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Aim: We examined key features of two outcome measures for social dysfunction and autism spectrum disorder traits, the Social Responsiveness Scale, Second Edition (SRS-2) and the Social Skills Improvement System - Rating Scales (SSIS-RS), in children with neurofibromatosis type 1 (NF1). The aim of the study was to provide objective evidence as to which behavioural endpoint should be used in clinical trials.Method: Cross-sectional behavioural and demographic data were pooled from four paediatric NF1 tertiary referral centres in Australia and the United States (N=122; 65 males, 57 females; mean age [SD] 9y 2mo [3y], range 3-15y).Results: Distributions of SRS-2 and SSIS-RS scores were unimodal and both yielded deficits, with a higher proportion of severely impaired scores on the SRS-2 (16.4%) compared to the SSIS-RS (8.2%). Pearson's product-moment correlations revealed that both questionnaires were highly related to each other (r=-0.72, p<0.001) and to measures of adaptive social functioning (both p<0.001). Both questionnaires were significantly related to attention-deficit/hyperactivity disorder symptoms, but only very weakly associated with intelligence.Interpretation: The SRS-2 and SSIS-RS capture social dysfunction associated with NF1, suggesting both may be suitable choices for assessing social outcomes in this population in a clinical trial. However, careful thought needs to be given to the nature of the intervention when selecting either as a primary endpoint.What This Paper Adds: The Social Responsiveness Scale, Second Edition yielded a large deficit relative to population norms. The Social Skills Improvement System - Rating Scales yielded a moderate deficit relative to population norms. Both scales were highly correlated, suggesting that they are measuring a unitary construct. [ABSTRACT FROM AUTHOR]

Aim: To assess: (1) the effect on drooling of bilateral submandibular duct ligation as surgical therapy after the administration of submandibular botulinum neurotoxin A (BoNT-A) for excessive drooling and (2) the predictive value of treatment success with BoNT-A on treatment success after bilateral submandibular duct ligation.Method: This was a within-participant retrospective observational study in which 29 children with severe drooling (15 males, 14 females) received BoNT-A treatment at a mean age of 9 years 6 months (SD 2y 5mo), followed by bilateral submandibular duct ligation at a mean age of 10 years 11 months (SD 2y 4mo). Fifteen children were diagnosed with cerebral palsy (CP), with 12 children classified in Gross Motor Function Classification System levels IV and V. The 14 children without CP had non-progressive developmental disorders. The primary drooling severity outcomes were the Visual Analogue Scale (VAS; subjective assessment) and drooling quotient (objective assessment). Measurements were taken before each intervention and again at 8 and 32 weeks.Results: The VAS was significantly lower after bilateral submandibular duct ligation at follow-up compared to BoNT-A treatment (mean difference -33, p≤0.001; 95% confidence interval [CI]=-43.3 to -22.9). The mean drooling quotient did not significantly differ between BoNT-A treatment and bilateral submandibular duct ligation at follow-up (3.3, p=0.457; 95% CI=-4.35 to 9.62) or between 8 and 32 weeks (4.7, p=0.188; 95% CI=-2.31 to 11.65).Interpretation: BoNT-A treatment and bilateral submandibular duct ligation are both effective treatment modalities for drooling. At 32-week follow-up, subjective drooling severity after bilateral submandibular duct ligation was significantly lower compared to previous BoNT-A injections in participants. However, treatment success with BoNT-A is no precursor to achieving success with bilateral submandibular duct ligation.What This Paper Adds: Bilateral submandibular duct ligation is an effective therapy for drooling after treatment with botulinum neurotoxin A (BoNT-A). Treatment success with BoNT-A is not a predictor of successful therapy with bilateral submandibular duct ligation. [ABSTRACT FROM AUTHOR]

Aim: To explore how patients with cerebral palsy (CP) perceive their gait and evaluate associations between subjective gait perception and: objective gait parameters, endurance, pain, and fatigue.Method: Sixty-two patients (21 females and 41 males; mean [SD] age 20y [5y 1mo], range 15-29y) performed a clinical gait analysis. Self-selected walking speed, Gait Profile Score, and Gait Variable Score were calculated. Subjective gait perception was assessed with a visual analogue scale using the question: 'On a scale from 0 (worst) to 10 (optimal), how would you describe your walking today?'. A 6-minute walk test (6MWT) measured endurance; the 36-Item Short Form Health Survey (SF-36) evaluated quality of life. T-tests, Pearson correlations, and univariate and multiple linear regression models were used to compare and find associations between the data.Results: Overall mean (SD) subjective gait perception was 7.5 (1.8) and was significantly higher for patients in Gross Motor Function Classification System (GMFCS) level I (7.9 [1.5]) than for patients in GMFCS levels II and III (5.9 [2.0]). Positive correlations were found between subjective gait perception and gait scores, walking speed, 6MWT distance, and SF-36 score. Only walking speed was a significant predictor of subjective gait perception.Interpretation: Subjective gait perception was influenced by GMFCS level and linked partially with the walking speed. The gait quality did not explain subjective gait perception. It is important to combine subjective and objective gait scores to develop personalized therapeutic goals.What This Paper Adds: Subjective gait perception is influenced by the physical impairment levels of patients with cerebral palsy. Subjective gait perception and objective gait scores are associated. Walking speed is the only predictor of gait perception. [ABSTRACT FROM AUTHOR]

Aim: To evaluate cortical excitability with transcranial magnetic stimulation (TMS) in children with new-onset epilepsy before and after antiepileptic drugs (AEDs).Method: Fifty-five drug-naïve patients (29 females, 26 males; 3-18y), with new-onset epilepsy were recruited from 1st May 2014 to 31st October 2017 at the Child Neurology Department, Queen Silvia's Children's Hospital, Gothenburg, Sweden. We performed TMS in 48 children (23 females, 25 males; mean [SD] age 10y [3y], range 4-15y) with epilepsy (27 generalized and 21 focal) before and after the introduction of AEDs. We used single- and paired-pulse TMS. We used single-pulse TMS to record resting motor thresholds (RMTs), stimulus-response curves, and cortical silent periods (CSPs). We used paired-pulse TMS to record intracortical inhibition and facilitation at short, long, and intermediate intervals.Results: There were no differences in cortical excitability between children with generalized and focal epilepsy at baseline. After AED treatment, RMTs increased (p=0.001), especially in children receiving sodium valproate (p=0.005). CSPs decreased after sodium valproate was administered (p=0.050). As in previous studies, we noted a negative correlation between RMT and age in our study cohort. Paired-pulse TMS could not be performed in most children because high RMTs made suprathreshold stimulation impossible.Interpretation: Cortical excitability as measured with RMT decreased after the introduction of AEDs. This was seen in children with both generalized and focal epilepsy who were treated with sodium valproate, although it was most prominent in children with generalized epilepsy. We suggest that TMS might be used as a prognostic tool to predict AED efficacy.What This Paper Adds: Resting motor threshold (RMT) correlated negatively with age in children with epilepsy. No differences in cortical excitability were noted between patients with generalized and focal epilepsy. Treatment with antiepileptic drugs decreased cortical excitability as measured with transcranial magnetic stimulation (TMS). Decreased cortical excitability with increased RMT was recorded, especially after sodium valproate treatment. Paired-pulse TMS was difficult to perform because of high RMTs in children. [ABSTRACT FROM AUTHOR]

Aim: To: (1) investigate the relationship between upper-limb impairment and health-related quality of life (HRQoL) for children with cerebral palsy and (2) develop a mapping algorithm from the Cerebral Palsy Quality of Life Questionnaire for Children (CPQoL-Child) onto the Child Health Utility 9D (CHU9D) measure.Method: The associations between physical and upper-limb classifications and HRQoL of 76 children (40 females, 36 males) aged 6 to 15 years (mean age 9 years 7 months [SD 3y]) were assessed. Five statistical techniques were developed and tested, which predicted the CHU9D scores from the CPQoL-Child total/domain scores, age, and sex.Results: Most participants had mild impairments. The Manual Ability Classification System (MACS) level was significantly negatively correlated with CHU9D and CPQoL-Child (r=-0.388 and r=-0.464 respectively). There was a negative correlation between the Neurological Hand Deformity Classification (NHDC) and CPQoL-Child (r=-0.476, p<0.05). The generalized linear model with participation, pain domain, and age had the highest predictive accuracy.Interpretation: The weak negative correlations between classification levels and HRQoL measures may be explained by the restricted range of impairment levels of the participants. The MACS and NHDC explained the impact of upper-limb impairment on HRQoL better than the other classifications. The generalized linear model with participation, pain, and age is the suggested mapping algorithm. The suggested mapping algorithm will facilitate the use of CPQoL-Child for economic evaluation and can be used to conduct cost-utility analyses.What This Paper Adds: The Manual Ability Classification System and Neurological Hand Deformity Classification were the best predictors of health-related quality of life measures. Age and Cerebral Palsy Quality of Life Questionnaire for Children participation and pain domain scores can predict Child Health Utility 9D scores. [ABSTRACT FROM AUTHOR]

Aim: To assess the reliability and predictive validity of the developmental and socio-emotional scales of the Standardized Infant NeuroDevelopmental Assessment (SINDA).Method: To assess reliability, two sets of three assessors forming eight assessor-pairs independently rated the developmental and socio-emotional scales of 60 infants. To evaluate predictive validity, 223 infants (gestational age 30wks [range 23-41wks]; 117 males, 106 females) attending a non-academic outpatient clinic were assessed by different assessors with SINDA's neurological, developmental, and socio-emotional scales. Atypical neurodevelopmental outcome at a corrected age of 24 months or older implied a Bayley Mental or Psychomotor Developmental Index score of less than 70 or neurological disorder (including cerebral palsy). Behavioural and emotional disorders were classified according to the International Classification of Diseases, 10th Revision. Predictive values were calculated from SINDA (2-12mo corrected age, median 7mo) and typical versus atypical outcome, and for intellectual disability only (Mental Developmental Index <70).Results: Assessors highly agreed on the developmental and socio-emotional assessments (developmental scores: Spearman's rank correlation coefficient ρ=0.972; single socio-emotional behaviour items: Cohen's κ=0.783-0.896). At 24 months or older, 65 children had atypical outcome. Atypical neurological scores predicted atypical outcome (sensitivity 83%, specificity 96%); atypical developmental scores predicted intellectual disability (sensitivity 77%, specificity 92%). Atypical emotionality and atypical self-regulation were associated with behavioural and emotional disorders.Interpretation: SINDA's three scales are reliable, and have a satisfactory predictive validity for atypical developmental outcome at 24 months or older in a non-academic outpatient setting. SINDA's developmental scale has promising predictive validity for intellectual disability. SINDA's socio-emotional scale is a tool for caregiver counselling.What This Paper Adds: Standardized Infant NeuroDevelopmental Assessment (SINDA)'s developmental and socio-emotional scales have excellent interrater reliability. Replication of the satisfactory validity of SINDA's neurological scale for atypical outcome. [ABSTRACT FROM AUTHOR]

Aim: To evaluate presence and severity of social impairments in alternating hemiplegia of childhood (AHC) and determine factors that are associated with social impairments.Method: This was a retrospective analysis of 34 consecutive patients with AHC (19 females, 15 males; mean age: 9y 7mo, SD 8y 2mo, range 2y 7mo-40y), evaluated with the Social Responsiveness Scale, Second Edition (SRS-2).Results: SRS-2 scores, indicating level of social impairment, were higher than population means (75, SD 14 vs 50, SD 10, p<0.001). Of these, 27 out of 34 had high scores: 23 severe (>76), four moderate (66-76). All subscale domains, including social cognition, social communication, social awareness, social motivation, restricted interests, and repetitive behavior, had abnormal scores compared to population means (p<0.001). High SRS-2 scores were associated with the presence of autism spectrum disorder (ASD) and epilepsy (p=0.01, p=0.04), but not with other scales of AHC disease symptomatology. All nine patients who received formal evaluations for ASD, because they had high SRS-2 scores, were diagnosed with ASD.Interpretation: Most patients with AHC have impaired social skills involving multiple domains. ASD is not uncommon. High SRS-2 scores in patients with AHC support referral to ASD evaluation. Our findings are consistent with current understandings of the pathophysiology of AHC and ASD, both thought to involve GABAergic dysfunction.What This Paper Adds: Most patients with alternating hemiplegia of childhood (AHC) have impaired social skills involving multiple domains. These impairments are significant compared to population means. Most patients with AHC have high Social Responsiveness Scale, Second Edition (SRS-2) scores. Patients with AHC with high SRS-2 scores are likely to have autism spectrum disorder. [ABSTRACT FROM AUTHOR]

This case series aimed to characterize the clinical features, management, and outcomes of apnea in infants with trisomy 18. Participants in this study were infants with trisomy 18 who were born alive and admitted to the neonatal intensive care unit in Kyushu University Hospital from 2000 to 2018. Retrospective analysis was performed on clinical data recorded in our department. Twenty-seven infants with trisomy 18 were admitted to our hospital during the study period, of which 25 (nine males, 16 females) were enrolled as eligible participants in this study. Among them, 14 started presenting with apnea from median 3.5 days of age (range 0-47d). In these infants with apnea, eight received respiratory support of positive pressure ventilation (PPV). The 1-year survival rate of infants in the PPV group was higher than that of non-PPV-supported infants (5 out of 8 vs 0 out of 6 infants). Five PPV-supported infants received a diagnosis of epilepsy, which was controlled by antiepileptic drugs. Postnatal respiratory intervention provides better prognosis in infants with trisomy 18. Improved survival leads to accurate diagnosis and treatment of apneic events in association with epilepsy. WHAT THIS PAPER ADDS: Respiratory support is effective against apnea in infants with trisomy 18. Intervention with ventilation provides a higher chance of prolonged survival. Improved survival leads to the accurate diagnosis and treatment of epilepsy-associated apnea. [ABSTRACT FROM AUTHOR]

Aim: To assess parental understanding of idiopathic nephrotic syndrome (INS) and its management, to enable targeted education in areas of deficit.Methods: Families of children with at least one relapse of INS were interviewed, following a template covering key domains of (a) disease understanding, (b) management of INS and (c) access to information. Common trends and responses were identified and notable observations recorded.Results: Twenty-one parents were interviewed. The mean duration of INS was 4.4 years (range 0.5-14.5 years), with a mean of two steroid-sparing agents used. Although 90% parents self-reported that they understood INS, only 29% could appropriately define relapse and 24% name potential complications. The management of INS was generally good, with most parents appropriately testing urine (81%) and managing relapses (90%). Unnecessary dietary restrictions were imposed on 57% during remission. The Internet was searched by 90% of parents for disease and drug information. Further information was desired in paper form (71%), hospital website (81%) and face-to-face workshop (90%), plus educational materials for schools.Conclusion: Parents overestimated their understanding of INS; however, their management was generally well done. Parents desired more information and support in various forms. [ABSTRACT FROM AUTHOR]

Large-scale association analyses based on observational health care databases such as electronic health records have been a topic of increasing interest in the scientific community. However, challenges due to nonprobability sampling and phenotype misclassification associated with the use of these data sources are often ignored in standard analyses. The extent of the bias introduced by ignoring these factors is not well-characterized. In this paper, we develop an analytic framework for characterizing the bias expected in disease-gene association studies based on electronic health records when disease status misclassification and the sampling mechanism are ignored. Through a sensitivity analysis approach, this framework can be used to obtain plausible values for parameters of interest given summary results from standard analysis. We develop an online tool for performing this sensitivity analysis. Simulations demonstrate promising properties of the proposed method. We apply our approach to study bias in disease-gene association studies using electronic health record data from the Michigan Genomics Initiative, a longitudinal biorepository effort within The University Michigan health system. [ABSTRACT FROM AUTHOR]

Aim: To test whether wearable textile electromyography (EMG) recording systems may detect differences in muscle activity levels during daily activities between children with cerebral palsy (CP) and age-matched typically developing children.Method: Wearable textile EMG recording systems were used to obtain leg muscle activity in 10 children with spastic CP (four females, six males; mean age 9y 6mo, standard deviation [SD] 2y 4mo, range: 6-13y; Gross Motor Function Classification System [GMFCS] level I and II) and 11 typically developing children (four females, seven males; mean age 9y 9mo, SD 1y 11mo, 7-12y) at rest and while performing seven daily activities.Results: Children with CP showed significantly lower absolute EMG levels during maximal voluntary contractions (MVCs) of muscles on the most affected side as compared to the least affected side and to typically developing children. None of the typically developing children or children with CP showed detectable EMG activity in resting situations. EMG activity relative to MVC was greater in children with CP during walking, jumping, and kicking on the most affected side as compared to the least affected side and to typically developing children.Interpretation: Wearable textile EMG recording systems may be used to determine differences in muscle activity during daily activities in children with CP. Children with CP showed reduced muscle activity during daily activities compared to their peers, but used a significantly larger part of their maximal voluntary muscle strength to perform these activities.What This Paper Adds: Wearable textile electromyography (EMG) systems are feasible for measurement of daily muscle activity in children with cerebral palsy (CP). Children with CP showed reduced EMG levels during maximal voluntary contractions. Neither typically developing children or children with CP showed EMG activity in resting situations. Children with CP used a larger part of their voluntary muscle strength during daily activities. [ABSTRACT FROM AUTHOR]

Aim: To compare anterior and posterior standing balance reactions, as measured by single-stepping thresholds, in children with and without spastic cerebral palsy (CP).Method: Seventeen ambulatory children with spastic CP (eight males, nine females) and 28 typically developing children (13 males, 15 females; age range 5-12y, mean [SD] 9y 2mo [2y 3mo]), were included in this cross-sectional, observational study. Balance reaction skill was quantified as anterior and posterior single-stepping thresholds, or the treadmill-induced perturbations that consistently elicited a step in that direction. In order to understand the underlying mechanisms of between-group differences in stepping thresholds, dynamic stability was quantified using the minimum margin of stability. Ankle muscle activation latency, magnitude, and co-contraction were assessed with surface electromyography.Results: We observed an age and group interaction for anterior thresholds (p=0.001, partial η2 =0.24). At older (≈11y; p<0.001, partial η2 =0.48), but not younger (≈7y; p=0.33, partial η2 =0.02) ages, typically developing children had larger anterior thresholds than those with CP. In response to near-threshold anterior perturbations, older typically developing children recovered from more instability than their peers with CP (p=0.004, partial η2 =0.18). Older children had no between-group differences in ankle muscle activity. No between-group differences were observed in posterior thresholds.Interpretation: The effects of CP on balance reactions are age- and direction-specific. Older typically developing children are more able or willing to withhold a step when unstable.What This Paper Adds: Children with spastic cerebral palsy have age- and direction-specific balance-reaction impairments. Lower anterior stepping thresholds were observed in older, but not younger children. Older typically developing children withheld a forward step at higher levels of instability. No between-group differences were seen in posterior stepping thresholds. [ABSTRACT FROM AUTHOR]

Aims: To describe stroke syndromes and transcranial Doppler (TCD) findings in children with human immunodeficiency virus (HIV) and examine the associations between TCD and clinical and laboratory data.Method: We enrolled 42 children (24 males, 18 females) with HIV (median age=7y 6mo; 2y 7mo-15y 6mo), with and without stroke who underwent a TCD examination of the anterior and posterior circulations to derive time-averaged maximum mean velocity (TAMMV) measurements for comparison with previous studies. Clinical and laboratory variables were extracted from the medical records.Results: Of the 42 children with HIV, five had right-sided hemiparesis, three had chronic lung disease, two occurred post-varicella infection, one after herpetic oral ulceration, and one had a poorly functioning left ventricle. Neuroimaging showed middle cerebral artery (MCA) TAMMV greater than 200cm/s, moyamoya-like arteriopathy, left basal ganglia infarction with ipsilateral stenosis, hygroma consistent with venous thrombosis, and a hyperdense left MCA. Eight neurologically asymptomatic children had atypical TCD. The CD4 cell count was non-significantly lower in 6 out of 30 children with atypical TCD (median=21.5; interquartile range=16.1-26.5) compared with the remainder (median=29; interquartile range=21.3-35.0; p=0.09).Interpretation: A variety of stroke syndromes occur in children with HIV. TCD suggests atypical intracranial vessels and/or haemodynamics in some children with HIV infection, consistent with vasculopathy, possibly related directly to immunodeficiency and/or infection.What This Paper Adds: A range of stroke syndromes are found in children with human immunodeficiency virus (HIV). Transcranial Doppler (TCD) velocities in HIV are commonly outside the range for typically developing children. TCD and neuroimaging data in children with HIV suggest intracranial vasculopathy as one mechanism for stroke. CD4 cell count is non-significantly lower in children with HIV and atypical TCD. [ABSTRACT FROM AUTHOR]

This exploratory experimental study investigates the impact of motivational strategies based on the Attention, Relevance, Confidence, Satisfaction, and Volition (ARCS‐V) model on online learners' academic performance, motivation, volition, and course interest. The research was conducted over an 11‐week semester with 122 undergraduate online learners within two groups. One group received a traditional e‐course, while the other group was offered the course with extra motivational strategies derived from the ARCS‐V model. The results revealed that the group who used motivational strategies showed significantly higher gains in motivation, academic performance, and course interest scores. However, there were no significant differences between the groups regarding the volition. Furthermore, the motivation and interest variables were measured with Attention, Relevance, Confidence, and Satisfaction subscales of the ARCS‐V model. In terms of interest variable, there was only a statistically significant difference on the Attention subscale. Regarding motivation variable, the results also showed a statistically significant difference on the attention, confidence, and satisfaction subsections of the ARCS‐V model. The findings of the present study offer insights into ARCSV model‐based research by examining the effects of the model as a valid and reliable framework for online learning environments. The implications and directions for future research are then discussed. Practitioner Notes/ Lay Description: What is already known about this topic: Learning motivation is the most vital factor that influencing effective and efficient learning process.The attention, relevance, confidence, and satisfactionARCS model of motivational design has been used myriad times to design motivational instructions in a wide range of educational settings (from traditional to computer‐assisted instruction and distance education).Few studies address the online learners" motivation through the attention, relevance, confidence, satisfaction, and volition (ARCS‐V) ‐based motivational strategies. What this paper adds to this: A quasi‐experimental study was conducted in online learning environment to research the effects of the ARCS‐V ‐based motivational strategies.The impact of the ARCS‐V ‐based motivational strategies on online learners" academic performance, motivation, volition, and course interest was investigated.The results showed that the ARCS‐V ‐based motivational strategies had positive effects on online learners' regarding to academic performance, motivation, volition, and course interest. The implications of study findings for practitioners: This research provided evidences for effects of the ARCS‐V motivational strategies on online learners.Online learners who took the ARCS‐V ‐based motivational messages had positive effects regarding to academic performance, motivation, volition, and course interest. [ABSTRACT FROM AUTHOR]

Aim: To explore cortical activation during bimanual tasks and functional correlates in unilateral cerebral palsy (CP).Method: This cross-sectional study included eight participants with unilateral CP (six females, two males; mean age [SD] 20y 10mo [5y 10mo], 13y 8mo-31y 6mo) in Manual Ability Classification System levels II to III and nine age-matched participants with typical development (seven females, two males; mean age [SD] 17y 8mo [5y 7mo], 9y 4mo-24y 2mo). They performed bimanual symmetric squeezing (BSS) and bimanual asymmetric squeezing (BAS) tasks at 1Hz, and a pouring task with dominant hand (DPour) and a pouring task with non-dominant hand (NDPour) at 0.67Hz, all while a custom array of functional near-infrared spectroscopy (fNIRS) optodes were placed over their sensorimotor area. Mixed-effects were used to contrast groups, tasks, and hemispheres (corrected p-values [q] reported). Analysis of variance and t-tests compared performance measures across groups and tasks.Results: Participants with unilateral CP showed greater activation in both hemispheres during BAS (non-lesioned: q<0.001; lesioned: q<0.001), and in the lesioned hemisphere during BSS (q<0.001), DPour (q=0.02), and NDPour (q=0.02) than those with typical development. The lesioned hemisphere in unilateral CP showed more activity than the non-lesioned one (BSS: q=0.01; BAS: q=0.009; NDPour: q=0.04). During BAS, higher cortical activity correlated with more synchronous arm activation (r=0.79; p=0.02); activity lateralized towards the non-lesioned hemisphere correlated with better Pediatric Evaluation of Disability Inventory computer adaptive test scores (r=0.81; p=0.03).Interpretation: Results suggest abnormally increased sensorimotor cortical activity in unilateral CP, with implications to be investigated.What This Paper Adds: Cortical activity in manual tasks is described with functional near-infrared spectroscopy in typical and atypical cohorts. Activation levels in unilateral cerebral palsy appear to escalate with task difficulty. Increased brain activity may be associated with poorer selective manual control. Specific patterns of brain activity may be related to impaired bimanual function. [ABSTRACT FROM AUTHOR]

Aim: To examine the association between brain magnetic resonance imaging (MRI) characteristics and executive function and bimanual performance in children with unilateral cerebral palsy (CP).Method: Clinical MRI brain scans were classified as: (1) predominant pathological pattern (normal, white matter injury [WMI]; grey matter injury; focal vascular insults [FVI]; malformations; or miscellaneous); and (2) focal lesions (frontal, basal ganglia, and/or thalamus). Assessments included: (1) bimanual performance; (2) unimanual dexterity; and (3) executive function tasks (information processing, attention control, cognitive flexibility, and goal setting) and behavioural ratings (parent).Results: From 131 recruited children, 60 were ineligible for analysis, leaving 71 children (47 males, 24 females) in the final sample (mean age 9y [SD 2y], 6y-12y 8mo). Brain MRIs were WMI (69%) and FVI (31%); and frontal (59%), thalamic (45%), basal ganglia (37%), and basal ganglia plus thalamic (21%). Bimanual performance was lower in FVI versus WMI (p<0.003), and with frontal (p=0.36), basal ganglia (p=0.032), and thalamic/basal ganglia lesions (p=0.013). Other than information processing, executive function tasks were not associated with predominant pattern. Frontal lesions predicted attention control (p=0.049) and cognitive flexibility (p=0.009) but not goal setting, information processing, or behavioural ratings.Interpretation: Clinical brain MRI predicts cognitive and motor outcomes when focal lesions and predominate lesion patterns are considered. What this paper adds Early brain magnetic resonance imaging (MRI) predicts bimanual performance and cognitive outcomes. Brain MRI may identify children requiring targeted interventions. Basal ganglia with/without thalamic lesions predicted bimanual performance. Frontal lesions were associated with attention control and cognitive flexibility. Brain MRI predominant patterns predicted motor, not cognitive outcomes, other than information processing. [ABSTRACT FROM AUTHOR]

Aim: To determine whether epilepsy surgery improved health-related quality of life (HRQoL) and whether seizure freedom after surgery mediated the improvement in HRQoL.Method: This multicenter cohort study compared HRQoL after epilepsy surgery to pharmacological management in children with drug-resistant epilepsy (DRE). HRQoL was measured using the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire at baseline and 1-year follow-up. The mediator between treatment type and HRQoL was seizure freedom.Results: Two hundred and thirty-seven patients were recruited (surgery group: n=147 [92 males, 45 females]; pharmacological group: n=90 [53 males, 37 females]). Mean age at seizure onset was 6 years (SD 4y 4mo) in the surgical group and 6 years 1 month (SD 4y) in the pharmacological group. The odds ratio of seizure freedom was higher for the surgery versus pharmacological group (β=4.24 [95% confidence interval {CI}: 2.26-7.93], p<0.001). Surgery had no direct effect on total QOLCE score at 1-year (β=0.24 [95% CI -2.04 to 2.51], p=0.839) compared to pharmacological management, but had an indirect effect on total QOLCE that was mediated by seizure freedom (β=0.92 [95% CI 0.19-1.65], p=0.013), adjusting for baseline total QOLCE score. Surgery had a direct effect on improving social function (p=0.043), and an indirect effect on improving physical function (p=0.016), cognition (p=0.042), social function (p=0.012) and behavior (p=0.032), mediated by seizure freedom.Interpretation: Greater seizure freedom achieved through epilepsy surgery mediated the improvement in HRQoL compared to pharmacological management in children with DRE.What This Paper Adds: Seizure freedom is higher after pediatric epilepsy surgery compared to pharmacologically managed epilepsy. Surgery indirectly improves health-related quality of life (HRQoL) mediated by seizure freedom compared to pharmacological management. Surgery has a direct effect on improving social function relative to pharmacological management. Baseline HRQoL was an important predictor of HRQoL after treatment. [ABSTRACT FROM AUTHOR]

Aim: To examine the impact of engagement in a self-chosen community-based activity on three relevant body functions (motor, cognitive, and affective) as well as on the performance of the selected activity.Method: An individual-based interrupted time series design with multiple baselines was used. Seven young people (four males, three females) aged 15 to 25 years (median 18y; interquartile range 17-20y) with physical disabilities participated in an 8-week community activity of choice (e.g. swimming, playing piano). Change in three relevant body functions, underpinning the specific chosen activity, including motor (e.g. Functional Reach Test, Trunk Impairment Scale, dynamometers), cognitive and affective (Behavior Assessment System for Children), as well as activity performance (Canadian Occupational Performance Measure) were measured repeatedly, providing individual outcome trajectories. Linear and mixed-effects models were used.Results: Significant improvements in at least one aspect of motor function (6 out of 6), cognition (3 out of 3), affect (5 out of 7), and performance (7 out of 7) were observed. Specifically, the intervention had a moderate to large effect on hyperactivity (1.45, 95% confidence interval [CI] 1.0-1.9) with a smaller effect on anxiety (0.21, 95% CI 0.10-0.32) and inadequacy (0.21, 95% CI 0.02-0.39). Concurrently, a notable effect size for activity performance (4.61, 95% CI 0.76-8.46) was observed. Average change across motor outcomes was substantial (3.7 SDs from baseline), yet non-significant.Interpertation: Findings provide initial evidence of the benefits resulting from participation-based interventions, emphasizing the merit of meaningful 'real-life' young people-engaging therapy.What This Paper Adds: Participation-based interventions can impact body-function level outcomes. Significant improvements in the performance of chosen activities were observed. Significant improvements were also seen in cognitive and affective body functions. Improvements in motor-related outcomes were substantial but not statistically significant. [ABSTRACT FROM AUTHOR]

Aim: To examine self- and proxy-reported symptoms of depression in children with epilepsy.Method: This was a prospective longitudinal cohort study of children with epilepsy. Participants were treated at six Canadian tertiary-care centers and followed over 28 months with repeated assessments of child self-reported symptoms of depression using the Children's Depression Inventory Short-Form (CDI-S). Trajectories of symptoms of depression were estimated using linear mixed effects (LME) modeling.Results: At baseline, 477 children had complete data (mean age [SD] 11y 5mo [2y 1mo], range 7y 7mo-15y 1mo; 234 females, 243 males). Mean CDI-S T score at baseline was 45.7 (SD=7.5) and at 28 months was 44.9 (SD=8.2), both were within the 'average' range. Results from LME modeling revealed mean raw CDI-S score of 1.897, corrected for age 10 years (corresponding to T scores slightly below the normed mean of 50), with no significant change over three measurements (slope=-0.113, p=0.135), indicating that CDI-S scores were stable over 28 months. Children with high initial CDI-S scores had lower subsequent scores, as demonstrated by the correlation of -0.827 between intercept and slope (p<0.001). Parents reported comparable findings.Interpretation: Self- and proxy-reported symptoms of depression were generally low and stable over an extended follow-up period. Normalization of scores was seen upon repeated assessment, even in children with higher scores of symptoms of depression at one point. These findings speak to the value and importance of repeated assessment over time.What This Paper Adds: In children with epilepsy, self- and proxy-reported symptoms of depression were generally low and stable over 28 months. The trajectory of symptoms of depression was not associated with seizure severity, whether considering the frequency or type of seizures. Parents' reports of symptoms of depression were comparable to the children's self-evaluations. [ABSTRACT FROM AUTHOR]

Aim: To report the differences between Performance of Upper Limb (PUL) versions 1.2 and 2.0, compare the measurement ability of the two versions, and compare their longitudinal performance in Duchenne muscular dystrophy.Method: Rasch analysis was performed on the dual data from three centres to confirm whether the two scales measure the same construct. Change scores in natural history for the different domains were compared for the two versions.Results: Rasch analysis demonstrated that both versions measure the same construct and that the PUL 2.0 was a better fit to the construct of motor performance and better able to detect change at 12 months in all levels of ability than the PUL 1.2. This was also true when change scores were reviewed over 2 years.Interpretation: Our results confirm that the PUL 1.2 and 2.0 versions detect change in all domains over 2 years. They also demonstrate that simplifying the original scoring of the PUL 1.2 for the revised PUL 2.0 maintains the validity of the construct and enhances the scale measurement qualities.What This Paper Adds: The original and revised Performance of Upper Limb (PUL) scales measure the same construct. Both scales detected change in all domains over 2 years. The PUL 2.0 enhances the measurement qualities of the scale. [ABSTRACT FROM AUTHOR]

Multiple imputation by chained equations (MICE) has emerged as a leading strategy for imputing missing epidemiological data due to its ease of implementation and ability to maintain unbiased effect estimates and valid inference. Within the MICE algorithm, imputation can be performed using a variety of parametric or nonparametric methods. Literature has suggested that nonparametric tree-based imputation methods outperform parametric methods in terms of bias and coverage when there are interactions or other nonlinear effects among the variables. However, these studies fail to provide a fair comparison as they do not follow the well-established recommendation that any effects in the final analysis model (including interactions) should be included in the parametric imputation model. We show via simulation that properly incorporating interactions in the parametric imputation model leads to much better performance. In fact, correctly specified parametric imputation and tree-based random forest imputation perform similarly when estimating the interaction effect. Parametric imputation leads to slightly higher coverage for the interaction effect, but it has wider confidence intervals than random forest imputation and requires correct specification of the imputation model. Epidemiologists should take care in specifying MICE imputation models, and this paper assists in that task by providing a fair comparison of parametric and tree-based imputation in MICE. [ABSTRACT FROM AUTHOR]

Surrogate endpoints play an important role in drug development when they can be used to measure treatment effect early compared to the final clinical outcome and to predict clinical benefit or harm. Such endpoints are assessed for their predictive value of clinical benefit by investigating the surrogate relationship between treatment effects on the surrogate and final outcomes using meta-analytic methods. When surrogate relationships vary across treatment classes, such validation may fail due to limited data within each treatment class. In this paper, two alternative Bayesian meta-analytic methods are introduced which allow for borrowing of information from other treatment classes when exploring the surrogacy in a particular class. The first approach extends a standard model for the evaluation of surrogate endpoints to a hierarchical meta-analysis model assuming full exchangeability of surrogate relationships across all the treatment classes, thus facilitating borrowing of information across the classes. The second method is able to relax this assumption by allowing for partial exchangeability of surrogate relationships across treatment classes to avoid excessive borrowing of information from distinctly different classes. We carried out a simulation study to assess the proposed methods in nine data scenarios and compared them with subgroup analysis using the standard model within each treatment class. We also applied the methods to an illustrative example in colorectal cancer which led to obtaining the parameters describing the surrogate relationships with higher precision. [ABSTRACT FROM AUTHOR]

Aim: To develop a detailed priority list of family-centred rehabilitation goals on the activity level within the International Classification of Functioning, Disability and Health (ICF) chapters d4 'Mobility' and d5 'Self-care' in a paediatric population with a broad range of health conditions.Method: Twenty-two months after implementing a systematic, family-centred, goal-setting process, the rehabilitation goals of 212 inpatients were retrospectively allocated to the most detailed level of ICF categories by two independent researchers. The overall frequencies of these goals were calculated and stratified by health condition, functional independence, and age.Results: Ninety-three females and 119 males were included in the study (mean age 10y 9mo, SD 4y 5mo, range 2y 1mo-21y 5mo). The five most frequent rehabilitation goals were ICF codes d4500 'Walking short distances' (11%), d4200 'Transferring oneself while sitting' (9%), d5400 'Putting on clothes' (7%), d451 'Going up and down stairs' (6%), and d4153 'Maintaining a sitting position' (5%). These top goals varied in the subgroups with regard to the underlying health condition, functional independence, and age.Interpretation: The findings of this study are not generalizable due to the large heterogeneity in priorities. However, they can be used to incorporate families' needs into future research designs and the development of new technologies.What This Paper Adds: Walking short distances is the most frequent mobility/self-care goal of paediatric rehabilitation. The top goals depend on health condition, functional independence, and age. Priorities vary considerably between children undergoing rehabilitation. Rehabilitation goals need to be assessed individually for each child. [ABSTRACT FROM AUTHOR]

Aim: To determine whether, and how, neonatal intensive care unit (NICU) parents want to receive early neurodevelopmental screening information about their child's future risk of cerebral palsy and other disabilities.Method: This was a qualitative interview study. Parents of hospitalized infants born preterm completed semi-structured interviews. Data were analysed using a directed content analysis approach.Results: Thematic saturation was achieved after 19 interviews. Four themes characterized parent perceptions of early neurodevelopmental screening: (1) acceptability: most parents were in favour of neurodevelopmental screening if parents could refuse; (2) disclosure of results: parents want emotional preparation for results, especially false positives; (3) emotional burden of uncertainty: parents of children in the NICU balance taking their infant's illness 'day by day' and preparing for an uncertain future. Parents expressed distress with screening that increased uncertainty about the future; and (4) disability: prior experience with disability informs parent concerns.Interpretation: Parents interpret the risks and benefits of NICU developmental screening through the lens of prior experiences with disability. Most expressed interest in screening and emphasized a desire for autonomy, pretest counselling, and emotional preparation.What This Paper Adds: Most parents with infants in the neonatal intensive care unit expressed interest in early screening for developmental disability. Prior experience with disability informed concerns about specific deficits. Parents emphasized a desire for autonomy, pretest counselling, and emotional preparation. [ABSTRACT FROM AUTHOR]

Aim: To determine the proportion of children with cerebral palsy (CP) who had major congenital anomalies, describe the types of disorders, and report on the children's functional outcomes.Method: Data were extracted from the Bangladesh Cerebral Palsy Register (BCPR). Descriptive analyses were conducted on children with CP and major congenital anomalies. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to measure the association between major congenital anomalies, clinical severity, and presence of comorbidities.Results: Between January 2015 and December 2016, 726 children with CP were newly registered with the BCPR (277 females, 449 males; mean age [SD] at registration 90mo [54mo], 4mo-18y). Seventy-eight children (11%) had a major congenital anomaly. Neurological (86%) and musculoskeletal congenital anomalies (10%) were the most common. Microcephaly was the most common congenital anomaly (83%). The odds of severe functional motor limitations (OR=2.4, 95% CI=1.9-2.9), epilepsy (OR=1.6, 95% CI=1.1-2.1), visual impairment (OR=2.6, 95% CI=2.0-3.2), presence of strabismus (OR=3.9, 95% CI=3.8-4.4), hearing (OR=1.2, 95% CI=0.6-1.9), speech (OR=5.4, 95% CI=4.6-6.2), and intellectual impairments (OR=2.3, 95% CI=1.8-2.8) were higher in children with congenital anomalies compared to children without.Interpretation: The proportion of children with major congenital anomalies in the BCPR (11%) was lower than that identified in higher-income countries. This may be because of differences in how congenital anomalies are diagnosed as well as the impact of survival bias. In Bangladesh, children with CP and major congenital anomalies are more likely to have severe functional motor limitations and associated comorbidities.What This Paper Adds: Eleven per cent of children with cerebral palsy (CP) in Bangladesh had major congenital anomalies. Neurological and musculoskeletal congenital anomalies were the most common. Severe functional motor limitations and associated comorbidities were more common in children presenting with CP and major congenital anomalies. [ABSTRACT FROM AUTHOR]

Aim: To compare the rate of falls between adults with and without cerebral palsy (CP).Method: We used primary care data on 1705 adults with CP and 5115 adults without CP matched for age, sex, and general practice attended. We compared odds of experiencing a fall between adults with and without CP using conditional logistic regression. We compared the rate of falls using a negative binomial model.Results: Participants were 3628 males (53%) and 3192 females (47%) (median age 29y, interquartile range 20-42y) at the start of follow-up. Follow-up was 14 617 person-years for adults with CP and 56 816 person-years for adults without CP. Of adults with CP, 15.3% experienced at least one fall compared to 5.7% of adults without CP. Adults with CP had 3.64 times (95% confidence interval [CI] 2.98-4.45) the odds of experiencing a fall compared to adults without CP. The rate of falls was 30.5 per 1000 person-years and 6.7 per 1000 person-years for adults with and without CP respectively (rate ratio 5.83, 95% CI 4.84-7.02) INTERPRETATION: Adults with CP are more likely to fall, and fall more often, than adults without CP. The causes and consequences of falls in adults with CP need examination.What This Paper Adds: Twenty adults with CP and 5.3 adults without CP experienced at least one fall per 1000 person-years. Adults with CP experienced 30.5 falls per 1000 person-years compared to 6.7 falls per 1000 person-years among adults without CP. Adults with CP had 3.64 times the odds of experiencing a fall compared to adults without CP. Adults with CP experienced 5.83 times more falls than adults without CP. [ABSTRACT FROM AUTHOR]

Aim: To describe the functional limitations and associated impairments of children with cerebral palsy (CP) in rural Uganda, and care-seeking behaviour and access to assistive devices and education.Method: Ninety-seven children with CP (42 females, 55 males; age range 2-17y) were identified in a three-stage population-based screening with subsequent medical examinations and functional assessments. Information on school and access to care was collected using questionnaires. The data were compared with Swedish and Australian cohorts of children with CP. We used the χ2 test and linear regression models to analyse differences between groups.Results: Younger children were more severely impaired than older children. Two-fifths of the children had severe impairments in communication, about half had intellectual disability, and one third had seizures. Of 37 non-walking children, three had wheelchairs and none had walkers. No children had assistive devices for hearing, seeing, or communication. Care-seeking was low relating to lack of knowledge, insufficient finances, and 'lost hope'. One-third of the children attended school. Ugandan children exhibited lower developmental trajectories of mobility and self-care than a Swedish cohort.Interpretation: The needs for children with CP in rural Uganda are not met, illustrated by low care-seeking, low access to assistive devices, and low school attendance. A lack of rehabilitation and stimulation probably contribute to the poor development of mobility and self-care skills. There is a need to develop and enhance locally available and affordable interventions for children with CP in Uganda.What This Paper Adds: Development of mobility and self-care skills is lower in Ugandan than Swedish children with cerebral palsy (CP). Older children in Uganda with CP are less impaired than younger children. Untreated seizures and impairments of communication and intellect are common. Access to health services, assistive devices, and education is low. Caregivers lack knowledge and finances to seek care and often lose hope of their child improving. [ABSTRACT FROM AUTHOR]

Aim: To describe and compare the socio-demographic characteristics and community-based participation of children with and without disabilities.Method: This cross-sectional study reports data on 1073 children with disabilities (663 males, 410 females) and 11 122 children without disabilities (5617 males, 5505 females) aged 10 to 12 years from the fifth sweep of the Millennium Cohort Study. χ2 was used to explore differences between the two groups. Logistic regression models were used to assess the relationships between childhood disability (dependent variable) and socio-demographic characteristics. Logistic regression models were also used to examine the associations between childhood disability (dependent variable) and participation in community-based activities.Results: Children with disabilities were more likely to be male, have psychosocial and behavioural problems, live in single-parent households, and have a parent with a longstanding illness. Patterns of community-based participation were similar between children with and without disabilities. However, the extent to which the two groups participated differed. Children with disabilities participated with lower frequency in unstructured physical activities (adjusted odds ratio [OR] 2.41; 95% confidence interval [CI]: 1.95-2.99), organized physical activities (adjusted OR 2.29; 95% CI: 1.83-2.86), religious gatherings (adjusted OR 2.08; 95% CI: 1.35-3.20), and getting together with friends (adjusted OR 3.31; 95% CI: 2.61-4.20).Interpretation: Socio-demographic characteristics differed between children with and without disabilities. Children with disabilities had greater restriction in participation compared to peers without disabilities. Participation promoting interventions are required to support the participation of children with disabilities in social and physical activities.What This Paper Adds: Patterns of community-based participation were similar between children with and without disabilities. Children with disabilities had lower frequency of participation in physical activities, religious gatherings, and getting together with friends. [ABSTRACT FROM AUTHOR]

Aim: To assess the responsiveness, concurrent validity, and feasibility of the Dyskinesia Impairment Scale (DIS) in non-ambulatory patients with dyskinetic cerebral palsy (CP).Method: The study is a secondary analysis of data collected in the IDYS trial, a randomized controlled trial on the effects of intrathecal baclofen (ITB). The DIS and Barry-Albright Dystonia Scale (BADS) were conducted at baseline and after 3 months of ITB or placebo treatment. Responsiveness was assessed by comparing the effect sizes and correlation of change after treatment between the DIS and BADS. Concurrent validity was evaluated by assessing the correlations between scales. Feasibility was evaluated for each DIS item by the number of participants who successfully accomplished the item.Results: Thirty-three non-ambulatory patients (9 females, 24 males) with dyskinetic CP (ITB-treated: n=17, mean [SD] age: 14y 1mo [4y 1mo]; placebo-treated: n=16, mean [SD] age: 14y 7mo [4y]) were included in the study. The effect sizes for BADS and DIS were similar in The ITB-treated group (-0.29 and -0.22 respectively). Changes after treatment on the DIS dystonia subscale correlated with changes on the BADS (r=0.64; p<0.001). The DIS dystonia subscale and BADS correlated at baseline and follow-up (r=0.78; p<0.001 and r=0.79; p<0.001). Not all DIS activity items could be performed in this sample of patients.Interpretation: For non-ambulatory patients with dyskinetic CP, the responsiveness of the DIS equalled the responsiveness of BADS. Concurrent validity was adequate. Feasibility for activity items was restricted in patients with severe dyskinetic CP.What This Paper Adds: The Dyskinesia Impairment Scale (DIS) and Barry-Albright Dystonia Scale showed similar responsiveness in non-ambulatory patients with dyskinetic cerebral palsy (CP). No floor or ceiling effect was observed for DIS in non-ambulatory participants. The concurrent validity of DIS was adequate in non-ambulatory participants. Patients with dyskinetic CP in Gross Motor Function Classification System levels IV and V could not perform all DIS activity items. [ABSTRACT FROM AUTHOR]

Aim: To compare language, speech, and voice of children born preterm and at term, and determine relevant predictors of outcome.Method: Three hundred infants (150 males, 150 females; 149 born at <30wks' gestation, 151 term-born) were prospectively recruited at birth from the Royal Women's Hospital. We administered the Preschool Language Scales, Fifth Edition, Diagnostic Evaluation of Articulation and Phonology, Grade Roughness Breathiness Asthenia Strain Scale, and Pediatric Voice Handicap Index at 3 years, and compared groups. We examined hypothesized predictors in children born preterm: gestational age at birth, birthweight, sex, chronic lung disease, high social risk, multilingualism, neurodevelopmental diagnosis, and oromotor feeding.Results: Children born preterm had poorer language than children born at term (coefficient -5.43). Speech and voice were similar between groups (coefficients -0.70 to 1.63). Chronic lung disease predicted voice (coefficient 6.05); male sex (coefficients 4.54-6.18), high social risk (coefficient -6.02 to -9.30), and neurodevelopmental diagnosis (coefficients -16.42 to -20.61) predicted language.Interpretation: Children born before 30 weeks' gestation had poorer language than children born at term. Children born preterm with neurodevelopmental disabilities or high social risk experience poorer language outcomes, and would benefit from enrichment of their language environment.What This Paper Adds: Speech and voice outcomes were similar between children born preterm and at term. Male sex, high social risk, and neurodevelopmental diagnosis predicted language outcomes. [ABSTRACT FROM AUTHOR]

Aim: To compare hospital admission patterns after the first year of life in Australian children with developmental disabilities and children with no known disability, according to maternal country of birth and Indigenous status.Method: This was a retrospective cohort study using linked data across health, disability, and hospital admission databases. The study investigated 656 174 children born in Western Australia between 1983 and 2008 with a total of 1 091 834 records of hospital admissions.Results: Children with no known disability born to Indigenous mothers had the highest rate of hospital admissions compared to children of non-Indigenous mothers. Children of foreign-born mothers from low-income countries had the highest rate of hospital admissions if disability was present. Children with cerebral palsy (CP) with or without associated intellectual disability had the highest rate of hospital admissions among children with developmental disability, especially if mothers were foreign-born.Interpretation: Children with CP and intellectual disability, particularly from minority backgrounds (Indigenous Australian and foreign-born mothers), were at higher risk of being admitted to hospital after the first year of life.What This Paper Adds: Hospital admissions in Australian children with and without disabilities differ according to maternal country of birth. Hospital admission rates in children without a developmental disability were greatest for Australian-born Indigenous children. Disabled Australian-born children of foreign-born mothers from low-income countries had the highest hospital admission rates. Hospital admission risk was greatest for Australian-born children with cerebral palsy, especially if mothers were foreign-born. [ABSTRACT FROM AUTHOR]

Aim: To identify maternal, obstetric, and neonatal risk factors related to perinatal arterial ischaemic stroke (PAIS) diagnosed within 28 days after birth and to understand the underlying pathophysiology.Method: For case and control ascertainment, we used active surveillance in 345 paediatric hospitals and a population-based perinatal database for quality assurance of hospital care. We analysed complete cases of PAIS using logistic regression. Multivariate analysis was guided by a directed acyclic graph.Results: After exclusion of records with missing data, we analysed 134 individuals with PAIS and 576 comparison individuals. In univariate analysis, male sex, preterm birth (<37wks gestational age), small for gestational age (SGA), low umbilical artery pH (<7.1), low 5-minute-Apgar score (<7), multiple pregnancies, hypoxia, intubation/mask ventilation, nulliparity, Caesarean section, vaginal-operative delivery, chorioamnionitis, and oligohydramnios were associated with an increased risk. Mutual adjustment yielded male sex (odds ratio [OR] 1.81; 95% confidence interval [CI] 1.20-2.73), multiple birth (OR 3.22; 95% CI 1.21-8.58), chorioamnionitis (OR 9.89; 95% CI 2.88-33.94), preterm birth (OR 1.86; 95% CI 1.01-3.43), and SGA (OR 3.05; 95% CI 1.76-5.28) as independent risk factors.Interpretation: We confirmed the increased risk in males and the role of chorioamnionitis and SGA for PAIS, pointing to the importance of inflammatory processes and fetal-placental insufficiency. Multiple birth and preterm birth were additional risk factors.What This Paper Adds: Chorioamnionitis and small for gestational age (SGA) precede perinatal arterial ischaemic stroke (PAIS). Chorioamnionitis and SGA are independent risk factors for PAIS. Inflammatory processes and fetal-placental insufficiency are the likely underlying mechanisms. Multiple birth and preterm birth are additional risk factors. [ABSTRACT FROM AUTHOR]

Aim: To determine factors associated with acquisition of a sitting position in patients with spinal muscular atrophy type 1 (SMA1) treated with nusinersen.Method: Using data from the registry of patients with SMA1 treated with nusinersen, we compared the subgroups of sitters and non-sitters after 14 months of therapy as a function of baseline level, SMN2 copy number, age at treatment initiation, and improvement at 2 and 6 months post-treatment initiation. We used Hammersmith Infant Neurological Examination, Section 2 (HINE-2) and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders for motor evaluation.Results: Fifty children (22 females, 28 males), mean age 22 months (SD 20.7; range 2.5-102.8mo) were treated. Data on sitting position acquisition were collected for 47 patients at month 14. Fifteen patients were able to sit unassisted; 11 of 15 had a baseline HINE-2 score of at least 2 points and 11 of 14 had an improvement over baseline of at least 2 points at month 6. Patients who improved by 2 or more points at month 6 were three times more likely to be sitters at month 14 than those who did not.Interpretation: High baseline motor function and improvement in HINE-2 score after 6 months of treatment are associated with the probability of acquiring a sitting position in patients with SMA1 treated with nusinersen.What This Paper Adds: Fifteen of 47 patients with spinal muscular atrophy could sit unaided 14 months after treatment with nusinersen. The number of SMN2 copies were not predictive of acquisition of a sitting position. Baseline condition and clinical response after 6 months of treatment were most predictive of sitting position acquisition. [ABSTRACT FROM AUTHOR]

Aim: To describe health-related quality of life (HRQoL), pain, fatigue, and other health variables in young adults with cerebral palsy (CP), and to explore associations with the Gross Motor Function Classification System - Expanded and Revised (GMFCS-ER) and physical activity.Method: This was a cross-sectional study of 61 young adults at a mean age of 21 years 2 months (standard deviation 8mo, range 20-22y) with CP, from a geographically defined area. Data collection included: Short Form 36 version 2 for HRQoL, Brief Pain Inventory - Short Form, Fatigue Severity Scale, level of physical activity, medical history, and physical examination.Results: Overall HRQoL equalled that of population norms; however self-reported physical health was lower in GMFCS-ER levels III to V compared to GMFCS-ER levels I to II. Self-reported mental health was, inversely, lower in GMFCS-ER levels I to II compared to GMFCS-ER levels III to V. Pain prevalence was 49%, and pain was present across all GMFCS-ER levels. Fatigue, as well as sleep problems, had 41% prevalence, with fatigue severity decreasing with increasing level of physical activity.Interpretation: General HRQoL in young adults with CP was comparable to population norms. Pain and fatigue are important to address in high motor-functioning individuals also. Physical activity could be a possible protective factor against fatigue.What This Paper Adds: Health-related quality of life in young adults with cerebral palsy (CP) was comparable to population norms. Pain, fatigue, and sleep problems occurred at all Gross Motor Function Classification System levels. There is a possible protective effect of physical activity on fatigue. [ABSTRACT FROM AUTHOR]

Aim: To evaluate whether spasticity measures are related to pain in adults with cerebral palsy (CP).Method: This cross-sectional study recruited individuals aged 16 to 89 years with a diagnosis of CP. Participants completed the Penn Spasm Frequency Scale (PSFS), Brief Pain Inventory (BPI), and PROMIS Pain Interference measures. The Modified Ashworth Scale (MAS) and Tardieu spasticity angles of six joints were rated and summed to composite MAS and Tardieu scores for each participant. Associations between spasticity and pain measures were evaluated.Results: Forty-seven participants (27 females, 20 males) with a mean age of 35 years 7 months (range 18-77y) spanning all Gross Motor Function Classification System (GMFCS) levels were included. Twenty-six participants reported their average pain level on BPI as greater than 0 over the past week (median pain level 4.0). Median PSFS was 1.0 (range 0.0-1.0) and this correlated with average BPI and Pain Interference T scores (median 40.7; ρ=0.33 and ρ=0.31 respectively [both p=0.01]). When adjusted for pain medication use and age, MAS correlated with BPI (ρ=0.30; p=0.04). Other pain and spasticity measures, or GMFCS level, were not significantly related with pain interference or BPI rating. Age was weakly associated with BPI (slope=0.10; p<0.01).Interpretation: PROMIS Pain Interference was lower than population-based norms. Patient-rated spasm frequency demonstrated better association with pain levels and interference than physician-rated MAS and Tardieu.What This Paper Adds: Pain was not associated with Gross Motor Function Classification System level. Pain increased with age, as anticipated. Self-reported spasm scores were associated with increased pain in contrast to clinical examination scales. Adjusted, summed spasticity on the Modified Ashworth Scale was associated with pain scores on the Brief Pain Inventory. Although pain is experienced by adults with cerebral palsy, pain did not interfere with activities. [ABSTRACT FROM AUTHOR]

Aim: To characterize the clinical and genetic characteristics of a large cohort of patients with pyridoxine-dependent epilepsy (PDE).Method: We retrospectively collected clinical and genetic information of 33 (15 males, 18 females; mean [SD] age 4y 11mo [2y 5mo]; 1y 3mo-10y 4mo) patients with PDE from 31 unrelated families at a single centre.Results: There were many types of seizures, with focal seizures in 32 cases. Dravet syndrome was suspected clinically in two patients. Electroencephalogram (EEG) was normal in seven patients at the initial stage and then in 17 patients during pyridoxine maintenance therapy. Genetic studies revealed 26 kinds of variants in ALDH7A1 and four in PLPBP with 18 variants unreported previously, and 48 ALDH7A1 variants were located in exon 11, 12, 14, and 17 or intron 9 and 11. In addition, three patients carried different exons deletion. Among these, seizures could be controlled for several years in one patient by levetiracetam monotherapy. Another patient remained seizure free for up to 7 months without therapy. All patients received oral pyridoxine treatment, with only one case (with exon 8-13 deletion) showing poor control.Interpretation: This study illustrates the range of clinical presentations and genetic causes in PDE, as well as responsiveness to antiepileptic drugs. A relationship between EEG and pyridoxine therapy could be seen in many cases. Seizure control was seen in all with pyridoxine monotherapy except for one patient.What This Paper Adds: There is a parallel relationship between electroencephalogram and pyridoxine therapy in many patients. Patients with pyridoxine-dependent epilepsy may respond well to low-dose pyridoxine. [ABSTRACT FROM AUTHOR]

Aim: This study examined children's health care service use, mothers' workforce participation, and mothers' community engagement based on children's risk of developmental delay.Method: We used data from the All Our Families study, a prospective pregnancy cohort. Ages and Stages Questionnaire (ASQ) scores at year 2 indicated risk of developmental delay. To investigate the impact of risk of developmental delay when children were not diagnosed, a sensitivity analysis excluded reports of neurodevelopmental disorder (NDD) diagnosis at year 3. Outcomes were maternal reports of children's health and allied health visits (and estimated costs), and maternal workforce participation and community engagement from year 2 to 3.Results: Among 1314 mother-child dyads, 209 (16%) children were classified as being at risk of developmental delay by the ASQ, and 42 (3%) had a reported diagnosis of NDD. Risk of developmental delay was related to increased use of allied health care services (incidence risk ratio 5.04 [year 3]; 95% confidence interval 2.49-10.2) and health visits (incidence risk ratio 1.33 [year 3]; 95% confidence interval 1.14-1.54). The average expected allied health costs were greater for children at risk versus not at risk of developmental delay. However, when excluding children with reported diagnoses of an NDD from this analysis, increased service use and costs in the remaining at-risk population were not observed. Community engagement and workplace participation among families did not differ on the basis of risk of developmental delay.Interpretation: These results suggest increased health care service use by families of children at risk of developmental delay is driven by those receiving a diagnosis of an NDD in the subsequent year.What This Paper Adds: Early developmental delay risk was related to health care service use and costs. Diagnosis of neurodevelopmental disorder drove increased health care service use and costs. Early developmental delay risk did not relate to parental workforce participation. Early developmental delay risk did not relate to community engagement participation. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate tolerability of and response to rituximab in children with myelin oligodendrocyte glycoprotein (MOG) antibody-positive relapsing neuroinflammatory disease. This was an observational study of prospectively collected data on 12 consecutive children (eight females, four males; median age at onset 10y 6mo [interquartile range {IQR} 7y 2mo-12y 5mo], median follow-up 2y 1mo [IQR 1y 7mo-2y 6mo]) with central nervous system inflammation and persistent serum MOG immunoglobulin G positivity more than 12 weeks after clinical presentation. Patients received a standardized rituximab treatment protocol. MOG antibody testing was performed following standardized cell-based methods. Median clinical follow-up after rituximab induction was 2 years (IQR 1y 7mo-2y 10mo). The relapse rate in the first 12 months posttreatment was 0 (IQR 0-0). After rituximab, two patients relapsed during B-cell suppression and four showed clinical or radiological disease recurrences at B-cell reconstitution. Mild-to-moderate infusion related adverse events occurred in two patients. Leukopenia developed in seven patients and serum immunoglobulin suppression in five patients with no significant age effect on the risk of their development. None developed severe life-threatening events. Rituximab-induced B-cell suppression was associated with absence of relapses in 10 patients who were MOG-positive with recurrent disease. Rituximab was well tolerated. The most frequent adverse effects were hypogammaglobulinemia and leukopenia. We recommend monitoring of complete blood counts and immunoglobulins in this population. WHAT THIS PAPER ADDS: Rituximab appears to control disease in most anti-myelin oligodendrocyte glycoprotein-positive patients with relapsing neuroinflammatory disease. Rituximab was associated with transitory, mild-to-moderate infusion-related effects. Half of patients treated with rituximab developed leukopenia or hypogammaglobulinemia. No opportunistic infections were observed. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the utility of Ability Captured Through Interactive Video Evaluation (ACTIVE) scaled scores to quantify meaningful change in individuals with spinal muscular atrophy (SMA) types 2 or 3 due to disease progression or treatment.Method: ACTIVE is a custom-designed video game that measures workspace volume (WSV). Participants included 62 individuals with SMA (mean age [SD] 10y 9mo [5y], range 2y 9mo-24y) and 362 frequency-matched controls (mean age [SD] 10y 9mo [3y 6mo], range 3y 2mo-24y 9mo). Participants completed ACTIVE, other traditional assessments, and patient-reported outcomes. Responsiveness to change was evaluated by comparing longitudinal data on untreated participants to those receiving Spinraza.Results: ACTIVE was significantly correlated to the Hammersmith Functional Motor Scales Expanded and Revised Upper Limb Module (ρ=0.85 and ρ=0.92 respectively; p<0.001). Relevance to patients and families was established by strong correlations to the Patient Reported Outcomes Measurement Information System self- and parent proxy-measures of upper extremity ability (ρ=0.63 and ρ=0.70 respectively; p<0.001). Responsiveness to change was demonstrated by significant change in scaled scores after treatment (median 15.9 points, Wilcoxon signed-rank test p<0.01). A preliminary minimum clinically important difference is presented.Interpretation: These results suggest that ACTIVE WSV scores are a meaningful assessment with which to quantify change over time in individuals with SMA types 2 and 3.What This Paper Adds: Ability Captured Through Interactive Video Evaluation (ACTIVE) quantifies upper extremity function in spinal muscular atrophy. ACTIVE's scaled workspace volume strongly correlates to self- and parent-report of function. ACTIVE quantifies meaningful change after treatment. [ABSTRACT FROM AUTHOR]

Aim: To describe the clinico-radiological phenotype of children with a CACNA1A mutation and to precisely evaluate their learning ability and cognitive status.Method: Children between the ages of 3 and 18 years harboring a pathogenic CACNA1A mutation associated with episodic ataxia, hemiplegic migraine, benign paroxysmal torticollis, benign paroxysmal vertigo, or benign paroxysmal tonic upgaze, were enrolled in this cross-sectional study. Data concerning psychomotor development, academic performance, educational management, clinical examination at inclusion, and brain imaging were collected. Cognitive assessment was performed using age-standardized scales.Results: Eighteen patients (nine males, nine females; mean age at inclusion: 11y 7mo [SD 4y 5mo; range 3y-17y 11mo]) from 14 families were enrolled. Eleven patients displayed the coexistence or consecutive occurrence of more than one type of episodic event. Nine patients exhibited abnormal neurological examination at inclusion. Brain magnetic resonance imaging (MRI) showed cerebellar atrophy in five patients. Psychomotor development was delayed in nine patients and academic difficulties were reported by the parents in 15 patients; nine patients were in special education. Impairment of intellectual function was assessed in six of the 12 patients with interpretable Full-scale IQ scores and was more frequent when cerebellar atrophy was present on MRI.Interpretation: Cognitive impairment is commonly associated with CACNA1A mutations. We suggest that CACNA1A-associated phenotype should be considered a neurodevelopmental disorder.What This Paper Adds: Cognitive disabilities and academic difficulties are common in children with CACNA1A mutations associated with episodic syndromes. Cognitive function ranges from normal to moderate intellectual disorder in wheelchair-dependent children. Patients with vermian atrophy are at a higher risk of cognitive impairment. [ABSTRACT FROM AUTHOR]

Few prior studies have examined the extent to which the behavior and characteristics of political extremists are related to their position within radical groups. In this paper we concentrate on one of the most fundamental distinctions in groups: That between leaders and followers. Our main goal is to investigate the comparative propensity of leaders and followers to engage in political violence. In a sample of individuals who have committed ideologically motivated political crimes in the United States (N = 1,331). we found that even though leaders were more ideologically committed to the group's goals and ideologies, they were at the same time less likely to engage in violent acts. Moreover, we found that leaders in radical criminal organizations shared many characteristics with leaders in noncriminal organizations. Specifically, in comparison to followers, they were more often male, older, and they were more likely to belong to an ethnic majority. We consider implications for future research and policy of the fundamental conclusion that compared to leaders, followers in terrorist organizations are more likely to engage in violent acts. [ABSTRACT FROM AUTHOR]

Data collected for a genome-wide association study of a primary phenotype are often used for additional genome-wide association analyses of secondary phenotypes. However, when the primary and secondary traits are dependent, naïve analyses of secondary phenotypes may induce spurious associations in non-randomly ascertained samples. Previously, retrospective likelihood-based methods have been proposed to correct for sampling biases arising in secondary trait association analyses. However, most methods have been introduced to handle studies featuring a case-control design based on a binary primary phenotype. As such, these methods are not directly applicable to more complicated study designs such as multiple-trait studies, where the sampling mechanism also depends on the secondary phenotype, or extreme-trait studies, where individuals with extreme primary phenotype values are selected. To accommodate these more complicated sampling mechanisms, only a few prospective likelihood approaches have been proposed. These approaches assume a normal distribution for the secondary phenotype (or the latent secondary phenotype) and a bivariate normal distribution for the primary-secondary phenotype dependence. In this paper, we propose a unified copula-based approach to appropriately detect genetic variant/secondary phenotype association in the presence of selected samples. Primary phenotype is either binary or continuous and the secondary phenotype is continuous although not necessary normal. We use both prospective and retrospective likelihoods to account for the sampling mechanism and use a copula model to allow for potentially different dependence structures between the primary and secondary phenotypes. We demonstrate the effectiveness of our approach through simulation studies and by analyzing data from the Avon Longitudinal Study of Parents and Children cohort. [ABSTRACT FROM AUTHOR]

In developing products for rare diseases, statistical challenges arise due to the limited number of patients available for participation in drug trials and other clinical research. Bayesian adaptive clinical trial designs offer the possibility of increased statistical efficiency, reduced development cost and ethical hazard prevention via their incorporation of evidence from external sources (historical data, expert opinions, and real-world evidence), and flexibility in the specification of interim looks. In this paper, we propose a novel Bayesian adaptive commensurate design that borrows adaptively from historical information and also uses a particular payoff function to optimize the timing of the study's interim analysis. The trial payoff is a function of how many samples can be saved via early stopping and the probability of making correct early decisions for either futility or efficacy. We calibrate our Bayesian algorithm to have acceptable long-run frequentist properties (Type I error and power) via simulation at the design stage. We illustrate our approach using a pediatric trial design setting testing the effect of a new drug for a rare genetic disease. The optimIA R package available at https://github.com/wxwx1993/Bayesian_IA_Timing provides an easy-to-use implementation of our approach. [ABSTRACT FROM AUTHOR]

Aim: To investigate long-term development of hand function after repeated botulinum neurotoxin A (BoNT-A) and occupational therapy at a young age.Method: Twenty children with unilateral spastic cerebral palsy (CP) (14 males, six females; median inclusion age 3y 1mo, range 1y 11mo-4y 3mo) participated in this longitudinal study. Ten children received occupational therapy after a randomized controlled trial and 10 repeated BoNT-A plus occupational therapy during 1-year. The Assisting Hand Assessment (AHA) and active supination, assessed the following 3 years. The assessments were compared with data from a reference group to investigate development over time.Results: The improvement in AHA (7.5 AHA units) after BoNT-A plus occupational therapy was maintained at final follow-up. The occupational therapy group, unchanged after 1-year, improved by 5 AHA units (96% confidence interval [CI] 2-10), thus there was no difference between the groups. Median active supination increased in comparison with the reference group. In the BoNT-A/occupational therapy group, 9 out of 10 (97.85% CI 45 115) children improved in active supination. In the occupational therapy group, 7 out of 10 (97.85% CI -2 to 68) children improved in active supination. No correlation between active supination and AHA was found.Interpretation: Bimanual performance achieved after BoNT-A plus occupational therapy was maintained, while it increased by follow-up in the occupational therapy group, suggesting that combined intervention gave earlier access to bimanual skills. Active supination was unrelated to AHA.What This Paper Adds: Children whose bimanual performance improved after botulinum neurotoxin A and/or occupational therapy, maintained skills or progressed during follow-up. Bimanual performance increased with age, similar to a quality-register reference group. Increased active supination after intervention improved at follow-up but was not related to bimanual performance. [ABSTRACT FROM AUTHOR]

Aim: To describe fatigue in Duchenne muscular dystrophy (DMD) from patients' and parents' perspectives and to explore risk factors for fatigue in children and adolescents with DMD.Method: A multicentre, cross-sectional study design was used. Seventy-one patients (all males; median age 12y, age range 5-17y) identified via the Canadian Neuromuscular Disease Registry, and their parents completed questionnaires. Subjective fatigue was assessed using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale by child self-report and parent proxy-report.Results: Patients with DMD across ages and disease stages experienced greater fatigue compared to typically developing controls from published data. Sleep disturbance symptoms were associated with greater fatigue by child self-report (ρ=-0.42; p=0.003) and parent proxy-report (ρ=-0.51; p<0.001). Depressive symptoms were associated with greater fatigue by child self-report (ρ=-0.46; p<0.001) and parent proxy-report (ρ=-0.45; p<0.001). Lower functional ability was associated with greater fatigue by parent proxy-report (ρ=0.26; p=0.03). Physical activity level, and musculoskeletal, respiratory, and cardiac function were not associated with fatigue.Interpretation: In paediatric DMD, sleep disturbance symptoms and depressive symptoms are potentially modifiable factors associated with fatigue, warranting additional investigation to facilitate the development of therapeutic strategies to reduce fatigue.What This Paper Adds: Fatigue is a major issue in paediatric Duchenne muscular dystrophy (DMD) across ages and disease stages. Sleep disturbance and depressive symptoms are significantly associated with fatigue in paediatric DMD. [ABSTRACT FROM AUTHOR]

Aim: To characterize fatigue in children with hemiparesis with perinatal stroke and explore associations with measures of motor performance and corticospinal excitability.Method: Forty-five children (16 females, 29 males), aged 6 to 18 years (mean [SD] 12y [4]), with magnetic resonance imaging-confirmed perinatal stroke participated. Associations between fatigue (Pediatric Quality of Life Inventory Version 3.0 cerebral palsy module fatigue subscale), motor performance (Assisting Hand Assessment [AHA], Box and Blocks Test, grip strength), and excitability of corticospinal projections to both hands were examined using ranked tests of correlation, robust regression, and the Mann-Whitney U test.Results: Nearly half of the participants (n=21) reported experiencing fatigue in the previous month. Function in the less affected hand (Box and Blocks Test, grip strength) was correlated with fatigue scores. Participants with preserved ipsilateral projections to the more affected hand had less fatigue, and scores correlated with the excitability of these projections. Fatigue scores were not associated with age, sex, or AHA score.Interpretation: Fatigue is common in children with hemiparesis with perinatal stroke and is associated with motor performance and the presence and excitability of ipsilateral corticospinal projections from the contralesional hemisphere to the more affected hand.What This Paper Adds: Fatigue is common in children with hemiparesis with perinatal stroke. Fatigue was associated with motor performance and strength in the less affected, but not the more affected, hand. Fatigue was associated with the presence and excitability of ipsilateral corticospinal projections from the contralesional hemisphere. [ABSTRACT FROM AUTHOR]

Aim: To evaluate fatigue, depression, and quality of life (QoL) of children with multiple sclerosis and compare to other acute demyelinating syndromes (ADS).Method: Children followed in the National Referral Centre of rare inflammatory brain and spinal diseases were included in this study. The Expanded Disability Status Scale, the fatigue severity scale, the Multiscore Depression Inventory for Children, and the Pediatric Quality of Life Inventory were used for evaluation.Results: Thirty-seven children (23 females, 14 males) were included in this study. Multiple sclerosis was diagnosed in 26 children and ADS in 11 children. Although not significant, severe fatigue was less frequently reported by patients with multiple sclerosis than children with ADS (44% vs 63%, p=0.2). Depression was reported more often in the multiple sclerosis group compared to the ADS group (24% vs 18%, p=0.6). Concerning the QoL in patients with multiple sclerosis, both parents and children reported poor emotional and school functioning. Physical and social functioning were rated as being good in both groups, and was significantly higher in the children's group (p=0.007).Interpretation: This study highlights the importance of fatigue and depression in children with ADS and particularly in paediatric onset multiple sclerosis. Moreover, difficulties in school and emotional functioning were the main concerns for parents and children in the multiple sclerosis group which need to be taken in account during their care and treatment proposal.What This Paper Adds: Invisible signs such as fatigue and depression affect all forms of acute demyelinating syndromes (ADS) in children. Depression seems to be higher in children with multiple sclerosis than with other forms of ADS. Fatigue seems to be lower in children with multiple sclerosis than with other forms of ADS. Children with multiple sclerosis and their parents are most concerned with emotional and academic functioning. [ABSTRACT FROM AUTHOR]

Background: The objective of our study was to analyze the prognostic value of the combination of serum ALP and pleural effusion LDH (AL score) for malignant pleural effusion (MPE) patients. Methods: This study includes retrospective, descriptive and observational research from 1 June 2006 to 1 December 2017, which aimed to identify prognostic factors related to MPE patients. We analyzed the association of various clinical features, routinely tested markers from peripheral blood and MPE at diagnosis and overall survival (OS). All MPE patients were assigned to three groups according to their AL score. The impact of the AL score and other prognostic factors were evaluated with multivariable regression. Results: According to their AL score, 193 patients were assigned to three groups with 25 in group 0 (sALP < 65 U/L and pLDH < 155 U/L), 121 in group 1 (sALP > 65 U/L or pLDH > 155 U/L) and 47 (sALP > 65 U/L and pLDH > 155 U/L) in group 2. For groups 0, 1 and 2, median survival times (MST) were 23, 15 and 7 months, respectively. Among the three groups, MST, serum albumin level, C reactive protein, erythrocyte sedimentation rate, the ratios of platelet‐to‐lymphocyte, neutrophil‐to‐lymphocyte showed significant differences. The counts of neutrophils, monocytes, platelets and AL score (0 vs. 1, P = 0.038, hazard ratio [HR]: 1.858, 95% confidence interval [CI]: [1.034, 3.339]; 0 vs. 2, P = 0.001, HR: 2.993, 95% CI: [1.556, 5.531]) were independent prognostic indicators for OS of MPE patients. Conclusion: AL score is a promising indicator which can be used to predict the prognosis of MPE patients. It can assist physicians in the selection of patients for appropriate palliative treatment. Key points: To our knowledge, this paper is the first study that combined two enzymes (sALP and pLDH) from serum and pleural effusion and studied the prognostic value for MPE patients. It has been proved to be a promising indicator to assist physicians select patients for appropriate palliative treatment. [ABSTRACT FROM AUTHOR]

Aim: To determine development curves of communication and social interaction from childhood into adulthood for individuals with cerebral palsy (CP).Method: This Pediatric Rehabilitation Research in the Netherlands (PERRIN)-DECADE study longitudinally assessed 421 individuals with CP, aged from 1 to 20 years at baseline, after 13 years (n=121 at follow-up). Communication and social interactions were assessed using the Vineland Adaptive Behavior Scales. We estimated the average maximum performance limit (level) and age at which 90% of the limit was reached (age90 ) using nonlinear mixed-effects modeling.Results: One-hundred individuals without intellectual disability were aged 21 to 34 years at follow-up (39 females, 61 males) (mean age [SD] 28y 5mo [3y 11mo]). Limits of individuals without intellectual disability, regardless of Gross Motor Function Classification System (GMFCS) level, approached the maximum score and were significantly higher than those of individuals with intellectual disability. Ages90 ranged between 3 and 4 years for receptive communication, 6 and 7 years for expressive communication and interrelationships, 12 and 16 years for written communication, 13 and 16 years for play and leisure, and 14 and 16 years for coping. Twenty-one individuals with intellectual disability were between 21 and 27 years at follow-up (8 females, 13 males) (mean age [SD] 24y 7mo [1y 8mo]). Individuals with intellectual disability in GMFCS level V showed the least favourable development, but variation between individuals with intellectual disability was large.Interpretation: Individuals with CP and without intellectual disability show developmental curves of communication and social interactions similar to typically developing individuals, regardless of their level of motor function. Those with intellectual disability reach lower performance levels and vary largely in individual development.What This Paper Adds: Communication and social interactions in individuals with cerebral palsy without intellectual disability develop similarly to typically developing individuals. Communication and social interactions of individuals with intellectual disability develop less favourably and show large variation. [ABSTRACT FROM AUTHOR]

Aim: To establish the incidence of infantile spasms in children in the southern region of the Republic of Ireland and to compare the incidence of infantile spasms before and after the introduction of therapeutic hypothermia in infants with hypoxic-ischemic encephalopathy (HIE).Method: Children born between 2003 and 2015 and diagnosed with infantile spasms (epileptic spasms with or without hypsarrhythmia) in the first 2 years of life were identified through audits of electroencephalography reports and paediatric neurology patient lists. Data on live births were obtained from the regional hospital statistics databases. Medical charts of infantile spasm cases were reviewed for demographic information, diagnostic workup results, treatment response, disease course, and developmental outcome.Results: Forty-two infants with infantile spasms were identified. The cumulative incidence of infantile spasms up to the age of 2 years was 4.01 per 10 000 live births. Difference due to sex was minimal (22 males, 20 females) and most infants were delivered at or near term with gestational ages ranging between 30.0 and 41.8 weeks (median [interquartile range] 39.6wks [38.1-40.0wks]). The aetiology for infantile spasms was identified in almost two-thirds of cases, with HIE being the single most common cause (n=7). Other causes included chromosomal and monogenetic abnormalities (n=8). Infantile spasms occurred in moderate and severe grades of HIE, with a significantly higher incidence in those with severe HIE (p=0.029). Infants with severe HIE who did not receive therapeutic hypothermia were six times more likely to develop infantile spasms compared to those who did, but the difference was not statistically significant (4 out of 16 vs 1 out of 24, p=0.138).Interpretation: This study provides detailed information about infantile spasms before and after the introduction of therapeutic hypothermia. HIE severity is a risk factor for the development of infantile spasms. The introduction of therapeutic hypothermia may have had an impact, but the effect was hard to ascertain in this cohort due to the small number of infants.What This Paper Adds: The incidence of infantile spasms and patient characteristics in the southern region of the Republic of Ireland is similar to internationally published data. None of the infants with a history of mild hypoxic-ischemic encephalopathy (HIE) developed infantile spasms. The risk of infantile spasms was higher in infants with severe HIE. Infantile spasms were more frequent in infants with severe HIE not treated with therapeutic hypothermia. [ABSTRACT FROM AUTHOR]