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Population Approach (population + approach)
Selected AbstractsPopulation-based Triage Management in Response to Surge-capacity Requirements during a Large-scale Bioevent DisasterACADEMIC EMERGENCY MEDICINE, Issue 11 2006Frederick M. Burkle Jr MD Both the naturally occurring and deliberate release of a biological agent in a population can bring catastrophic consequences. Although these bioevents have similarities with other disasters, there also are major differences, especially in the approach to triage management of surge capacity resources. Conventional mass-casualty events use uniform methods for triage on the basis of severity of presentation and do not consider exposure, duration, or infectiousness, thereby impeding control of transmission and delaying recognition of victims requiring immediate care. Bioevent triage management must be population based, with the goal of preventing secondary transmission, beginning at the point of contact, to control the epidemic outbreak. Whatever triage system is used, it must first recognize the requirements of those Susceptible but not exposed, those Exposed but not yet infectious, those Infectious, those Removed by death or recovery, and those protected by Vaccination or prophylactic medication (SEIRV methodology). Everyone in the population falls into one of these five categories. This article addresses a population approach to SEIRV-based triage in which decision making falls under a two-phase system with specific measures of effectiveness to increase likelihood of medical success, epidemic control, and conservation of scarce resources. [source] Historiography and forensic analysis of the Fort King George "skull": Craniometric assessment using the specific population approachAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 2 2009Christopher M. Stojanowski Abstract In this article, we evaluate the association between the Fort King George "skull" and two Franciscans who were killed during a Guale revolt in 1597 and whose remains were never recovered (Pedro de Corpa and Francisco de Veráscola). The history and historiography of the revolt is summarized to generate a forensic profile for the individuals. The calvaria is described in terms of preservation, taphonomy, possible trauma, age, and sex. Because these factors are consistent with the individuals in question, population affinity is assessed using comparative craniometric analysis. In response to recent criticism of the typological nature of forensic population affinity assessment, we use a population specific approach, as advocated by Alice Brues (1992). Archaeological and historical data inform the occupation history of the site, and data from those specific populations are used in the comparative analysis. Results of linear discriminant function analysis indicate a low probability that the calvaria is a Guale (the precontact inhabitants of southeastern Georgia) or an individual of African descent. Comparison among European and Euro-American populations indicated poor discriminatory resolution; however, the closest match suggests a New World affinity rather than an Old World English, Scottish, or Iberian affinity for the specimen. Future analyses that will provide greater resolution about the identity of the calvaria are outlined. The case highlights the unique challenges of historical forensics cases relative to those of traditional jurisprudence, as well as the potential for using historiography to overcome those challenges in future analyses. Am J Phys Anthropol, 2009. © 2009 Wiley-Liss, Inc. [source] Population pharmacokinetic modelling of aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patientsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2008Jung-Ryul Kim WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Almost all reported studies have investigated the pharmacokinetics of aripiprazole in healthy volunteers. , The pharmacokinetics of dehydroaripiprazole have not been identified in a combined model with aripiprazole. WHAT THIS STUDY ADDS , The data on aripiprazole and dehydroaripiprazole in psychiatric patients were modelled jointly using a population approach. , The apparent clearance of aripiprazole in cytochrome P450 (CYP) 2D6 intermediate metabolizers (IM) was approximately 60% of that in CYP2D6 extensive metabolizers (EM) having two functional alleles, but the exposure to dehydroaripiprazole in CYP2D6 IM was similar to that in EM. AIMS The aims of this study were to develop a combined population pharmacokinetic model for both aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patients and to identify to what extent the genetic polymorphisms of cytochrome P450 (CYP) enzymes contribute to the variability in pharmacokinetics (PK). METHODS A population pharmacokinetic analysis was performed using NONMEM software based on 141 plasma concentrations at steady state from 80 patients receiving multiple oral doses of aripiprazole (10,30 mg day,1). RESULTS A one-compartment model with first-order kinetics for aripiprazole and dehydroaripiprazole each was developed to describe simultaneously the concentration data. The absorption rate constant was fixed to 1.06 h,1. The typical value of apparent distribution volume of aripiprazole was estimated to be 192 l. Covariate analysis showed that CYP2D6 genetic polymorphisms significantly influenced the apparent clearance of aripiprazole (CL/F), reducing the interindividual variability on CL/F from 37.8% CV (coefficient of variation) to 30.5%. The CL/F in the CYP2D6 IMs was approximately 60% of that in CYP2D6 EMs having two functional alleles. Based on the CYP2D6 genotype, the metabolic ratios were calculated at 0.20,0.34. However, the plasma concentration : dose ratios of dehydroaripiprazole were not different across the CYP2D6 genotype. CONCLUSIONS This population pharmacokinetic model provided an adequate fit to the data for both aripiprazole and dehydroaripiprazole in psychiatric patients. The usefulness of CYP genotyping as an aid to select the starting dose should be further investigated. [source] Population pharmacokinetics and bioavailability of tacrolimus in kidney transplant patientsBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2007Marie Antignac What is already known about this subject , ,In spite of its success in ensuring graft survival, therapeutic use of tacrolimus is complicated by its narrow therapeutic index and wide intra- and interpatient variability. , ,Some studies of population pharmacokinetics have already been conducted in liver transplant recipients and in paediatric patients. What this study adds , ,Our work determined population pharmacokinetic parameters, in particular bioavailability, in kidney transplant recipients and the relative importance of factors influencing the disposition of tacrolimus. , ,Clearance was modelled and days postoperation and corticosteroids dose were significant covariates. Aims The use of tacrolimus is complicated by its narrow therapeutic index and wide intra- and interpatient variability. Tacrolimus population pharmacokinetics, including bioavailability, were investigated in an adult kidney transplant cohort to identify patient characteristics that influence pharmacokinetics. Methods The database (drug monitoring data) included 83 adult kidney transplant recipients and analysis was performed by a population approach with NONMEM. Data were collected during the first months after transplantation. Patients were administered oral or intravenous tacrolimus as part of a triple immunosuppressive regimen that also included mycophenolate mofetil and corticosteroids. Subsequent doses were adjusted on the basis of clinical evidence of efficacy and toxicity as in routine therapeutic drug monitoring. Results A one compartment open model with linear absorption and elimination adequately described the data. The typical value of minimal clearance was 1.8 ± 0.2 l h,1. Clearance increased with time post transplantation to reach 50% of maximal value after 3.8 ± 0.5 days, with a maximal value of 5.6 l h,1. Moreover clearance increased by approximately 1.6 fold (range 0.5,1.6) if the dose of prednisone was >25 mg. The typical value for volume of distribution, V, (98 ± 13 l kg,1) was similar to reported values in kidney transplant patients. The oral bioavailability of tacrolimus was poor and ranged from 11.2 to 19.1%. No covariates significantly influenced V or F. Conclusions The number of days postoperation and corticosteroid dose were significant covariates influencing tacrolimus clearance. [source] Age-related differences in the pharmacokinetics of stavudine in 272 children from birth to 16 years: a population analysisBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2007V. Jullien Aims To develop a population pharmacokinetic model for stavudine in children and to investigate the consistency of the currently recommended dose based on adult target concentrations. Methods The pharmacokinetics of stavudine were investigated using a population approach. Individual estimates of CL/F were used to calculate the stavudine dose required to achieve the area under the concentration-time curve reported in adults given recommended doses. Results Stavudine pharmacokinetics were well described by a one-compartment model with zero-order absorption. Typical population estimates (% interindividual variability) of the apparent distribution volume (V/F) and plasma clearance (CL/F) were 40.9 l (32%) and 16.5 l h,1 (38%), respectively. Stavudine V/F and CL/F were similarly related to age. Mean calculated doses (0.61 mg kg,1 for children less than 2 weeks, 1.23 mg kg,1 for children more than 2 weeks with bodyweight less than 30 kg, and 31.5 mg for children with a bodyweight between 30 and 60 kg) were in agreement with the current paediatric doses (0.5 mg kg,1, 1 mg kg,1, and 30 mg, respectively). Conclusions Our findings support the current recommended paediatric dosage regimens for stavudine, as they result in the same exposure to the drug as in adults. [source] Pharmacokinetic,pharmacodynamic modelling of the analgesic effects of lumiracoxib, a selective inhibitor of cyclooxygenase-2, in ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2010DA Vásquez-Bahena Background and purpose:, This study establishes a pharmacokinetic/pharmacodynamic (PK/PD) model to describe the time course and in vivo mechanisms of action of the antinociceptive effects of lumiracoxib, evaluated by the thermal hyperalgesia test in rats. Experimental approach:, Female Wistar fasted rats were injected s.c. with saline or carrageenan in the right hind paw, followed by either 0, 1, 3, 10 or 30 mg·kg,1 of oral lumiracoxib at the time of carrageenan injection (experiment I), or 0, 10 or 30 mg·kg,1 oral lumiracoxib at 4 h after carrageenan injection (experiment II). Antihyperalgesic responses were measured as latency time (LT) to a thermal stimulus. PK/PD modelling of the antinociceptive response was performed using the population approach with NONMEM VI. Results:, A two-compartment model described the plasma disposition. A first-order model, including lag time and decreased relative bioavailability as a function of the dose, described the absorption process. The response model was: LT=LT0/(1 +MED). LT0 is the baseline response, and MED represents the level of inflammatory mediators. The time course of MED was assumed to be equivalent to the predicted profile of COX-2 activity and was modelled according to an indirect response model with a time variant synthesis rate. Drug effects were described as a reversible inhibition of the COX-2 activity. The in vivo estimate of the dissociation equilibrium constant of the COX-2-lumiracoxib complex was 0.24 µg·mL,1. Conclusions:, The model developed appropriately described the time course of pharmacological responses to lumiracoxib, in terms of its mechanism of action and pharmacokinetics. [source] Pharmacokinetic-pharmacodynamic modelling in the early development phase of anti-psychotics: a comparison of the effects of clozapine, S 16924 and S 18327 in the EEG model in ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2001T J Parker The use of pharmacokinetic/pharmacodynamic (PK/PD) analysis in early compound development was investigated in the rat for two developmental anti-psychotic compounds with clozapine as a positive control. Three plasma samples were collected from each of eight animals according to a pre-defined sampling matrix allowing a total of 12 time points for PK analysis. Quantitative electroencephalography (QEEG), particularly the theta and beta frequencies, was used as a measurement of pharmacological effect. PK/KD modelling of the sparse PK data available relative to a rich set of PD data was achieved using a population approach in NONMEM (IV). Individual PK parameter estimates were incorporated into a PK/PD model. Qualitative EEG changes in rat and human were similar for clozapine, but different for the two developmental compounds, suggesting that changes in these PD parameters may not be specifically related to the anti-psychotic activity. Although no definitive data are available concerning the signal specificity of EEG frequency bands with respect to dopaminergic or serotonergic receptor activity, qualitative and quantitative differences seen in EEG parameters are likely to result from the multiple receptor occupancy for these compounds. The results confirm the value of population PK/PD modelling in conjunction with sparse sampling to enable determination of concentration effect relationships in the pre-clinical development programme of CNS-active drugs. British Journal of Pharmacology (2001) 132, 151,158; doi:10.1038/sj.bjp.0703791 [source] Establishing a service: a whole population approachCHILD: CARE, HEALTH AND DEVELOPMENT, Issue 3 2004M. Lewis First page of article [source] | ||||||||||