Down syndrome and postoperative complications after paediatric cardiac surgery: a propensity-matched analysis

OBJECTIVESThe incidence of congenital heart disease is approximately 50%, mostly related to endocardial cushion defects. The aim of our study was to investigate the postoperative complications that occur after paediatric cardiac surgery.METHODSOur perioperative data were analysed in paediatric patients with Down syndrome undergoing cardiac surgery. We retrospectively analysed the data from 2063 consecutive paediatric patients between January 2003 and December 2008. After excluding the patients who died or had missing data, the analysed database (before propensity matching) contained 129 Down patients and 1667 non-Down patients. After propensity matching, the study population comprised 222 patients and 111 patients had Down syndrome.RESULTSBefore propensity matching, the occurrences of low output syndrome (21.2 vs 32.6%, P = 0.003), pulmonary complication (14 vs 28.7%, P < 0.001) and severe infection (11.9 vs 22.5%, P = 0.001) were higher in the Down group. Down patients were more likely to have prolonged mechanical ventilation [median (interquartile range) 22 (9-72) h vs 49 (24-117) h, P = 0.007]. The total intensive care unit length of stay [6.9 (4.2-12.4) days vs 8.3 (5.3-13.2) days, P = 0.04] and the total hospital length of stay [17.3 (13.3-23.2) days vs 18.3 (15.1-23.6) days, P = 0.05] of the Down patients were also longer. Mortality was similar in the two groups before (3.58 vs 3.88%, P = 0.86) and after (5.4 vs 4.5%, P = 1.00) propensity matching. After propensity matching, there was no difference in the occurrence of adverse events.CONCLUSIONSAfter propensity matching Down syndrome was not associated with increased mortality or complication rate following congenital cardiac surgery

Integrative Genomics Identifies Gene Signature Associated with Melanoma Ulceration

Abstract Background: Despite the extensive research approaches applied to characterise malignant melanoma, no specific molecular markers are available that are clearly related to the progression of this disease. In this study, our aims were to define a gene expression signature associated with the clinical outcome of melanoma patients and to provide an integrative interpretation of the gene expression -, copy number alterations -, and promoter methylation patterns that contribute to clinically relevant molecular functional alterations

Unimpaired attentional disengagement in toddlers with autism spectrum disorder

A prominent hypothesis holds that ‘sticky’ attention early in life in children with autism spectrum disorder (ASD) limits their ability to explore and learn about the world. Under this hypothesis, the core clinical symptoms of ASD – restricted interests, repetitive behaviors and impaired social/communication abilities – could all result from impaired attentional disengagement during development. However, the existence of disengagement deficits in children with ASD is controversial, and a recent study found no deficit in 5- to 12-year-olds with ASD. Nonetheless, the possibility remains that disengagement is impaired earlier in development in children with ASD, altering their developmental trajectory even if the attentional deficit itself is remediated or compensated for by the time children with ASD reach school age. Here, we tested this possibility by characterizing attentional disengagement in a group of toddlers just diagnosed with ASD (age 21 to 37 months). We found strikingly similar performance between the ASD and age-matched typically developing (TD) toddlers, and no evidence of impaired attentional disengagement. These results show that even at a young age when the clinical symptoms of ASD are first emerging, disengagement abilities are intact. Sticky attention is not a fundamental characteristic of ASD, and probably does not play a causal role in its etiology.Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.) (Award F32-HD075427

GOLIAH: A Gaming Platform for Home-Based Intervention in Autism – Principles and Design

Meeting the required intensive intervention hour for treating children with autism is challenging in terms of trained manpower needed and costs. Advances in Information Communication Technology and computer gaming may help in this respect by creating a nomadically deployable closed loop intervention system involving the child and active participation of parents and therapists.An automated serious gaming platform enabling intensive intervention in nomadic settings has been developed by mapping two pivotal skills in autism spectrum disorder: Imitation and Joint Attention (JA). Eleven games – seven Imitation and four JA – were derived from the Early Start Denver Model. The games involved application of visual and audio stimuli with multiple difficulty levels and a wide variety of tasks and actions pertaining to the Imitation and JA. The platform runs on mobile devices and allows the therapist to (1) characterize the child’s initial difficulties/strengths, ensuring tailored and adapted intervention by choosing appropriate games and (2) investigate and track the temporal evolution of the child’s progress through a set of automatically extracted quantitative performance metrics. The platform allows the therapist to change the game or its difficulty levels during the intervention depending on the child’s progress. Performance of the platform was assessed in a 3-month open trial with 10 children with autism. The children and the parents participated in 80% of the sessions both at home (77.5%) and at hospital (90%). All children went through all games but, given the diversity of the games and the heterogeneity of children profiles and abilities, for a given game the number of sessions dedicated to the game varied and could be tailored through automatic scoring. Parents (N = 10) highlighted enhancement in the child’s concentration, flexibility and self-esteem in 78%, 89% and 44% of the cases respectively and 56% observed an enhanced parents-child relationship. This pilot study shows the feasibility of using the developed gaming platform for home-based intensive intervention. However, the overall capability of the platform in delivering intervention needs to be assessed in a bigger open trial

GOLIAH (Gaming Open Library for Intervention in Autism at Home): a 6-month single blind matched controlled exploratory study

BackgroundTo meet the required hours of intensive intervention for treating children with autism spectrum disorder (ASD), we developed an automated serious gaming platform (11 games) to deliver intervention at home (GOLIAH) by mapping the imitation and joint attention (JA) subset of age-adapted stimuli from the Early Start Denver Model (ESDM) intervention. Here, we report the results of a 6-month matched controlled exploratory study.MethodsFrom two specialized clinics, we included 14 children (age range 5–8 years) with ASD and 10 controls matched for gender, age, sites, and treatment as usual (TAU). Participants from the experimental group received in addition to TAU four 30-min sessions with GOLIAH per week at home and one at hospital for 6 months. Statistics were performed using Linear Mixed Models.ResultsChildren and parents participated in 40% of the planned sessions. They were able to use the 11 games, and participants trained with GOLIAH improved time to perform the task in most JA games and imitation scores in most imitation games. GOLIAH intervention did not affect Parental Stress Index scores. At end-point, we found in both groups a significant improvement for Autism Diagnostic Observation Schedule scores, Vineland socialization score, Parental Stress Index total score, and Child Behavior Checklist internalizing, externalizing and total problems. However, we found no significant change for by time × group interaction.ConclusionsDespite the lack of superiority of TAU + GOLIAH versus TAU, the results are interesting both in terms of changes by using the gaming platform and lack of parental stress increase. A large randomized controlled trial with younger participants (who are the core target of ESDM model) is now discussed. This should be facilitated by computing GOLIAH for a web platform.Trial registration Clinicaltrials.gov NCT0256041

Pragmatic Language and School Related Linguistic Abilities in Siblings of Children with Autism

Siblings of probands with autism spectrum disorders are at higher risk for developing the broad autism phenotype (BAP). We compared the linguistic abilities (i.e., pragmatic language, school achievements, and underling reading processes) of 35 school-age siblings of children with autism (SIBS-A) to those of 42 siblings of children with typical development. Results indicated lower pragmatic abilities in a subgroup of SIBS-A identified with BAP related difficulties (SIBS-A-BAP) whereas school achievements and reading processes were intact. Furthermore, among SIBS-A-BAP, significant negative correlations emerged between the severity scores on the Autism Diagnostic Observation Schedule and full and verbal IQ scores. These results are discussed in the context of the developmental trajectories of SIBS-A and in relation to the BAP

Systematic review of tools to measure outcomes for young children with autism spectrum disorder

Background: The needs of children with autism spectrum disorder (ASD) are complex and this is reflected in the number and diversity of outcomes assessed and measurement tools used to collect evidence about children's progress. Relevant outcomes include improvement in core ASD impairments, such as communication, social awareness, sensory sensitivities and repetitiveness, skills such as social functioning and play, participation outcomes such as social inclusion, and parent and family impact. Objectives: To examine the measurement properties of tools used to measure progress and outcomes in children with ASD up to the age of 6 years. To identify outcome areas regarded as important by people with ASD and parents. Methods: The MeASURe (Measurement in Autism Spectrum disorder Under Review) research collaboration included ASD experts and review methodologists. We undertook systematic review of tools used in ASD early intervention and observational studies from 1992 to 2013, systematic review, using the COSMIN checklist (Consensus-based Standards for the selection of health Measurement Instruments) of papers addressing the measurement properties of identified tools in children with ASD, and synthesis of evidence and gaps. The review design and process was informed throughout by consultation with stakeholders including parents, young people with ASD, clinicians and researchers. Results: The conceptual framework developed for the review was drawn from the International Classification of Functioning, Disability and Health, including the domains 'Impairments', 'Activity Level Indicators', 'Participation', and 'Family Measures'. In review 1, 10,154 papers were sifted - 3091 by full text - and data extracted from 184, in total, 131 tools were identified, excluding observational coding, study-specific measures and those not in English. In review 2, 2665 papers were sifted and data concerning measurement properties of 57 (43%) tools were extracted from 128 papers. Evidence for the measurement properties of the reviewed tools was combined with information about their accessibility and presentation. Twelve tools were identified as having the strongest supporting evidence, the majority measuring autism characteristics and problem behaviour. The patchy evidence and limited scope of outcomes measured mean these tools do not constitute a 'recommended battery' for use. In particular,there is little evidence that the identified tools would be good at detecting change in intervention studies. The obvious gaps in available outcome measurement include well-being and participation outcomes for children, and family quality-of-life outcomes, domains particularly valued by our informants (young people with ASD and parents). Conclusions: This is the first systematic review of the quality and appropriateness of tools designed to monitor progress and outcomes of young children with ASD. Although it was not possible to recommend fully robust tools at this stage, the review consolidates what is known about the field and will act as a benchmark for future developments. With input from parents and other stakeholders, recommendations are made about priority targets for research. Future work: Priorities include development of a tool to measure child quality of life in ASD, and validation of a potential primary outcome tool for trials of early social communication intervention. Study registration: This study is registered as PROSPERO CRD42012002223. Funding: The National Institute for Health Research Health Technology Assessment programme