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.
SCOPE OF REVIEW: This review paper concisely collates and reviews the information reported in the simulation research in terms of MC simulation of radiosensitization and dose enhancement effects caused by the inclusion of Au NPs in tumor cells, simulation mechanisms, benefits and limitations.
MAJOR CONCLUSIONS: In this review, we first explore the recent advances in MC simulation on Au NPs radiosensitization. The MC methods, physical dose enhancement and enhanced chemical and biological effects is discussed, followed by some results regarding the prediction of dose enhancement. We then review Multi-scale MC simulations of Au NP-induced DNA damages for X-ray irradiation. Moreover, we explain and look at Multi-scale MC simulations of Au NP-induced DNA damages for X-ray irradiation.
GENERAL SIGNIFICANCE: Using advanced chemical module-implemented MC simulations, there is a need to assess the radiation-induced chemical radicals that contribute to the dose-enhancing and biological effects of multiple Au NPs.
METHODS: A 'meta-model' with 4894 concentrations from 1631 neonates was built using NONMEM, and Monte Carlo simulations were performed to design an optimal intermittent infusion, aiming to reach a target AUC0-24 of 400 mg·h/L at steady-state in at least 80% of neonates.
RESULTS: A two-compartment model best fitted the data. Current weight, postmenstrual age (PMA) and serum creatinine were the significant covariates for CL. After model validation, simulations showed that a loading dose (25 mg/kg) and a maintenance dose (15 mg/kg q12h if <35 weeks PMA and 15 mg/kg q8h if ≥35 weeks PMA) achieved the AUC0-24 target earlier than a standard 'Blue Book' dosage regimen in >89% of the treated patients.
CONCLUSIONS: The results of a population meta-analysis of vancomycin data have been used to develop a new dosing regimen for neonatal use and to assist in the design of the model-based, multinational European trial, NeoVanc.
METHODS: All relevant studies were identified through keyword searches in electronic databases from inception until September 2020. The searched publications were reviewed, categorised and analysed based on their respective methodology.
RESULTS: Hundred and one publications were identified which utilised existing MC-based applications/programs or customised MC simulations. Two outstanding challenges were identified that contribute to uncertainties in the virtual simulation reconstruction. The first challenge involves the use of anatomical models to represent individuals. Currently, phantom libraries best balance the needs of clinical practicality with those of specificity. However, mismatches of anatomical variations including body size and organ shape can create significant discrepancies in dose estimations. The second challenge is that the exact positioning of the patient relative to the beam is generally unknown. Most dose prediction models assume the patient is located centrally on the examination couch, which can lead to significant errors.
CONCLUSION: The continuing rise of computing power suggests a near future where MC methods become practical for routine clinical dosimetry. Dynamic, deformable phantoms help to improve patient specificity, but at present are only limited to adjustment of gross body volume. Dynamic internal organ displacement or reshaping is likely the next logical frontier. Image-based alignment is probably the most promising solution to enable this, but it must be automated to be clinically practical.