Hope Awakens with Early Diagnosis of Parkinson's Disease Based on Skin Odor
According to scientists from the United Kingdom, a simple test based on an individual's skin odor could aid the early diagnosis of Parkinson's disease. A study has already been launched to investigate the chemicals secreted by the skin of patients with Parkinson's disease.
Introduction
Patients aged > 75 years using dabigatran are significantly at higher risk of gastrointestinal bleeding compared to those on warfarin. High residual concentrations of dabigatran present in the blood just before the next dose (known as trough levels) have a significant impact on the increased risk of bleeding.
Study Goals and Methodology, Patient Population
A Dutch pilot study compared dabigatran concentrations in three age categories: < 75 years (n = 25), 75–84 years (n = 25), and ≥ 85 years (n = 25). Patients with atrial fibrillation were using dabigatran for at least 1 week before being included in the study. Dosing was age-appropriate and based on other clinical characteristics: 150 mg 2× daily or 110 mg 2× daily. Patients using other anticoagulants, antithrombotics, or medications with pharmacokinetic interactions involving P-glycoprotein (P-gp) inhibition were not included in the study. Other exclusion criteria included an estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2, transaminase elevation over twice the upper limit of normal, current malignancy, and weight < 50 kg or > 110 kg.
Blood samples were taken from patients just before the next dose of dabigatran. The plasma samples were then stored at –80 °C and later analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
Residual concentrations in each age category were compared using the Kruskal-Wallis test, and concentrations were normalized for the dose taken. The prevalence of patients with absolute concentrations > 150 ng/ml was determined using Fisher's exact test. Regression analysis was used to examine the influence of kidney function on differences between age groups.
Results
High residual concentrations of dabigatran (> 150 ng/ml) are considered risky for gastrointestinal bleeding. The study found that 40% (n = 10) of observed patients aged ≥ 85 years had residual concentrations exceeding this level, whereas the prevalence in patients aged < 75 years was 16% (n = 4; p = 0.059).
The median residual dabigatran concentration was 9% higher in patients aged 75 to 84 years (median: 99 ng/ml; range: 29–214). Additionally, patients aged ≥ 85 years had 33% higher residual dabigatran levels (median: 132 ng/ml; range: 36–324) compared to patients aged < 75 years (median: 108 ng/ml; range: 33–327), even though they generally used lower doses of dabigatran.
The dose-normalized medians were 0.66 ng/ml/mg in the age group < 75 years, 0.83 ng/ml/mg among patients aged 75–84 years, and 1.20 ng/ml/mg among patients ≥ 85 years (p = 0.004).
Conclusion
The study conducted in an elderly real-world population revealed significantly higher residual dabigatran concentrations in the oldest age category. Residual concentrations > 150 ng/ml were 2.5 times more common in patients aged ≥ 85 years. From a safety perspective, awareness of higher residual dabigatran concentrations is necessary to minimize bleeding risks in older patients, even with reduced dosing.
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Sources:
1. Gommans E., Grouls R. J. E., Kerkhof D. et al. Dabigatran trough concentrations in very elderly patients. Eur J Hosp Pharm 2021; 28 (4): 231–233, doi: 10.1136/ejhpharm-2020-002456.
2. SPC Pradaxa. Available at: www.ema.europa.eu/en/documents/product-information/pradaxa-epar-product-information_cs.pdf
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