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
Surgical site infections (SSI) are the most-common healthcare-associated infections among surgical patients and have severe adverse consequences. Surveillance is the ongoing systematic collection,... Show moreSurgical site infections (SSI) are the most-common healthcare-associated infections among surgical patients and have severe adverse consequences. Surveillance is the ongoing systematic collection, analysis, interpretation, and feedback of data, and has been accepted worldwide as a primary step toward prevention of healthcare-associated infections. In the Netherlands, a national network for the surveillance of healthcare-associated infections was set up in 1996 and called PREZIES (__PREventie van ZIEkenhuisinfecties door Surveillance__). In this thesis, the quality of the SSI surveillance within this network is evaluated. The method for postdischarge surveillance recommended by PREZIES seemed feasible and effective, and the mandatory validation visits ensured reliability and robustness of the surveillance data. Furthermore, the predictive power of the NNIS risk index was sufficient for several surgical procedures and could not be significantly improved by using other procedure-specific determinants. Analysis of the time-trend in SSI rates for five surgical procedures showed encouraging decreasing trends, although mostly not statistically significant. Comparison of the Dutch and German SSI surveillance data revealed that even though similar infection surveillance protocols were used, differences occurred in the implementation which hampered the comparison of SSI rates. Additionally, PREZIES contributed to a multi-center intervention project to improve the quality of surgical prophylaxis. Show less
This thesis focuses on the incidence and risk factors for nephropathy in diabetic and non-diabetic Surinamese South Asians. The Surinamese South Asians, originally descended from the North-East... Show moreThis thesis focuses on the incidence and risk factors for nephropathy in diabetic and non-diabetic Surinamese South Asians. The Surinamese South Asians, originally descended from the North-East India. Due to the former colonial bounds with the Netherlands, a relatively young South Asian migrant population settled in the Netherlands. South Asians have a high prevalence of central obesity and an eight-fold higher prevalence for type 2 diabetes mellitus. We found the following conclusions: 1.Surinamese South Asian persons have a nearly 40-fold higher risk for end-stage diabetic nephropathy in comparison to Dutch European persons. 2.There was no familial predisposition for diabetic nephropathy among South Asian families. 3.South Asian type 2 diabetic patients have a three-fold higher risk for diabetic nephropathy and faster progression of renal insufficiency in comparison to Dutch European patients. 4.Central obesity is an early and independent risk factor for increased albuminuria in normoglycemic South Asian subjects. We assume that the nearly 40-fold higher risk of end-stage diabetic nephropathy in South Asian migrants is primarily caused by central obesity which leads to: a. Early renal injury in the pre-diabetic state. b. Eight-times higher prevalence of type 2 diabetes mellitus. b. More diabetic nephropathy and faster decline in renal function. Show less
Reumatoide arthritis (RA) is een ernstige, chronische ontstekingsziekte van de gewrichten. Hoofdstuk 1 is een introductie in epidemiologische gegevens over RA en factoren van invloed op... Show moreReumatoide arthritis (RA) is een ernstige, chronische ontstekingsziekte van de gewrichten. Hoofdstuk 1 is een introductie in epidemiologische gegevens over RA en factoren van invloed op ziektebeloop. Hoofdstuk 2 bespreekt de voorspellende waarde van anti-CCP antistoffen bij patiënten met nog niet te classificeren artritis voor het ontstaan van RA binnen 3 jaar. Deze antistoffen blijken belangrijke voorspellers te zijn voor het ontwikkelen van RA bij deze groep patiënten en een waardevolle aanvulling voor het vroegtijdig stellen van de diagnose RA. Hoofdstuk 3 onderzoekt de voorspellende waarde van de verdeling van ontstoken gewrichten bij eerste polibezoek op de ernst van röntgenologische schade in de toekomst. Artritis van de grote gewrichten vooral van de knie hangt hiermee samen. Hoofdstuk 4 analyseert volledige klinische remissie bij patiënten met RA. In een RA cohort uit Leiden vertoonde 10% blijvende remissie. Deze patiëntengroep werden gekenmerkt door afwezigheid van antistoffen. Hoofdstuk 5 beschrijft een gen-omgevingsinteractie tussen roken en de aanwezigheid van anti-CCP antistoffen bij patiënten met RA die drager zijn van bepaalde HLA klasse II allelen (de shared epitope allelen). Hoofdstuk 6 is een theorie over de oorzaak van de afgenomen incidentie van RA in de afgelopen decennia door een veranderde genetische samenstelling van de populatie. Show less
In a surveillance study in Jakarta, Indonesia, 88 typhoid and 26 paratyphoid fever patients were identified by blood culture. Risk factors for transmission of typhoid fever were mainly intra... Show moreIn a surveillance study in Jakarta, Indonesia, 88 typhoid and 26 paratyphoid fever patients were identified by blood culture. Risk factors for transmission of typhoid fever were mainly intra-household factors (poor hand-washing hygiene, recent household contacts), whereas paratyphoid was mainly contracted through street food. In an additional study, street vendors observed poorer hand-washing and food-handling hygiene compared to food handlers in restaurants, and had higher bacterial loads in dishwater. Further host factor-studies in (para)typhoid patients revealed that polymorphisms in genes encoding pro-inflammatory cytokines (IFN-_, IL1A/B, IL1R1, TNFRSF1A, CASP1 and CRP) were not associated with susceptibility to typhoid fever, and might therefore at most be associated with severity of disease. An association was found of typhoid fever and a polymorphism in the PARK2/PACRG proteasome-mediated protein degradation pathway through ubiquitination, similar to infection with Mycobacterium leprae. Also an association between genotypes in the Cystic Fibrosis Transmembrane Conductance Regulator (the affected protein in Cystic Fibrosis) and susceptibility to typhoid fever was found, suggesting a decreased adherence potential of S. typhi to intestinal mucosal cells with these polymorphisms. Finally, bacterial characteristics were compared by use of AFLP and biochemical/antibiotic susceptibility profiles, showing very homogeneous S. typhi and S. paratyphi A strains circulating in the study area. Show less
