Two single arm trials of AKL-T01, a digital therapeutic for adolescents and adults with ADHD.

Inattention symptoms represent a key driver of functional impairment in ADHD and often persist into adolescence and adulthood, underscoring a need for novel treatments targeting attentional control. We evaluated AKL-T01-a digital therapeutic that is FDA-cleared for children 8-12 y with ADHD-in adolescents and adults with ADHD in two independent single-arm trials: STARS-ADHD-Adolescent, a 4-week trial in adolescents 13-17 y (n = 162 enrolled), and STARS-ADHD-Adult, a 6-week trial in adults 18 and older (n = 221 enrolled). AKL-T01 was linked with improvements on the Test of Variables of Attention (TOVA) Attention Comparison Score (ACS) of 2.

Evaluation of an artificial intelligence-based medical device for diagnosis of autism spectrum disorder.

Autism spectrum disorder (ASD) can be reliably diagnosed at 18 months, yet significant diagnostic delays persist in the United States. This double-blinded, multi-site, prospective, active comparator cohort study tested the accuracy of an artificial intelligence-based Software as a Medical Device designed to aid primary care healthcare providers (HCPs) in diagnosing ASD. The Device combines behavioral features from three distinct inputs (a caregiver questionnaire, analysis of two short home videos, and an HCP questionnaire) in a gradient boosted decision tree machine learning algorithm to produce either an ASD positive, ASD negative, or indeterminate output.

The STARS Phase 2 Study: A Randomized Controlled Trial of Gaboxadol in Angelman Syndrome.

Objective: To evaluate safety and tolerability and exploratory efficacy end points for gaboxadol (OV101) compared with placebo in individuals with Angelman syndrome (AS).

Methods: Gaboxadol is a highly selective orthosteric agonist that activates δ-subunit-containing extrasynaptic γ-aminobutyric acid type A (GABA) receptors. In a multicenter, double-blind, placebo-controlled, parallel-group trial, adolescent and adult individuals with a molecular diagnosis of AS were randomized (1:1:1) to 1 of 3 dosing regimens for a duration of 12 weeks: placebo morning dose and gaboxadol 15 mg evening dose (qd), gaboxadol 10 mg morning dose and 15 mg evening dose (bid), or placebo morning and evening dose.

The SOFIA Study: Negative Multi-center Study of Low Dose Fluoxetine on Repetitive Behaviors in Children and Adolescents with Autistic Disorder.

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that reduces obsessive-compulsive symptoms. There is limited evidence supporting its efficacy for repetitive behaviors (RRBs) in autistic spectrum disorder (ASD). We conducted a randomized controlled trial (RCT) of fluoxetine in 158 individuals with ASD (5-17 years).

Pediatric Prolonged-Release Melatonin for Sleep in Children with Autism Spectrum Disorder: Impact on Child Behavior and Caregiver's Quality of Life.

A randomized, 13-weeks, placebo-controlled double-blind study in 125 subjects aged 2-17.5 years with Autism Spectrum Disorder or Smith-Magenis syndrome and insomnia demonstrated efficacy and safety of easily-swallowed prolonged-release melatonin mini-tablets (PedPRM; 2-5 mg) in improving sleep duration and onset. Treatment effects on child behavior and caregiver's quality of life were evaluated.

Efficacy and safety of memantine in children with autism spectrum disorder: Results from three phase 2 multicenter studies.

Three phase 2 trials were conducted to assess the efficacy and long-term safety of weight-based memantine extended release (ER) treatment in children with autism spectrum disorder. MEM-MD-91, a 50-week open-label trial, identified memantine extended-release treatment responders for enrollment into MEM-MD-68, a 12-week randomized, double-blind, placebo-controlled withdrawal trial. MEM-MD-69 was an open-label extension trial in which participants from MEM-MD-68, MEM-MD-91, and open-label trial MEM-MD-67 were treated ⩽48 weeks with memantine extended release.

Safety and Efficacy of Memantine in Children with Autism: Randomized, Placebo-Controlled Study and Open-Label Extension.

Objective: Abnormal glutamatergic neurotransmission is implicated in the pathophysiology of autism spectrum disorder (ASD). In this study, the safety, tolerability, and efficacy of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist memantine (once-daily extended-release [ER]) were investigated in children with autism in a randomized, placebo-controlled, 12 week trial and a 48 week open-label extension.

Methods: A total of 121 children 6-12 years of age with Diagnostic and Statistical Manual of Mental Disorders, 4th ed.

STX209 (arbaclofen) for autism spectrum disorders: an 8-week open-label study.

STX209 (arbaclofen), a selective GABA-B agonist, is hypothesized to modulate the balance of excitatory to inhibitory neurotransmission, and has shown preliminary evidence of benefit in fragile X syndrome. We evaluated its safety, tolerability, and efficacy in non-syndromic autism spectrum disorders, in an 8-week open-label trial enrolling 32 children and adolescents with either Autistic Disorder or Pervasive Developmental Disorder-Not Otherwise Specified, and a score ≥17 on the Aberrant Behavior Checklist (ABC)-Irritability subscale. STX209 was generally well-tolerated.

Plasma cytokine profiling in sibling pairs discordant for autism spectrum disorder.

Objective: Converging lines of evidence point to the existence of immune dysfunction in autism spectrum disorder (ASD), which could directly affect several key neurodevelopmental processes. Previous studies have shown higher cytokine levels in patients with autism compared with matched controls or subjects with other developmental disorders. In the current study, we used plasma-cytokine profiling for 25 discordant sibling pairs to evaluate whether these alterations occur within families with ASD.

The difference between fingerstick and venous hemoglobin and hematocrit varies by sex and iron stores.

Background: Fingerstick blood samples are used to estimate donor venous hemoglobin (Hb).

Study Design And Methods: Fingerstick Hb or hematocrit (Hct) was determined routinely for 2425 selected donors at six blood centers, along with venous Hb. Using sex and measures of iron status including absent iron stores (AIS; ferritin < 12 ng/mL), linear regression models were developed to predict venous Hb from fingerstick.

Autism and increased paternal age related changes in global levels of gene expression regulation.

A causal role of mutations in multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations in global levels of gene expression regulation might also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for changes in the overall distribution of gene expression levels. For instance, in mice, variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus.

Family-based association study of ITGB3 in autism spectrum disorder and its endophenotypes.

The integrin-β 3 gene (ITGB3), located on human chromosome 17q21.3, was previously identified as a quantitative trait locus (QTL) for 5-HT blood levels and has been implicated as a candidate gene for autism spectrum disorder (ASD). We performed a family-based association study in 281 simplex and 12 multiplex Caucasian families.

A randomized, double-blind, multicenter, parallel-group, placebo-controlled, dose-optimization study of the methylphenidate transdermal system for the treatment of ADHD in adolescents.

Introduction: The current report evaluates the efficacy and safety of methylphenidate transdermal system (MTS) compared with placebo transdermal system (PTS) in adolescents with attention-deficit/hyperactivity disorder (ADHD).

Methods: A total of 217 subjects participated in a 7-week, randomized, double-blind, multicenter, parallel-group, placebo-controlled, dose-optimization study of MTS (10-, 15-, 20- or 30-mg/9 hours). Subjects were randomized into a 2:1 MTS to PTS ratio and titrated to an optimal dose during an initial 5-week period.

Decreased serum arylesterase activity in autism spectrum disorders.

The PON1 gene, previously found associated with autism spectrum disorders (ASDs), encodes a serum protein responsible for the detoxification of organophosphates (OPs) and able to exert several enzymatic activities. PON1 arylesterase, but not diazoxonase activity, was significantly decreased in 174 ASD patients compared to 175 first-degree relatives and 144 controls (P=2.65×10⁻¹⁶).

Atomoxetine treatment in adolescents with attention-deficit/hyperactivity disorder.

Introduction: This study compared two atomoxetine titration dosing schedules and two atomoxetine maintenance doses for treating adolescent attention-deficit/hyperactivity disorder (ADHD) inattention and hyperactivity/impulsivity.

Methods: Adolescents (N = 267) were randomized to a slow or fast titration schedule. Patients who responded continued on a 40-week maintenance treatment, randomized to either 0.

Direct assessment of cytomegalovirus transfusion-transmitted risks after universal leukoreduction.

Background: Cytomegalovirus (CMV) transfusion-transmitted disease (TTD) remains a clinical concern. Universal leukoreduction has become one of the main strategies for the prevention of CMV-TTD. Through prospective clinical follow-up and testing of transfusion recipients (TRs), the risk for CMV-TTD was studied.

A prospective study of multiple donor exposure blood recipients: surveillance value and limitations for hemovigilance.

Background: There have been few recent systematic studies of blood recipients for direct evidence of blood safety, especially for emerging pathogens that may pose a threat to the blood supply.

Study Design And Methods: Recipients who would likely require transfusion from multiple donors were recruited and a blood specimen was collected before their first study transfusion and at intervals after their study transfusion(s). Blood samples associated with the units that were transfused to enrolled recipients were also collected.

Effect of sensory adaptation on anxiety of children with developmental disabilities: a new approach.

Purpose: The aim of this study was to evaluate the effect of a sensory-adapted dental environment (SADE) on anxiety, relaxation, and cooperation of children with developmental disabilities (CDDs). Pharmacological treatment has been widely used to reduce anxiety, but nonpharmacological methods may be similarly effective. The standardized clinical situation chosen was a dental hygiene cleaning.

Influence of adapted environment on the anxiety of medically treated children with developmental disability.

Objectives: To examine the influence of a sensory adapted environment (SAE) on the behavior and arousal levels of children with developmental disability in comparison with typical children, during a stress-provoking medical situation.

Study Design: Sixteen children (6-11 years old) with developmental disability and 19 age-matched typical children participated in a cross-over trial measuring behavioral and psychophysiological variables, performed during a dental intervention.

Results: Both groups performed better in the SAE compared with the regular environment (RE), by comparing: the mean duration of anxious behaviors in the SAE and RE (5.

Long-term, open-label extension study of guanfacine extended release in children and adolescents with ADHD.

Introduction: Guanfacine is a noradrenergic agonist that is believed to improve symptoms of attention-deficit/hyperactivity disorder (ADHD) through selective actions at alpha2A-adrenoceptors in the prefrontal cortex. A recent double-blind, multicenter trial supports the efficacy and safety of guanfacine extended release (GXR) for pediatric ADHD. This long-term, open-label extension was conducted to study the safety profile and effectiveness of GXR for up to 2 years.

A double-blind, placebo-controlled trial of oral human immunoglobulin for gastrointestinal dysfunction in children with autistic disorder.

Controversy exists regarding the extent and possible causal relationship between gastrointestinal symptoms and autism. A randomized, double-blind, placebo-controlled, parallel groups, dose-ranging study of oral, human immunoglobulin (IGOH 140, 420, or 840 mg/day) was utilized with 125 children (ages 2-17 years) with autism and persistent GI symptoms. Endpoint analysis revealed no significant differences across treatment groups on a modified global improvement scale (validated in irritable bowel syndrome studies), number of daily bowel movements, days of constipation, or severity of problem behaviors.

Altered calcium homeostasis in autism-spectrum disorders: evidence from biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier AGC1.

Autism is a severe developmental disorder, whose pathogenetic underpinnings are still largely unknown. Temporocortical gray matter from six matched patient-control pairs was used to perform post-mortem biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier (AGC), which participates in the aspartate/malate reduced nicotinamide adenine dinucleotide shuttle and is physiologically activated by calcium (Ca(2+)). AGC transport rates were significantly higher in tissue homogenates from all six patients, including those with no history of seizures and with normal electroencephalograms prior to death.

Involvement of the PRKCB1 gene in autistic disorder: significant genetic association and reduced neocortical gene expression.

Protein kinase C enzymes play an important role in signal transduction, regulation of gene expression and control of cell division and differentiation. The fsI and betaII isoenzymes result from the alternative splicing of the PKCbeta gene (PRKCB1), previously found to be associated with autism. We performed a family-based association study in 229 simplex and 5 multiplex families, and a postmortem study of PRKCB1 gene expression in temporocortical gray matter (BA41/42) of 11 autistic patients and controls.