Introduction: Atrial fibrillation (AF) increases cardiovascular morbidity and mortality. To reduce thrombosis and bleeding risks, and due to high variability of unfractionated heparin (UFH) effect, activated clotting time (ACT) is used during radiofrequency catheter ablation (RFCA) of AF to guide UFH dose. This study aimed to develop a population PK-PD model and perform multivariable analysis in order to identify the most significant covariates associated with interindividual variability of UFH.
Methods: Electronic medical records from 668 patients undergoing RFCA were analyzed, including relevant covariates. The relationship between UFH dose and ACT and the impact of the main covariates were characterized using a mixed-effect PK-PD model. Multivariable analysis was then used to identify predictors of ACT 15 minutes after UFH administration (ACT15).
Results: A two-compartment PK model with linear elimination and a direct Emax PD model with a baseline and sigmoidicity best described the observed ACT values. Pretreatment with dabigatran, warfarin, or fluindione significantly influenced baseline ACT. Pretreatment with vitamin K antagonists or low molecular weight heparin explained Emax variability. The multivariable model identified baseline ACT, initial UFH dose, and previous anticoagulant as the main predictors of ACT15. Model evaluation through resampling and external validation showed accurate ACT15 predictions.
Conclusion: This study presents the first population PK-PD model characterizing the relationship between UFH doses and ACT during RFCA, along with multivariable analysis. Additionally, predictive calculators for ACT15 and UFH dose based on patient and procedural characteristics were developed, enhancing personalized anticoagulation management during RFCA.
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http://dx.doi.org/10.1016/j.biopha.2024.117700 | DOI Listing |
Sci Rep
December 2024
Gateway Antarctica, University of Canterbury, Christchurch, New Zealand.
The Tibetan Plateau is home to numerous glaciers that are important for freshwater supply and climate regulation. These glaciers, which are highly sensitive to climatic variations, serve as vital indicators of climate change. Understanding glacier-fed hydrological systems is essential for predicting water availability and formulating climate adaptation strategies.
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December 2024
Department of Environmental Management and Toxicology, Michael Okpara University of Agriculture, Umudike, Nigeria.
The geochemical and chemical constituents of river water quality could be influenced by human activities and organic processes like water interacting with the lithogenic structure that the river flows through. Evaluating evidence based primary root of the predominant pollutant ions, their interactions as well as the factors controlling their dominance is crucial in studies regarding water environment and hydrology especially as most studies focus on theoretical methods. In order to understand the water cycle, safeguard surface water resources, and preserve the human environment, this study evaluated surface water hydro-chemical facies, quality dynamics, and portability in southern Nigeria using multivariate statistical approaches by analyzing selected hydro-chemical characteristics as indicators of pollution along the river during wet and dry seasons.
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December 2024
Department of Medical and Surgical Sciences, Institute of Cardiology, University of Bologna, Policlinico S.Orsola-Malpighi, via Massarenti 9, Bologna, 40138, Italy.
Cardiac implantable electronic devices infections (CIEDI) are associated with poor survival despite the improvement in transvenous lead extraction (TLE). Aetiology and systemic involvement are driving factors of clinical outcomes. The aim of this study was to explore their contribute on overall mortality.
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December 2024
College of Mechanical Engineering, Hubei University of Technology, Wuhan, Hubei, 430068, China.
The defoliation quality of mugwort defoliation equipment is an important factor to measure the defoliation efficiency, and the tensile properties of mugwort petiole will have an impact on the defoliation quality, such as the crushing rate and the abscission rate. In order to reduce the crushing rate and improve the abscission rate during mechanical harvesting of mugwort leaves, the tensile properties of mugwort petiole need to be studied. The tensile properties of mugwort petiole are closely related to its macroscopic and microscopic physicochemical parameters.
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December 2024
School of Data Science, The Chinese University of Hong Kong-Shenzhen, Shenzhen, China.
Recently, RNA velocity has driven a paradigmatic change in single-cell RNA sequencing (scRNA-seq) studies, allowing the reconstruction and prediction of directed trajectories in cell differentiation and state transitions. Most existing methods of dynamic modeling use ordinary differential equations (ODE) for individual genes without applying multivariate approaches. However, this modeling strategy inadequately captures the intrinsically stochastic nature of transcriptional dynamics governed by a cell-specific latent time across multiple genes, potentially leading to erroneous results.
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