132 Chapter 4 The main strength of our study is the fact that we were able to invite all eligible ALL patients due to our national centralized pediatric cancer care. This rendered a representative study population, and the largest prospective series thus far. We were also able to study a broad range of possible determinants. Limitations are risk of bias in inclusion, as families of patients who experience more dexamethasone-induced side effects may have been more interested to participate. Besides, it may be possible that certain predisposing factors, e.g. differences in dexamethasone kinetics, were not found to be significantly associated with the outcomes due to the relatively small sample size. Additionally, the study was not primarily powered for the multivariable analyses. Our results are based on proxy reports, since most included patients were too young to fill in questionnaires themselves. Only nineteen children were ≥11 years and therefore offered the SDQ selfreport. When comparing the delta SDQ of the twelve patients who completed the SDQ on both timepoints with their parents, we found a poor agreement between these scores. It has been described before that parents and children report side effects differently.54,55The group of patients who were able to complete a self-report was very small, therefore no conclusions regarding determinants could be made. The use of proxy-reports may also be an explanation for the fact that we only found parental factors to be associated with the reported outcomes. To conclude, we identified parenting stress during dexamethasone as determinant for parent-reported neurobehavioral and sleep problems, which may be a modifiable target. Future studies including larger cohorts that incorporate other possible risk factors such as coping with stress, (family) psychiatric history, stressful life events and parenting strategies, as well as more extensive genetic evaluation, may be of value.
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