Criteria for assessing high-priority drug-drug interactions for clinical decision support in electronic health records.

BACKGROUND: High override rates for drug-drug interaction (DDI) alerts in electronic health records (EHRs) result in the potentially dangerous consequence of providers ignoring clinically significant alerts. Lack of uniformity of criteria for determining the severity or validity of these interactions often results in discrepancies in how these are evaluated. The purpose of this study was to identify a set of criteria for assessing DDIs that should be used for the generation of clinical decision support (CDS) alerts in EHRs. METHODS: We conducted a 20-year systematic literature review of MEDLINE and EMBASE to identify characteristics of high-priority DDIs. These criteria were validated by an expert panel consisting of medication knowledge base vendors, EHR vendors, in-house knowledge base developers from academic medical centers, and both federal and private agencies involved in the regulation of medication use. RESULTS: Forty-four articles met the inclusion criteria for assessing characteristics of high-priority DDIs. The panel considered five criteria to be most important when assessing an interaction- Severity, Probability, Clinical Implications of the interaction, Patient characteristics, and the Evidence supporting the interaction. In addition, the panel identified barriers and considerations for being able to utilize these criteria in medication knowledge bases used by EHRs. CONCLUSIONS: A multi-dimensional approach is needed to understanding the importance of an interaction for inclusion in medication knowledge bases for the purpose of CDS alerting. The criteria identified in this study can serve as a first step towards a uniform approach in assessing which interactions are critical and warrant interruption of a provider's workflow.

Exploring Breast Cancer Systemic Drug Therapy Patterns in Real-World Data.

PURPOSE: To explore medications and their administration patterns in real-world patients with breast cancer. METHODS: A retrospective study was performed using TriNetX, a federated network of deidentified, Health Insurance Portability and Accountability Act-compliant data from 21 health care organizations across North America. Patients diagnosed with breast cancer between January 1, 2013, and May 31, 2022, were included. We investigated a rule-based and unsupervised learning algorithm to extract medications and their administration patterns. To group similar administration patterns, we used three features in k-means clustering: total number of administrations, median number of days between administrations, and standard deviation of the days between administrations. We explored the first three lines of therapy for patients classified into six groups on the basis of their stage at diagnosis (early as stages I-III v late as stage IV) and the sensitivity of the tumor's receptors to targeted therapies: hormone receptor-positive/human epidermal growth factor 2-negative (HR+/ERBB2-), ERBB2-positive (ERBB2+/HR±), or triple-negative (TN; HR-/ERBB2-). To add credence to the derived regimens, we compared them to the National Comprehensive Cancer Network (NCCN): Breast Cancer (version 2.2023) recommendations. RESULTS: In early-stage HR+/ERBB2- and TN groups, the most common regimens were (1) cyclophosphamide and docetaxel, administered once every 3 weeks for three to six cycles and (2) cyclophosphamide and doxorubicin, administered once every 2 weeks for four cycles, followed by paclitaxel administered once every week for 12 cycles. In the early-stage ERBB2+/HR± group, most patients were administered carboplatin and docetaxel with or without pertuzumab and with trastuzumab (for six or more cycles). Medications most commonly administered in our data set (7,798 patients) agreed with recommendations from the NCCN in terms of medications (regimens), number of administrations (cycles), and days between administrations (cycle length). CONCLUSION: Although there is a general agreement with the NCCN Guidelines, real-world medication data exhibit variability in the medications and their administration patterns.

Recurrent erythema multiforme triggered by progesterone sensitivity.

Determining the underlying etiology of recurrent erythema multiforme (EM) can be a difficult endeavor. Although infection with herpes simplex virus (HSV) has been implicated in some cases, the precise trigger of a given patient's recurrent EM often remains elusive. We discuss the case of a woman with a recurrent blistering eruption that was clinically and histopathologically consistent with EM. An investigation into the etiology of the patient's EM suggested that HSV was not the causative factor but instead pointed toward a hormonal influence that we interpret as autoimmune progesterone dermatitis (APD). This case is presented to highlight the importance of considering hormonal triggers in women with recurrent EM that consistently flares during the luteal phase of the menstrual cycle, the point at which serum progesterone levels peak. A brief review of the literature regarding the diagnosis, histopathology, etiology and treatment of APD is further provided.

Effect of additive selection on calculated aluminum content of parenteral nutrient solutions.

PURPOSE: The quantity of aluminum in common ingredients used to compound parenteral nutrient (PN) solutions was calculated to quantify the actual aluminum content, and opportunities to modify the aluminum content by changing the manufacturer of the ingredients were explored. METHODS: A retrospective evaluation of a random sample of 10 neonatal, 10 pediatric, and 10 adult patients who received PN solutions was performed to quantify the aluminum content in these solutions on the basis of the ingredients used at the authors' institution. A recalculation was performed using the lowest aluminumcontaining ingredients to determine the potential for aluminum minimization in each PN solution. RESULTS: Various manufacturers produce each ingredient required to make PN solutions. Significant variation exists among manufacturers, vial size, and concentrations. Statistically significant differences in the mean aluminum content of PN solutions before and after aluminum minimization were found to exist within each sample of patients. Among the neonatal PN solutions, aluminum content was significantly reduced from a mean +/- S.D. of 84.16 +/- 47.61 to 33.6 +/- 16.69 mug/kg/day. The pediatric PN solutions had a significant decline in aluminum content from a mean +/- S.D. of 16.24 +/- 3.66 to 6.84 +/- 2.66 mug/kg/day. Aluminum content in the high-risk adult PN solutions significantly decreased from a mean +/- S.D. of 4.58 +/- 2.06 to 2.31 +/- 0.63 mug/kg/day. CONCLUSION: There is wide variability in the aluminum concentration of injectable products used in the compounding of PN solutions. Selecting products with low aluminum concentration may substantially reduce the amount of the element administered to patients.

High-priority drug-drug interactions for use in electronic health records.

OBJECTIVE: To develop a set of high-severity, clinically significant drug-drug interactions (DDIs) for use in electronic health records (EHRs). METHODS: A panel of experts was convened with the goal of identifying critical DDIs that should be used for generating medication-related decision support alerts in all EHRs. Panelists included medication knowledge base vendors, EHR vendors, in-house knowledge base developers from academic medical centers, and both federal and private agencies involved in the regulation of medication use. Candidate DDIs were assessed by the panel based on the consequence of the interaction, severity levels assigned to them across various medication knowledge bases, availability of therapeutic alternatives, monitoring/management options, predisposing factors, and the probability of the interaction based on the strength of evidence available in the literature. RESULTS: Of 31 DDIs considered to be high risk, the panel approved a final list of 15 interactions. Panelists agreed that this list represented drugs that are contraindicated for concurrent use, though it does not necessarily represent a complete list of all such interacting drug pairs. For other drug interactions, severity may depend on additional factors, such as patient conditions or timing of co-administration. DISCUSSION: The panel provided recommendations on the creation, maintenance, and implementation of a central repository of high severity interactions. CONCLUSIONS: A set of highly clinically significant drug-drug interactions was identified, for which warnings should be generated in all EHRs. The panel highlighted the complexity of issues surrounding development and implementation of such a list.