Resources Assessment for Penicillin Allergy Testing Performed by Pharmacists at the Patient's Bedside.

BACKGROUND: False penicillin allergies lead to increased antimicrobial resistance, adverse effects, and health care costs by promoting the use of broad-spectrum antibiotics. The Infectious Diseases Society of America recommends the implementation of allergy testing. OBJECTIVES: The primary objective of this research was to estimate the number of pharmacist full-time equivalents (FTEs) required for an intervention aimed at determining penicillin allergy in hospitalized patients. Acceptance of pharmacists' suggestions on antibiotic therapy are described. METHODS: A quasi-experimental study was conducted in a 712-bed university hospital involving hospitalized patients with a suspected penicillin allergy and an infection treatable with penicillin. The time required for the intervention, which included a questionnaire, penicillin allergy testing (skin-prick test, intradermal injection, and oral provocation test), and recommendations on antibiotic therapy were measured to calculate the number of pharmacist FTEs. RESULTS: A total of 55 patients were included. Scarification allergy testing was performed on 37, intradermal allergy test on 33, and oral provocation test on 26 patients. The intervention ruled out penicillin allergy in 26 patients, with no serious adverse effects. The intervention was associated with a median weekly pharmacist FTE of 0.15 (interquartile range = 0.12-0.25). The acceptance of pharmacists' suggestions was high and led to 9 patients being switched to an antibiotic with a narrower spectrum of activity. CONCLUSIONS AND RELEVANCE: This study describes penicillin allergy testing and the number of median weekly hospital pharmacist FTEs required, which was approximately 0.15. These data may aid in the implementation of this safe intervention that promotes narrower-spectrum antibiotherapy.

The overexpression of presenilin2 and Alzheimer's-disease-linked presenilin2 variants influences TRPC6-enhanced Ca2+ entry into HEK293 cells.

Mutations in the presenilin (PS) genes are linked to the development of early-onset Alzheimer's disease by a gain-of-function mechanism that alters proteolytic processing of the amyloid precursor protein (APP). Recent work indicates that Alzheimer's-disease-linked mutations in presenilin1 and presenilin2 attenuate calcium entry and augment calcium release from the endoplasmic reticulum (ER) in different cell types. However, the regulatory mechanisms underlying the altered profile of Ca(2+) signaling are unknown. The present study investigated the influence of two familial Alzheimer's-disease-linked presenilin2 variants (N141I and M239V) and a loss-of-function presenilin2 mutant (D263A) on the activity of the transient receptor potential canonical (TRPC)6 Ca(2+) entry channel. We show that transient coexpression of Alzheimer's-disease-linked presenilin2 mutants and TRPC6 in human embryonic kidney (HEK) 293T cells abolished agonist-induced TRPC6 activation without affecting agonist-induced endogenous Ca(2+) entry. The inhibitory effect of presenilin2 and the Alzheimer's-disease-linked presenilin2 variants was not due to an increase in amyloid beta-peptides in the medium. Despite the strong negative effect of the presenilin2 and Alzheimer's-disease-linked presenilin2 variants on agonist-induced TRPC6 activation, conformational coupling between inositol 1,4,5-trisphosphate receptor type 3 (IP(3)R3) and TRPC6 was unaffected. In cells coexpressing presenilin2 or the FAD-linked presenilin2 variants, Ca(2+) entry through TRPC6 could still be induced by direct activation of TRPC6 with 1-oleoyl-2-acetyl-sn-glycerol (OAG). Furthermore, transient coexpression of a loss-of-function PS2 mutant and TRPC6 in HEK293T cells enhanced angiotensin II (AngII)- and OAG-induced Ca(2+) entry. These results clearly indicate that presenilin2 influences TRPC6-mediated Ca(2+) entry into HEK293 cells.