16 Chapter 1 GLUCOCORTICOID-INDUCED SIDE EFFECTS Besides the anti-leukemic effect of dexamethasone and prednisolone, both glucocorticoids can also induce various undesirable side effects. These side effects involve almost every organ system and range from acute side effects, to side effects that become apparent later in life. Overall, dexamethasone is associated with more (severe) side effects than prednisolone.26 Both glucocorticoid-induced adverse psychological reactions and somatic side effects may occur during ALL treatment. Adverse psychological reactions Adverse psychological and neurocognitive reactions due to glucocorticoids may include neurobehavioral problems (e.g. increased distress, compulsive behavior or altered emotions), psychiatric deterioration (e.g. psychosis, depression), cognitive decline, changes in sleep, increased fatigue or preoccupation with food.27-30 All these side effects may potentially impact quality of life during treatment of childhood ALL for both the patient and family, for a substantial period of time, since ALL treatment lasts 2-3 years.31,32 Reports on estimated frequencies of glucocorticoid-induced neurobehavioral problems in children range from 5% to 75%,28,33-36 whereas sleep problems are reported in 19% to 87%.35,37 In this thesis, the emphasis lies on dexamethasone-induced neurobehavioral and sleep problems, as well as the feeling of hunger children experience during dexamethasone treatment. Patients at risk The inter-individual variation in the severity of glucocorticoid-induced side effects is high. For better understanding of this inter-individual variation, more insight in contributing factors that may influence neurobehavioral and sleep problems during dexamethasone treatment would be of value. The risk factors for developing neurobehavioral side effects during dexamethasone treatment are multi-dimensional and therefore gathering insight in the full scope of possible determinants is important. Patient and treatment characteristics In adults (both with and without cancer diagnosis), a higher steroid dose as well as psychiatric history increased the risk of neurobehavioral side effects.38,39. In children, dexamethasone, as compared to prednisolone, as well as a younger age appear to increase the risk of steroid-induced neurobehavioral problems.40,41 Previously established risk factors for sleep problems in healthy children are female sex, a difficult temperament and unhealthy sleep behavior.42 In childhood cancer survivors, female sex, co-morbidities and lower educational level were associated with insomnia.43
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