ABSTRACT
It has been shown that computerized algorithms for the prescription of coumarin derivates can improve the quality of long-term anticoagulation treatment. These algorithms are usually based on an empiric relationship between dosage and International Normalized Ratio and do not quantify the delaying effect of the drug's pharmacokinetics or the effect of alternating doses that are used to approximate a certain average dosage. Our objective was to develop a mathematical model that takes into account these effects and to develop a new algorithm based on this model that can be used to further optimize the quality of long-term anticoagulation treatment. We simplified a general model structure that was proposed by Holford in 1986 so that the parameters can be estimated using data that are available during long-term anticoagulation treatment. The constant parameters in the model were estimated separately for phenprocoumon and acenocoumarol using data from 1279 treatment courses from three different anticoagulation clinics in the Netherlands. The only variable parameter in the model is the sensitivity of the patient, which is estimated during the course of each treatment. A total of 194 dosage and appointment intervals that were proposed by the new algorithm were scored as 'good', 'acceptable', or 'bad' by two dosing experts. One hundred and seventy-eight (91.8%) proposals were considered good by at least one expert and bad by none. In 39 cases the experts disagreed. We believe that this algorithm will allow further improvement of anticoagulation treatments.
Subject(s)
Anticoagulants/pharmacokinetics , Drug Monitoring/methods , Acenocoumarol/pharmacokinetics , Aged , Algorithms , Databases as Topic , Female , Humans , International Normalized Ratio , Male , Middle Aged , Models, Biological , Models, Statistical , Models, Theoretical , Monitoring, Physiologic , Phenprocoumon/pharmacokineticsABSTRACT
Since the first systematic analysis concerning the functional properties of mechanoreceptors in the glabrous skin of the human hand was made in 1970, the amount of available data has grown tremendously. Whereas the first research in the seventies was aimed at achieving a standard functional description of the mechanoreceptors, research of the last two decades mostly has been directed towards developing a more detailed and extended model of these receptors. For example, recent investigations attempted to examine the role of populations of mechanoreceptors with respect to the recognition of texture and shape of an object touched by the human hand. Knowledge of the behaviour of the mechanoreceptive units in the glabrous skin of the human hand is especially relevant to people with a diminished or lost vision who depend on their tactile system to perceive objects they cannot hear or smell. This essay tries to give a brief overview of the development of this field from the first experiments on human beings to the state of knowledge that has been gained today.
