Priority setting for children and young people with chronic conditions and disabilities.

BACKGROUND: The aim of this project was to identify the top 10 priorities for childhood chronic conditions and disability (CCD) research from the perspectives of children and young people with lived experience, their parents and caregivers and the professionals who work with them. METHODS: We conducted a three-stage study based on the James Lind Alliance priority-setting partnership methods. It comprised two online surveys (n = 200; n = 201) and a consensus workshop (n = 21) with these three stakeholder groups in Australia. RESULTS: In the first stage, 456 responses were submitted, which were coded and collapsed into 40 overarching themes. In the second stage, 20 themes were shortlisted, which were further refined in stage 3, before the top 10 priorities being selected. Of these, the top three priorities were improving awareness and inclusion in all aspects of their life (school, work and social relationships), improving access to treatments and support and improving the process of diagnosis. CONCLUSIONS: The top 10 priorities identified reflect the need to focus on the individual, health systems and social aspects of the CCD experience when conducting research in this area. PATIENT OR PUBLIC CONTRIBUTION: This study was guided by three Advisory Groups, comprising (1) young people living with CCD; (2) parents and caregivers of a child or young person with CCD and (3) professionals working with children and young people with CCD. These groups met several times across the course of the project and provided input into study aims, materials, methods and data interpretation and reporting. Additionally, the lead author and seven members of the author group have lived and experienced CCD.

Investigating associations between birth order and autism diagnostic phenotypes.

BACKGROUND: Birth order effects have been linked to variability in intelligence, educational attainment and sexual orientation. First- and later-born children have been linked to an increased likelihood of an Autism Spectrum Disorder (ASD) diagnosis, with a smaller body of evidence implicating decreases in cognitive functioning with increased birth order. The present study investigated the potential association between birth order and ASD diagnostic phenotypes in a large and representative population sample. METHODS: Data were obtained from an ongoing prospective diagnostic registry, collected between 1999 and 2017, including children (1-18 years of age, n = 5,404) diagnosed with ASD in the state of Western Australia. Children with ASD were ranked relative to sibling's birth to establish birth order within families at time of ASD diagnosis. Information reported to the registry by health professionals at the time of diagnostic evaluation included demographic and family characteristics, functional abilities and intellectual capacity. RESULTS: Adaptive functioning and intelligence scores decreased with increasing birth order, with later-born children more likely to have an intellectual disability. Compared to first-born children with siblings, first-born children without siblings at the time of diagnosis also exhibited decreased cognitive functioning. CONCLUSIONS: These findings demonstrate for the first time an association between increasing birth order and variability in ASD clinical phenotypes at diagnosis, with potential evidence of reproductive curtailment in children without siblings. Taken together, these findings have significant implications for advancing understanding about the potential mechanisms that contribute to heterogeneity in ASD clinical presentations as a function of birth order and family size.

Deconstructing the repetitive behaviour phenotype in autism spectrum disorder through a large population-based analysis.

OBJECTIVE: Restricted and repetitive pattern of behaviours and interests (RRB) are a cardinal feature of autism spectrum disorder (ASD), but there remains uncertainty about how these diverse behaviours vary according to individual characteristics. This study provided the largest exploration to date of the relationship between Repetitive Motor Behaviours, Rigidity/Insistence on Sameness and Circumscribed Interests with other individual characteristics in newly diagnosed individuals with ASD. METHOD: Participants (N = 3,647; 17.7% females; Mage = 6.6 years [SD = 4.7]) were part of the Western Australian (WA) Register for ASD, an independent, prospective collection of demographic and diagnostic data of newly diagnosed cases of ASD in WA. Diagnosticians rated each of the DSM-IV-TR criteria on a 4-point Likert severity scale, and here we focused on the Repetitive Motor Behaviours, Insistence on Sameness and Circumscribed Interests symptoms. RESULTS: The associations between RRB domains, indexed by Kendall's Tau, were weak, ranging from non-significant for both Circumscribed Interests and Repetitive Motor Behaviours to significant (.20) for Insistence on Sameness and Repetitive Motor Behaviours. Older age at diagnosis was significantly associated with lower Circumscribed Interests and significantly associated with higher Insistence on Sameness and Repetitive Motor Behaviours. Male sex was significantly associated with higher Repetitive Motor Behaviours but not Insistence on Sameness or Circumscribed Interests. CONCLUSIONS: The pattern of associations identified in this study provides suggestive evidence for the distinctiveness of Repetitive Motor Behaviours, Insistence on Sameness and Circumscribed Interests, highlighting the potential utility of RRB domains for stratifying the larger ASD population into smaller, more phenotypically homogeneous subgroups that can help to facilitate efforts to understand diverse ASD aetiology and inform design of future interventions.

Glycemic and Psychosocial Outcomes of Advanced Hybrid Closed Loop Therapy in Youth With High HbA1c: A Randomized Clinical Trial.

OBJECTIVE: To determine the efficacy of advanced hybrid closed loop (AHCL) therapy in a high-risk cohort of youth on continuous subcutaneous insulin infusion (CSII) ± continuous glucose monitoring (CGM) with suboptimal glycemia. RESEARCH DESIGN AND METHODS: In a 6-month multicenter clinical trial, youth with type 1 diabetes with mean and most recent HbA1c > 8.5% (65 mmol/mol) were randomly assigned 1:1 to AHCL or treatment as usual (CSII ± CGM). The primary outcome was the 24-week between-group difference in HbA1c. Secondary outcomes included CGM metrics from masked CGM and psychological measures (youth-reported problem areas in diabetes [PAID], quality of life, anxiety, depression, and hypoglycemia fear) assessed using validated questionnaires. RESULTS: A total of 42 participants were randomized (mean [SD] age 16.2 [2.5] years, HbA1c 9.8 [1.1]% or 84 [12] mmol/mol, PAID score 50.3 [19.8]). At study end, the mean (SD) HbA1c was 8.8 (1.1)% or 73 (12) mmol/mol with AHCL and 9.9 (1.2)% or 85 (13.1) mmol/mol with CSII ± CGM, with mean adjusted group difference of -0.77% (95% CI -1.45 to -0.09) or -8.4 mmol/mol (-15.8 to -1.0); P = 0.027. AHCL increased time in range 70-180 mg/dL (difference 19.1%; 95% CI 11.1 to 27.1), reduced time >180 mg/dL (difference -17.7%; 95% CI -26.6 to -8.8), with no increase in time spent <70 mg/dL (difference -0.8%; 95% CI -2.7 to 0.6). There was no evidence for difference in psychosocial outcomes between the two groups at study end. CONCLUSIONS: AHCL should be encouraged in youth with suboptimal glycemia, as AHCL improves glycemia. However, psychological support remains vital, as technology alone may not be able to reduce the burden of diabetes care in this subgroup.

Wellbeing and distress in young people with chronic conditions: how do positive psychology variables relate to mental health outcomes?

Objective: The aim of this study was to determine the unique and shared contributions of various positive psychology constructs (gratitude, optimism, hope, self-compassion, self-efficacy, and emotion regulation) to wellbeing and distress outcomes in young people living with a diverse range of chronic health conditions. Methods and Measures: 169 Australians (84.0% female, mean age = 21.2) who reported living with a chronic physical condition completed a cross-sectional survey assessing wellbeing, distress, and each positive psychology variable. Two multiple regressions were used to determine the unique and shared contributions of the positive psychology variables to wellbeing and distress outcomes. Results: When considered alongside symptom severity, the variables explained 53.4% and 38.1% of variance in distress and wellbeing, respectively. Only optimism and self-efficacy accounted for unique and significant variance in the model predicting wellbeing, accounting for 6.1% and 4.6% of unique variance, respectively. For the distress model, optimism, self-compassion, and emotion regulation each accounted for significant variance. When considered alongside other variables, hope and gratitude did not contribute to either model. Conclusion: Findings suggest that individual positive psychology variables differentially contribute to wellbeing and distress outcomes in young people with chronic conditions. Optimism appears to account for unique variance in both outcomes, suggesting it may be a parsimonious target to promote complete mental health in this population.

Experiences and Attitudes of Parents Reducing Carbohydrate Intake in the Management of Their Child's Type 1 Diabetes: A Qualitative Study.

Reducing carbohydrate (CHO) intake is being used as an approach to manage type 1 diabetes (T1D) in children. This study aimed to investigate the experiences and attitudes of parents of children with T1D who are reducing CHO intake to help manage blood glucose levels (BGLs). Semi-structured interviews were conducted with the parents of children with T1D for >1 year who reported implementing a low CHO approach to manage BGLs. Data were analysed using a constant comparative analysis approach. Participants (n = 14) were parents of children (6.6 ± 2.0 years) with T1D in Western Australia. All parents reported different methods of CHO restriction and all perceived that benefits outweighed challenges. Parents reported feeling less worried, had improved sleep and felt their child was safer when using a low CHO approach due to more stable BGLs. Reported challenges included: increased cost and time spent preparing food; perceived judgement from others; and child dissatisfaction with restricted food choices. Parents reported accessing information and support through social media networks. Parents reported a desire for more research into this approach. Understanding the promoters and barriers for this dietary approach may inform strategies to better engage and support families with approaches that align with current evidence while considering their concerns around safety and hyperglycaemia.

Selective attention to threat, anxiety and glycaemic management in adolescents with type 1 diabetes.

Objective: Previous research has established that adolescents with type 1 diabetes (T1D) experience more anxiety symptoms than their healthy peers and are also more likely to develop an anxiety disorder. Research in cognitive psychology has found that selective attention favouring the processing of threatening information causally contributes to elevated levels of anxiety; however, this process has not been investigated in the context of T1D. The current study examined whether selective attention for threatening information contributes to the association between anxiety and glycaemic management in adolescents with T1D. Methods: Participants completed a dot-probe task to assess selective attention for diabetes-related threatening information and general non-diabetes-related threatening information and we examined the associations between these measures and measures of HbA1c and anxiety. Results: Findings suggest that individual differences in anxiety vulnerability do not predict HbA1c alongside the attentional bias for threatening information. Conclusions: The attentional bias for threatening information makes a contribution to the relationship between anxiety and glycaemic management and may represent a target for therapeutic intervention to both reduce anxiety and improve glycaemic management.

Prevalence of Motor Difficulties in Autism Spectrum Disorder: Analysis of a Population-Based Cohort.

Motor impairment is not currently included in the diagnostic criteria or evaluation of autism. This reflects the lack of large-scale studies demonstrating its prominence to advocate for change. We examined the prevalence of motor difficulties at the time of diagnosis in a large sample of children with autism utilizing standardized assessment, and the relationship between motor difficulties, core autism symptomology, and other prominent clinical features. Vineland Adaptive Behavior Scales were administered to children from the Western Australian Register for Autism Spectrum Disorders aged ≤6 years (N = 2,084; 81.2% males, 18.8% females). Prevalence of motor difficulties was quantified based on scores from the motor domain of the Vineland and then compared to other domains of functioning within the Vineland (communication, daily living, and socialization), the DSM criteria, intellectual level, age, and gender. Scores on the Vineland indicated that 35.4% of the sample met criteria for motor difficulties (standard score <70), a rate almost as common as intellectual impairment (37.7%). Motor difficulties were reported by diagnosing clinicians in only 1.34% of cases. Motor difficulties were common in those cases meeting diagnostic criteria for impairments in nonverbal behavior and the presence of restricted and repetitive behaviors. The prevalence of motor difficulties also increased with increasing age of diagnosis (P < 0.001). Findings from the present study highlight the need for further consideration of motor difficulties as a distinct specifier within the diagnostic criteria for ASD. Autism Res 2020, 13: 298-306. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this population-based cohort that included 2,084 children with autism aged ≤6 years, over one-third met the criteria for motor difficulties, a rate almost as common as intellectual disability. This study demonstrates that motor difficulties are a prominent feature of the autism phenotype requiring further consideration in both the diagnostic criteria and evaluation of autism.

The misnomer of 'high functioning autism': Intelligence is an imprecise predictor of functional abilities at diagnosis.

'High functioning autism' is a term often used for individuals with autism spectrum disorder without an intellectual disability. Over time, this term has become synonymous with expectations of greater functional skills and better long-term outcomes, despite contradictory clinical observations. This study investigated the relationship between adaptive behaviour, cognitive estimates (intelligence quotient) and age at diagnosis in autism spectrum disorder. Participants (n = 2225, 1-18 years of age) were notified at diagnosis to a prospective register and grouped by presence (n = 1041) or absence (n = 1184) of intellectual disability. Functional abilities were reported using the Vineland Adaptive Behaviour Scales. Regression models suggested that intelligence quotient was a weak predictor of Vineland Adaptive Behaviour Scales after controlling for sex. Whereas the intellectual disability group's adaptive behaviour estimates were close to reported intelligence quotients, Vineland Adaptive Behaviour Scales scores fell significantly below intelligence quotients for children without intellectual disability. The gap between intelligence quotient and Vineland Adaptive Behaviour Scales scores remained large with increasing age at diagnosis for all children. These data indicate that estimates from intelligence quotient alone are an imprecise proxy for functional abilities when diagnosing autism spectrum disorder, particularly for those without intellectual disability. We argue that 'high functioning autism' is an inaccurate clinical descriptor when based solely on intelligence quotient demarcations and this term should be abandoned in research and clinical practice.

Diagnosis of Autism Spectrum Disorder According to Maternal-Race Ethnicity and Country of Birth: A Register-Based Study.

An increased prevalence of autism spectrum disorder (ASD) among children of immigrant backgrounds has been observed but clinical profiles are rarely compared. Diagnostic data from children with ASD notified to the Western Australian Register for Autism Spectrum Disorders were analysed according to maternal-race ethnicity and country of birth. A total of 4776 children aged between 0 and 18 years diagnosed with ASD from 1999 to 2017 were included. Those born to immigrant mothers from lower income countries were younger at the time of diagnosis, had an increased risk of intellectual disability and poorer presentations in the social and communication domains. Further work is required to understand environmental influences that may affect children born to immigrant mothers and to improve monitoring and assessments.

Vagus nerve stimulation for the treatment of refractory epilepsy in the CDKL5 Deficiency Disorder.

BACKGROUND: Variants within the CDKL5 gene result in a severe epileptic encephalopathy now known as the CDKL5 Deficiency Disorder. Phenotypic characteristics include global developmental delay and early seizure onset with poor response to anti-epileptic medications. Vagus nerve stimulation (VNS) has been used in other populations as an adjunct treatment for refractory epilepsy with seizure reduction reported in over half of patients. This study aimed to investigate the role of VNS in the CDKL5 Deficiency Disorder. METHODS: The International CDKL5 Disorder Database collects information on individuals with the CDKL5 Deficiency Disorder. Families provide information regarding seizure characteristics and their pharmaceutical and non-pharmaceutical management including VNS use. Descriptive statistics and time to event analyses were performed. Clinical vignettes were also provided from patients attending the CDKL5 Center of Excellence at Children's Hospital Colorado. RESULTS: Individuals who had a pathogenic CDKL5 variant and on whom information regarding VNS treatment was available were identified (n = 222). Previous or current use of VNS was reported for 38 (17.1%), with a median age at implantation of 4.9 years. Improvements in seizure control were reported in over two-thirds (25/36, 69%); including reduction in frequency (17/25, 68%), duration (18/25, 72%) and intensity (15/25, 60%) of seizures. Median duration of VNS use before any seizure improvement was 73 days. Behavioural changes such as improved mood and alertness were reported in nine individuals. Early termination of VNS secondary to side effects was reported in three cases. There was no reduction in number of AEDs for those with VNS treatment. CONCLUSION: Our study suggests that VNS is a generally safe and effective adjunct treatment for CDKL5-associated epilepsy. Additional benefits such as mood and behavioural improvements provide further support of its use in the CDKL5 Deficiency Disorder. Future studies are required to determine the optimal settings and therapeutic potential for this treatment.

Evidence of a reduction over time in the behavioral severity of autistic disorder diagnoses.

The increasing prevalence of Autism Spectrum Disorders (ASD) may in part be due to a shift in the diagnostic threshold that has led to individuals with a less severe behavioral phenotype receiving a clinical diagnosis. This study examined whether there were changes over time in the qualitative and quantitative phenotype of individuals who received the diagnosis of Autistic Disorder. Data were from a prospective register of new diagnoses in Western Australia (n = 1252). From 2000 to 2006, we examined differences in both the percentage of newly diagnosed cases that met each criterion as well as severity ratings of the behaviors observed (not met, partially met, mild/moderate and extreme). Linear regression determined there was a statistically significant reduction from 2000 to 2006 in the percentage of new diagnoses meeting two of 12 criteria. There was also a reduction across the study period in the proportion of new cases rated as having extreme severity on six criteria. There was a reduction in the proportion of individuals with three or more criteria rated as extreme from 2000 (16.0%) to 2006 (1.6%), while percentage of new cases with no "extreme" rating on any criteria increased from 58.5% to 86.6% across the same period. This study provides the first clear evidence of a reduction over time in the behavioral severity of individuals diagnosed with Autistic Disorder during a period of stability in diagnostic criteria. A shift toward diagnosing individuals with less severe behavioral symptoms may have contributed to the increasing prevalence of Autistic Disorder diagnoses. Autism Res 2017, 10: 179-187. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.