Communication of individuals with CDKL5 deficiency disorder as observed by caregivers: A descriptive qualitative study.

CDKL5 deficiency disorder (CDD) is a genetically caused developmental epileptic encephalopathy that causes severe communication impairments. Communication of individuals with CDD is not well understood in the literature and currently available measures are not well validated in this population. Accurate and sensitive measurement of the communication of individuals with CDD is important for understanding this condition, clinical practice, and upcoming interventional trials. The aim of this descriptive qualitative study was to understand how individuals with CDD communicate, as observed by caregivers. Participants were identified through the International CDKL5 Disorder Database and invited to take part if their child had a pathogenic variant of the CDKL5 gene and they had previously completed the Communication and Symbolic Behavior Checklist (CSBS-DP ITC). The sample comprised caregivers of 23 individuals with CDD, whose ages ranged from 2 to 30 years (median 13 years), 15 were female, and most did not use words. Semistructured interviews were conducted via videoconference and analyzed using a conventional content analysis. Three overarching categories were identified: mode, purpose and meaning, and reciprocal exchanges. These categories described the purposes and mechanism of how some individuals with CDD communicate, including underpinning influential factors. Novel categories included expressing a range of emotions, and reciprocal exchanges (two-way interactions that varied in complexity). Caregivers observed many communication modes for multiple purposes. Understanding how individuals with CDD communicate improves understanding of the condition and will guide research to develop accurate measurement for clinical practice and upcoming medication trials.

How Well Does the EQ-5D-Y-5L Describe Children With Intellectual Disability?: "There's a Lot More to My Child Than That She Can't Wash or Dress Herself."

OBJECTIVES: The EQ-5D-5L is a generic health utility instrument for measuring health-related quality of life (HRQoL), with self-report and proxy report versions for children (EQ-5D-Y-5L). Children with intellectual disability (ID) are a heterogeneous population whose impairments and comorbidities place them at risk of poor HRQoL. This study aimed to describe the content validity and suitability for children with ID of a proxy report version of the EQ-5D-Y-5L as seen by their caregivers. METHODS: A proxy report EQ-5D-Y-5L was administered to caregivers of children with ID. Using cognitive think-aloud interviewing, participants were encouraged to provide the reasoning for their choices, assess the questions' relevance, comprehensibility, and comprehensiveness, and comment on the tool's strengths and weaknesses. Qualitative content analysis used both directed (deductive) and conventional (inductive) methods. RESULTS: There were 28 interviews with 30 caregivers of children with ID (aged 8-22 years, 17 boys, with autism spectrum disorder, cerebral palsy, Down syndrome, and rare genetic disorders). The EQ-5D-Y-5L was considered clear, concise, and largely relevant, but insufficiently comprehensive for this population. Interviewees sought clarification of the definition of HRQoL, whether it included unchanging impairments (vs fluctuating health states), and what basis of comparison to use (child or peer). Many interviewees suggested inclusion of questions for other domains, including communication and social engagement, equipment and human supports required, and a wider range of mental health questions. CONCLUSIONS: The study suggests that further work is required to ensure accurate responses to the EQ-5D-Y-5L from caregivers of children with ID and to describe these children adequately.

Psychometric Properties of the EQ-5D-Y-5L for Children With Intellectual Disability.

OBJECTIVES: The EQ-5D-Y-5L is a generic preference-based measure of health-related quality of life for children. This study aimed to describe the distributional properties, test-retest reliability, and convergent validity of the EQ-5D-Y-5L in children with intellectual disability (ID). METHODS: Caregivers of children with ID (aged 4 to 18 years) completed an online survey, including a proxy-report EQ-5D-Y-5L, the Quality-of-life Inventory-Disability, and disability-appropriate measures corresponding to the EQ-5D dimensions: mobility, self-care (SC), usual activities (UA), pain/discomfort (PD), and worry/sadness/unhappiness. Twenty-one participants repeated the EQ-5D-Y-5L a few weeks later. Test-retest reliability was computed using weighted kappa and intraclass correlation coefficients, and convergent validity using Spearman's and Pearson's correlation coefficients. RESULTS: Caregivers of 234 children completed the survey, with <1% missing values. Only 1.7% reported "no problems" on all dimensions (11111). The dimensions with the lowest percentage of "no problems" were SC and UA (both 8%). Test-retest reliability coefficients were fair to substantial for 4 dimensions (weighted kappa .30 to .79) but low for PD and overall health, as measured by the visual analog scale (EQ-VAS). Convergent validity was strong (Spearman's correlation .65 to .87) for mobility, SC, and PD; moderate to strong for worry/sadness/unhappiness (.47 to .60) and the EQ-VAS (Pearson's correlation .49); and weak to moderate for UA (.21 to .52). CONCLUSIONS: Convergent validity was generally good; test-retest reliability varied. Children with ID had lower scores on SC and UA than other populations, and their EQ-VAS could fluctuate greatly, indicating poorer and less stable health-related quality of life.

Psychometric properties of QI-Disability in CDKL5 Deficiency Disorder: Establishing readiness for clinical trials.

CDKL5 Deficiency Disorder (CDD) is a rare genetic disorder with symptoms of epilepsy, developmental impairments, and other comorbidities. Currently, there are no outcome measures for CDD with comprehensive evidence of validation. This study aimed to evaluate the psychometric properties of the Quality of Life Inventory-Disability (QI-Disability) in CDD. Quality of Life Inventory-Disability was administered to 152 parent caregivers registered with the International CDKL5 Disorder Database (ICDD). Confirmatory factor analysis was conducted and the goodness of fit of the factor structure was assessed. Fixed-effects linear regression models examined the responsiveness of QI-Disability to reported changes in child health. A subset of parent caregivers (n = 56) completed QI-Disability, as well as additional health-related questions, on two occasions separated by four weeks to evaluate test-retest reliability. Test-retest reliability was assessed using intra-class correlations (ICCs) calculated from QI-Disability scores. Based upon adjustments for changes in child health, ICCs were recalculated to estimate responsiveness to change. Confirmatory factor analysis, internal consistency, and divergent validity were mostly satisfactory, except divergent validity was not satisfactory for the Social Interactions and Independence domains. The Physical Health, Social Interactions, Leisure, and Total scores responded to changes in the child's Physical health, and the Negative Emotions and Leisure domains responded to changes in the child's behavior. Unadjusted and adjusted ICC values were above 0.8 for the Positive Emotions, Negative Emotions, Social Interactions, Leisure, Independence domains and Total score, and above 0.6 for the Physical Health domain. Findings suggest that QI-Disability is suitable to assess the quality of life of children and adults with CDD and could be of value for upcoming clinical trials.

Early onset of otitis media is a strong predictor of subsequent disease in urban Aboriginal infants: Djaalinj Waakinj cohort study.

AIM: Australian Aboriginal and/or Torres Strait Islander children in rural/remote areas suffer high rates of persistent otitis media (OM) from early infancy. We aimed to determine the proportion of Aboriginal infants living in an urban area who have OM and investigate associated risk factors. METHODS: Between 2017 and 2020, the Djaalinj Waakinj cohort study enrolled 125 Aboriginal infants at 0-12 weeks of age in the Perth South Metropolitan region, Western Australia. Proportion of children with OM based on tympanometry at ages 2, 6 and 12 months was evaluated, type B tympanogram indicating middle ear effusion. Potential risk factors were investigated by logistic regression with generalised estimating equations. RESULTS: The proportion of children with OM was 35% (29/83) at 2 months, 49% (34/70) at 6 months and 49% (33/68) at 12 months of age. About 70% (16/23) of those with OM at ages 2 and/or 6 months had OM at 12 months compared with 20% (3/15) if no prior OM (relative risk = 3.48, 95% confidence interval (CI): 1.22-40.1). On multivariate analysis, infants living in houses with ≥1 person/room were at increased risk of OM (odds ratio = 1.78, 95% CI: 0.96-3.32). CONCLUSION: Approximately half of Aboriginal infants enrolled into the South Metropolitan Perth project have OM by the age of 6 months and early onset of disease strongly predicts subsequent OM. Early surveillance for OM in urban areas is needed for early detection and management to reduce the risk of long-term hearing loss which can have serious developmental, social, behavioural, educational and economic consequences.

Negative impact of insomnia and daytime sleepiness on quality of life in individuals with the cyclin-dependent kinase-like 5 deficiency disorder.

Cyclin-dependent kinase-like 5 (CDKL5) gene pathogenic variants result in CDKL5 deficiency disorder (CDD). Early onset intractable epilepsy and severe developmental delays are prominent symptoms of CDD. Comorbid sleep disturbances are a major concerning symptom for families. We aimed to explore the relationship between insomnia, daytime sleepiness, sleep medications and quality of life in children with CDD. Caregivers of 129 children with CDD in the International CDKL5 Disorder Database completed the Quality-of-Life Inventory-Disability (QI-Disability) questionnaire and "Disorders of Maintaining Sleep" (DIMS) and the "Disorders of Excessive Somnolence" (DOES) items of the Sleep Disturbance Scale for Children. Adjusting for covariates, a unit increase in DOES score was associated with reduced quality of life total (coefficient -3.06, 95% confidence interval [CI] 1.35-7.80), physical health (coefficient -7.20, 95% CI -10.64, -3.76) and negative emotions (coefficient -3.90, 95% CI -7.38, -0.42) scores. Adjusting for covariates, a unit increase in DIMS score was associated with reduced negative emotions (coefficient -6.02, 95% CI -10.18, -2.86). Use of sleep medications had small influences on the effect sizes. This study highlights the importance of sleep problems as a determinant of quality of life in children with CDD, consistent with effects observed for other groups of children with intellectual disability. Excessive daytime sleepiness was particularly associated with detrimental effects on quality of life. Further research in optimal behavioural and pharmaceutical management of sleep problems for this population is required.

Modelling quality of life in children with intellectual disability using regression trees.

AIM: To identify factors associated with quality of life (QoL) in children with intellectual disability. We aimed to identify patterns of association not observable in previous hypothesis-driven regression modelling using the same data set from a cross-sectional observational study. METHOD: A questionnaire was completed by 442 caregivers of children with confirmed intellectual disability and a diagnosis of autism spectrum disorder, cerebral palsy, Down syndrome, or Rett syndrome. The Quality of Life Inventory-Disability (QI-Disability) questionnaire was used to assess child QoL. Independent variables described the child's health, functional abilities, community participation, and sociodemographics. The R package rpart was used to build the regression trees. RESULTS: The mean total QI-Disability score was 69.2 out of a maximum 100. The subgroup with the lowest QoL scores comprised children with a high degree of daytime sleepiness (n=74, mean 57.5) while the subgroup with the highest QoL scores (n=91, mean 80.3) comprised children with little daytime sleepiness who participated more frequently in community activities and displayed good eye contact while listening. INTERPRETATION: Regression tree analysis provides insights into the relative importance of associated factors. Sleep problems and community participation were more important than functional abilities in accounting for differences in QoL. WHAT THIS PAPER ADDS: A hypothesis-free regression tree analysis enables examination of multiple factors potentially influencing quality of life (QoL) in children with intellectual disability. Functional abilities were less strongly associated with QoL than sleep problems and community participation.

Daytime sleepiness and emotional and behavioral disturbances in Prader-Willi syndrome.

Individuals with Prader-Willi syndrome (PWS) often have excessive daytime sleepiness and emotional/behavioral disturbances. The objective of this study was to examine whether daytime sleepiness was associated with these emotional/behavioral problems, independent of nighttime sleep-disordered breathing, or the duration of sleep. Caregivers of individuals with PWS (aged 3 to 25 years) completed the Pediatric Sleep Questionnaire (PSQ), Epworth Sleepiness Scale for Children and Adolescents (ESS-CHAD), and the parent version of the Developmental Behavior Checklist (DBC-P). Sleep adequacy was adjusted for age by computing sleep duration against age-specific recommendations. The associations between ESS-CHAD and the total DBC and its subscale scores were evaluated by linear regression, adjusted for sleep-related breathing difficulties, sleep adequacy, and body mass index (BMI). There were 54 responses for individuals with PWS (including 22 males) aged 4.4-24.0 (mean 12.5) years. Daytime sleepiness predicted a substantial proportion of the variance in total DBC-P scores in the unadjusted model (28%; ß = 0.028; p < 0.001) and when adjusted for sleep adequacy, BMI, and sleep-related breathing difficulties (29%; ß = 0.023; p = 0.007). This relationship was not moderated by BMI Z-scores, but the relationship was more prominent for children younger than 12 years than for children older than 12 years.Conclusions: These findings provide preliminary novel evidence that daytime sleepiness may drive the expression of emotional/behavioral disturbances, and should be explored as a potential modifiable risk factor for these disturbances in PWS, particularly pre-adolescent children.

Sleep-disordered breathing in Australian children with Prader-Willi syndrome following initiation of growth hormone therapy.

AIM: In children with Prader-Willi syndrome (PWS), growth hormone (GH) improves height and body composition; however, may be associated with worsening sleep-disordered breathing (SDB). Some studies have reported less SDB after GH initiation, but follow-up with polysomnography is still advised in most clinical guidelines. METHODS: This retrospective, multicentre study, included children with PWS treated with GH at seven PWS treatment centres in Australia over the last 18 years. A paired analysis comparing polysomnographic measures of central and obstructive SDB in the same child, before and after GH initiation was performed with Wilcoxon signed-rank test. The proportion of children who developed moderate/severe obstructive sleep apnoea (OSA) was calculated with their binomial confidence intervals. RESULTS: We included 112 patients with available paired data. The median age at start of GH was 1.9 years (range 0.1-13.5 years). Median obstructive apnoea hypopnoea index (AHI) at baseline was 0.43/h (range 0-32.9); 35% had an obstructive AHI above 1.0/h. Follow-up polysomnography within 2 years after the start of GH was available in 94 children who did not receive OSA treatment. After GH initiation, there was no change in central AHI. The median obstructive AHI did not increase significantly (P = 0.13), but 12 children (13%, CI95% 7-21%) developed moderate/severe OSA, with clinical management implications. CONCLUSIONS: Our findings of a worsening of OSA severity in 13% of children with PWS support current advice to perform polysomnography after GH initiation. Early identification of worsening OSA may prevent severe sequelae in a subgroup of children.

Determinants of sleep problems in children with intellectual disability.

Children with intellectual disabilities are more likely to experience sleep disorders of insomnia, excessive daytime sleepiness and sleep breathing disorders than typically developing children. The present study examined risk factors for these sleep disorders in 447 children (aged 5-18 years), diagnosed with an intellectual disability and comorbid autism spectrum disorder, cerebral palsy, Down syndrome or Rett syndrome. Primary caregivers reported on their child's sleep using the Sleep Disturbance Scale for Children (SDSC), as well as medical comorbidities and functional abilities. Multivariate linear and logistic regressions were used to examine the effects of these factors on SDSC t scores and a binary indicator, respectively for the relevant subscales. Receiving operating characteristic curves were generated for each logistic regression model to determine their ability to discriminate between poor and good sleep. Comorbidities rather than functional abilities were associated with poorer sleep. In particular, recurrent pain, frequent seizures, frequent coughing, constipation and prescription of sleep medications were associated with abnormal sleep across the entire sample, but predictors differed between diagnostic groups. The present study suggests that comorbidities are more strongly associated with quality of sleep than functional impairments. The present study provides new information on potential associations between frequent coughing, prescription sleep medications and sleep quality that should be further investigated.

Functioning, participation, and quality of life in children with intellectual disability: an observational study.

AIMS: To investigate associations between functioning, community participation, and quality of life (QoL) and identify whether participation mediates the effects of functioning on QoL. METHOD: The caregivers of 435 children (211 females, 224 males; mean age 12y; SD 3y 11mo; age range 5-18y) with intellectual disability and autism spectrum disorder, cerebral palsy, Down syndrome, or Rett syndrome reported on their child's functioning (dependence for managing personal needs, mobility, communication, eye contact when speaking), frequency of participation, and QoL. Linear regression and mediation analyses were used to evaluate the relationships between child functioning, participation, and QoL. RESULTS: Children with greater dependency for managing personal needs and limited eye contact when speaking experienced poorer QoL. Less impaired functioning was associated with more frequent participation, which, in turn, was associated with a 3-point gain in QoL for each additional point in frequency of participation (coefficient=2.67, 95% confidence interval 1.56-3.78). The effect of impaired functioning on QoL was partially mediated by participation in children with greater dependency in managing personal needs and those with mildly impaired communication. INTERPRETATION: Greater levels of impairments with poorer functioning, notably a high level of dependence, were associated with poorer QoL. Poorer QoL can be partly explained by less frequent community participation.

Energy drink intake is associated with insomnia and decreased daytime functioning in young adult females.

OBJECTIVE: To investigate the association between energy drink (ED) use and sleep-related disturbances in a population-based sample of young adults from the Raine Study. DESIGN: Analysis of cross-sectional data obtained from self-administered questionnaires to assess ED use and sleep disturbance (Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire (FOSQ-10) and the Pittsburgh Sleep Symptoms Questionnaire-Insomnia (PSSQ-I)). Regression modelling was used to estimate the effect of ED use on sleep disturbances. All models adjusted for various potential confounders. SETTING: Western Australia. PARTICIPANTS: Males and females, aged 22 years, from Raine Study Gen2-22 year follow-up. RESULTS: Of the 1115 participants, 66 % were never/rare users (i.e. once/month to

Comorbidities and quality of life in children with intellectual disability.

BACKGROUND: Many children with intellectual disability live with medical comorbidities. This study examined the impacts of comorbidities on quality of life (QOL) of children with intellectual disabilities and whether impacts varied with caregiver perceptions that medical needs had been met. METHODS: Primary caregivers of 447 children (aged 5-19 years) with an intellectual disability reported on their child's medical comorbidities and the extent to which they perceived their child's medical needs had been met in a cross-sectional observational study. The Quality of Life Inventory-Disability was used to measure QOL on a 100-point scale. Linear regression models including interaction terms were used to evaluate their associations. RESULTS: Parent-reported recurrent child pain (-4.97, 95% CI -8.21, -1.72), night-time sleep disturbances (-4.98, 95% CI -7.23, -2.73), daytime somnolence (-8.71, 95% CI -11.30, -2.73), seizures that occurred at least weekly (-7.59, 95% CI -13.50, -1.68) and conservatively managed severe scoliosis (-7.39, 95% CI -12.97, -1.81) were negatively associated with child QOL. Despite the majority of parents (~70%) perceiving that their child's medical needs had been met to a great extent, this did not significantly moderate the association between any comorbidities and QOL. CONCLUSIONS: Comorbidities were common and had marked associations with QOL. Evaluation and management of pain and sleep disturbance continue to be high priorities in improving QOL of young people with intellectual disabilities. Further research on the optimal methods of managing these comorbidities is warranted.

Risk of Hospitalizations Following Gastrostomy in Children with Intellectual Disability.

OBJECTIVE: To examine the frequency of hospital admissions before and after gastrostomy insertion in children with severe intellectual disability. STUDY DESIGN: We conducted a retrospective cohort study using linked health administrative and disability data from Western Australia (WA) and New South Wales (NSW). Children born between 1983 and 2009 in WA and 2002 and 2010 in NSW who had a gastrostomy insertion performed (n = 673 [WA, n = 325; NSW, n = 348]) by the end of 2014 (WA) and 2015 (NSW) were included. Conditional Poisson regression models were used to evaluate the age-adjusted effect of gastrostomy insertion on acute hospitalizations for all-cause, acute lower respiratory tract infections (LRTI), and epilepsy admissions. RESULTS: The incidence of all-cause hospitalizations declined at 5 years after procedure (WA cohort 1983-2009: incidence rate ratio, 0.70 [95% CI, 0.60-0.80]; WA and NSW cohort 2002-2010: incidence rate ratio, 0.63 [95% CI, 0.45-0.86]). Admissions for acute LRTI increased in the WA cohort and remained similar in the combined cohort. Admissions for epilepsy decreased 4 years after gastrostomy in the WA cohort and were generally lower in the combined cohort. Fundoplication seemed to decrease the relative incidence of acute LRTI admissions in the combined cohort. CONCLUSIONS: Gastrostomy was associated with health benefits including reduced all-cause and epilepsy hospitalizations, but was not protective against acute LRTI. These decreases in hospitalizations may reflect improved delivery of nutrition and medications.

Energy drink intake and metabolic syndrome: A prospective investigation in young adults.

BACKGROUND AND AIMS: There are concerns that energy drinks (EDs) are contributing to upward trends in overweight, obesity, and cardiometabolic conditions in young people. We investigated cross-sectional and prospective associations between frequency of ED-intake in young-adults and (i) body mass index (BMI) and (ii) Metabolic Syndrome (MetS) and its components. METHODS AND RESULTS: Participants from the Raine Study at 20-years (n = 1236) and 22 years (n = 1117) self-reported ED-intake, dietary intake, and physical activity, and had blood and anthropometric measures taken. Regression modelling examined associations between ED-intake and BMI, MetS and its components. There was a positive, but not significant, cross-sectional association with BMI and likelihood of MetS with frequent ED use at 20-years (BMI: ß = 0.19; MetS: OR = 1.11) and 22-years (BMI: ß = 0.51; MetS: OR = 1.28). There were no associations in the prospective analysis. After adjustment, significant associations existed between occasional ED-intake and lower HDL-cholesterol (ß = -0.07) and higher fasting triglycerides (ß = 0.16) at 20-years, and lower fasting triglycerides at 22-years (ß = -0.10), but no significant associations in the prospective analyses. CONCLUSION: No significant associations existed between frequency of ED-intake, and BMI, MetS or its individual components over two years (ages 20-22 years). Future studies should include volume of EDs consumed and longer follow-up.

Prevalence estimates of mental health problems in children and adolescents with intellectual disability: A systematic review and meta-analysis.

BACKGROUND: Children and adolescents with intellectual disability are at risk of developing psychiatric symptoms and disorders; yet, the estimates reported in the literature have been inconsistent, presenting a potential barrier for service planning and delivery. Sources of variability could arise from differences in measurement instruments as well as subgroup membership by severity of intellectual disability, gender and age. This systematic review aimed to address these gaps. METHOD: MEDLINE and PsycINFO databases were searched from inception to 2018 and selected studies were reviewed. Studies were included if they reported point prevalence estimates of mental health symptomology or diagnoses in a general population of 6- to 21-year-old individuals with intellectual disability. The Joanna Briggs Institute Prevalence Critical Appraisal Checklist was applied to eligible papers to appraise their scientific strength. Pooled prevalence for mental health symptomology was determined using a random-effects meta-analysis. RESULTS: A total of 19 studies were included, including 6151 children and adolescents. The pooled prevalence estimate captured by the Developmental Behaviour Checklist was 38% (95% confidence interval = [31, 46]), contrasting with 49% (95% confidence interval = [46, 51]) captured by the Child Behaviour Checklist; both rates were higher than a non-intellectual disability population. Severity of intellectual disability did not significantly influence the Developmental Behaviour Checklist risks. Insufficient data were available to conduct statistical analyses on the effects of age, gender and socioeconomic status. Of diagnosed psychiatric disorders, attention deficit/hyperactivity disorder (30%), conduct disorder (3-21%) and anxiety disorders (7-34%) were the most prevalent conditions. CONCLUSION: This review consists of the largest sample hitherto evaluated. In the intellectual disability population, mental health comorbidities could be better detected by a symptom phenotype than a psychiatric diagnostic phenotype. Crucially, future research needs to address the effect of measurement validity in the intellectual disability population. Estimated prevalence rates were high compared to the general population, indicating the importance of systematic screening, case detection and appropriate management.

Benefits of powered standing wheelchair devices for adolescents with Duchenne muscular dystrophy in the first year of use.

AIM: Poorer physical and mental health often accompany loss of walking in Duchenne muscular dystrophy. This study assessed the impacts of powered wheelchair standing device (PWSD) use on muscle and joint pain, joint angles when standing and mental health in adolescents with Duchenne muscular dystrophy. METHODS: Fourteen adolescents and parents participated in a stepped wedge design study over 12 months. During a baseline and intervention period, adolescents described pain and mental health, and parents reported their child's mental health. Video data were collected to measure hip, knee and ankle joint angles in the preferred standing position. RESULTS: Compared with baseline and adjusting for covariates, standing wheelchair use was associated with no change in muscle or joint pain or videoed joint angles in standing. Child-reported Strengths and Difficulties total scores decreased (coefficient -3.1, 95% confidence interval -4.6, -1.5); and parent-reported Personal Adjustment and Role Skills Scale total scores increased (coefficient 7.9, 95% confidence interval 3.3-12.5). CONCLUSIONS: PWSD use was associated with maintenance of musculoskeletal status and advantages to mental health. Long-term observations are necessary to improve understanding of how to support wellbeing in adolescents with Duchenne muscular dystrophy.

Safety and Immunogenicity of Pneumococcal Conjugate Vaccines in a High-risk Population: A Randomized Controlled Trial of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccine in Papua New Guinean Infants.

BACKGROUND: There are little data on the immunogenicity of PCV10 and PCV13 in the same high-risk population. METHODS: PCV10 and PCV13 were studied head-to-head in a randomized controlled trial in Papua New Guinea in which 262 infants received 3 doses of PCV10 or PCV13 at 1, 2, and 3 months of age. Serotype-specific immunoglobulin G (IgG) concentrations, and pneumococcal and nontypeable Haemophilus influenzae (NTHi) carriage were assessed prevaccination and at 4 and 9 months of age. Infants were followed up for safety until 9 months of age. RESULTS: One month after the third dose of PCV10 or PCV13, ˃80% of infants had IgG concentrations ≥0.35µg/mL for vaccine serotypes, and 6 months postvaccination IgG concentrations ≥0.35 µg/mL were maintained for 8/10 shared PCV serotypes in > 75% of children vaccinated with either PCV10 or PCV13. Children carried a total of 65 different pneumococcal serotypes (plus nonserotypeable). At 4 months of age, 92% (95% confidence interval [CI] 85-96) of children vaccinated with PCV10 and 81% (95% CI 72-88) vaccinated with PCV13 were pneumococcal carriers (P = .023), whereas no differences were seen at 9 months of age, or for NTHi carriage. Both vaccines were well tolerated and not associated with serious adverse events. CONCLUSIONS: Infant vaccination with 3 doses of PCV10 or PCV13 is safe and immunogenic in a highly endemic setting; however, to significantly reduce pneumococcal disease in these settings, PCVs with broader serotype coverage and potency to reduce pneumococcal carriage are needed. CLINICAL TRIALS REGISTRATION: NCT01619462.

Psychometric properties of the Quality of Life Inventory-Disability (QI-Disability) measure.

PURPOSE: Children with intellectual disability encounter daily challenges beyond those captured in current quality of life measures. This study evaluated a new parent-report measure for children with intellectual disability, the Quality of Life Inventory-Disability (QI-Disability). METHODS: QI-Disability was administered to 253 primary caregivers of children (aged 5-18 years) with intellectual disability across four diagnostic groups: Rett syndrome, Down syndrome, cerebral palsy or autism spectrum disorder. Exploratory and confirmatory factor analyses were conducted and goodness of fit of the factor structure assessed. Associations between QI-Disability scores, and diagnostic and age groups were examined with linear regression. RESULTS: Six domains were identified: physical health, positive emotions, negative emotions, social interaction, leisure and the outdoors, and independence. Goodness-of-fit statistics were satisfactory and similar for the whole sample and when the sample was split by ability to walk or talk. On 100 point scales and compared to Rett syndrome, children with Down syndrome had higher leisure and the outdoors (coefficient 10.6, 95% CI 3.4,17.8) and independence (coefficient 29.7, 95% CI 22.9, 36.5) scores, whereas children with autism spectrum disorder had lower social interaction scores (coefficient - 12.8, 95% CI - 19.3, - 6.4). Scores for positive emotions (coefficient - 6.1, 95% CI - 10.7, - 1.6) and leisure and the outdoors (coefficient 5.4, 95% CI - 10.6, - 0.1) were lower for adolescents compared with children. CONCLUSIONS: Initial evaluation suggests that QI-Disability is a reliable and valid measure of quality of life across the spectrum of intellectual disability. It has the potential to allow clearer identification of support needs and measure responsiveness to interventions.

Epidemiology of gastrostomy insertion for children and adolescents with intellectual disability.

The largest group of recipients of pediatric gastrostomy have neurological impairment with intellectual disability (ID). This study investigated trends in first gastrostomy insertion according to markers of disadvantage and ID etiology. Linked administrative and health data collected over a 32-year study period (1983-2014) for children with ID born between 1983 and 2009 in Western Australia were examined. The annual incidence rate change over calendar year was calculated for all children and according to socioeconomic status, geographical remoteness, and Aboriginality. The most likely causes of ID were identified using available diagnosis codes in the linked data set. Of 11,729 children with ID, 325 (2.8%) received a first gastrostomy within the study period. The incidence rate was highest in the 0-2 age group and there was an increasing incidence trend with calendar time for each age group under 6 years of age. This rate change was greatest in children from the lowest socioeconomic status quintile, who lived in regional/remote areas or who were Aboriginal. The two largest identified groups of ID were genetically caused syndromes (15.1%) and neonatal encephalopathy (14.8%).Conclusion: Gastrostomy is increasingly used in multiple neurological conditions associated with ID, with no apparent accessibility barriers in terms of socioeconomic status, remoteness, or Aboriginality. What is Known: • The use of gastrostomy insertion in pediatrics is increasing and the most common recipients during childhood have neurological impairment, most of whom also have intellectual disability (ID). What is New: • Nearly 3% of children with ID had gastrostomy insertion performed, with the highest incidence in children under 3 years of age. • Gastrostomy use across different social groups was equitable in the Australian setting.