183 Hydrocortisone as an intervention (RCT) 6 ◀ Figure 1. DexaDays-2 Study Design Eligible ALL patients were first enrolled to identify clinically relevant dexamethasone-induced neurobehavioral problems. Parents filled in several questionnaires before (T1) and after (T2) a 5 day ‘dexamethasone only’ treatment. If patients showed ≥5 points increase on the SDQ Total difficulties score, they were included in the RCT and subsequently randomized to start with either placebo or hydrocortisone. After two courses cross-over took place. Before and after each treatment block, parents filled in several questionnaires (T3-T10). During the first course of each treatment (hydrocortisone and placebo), patients also wore an actigraph to measure sleep objectively. T11 was used as a close-out visit. Abbreviations: ALL: acute lymphoblastic leukemia, dexa: dexamethasone, DT-P: distress thermometer for parents, ET: eating thermometer, HC: hydrocortisone, MR: medium risk, PedsQL: pediatric quality of life questionnaire, RCT: randomized placebo-controlled trial SDSC: sleep disturbance scale for children, SDQ: Strengths and Difficulties Questionnaire Statistical analysis Descriptive statistics for baseline characteristics with either means and standard deviations or medians with interquartile ranges, depending on distribution, were calculated. Comparison of baseline characteristics between included patients and not included patients was done with χ2 test or Mann-Whitney U test in case of violation of normality assumption. First, the data was analyzed for carry-over effect or period effect (i.e. the order of treatment), using a paired-samples T-test or Mann-Whitney U test. To assess the effect of hydrocortisone on neurobehavioral problems we calculated delta SDQ scores by subtracting the SDQ score at the start of a dexamethasone course, from the SDQ score after five days of dexamethasone (e.g. T6-T5 or T4-T3, Figure 1). These delta scores were compared using the Wilcoxon signed-rank test, as was described in our study design.11 Furthermore, due to the presence of repeated measures, a generalized mixed model was estimated to study the effect of hydrocortisone. Included covariates were age, sex, start group (hydrocortisone/placebo), week of maintenance treatment, concomitant asparaginase treatment (yes/no),24 and whether mother or father completed the questionnaire.25 An interaction term between intervention and time was also included. To assess the effect of hydrocortisone compared to placebo, we estimated a mixed model for timepoints T3 to T10. The toeplitz covariance matrix structure was used in the model since the within subjects’ correlation gets weaker for times further apart. Subscores and secondary outcomes were analyzed in a similar way as described above. A decrease on the SDQ Total Difficulties score of 5 points (1 standard deviation (SD) of the norm) was considered clinically significant. A p-value <0.05 was considered statistically significant. All analyses were performed using IBM SPSS Statistics version 26.0.
RkJQdWJsaXNoZXIy MTk4NDMw