Assessment of Prophylactic Antibiotic Coverage in Culture-positive Traumatic Open Fractures.

Guidelines provide varying recommendations for the prophylactic antimicrobial treatment of open fractures. This single-center, retrospective cohort study was conducted to determine how well an institutional prophylactic antibiotic protocol covered pathogens associated with open fractures. The authors included adult trauma patients with one or more open fractures and a positive culture from the site of the open fracture, and compared outcomes between patients who were covered by prophylactic antibiotics with patients not covered by prophylactic antibiotics.

Developing electronic health record algorithms that accurately identify patients with juvenile idiopathic arthritis.

Background: The objective of this study was to develop an algorithm that accurately identifies juvenile idiopathic arthritis (JIA) patients in the electronic health record (EHR).

Methods: Algorithms were developed in a de-identified EHR by searching for a priori JIA ICD-9 (International Classification of Diseases, Ninth Revision) and ICD-10-CM (International Classification of Diseases, Tenth Revision, Clinical Modification) codes and JIA-related keywords. Exclusion criteria were selected to remove other autoimmune diseases.

Out With the Old, in With the New: What Rising Pharmacists Need to Know About Vancomycin Therapeutic Drug Monitoring in Adults.

The goal of this commentary is to provide recent pharmacy school graduates and student pharmacists completing APPEs the essential background for correct vancomycin therapeutic drug monitoring (TDM) in the inpatient setting.

Geriatric Pharmacotherapy Case Series: Thiazide-Induced Hypokalemia.

The patient was a 72-year-old man with a history of hypertension, hyperlipidemia, benign prostatic hyperplasia, and oropharyngeal cancer. His home medications include amlodipine, atorvastatin, hydrochlorothiazide, and tamsulosin. He lives alone and eats a soft, bland, nutrient-poor diet.

Morbidity Due to Disparity in Pediatric Electroconvulsive Therapy.

Dr. Miller and colleagues recently submitted a Letter to the Editor discussing current state laws that result in disparity of electroconvulsive therapy (ECT) availability. In this current letter, we present a case of treatment-resistant childhood-onset schizophrenia (COS), with morbidity due to limited access to ECT.

Cytochromes P450 2C8 and 3A Catalyze the Metabolic Activation of the Tyrosine Kinase Inhibitor Masitinib.

Masitinib is a small molecule tyrosine kinase inhibitor under investigation for the treatment of amyotrophic lateral sclerosis, mastocytosis, and COVID-19. Hepatotoxicity has been reported in some patients while taking masitinib. The liver injury is thought to involve hepatic metabolism of masitinib by cytochrome P450 (P450) enzymes to form chemically reactive, potentially toxic metabolites.

Bioactivation and reactivity research advances - 2021 year in review.

This year's review on bioactivation and reactivity began as a part of the annual review on biotransformation and bioactivation led by Cyrus Khojasteh (see references). Increased contributions from experts in the field led to the development of a stand alone edition for the first time this year focused specifically on bioactivation and reactivity. Our objective for this review is to highlight and share articles which we deem influential and significant regarding the development of covalent inhibitors, mechanisms of reactive metabolite formation, enzyme inactivation, and drug safety.

Biotransformation novel advances - 2021 year in review.

Biotransformation field is constantly evolving with new molecular structures and discoveries of metabolic pathways that impact efficacy and safety. Recent review by Kramlinger et al. (2022) nicely captures the future (and the past) of highly impactful science of biotransformation (see the first article).

Interindividual Variability in Cytochrome P450 3A and 1A Activity Influences Sunitinib Metabolism and Bioactivation.

Sunitinib is an orally administered tyrosine kinase inhibitor associated with idiosyncratic hepatotoxicity; however, the mechanisms of this toxicity remain unclear. We have previously shown that cytochromes P450 1A2 and 3A4 catalyze sunitinib metabolic activation via oxidative defluorination leading to a chemically reactive, potentially toxic quinoneimine, trapped as a glutathione (GSH) conjugate (M5). The goals of this study were to determine the impact of interindividual variability in P450 1A and 3A activity on sunitinib bioactivation to the reactive quinoneimine and sunitinib -dealkylation to the primary active metabolite -desethylsunitinib (M1).

Factors Associated With Prolonged Antibiotic Use in the Setting of Suspected Pneumonia and Negative Bronchoalveolar Lavage Cultures.

Diagnostic criterion for pneumonia includes clinical data and bronchoalveolar lavage cultures (BALCx) to identify pathogens. Although ~60% of BALCx are negative, there may be reluctance to discontinue antibiotics, leading to prolonged antibiotic use (PAU). The purpose of this study is to compare outcomes of subjects with negative BALCx with PAU versus without prolonged antibiotic use (nPAU).

Exploration of the Role of the C-Terminal Domain of Human DNA Topoisomerase IIα in Catalytic Activity.

Human topoisomerase IIα (TOP2A) is a vital nuclear enzyme involved in resolving knots and tangles in DNA during replication and cell division. TOP2A is a homodimer with a symmetrical, multidomain structure. While the N-terminal and core regions of the protein are well-studied, the C-terminal domain is poorly understood but is involved in enzyme regulation and is predicted to be intrinsically disordered.

Clinically Significant Bradycardia and Hypotension Following Consumption of Betel Leaf in a Patient Treated for Chronic Atrial Fibrillation.

A case of new onset bradycardia and hypotension following betel leaf consumption in combination with verapamil and metoprolol in an atrial fibrillation (AF) patient. A 66-year-old Nigerian woman presented to the emergency department for evaluation of multiple near syncope episodes with underlying AF and slow ventricular response. After initial evaluation, the patient disclosed she had ingested several betel leaves that morning.

Impaired Absorption of Extended-Release Potassium Chloride in a Patient With a High-Output Ileostomy.

Background: Best practices in the management of ileostomies include use of immediate release (IR) medications and elimination of enteric coated and prokinetic agents. Extended-release (ER) potassium chloride is designed for postpyloric release rather than colonic absorption and is postulated to be an appropriate option for potassium repletion in this patient subset.

Case: We present a patient with an ileostomy who received intravenous ER and IR oral potassium chloride supplementation following diverting loop ileostomy.

Case Study 11: Considerations for Enzyme Mapping Experiments-Interaction Between the Aldehyde Oxidase Inhibitor Hydralazine and Glutathione.

Often it may be convenient and efficient to address multiple research questions with a single experiment. In many instances, however, the best approach is to design the experiment to address one question at a time. The design of enzyme mapping experiments is discussed in this chapter, focusing on considerations pertinent to the study of aldehyde oxidase (AO) vs.

Cannabidiol oxidation product HU-331 is a potential anticancer cannabinoid-quinone: a narrative review.

Cannabidiol and related cannabinoids are under exploration for the treatment of a number of disease states. The cannabinoid-quinone HU-331 has been studied as a potential anticancer therapeutic. Previous studies provide evidence that HU-331 displays anticancer activity without some of the known adverse events associated with traditional anticancer agents.

Classics in Chemical Neuroscience: Amitriptyline.

Amitriptyline was the second tricyclic antidepressant to appear on the market for major depressive disorder under the brand name Elavil in 1961. Since its emergence, amitriptyline has been an effective therapeutic in various disease states and disorders but has also been a concerning source of cardiotoxicity. Amitriptyline inhibits serotonin and norepinephrine reuptake as well as produces off-target activity at histaminergic, muscarinic, and various other receptors.

Reducing Inappropriate Outpatient Medication Prescribing in Older Adults across Electronic Health Record Systems.

Background: The American Geriatrics Society recommends against the use of certain potentially inappropriate medications (PIMs) in older adults. Prescribing of these medications correlates with higher rates of hospital readmissions, morbidity, and mortality. Vanderbilt University Medical Center previously deployed clinical decision support (CDS) to decrease PIM prescribing rates, but recently transitioned to a new electronic health record (EHR).

Detoxication versus Bioactivation Pathways of Lapatinib In Vitro: UGT1A1 Catalyzes the Hepatic Glucuronidation of Debenzylated Lapatinib.

-Dealkylation of the tyrosine kinase inhibitor lapatinib by cytochrome P450 3A enzymes is implicated in the development of lapatinib-induced hepatotoxicity. Conjugative metabolism of debenzylated lapatinib (M1) via glucuronidation and sulfation is thought to be a major detoxication pathway for lapatinib in preclinical species (rat and dog), limiting formation of the quinoneimine reactive metabolite. Glucuronidation of M1 by human recombinant UDP-glucuronosyltransferases (UGTs) has been reported in vitro; however, the relative UGT enzyme contributions are unknown, and the interspecies differences in the conjugation versus bioactivation pathways of M1 have not been fully elucidated.

Synthesis and evaluation of etoposide and podophyllotoxin analogs against topoisomerase IIα and HCT-116 cells.

Etoposide is a widely-used anticancer agent that targets human type II topoisomerases. Evidence suggests that metabolism of etoposide in myeloid progenitor cells is associated with translocations involved in leukemia development. Previous studies suggest halogenation at the C-2' position of etoposide reduces metabolism.