Publications by authors named "Valsamma Eapen"

142 Publications

An evidence-based framework for determining the optimal amount of intervention for autistic children.

Lancet Child Adolesc Health 2021 Oct 18. Epub 2021 Oct 18.

Telethon Kids Institute, Northern Entrance, Perth Children's Hospital, Nedlands, WA, Australia. Electronic address:

The provision of timely, effective, and socially valid non-pharmacological intervention is at the core of efforts to support the development of young autistic children. These efforts are intended to support children to develop skills, empower their caregivers, and lay the foundation for optimal choice, independence, and quality of life into adulthood. But what is the optimal amount of intervention? In this Viewpoint, we review current guidelines and consider evidence from an umbrella review of non-pharmacological interventions for autistic children aged up to 12 years. We show the lack of consensus on the issue, identify factors that might be relevant to consider, and present an evidence-based framework for determining the optimal amount of intervention for each child, along with recommendations for future research.
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http://dx.doi.org/10.1016/S2352-4642(21)00285-6DOI Listing
October 2021

Impact of the COVID-19 Pandemic on Family Wellbeing in the Context of Neurodevelopmental Disorders.

Neuropsychiatr Dis Treat 2021 24;17:3007-3014. Epub 2021 Sep 24.

School of Psychiatry, UNSW, Sydney, NSW, Australia.

Objective: The primary aim was to assess both the type and degree of impact of the COVID-19 pandemic on child and family wellbeing in a cohort with neurodevelopmental disorders.

Design: This was a single time-point observational study utilizing a combination of surveys and standardized measures, which were administered to parents by researchers by telephone.

Setting: The Child and Adolescent Neuropsychiatric Clinic of the Department of Clinical and Experimental Medicine, Catania University, Italy.

Participants: In total, 200 caregivers completed the questionnaires on behalf of themselves and their child. They were predominantly mothers (88.00%) and primary caregivers (93.50%), with a mean age of 42.84 years (sd = 7.13).

Primary And Secondary Outcomes Measures: A questionnaire featured in a previous study was used to assess the impact of COVID-19 on general wellbeing, types of support, family health, home-based learning, and child behaviors. Children's diagnoses were recorded. Caregivers provided information about physical, mental, financial, and vocational wellbeing, and completed several standardised measures of mental health and well-being: the Kessler Psychological Distress Scale - K6; the General Anxiety Disorder Scale - GAD-2; and the WHO Well-being Scale - WHO-5.

Results: Overall, 58.50% of respondents agreed somewhat or strongly that their child's overall health and wellbeing had been impacted by the pandemic, while 47.74% felt that their own wellbeing as parents had been affected. Whilst home-based learning and disruption to services for children were noted as being significant, child wellbeing appeared to not be correlated with these but rather to restrictions, home isolation, and disruption to routine.

Conclusion: Children with neurocognitive disorders and their families have been substantially impacted by the COVID-19 pandemic. It is expected that targeted resources and support services will be required in response to this increase in need.
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http://dx.doi.org/10.2147/NDT.S327092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8478336PMC
September 2021

Knockdown in a Family with Multiple Synostosis Syndrome and Speech Impairment.

Genes (Basel) 2021 Aug 29;12(9). Epub 2021 Aug 29.

Ingham Institute, School of Psychiatry, University of NSW, Sydney, NSW 2170, Australia.

Multiple synostoses syndrome type 4 (SYNS4; MIM 617898) is an autosomal dominant disorder characterized by carpal-tarsal coalition and otosclerosis-associated hearing loss. SYSN4 has been associated with GDF6 gain-of-function mutations. Here we report a five-generation SYNS4 family with a reduction in expression resulting from a chromosomal breakpoint 3' of . A 30-year medical history of the family indicated bilateral carpal-tarsal coalition in ~50% of affected family members and acquired otosclerosis-associated hearing loss in females only, whereas vertebral fusion was present in all affected family members, most of whom were speech impaired. All vertebral fusions were acquired postnatally in progressive fashion from a very early age. Thinning across the 2nd cervical vertebral interspace (C2-3) in the proband during infancy progressed to block fusion across C2-7 and T3-7 later in life. Carpal-tarsal coalition and pisiform expansion were bilaterally symmetrical within, but varied greatly between, affected family members. This is the first report of SYNS4 in a family with reduced expression indicating a prenatal role for in regulating development of the joints of the carpals and tarsals, the pisiform, ears, larynx, mouth and face and an overlapping postnatal role in suppression of aberrant ossification and synostosis of the joints of the inner ear (otosclerosis), larynx and vertebrae. RNAseq gene expression analysis indicated >10 fold knockdown of , and in both primary fibroblast cultures and fresh white blood cells. Together these results provide greater insight into the role of GDF6 in skeletal joint development.
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http://dx.doi.org/10.3390/genes12091354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470939PMC
August 2021

Combining CBT and sertraline does not enhance outcomes for anxious youth: a double-blind randomised controlled trial.

Psychol Med 2021 Aug 31:1-9. Epub 2021 Aug 31.

Department of Psychology, Centre for Emotional Health, Macquarie University, Sydney, NSW2109, Australia.

Background: Anxiety disorders are the most prevalent mental disorder in children and young people. Developing effective therapy for these children is critical to reduce mental disorders across the lifespan. The study aimed to evaluate the efficacy of combining cognitive behavioural therapy (CBT) and sertraline (SERT) in the treatment of anxiety in youth, using a double-blind randomised control trial design.

Methods: Ninety-nine youth (ages 7-15 years) with an anxiety disorder were randomly allocated to either individual (CBT) and SERT or individual CBT and pill placebo and assessed again immediately and 6 months after treatment.

Results: There were no significant differences between conditions in remission of primary anxiety disorder or all anxiety disorders. Furthermore, there were no significant differences in rates of change in diagnostic severity, parent-reported anxiety symptoms, child-reported anxiety symptoms or life interference due to anxiety.

Conclusions: The efficacy of CBT for children and adolescents with anxiety disorders is not significantly enhanced by combination with a short-term course of anti-depressants over and above the combined effects of pill placebo.
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http://dx.doi.org/10.1017/S0033291721003329DOI Listing
August 2021

Machine Learning Approaches to Identify Patient Comorbidities and Symptoms That Increased Risk of Mortality in COVID-19.

Diagnostics (Basel) 2021 Jul 31;11(8). Epub 2021 Jul 31.

The Garvan Institute of Medical Research, Healthy Ageing Theme, Darlinghurst, NSW 2010, Australia.

Providing appropriate care for people suffering from COVID-19, the disease caused by the pandemic SARS-CoV-2 virus, is a significant global challenge. Many individuals who become infected may have pre-existing conditions that may interact with COVID-19 to increase symptom severity and mortality risk. COVID-19 patient comorbidities are likely to be informative regarding the individual risk of severe illness and mortality. Determining the degree to which comorbidities are associated with severe symptoms and mortality would thus greatly assist in COVID-19 care planning and provision. To assess this we performed a meta-analysis of published global literature, and machine learning predictive analysis using an aggregated COVID-19 global dataset. Our meta-analysis suggested that chronic obstructive pulmonary disease (COPD), cerebrovascular disease (CEVD), cardiovascular disease (CVD), type 2 diabetes, malignancy, and hypertension as most significantly associated with COVID-19 severity in the current published literature. Machine learning classification using novel aggregated cohort data similarly found COPD, CVD, CKD, type 2 diabetes, malignancy, and hypertension, as well as asthma, as the most significant features for classifying those deceased versus those who survived COVID-19. While age and gender were the most significant predictors of mortality, in terms of symptom-comorbidity combinations, it was observed that Pneumonia-Hypertension, Pneumonia-Diabetes, and Acute Respiratory Distress Syndrome (ARDS)-Hypertension showed the most significant associations with COVID-19 mortality. These results highlight the patient cohorts most likely to be at risk of COVID-19-related severe morbidity and mortality, which have implications for prioritization of hospital resources.
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http://dx.doi.org/10.3390/diagnostics11081383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393412PMC
July 2021

siRNA Mediate RNA Interference Concordant with Early On-Target Transient Transcriptional Interference.

Genes (Basel) 2021 Aug 23;12(8). Epub 2021 Aug 23.

Ingham Institute, School of Psychiatry, University of NSW, Sydney, NSW 2170, Australia.

Exogenous siRNAs are commonly used to regulate endogenous gene expression levels for gene function analysis, genotype-phenotype association studies and for gene therapy. Exogenous siRNAs can target mRNAs within the cytosol as well as nascent RNA transcripts within the nucleus, thus complicating siRNA targeting specificity. To highlight challenges in achieving siRNA target specificity, we targeted an overlapping gene set that we found associated with a familial form of multiple synostosis syndrome type 4 (SYSN4). In the affected family, we found that a previously unknown non-coding gene was disrupted and the adjacent gene was downregulated. Moreover, a conserved long-range enhancer for was found located within which in turn overlapped another gene which we named . In fibroblast cell lines, is transcribed at much higher levels in the opposite (convergent) direction to . siRNA targeting of resulted in post transcriptional gene silencing (PTGS/RNAi) of that peaked at 72 h together with a rapid early increase in the level of both and that peaked and waned after 24 h. These findings indicated the following sequence of events: Firstly, the siRNA designed to target mRNA for RNAi in the cytosol had also caused an early and transient transcriptional interference of in the nucleus; Secondly, the resulting interference of transcription increased the transcription of ; Thirdly, the increased transcription of increased the transcription of . These findings have implications for the design and application of RNA and DNA targeting technologies including siRNA and CRISPR. For example, we used siRNA targeting of to successfully restore levels in the gene therapy of SYNS4 family fibroblasts in culture. To confidently apply gene targeting technologies, it is important to first determine the transcriptional interference effects of the targeting reagent and the targeted gene.
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http://dx.doi.org/10.3390/genes12081290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393430PMC
August 2021

[International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder].

Z Kinder Jugendpsychiatr Psychother 2021 Aug 16. Epub 2021 Aug 16.

Klinik für Abhängiges Verhalten und Suchtmedizin, Zentralinstitut für seelische Gesundheit, Mannheim, Deutschland.

International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations. The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience. A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD. After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general ( = 4), risk of developing SUD ( = 3), screening and diagnosis ( = 7), psychosocial treatment ( = 5), pharmacological treatment ( = 11), and complementary treatments ( = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion. This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD.
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http://dx.doi.org/10.1024/1422-4917/a000828DOI Listing
August 2021

Clinical outcomes and associated predictors of early intervention in autism spectrum disorder: a study protocol.

BMJ Open 2021 08 9;11(8):e047290. Epub 2021 Aug 9.

School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia

Introduction: Research highlights the importance of early intervention for children with autism spectrum disorder with better outcomes associated with earlier access to early intensive intervention (EII) programmes. However, there is significant variability in response to EII despite children receiving the same programmes.

Methods And Analysis: A prospective, multisite cohort study using a pre-post design assesses the predictors of early intervention outcomes for children who receive EII through six early intervention services (Autism Specific Early Learning and Care Centres, ASELCCs) across Australia. Child and family characteristics at entry to and exit from ASELCCs are ascertained using measures of autism symptoms (Autism Diagnostic Observation Schedule-2; Social Communication Questionnaire); cognitive, language and developmental skills (Mullen Scale of Early Learning); adaptive function (Vineland Adaptive Behaviour Scale-second Edition); behaviours (Child Behaviour Checklist-1.5 to 5 years; Restricted Repetitive Behaviour Scale); parental stress (Parent Stress Index-4 Short Form); quality of life (Quality of Life in Autism Scale) and a semistructured family history questionnaire for sociodemographic, family and psychosocial characteristics. Characteristics at entry are used as predictors of outcome at exit following EII approximately 12 months later. The change in score from baseline to exit will be the primary outcome of interest. The mediating role of family and psychosocial factors will also be considered.

Ethics Approval: University of New South Wales Human Research Ethics Committee (HC14267).

Dissemination Of Results: Findings will be published in peer-reviewed journals and presented at conferences. A report summarising data and the interpretation of data will be published.
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http://dx.doi.org/10.1136/bmjopen-2020-047290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354249PMC
August 2021

Meta-Analysis of RCTs of Technology-Assisted Parent-Mediated Interventions for Children with ASD.

J Autism Dev Disord 2021 Jul 27. Epub 2021 Jul 27.

UNSW, Sydney, Australia.

Technology-assisted parent-mediated interventions improve accessibility and are acceptable but not proven to be effective. We conducted a systematic search of 6 databases. We included and analysed results from studies on social and communication outcomes. Sixteen Randomised-Controlled-Trials (RCTs) with 748 participants were included. Most studies were rated as of good quality. Meta-analysis suggested that interventions were probably effective in improving emotion recognition. No significant differences were found in social communication, social functioning or language outcomes. At present, isolated tech interventions do not fulfil criteria for promising or established evidence-based interventions for ASD. Future research needs to focus on improving the effectiveness of technology-assisted parent-mediated interventions for ASD. Prospero Registration Number: CRD42020162825.
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http://dx.doi.org/10.1007/s10803-021-05206-2DOI Listing
July 2021

Psychological distress, resettlement stress, and lower school engagement among Arabic-speaking refugee parents in Sydney, Australia: A cross-sectional cohort study.

PLoS Med 2021 07 12;18(7):e1003512. Epub 2021 Jul 12.

School of Psychiatry, University of New South Wales, Sydney, Australia.

Background: Schools play a key role in supporting the well-being and resettlement of refugee children, and parental engagement with the school may be a critical factor in the process. Many resettlement countries have policies in place to support refugee parents' engagement with their children's school. However, the impact of these programs lacks systematic evaluation. This study first aimed to validate self-report measures of parental school engagement developed specifically for the refugee context, and second, to identify parent characteristics associated with school engagement, so as to help tailor support to families most in need.

Methods And Findings: The report utilises 2016 baseline data of a cohort study of 233 Arabic-speaking parents (77% response rate) of 10- to 12-year-old schoolchildren from refugee backgrounds across 5 schools in Sydney, Australia. Most participants were born in Iraq (81%) or Syria (11%), and only 25% spoke English well to very well. Participants' mean age was 40 years old, and 83% were female. Confirmatory factor analyses were run on provisional item sets identified from a literature review and separate qualitative study. The findings informed the development of 4 self-report tools assessing parent engagement with the school and school community, school belonging, and quality of the relationship with the schools' bilingual cultural broker. Cronbach alpha and Pearson correlations with an established Teacher-Home Communication subscale demonstrated adequate reliability (α = 0.67 to 0.80) and construct and convergent validity of the measures (p < 0.01), respectively. Parent characteristics were entered into respective least absolute shrinkage and selection operator (LASSO) regression analyses. The degree of parents' psychological distress (as measured by the Kessler10 self-report instrument) and postmigration living difficulties (PLMDs) were each associated with lower school engagement and belonging, whereas less time lived in Australia, lower education levels, and an unemployed status were associated with higher ratings in relationship quality with the schools' cultural broker. Study limitations include the cross-sectional design and the modest amount of variance (8% to 22%) accounted for by the regression models.

Conclusions: The study offers preliminary refugee-specific measures of parental school engagement. It is expected they will provide a resource for evaluating efforts to support the integration of refugee families into schools. The findings support the need for initiatives that identify and support parents with school-attending children from refugee backgrounds who are experiencing psychological distress or resettlement stressors. At the school level, the findings suggest that cultural brokers may be effective in targeting newly arrived families.
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http://dx.doi.org/10.1371/journal.pmed.1003512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312975PMC
July 2021

E-mental health in child psychiatry during COVID-19: an initial attitudinal study.

Australas Psychiatry 2021 Oct 14;29(5):498-503. Epub 2021 Jun 14.

Child and Adolescent and Forensic Psychiatry, Justice Health, Malabar, NSW, Australia.

Objective: COVID-19 propelled e-mental health within the Australian health system. It is important to learn from this to inform mental healthcare during future crises.

Method: A lexical analysis was conducted of clinician reflections during COVID-19 as they delivered psychiatry services to children and families in New South Wales ( = 6) and transitioned to e-mental health.

Results: E-mental health can extend the reach of, and access to psychiatry services, particularly for individuals disadvantaged by inequity. Yet e-mental health can be problematic. It is partly contingent on technological prowess, equipment, internet access as well as space and privacy. Relatedly, e-mental health can hinder clinician capacity to conduct examinations, monitor child development as well as assess risk and the need for child protection.

Conclusions: Given the benefits and limitations of e-mental health, a model that supports face-to-face mental healthcare and e-mental health may be of value. This model would require practical, yet flexible policies and protocols that protect the privacy of children and families, safeguard them from harm, and respect the needs and preferences of children, families and clinicians.
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http://dx.doi.org/10.1177/10398562211022748DOI Listing
October 2021

Speaking Softly and Listening Hard: The Process of Involving Young Voices from a Culturally and Linguistically Diverse School in Child Health Research.

Int J Environ Res Public Health 2021 05 28;18(11). Epub 2021 May 28.

Population Child Health, School of Women's and Children's Health, Faculty of Medicine, UNSW, Sydney 2031, Australia.

The involvement of young people in the planning of research continues to be rare, particularly for young people from culturally and linguistically diverse communities. This paper describes our experience in establishing a Youth Research Advisory Group (YRAG) in South West Sydney (SWS), including barriers and successful strategies. One hundred and fifteen students between school Years 7 and 12 (ages 11-18) took part in at least one of five sessions between 2019 and 2021. In total, we carried out 26 YRAG sessions, with between five and 30 students in each. Sessions focused on mapping the health priorities of the participants and co-developing research project proposals related to their health priorities. Our work with students revealed that their main areas of concern were mental health and stress. This led to material changes in our research strategy, to include "Mental Health" as a new research stream and co-develop new mental health-related projects with the students. Important strategies that enabled our research included maintaining flexibility to work seamlessly with organisational and individual preferences, and ensuring our processes were directed by the schools and-most importantly-the students themselves. Strategies such as maintaining an informal context, responding rapidly to student preference, and regularly renegotiating access enabled us to engage with the students to deepen our understanding of their experiences.
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http://dx.doi.org/10.3390/ijerph18115808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198054PMC
May 2021

A Framework-Based Approach to Assessing Mental Health Impacts of the COVID-19 Pandemic on Children and Adolescents.

Front Psychiatry 2021 13;12:655481. Epub 2021 May 13.

School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.

The COVID-19 pandemic has yielded extensive impacts globally in the year of 2020. Although the mental health of children and adolescents may be particularly susceptible to stressors stemming from the pandemic and anti-contagion policies, most ongoing efforts are geared toward curbing the viral spread. In the current perspective, we have identified four domains of factors corresponding to an ecological framework that may directly or indirectly influence the mental health of children and adolescents during the pandemic. The evidence suggests that anti-contagion policies might trigger cascades that impact the mental health of children and their families through multiple different sectors that used to form a safety net for youths. Additionally, children with neuropsychiatric disorders could experience exacerbated symptoms during the pandemic. Furthermore, the risk of domestic violence has surged during the pandemic, which further compounds the imminent mental health crisis. A mental health pandemic could be inevitable if no proactive prevention strategies were in place. Therefore, we recommend understanding each individual mental health risk pathway via the ecological framework in order to develop integrative prevention and intervention strategies.
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http://dx.doi.org/10.3389/fpsyt.2021.655481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155579PMC
May 2021

Identifying Subgroups of Patients With Autism by Gene Expression Profiles Using Machine Learning Algorithms.

Front Psychiatry 2021 12;12:637022. Epub 2021 May 12.

School of Psychiatry, The University of New South Wales, Sydney, NSW, Australia.

The identification of subgroups of autism spectrum disorder (ASD) may partially remedy the problems of clinical heterogeneity to facilitate the improvement of clinical management. The current study aims to use machine learning algorithms to analyze microarray data to identify clusters with relatively homogeneous clinical features. The whole-genome gene expression microarray data were used to predict communication quotient (SCQ) scores against all probes to select differential expression regions (DERs). Gene set enrichment analysis was performed for DERs with a fold-change >2 to identify hub pathways that play a role in the severity of social communication deficits inherent to ASD. We then used two machine learning methods, random forest classification (RF) and support vector machine (SVM), to identify two clusters using DERs. Finally, we evaluated how accurately the clusters predicted language impairment. A total of 191 DERs were initially identified, and 54 of them with a fold-change >2 were selected for the pathway analysis. Cholesterol biosynthesis and metabolisms pathways appear to act as hubs that connect other trait-associated pathways to influence the severity of social communication deficits inherent to ASD. Both RF and SVM algorithms can yield a classification accuracy level >90% when all 191 DERs were analyzed. The ASD subtypes defined by the presence of language impairment, a strong indicator for prognosis, can be predicted by transcriptomic profiles associated with social communication deficits and cholesterol biosynthesis and metabolism. The results suggest that both RF and SVM are acceptable options for machine learning algorithms to identify AD subgroups characterized by clinical homogeneity related to prognosis.
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http://dx.doi.org/10.3389/fpsyt.2021.637022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149626PMC
May 2021

A Multistate Trial of an Early Surveillance Program for Autism Within General Practices in Australia.

Front Pediatr 2021 23;9:640359. Epub 2021 Apr 23.

Cooperative Research Centre for Living With Autism (Autism CRC), The University of Queensland, Indooroopilly, QLD, Australia.

The early detection of developmental conditions such as autism is vital to ensure children can access appropriate and timely evidence-based supports, services, and interventions. Children who have undetected developmental conditions early in life are more likely to develop later health, developmental, learning, and behavioral issues, which in turn can have a cumulative effect over the life course. The current protocol describes a multi-site, cluster randomized control trial comparing a developmental surveillance pathway for autism to usual care, using opportunistic visits to general practitioners (GPs). Units of randomization are GP clinics across two Australian states (New South Wales and Victoria), with thirty clinics within each state, each of which will aim to recruit approximately forty children aged between ~18- and 24-months, for a total of ~2,400 participants. Children will be randomized to two clusters; namely, an autism surveillance pathway (ASP) or surveillance as usual (SaU). The screening process for the ASP arm involves primary and secondary screenings for developmental concerns for autism, using both parent and GP reports and observations. Children in both arms who show signs of developmental concerns for autism will be offered a full developmental assessment by the research team at 24 months of age to determine the efficacy of developmental surveillance in successfully identifying children with autism. The trial is registered with ANZCTR (ACTRN12619001200178) and reporting of the trial results will be according to recommendations in the CONSORT Statement.
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http://dx.doi.org/10.3389/fped.2021.640359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102783PMC
April 2021

System biology and bioinformatics pipeline to identify comorbidities risk association: Neurodegenerative disorder case study.

PLoS One 2021 6;16(5):e0250660. Epub 2021 May 6.

Healthy Ageing Theme, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.

Alzheimer's disease (AD) is the commonest progressive neurodegenerative condition in humans, and is currently incurable. A wide spectrum of comorbidities, including other neurodegenerative diseases, are frequently associated with AD. How AD interacts with those comorbidities can be examined by analysing gene expression patterns in affected tissues using bioinformatics tools. We surveyed public data repositories for available gene expression data on tissue from AD subjects and from people affected by neurodegenerative diseases that are often found as comorbidities with AD. We then utilized large set of gene expression data, cell-related data and other public resources through an analytical process to identify functional disease links. This process incorporated gene set enrichment analysis and utilized semantic similarity to give proximity measures. We identified genes with abnormal expressions that were common to AD and its comorbidities, as well as shared gene ontology terms and molecular pathways. Our methodological pipeline was implemented in the R platform as an open-source package and available at the following link: https://github.com/unchowdhury/AD_comorbidity. The pipeline was thus able to identify factors and pathways that may constitute functional links between AD and these common comorbidities by which they affect each others development and progression. This pipeline can also be useful to identify key pathological factors and therapeutic targets for other diseases and disease interactions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250660PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101720PMC
October 2021

Editorial: Gilles de la Tourette Syndrome: Cross-Cultural Perspectives With a Focus on the Asia-Pacific Region.

Authors:
Valsamma Eapen

Front Psychiatry 2021 12;12:678089. Epub 2021 Apr 12.

South Western Sydney Local Health District, Sydney, NSW, Australia.

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http://dx.doi.org/10.3389/fpsyt.2021.678089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072058PMC
April 2021

Machine Learning Approach to Predicting COVID-19 Disease Severity Based on Clinical Blood Test Data: Statistical Analysis and Model Development.

JMIR Med Inform 2021 Apr 13;9(4):e25884. Epub 2021 Apr 13.

School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, Australia.

Background: Accurate prediction of the disease severity of patients with COVID-19 would greatly improve care delivery and resource allocation and thereby reduce mortality risks, especially in less developed countries. Many patient-related factors, such as pre-existing comorbidities, affect disease severity and can be used to aid this prediction.

Objective: Because rapid automated profiling of peripheral blood samples is widely available, we aimed to investigate how data from the peripheral blood of patients with COVID-19 can be used to predict clinical outcomes.

Methods: We investigated clinical data sets of patients with COVID-19 with known outcomes by combining statistical comparison and correlation methods with machine learning algorithms; the latter included decision tree, random forest, variants of gradient boosting machine, support vector machine, k-nearest neighbor, and deep learning methods.

Results: Our work revealed that several clinical parameters that are measurable in blood samples are factors that can discriminate between healthy people and COVID-19-positive patients, and we showed the value of these parameters in predicting later severity of COVID-19 symptoms. We developed a number of analytical methods that showed accuracy and precision scores >90% for disease severity prediction.

Conclusions: We developed methodologies to analyze routine patient clinical data that enable more accurate prediction of COVID-19 patient outcomes. With this approach, data from standard hospital laboratory analyses of patient blood could be used to identify patients with COVID-19 who are at high risk of mortality, thus enabling optimization of hospital facilities for COVID-19 treatment.
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http://dx.doi.org/10.2196/25884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045777PMC
April 2021

Tourette Syndrome Risk Genes Regulate Mitochondrial Dynamics, Structure, and Function.

Front Psychiatry 2020 10;11:556803. Epub 2021 Mar 10.

School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.

Gilles de la Tourette syndrome (GTS) is a neurodevelopmental disorder characterized by motor and vocal tics with an estimated prevalence of 1% in children and adolescents. GTS has high rates of inheritance with many rare mutations identified. Apart from the role of the neurexin trans-synaptic connexus (NTSC) little has been confirmed regarding the molecular basis of GTS. The NTSC pathway regulates neuronal circuitry development, synaptic connectivity and neurotransmission. In this study we integrate GTS mutations into mitochondrial pathways that also regulate neuronal circuitry development, synaptic connectivity and neurotransmission. Many deleterious mutations in GTS occur in genes with complementary and consecutive roles in mitochondrial dynamics, structure and function (MDSF) pathways. These genes include those involved in mitochondrial transport (), mitochondrial fusion (), fission (), mitochondrial metabolic and bio-energetic optimization (). This study is the first to develop and describe an integrated mitochondrial pathway in the pathogenesis of GTS. The evidence from this study and our earlier modeling of GTS molecular pathways provides compounding support for a GTS deficit in mitochondrial supply affecting neurotransmission.
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http://dx.doi.org/10.3389/fpsyt.2020.556803DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987655PMC
March 2021

Predictors of adaptive functioning in preschool aged children with autism spectrum disorder.

Autism Res 2021 07 22;14(7):1444-1455. Epub 2021 Mar 22.

Child Development Unit, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.

Difficulties in adaptive functioning are common in autism spectrum disorder (ASD) and contribute to negative outcomes across the lifespan. Research indicates that cognitive ability is related to degree of adaptive functioning impairments, particularly in young children with ASD. However, the extent to which other factors, such as socioeconomic status (SES) and ASD symptom severity, predict impairments in adaptive functioning remains unclear. The goal of this study was to determine the extent to which SES, ASD symptom severity, and cognitive ability contribute to variability in domain-specific and global components of adaptive functioning in preschool-aged children with ASD. Participants were 99 preschool-aged children (2-6 years) with ASD who attended a tertiary diagnostic service. Results demonstrate that cognitive ability accounted for a significant proportion of variance in domain-specific and global components of adaptive functioning, with higher cognitive ability predicting better adaptive functioning. Results also demonstrate that SES accounted for some variability in domain-specific communication skills and global adaptive functioning when compared to basic demographic factors alone (age and gender). By contrast, ASD symptom severity did not predict variability in domain-specific or global components of adaptive functioning. These findings provide support for a relationship between cognitive ability and adaptive functioning in preschool-aged children with ASD and help to explain specific contributions of verbal and nonverbal ability to adaptive functioning; from this, we can better understand which children are likely to show the greatest degree of impairments across components of adaptive functioning early in development. LAY SUMMARY: People with autism often have difficulties with everyday communication, daily living, and social skills, which are also called adaptive functioning skills. This study investigated factors that might be related to these difficulties in preschoolers with autism. We found that better cognitive ability, but not autism symptoms, were associated with better adaptive functioning. This suggests that interventions for young children with autism should take into account cognitive ability to better understand which children are likely to have difficulties with adaptive functioning.
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http://dx.doi.org/10.1002/aur.2501DOI Listing
July 2021

School-based integrated healthcare model: how Our Mia Mia is improving health and education outcomes for children and young people.

Aust J Prim Health 2021 Mar 18. Epub 2021 Mar 18.

Integrating healthcare into education settings represents a promising model to address complex health problems in disadvantaged communities through improving access to health and social services. One such example of an effective school-based health hub is the Our Mia Mia (OMM) Wellbeing Hub, located in a primary school in Nowra and servicing a community experiencing significant socioeconomic disadvantage. The efficacy of OMM rests on its success in facilitating access to services by removing the barriers of cost and transport and establishing connection to community. The OMM fosters collaborations between health professionals and educators to coordinate holistic treatment and implement appropriate student supports in a timely manner. The support of key individuals and groups, in addition to the flexibility of the model, has allowed the hub to pivot and adapt to meet the changing needs of its community, particularly as challenges pertaining to bureaucracy, financial sustainability and community mistrust have presented themselves. Future directions for the OMM hub, and the possibility of adapting and translating school-based healthcare delivery models in other disadvantaged communities, is discussed.
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http://dx.doi.org/10.1071/PY20177DOI Listing
March 2021

COVID-19 patient transcriptomic and genomic profiling reveals comorbidity interactions with psychiatric disorders.

Transl Psychiatry 2021 03 15;11(1):160. Epub 2021 Mar 15.

Faculty of Medicine, School of Psychiatry, University of New South Wales, Sydney, NSW, 2052, Australia.

Psychiatric symptoms are seen in some COVID-19 patients, as direct or indirect sequelae, but it is unclear whether SARS-CoV-2 infection interacts with underlying neuronal or psychiatric susceptibilities. Such interactions might arise from COVID-19 immune responses, from infection of neurons themselves or may reflect social-psychological causes. To clarify this we sought the key gene expression pathways altered in COVID-19 also affected in bipolar disorder, post-traumatic stress disorder (PTSD) and schizophrenia, since this may identify pathways of interaction that could be treatment targets. We performed large scale comparisons of whole transcriptome data and immune factor transcript data in peripheral blood mononuclear cells (PBMC) from COVID-19 patients and patients with psychiatric disorders. We also analysed genome-wide association study (GWAS) data for symptomatic COVID-19 patients, comparing GWAS and whole-genome sequence data from patients with bipolar disorder, PTSD and schizophrenia patients. These studies revealed altered signalling and ontology pathways shared by COVID-19 patients and the three psychiatric disorders. Finally, co-expression and network analyses identified gene clusters common to the conditions. COVID-19 patients had peripheral blood immune system profiles that overlapped with those of patients with psychiatric conditions. From the pathways identified, PTSD profiles were the most highly correlated with COVID-19, perhaps consistent with stress-immune system interactions seen in PTSD. We also revealed common inflammatory pathways that may exacerbate psychiatric disorders, which may support the usage of anti-inflammatory medications in these patients. It also highlights the potential clinical application of multi-level dataset studies in difficult-to-treat psychiatric disorders in this COVID-19 pandemic.
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http://dx.doi.org/10.1038/s41398-020-01151-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957287PMC
March 2021

Investigating Shared Genetic Basis Across Tourette Syndrome and Comorbid Neurodevelopmental Disorders Along the Impulsivity-Compulsivity Spectrum.

Biol Psychiatry 2021 09 8;90(5):317-327. Epub 2021 Jan 8.

Department of Biological Sciences, Purdue University, West Lafayette, Indiana. Electronic address:

Background: Tourette syndrome (TS) is often found comorbid with other neurodevelopmental disorders across the impulsivity-compulsivity spectrum, with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) as most prevalent. This points to the possibility of a common etiological thread along an impulsivity-compulsivity continuum.

Methods: Investigating the shared genetic basis across TS, ADHD, ASD, and OCD, we undertook an evaluation of cross-disorder genetic architecture and systematic meta-analysis, integrating summary statistics from the latest genome-wide association studies (93,294 individuals, 6,788,510 markers).

Results: As previously identified, a common unifying factor connects TS, ADHD, and ASD, while TS and OCD show the highest genetic correlation in pairwise testing among these disorders. Thanks to a more homogeneous set of disorders and a targeted approach that is guided by genetic correlations, we were able to identify multiple novel hits and regions that seem to play a pleiotropic role for the specific disorders analyzed here and could not be identified through previous studies. In the TS-ADHD-ASD genome-wide association study single nucleotide polymorphism-based and gene-based meta-analysis, we uncovered 13 genome-wide significant regions that host single nucleotide polymorphisms with a high posterior probability for association with all three studied disorders (m-value > 0.9), 11 of which were not identified in previous cross-disorder analysis. In contrast, we also identified two additional pleiotropic regions in the TS-OCD meta-analysis. Through conditional analysis, we highlighted genes and genetic regions that play a specific role in a TS-ADHD-ASD genetic factor versus TS-OCD. Cross-disorder tissue specificity analysis implicated the hypothalamus-pituitary-adrenal gland axis in TS-ADHD-ASD.

Conclusions: Our work underlines the value of redefining the framework for research across traditional diagnostic categories.
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http://dx.doi.org/10.1016/j.biopsych.2020.12.028DOI Listing
September 2021

Tourette syndrome in children.

Aust J Gen Pract 2021 03;50(3):120-125

Tim Usherwood BSc, MBBS, MD (Res), DMS, FRCP, FRCGP, FRACGP, FAICD, Head, Westmead Clinical School, The University Of Sydney, NSW; Professor of General Practice, Faculty of Medicine and Health, The University of Sydney, NSW; Honorary Professorial Fellow, The George Institute for Global Health, Sydney, NSW.

Background: Gilles de la Tourette syndrome (GTS), characterised by motor and vocal tics, has a prevalence of approximately 1% in school-aged children. Commonly encountered comorbidities of GTS include attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive behaviour/disorder (OCB/OCD). Genetic factors play an important part in the aetiology of GTS, and family members may exhibit tics or related disorders such as ADHD, OCB or OCD.

Objective: The aim of this article is to present a summary of the current evidence to assist the assessment and management of GTS in primary care.

Discussion: A comprehensive assessment should include exploration of not only tics but also associated features and comorbidities. The stigmatising and impairing nature of tics can have a significant impact on the quality of life of the young person and their parents/carers, as well as on family functioning. Management includes education and explanation, behavioural treatments and (sometimes) medication.
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http://dx.doi.org/10.31128/AJGP-10-20-5700DOI Listing
March 2021

Analysis of common genetic variation and rare CNVs in the Australian Autism Biobank.

Mol Autism 2021 02 10;12(1):12. Epub 2021 Feb 10.

Cooperative Research Centre for Living With Autism (Autism CRC), Long Pocket, Brisbane, QLD, Australia.

Background: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition whose biological basis is yet to be elucidated. The Australian Autism Biobank (AAB) is an initiative of the Cooperative Research Centre for Living with Autism (Autism CRC) to establish an Australian resource of biospecimens, phenotypes and genomic data for research on autism.

Methods: Genome-wide single-nucleotide polymorphism genotypes were available for 2,477 individuals (after quality control) from 546 families (436 complete), including 886 participants aged 2 to 17 years with diagnosed (n = 871) or suspected (n = 15) ASD, 218 siblings without ASD, 1,256 parents, and 117 unrelated children without an ASD diagnosis. The genetic data were used to confirm familial relationships and assign ancestry, which was majority European (n = 1,964 European individuals). We generated polygenic scores (PGS) for ASD, IQ, chronotype and height in the subset of Europeans, and in 3,490 unrelated ancestry-matched participants from the UK Biobank. We tested for group differences for each PGS, and performed prediction analyses for related phenotypes in the AAB. We called copy-number variants (CNVs) in all participants, and intersected these with high-confidence ASD- and intellectual disability (ID)-associated CNVs and genes from the public domain.

Results: The ASD (p = 6.1e-13), sibling (p = 4.9e-3) and unrelated (p = 3.0e-3) groups had significantly higher ASD PGS than UK Biobank controls, whereas this was not the case for height-a control trait. The IQ PGS was a significant predictor of measured IQ in undiagnosed children (r = 0.24, p = 2.1e-3) and parents (r = 0.17, p = 8.0e-7; 4.0% of variance), but not the ASD group. Chronotype PGS predicted sleep disturbances within the ASD group (r = 0.13, p = 1.9e-3; 1.3% of variance). In the CNV analysis, we identified 13 individuals with CNVs overlapping ASD/ID-associated CNVs, and 12 with CNVs overlapping ASD/ID/developmental delay-associated genes identified on the basis of de novo variants.

Limitations: This dataset is modest in size, and the publicly-available genome-wide-association-study (GWAS) summary statistics used to calculate PGS for ASD and other traits are relatively underpowered.

Conclusions: We report on common genetic variation and rare CNVs within the AAB. Prediction analyses using currently available GWAS summary statistics are largely consistent with expected relationships based on published studies. As the size of publicly-available GWAS summary statistics grows, the phenotypic depth of the AAB dataset will provide many opportunities for analyses of autism profiles and co-occurring conditions, including when integrated with other omics datasets generated from AAB biospecimens (blood, urine, stool, hair).
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http://dx.doi.org/10.1186/s13229-020-00407-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874616PMC
February 2021

A Deep Convolutional Neural Network Method to Detect Seizures and Characteristic Frequencies Using Epileptic Electroencephalogram (EEG) Data.

IEEE J Transl Eng Health Med 2021 11;9:2000112. Epub 2021 Jan 11.

Faculty of Medicine, School of PsychiatryUniversity of New South WalesSydneyNSW2052Australia.

Background: Diagnosing epileptic seizures using electroencephalogram (EEG) in combination with deep learning computational methods has received much attention in recent years. However, to date, deep learning techniques in seizure detection have not been effectively harnessed due to sub-optimal classifier design and improper representation of the time-domain signal.

Methods: In this study, we focused on designing and evaluating deep convolutional neural network-based classifiers for seizure detection. Signal-to-image conversion methods are proposed to convert time-domain EEG signal to a time-frequency represented image to prepare the input data for classification. We proposed and evaluated three classification methods comprising of five classifiers to determine which is more accurate for seizure detection. Accuracy data were then compared to previous studies of the same dataset.

Results: We found our proposed model and signal-to-image conversion method outperformed all previous studies in the most cases. The proposed FT-VGG16 classifier achieved the highest average classification accuracy of 99.21%. In addition, the Shapley Additive exPlanations (SHAP) analysis approach was employed to uncover the feature frequencies in the EEG that contribute most to improved classification accuracy. To the best of our knowledge, this is the first study to compute the contribution of frequency components to target seizure classification; thus allowing the identification of distinct seizure-related EEG frequency components compared to normal EEG measures.

Conclusion: Thus our developed deep convolutional neural network models are useful to detect seizures and characteristic frequencies using EEG data collected from the patients and this model could be clinically applicable for the automated seizures detection.
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http://dx.doi.org/10.1109/JTEHM.2021.3050925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851059PMC
January 2021

"The big wide world of school": Supporting children on the autism spectrum to successfully transition to primary school: Perspectives from parents and early intervention professionals.

Scand J Child Adolesc Psychiatr Psychol 2020 11;8:91-100. Epub 2020 Aug 11.

School of Occupational Therapy Social Work and Speech Pathology, Curtin University, Perth, Western Australia, Australia.

Background: The transition to primary school is often a complex and uncertain time for autistic children and their families. Understanding how best to develop school readiness and support transition to primary school for autistic children is essential. School readiness and transition planning are influenced by a range of personal and contextual factors, and it is important to understand the perspectives of the various stakeholders involved in the transition process.

Methods: A qualitative exploration employing focus groups and interviews was undertaken with early intervention (EI) staff (n = 45) and parents (n = 18) across Australia to understand their perspectives on school readiness and the transition to primary school.

Results: Thematic analysis identified four emerging themes facilitating transition including: 1) building the child; 2) building the parents; 3) building the receiving school; and, 4) connecting the system.

Conclusion: Findings highlight the need to consider school readiness and transition planning from a holistic perspective, ensuring clear, collaborative and ongoing communication between parents, teachers and EI staff, using a strength-based approach, and individualizing transition planning.
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http://dx.doi.org/10.21307/sjcapp-2020-009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685497PMC
August 2020

Impact of the COVID-19 pandemic on the well-being of children with neurodevelopmental disabilities and their parents.

J Paediatr Child Health 2021 05 10;57(5):631-636. Epub 2021 Jan 10.

School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.

Aims: To examine the impact of COVID-19 pandemic on child mental health and socio-emotional and physical well-being (including sleep, diet, exercise, use of electronic media; care giver perceptions of symptoms of child neurodevelopmental disability [NDD] and comorbidities), and care giver mental health and well-being, social support and service use.

Methods: An online cross-sectional self-report survey was distributed via disability service providers and support groups. Care givers of children aged 2-17 years with a NDD were invited to respond to questions on child symptom severity and well-being, parent well-being and service access and satisfaction.

Results: Overall, 302 care givers (94.7% female) completed the survey. Average child age was 9.7 years and 66.9% were male. Worsening of any child NDD or comorbid mental health symptom was reported by 64.5% of respondents and 76.9% reported child health and well-being was impacted by COVID-19. Children were viewing more television and digital media (81.6%), exercising less (68.0%), experiencing reduced sleep quality (43.6%) and had a poorer diet (32.4%). Almost one fifth (18.8%) of families reported an increase in the dosage of medication administered to their child. Parents reported COVID-19 had impacted their own well-being (76.1%). Over half of respondents were not satisfied with services received during COVID-19 (54.8%) and just 30% reported that telehealth works well for their child.

Conclusion: Targeted interventions are required to address worsening child neurodevelopmental disability, mental health symptoms and poor diet, sleep and exercise patterns. Improved access to telehealth services is indicated, as is further research on barriers and enablers of effective telehealth services.
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http://dx.doi.org/10.1111/jpc.15285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014782PMC
May 2021

Impact of the COVID-19 pandemic on the well-being of children with neurodevelopmental disabilities and their parents.

J Paediatr Child Health 2021 05 10;57(5):631-636. Epub 2021 Jan 10.

School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.

Aims: To examine the impact of COVID-19 pandemic on child mental health and socio-emotional and physical well-being (including sleep, diet, exercise, use of electronic media; care giver perceptions of symptoms of child neurodevelopmental disability [NDD] and comorbidities), and care giver mental health and well-being, social support and service use.

Methods: An online cross-sectional self-report survey was distributed via disability service providers and support groups. Care givers of children aged 2-17 years with a NDD were invited to respond to questions on child symptom severity and well-being, parent well-being and service access and satisfaction.

Results: Overall, 302 care givers (94.7% female) completed the survey. Average child age was 9.7 years and 66.9% were male. Worsening of any child NDD or comorbid mental health symptom was reported by 64.5% of respondents and 76.9% reported child health and well-being was impacted by COVID-19. Children were viewing more television and digital media (81.6%), exercising less (68.0%), experiencing reduced sleep quality (43.6%) and had a poorer diet (32.4%). Almost one fifth (18.8%) of families reported an increase in the dosage of medication administered to their child. Parents reported COVID-19 had impacted their own well-being (76.1%). Over half of respondents were not satisfied with services received during COVID-19 (54.8%) and just 30% reported that telehealth works well for their child.

Conclusion: Targeted interventions are required to address worsening child neurodevelopmental disability, mental health symptoms and poor diet, sleep and exercise patterns. Improved access to telehealth services is indicated, as is further research on barriers and enablers of effective telehealth services.
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http://dx.doi.org/10.1111/jpc.15285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014782PMC
May 2021

Adaptive innovations to provide services to children with developmental disabilities during the COVID-19 pandemic.

J Paediatr Child Health 2021 01 6;57(1):9-11. Epub 2020 Nov 6.

Department of Paediatrics, Monash University, Melbourne, Victoria, Australia.

Children with developmental disabilities are experiencing significant challenges to service access due to suspension of in-person assessments during the current COVID-19 pandemic. Telehealth is rapidly becoming the new service delivery model, which presents a unique opportunity for innovation in care that could be beneficial in the post-pandemic period. For example, using a combination of in-home video and telehealth options could form the first step in developmental assessment, allowing children to receive the necessary supports without delay. Recent telehealth funding is welcome but additional Medicare items for joint consultations including general practitioners (GPs), and paediatric, mental health and allied health professionals is critical.
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http://dx.doi.org/10.1111/jpc.15224DOI Listing
January 2021
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