Reliability of the Sexual Knowledge Picture Instrument: a potential diagnostic instrument for sexual abuse in young children.

OBJECTIVE: To determine the intra-rater and inter-rater reliability of the Sexual Knowledge Picture Instrument (SKPI), a potential diagnostic instrument for young suspected victims of sexual abuse containing three scoring forms, that is, verbal responses, non-verbal reactions and red flags. DESIGN: Video-recorded SKPI interviews with children with and without suspicion of child sexual abuse were observed and scored by two trained, independent raters. The second rater repeated the assessment 6 weeks after initial rating to evaluate for intra-rater reliability. SUBJECTS: 78 children aged 3-9 years old were included in the study. 39 of those included had known suspicion of sexual abuse and the other 39 had no suspicion. MAIN OUTCOME MEASURES: Intra-rater and inter-rater reliability of the scores per study group and in the total sample were assessed by Cohen's kappa and percentage of agreement (POA). RESULTS: The median intra-rater Cohen's kappa exceeded 0.90 and the POA exceeded 95 for all three forms in both study groups, except for the red flag form (median Cohen's kappa 0.54 and POA 87 in the suspected group, and 0.84 and 92, respectively, in the total sample). For the verbal scoring form the median inter-rater Cohen's kappa and POA were 1.00 and 100, respectively, in both groups. For the non-verbal form the median inter-rater kappa and POA were 0.37 and 97, respectively, in the suspected group, and 0.47 and 100, respectively, in the control group. For the red flag form, they were 0.37 and 76, respectively, in the suspected group and 0.42 and 77, respectively, in the control group. CONCLUSION: The reliability of the SKPI verbal form was sufficient, but there is room for improvement in the non-verbal and red flag scoring forms. These forms may be improved by adjusting the manual and improving rater training.

Validation of the Sexual Knowledge Picture Instrument as a diagnostic instrument for child sexual abuse: study protocol.

BACKGROUND: The consequences of child sexual abuse (CSA) can be significant and can affect short-term and long-term mental, sexual and physical health. In order to offer timely and appropriate care for the child, early recognition of CSA is necessary. The lack of specific physical and psychological signs and barriers to abuse disclosure that these young victims face makes it difficult for medical and psychological professionals to recognise and confirm CSA signs. We aimed to validate the Sexual Knowledge Picture Instrument (SKPI) as a diagnostic instrument for CSA. METHODS AND ANALYSIS: An observational study to quantify the intraobserver and interobserver reliability and diagnostic accuracy of the SKPI will be performed. A total of 250 subjects from three groups will be included in the study: (1) a group of suspected CSA victims, recruited from three academic paediatric hospitals; (2) a case group of (proven) victims of CSA, recruited in cooperation with the Dutch Police Vice Squad; and (3) a control group of children, recruited from preschools and primary schools. All children will be interviewed using the SKPI, and to investigate reliability, video recordings will be assessed and reassessed by the same and a different blinded rater, respectively. Within 1 year, the results of the SKPI will be compared with the conclusions from the independent child protective services or police reports. If necessary, the SKPI will be modified to improve its reliability and accuracy. ETHICS AND DISSEMINATION: This validation study of the SKPI is necessary for obtaining a reliable diagnostic tool, which will enable medical and psychological professionals to detect CSA in young victims at an early age and start intervention/treatment. TRIAL REGISTRATION NUMBER: NL 50903.018.15.

Safety of Rapid Infliximab Infusions in Children: A Systematic Review.

OBJECTIVES: The aim of the study was to assess whether the incidence of infusion reactions (IR) increases after rapid (≤1 hour) infliximab (IFX) infusions, compared with standard (2-3 hour) infusions in children. METHODS: Systematic review including studies describing the number of IR after rapid IFX infusion in children ages 0 to 18 years. RESULTS: Four records were included (3 retrospective, n = 498, 347 standard infusions, 3703 rapid infusions). Reported incidences of IR ranged from 0% to 2% of infusions in standard groups (reported 95% confidence intervals [CIs] ranged from 0% to 7%) and from 0% to 2% of infusions in rapid groups (reported 95% CIs ranged from 0% to 12%). None of the studies included reported a significant difference in incidence of IR between the 2 groups. CONCLUSIONS: There is insufficient evidence to conclude whether the rate of IR after rapid IFX increases. The consistent finding of no increase in IR in all studies and the low rate of observed IR suggests there is no significant difference in rate of IR.

Altered gentamicin pharmacokinetics in term neonates undergoing controlled hypothermia.

AIM(S): Little is known about the pharmacokinetic (PK) properties of gentamicin in newborns undergoing controlled hypothermia after suffering from hypoxic−ischaemic encephalopathy due to perinatal asphyxia. This study prospectively evaluates and describes the population PK of gentamicin in these patients METHODS: Demographic, clinical and laboratory data of patients included in a multicentre prospective observational cohort study (the 'PharmaCool Study') were collected. A non-linear mixed-effects regression analysis (nonmem®) was performed to describe the population PK of gentamicin. The most optimal dosing regimen was evaluated based on simulations of the final model. RESULTS: A total of 47 patients receiving gentamicin were included in the analysis. The PK were best described by an allometric two compartment model with gestational age (GA) as a covariate on clearance (CL). During hypothermia the CL of a typical patient (3 kg, GA 40 weeks, 2 days post-natal age (PNA)) was 0.06 l kg−1 h−1 (inter-individual variability (IIV) 26.6%) and volume of distribution of the central compartment (Vc) was 0.46 l kg−1 (IIV 40.8%). CL was constant during hypothermia and rewarming, but increased by 29% after reaching normothermia (>96 h PNA). CONCLUSIONS: This study describes the PK of gentamicin in neonates undergoing controlled hypothermia. The 29% higher CL in the normothermic phase compared with the preceding phases suggests a delay in normalization of CL after rewarming has occurred. Based on simulations we recommend an empiric dose of 5 mg kg−1 every 36 h or every 24 h for patients with GA 36­40 weeks and GA 42 weeks, respectively.

Small sample approach, and statistical and epidemiological aspects.

In this chapter, the design of pharmacokinetic studies and phase III trials in children is discussed. Classical approaches and relatively novel approaches, which may be more useful in the context of drug research in children, are discussed. The burden of repeated blood sampling in pediatric pharmacokinetic studies may be overcome by the population pharmacokinetics approach using nonlinear mixed effect modeling as the statistical solution to sparse data. Indications and contraindications for phase III trials are discussed: only when there is true "equipoise" in the medical scientific community, it is ethical to conduct a randomized clinical trial. The many reasons why a pediatric trial may fail are illustrated with examples. Inadequate sample sizes lead to inconclusive results. Twelve classical strategies to minimize sample sizes are discussed followed by an introduction to group sequential design, boundaries design, and adaptive design. The evidence that these designs reduce sample sized between 35 and 70% is reviewed. The advantages and disadvantages of the different approaches are highlighted to give the reader a broad idea of the design types that can be considered. Finally, working with DMCs during the conduct of trials is introduced. The evidence regarding DMC activities, interim analysis results, and early termination of pediatric trials is presented. So far reporting is incomplete and heterogeneous, and users of trial reports may be misled by the results. A proposal for a checklist for the reporting of DMC issues, interim analyses, and early stopping is presented.