Expanding the phenotype of Kleefstra syndrome: speech, language and cognition in 103 individuals.

OBJECTIVES: Speech and language impairments are core features of the neurodevelopmental genetic condition Kleefstra syndrome. Communication has not been systematically examined to guide intervention recommendations. We define the speech, language and cognitive phenotypic spectrum in a large cohort of individuals with Kleefstra syndrome. METHOD: 103 individuals with Kleefstra syndrome (40 males, median age 9.5 years, range 1-43 years) with pathogenic variants (52 9q34.3 deletions, 50 intragenic variants, 1 balanced translocation) were included. Speech, language and non-verbal communication were assessed. Cognitive, health and neurodevelopmental data were obtained. RESULTS: The cognitive spectrum ranged from average intelligence (12/79, 15%) to severe intellectual disability (12/79, 15%). Language ability also ranged from average intelligence (10/90, 11%) to severe intellectual disability (53/90, 59%). Speech disorders occurred in 48/49 (98%) verbal individuals and even occurred alongside average language and cognition. Developmental regression occurred in 11/80 (14%) individuals across motor, language and psychosocial domains. Communication aids, such as sign and speech-generating devices, were crucial for 61/103 (59%) individuals including those who were minimally verbal, had a speech disorder or following regression. CONCLUSIONS: The speech, language and cognitive profile of Kleefstra syndrome is broad, ranging from severe impairment to average ability. Genotype and age do not explain the phenotypic variability. Early access to communication aids may improve communication and quality of life.

Patterns of Psychotropic Prescribing Practices in Autistic Children and Adolescents: An Australian Perspective of Two Cohorts Five Years Apart.

This study aims to describe the utilisation of psychotropic medications in Australian autistic children and adolescents. All children and adolescents with available Pharmaceutical Benefits Scheme data who endorsed an autism diagnosis in The Longitudinal Study of Australian Children, including both B (n = 233, age 0-1 years in wave 1) and K cohorts (n = 157, age 4-5 years in wave 1), were included to describe psychotropic prescribing patterns. 212 (54.4%) autistic children and adolescents received at least one psychotropic prescription and 99 (25.4%) had polypharmacy. The most common psychotropic class prescribed was antidepressants (31.3%). Children in the B cohort were more likely to have a parent-reported diagnosis of anxiety or depression (χ2 = 12.18, p < 0.001) and tended to be more likely to have received a psychotropic prescription (χ2 = 3.54, p = 0.06). Psychotropic prescribing in Australian autistic children is common despite limited evidence for efficacy and tolerability of psychotropics in this group.

Memantine for autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is characterised by social communication difficulties and repetitive and restricted behaviours and routines that can have a negative impact on a child's quality of life, achievement at school, and social interactions with others. It has been hypothesised that memantine, which is traditionally used to treat dementia, may be effective in reducing the core symptoms of autism as well as some co-occurring symptoms such as hyperactivity and language difficulties. If memantine is being used to treat the core symptoms of autism, it is important to review the evidence of its effectiveness. OBJECTIVES: To assess the effects of memantine on the core symptoms of autism, including, but not limited to, social communication and stereotypical behaviours. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, nine other databases and three trials registers up to February 2022. We also checked reference lists of key studies and checked with experts in the field for any additional papers. We searched for retractions of the included studies in MEDLINE, Embase, and the Retraction Watch Database. No retractions or corrections were found. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of any dose of memantine compared with placebo in autistic people. We also included RCTs in which only one group received memantine, but both groups received the same additional therapy (e.g. a behaviour intervention). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were core autism symptoms and adverse effects. Secondary outcomes were language, intelligence, memory, adaptive behaviour, hyperactivity, and irritability. We used GRADE to assess certainty of evidence. MAIN RESULTS: We included three RCTs (two double-blind and one single-blind) with 204 participants that examined the short-term effect (immediately postintervention) of memantine in autistic people. Two studies took place in the USA and the other in Iran. All three studies focused on children and adolescents, with a mean age of 9.40 (standard deviation (SD) 2.26) years. Most participants were male (range across studies 73% to 87%). The diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders (4th edition; 4th edition, text revision; or 5th edition). To confirm the diagnosis, one study used the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R); one used ADOS, ADI-R or the Autism Diagnostic Interview Screener; and one used the Gilliam Autism Rating Scale. Dosage of memantine was based on the child's weight and ranged from 3 mg to 15 mg per day.  Comparisons  Two studies examined memantine compared with placebo; in the other study, both groups had a behavioural intervention while only one group was given memantine.  Risk of bias All studies were rated at high risk of bias overall, as they were at high or unclear risk of bias across all but four domains in one study, and all but two domains in the other two studies. One study was funded by Forest Laboratories, LLC, (Jersey City, New Jersey), Allergan. The study sponsor was involved in the study design, data collection (via contracted clinical investigator sites), analysis and interpretation of data, and the decision to present these results. The other two studies reported no financial support or sponsorship; though in one of the two, the study medication was an in-kind contribution from Forest Pharmaceuticals. Primary outcomes There was no clear evidence of a difference between memantine and placebo with respect to severity of core symptoms of autism, although we are very uncertain about the evidence. The standardised mean difference in autism symptoms score in the intervention group versus the control group was -0.74 standard deviations (95% confidence interval (CI) -2.07 to 0.58; 2 studies, 181 participants; very low-certainty evidence; medium effect size); lower scores indicate less severe autistic symptoms. Two studies (144 participants) recorded adverse effects that the authors deemed related to the study and found there may be no difference between memantine and placebo (odds ratio (OR) 0.64, 95% CI 0.17 to 2.39; low-certainty evidence). Secondary outcomes There may be no difference between memantine and placebo on language (2 studies, 144 participants; low-certainty evidence); memory or adaptive behaviour (1 study, 23 participants; both low-certainty evidence); or hyperactivity or irritability (1 study, 121 participants; both low-certainty evidence). AUTHORS' CONCLUSIONS: It is unclear whether memantine is an effective treatment for autistic children. None of the three included trials reported on the effectiveness of memantine in adults. Further studies using rigorous designs, larger samples, longer follow-up and clinically meaningful outcome measures that are important to autistic people and their families will strengthen our knowledge of the effects of memantine in autism.

Overall prognosis of preschool autism spectrum disorder diagnoses.

BACKGROUND: Autism spectrum disorder is a neurodevelopmental disorder characterised by social communication difficulties, restricted interests and repetitive behaviours. The clinical pathway for children with a diagnosis of autism spectrum disorder is varied, and current research suggests some children may not continue to meet diagnostic criteria over time. OBJECTIVES: The primary objective of this review was to synthesise the available evidence on the proportion of preschool children who have a diagnosis of autism spectrum disorder at baseline (diagnosed before six years of age) who continue to meet diagnostic criteria at follow-up one or more years later (up to 19 years of age). SEARCH METHODS: We searched MEDLINE, Embase, PsycINFO, and eight other databases in October 2017 and ran top-up searches up to July 2021. We also searched reference lists of relevant systematic reviews. SELECTION CRITERIA: Two review authors independently assessed prospective and retrospective follow-up studies that used the same measure and process within studies to diagnose autism spectrum disorder at baseline and follow-up. Studies were required to have at least one year of follow-up and contain at least 10 participants. Participants were all aged less than six years at baseline assessment and followed up before 19 years of age. DATA COLLECTION AND ANALYSIS: We extracted data on study characteristics and the proportion of children diagnosed with autism spectrum disorder at baseline and follow-up. We also collected information on change in scores on measures that assess the dimensions of autism spectrum disorder (i.e. social communication and restricted interests and repetitive behaviours). Two review authors independently extracted data on study characteristics and assessed risk of bias using a modified quality in prognosis studies (QUIPS) tool. We conducted a random-effects meta-analysis or narrative synthesis, depending on the type of data available. We also conducted prognostic factor analyses to explore factors that may predict diagnostic outcome. MAIN RESULTS: In total, 49 studies met our inclusion criteria and 42 of these (11,740 participants) had data that could be extracted. Of the 42 studies, 25 (60%) were conducted in North America, 13 (31%) were conducted in Europe and the UK, and four (10%) in Asia. Most (52%) studies were published before 2014. The mean age of the participants was 3.19 years (range 1.13 to 5.0 years) at baseline and 6.12 years (range 3.0 to 12.14 years) at follow-up. The mean length of follow-up was 2.86 years (range 1.0 to 12.41 years). The majority of the children were boys (81%), and just over half (60%) of the studies primarily included participants with intellectual disability (intelligence quotient < 70). The mean sample size was 272 (range 10 to 8564). Sixty-nine per cent of studies used one diagnostic assessment tool, 24% used two tools and 7% used three or more tools. Diagnosis was decided by a multidisciplinary team in 41% of studies. No data were available for the outcomes of social communication and restricted and repetitive behaviours and interests. Of the 42 studies with available data, we were able to synthesise data from 34 studies (69% of all included studies; n = 11,129) in a meta-analysis. In summary, 92% (95% confidence interval 89% to 95%) of participants continued to meet diagnostic criteria for autism spectrum disorder from baseline to follow-up one or more years later; however, the quality of the evidence was judged as low due to study limitations and inconsistency. The majority of the included studies (95%) were rated at high risk of bias. We were unable to explore the outcomes of change in social communication and restricted and repetitive behaviour and interests between baseline and follow-up as none of the included studies provided separate domain scores at baseline and follow-up. Details on conflict of interest were reported in 24 studies. Funding support was reported by 30 studies, 12 studies omitted details on funding sources and two studies reported no funding support. Declared funding sources were categorised as government, university or non-government organisation or charity groups. We considered it unlikely funding sources would have significantly influenced the outcomes, given the nature of prognosis studies. AUTHORS' CONCLUSIONS: Overall, we found that nine out of 10 children who were diagnosed with autism spectrum disorder before six years of age continued to meet diagnostic criteria for autism spectrum disorder a year or more later, however the evidence was uncertain. Confidence in the evidence was rated low using GRADE, due to heterogeneity and risk of bias, and there were few studies that included children diagnosed using a current classification system, such as the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) or the eleventh revision of the International Classification of Diseases (ICD-11). Future studies that are well-designed, prospective and specifically assess prognosis of autism spectrum disorder diagnoses are needed. These studies should also include contemporary diagnostic assessment methods across a broad range of participants and investigate a range of relevant prognostic factors.

Predicting speech-sound disorder outcomes in school-age children with hearing loss: The VicCHILD experience.

BACKGROUND: Congenital hearing loss is the most common birth anomaly, typically influencing speech and language development, with potential for later academic, social and employment impacts. Yet, surprisingly, the nuances of how speech is affected have not been well examined with regards to the subtypes of speech-sound disorder (SSD). Nor have the predictors of speech outcome been investigated within a sizeable population cohort. AIMS: (1) To describe the subtypes and prevalence of SSD in children with hearing loss. (2) To determine which characteristics of hearing loss predict the presence of SSD. METHODS & PROCEDURES: A total of 90 children (5-12 years of age) with permanent hearing loss were recruited from an Australian population cohort. Children completed a standardized speech assessment to determine the presence and subtype of SSD. Logistic regression was used to determine the predictors of speech outcome. Demographic, developmental and hearing-related predictors were examined. OUTCOMES & RESULTS: The prevalence of speech disorder overall was 58%, with the most common subtype being phonological delay in 49% of the sample. Factors most predictive of speech disorder were being male, younger and a bimodal user (i.e., using both a hearing aid and a cochlear implant). CONCLUSIONS & IMPLICATIONS: This is the first study, in a sizeable cohort, to describe the prevalence and predictive factors for SSD associated with hearing loss. Clinically, it could be beneficial to implement earlier targeted phonological interventions for children with hearing loss. What this paper adds What is already known on this subject Speech issues are common in children with hearing loss; however, the breakdown of subtypes of SSD (e.g., articulation versus phonological disorder) have not been previously described in a population cohort. This distinction is relevant, as each subtype calls for specific targeted intervention. Studies examining factors predictive of speech outcomes, across a range of hearing levels, are also lacking in a population cohort. What this paper adds to existing knowledge Data suggest the most common type of SSD in children with hearing loss is phonological delay. Males, younger children, and bimodal users were at greater risk of having a subtype of SSD. What are the potential or actual clinical implications of this work? The results are clinically pertinent as the speech diagnosis determines the targeted treatment. Phonological delay is responsive to treatment, and early targeted intervention may improve prognosis for speech outcomes for children with hearing loss.

Communication interventions for autism spectrum disorder in minimally verbal children.

BACKGROUND: Autism spectrum disorder (ASD) has an estimated prevalence of around 1.7% of the population. People with ASD often also have language difficulties, and about 25% to 30% of children with ASD either fail to develop functional language or are minimally verbal. The ability to communicate effectively is an essential life skill, and difficulties with communication can have a range of adverse outcomes, including poorer academic achievement, behavioural difficulties and reduced quality of life. Historically, most studies have investigated communication interventions for ASD in verbal children. We cannot assume the same interventions will work for minimally verbal children with ASD. OBJECTIVES: To assess the effects of communication interventions for ASD in minimally verbal children. SEARCH METHODS: We searched CENTRAL, MEDLINE and Embase as well as 12 other databases and three trials registers in November 2017. We also checked the reference lists of all included studies and relevant reviews, contacting experts in the field as well as authors of identified studies about other potentially relevant ongoing and unpublished studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of communication-focused interventions for children (under 12 years of age) diagnosed with ASD and who are minimally verbal (fewer than 30 functional words or unable to use speech alone to communicate), compared with no treatment, wait-list control or treatment as usual. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. MAIN RESULTS: This review includes two RCTs (154 children aged 32 months to 11 years) of communication interventions for ASD in minimally verbal children compared with a control group (treatment as usual). One RCT used a verbally based intervention (focused playtime intervention; FPI) administered by parents in the home, whereas the other used an alternative and augmentative communication (AAC) intervention (Picture Exchange Communication System; PECS) administered by teachers in a school setting.The FPI study took place in the USA and included 70 participants (64 boys) aged 32 to 82 months who were minimally verbal and had received a diagnosis of ASD. This intervention focused on developing coordinated toy play between child and parent. Participants received 12 in-home parent training sessions for 90 minutes per session for 12 weeks, and they were also invited to attend parent advocacy coaching sessions. This study was funded by the National Institute of Child Health and Human Development, the MIND Institute Research Program and a Professional Staff Congress-City University of New York grant. The PECS study included 84 minimally verbal participants (73 boys) aged 4 to 11 years who had a formal diagnosis of ASD and who were not using PECS beyond phase 1 at baseline. All children attended autism-specific classes or units, and most classes had a child to adult ratio of 2:1. Teachers and parents received PECS training (two-day workshop). PECS consultants also conducted six half-day consultations with each class once per month over five months. This study took place in the UK and was funded by the Three Guineas Trust.Both included studies had high or unclear risk of bias in at least four of the seven 'Risk of bias' categories, with a lack of blinding for participants and personnel being the most problematic area. Using the GRADE approach, we rated the overall quality of the evidence as very low due to risk of bias, imprecision (small sample sizes and wide confidence intervals) and because there was only one trial identified per type of intervention (i.e. verbally based or AAC).Both studies focused primarily on communication outcomes (verbal and non-verbal). One of the studies also collected information on social communication. The FPI study found no significant improvement in spoken communication, measured using the expressive language domain of the Mullen Scale of Early Learning expressive language, at postintervention. However, this study found that children with lower expressive language at baseline (less than 11.3 months age-equivalent) improved more than children with better expressive language and that the intervention produced expressive language gains in some children. The PECS study found that children enrolled in the AAC intervention were significantly more likely to use verbal initiations and PECS symbols immediately postintervention; however, gains were not maintained 10 months later. There was no evidence that AAC improved frequency of speech, verbal expressive vocabulary or children's social communication or pragmatic language immediately postintervention. Overall, neither of the interventions (PECS or FPI) resulted in maintained improvements in spoken or non-verbal communication in most children.Neither study collected information on adverse events, other communication skills, quality of life or behavioural outcomes. AUTHORS' CONCLUSIONS: There is limited evidence that verbally based and ACC interventions improve spoken and non-verbal communication in minimally verbal children with ASD. A substantial number of studies have investigated communication interventions for minimally verbal children with ASD, yet only two studies met inclusion criteria for this review, and we considered the overall quality of the evidence to be very low. In the study that used an AAC intervention, there were significant gains in frequency of PECS use and verbal and non-verbal initiations, but not in expressive vocabulary or social communication immediately postintervention. In the study that investigated a verbally based intervention, there were no significant gains in expressive language postintervention, but children with lower expressive language at the beginning of the study improved more than those with better expressive language at baseline. Neither study investigated adverse events, other communication skills, quality of life or behavioural outcomes. Future RCTs that compare two interventions and include a control group will allow us to better understand treatment effects in the context of spontaneous maturation and will allow further comparison of different interventions as well as the investigation of moderating factors.

Characterization of speech and language phenotype in children with NRXN1 deletions.

Neurexin 1 gene (NRXN1) deletions are associated with several neurodevelopmental disorders. Communication difficulties have been reported, yet no study has examined specific speech and language features of individuals with NRXN1 deletions. Here, we characterized speech and language phenotypes in 21 children (14 families), aged 1.8-17 years, with NRXN1 deletions. Deletions ranged from 74 to 702 kb and consisted mostly of either exons 1-3 or 1-5. Speech sound disorders were frequent (69%), although few were severe. The majority (57%) of children had difficulty with receptive and/or expressive language, although no homogeneous profiles of deficit were seen across semantic, morphological, or grammatical systems. Social language difficulties were seen in over half the sample (53%). All but two individuals with language difficulties also had intellectual disability/developmental delay. Overall, while speech and language difficulties were common, there was substantial heterogeneity in the severity and type of difficulties observed and no striking communication phenotype was seen. Rather, the speech and language deficits are likely part of broader concomitant neurodevelopmental profiles (e.g., intellectual disability, social skill deficits). Nevertheless, given the high rate of affectedness, it is important speech/language development is assessed so interventions can be applied during childhood in a targeted and timely manner.

Autism spectrum disorder: Presentation and prevalence in a nationally representative Australian sample.

OBJECTIVE: The aim of this study was to identify the prevalence of parent-reported autism spectrum disorder diagnosis in Australia, and examine the developmental profile of children with autism spectrum disorder compared to their peers. DESIGN/SETTING: Secondary analyses were undertaken on data from the Longitudinal Study of Australian Children. PARTICIPANTS: Children were recruited at kindergarten (K cohort) and birth (B cohort), and subsequently completed two-yearly 'waves' of assessments. MAIN OUTCOMES: Autism spectrum disorder diagnostic status was ascertained at Wave 4 along with age of diagnosis by parent report. Standardised tools were used to assess children's quality of life, behaviour, receptive vocabulary and non-verbal intelligence. RESULTS: Prevalence of autism spectrum disorder was 2.5% (95% confidence interval = [2.0, 3.0]) in the B cohort compared to 1.5% (95% confidence interval = [1.2, 2.0]) in the K cohort. In both cohorts, children with autism spectrum disorder had poorer mean quality of life, emotional-behavioural functioning and receptive vocabulary compared with non-autism spectrum disorder peers, and a higher proportion of children with autism spectrum disorder had problems in these areas. However, between 6% and 9% of children with moderate to severe autism spectrum disorder and 12-20% with mild autism spectrum disorder were not reported to have problems with social interaction. CONCLUSION: The prevalence of a parent-reported diagnosis of autism spectrum disorder before age 7 in Australia was higher in the B cohort. Data from future Longitudinal Study of Australian Children waves will clarify whether autism spectrum disorder has been diagnosed earlier in the B cohort or if there is a continued increase in prevalence. Future waves will also provide crucial information about the types and severity of problems experienced during the primary and secondary school years which will assist service planning.

Diagnosing autism: Australian paediatric research network surveys.

AIM: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with reported prevalence of more than 1/100. In Australia, paediatricians are often involved in diagnosing ASD and providing long-term management. However, it is not known how paediatricians diagnose ASD. This study aimed to investigate whether the way Australian paediatricians diagnose ASD is in line with current recommendations. METHODS: Members of the Australian Paediatric Research Network were invited to answer questions about their ASD diagnostic practice in a multi-topic survey and also as part of a study about parents needs around the time of a diagnosis of ASD. RESULTS: The majority of the 124 paediatricians who responded to the multi-topic survey and most who responded to the parent needs survey reported taking more than one session to make a diagnosis of ASD. Most paediatricians included information from preschool, child care or school when making a diagnosis, and over half included information from speech pathology or psychology colleagues more than 50% of the time. The main reasons for not including assessment information in the diagnostic process were service barriers such as no regular service available or long waiting lists. More than 70% reported ordering audiology and genetic tests more than half of the time. CONCLUSION: Not all paediatricians are following current recommendations for diagnosing ASD more than 50% of the time. While there are good reasons why current diagnostic approaches may fall short of expected standards, these need to be overcome to ensure diagnostic validity and optimal services for all children and their families.

Regression in autism spectrum disorders.

Since the Journal of Paediatrics and Child Health was first published, there has been substantial change in the field of autism spectrum disorders (ASDs) with an exponential increase in the amount of funded and published research. In this paper, we focus on regression in children with ASD, a phenomenon that remains poorly understood. We discuss the implications of what we know about regression in ASD for the way we think about ASD more broadly and for paediatric practice.

Language growth in verbal autistic children from 5 to 11 years.

To examine predictors and growth in language for verbal autistic and non-autistic children with/without low language from 4 to 11 years. Receptive and expressive language trajectories were compared in a community sample of 1026 children at ages 5, 7, and 11 years, across four groups: two autistic groups; one with and one without low language; and two non-autistic groups; one with and one without low language. Groups were delineated on baseline assessment at 4 years. Non-autistic and autistic children with low language had lower mean expressive language scores than the non-autistic typical language group (22.26 and 38.53 units lower, respectively, p < 0.001), yet demonstrated faster language growth across 5 to 11 years (p < 0.001 and p = 0.002, respectively). Both groups without low language had similar mean expressive language scores (p = 0.864) and a comparable rate of growth (p = 0.645). Language at 4 years was the only consistent predictor of language at 11 years for autistic children. Results were similar for receptive language in all analyses except there was no significant difference in rate of progress (slope) for the autistic with low language group compared with the typical language group (p = 0.272). Findings suggest early language ability, rather than a diagnosis of autism, is key to determining language growth and outcomes at 11 years in verbal children. Furthermore, children with low language showed developmental acceleration compared with same age peers.

Simulation-based education for teaching aggression management skills to healthcare providers in acute healthcare settings: A systematic review.

BACKGROUND: Behavioural emergencies involving aggression in acute care hospitals are increasing globally. Acute care staff are often not trained or confident in their prevention or management. Of available training options simulation-based education is superior for clinical medical education and is gaining acceptance for teaching clinical aggression management skills. OBJECTIVE: The aim of this study was to conduct a systematic review of the effectiveness of simulation-based education for teaching aggression management skills for health professionals working in acute healthcare settings. METHODS: The study protocol was prepared in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) statement, registered (27/02/2020) and published. We included randomised controlled trials, non-randomised controlled trials, quasi-experimental studies, and observational studies involving healthcare professionals in acute hospital settings or trainee health professionals who received simulation-based training on managing patient aggression. Comprehensive searches were conducted in PubMed, Ovid MEDLINE, PsycINFO, CINAHL and The Cochrane Library. Two reviewers independently screened all records, extracted data and assessed risk of bias. The primary outcomes included patient outcomes, quality of care, and adverse effects. Secondary outcomes included workplace resource use, healthcare provider related outcomes, knowledge (de-escalation techniques), performance, attitudes, and satisfaction. A narrative synthesis of included studies was performed because substantial variation of interventions and outcome measures precluded meta-analyses. RESULTS: Twenty-five studies were included with 2790 participants, 2585 (93 %) acute care hospital staff and 205 (7 %) undergraduate university students. Twenty-two studies combined simulation-based education with at least one other training modality. Three studies were randomised controlled trials, one was a pilot and feasibility cluster randomised controlled trial, one was a three-group post-test design and twenty were pre-/post-test design. Twenty-four studies were deemed to be high/critical or serious risk of bias. Four studies collected primary outcome data, all using different methods and with inconsistent findings. Twenty-one studies assessed performance in the test situation, seven studies provided objective ratings of performance and eighteen provided self-report data. Twenty-three studies reported objective or subjective improvements in secondary outcomes. CONCLUSIONS: Acute healthcare staff who completed simulation-based education on managing clinical aggression showed statistically significant improvements in knowledge and self-reported confidence. However, there is a lack of evidence about the magnitude of these improvements and impact on patient outcomes. REGISTRATION: PROSPERO Registration Number CRD42020151002. TWEETABLE ABSTRACT: Simulation-based education improved acute healthcare clinician knowledge and confidence in managing aggression.

Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD).

BACKGROUND: Autism spectrum disorders (ASD) are characterised by abnormalities in social interaction and communication skills, as well as stereotypic behaviours and restricted activities and interests. Selective serotonin reuptake inhibitors (SSRIs) are prescribed for the treatment of conditions often comorbid with ASD such as depression, anxiety and obsessive-compulsive behaviours. OBJECTIVES: To determine if treatment with an SSRI:1. improves the core features of autism (social interaction, communication and behavioural problems);2. improves other non-core aspects of behaviour or function such as self-injurious behaviour;3. improves the quality of life of adults or children and their carers;4. has short- and long-term effects on outcome;5. causes harm. SEARCH METHODS: We searched the following databases up until March 2013: CENTRAL, Ovid MEDLINE, Embase, CINAHL, PsycINFO, ERIC and Sociological Abstracts. We also searched ClinicalTrials.gov and the International Clinical Trials Registry Platform (ICTRP). This was supplemented by searching reference lists and contacting known experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any dose of oral SSRI compared with placebo, in people with ASD. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion, extracted data and appraised each study's risk of bias. MAIN RESULTS: Nine RCTs with a total of 320 participants were included. Four SSRIs were evaluated: fluoxetine (three studies), fluvoxamine (two studies), fenfluramine (two studies) and citalopram (two studies). Five studies included only children and four studies included only adults. Varying inclusion criteria were used with regard to diagnostic criteria and intelligence quotient of participants. Eighteen different outcome measures were reported. Although more than one study reported data for Clinical Global Impression (CGI) and obsessive-compulsive behaviour (OCB), different tool types or components of these outcomes were used in each study. As such, data were unsuitable for meta-analysis, except for one outcome (proportion improvement). One large, high-quality study in children showed no evidence of positive effect of citalopram. Three small studies in adults showed positive outcomes for CGI and OCB; one study showed improvements in aggression, and another in anxiety. AUTHORS' CONCLUSIONS: There is no evidence of effect of SSRIs in children and emerging evidence of harm. There is limited evidence of the effectiveness of SSRIs in adults from small studies in which risk of bias is unclear.

Is language ability associated with behaviors of concern in autism? A systematic review.

This review systematically synthesized evidence on the association between structural language ability and behaviors of concern (BoC) in autism. Four databases were searched for studies that included >10 autistic participants, measures of structural language (content and/or form of language) and BoC, and an analysis of their association. BoCs included self-injurious behavior (SIB), aggression, tantrums, and externalizing behavior. Methodological quality of studies were assessed using the Newcastle Ottawa Scale. Forty-five publications (n = 11,961) were included. Forty studies were cross-sectional and five were prospective cohort studies. Over 70% of the studies investigating expressive language and SIB (n = 10), aggression (n = 5), tantrums (n = 3), and externalizing behavior (n = 17) reported an inverse association, where lower expressive language ability was associated with increased BoC. Eleven out of sixteen studies of combined expressive and receptive language reported an inverse relationship with SIB or aggression. All outcomes were rated as moderate to very low certainty of evidence. This review highlights evidence showing an inverse association between expressive or combined language ability and SIB, and externalizing behavior in autism. However, further high-quality studies that use standardized, consistent measures of language and behavior and investigate longitudinal associations are needed. Early detection and support for reduced structural language difficulties have substantial potential to assist in reducing BoC.

Integrating interprofessional electronic medical record teaching in preregistration healthcare degrees: A case study.

BACKGROUND: Electronic medical record (EMR) adoption across healthcare necessitates a purposeful curriculum design to prepare graduates for the delivery of safe and effective patient care in digitally-enabled environments. OBJECTIVE: To describe the design and development of an Interprofessional Electronic Medical Record (iEMR) subject that introduces healthcare students to its utility in clinical settings. METHODS: A six-stage design-based educational research framework (Focus, Formulation, Contextualisation, Definition, Implementation, Evaluation) was used to instigate the iEMR design and development in nursing and five allied health graduate entry to practice (preregistration) degrees at an Australian university. RESULTS: In the Focus process, the concept and interdisciplinary partnerships were developed. The Formulation process secured grant support for subject design and development, including a rapid literature review to accommodate various course and curriculum structures. Discipline-specific subject themes were created through the Contextualisation process. During the Definition process, learning objectives and content resources were built. The Implementation process describes the pilot implementation in the nursing program, where assessment tasks were refined, and interdisciplinary clinical case studies originated. DISCUSSION: The design and development of an iEMR subject is underpinned by internal support for educational innovation and in alignment with digital health strategies in employer organisations. Identified barriers include faculty-level changes in strategic support for teaching innovation, managerial expectations of workload, the scope of work required by academics and learning designers, and the gap between the technology platform required to support online learning and the infrastructure needed to support simulated EMR use. A key discovery was the difficulty of finding EMR software, whether designed for teaching purposes or for clinical use, that could be adapted to meet the needs of this project. CONCLUSION: The lessons learned are relevant to educators and learning designers attempting a similar process. Issues remain surrounding the sustainability of the iEMR subject and maintaining academic responsibility for ongoing curriculum management.

Sex- and age-related differences in autistic behaviours in children with neurofibromatosis type 1.

This study investigated sex and age differences in autistic behaviours in children with neurofibromatosis type 1 (NF1) who scored within the clinical range on the Social Responsiveness Scale - Second Edition (T score ≥ 60). Thirty-four males and 28 females (3-16 years) were assessed with the Autism Diagnostic Observation Schedule - Second Edition and Autism Diagnostic Interview - Revised. Across both measures, males exhibited greater social communication deficits relative to females. Age-related abatement of social communication difficulties was observed for males but not females. Conversely, no sex differences were found for restricted/repetitive behaviours, which were stable over time for both males and females. The findings are discussed within the context of broader neurodevelopmental considerations that are common in NF1.

Social motivation a relative strength in DYRK1A syndrome on a background of significant speech and language impairments.

Speech and language impairments are commonly reported in DYRK1A syndrome. Yet, speech and language abilities have not been systematically examined in a prospective cohort study. Speech, language, social behaviour, feeding, and non-verbal communication skills were assessed using standardised tools. The broader health and medical phenotype was documented using caregiver questionnaires, interviews and confirmation with medical records. 38 individuals with DYRK1A syndrome (23 male, median age 8 years 3 months, range 1 year 7 months to 25 years) were recruited. Moderate to severe intellectual disability (ID), autism spectrum disorder (ASD), vision, motor and feeding impairments were common, alongside epilepsy in a third of cases. Speech and language was disordered in all participants. Many acquired some degree of verbal communication, yet few (8/38) developed sufficient oral language skills to rely solely on verbal communication. Speech was characterised by severe apraxia and dysarthria in verbal participants, resulting in markedly poor intelligibility. Those with limited verbal language (30/38) used a combination of sign and graphic augmentative and alternative communication (AAC) systems. Language skills were low across expressive, receptive, and written domains. Most had impaired social behaviours (25/29). Restricted and repetitive interests were most impaired, whilst social motivation was a relative strength. Few individuals with DYRK1A syndrome use verbal speech as their sole means of communication, and hence, all individuals need early access to tailored, graphic AAC systems to support their communication. For those who develop verbal speech, targeted therapy for apraxia and dysarthria should be considered to improve intelligibility and, consequently, communication autonomy.

Delineating the autistic phenotype in children with neurofibromatosis type 1.

BACKGROUND: Existing research has demonstrated elevated autistic behaviours in children with neurofibromatosis type 1 (NF1), but the autistic phenotype and its relationship to other neurodevelopmental manifestations of NF1 remains unclear. To address this gap, we performed detailed characterisation of autistic behaviours in children with NF1 and investigated their association with other common NF1 child characteristics. METHODS: Participants were drawn from a larger cross-sectional study examining autism in children with NF1. The population analysed in this study scored above threshold on the Social Responsiveness Scale-Second Edition (T-score ≥ 60; 51% larger cohort) and completed the Autism Diagnostic Interview-Revised (ADI-R) and/or the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2). All participants underwent evaluation of their intellectual function, and behavioural data were collected via parent questionnaires. RESULTS: The study cohort comprised 68 children (3-15 years). Sixty-three per cent met the ADOS-2 'autism spectrum' cut-off, and 34% exceeded the more stringent threshold for 'autistic disorder' on the ADI-R. Social communication symptoms were common and wide-ranging, while restricted and repetitive behaviours (RRBs) were most commonly characterised by 'insistence on sameness' (IS) behaviours such as circumscribed interests and difficulties with minor changes. Autistic behaviours were weakly correlated with hyperactive/impulsive attention deficit hyperactivity disorder (ADHD) symptoms but not with inattentive ADHD or other behavioural characteristics. Language and verbal IQ were weakly related to social communication behaviours but not to RRBs. LIMITATIONS: Lack of genetic validation of NF1, no clinical diagnosis of autism, and a retrospective assessment of autistic behaviours in early childhood. CONCLUSIONS: Findings provide strong support for elevated autistic behaviours in children with NF1. While these behaviours were relatively independent of other NF1 comorbidities, the importance of taking broader child characteristics into consideration when interpreting data from autism-specific measures in this population is highlighted. Social communication deficits appear similar to those observed in idiopathic autism and are coupled with a unique RRB profile comprising prominent IS behaviours. This autistic phenotype and its relationship to common NF1 comorbidities such as anxiety and executive dysfunction will be important to examine in future research. Current findings have important implications for the early identification of autism in NF1 and clinical management.

Parent-reported Autism Diagnostic Stability and Trajectories in the Longitudinal Study of Australian Children.

This study aimed to explore the stability of parent-reported diagnosis of Autism Spectrum Disorder (ASD) and factors influencing the trajectories in two cohorts from the prospective Longitudinal Study of Australian Children (LSAC). Parent-reported ASD diagnosis was collected for children from 6 years of age in a Birth cohort and 10 years of age in a Kinder cohort; allowing for exploration of diagnostic stability at age 6, 8, 10, and 12 years (Birth cohort) and 10, 12, 14, 16 years (Kinder cohort). Children were grouped based on persisting, desisting, inconsistent and late (diagnosis after 6 years-Birth cohort; after 10 years-Kinder) subgroups over four timepoints. Multinomial logistic regression explored predictors of diagnostic trajectories; generalized estimating equations examined trajectories of emotional and behavioral problems. Of 66 Birth cohort children parent-reported to have ASD at age 6, with data at all four time points, 14% did not at 12 years; of 73 Kinder cohort children at age 10 years, 26% no longer had parent-reported ASD at 16 years. Children with late diagnoses showed increasing trajectories of emotional and behavioral problems, while children with persisting or desisting diagnoses showed decreasing trajectories. Between 86% and 74% had a reported ASD diagnosis after 6 years. Findings indicate that children with ASD need services and supports that can adapt to their changing needs, which may be increasing, decreasing or different. This has implications for the provision of services and funding. LAY SUMMARY: This study explored how consistent parent-reported ASD diagnosis is over time in two groups of children from the Longitudinal Study of Australian Children (LSAC). Although up to 26% of children no longer had parent-reported ASD after 6-years follow up, persisting or late trajectories were more common. The outcome of late onset trajectories requires ongoing review. Autism Res 2021, 14: 773-786. © 2021 International Society for Autism Research and Wiley Periodicals LLC.