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https://www.readbyqxmd.com/read/27863483/estimation-of-tulathromycin-depletion-in-plasma-and-milk-after-subcutaneous-injection-in-lactating-goats-using-a-nonlinear-mixed-effects-pharmacokinetic-modeling-approach
#1
Zhoumeng Lin, Matthew Cuneo, Joan D Rowe, Mengjie Li, Lisa A Tell, Shayna Allison, Jan Carlson, Jim E Riviere, Ronette Gehring
BACKGROUND: Extra-label use of tulathromycin in lactating goats is common and may cause violative residues in milk. The objective of this study was to develop a nonlinear mixed-effects pharmacokinetic (NLME-PK) model to estimate tulathromycin depletion in plasma and milk of lactating goats. Eight lactating goats received two subcutaneous injections of 2.5 mg/kg tulathromycin 7 days apart; blood and milk samples were analyzed for concentrations of tulathromycin and the common fragment of tulathromycin (i...
November 18, 2016: BMC Veterinary Research
https://www.readbyqxmd.com/read/27834486/a-note-on-recurring-misconceptions-when-fitting-nonlinear-mixed-models
#2
Jeffrey R Harring, Shelley A Blozis
Nonlinear mixed-effects (NLME) models are used when analyzing continuous repeated measures data taken on each of a number of individuals where the focus is on characteristics of complex, nonlinear individual change. Challenges with fitting NLME models and interpreting analytic results have been well documented in the statistical literature. However, parameter estimates as well as fitted functions from NLME analyses in recent articles have been misinterpreted, suggesting the need for clarification of these issues before these misconceptions become fact...
November 11, 2016: Multivariate Behavioral Research
https://www.readbyqxmd.com/read/27770596/modeling-of-large-pharmacokinetic-data-using-nonlinear-mixed-effects-a-paradigm-shift-in-veterinary-pharmacology-a-case-study-with-robenacoxib-in-cats
#3
L Pelligand, A Soubret, J N King, J Elliott, J P Mochel
The objective of this study was to model the pharmacokinetics (PKs) of robenacoxib in cats using a nonlinear mixed-effects (NLME) approach, leveraging all available information collected from cats receiving robenacoxib s.c. and/or i.v.: 47 densely sampled laboratory cats and 36 clinical cats sparsely sampled preoperatively. Data from both routes were modeled sequentially using Monolix 4.3.2. Influence of parameter correlations and available covariates (age, gender, bodyweight, and anesthesia) on population parameter estimates were evaluated by using multiple samples from the posterior distribution of the random effects...
October 22, 2016: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/27535556/population-pharmacokinetic-modeling-of-olmesartan-the-active-metabolite-of-olmesartan-medoxomil-in-patients-with-hypertension
#4
Devender Kodati, Harish Kaushik Kotakonda, Narsimhareddy Yellu
BACKGROUND: Olmesartan medoxomil is an orally given angiotensin II receptor antagonist indicated for the treatment of hypertension. OBJECTIVE: The aim of the study was to establish a population pharmacokinetic model for olmesartan, the active metabolite of olmesartan medoxomil, in Indian hypertensive patients, and to evaluate effects of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of olmesartan. METHODS: The population pharmacokinetic model for olmesartan was developed using Phoenix NLME 1...
August 17, 2016: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/27461460/dynamic-models-for-estimating-the-effect-of-haart-on-cd4-in-observational-studies-application-to-the-aquitaine-cohort-and-the-swiss-hiv-cohort-study
#5
Mélanie Prague, Daniel Commenges, Jon Michael Gran, Bruno Ledergerber, Jim Young, Hansjakob Furrer, Rodolphe Thiébaut
Highly active antiretroviral therapy (HAART) has proved efficient in increasing CD4 counts in many randomized clinical trials. Because randomized trials have some limitations (e.g., short duration, highly selected subjects), it is interesting to assess the effect of treatments using observational studies. This is challenging because treatment is started preferentially in subjects with severe conditions. This general problem had been treated using Marginal Structural Models (MSM) relying on the counterfactual formulation...
July 26, 2016: Biometrics
https://www.readbyqxmd.com/read/27245328/modeling-the-oxygen-uptake-kinetics-during-exercise-testing-of-patients-with-chronic-obstructive-pulmonary-diseases-using-nonlinear-mixed-models
#6
Florent Baty, Christian Ritz, Arnoldus van Gestel, Martin Brutsche, Daniel Gerhard
BACKGROUND: The six-minute walk test (6MWT) is commonly used to quantify exercise capacity in patients with several cardio-pulmonary diseases. Oxygen uptake ([Formula: see text]O2) kinetics during 6MWT typically follow 3 distinct phases (rest, exercise, recovery) that can be modeled by nonlinear regression. Simultaneous modeling of multiple kinetics requires nonlinear mixed models methodology. To the best of our knowledge, no such curve-fitting approach has been used to analyze multiple [Formula: see text]O2 kinetics in both research and clinical practice so far...
2016: BMC Medical Research Methodology
https://www.readbyqxmd.com/read/27010278/population-pharmacokinetics-of-enrofloxacin-and-its-metabolite-ciprofloxacin-in-the-green-sea-urchin-strongylocentrotus-droebachiensis-following-intracoelomic-and-immersion-administration
#7
Brianne E Phillips, Craig A Harms, Gregory A Lewbart, Lesanna L Lahner, Martin Haulena, Justin F Rosenberg, Mark G Papich
Sea urchin mass mortality events have been attributed to both infectious and noninfectious etiologies. Bacteria, including Vibrio spp. and Pseudoalteromonas spp., have been isolated during specific mortality events. Aquarium collection sea urchins are also subject to bacterial infections and could benefit from antimicrobial treatment, but pharmacokinetic studies have been lacking for this invertebrate group until recently. This study evaluated the pharmacokinetics of enrofloxacin and its active metabolite ciprofloxacin in the green sea urchin (Strongylocentrotus droebachiensis) after intracoelomic injection and medicated bath immersion administration...
March 2016: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/26915793/formation-of-parametric-images-using-mixed-effects-models-a-feasibility-study
#8
Husan-Ming Huang, Yi-Yu Shih, Chieh Lin
Mixed-effects models have been widely used in the analysis of longitudinal data. By presenting the parameters as a combination of fixed effects and random effects, mixed-effects models incorporating both within- and between-subject variations are capable of improving parameter estimation. In this work, we demonstrate the feasibility of using a non-linear mixed-effects (NLME) approach for generating parametric images from medical imaging data of a single study. By assuming that all voxels in the image are independent, we used simulation and animal data to evaluate whether NLME can improve the voxel-wise parameter estimation...
March 2016: NMR in Biomedicine
https://www.readbyqxmd.com/read/26585899/stochastic-nonlinear-mixed-effects-a-metformin-case-study
#9
Brett Matzuka, Jason Chittenden, Jonathan Monteleone, Hien Tran
In nonlinear mixed effect (NLME) modeling, the intra-individual variability is a collection of errors due to assay sensitivity, dosing, sampling, as well as model misspecification. Utilizing stochastic differential equations (SDE) within the NLME framework allows the decoupling of the measurement errors from the model misspecification. This leads the SDE approach to be a novel tool for model refinement. Using Metformin clinical pharmacokinetic (PK) data, the process of model development through the use of SDEs in population PK modeling was done to study the dynamics of absorption rate...
February 2016: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/26335227/nonlinear-mixed-effects-modelling-for-single-cell-estimation-when-why-and-how-to-use-it
#10
Markus Karlsson, David L I Janzén, Lucia Durrieu, Alejandro Colman-Lerner, Maria C Kjellsson, Gunnar Cedersund
BACKGROUND: Studies of cell-to-cell variation have in recent years grown in interest, due to improved bioanalytical techniques which facilitates determination of small changes with high uncertainty. Like much high-quality data, single-cell data is best analysed using a systems biology approach. The most common systems biology approach to single-cell data is the standard two-stage (STS) approach. In STS, data from each cell is analysed in a separate sub-problem, meaning that only data from the same cell is used to calculate the parameter values within that cell...
2015: BMC Systems Biology
https://www.readbyqxmd.com/read/26326696/adult-observer-s-sensitivity-to-optic-flow-varies-by-pattern-and-speed
#11
William Adamiak, Amanda Thomas, Shivani Patel, Rick Gilmore
In adults, radial optic flow evokes stronger brain activity than laminar or rotational flow. Optic flow also evokes different activation patterns depending on motion speed (Fesi et al., 2014). This study examined whether the detection of optic flow in adult observers varies by pattern and speed in ways consistent with prior physiological evidence. Adult observers (n=10; 19.2-22.2 years, M=21.4) viewed two side-by-side, time varying (1.2 Hz coherent/incoherent cycle) annular shaped (18 deg outer/5 deg inner diameter) optic flow displays at a viewing distance of 60 cm...
2015: Journal of Vision
https://www.readbyqxmd.com/read/25893847/a-nonlinear-mixed-effects-approach-for-modeling-the-cell-to-cell-variability-of-mig1-dynamics-in-yeast
#12
Joachim Almquist, Loubna Bendrioua, Caroline Beck Adiels, Mattias Goksör, Stefan Hohmann, Mats Jirstrand
The last decade has seen a rapid development of experimental techniques that allow data collection from individual cells. These techniques have enabled the discovery and characterization of variability within a population of genetically identical cells. Nonlinear mixed effects (NLME) modeling is an established framework for studying variability between individuals in a population, frequently used in pharmacokinetics and pharmacodynamics, but its potential for studies of cell-to-cell variability in molecular cell biology is yet to be exploited...
2015: PloS One
https://www.readbyqxmd.com/read/25867935/effects-of-fluid-and-computed-tomographic-technical-factors-on-conspicuity-of-canine-and-feline-nasal-turbinates
#13
Raimonda Uosyte, Darren J Shaw, Danielle A Gunn-Moore, Eduardo Fraga-Manteiga, Tobias Schwarz
Turbinate destruction is an important diagnostic criterion in canine and feline nasal computed tomography (CT). However decreased turbinate visibility may also be caused by technical CT settings and nasal fluid. The purpose of this experimental, crossover study was to determine whether fluid reduces conspicuity of canine and feline nasal turbinates in CT and if so, whether CT settings can maximize conspicuity. Three canine and three feline cadaver heads were used. Nasal slabs were CT-scanned before and after submerging them in a water bath; using sequential, helical, and ultrahigh resolution modes; with images in low, medium, and high frequency image reconstruction kernels; and with application of additional posterior fossa optimization and high contrast enhancing filters...
September 2015: Veterinary Radiology & Ultrasound
https://www.readbyqxmd.com/read/25801663/using-sensitivity-equations-for-computing-gradients-of-the-foce-and-focei-approximations-to-the-population-likelihood
#14
Joachim Almquist, Jacob Leander, Mats Jirstrand
The first order conditional estimation (FOCE) method is still one of the parameter estimation workhorses for nonlinear mixed effects (NLME) modeling used in population pharmacokinetics and pharmacodynamics. However, because this method involves two nested levels of optimizations, with respect to the empirical Bayes estimates and the population parameters, FOCE may be numerically unstable and have long run times, issues which are most apparent for models requiring numerical integration of differential equations...
June 2015: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/25700977/population-pharmacokinetic-modeling-of-oxcarbazepine-active-metabolite-in-chinese-patients-with-epilepsy
#15
Yunli Yu, Quanying Zhang, Wenjun Xu, Chengzhe Lv, Gang Hao
The aim of the study was to develop a population pharmacokinetic (PPK) model of oxcarbazepine and optimize the treatment of oxcarbazepine in Chinese patients with epilepsy. A total of 108 oxcarbazepine therapeutic drug monitoring samples from 78 patients with epilepsy were collected in this study. The pharmacologically active metabolite 10,11-dihydro-10-hydrocarbamazepine (MHD) was used as the analytical target for monitoring therapy of oxcarbazepine. Patients' clinical data were retrospectively collected. The PPK model for MHD was developed using Phoenix NLME 1...
August 2016: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/25629642/a-mixture-of-hierarchical-joint-models-for-longitudinal-data-with-heterogeneity-non-normality-missingness-and-covariate-measurement-error
#16
Yangxin Huang, Chunning Yan, Ping Yin, Meixia Lu
Longitudinal data arise frequently in medical studies and it is a common practice to analyze such complex data with nonlinear mixed-effects (NLME) models. However, the following four issues may be critical in longitudinal data analysis. (i) A homogeneous population assumption for models may be unrealistically obscuring important features of between-subject and within-subject variations; (ii) normality assumption for model errors may not always give robust and reliable results, in particular, if the data exhibit skewness; (iii) the responses may be missing and the missingness may be nonignorable; and (iv) some covariates of interest may often be measured with substantial errors...
2016: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/25537545/-slco1b1c-521t-c-gene-polymorphisms-are-associated-with-high-dose-methotrexate-pharmacokinetics-and-clinical-outcome-of-pediatric-acute-lymphoblastic-leukemia
#17
Huanian Zhang, Xuelian He, Jianxin Li, Yang Wang, Cheng Wang, Yujun Chen, Changhe Niu, Ping Gao
OBJECTIVE: To provide guidance for the high-dose methotrexate (HD-MTX) treatment of pediatric acute lymphoblastic leukemia (ALL), and to understand the impact of SLCO1B1c.521T>C (rs4149056) variant on methotrexate (MTX) pharmacokinetics and clinical outcome in children with ALL. METHOD: Eighty-two children with ALL in Division of Hematology of Wuhan Children's Hospital from January 2008 to February 2013 were enrolled. All patients were genotyped for rs4149056 single nucleotide polymorphism (SNP) into wild-type group (TT genotype) and variant group (TC/CC genotype)...
October 2014: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/25322214/a-bayesian-nonlinear-mixed-effects-regression-model-for-the-characterization-of-early-bactericidal-activity-of-tuberculosis-drugs
#18
Divan Aristo Burger, Robert Schall
Trials of the early bactericidal activity (EBA) of tuberculosis (TB) treatments assess the decline, during the first few days to weeks of treatment, in colony forming unit (CFU) count of Mycobacterium tuberculosis in the sputum of patients with smear-microscopy-positive pulmonary TB. Profiles over time of CFU data have conventionally been modeled using linear, bilinear, or bi-exponential regression. We propose a new biphasic nonlinear regression model for CFU data that comprises linear and bilinear regression models as special cases and is more flexible than bi-exponential regression models...
2015: Journal of Biopharmaceutical Statistics
https://www.readbyqxmd.com/read/25320779/subject-specific-prediction-using-nonlinear-population-modeling-application-to-early-brain-maturation-from-dti
#19
Neda Sadeghi, P Thomas Fletcher, Marcel Prastawa, John H Gilmore, Guido Gerig
The term prediction implies expected outcome in the future, often based on a model and statistical inference. Longitudinal imaging studies offer the possibility to model temporal change trajectories of anatomy across populations of subjects. In the spirit of subject-specific analysis, such normative models can then be used to compare data from new subjects to the norm and to study progression of disease or to predict outcome. This paper follows a statistical inference approach and presents a framework for prediction of future observations based on past measurements and population statistics...
2014: Medical Image Computing and Computer-assisted Intervention: MICCAI ..
https://www.readbyqxmd.com/read/25316328/population-pharmacokinetic-pharmacodynamic-modelling-to-describe-the-effects-of-paracetamol-and-n-acetylcysteine-on-the-international-normalized-ratio
#20
RANDOMIZED CONTROLLED TRIAL
Katie H Owens, Natalie J Medlicott, Mathew Zacharias, Ian M Whyte, Nicholas A Buckley, David M Reith
Paracetamol is one of the most common pharmaceutical agents taken in self-poisonings, and can increase the prothrombin time (PT) through liver injury, and in overdose without hepatic injury by reducing functional factor VII. PT is a measure of hepatic injury used to predict and monitor hepatotoxicity, reported as the international normalized ratio (INR). The antidote for paracetamol poisoning, N-acetylcysteine (NAC), has been reported to have an effect on the PT. This analysis included patients from a retrospective case series, a prospective inception cohort of paracetamol and psychotropic (control) overdoses, and a cross-over clinical trial...
January 2015: Clinical and Experimental Pharmacology & Physiology
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