METHODS: Patients were recruited from four hospitals. Clinical data were recorded and blood samples were taken for PK and genetic studies. Population PK parameters were estimated by nonlinear mixed-effects modelling in Monolix®. Models were evaluated using the difference in objective function value, goodness-of-fit plots, visual predictive check and bootstrap analysis. Monte Carlo simulation was conducted to evaluate different dosing regimens for IVIG.
RESULTS: A total of 30 blood samples were analysed from 10 patients. The immunoglobulin G concentration data were best described by a one-compartment model with linear elimination. The final model included both volume of distribution (Vd) and clearance (CL) based on patient's individual weight. Goodness-of-fit plots indicated that the model fit the data adequately, with minor model mis-specification. Genetic polymorphism of the FcRn gene and the presence of bronchiectasis did not affect the PK of IVIG. Simulation showed that 3-4-weekly dosing intervals were sufficient to maintain IgG levels of 5 g L-1 , with more frequent intervals needed to achieve higher trough levels.
CONCLUSIONS: Body weight significantly affects the PK parameters of IVIG. Genetic and other clinical factors investigated did not affect the disposition of IVIG.
METHODS: Computational Fluid Dynamics (CFD) approach is used to simulate the airflow in a neonate, an infant and an adult in sedentary breathing conditions. The healthy CT scans are segmented using MIMICS 21.0 (Materialise, Ann arbor, MI). The patient-specific 3D airway models are analyzed for low Reynolds number flow using ANSYS FLUENT 2020 R2. The applicability of the Grid Convergence Index (GCI) for polyhedral mesh adopted in this work is also verified.
RESULTS: This study shows that the inferior meatus of neonates accounted for only 15% of the total airflow. This was in contrast to the infants and adults who experienced 49 and 31% of airflow at the inferior meatus region. Superior meatus experienced 25% of total flow which is more than normal for the neonate. The highest velocity of 1.8, 2.6 and 3.7 m/s was observed at the nasal valve region for neonates, infants and adults, respectively. The anterior portion of the nasal cavity experienced maximum wall shear stress with average values of 0.48, 0.25 and 0.58 Pa for the neonates, infants and adults.
CONCLUSIONS: The neonates have an underdeveloped nasal cavity which significantly affects their airway distribution. The absence of inferior meatus in the neonates has limited the flow through the inferior regions and resulted in uneven flow distribution.