Construct Validity of the Both Hands Assessment Using Wrist-Worn Accelerometers.

AIM: The aim of this study was to evaluate the construct validity of the Both Hands Assessment (BoHA) using activity of the upper limbs as detected by accelerometry in children with bilateral cerebral palsy (CP). METHODS: Observational study of children with CP (n = 44, n = 27 boys, aged 9.1 ± 1.6 years; Manual Ability Classification Scale I: n = 15, II: n = 22, III: n = 7) completing a BoHA assessment while wearing a triaxial accelerometer on each wrist. BoHA Each-Hand sub-scores, BoHA percentage difference between hands, BoHA Units, mean activity for each hand, mean activity asymmetry index and total mean activity were calculated. Linear regressions were used to analyze associations between measures. RESULTS: There were significant, positive associations between BoHA Units and total mean activity (B = 0.86, 95%CI: 0.32, 1.40), BoHA Percentage difference between hands and mean activity asymmetry index (B = 0.95, 95%CI: 0.75,1.15), and BoHA Each-Hand sub-score and mean activity for the non-dominant hand (B = 1.71, 95%CI: 1.16, 2.28), but not the dominant hand (B = 0.50, 95%CI: -0.45, 1.45). CONCLUSIONS: This study provides further evidence for the construct validity of the BoHA as a measure of upper limb performance. Wearable wrist sensors such as accelerometers capture and quantify gross upper limb movement in children with CP but cannot measure fine finger movements captured by the BoHA. CLINICAL TRIALS REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12616001488493 and ACTRN12618000164291).

Development of social functioning in children with cerebral palsy: A longitudinal study.

AIM: To describe the development of social function in children with cerebral palsy (CP) classified in all levels of the Communication Function Classification System (CFCS). METHOD: This prospective, longitudinal population-based cohort study recruited children with CP born in Queensland, Australia. Social functioning was measured using the Pediatric Evaluation of Disability Inventory (PEDI) social function domain at 2 years, 2 years 6 months, 3 years, 4 years, and 5 years, and the PEDI Computer Adaptive Test (PEDI-CAT) social/cognitive domain at 8 to 12 years. RESULTS: Seventy-four children provided 356 observations. PEDI-CAT social/cognitive scaled scores at 8 to 12 years were (mean [SD] n) CFCS level I, 68.6 (2.7) 45; CFCS level II, 64.0 (3.4) 10; CFCS level III, 63.5 (3.7) 4; CFCS level IV, 56.8 (5.0) 9; CFCS level V, 47.2 (5.8) 6. Scores within expected range for age (not less than 2 SD below mean) at 8 to 12 years were achieved by 35 (78%) children in CFCS level I and four (14%) in CFCS levels II to V. Forty-nine per cent of children scored at least two standard deviations below the population mean on a proxy measure of fluid intelligence. Intellectual impairment was associated with lower PEDI-CAT social/cognitive scaled scores in univariable analysis (ß = -8.3, 95% confidence interval - 10.91 to -5.63; p < 0.001) but had a smaller effect when modelled together with CFCS. INTERPRETATION: Social function attained by 8 to 12 years of age was strongly related to level of communication function (CFCS). The small number of children classified in CFCS levels II to V necessitates caution when viewing these individual CFCS level trajectories. WHAT THIS PAPER ADDS: There is a strong relation between social functioning and Communication Function Classification System (CFCS) levels. At 8 to 12 years, 35 out of 45 children in CFCS level I met social functioning age expectations. Twenty-five out of 29 in CFCS levels II to V had social functioning below that expected for age. CFCS and age were more strongly associated with development of social functioning than Gross Motor Function Classification System or Manual Ability Classification System and age.

Development of gross motor capacity and mobility performance in children with cerebral palsy: a longitudinal study.

AIM: To describe development of gross motor capacity and mobility performance in children with cerebral palsy. METHOD: This longitudinal cohort study measured gross motor capacity with the Gross Motor Function Measure and mobility performance with the Pediatric Evaluation of Disability Inventory (PEDI) between 18 months and 5 years, and the PEDI - Computer Adaptive Test (PEDI-CAT) between 8 years and 12 years. Longitudinal analyses used mixed-effects regression modelling with interaction between age and Gross Motor Function Classification System (GMFCS). Stability of GMFCS levels over time was measured using agreement. RESULTS: Two hundred and twenty-two children provided 871 observations (median 4 observations, range 1-7). Children classified in GMFCS level I improved in both capacity and performance until 8 to 12 years. Children classified in GMFCS levels II and III continued to develop mobility performance after gross motor capacity had plateaued at 5 years. Children classified in GMFCS level IV plateaued at 5 years in capacity and performance. Children classified in GMFCS level V showed no changes in capacity or performance between 18 months and 8 to 12 years. Stability of GMFCS levels was 73%. INTERPRETATION: Change in mobility performance over time somewhat reflected gross motor capacity trajectories. Continued improvement in mobility performance after plateau of gross motor capacity for children classified in GMFCS levels II and III suggests importance of other personal or environmental factors.

Hand function and self-care in children with cerebral palsy.

AIM: To examine the relationship between self-care and bimanual performance in children aged 8 to 12 years with cerebral palsy (CP). METHOD: This was a cross-sectional study of 74 children with CP (unilateral n=30, bilateral n=44; 48 males, 26 females; median age 9y 8mo [25th, 75th centiles 9y 1mo, 10y 8mo], Manual Abilities Classification System level I=30, II=28, III=16). Self-care was measured using the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT), and bimanual performance using the Assisting Hand Assessment (AHA) and Both Hands Assessment (BoHA). Measures of cognition, behavioural regulation, inattention, and gross motor function were included. Analyses used a directed acyclic graph to select variables for linear regression modelling. RESULTS: Higher AHA and BoHA scores were associated with higher PEDI-CAT scores. An increase of 1 AHA unit was associated with an increase of 0.12 PEDI-CAT scores, and a 1 BoHA unit increase was associated with an increase of 0.17 PEDI-CAT scores. The BoHA accounted for 57% of variance in PEDI-CAT scores for children with bilateral CP, while BoHA and cognition accounted for 68% of variance. The AHA accounted for 40% of variance in PEDI-CAT scores for unilateral CP with no effect of cognition on self-care. INTERPRETATION: Self-care was strongly and positively associated with bimanual performance. Associations between self-care and bimanual performance differed for those with unilateral and bilateral CP. WHAT THIS PAPER ADDS: There is a strong positive relationship between self-care and bimanual performance for unilateral and bilateral cerebral palsy (CP). Both Hands Assessment (BoHA) scores have a stronger association with self-care than Assisting Hand Assessment scores. BoHA scores also account for more variation in self-care. There is a strong positive relationship between self-care and cognition overall. The effect of cognition on self-care performance differed for bilateral and unilateral CP.

Hand Function in 8- to 12-Year-Old Children with Bilateral Cerebral Palsy and Interpretability of the Both Hands Assessment.

AIM: To describe bimanual performance in a sample of Australian children with bilateral cerebral palsy (CP) and, examine the qualitative meaning (or interpretability) of scores on the Both Hands Assessment (BoHA). METHODS: Children with bilateral CP aged 8-12 years (n = 54) classified Manual Ability Classification System (MACS) level I = 20, II = 18, III = 16 were examined using the BoHA. RESULTS: Bimanual performance was significantly different across MACS levels I-III (p < 0.001). Mean (95%CI) BoHA-unit for each MACS level were I = 85 (81-89), II = 72 (68-76) and III = 53 (49-56). Children with asymmetrical hand use (≥ 20% difference between upper limbs, n = 10) were classified MACS levels II and III and had a mean (95%CI) BoHA-unit of 56 (51-62). Children with symmetrical hand use were classified in MACS level I-III and had a mean (95%CI) BoHA-unit of 74 (70-79). CONCLUSIONS: The BoHA quantified observations of bimanual performance for children with bilateral CP, differentiated between MACS levels I-III and provided clinically meaningful information. The BoHA may facilitate tailoring of upper limb intervention. Future research is recommended to examine inter-rater and intra-rater reliability and responsiveness of the BoHA, as well as longitudinal studies of bimanual hand skill development in children with bilateral CP.

Self-care performance in children with cerebral palsy: a longitudinal study.

AIM: To investigate self-care developmental trajectories in children with cerebral palsy (CP) across all functional ability levels, according to Manual Ability Classification System (MACS) levels. METHOD: This was a prospective longitudinal population-based study of 71 children aged from 2 years 6 months to 12 years, with CP (47 [66%] males, 24 [34%] females). Pediatric Evaluation of Disability Inventory (PEDI) measures were taken at 2 years 6 months, 3, 4, and 5 years, and the PEDI - Computer Adaptive Test (PEDI-CAT) between 8 and 12 years. At 8 to 12 years, children were classified in MACS levels I (21; 30%), II (22; 31%), III (16; 23%), IV (6; 8%), and V (6; 8%). Longitudinal analysis of the PEDI Functional Skills Scale self-care and PEDI-CAT daily activities domains used the published linking equation, and multilevel mixed-effects regression modelling with interaction between age and MACS. RESULTS: Between 5 and 12 years of age, children classified in MACS levels I to III continued to show progress in self-care development (PEDI-CAT scaled scores estimated change per year: I, 0.72; II, 0.49; III, 0.48). Children classified in MACS level IV showed an upward non-significant trend between 5 and 8 to 12 years (estimated change 0.42; 95% confidence interval [CI] -0.04 to 0.88). Children in MACS level V showed a decline in self-care (estimated change: -0.65; 95% CI -1.16 to -0.14). INTERPRETATION: Self-care development attained by 8 to 12 years of age was related to the severity of manual ability impairment. Application of the linking equation from PEDI to PEDI-CAT is somewhat uncertain at the extreme lower end of the scale. Our study supports recommendations for items to be added to the PEDI-CAT to address floor effect.

Self-care and manual ability in preschool children with cerebral palsy: a longitudinal study.

AIM: To describe longitudinal development of self-care and its relationship to manual ability in children with cerebral palsy (CP) aged 18 months to 5 years across all functional abilities. METHOD: This was a prospective longitudinal population-based study of 290 children with CP (178 [61%] males, 112 [39%] females). Self-care was assessed using the Pediatric Evaluation of Disability Inventory (PEDI). At 60 months (n=242), children were classified using the Manual Ability Classification System (MACS); 113 in level I (47%), 61 in MACS level II (25%), 24 in MACS level III (10%), 14 in MACS level IV (6%), and 30 in MACS level V (12%). Measures were taken at 18 months, 24 months, 30 months, 36 months, 48 months, and 60 months of age. Longitudinal analyses were performed using mixed-effects linear regression models. RESULTS: Self-care development achieved by 60 months was negatively associated with the severity of manual ability impairment. Distinct self-care developmental trajectories were found with estimated changes in PEDI self-care scaled scores per month: 0.61 for MACS level I, 0.46 for MACS levels II, 0.31 for MACS level III, 0.16 for MACS level IV, and 0.03 for MACS level V. Children classified in MACS level V had the lowest level of self-care skills at 18 months and showed no progress in self-care development. INTERPRETATION: This study reports rate of self-care development in preschool children with CP. Self-care performance was highest in children with greatest manual ability. Clinicians may use rates of change to predict or monitor self-care performance. PEDI trajectories inform goal setting in discussions with families regarding expected levels of independence in self-care. WHAT THIS PAPER ADDS: Distinct self-care developmental trajectories in children with cerebral palsy were found according to Manual Ability Classification System (MACS) levels. Children in MACS levels IV and V with epilepsy did not show any significant change in self-care. Children in MACS levels IV and V without epilepsy demonstrated small yet significant gains in self-care performance.

AUTOCUIDADO Y HABILIDAD MANUAL EN NIÑOS PREESCOLARES CON PARÁLISIS CEREBRAL: UN ESTUDIO LONGITUDINAL: OBJETIVO: Describir el desarrollo longitudinal del autocuidado en niños con parálisis cerebral (PC) de edades comprendidas entre los 18 meses y los 5 años de edad en todas las habilidades funcionales y su relación con la habilidad manual. MÉTODO: Se trata de un estudio prospectivo longitudinal basado en una población de 290 niños con PC (178 [61%] niños, 112 [39%] niñas). El autocuidado se evaluó utilizando el Inventario de Evaluación Pediátrica de Discapacidad (Pediatric Evaluation of Disability Inventory, PEDI). A los 60 meses (n=242), los niños se clasificaron usando el Sistema de Clasificación de la Habilidad Manual (Manual Ability Classification System, MACS); 113 en el nivel I (47%), 61 en el nivel MACS II (25%), 24 en el nivel MACS III (10%), 14 en el nivel MACS IV (6%), y 30 en el nivel MACS V (12%). Las mediciones se tomaron a los 18 meses, 24 meses, 30 meses, 36 meses, 48 meses, y 60 meses de edad. Los análisis longitudinales se realizaron utilizando modelos de regresión lineal de efectos mixtos. RESULTADOS: El desarrollo del autocuidado logrado a los 60 meses se asoció negativamente a la severidad de la alteración de la habilidad manual. Se encontraron trayectorias del desarrollo del autocuidado distintas con cambios estimados de los puntajes escalados del autocuidado de PEDI por mes: 0,61 para el nivel MACS de I, 0,46 para el nivel MACS de II, 0,31 para el nivel MACS de III, 0,16 para el nivel MACS de IV, y 0,03 para el nivel MACS de V. Los niños clasificados con el nivel MACS de V tuvieron el nivel más bajo de las destrezas de autocuidado a los 18 meses y no mostraron progreso en el desarrollo del autocuidado. INTERPRETACIÓN: Este estudio informa sobre la tasa de desarrollo del autocuidado en niños preescolares con PC. El desempeño del autocuidado fue mayor en niños con la mayor habilidad manual. Los profesionales podrian utilizar las tasas de cambio para predecir o monitorizar el desempeño del autocuidado. Las trayectorias de PEDI informan el establecimiento de objetivos, mediante un dialogo con las familias, basados en los niveles de independencia esperados en el autocuidado.

AUTO-CUIDADO E HABILIDADE MANUAL EM CRIANÇAS PRÉ-ESCOLARES COM PARALISIA CEREBRAL: UM ESTUDO LONGITUDINAL: OBJETIVO: Descrever o desenvolvimento longitudinal do auto-cuidado em crianças com paralisia cerebral (PC) com idades entre 18 meses e 5 anos em todos os níveis de capacidade funcional e sua relação com a habilidade manual. MÉTODO: Este estudo populacional com desenho prospectivo e longitudinal incluiu 290 crianças com PC (178 [61%] do sexo masculino, 112 [39%] do sexo feminino). O auto-cuidado foi avaliado usando o Inventário pediátrico de avaliação da disfunção (PEDI). Aos 60 meses (n=242), as crianças foram classificadas usando o Sistema de Classificação da Habilidade Manual (MACS); 113 no nível I (47%), 61 no nível MACS II (25%), 24 no nível MACS III (10%), 14 no nível MACS level IV (6%), e 30 no nível MACS V (12%). As medidas foram realizadas aos 18, 24, 30, 36, 48 e 60 meses de idade. RESULTADOS: O desenvolvimento do auto-cuidado atingido aos 60 meses foi negativamente associado com a severidade do comprometimento da habilidade manual. Trajetórias distintas do desenvolvimento do auto-cuidado foram encontradas com mudanças estimadas nos scaled escores de auto-cuidado do PEDI por mês: 0,61 para nível MACS I, 0.46 para nível MACS II, 0,31 para nível MACS III, 0,16 para nível MACS IV, e 0,03 para nível MACS V. Crianças classificadas no nível MACS V tiveram o menor nível de habilidades de auto-cuidado aos 18 meses e não mostraram nenhum progresso no desenvolvimento do auto-cuidado. INTERPRETAÇÃO: Este estudo relata a taxa do desenvolvimento do auto-cuidado em crianças pré-escolares com PC. O desempenho do auto-cuidado foi o mais alto em crianças com maior habilidade manual. Clínicos podem usar as taxas de mudança para predizer ou monitorar o desempenho do auto-cuidado. As trajetórias do PEDI informam o estabelecimento de objetivos nas discussões com as famílias com relação aos níveis esperados de independência no auto-cuidado.

Stability of the Manual Ability Classification System in young children with cerebral palsy.

AIM: To examine the stability over time of the Manual Ability Classification System (MACS) levels in children with cerebral palsy (CP) aged 18 to 60 months. METHOD: This was a prospective longitudinal population-based study of 252 Australian children (160 males [63%] 92 females [37%]; mean age [SD] 41.7mo [14], range 17.2mo-69.2mo) with CP. Children were classified at 18 months (n=70), 24 months (n=131), 30 months (n=173), 36 months (n=209), 48 months (n=226), and 60 months (n=221) of age. Stability of the MACS was examined using the proportion of specific positive agreement and transition proportions, which are measures of agreement. RESULTS: There were 1030 unique observations, with each of the 252 participants seen between two and six occasions (median=4). Average specific positive agreement over the study period was 76% for MACS level I, 67% for level II, 50% for level III, 51% for level IV, and 83% for level V. MACS levels I and V have the highest degree of stability, while levels III and IV have the lowest. We show how this may be explained by the proportion of children in each MACS level. INTERPRETATION: Using measures of agreement rather than measures of reliability provides accurate information when measuring stability over time of an ordinal classification system. The relative stability of MACS levels can be explained by the proportion of children in each level. WHAT THIS PAPER ADDS: Children classified in Manual Ability Classification System (MACS) levels III and IV change levels at next assessment about 50% of the time. Children should be assessed with the MACS regularly, particularly those in levels III and IV. Stability within ordinal classification level categories can be predicted using a measurement error model. Transition proportions or specific agreement is recommended for reporting stability of ordinal classification systems.

Estabilidade do Sistema de Classificação da Habilidade Manual (MACS) em crianças jovens com paralisia cerebral OBJETIVO: Examinar a estabilidade ao longo do tempo dos níveis do Sistema de Classificação da Habilidade Manual (MACS) em crianças com paralisia cerebral (PC) com idade entre 18 e 60 meses. MÉTODO: Este foi um estudo prospectivo de caráter longitudinal, com amostra baseada no estudo da população de 252 crianças Australianas (160 meninos [63%], 92 meninas [37%]; idade média [desvio padrão] de 41,7 meses [14], variação de 17, 2 a 69, 2 meses de idade]) com PC. As crianças foram classificadas aos 18 meses (n = 70), 24 meses (n = 131), 30 meses (n = 173), 36 meses (n = 209), 48 meses (n = 226), e aos 60 meses (n = 221) de idade. A estabilidade do MACS foi examinada utilizando a proporção de concordância positiva específica e proporções de transição, sendo estas as medidas de concordância. RESULTADOS: Foram realizadas um total de 1.030 observações com os 252 participantes, os quais foram avaliados individualmente entre dois e seis momentos (média = 4). A média de concordância específica positiva durante o estudo foi de 76% para MACS nível I, 67% para nível II, 50% para nível III, 51% para nível IV, e 83% para nível V. Os classificados com MACS nível I e V tiveram os maiores graus de estabilidade, enquanto os classificados com os níveis III e IV tiveram os menores graus de estabilidade. Estes resultados podem ser explicados pela proporção de crianças classificadas em cada nível do MACS. INTERPRETAÇÃO: A utilização de medidas de concordância ao invés de medidas de confiabilidade proporciona informações mais precisas quando se mensura estabilidade ao longo do tempo com um sistema de classificação ordinal. A estabilidade relativa dos níveis do MACS pode ser explicada pela proporção de crianças classificadas em cada nível.

Estabilidad del Sistema de Clasificación de Habilidad Manual (MACS) en niños pequeños con parálisis cerebral OBJETIVO: Examinar la estabilidad en el tiempo de los niveles del Sistema de Clasificación de Habilidad Manual (MACS) en niños con parálisis cerebral (PC) de 18 a 60 meses. MÉTODO: Este fue un estudio prospectivo longitudinal basado en la población de 252 niños australianos (160 [63%] hombres, 92 mujeres [37%]; edad media [DE] 41.7mo [14], rango 17.2mo-69.2mo]) con PC. Los niños se clasificaron a los 18 meses (n = 70), 24 meses (n = 131), 30 meses (n = 173), 36 meses (n = 209), 48 meses (n = 226) y 60 meses (n = 221) de edad. La estabilidad del MACS se examinó utilizando la proporción de acuerdo positivo específico y las proporciones de transición, que son medidas de acuerdo. RESULTADOS: Con cada uno de los 252 participantes vistos entre dos y seis ocasiones (mediana = 4) hubo 1030 observaciones únicas. La concordancia positiva específica promedio durante el período de estudio fue de 76% para MACS nivel I, 67% para nivel II, 50% para nivel III, 51% para nivel IV y 83% para nivel V. Los niveles I y V de MACS son los más altos de estabilidad, mientras que los niveles III y IV tienen los más bajos. Mostramos cómo esto puede explicarse por la proporción de niños en cada nivel de MACS. INTERPRETACIÓN: El uso de medidas de acuerdo - en lugar de medidas de confiabilidad - proporciona información precisa cuando se mide la estabilidad en el tiempo de un sistema de clasificación ordinal. La estabilidad relativa de los niveles de MACS puede explicarse por la proporción de niños en cada nivel.

A systematic review of upper limb activity measures for 5- to 18-year-old children with bilateral cerebral palsy.

AIM: To investigate measurement properties and feasibility of upper limb activity measures in children aged 5-18 years with bilateral cerebral palsy (CP). METHODS: Five electronic databases were searched to identify measures of upper limb activity with published psychometric data for children with bilateral CP aged 5-18 years. Measures included both Patient-Reported Outcome Measures (PROMs) and observational measures. The COnsensus-based Standards for selection of health Measurement Instruments checklist was used to evaluate methodological quality of studies for each measure. RESULTS: Forty-eight measures were identified, eight of which met inclusion criteria for reliability and validity. Four PROMs were included: the ABILHAND-Kids and Children's Arm Rehabilitation Measure are parent questionnaires measuring overall manual ability; the ACTIVLIM-CP is a parent questionnaire measuring global activity (upper and lower extremity) performance, and, the Pediatric Upper Limb Measure, Short Form is a child self-report questionnaire. Four observational measures were included: the Both Hands Assessment (BoHA) is an observational measure of bimanual activity performance; the Melbourne Assessment of Unilateral Upper Limb Function and the Melbourne Assessment 2 measure quality of movement of each upper limb separately, and the Peabody Developmental Motor Scales-Second Edition assesses fine motor skill capacity in young children. Based upon available evidence, the most suitable PROM for evaluation of upper limb activity in children with bilateral CP is the ACTIVLIM-CP, and the most suitable observational measure is the BoHA. CONCLUSION: Selection of upper limb measures depend on clinical information required and available resources. The BoHA is the only observational-based assessment which measures bimanual upper limb activity performance in children with bilateral CP. Recommendation for future measurement studies include familiarisation with the standards required for excellence, which include adequate sample size and content validity studies for PROMs.

Low Concentrations of Nitric Oxide Modulate Streptococcus pneumoniae Biofilm Metabolism and Antibiotic Tolerance.

Streptococcus pneumoniaeis one of the key pathogens responsible for otitis media (OM), the most common infection in children and the largest cause of childhood antibiotic prescription. Novel therapeutic strategies that reduce the overall antibiotic consumption due to OM are required because, although widespread pneumococcal conjugate immunization has controlled invasive pneumococcal disease, overall OM incidence has not decreased. Biofilm formation represents an important phenotype contributing to the antibiotic tolerance and persistence ofS. pneumoniaein chronic or recurrent OM. We investigated the treatment of pneumococcal biofilms with nitric oxide (NO), an endogenous signaling molecule and therapeutic agent that has been demonstrated to trigger biofilm dispersal in other bacterial species. We hypothesized that addition of low concentrations of NO to pneumococcal biofilms would improve antibiotic efficacy and that higher concentrations exert direct antibacterial effects. Unlike in many other bacterial species, low concentrations of NO did not result inS. pneumoniaebiofilm dispersal. Instead, treatment of bothin vitrobiofilms andex vivoadenoid tissue samples (a reservoir forS. pneumoniaebiofilms) with low concentrations of NO enhanced pneumococcal killing when combined with amoxicillin-clavulanic acid, an antibiotic commonly used to treat chronic OM. Quantitative proteomic analysis using iTRAQ (isobaric tag for relative and absolute quantitation) identified 13 proteins that were differentially expressed following low-concentration NO treatment, 85% of which function in metabolism or translation. Treatment with low-concentration NO, therefore, appears to modulate pneumococcal metabolism and may represent a novel therapeutic approach to reduce antibiotic tolerance in pneumococcal biofilms.

Sleep problems in a population-based cohort of primary school age children with Cerebral Palsy.

AIMS: To examine sleep problems in a population-based sample of school-aged children (8-12yo) with Cerebral Palsy (CP) METHOD: Eighty-six children (mean 9 years, 5 months, SD = 1 year, 6 months; male = 60) with CP (Gross Motor Function Classification System; GMFCS I=46; II=21; III=9; IV=6; V=6) participated. Classifications/assessments included: Sleep Disturbance Scale for Children (SDSC), Gross Motor Function Measure (GMFM-66), Manual Ability Classification System (MACS), Communication Function Classification System (CFCS), Strengths and Difficulties Questionnaire (SDQ) and the Cerebral Palsy- Quality of Life (CP-QOL) Pain Impact subscale. Analysis included linear and logistic regression. RESULTS: 38 (44 %) children were within the clinical range for sleep problems. Sleep problems were significantly associated with epilepsy, (95 % CI) = 14.48 (7.95 to 21.01), gross motor function, -0.13 (-0.26 to -0.01), manual ability, 7.26 (0.82 to 13.69), communication, 10.01 (2.21 to 17.80), child behaviour, 1.134 (0.74 to 1.53), and pain related QOL, 0.33 (0.12 to 0.53). For the multivariable model, sleep problems remained significantly associated with epilepsy, b (95 % CI) = 11.72 (4.88 to 18.57), child behaviour, 1.03 (0.65 to 1.41) and pain-related QOL, 0.21 (0.29 to 0.38). CONCLUSIONS: Sleep problems are common and associated with epilepsy, child behaviour and pain related QOL.

Association between upper and lower respiratory disease among patients with primary ciliary dyskinesia: an international study.

Introduction: Nearly all patients with primary ciliary dyskinesia (PCD) report ear-nose-throat (ENT) symptoms. However, scarce evidence exists about how ENT symptoms relate to pulmonary disease in PCD. We explored possible associations between upper and lower respiratory disease among patients with PCD in a multicentre study. Methods: We included patients from the ENT Prospective International Cohort (EPIC-PCD). We studied associations of several reported ENT symptoms and chronic rhinosinusitis (defined using patient-reported information and examination findings) with reported sputum production and shortness of breath, using ordinal logistic regression. In a subgroup with available lung function results, we used linear regression to study associations of chronic rhinosinusitis and forced expiratory volume in 1 s (FEV1) accounting for relevant factors. Results: We included 457 patients (median age 15 years, interquartile range 10-24 years; 54% males). Shortness of breath associated with reported nasal symptoms and ear pain of any frequency, often or daily hearing problems, headache when bending down (OR 2.1, 95% CI 1.29-3.54) and chronic rhinosinusitis (OR 2.3, 95% CI 1.57-3.38) regardless of polyp presence. Sputum production associated with daily reported nasal (OR 2.2, 95% CI 1.20-4.09) and hearing (OR 2.0, 95% CI 1.10-3.64) problems and chronic rhinosinusitis (OR 2.1, 95% CI 1.48-3.07). We did not find any association between chronic rhinosinusitis and FEV1. Conclusion: Reported upper airway symptoms and signs of chronic rhinosinusitis associated with reported pulmonary symptoms, but not with lung function. Our results emphasise the assessment and management of upper and lower respiratory disease as a common, interdependent entity among patients with PCD.

The behavioral and neurobiological relationships between executive function and reading: A review and preliminary findings.

Despite decades of prior research, the mechanisms for how skilled reading develops remain elusive. Numerous studies have identified word recognition and oral language ability as key components to explain later reading comprehension performance. However, these components alone do not fully explain differences in reading achievement. There is ongoing work exploring other candidate processes important for reading, such as the domain-general cognitive ability of executive function (EF). Here, we summarize our work on the behavioral and neurobiological connections between EF and reading and present preliminary neuroimaging findings from ongoing work. Together, these studies suggest 1) that EF plays a supportive and perhaps indirect role in reading achievement and 2) that EF-related brain regions interface with the reading and language networks. While further work is needed to dissect the specifics of how EF interacts with reading, these studies begin to reveal the complex role that EF plays in reading development.

Female and male obese Zucker rats display differential inflammatory mediator and long non-coding RNA profiles.

AIMS: The goal of this study was to identify mediators in peri-lymphatic adipose tissue (PLAT) that are altered in obese versus lean Zucker rats, with focus on potential sex differences MAIN METHODS: Mesenteric PLAT was analyzed with protein and lncRNA arrays. Additional RT-PCR confirmation was performed with epididymal/ovarian fat. KEY FINDINGS: MCP-1, TCK-1, Galectin-1, Galectin-3, and neuropilin-1 were elevated in PLAT from obese rats of both sexes. However, 11 additional proteins were elevated only in obese males while 24 different proteins were elevated in obese females. Profiling of lncRNAs revealed lean males have elevated levels of NEAT1, MALAT1 and GAS5 compared to lean females. NEAT1, MALAT1, and GAS5 were significantly reduced with obesity in males but not in females. Another lncRNA, HOTAIR, was higher in lean females compared to males, and its levels in females were reduced with obesity. Obese rats of both sexes had similar histologic findings of mesenteric macrophage crown-like structures and hepatocyte fat accumulation. SIGNIFICANCE: While obese male and female Zucker rats both have increased inflammation, they have distinct signals. Future studies of the proteome and lncRNA landscape of obese males vs. females in various animal models and in human subjects are warranted to better guide development of therapeutics for obesity-induced inflammation.

School readiness of children at high risk of cerebral palsy randomised to early neuroprotection and neurorehabilitation: protocol for a follow-up study of participants from four randomised clinical trials.

INTRODUCTION: School readiness includes cognitive, socio-emotional, language and physical growth and development domains which share strong associations with life-course opportunities. Children with cerebral palsy (CP) are at increased risk of poor school readiness compared with their typically developing peers. Recently, earlier diagnosis of CP has allowed interventions to commence sooner, harnessing neuroplasticity. First, we hypothesise that early referral to intervention for children at-risk of CP will lead to improved school readiness at 4-6 years relative to placebo or care as usual. Second, we hypothesise that receipt of early diagnosis and early intervention will lead to cost-savings in the form of reduced healthcare utilisation. METHODS AND ANALYSIS: Infants identified as at-risk of CP ≤6 months corrected age (n=425) recruited to four randomised trials of neuroprotectants (n=1), early neurorehabilitation (n=2) or early parenting support (n=1) will be re-recruited to one overarching follow-up study at age 4-6 years 3 months. A comprehensive battery of standardised assessments and questionnaires will be administered to assess all domains of school readiness and associated risk factors. Participants will be compared with a historical control group of children (n=245) who were diagnosed with CP in their second year of life. Mixed-effects regression models will be used to compare school readiness outcomes between those referred for early intervention versus placebo/care-as-usual. We will also compare health-resource use associated with early diagnosis and intervention versus later diagnosis and intervention. ETHICS AND DISSEMINATION: The Children's Health Queensland Hospital and Health Service, The University of Queensland, University of Sydney, Monash University and Curtin University Human Research Ethics Committees have approved this study. Informed consent will be sought from the parent or legal guardian of every child invited to participate. Results will be disseminated in peer-reviewed journals, scientific conferences and professional organisations, and to people with lived experience of CP and their families. TRIAL REGISTRATION NUMBER: ACTRN12621001253897.

Sinonasal disease among patients with primary ciliary dyskinesia: an international study.

Background: Sinonasal symptoms are a common feature of primary ciliary dyskinesia (PCD); however, literature about their severity and frequency, particularly during the life course, is scarce. Using baseline data from the Ear, nose and throat (ENT) Prospective International Cohort of PCD patients, we describe sinonasal disease in PCD. Methods: We included participants who had a routine sinonasal examination during which they completed a symptoms questionnaire. We compared frequency of reported symptoms and examination findings among children and adults, and identified characteristics potentially associated with higher risk of sinonasal disease using ordinal regression. Results: 12 centres contributed 384 participants; median age was 16 years (IQR 9-22), and 54% were male. Chronic nasal problems were the most common feature, reported by 341 (89%). More adults (33; 24%) than children (10; 4%) described hyposmia. Quality of life was moderately affected by rhinosinusitis among 136 participants with completed SNOT-22 questionnaires (median score 31; IQR 23-45). Examinations revealed nasal polyps among 51 of 345 participants (15%) and hypertrophic inferior nasal turbinates among 127 of 341 participants (37%). Facial pain was detected in 50 of 342 participants (15%). Nasal polyps, hypertrophic turbinates, deviated septum and facial pain were found more commonly in adults than children. The only characteristic associated with higher risk of sinonasal disease was age 10 years and older. Conclusions: Based on our findings, regular sinonasal examinations are relevant for patients with PCD of all ages. There is a need for improved management of sinonasal disease supported by evidence-based guidelines.

Characteristics of Otologic Disease Among Patients With Primary Ciliary Dyskinesia.

Importance: Otologic disease is common among people with primary ciliary dyskinesia (PCD), yet little is known about its spectrum and severity. Objective: To characterize otologic disease among participants with PCD using data from the Ear-Nose-Throat Prospective International Cohort. Design, Setting, and Participants: This cross-sectional analysis of baseline cohort data from February 2020 through July 2022 included participants from 12 specialized centers in 10 countries. Children and adults with PCD diagnoses; routine ear, nose, and throat examinations; and completed symptom questionnaires at the same visit or within 2 weeks were prospectively included. Exposures: Potential risk factors associated with increased risk of ear disease. Main Outcomes and Measures: The prevalence and characteristics of patient-reported otologic symptoms and findings from otologic examinations, including potential factors associated with increased risk of ear inflammation and hearing impairment. Results: A total of 397 individuals were eligible to participate in this study (median [range] age, 15.2 [0.2-72.4] years; 186 (47%) female). Of the included participants, 204 (51%) reported ear pain, 110 (28%) reported ear discharge, and 183 (46%) reported hearing problems. Adults reported ear pain and hearing problems more frequently when compared with children. Otitis media with effusion-usually bilateral-was the most common otoscopic finding among 121 of 384 (32%) participants. Retracted tympanic membrane and tympanic sclerosis were more commonly seen among adults. Tympanometry was performed for 216 participants and showed pathologic type B results for 114 (53%). Audiometry was performed for 273 participants and showed hearing impairment in at least 1 ear, most commonly mild. Season of visit was the strongest risk factor for problems associated with ear inflammation (autumn vs spring: odds ratio, 2.40; 95% CI, 1.51-3.81) and age 30 years and older for hearing impairment (41-50 years vs ≤10 years: odds ratio, 3.33; 95% CI, 1.12-9.91). Conclusion and Relevance: In this cross-sectional study, many people with PCD experienced ear problems, yet frequency varied, highlighting disease expression differences and possible clinical phenotypes. Understanding differences in otologic disease expression and progression during lifetime may inform clinical decisions about follow-up and medical care. Multidisciplinary PCD management should be recommended, including regular otologic assessments for all ages, even without specific complaints.

Identifying a brain network for musical rhythm: A functional neuroimaging meta-analysis and systematic review.

We conducted a systematic review and meta-analysis of 30 functional magnetic resonance imaging studies investigating processing of musical rhythms in neurotypical adults. First, we identified a general network for musical rhythm, encompassing all relevant sensory and motor processes (Beat-based, rest baseline, 12 contrasts) which revealed a large network involving auditory and motor regions. This network included the bilateral superior temporal cortices, supplementary motor area (SMA), putamen, and cerebellum. Second, we identified more precise loci for beat-based musical rhythms (Beat-based, audio-motor control, 8 contrasts) in the bilateral putamen. Third, we identified regions modulated by beat based rhythmic complexity (Complexity, 16 contrasts) which included the bilateral SMA-proper/pre-SMA, cerebellum, inferior parietal regions, and right temporal areas. This meta-analysis suggests that musical rhythm is largely represented in a bilateral cortico-subcortical network. Our findings align with existing theoretical frameworks about auditory-motor coupling to a musical beat and provide a foundation for studying how the neural bases of musical rhythm may overlap with other cognitive domains.

Preschool HABIT-ILE: study protocol for a randomised controlled trial to determine efficacy of intensive rehabilitation compared with usual care to improve motor skills of children, aged 2-5 years, with bilateral cerebral palsy.

INTRODUCTION: Young children with bilateral cerebral palsy (BCP) often experience difficulties with gross motor function, manual ability and posture, impacting developing independence in daily life activities, participation and quality of life. Hand Arm Bimanual Intensive Training Including Lower Extremity (HABIT-ILE) is a novel intensive motor intervention integrating upper and lower extremity training that has been developed and tested in older school-aged children with unilateral and BCP. This study aims to compare an adapted preschool version of HABIT-ILE to usual care in a randomised controlled trial. METHODS AND ANALYSIS: 60 children with BCP aged 2-5 years, Gross Motor Function Classification System (GMFCS) II-IV will be recruited. Children will be stratified by GMFCS and randomised using concealed allocation to either receive Preschool HABIT-ILE or usual care. Preschool HABIT-ILE will be delivered in groups of four to six children, for 3 hours/day for 10 days (total 30 hours). Children receiving Preschool HABIT-ILE be provided a written home programme with the aim of achieving an additional 10 hours of home practice (total dose 40 hours). Outcomes will be assessed at baseline, immediately following intervention and then retention of effects will be tested at 26 weeks. The primary outcome will be the Peabody Developmental Motors Scales-Second Edition to evaluate gross and fine motor skills. Secondary outcomes will be gross motor function (Gross Motor Function Measure-66), bimanual hand performance (Both Hands Assessment), self-care and mobility (Pediatric Evaluation of Disability Inventory-Computer Adapted Test), goal attainment (Canadian Occupational Performance Measure), global performance of daily activities (ACTIVLIM-CP), cognition and adaptive function (Behavior Rating Inventory of Executive Function-Preschool Version), habitual physical activity (ActiGraph GT3X+) and quality of life (Infant Toddler Quality of Life Questionnaire and Child Health Utility Index-9). Analyses will follow standard principles for RCTs using two-group comparisons on all participants on an intention-to-treat basis. Comparisons between groups for primary and secondary outcomes will be conducted using regression models. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Medical Research Ethics Committee Children's Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC/19/QCHQ/59444) and The University of Queensland (2020000336/HREC/19/QCHQ/59444). TRIAL REGISTRATION NUMBER: ACTRN126200000719.