The Impact of Cognitive Behavioral Therapy on Sleep Problems in Autistic Children with Co-occurring Anxiety.

PURPOSE: This study seeks to examine the relationship between anxiety-symptom severity and sleep behaviors in autistic children receiving cognitive behavioral therapy (CBT). METHODS: We conducted a secondary-data analysis from a sample of 93 autistic youth, 4 to 14 years, participating in 24 weeks of CBT. Clinicians completed the Pediatric Anxiety Rating Scale (PARS) and parents completed the Children's Sleep Habits Questionnaire, Abbreviated/Short Form (CSHQ-SF) at baseline, mid-treatment, post-treatment and 3 months post-treatment. Mediation analysis evaluated the role of anxiety symptoms in mediating the effect of time in treatment on sleep. RESULTS: There was a negative association between time in treatment and scores on the CSHQ-SF (b = - 3.23, SE = 0.493, t = - 6.553, p < 0.001). Increased time in treatment was associated with decreased anxiety (b = - 4.66, SE = 0.405, t = - 11.507, p < 0.001), and anxiety symptoms decreased with CSHQ-SF scores (b = 0.322, SE = 0.112, t = 2.869, p = 0.005). The indirect effect of time in treatment on CSHQ-SF scores through PARS reduction was negative, but not statistically significant. CONCLUSION: Increased time in CBT was associated with decreased anxiety severity and improved sleep behaviors. Reductions in anxiety symptoms may mediate improvements in sleep problems, but larger sample sizes are necessary to explore this further.

Sensory experiences questionnaire unravels differences in sensory profiles between MECP2-related disorders.

The methyl CpG-binding protein-2 (MECP2) gene is located on the Xq28 region. Loss of function mutations or increased copies of MECP2 result in Rett syndrome (RTT) and MECP2 duplication syndrome (MDS), respectively. Individuals with both disorders exhibit overlapping autism symptoms, yet few studies have dissected the differences between these gene dosage sensitive disorders. Further, research examining sensory processing patterns in persons with RTT and MDS is largely absent. Thus, the goal of this study was to analyze and compare sensory processing patterns in persons with RTT and MDS. Towards this goal, caregivers of 50 female individuals with RTT and 122 male individuals with MDS, between 1 and 46 years of age, completed a standardized measure of sensory processing, the Sensory Experiences Questionnaire. Patterns detected in both disorders were compared against each other and against normative values. We found sensory processing abnormalities for both hyper- and hypo-sensitivity in both groups. Interestingly, abnormalities in MDS were more pronounced compared with in RTT, particularly with items concerning hypersensitivity and sensory seeking, but not hyposensitivity. Individuals with MDS also exhibited greater sensory symptoms compared with RTT in the areas of tactile and vestibular sensory processing and for both social and nonsocial stimuli. This study provides a first description of sensory symptoms in individuals with RTT and individuals with MDS. Similar to other neurodevelopmental disorders, a variety of sensory processing abnormalities was found. These findings reveal a first insight into sensory processing abnormalities caused by a dosage sensitive gene and may ultimately help guide therapeutic approaches for these disorders.

Optimizing Care for Autistic Patients in Health Care Settings: A Scoping Review and Call to Action.

OBJECTIVE: We conducted a scoping review of interventions designed to improve the health care experiences of autistic individuals and assessed the methodology and outcomes used to evaluate them. METHODS: Literature from January 2005 to October 2020 was searched using PubMed, Excerpta Medica dataBASE (EMBASE), Cumulated Index to Nursing and Allied Health Literature (CINAHL), PsycINFO as well as hand searching. Studies included described an intervention for autistic individuals in inpatient or outpatient settings and evaluated the intervention using standardized methodology. Results were exported to Covidence software. Ten reviewers completed abstract screening, full text review, and then systematic data extraction of the remaining articles. Two reviewers evaluated each article at each stage, with a third reviewer arbitrating differences. RESULTS: A total of 38 studies, including three randomized controlled trials (RCTs) were included. Twenty-six (68%) took place in dental, psychiatric, or procedural settings. Interventions primarily focused on visit preparation and comprehensive care plans or pathways (N = 29, 76%). The most frequent outcome was procedural compliance (N = 15), followed by intervention acceptability (N = 7) and parent satisfaction (N = 6). Two studies involved autistic individuals and caregivers in study design, and no studies assessed racial/ethnic diversity on intervention impact. CONCLUSIONS: Well-designed evaluations of interventions to support autistic individuals in pediatric health care settings are limited. There is a need to conduct large multi-site intervention implementation studies.

Male and Female Toddlers with DSM-5 Autism Spectrum Disorder have Similar Developmental Profiles and Core Autism Symptoms.

Compare developmental profiles and core ASD symptom manifestation between male and female toddlers with DSM-5 ASD. Retrospective record review of 500 toddlers (79% male) at time of ASD diagnosis. There were no differences in developmental functioning between males and females. When adjusting for multiple comparisons, sex differences were only noted for sensory seeking behavior occurring at a higher frequency in females. Overall, there were no significant differences in demographic characteristics, developmental functioning, or manifestation of core ASD symptoms between males versus female toddlers at the time of DSM-5 ASD diagnosis.

Latent Class Analysis Identifies Distinctive Behavioral Subtypes in Children with Fragile X Syndrome.

Fragile X syndrome (FXS) is characterized by variable neurobehavioral abnormalities, which leads to difficulties in developing and evaluating treatments and in determining accurate prognosis. We employed a pediatric cross-sectional sample (1,072 males, 338 females) from FORWARD, a clinic-based natural history study, to identify behavioral subtypes by latent class analysis. Input included co-occurring behavioral conditions, sleep and sensory problems, autistic behavior scales (SCQ, SRS-2), and the Aberrant Behavior Checklist revised for FXS (ABCFX). A 5-class solution yielded the most clinically meaningful, pharmacotherapy independent behavioral groups with distinctive SCQ, SRS-2, and ABCFX profiles, and adequate non-overlap (≥ 71%): "Mild" (31%), "Moderate without Social Impairment" (32%), "Moderate with Social Impairment" (7%), "Moderate with Disruptive Behavior" (20%), and "Severe" (9%). Our findings support FXS subtyping, for improving clinical management and therapeutic development.

Disruption of RFX family transcription factors causes autism, attention-deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior.

PURPOSE: We describe a novel neurobehavioral phenotype of autism spectrum disorder (ASD), intellectual disability, and/or attention-deficit/hyperactivity disorder (ADHD) associated with de novo or inherited deleterious variants in members of the RFX family of genes. RFX genes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis. METHODS: We assembled a cohort of 38 individuals (from 33 unrelated families) with de novo variants in RFX3, RFX4, and RFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes. RESULTS: These individuals share neurobehavioral features including ASD, intellectual disability, and/or ADHD; other frequent features include hypersensitivity to sensory stimuli and sleep problems. RFX3, RFX4, and RFX7 are strongly expressed in developing and adult human brain, and X-box binding motifs as well as RFX ChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes. CONCLUSION: These results establish a likely role of deleterious variation in RFX3, RFX4, and RFX7 in cases of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.

Identifying Subgroups of Toddlers with DSM-5 Autism Spectrum Disorder Based on Core Symptoms.

The objective of this study was to identify subgroups of toddlers with DSM-5 ASD based on core ASD symptoms using a person-based analytical framework. This is a retrospective study of 500 toddlers (mean age 26 months, 79% male) with DSM-5 ASD. Data were analyzed using latent class analyses in which profiles were formed based on ASD symptomatology. Social communication (SC) symptoms favored a three-class solution, while restricted/repetitive behaviors (RRBs) favored a two-class solution. Classes with higher consistency of SC deficits were younger, with lower developmental functioning. The class with more RRBs was older, with higher functioning. If confirmed in other populations, these classes may more precisely characterize subgroups within the heterogeneous group of toddlers at time of ASD diagnosis.

Pathogenic Yield of Genetic Testing in Autism Spectrum Disorder.

BACKGROUND AND OBJECTIVES: Genetic testing is recommended for individuals with autism spectrum disorder (ASD). Pathogenic yield varies by clinician and/or patient characteristics. Our objectives were to determine the pathogenic yield of genetic testing, the variability in rate of pathogenic results based on subject characteristics, and the percentage of pathogenic findings resulting in further medical recommendations in toddlers with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of ASD. METHODS: We conducted a retrospective chart review of 500 toddlers, 18 to 36 months, diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ASD (mean age: 25.8 months, 79% male). Subject demographics, medical and neuropsychological characteristics, and genetic test results were abstracted. Genetic results were divided into negative or normal, variants of unknown significance, and pathogenic. Subject characteristics were compared across results. Manual chart review determined if further recommendations were made after pathogenic results. RESULTS: Over half of subjects (59.8%, n = 299) completed genetic testing, and of those, 36 (12.0%) had pathogenic findings. There were no significant differences in Bayley Scales of Infant Development cognitive (P = .112), language (P = .898), or motor scores (P = .488) among children with negative or normal findings versus a variant of unknown significance versus pathogenic findings. Medical recommendations in response to the genetic finding were made for 72.2% of those with pathogenic results. CONCLUSIONS: Our findings reinforce the importance of genetic testing for toddlers diagnosed with ASD given the 12% yield and lack of phenotypic differences between subjects with and without pathogenic findings. The majority of pathogenic results lead to further medical recommendations.

Presentation, Diagnostic Evaluation, Management, and Rates of Serious Bacterial Infection in Infants With Acute Dacryocystitis Presenting to the Emergency Department.

BACKGROUND: Dacryocystitis is considered benign, yet infants represent a population at risk of complications. The presentation, management, and rates of serious bacterial infection in infants with dacryocystitis have not been described. METHODS: We conducted a retrospective study of infants (12 months or younger) presenting to a single urban tertiary care pediatric emergency department between January 1995 and March 2014 with concern for dacryocystitis. Exclusion criteria included immune compromise or craniofacial anomalies. Cases were identified using text search software, followed by manual chart review. RESULTS: We identified 333 subjects, and median age was 38 days (interquartile range, 12; 106). Fifty-three percent were female. Most were afebrile (81%, T < 38°C) at triage while 6% had fever of ≥39°C. Two of 135 blood cultures sent were positive (both Streptococcus pneumoniae). Lumbar punctures were performed on 40 patients (12%), and no cerebrospinal fluid (CSF) cultures were positive. Eye cultures were positive in 47% (N = 58) of infants cultured (N = 123); the most common pathogens were Haemophilus species (N = 17), Staphylococcus aureus (N = 13), Gram-negative rods (N = 7), and Moraxella species (N = 4). Imaging was obtained in 11 subjects (3.3%) with 3 demonstrating cellulitis and 1 a hemangioma. Ophthalmology was consulted for 21%, and an intervention/probe performed in 6%. Topical antibiotics were used in 147 subjects (44%), oral antibiotics in 100 (33%), and parenteral antibiotics in 87 (26%). CONCLUSION: Infants with dacryocystitis have a variable presentation and management ranges from observation to aggressive management. The rates of serious bacterial infection were low in this sample and not associated with any presenting risk factors.

TEACH and repeat: Deliberate practice for teaching.

BACKGROUND: Deliberate practice facilitates skill mastery. We aimed to create a novel resident-as-teacher rotation, leveraging a deliberate practice framework with repeated practice in real-life teaching settings, with feedback from dedicated faculty member coaches. METHODS: A resident-as-teacher rotation was designed for 35 Postgraduate Year-2 (PGY2) paediatric residents. To facilitate deliberate practice, teaching experiences were observed by faculty member coaches and were repeated with different audiences. Participating residents received pre-rotation, post-rotation and follow-up surveys on their confidence and comfort with teaching, supervision and feedback skills. All residents were also surveyed the year before and the year after implementation on their perceptions of their teaching, supervision and feedback skills, and whether the residency provided adequate training on these topics. RESULTS: Survey response rates varied from 40 to 71%. The rotation was highly valued, and deliberate practice was a most valued aspect. Mean scores in comfort and confidence significantly increased from pre- to post-rotation, with these increases sustained months later. Prior to implementation, residents' perceptions of their teaching skills and the adequacy of their training increased incrementally with each postgraduate year. After the inaugural year of the rotation, the PGY2 class rated their teaching skills and training as higher than more experienced residents. DISCUSSION: A novel resident-as-teacher rotation successfully incorporated deliberate practice in real-life settings by repeating teaching activities with feedback from dedicated coaches. The rotation led to sustained increases in residents' confidence in their teaching, supervising and feedback skills, and improved perceptions of their teaching training during residency.