Standardisierte Kontrastmittelsonographie (CEUS) in der klinischen Akut- und Notfallmedizin sowie Intensivmedizin (CEUS-Akut)

Die Anaesthesiologie -     

The proteome microenvironment determines the protective effect of preconditioning in cisplatin-induced acute kidney injury

1. Download high-res image (341KB)
2. Download full-size image

     

Mathematically optimal decisions in forensic age assessment

Forensic age estimation generally involves considerable amounts of uncertainty. Forensic age indicators such as teeth or skeleton images predict age only approximately, and this is likely to remain true even for future forensic age indicators. Thus, forensic age assessment should aim to make the best possible decisions under uncertainty. In this paper, we apply mathematical theory to make statistically optimal decisions to age assessment. Such an application is fairly straightforward assuming there is a standardized procedure for obtaining age indicator information from individuals, assuming we have data from the application of this procedure to a group of persons with known ages, and assuming the starting point for each individual is a probability distribution describing prior knowledge about the persons age. The main problem is then to obtain such a prior. Our analysis indicates that individual priors rather than a common prior for all persons may be necessary. We suggest that caseworkers, based on individual case information, may select a prior from a menu of priors. We show how information may then be collected over time to gradually increase the robustness of the decision procedure. We also show how replacing individual prior distributions for age with individual prior odds for being above an age limit cannot be recommended as a general method. Our theoretical framework is applied to data where the maturity of the distal femur and the third molar is observed using MRI. As part of this analysis we observe a weak positive conditional correlation between maturity of the two body parts.

     

Population pharmacokinetics of tanezumab in phase 3 clinical trials for osteoarthritis pain

AimsThe aims were to 1) develop the pharmacokinetics model to describe and predict observed tanezumab concentrations over time, 2) test possible covariate parameter relationships that could influence clearance and distribution and 3) assess the impact of fixed dosing vs. a dosing regimen adjusted by body weight.MethodsIndividual concentration–time data were determined from 1608 patients in four phase 3 studies conducted to assess efficacy and safety of intravenous tanezumab. Patients received two or three intravenous doses (2.5, 5 or 10 mg) every 8 weeks. Blood samples for assessment of tanezumab PK were collected at baseline, 1 h post‐dose and at weeks 4, 8, 16 and 24 (or early termination) in all studies. Blood samples were collected at week 32 in two studies. Plasma samples were analyzed using a sensitive, specific, validated enzyme‐linked immunosorbent assay.ResultsA two compartment model with parallel linear and non‐linear elimination processes adequately described the data. Population estimates for clearance (CL), central volume (V ₁), peripheral volume (V ₂), inter‐compartmental clearance, maximum elimination capacity (VM) and concentration at half‐maximum elimination capacity were 0.135 l day^–1, 2.71 l, 1.98 l, 0.371 l day^–1, 8.03 μg day^–1 and 27.7 ng ml^–1, respectively. Inter‐individual variability (IIV) was included on CL, V ₁, V ₂ and VM. A mixture model accounted for the distribution of residual error. While gender, dose and creatinine clearance were significant covariates, only body weight as a covariate of CL, V ₁ and V ₂ significantly reduced IIV.ConclusionsThe small increase in variability associated with fixed dosing is consistent with other monoclonal antibodies and does not change risk : benefit.