Rayzel Shulman MD, PhD CAHSPR May 10, 2016

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+ Low Socioeconomic Status is Associated with Adverse Events in Children and Teens on Insulin Pumps Under a Universal Access Program: A population-based Cohort Study Rayzel Shulman MD, PhD CAHSPR May 10, 2016

+ Background and Rationale High incidence of type 1 diabetes (T1D) in Canada (25.9/100,000/year) The Ontario Pediatric Diabetes Network (PDN) oversees care delivery Differences in PDN center characteristics (2012): 24-hour support Centre type Physician model of care Nursing patient load Universal funding for pediatric insulin pump therapy in Ontario since 2006 PDN Current State Survey 2013

Shulman, R et al. Pediatr Diabetes. 2016 Jan 8.

+ Background and rationale Diabetic ketoacidosis (DKA) can occur if pump fails 24-hour telephone support may prevent acute diabetes adverse events such as DKA Low socioeconomic status (SES) is associated with pediatric diabetes management and outcomes In Ontario, low-income children are less likely to use a pump Shulman, R et al. Pediatr Diabetes. 2016 Jan 8 http://www.jdrf.org.uk/life- with-type-1- diabetes/managing-type- 1/treatments/insulin-pumps

+ Objectives and Hypothesis To explore the relationship between 24-hour support, SES and 1) The risk of DKA or death 2) The rate of diabetes-related admissions and emergency department (ED) visits We hypothesized that lack of 24-hour support and lower SES would be associated with an increased risk of adverse events

+ Study Design and Data Sources Observational population-based cohort study All individuals <19 years with pump funding (2006-2011) followed until 2013 PDN centre survey (2012) Centre characteristics and resources Administrative Data (Institute for Clinical and Evaluative Sciences (ICES) Assistive devices program (ADP) Ontario Diabetes Database (ODD) Hospitalizations and ED visits Population and Demographic Data

+ Analyses Cox proportional hazards model: association between time to DKA or death and 24 hour support and deprivation Poisson model: association between the rate of diabetes-related ED visits or admissions and 24 hour support and deprivation Other variables Centre-level: centre type, model of physician care, nursing patient load Patient-level: Prior DKA, age, duration of T1D, baseline glycemic control, comorbid condition, and rurality Generalized estimating equations (GEE) used to account for patient clustering at centres

+ Baseline characteristics Deprivation Quintile, n (%) 1 (least deprived) 2 3 4 5 (most deprived) Missing 24-hour support available (n=1463) 529 (36.2%) 401 (27.4%) 257 (17.6%) 164 (11.2%) 102 (7.0%) 10 (0.7%) No 24-hour support available (n=1730) 544 (31.5%) 460 (26.6%) 340 (19.7%) 223 (12.9%) 150 (8.7%) 13 (0.8%) At least one DKA admission in 2 years prior to index date Yes 139 (9.5%) 252 (14.6%) Centre type, n (%) Large community Small community Tertiary Physician model, n (%) Generalist Pediatric Endocrinologist Visiting pediatric endocrinologist 748 (51.1%) 72 (4.9%) 643 (44.0%) 323 (22.1%) 965 (66.0%) 175 (12.0%) 598 (34.6%) 570 (33.0%) 562 (32.5%) 283 (16.4%) 981 (56.7%) 466 (26.9%)

+ DKA or Death Mean time on pump was 3.77 years (SD 1.64) DKA rate: 5.28/100 person-years Baseline DKA rate of 6.97/100 person-years <6 deaths Death rate: 0.033/100 person-years

Event free probability + Cumulative Probability of DKA or death according to time since pump start 1 0.98 0.96 0.94 0.92 0.9 0.88 0.86 0.84 0.82 0.8 0 10 20 30 40 50 60 70 Months since pump start

+ Time to first DKA or death (n=3193) DKA or death Adjusted Hazard Ratio (95% CI) p-value Deprivation Quintile 1 (least deprived) (n=1073) (Ref) 1.0 2 (n=861) 1.53 (1.22-1.91) 0.0002 3 (n=597) 0.96 (0.67-1.36) 0.8053 4 (n=387) 1.45 (1.07-1.95) 0.0161 5 (most deprived) (n=252) 1.58 (1.05-2.38) 0.0272 Missing (n=23) 1.87 (0.96-3.62) 0.0654 24 hr support No (n=1730) (Ref) 1.0 Yes (n=1463) 0.90 (0.73-1.10) 0.3023

+ Time to first DKA or death (n=3193) DKA or death Adjusted Hazard Ratio (95% CI) p-value At least one DKA admission in 2 years prior to index date No (n=2802) (Ref) 1.0 Yes (n=391) 1.63 (1.28-2.07) <0.0001 Baseline HbA1c <7.5% (n=718) (Ref) 1.0 7.5-9.0% (n=1845) 1.69 (1.31-2.18) <0.0001 >9.0% (n=630) 2.63 (1.89-3.67) <0.0001 Age group <6 th birthday (n=224) 0.88 (0.57-1.36) 0.5569 6 th -13 th birthday (n=1448) (Ref) 1.0 13 th birthday (n=1521) 2.35 (1.90-2.90) <0.0001 Annual nursing patient load <200 (n=1283) (Ref) 1.0 200 (n=1910) 1.24 (1.00-1.52) 0.0468

+ Diabetes-related admissions or ED visits Rate of diabetes-related admissions and ED visits: 14.73/100 person-years Baseline rate: 27.59/100 person years Being more deprived is associated with a higher rate of events (HR 1.60 (95% CI 1.27-2.00), p=<0.0001) 24-hour support was not significantly associated (HR 0.86 (95% CI 0.70-1.05), p=0.1265)

+ Discussion: Adverse event rate Rate of DKA in Ontario pediatric pump users similar to other countries Sweden (2000) (3.6/100 patient-years) Hanas R. et al. Pediatr Diabetes 2009; 10:33-37 Europe and Israel (2004-2005) (6.26 /100 patient-years) Danne T. et al. Diabetologia 2008; 51:1594-1601 Risk DKA or death in first 2 years of pump use is low and rate of adverse events after pump start is lower compared to baseline

+ Discussion: 24 hour support Our results question previous work 24-hour telephone care for T1D: Prevents ED and office visits Allen HF, et al. Pediatr Diabetes 2002; 3:95-100 Increases ED visits but decreases likelihood of hospitalization Franklin BE, et al. Diabetes Care 2014; 37:81-87 24-hour support may not be an important service or barriers to its effective use may exist

+ Discussion: SES Our results support existing evidence for SES disparity in diabetes management and outcomes US Type 1 Diabetes Exchange clinic registry (n=13,487), low income is associated with a higher frequency of DKA Cengiz, E. et al. Pediatr Diabetes 2013; 14:447-454 In Ontario, children of lower SES are less likely to be using pumps Shulman, R. et al. Pediatr Diabetes. 2016 Jan 8 Single Ontario center: no association between deprivation and glycemic control in pump users Zuijdwijk, C.S. et al. J Pediatr 2013; 162:730-735

+ Limitations We measured applications for pump funding, not actual pump use Some individuals who applied for pump funding may have been using a pump prior to universal funding HbA1c data is unavailable Self-reported nature of the centre data

+ Conclusions Implementation in Ontario not resulted in safety concerns Need to examine potential barriers and benefits of 24 hour support Impact on parental anxiety Reduction in disparity in SES of diabetes outcomes Need to further investigate underlying causes of SES disparities in the risk of DKA Inform interventions aimed at reducing the inequity Targeted interventions for high risk groups may be beneficial

+ Acknowledgements Canadian Child Health Clinician Scientist Program (CCHCSP) Department of Pediatrics, the Hospital for Sick Children Funding from: Creative Professional Activities grant from the Department of Pediatrics, Hospital for Sick Children Dr. Guttmann s Canadian Institute for Health Research Applied Chair in Child Health Services and Policy Research award Thesis committee Dr. Astrid Guttmann Dr. Fiona Miller Dr. Therese Stukel Dr. Denis Daneman

+ Disclaimer This study was supported by the Institute for Clinical Evaluative Sciences (ICES), which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the MOHLTC is intended or should be inferred. These datasets were linked using unique encoded identifiers and analyzed at the Institute for Clinical Evaluative Sciences (ICES). This study was approved by the institutional review boards at Sunnybrook Health Sciences Centre, Toronto, Canada, the University of Toronto, and The Hospital for Sick Children. Parts of this material are based on data and information compiled and provided by CIHI. However, the analyses, conclusions, opinions and statements expressed herein are those of the author, and not necessarily those of CIHI.