58 Chapter 2 to sleep problems. Younger patients seem at risk for behavioral problems and older patients for sleep problems. Overall, these conclusions should be interpreted with caution. We made recommendations to improve evidence for findings regarding risk factors for steroid-induced APRs and sleep problems (Table 5). One important recommendation is to implement a standardized prospective registration of both steroid-induced APRs and sleep problems and risk factors in future studies in children with ALL, since identifying children at risk and determining effective care can improve health-related quality of life during treatment. Table 5. Summary of findings, gaps of knowledge and recommendations Summary of findings Age APR: younger patients (0-6 years old) seem more at risk for behavioral problems Sleep: adolescent patients seem at risk for more sleep problems (less sleep duration) Sex APR: boys and girls do not differ in risk Sleep: most sleep parameters are not differently impacted, however WASO, napping and number of nocturnal awakening may differ for boys and girls Steroid type APR: no clear difference between dexamethasone versus prednisone Sleep: receiving dexamethasone increased sleep problems compared to prednisone Steroid dose APR: higher dose does not increase risk for APRs Sleep: higher dose does increase risk for sleep problems Gaps of knowledge Recommendations Scarce evidence on prospectively measured steroid-induced APR and sleep problems and related risk factors (only 6 out of 245 c Systematically monitor psychological and sleep toxicities in new studies and specifically in clinical pediatric ALL trials. Lack of high quality studies investigating steroid-induced APR and sleep problems Current evidence is of very low quality. Develop larger studies that are a priori designed to investigate risk factors for steroidinduced APR and sleep problems. Use validated measures to study APR and sleep, e.g. validated questionnaires, sleep diary or actigraphy Replication studies, particularly for sleep problems, to increase quality of evidence. Studies investigating parental coping, stress, family and medical history are currently lacking. Include parental coping, stress, family and medical history in new studies, since they are potentially risk factors. Genetic susceptibility studies are scarce, patient cohorts are small, no adjustments for multiple testing or confounding variables are made and findings remain to be replicated Larger studies on the influence of genetic variation are needed, including appropriate replication cohorts Abbreviations: ALL: acute lymphoblastic leukemia, APR: adverse psychological reaction
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