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- This cohort study analyzed 3,199 new antidepressant prescriptions among elderly residents of Olmsted County, Minnesota (2005–2012), to quantify potential overprescribing and its predictors. They defined overprescribing based on regulatory approval, evidence level, and expert review. Overall, 24% of incident prescriptions met criteria for potential overprescribing—primarily newer drugs used for non‑specific psychiatric symptoms or subthreshold diagnoses bps.ac.uk . Using stratified logistic regression, the authors found that the odds of potential overprescribing were significantly higher for nursing‑home residents (OR > 1), patients with more medical comorbidities, those seeing more outpatient prescribers, taking more concomitant medications, and those with increased use of acute/urgent care in the prior year. Moreover, prescriptions issued via telephone, e‑mail, or patient portal (versus face‑to‑face) also significantly increased the odds. In essence, nearly one in four elderly patients received potentially inappropriate antidepressants, particularly in complex clinical settings and when care was delivered remotely.
- In a cohort of hypertensive patients, the authors measured serum amlodipine levels and corresponding blood pressure (BP) responses. They reported a ~47% coefficient of variation (CV) in steady‑state trough concentrations, highlighting substantial inter‑individual PK variability. A linear mixed‑effects model estimated that each 5 ng/mL increase in amlodipine concentration was associated with approximately a 4.2 mmHg decrease in systolic blood pressure (95% CI: 2.8–5.6 mmHg; p < 0.001). However, there was no significant relationship with diastolic pressure after adjusting for confounders. Factors such as age, body mass index, and concurrent medications only modestly explained the variability (R² ≈ 0.12), suggesting most differences remained unexplained. The study underscores a nearly 50% inter-patient variability in drug exposure, which translates into clinically meaningful differences in BP control.
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- This investigation into clopidogrel pharmacokinetics (PK) and pharmacodynamics (PD) among healthy volunteers (excluding known genetic polymorphisms, non-compliance, and co‑medications) found surprisingly high variability: the coefficient of variation (CV) for the active metabolite’s AUCₜ and Cₘₐₓ was 33.8 % and 40.2 %, respectively, while PD measures like VASP PRI, maximal platelet aggregation, and PRU showed CVs ranging from 32 % to 53 % . Regression analysis showed that known factors accounted for only 18 % of PK variability and 32–64 % of PD variability search.library.wisc.edu . Notably, even with 9 days of 75 mg/day dosing in homozygous CYP2C19 extensive metabolizers, 45 % exhibited high on‑treatment platelet reactivity search.library.wisc.edu+1accp1.onlinelibrary.wiley.com+1 . The findings highlight substantial unexplained inter-individual variation in clopidogrel response, underscoring the need for additional predictors to reduce cardiovascular risk.