Elderly patients are at high risk of over-anticoagulation and of haemorrhagic risk when on warfarin, especially during treatment induction. In Charles Foix Hospital, a 800-bed geriatric hospital, we specifically developed for in-patients older than 70 years (target INR 2.5) a simple low-dose warfarin induction regimen. The dosing recommendations were summarized on a prescribing guidance pocket chart. Eighteen months after the distribution of the chart, we conducted a one-year observational study in order to evaluate: i/ the time needed to achieve the warfarin maintenance dose; ii/ the prescriber'adherence to the recommendations; iii/ the benefit for elderly patients receiving warfarin therapy. The mean time needed to achieve the warfarin maintenance dose was 12.3 +/- 7.0 days for the 89 patients included in the study: 10.6 +/- 5.9 days for the 30 patients whose prescribers followed the recommendations versus 13.5 +/- 7.6 days for the 59 patients whose prescribers did not follow the recommendations. There is a trend to a more frequent over-anticoagulation in patients whose prescribers did not follow the recommendations. The duration of the heparin-warfarin overlap was significantly shorter when the recommendations were followed. Finally, the reasons for non-adherence to the recommendations were analyzed. This study illustrates an assessment of practice in an health care institution.
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Cancers (Basel)
December 2024
Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Triple-negative breast cancers (TNBCs) typically have a greater immune cell infiltrate and are more likely to respond to immune checkpoint inhibition (ICI) than ER+ or HER2+ breast cancers. However, there is a crucial need to optimize combining chemotherapy strategies with ICI to enhance overall survival in TNBC. Therefore, we developed a high-throughput co-culture screening assay to identify compounds that enhance CD8+ T-cell-mediated tumor cell cytotoxicity.
View Article and Find Full Text PDFMol Pharmacol
February 2024
Departments of Anesthesiology (K.L., S.J.M., J.S.D.), Pharmacology (K.L., C.H., J.D.B., U.R., O.B., C.W.L., J.S.D.), Pediatrics (E.L.S.), and Biochemistry (J.A.B.), Vanderbilt University Medical Center, Nashville, Tennessee and Vanderbilt Institute of Chemical Biology, Vanderbilt University, Nashville, Tennessee (J.A.B., E.L.D., J.S.D.)
Vascular smooth muscle K channels critically regulate blood flow and blood pressure by modulating vascular tone and therefore represent attractive drug targets for treating several cardiovascular disorders. However, the lack of potent inhibitors that can selectively inhibit Kir6.1/SUR2B (vascular K) over Kir6.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
July 2023
Department of Chemistry, University of Manchester, Manchester, M13 9PL, UK.
We report the modulation of reactivity of nitrogen dioxide (NO ) in a charged metal-organic framework (MOF) material, MFM-305-CH in which unbound N-centres are methylated and the cationic charge counter-balanced by Cl ions in the pores. Uptake of NO into MFM-305-CH leads to reaction between NO and Cl to give nitrosyl chloride (NOCl) and NO anions. A high dynamic uptake of 6.
View Article and Find Full Text PDFBioorg Med Chem Lett
May 2023
Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN 37232, USA; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address:
Kir6.2/SUR1 is an ATP-regulated potassium channel that acts as an intracellular metabolic sensor, controlling insulin and appetite-stimulatory neuropeptides secretion. In this Letter, we present the SAR around a novel Kir6.
View Article and Find Full Text PDFAssay Drug Dev Technol
April 2023
Department of Biomedical Engineering, Vanderbilt University, Nashville, Tennessee, USA.
Antagonists of the serotonin receptor 2B (5-HT) have shown great promise as therapeutics for the treatment of pulmonary arterial hypertension, valvular heart disease, and related cardiopathies. Herein, we describe a high-throughput screen campaign that led to the identification of highly potent and selective 5-HT antagonists. Furthermore, selected compounds were profiled for their predicted ability to cross the blood-brain barrier.
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