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P Jarvis

Publications and source records attributed to P Jarvis.

43 records · Page 3Linked to original sources
PubMedDate not supplied

Some statistical issues in modelling pharmacokinetic data.

A fundamental assumption underlying pharmacokinetic compartment modelling is that each subject has a different individual curve. To some extent this runs counter to the statistical principle that similar individuals will have similar curves, thus making inferences to a wider population possible. In population pharmacokinetics, the compromise is to use random effects. We recommend that such models also be used in data rich situations instead of independently fitting individual curves. However, the additional information available in such studies shows that random effects are often not sufficient; generally, an autoregressive process is also required. This has the added advantage that it provides a means of tracking each individual, yielding predictions for the next observation. The compartment model curve being fitted may also be distorted in other ways. A widely held assumption is that most, if not all, pharmacokinetic concentration data follow a log-normal distribution. By examples, we show that this is not generally true, with the gamma distribution often being more suitable. When extreme individuals are present, a heavy-tailed distribution, such as the log Cauchy, can often provide more robust results. Finally, other assumptions that can distort the results include a direct dependence of the variance, or other dispersion parameter, on the mean and setting non-detectable values to some arbitrarily small value instead of treating them as censored. By pointing out these problems with standard methods of statistical modelling of pharmacokinetic data, we hope that commercial software will soon make more flexible and suitable models available.

Humans↗
PubMedDate not supplied

An in vitro evaluation of an artificial heart.

Interactions between human blood and the Penn State Artificial Heart were examined in vitro to study the effects of various operating conditions on the hematologic response. A dual-loop recirculating flow system that accommodated human blood was developed and blood was subjected for 3 hr to various operating conditions known to alter fluid mechanics in the artificial ventricle. The operating conditions investigated were: 60 beats/min at 50% systolic duration, 60 beats/min at 30% systolic duration, and 90 beats/min at 50% systolic duration. Quantification of plasma free hemoglobin provided a direct indicator of hemolysis in the flow system. Platelet number and beta-thromboglobulin levels were monitored to investigate thrombotic activity, and levels of complement 3a were measured to examine complement system activation. The system was effective in demonstrating the relative hemolytic properties of the operating conditions. Ninety beats/min induced 37% more hemolysis than 60 beats/min at 50% systolic duration, and 50% systolic duration induced 32% more hemolysis than 30% systolic duration at 60 beats/min. There were no statistically significant changes in either platelet number or beta-thromboglobulin levels during the 3 hr recirculation period. Increases were seen in complement 3a levels, but these appeared to be surface-induced and not sensitive to the different operating conditions. These studies demonstrate the usefulness of the flow system in examining the relative hemolytic properties of the artificial ventricle, and suggest that bulk turbulent stresses may play a more important role than laminar wall shear stresses in mediating blood damage in this artificial ventricle.

Blood Physiological Phenomena↗