Findings from a pilot open-label trial of N-acetylcysteine for the treatment of pediatric mania and hypomania.

BACKGROUND: Pediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the risk of serious side effects. Therefore, this study assessed the efficacy and tolerability of N-acetylcysteine (NAC), in children and adolescents with bipolar spectrum disorder. METHODS: We conducted a 12-week open-label trial of NAC for treatment of mania and hypomania in children and adolescents ages 5-17 with bipolar spectrum disorder including participants with full and subthreshold manic symptoms, accepting those with and without mixed states with co-occurring depression, and Young Mania Rating Scale scores ≥ 20 and < 40. Symptoms of mania and depression were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Children's Depression Rating Scale (CDRS), and Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) scales for mania and depression. RESULTS: This study had a high drop-out rate with only 53% completing all 12 weeks. There was a significant reduction in YMRS, HDRS, and CDRS mean scores from baseline to endpoint. Of the 24 exposed participants, 54% had an anti-manic response measured by a reduction in YMRS ≥ 30% and 46% had a CGI-I mania score ≤ 2 at endpoint. Additionally, 62% of participants had an anti-depressive response measured by a reduction in HDRS ≥ 30%, 31% had an anti-depressive response measured by a reduction in CDRS ≥ 30%, and 38% had a CGI-I depression score ≤ 2 at endpoint. CONCLUSIONS: These pilot open-label findings in a small sample provide preliminary data supporting the tolerability and safety of NAC in a pediatric population. The findings of this pilot scale study indicating improvement in mania and depression are promising, but require replication with a monotherapy randomized placebo controlled clinical trial and larger sample. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02357290 . First Registration 06/02/2015.

Measuring the Impact of Burn Injury on the Parent-Reported Health Outcomes of Children 1 to 5 Years: A Conceptual Framework for Development of the Preschool Life Impact Burn Recovery Evaluation Profile CAT.

Due to the rapid developmental growth in preschool-aged children, more precise measurement of the effects of burns on child health outcomes is needed. Expanding upon the Shriners Hospitals for Children/American Burn Association Burn Outcome Questionnaire 0 to 5 (BOQ0-5), we developed a conceptual framework describing domains important in assessing recovery from burn injury among preschool-aged children (1-5 years). We developed a working conceptual framework based on the BOQ0-5, the National Research Council and Institute of Medicine's Model of Child Health, and the World Health Organization's International Classification of Functioning, Disability, and Health for Children and Youth. We iteratively refined our framework based on a literature review, focus groups, interviews, and expert consensus meetings. Data were qualitatively analyzed using methods informed by grounded theory. We reviewed 95 pediatric assessments, conducted two clinician focus groups and six parent interviews, and consulted with 23 clinician experts. Three child health outcome domains emerged from our analysis: symptoms, functioning, and family. The symptoms domain describes parents' perceptions of their child's pain, skin-related discomfort, and fatigue. The functioning domain describes children's physical functioning (gross and fine motor function), psychological functioning (internalizing, externalizing, and dysregulation behavior; trauma; toileting; resilience), communication and language development (receiving and producing meaning), and social functioning (connecting with family/peers, friendships, and play). The family domain describes family psychological and routine functioning outcomes.

A prospective open-label trial of long-acting liquid methylphenidate for the treatment of attention deficit/hyperactivity disorder in intellectually capable adults with autism spectrum disorder.

Objectives: This treatment trial is aimed at assessing the short-term tolerability and efficacy of liquid-formulation extended-release methylphenidate (MPH-ER) for the treatment of attention deficit/hyperactivity disorder (ADHD) in adults with high-functioning autism spectrum disorder (HF-ASD).Methods: A 6-week open-label trial (ClinicalTrials.gov: NCT02096952) was conducted in 15 HF-ASD adults (mean age 24.9 ± 4.6; male, 12 (80%)) suffering from moderate-severe ADHD. MPH-ER was administered based on a flexible titration schedule. Efficacy was assessed on clinician- and self-rated measures. Tolerability was assessed by documenting treatment-emergent adverse events (AEs) and other safety measures.Results: Short-term MPH-ER treatment was associated with significant improvement in ADHD severity (Adult ADHD Investigator Symptom Report Scale (AISRS) mean change (MC), -22.8 ± 8.8, P < 0.001; Adult ADHD Self-Report Scale (ASRS) MC, -8.2 ± 15.3, P < 0.001). Twelve (80%) participants were deemed responders, based on ≥30% reduction in AISRS score and an ADHD Clinical Global Impression-Improvement score ≤2. MPH-ER was well-tolerated (treatment-limiting AEs, 1/15; severe AEs, 1/15) at mean dose of 48.7 ± 15 mg/day. AEs were transient and experienced by 13/15 (87%) participants at mild to moderate severity. Frequently reported AEs were as typically expected (headache (53%), insomnia (33%), anxiety (33%), decreased appetite (27%)).Conclusions: Our findings suggest that MPH-ER is effective and well-tolerated in the treatment of ADHD in HF-ASD adults.

Attention problems and pathological gaming: resolving the 'chicken and egg' in a prospective analysis.

Pathological gaming (PG) behaviors are behaviors which interfere with other life responsibilities. Continued debate exists regarding whether symptoms of PG behaviors are a unique phenomenon or arise from other mental health problems, including attention problems. Development of attention problems and occurrence of pathological gaming in 144 adolescents were followed during a 1-year prospective analysis. Teens and their parents reported on pathological gaming behaviors, attention problems, and current grade point average, as well as several social variables. Results were analyzed using regression and path analysis. Attention problems tended to precede pathological gaming behaviors, but the inverse was not true. Attention problems but not pathological gaming predicted lower GPA 1 year later. Current results suggest that pathological gaming arises from attention problems, but not the inverse. These results suggest that pathological gaming behaviors are symptomatic of underlying attention related mental health issues, rather than a unique phenomenon.

Preliminary evidence for the effects of morphine on posttraumatic stress disorder symptoms in one- to four-year-olds with burns.

This study tested the hypothesis that very young children who received more morphine for acute burns would have larger decreases in posttraumatic symptoms 3 to 6 months later. This has never before been studied in very young children, despite the high frequency of burns and trauma in this age group. Seventy 12- to 48-month-old nonvented children with acute burns admitted to a major pediatric burn center and their parents participated. Parents were interviewed at three time points: during their child's hospitalization, 1 month, and 3 to 6 months after discharge. Measures included the Child Stress Disorders Checklist - Burn Version (CSDC-B). Chart reviews were conducted to obtain children's morphine dosages during hospitalization. Mean equivalency dosages of morphine (mg/kg/d) were calculated to combine oral and intravenous administrations. Eleven participants had complete 3 to 6-month data on the CSDC. The correlation between average morphine dose and amount of decrease in posttraumatic stress disorder symptoms on the CSDC (r = -0.32) was similar to that found in studies with older children. The correlation between morphine dose and amount of decrease in symptoms on the arousal cluster of the CSDC was significant (r = -0.63, P < .05). Findings from the current study suggest that, for young children, management of pain with higher doses of morphine may be associated with a decreasing number of posttraumatic stress disorder symptoms, especially those of arousal, in the months after major trauma. This extends, with very young children, the previous findings with 6- to 16-year olds.

Posttraumatic stress disorder in the child of an adult burn victim: a case report and review of the literature.

Adults with a myriad of medical and surgical conditions are at risk for pain, delirium, and disfigurement. Needless to say, these critical illnesses are profoundly stressful for patients and their caregivers. However, physicians rarely consider the reactions of children to their parents' illnesses. The article presents the case of a 15-year-old girl who developed posttraumatic stress disorder following her mother's severe burn and complicated course in a critical care unit; the case is used to discuss strategies for the detection of psychological vulnerability and for the implementation of care. By learning more about the children of adult patients, by screening for interpersonal dysfunction, and by maximizing support systems, clinicians can improve function and minimize distress.

Performance of clinician versus self-report measures to identify obsessive-compulsive disorder in children and adolescents.

OBJECTIVE: The aim of this study was to study agreement between clinician-rated measures and self-report measures previously used in epidemiologic studies to identify obsessive-compulsive disorder (OCD) in youth and to determine the adequacy of self-report measures as screening instruments. METHOD: Leyton Obsessional Inventory-Child Version (LOI-CV) survey form self-report and Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) clinician-report measures were compared in a sample of 81 OCD-affected youths diagnosed using structured diagnostic interviews and the best-estimate method. Sensitivities and agreement between tests are determined for different cutoff scores. RESULTS: The LOI-CV survey form total (item+interference) score is correlated with KSADS-E OCD severity (r=0.37, p=0.001) but not clinician-rated GAF scores (r=-0.18, p=0.12). LOI-CV survey form sensitivities at cutoff scores of 15, 20, 25, and 30 are 55%, 36%, 28%, and 19%, respectively. CY-BOCS scores are correlated with subject-rated interview severity (p<0.001) and clinician-rated GAF scores (por=0.03), but correlate with the CY-BOCS compulsion subscore. CONCLUSIONS: The clinician-rated CY-BOCS measure using parent and child reporting performs superiorly to the subject-rated LOI-CV measure using child reporting to identify pediatric OCD in a clinically referred population. Because self-report measures have been used in epidemiological studies, youth OCD prevalence rates may be higher than previously reported.