Predictors of Glycemic Control in Children and Adolescents with Type 1 Diabetes in Southwestern Ontario

Objective: To examine factors that predict glycemic control in children and adolescents with Type 1 diabetes in Southwestern Ontario from 1998-2008. Methodology: A population based cohort study was conducted using local pediatric clinical diabetes database (Humabase) to determine demographic and diabetes-related clinical factors that predict achievement of the target glycemic control under \u27real world\u27 conditions. Clinical parameters including the outcome (A1C level) were documented in Humabase. Socio-economic variables were derived using Forward Sortation Area and linking it to the Census of Canada Data. Results: Factors associated with improved glycemic control were age-specific. Longer distance from the treatment center (OR 0.35), female gender (OR 0.45), longer diabetes duration (OR 1.12), and greater body mass index at diagnosis (OR 1.07) predicted achievement of the target glycemic control on multivariable analyses. Conclusions: In this regional cohort we identified factors that predict glycemic control. Targeted support should be considered for high risk individual

Recombinant Human Thyroid Stimulating Hormone versus Thyroid Hormone Withdrawal for Radioactive Iodine Treatment of Differentiated Thyroid Cancer with Nodal Metastatic Disease

Introduction. Recombinant human thyroid stimulating hormone (rhTSH) is approved for preparation of thyroid remnant ablation with radioactive iodine (RAI) in low risk patients with well differentiated thyroid cancer (DTC). We studied the safety and efficacy of rhTSH preparation for RAI treatment of thyroid cancer patients with nodal metastatic disease. Methods. A retrospective analysis was performed on 108 patients with histopathologically confirmed nodal metastatic DTC, treated with initial RAI between January 1, 2000, and December 31, 2007. Within this selected group, 31 and 42 patients were prepared for initial and all subsequent RAI treatments by either thyroid hormone withdrawal (THW) or rhTSH protocols and were followed up for at least 3 years. Results. The response to initial treatment, classified as excellent, acceptable, or incomplete, was not different between the rhTSH group (57%, 21%, and 21%, resp.) and the THW group (39%, 13%, and 48%, resp.; = 0.052). There was no significant difference in the final clinical outcome between the groups. The rhTSH group received significantly fewer additional doses of RAI than the THW group ( = 0.03). Conclusion. In patients with nodal-positive DTC, preparation for RAI with rhTSH is a safe and efficacious alternative to THW protocol

Recombinant Human Thyroid Stimulating Hormone versus Thyroid Hormone Withdrawal for Radioactive Iodine Treatment of Differentiated Thyroid Cancer with Nodal Metastatic Disease

Introduction. Recombinant human thyroid stimulating hormone (rhTSH) is approved for preparation of thyroid remnant ablation with radioactive iodine (RAI) in low risk patients with well differentiated thyroid cancer (DTC). We studied the safety and efficacy of rhTSH preparation for RAI treatment of thyroid cancer patients with nodal metastatic disease. Methods. A retrospective analysis was performed on 108 patients with histopathologically confirmed nodal metastatic DTC, treated with initial RAI between January 1, 2000, and December 31, 2007. Within this selected group, 31 and 42 patients were prepared for initial and all subsequent RAI treatments by either thyroid hormone withdrawal (THW) or rhTSH protocols and were followed up for at least 3 years. Results. The response to initial treatment, classified as excellent, acceptable, or incomplete, was not different between the rhTSH group (57%, 21%, and 21%, resp.) and the THW group (39%, 13%, and 48%, resp.; P=0.052). There was no significant difference in the final clinical outcome between the groups. The rhTSH group received significantly fewer additional doses of RAI than the THW group (P=0.03). Conclusion. In patients with nodal-positive DTC, preparation for RAI with rhTSH is a safe and efficacious alternative to THW protocol

Multicentre randomized controlled trial of structured transition on diabetes care management compared to standard diabetes care in adolescents and young adults with type 1 diabetes (Transition Trial)

Background: Transition from pediatric to adult diabetes care is a high risk period during which there is an increased rate of disengagement from care. Suboptimal transition has been associated with higher risks for acute and chronic diabetes-related complications. The period of emerging adulthood challenges current systems of healthcare delivery as many young adults with type 1 diabetes (T1D) default from diabetes care and are at risk for diabetes complications which are undetected and therefore untreated. Despite the importance of minimizing loss to follow-up there are no randomized control trials evaluating models of transition from pediatric to adult diabetes care.Methods/Design: This is a multicentre randomized controlled trial. A minimum of 188 subjects with T1D aged between 17 and 20 years will be evaluated. Eligible subjects will be recruited from three pediatric care centres and randomly assigned in a 1:1 ratio to a structured transition program that will span 18 months or to receive standard diabetes care. The structured transition program is a multidisciplinary, complex intervention aiming to provide additional support in the transition period. A Transition Coordinator will provide transition support and will provide the link between pediatric and adult diabetes care. The Transition Coordinator is central to the intervention to facilitate ongoing contact with the medical system as well as education and clinical support where appropriate. Subjects will be seen in the pediatric care setting for 6 months and will then be transferred to the adult care setting where they will be seen for one year. There will then be a one-year follow-up period for outcome assessment. The primary outcome is the proportion of subjects who fail to attend at least one outpatient adult diabetes specialist visit during the second year after transition to adult diabetes care. Secondary outcome measures include A1C frequency measurement and levels, diabetes related emergency room visits and hospital admissions, frequency of complication screening, and subject perception and satisfaction with care.Discussion: This trial will determine if the support of a Transition Coordinator improves health outcomes for this at-risk population of young adults.Trial registration: Trial Registration Number: NCT01351857. © 2013 Spaic et al.; licensee BioMed Central Ltd

Multicentre randomized controlled trial of structured transition on diabetes care management compared to standard diabetes care in adolescents and young adults with type 1 diabetes (Transition Trial)

Background: Transition from pediatric to adult diabetes care is a high risk period during which there is an increased rate of disengagement from care. Suboptimal transition has been associated with higher risks for acute and chronic diabetes-related complications. The period of emerging adulthood challenges current systems of healthcare delivery as many young adults with type 1 diabetes (T1D) default from diabetes care and are at risk for diabetes complications which are undetected and therefore untreated. Despite the importance of minimizing loss to follow-up there are no randomized control trials evaluating models of transition from pediatric to adult diabetes care.Methods/Design: This is a multicentre randomized controlled trial. A minimum of 188 subjects with T1D aged between 17 and 20 years will be evaluated. Eligible subjects will be recruited from three pediatric care centres and randomly assigned in a 1:1 ratio to a structured transition program that will span 18 months or to receive standard diabetes care. The structured transition program is a multidisciplinary, complex intervention aiming to provide additional support in the transition period. A Transition Coordinator will provide transition support and will provide the link between pediatric and adult diabetes care. The Transition Coordinator is central to the intervention to facilitate ongoing contact with the medical system as well as education and clinical support where appropriate. Subjects will be seen in the pediatric care setting for 6 months and will then be transferred to the adult care setting where they will be seen for one year. There will then be a one-year follow-up period for outcome assessment. The primary outcome is the proportion of subjects who fail to attend at least one outpatient adult diabetes specialist visit during the second year after transition to adult diabetes care. Secondary outcome measures include A1C frequency measurement and levels, diabetes related emergency room visits and hospital admissions, frequency of complication screening, and subject perception and satisfaction with care.Discussion: This trial will determine if the support of a Transition Coordinator improves health outcomes for this at-risk population of young adults.Trial registration: Trial Registration Number: NCT01351857. © 2013 Spaic et al.; licensee BioMed Central Ltd

Simplifying Detection of Copy-Number Variations in Maturity-Onset Diabetes of the Young

Copy-number variations (CNVs) are large-scale deletions or duplications of DNA that have required specialized detection methods, such as microarray-based genomic hybridization or multiplex ligation probe amplification. However, recent advances in bioinformatics have made it possible to detect CNVs from next-generation DNA sequencing (NGS) data. Maturity-onset diabetes of the young (MODY) 5 is a subtype of autosomal-dominant diabetes that is often caused by heterozygous deletions involving the HNF1B gene on chromosome 17q12. We evaluated the utility of bioinformatic processing of raw NGS data to detect chromosome 17q12 deletions in MODY5 patients. NGS data from 57 patients clinically suspected to have MODY but who were negative for pathogenic mutations using a targeted panel were re-examined using a CNV calling tool (CNV Caller, VarSeq version 1.4.3). Potential CNVs for MODY5 were then confirmed using whole-exome sequencing, cytogenetic analysis and breakpoint analysis when possible. Whole-gene deletions in HNF1B, ranging from 1.46 to 1.85 million basepairs in size, were detected in 3 individuals with features of MODY5. These were confirmed by independent methods to be part of a more extensive 17q12 deletion syndrome. Two additional patients carrying a 17q12 deletion were subsequently diagnosed using this method. Large-scale deletions are the most common cause of MODY5 and can be detected directly from NGS data, without the need for additional methods. La variabilité du nombre de copies (CNV, de l’anglais copy-number variation) est due à des événements de délétion ou de duplication de l’ADN à grande échelle qui ont requis des méthodes spécialisées de détection telles que l’hybridation génomique sur microréseau ou la MLPA (de l’anglais multiplex ligation probe amplification). Toutefois, les avancées récentes en bio-informatique ont permis de détecter la CNV à partir des données du séquençage de nouvelle génération (SNG) de l’ADN. Le diabète de la maturité apparaissant chez le jeune (MODY, de l’anglais maturity-onset diabetes of the young) 5 est un sous-type de diabète à transmission autosomique dominante souvent causé par les délétions hétérozygotes du gène HNF1B sur le chromosome 17q12. Nous avons évalué l’utilité du traitement bio-informatique des données brutes du SNG pour détecter les délétions du chromosome 17q12 chez les patients atteints de MODY5. Les données du SNG de 57 patients chez qui il y avait une suspicion clinique de MODY, mais dont les résultats au dépistage des mutations pathogéniques à l’aide d’un panel de mutations ciblées étaient négatifs, ont été revues à l’aide de l’outil d’algorithme appelant CNV (CNV Caller, VarSeq version 1.4.3). La CNV de MODY5 a alors été confirmée au moyen du séquençage de l’exome entier, l’analyse cytogénétique et l’analyse des points de cassure lorsque c’était possible. Les délétions du gène entier en HNF1B, qui vont de 1,46 à 1,85 million de paires de base en taille, ont été détectées chez 3 individus ayant des caractéristiques de MODY5. Celles-ci ont été confirmées par des méthodes indépendantes comme faisant partie d’un syndrome de délétion plus importante du 17q12. Deux autres patients porteurs d’une délétion 17q12 ont subséquemment reçu un diagnostic à l’aide de cette méthode. Les délétions à grande échelle sont la cause la plus fréquente de MODY5 et peuvent être détectées directement à partir des données du SNG sans avoir recours à d’autres méthodes

Closing the Gap: Results of the Multicenter Canadian Randomized Controlled Trial of Structured Transition in Young Adults With Type 1 Diabetes.

OBJECTIVE: To determine if a structured transition program for young adults with type 1 diabetes improves clinic attendance, glycemic control, diabetes-related distress, quality of life, and satisfaction with care. RESEARCH DESIGN AND METHODS: In this multicenter randomized controlled trial, young adults (17-20 years) with type 1 diabetes were randomly assigned to a transition program with a transition coordinator or to standard care. The intervention lasted 18 months (6 in pediatric and 12 in adult care). The primary outcome was the proportion of participants who failed to attend at least one adult diabetes clinic visit during the 12-month follow-up after completion of the intervention. RESULTS: We randomized 205 participants, 104 to the transition program and 101 to standard care. Clinic attendance was improved in the transition program (mean [SD] number of visits 4.1 [1.1] vs. 3.6 [1.2], CONCLUSIONS: Transition support during this 18-month intervention was associated with increased clinic attendance, improved satisfaction with care, and decreased diabetes-related distress, but these benefits were not sustained 12 months after completion of the intervention