Hospital for Sick Children

About: Hospital for Sick Children is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Medicine. The organization has 4097 authors who have published 3746 publications receiving 129066 citations. The organization is also known as: Sick Kids Hospital & SickKids.

Epigenetics of Autism Spectrum Disorder.

Abstract: Autism spectrum disorder (ASD), one of the most common childhood neurodevelopmental disorders (NDDs), is diagnosed in 1 of every 68 children ASD is incredibly heterogeneous both clinically and aetiologically The etiopathogenesis of ASD is known to be complex, including genetic, environmental and epigenetic factors Normal epigenetic marks modifiable by both genetics and environmental exposures can result in epigenetic alterations that disrupt the regulation of gene expression, negatively impacting biological pathways important for brain development In this chapter we aim to summarize some of the important literature that supports a role for epigenetics in the underlying molecular mechanism of ASD We provide evidence from work in genetics, from environmental exposures and finally from more recent studies aimed at directly determining ASD-specific epigenetic patterns, focusing mainly on DNA methylation (DNAm) Finally, we briefly discuss some of the implications of current research on potential epigenetic targets for therapeutics and novel avenues for future work

Eating Disorders in Girls and Women With Type 1 Diabetes: A Longitudinal Study of Prevalence, Onset, Remission, and Recurrence

Abstract: OBJECTIVE Girls and women with type 1 diabetes are at increased risk for developing eating disorders (EDs), and these disorders are associated with serious diabetes-related medical complications. This study describes the longitudinal course of disturbed eating behavior (DEB) and EDs in a cohort with type 1 diabetes. RESEARCH DESIGN AND METHODS A total of 126 girls with type 1 diabetes receiving care for diabetes at The Hospital for Sick Children in Toronto participated in a series of seven interview-based assessments of ED behavior and psychopathology over a 14-year period, beginning in late childhood. Survival analysis was used. RESULTS Mean age was 11.8 ± 1.5 years at time 1 and 23.7 ± 2.1 years at time 7. At time 7, 32.4% (23/71) met the criteria for a current ED, and an additional 8.5% (6/71) had a subthreshold ED. Mean age at ED onset (full syndrome or below the threshold) was 22.6 years (95% CI 21.6–23.5), and the cumulative probability of onset was 60% by age 25 years. The average time between onset of ED and subsequent ED remission was 4.3 years (95% CI 3.1–5.5), and the cumulative probability of remission was 79% by 6 years after onset. The average time between remission of ED and subsequent recurrence was 6.5 years (95% CI 4.4–8.6), and the cumulative probability of recurrence was 53% by 6 years after remission. CONCLUSIONS In this longitudinal study EDs were common and persistent, and new onset of ED was documented well into adulthood. Further research regarding prevention and treatment for this vulnerable group is urgently needed.

Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis

Abstract: BACKGROUND Cystic fibrosis is an inherited condition resulting in thickened, sticky respiratory secretions. Respiratory failure, due to recurrent pulmonary infection and inflammation, is the most common cause of mortality. Muco-active therapies (e.g. dornase alfa and nebulized hypertonic saline) may decrease sputum viscosity, increase airway clearance of sputum, reduce infection and inflammation and improve lung function. Thiol derivatives, either oral or nebulized, have shown benefit in other respiratory diseases. Their mode of action is likely to differ according to the route of administration. There are several thiol derivatives, and it is unclear which of these may be beneficial in cystic fibrosis. OBJECTIVES To evaluate the efficacy and safety of nebulized and oral thiol derivatives in people with cystic fibrosis. SEARCH STRATEGY We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register, comprising references identified from comprehensive electronic database searches, hand searches of relevant journals, abstract books and conference proceedings.Most recent search: November 2008. SELECTION CRITERIA Randomized and quasi-randomized controlled trials comparing nebulized or oral thiol derivatives to placebo or another thiol derivative in people with cystic fibrosis. DATA COLLECTION AND ANALYSIS The authors independently assessed trials for inclusion, analysed methodological quality and extracted data. MAIN RESULTS Searches identified 18 trials; eight (seven older than 10 years) (234 participants) are included. Three trials of nebulized thiol derivatives were identified (one compared 20% n-acetylcysteine to 2% n-acetylcysteine; another compared sodium-2-mercaptoethane sulphonate to 7% hypertonic saline; and another compared glutathione to 4% hypertonic saline). Although generally well-tolerated with no significant adverse effects, there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments.Five studies of oral thiol derivatives were identified. Three studies compared n-acetylcysteine to placebo; one compared n-acetylcysteine, ambroxol and placebo; and one compared carbocysteine to ambroxol. Oral thiol derivatives were generally well-tolerated with no significant adverse effects, however there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments. AUTHORS' CONCLUSIONS We found no evidence to recommend the use of either nebulized or oral thiol derivatives in people with cystic fibrosis. There are very few good quality trials investigating the effect of these medications in cystic fibrosis, and further research is required to investigate the potential role of these medications in improving the outcomes of people with cystic fibrosis.

2016 American College of Rheumatology/European League Against Rheumatism Criteria for Minimal, Moderate, and Major Clinical Response in Juvenile Dermatomyositis: An International Myositis Assessment and Clinical Studies Group/Paediatric Rheumatology International Trials Organisation Collaborative Initiative.

Abstract: To develop response criteria for adult dermatomyositis (DM) and polymyositis (PM). Expert surveys, logistic regression, and conjoint analysis were used to develop 287 definitions using core set measures. Myositis experts rated greater improvement among multiple pairwise scenarios in conjoint analysis surveys, where different levels of improvement in 2 core set measures were presented. The PAPRIKA (Potentially All Pairwise Rankings of All Possible Alternatives) method determined the relative weights of core set measures and conjoint analysis definitions. The performance characteristics of the definitions were evaluated on patient profiles using expert consensus (gold standard) and were validated using data from a clinical trial. The nominal group technique was used to reach consensus. Consensus was reached for a conjoint analysis-based continuous model using absolute per cent change in core set measures (physician, patient, and extramuscular global activity, muscle strength, Health Assessment Questionnaire, and muscle enzyme levels). A total improvement score (range 0-100), determined by summing scores for each core set measure, was based on improvement in and relative weight of each core set measure. Thresholds for minimal, moderate, and major improvement were ≥20, ≥40, and ≥60 points in the total improvement score. The same criteria were chosen for juvenile DM, with different improvement thresholds. Sensitivity and specificity in DM/PM patient cohorts were 85% and 92%, 90% and 96%, and 92% and 98% for minimal, moderate, and major improvement, respectively. Definitions were validated in the clinical trial analysis for differentiating the physician rating of improvement (p<0.001). The response criteria for adult DM/PM consisted of the conjoint analysis model based on absolute per cent change in 6 core set measures, with thresholds for minimal, moderate, and major improvement.