes in the U.S.: cost comparison from 2010 to 2015.

CONTEXT: Our poison control center observed a large increase in the cost of many antidotes over the past several years. The high cost of antidotes has previously been cited as a factor leading to inadequate antidote supply at some hospitals. Continued increases in the cost of antidotes may lead to further reductions in antidote supply and represent serious concerns. This research aims to quantify recent trends in the costs of antidotes in the U.S. METHODS: Antidotes and minimum stocking recommendations were retrieved from published guidelines. RED BOOK Online® was used to identify the U.S. average wholesale price (AWP) of each antidote in 2010 and 2015. The AWP in 2010 was adjusted using the U.S. Consumer Price Index to adjust for inflation. The cost of minimum stocking levels for each antidote was calculated and compared between the year 2010 and 2015. RESULTS: The cost of stocking many antidotes demonstrated a large increase in AWP from 2010 to 2015. Of the antidotes evaluated, 15 out of 33 had greater than 50% increase in AWP and 8 out of 33 had greater than $1000 increase in AWP. Only four antidotes demonstrated decreases in AWP greater than 10% and only one antidote had its cost of stocking decrease in AWP by more than $1000. DISCUSSION: The price increase over the last 5 years may further hinder the willingness of hospitals to stock recommended antidotes at adequate quantities. This may impede timely treatment of patients, and negatively impact poisoning outcomes. CONCLUSIONS: The price of many antidotes substantially increased in the United States from 2010 to 2015. Strategies should be investigated to help decrease the cost associated with stocking and use of antidotes, including dose rounding, consignment, and regional sharing.

Organic anion transporter 3 interacts selectively with lipophilic ß-lactam antibiotics.

Transporters are major determinants of the disposition of xenobiotics and endogenous chemicals in the body. Organic anion transporter 3 (Oat3) functions in the kidney and brain to remove metabolic waste, toxins, and drugs, and thus transports diverse chemicals. Some ß-lactam antibiotics interact with Oat3, and penicillin G exhibits a strong dependence on Oat3 for renal elimination. However, over 80 ß-lactams exist, and many have not been assessed for an interaction with Oat3. Moreover, ß-lactams continue to receive U.S. Food and Drug Administration approval. This study identified new ß-lactam-Oat3 interactions, provided a head-to-head comparison with Oat1, and characterized the physicochemical determinants of affinity for Oat3. Cells expressing mouse Oat3 (mOat3) and Oat1 (mOat1), and human OAT3 (hOAT3) were used to test inhibitors, and high-performance liquid chromatography (HPLC) was used to measure transport. Of 26 ß-lactams tested, 12 were clear inhibitors of Oat3, and 14 exhibited poor interactions. Inhibitors exhibited a nearly identical rank-order of potency against mOat3 and hOAT3. Oat1 demonstrated a poor interaction with most ß-lactams. The majority of Oat3 inhibitors were substrates, and there were clear physicochemical differences between inhibitors and noninhibitors. That is, inhibitors had nearly 40% fewer hydrogen bond donors (P < 0.001), a lower total polar surface area (P < 0.05), and greater lipophilicity (LogP of inhibitors, +1.41; noninhibitors, -1.54; P < 0.001). Pharmacophore mapping revealed a prohibitive hydrogen bond donor group in noninhibitors adjacent to a hydrophobic moiety that was important for binding to Oat3. These findings indicate that Oat3 recognizes lipophilic ß-lactams more readily. Moreover, this study has potential implications for designing ß-lactams to avoid renal accumulation or brain efflux via Oat3.