Analysis of appropriateness and safety when discharging patients on triple-antithrombotic therapies.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: To analyze the appropriateness of triple-antithrombotic therapy based on the 2020 American College of Cardiology (ACC) consensus statement while evaluating safety outcomes for patients with respect to adverse events. METHODS: A single-center, retrospective chart review was conducted using electronic medical records from December 18, 2020, to August 31, 2022. The primary endpoint was the rate of appropriateness for triple-antithrombotic therapy in patients discharged from Ochsner LSU Health Shreveport. Appropriateness was a composite endpoint extrapolated from the 2020 ACC consensus statement. For therapy to be defined as appropriate, patients had to have had the correct therapy indication, medications, dosing, and 30-day duration. Secondary safety endpoints included the percentage of patients rehospitalized at 14 and 30 days, the rate of major bleeding events, and the percentage of patients on gastrointestinal prophylaxis while on triple-antithrombotic therapy. RESULTS: A total of 93 patients were included in the study, of whom 31 (33%) received appropriate triple-antithrombotic therapy. Prolonged duration of triple-antithrombotic therapy was the most common reason that therapy did not meet the primary endpoint. The readmission rate due to bleeding was 2.2% at 14 days and 6.5% at 30 days. Within 30 days of initiation of triple therapy, 4.3% of patients endured major bleeding as defined by the International Society on Thrombosis and Hemostasis and 2 patients died. CONCLUSION: In this single-center study, triple-antithrombotic therapy appropriately adhered to the 2020 ACC consensus statement for one-third of patients discharged on this therapy.

Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents.

INTRODUCTION: Kratom, an unregulated herbal supplement, has emerged as self-treatment for anxiety/depression. Kratom exhibits inhibition at multiple cytochrome P450 isozymes involved in metabolism of prescription medications, including serotonergic agents. We report a case of possible serotonin syndrome induced by kratom use in combination with prescription psychotropic medications. CASE: A 63-year-old male presented with diaphoresis, flushing, aphasia, confusion, dysarthria, right facial droop, and oral temperature of 39.6oC (103.2oF), lactate 2.7 mmol/L, and creatine phosphokinase of 1507 IU/L. Initial differential diagnoses included acute ischemic stroke and bacterial meningitis. Despite partial treatment with alteplase and broad-spectrum antibiotics, symptoms persisted, and subsequent physical exam noted hyperreflexia, clonus, tremors, and temperature of 41.1oC (106oF). Home medications included a chronic regimen for anxiety/depression with bupropion, buspirone, desvenlafaxine, trazodone, and ziprasidone, in addition to kratom. Clinical suspicion for serotonin syndrome led to initiation of cyproheptadine, lorazepam, and cooling blankets. Aphasia, facial droop, and confusion improved after administration of cyproheptadine. Bupropion was restarted during hospitalization; remaining medications restarted at the discretion of the primary care provider. DISCUSSION: Risk of serotonin syndrome with multiple serotonergic agents is well-known. Kratom is metabolized by cytochrome P40 isozymes 3A4, 2C9, and 2D6, and exhibits inhibition at those enzymes, in addition to 1A2. Pharmacokinetic interactions of kratom with prescription serotonergic agents metabolized through these isozymes has the potential to increase systemic exposure of serotonin, potentially leading to serotonin syndrome. CONCLUSION: Because substances contained in kratom can inhibit metabolism of prescription serotonergic medications, clinicians must be aware of potential development of serotonin syndrome.

Evaluation of student-perceived growth in entrustable professional activities after involvement in a transitions-of-care process within an adult medicine advanced pharmacy practice experience.

BACKGROUND AND PURPOSE: Involvement of pharmacists and trainees in care transitions reduces medication-related problems. Participation in the transitions-of-care (TOC) process may impact self-perceived growth of autonomy within selected entrustable professional activities (EPAs). EDUCATIONAL ACTIVITY AND SETTING: A student-driven TOC documentation process was implemented within an inpatient family medicine advanced pharmacy practice experience. During the month-long rotation, students rounded with an interdisciplinary care team. Responsibilities included ensuring accurate medication reconciliation at care transitions throughout hospitalization and prior to discharge as well as medication optimization during hospitalization. Another responsibility was completing a medication-specific TOC note in the clinic-based electronic health record at discharge for patients receiving primary care from the associated clinic. The note was available to the outpatient interdisciplinary care team during the hospital follow-up appointment. Student-perceived growth in autonomy within selected EPAs was determined through an online anonymous survey. FINDINGS: Ninety percent (n = 18) of eligible students completed the survey. For specific EPA statements (collecting information, establishing patient-centered goals and establishing a care plan, implementing a care plan, collaborating as an interdisciplinary team member, and ensuring immunization), student-perceived autonomy increased after involvement in this student-driven TOC process. During the study period, 215 notes were generated by student pharmacists and included interventions/recommendations within the following themes: evidence-based changes in therapy, patient counseling, and medication access. SUMMARY: The importance of pharmacist and pharmacy trainee involvement in the TOC process has been well-documented. Involving students in student-driven TOC documentation processes serves to facilitate student-perceived growth in autonomy within selected EPAs.

Student Performance on Graded Versus Ungraded Readiness Assurance Tests in a Team-Based Learning Elective.

Objective. Team-based learning is widely used in pharmacy education. In this context, students need to be incentivized to do preclass preparation, thus ensuring they are ready for team-based learning, via graded readiness assurance tests (RATs). The purpose of this study was to determine the effect of graded versus ungraded RATs on examination performance in an ambulatory care elective course for third-year student pharmacists.Methods. For the course offered in spring 2020 and 2021, a standard team-based learning framework was employed. In 2020 the RATs were graded and contributed to the overall course grade (graded RAT cohort), but in 2021 RAT grades did not contribute to the course grade (ungraded RAT cohort). For the ungraded RAT cohort, at the end of the course students completed an online anonymous survey regarding class preparation and perceived team accountability.Results. No significant difference was found between the graded RAT (n=47) and ungraded RAT cohorts (n=36) in the overall mean percentage score on individual RATs (76% vs 74%) and individual examinations (82% vs 80%). Most students (69%-91%) in the ungraded RAT cohort reported completing preclass preparation assignments. In the postcourse survey, 94% of students agreed or strongly agreed that RATs contributed to team members' learning, and 86% agreed or strongly agreed that they were proud of their ability to assist in the team's learning.Conclusion. Ungraded RATs did not significantly impact students' examination performance in an elective course. Removing the grading of this test, whereby grading promotes the performance approach to learning, may have shifted the students' motivation to the mastery approach in the context of preclass preparation. This challenges a widely held belief that grades are necessary incentives for preclass preparation within team-based learning.

Best practices for recruitment of adolescents for biobanking and precision health research: a retrospective analysis comparing juvenile idiopathic arthritis cases with healthy controls.

BACKGROUND: Precision health in adolescents relies on the successful collection of data and biospecimens from an adequately sized sample of cases and comparison group(s), often healthy controls, to answer the research question. This research report describes the recruitment strategy, enrollment rates, and approach utilized in a successful biobehavioral research study. The study was designed to examine key health indicators in adolescents (13-17 years of age) with juvenile idiopathic arthritis (JIA) compared to a control group of healthy adolescents. The purpose of this analysis is to establish best practices and identify strategies to overcome barriers to recruitment of older adolescents, an age group that tends to be underrepresented in research studies. METHODS: A retrospective secondary analysis of data from a parent study about JIA with high consent rates was employed to explore factors affecting enrollment into the biobehavioral study. RESULTS: Of the 113 subjects who were recruited to the study, 74 met the eligibility criteria and reviewed the consent form. The consented group (n=40) represents 54% of those who were eligible upon initial screening. The rate of project enrollment was 2.7 participants per month. The pediatric rheumatologists referred 85% of the JIA group, and the study's principal investigator, a nurse scientist, referred 95% of the control group. Typical recruitment strategies, such as posting on social media, distributing flyers, and cold-calling potential participants from the clinic schedule were ineffective for both cases and controls. Barriers to enrollment included scheduling and fear of venipuncture. There were no demographic characteristics that significantly explained enrollment, differentiating between those who agreed to participate compared to those who refused. Successful strategies for enrollment of adolescents into this biobehavioral research study included scheduling study visits on weekends and school holidays; an informed consent and assent process that addressed adolescent fears of venipuncture; including a JIA patient on the study team; and utilizing existing relationships to maximize enrollment efforts. CONCLUSIONS: Effective recruitment and enrollment practices were relationship-specific and patient-centered. Researchers should utilize best practices to ensure that precision health for adolescents is advanced.

Structural and Mechanistic Insights into Caffeine Degradation by the Bacterial N-Demethylase Complex.

Caffeine, found in many foods, beverages, and pharmaceuticals, is the most used chemical compound for mental alertness. It is originally a natural product of plants and exists widely in environmental soil. Some bacteria, such as Pseudomonas putida CBB5, utilize caffeine as a sole carbon and nitrogen source by degrading it through sequential N-demethylation catalyzed by five enzymes (NdmA, NdmB, NdmC, NdmD, and NdmE). The environmentally friendly enzymatic reaction products, methylxanthines, are high-value biochemicals that are used in the pharmaceutical and cosmetic industries. However, the structures and biochemical properties of bacterial N-demethylases remain largely unknown. Here, we report the structures of NdmA and NdmB, the initial N1- and N3-specific demethylases, respectively. Reverse-oriented substrate bindings were observed in the substrate-complexed structures, offering methyl position specificity for proper N-demethylation. For efficient sequential degradation of caffeine, these enzymes form a unique heterocomplex with 3:3 stoichiometry, which was confirmed by enzymatic assays, fluorescent labeling, and small-angle x-ray scattering. The binary structure of NdmA with the ferredoxin domain of NdmD, which is the first structural information for the plant-type ferredoxin domain in a complex state, was also determined to better understand electron transport during N-demethylation. These findings broaden our understanding of the caffeine degradation mechanism by bacterial enzymes and will enable their use for industrial applications.

Polysaccharide-based liquid storage and transport media for non-refrigerated preservation of bacterial pathogens.

The preservation of biological samples for an extended time period of days to weeks after initial collection is important for the identification, screening, and characterization of bacterial pathogens. Traditionally, preservation relies on cold-chain infrastructure; however, in many situations this is impractical or not possible. Thus, our goal was to develop alternative bacterial sample preservation and transport media that are effective without refrigeration or external instrumentation. The viability, nucleic acid stability, and protein stability of Bacillus anthracis Sterne 34F2, Francisella novicida U112, Staphylococcus aureus ATCC 43300, and Yersinia pestis KIM D27 (pgm-) was assessed for up to 28 days. Xanthan gum (XG) prepared in PBS with L-cysteine maintained more viable F. novicida U112 cells at elevated temperature (40°C) compared to commercial reagents and buffers. Viability was maintained for all four bacteria in XG with 0.9 mM L-cysteine across a temperature range of 22-40°C. Interestingly, increasing the concentration to 9 mM L-cysteine resulted in the rapid death of S. aureus. This could be advantageous when collecting samples in the built environment where there is the potential for Staphylococcus collection and stabilization rather than other organisms of interest. F. novicida and S. aureus DNA were stable for up to 45 days upon storage at 22°C or 40°C, and direct analysis by real-time qPCR, without DNA extraction, was possible in the XG formulations. XG was not compatible with proteomic analysis via LC-MS/MS due to the high amount of residual Xanthomonas campestris proteins present in XG. Our results demonstrate that polysaccharide-based formulations, specifically XG with L-cysteine, maintain bacterial viability and nucleic acid integrity for an array of both Gram-negative and Gram-positive bacteria across ambient and elevated temperatures.

Consistent production of chlorine-stressed bacteria from non-chlorinated secondary sewage effluents for use in the U.S. Environmental Protection Agency Alternate Test Procedure protocol.

The U.S. Environmental Protection Agency Alternative Test Procedure protocol outlines a method to produce chlorine-stressed bacteria for water quality testing. Achieving consistent results is challenging due effluent variability. We describe a starting point for generating chlorine-stressed samples from secondary effluent to evaluate detection technologies to demonstrate comparability to EPA reference methods.

Ancient Regulatory Role of Lysine Acetylation in Central Metabolism.

Lysine acetylation is a common protein post-translational modification in bacteria and eukaryotes. Unlike phosphorylation, whose functional role in signaling has been established, it is unclear what regulatory mechanism acetylation plays and whether it is conserved across evolution. By performing a proteomic analysis of 48 phylogenetically distant bacteria, we discovered conserved acetylation sites on catalytically essential lysine residues that are invariant throughout evolution. Lysine acetylation removes the residue's charge and changes the shape of the pocket required for substrate or cofactor binding. Two-thirds of glycolytic and tricarboxylic acid (TCA) cycle enzymes are acetylated at these critical sites. Our data suggest that acetylation may play a direct role in metabolic regulation by switching off enzyme activity. We propose that protein acetylation is an ancient and widespread mechanism of protein activity regulation.IMPORTANCE Post-translational modifications can regulate the activity and localization of proteins inside the cell. Similar to phosphorylation, lysine acetylation is present in both eukaryotes and prokaryotes and modifies hundreds to thousands of proteins in cells. However, how lysine acetylation regulates protein function and whether such a mechanism is evolutionarily conserved is still poorly understood. Here, we investigated evolutionary and functional aspects of lysine acetylation by searching for acetylated lysines in a comprehensive proteomic data set from 48 phylogenetically distant bacteria. We found that lysine acetylation occurs in evolutionarily conserved lysine residues in catalytic sites of enzymes involved in central carbon metabolism. Moreover, this modification inhibits enzymatic activity. Our observations suggest that lysine acetylation is an evolutionarily conserved mechanism of controlling central metabolic activity by directly blocking enzyme active sites.