Developmental and sequenced one-to-one educational intervention (DS1-EI) for autism spectrum disorder and intellectual disability: a two-year interim report of a randomized single-blind multicenter controlled trial.

BACKGROUND: Children with autism spectrum disorder (ASD) and moderate to severe intellectual disability (ID) face many challenges. There is little evidence-based research into educational settings for children with ID and ASD and in France. Little is known about how this unserved population could benefit from intervention and education. This study assessed the feasibility and efficacy of a new intervention model using an individualized educational approach. METHODS: We conducted a randomized, single-blind controlled trial to assess a novel intervention: the "Developmental and Sequenced One-to-One Intervention (DS1-EI)". In DS1-EI, trained teachers worked one-to-one with each child in a small classroom setting, offering 10 h per week of the intervention. The focus was on encouraging spontaneous communication, promoting skills through play with peers, supporting positive interactions, and developmental and sequenced learning. We enrolled 5- to 9-year-old children with ASD and ID across 11 French child care institutions for children with co-occurring ASD and ID. Participants were matched in dyads by developmental quotient and randomized to the treatment-as-usual (TAU) group or the DS1-EI group. Independent raters blindly assessed the primary variables: The Childhood Autism Rating scale (CARS) and the Psychoeducational Profile, third edition (PEP-3). The secondary variables included the Vineland Adaptive Behavior Scale II (VABS-II) and the Clinical Global Assessment Scale (CGAS). Here we perform interim analyses at 24 months. RESULTS: At baseline, 72 participants were randomized. Nine patients (5 in the DS1-EI group and 4 in the TAU group) dropped out of the study. Using linear mixed models, both intent-to-treat (ITT) and per-protocol (PP) analyses at the 12-, 18- and 24-month outcomes showed no significant group nor group-by-time interaction effects. However, we found significant improvements in most primary and secondary variables over time in both groups. CONCLUSIONS: The study did not show that DS1-EI was superior to TAU in treating children with ASD and ID over 24 months. However, the low dropout rate shows that DS1-EI is feasible, and well accepted. As the study is still ongoing, we need to wait for data at 36 months to ensure whether DS1-EI could be recommended. TRIAL REGISTRATION: ANSM130282B-31 (April 16, 2013) and ACTRN12616000592448. Registered 6 May 2016, retrospectively registered, http://www.anzctr.org.au/.

A developmental and sequenced one-to-one educational intervention (DS1-EI) for autism spectrum disorder and intellectual disability: A three-year randomized, single-blind controlled trial.

BACKGROUND: Children with autism spectrum disorder (ASD) and intellectual disability (ID) are an understudied population whose school inclusion is challenging. METHODS: We assessed the effects of "Developmental and Sequenced one-to-one Educational Intervention" (DS1-EI), a ten-hour-per-week adapted instruction programme for five- to nine-year-old children with ASD and ID treated in outpatient health care institutions. A single-blind multisite randomized controlled trial was conducted to compare DS1-EI given for three years with treatment as usual (TAU)(trial registration numbers: ANSM130282B-31 (April 16, 2013) and ACTRN12616000592448). The primary outcome was the change in the psycho-educational profile (PEP). Secondary variables included the Childhood Autism Rating Scale (CARS), Autism Diagnostic Interview-Revised (ADI-R), Vineland Adaptive Behaviour Scale-II (VABS-II), Children's Global Assessment Scale (CGAS) and annual assessment of educational achievement. Statistical analyses used linear mixed models. FINDINGS: Seventy-two participants with severe ASD and ID were recruited. Intention-to-treat and per-protocol analyses showed no significant group*time interaction for the PEP, CARS, ADI-R, VABS-II and CGAS but a significant effect for educational achievement with a better improvement in the DS1-EI group. At the 36-month time point, more DS1-EI children were included in mainstream classrooms. Additional analyses using multivariate models taking into account moderating variables at the baseline (e.g., Developmental Quotient) confirmed that DS1-EI had a significant effect on educational outcomes. INTERPRETATION: DS1-EI did not improve communication or social skills in children with ASD and ID compared with TAU. However, DS1-EI enhanced school skills in four domains (language, mathematics, inter modality, and school autonomy) favouring inclusion in mainstream classrooms more than TAU. Providing such adapted instruction is feasible and should be encouraged. FUNDING: CNSA; Fondation Bettencourt-Schueller; Fondation EDF.

Long-term pharmacoclinical follow-up in schizophrenic patients treated with risperidone. Plasma and red blood cell concentrations of risperidone and its 9-hydroxymetabolite and their relationship to whole blood serotonin and tryptophan, plasma homovanillic acid, 5-hydroxyindoleacetic acid, dihydroxyphenylethyleneglycol and clinical evaluations.

The aim of the study was to establish a relationship between the clinical efficacy of risperidone (Risp), the biological levels of Risp and its metabolite, 9-hydroxyrisperidone (9-OH-Risp), and the turnover of blood biogenic amines during a long-term treatment (1 year). Risp is one of the newer atypical antipsychotic drugs with potent serotonin (5HT2), moderate D2 and real alpha 1-alpha 2 adrenoreceptor antagonistic effects. The study has been performed in an open setting and included 17 patients, but only 15 were followed-up from 3 to 12 months. Pharmacokinetic analyses were conducted at the same time as clinical evaluations, grading using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impressions (CGI), the Global Assessment of Functioning Scale (GAF), the Quality of Life Scale (QLS) and the Extrapyramidal Symptoms Rating Scale (ESRS) and the determinations of plasma and red blood cell (RBC) Risp and 9-OH-Risp, whole blood 5HT and tryptophan (Trp), plasma homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5HIAA) and dihydroxyphenylethyleneglycol (DHPG). The therapeutic drug monitoring needed oral Risp daily dose of 4.5 +/- 2.3 mg (range 2-8) and the stabilized concentrations (ng/ml) at endpoint in plasma and RBC were 10 +/- 8 (range 1-23) and 3.5 +/- 2 (range 1-8) for Risp and 29 +/- 19 (range 8-70) and 11.5 +/- 6.6 (range 2.6-22.5) for 9-OH-Risp, respectively. 9-OH-Risp appears to be the major active metabolite compound at higher concentrations than Risp. Positive linear correlations were found only between plasma and RBC 9-OH-Risp and the daily dose and the score of the GAF. Statistically significant clinical results showed that Risp is a potent antipsychotic agent efficacious both on positive and negative symptoms and on quality of life. Positive symptoms decreased after about the second month and the negative symptoms improved secondly. Patients (n = 8) who responded to Risp were characterized, on the long-term, by a statistically significant decrease of whole blood 5HT and increase of plasma DHPG.