The content of this thesis is of two sorts: in one part, three topics about the early origins of adult disease are addressed, preceded by three related methodological studies which form the other... Show moreThe content of this thesis is of two sorts: in one part, three topics about the early origins of adult disease are addressed, preceded by three related methodological studies which form the other part. The thesis starts with a systematic review of the literature about the growth of infants born preterm. Next, three specific methodological issues related to early origins of adult disease studies are addressed. A: the most favorable regression model for analyzing and interpreting the effect of both prenatal and subsequent postnatal growth on adult health outcomes. B: the efficiency of reliability studies in the context of a multi-centre study. And C: the correct and clear assessment of reliability in case of log transformed outcomes. These methods are used ind the second part, in which three topics about the effects of prenatal and early postnatal growth on adult health outcomes are addressed, namely: A the association between birth weight and adult renal function in non-premature subjects. B: The association between birth weight and the adult metabolic syndrome, and its separate components in the same population. And finally, C: the association between early growth and adult body composition in subjects born very preterm. Show less
The aim of this thesis was to obtain insight into the epidemiology and molecular basis of multidrug resistance of Acinetobacter baumannii at the population level. To this aim a number of studies... Show moreThe aim of this thesis was to obtain insight into the epidemiology and molecular basis of multidrug resistance of Acinetobacter baumannii at the population level. To this aim a number of studies were performed on strains mainly from the Czech Republic (CR) which have shown in particular that (i) the vast majority of multidrug resistant (MDR) clinical isolates of A. baumannii from CR belong to clonal lineages termed EU clone I and II; (ii) these two clones have predominated among MDR hospital isolates in CR since at least 1991; (iii) recent emergence of A. baumannii resistance to carbapenems in CR was associated with the country-wide spread of a subclone of EU clone II; (iv) multidrug resistance is a general feature of strains of EU clones I and II, yet strains belonging to one clone may vary in the content of resistance genes; (v) upregulation of genes intrinsic to A. baumannii as well as horizontal acquisition of resistance genes can be sources of development of multidrug resistance and intraclonal diversification; (vi) the genes encoding the non-specific efflux system AdeABC are present in nearly all A. baumannii strains, yet the AdeABC overexpression is seen mostly in MDR strains harbouring additional resistance genes. Show less
Although the quality of oral anticoagulant treatment is already high, improvement is important. We performed several studies which all aimed to optimize dosing of vitamin K antagonists and control... Show moreAlthough the quality of oral anticoagulant treatment is already high, improvement is important. We performed several studies which all aimed to optimize dosing of vitamin K antagonists and control of anticoagulant treatment. In our double-blind controlled trial comparing a simple dosing algorithm to an algorithm that incorporated the patients__ sensitivity for vitamin K antagonists, we showed that there was no increase in treatment quality. However, the new algorithm was more efficient, as more dosage proposals were generated and accepted. We studied the relationships between maintenance dosages between acenocoumarol, warfarin and phenprocoumon and calculated transition factors. In a prospective cohort study among 220 Italians initiating anticoagulant treatment with acenocoumarol we showed that CYP2C9*3 was associated with a 25% dose-reduction and an increased risk of over-anticoagulation (INR>6) on day 4. Two copies of the VKORC1*2 alleles were associated with a 45% dose-reduction and an increased risk of over-anticoagulation. Instability is a risk factor for developing complications. We studied several methods to reflect instability and investigated which method was best associated with complications. We also investigated determinants of instability. Finally, we present the design and general results of a trial with primary aim to compare the quality of treatment with warfarin to phenprocoumon. Show less
