Aripiprazole in youth with intellectual disabilities:A retrospective chart study

A retrospective chart study of patients on open-label aripiprazole treatment was conducted in the Netherlands to add to the knowledge of aripiprazole in children and young adults with mild and borderline intellectual disabilities (IDs). Fifty-three youths, mean age 14.7 +/- 3.4 years and mean IQ 64.5 +/- 13.8, were included. Treatment responders were defined as "much improved" or "very much improved" based on the Clinical Global Impression -Improvement scale. For 83% of the patients, disruptive behavior was the main target symptom. The overall response rate was 30% after 1-4 weeks and 69% after 5-8 weeks. The 5-8 weeks responders showed a response rate of 64% at 22-26 weeks. Mild adverse events were observed in 53% of the patients of which fatigue and weight gain were the most common. Seven patients (13.2%) discontinued because of adverse events. In 53 children and young adults with mild and borderline IDs, aripiprazole was effective in both the short and the long term. No serious adverse events were observed

Feasibility of an Assessment Tool for Children\u27s Competence to Consent to Predictive Genetic Testing: a Pilot Study

Knowledge on children\u27s capacities to consent to medical treatment is limited. Also, age limits for asking children\u27s consent vary considerably between countries. Decision-making on predictive genetic testing (PGT) is especially complicated, considering the ongoing ethical debate. In order to examine just age limits for alleged competence to consent in children, we evaluated feasibility of a standardized assessment tool, and investigated cutoff ages for children\u27s competence to consent to PGT. We performed a pilot study, including 17 pediatric outpatients between 6 and 18 years at risk for an autosomal dominantly inherited cardiac disease, eligible for predictive genetic testing. The reference standard for competence was established by experts trained in the relevant criteria for competent decision-making. The MacArthur Competence Assessment Tool for Treatment (MacCAT-T) served as index test. Data analysis included raw agreement between competence classifications, difference in mean ages between children judged competent and judged incompetent, and estimation of cutoff ages for judgments of competence. Twelve (71 %) children were considered competent by the reference standard, and 16 (94 %) by the MacCAT-T, with an overall agreement of 76 %. The expert judgments disagreed in most cases, while the MacCAT-T judgments agreed in 65 %. Mean age of children judged incompetent was 9.3 years and of children judged competent 12.1 years (p = .035). With 90 % sensitivity, children younger than 10.0 years were judged incompetent, with 90 % specificity children older than 11.8 years were judged competent. Feasibility of the MacCAT-T in children is confirmed. Initial findings on age cutoffs are indicative for children between the age of 12 and 18 to be judged competent for involvement in the informed consent process. Future research on appropriate age-limits for children\u27s alleged competence to consent is needed

Guideline Adherence of Monitoring Antipsychotic Use for Nonpsychotic Indications in Children and Adolescents A Patient Record Review:A Patient Record Review

Contains fulltext : 231603.pdf (Publisher’s version ) (Open Access

Key factors in children's competence to consent to clinical research

Background: Although law is established on a strong presumption that persons younger than a certain age are not competent to consent, statutory age limits for asking children's consent to clinical research differ widely internationally. From a clinical perspective, competence is assumed to involve many factors including the developmental stage, the influence of parents and peers, and life experience. We examined potential determining factors for children's competence to consent to clinical research and to what extent they explain the variation in competence judgments. Methods: From January 1, 2012 through January 1, 2014, pediatric patients aged 6 to 18 years, eligible for clinical research studies were enrolled prospectively at various in- and outpatient pediatric departments. Children's competence to consent was assessed by MacArthur Competence Assessment Tool for Clinical Research. Potential determining child variables included age, gender, intelligence, disease experience, ethnicity and socio-economic status (SES). We used logistic regression analysis and change in explained variance in competence judgments to quantify the contribution of a child variable to the total explained variance. Contextual factors included risk and complexity of the decision to participate, parental competence judgment and the child's or parents decision to participate. Results: Out of 209 eligible patients, 161 were included (mean age, 10.6 years, 47.2 % male). Age, SES, intelligence, ethnicity, complexity, parental competence judgment and trial participation were univariately associated with competence (P∈∈0.05). Conclusions: Age is the factor that explaines most of to the variance in children's competence to consent, followed by intelligence. Experience with disease did not affect competence in this study, nor did other variables. Clinical trial registration: Development and use of a standardized instrument for assessing children's competence to consent in drug trials: Are legally established age limits valid?, NTR3918

Plasma kynurenine and related measures in tic disorder patients

Objective Increased plasma kynurenine has been reported in tic disorder patients, and this observation has been suggested to be indicative of immune dysregulation. In the present study, we examined plasma levels of kynurenine and related molecules in a group of tic disorder patients. Methods Plasma concentrations of tryptophan, kynurenine, cortisol, and neopterin were determined in Dutch tic disorder patients (N = 59), and healthy volunteers (N = 32). Group means were compared and age-controlled intra-individual correlations between tic severity and plasma levels of these molecules were examined. Results No significant differences were found between patient and control groups in plasma levels of tryptophan, kynurenine, and cortisol concentrations, nor in the kynurenine/tryptophan ratio. However, neopterin was significantly (p = 0.035) higher in patients (mean = 5.13 nmol/1) than in controls (mean = 3.30 nmol/1). Plasma levels of these molecules did not correlate with tic severity, with the exception of tryptophan (r = -0.289, p = 0.049). In patients, plasma neopterin correlated with kynurenine (r = 0.438, P = 0.002); in healthy subjects, tryptophan correlated with kynurenine (r = 0.670, p <0.00 1). Conclusion While the observed elevation in plasma neopterin is consistent with immune activation in a subset of tic disorder patients, metabolism of tryptophan through the kynurenine pathway appears to be unaltered in tic disorder patients

Risperidone-Induced Weight Gain in Referred Children with Autism Spectrum Disorders Is Associated with a Common Polymorphism in the 5-Hydroxytryptamine 2C Receptor Gene

Weight gain is an important adverse effect of risperidone, but predictors of significant weight gain have yet to be identified in pediatric patients. Here, we investigated differences between age- and gender-normed body mass index–standardized z scores at baseline and after 8 weeks of open-label, flexible-dose risperidone treatment (mean dose: 1.70 mg/day) in 32 youths with pervasive developmental disorder (mean age = 8.74, range = 5–16 years) in relation to −759C/T 5-hydroxytryptamine 2C receptor (HTR2C) promoter and rs1414334 HTR2C intragenic C/G alleles, along with gender, age, and risperidone dose, using repeated measures analyses of variance. Carriers of the HTR2C promoter T allele gained an average of 0.043 ± 0.017 body mass index–standardized z scores (1.84 ± 1.51 kg) versus 0.64 ± 0.35 z (3.23 ± 1.47 kg) for non–T-allele carriers (p < 0.001). Presence of the rs1414334 C allele played no significant role. Further, weight gain appeared to be associated with younger age and higher doses of risperidone. The current preliminary findings suggest that the variant T allele of the −759C/T HTR2C promoter polymorphism is protective against risperidone-induced weight gain. Younger children and those treated with higher doses of risperidone may be at higher risk for weight gain

Accuracy of the MacArthur competence assessment tool for clinical research (MacCAT-CR) for measuring children's competence to consent to clinical research

An objective assessment of children's competence to consent to research participation is currently not possible. Age limits for asking children's consent vary considerably between countries, and, to our knowledge, the correlation between competence and children's age has never been systematically investigated. To test a standardized competence assessment instrument for children by modifying the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), to investigate its reliability and validity, and to examine the correlation of its assessment with age and estimate cutoff ages. This prospective study included children and adolescents aged 6 to 18 years in the inpatient and outpatient departments of allergology, gastroenterology, oncology, ophthalmology, and pulmonology from January 1, 2012, through January 1, 2014. Participants were eligible for clinical research studies, including observational studies and randomized clinical trials. Competence judgments by experts aware of the 4 relevant criteria-understanding, appreciation, reasoning, and choice-were used to establish the reference standard. The index test was the MacCAT-CR, which used a semistructured interview format. Interrater reliability, validity, and dimensionality of the MacCAT-CR and estimated cutoff ages for competence. Of 209 eligible patients, we included 161 (mean age, 10.6 years; 47.2% male). Good reproducibility of MacCAT-CR total and subscale scores was observed (intraclass correlation coefficient range, 0.68-0.92). We confirmed unidimensionality of the MacCAT-CR. By the reference standard, we judged 54 children (33.5%) to be incompetent; by the MacCAT-CR, 61 children (37.9%). Criterion-related validity of MacCAT-CR scores was supported by high overall accuracy in correctly classifying children as competent against the reference standard (area under the receiver operating characteristics curve, 0.78). Age was a good predictor of competence on the MacCAT-CR (area under the receiver operating characteristics curve, 0.90). In children younger than 9.6 years, competence was unlikely (sensitivity, 90%); in those older than 11.2 years, competence was probable (specificity, 90%). The optimal cutoff age was 10.4 years (sensitivity, 81%; specificity, 84%). The MacCAT-CR demonstrated strong psychometric properties. In children aged 9.6 to 11.2 years, consent may be justified when competence can be demonstrated in individual cases by the MacCAT-CR. The results contribute to a scientific underpinning of regulations for clinical research directed toward childre

Prescribing antipsychotics in child and adolescent psychiatry: guideline adherence

Antipsychotics are often prescribed to children and adolescents, mostly off-label. We aimed to assess adherence to recommendations of guidelines for antipsychotic prescription. We reviewed 436 medical records from 155 clinicians from 26 clinics within three Dutch child and adolescent psychiatry organizations (n = 398 outpatient, n = 38 inpatient care). We assessed target symptoms, diagnostic process, prior and concomitant treatment, and consideration of contra-indications. Multiple logistic regression assessed the role of age, sex, and psychiatric diagnosis on adherence to three main recommendations: to (1) prescribe antipsychotics only after other treatments proved insufficient, (2) always combine antipsychotics with psychosocial interventions, and (3) not prescribe multiple antipsychotics simultaneously. Most patients received off-label antipsychotics. Main target symptoms were inattention/hyperactivity (25%), aggression (24%), and other disruptive behaviors (41%). Most patients underwent diagnostic evaluation before the first prescription; however, screening of contra-indications was low (0.2-19%). About 84% had previously received psychosocial treatment and 48% other psychoactive medication, but 9% had not received any treatment. Notably, only 37% continuously received concomitant psychosocial treatment. Simultaneous use of multiple antipsychotics occurred in 3.2%. Younger children were at higher risk of non-adherence to guideline recommendations regarding prior and concomitant treatment, children with autism spectrum disorder or attention-deficit/hyperactivity disorder more likely not to receive concomitant psychosocial treatment. Sex did not significantly affect adherence. Our findings implicate insufficient adherence to important recommendations regarding antipsychotic use in children and adolescents. Especially younger children are at higher risk of receiving suboptimal care. There is an urgency to consistently offer psychosocial interventions during antipsychotic treatment