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Population pharmacokinetic analysis and modeling procedures typically require estimates of both population and individual pharmacokinetic parameters. However, only some of these parameters are contained in models and only parameters in the model can be estimated. In this paper, we introduce a new R package, PKconverter, to calculate pharmacokinetic parameters using the relationships among them. After fitting the model, other parameters can be calculated from the functional relationship among the parameters. PKconverter provides the functions to calculate whole parameters along with a Shiny application for converting the parameters. With this package, it is also possible to calculate the standard errors of the other parameters that are not in the model and estimate individual parameters simultaneously.
Subject(s)
Drug Packaging , Pharmaceutical Preparations , Models, Biological , Computer Simulation , SoftwareABSTRACT
Near-infrared spectroscopy ( NIR ) is widely used in the area of food quantitative and qualitative analysis.Variable selection technique is a critical step of the spectrum modeling with the development of chemometrics.In this study, a novel variable selection strategy, automatic weighting variable combination population analysis (AWVCPA), was proposed.Firstly, binary matrix sampling (BMS) strategy that gives each variable the same chance to be selected and generates different variable combinations, was used to produce a population of subsets to construct a population of sub-models.Then, the variable frequency ( Fre) and partial least squares regression ( Reg) , which were two kinds of information vector ( IVs) were weighted to obtain the value of the contribution of each spectral variables, the influence of two IVs of Rre and Reg was considered to each spectral variable.Finally, it used the exponentially decreasing function ( EDF) to remove the low contribution wavelengths so as to select the characteristic variable.In the case of near infrared spectrum of beer and corn, the prediction model based on partial least squares ( PLS ) was established.Compared with other variable selection methods, the research showed that AWVCPA was the best variable selection strategy in the same situation.It had 72.7% improvement compared AWVCPA-PLS with PLS and the predicted root mean square error (RMSEP) decreased from 0.5348 to 0.1457 on beer dataset.It had 64.7% improvement compared AWVCPA-PLS with PLS and the RMSEP decreased from 0.0702 to 0.0248 on corn dataset.
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Objective To evaluate the diagnostic accuracy of 4 μg/mL vancomycin screening plate (4VA)for vancomycin-non-susceptible Staphylococcus aureus.Methods The diagnosis trials on 4VA for vancomycin-non-susceptible Staphylococcus aureus were searched in the databases such as PubMed(1 966 to Aug.2013),The Cochrane Library(the second phase of 2013),ISI Web of Knowledge(1 980 to Aug.2013),CNKI (1 964 to Aug.2013),VIP (1 989 to Aug.2013)and Wanfang(1 998 to Aug.2013),mean-while the manual.Two reviewers evaluated the quality of the included trials according to the quality assessment of diagnostic accu-racy studies,and then meta-analysis was performed using Meta-Disc 1.4 software.Results A total of 3 trials involving 974 partici-pants were included.The results of meta-analysis showed that the weighted sensitivity,specificity,positive likelihood ratio,negative likelihood ratio and diagnostic odds ratio,were 0.805 [95%CI (0.047 to 0.563)],0.921 [95%CI (0.901 to 0.938)],10.804 [95%CI (5.5 1 1 to 21.181)],0.1 62 [95%CI (0.71 to 1.0)]and 69.721 [95%CI (1 1.740 to 414.06)]respectively.Conclusion 4VA for vancomycin-non-susceptible Staphylococcus aureus has a very high specificity and sensitivity,so 4VA could be used to creening plate (4VA)for vancomycin-non-susceptible Staphylococcus aureus in clinic.
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In this review, the concept and idea of chemical modeling and model population analysis ( MPA) were introduced, and the recent applications of MPA-based methods to different aspects of chemical modeling were listed, including outlier detection, variable selection, model evaluation and applicability domain. In addition, the feasibility and applicability of MPA to different kinds of dataset was illustrated, such as near infrared spectroscopy, quantitative structure-activity relationship and metabolomics, which provided a better idea and framework to develop a new algorithm in chemical modeling.
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Objective To investigate the prevalence and molecular characteristic of heterogeneous‐ vancomycin intermediate Staphylococcus aureus(hVISA) among methicillin‐resistant Staphylococcus aureus (MRSA)strains isolated from sterile body fluid specimens from 2009 to 2013 in Huangzhou District People′s Hospital in Huanggang City .Methods The minimum inhibitory con‐centrations (MIC) of antibiotics was determined by agar dilution method .The hVISA strains were detected by population analysis profile/area under the curve method (PAP/AUC) .The staphylococcal cassette chromosome mec (SCCmec) ,multilocus‐sequence typing (MLST) ,accessory gene regulator (agr) and Staphylococcus aureus protein A(spa) typing of hVISA strains were detected using PCR method .Results 32 hVISA strains were detected among 285 MRSA strains ,the prevalence rate of hVISA was 11 .2% , and the detection rates of hVISA from 2009 to 2013 were 0 .0% ,6 .4% ,9 .0% ,14 .3% and 18 .8% ,respectively ,showed an increas‐ing trend .The main hVISA epidemic clone was ST239‐SCCmecIII‐ t030‐agrI type(28strains ,accounting for 87 .5% ) .Conclusion The detection rate of hVISA showed an increasing trend in the past 5 years ,should be paid attention to strictly control the utiliza‐tion of glycopeptide drugs .
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Models are simplified descriptions of true biological processes. Pharmacokinetic/pharmacodynamic (PK/PD) modeling is a mathematical description on the relationship between pharmacokinetics and pharmacodynamics. The PK/PD modeling allows estimation of PK/PD parameters and it can establish dose-concentration-response relationships which describe and predict the effect-time courses of a drug. PK/PD modeling has recently emerged as a major tool in clinical pharmacology in order to optimize drug uses by designing rational dosage forms. Population analysis is used to estimate the variability in the population and also to establish guidelines for the individualization of drug dosage regimen. Non-linear mixed effect model is the basis of population approach. This approach permits the simultaneous analysis for all the data of the studied population, by using either PK or PD models to describe the typical trends (population means) and individual profiles. The target controlled infusion system is based on the population PK models which describe the inter-individual PK variability by individualizing the PK parameters according to the patient's covariate. The PK/PD modeling is highly useful for the development of drugs as well as for pharmacotherapy.
Subject(s)
Biological Phenomena , Dosage Forms , Drug Therapy , Pharmacokinetics , Pharmacology, ClinicalABSTRACT
This study was conducted to detect the presence of heterogenous vancomycin-intermediate Staphylococcus aureus (heteroVISA) among MRSA isolates in a major hospital. Forty-three MRSA isolates with vancomycin MIC 2 μg/ml collected in 2009 was screened for heteroVISA using Etest Glycopeptide Resistance Detection (GRD) and confirmed by population analysis profile-area under curve method. The genetic relatedness of heteroVISA strains with other MRSA was examined by pulsed-field gel electrophoresis (PFGE) method. Two isolates were shown to be heteroVISA and derived from the same clone. This showed that heteroVISA strains were already present among our local strains since 2009 and were genetically related to other susceptible strains.
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Background: Staphylococcus aureus with reduced susceptibility to vancomycin or heterogeneous vancomycinintermediate S. aureus (hVISA) have become increasingly reported from various parts of the world. hVISA cannot be detected by routine test for minimal inhibitory concentration (MIC) for vancomycin. The gold standard method for detection, population analysis profiles (PAP) method, is complicated, time-consuming, expensive, and needs well-trained microbiologists. Objective: Evaluate of 2.0 McFarland Etest method, in comparison with the PAP method, for detection of hVISA in clinical specimens. Methods: All methicillin-resistant S. aureus strains from clinical specimens isolated from consecutive patients attended at King Chulalongkorn Memorial Hospital and Siriraj Hospital, Bangkok between 2006 and 2007 were studied. 1 hundred nineteen specimens were obtained. The PAP method detected six hVISA strains 5 from blood and from cultures) from four patients at King Chulalongkorn Memorial Hospital, accounting for a prevalence of 6.35%. The MIC determined by agar dilution method was in the range of 2-3 μg/mL. Results: 2.0 McFarland Etest method detected no false positive and five false negatives (42%), and gave a sensitivity and a specificity of 16.7% and 100%, respectively. The one-point population analysis screening method detected two false positives and 1 false negative, and gave a sensitivity of 83.3% and a specificity and 98.2%. Conclusion: The 2.0 McFarland Etest method had a very good specificity but a poor sensitivity for detecting hVISA. It may be used as an alternative method to confirm detection of hVISA.
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Scomberomorus cavalla is a pelagic fish species widely distributed on the Atlantic west coast, and a noticeable decrease in its capture level in the USA and Gulf of Mexico is occurring, compared to the levels reached by the species in the past. Likewise, in some areas of Brazil, there has been indication of over-harvesting. However, there are no molecular studies focusing on the management of such an important item. Thus, in the present study, 380 nucleotide base pairs of the mitochondrial DNA D-Loop region of samples from Macapá, Bragança, and Fortaleza were sequenced. Phylogenetic and population analyses revealed that there is only one panmitic population, and low levels of genetic variability were verified. These results, as well as the noticed over-harvesting of S. cavalla, represent very important data to determine the management of such stock in order to prevent a collapse or the risk of future extinction.
Scomberomorus cavalla é uma espécie de peixe pelágico amplamente distribuído na costa oeste do Atlântico, e uma diminuição no seu nível de captura tem sido verificada nos E.U.A e Golfo do México, comparada com os níveis alcançados pela espécie no passado. Da mesma forma, em algumas áreas do Brasil, há indícios de sobre-exploração. Entretanto, não existem estudos moleculares que visam o manejo deste importante item. Desta forma, no presente estudo, foram seqüenciados 380 pares de bases nucleotídicas da região da Alça-D do DNA mitocondrial de amostras provenientes de desembarque em Macapá, Bragança e Fortaleza. As análises filogenéticas e populacionais revelaram que há apenas uma população panmítica e baixos níveis de variabilidade genética foram observados. Estes resultados, assim como a observada sobre-exploração de S. cavala, representam dados muito importantes para o estabelecimento do manejo deste estoque a fim de prevenir um colapso ou risco de extinção no futuro.
Subject(s)
Animals , DNA, Mitochondrial/analysis , Genetic Variation , Perciformes/genetics , Brazil , GeographyABSTRACT
Scomberomorus cavalla is a pelagic fish species widely distributed on the Atlantic west coast, and a noticeable decrease in its capture level in the USA and Gulf of Mexico is occurring, compared to the levels reached by the species in the past. Likewise, in some areas of Brazil, there has been indication of over-harvesting. However, there are no molecular studies focusing on the management of such an important item. Thus, in the present study, 380 nucleotide base pairs of the mitochondrial DNA D-Loop region of samples from Macapá, Bragança, and Fortaleza were sequenced. Phylogenetic and population analyses revealed that there is only one panmitic population, and low levels of genetic variability were verified. These results, as well as the noticed over-harvesting of S. cavalla, represent very important data to determine the management of such stock in order to prevent a collapse or the risk of future extinction.
Scomberomorus cavalla é uma espécie de peixe pelágico amplamente distribuído na costa oeste do Atlântico, e uma diminuição no seu nível de captura tem sido verificada nos E.U.A e Golfo do México, comparada com os níveis alcançados pela espécie no passado. Da mesma forma, em algumas áreas do Brasil, há indícios de sobre-exploração. Entretanto, não existem estudos moleculares que visam o manejo deste importante item. Desta forma, no presente estudo, foram seqüenciados 380 pares de bases nucleotídicas da região da Alça-D do DNA mitocondrial de amostras provenientes de desembarque em Macapá, Bragança e Fortaleza. As análises filogenéticas e populacionais revelaram que há apenas uma população panmítica e baixos níveis de variabilidade genética foram observados. Estes resultados, assim como a observada sobre-exploração de S. cavala, representam dados muito importantes para o estabelecimento do manejo deste estoque a fim de prevenir um colapso ou risco de extinção no futuro.
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Objective To develop a new method for the isolation of heterogeneous methecillin-resistant staphylococcus aureus(hetero-MRSA)and study its application in clinical practice.Methods Both the methods of disc agar diffusion and population analysis were used to detect hetero-MRSA from 60 strains of methecillin susceptible staphylococcus aureus(MSSA) which were identified by VITEK AMS.Results Twelve subclones of hetero-MRSA were isolated by population analysis,while only 2 subclones were identified by disc agar diffusion.Conclusion Population analysis is an effective method for the isolation of hetero-MRSA,and its detection rate is higher than that of disc agar diffusion.The heterogeneous methecillin resistance of MSSA should not be overlooked by medical workers.