Item-level data from composite scales can be analyzed with pharmacometric item response theory (IRT) models to improve the quantification of disease severity compared with the use of total... Show moreItem-level data from composite scales can be analyzed with pharmacometric item response theory (IRT) models to improve the quantification of disease severity compared with the use of total composite scores. However, regular IRT models assume unidimensionality, which is violated in the scale measuring iatrogenic withdrawal in children because some items are also affected by pain, undersedation, or delirium. Here, we compare regular IRT modelling of pediatric iatrogenic withdrawal symptom data with two new analysis approaches in which the latent variable is guided towards the condition of interest using numerical withdrawal severity scored by nurses as a "supervising variable": supervised IRT (sIRT) and supervised multi-dimensional (smIRT) modelling. In this example, in which the items scores are affected by multiple conditions, regular IRT modeling is worse to quantify disease severity than the total composite score, whereas improved performance compared with the composite score is observed for the sIRT and smIRT models. Show less
Dijk, M. van; Kracht, P.A.M.; Arends, J.E.; Blokzijl, H.; Burger, D.M.; Erpecum, K.J. van; ... ; HepNed Study Grp 2019
) was related to dose and gestational age.ResultsBetween 10 and 20 mg/kg dose, median AUCs of acetaminophen, glucuronide, sulfate, and cysteine increased significantly resulting in unchanged ratios... Show more) was related to dose and gestational age.ResultsBetween 10 and 20 mg/kg dose, median AUCs of acetaminophen, glucuronide, sulfate, and cysteine increased significantly resulting in unchanged ratios of AUC of metabolite to acetaminophen. The AUC ratio of glucuronide to acetaminophen increased with gestational age, that of sulfate decreased, and the ratio of cysteine and mercapturate remained unchanged.ConclusionWe found a gestational-age-dependent increase in glucuronidation but no evidence for saturation of a specific pathway as there was a proportional increase in exposure of acetaminophen and all metabolites. Compared with adults, very low exposure to glucuronide but higher exposure to sulfate, cysteine, and mercapturate metabolites was found, of which the relevance is not yet known. Show less
Pain cannot be directly measured in neonates. Therefore, scores based on indirect behavioural signals such as crying, or physiological signs such as blood pressure, are used to quantify neonatal... Show morePain cannot be directly measured in neonates. Therefore, scores based on indirect behavioural signals such as crying, or physiological signs such as blood pressure, are used to quantify neonatal pain both in clinical practice and in clinical studies. The aim of this study was to determine which of the physiological and behavioural items of 2 validated pain assessment scales (COMFORT and premature infant pain profile) are best able to detect pain during endotracheal and nasal suctioning in ventilated newborns. We analysed a total of 516 PIPP and COMFORT scores from 118 newborns. A graded response model was built to describe the data and item information was calculated for each of the behavioural and physiological items. We found that the graded response model was able to well describe the data, as judged by agreement between the observed data and model simulations. Furthermore, a good agreement was found between the pain estimated by the graded response model and the investigator-assessed visual analogue scale scores (Spearman rho correlation coefficient = 0.80). The information scores for the behavioural items ranged from 1.4 to 27.2 and from 0.0282 to 0.131 for physiological items. In these data with mild to moderate pain levels, behavioural items were vastly more informative of pain and distress than were physiological items. The items that were the most informative of pain are COMFORT items "calmness/agitation," "alertness," and "facial tension." Show less
OBJECTIVE:To compare the pharmacodynamics and pharmacokinetics of IV morphine after cardiac surgery in two groups of children-those with and without Down syndrome.DESIGN:Prospective, single-center... Show moreOBJECTIVE:To compare the pharmacodynamics and pharmacokinetics of IV morphine after cardiac surgery in two groups of children-those with and without Down syndrome.DESIGN:Prospective, single-center observational trial.SETTING:PICU in a university-affiliated pediatric teaching hospital.PATIENTS:Twenty-one children with Down syndrome and 17 without, 3-36 months old, scheduled for cardiac surgery with cardiopulmonary bypass.INTERVENTIONS:A loading dose of morphine (100 μg/kg) was administered after coming off bypass; thereafter, morphine infusion was commenced at 40 μg/kg/hr. During intensive care, nurses regularly assessed pain and discomfort with validated observational instruments (COMFORT-Behavior scale and Numeric Rating Scale-for pain). These scores guided analgesic and sedative treatment. Plasma samples were obtained for pharmacokinetic analysis.MEASUREMENTS AND MAIN RESULTS:Median COMFORT-Behavior and Numeric Rating Scale scores were not statistically significantly different between the two groups. The median morphine infusion rate during the first 24 hours after surgery was 31.3 μg/kg/hr (interquartile range, 23.4-36.4) in the Down syndrome group versus 31.7 μg/kg/hr (interquartile range, 25.1-36.1) in the control group (p = 1.00). Population pharmacokinetic analysis revealed no statistically significant differences in any of the pharmacokinetic variables of morphine between the children with and without Down syndrome.CONCLUSIONS:This prospective trial showed that there are no differences in pharmacokinetics or pharmacodynamics between children with and without Down syndrome if pain and distress management is titrated to effect based on outcomes of validated assessment instruments. We have no evidence to adjust morphine dosing after cardiac surgery in children with Down syndrome. Show less
Pop, E.; Bakels, C.; Kuijper, W.; Mücher, H.; Dijk, M. van 2015
Due to favorable conditions of preservation, sedimentary basins provide rich records of human behavior and its environmental context. The conditions for the preservation of archaeological material... Show moreDue to favorable conditions of preservation, sedimentary basins provide rich records of human behavior and its environmental context. The conditions for the preservation of archaeological material however vary between basin types (large, river-fed or small, closed basins), while conditions also differ within a particular basin environment. The goal of this paper is to understand how the dynamics of a small postglacial basin such as Neumark-Nord 2, a context that dominates the Eemian archaeological record, affected the archaeology situated at its basin margin. The approach used here is to correlate the archaeological record with reconstructions of patterns of deposition and the water conditions within the basin, using lithology, micromorphology, pollen, and macroremains from a transect running from the basin center to the margin. The results show that (1) find levels were exposed to overland flow-induced winnowing, which vertically concentrated finds but did not cause significant transport, (2) find levels correspond to phases of increased water presence in the basin, and (3) lateral shifts in hominin activity areas may reflect adjustments in the water level. The research shows the importance of large-scale archaeological excavations and a multidisciplinary sampling strategy that covers both the basin center and the margins, when studying postglacial basin localities like Neumark-Nord 2. Show less
Both, S.; Kuile, M. ter; Enzlin, P.; Dekkers, O.; Dijk, M. van; Weijenborg, P. 2015
The present thesis described the interaction between impaired sleep characteristics and glucose regulation in patients with T1DM and healthy controls. In addition, we described the impact of... Show moreThe present thesis described the interaction between impaired sleep characteristics and glucose regulation in patients with T1DM and healthy controls. In addition, we described the impact of impaired sleep characteristics on sustained attention in patients with T1DM. From the studies described in this thesis we can conclude that : 1. A single night of partial sleep restriction decreased insulin sensitivity of multiple metabolic pathways in controls. 2. A single night of partial sleep deprivation reduced insulin-mediated peripheral glucose uptake in patients with T1DM. 3. A single night of selective SWS suppression did not induce insulin resistance in healthy controls; reduced sleep duration rather than altered sleep composition is therefore an important determinant of insulin sensitivity in controls. 4. Disturbed sleep characteristics are part of the complex syndrome of patients with longstanding T1DM. 5. No effect of short-term controlled hyperglycemic dysregulation on objective sleep characteristics in patients with T1DM. 6. Diabetes per se is independently associated with impaired sustained attention in patients with T1DM. Optimizing sleep duration could be a therapeutic target to optimize glucoregulation in these patients, since voluntary sleep curtailment is common in this 24-hr modern society. Show less
Pop, E.; Bakels, C.; Kuijper, W.; Mücher, H.; Dijk, M. van 2015
