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The purpose of this study was to investigate comorbid psychiatric disorders and psychotropic medication use among adults with autism spectrum disorder (ASD) ascertained as children during a 1980’s statewide Utah autism prevalence study ( n  = 129). Seventy-three individuals (56.6 %) met criteria for a current psychiatric disorder; 89 participants (69.0 %) met lifetime criteria for a psychiatric disorder. Caregivers reported a psychiatric diagnosis in 44 participants (34.1 %). Anxiety disorder had the highest current and lifetime prevalence (39.5 and 52.7 %, respectively). Participants with intellectual disability ( n  = 94, 72.8 %) were significantly less likely to have community-based diagnoses of anxiety (χ 2  = 5.37, p  = 0.02) or depression (χ 2  = 13.18, p  < 0.001) reported by caregivers. Seventy-six participants (58.9 %) were taking ≥1 psychotropic medication. Comorbid psychiatric disorders occur frequently in adults with ASD, though identifying these disorders poses a challenge in community settings. A greater understanding of the presentation of these conditions within this population will increase assessment validity and the potential for efficacious intervention.

This study’s purpose was to investigate mortality among individuals with autism spectrum disorders (ASD) ascertained during a 1980s statewide autism prevalence study (n = 305) in relation to controls. Twenty-nine of these individuals (9.5 %) died by the time of follow up, representing a hazard rate ratio of 9.9 (95 % CI 5.7–17.2) in relation to population controls. Death certificates identified respiratory, cardiac, and epileptic events as the most common causes of death. The elevated mortality risk associated with ASD in the study cohort appeared related to the presence of comorbid medical conditions and intellectual disability rather than ASD itself suggesting the importance of coordinated medical care for this high risk sub-population of individuals with ASD.

Parents of children with Autism Spectrum Disorder (ASD) living in underserviced rural areas were provided with training based on Applied Behavior Analysis (ABA) through a combination of teleconsultation and the online Rethink Autism program. Primary study aims were gains in child behavior and parent ABA implementation integrity, with secondary aims of social validity and cost-benefit analyses. A nonconcurrent multiple baseline design was used across three rural families. Following in-vivo orientation, three phases were completed remotely through Rethink and teleconsultation. The baseline phase involved novice participants implementing ABA using only a one-page lesson printout. This was followed by successful completion of four Rethink ABA training modules. During the intervention phase, participants had access to Rethink’s high definition video modeling and coaching delivered via teleconsultation. The generalization phase replicated baseline conditions with a never-before-seen lesson; participants had only the lesson printout without coaching or video modeling. Outcomes reveal large effect sizes for parent increases in ABA implementation integrity from baseline to generalization (Tau-U = 0.82), coupled with child skill gains in their ABA lesson programming (Tau-U = 0.80). Both Rethink and teleconsultation were rated with high acceptability and perceived effectiveness. Cost analyses show financial benefits of Rethink and teleconsultation in terms of ABA programming (annual savings = $18,051 per child), logistical expense (average travel of 49 driving hours over 2,900 miles), and ABA consultation costs (average savings by teleconsultation = $300.16). These results are discussed within the scope of the current literature base, along with implications, limitations, and directions for future research.

Abstract Context Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy. Objective To evaluate safety and efficacy of intranasal carbetocin in PWS. Design Randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up. Setting Twenty-four ambulatory clinics at academic medical centers. Participants A total of 130 participants with PWS aged 7 to 18 years. Interventions Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo 3 times daily during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their previous dose. Main outcome measures Primary endpoints assessed change in hyperphagia (Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for 9.6 mg vs placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg vs placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C). Results Because of onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS which were not statistically significant; however, the 3.2-mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs placebo. Improvements were sustained in the long-term follow-up period. The most common adverse event during the PCP was mild to moderate flushing. Conclusions Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS. Clinical Trials Registration Number NCT03649477

Background. Worse chemotherapy response for neurofibromatosis type 1- (NF1-) associated compared to sporadic malignant peripheral nerve sheath tumors (MPNST) has been reported. Methods. We evaluated the objective response (OR) rate of patients with AJCC Stage III/IV chemotherapy-naive NF1 MPNST versus sporadic MPNST after 4 cycles of neoadjuvant chemotherapy, 2 cycles of ifosfamide/doxorubicin, and 2 cycles of ifosfamide/etoposide. A Simon optimal two-stage design was used (target response rate 40%). Results. 34 NF1 (median age 33 years) and 14 sporadic (median age 40 years) MPNST patients enrolled. Five of 28 (17.9%) evaluable NF1 MPNST patients had a partial response (PR), as did 4 of 9 (44.4%) patients with sporadic MPNST. Stable disease (SD) was achieved in 22 NF1 and 4 sporadic MPNST patients. In both strata, results in the initial stages met criteria for expansion of enrollment. Only 1 additional PR was observed in the expanded NF1 stratum. Enrollment was slower than expected and the trial closed before full accrual. Conclusions. This trial was not powered to detect differences in response rates between NF1 and sporadic MPNST. While the OR rate was lower in NF1 compared to sporadic MPNST, qualitative responses were similar, and disease stabilization was achieved in most patients.

Objective Rapid developments in understanding the molecular mechanisms underlying cognitive deficits in neurodevelopmental disorders have increased expectations for targeted, mechanism‐based treatments. However, translation from preclinical models to human clinical trials has proven challenging. Poor reproducibility of cognitive endpoints may provide one explanation for this finding. We examined the suitability of cognitive outcomes for clinical trials in children with neurofibromatosis type 1 (NF1) by examining test‐retest reliability of the measures and the application of data reduction techniques to improve reproducibility. Methods Data were analyzed from the STARS clinical trial (n = 146), a multi‐center double‐blind placebo‐controlled phase II trial of lovastatin, conducted by the NF Clinical Trials Consortium. Intra‐class correlation coefficients were generated between pre‐ and post‐performances (16‐week interval) on neuropsychological endpoints in the placebo group to determine test‐retest reliabilities. Confirmatory factor analysis was used to reduce data into cognitive domains and account for measurement error. Results Test‐retest reliabilities were highly variable, with most endpoints demonstrating unacceptably low reproducibility. Data reduction confirmed four distinct neuropsychological domains: executive functioning/attention, visuospatial ability, memory, and behavior. Test‐retest reliabilities of latent factors improved to acceptable levels for clinical trials. Applicability and utility of our model was demonstrated by homogeneous effect sizes in the reanalyzed efficacy data. Interpretation These data demonstrate that single observed endpoints are not appropriate to determine efficacy, partly accounting for the poor test‐retest reliability of cognitive outcomes in clinical trials in neurodevelopmental disorders. Recommendations to improve reproducibility are outlined to guide future trial design.