RESUMEN
BACKGROUND: Atrial fibrillation occurs in nearly half of geriatric inpatients and is a major cause of morbidity and mortality. Suboptimal anticoagulation use is an important concern in this population. This study aimed to evaluate the appropriateness of antithrombotic therapies in this patient cohort. METHODS: A retrospective analysis was conducted on the geriatric wards of a teaching hospital in Belgium, on a background of clinical pharmacy services. The first 90 atrial fibrillation patients from 2020 to 2022 were included if they received an oral anticoagulant. We assessed utilisation and appropriateness of antithrombotics at discharge, examined reasons for guideline deviations, and explored factors associated with underdosing. Temporal associations for appropriateness and type of anticoagulant (vitamin K antagonist (VKA) vs direct oral anticoagulant (DOAC)) were assessed. RESULTS: The mean age of patients was 86.5 (±5.3) years and the median CHA2DS2-VASc score was 5 (interquartile range (IQR) 4-6). At discharge, 256 (94.8%) patients used a DOAC; nine (3.3%) used a VKA; one (0.4%) a DOAC-antiplatelet combination, and in four patients (1.5%) all antithrombotics were discontinued. The majority (64.4%) of patients received reduced DOAC doses with apixaban prescribed in 40.7%. In 39 (14.4%) patients, antithrombotic use was considered inappropriate, mostly without a rationale (23/39). Year 2022 (odds ratio (OR) 0.104; 95% confidence interval (CI), 0.012-0.878) was the sole determinant for underdosing. No significant differences were found with respect to appropriateness (p=0.533) or anticoagulant class (p=0.479) over time. CONCLUSION: Most geriatric inpatients received a justified reduced DOAC dose. A significant proportion was managed inappropriately with underdosing (= unjustified reduced dose) being most common. Frequently no rationale was provided for deviating from trial-tested doses.
RESUMEN
The cerebellar pathologies in peroxisomal diseases underscore that these organelles are required for the normal development and maintenance of the cerebellum, but the mechanisms have not been resolved. Here we investigated the origins of the early-onset coordination impairment in a mouse model with neural selective deficiency of multifunctional protein-2, the central enzyme of peroxisomal ß-oxidation. At the age of 4weeks, Nestin-Mfp2(-/-) mice showed impaired motor learning on the accelerating rotarod and underperformed on the balance beam test. The gross morphology of the cerebellum and Purkinje cell arborization were normal. However, electrophysiology revealed a reduced Purkinje cell firing rate, a decreased excitability and an increased membrane capacitance. The distribution of climbing and parallel fiber synapses on Purkinje cells was immature and was accompanied by an increased spine length. Despite normal myelination, Purkinje cell axon degeneration was evident from the occurrence of axonal swellings containing accumulated organelles. In conclusion, the electrical activity, axonal integrity and wiring of Purkinje cells are exquisitely dependent on intact peroxisomal ß-oxidation in neural cells.
