"Making Data the Drug": A Pragmatic Pilot Feasibility Randomized Crossover Trial of Data Visualization as an Intervention for Pediatric Chronic Pain.

Data tracking is a common feature of pain e-health applications, however, viewing visualizations of this data has not been investigated for its potential as an intervention itself. We conducted a pilot feasibility parallel randomized cross-over trial, 1:1 allocation ratio. Participants were youth age 12-18 years recruited from a tertiary-level pediatric chronic pain clinic in Western Canada. Participants completed two weeks of Ecological Momentary Assessment (EMA) data collection, one of which also included access to a data visualization platform to view their results. Order of weeks was randomized, participants were not masked to group assignment. Objectives were to establish feasibility related to recruitment, retention, and participant experience. Of 146 youth approached, 48 were eligible and consented to participation, two actively withdrew prior to the EMA. Most participants reported satisfaction with the process and provided feedback on additional variables of interest. Technical issues with the data collection platform impacted participant experience and data analysis, and only 48% viewed the visualizations. Four youth reported adverse events not related to visualizations. Data visualization offers a promising clinical tool, and patient experience feedback is critical to modifying the platform and addressing technical issues to prepare for deployment in a larger trial.

Child functional characteristics explain child and family outcomes better than diagnosis: Population-based study of children with autism or other neurodevelopmental disorders/disabilities.

BACKGROUND: Allocation of resources for services and supports for children with neurodevelopmental disorders/disabilities (NDD/D) is often based on the presence of specific health conditions. This study investigated the relative roles of a child's diagnosed health condition and neurodevelopmental and related functional characteristics in explaining child and family health and well-being. DATA AND METHODS: The data on children with NDD/D (ages 5 to 14; weighted n = 120,700) are from the 2006 Participation and Activity Limitation Survey (PALS), a population-based Canadian survey of parents of children with functional limitations/disabilities. Direct and indirect effects of child diagnosis status-autism spectrum disorder (ASD)/not ASD-and functional characteristics (particularly, ASD-related impairments in speech, cognition, and emotion and behaviour) on child participation and family health and well-being were investigated in a series of structural equation models, while controlling for covariates. RESULTS: All models adequately fitted the data. Child ASD diagnosis was significantly associated with child participation and family health and well-being. When ASD-related child functional characteristics were added to the model, all direct effects from child diagnosis on child and family outcomes disappeared; the effect of child diagnosis on child and family outcomes was fully mediated via ASD-related child functional characteristics. INTERPRETATION: Children's neurodevelopmental functional characteristics are integral to understanding the child and family health-related impact of neurodevelopmental disorders such as ASD. These findings have implications for the relative weighting given to functional versus diagnosis-specific factors in considering needs for services and supports.

Effects of AgRP inhibition on energy balance and metabolism in rodent models.

Activation of brain melanocortin-4 receptors (MC4-R) by α-melanocyte-stimulating hormone (MSH) or inhibition by agouti-related protein (AgRP) regulates food intake and energy expenditure and can modulate neuroendocrine responses to changes in energy balance. To examine the effects of AgRP inhibition on energy balance, a small molecule, non-peptide compound, TTP2515, developed by TransTech Pharma, Inc., was studied in vitro and in rodent models in vivo. TTP2515 prevented AgRP from antagonizing α-MSH-induced increases in cAMP in HEK 293 cells overexpressing the human MC4-R. When administered to rats by oral gavage TTP2515 blocked icv AgRP-induced increases in food intake, weight gain and adiposity and suppression of T4 levels. In both diet-induced obese (DIO) and leptin-deficient mice, TTP2515 decreased food intake, weight gain, adiposity and respiratory quotient. TTP2515 potently suppressed food intake and weight gain in lean mice immediately after initiation of a high fat diet (HFD) but had no effect on these parameters in lean chow-fed mice. However, when tested in AgRP KO mice, TTP2515 also suppressed food intake and weight gain during HFD feeding. In several studies TTP2515 increased T4 but not T3 levels, however this was also observed in AgRP KO mice. TTP2515 also attenuated refeeding and weight gain after fasting, an effect not evident in AgRP KO mice when administered at moderate doses. This study shows that TTP2515 exerts many effects consistent with AgRP inhibition however experiments in AgRP KO mice indicate some off-target effects of this drug. TTP2515 was particularly effective during fasting and in mice with leptin deficiency, conditions in which AgRP is elevated, as well as during acute and chronic HFD feeding. Thus the usefulness of this drug in treating obesity deserves further exploration, to define the AgRP dependent and independent mechanisms by which TTP2515 exerts its effects on energy balance.

Patterns of participation across a range of activities among Canadian children with neurodevelopmental disorders and disabilities.

AIM: Children with neurodevelopmental disorders and disabilities (NDD/D) may experience barriers or restrictions to participation in activities. We examined the extent to which this is a problem for children in particular NDD/D subgroups. METHOD: We analysed the 2006 Participation and Activity Limitation Survey children data set (5-14y) collected by Statistics Canada (n = 7072 and weighted n = 340 340), having identified the following NDD/D subgroups (weighted n = 77 470; 69.1% males and 30.9% females): gross or gross and fine motor (Motor(+) ), communication/cognition/learning (CCL), social interaction, neurosensory (vision or vision and hearing), and psychological. We used logistic regression to assess differences in participation in supervised and unsupervised physical activities, educational activities, and social/recreational activities. RESULTS: Participation in some school-based activities differed significantly among children in the NDD/D subgroups (p<0.01). Participation in supervised and unsupervised physical activity was lowest for the Motor(+) and social interaction subgroups, and highest for the neurosensory and CCL subgroups. Participation for the psychological subgroup was mostly in the intermediate range. In contrast, participation in educational activities was lowest for the social interaction and psychological subgroups, and higher for the other groups. INTERPRETATION: Given the importance of participation to child health and well-being, these differences in participation in various in-school activities highlight an area of need regarding policies/programmes to support subgroups of children with NDD/D.

Diagnostic status, functional status and complexity among Canadian children with neurodevelopmental disorders and disabilities: a population-based study.

PURPOSE: To identify and describe selected key characteristics of children with neurodevelopmental disorders and disabilities (NDD/D) in a national disability survey database. METHOD: Secondary analysis of data on children aged 5-14 years in the Canadian Participation and Activity Limitation Survey (PALS). Children with NDD/D were ascertained from ICD-10 diagnoses "fine-tuned" with functional limitation information, and classified into six predetermined NDD/D subtypes by independent expert evaluators. RESULTS: Children with NDD/D accounted for 73.5% of children with disabilities. Amongst children with a single NDD/D type, 28.8% were in the Cognition-Learning subgroup, 22.2% Psychological, 19.9% Social interactive, 13.3% Sensory, 10.6% Motor and 5.2% Speech-Language disorders/disabilities. Complexity, both diagnostic (more than one ICD-10 diagnosis) and functional (more than one parent-identified functional limitation), was encountered frequently though variably across NDD/D subtypes. In aligning parent-identified functional limitation information with researcher-ascertained assignment of children to NDD/D subgroups, matching with additional limitations (61.3% of children) occurred far more commonly than simple 1:1 matches (14.0%) or non-matching (24.7%). CONCLUSIONS: Conceptual, definitional and terminology issues affect population-based research on children with NDD/D. Ascertainment methods can use diagnostic as well as functional information. Diagnostic information alone is likely to under-represent the complexity and needs of children with NDD/D and their families.

Comparing participation in activities among children with disabilities.

INTRODUCTION: Compared to typically developing peers, children with disabilities due to neurodevelopmental disorders and disabilities (NDD/D) and to chronic medical conditions (CMC) have reduced participation in activities. The extent to which these two groups of children have different levels of participation is unknown and was examined in this study. METHODS: The 2006 Participation and Activity Limitation Survey children dataset collected by Statistics Canada was analyzed. Children with disabilities due to NDD/D and CMC were identified following review and classification of all ICD-10 codes in the dataset by two pediatricians. Dependent variables were parent-reported child participation in supervised and unsupervised physical activities within and outside of school, educational activities, and social/recreational activities. Logistic regression analyses, with relevant covariates (child and familial characteristics), were used to analyze the data. RESULTS: Children with NDD/D were significantly more likely to take part in supervised and unsupervised physical activity at school than children with CMC (p<0.001). A similar trend was observed for participation in school outings, although the effect was not significant at p<0.01. Finally, a trend in the opposite direction was observed for educational activities, as children with NDD/D were less likely to take part in these activities than children with CMC. DISCUSSION: Finding decreased participation among children with CMC compared with NDD/D was not predicted a priori but has potential implications for their mental and physical health. CONCLUSIONS: Gaining a better understanding of the barriers to participation in physical activity may contribute to improving the overall health status of children with CMC.

Performance measurement and improvement frameworks in health, education and social services systems: a systematic review.

PURPOSE: To perform a systematic review, supplemented by a targeted grey literature scan, for performance measurement and improvement frameworks within and across the health, education and social service systems. The intended outcome was the creation of a foundation of evidence to inform the development of cross-sectoral quality improvement frameworks. DATA SOURCES: MEDLINE, CINAHL, PsycINFO, ERIC, EMBASE, Social Services Abstracts, Social Work Abstracts and Education Index Full Text were searched up to April/May 2007. In addition, 26 governmental and 27 organizational websites were searched. STUDY SELECTION: English language material with a publication date of 1986 or more recent that described a health, education or social services multidimensional framework for performance measurement and improvement. Data extraction The framework name; administrative sector; level of application; setting; population of interest; categories of quality described within the framework; country of application; and citations to other performance measurement and improvement frameworks were extracted from each article. RESULTS: In total, 111 frameworks were identified. Most frameworks (n = 97) were developed in or for the health sector. A concept sorting exercise identified 16 quality concepts applicable across many settings, sectors and levels of application. CONCLUSION: This systematic review of quality domains will be relevant and useful to those who are developing and using performance measurement and improvement frameworks for adult and child populations within or across the health, social service or education sectors.

Waiting for child developmental and rehabilitation services: an overview of issues and needs.

Concern about the length of time that children, young people, and families may have to wait to access assessment, diagnostic, interventional, therapeutic, and supportive child developmental and rehabilitation (CDR) services is widespread, but adequate data collection and research on this issue remain limited. We review key concepts and issues relevant to waiting for CDR services from the published literature, a national workshop devoted to this topic, and international experience. We conclude that gaps in data, evidence, and consensus challenge our ability to address the issue of waiting for CDR services in a systematic way. A program of research coupled with actions based on consensus-building is required. Research priorities include acquiring evidence of the appropriateness and effectiveness of different models of intervention and rehabilitation services, and documenting the experience and expectations of waiting families. Consensus-building processes are critical to identify, categorize, and prioritize 'sentinel' components of CDR service pathways: (1) to reduce the inherent complexity of the field; (2) to create benchmarks for waiting for these respective services; and (3) to develop definitions for wait-time subcomponents in CDR services. Collection of accurate and replicable data on wait times for CDR services can be used to document baseline realities, to monitor and improve system performance, and to conduct comparative and analytic research in the field of CDR services.

RAGE ligation affects T cell activation and controls T cell differentiation.

The pattern recognition receptor, RAGE, has been shown to be involved in adaptive immune responses but its role on the components of these responses is not well understood. We have studied the effects of a small molecule inhibitor of RAGE and the deletion of the receptor (RAGE-/- mice) on T cell responses involved in autoimmunity and allograft rejection. Syngeneic islet graft and islet allograft rejection was reduced in NOD and B6 mice treated with TTP488, a small molecule RAGE inhibitor (p < 0.001). RAGE-/- mice with streptozotocin-induced diabetes showed delayed rejection of islet allografts compared with wild type (WT) mice (p < 0.02). This response in vivo correlated with reduced proliferative responses of RAGE-/- T cells in MLRs and in WT T cells cultured with TTP488. Overall T cell proliferation following activation with anti-CD3 and anti-CD28 mAbs were similar in RAGE-/- and WT cells, but RAGE-/- T cells did not respond to costimulation with anti-CD28 mAb. Furthermore, culture supernatants from cultures with anti-CD3 and anti-CD28 mAbs showed higher levels of IL-10, IL-5, and TNF-alpha with RAGE-/- compared with WT T cells, and WT T cells showed reduced production of IFN-gamma in the presence of TTP488, suggesting that RAGE may be important in the differentiation of T cell subjects. Indeed, by real-time PCR, we found higher levels of RAGE mRNA expression on clonal T cells activated under Th1 differentiating conditions. We conclude that activation of RAGE on T cells is involved in early events that lead to differentiation of Th1(+) T cells.