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Race and sex associations with tacrolimus pharmacokinetics in stable kidney transplant recipients
Get PDFStudy Objective: This study investigated race and sex differences in tacrolimus pharmacokinetics and pharmacodynamics in stable kidney transplant recipients.
Design and Setting: A cross-sectional, open-label, single center, 12-h pharmacokinetic-pharmacodynamic study was conducted. Tacrolimus pharmacokinetic parameters included area under the concentration-time curve (AUC0–12), AUC0–4, 12-h troughs (C12 h), maximum concentrations (Cmax), oral clearance (Cl), with dose-normalized AUC0–12, troughs, and Cmax with standardized adverse effect scores. Statistical models were used to analyze end points with individual covariate-adjustment including clinical factors, genotypic variants CYP3A5*3, CYP3A5*6, CYP3A5*7(CYP3A5*3*6*7) metabolic composite, and ATP binding cassette gene subfamily B member 1 (ABCB1) polymorphisms.
Patients: 65 stable, female and male, Black and White kidney transplant recipients receiving tacrolimus and mycophenolic acid ≥6 months post-transplant were evaluated.
Measurements and Main Results: Black recipients exhibited higher tacrolimus AUC0–12 (Race: p = 0.005), lower AUC* (Race: p \u3c 0.001; Race × Sex: p = 0.068), and higher Cl (Race: p \u3c 0.001; Sex: p = 0.066). Greater cumulative (Sex: p \u3c 0.001; Race × Sex: p = 0.014), neurologic (Sex: p = 0.021; Race × Sex: p = 0.005), and aesthetic (Sex: p = 0.002) adverse effects were found in females, with highest scores in Black women. In 84.8% of Black and 68.8% of White patients, the target AUC0–12 was achieved (p = 0.027). In 31.3% of White and 9.1% of Black recipients, AUC0–12 was \u3c100 \u3eng‧h/ml despite tacrolimus troughs in the target range (p = 0.027). The novel CYP3A5*3*6*7 metabolic composite was the significant covariate accounting for 15%–19% of tacrolimus variability in dose (p = 0.002); AUC0–12 h* (p \u3c 0.001), and Cl (p \u3c 0.001).
Conclusions: Tacrolimus pharmacokinetics and adverse effects were different among stable kidney transplant recipient groups based upon race and sex with interpatient variability associated with the CYP3A5*3*6*7 metabolic composite. More cumulative, neurologic, and aesthetic adverse effects were noted among females. Tacrolimus regimens that consider race and sex may reduce adverse effects and enhance allograft outcomes by facilitating more patients to achieve the targeted AUC0–12 h
0880: Don Ferguson Sheet Music Collection, 1850-1981
Get PDFDon Ferguson’s collection consists of 358 individual pieces of piano sheet music spanning the first seven decades of the 20th century. There are also two string quartette scores named Quartette by Mozart and Beethoven for two violins, viola, and cello. They were published in Leipzig, Germany in the 1940s and were given to Mr. Ferguson by a member of the Bern, Switzerland Symphony Orchestra
The Best New Year\u27s Resolution I Ever Made Was To Exercise Less
No full text“There’s a New Year’s resolution I think you need to make,” said my husband, James, a resident physician. “I think you should only run four days a week. Only four days of working out each week.”
“Are you just jealous that I can run more than you?” I responded with a wink
Retention and Career Success of Faculty: The Case for Building a Sense of Belonging to the Academic Medicine Community
Get PDFAs attrition in the healthcare workforce rises, factors that positively impact retention, engagement, work satisfaction, and vitality for faculty in Colleges of Medicine are of critical importance. One important factor that is less often discussed is the need to develop a sense of belonging and connectedness to the institutional community. Underrepresented minority faculty particularly feel the benefit of feeling like they belong. Recommendations for enhancing faculty connectedness to a community in support of developing a sense of belonging to that community are offered
Syphilis and Proteinuria in Pregnancy
Get PDFSyphilis has the potential to result in serious irreversible morbidity and mortality during pregnancy and has been increasing in incidence across the United States. While syphilis is a common disease and a known but rare cause of membranous nephropathy, it can complicate the clinical picture and obscure accurate diagnosis of women presenting with proteinuria during pregnancy. We report a case of proteinuria with syphilis in the second trimester of pregnancy as an educational review
