Yoo Sook Joung

Psychiatric Comorbidity in Korean Children and Adolescents with Attention-Deficit Hyperactivity Disorder: Psychopathology According to Subtype

It is well-known that more than 50% of attention-deficit hyperactivity disorder (ADHD) cases also have comorbid psychiatric disorders. We evaluated the comorbid psychopathology of Korean children and adolescents with ADHD using a standardized diagnostic instrument. The Korean Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version (K-SADS-PL-K) was administered and completed in 105 patients who had been referred to the outpatient and inpatient clinics at the Samsung Medical Center from March 2004 to May 2005. All of the cases were diagnosed as ADHD according to DSM-IV criteria. We analyzed their clinical characteristics and psychiatric comorbidities, and assessed the correlation of any comorbidity with gender, age and ADHD subtype. Among our 105 participants, 70 (66.7%) subjects were diagnosed with combined-type ADHD, 22 (21.0%) were the predominantly inattentive type, only 1 (1.0%) was determined to have the predominantly hyperactive-impulsive type of ADHD, and 12 (11.4%) were classified as not otherwise specified (NOS) ADHD. Eighty (76.2%) subjects had at least one comorbid disorder such as oppositional defiant disorder (n = 53, 50.5%), anxiety disorders (n = 35, 33.3%) and affective disorders (n = 15, 14.3%). Our patients ranged in age from five to 16 years. Among the factors including gender, age, and ADHD subtype, ADHD subtype was the only one significant to comorbidity in our study. The results of this study suggest that psychiatric comorbidity in Korean children with ADHD is similar to the results of previous studies in western countries. Out of all the ADHD subtypes, the combined-type group had a significantly higher ratio of comorbid disorders and psychopathologies.

Reduced-dose craniospinal radiotherapy followed by tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk medulloblastoma

BACKGROUNDnWe assessed the feasibility and effectiveness of reduced-dose craniospinal (CS) radiotherapy (RT) followed by tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) in reducing late adverse effects without jeopardizing survival among children with high-risk medulloblastoma (MB).nnnMETHODSnFrom October 2005 through September 2010, twenty consecutive children aged >3 years with high-risk MB (presence of metastasis and/or postoperative residual tumor >1.5 cm(2)) were assigned to receive 2 cycles of pre-RT chemotherapy, CSRT (23.4 or 30.6 Gy) combined with local RT to the primary site (total 54.0 Gy), and 4 cycles of post-RT chemotherapy followed by tandem HDCT/autoSCT. Carboplatin-thiotepa-etoposide and cyclophosphamide-melphalan regimens were used for the first and second HDCT, respectively.nnnRESULTSnOf 20 patients with high-risk MB, 17 had metastatic disease and 3 had a postoperative residual tumor >1.5 cm(2) without metastasis. The tumor relapsed/progressed in 4 patients, and 2 patients died of toxicities during the second HDCT/autoSCT. Therefore, 14 patients remained event-free at a median follow-up of 46 months (range, 23-82) from diagnosis. The probability of 5-year event-free survival was 70.0% ± 10.3% for all patients and 70.6% ± 11.1% for patients with metastases. Late adverse effects evaluated at a median of 36 months (range, 12-68) after tandem HDCT/autoSCT were acceptable.nnnCONCLUSIONSnIn children with high-risk MB, CSRT dose might be reduced when accompanied by tandem HDCT/autoSCT without jeopardizing survival. However, longer follow-up is needed to evaluate whether the benefits of reduced-dose CSRT outweigh the long-term risks of tandem HDCT/autoSCT.

Tandem high-dose chemotherapy and autologous stem cell transplantation for anaplastic ependymoma in children younger than 3 years of age

The present study evaluates the feasibility and effectiveness of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) in very young children with anaplastic ependymoma. We aimed both to improve survival and to avoid unacceptable late adverse effects of radiation therapy (RT) by avoiding or deferring RT until 3xa0years of age. Five consecutive patients younger than 3xa0years of age with anaplastic ependymoma were enrolled from April 2006 to November 2008. Tandem HDCT/autoSCT was given following six cycles of induction chemotherapy. RT was either not given or deferred until 3xa0years of age if the patient was in complete response after tandem HDCT/autoSCT. Median age at diagnosis was 16 (range 12–28) months. Four patients had significant residual tumor (>1.5xa0cm2) after initial surgery, and three had leptomeningeal seeding. Toxicities during induction chemotherapy and tandem HDCT/autoSCT were manageable. No tumor progressed during induction chemotherapy and tandem HDCT/autoSCT, and RT was thus avoided or deferred until 3xa0years of age in all patients. All patients are alive at median follow-up of 45 (range 31–62) months from diagnosis, although tumor progressed in one patient. No significant endocrine dysfunction occurred except for hypothyroidism in one patient. Cognitive function was also acceptable in all patients but one who had significant neurologic injury during surgery. Our results indicate that treatment with tandem HDCT/autoSCT is feasible in very young children with anaplastic ependymoma and may improve the survival of patients with acceptable long-term toxicity.

Intensive chemotherapy followed by reduced-dose radiotherapy for biopsy-proven CNS germinoma with elevated beta-human chorionic gonadotropin

In this study, 10 patients with biopsy-proven germinoma with a beta-human chorionic gonadotropin (β-HCG) level >50 mIU/ml received intensive chemotherapy followed by reduced-dose radiotherapy (RT) to reduce late effects from RT. CSF β-HCG levels were >200 mIU/ml in five patients. After endoscopic or stereotactic biopsy, four cycles of induction chemotherapy were administered prior to RT. A CEB regimen (carboplatinxa0+xa0etoposidexa0+xa0bleomycin) and a CyEB regimen (cyclophosphamidexa0+xa0etoposidexa0+xa0bleomycin) were alternated. No residual tumor remained after induction chemotherapy in six patients, only cystic lesions were present at the primary tumor site in three, and a small solid residual tumor was observed in the remaining patient; however, all these patients had normal β-HCG levels. If complete response was achieved before initiation of RT, 19.5xa0Gy craniospinal RT (CSRT)xa0+xa010.8xa0Gy local RT was administered to the tumor bed. If residual lesion was suspected, the dose of RT was selected according to the presence/absence of tumor dissemination at diagnosis (19.5xa0Gy CSRTxa0+xa019.8xa0Gy local RT for localized tumors and 24.0xa0Gy CSRTxa0+xa016.2xa0Gy local RT for disseminated tumors). Eight patients, including four patients with a β-HCG level >200xa0mIU/ml, received 19.5xa0Gy CSRT. All patients remain disease free at a median follow-up of 58 (range 35–94) months from diagnosis. Our data suggest that pathologically pure germinoma with a significantly elevated β-HCG level might be cured with reduced-dose RT if intensive chemotherapy is provided.

Titrating Optimal Dose of Osmotic-Controlled Release Oral Delivery (OROS)-Methylphenidate and Its Efficacy and Safety in Korean Children with ADHD: A Multisite Open Labeled Study

Objective This study was aimed to determine effectiveness and tolerability of Osmotic-controlled Release Oral delivery (OROS) methylphenidate (MPH) and its optimal dose administered openly over a period of up to 12 weeks in drug naïve Korean children with ADHD. Methods Subjects (n=143), ages 6 to 18-years, with a clinical diagnosis of any subtype of ADHD were recruited from 7 medical centers in Korea. An individualized dose of OROS-MPH was determined for each subject depending on the response criteria. The subjects were assessed with several symptom rating scales in week 1, 3, 6, 9 and 12. Results 77 of 116 subjects (66.4%) achieved the criteria for response and the average of optimal daily dose for response was to 30.05±12.52 mg per day (0.90±0.31 mg/kg/d) at the end of the study. Optimal dose was not significantly different between ADHD subtypes, whereas, significant higher dose was needed in older aged groups than younger groups. The average of optimal daily dose for response for the subjects aged above 12 years old was 46.38±15.52 per day (0.81±0.28 mg/kg/d) compared to younger groups (p<0.01). No serious adverse effects were reported and the dose did not have a significant effect on adverse effects. Conclusion Optimal mean dose of OROS-MPH was significantly different by age groups. Higher dose was needed in older aged groups than younger groups. Effectiveness and tolerability of OROS-MPH in symptoms of ADHD is sustained for up to 12 weeks.

Effect of osmotic-release oral system methylphenidate on learning skills in adolescents with attention-deficit/hyperactivity disorder: an open-label study.

We evaluated the effect of osmotic-release oral system (OROS) methylphenidate on learning skills in adolescents with attention-deficit/hyperactivity disorder (ADHD). In an open-label study, 121 adolescents with ADHD were administered flexible doses of OROS methylphenidate for 12 weeks. The efficacy of methylphenidate on ADHD symptoms was evaluated by ADHD Rating Scale (ARS) and Clinical Global Impression Scale (CGI). Learning Skills Test (LST) was used to measure the learning skills of the participants at the baseline and the endpoint. Continuous performance test, visuospatial and verbal working memory, verbal fluency, and inhibition were evaluated before and after the 12 weeks of treatment. The mean total and subscores of LST were significantly increased after the 12-week treatment with OROS methylphenidate. Executive functions were also improved during the trial, with the exception of inhibition measured by the Stroop Test. To the best of our knowledge, this is the first study to examine the influence of OROS methylphenidate on learning skill. As a result, OROS methylphenidate was effective in enhancing learning skills in adolescents with ADHD.

The relationship between symptomatic and functional changes of Korean children and adolescents with attention-deficit/hyperactivity disorder treated with osmotic-controlled release oral delivery system-methylphenidate.

ObjectivesThis study examined the effect of osmotic-controlled release oral delivery system–methylphenidate (OROS-MPH) on the adaptive functioning of children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and investigated the relationship between reduced ADHD symptoms and improvements in functioning and factors that are predictive of functional improvement. MethodsThis study was a prospective, multicenter, open-label study of 116 children with ADHD treated with OROS-MPH for 12 weeks. Attention-deficit/hyperactivity disorder symptoms, functional impairment, and other comorbid disorders were evaluated using various clinical scales. Correlational and multiple regression analyses were conducted to examine the relationship between symptomatic versus functional changes after OROS-MPH treatment. ResultsCorrelation analysis showed a moderately strong association between changes in the ADHD core symptoms versus functional measure scores (r = −0.65). The self-control subscale of the Life Participation Scale showed higher correlations with symptomatic measures than did the happy/social subscale. Functional outcomes were impacted by several factors including the baseline severity of ADHD symptoms, changes in ADHD, and oppositional defiant symptoms after treatment. Attention was more associated with functional outcomes than hyperactivity/impulsivity. ConclusionsTreatment with OROS-MPH was associated with symptomatic functional changes that were moderately correlated; therefore, symptomatic functional outcomes appear to be partially overlapped but distinct domains. Consequently, functional measures should be incorporated as important outcome measures in future treatment studies; the importance of treatments targeting functional improvement should be emphasized in the treatment of children with ADHD.

Two different solicitation methods for obtaining information on adverse events associated with methylphenidate in adolescents: A 12-week multicenter, open-label study

OBJECTIVEnWe explored two different methods of determining adverse events (AEs) among methylphenidate (MPH)-treated adolescents with attention-deficit/hyperactivity disorder (ADHD).nnnMETHODSnWe performed a 12-week open label study of osmotic-release oral system (OROS) MPH in adolescents with ADHD who were recruited from four child and adolescent psychiatric outpatient clinics. The AEs were evaluated via a two-step procedure at weeks 1, 3, 6, and 12. The first step was to ask a general question to subjects and their parents regarding AEs. The second step included an AE evaluation process by the investigators, which was performed using a drug-specific checklist. One-way repeated measures ANOVA were used to compare the number of AEs reported by patients and their parents compared with the number reported by clinicians. This statistical technique was also used to compare the number of AEs reported by various sources (i.e., patients, parents, and clinicians) at weeks 1, 3, 6, and 12.nnnRESULTSnOf the 55 participants (43 males, 12 females) between the ages of 12 and 18 enrolled in this study, 47 participants completed the trial. When the number of AEs reported by patients, parents and clinicians were compared, there were no statistically significant differences. When the numbers of AEs obtained from the three different information sources at each study visit were compared, we noted differences. At week 6, the number of AEs evaluated by clinical investigators was higher than those reported by patients and their parents (p=0.003). Although the results did not reach statistical significance, the number of AEs reported by clinical investigators appeared to be greater than those obtained from patients or parents at weeks 3 and 12. The number of AEs reported by patients and their parents were similar at every visit. There were some differences in the pattern of AEs reported between patients and their parents.nnnCONCLUSIONSnClinicians should supplement the subjective report on AEs from patients or their parents with a more drug-specific checklist to obtain drug side effects more effectively. As there are some differences in the pattern of AEs reported by patients and their parents, it is generally recommended that clinicians obtain information from both parties when possible.

Differences in Utilization Patterns among Medications in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: a 36-Month Retrospective Study Using the Korean Health Insurance Review and Assessment Claims Database

We evaluated the differences in utilization patterns including persistence and adherence among medications in children and adolescents with attention deficit hyperactivity disorder (ADHD). The current study was performed using data from the Korean Health Insurance Review and Assessment claims database from January 1, 2009 to December 31, 2013. Our study sample consisted of 10,343 children and adolescents with ADHD who were not given their newly prescribed medication in 360 days before the initial claim in 2010. Data were followed up from the initiation of treatment with ADHD medications in 2010 to December 31, 2013. Discontinuation rates for 4 ADHD medications in our sample ranged from 97.7% for immediate-release methylphenidate to 99.4% for atomoxetine using refill gap more than 30 days and from 56.7% for immediate-release methylphenidate to 62.3% for extended-release methylphenidate using refill gap more than 60 days. In the number of discontinued, we found significant differences among medications using refill gap more than 30 days. Among 4 ADHD medications, extended-release methylphenidate and atomoxetine had more days than immediate-release methylphenidate and osmotic-controlled oral delivery system methylphenidate. In logistic regression analyses, extended-release methylphenidate, osmotic-controlled oral delivery system methylphenidate, and atomoxetine showed less discontinuation compared to immediate-release methylphenidate group when a refill gap more than 30 days was used. In logistic regression analysis of adherence, we could not find any differences among 4 medication types. We suggest that the utilization patterns should be assessed regularly in order to improve future outcomes in children and adolescents with ADHD.

The Effects of Attention Problems on Psychosocial Functioning in Childhood Brain Tumor Survivors: A 2-Year Postcraniospinal Irradiation Follow-up

Objective: To examine the psychosocial outcomes and impact of attention problems in survivors of pediatric brain tumor. Study Design: The survivors’ cognitive functioning was measured using the Wechsler Intelligence Scale for Children. The Child Behavior Checklist-Attention Problems scale was used to screen for attention problems, and participants were classified as having attention problems (n=15) or normal attention (n=36). Psychosocial functioning was examined with the Korean Personality Rating scale for Children (K-PRC) at precraniospinal radiation and at 2-year follow-up. Results: The attention problem group showed significantly higher depression and externalizing symptoms (delinquency, hyperactivity) and more significant impairment in family relationships than did the normal attention group at baseline. At follow-up, the attention problem group demonstrated significantly more delinquency and impaired family and social relationships. With the K-PRC scores, except for the somatization, social relationship subscale, there were significant differences between groups, but not in terms of treatment by time interaction or within time. At follow-up, multiple linear regressions showed that age at diagnosis significantly predicted K-PRC somatization (B=−1.7, P=0.004) and social relationships (B=−1.7, P=0.004), baseline full-scale intelligence quotient predicted K-PRC depression (B=−0.4, P=0.032) and somatization (B=−0.3, P=0.015), and attention problems at baseline predicted K-PRC depression (B=−15.2, P=0.036) and social relationships (B=−11.6, P=0.016). Conclusion: Pediatric brain tumor survivors, in particular, patients with attention problems, had worse psychosocial functioning at baseline and follow-up. Attention problems at baseline need to be carefully evaluated in assessing psychosocial functioning of pediatric brain tumor survivors.