36 Chapter 2 RESULTS Our search yielded 8626 unique records after duplicate removal (Supplemental Figure 1: PRISMA Flow diagram). Hundred and ninety full texts were screened of which 23 articles were included. Furthermore, 245 ALL trial papers were screened of which one article was eligible, resulting in a total of 24 articles included in this review. Nineteen studies reported on risk factor(s) for steroid-induced APRs, whereas seven studies reported on risk factor(s) for steroid-induced sleep problems. Two studies described risk factors for both APRs and sleep problems. See Tables 1 and 2 for all study characteristics, results and quality of each individual study based on risk of bias. Supplemental Table 4 depicts the risk of bias domain scoring within the separate studies. The summated evidence for each identified risk factor of either APRs or sleep problems and the evaluation of evidence using GRADE is shown in Tables 3 and 4 respectively. Adverse psychological reactions Different APRs were described in the included articles: neuropsychiatric signs, toxicities, or adverse events, personality or behavioral change, steroid psychosis, child difficulties, psychiatric disorders and (neuro)behavioral problems. The measurement of these APRs ranged from using validated questionnaires to retrospective collection from patient files. Eleven studies collected any information of APRs without the use of a validated questionnaire.37-47 The other eight studies used five different parent reported questionnaires: Conners rating scale,48,49 Child Difficulties questionnaire,50,51 Child Behavior Checklist,4,25,49,52 Children’s Depression Inventory,49 and the Strength and Difficulties Questionnaire.9,53 Assessment of the different risk factors depended on the nature of the risk factor. For example, sociodemographic factors were retrieved from patient records, whereas treatment factors usually were per protocol. APRs were measured during (remission-)induction4,37-40,43-47 or maintenance phase9,25,37,41,46,48,49,51-53 (unclear in one study42). Overall, the quality of evidence regarding risk factors for APRs was very low (Table 3). Sociodemographic factors (age and sex) Nine studies evaluated age as a risk factor for steroid-induced APRs. Three studies found younger age (0–6 years old) to be a risk factor for behavioral problems of which two were of higher quality.25,41,52 One study of lower quality comparing patients aged 10–15 years with 16–24 years old described an increased frequency of steroid-induced psychosis in the older age group.42 Five studies of lower quality found no significant impact of age on the development of steroid-induced behavior problems or psychosis.9,40,46,48,49 Two studies used age as interval variable,9,49 but most studies used age group categories with variable
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