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Aim: Children born very preterm require additional specialist care because of the health and developmental risks associated with preterm birth, but information on their health service use is sparse. We sought to describe the use of specialist services by children born very preterm in Europe.Method: We analysed data from the multi-regional, population-based Effective Perinatal Intensive Care in Europe (EPICE) cohort of births before 32 weeks' gestation in 11 European countries. Perinatal data were abstracted from medical records and parents completed a questionnaire at 2 years corrected age (4322 children; 2026 females, 2296 males; median gestational age 29wks, interquartile range [IQR] 27-31wks; median birthweight 1230g, IQR 970-1511g). We compared parent-reported use of specialist services by country, perinatal risk (based on gestational age, small for gestational age, and neonatal morbidities), maternal education, and birthplace.Results: Seventy-six per cent of the children had consulted at least one specialist, ranging across countries from 53.7% to 100%. Ophthalmologists (53.4%) and physiotherapists (48.0%) were most frequently consulted, but individual specialists varied greatly by country. Perinatal risk was associated with specialist use, but the gradient differed across countries. Children with more educated mothers had higher proportions of specialist use in three countries.Interpretation: Large variations in the use of specialist services across Europe were not explained by perinatal risk and raise questions about the strengths and limits of existing models of care.What This Paper Adds: Use of specialist services by children born very preterm varied across Europe. This variation was observed for types and number of specialists consulted. Perinatal risk was associated with specialist care, but did not explain country-level differences. In some countries, mothers' educational level affected use of specialist services. [ABSTRACT FROM AUTHOR]

Aim: This cross-sectional investigation evaluated whether recurrent botulinum neurotoxin A (BoNT-A) interventions to the medial gastrocnemius have an influence on muscle morphology, beyond Gross Motor Function Classification System (GMFCS) level.Method: A cohort of typically developing children (n=67; 43 males, 24 females; median age 9y 11mo [range 7y 10mo-11y 6mo]), a cohort of children with spastic cerebral palsy (CP) naive to BoNT-A interventions (No-BoNT-A; n=19; 10 males, nine females; median age 9y 3mo [range 8y 5mo-10y 10mo]) and a cohort of children with spastic CP with a minimum of three recurrent BoNT-A interventions to the medial gastrocnemius (BoNT-A; n=19; 13 males, six females; median age 9y 8mo [range 7y 3mo-10y 7mo]) were recruited. Three-dimensional freehand ultrasound was used to estimate medial gastrocnemius volume normalized to body mass and echo-intensity.Results: Normalized medial gastrocnemius volume and echo-intensity significantly differed between the two spastic CP cohorts (p≤0.05), with the BoNT-A cohort having larger alterations. Associations between normalized medial gastrocnemius volume and echo-intensity were highest in the No-BoNT-A cohort, followed by the BoNT-A cohort. Multiple regression analyses revealed that both GMFCS level and BoNT-A intervention history were significantly associated with smaller normalized medial gastrocnemius volume and higher echo-intensity.Interpretation: Recurrent BoNT-A interventions may induce alterations to medial gastrocnemius volume and echo-intensity beyond the natural history of the spastic CP pathology.What This Paper Adds: In spastic cerebral palsy, medial gastrocnemius volumes are smaller and echo-intensities higher compared with typical development. Alterations after botulinum neurotoxin A intervention (BoNT-A) are larger than in no BoNT-A intervention. Gross Motor Function Classification System level and BoNT-A history significantly associate with medial gastrocnemius and echo-intensity alterations. [ABSTRACT FROM AUTHOR]

Aim: To examine: (1) relationships between brain structure, and concurrently assessed neurological and behavioural functioning, in infants born preterm at term-equivalent age (TEA; approximately 38-44wks); and (2) whether brain structure-function relationships differ between infants born very (24-29wks) and moderate-late (32-36wks) preterm.Method: A total of 257 infants (91 very preterm, 166 moderate-late preterm; 120 males, 137 females) had structural magnetic resonance imaging (MRI) and neurological and behavioural assessments (Prechtl's general movements assessment, Neonatal Intensive Care Unit Network Neurobehavioral Scale [NNNS] and Hammersmith Neonatal Neurological Examination [HNNE]). Two hundred and sixty-three infants (90 very preterm, 173 moderate-late preterm; 131 males, 132 females) had diffusion MRI and assessments. Associations were investigated between assessment scores and global brain volumes using linear regressions, regional brain volumes using Voxel-Based Morphometry, and white matter microstructure using Tract-Based Spatial Statistics.Results: Suboptimal scores on some assessments were associated with lower fractional anisotropy and/or higher axial, radial, and mean diffusivities in some tracts: NNNS attention and reflexes, and HNNE total score and tone, were associated with the corpus callosum and optic radiation; NNNS quality of movement with the corona radiata; HNNE abnormal signs with several major tracts. Brain structure-function associations generally did not differ between the very and moderate-late preterm groups.Interpretation: White matter microstructural alterations may be associated with suboptimal neurological and behavioural performance in some domains at TEA in infants born preterm. Brain structure-function relationships are similar for infants born very preterm and moderate-late preterm.What This Paper Adds: Brain volume is not related to neurological/behavioural function in infants born preterm at term. White matter microstructure is related to some neurological/behavioural domains at term. Brain-behaviour relationships are generally similar for infants born very preterm and moderate-late preterm. [ABSTRACT FROM AUTHOR]

Background: Longitudinal cohort studies gather large amounts of data over time, often without direct benefit to participants. A positive experience may encourage retention in the study, and participants may benefit in unanticipated ways. Objective: To explore first‐time mothers' experiences of taking part in a longitudinal cohort study and completing self‐administered surveys during pregnancy and at 3, 6, 9 and 12 months' postpartum. Design: Content analysis of comments written by participants in the Maternal health And Maternal Morbidity in Ireland study's five self‐completion surveys, a multisite cohort study exploring women's health and health problems during and after pregnancy. This paper focuses on what women wrote about taking part in the research. Ethical approval was granted by the site hospitals and university. Setting and participants: A total of 2174 women were recruited from two maternity hospitals in Ireland between 2012 and 2015. Findings: A total of 1000 comments were made in the five surveys. Antenatally, barriers related to surveys being long and questions being intimate. Postpartum, barriers related to being busy with life as first‐time mothers. Benefits gained included gaining access to information, taking time to reflect, stopping to think and being prompted to seek help. Survey questions alone were described as valuable sources of information. Discussion and conclusions: Findings suggest that survey research can "give back" to women by being a source of information and a trigger to seek professional help, even while asking sensitive questions. Understanding this can help researchers construct surveys to maximize benefits, real and potential, for participants. [ABSTRACT FROM AUTHOR]

Aim: To examine the longitudinal trends of cardiometabolic diseases in a large sample of adults with cerebral palsy (CP).Method: The Optum Clinformatics Data Mart is a de-identified nationwide claims database of beneficiaries from a single private payer. Beneficiaries were included if they had an International Classification of Diseases, Ninth Revision, Clinical Modification code for a diagnosis of CP. Adults with at least 3 years of continuous enrollment on a single plan between 2002 and 2009 were included in the final analyses (n=2659). We examined the longitudinal trends of incident diabetes mellitus, hypercholesterolemia, hypertension, cardiac dysrhythmias, and atherosclerosis, stratified by age categories: 18 to 39 years, 40 to 59 years, and 60 years and over. Kaplan-Meier product-limit survival curves were compared across age categories for each of the cardiometabolic outcomes, and a Cox proportional hazards regression was run to determine adjusted hazard ratios.Results: The cumulative incidence of each of the cardiometabolic diseases ranged from 6.0% for atherosclerosis to 34.4% for hypercholesterolemia at 3 years and over. Risk-adjusted Cox proportional hazard models revealed that age was a robust predictor of survival for each outcome, with higher hazard ratio ranges in middle age (hazard ratio 1.41-2.72) and older adults (hazard ratio 2.20-5.93) compared with young adults.Interpretation: Adults with CP have high rates of cardiometabolic diseases; and disease-free survival shortens significantly with higher ages.What This Paper Adds: Adults with cerebral palsy have high rates of cardiometabolic diseases. Disease-free survival of all cardiometabolic diseases shortens significantly with higher ages. The highest rates were for hypercholesterolemia and hypertension. [ABSTRACT FROM AUTHOR]

Aim: Neurodevelopmental outcomes in children with congenital cerebellar malformations (CCMs) remain poorly defined. We aimed to assess whether specific neuroimaging features in CCM patients correlate with neurodevelopmental outcomes.Method: Hospital records and neuroimaging of 67 children with CCMs were systematically reviewed. Logistic regression analyses were used to assess associations between specific imaging features and neurodevelopmental outcomes.Results: CCM categories were distributed as follows: 28 percent isolated vermis hypoplasia (n=19), 28 percent global cerebellar hypoplasia (n=19), 15 percent Dandy-Walker malformation (n=10), 13 percent pontocerebellar hypoplasia (PCH, n=9), 9 percent molar tooth malformation (n=6), 3 percent rhombencephalosynapsis (n=2), and 3 percent unilateral cerebellar malformation (n=2). Overall, 85 percent (55/65) of the cohort had global developmental delay (GDD). Intellectual disability was present in 61 percent (27/43) and autism spectrum disorder (ASD) in 12 percent (6/52). Adjusting for supratentorial malformations and presence of genetic findings, severe GDD was associated with cerebellar hypoplasia (p=0.049) and PCH (p=0.030), whereas children with vermis hypoplasia were less likely to have severe GDD (p=0.003). Presence of supratentorial abnormalities was not significantly associated with worse neurodevelopmental outcome but was associated with epilepsy.Interpretation: Children with CCMs have high prevalence of neurodevelopmental deficits. Specific features on imaging can aid prognostication and establish early intervention strategies.What This Paper Adds: Atypical long-term neurodevelopmental outcome is very common in patients with congenital cerebellar malformations (CCMs). Involvement of the brainstem and cerebellar hemispheres predicts more severe neurodevelopmental disability. Most patients with vermis hypoplasia have language delay but are verbal. Supratentorial abnormalities are not significantly associated with worse neurodevelopmental outcome but are associated with epilepsy. Comorbidities are common in CCMs, especially ophthalmological issues in cerebellar hypoplasia and sensorineural hearing loss in pontocerebellar hypoplasia. [ABSTRACT FROM AUTHOR]

Aim: To investigate trends in birth prevalence of cerebral palsy (CP) overall and by gestational age, and examine the distribution of motor type, spastic topography, and severity using Australian CP Register data from 1995 to 2009.Method: Prenatal and perinatal CP data were collated from state/territory CP registers. Birth prevalence estimates per 1000 live births and per 1000 neonatal survivors (NNS) were calculated in five epochs. Data from three state registers with population-level ascertainment were used to investigate birth prevalence trends by gestational age using Poisson regression. Distribution of motor type, spastic topography, and moderate to severe disability (IQ≤50 and/or Gross Motor Function Classification System levels III-V) were evaluated within birthweight categories.Results: Birth prevalence of CP varied across population-level states but within each state declined significantly over time (p<0.05). Birth prevalence per 1000 neonatal survivors declined amongst children born before 28 weeks (South Australia, Victoria p<0.001) and those born at or after 37 weeks (Victoria p<0.001, Western Australia p<0.002). Across Australia the percentage of children with bilateral spastic CP declined amongst those born less than 1000g. The percentage of children with moderate to severe disability decreased (48%-34%, p<0.001).Interpretation: Birth prevalence of CP declined. Encouragingly, the percentage of children with CP whose disability was moderate to severe also decreased.What This Paper Adds: Birth prevalence of cerebral palsy (CP) differed but declined across Australian states (1995-2009). Australian CP birth prevalence declined significantly amongst children born before 28 weeks and those born at or after 37 weeks. The percentage of children with moderate to severe disability decreased. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the longitudinal development of passive range of motion (ROM) in the upper limbs in a population-based sample of children with cerebral palsy (CP), and to investigate which children are more likely to develop contractures related to functional level, CP subtype, and age.Method: Registry data of annual passive ROM measurements of the upper limbs from 771 children with CP (417 males, 354 females; mean age 11y 8mo, [SD 5mo] range 1-18y) were analysed. Mixed models were used to investigate at what age decreased passive ROM occurs. Odds ratios were calculated to compare risks and logistic regression analysis was used to predict contracture development.Results: Thirty-four per cent of the children had developed contractures. Among these children, decreased passive ROM was significant at a mean age of 4 years for wrist extension and 7 years for shoulder flexion, elbow extension, and supination. Children at Manual Ability Classification System (MACS) level V had a 17-times greater risk of contractures than children at MACS level I.Interpretation: One-third of the children in the total population developed upper-limb contractures while passive ROM decreased with age. MACS level was the strongest predictor of contracture development.What This Paper Adds: In a population-based sample of 771 children with cerebral palsy, 34% developed an upper-limb contracture. Contracture development started at preschool age. The first affected movements were wrist extension and supination. Passive range of motion decreased with age. High Manual Ability Classification System level was the most important predictor of contractures. [ABSTRACT FROM AUTHOR]

Aim: To determine the long-term course of difficulty in participation of individuals with cerebral palsy (CP) without intellectual disability between 16 years and 34 years of age.Method: One hundred and fifty-one individuals with CP aged 16 to 20 years were included (63% male, 37% female; Gross Motor Function Classification System [GMFCS] levels I-IV; without intellectual disability). The Assessment of Life Habits questionnaire 3.0 general short form was used up to three times biennially and at 13-year follow-up (13-year follow-up: n=98). Scores (range 0-10) reflect difficulty and assistance in participation in housing, education and employment, interpersonal relationships, recreation, community life, and responsibilities. Multilevel models were used to determine the course of difficulty in participation by GMFCS level.Results: Despite high average participation levels, 41% to 95% of adolescents and young adults with CP experienced difficulty. Difficulty in participation in housing and interpersonal relationships increased from age 16 years onwards and in most other life areas in the mid- and late 20s. In adolescents in GMFCS levels III and IV, participation in recreation and community life improved up to age 23 years.Interpretation: Individuals with CP experience increasing difficulties in participation in their mid- and late 20s. Clinicians should systematically check for participation difficulties in young adults with CP and offer timely personalized treatment.What This Paper Adds: Many individuals with cerebral palsy (CP) aged 16 to 34 years experience difficulty in participation. Difficulty in participation increases in the mid- and late 20s for individuals with CP. Participation in recreation/community life improves before age 23 years for those in Gross Motor Function Classification System levels III and IV. [ABSTRACT FROM AUTHOR]

Aim: To compare the efficacy of the main methodologies in attaining sleep and electroencephalography (EEG) abnormalities in children with a view to producing recommendations on best practice.Method: Fifty-one UK centres participated. Methods for sleep induction (sleep deprivation, melatonin, and combined sleep deprivation/melatonin) were compared. Data pertaining to demographics, achievement of stage II sleep, and recording characteristics (duration of study, presence of epileptiform activity in awake/sleep states) were prospectively collected for consecutive patients in November and December 2013.Results: Five hundred and sixty-five patients were included. Age range was 1 years to 17 years (mean 7y 10mo), 27.7 per cent had an underlying neurobehavioural condition. Stage II sleep was achieved in 69 per cent of sleep deprived studies, 77 per cent of melatonin studies, and 90 per cent of combined intervention studies (p<0.001, χ2 ). In children who slept, there was no difference between the three interventions in eliciting epileptiform discharges. In children who did not sleep, epileptiform abnormalities were seen more often than after sleep deprivation alone (p=0.02, χ2 ). Seizures were rare.Interpretation: Combined sleep deprivation/melatonin is more effective than either method alone in achieving sleep. The occurrence of epileptiform activity during sleep is broadly similar across the three groups. We recommend the combined intervention to induce sleep for paediatric EEG.What This Paper Adds: Combined sleep deprivation/melatonin is more effective in achieving sleep than either sleep deprivation or melatonin alone. Sleep latency is shorter with combined sleep deprivation/melatonin. When children do sleep, there is no difference in the occurrence of epileptiform abnormalities between different induction methods. Seizures are rare in sleep electroencephalography recordings. [ABSTRACT FROM AUTHOR]

Rationale: Defensive caesarean section (CS) has become one of the most common medical procedure worldwide. Additionally, performing CS in accordance with the patient's choice is an appropriate professional practice. Aims and Objective: This paper reports a prospective, observational, multicenter study to quantify the use of this type of practice that is performed by obstetricians to avoid medico‐legal complaints and decrease the frequency of malpractice litigations. Methods: We interviewed 73 obstetricians from three distinct units of obstetrics and gynaecology, to assess their opinion regarding defensive caesarean delivery and caesarean delivery performed upon maternal request. We conducted an opinion‐based survey using questionnaires based on nine, close‐ended questions. Results: Out of 73 respondents, 51 (69.9%) stated that they perform defensive CS; 63 (86.3%) declared that their choice of birth delivery is influenced by the risk of being accused of malpractice; 60 (82.2%) indicated that it is normal for the patient to be able to decide on the type of delivery; and 63 (86.3%) declared that they consult their patients regarding their delivery preferences. We found statistically significant differences between the respondents who declare that they perform defensive CS (69.9%) and those who said that they are influenced by the risk of malpractice when they choose the method of delivery for their patients (86.3%) (P < .001; McNemar Test). Conclusions: The results of our study indicate that defensive caesarean section is a widespread practice among obstetrics practitioners in Romania. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to track alterations in muscle volume for 6 months in children with cerebral palsy (CP) after the first exposure to botulinum neurotoxin A (BoNT-A), a commonly used focal spasticity treatment.Method: Eleven ambulant children (eight males, three females) with spastic CP, mean age 8 years 10 months (SD 3y 1mo) participated. Participants received injections to the affected gastrocnemius. The muscle volume of the gastrocnemius, soleus, tibialis anterior, and hamstrings was measured using magnetic resonance imaging. Muscle volume was normalized to bone length, and changes analysed relative to baseline. Assessments were conducted 1 week before, and 4 weeks, 13 weeks, and 25 weeks after BoNT-A treatment.Results: All children demonstrated positive clinical and functional gains. Muscle volume of the injected gastrocnemius was found to be significantly reduced at 4 weeks (-5.9%), 13 weeks (-9.4%), and 25 weeks (-6.8%). Significant increases in normalized soleus muscle volume were identified at each follow-up, while hamstrings showed significant increase at 4 weeks only.Interpretation: Absolute and normalized muscle volume of the injected muscle reduces after first BoNT-A exposure, and does not return to baseline volume by 25 weeks. Hypertrophy is seen in the soleus up to 25 weeks; the volume of the plantar flexor compartment is stable.What This Paper Adds: Muscle atrophy after first botulinum neurotoxin A (BoNT-A) exposure in children with cerebral palsy is noted. Mild BoNT-A-induced muscle atrophy is still apparent 6 months after BoNT-A exposure. Hypertrophy is evident in soleus after gastrocnemius BoNT-A exposure. Total plantarflexor volume is unchanged. [ABSTRACT FROM AUTHOR]

Aim: To investigate the responsiveness of the ACTIVLIM-CP questionnaire after two evidence-based interventions for children with cerebral palsy (CP).Method: Seventy-five children with CP either participated in an intensive motor-skill learning intervention (hand-arm bimanual intensive therapy including lower extremities [HABIT-ILE], n=47) or received botulinum neurotoxin-A (BoNT-A) injection(s) into lower extremities combined with conventional physical therapy (n=28). All children were assessed three times: at baseline (T0 ; before HABIT-ILE/the day of BoNT-A injection), at T1 (last day of HABIT-ILE/6wks after BoNT-A injection), and at follow-up (T2 ; 3-4mo after the beginning of intervention). Parents completed ACTIVLIM-CP and three other activity questionnaires. Responsiveness was analysed using group (based on intervention), subgroup (based on gross motor function level), and individual approaches.Results: For the HABIT-ILE group, significant improvements in ACTIVLIM-CP were observed for the T0 -T1 period (p<0.001) but not for the T1 -T2 period. No significant changes were found in the BoNT-A group during assessments (p=0.84). In the subgroup analysis for the HABIT-ILE group (T0 -T1 ), greater changes were demonstrated for children in Gross Motor Function Classification System levels III and IV (p<0.001, effect size=1.36). The individual approach was congruent with the group approach.Interpretation: ACTIVLIM-CP demonstrated high responsiveness after HABIT-ILE, showing that this scale may be used to investigate global activity performance in clinical trials focusing on improving daily life activities.What This Paper Adds: Good responsiveness of ACTIVLIM-CP questionnaire during intensive motor-skill learning intervention. Higher responsiveness for children in Gross Motor Function Classification System (GMFCS) levels III and IV versus I and II after intensive intervention. ACTIVLIM-CP is useful to identify children improving their performance after botulinum neurotoxin-A injection. [ABSTRACT FROM AUTHOR]

Aim: Evidence is accumulating that motor and cognitive development are interrelated. This study investigates associations between motor development in infancy and cognitive function at 4 years of age.Method: This study is part of the Groningen prospective cohort study on the development of children born after assisted reproductive techniques such as in vitro fertilization. The study group consisted of 223 children (119 males, 104 females) born to subfertile couples (median gestational age 39.6wks, range 30-43wks). Motor behaviour was assessed with the Infant Motor Profile (IMP) at 4 months, 10 months, and 18 months. IQ was evaluated at 4 years with the Kaufman Assessment Battery for Children, Second Edition. Latent class growth modelling was used to analyse relations between IMP and IQ scores.Results: Infants with low total IMP scores had an IQ that was 8.9 points lower at 4 years than infants with typical IMP scores (95% confidence interval 3.6-14.1). Also, low scores in the domains of variation and performance were associated with a lower IQ at 4 years of age, by 6.1 points and 13.2 points respectively.Interpretation: Motor development in relatively low-risk infants is associated with cognition at 4 years of age. In particular, low motor variation and performance are associated with a lower IQ at 4 years of age.What This Paper Adds: Motor development in infancy is directly related to cognitive function at 4 years of age. This relationship is most pronounced for infant motor variation and performance. The size of the differences in IQ is clinically relevant. [ABSTRACT FROM AUTHOR]

Aim: The International Paediatric Multiple Sclerosis Study Group (IPMSSG) has proposed criteria for acute disseminated encephalomyelitis (ADEM) not evaluated in clinical practice. Our objective was to assess epidemiological implications of the IPMSSG criteria for ADEM in a cohort study using prospectively collected data.Method: We identified all diagnosed cases of ADEM in Denmark between 2008 and 2015 from the Danish National Patient Register by International Classification of Diseases 10 codes assigned to acute demyelinating episodes, and we reviewed all medical records to validate ADEM.Results: We found 52 children up to the age of 18 years with a verified clinical diagnosis of ADEM (incidence rate 0.54/100 000 person-years; all had abnormal brain magnetic resonance imaging). Only 18 (35%) fulfilled the IPMSSG criteria regarding encephalopathy and polyfocal neurological deficits. Among all 52 children with ADEM, 33 per cent had clinical sequelae after a median follow-up of 4 years 6 months (range: 10mo-8y 3mo). Surprisingly, none progressed to multiphasic ADEM or multiple sclerosis, but median age at end of follow-up was only 10 years 9 months (range: 2y-24y 3mo).Interpretation: Among 52 children with ADEM, none converted to multiphasic ADEM or multiple sclerosis (median follow-up: 4y 6mo; range: 10mo-8y 3mo). Applying the IPMSSG criteria to all children with a diagnosis of ADEM leaves 65 per cent of the cases without a diagnosis and lowers the incidence rate of paediatric ADEM.What This Paper Adds: The incidence of paediatric acute disseminated encephalomyelitis (ADEM) was 0.54 per 100 000 person-years in children younger than 18 years. Only 35 per cent of children with ADEM fulfilled the International Paediatric Study Group consensus criteria. ADEM in clinical practice was primarily based on magnetic resonance imaging findings. Paediatric neurologists diagnosed ADEM in the absence of encephalopathy. None of the children with ADEM progressed to multiple sclerosis/multiphasic ADEM during follow-up. [ABSTRACT FROM AUTHOR]

Aim: To estimate the strengths of association between clinical features and migraine or arterial ischaemic stroke (AIS) in children presenting to the emergency department.Method: Eighty-four children with migraine, prospectively recruited from 2009 to 2010, were compared with 55 children with AIS, prospectively/retrospectively recruited from 2003 to 2010. Odds ratios were calculated via logistic regression to measure associations between clinical features and process-of-care factors, and migraine and AIS.Results: Median age was 13 years 5 months (interquartile range 12y 11mo-13y 10mo) for migraine and 5 years (interquartile range 3y 7mo-8y) for patients with AIS. All cases of AIS and 30% of migraine cases underwent neuroimaging. Over 40% of children with migraine had vomiting, numbness, or visual disturbance; other symptoms were uncommon. Fifty-five per cent had no signs on physician assessment. Weakness or speech disturbance were common in patients with AIS. Significant clinical features associated with increased odds of AIS included sudden symptom onset, weakness, seizures, speech disturbance, and ataxia, and signs of face, arm, or leg weakness, inability to walk, dysarthria, dysphasia, and altered consciousness (p<0.05). Significant features associated with decreased odds of AIS included older age, vomiting, visual, sensory, other symptoms, and absent focal signs on assessment (p<0.05).Interpretation: Presenting features can discriminate childhood AIS from migraine. These differences inform decisions about urgency and type of neuroimaging in children presenting to the emergency department with brain attack symptoms.What the Paper Adds: Weakness, seizures, ataxia, speech, or walking difficulties are more frequent in arterial ischaemic stroke (AIS). Vomiting, visual, or sensory disturbance and absent focal signs are more frequent in migraine. Identifying features of AIS and migraine guides neuroimaging in children with brain attack symptoms. [ABSTRACT FROM AUTHOR]

Aim: To determine the stability of the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and Communication Function Classification System (CFCS) over 1-year and 2-year intervals using a process for consensus classification between parents and therapists.Method: Participants were 664 children with cerebral palsy (CP), 18 months to 12 years of age, one of their parents, and 90 therapists. Consensus between parents and therapists on level of function was ≥92% for the GMFCS, MACS, and CFCS. A linearly weighted kappa coefficient of ≥0.75 was the criterion for stability.Results: Kappa coefficients varied from 0.76 to 0.88 for the GMFCS, 0.59 to 0.73 for the MACS, and 0.57 to 0.77 for the CFCS. For children younger than 4 years of age, level of function did not change for 58.2% on the GMFCS, 30.3% on the MACS, and 39.3% on the CFCS. For children 4 years of age or older, level of function did not change for 72.3% on the GMFCS, 49.1% on the MACS, and 55% on the CFCS.Interpretation: The findings support repeated classification of children over time. The kappa coefficients for the GMFCS are attributed to descriptions of levels for each age band. Consensus classification facilitates discussion between parents and professionals that has implications for shared decision-making.What This Paper Adds: The findings support repeated classification of children over time. Stability was higher for the Gross Motor Function Classification System than the Manual Ability Classification System and Communication Function Classification System. The function of younger children was more likely to be reclassified. Percentage agreement between parents and therapists using consensus classification varied from 92% to 97%. The intraclass correlation coefficient overestimated stability compared with the weighted kappa coefficient. [ABSTRACT FROM AUTHOR]

Aim: To disentangle the respective impacts of manual dexterity and cerebral palsy (CP) in cognitive functioning after neonatal arterial ischaemic stroke.Method: The population included 60 children (21 females, 39 males) with neonatal arterial ischaemic stroke but not epilepsy. The presence of CP was assessed clinically at the age of 7 years and 2 months (range 6y 11mo-7y 8mo) using the definition of the Surveillance of CP in Europe network. Standardized tests (Nine-Hole Peg Test and Box and Blocks Test) were used to quantify manual (finger and hand respectively) dexterity. General cognitive functioning was evaluated with the Wechsler Intelligence Scale for Children, Fourth Edition. Simple and multiple linear regression models were performed while controlling for socio-economic status, lesion side, and sex.Results: Fifteen children were diagnosed with CP. In simple regression models, both manual dexterity and CP were associated with cognitive functioning (β=0.41 [p=0.002] and β=0.31 [p=0.019] respectively). However, in multiple regression models, manual dexterity was the only associated variable of cognitive functioning, whether or not a child had CP (β=0.35; p=0.007). This result was reproduced in models with other covariables (β=0.31; p=0.017).Interpretation: As observed in typically developing children, manual dexterity is related to cognitive functioning in children having suffered a focal brain insult during the neonatal period.What This Paper Adds: Manual dexterity predicts cognitive functioning after neonatal arterial ischaemic stroke. Correlations between manual dexterity and cognitive functioning occur irrespective of sex, lesion side, presence of cerebral palsy, and socio-economic status. Residual motor ability may support cognitive functioning. [ABSTRACT FROM AUTHOR]

Aim: To study the prevalence of minor neurological dysfunction (MND) at 6 years of age in a cohort of children born extremely preterm without cerebral palsy (CP) and to investigate associations with motor function, cognitive abilities, and behaviour.Method: This study assessed 80 children born at less than 27 weeks of gestation and 90 children born at term age between 2004 and 2007 at a mean age of 6 years 6 months. The assessments included a simplified version of the Touwen Infant Neurological Examination, the Movement Assessment Battery for Children, Second Edition (MABC-2), Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV), the Strengths and Difficulties Questionnaire (SDQ), and the parent version of the Five to Fifteen questionnaire.Results: Fifty-one of the children born preterm had normal neurology, 23 had simple MND, and six had complex MND compared with 88 who had normal neurology and two simple MND in the term-born group (p<0.001). There were significant differences between the children with normal neurology and MND in the preterm group in MABC-2-assessed motor function (p<0.001), general cognitive abilities with WISC-IV (p=0.005), and SDQ overall behavioural problems and peer problems reported by the parents (p=0.021 and p=0.003 respectively). SDQ teacher-reported overall behavioural and hyperactivity problems were significantly different between children with normal and simple MND (p=0.036 and p=0.019).Interpretation: Children born extremely preterm, in the absence of CP, are at risk of MND and this is associated with motor function, cognitive ability, and behaviour.What This Paper Adds: Extremely preterm birth carries a risk of minor neurological dysfunction (MND). MND in children born extremely preterm is associated with impaired motor function and cognitive abilities, and behavioural problems. Male sex is associated with MND in children born extremely preterm. [ABSTRACT FROM AUTHOR]

Aim: Gamma-aminobutyric acid (GABA) is a major modulator in brain maturation and its role in many different neurodevelopmental disorders has been widely reported. Although the involvement of GABA in different disorders has been related to its regulatory function as an inhibitory neurotransmitter in the mature brain, co-transmitter, and signalling molecule, little is known about its role as a clinical biomarker in neuropaediatric disorders. The aim of this study is to report the cerebrospinal fluid (CSF) free-GABA concentrations in a large cohort of patients (n=85) with different neurological disorders.Method: GABA was measured in the CSF of neuropaediatric patients using capillary electrophoresis with laser-induced fluorescence detection. Other neurotransmitters (amino acids and monoamines) were also analysed.Results: GABA concentrations in CSF were abnormal, with a greater frequency (44%) than monoamines (20%) in neuropaediatric patients compared with our reference values. Although we included a few patients with inborn errors of metabolism, GABA levels in CSF were more frequently abnormal in metabolic disorders than in other nosological groups.Interpretation: Our work suggests further research into brain GABAergic status in neuropaediatric disorders, which could also lead to new therapeutic strategies.What This Paper Adds: Homeostasis of GABA seems more vulnerable than that of monoamines in the developing brain. The highest GABA levels are found in the primary GABA neurotransmitter disorder SSADH deficiency. GABA alterations are not specific for any clinical or neuroimaging presentation. [ABSTRACT FROM AUTHOR]

Aim: Flexed knee gait can be treated with distal femoral extension osteotomy (DFEO) and additional patellar tendon advancement (PTA) in children with cerebral palsy (CP). This study assesses changes in hamstring muscle tendon length (MTL) and velocity after DFEO (+PTA).Method: Nineteen children (mean age 13y [standard deviation 3y] at surgery) with CP and flexed knee gait who were treated with DFEO (15 limbs) or DFEO+PTA (10 limbs) were retrospectively included in this study. Gait analyses were performed preoperatively (E0), 1 year postoperatively (E1), and for 10 limbs additionally 2 to 5 years postoperatively (E2). Hamstring MTL and velocities were assessed at all examination dates using OpenSim.Results: Hamstring MTL and velocity did not change significantly over time. From E0 to E1, knee flexion in stance improved for both DFEO and DFEO+PTA (p<0.05), knee flexion in swing only improved after DFEO+PTA (p<0.05). The improved knee flexion in stance and swing was maintained at E2.Interpretation: DFEO led to a significant improvement in knee kinematics at E1 which was maintained at E2. DFEO seems to prevent recurrent hamstring tightness but does not lead to lengthened or fastened hamstrings.What This Paper Adds: Distal femoral extension osteotomy (DFEO) does not change hamstring muscle tendon length. DFEO does not change hamstring lengthening velocity. DFEO leads to a significant improvement in knee kinematics. Changes in knee kinematics after DFEO can be maintained at mid-term. DFEO seems to prevent recurrent hamstring tightness. [ABSTRACT FROM AUTHOR]

Aim: Project TEAM (Teens making Environment and Activity Modifications) teaches transition-age young people with developmental disabilities, including those with co-occurring intellectual or cognitive disabilities, to identify and resolve environmental barriers to participation. We examined its effects on young people's attainment of participation goals, knowledge, problem-solving, self-determination, and self-efficacy.Method: We used a quasi-experimental, repeated measures design (initial, outcome, 6-week follow-up) with two groups: (1) Project TEAM (28 males, 19 females; mean age 17y 6mo); and (2) goal-setting comparison (21 males, 14 females; mean age 17y 6mo). A matched convenience sample was recruited in two US states. Attainment of participation goals and goal attainment scaling (GAS) T scores were compared at outcome. Differences between groups for all other outcomes were analyzed using linear mixed effects models.Results: At outcome, Project TEAM participants demonstrated greater knowledge (estimated mean difference: 1.82; confidence interval [CI]: 0.90, 2.74) and ability to apply knowledge during participation (GAS: t[75]=4.21; CI: 5.21, 14.57) compared to goal-setting. While both groups achieved significant improvements in knowledge, problem-solving, and self-determination, increases in parent reported self-determination remained at 6-week follow-up only for Project TEAM (estimated mean difference: 4.65; CI: 1.32, 7.98). Significantly more Project TEAM participants attained their participation goals by follow-up (Project TEAM=97.6%, goal-setting=77.1%, p=0.009).Interpretation: Both approaches support attainment of participation goals. Although inconclusive, Project TEAM may uniquely support young people with developmental disabilities to act in a self-determined manner and apply an environmental problem-solving approach over time.What This Paper Adds: Individualized goal-setting, alone or during Project TEAM (Teens making Environment and Activity Modifications) appears to support attainment of participation goals. Project TEAM appears to support young people with developmental disabilities to apply an environmental problem-solving approach to participation barriers. Parents of young people with developmental disabilities report sustained changes in self-determination 6 weeks after Project TEAM. [ABSTRACT FROM AUTHOR]

Aim: To estimate changes in home participation among critically ill children in the first 6 months after discharge from a pediatric intensive care unit (PICU), and to explore the effect of child, service, and environmental factors on change in home participation.Method: This was a prospective bi-center, longitudinal cohort study. Caregivers of 180 children, aged 1 to 17 years, who were admitted into the PICU for at least 48 hours were included. Patient-reported outcomes were used to capture caregivers' perspectives of their child's participation and environmental supports for participation in home activities. Data were collected at enrollment, and 3 and 6 months after discharge.Results: There were no significant changes in home participation frequency or involvement, but involvement rates across time were moderated by functional status. Age significantly predicted participation frequency. Pre-PICU functional status and capabilities were significant predictors of participation frequency and involvement, and home environmental support significantly predicted home involvement.Interpretation: Results suggest relatively stable participation trajectories in the 6 months after PICU admission. Children with abnormal baseline function experienced a greater increase in home involvement after PICU. Rehabilitation interventions targeting functional capabilities and home environment may be viable approaches during the early phase of recovery. Environmental interventions may be more time-efficient after PICU stay and merit further study.What This Paper Adds: Children's pre-pediatric intensive care unit (PICU) functional status and capabilities impact their participation after critical illness. Children's trajectories of home involvement may differ over time based on their pre-PICU functional status. Caregiver perceptions of environmental support impact a child's home involvement after discharge from a PICU. [ABSTRACT FROM AUTHOR]

Aim: This cross-sectional study aimed to examine the preliteracy abilities of young children with neurofibromatosis type 1 (NF1) and to identify which of these abilities best predicted conventional literacy (spelling).Method: Forty-two children with NF1 (23 males, 19 females; mean age [SD] 5y 6mo [6mo]) were compared with 32 unaffected children (15 males, 17 females; mean age [SD] 5y 4mo [6mo]). All children completed a comprehensive cognitive assessment including measures of phonological processing (phonological awareness, phonological memory, rapid automatic naming) and letter-sound knowledge.Results: Children with NF1 performed significantly poorer than the comparison group across all cognitive and preliteracy domains, with specific weaknesses evident in phonological awareness (F1,68 =14.13, p<0.001, partial η2 =0.17), phonological memory (F1,68 =13.87, p<0.001, partial η2 =0.17), and letter-sound knowledge (F1,71 =5.65, p=0.020, partial η2 =0.07). Within the group with NF1 group, over a third of children demonstrated impairment in at least one phonological processing domain and the risk of phonological impairment was 5.60 times that of unaffected children. Children's letter-sound knowledge was the strongest predictor of conventional literacy (spelling).Interpretation: This study establishes that preliteracy deficits are present and detectable in young children with NF1. As a result of the high incidence of preliteracy impairment, we recommend screening phonological awareness and letter-sound knowledge to identify risk of future learning disorders.What This Paper Adds: Young children with neurofibromatosis type 1 are at elevated risk of preliteracy deficits. The most affected domains are phonological awareness and phonological memory. Letter-sound knowledge is the strongest predictor of conventional literacy (spelling). [ABSTRACT FROM AUTHOR]

Aim: Health-related quality of life (HRQoL) and peer relationships were investigated in adolescents with developmental coordination disorder (DCD) and attention-deficit-hyperactivity disorder (ADHD).Method: Adolescents with DCD (n=9), ADHD (n=9), DCD and ADHD (n=10), and typically developing adolescents (n=16) completed the following questionnaires: KIDSCREEN-52 Health-Related Quality of Life Questionnaire and Peer Relations Questionnaire for Children. Twenty-five participants took part in semi-structured interviews.Results: Adolescents with DCD and ADHD had lower HRQoL on the mood and emotions, school environment, and financial resources scales of the KIDSCREEN-52 than adolescents in the DCD and typically developing groups (all p<0.05). On the Peer Relations Questionnaire for Children, the DCD and ADHD group reported significantly higher victimization compared with those in the typically developing (p=0.030) and DCD (p=0.010) groups. Qualitative interviews among young people with DCD and ADHD revealed feelings of marginalization and victimization. Descriptors such as 'misfits', 'oddballs', 'weird', and 'the rejects' were used to describe themselves.Interpretation: HRQoL and peer relationships are negatively affected in adolescents with DCD and ADHD. WHAT THIS PAPER ADDS?: Children with developmental coordination disorder (DCD) do not display poorer overall health-related quality of life (HRQoL) versus typically developing controls. Having DCD and attention-deficit-hyperactivity disorder (ADHD) was associated with poorer HRQoL. Adolescents with DCD and ADHD experience significantly higher levels of peer victimization than typically developing adolescents. HRQoL and peer relationships are significantly associated in adolescent respondents. [ABSTRACT FROM AUTHOR]

Aim: To examine the long-term consequences of glycogen storage in the central nervous system (CNS) for classic infantile Pompe disease using enzyme replacement therapy.Method: Using neuropsychological tests and brain magnetic resonance imaging (MRI), we prospectively assessed a cohort of 11 classic infantile Pompe patients aged up to 17 years.Results: From approximately age 2 years onwards, brain MRI showed involvement of the periventricular white matter and centrum semiovale. After 8 years of age, additional white-matter abnormalities occurred in the corpus callosum, internal and external capsule, and subcortical areas. From 11 years of age, white-matter abnormalities were also found in the brainstem. Although there seemed to be a characteristic pattern of involvement over time, there were considerable variations between patients, reflected by variations in neuropsychological development. Cognitive development ranged from stable and normal to declines that lead to intellectual disabilities.Interpretation: As treatment enables patients with classic infantile Pompe disease to reach adulthood, white-matter abnormalities are becoming increasingly evident, affecting the neuropsychological development. Therefore, we advise follow-up programs are expanded to capture CNS involvement in larger, international patient cohorts, to incorporate our findings in the counselling of parents before the start of treatment, and to include the brain as an additional target in the development of next-generation therapeutic strategies for classic infantile Pompe disease.What This Paper Adds: In our long-term survivors treated intravenously with enzyme replacement therapy, we found slowly progressive symmetric white-matter abnormalities. Cognitive development varied from stable and normal to declines towards intellectual disabilities. [ABSTRACT FROM AUTHOR]

Aim: Adolescents with physical disabilities may have co-occurring chronic pain, but the prevalence and specific associated factors are unknown. The aims of this study were to determine (1) the prevalence of chronic pain in adolescents with physical disabilities and (2) whether known correlates of chronic pain in the general population are also present in young people both with physical disability and with chronic pain relative to peers.Method: We conducted a secondary analysis of cross-sectional nationally representative data from the National Longitudinal Study of Adolescent to Adult Health. Multivariate linear regression analysis was used to identify demographic and psychosocial factors associated with chronic pain.Results: A total of 989 (4.3%) adolescents reported physical disabilities. They had a significantly higher rate of pain (27.2%) compared with able-bodied peers (15.6%, χ2 =86.3550, p<0.001). There was no significant interaction between physical disability status and chronic pain in relation to depressive symptoms, anxiety, or insomnia.Interpretation: Adolescents with physical disabilities experience chronic pain at a significantly higher rate than able-bodied peers, but the comorbidity of physical disability and chronic pain is not related to depression, anxiety, or insomnia. Evaluation of chronic pain and tailored pain interventions need to be developed for this population.What This Paper Adds: Chronic pain and its correlates are important problems for adolescents with physical disabilities. These adolescents present with higher rates of chronic pain than other young people. Chronic pain is associated with increased levels of depressive symptoms, anxiety, and insomnia regardless of disability status. [ABSTRACT FROM AUTHOR]

Aim: To assess long-term safety and efficacy of stiripentol as an antiepileptic medication for people with Dravet syndrome.Method: A prospective, observational open-label study (2003-2015) of the efficacy and long-term safety of stiripentol in patients with Dravet syndrome and ongoing seizures. Frequency of generalized tonic-clonic seizures, focal seizures, status epilepticus, and adverse events were recorded.Results: Forty-one patients started stiripentol, with median age at enrolment 5 years 7 months (range 11mo-22y) and median duration of treatment 37 months (range 2-141mo). Twenty out of 41 patients had greater than or equal to 50% long-term reduction in frequency of generalized tonic-clonic seizures. Frequency of focal seizures was decreased by greater than or equal to 50% in 11 out of 23 patients over the long-term. Frequency of status epilepticus was decreased by 50% or more in 11 out of 26 patients. The most common adverse events were anorexia, weight loss, sedation, and behavioural changes. One patient had worsening of absence and myoclonic seizures. Another developed recurrent pancreatitis on concurrent valproate.Interpretation: Stiripentol improves long-term seizure frequency in approximately 50% of patients with Dravet syndrome, when used as part of unrestricted polytherapy. Long-term use appears safe. In more than 40% of patients, episodes of status epilepticus markedly decrease after stiripentol initiation. What this paper adds Frequency of status epilepticus is reduced in 40% of patients with Dravet syndrome after stiripentol initiation. Stiripentol is effective for generalized tonic-clonic and focal seizures. Stiripentol can be safely used with a range of antiepileptic drugs. [ABSTRACT FROM AUTHOR]

Objective: Distress screening programs aim to ensure appropriate psychooncological support for cancer patients, but many eligible patients do not use these services. To improve distress management, we need to better understand patients' supportive care needs. In this paper, we report the first key finding from a longitudinal study that focused on patients' intentions to use psychooncological support and its association with distress and uptake of the psychooncology service.Methods: We conducted a prospective, observational study in an Oncology Outpatient Clinic and assessed distress, intention to use psychooncological support, and uptake of the psychooncology service by using the Distress Thermometer, a semistructured interview, and hospital records. We analyzed data with a mixed-methods approach.Results: Of 333 patients (mean age 61 years; 55% male; 54% Distress Thermometer ≥ 5), 25% intended to use the psychooncology service (yes), 33% were ambivalent (maybe), and 42% reported no intention (no). Overall, 23% had attended the psychooncology service 4 months later. Ambivalent patients reported higher distress than patients with no intention (odds ratio = 1.18, 95% confidence interval [1.06-1.32]) but showed significantly lower uptake behavior than patients with an intention (odds ratio = 14.04, 95% confidence interval [6.74-29.24]). Qualitative analyses revealed that ambivalent patients (maybe) emphasized fears and uncertainties, while patients with clear intentions (yes/no) emphasized knowledge, attitudes, and coping concepts.Conclusions: We identified a vulnerable group of ambivalent patients with high distress levels and low uptake behavior. To optimize distress screening programs, we suggest addressing and discussing patients' supportive care needs in routine clinical practice. [ABSTRACT FROM AUTHOR]

Introduction and Aims: Tranquilizer use is associated with negative health outcomes among people who use drugs. This paper aims to estimate the incidence rate (initiation) and identify predictors of tranquilizer misuse (TM) among cocaine users.Design and Methods: A prospective cohort study was conducted in Montreal, Canada. Interviewer-administered questionnaires were carried out at 3-month intervals. Initiation was defined as misusing a tranquilizer for the first time during follow-up. 'Lasting-initiation', defined as reporting TM at the next visit following first use, was also examined. Cox proportional hazard regression analyses were carried out to assess predictors of initiation to TM.Results: Among the 245 participants who were eligible for the initiation analyses, 123 started TM during follow-up for an incidence rate of 40.49 per 100 person-years (95% confidence interval, CI: 33.80-48.15). Of the 123 initiates, 35.7% were still using at the interview following initiation for an incidence rate of 14.70 per 100 person-years (95% CI: 10.82-19.56). Multivariate models showed that independent predictors of initiation and 'lasting initiation' were identical as having had a criminal activity as the main source of income, having been recently in treatment for a substance use disorder (SUD) and reporting non-medical use of prescription opioids.Discussion and Conclusions: The incidence rate of TM initiation was high among a sample of cocaine users. Initiation was predicted by a problematic drug use pattern involving polydrug use, involvement in the street economy and having been in treatment for a SUD. These findings have implications for prevention and harm reduction strategies. [ABSTRACT FROM AUTHOR]

Aim: To determine whether intrathecal baclofen (ITB) therapy improves performance and performance satisfaction in goal areas identified by patients' parents.Method: This study formed part of an ongoing multicentre national audit involving six paediatric ITB pump implant centres across Australia. The Canadian Occupational Performance Measure was the primary outcome measure utilized at baseline, 6 months, and 12 months after pump implants in paediatric patients receiving ITB therapy for the first time between 31st December 2009 and 31st December 2014.Results: Twenty-five children had goals identified (mean age 11y 1mo), 19 had a diagnosis of cerebral palsy and 22 were at Gross Motor Function Classification System level IV, V, or equivalent. Strong evidence for an improvement in goal performance (2.33, 95% CI 1.70, 2.96, p<0.001) and performance satisfaction scores (3.08, 95% CI 2.28, 3.88, p<0.001) were demonstrated at 6 months, compared to baseline. The differences were clinically significant and were sustained to 12 months.Interpretation: ITB therapy in paediatric patients with hypertonia results in clinically significant improvements in average performance and performance satisfaction scores.What This Paper Adds: The most commonly identified goals of parents of children treated with intrathecal (ITB) therapy were: improving ease of dressing, positioning, and transfers. ITB therapy is effective in improving performance and performance satisfaction in children with hypertonia. Score improvements are mainly evident within the first 6 months of therapy. [ABSTRACT FROM AUTHOR]

Aim: To identify a cohort of children with cerebral palsy (CP) from hospital data; determine the proportion that participated in standardized educational testing and attained a score within the normal range; and describe the relationship between test results and motor symptoms.Method: This population-based retrospective cohort study used data from New South Wales, Australia. We linked hospital data for children younger than 16 years of age admitted between 1st July 2000 and 31st March 2014 to education data from 2009 to 2014. Hospital diagnosis codes were used to identify a cohort of children with CP (n=3944) and describe their motor symptoms. Educational outcomes in the CP cohort were compared with those among children without CP.Results: Of those with educational data (n=1770), 46% were exempt from reading assessment because of intellectual or functional disability, 7% were absent or withdrawn from testing and 47% participated in testing. About 30% of all children with educational data had test scores in the normal range. The proportion was greatest among those with hemiplegia (>40%) and lowest among those with tetraplegia (<10%).Interpretation: One-third of children with CP participated in standardized testing and achieved a result in the normal range. The proportions were lower in children with more severe motor symptoms.What This Paper Adds: From 2009 to 2014, most Australian children with cerebral palsy (CP) attended a mainstream school. The rate of disability-related exemption from standardized educational testing was almost 50%. Thirty per cent of children with CP achieved educational scores in the normal range. [ABSTRACT FROM AUTHOR]

Aim: To describe behavioural and psychiatric outcomes of children within 10 years of convulsive status epilepticus (CSE).Method: Children originally identified by the population-based North London Convulsive Status Epilepticus in Childhood Surveillance Study were followed-up between July 2009 and February 2013. They were grouped into epilepsy- and non-epilepsy-related CSE, and compared with population norms and healthy controls using the Strengths and Difficulties Questionnaire; the Autism Spectrum Screening Questionnaire; and the Swanson, Nolan, and Pelham questionnaire. Children who scored above recommended clinical cut-offs on any scale were invited for a neuropsychiatric assessment. Regression models were fitted to identify clinically relevant covariates associated with behavioural outcomes.Results: At a mean follow-up of 8.1 years post-CSE, 28% of enrolled children were found to have a psychiatric disorder. Children with epilepsy-related CSE scored higher than norms on all scales and children with non-epilepsy-related CSE scored higher than norms on the Strengths and Difficulties Questionnaire and the Autism Spectrum Screening Questionnaire. Presence of seizures at baseline and recurrence of CSE was associated with worse outcomes in the group with epilepsy. Intellectual abilities were associated with behavioural outcomes in all participants.Interpretation: A large proportion of children manifest behavioural issues 8 years after CSE. The present data highlight the need for behavioural screening in children with neurodevelopmental impairments post-CSE.What This Paper Adds: Eight years post convulsive status epilepticus (CSE), 37% of parents report behavioural issues. Of enrolled children, 28% were found to have a Diagnostic and Statistical Manual mental disorder. Intellectual abilities are strongly associated with behavioural outcomes in children post-CSE. [ABSTRACT FROM AUTHOR]

Aim: This study examined cross-sectional and longitudinal patterns of parenting stress, adult anxiety, and depression in mothers of children with profound or severe visual impairment (PVI or SVI) at 1 year and 2 years of age.Method: Mothers of a national longitudinal cohort (OPTIMUM Project) of infants with congenital disorders of the peripheral visual system and PVI (light perception at best) or SVI (basic 'form' vision of non-light reflecting objects) participated. Infant age at baseline (T1 ) was 8 to 16 months. Mothers completed the Parenting Stress Index - Short Form and the Hospital Anxiety and Depression Scale at T1 (n=79) and at follow-up 12 months later (T2 ) (n=73).Results: Mothers of the total group had higher parenting stress levels (34.6% in clinical range) than community normative data at T1 (p=0.017). Mothers of infants in the PVI subgroup had elevated stress at T1 (p=0.014) and T2 (p=0.009). The PVI subgroup was also elevated in the Difficult Child subscale at T2 (p=0.001). Within-sample differences in parenting stress between the visual impairment subgroups were found at T2 only: the PVI subgroup scored higher than the SVI subgroup (p=0.029). Adult anxiety and depression in the total group were not elevated compared with community normative data at T1 and T2 ; however, higher parenting stress was related to raised adult anxiety and depression levels at T1 and T2 (p=0.001). Regression analysis found parenting stress and lower child vision level (T1 ) predicted parenting stress (T2 ) (p=0.001; 42% variance).Interpretation: Mothers of 1-year-old infants with visual impairment showed raised risk for parenting stress, which continued to be elevated for children with PVI and those perceived as 'difficult' at 2 years. This was also a psychological risk, with greater adult anxiety and depression in those mothers with raised parenting stress. The clinical significance is that identification of parenting stress and targeted parenting, and behavioural support of the child in the first years of life is highly indicated.What This Paper Adds: Mothers of infants with visual impairment are at increased risk of parenting stress. Parenting stress was higher in mothers of children with profound visual impairment than those with severe visual impairment. High levels of parenting stress and lower infant vision at 1 year of age predicted higher parenting stress at 2 years of age. [ABSTRACT FROM AUTHOR]

Aim: Executive function impairments have been identified in children with poor motor skills, with and without a diagnosis of developmental coordination disorder (DCD). However, most studies are cross-sectional. This study investigates the development of executive function in children with poor motor skills over 2 years.Method: Children aged 7 to 11 years (n=51) were assessed twice, 2 years apart, on verbal and nonverbal measures of executive functions: executive-loaded working memory (ELWM); fluency; response inhibition; planning; and cognitive flexibility. Typically developing children (n=17) were compared with those with a clinical diagnosis of DCD (n=17) and those with identified motor difficulties (n=17) but no formal diagnosis of DCD.Results: Developmental gains in executive function were similar between groups, although a gap between children with poor motor skills and typically developing children on nonverbal executive functions persisted. Specifically, children with DCD performed significantly more poorly than typically developing children on all nonverbal executive function tasks and verbal fluency tasks at both time points; and children with motor difficulties but no diagnosis of DCD showed persistent executive function problems in nonverbal tasks of ELWM and fluency.Interpretation: Children with DCD and motor difficulties demonstrated executive function difficulties over 2 years, which may affect activities of daily living and academic achievement, in addition to their motor deficit.What This Paper Adds: Executive function difficulties in children with poor motor skills persist throughout middle childhood. Children with motor difficulties, without a developmental coordination disorder (DCD) diagnosis, demonstrate less pervasive executive function difficulties than those with DCD. Executive function problems in the groups with motor difficulties and DCD affect mostly nonverbal domains. All groups showed similar developmental gains in executive function. [ABSTRACT FROM AUTHOR]

Aim: This study examined whether late-preterm birth (34+0 to 36+6wks+d gestational age) was associated with neurocognitive deficit in young adulthood, and whether small for gestational age (SGA) birth amplified any adversity.Method: Participants derived from the prospective regional cohort study, the Arvo Ylppö Longitudinal Study (n=786; 398 females, 388 males) (mean age 25y 4mo, SD 8mo), born 1985 to 1986 late-preterm (n=119; 21 SGA, <-2 SD) and at term (37+0 to 41+6wks+d; n=667; 28 SGA) underwent tests of intelligence, executive functioning, attention, and memory, and reported their education.Results: Those born late-preterm scored -3.71 (95% confidence interval [CI] -6.71 to -0.72) and -3.11 (95% CI -6.01 to -0.22) points lower on Full-scale and Verbal IQ than peers born at term. Compared with those born at term and appropriate for gestational age (≥-2 to <2 SD) Full-scale, Verbal, and Performance IQ scores of those born late-preterm and SGA were -9.45 to -11.84 points lower. After adjustments, differences were rendered non-significant, except that scores in Full-scale and Performance IQ remained lower among those born late-preterm and SGA.Interpretation: Late-preterm birth, per se, may not increase the risk of poorer neurocognitive functioning in adulthood. But the double burden of being born late-preterm and SGA seems to increase this risk.What This Paper Adds: Late-preterm birth did not increase the risk of poorer neurocognitive functioning in adulthood. But the double burden of being born late-preterm and being small for gestational age did increase this risk. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy of clobazam treatment in reducing epileptiform discharges and modifying neuropsychological function in continuous spike-wave during slow wave sleep.Method: We performed a prospective clinical trial in patients with continuous spike-wave during sleep aged 4 to 10 years. Patients underwent neuropsychological assessment and overnight electroencephalographic monitoring before treatment, and subsequent repeat assessment and overnight electroencephalographic monitoring 3 months after treatment. Treatment consisted of 1mg/kg clobazam up to a maximum dose of 30mg during the first night, followed by 0.5mg/kg nightly for 3 months.Results: Nine patients completed the study and had pre- and post-neuropsychological evaluation. There was a qualitative reduction in median (p25 -p75 ) spike percentage after 3 months (72.2 [68.0-75.8] vs 32.7 [4.7-81.7]). There were no marked changes in median (p25 -p75 ) IQ comparing pre- and post-clobazam treatment (80.0 [74.0-88.0] vs 80.0 [67.0-89.0]). There was a qualitative increase in Verbal IQ (83.0 [69.0-92.0] vs 95.0 [83.0-99.0]) and a qualitative decrease in Non-verbal IQ (84.0 [74.0-87.0] vs 71.0 [60.0-84.0]).Interpretation: Qualitative improvements in epileptiform activity and cognition occurred in patients treated with clobazam for 3 months and the relationship between epileptiform activity and cognitive outcome should be studied in larger studies.What This Paper Adds: Verbal IQ in patients with continuous spike-wave during sleep improved following short-term treatment with clobazam. Other neuropsychological improvements were observed, but varied by patient. Cognitive improvement was observed despite some worsening of epileptiform discharges. [ABSTRACT FROM AUTHOR]

Aim: To monitor the evolution of the motor function of ambulatory patients with Duchenne muscular dystrophy (DMD) treated by corticosteroids for 2 years in comparison with untreated patients.Method: This observational, multicentre cohort study explores the evolution of the motor function measure (MFM) over a 24-month period for 29 ambulant corticosteroids-treated and 45 ambulant untreated patients with DMD.Results: Significant differences were found between mean MFM scores in corticosteroids-treated and untreated groups for domain 1 of the MFM (standing position and transfers; D1), domain 2 of the MFM (axial and proximal motor function; D2), and domain 3 of the MFM (distal motor function; D3). Subscores were between 0 months and 6 months, and 0 months and 24 months. For the D1 subscore specifically, there was a significant increase in the corticosteroids-treated group (mean±standard deviation [SD] slope of change=12.6±15.5%/y), while a decrease was observed in the untreated group (-17.8±17.7%/y) between 0 months and 6 months (p<0.001). Sensitivity to change as assessed by standardized response means was high between 12 months and 24 months for D1 of both corticosteroids-treated and untreated groups (1.0 and 1.2 respectively), and low for D2 and D3 of both treated and untreated groups.Interpretation: Patients with DMD treated by corticosteroids present a different course of the disease as assessed by MFM, confirming the sensitivity to change of the MFM in this population.What This Paper Adds: Corticosteroids have a quantitative impact on muscle strength 6 to 24 months after starting treatment. Motor function measure is a valid outcome measure in Duchenne muscular dystrophy patients under corticosteroid treatment. [ABSTRACT FROM AUTHOR]

Aim: To test the hypothesis that higher seizure burden in Dravet syndrome is associated with increased comorbidities and lower quality of life (QoL) in a large cohort of patients with Dravet syndrome and their caregivers in Europe.Method: An extensive survey of caregivers of patients with Dravet syndrome on experiences of diagnosis, seizure burden, management, social and financial impact, and health services use was administered online in 10 languages.Results: The survey received 584 unique responses from caregivers of paediatric (83%) and adult (17%) patients with Dravet syndrome (aged <1-48y). Despite broadly following current treatment guidance, less than 10% of patients were seizure free in the previous 3 months. Nearly all (99.6%) patients aged 5 years or older experienced at least one or more motor, speech, learning, or behavioural impairment. High seizure frequency was related to more reports of emergency treatment, comorbidities, and a lower QoL (as measured by the standardized instrument EQ-5D-5L). If not diagnosed at the first instance, the majority (83%) of adults, but less than 20% of 6- to 11-year-olds were diagnosed after 4 or more years.Interpretation: Patients with Dravet syndrome with the highest current seizure frequency suffer from more comorbidities and have a lower QoL. Therefore, more effective antiepileptic treatments are needed.What This Paper Adds: The survey captured about 15% of all patients with Dravet syndrome in Europe. Less than 10% of patients had current seizure freedom. Patients with a high current seizure burden have more comorbidities and lower quality of life. [ABSTRACT FROM AUTHOR]

Aim: We investigated the long-term efficacy and safety of multilevel surgery (MLS) in ambulatory children with bilateral spastic cerebral palsy (CP).Method: Two hundred and thirty-one children were evaluated at short term (1.1y, SD 0.4) and long term (9.1y, SD 3.0) follow-up using clinical examination and gait analysis. MLS was investigated by studying changes in the Gait Profile Score (GPS) referenced to the minimally important clinical difference.Results: Ambulatory children aged 10 years and 7 months (SD 2y 11mo) at MLS in Gross Motor Function Classification System levels I (19), II (144), and III (68) showed a decrease (improvement) in preoperative GPS from 16.3° (SD 4.8) to 11.3° (SD 3.2) at short-term follow-up, an improvement of 5°. At long-term follow-up, GPS was maintained at 11.4° (SD 3.1). Overall, 177 (76.6%) children maintained their improvement in GPS after 9 years.Interpretation: Multilevel surgery is a safe and effective surgical intervention, which leads to a significant improvement in gait kinematics in children with bilateral spastic CP. This study improves our understanding of MLS in the long term and will help to inform families and children when planning for MLS.What This Paper Adds: Largest study of multilevel surgery (MLS) for children with bilateral spastic cerebral palsy, with longest follow-up. MLS resulted in significant long-term improvements in gait function. Minor adverse events were common, while events requiring intervention were uncommon (4% of children). Thirty-nine per cent of children required additional surgery during follow-up. 'Single-event multilevel surgery' was changed to the more realistic term 'multilevel surgery'. [ABSTRACT FROM AUTHOR]

Aim: To characterize carpal tunnel syndrome (CTS) in patients with mucopolysaccharidosis I (MPS I).Method: Data were included for patients with MPS I who had either nerve conduction examination that included a diagnosis of CTS or who had CTS release surgery. Although this represented a subset of patients with CTS in the MPS I Registry, the criteria were considered the most objective for data analysis.Results: As of March 2016, 994 patients were categorized with either severe (Hurler syndrome) or attenuated (Hurler-Scheie or Scheie syndromes) MPS I. Among these, 291 had a CTS diagnosis based on abnormal nerve conduction (n=54) or release surgery (n=237). Median ages (minimum, maximum) at first CTS diagnosis were 5 years 2 months (10mo, 16y 2mo) and 9y 11mo (1y 8mo, 44y 1mo) for patients with severe and attenuated MPS I respectively. Most patients had their first CTS diagnosis after MPS I diagnosis (94%) and treatment (hematopoietic stem cell transplant and/or enzyme replacement therapy) (74%). For 11% of patients with attenuated disease, CTS diagnosis preceded MPS I diagnosis by a mean of 7 years 6 months.Interpretation: CTS is a rare complication in pediatric patients and should alert medical care providers to the potential diagnosis of MPS I. Significant delays exist between diagnosis of CTS and MPS I for patients with attenuated disease.What This Paper Adds: There are significant delays in diagnosing carpal tunnel syndrome (CTS) in patients with mucopolysaccharidosis I (MPS I). Enzyme replacement therapy or hematopoietic stem cell transplant do not prevent the development of CTS. Testing for CTS in patients with MPS I is recommended to prevent irreparable damage. CTS in pediatric patients should alert physicians to potential diagnosis of MPS I. [ABSTRACT FROM AUTHOR]

The method of generalized estimating equations (GEE) is popular in the biostatistics literature for analyzing longitudinal binary and count data. It assumes a generalized linear model for the outcome variable, and a working correlation among repeated measurements. In this paper, we introduce a viable competitor: the weighted scores method for generalized linear model margins. We weight the univariate score equations using a working discretized multivariate normal model that is a proper multivariate model. Because the weighted scores method is a parametric method based on likelihood, we propose composite likelihood information criteria as an intermediate step for model selection. The same criteria can be used for both correlation structure and variable selection. Simulations studies and the application example show that our method outperforms other existing model selection methods in GEE. From the example, it can be seen that our methods not only improve on GEE in terms of interpretability and efficiency but also can change the inferential conclusions with respect to GEE. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Generalized estimating equations (GEE) is a general statistical method to fit marginal models for longitudinal data in biomedical studies. The variance-covariance matrix of the regression parameter coefficients is usually estimated by a robust "sandwich" variance estimator, which does not perform satisfactorily when the sample size is small. To reduce the downward bias and improve the efficiency, several modified variance estimators have been proposed for bias-correction or efficiency improvement. In this paper, we provide a comprehensive review on recent developments of modified variance estimators and compare their small-sample performance theoretically and numerically through simulation and real data examples. In particular, Wald tests and t-tests based on different variance estimators are used for hypothesis testing, and the guideline on appropriate sample sizes for each estimator is provided for preserving type I error in general cases based on numerical results. Moreover, we develop a user-friendly R package "geesmv" incorporating all of these variance estimators for public usage in practice. [ABSTRACT FROM AUTHOR]

The present paper reports on a 5-year follow-up of a randomized reading intervention in grade 3 in Sweden. An intervention group (n = 57) received daily training for 12 weeks in phoneme/grapheme mapping, reading comprehension and reading speed, whereas a control group (n = 55) participated in ordinary classroom activities. The main aim was to investigate if there were remaining effects of the intervention on reading-related skills. Previous analyses showed that the intervention group performed significantly better than the control group on spelling, reading speed, reading comprehension and phoneme awareness at the immediate post-test with sustained effects 1 year later. Results from the 5-year follow-up show that the only significant difference between the intervention (n = 47) and the control group (n = 37) was on word decoding. There was also a significant interaction effect of group assignment and initial word decoding, in the way that the lowest-performing students benefitted the most from the intervention. Another aim was to examine if the children identified in a screening (n = 2212) as poor readers in grade 2 still performed worse than typical readers. The analyses showed that the typically developing students (n = 66) outperformed the students identified as poor readers in grade 2 on working memory, spelling, reading comprehension and word decoding. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: The aim of this paper was to assess the relationship between pain and sleep in older adults taking depression, stress, and medical comorbidities into account.Methods: A cross-sectional analysis was performed using Einstein Aging Study, a community-based cohort study of adults aged 70 years and older. Ratings of pain intensity and interference from the Medical Outcomes Study (MOS) Short-Form 36 were used to assign individuals to low-pain versus high-pain severity. Sleep disturbance was assessed using the nine-item sleep problems index from the Medical Outcomes Study Sleep Scale. Other measures included the Geriatric Depression Scale and Perceived Stress Scale (PSS). Linear regression models were used to assess the association between pain grade and sleep disturbance adjusted for demographics, PSS, Geriatric Depression Scale, and other comorbidities.Results: Five hundred sixty-two eligible participants with a mean age of 78.22 years (standard deviation = 5.43) were included; 64% were women. Pain grade [β = 5.40, 95% confidence interval (CI) 2.56-8.21, p < 0.001] was associated with sleep disturbance after adjusting for demographic variables. In models including pain grade (β = 3.08, 95% CI 0.32-5.85, p = 0.03) and PSS (β = 0.57, 95% CI 0.39-0.75, p < 0.001), both were associated with sleep disturbance, although the PSS attenuated the relationship between pain and sleep by 34%. Depression, when added to previous model, was also associated with sleep (β = 2.17, 95% CI 1.48-2.85, p < 0.001) and attenuated the relationship between pain (β = 2.41, 95% CI -0.25 to 5.08, p = 0.07) and sleep by 22%. Stratified for depression, we found that pain, stress, and other medical comorbidities were significantly associated with sleep disturbance in non-depressed individuals but not individuals with depression.Conclusions: Pain, stress, and medical comorbidities are associated with sleep disturbance, especially in non-depressed older adults. [ABSTRACT FROM AUTHOR]

Background Alcohol-related blackouts are periods of amnesia that reflect the failure of the brain to record memories of what transpires while drinking. This paper examined the incidence, predictors, and behavioral correlates of blackouts among emerging adults and examined whether questions about blackouts could serve as better markers of risk for other alcohol related harms than questions about levels of consumption. Methods In 2012 to 2013, 1,463 (68%) of 2,140 respondents 1-year past high school reported having consumed alcohol. They were asked whether, in the past 6 months because of drinking, they forgot where they were or what they did. The survey also explored demographics, substance use behaviors, and other alcohol-related problems in the past 6 months. Chi-square and logistic regression analyses explored bivariate and multivariate predictors of blackouts and other alcohol-related problems. Results Twenty percent of respondents who ever drank alcohol reported a blackout in the past 6 months. Blackouts were more prevalent among females and those who, in the past 30 days, used multiple drugs, more frequently binged, were drunk, smoked, had lower body weight, and lived in college dorms. After controlling for drinking levels, having a blackout was the strongest independent predictor of most other alcohol problems examined, including in the past 6 months because of drinking, missing class or work, getting behind in work or school, doing something respondents later regretted, arguing with friends, experiencing an overdose, and total number of alcohol problems reported. It was also an independent predictor of hangovers, damaging property, getting hurt, and trouble with police. Conclusions Because blackouts indicate drinking at levels that result in significant cognitive and behavioral impairment, questions about blackouts could serve as important, simple screeners for the risk of experiencing other alcohol related harms. Additional work on this subject is warranted. [ABSTRACT FROM AUTHOR]

Objective: Melanoma is on the rise, especially in Caucasian populations exposed to high ultraviolet radiation such as in Australia. This paper examined the psychological components facilitating change in skin cancer prevention or early detection behaviours following a text message intervention.Methods: The Queensland-based participants were 18 to 42 years old, from the Healthy Text study (N = 546). Overall, 512 (94%) participants completed the 12-month follow-up questionnaires. Following the social cognitive model, potential mediators of skin self-examination (SSE) and sun protection behaviour change were examined using stepwise logistic regression models.Results: At 12-month follow-up, odds of performing an SSE in the past 12 months were mediated by baseline confidence in finding time to check skin (an outcome expectation), with a change in odds ratio of 11.9% in the SSE group versus the control group when including the mediator. Odds of greater than average sun protective habits index at 12-month follow-up were mediated by (a) an attempt to get a suntan at baseline (an outcome expectation) and (b) baseline sun protective habits index, with a change in odds ratio of 10.0% and 11.8%, respectively in the SSE group versus the control group.Conclusions: Few of the suspected mediation pathways were confirmed with the exception of outcome expectations and past behaviours. Future intervention programmes could use alternative theoretical models to elucidate how improvements in health behaviours can optimally be facilitated. [ABSTRACT FROM AUTHOR]

Experienced Carers Helping Others (ECHO) is an intervention for carers of people with eating disorders. This paper describes the theoretical background and protocol of a pilot multicentre randomised controlled trial that will explore the use of two variants of ECHO for improving outcomes for adolescents with anorexia nervosa (AN) referred for outpatient care. Adolescent patients and their carers (typically parents and close others in a supportive role) will be recruited from 38 eating disorder outpatient services across the UK. Carers will be randomly allocated to receive 'ECHOc' guided self-help (in addition to treatment as usual), 'ECHO' self-help only (in addition to treatment as usual) or treatment as usual only. Primary outcomes are a summary measure of the Short Evaluation of Eating Disorders at 6- and 12-month follow-ups. Secondary outcomes are general psychiatric morbidity of AN patients and carer, carers' coping and behaviour, and change in healthcare use and costs at 6- and 12-month follow-ups. Therapist effects will be examined, and process evaluation of ECHOc will be completed. The findings from this pilot trial will be used in preparation for executing a definitive trial to determine the impact of the preferred variant of ECHO to improve treatment outcomes for AN. Copyright © 2014 John Wiley & Sons, Ltd and Eating Disorders Association. [ABSTRACT FROM AUTHOR]

Background Retrospective and cross-sectional studies have suggested a bidirectional relationship between migraine and mood disturbance. Objective The present prospective daily diary study examined the prevalence and temporal associations between migraine and daily mood, mood and next-day headache, and headache and next-day mood. Methods Sixty-nine children (50 females, 19 males) between the ages of 7 and 12 years and their parents attending neurology clinic appointments and having a diagnosis of migraine as defined by International Headache Classification 2nd edition criteria completed measures on the quality of life, headache disability, child emotions, and child behaviors. Children and parents then recorded children's headache occurrence, headache duration, headache severity, mood, daily hassles, and medication use on paper diaries once a day for 2 consecutive weeks. 'Mood' was defined using the Facial Affective Scale, which is a visual representation of negative and positive affect. Data were analyzed using multilevel models. Results Controlling for age, sex, quality of life, headache disability, and medication use, worse mood was associated with same-day occurrence, longer duration, and more severe headache in both child and parent report. Today's mood was not consistently associated with next-day headache, and today's headache was not associated with next-day mood in either child or parent report. Conclusions Results of this study lend support to a complex relationship between mood and headache in children with migraine. More research is needed to further elucidate the temporal nature of this relationship within a given day and over an extended period of time. [ABSTRACT FROM AUTHOR]

ABSTRACT This paper presents the results of a study comparing the impacts on helping relationships of locating front-line child protection service providers in central locations or in accessible school and neighbourhood service delivery sites. Creating easier access to front-line child protection service providers, fostering more positive community perceptions of child welfare services, improving client and service provider satisfaction with helping relationships and services, and increasing families' willingness to ask for help were core objectives at the accessible sites. Using a quasi-experimental outcome design, file reviews and qualitative interviews with service providers and parents, this study presents evidence that accessible sites had substantial success in achieving these objectives when compared with central service delivery locations. [ABSTRACT FROM AUTHOR]