Article
Microbiology
N. Layios, C. Visee, V Mistretta, R. Denooz, N. Maes, J. Descy, F. Frippiat, S. Marchand, N. Gregoire
Summary: This article describes the population pharmacokinetics of temocillin administered via continuous infusion versus intermittent infusion in critically ill patients with pneumonia. The study also examines the penetration ratios of the drug in the epithelial lining fluid/plasma and determines the probability of achieving target concentrations for a range of MICs. The results show that continuous infusion provides better PK/PD indexes but still falls below recommended doses for systemic infections, unless the patient has moderate renal impairment.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Mohammad H. Al-Shaer, Carolyn D. Philpott, Christopher A. Droege, Joshua D. Courter, Daniel P. Healy, Molly E. Droege, Neil E. Ernst, Eric W. Mueller, Charles A. Peloquin
Summary: Sepsis contributes to 50% of acute kidney injuries in the ICU, often requiring CRRT which impacts antimicrobial exposure. A cefepime PK model was built for CRRT ICU patients, showing good target attainment with intermittent infusion regimens at MICs <= 8 mg/l and extended infusion at MICs of 16 mg/l. This regimen may be considered for resistant bacterial infections.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Infectious Diseases
Irena Murinova, Martin Svidrnoch, Tomas Gucky, Jan Hlavac, Pavel Michalek, Ondrej Slanar, Martin Sima
Summary: This study describes the population pharmacokinetics of oxacillin and proposes continuous infusion and dosing based on renal function for optimal achievement of target PK/PD values.
Article
Microbiology
Jiao Xie, Qianting Yang, Xinyan Han, Yuzhu Dong, Tao Zhang, Youjia Li, Meixi Ji, Chenwei Liu, Yan Cai, Yan Wang
Summary: This study found that differences in pharmacokinetics/pharmacodynamics target attainment are often overlooked when antifungals are switched in critically ill patients. The results showed that triazoles at guideline-recommended doses could achieve target exposure for de-escalation treatment, while fluconazole and voriconazole performed poorly. Additionally, the achievement of target exposure for echinocandins decreased as body weight increased, with intermittent dosing strategy showing slightly higher CFR values in most simulations compared to conventional dosing strategy.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Microbiology
Venkata K. Yellepeddi, Bryn Lindley, Emi Radetich, Shaun Kumar, Zubin Bhakta, Laurie Leclair, Madison Parrot, David C. Young
Summary: In this study, the pharmacokinetics (PK) of vancomycin in people with cystic fibrosis (PwCF) were characterized using a population PK approach. The study evaluated the probability of target attainment (PTA) for 12 different initial dosing scenarios using comprehensive Monte Carlo simulations. The results provide important guidance for vancomycin dosing in the treatment of pulmonary infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in PwCF.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Multidisciplinary Sciences
Jan Kessler, Francesco Calcavecchia, Thomas D. Kuehne
Summary: Inspired by the universal approximation theorem and the widespread adoption of artificial neural network techniques, feed-forward neural networks are proposed as a general purpose trial wave function for quantum Monte Carlo simulations of continuous many-body systems. The accuracy of the trial wave functions was demonstrated by studying an exactly solvable model system of two trapped interacting particles and the hydrogen dimer. The whole many-body wave function can be represented by a neural network for simple model systems, while the antisymmetry condition of non-trivial fermionic systems is incorporated by means of a Slater determinant.
ADVANCED THEORY AND SIMULATIONS
(2021)
Article
Computer Science, Information Systems
Huanlong Zhang, Jiapeng Zhang, Guohao Nie, Jingjing Wu, Yanchun Zhao, W. J. (Chris) Zhang, Fusheng Li
Summary: Traditional correlation filter trackers are prone to failure in uncertain motion or distractor scenarios, but the proposed TOP tracker effectively utilizes target-objectness proposals to improve tracking performance.
INFORMATION SCIENCES
(2022)
Article
Engineering, Biomedical
Emilie Jean, Simon Lambert-Girard, Francois Therriault-Proulx, Luc Beaulieu
Summary: This study investigates the limitations of a hybrid Cerenkov-scintillation detector and the associated method for irradiation angle measurements using Monte Carlo simulations. The simulations show good agreement with experimental values, with smaller errors in irradiation angle measurements. The accuracy of the detector is affected by the energy dependency and the slope of the angular calibration curve.
PHYSICS IN MEDICINE AND BIOLOGY
(2023)
Article
Polymer Science
Jiang Zhang, Wenbing Hu
Summary: The effects of specific chain-end hydrogen-bonding interactions on the once-folding crystallization of 16-mers in PEG were investigated. It was found that these interactions have little influence on the kinetics of nucleation and lateral growth, but create a significant gap at the growth front, leading to the double-lamella phenomenon. The chain-end hydrogen-bonding interactions are abundant at the surfaces of once-folded lamellar crystals, enhancing their metastability and hindering their thickening into chain-extended crystals. Additionally, intra- and inter-molecular secondary nucleation at the folded and extended growth fronts exhibit different growth rate dependencies on the interaction strengths. The study reveals the role of specific chain-end interactions in PEG crystallization.
Article
Physics, Fluids & Plasmas
Cole Miles, Benjamin Cohen-Stead, Owen Bradley, Steven Johnston, Richard Scalettar, Kipton Barros
Summary: We present a method to simplify Monte Carlo simulations in the grand canonical ensemble by imposing a fictitious dynamics on the chemical potential. The method runs concurrently with the Monte Carlo sampling of the physical system and corrects the chemical potential based on time-averaged estimates of the mean and variance of the particle number. We performed various tests and found rapid convergence of the chemical potential in all cases, with the inexactness of the tuning algorithm contributing only a minor part of the total measurement error for realistic simulations.
Article
Chemistry, Physical
Dilimulati Aierken, Michael Bachmann
Summary: We systematically investigate the effect of bending stiffness on the ground-state conformations of semiflexible polymers. The formation of different conformations depends strongly on the strength of the bending restraint, as observed through detailed analysis of contact and distance maps.
JOURNAL OF CHEMICAL PHYSICS
(2023)
Article
Infectious Diseases
Pier Giorgio Cojutti, Elisa Morandin, Massimo Baraldo, Federico Pea
Summary: Through a population pharmacokinetic analysis of continuous infusion piperacillin/tazobactam, this study identified optimal dosages based on creatinine clearance rates, and calculated the probability of target attainment against specific bacteria. Tailoring the dosage to individual patients is crucial for successful treatment outcomes.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2021)
Article
Engineering, Environmental
Giovanna J. Lavado, Diego Baderna, Edoardo Carnesecchi, Alla P. Toropova, Andrey A. Toropov, Jean Lou C. M. Dorne, Emilio Benfenati
Summary: Soil pollution is a critical environmental challenge that can have adverse effects on both humans and the ecosystem. Various bioassays have been developed to investigate the soil ecotoxicity of chemicals, including a 28-day collembolan reproduction test with the springtail Folsomia candida. Despite limited toxicity data for Collembola, QSAR models have been developed for predicting reproductive toxicity induced by organic compounds in Folsomia candida, showing good predictive performance for ecological risk assessment of chemicals.
JOURNAL OF HAZARDOUS MATERIALS
(2022)
Article
Astronomy & Astrophysics
William Detmold, Gurtej Kanwar, Henry Lamm, Michael L. Wagman, Neill C. Warrington
Summary: Path integral contour deformations have been proposed as a solution to sign and signal-to-noise problems in lattice field theories, particularly those related to phase fluctuations. By defining a family of contour deformations suitable for SU(N) lattice gauge theory, these problems associated with complex actions and observables can be significantly reduced. Experimental results show that this approach can achieve a significant reduction in variance.
Article
Chemistry, Physical
Mahmoud EL Katib, El Mahjoub Chakir, Rajaa Sebihi, Hind Saikouk, Oussama Nhila
Summary: The purpose of this study was to develop and validate a GATE model of the newly manufactured total-body PET scanner (uEXPLORER) to evaluate its simulation capability and provide a reliable model for optimization studies. The simulation results demonstrated good agreement with the experimental results, indicating that the developed model accurately predicted the performance of the uEXPLORER PET scanner.
RADIATION PHYSICS AND CHEMISTRY
(2023)
Article
Medical Laboratory Technology
Tim M. J. Ewoldt, Alan Abdulla, Nicole G. M. Hunfeld, Anouk E. Muller, Diederik Gommers, Suzanne Polinder, Birgit C. P. Koch, Henrik Endeman
Summary: This study found that target attainment for beta-lactam antibiotics in ICU patients shows a trend towards higher total costs, which can be attributed to the costs of long ICU stays and renal replacement therapy.
THERAPEUTIC DRUG MONITORING
(2022)
Article
Infectious Diseases
Thijs ten Doesschate, Kelly Hendriks, Cornelis Henri van Werkhoven, Evelien C. van der Hout, Tamara N. Platteel, Irene A. M. Groenewegen, Anouk E. Muller, Andy I. M. Hoepelman, Marc J. M. Bonten, Suzanne E. Geerlings
Summary: This study compares the effectiveness and safety of daily prophylaxis with 50 mg or 100 mg nitrofurantoin for recurrent urinary tract infection. The results show that there is no significant difference in the risk of UTI or pyelonephritis between the two dosages, but there is a higher risk of cough, dyspnea, and nausea with the 100 mg dosage.
CLINICAL MICROBIOLOGY AND INFECTION
(2022)
Review
Medical Laboratory Technology
Birgit C. P. Koch, Anouk E. Muller, Nicole G. M. Hunfeld, Brenda C. M. de Winter, Tim M. J. Ewoldt, Alan Abdulla, Henrik Endeman
Summary: Early initiation of antibiotics and correct dosing are essential for improving infections in critically ill patients. However, the altered pharmacokinetic parameters and less susceptible microorganisms pose challenges to ensuring optimal antibiotic exposure. Therapeutic drug monitoring (TDM) is a commonly used strategy to support individualized dosing of antibiotics. This review recommends implementing TDM for glycopeptides and aminoglycosides, and suggests performing TDM in specific patient cases for antibiotics such as beta-lactams, fluoroquinolones, and linezolid. Future possibilities for improving TDM include model-informed precision dosing and the use of rapid bioanalytical techniques or biosensors for real-time monitoring of drug concentrations.
THERAPEUTIC DRUG MONITORING
(2022)
Review
Medical Laboratory Technology
Alan Abdulla, Puck van den Broek, Tim M. J. Ewoldt, Anouk E. Muller, Henrik Endeman, Birgit C. P. Koch
Summary: This study provides an overview of the current practices of beta-lactam therapeutic drug monitoring (TDM) and identifies barriers and facilitators in its clinical implementation. The main barriers include insufficient knowledge and unavailability of assays, while doubts about cost-effectiveness and clinical effectiveness hinder its broad implementation. Collaboration between physicians and clinical pharmacists and microbiologists can improve physicians' willingness to use beta-lactam TDM.
THERAPEUTIC DRUG MONITORING
(2022)
Article
Pharmacology & Pharmacy
Femke de Velde, Brenda C. M. de Winter, Michael N. Neely, Jan Strojil, Walter M. Yamada, Stephan Harbarth, Angela Huttner, Teun van Gelder, Birgit C. P. Koch, Anouk E. Muller
Summary: Population pharmacokinetic modeling and simulation are used in antibiotic dosing optimization, with parametric and nonparametric models showing differences in predictive performance and target attainment probability calculations. The study found that while both models had satisfactory predictive performance for high eGFR values, they were insufficient for lower eGFR values, with the nonparametric model resulting in lower MICs due to higher estimated between-subject variability.
Review
Pharmacology & Pharmacy
Fleur M. Keij, Gerdien A. Tramper-Stranders, Birgit C. P. Koch, Irwin K. M. Reiss, Anouk E. Muller, Rene F. Kornelisse, Karel Allegaert
Summary: The pharmacokinetics of clavulanic acid in pediatric patients is highly variable, similar to reports in adults, but more pronounced. There is a lack of knowledge regarding the specific population-specific explanation for this variability. Model-based pharmacokinetic studies addressing maturational and disease-specific changes in the pediatric population as well as additional pharmacodynamic studies are needed to define a clear target.
CLINICAL PHARMACOKINETICS
(2022)
Article
Pharmacology & Pharmacy
Eric Rozenveld, Nieko Punt, Martijn van Faassen, Andre P. van Beek, Daan J. Touw
Summary: This study analyzed the pharmacokinetics of hydrocortisone in patients with adrenal insufficiency, incorporating protein binding states into the PK model. The new model showed improved predictive ability for free cortisol concentrations and better correlations between total and free hydrocortisone AUC(24) compared to the old model.
Article
Infectious Diseases
Eveline E. Roelofsen, Brenda C. M. de Winter, Heleen van der Spek, Susan Snijders, Birgit C. P. Koch, Sanne van den Berg, Anouk E. Muller
Summary: For decades, flucloxacillin has been used to treat methicillin-susceptible Staphylococcus aureus (MSSA). This study aimed to determine the pharmacokinetic/pharmacodynamic (PK/PD) index and the required PD-index value for efficacy. The results provide insights for optimizing dosing regimens in humans.
Article
Microbiology
Anouk E. E. Muller, Merel Raaphorst, Aart van der Meijden, Brenda C. M. de Winter, Joseph Meletiadis, Sanne van den Berg
Summary: This study investigated the pharmacokinetics of temocillin in plasma and epithelial lining fluid in infected neutropenic mice, and determined the exposure-response relationships for Escherichia coli and Klebsiella pneumoniae. The results showed that temocillin achieved a static effect in the lung infection model with a lower median %fT>MIC compared to the thigh infection model, indicating its potential use in patients with pneumonia.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Infectious Diseases
Aart van der Meijden, Vincent Aranzana-Climent, Heleen van der Spek, Brenda C. M. de Winter, William Couet, Joseph Meletiadis, Anouk E. Muller, Sanne van den Berg
Summary: In this study, the pharmacokinetics and pharmacodynamics of polymyxin B were determined in neutropenic infected mice. The fAUC/MIC index was found to best describe the drug’s effectiveness. However, the standard dosing regimen did not achieve the PK/PD targets for the majority of clinical isolates, suggesting that polymyxin B may be ineffective as monotherapy for serious infections.
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
(2023)
Article
Infectious Diseases
D. Abraham Van den Born, Anne-Grete Martson, Anette Veringa, Nieko C. Punt, Tjip S. Van der Werf, Jan-Willem C. Alffenaar, Marieke G. G. Sturkenboom, Daan J. Touw
Summary: This study investigated the effect of inflammation on the metabolism of voriconazole and found that C-reactive protein (CRP) was the only significant covariate. The final pharmacokinetic model, which included CRP as a covariate, can be applied in clinical care.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Infectious Diseases
Letao Li, Sebastiaan D. T. Sassen, Tim M. J. Ewoldt, Alan Abdulla, Nicole G. M. Hunfeld, Anouk E. Muller, Brenda C. M. de Winter, Henrik Endeman, Birgit C. P. Koch
Summary: The suitability of published meropenem pharmacokinetic models for clinical practice was evaluated using real-world ICU data, and two models were found to perform well when using two to three plasma concentrations for therapeutic drug monitoring, while the other models performed poorly.
Article
Microbiology
Joseph Meletiadis, Maria-Ioanna Beredaki, Antigoni Elefanti, Spyros Pournaras, Anouk Muller
Summary: In order to evaluate the efficacy of combination therapy, it is necessary to study the correlation between in vitro and in vivo testing. This study attempted to correlate the in vitro chequerboard testing of posaconazole and amphotericin B with the in vivo outcome of combination therapy. The results showed consistency between the in vitro and in vivo testing.
Article
Pharmacology & Pharmacy
Zachary L. Taylor, Ethan A. Poweleit, Kelli Paice, Katherine M. Somers, Kathryn Pavia, Alexander A. Vinks, Nieko Punt, Tomoyuki Mizuno, Sonya Tang Girdwood
Summary: There is increasing interest in using model-informed precision dosing to provide personalized medicine at the bedside. This tutorial provides a comprehensive approach to evaluating, selecting, and validating a model for implementation into a precision dosing program.
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
(2023)
Article
Critical Care Medicine
Sjoerd D. D. Meenks, Nieko Punt, Jos L. M. L. le Noble, Norbert A. A. Foudraine, Kees Neef, Paddy K. C. Janssen
Summary: This study assessed the population pharmacokinetics and target attainment of flucloxacillin in critically ill patients. The results showed that standard daily doses may substantially increase the risk of underdosing in critically ill patients. Further validation of these model predictions is needed.
