Abstract Background There is a paucity of treatments targeting core symptom domains in Autism Spectrum Disorder (ASD). Several animal models and research in typically developing volunteers suggests ...that manipulation of the oxytocin system may have therapeutic potential for the treatment of social deficits. We review the literature for oxytocin and ASD and report on early dosing, safety and efficacy data of multi-dose oxytocin on aspects of social cognition/function, as well as repetitive behaviors and co-occurring anxiety within ASD. Methods : Fifteen children and adolescents with verbal IQs≥70 were diagnosed with ASD using the ADOS and the ADI-R. They participated in a modified maximum tolerated dose study of intranasal oxytocin (Syntocinon). Data were modeled using repeated measures regression analysis controlling for week, dose, age, and sex. Results : Among 4 doses tested, the highest dose evaluated, 0.4 IU/kg/dose, was found to be well tolerated. No serious or severe adverse events were reported and adverse events reported/observed were mild to moderate. Over 12 weeks of treatment, several measures of social cognition/function, repetitive behaviors and anxiety showed sensitivity to change with some measures suggesting maintenance of effect 3 months past discontinuation of intranasal oxytocin. Conclusions : This pilot study suggests that daily administration of intranasal oxytocin at 0.4 IU/kg/dose in children and adolescents with ASD is safe and has therapeutic potential. Larger studies are warranted. This article is part of a Special Issue entitled Oxytocin and Social Behav.
A 4-year-old nonverbal boy with autism-spectrum disorder, presents with a 6-month history of gradually refusing to eat preferred foods, intermittently hitting his abdomen for 1 month, lethargy and no ...bowel movement for 5 days. He currently eats crackers, chicken nuggets and dirt. His diet is supplemented with 2 bottles of pediatric nutrition drink per day. He has lost 6 kg over the last 6 months (weight 12.8 kg, < 3rd percentile; height 99.5 cm, 25th percentile). Pharmacotherapy for constipation includes lactulose (70% solution), sorbitol (70% solution) or polyethylene glycol 3350. Owing to variable tolerability, pharmacotherapy should be supplemented with nonpharmacological interventions including parent education, toileting regimen, use of positive reinforcers and dietary modification. On abdominal examination, the patient had no masses but did have discomfort in lower left quadrant. Rectal examination was unsuccessful. He was hemodynamically stable.
Pioglitazone is a promising compound for treatment of core autism spectrum disorder (ASD) symptoms as it targets multiple relevant pathways, including immune system alterations.
This pilot study ...aimed to elucidate the maximum tolerated dose, safety, preliminary evidence of efficacy, and appropriate outcome measures in autistic children ages 5-12 years old.
We conducted a 16-week prospective cohort, single blind, single arm, 2-week placebo run-in, dose-finding study of pioglitazone. Twenty-five participants completed treatment. A modified dose finding method was used to determine safety and dose response among three dose levels: 0.25 mg/kg, 0.5 mg/kg, and 0.75 mg/kg once daily.
there were no serious adverse events (SAEs) and as such the maximum tolerated dose within the range tested was 0.75 mg/Kg once daily.
overall, pioglitazone was well tolerated. Two participants discontinued intervention due to perceived non-efficacy and one due to the inability to tolerate interim blood work. Three participants experienced mild neutropenia.
statistically significant improvement was observed in social withdrawal, repetitive behaviors, and externalizing behaviors as measured by the Aberrant Behavior Checklist (ABC), Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS), and Repetitive Behavior Scale-Revised (RBS-R). Forty-six percent of those enrolled were deemed to be global responders.
Pioglitazone is well-tolerated and shows a potential signal in measures of social withdrawal, repetitive, and externalizing behaviors. Randomized controlled trials using the confirmed dose are warranted.
ClinicalTrials.gov, NCT01205282. Registration date: September 20, 2010.
Eliminating racism in research Smile, Sharon; Williams, Alison
Canadian Medical Association journal (CMAJ),
2021-Apr-06, 2021-04-06, 20210406, Letnik:
193, Številka:
14
Journal Article
Recenzirano
Odprti dostop
Racism has no place in research. The proposed establishment of an Institute of Racism and Health to develop Canada's research capacity to assess and eliminate race-based inequalities in health may be ...useful as a long-term approach to coordinating and harnessing the wisdom that exists and best practices being developed. All those engaged in the research ecosystem - funders, researchers, Research Ethics Boards - have an immediate role to play in eliminating racism. Right now, researchers identifying as Black, Indigenous people, or people of color should have the opportunity to co-lead the process of dismantling racism throughout the research ecosystem. Right now, Research Ethics Boards can begin to think critically about how race is used in study protocols to minimize race-based harm and be intentional about including members of racialized groups in meaningful, nontokenistic ways to reinforce Institute-level priorities from the ground up.
Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Over the past decades, much research has been conducted to elucidate a single etiological factor and effective ...pharmacotherapuetics to address the core symptom domains of ASD with limited success. Research has changed focus from behavioral observations of ASD to translating findings from animal models, genomic manipulation studies and basic science studies to pharmacological agents with the aim to lessen or reverse core symptoms of ASD. This paper evaluates potential models for translating information from the biology of ASD to pharmacological treatments.
Abstract
Research offers the potential for new treatments, programs and services, and underlies decisions about funding that can have profound implications for people’s lives. When racism in research ...is not addressed, children and their families will be unjustly impacted by systemic discrimination, exclusion, and inequity. With a growing acknowledgement that racism is a social determinant of health, and as COVID-19 reveals staggering racial disparities, we believe now is the time for intentional anti-racism initiatives throughout the research ecosystem to prevent further harms in patient care and the lives and futures of children. We aim to highlight this need for justice, and conclude with a series of practical recommendations, ranging from the collection and use of race-based data, to equity, diversity, and inclusion (EDI) education, to mentorship opportunities.
Duchenne muscular dystrophy is a progressive neuromuscular condition that has a high rate of cognitive and learning disabilities as well as neurobehavioral disorders, some of which have been ...associated with disruption of dystrophin isoforms. Retrospective cohort of 59 boys investigated the cognitive and neurobehavioral profile of boys with Duchenne muscular dystrophy. Full-scale IQ of < 70 was seen in 27%; learning disability in 44%, intellectual disability in 19%; attention-deficit/hyperactivity disorder in 32%; autism spectrum disorders in 15%; and anxiety in 27%. Mutations affecting Dp260 isoform and 5’untranslated region of Dp140 were observed in 60% with learning disability, 50% intellectual disability, 77% with autism spectrum disorders, and 94% with anxiety. No statistically significant correlation was noted between comorbidities and dystrophin isoforms; however, there is a trend of cumulative loss of dystrophin isoforms with declining full-scale IQ. Enhanced psychology testing to include both cognitive and neurobehavioral disorders is recommended for all individuals with Duchenne muscular dystrophy.
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