21 General introduction 1 SCOPE AND OUTLINE OF THIS THESIS In this thesis, we aim to increase existing knowledge on the prevalence and determinants of dexamethasone-induced side effects in children with ALL. Moreover, we aim to validate the finding that hydrocortisone addition to dexamethasone treatment leads to a significant reduction of clinically relevant dexamethasone-induced neurobehavioral and sleep problems. Furthermore, we aim to describe the role of the mineralocorticoid receptor in steroid-induced cytotoxicity. Chapter 2 provides a systematic review of the literature regarding the risk factors for glucocorticoid-induced neurobehavioral and sleep problems. In Chapter 3, we describe the design of the DexaDays-2 study, which consists of two parts. First, we measured which patients experience clinically relevant dexamethasone-induced neurobehavioral problems. The risk factors for developing these problems are described in Chapter 4. Related somatic effects were studied in this cohort by measuring the influence of a five-day dexamethasone course on leptin levels, fat mass and feeling of hunger (Chapter 5). The core part of the DexaDays-2 study comprised a randomized placebo-controlled trial, which evaluated the beneficial effect of hydrocortisone addition to dexamethasone treatment on neurobehavioral and sleep problems, as well as quality of life. The results of this study are described in Chapter 6. Finally, in addition to studying glucocorticoid related side effects in children with ALL, in Chapter 7 we describe our study that was designed to get insight into biological mechanisms of the in vitro effect of various steroids on glucocorticoidinduced cytotoxicity through glucocorticoid and mineralocorticoid receptor activation.
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