http://repub.eur.nl/res/aut/8134/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39928/ 2013-04-22T00:00:00Z In this systematic review and meta-analysis the risk of a subsequent basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or melanoma in patients with a previous keratinocyte carcinoma (KC) was investigated. PubMed, Embase, Web of Science and the Cochrane library were searched for studies published before 1st January 2012 that reported risks (i.e. proportions, cumulative risks or standardised incidence ratios [SIR]) of developing a subsequent BCC, SCC or melanoma in patients with prior KC. 45 articles fulfilled the inclusion criteria. In BCC patients, the pooled proportion for a subsequent BCC, SCC or melanoma was respectively 29.2% (95% confidence interval (CI) 24.6-34.3%), 4.3% (1.7-10.1%) and 0.5% (0.4-0.8%). The pooled proportion of a subsequent SCC, BCC or melanoma in SCC patients was respectively 13.3% (95% CI 7.4-22.8%), 15.9% (5.6-37.6%) and 0.5% (0.3-0.6%). The pooled SIRs for a subsequent BCC, SCC or melanoma were respectively 17.4 (95% CI 0.0-37.4), 3.2 (0.0-6.5) and 2.4 (2.3-2.6) in BCC and 4.2 (95% CI 2.0-6.5), 15.0 (14.0-16.0) and 2.7 (2.3-3.2) in SCC patients. In the subgroup analyses, strongest differences in risks were found in the continent strata (risks Australia > North America > Europe). http://repub.eur.nl/res/pub/39269/ 2013-01-23T00:00:00Z In this era of organ donor shortage, live kidney donation has been proven to increase the donor pool; however, it is extremely important to make careful decisions in the selection of possible live donors. A body mass index (BMI) above 35 is generally considered as a relative contraindication for donation. To determine whether this is justified, a systematic review and meta-analysis were carried out to compare perioperative outcome of live donor nephrectomy between donors with high and low BMI. A comprehensive literature search was performed in MEDLINE, Embase, and CENTRAL (the Cochrane Library). All aspects of the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement were followed. Of 14 studies reviewed, eight perioperative donor outcome measures were meta-analyzed, and, of these, five were not different between BMI categories. Three found significant differences in favor of low BMI (29.9 and less) donors with significant mean differences in operation duration (16.9 min (confidence interval (CI) 9.1-24.8)), mean difference in rise in serum creatinine (0.05 mg/dl (CI 0.01-0.09)), and risk ratio for conversion (1.69 (CI 1.12-2.56)). Thus, a high body mass index (BMI) alone is no contraindication for live kidney donation regarding short-term outcome.Kidney International advance online publication, 23 January 2013; doi:10.1038/ki.2012.485. http://repub.eur.nl/res/pub/37736/ 2012-09-01T00:00:00Z The present paper reports on the development and the psychometric properties of a brief observational assessment of home environments for use in large-scale investigations with young infants. We generated observational items conceptually relevant for child development by two methods. First, we adapted the Infant Toddler Home Observation for Measurement of the Environment (IT-HOME) inventory for use in an exclusively observational context. Second, we added new observational items following a review of relevant literature and consulting professionals. The quality of the instrument was first evaluated in a pilot study (n = 926). In our study sample of 3406 families and their children (median age = 3.1 months, range = 1.6-6.0), exploratory factor analysis was used to identify latent constructs, Cronbach's alpha was used as a measure of internal consistency, and convergent validity was evaluated against family socio-demographic characteristics. Inter-observer agreement was investigated in a sub-sample of the respondents (n = 124). The results supported good psychometric properties of the instrument based on: (a) exploratory factor analysis yielding three meaningful latent constructs, (b) Cronbach's alphas ranging from α = 0.66 to α = 0.90, (c) inter-observer agreement ranging from r = 0.75 to r = 0.91, and (d) associations between the instrument and socio-demographic characteristics in the expected direction [e.g. Odds Ratio for low income = 15.24, 95% confidence interval (11.60, 20.01)] http://repub.eur.nl/res/pub/34907/ 2012-01-01T00:00:00Z Endophenotypes are intermediate phenotypes on the putative causal pathway from genotype to phenotype and can aid in discovering the genetic etiology of a disorder. There are currently very few suitable endophenotypes available for substance use disorders (SUD). The amplitude of the P300 event-related brain potential is a possible candidate. The present study determined whether the P300 amplitude fulfils two fundamental criteria for an endophenotype: (1) an association with the disorder (disease marker), and (2) presence in unaffected biological relatives of those who have the disorder (vulnerability marker). For this purpose, two separate meta-analyses were performed. Meta-analysis 1 investigated the P300 amplitude in relation to SUD in 39 studies and Meta-analysis 2 investigated P300 amplitude in relation to a family history (FH+) of SUD in 35 studies. The findings indicate that a reduced P300 amplitude is significantly associated with SUD (d=0.51) and, though to a lesser extent, with a FH+ of SUD (d=0.28). As a disease maker, the association between reduced P300 amplitude and SUD is significantly larger for participants that were exclusively recruited from treatment facilities (d=0.67) than by other methods (i.e., community samples and family studies; d=0.45 and 0.32, respectively), and larger for abstinent SUD patients (d=0.71) than for current substance users (d=0.37). Furthermore, in contrast to FH+ males, a P300 amplitude reduction seems not to be present in FH+ females (d=-0.07). Taken together, these results suggest that P300 amplitude reduction can be both a useful disease and vulnerability marker and is a promising neurobiological endophenotype for SUD, though only in males. Implications and future directions are discussed. http://repub.eur.nl/res/pub/33402/ 2011-06-14T00:00:00Z Breast-feeding has been suggested to be associated with lower risks of obesity in older children and adults. We assessed whether the duration and exclusiveness of breast-feeding are associated with early postnatal growth rates and the risks of overweight and obesity in preschool children. The present study was embedded in a population-based prospective cohort study from early fetal life onwards, among 5047 children and their mothers in The Netherlands. Compared with children who were breast-fed, those who were never breast-fed had a lower weight at birth (difference 134 (95 % CI ' 190,' 77) g). No associations between breast-feeding duration and exclusivity with growth rates before the age of 3 months were observed. Shorter breast-feeding duration was associated with an increased gain in age- and sex-adjusted standard deviation scores for length, weight and BMI (P for trend < 0•05) between 3 and 6 months of age. Similar tendencies were observed for the associations of breast-feeding exclusivity with change in length, weight and BMI. Breast-feeding duration and exclusivity were not consistently associated with the risks of overweight and obesity at the ages of 1, 2 and 3 years. In conclusion, shorter breast-feeding duration and exclusivity during the first 6 months tended to be associated with increased growth rates for length, weight and BMI between the age of 3 and 6 months but not with the risks of overweight and obesity until the age of 3 years. http://repub.eur.nl/res/pub/25130/ 2011-06-01T00:00:00Z Chlamydia trachomatis infection is the most prevalent bacterial sexually transmitted infection and may influence pregnancy outcome. This study was conducted to assess the effect of chlamydial infection during pregnancy on premature delivery and birthweight. Pregnant women attending a participating midwifery practice or antenatal clinic between February 2003 and January 2005 were eligible for the study. From 4,055 women self-administered questionnaires and urine samples, tested by PCR, were analysed for C. trachomatis infection. Pregnancy outcomes were obtained from midwives and hospital registries. Gestational ages and birthweights were analysed for 3,913 newborns. The C. trachomatis prevalence was 3.9%, but varied by age and socio-economic background. Chlamydial infection was, after adjustment for potential confounders, associated with preterm delivery before 32 weeks (OR 4.35 [95% CI 1.3, 15.2]) and 35 weeks gestation (OR 2.66 [95% CI 1.1, 6.5]), but not with low birthweight. Of all deliveries before 32 weeks and 35 weeks gestation 14.9% [95% CI 4.5, 39.5] and 7.4% [95% CI 2.5, 20.1] was attributable to C. trachomatis infection. Chlamydia trachomatis infection contributes significantly to early premature delivery and should be considered a public health problem, especially in young women and others at increased risk of C. trachomatis infection. http://repub.eur.nl/res/pub/23732/ 2011-05-01T00:00:00Z Abstract. BACKGROUND: After total hip arthroplasty (THA), patients today (who tend to be younger and more active than those who previously underwent this surgical procedure) have high expectations regarding functional outcome. Therefore, patients need to be well informed about recovery of physical functioning after THA. PURPOSE: The purpose of this study was to review publications on recovery of physical functioning after THA and examine the degree of recovery with regard to 3 aspects of functioning (ie, perceived physical functioning, functional capacity to perform activities, and actual daily activity in the home situation). DATA SOURCES: Data were obtained from the MEDLINE and EMBASE databases from inception to July 2009, and references in identified articles were tracked. STUDY SELECTION: Prospective studies with a before-after design were included. Patients included in the analysis had to have primary THA for osteoarthritis. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently checked the inclusion criteria, conducted the risk of bias assessment, and extracted the results. Data were pooled in a meta-analysis using a random-effects model. RESULTS: A total of 31 studies were included. For perceived physical functioning, patients recovered from less than 50% preoperatively to about 80% of that of controls (individuals who were healthy) 6 to 8 months postsurgery. On functional capacity, patients recovered from 70% preoperatively to about 80% of that of controls 6 to 8 months postsurgery. For actual daily activity, patients recovered from 80% preoperatively to 84% of that of controls at 6 months postsurgery. LIMITATIONS: Only a few studies were retrieved that investigated the recovery of physical functioning longer than 8 months after surgery. CONCLUSIONS: Compared with the preoperative situation, the 3 aspects of physical functioning showed varying degrees of recovery after surgery. At 6 to 8 months postoperatively, physical functioning had generally recovered to about 80% of that of controls. http://repub.eur.nl/res/pub/25863/ 2011-04-01T00:00:00Z Very few large-scale studies have focused on emotional facial expression recognition (FER) in 3-year-olds, an age of rapid social and language development. We studied FER in 808 healthy 3-year-olds using verbal and nonverbal computerized tasks for four basic emotions (happiness, sadness, anger, and fear). Three-year-olds showed differential performance on the verbal and nonverbal FER tasks, especially with respect to fear. That is to say, fear was one of the most accurately recognized facial expressions as matched nonverbally and the least accurately recognized facial expression as labeled verbally. Sex did not influence emotion-matching nor emotion-labeling performance after adjusting for basic matching or labeling ability. Three-year-olds made systematic errors in emotion-labeling. Namely, happy expressions were often confused with fearful expressions, whereas negative expressions were often confused with other negative expressions. Together, these findings suggest that 3-year-olds' FER skills strongly depend on task specifications. Importantly, fear was the most sensitive facial expression in this regard. Finally, in line with previous studies, we found that recognized emotion categories are initially broad, including emotions of the same valence, as reflected in the nonrandom errors of 3-year-olds. http://repub.eur.nl/res/pub/26316/ 2011-04-01T00:00:00Z Using the theory of planned behavior, we examined the effects of different recruitment-related information sources on the job pursuit of highly educated graduates. The study was conducted using a real-life longitudinal design. Participants reported on potential employers they were interested in. We used hierarchical linear modeling to analyze within-participant relationships of different information sources with the theory of planned behavior variables, job pursuit behavior, and actual job choice. The theory of planned behavior relationships was supported. Recruitment advertising and positive word of mouth related positively to job pursuit intention and behavior. Negative publicity and word of mouth partly related to job pursuit behavior, indicating their role in the recruitment process. On-campus presence related negatively to job pursuit intention and behavior, suggesting that recruiters should convey parsimonious and realistic job-related information. http://repub.eur.nl/res/pub/20610/ 2010-12-01T00:00:00Z Objective: To assess whether socioeconomic inequalities were already present in preschool children. Study design: We used data from 2954 Dutch children participating in a longitudinal birth cohort study. Indicators of socioeconomic status were mother's educational level and household income. Body mass index (BMI)-for-age standard deviation scores were derived from a national reference. Overweight was defined at 24 and 36 months according to age- and sex-specific cut-off points for BMI. Multivariable regression analyses were performed. Results: Relative to children from mothers with the highest educational level, mean BMI standard deviation scores was lower at age 24 months in children from mothers with the low, mid-low, and mid-high educational level, and in the mid-low group at 36 months (P < .001). Prevalence of overweight was lower in children from mothers with the mid-low educational level at age 24 and 36 months (adjusted odds ratio at 24 months: 0.61; 95% confidence interval: 0.43-0.87 and at 36 months: 0.65; 95% confidence interval: 0.44-0.96) but was not significantly different for the other educational levels. There were no significant differences in childhood overweight by income level. Conclusions: The inverse association between socioeconomic status and childhood overweight presumably emerges after age 3 years. Before this age, the gradient may be the reverse. http://repub.eur.nl/res/pub/22038/ 2010-11-01T00:00:00Z Aim To examine the incidence of paroxysmal epileptic and non-epileptic disorders and the associated prenatal and perinatal factors that might predict them in the first year of life in a population-based cohort.Method This study was embedded in the Generation R Study, a population-based prospective cohort study from early fetal life onwards. Information about the occurrence of paroxysmal events, defined as suddenly occurring episodes with an altered consciousness, altered behaviour, involuntary movements, altered muscle tone, and/or a changed breathing pattern, was collected by questionnaires at the ages of 2, 6, and 12 months. Information on possible prenatal and perinatal determinants was obtained by measurements and questionnaires during pregnancy and after birth.Results Information about paroxysmal events in the first year of life was available in 2860 participants (1410 males, 1450 females). We found an incidence of paroxysmal disorders of 8.9% (n=255) in the first year of life. Of these participants, 17 were diagnosed with febrile seizures and two with epilepsy. Non-epileptic events included physiological events, apnoeic spells, loss of consciousness by causes other than epileptic seizures or apnoeic spells, parasomnias, and other events. Preterm birth (p<0.001) and low Apgar score at 1 minute (p<0.05) were significantly associated with paroxysmal disorders in the first year of life. Continued maternal smoking during pregnancy and preterm birth were significantly associated with febrile seizures in the first year of life (p<0.05).Interpretation Paroxysmal disorders are frequent in infancy. They are associated with preterm birth and a low Apgar score. Epileptic seizures only form a minority of the paroxysmal events in infancy. In this study, children whose mothers continued smoking during pregnancy had a higher reported incidence of febrile seizures in the first year of life. These findings may generate various hypotheses for further investigations. http://repub.eur.nl/res/pub/27891/ 2010-10-01T00:00:00Z Background: Women of low socio-economic status (SES) give birth to lighter babies. It is unknown from which moment during pregnancy socio-economic differences in fetal weight can be observed, whether low SES equally affects different fetal-growth components, or what the effect of low SES is after taking into account mediating factors. Methods: In 3545 pregnant women participating in the Generation R Study, we studied the association of maternal educational level (high, mid-high, mid-low and low) as a measure of SES with fetal weight, head circumference, abdominal circumference and femur length. We did this before and after adjusting for potential mediators, including maternal height, pre-pregnancy body mass index and smoking. Results: In fetuses of low-educated women relative to those of high-educated women, fetal growth was slower, leading to a lower fetal weight that was observable from late pregnancy onwards. In these fetuses, growth of the head [-0.16 mm/week; 95% confidence interval (CI): -0.25 to -0.07; P = 0.0004], abdomen (-0.10 mm/week; 95% CI: -0.21 to 0.01; P = 0.08) and femur (-0.03 mm/week; 95% CI: -0.05 to -0.006; P = 0.01) were all slower; from mid-pregnancy onwards, head circumference was smaller, and from late pregnancy onwards, femur length was also smaller. The negative effect of low education was greatest for head circumference (difference in standard deviation score in late pregnancy: -0.26; 95% CI: -0.36 to -0.15; P < 0.0001). This effect persevered even after adjustment for the potential mediators (adjusted difference: -0.14; 95% CI: -0.25 to -0.03; P = 0.01). Conclusions: Low maternal education is associated with a slower fetal growth and this effect appears stronger for growth of the head than for other body parts. Published by Oxford University Press on behalf of the International Epidemiological Association http://repub.eur.nl/res/pub/21209/ 2010-04-30T00:00:00Z http://repub.eur.nl/res/pub/18597/ 2010-04-01T00:00:00Z OBJECTIVES:Food allergy and celiac disease may lead to childhood constipation. Early introduction of food allergens and gluten in the first year of life has been suggested to have a function in these food intolerances, but it is unclear whether this also holds true for development of childhood constipation. The aim of this study was to assess the association between the timing of introduction of food allergens and gluten early in life and functional constipation in childhood.METHODS:This study was embedded in the Generation R study, a population-based prospective cohort study from fetal life until young adulthood. Functional constipation at 24 months of age was defined in 4,651 children according to the Rome II criteria of defecation frequency <3 times a week or the presence of mainly hard feces for at least 2 weeks.RESULTS:At the age of 24 months, 12% of the children had functional constipation. Children with functional constipation got introduced to gluten more often before or at the age of 6 months than children without functional constipation (37% and 27%, respectively). After adjustment for birth weight, gestational age, gender, ethnicity, maternal education, and family history of atopy and chronic intestinal disorders, functional constipation was significantly associated with early gluten introduction (odds ratio (OR): 1.35; 95% confidence interval (CI): 1.10-1.65). No association was found between timing of introduction of cow's milk, hen's egg, soy, peanuts, and tree nuts with functional constipation. A history of cow's milk allergy in the first year of life was significantly associated with functional constipation in childhood (OR: 1.57; 95% CI: 1.04-2.36).CONCLUSIONS:These results suggest that early gluten introduction in the first year of life provide a trigger for functional constipation in a subset of children. In case of functional constipation, there also might be a role for cow's milk allergy initiated in the first year of life.Am J Gastroenterol advance online publication, 2 March 2010; doi:10.1038/ajg.2010.96. http://repub.eur.nl/res/pub/28213/ 2010-04-01T00:00:00Z Objectives: To assess, using a modelling approach, the effectiveness and costs of breech version with acupuncture-type interventions on BL67 (BVA-T), including moxibustion, compared to expectant management for women with a foetal breech presentation at 33 weeks gestation. Design: A decision tree was developed to predict the number of caesarean sections prevented by BVA-T compared to expectant management to rectify breech presentation. The model accounted for external cephalic versions (ECV), treatment compliance, and costs for 10,000 simulated breech presentations at 33 weeks gestational age. Event rates were taken from Dutch population data and the international literature, and the relative effectiveness of BVA-T was based on a specific meta-analysis. Sensitivity analyses were conducted to evaluate the robustness of the results. Main outcome measures: We calculated percentages of breech presentations at term, caesarean sections, and costs from the third-party payer perspective. Odds ratios (OR) and cost differences of BVA-T versus expectant management were calculated. (Probabilistic) sensitivity analysis and expected value of perfect information analysis were performed. Results: The simulated outcomes demonstrated 32% breech presentations after BVA-T versus 53% with expectant management (OR 0.61, 95% CI 0.43, 0.83). The percentage caesarean section was 37% after BVA-T versus 50% with expectant management (OR 0.73, 95% CI 0.59, 0.88). The mean cost-savings per woman was €451 (95% CI €109, €775; p=0.005) using Moxibustion. Sensitivity analysis showed that if 16% or more of women offered moxibustion complied, it was more effective and less costly than expectant management. To prevent one caesarean section, 7 women had to use BVA-T. The expected value of perfect information from further research was €0.32 per woman. Conclusions: The results suggest that offering BVA-T to women with a breech foetus at 33 weeks gestation reduces the number of breech presentations at term, thus reducing the number of caesarean sections, and is cost-effective compared to expectant management, including external cephalic version. http://repub.eur.nl/res/pub/28182/ 2010-02-01T00:00:00Z Information about growth of kidney structures in early life is limited. In a population-based prospective cohort study, from foetal life onwards, we constructed reference curves for kidney growth from the third trimester of pregnancy until early childhood, using data from 1,158 healthy children. Kidney size, defined as length, width, depth and volume, was measured in the third trimester of pregnancy and at the postnatal ages of 6 months and 24 months. Analyses were based on more than 2,500 kidney measurements. In the third trimester of pregnancy and at 6 months of age all kidney measurements were larger in boys than in girls. At 24 months of age, these gender differences were only significant for left kidney structures and right kidney length. Both groups showed trends towards smaller left kidney measurements than right kidney measurements at all ages. Gender-specific reference curves based on post-conceptional and postnatal ages were constructed for left and right kidney length, width, depth and volume. We concluded that kidney size is influenced by age and gender. Left kidney size tended to be smaller than right kidney size, except for kidney length. The reference curves can be used for assessing kidney structures by ultrasound in foetal life and early childhood. http://repub.eur.nl/res/pub/32756/ 2010-02-01T00:00:00Z What is a good measure for happiness inequality? In the context of this question, we have developed an approach in which individual happiness values in a sample are considered as elements of a set and inequality as a binary relation on that set. The total number of inequality relations, each weighed by the distance on the scale of measurement between the pair partners, has been adopted as an indicator for the inequality of the distribution as a whole. For models in which the happiness occurs as a continuous latent variable, an analogous approach has been developed on the basis of differentials. In principle, this fundamental approach results in a (zero) minimum value, and, more importantly, also in a maximum value. In the case where happiness is measured using a k-points scale, the maximum inequality is obtained if all 1/2N sample members select the lowest possible rating (Eq. 1) and the other 1/2N the highest possible one (k). This finding even applies to the truly ordinal case, i.e., if the distances between the successive ratings on the scale are unknown. It is, however, impossible to quantify the inequality of some measured sample distribution, unless all distances of the k categories of the scale of measurement are known or at least estimated, either on an empirical basis or on the basis of assumptions. In general, the numerical application of the method to continuous distributions is very complicated. An exploration on the basis of a relatively simple model with a linear probability density function suggests that the inequality of a beta probability distribution with shape parameters a and b increases as the value of these parameters decreases. A contour plot, obtained by numerical integration, demonstrates this relationship in a quantitative way. This approach is applicable to judge the aptness of common statistics of dispersion, among which the standard deviation and the Gini coefficient. The former is shown to be more appropriate than the latter for measuring inequality of happiness within nations. http://repub.eur.nl/res/pub/20939/ 2010-01-01T00:00:00Z The Happiness Scale Interval Study deals with survey questions on happiness, using verbal response options, such as 'very happy' and 'pretty happy'. The aim is to estimate what degrees of happiness are denoted by such terms in different questions and languages. These degrees are expressed in numerical values on a continuous [0,10] scale, which are then used to compute 'transformed' means and standard deviations. Transforming scores on different questions to the same scale allows to broadening the World Database of Happiness considerably. The central purpose of the Happiness Scale Interval Study is to identify the happiness values at which respondents change their judgment from e.g. 'very happy' to 'pretty happy' or the reverse. This paper deals with the methodological/statistical aspects of this approach. The central question is always how to convert the frequencies at which the different possible responses to the same question given by a sample into information on the happiness distribution in the relevant population. The primary (cl)aim of this approach is to achieve this in a (more) valid way. To this end, a model is introduced that allows for dealing with happiness as a latent continuous random variable, in spite of the fact that it is measured as a discrete one. The [0,10] scale is partitioned in as many contiguous parts as the number of possible ratings in the primary scale sums up to. Any subject with a (self-perceived) happiness in the same subinterval is assumed to select the same response. For the probability density function of this happiness random variable, two options are discussed. The first one postulates a uniform distribution within each of the different subintervals of the [0,10] scale. On the basis of these results, the mean value and variance of the complete distribution can be estimated. The method is described, including the precision of the estimates obtained in this way. The second option assumes the happiness distribution to be described as a beta distribution on the interval [0,10] with two shape parameters (α and β). From their estimates on the basis of the primary information, the mean value and the variance of the happiness distribution in the population can be estimated. An illustration is given in which the method is applied to existing measurement results of 20 surveys in The Netherlands in the period 1990-2008. The results clarify our recommendation to apply the model with a uniform distribution within each of the category intervals, in spite of a better validity of the alternative on the basis of a beta distribution. The reason is that the recommended model allows to construct a confidence interval for the true but unknown population happiness distribution. The paper ends with a listing of actual and potential merits of this approach, which has been described here for verbal happiness questions, but which is also applicable to phenomena which are measured along similar lines http://repub.eur.nl/res/pub/24944/ 2009-12-01T00:00:00Z Background. Bivariate random effects meta-analysis of diagnostic tests is becoming a well established approach when studies present one two-by-two table or one pair of sensitivity and specificity. When studies present multiple thresholds for test positivity, usually meta-analysts reduce the data to a two-by-two table or take one threshold value at a time and apply the well developed meta-analytic approaches. However, this approach does not fully exploit the data. Methods. In this paper we generalize the bivariate random effects approach to the situation where test results are presented with k thresholds for test positivity, resulting in a 2 by (k+1) table per study. The model can be fitted with standard likelihood procedures in statistical packages such as SAS (Proc NLMIXED). We follow a multivariate random effects approach; i.e., we assume that each study estimates a study specific ROC curve that can be viewed as randomly sampled from the population of all ROC curves of such studies. In contrast to the bivariate case, where nothing can be said about the shape of study specific ROC curves without additional untestable assumptions, the multivariate model can be used to describe study specific ROC curves. The models are easily extended with study level covariates. Results. The method is illustrated using published meta-analysis data. The SAS NLMIXED syntax is given in the appendix. Conclusion. We conclude that the multivariate random effects meta-analysis approach is an appropriate and convenient framework to meta-analyse studies with multiple threshold without losing any information by dichotomizing the test results. http://repub.eur.nl/res/pub/16487/ 2009-06-03T00:00:00Z The vulnerability for behavioral problems is partly shaped in fetal life. Numerous studies have related indicators of intrauterine growth, for example, birth weight and body size, to behavioral development. We investigated whether fetal size in mid- and late pregnancy is related to infant irritability and alertness. In a population-based birth cohort of 4,255 singleton full-term infants ultrasound measurements of fetal head and abdominal circumference in mid- and late pregnancy were performed. Infant irritability and alertness scores were obtained by the Mother and Baby Scales at 3 months and z-standardized. Multiple linear regression analyses revealed curvilinear associations (inverted J-shape) of measures of fetal size in both mid- and late pregnancy with infant alertness. Fetal size characteristics were not associated with infant irritability. These results suggest that alterations of intrauterine growth affecting infant alertness are already detectable from mid-pregnancy onwards. http://repub.eur.nl/res/pub/18405/ 2009-03-01T00:00:00Z Objectives: We aimed to study the effects of active-learning curricula on graduation rates of students and on the length of time needed to graduate. Methods: Graduation rates for 10 generations of students enrolling in the eight Dutch medical schools between 1989 and 1998 were analysed. In addition, time needed to graduate was recorded. Three of the eight schools had curricula emphasising active learning, small-group instruction and limited numbers of lectures; the other five had conventional curricula to varying degrees. Results: Overall, the active-learning curricula graduated on average 8% more students per year, and these students graduated on average 5 months earlier than their colleagues from conventional curricula. Conclusions: Four hypotheses potentially explaining the effect of active learning on graduation rate and study duration were considered: (i) active-learning curricula promote the social and academic integration of students; (ii) active-learning curricula attract brighter students; (iii) active-learning curricula retain more poor students, and (iv) the active engagement of students with their study required by active-learning curricula induces better academic performance and, hence, lower dropout rates. The first three hypotheses had to be rejected. It was concluded that the better-learning hypothesis provides the most parsimonious account for the data. http://repub.eur.nl/res/pub/15072/ 2009-01-01T00:00:00Z Background: Minimally invasive techniques such as endovenous laser therapy, radiofrequency ablation, and ultrasound-guided foam sclerotherapy are widely used in the treatment of lower extremity varicosities. These therapies have not yet been compared with surgical ligation and stripping in large randomized clinical trials. Methods: A systematic review of Medline, Cochrane Library, and Cinahl was performed to identify studies on the effectiveness of the four therapies up to February 2007. All clinical studies (open, noncomparative, and randomized clinical trials) that used ultrasound examination as an outcome measure were included. Because observational and randomized clinical trial data were included, both the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) and Quality Of Reporting Of Meta-analyses (QUORUM) guidelines were consulted. A random effects meta-analysis was performed, and subgroup analysis and meta-regression were done to explore sources of between-study variation. Results: Of the 119 retrieved studies, 64 (53.8%) were eligible and assessed 12,320 limbs. Average follow-up was 32.2 months. After 3 years, the estimated pooled success rates (with 95% confidence intervals [CI]) for stripping, foam sclerotherapy, radiofrequency ablation, and laser therapy were about 78% (70%-84%), 77% (69%-84%), 84% (75%-90%), and 94% (87%-98%), respectively. After adjusting for follow-up, foam therapy and radiofrequency ablation were as effective as surgical stripping (adjusted odds ratio [AOR], 0.12 [95% CI, -0.61 to 0.85] and 0.43 [95% CI, -0.19 to 1.04], respectively). Endovenous laser therapy was significantly more effective compared with stripping (AOR, 1.13; 95% CI, 0.40-1.87), foam therapy (AOR, 1.02; 95% CI, 0.28-1.75), and radiofrequency ablation (AOR, 0.71; 95% CI, 0.15-1.27). Conclusion: In the absence of large, comparative randomized clinical trials, the minimally invasive techniques appear to be at least as effective as surgery in the treatment of lower extremity varicose veins. http://repub.eur.nl/res/pub/14113/ 2008-12-01T00:00:00Z Objective: To study the prevalence, risk factors, and dynamics of pneumococcal carriage in infancy. Study design: In a population-based prospective cohort study conducted in Rotterdam, the Netherlands between June 2003 and November 2006, nasopharyngeal swabs were obtained from children at age of 1.5, 6, and 14 months. Data on risk factors were obtained from midwives, hospital registries, and questionnaires. Results: The prevalence of pneumococcal carriage increased from 8.3% at age 1.5 months (n = 627) to 31.3% at age 6 months (n = 832) and 44.5% at age 14 months (n = 757). The prevalence of serotypes covered by the 7-valent conjugate increased from 3.0% to 16.2% and 27.7% at these respective ages. Having siblings (adjusted odds ratio [aOR] = 4.33; 95% confidence interval [CI] = 1.22 to 15.35) and day care attendance (aOR = 3.05, 95% CI = 1.88 to 4.95 at 6 months; aOR = 2.78, 95% CI 1.= 70 to 4.55 at 14 months) were associated with pneumococcal carriage. Pneumococcal carriage at age 6 months was associated with pneumococcal carriage at age 14 months (aOR = 2.43; 95% CI = 1.50 to 3.94). Pneumococcal carriage was not associated with sex, maternal smoking, maternal educational level, or breast-feeding. Conclusions: The prevalence of serotypes covered by the 7-valent conjugate vaccine increased in the first year of life. Siblings, day care attendance, and previous pneumococcal carriage were independent factors associated with pneumococcal carriage. http://repub.eur.nl/res/pub/14448/ 2008-10-01T00:00:00Z Low socioeconomic status has been associated with preeclampsia. The underlying mechanism, however, is unknown. Preeclampsia is associated with relatively high blood pressure levels in early pregnancy and with an absent midpregnancy fall in blood pressure. At present, little is known about the associations among socioeconomic status, blood pressure level in early pregnancy, blood pressure change during pregnancy, and preeclampsia. We studied these associations in 3142 pregnant women participating in a population-based cohort study. Maternal educational level (high, midhigh, midlow, and low) was used as an indicator of socioeconomic status. Systolic and diastolic blood pressure was measured in early, mid-, and late pregnancy. Relative to women with high education, those with low and midlow education had higher mean systolic and diastolic blood pressure levels in early pregnancy; this was explained largely by a higher prepregnancy body mass index. Although women with high, midhigh, and midlow education had a significant midpregnancy fall in diastolic blood pressure, those with low education did not (change from early to midpregnancy: -0.38 mm Hg; 95% CI: -1.33 to 0.58). The latter could not be explained by prepregnancy body mass index, smoking, or alcohol consumption during pregnancy. The absence of a midpregnancy fall also tended to be related to the development of preeclampsia, especially among women with a low educational level (OR: 3.8; 95% CI: 0.80 to 18.19). The absence of a midpregnancy fall in diastolic blood pressure in women with a low education level may be a sign of endothelial dysfunction that is manifested during pregnancy. This might partly explain these women's susceptibility to preeclampsia. http://repub.eur.nl/res/pub/14711/ 2008-10-01T00:00:00Z Aim: To examine the extent to which infant neuromotor development is determined by gestational duration and birth weight within the normal range. Methods: The study was embedded within the Generation R Study, a population-based cohort in Rotterdam, the Netherlands. An adapted version of Touwen's Neurodevelopmental Examination was used to assess 3224 infants (1576 males and 1648 females) at corrected ages between 9 and 15 weeks. Non-optimal neuromotor development was defined as a score in the highest tertile. Results: Infant neuromotor development was significantly affected by gestational duration (odds ratio 0.8, 95% confidence interval 0.7;0.8). Adding a quadratic term of gestational duration to the model revealed a highly significant curvilinear association between gestational duration and neuromotor development; after adjusting for post-conceptional age this was still significant. Although babies with a 1 kg lower birth weight had a 30% higher risk of non-optimal neuromotor development, this association disappeared after adjustment for post-conceptional age. Conclusions: Our findings indicate that differences in infant neuromotor development can be explained even by variations in gestational duration within the normal range. If an infant is found to have minor neuromotor delays, account should be taken of this. http://repub.eur.nl/res/pub/14687/ 2008-09-30T00:00:00Z The use of standard univariate fixed- and fandom-effects models in meta-analysis has become well known in the last 20 years. However, these models are unsuitable for meta-analysis of clinical trials that present multiple survival estimates (usually illustrated by a survival curve) during a follow-up period. Therefore, special methods are needed to combine the survival curve data from different trials in a meta-analysis. For this purpose, only fixed-effects models have been suggested in the literature. In this paper, we propose a multivariate random-effects model for joint analysis of survival proportions reported at multiple time points and in different studies, to be combined in a meta-analysis. The model could be seen as a generalization of the fixed-effects model of Dear (Biometrics 1994; 50:989-1002). We illustrate the method by using a simulated data example as well as using a clinical data example of meta-analysis with aggregated survival curve data. All analyses can be carried out with standard general linear MIXED model software. http://repub.eur.nl/res/pub/14905/ 2008-09-01T00:00:00Z Meta-analysis of receiver operating characteristic (ROC)-curve data is often done with fixed-effects models, which suffer many shortcomings. Some random-effects models have been proposed to execute a meta-analysis of ROC-curve data, but these models are not often used in practice. Straightforward modeling techniques for multivariate random-effects meta-analysis of ROC-curve data are needed. The 1st aim of this article is to present a practical method that addresses the drawbacks of the fixedeffects summary ROC (SROC) method of Littenberg and Moses. Sensitivities and specificities are analyzed simultaneously using a bivariate random-effects model. The 2nd aim is to show that other SROC curves can also be derived from the bivariate model through different characterizations of the estimated bivariate normal distribution. Thereby the authors show that the bivariate random-effects approach not only extends the SROC approach but also provides a unifying framework for other approaches. The authors bring the statistical meta-analysis of ROC-curve data back into a framework of relatively standard multivariate meta-analysis with random effects. The analyses were carried out using the software package SAS (Proc NLMIXED). http://repub.eur.nl/res/pub/11579/ 2007-09-01T00:00:00Z Objectives: The Medical Outcomes Study Short Form 36-Item Health Survey (SF-36) is the most widely used generic instrument to estimate quality of life of patients on renal replacement therapy. Purpose of this study was to summarize and compare the published literature on quality of life of hemodialysis (HD), peritoneal dialysis (PD), and renal transplant (RTx) patients. Methods: We used random-effects regression analyses to compare the SF-36 scores across treatment groups and adjusted this comparison for age and prevalence of diabetes using random-effects meta-regression analyses. Results: We found 52 articles that met the inclusion criteria, reporting quality of life of 36,582 patients. The unadjusted scores of all SF-36 health dimensions were not significantly different between HD and PD patients, but the scores of RTx patients were higher than those of dialysis patients, except for the dimensions Mental Health and Bodily Pain. Point differences between dialysis and RTx patients varied from 2 to 32. With adjustment for age and diabetes, the differences became smaller (point difference 2–22). The significance of the differences of both dialysis groups compared with RTx recipients disappeared for the dimensions Vitality and Social Functioning. The significance of the differences between HD and RTx patients disappeared on the dimensions Physical Functioning, Role Physical, and Bodily Pain. Conclusion: We conclude that dialysis patients have a lower quality of life than RTx patients, but this difference can partly be explained by differences in age and prevalence of diabetes. Keywords: hemodialysis, meta-analysis, peritoneal dialysis, quality of life, renal transplantation. http://repub.eur.nl/res/pub/36043/ 2007-08-03T00:00:00Z Objective: Temporomandibular joint (TMJ) involvement is a frequent feature in cross-sectional prevalence studies among juvenile idiopathic arthritis (JIA) patients. The cross-sectional design makes it almost impossible to study the incidence. Follow-up data on TMJ involvement are sparse. In this study patients were reviewed with an interval of a minimum of 1 year and a maximum of 2 years to study the yearly incidence of TMJ involvement and to obtain follow-up data on TMJ involvement and orthopantomogram (OPT) alterations. Methods: Children with JIA from a previous study on TMJ involvement were included. OPTs were scored according to Rohlin's grading system (grade 0-5). A paediatric rheumatologist measured the level of disease activity during the interval. Results: Eighty-nine of the 97 patients were included in this study with a mean follow-up of 14 months. The yearly incidence of TMJ involvement was 7.1% in patients with JIA. Improvement on the OPT was seen in 27 patients (66%), and 19 of these patients no longer showed any signs of TMJ involvement. Worsening on the OPT was seen in four patients (10%). Disease activity was significantly lower in the improved patients than in the patients with worsening. Conclusion: Condylar lesions due to arthritis can improve over time, indicating a regenerative capacity of the mandibular condyle. As condylar improvement seems to be associated with low disease activity, it is important to consider the TMJ when deciding on a therapeutic regimen. http://repub.eur.nl/res/pub/7845/ 2006-06-28T00:00:00Z Meta-analysis may be broadly defined as the quantitative review and synthesis of the results of related but independent studies. For the simple case where meta-analysis concerns only one outcome measure in each study, the statistical methods are well established now. However, in many practical situations there are several outcome measures presented in the individual studies included in a meta- analysis. In that case analyzing each outcome measure separately in a univariate manner is often suboptimal, and analyzing all outcome measures jointly using multivariate methods is indicated. For many situations with multivariate outcome, appropriate meta-analytic methods are still lacking or underdeveloped. The work presented in this thesis aims at the development of statistical methods that are suited to analyse meta-analytic data with a multivariate nature in a right and optimal way. With our proposed methods one can answer more comprehensive research questions than with the standard univariate methods that are usually used in practice. Our explicit aim is that our suggested statistical methods are relatively easy to use for most researchers. Chapter 1 is a general introduction to the topic of this thesis. In this chapter some basic terms from the field of meta-analysis are explained and an outline of the thesis is given. The first situation of a meta-analysis with multivariate outcome in this thesis (Chapter 2) is the analysis of the relationship between treatment effect and baseline risk. A straightforward way of assessing this relationship is to compute the ordinary weighted least squares (WLS) regression line of the treatment effects estimated from the different trials on the estimated so called baseline risks observed in the control groups. This conventional method has potential pitfalls and has been seriously criticised. We propose another method based on a bivariate meta-analysis. Although we did most of the analyses using the BUGS implementation of Markov Chain Monte Carlo (MCMC) numerical integration techniques, we also show for one of the examples how it can be carried out with a general linear mixed model in SAS Proc Mixed. The advantage of using BUGS is that an exact measurement error model can be specified. On the other hand, in practice it is easier to use the procedure P! roc Mixed of SAS. In Chapter 3 we discuss the general linear mixed model as a natural and convenient framework for meta-analysis. It is thoroughly pointed out how many existing metaanalysis methods can be carried out using Proc Mixed of SAS, one of the most important statistical packages. Thus far ad hoc programs had to be used. We discuss several methods to analyse univariate as well as bivariate outcomes in meta-analysis and meta-regression analysis. Several extensions of the models are presented, like exact likelihood, non-normal mixtures and multiple endpoints. All methods are illustrated by a clinical meta-analysis example for which the complete syntax needed for the software program SAS is given. In Chapter 4 we discuss a meta-analysis of the effect of surgery (endarterectomy) compared to conservative treatment on the short and long term risk of stroke in patients with increased risk of stroke. Three summary measures per trial are available, which we jointly meta-analyse with a general linear mixed model. As far as we know this is the first published example of a multivariate random effects metaanalysis combining more than two outcomes simultaneously. We demonstrate the advantages of the multivariate analysis upon the univariate analyses where only one outcome measure at a time is measured. The multivariate approach reveals the relations between the different outcomes and gives simple expressions for estimation of derived treatment effect parameters such as the cumulative survival probability ratio as a function of follow-up duration. Besides, the results of the multivariate approach enable us also to estimate the relation of the different treatment effect parameters and the underlying risk. We fit the trivariate model in the standard general linear mixed model program of SAS using approximate likelihood. In a few special cases an exact likelihood approach is possible as well. For the multivariate case we fit the model using Bayesian methods to specify a binomial distribution for the number of post-operative events and a Poisson distribution for the events on long term in both treatment groups. The results of the approximate and exact likelihood approach are very similar. Another application of multivariate meta-analysis in this thesis (Chapter 5) is the meta-analysis of ROC curve data. We consider the situation where per study on pair of estimated sensitivity and specificity is available. Meta-analysis of ROC-curve data is usually done with fixed effects models. Despite some random effects models have been published to execute a meta-analysis of ROC-curve data, these models are not often used in practice. Therefore we propose a more straightforward modelling technique for multivariate random effects meta-analysis of ROC-curve data, which can be fitted with standard software. The sensitivities and specificities of the diagnostic studies were analysed simultaneously using a two- dimensional random effects model. We show that different choices could be made to characterise the estimated bivariate normal distribution by a regression line or a so- called summary ROC curve. Under an extra assumption the model also provides individual study specific ROC curves. When a random intercept model is used to get individual study specific ROC curves, all study specific curves are parallel around the summary ROC curve. We have shown that it is also possible to fit a random slope next to a random intercept, even when there is only one point per study. With the random intercept and slope model, the study specific ROC curves are not necessary parallel to the summary ROC curve anymore. The general linear mixed model is also suited for meta-analysis of survival curve data (Chapter 6), where clinical trials each present several survival percentages and their standard errors during a follow-up period. In practice the follow-up times and the number of follow-up times are different among studies. To tackle this problem, investigators often reduce the survival curve to one or some fixed points in time, e.g. the five-years survival rate. Then the data can be analysed with the standard univariate random (or fixed) effects model for each of the chosen time points separately. However, doing separate analyses for each point in time and thus carrying out many meta-analyses, is inefficient and could lead to inappropriate conclusions. Better methods have been proposed, but all of them are fixed effects methods. One of the most recommended methods is the one of Dear. Dear proposed a general linear model with survival estimate as dependent variable and follow-up time, treatment and study as categorical covariates. The parameters are estimated by generalised weighted least squares (GLS). In this thesis we generalise the GLS-method of Dear towards a multivariate random effects model, which could be applied on data with an arbitrary number of survival estimates and spacing of times between them per curve, possibly different between studies. This enables the meta-analyst to analyse all available data as provided in the publications, without need to inter- or extrapolate to fixed times. The method fits in principle in the framework of the general linear mixed model. However, it has to be adapted in this case, because the correlations between the different survival estimates of the same curve have to be estimated as well. Finally, in Chapter 7, the main findings of this thesis are considered. In addition we discuss some limitations and make recommendations for future research. http://repub.eur.nl/res/pub/13190/ 2003-08-15T00:00:00Z BACKGROUND: Since esophageal variceal bleeding is associated with a high mortality rate, prevention of bleeding might be expected to result in improved survival. The first trials to evaluate prophylactic sclerotherapy found a marked beneficial effect of prophylactic treatment. These results, however, were not generally accepted because of methodological aspects and because the reported incidence of bleeding in control subjects was considered unusually high. The objective of this study was to compare endoscopic sclerotherapy (ES) with nonactive treatment for the primary prophylaxis of esophageal variceal bleeding in patients with cirrhosis. METHODS: 166 patients with esophageal varices grade II, III of IV according to Paquet's classification, with evidence of active or progressive liver disease and without prior variceal bleeding, were randomized to groups receiving ES (n = 84) or no specific treatment (n = 82). Primary end-points were incidence of bleeding and mortality; secondary end-points were complications and costs. RESULTS: During a mean follow-up of 32 months variceal bleeding occurred in 25% of the patients of the ES group and in 28% of the control group. The incidence of variceal bleeding for the ES and control group was 16% and 16% at 1 year and 33% and 29% at 3 years, respectively. The 1-year survival rate was 87% for the ES group and 84% for the control group; the 3-year survival rate was 62% for each group. In the ES group one death occurred as a direct consequence of variceal bleeding compared to 9 in the other group (p = 0.01, log-rank test). Complications were comparable for the two groups. Health care costs for patients assigned to ES were estimated to be higher. Meta-analysis of a large number of trials showed that the effect of prophylactic sclerotherapy is significantly related to the baseline bleeding risk. CONCLUSION: In the present trial, prophylactic sclerotherapy did not reduce the incidence of bleeding from varices in patients with liver cirrhosis and a low to moderate bleeding risk. Although sclerotherapy lowered mortality attributable to variceal bleeding, overall survival was not affected. The effect of prophylactic sclerotherapy seems dependent on the underlying bleeding risk. A beneficial effect can only be expected for patients with a high risk for bleeding. http://repub.eur.nl/res/pub/9170/ 1999-01-01T00:00:00Z BACKGROUND: Guidelines state that oral and inhaled corticosteroids are the cornerstone of asthma treatment. The effect of both types of treatment can be assessed by measuring lung and systemic parameters. Treatment for two weeks with either oral prednisolone (30 mg/day), high dose fluticasone propionate (2000 microg/day, FP2000), or lower dose FP (500 microg/day, FP500), both given by a dry powder inhaler, were compared. METHODS: One hundred and twenty patients with asthma were treated for two weeks in a double blind parallel group design. Lung function, asthma symptoms, airway hyperresponsiveness (PC(20) methacholine and adenosine-5'-monophosphate), sputum eosinophil and eosinophilic cationic protein (ECP) levels were measured as lung parameters. In addition, morning serum blood cortisol, blood eosinophil, and serum ECP levels were measured as systemic parameters. RESULTS: PC(20) methacholine and adenosine-5'-monophosphate showed significantly greater improvement with FP2000 (1.99 and 4.04 doubling concentrations (DC), respectively) than prednisolone (0.90 DC, p = 0.02; 2.15 DC, p = 0. 05) and marginally more than with FP500 (1.69 and 3.54 DC). Changes in sputum eosinophil and ECP concentrations showed similar trends; the decrease in ECP was significantly greater with FP2000 than with FP500. In contrast, the systemic parameters of steroid activity (cortisol, peripheral blood eosinophils, and serum ECP) decreased to a similar extent with FP2000 and prednisolone but significantly less with FP500. CONCLUSIONS: Oral prednisolone (30 mg/day) was inferior to FP2000 in improving airway hyperresponsiveness to both methacholine and AMP, with similar trends in forced expiratory volume in one second (FEV(1)), sputum eosinophil and ECP concentrations. Systemic effects were similar with prednisolone and FP2000 and less with FP500.