Objective:Voriconazole(VCZ)is a triazole antifungal agent widely used in immunocompromised patients with suspected or proven invasive fungal infections.The achievement of therapeutic range(1-5 mg/L)is essential to max...Objective:Voriconazole(VCZ)is a triazole antifungal agent widely used in immunocompromised patients with suspected or proven invasive fungal infections.The achievement of therapeutic range(1-5 mg/L)is essential to maximize VCZ efficacy,as its pharmacokinetics is characterized by a wide inter-and intra-individual variability.This study aims to quantify the variability of VCZ trough concentrations in children and adolescents with haematological diseases and optimize therapeutic drug monitoring in clinical practice.Methods:We analysed the monitoring concentrations of all children(<18 years old)treated with VCZ in the Haematology Department of Robert DebréHospital between January 2014 and December 2016.Demographic,clinical data,and VCZ dosing and monitoring concentrations measured by high-performance liquid chromatography with ultraviolet detection(HPLC-UV)were analysed.Non-parametric tests were performed using SPSS IBM 24.0.Results:380 trough VCZ concentrations at steady-state(Ctrough,ss)were available in 79 children:45.6%had first Ctrough,ss in the therapeutic range at first monitoring,46.8%had Ctrough,ss below 1 mg/L and 7.6%had Ctrough,ss over 5 mg/L.Forty-one patients were treated with recommended doses but only 53%of them reached the therapeutic range.There was no impact of age,sex,biological parameters,or indication of VCZ on Ctrough,ss values.The number of Ctrough,ss in the therapeutic range increases with the number of monitoring per patient following dosage adaptations.Conclusion:The wide inter-and intra-individual variability of VCZ trough concentrations at recommended doses confirm the need to standardize VCZ monitoring and identify factors to be considered to prospectively adapt treatment for each patient.展开更多
Aims Individual growth constitutes a major component of individual fitness.However,measuring growth rates of herbaceous plants non-destructively at the individual level is notoriously difficult.This study,based on an ...Aims Individual growth constitutes a major component of individual fitness.However,measuring growth rates of herbaceous plants non-destructively at the individual level is notoriously difficult.This study,based on an accurate non-destructive method of aboveground biomass estimation,aims to assess individual relative growth rates(RGRs)of some species,identify its environmental drivers and test its consequences on community patterning.We specifically address three questions:(i)to what extent environmental conditions explain differences in individual plant growth between sites,(ii)what is the magnitude of intraspecific variability of plant individual growth within and between sites and(iii)do species-averaged(dis-)advantage of individual growth compared with the whole vegetation within a site correlate with species ranking at the community level?Methods We monitored the growth of individuals of four common perennial species in 18 permanent grasslands chosen along a large pedoclimatic gradient located in the Massif Central,France.We measured soil properties,levels of resources and meteorological parameters to characterize environmental conditions at the site level.This design enables us to assess the influence of environmental conditions on individual growth and the relative extent of inter-individual variability of growth explained within and between sites.We determined the ranking of each of the four species in each site with botanical surveys to assess the relationship between species-averaged growth(dis-)advantage relative to the whole community and species rank in the community.Important Findings We found that environmental conditions explain a significant proportion of individual growth variability,and that this proportion is strongly variable between species.Light availability was the main driver of plant growth,followed by rainfall amount and potential evapotranspiration,while soil properties had only a slight effect.We further highlighted a moderate to high within-site inter-individual variability of growth.We finally showed that there was no correlation between species ranking and species-averaged individual growth.展开更多
文摘Objective:Voriconazole(VCZ)is a triazole antifungal agent widely used in immunocompromised patients with suspected or proven invasive fungal infections.The achievement of therapeutic range(1-5 mg/L)is essential to maximize VCZ efficacy,as its pharmacokinetics is characterized by a wide inter-and intra-individual variability.This study aims to quantify the variability of VCZ trough concentrations in children and adolescents with haematological diseases and optimize therapeutic drug monitoring in clinical practice.Methods:We analysed the monitoring concentrations of all children(<18 years old)treated with VCZ in the Haematology Department of Robert DebréHospital between January 2014 and December 2016.Demographic,clinical data,and VCZ dosing and monitoring concentrations measured by high-performance liquid chromatography with ultraviolet detection(HPLC-UV)were analysed.Non-parametric tests were performed using SPSS IBM 24.0.Results:380 trough VCZ concentrations at steady-state(Ctrough,ss)were available in 79 children:45.6%had first Ctrough,ss in the therapeutic range at first monitoring,46.8%had Ctrough,ss below 1 mg/L and 7.6%had Ctrough,ss over 5 mg/L.Forty-one patients were treated with recommended doses but only 53%of them reached the therapeutic range.There was no impact of age,sex,biological parameters,or indication of VCZ on Ctrough,ss values.The number of Ctrough,ss in the therapeutic range increases with the number of monitoring per patient following dosage adaptations.Conclusion:The wide inter-and intra-individual variability of VCZ trough concentrations at recommended doses confirm the need to standardize VCZ monitoring and identify factors to be considered to prospectively adapt treatment for each patient.
基金supported by the Region Auvergne-Rhône-Alpes and the European Regional Development Fund(FEDER)(grant no.AV0008781).
文摘Aims Individual growth constitutes a major component of individual fitness.However,measuring growth rates of herbaceous plants non-destructively at the individual level is notoriously difficult.This study,based on an accurate non-destructive method of aboveground biomass estimation,aims to assess individual relative growth rates(RGRs)of some species,identify its environmental drivers and test its consequences on community patterning.We specifically address three questions:(i)to what extent environmental conditions explain differences in individual plant growth between sites,(ii)what is the magnitude of intraspecific variability of plant individual growth within and between sites and(iii)do species-averaged(dis-)advantage of individual growth compared with the whole vegetation within a site correlate with species ranking at the community level?Methods We monitored the growth of individuals of four common perennial species in 18 permanent grasslands chosen along a large pedoclimatic gradient located in the Massif Central,France.We measured soil properties,levels of resources and meteorological parameters to characterize environmental conditions at the site level.This design enables us to assess the influence of environmental conditions on individual growth and the relative extent of inter-individual variability of growth explained within and between sites.We determined the ranking of each of the four species in each site with botanical surveys to assess the relationship between species-averaged growth(dis-)advantage relative to the whole community and species rank in the community.Important Findings We found that environmental conditions explain a significant proportion of individual growth variability,and that this proportion is strongly variable between species.Light availability was the main driver of plant growth,followed by rainfall amount and potential evapotranspiration,while soil properties had only a slight effect.We further highlighted a moderate to high within-site inter-individual variability of growth.We finally showed that there was no correlation between species ranking and species-averaged individual growth.
