Insights from user experience and evaluation of a mobile health nutrition intervention for children with autism: A qualitative study.

BACKGROUND: Children with autism spectrum disorder (ASD) experience high rates of atypical eating behaviours, such as food neophobia. Mobile health (mHealth) interventions have been found to improve communication, behaviour and social skills for children with ASD. However, there is limited evidence examining mHealth nutrition interventions among children with ASD. METHODS: The present study comprised a qualitative descriptive study that used qualitative content analysis to explore parent and child experiences with a novel mHealth nutrition intervention. Ten parent-child dyads provided user feedback and evaluation of the intervention. Data collection tools included a semistructured interview guide and a quantitative questionnaire with open-ended questions. Data analysis of the interview transcripts and open-ended questionnaire responses was an iterative process that continued until saturation was achieved. Descriptive statistics were used to analyse quantitative questionnaire data. RESULTS: Analysis of the qualitative semistructured interviews led to emergence of three themes: (1) positive intervention outcomes; (2) parent suggestions for improvement; and (3) barriers to engagement. Each theme included subthemes. Questionnaire data revealed the ability to pick rewards and the virtual character that reinforced dietary goals ("Nutrition Ninja") were the most liked components of the application. Sending messages within the application and the Nutrition Ninja game were the least liked components of the application. CONCLUSIONS: Collectively, findings indicated that the app served as an interactive tool prompting dietary change and conversations within families. Yet, for some families, the intervention design, resistance to change or child disinterest hindered use and implementation of the intervention.

A remotely delivered, peer-led intervention to improve physical activity and quality of life in younger breast cancer survivors.

Younger breast cancer survivors (YBCS) consistently report poorer quality of life (QOL) than older survivors. Increasing physical activity (PA) may improve QOL, but this has been understudied in YBCS. This single arm pilot study evaluated the feasibility and acceptability of a 3-month, peer-delivered, remote intervention to increase PA and improve QOL in YBCS. Data were collected from October 2019 - July 2020. Participants (n = 34, 43.1 ± 5.5 years old, 46 ± 34.4 months post-diagnosis, BMI = 30.2 ± 7.4 kg/m2) completed six video sessions with a trained peer mentor; self-monitored PA with a Fitbit activity tracker; and interacted with a private Fitbit Community for social support. At baseline, 3-and 6-months, participants completed QOL questionnaires and PA was measured through accelerometer (moderate-to-vigorous PA [MVPA]) and self-report (strength and flexibility). A parallel mixed-methods approach (qualitative interviews and quantitative satisfaction survey at 3-months) explored intervention feasibility and acceptability. One-way repeated-measures ANOVAs examined impacts on PA and QOL at 3-and 6-months. The intervention was feasible as evidenced by efficient recruitment, high retention, and adherence to intervention components. Remote delivery, working with a peer mentor, and using Fitbit tools were highly acceptable. From baseline to 3-months, participants increased time spent in objectively measured MVPA, strength, and flexibility exercises, and reported meaningful improvements to body image, fatigue, anxiety, and emotional support. A fully remote, peer-to-peer intervention is an acceptable and promising strategy to increase PA and improve QOL in YBCS. Refinements to the intervention and its delivery should be further assessed in future studies, toward the goal of disseminating an evidence-based, scalable intervention to the growing number of YBCS.Trial registration Prospectively registered as NCT04064892.

Many Young Children with Autism Who Use Psychotropic Medication Do Not Receive Behavior Therapy: A Multisite Case-Control Study.

OBJECTIVES: To explore how many pre-school aged children with autism spectrum disorder (ASD) used psychotropic medication, child and geographic factors associated with psychotropic medication use, and how many children who used psychotropic medication did or did not ever receive behavior therapy. STUDY DESIGN: Children 2-5 years of age were enrolled from 2012 to 2016 in a multisite case-control study designed to investigate the development and risk factors of ASD. Children with a positive ASD screen or ASD diagnosis upon enrollment were asked to complete a comprehensive evaluation to determine ASD status and developmental level. Caregivers completed a Services and Treatments Questionnaire and multiple self-administered questionnaires to determine child use of psychotropic medication, ever receipt of behavior therapy, and presence of co-occurring symptoms. RESULTS: There were 763 children who were classified as ASD and had data collected on the Services and Treatments Questionnaire. Of those, 62 (8.1%) used psychotropic medication to treat behavioral symptoms and 28 (3.7%) were ≤3 years of age when medication was first started. Attention problems (aOR, 7.65; 95% CI, 3.41-16.1; P < .001) and study site (aOR, 2.62; 95% CI, 1.04-6.56; P = .04) were significantly associated with psychotropic medication use after controlling for maternal race/ethnicity. More than one-half (59.7%) of those who used psychotropic medication did not ever receive behavior therapy. CONCLUSIONS: Many preschool-aged children with ASD who use psychotropic medication do not receive behavior therapy. Pediatricians are an important resource for children and families and can help facilitate behavioral treatment for children with ASD and other disorders.

Health Status and Health Care Use Among Adolescents Identified With and Without Autism in Early Childhood - Four U.S. Sites, 2018-2020.

Persons identified in early childhood as having autism spectrum disorder (autism) often have co-occurring health problems that extend into adolescence (1-3). Although only limited data exist on their health and use of health care services as they transition to adolescence, emerging data suggest that a minority of these persons receive recommended guidance* from their primary care providers (PCPs) starting at age 12 years to ensure a planned transition from pediatric to adult health care (4,5). To address this gap in data, researchers analyzed preliminary data from a follow-up survey of parents and guardians of adolescents aged 12-16 years who previously participated in the Study to Explore Early Development (https://www.cdc.gov/ncbddd/autism/seed.html). The adolescents were originally studied at ages 2-5 years and identified at that age as having autism (autism group) or as general population controls (control group). Adjusted prevalence ratios (aPRs) that accounted for differences in demographic characteristics were used to compare outcomes between groups. Adolescents in the autism group were more likely than were those in the control group to have physical difficulties (21.2% versus 1.6%; aPR = 11.6; 95% confidence interval [CI] = 4.2-31.9), and to have additional mental health or other conditions† (one or more condition: 63.0% versus 28.9%; aPR = 1.9; 95% CI = 1.5-2.5). Adolescents in the autism group were more likely to receive mental health services (41.8% versus 22.1%; aPR = 1.8, 95% CI = 1.3-2.6) but were also more likely to have an unmet medical or mental health service need§ (11.0% versus 3.2%; aPR = 3.1; 95% CI = 1.1-8.8). In both groups, a small percentage of adolescents (autism, 7.5%; control, 14.1%) received recommended health care transition (transition) guidance. These findings are consistent with previous research (4,5) indicating that few adolescents receive the recommended transition guidance and suggest that adolescents identified with autism in early childhood are more likely than adolescents in the general population to have unmet health care service needs. Improved provider training on the heath care needs of adolescents with autism and coordination of comprehensive programs¶ to meet their needs can improve delivery of services and adherence to recommended guidance for transitioning from pediatric to adult health care.

Motivation for Physical Activity among U.S. Adolescents: A Self-Determination Theory Perspective.

BACKGROUND: Promoting adolescent physical activity is crucial as this marks a time when physical activity rates decline. PURPOSE: This study examined motivation for physical activity from a self-determination theory (SDT) perspective in a large sample of adolescents in the USA across three settings: in school, out of school, and on weekends. METHODS: Participants (N = 1,661) were adolescents from the National Cancer Institute's Family Life, Activity, Sun, Health, and Eating study. Participants had a mean age of 14.47 (standard deviation = 1.61) and were 50.2% female. In this national sample balanced to match the U.S. population on several key demographics, 64.2% were non-Hispanic White. Analyses included three linear regression models in which estimated weekly minutes of moderate-to-vigorous physical activity (MVPA) in school, out of school, and on weekends were entered as dependent variables. Five forms of motivation (intrinsic, integrated, identified, introjected, and external) were entered simultaneously as independent variables. Age, body mass index, gender, and race/ethnicity were also included as covariates. RESULTS: All models were significant. For MVPA in school, external regulation, introjected regulation, identified regulation, and intrinsic motivation were positively associated with MVPA. For MVPA out of school, external regulation, introjected regulation, identified regulation, integrated regulation, and intrinsic motivation were positively associated with MVPA. For MVPA on weekends, integrated regulation, and intrinsic motivation were positively associated with MVPA. CONCLUSIONS: The relationship between motivation and MVPA varies across settings. These findings have important implications for motivating adolescents to engage in physical activity and may inform future interventions aimed at increasing physical activity.

Stand Up Now: A Sedentary Behavior Intervention in Older Adults of Moderate to Low Physical Function.

OBJECTIVES: To examine the efficacy of an the intervention Stand Up Now (SUN) to reduce sedentary behavior (SB) and improve physical function and mobility. METHODS: SUN included two groups: (a) focused on reducing total SB (SUNSL) and (b) focused on increasing sit-to-stand (STS) transitions (SUNSTS). The participants (N = 71; Mage = 87 ± 7 years) had 12 weekly health coaching sessions. SB, physical function, and mobility were measured at the baseline, 6, and 12 weeks via the activPAL, Short Physical Performance Battery, and the 8-foot up and go, respectively. Linear mixed models examined the outcome variables over time. RESULTS: Both groups decreased sedentary time (1.3 ± 0.3 hr, p < .001), increased standing time (0.5 ± 0.2 hr, p < .02), and improved physical function (1.5 ± 0.4 points, p < .001) from the baseline to 6 weeks, and they maintained it at 12 weeks. SUNSTS increased STS transitions (5.4 ± 4.1, p < .001), while SUNSL had no changes (0.5 ± 3.1, p > .9). There were no changes in mobility for either group (0.5 ± 1.5 s, p > .05). DISCUSSION: SUN demonstrates the efficacy to improve SB and physical function in older adults.

Realistic driving simulation during generalized epileptiform discharges to identify electroencephalographic features related to motor vehicle safety: Feasibility and pilot study.

OBJECTIVE: Generalized epileptiform discharges (GEDs) can occur during seizures or without obvious clinical accompaniment. Motor vehicle driving risk during apparently subclinical GEDs is uncertain. Our goals were to develop a feasible, realistic test to evaluate driving safety during GEDs, and to begin evaluating electroencephalographic (EEG) features in relation to driving safety. METHODS: Subjects were aged ≥15 years with generalized epilepsy, GEDs on EEG, and no clinical seizures. Using a high-fidelity driving simulator (miniSim) with simultaneous EEG, a red oval visual stimulus was presented every 5 minutes for baseline testing, and with each GED. Participants were instructed to pull over as quickly and safely as possible with each stimulus. We analyzed driving and EEG signals during GEDs. RESULTS: Nine subjects were tested, and five experienced 88 GEDs total with mean duration 2.31 ± 1.89 (SD) seconds. Of these five subjects, three responded appropriately to all stimuli, one failed to respond to 75% of stimuli, and one stopped driving immediately during GEDs. GEDs with no response to stimuli were significantly longer than those with appropriate responses (8.47 ± 3.10 vs 1.85 ± 0.69 seconds, P < .001). Reaction times to stimuli during GEDs were significantly correlated with GED duration (r = 0.30, P = .04). In addition, EEG amplitude was greater for GEDs with no response to stimuli than GEDs with responses, both for overall root mean square voltage amplitude (66.14 µV vs 52.99 µV, P = .02) and for fractional power changes in the frequency range of waves (P < .05) and spikes (P < .001). SIGNIFICANCE: High-fidelity driving simulation is feasible for investigating driving behavior during GEDs. GEDs with longer duration and greater EEG amplitude showed more driving impairment. Future work with a large sample size may ultimately enable classification of GED EEG features to predict individual driving risk.

Relationship of Weight Outcomes, Co-Occurring Conditions, and Severity of Autism Spectrum Disorder in the Study to Explore Early Development.

OBJECTIVE: To assess contributing factors to increased obesity risk, by comparing children with autism spectrum disorder (ASD), developmental delays/disorders, and general population controls in weight status, and to examine associations between weight status and presence of co-occurring medical, behavioral, developmental, or psychiatric conditions across groups and ASD severity among children with ASD. STUDY DESIGN: The Study to Explore Early Development is a multisite cross-sectional study of children, 2-5 years of age, classified as children with ASD (n = 668), children with developmental delays/disorders (n = 914), or general population controls (n = 884). Using an observational cohort design, we compared the 3 groups. Children's heights and weights were measured during a clinical visit. Co-occurring conditions (medical, behavioral, developmental/psychiatric) were derived from medical records, interviews, and questionnaires. ASD severity was measured by the Ohio State University Global Severity Scale for Autism. RESULTS: The odds of overweight/obesity were 1.57 times (95% CI 1.24-2.00) higher in children with ASD than general population controls and 1.38 times (95% CI 1.10-1.72) higher in children with developmental delays/disorders than general population controls. The aORs were elevated for children with ASD after controlling for child co-occurring conditions (ASD vs general population controls: aOR = 1.51; 95% CI 1.14-2.00). Among children with ASD, those with severe ASD symptoms were 1.7 times (95% CI 1.1-2.8) more likely to be classified as overweight/obese compared with children with mild ASD symptoms. CONCLUSIONS: Prevention of excess weight gain in children with ASD, especially those with severe symptoms, and in children with developmental delays/disorders represents an important target for intervention.

DSM-5 criteria for autism spectrum disorder maximizes diagnostic sensitivity and specificity in preschool children.

PURPOSE: The criteria for autism spectrum disorder (ASD) were revised in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM). The objective of this study was to compare the sensitivity and specificity of DSM-IV-Text Revision (DSM-IV-TR) and DSM-5 definitions of ASD in a community-based sample of preschool children. METHODS: Children between 2 and 5 years of age were enrolled in the Study to Explore Early Development-Phase 2 (SEED2) and received a comprehensive developmental evaluation. The clinician(s) who evaluated the child completed two diagnostic checklists that indicated the presence and severity of DSM-IV-TR and DSM-5 criteria. Definitions for DSM-5 ASD, DSM-IV-TR autistic disorder, and DSM-IV-TR Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) were created from the diagnostic checklists. RESULTS: 773 children met SEED2 criteria for ASD and 288 met criteria for another developmental disorder (DD). Agreement between DSM-5 and DSM-IV-TR definitions of ASD were good for autistic disorder (0.78) and moderate for PDD-NOS (0.57 and 0.59). Children who met DSM-IV-TR autistic disorder but not DSM-5 ASD (n = 71) were more likely to have mild ASD symptoms, or symptoms accounted for by another disorder. Children who met PDD-NOS but not DSM-5 ASD (n = 66), or vice versa (n = 120) were less likely to have intellectual disability and more likely to be female. Sensitivity and specificity were best balanced with DSM-5 ASD criteria (0.95 and 0.78, respectively). CONCLUSIONS: The DSM-5 definition of ASD maximizes diagnostic sensitivity and specificity in the SEED2 sample. These findings support the DSM-5 conceptualization of ASD in preschool children.

Demographic and Operational Factors Predicting Study Completion in a Multisite Case-Control Study of Preschool Children.

Participant attrition can limit inferences drawn from study results and inflate research costs. We examined factors associated with completion of the Study to Explore Early Development (2007-2011), a multiple-component, case-control study of risk factors for autism spectrum disorder in preschoolers, conducted in California, Colorado, Georgia, Maryland, North Carolina, and Pennsylvania. Participants (n = 3,769) were asked to complete phone interviews, questionnaires, an in-person evaluation, and biologic sampling. We examined whether participant demographic and administrative factors predicted completion using mixed-effects logistic regression models. Completion of individual key study components was generally 70% or higher. However, 58% of families completed all per-protocol data elements (defined a priori as key study components). Per-protocol completion differed according to mother's age, race, educational level, driving distance to clinic, number of contact attempts to enroll, and number of telephone numbers provided (all P < 0.05). Case status was not associated with completion, despite additional data collection for case-confirmation. Analysis of a subset that completed an early interview revealed no differences in completion by household factors of income, primary language spoken, number of adults, or number of children with chronic conditions. Differences in completion by race and education were notable and need to be carefully considered in developing future recruitment and completion strategies.

Evolution and course of early life developmental encephalopathic epilepsies: Focus on Lennox-Gastaut syndrome.

OBJECTIVES: Developmental encephalopathic epilepsies (DEEs) are characterized by refractory seizures, disability, and early death. Opportunities to improve care and outcomes focus on West syndrome/infantile spasms (WS/IS). Lennox-Gastaut syndrome (LGS) is almost as common but receives little attention. We examined initial presentations of DEEs and their evolution over time to identify risk and indicators of developing LGS. METHODS: Data are from the Connecticut Study of Epilepsy, a prospective, longitudinal study of 613 children with newly diagnosed epilepsy recruited in 1993-1997. Central review of medical records permitted classification of epilepsy syndromes at diagnosis and at reclassification 2, 5, and 9 years later. DEEs were compared to other epilepsies for seizure and cognitive outcomes and mortality. Analyses examined the evolution of DEE syndromes after initial presentation, with specific comparisons made between WS/IS and LGS. Statistical analyses were performed with t tests and chi-square tests. RESULTS: Fifty-eight children (9.4%) had DEEs, median onset age = 1.1 years (interquartile range ([IQR] 0.3-1.3) in DEEs and 6.0 years (IQR 3.0-9.0) in other epilepsies (P < 0.001). DEEs vs other epilepsies had more pharmacoresistance (71% vs 18%), intellectual disability (84% vs 11%), and mortality (21% vs <1%; all P < 0.001). During follow-up, the form of epilepsy evolved in 33 children. WS/IS was the most common initial diagnosis (N = 23) and in 5 children WS/IS evolved later. LGS was diagnosed initially in 4 children (1 later revised) and in 22 by the end of follow-up, including 7 evolving from WS/IS and 12 from nonsyndromic generalized, focal, or undetermined epilepsies. Evolution to LGS took a median of 1.9 years. LGS developed in 13% of infants, including 9% of those who did not present initially with WS/IS. SIGNIFICANCE: DEEs account for disproportionate amounts of pharmacoresistance, disability, and early mortality. LGS often has a window between initial presentation and full expression. LGS should become targeted for early detection and prevention.

BTrackS Balance Test for Concussion Management is Resistant to Practice Effects.

OBJECTIVE: Recent guidelines advocate for ongoing balance testing in the assessment of management of concussion injuries. This study sought to determine whether the Balance Tracking System (BTrackS) provides stable balance results over repeated administration and, thus, is a reliable tool for concussion management. DESIGN: Repeated measures and test-retest reliability. SETTING: University Biomechanics Laboratory. PARTICIPANTS: Random sample of 20 healthy young adults. INTERVENTIONS: Force plate balance testing using BTrackS on days 1, 3, 8, and 15. MAIN OUTCOME MEASURES: Practice-induced changes in the average center of pressure excursion over 4 repeated administrations of the BTrackS Balance Test (BBT). Test-retest reliability of center of pressure excursion from day 1 to day 15. RESULTS: No significant practice-induced balance differences were found across testing days (P > 0.4), and test-retest reliability of the BBT was excellent from day 1 to day 15 (R 0.92). CONCLUSIONS: These findings indicate that the BBT does not elicit a practice effect over repeat administrations. BTrackS provides excellent reliability and objectivity, which can increase clinician accuracy when monitoring sport-related concussions.

The Association Between Self-Reported Adherence to Physical Activity Recommendations and Criteria for Maintaining Physical Independence of Older Adults.

While physical activity (PA) improves functions for activities of daily living, little is known of the association between meeting published PA Guidelines for Americans (PAGA) and meeting published physical function guidelines for maintaining independence. The purpose of this study was to examine the association between meeting the PAGA and meeting independence criteria on the Senior Fitness Tests (SFT). Older adults (N = 265) completed SFTs, assessing cardiorespiratory fitness, lower and upper body strength, mobility, and self-reported aerobic and resistance PA. Chi-square tests and logistic regressions examined associations between meeting PAGA and SFT independence criteria. A significant relationship was found between meeting aerobic PAGA and cardiorespiratory and upper body SFT criteria; a significant relationship was found between meeting resistance PAGA and upper body strength criteria. Although research suggests that PAGA are effective in maintaining fitness in older adults when PA is structured and monitored, mixed results were found for self-reported PA and SFT criteria.

Surgical outcome in adolescents with mesial temporal sclerosis: Is it different?

There are extensive studies evaluating mesial temporal sclerosis (MTS) in adults and limited studies in children, with adolescents being included within both patient populations. Our aim was to evaluate predictors of surgical outcome solely in adolescent patients with MRI- and pathology -proven MTS. The Yale Epilepsy Surgery Database was reviewed from 1987 to 2012 for adolescent patients with confirmed MTS on MRI and pathology who underwent temporal lobectomy and had greater than two-year postsurgical follow-up. Clinical and electrographic data were reviewed. Eighteen patients were identified. Eleven patients (61%) were seizure-free. All seven patients (39%) who were not seizure-free free were found to have lateralized ictal onset within one hemisphere involving two or more lobes on scalp EEG (p<0.001). Of the 7 patients who were not seizure-free, 4 had a history of status epilepticus (compared to 1/11 seizure-free patients; p=0.047), and 4 had lateralized hypometabolism involving two or more lobes within a hemisphere seen on PET (compared to 0/8 seizure-free patients; p=0.002). A novel finding in our study was that lateralized (rather than localized) ictal onset on scalp EEG, lateralized hypometabolism on PET, and history of status epilepticus were risk factors for not attaining seizure freedom in adolescents with MTS who underwent temporal lobectomy.

Differences in lumbar spine and lower extremity kinematics in people with and without low back pain during a step-up task: a cross-sectional study.

BACKGROUND: Low back pain (LBP) affects more than one third of the population at any given time, and chronic LBP is responsible for increased medical costs, functional limitations and decreased quality of life. A clear etiology is often difficult to identify, but aberrant posture and movement are considered contributing factors to chronic LBP that are addressed during physiotherapy intervention. Information about aberrant movement during functional activities in people with LBP can help inform more effective interventions. The purpose of this study was to determine if there are differences in lumbar spine and lower extremity kinematics in people with and without LBP during a step-up task. METHODS: A convenience sample of 37 participants included 19 with LBP and 18 without a history of LBP. All participants were between the ages of 18 and 65, and controls were matched to participants with LBP based on age, gender and BMI. A motion capture system was used to record spine and lower extremity kinematics during the step-up task. ANOVA tests were used to determine differences in three-dimensional kinematics between groups. RESULTS: Participants with LBP displayed less lower lumbar motion in the sagittal plane (P = 0.001), more knee motion in the coronal plane (P = 0.001), and more lower extremity motion in the axial plane (P = 0.002) than controls. CONCLUSIONS: People with LBP display less lower lumbar spine motion in the sagittal plane and more out-of-plane lower extremity motion. Clinically, the step-up task can be used to identify these aberrant movements to develop more focused functional interventions for patients with LBP. TRIAL REGISTRATION: Not applicable.

A Longitudinal Assessment Of Standing Balance In Healthy Adults.

Background/Study Context: The study was a longitudinal assessment of age-related changes in standing balance and response strategy usage in healthy adults. METHODS: Balance of 17 individuals with a mean age of 44.5 years was assessed and then reassessed 19.5 years later. Participants stood on computer-controlled dual-force platforms enclosed by a visual surround and completed six tests in which visual and/or somatosensory information was systematically degraded or eliminated. RESULTS: Results for each test and a weighted composite balance score revealed no significant change in postural control over the time period studied. However, response strategy scores indicated some significant change with age. Specifically, compensatory movement corrections about the ankle complex increased when standing on a stable support surface with and without vision, and hip-centered corrections were prominent when standing on an unstable surface with eyes open or closed. CONCLUSION: Increased reliance on response strategy usage with time is interpreted as a compensatory adjustment to age-related increases in postural instability and accounts for the absence of any change in standing balance under different conditions of sensory input.

Complete remission of childhood-onset epilepsy: stability and prediction over two decades.

The ultimate seizure outcome of childhood epilepsy is complete resolution of all seizures without further treatment. How often this happens and how well it can be predicted early in the course of epilepsy could be valuable in helping families understand the nature of childhood epilepsy and what to expect over time. In the Connecticut study of epilepsy, a prospective cohort of 613 children with newly-diagnosed epilepsy (onset age 0-15 years), complete remission, ≥5 years both seizure-free and medication-free, was examined as a proxy of complete seizure resolution. Predictors at initial diagnosis were tested. Information about seizure outcomes within 2 years and from 2-5 years after diagnosis was sequentially added in a proportional hazards model. The predictive value of the models was determined with logistic regression. Five hundred and sixteen subjects were followed ≥10 years. Three hundred and twenty-eight (63%) achieved complete remission; 23 relapsed. The relapse rate was 8.2 per 1000 person-years and decreased over time: 10.7, 6.7, and 0 during first 5 years, the next 5 years, and then >10 years after complete remission (P=0.06 for trend). Six participants regained complete remission; 311 (60%) were in complete remission at last contact. Baseline factors predicting against complete remission at last contact included onset age≥10 years (hazard ratio=0.55, P=0.0009) and early school or developmental problems (hazard ratio=0.74, P=0.01). Factors predicting for complete remission were uncomplicated epilepsy presentation (hazard ratio=2.23, P<0.0001), focal self-limited epilepsy syndrome (hazard ratio=2.13, P<0.0001), and uncharacterized epilepsy (hazard ratio=1.61, P=0.04). Remission (hazard ratio=1.95, P<0.0001) and pharmaco-resistance (hazard ratio=0.33, P<0.0001) by 2 years respectfully predicted in favour and against complete remission. From 2 to 5 years after diagnosis, relapse (hazard ratio=0.21, P<0.0001) and late pharmaco-resistance (hazard ratio=0.21, P=0.008) decreased and late remission (hazard ratio=2.40, P<0.0001) increased chances of entering complete remission. The overall accuracy of the models increased from 72% (baseline information only), to 77% and 85% with addition of 2-year and 5-year outcomes. Relapses after complete remission are rare making this an acceptable proxy for complete seizure resolution. Complete remission after nearly 20 years is reasonably well predicted within 5 years of initial diagnosis.

Common genetic variants on 5p14.1 associate with autism spectrum disorders.

Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental and neuropsychiatric disorders characterized by deficits in verbal communication, impairment of social interaction, and restricted and repetitive patterns of interests and behaviour. To identify common genetic risk factors underlying ASDs, here we present the results of genome-wide association studies on a cohort of 780 families (3,101 subjects) with affected children, and a second cohort of 1,204 affected subjects and 6,491 control subjects, all of whom were of European ancestry. Six single nucleotide polymorphisms between cadherin 10 (CDH10) and cadherin 9 (CDH9)-two genes encoding neuronal cell-adhesion molecules-revealed strong association signals, with the most significant SNP being rs4307059 (P = 3.4 x 10(-8), odds ratio = 1.19). These signals were replicated in two independent cohorts, with combined P values ranging from 7.4 x 10(-8) to 2.1 x 10(-10). Our results implicate neuronal cell-adhesion molecules in the pathogenesis of ASDs, and represent, to our knowledge, the first demonstration of genome-wide significant association of common variants with susceptibility to ASDs.

Autism genome-wide copy number variation reveals ubiquitin and neuronal genes.

Autism spectrum disorders (ASDs) are childhood neurodevelopmental disorders with complex genetic origins. Previous studies focusing on candidate genes or genomic regions have identified several copy number variations (CNVs) that are associated with an increased risk of ASDs. Here we present the results from a whole-genome CNV study on a cohort of 859 ASD cases and 1,409 healthy children of European ancestry who were genotyped with approximately 550,000 single nucleotide polymorphism markers, in an attempt to comprehensively identify CNVs conferring susceptibility to ASDs. Positive findings were evaluated in an independent cohort of 1,336 ASD cases and 1,110 controls of European ancestry. Besides previously reported ASD candidate genes, such as NRXN1 (ref. 10) and CNTN4 (refs 11, 12), several new susceptibility genes encoding neuronal cell-adhesion molecules, including NLGN1 and ASTN2, were enriched with CNVs in ASD cases compared to controls (P = 9.5 x 10(-3)). Furthermore, CNVs within or surrounding genes involved in the ubiquitin pathways, including UBE3A, PARK2, RFWD2 and FBXO40, were affected by CNVs not observed in controls (P = 3.3 x 10(-3)). We also identified duplications 55 kilobases upstream of complementary DNA AK123120 (P = 3.6 x 10(-6)). Although these variants may be individually rare, they target genes involved in neuronal cell-adhesion or ubiquitin degradation, indicating that these two important gene networks expressed within the central nervous system may contribute to the genetic susceptibility of ASD.