Canadian Institutes Of Health Research Research Articles

Pan-Canadian survey on the impact of the COVID-19 pandemic on cervical cancer screening and management: cross-sectional survey of healthcare professionals.

The coronavirus disease 2019 (COVID-19) pandemic has caused disruptions to cancer care by delaying diagnoses and treatment, presenting challenges and uncertainties for both patients and physicians. We conducted a nationwide online survey to investigate the effects of the pandemic and capture modifications, prompted by pandemic-related control measures, on cervical cancer screening-related activities from mid-March to mid-August 2020, across Canada. The survey consisted of 61 questions related to the continuum of care in cervical cancer screening and treatment: appointment scheduling, tests, colposcopy, follow-up, treatment of pre-cancerous lesions/cancer, and telemedicine. We piloted the survey with 21 Canadian experts in cervical cancer prevention and care. We partnered with the Society of Canadian Colposcopists, Society of Gynecologic Oncology of Canada, Canadian Association of Pathologists, and Society of Obstetricians and Gynecologists of Canada, which distributed the survey to their members via email. We reached out to family physicians and nurse practitioners via MDBriefCase. The survey was also posted on McGill Channels (Department of Family Medicine News and Events) and social media platforms. The data were analyzed descriptively. Unique responses were collected from 510 participants (November 16, 2020, to February 28, 2021), representing 418 fully and 92 partially completed surveys. Responses were from Ontario (41.0%), British Columbia (21.0%), and Alberta (12.8%), and mostly comprised family physicians/general practitioners (43.7%), and gynecologist/obstetrician professionals (21.6%). Cancelled screening appointments were mainly reported by family physicians/general practitioners (28.3%), followed by gynecologist/obstetrician professionals (19.8%), and primarily occurred in private clinics (30.5%). Decreases in the number of screening Pap tests and colposcopy procedures were consistently observed across Canadian provinces. About 90% reported that their practice/institution adopted telemedicine to communicate with patients. The area most severely impacted by the pandemic was appointment scheduling, with an important level of cancellations reported. Survey results may inform resumptions of various fronts in cervical cancer screening and management. The present work was supported by the Canadian Institutes of Health Research (operating grant COVID-19 May 2020 Rapid Research Funding Opportunity VR5-172666 Rapid Research competition and foundation grant 143347 to Eduardo L Franco). Eliya Farah and Rami Ali each received an MSc stipend from the Department of Oncology, McGill University.

Indefinite Anticoagulant Therapy for First Unprovoked Venous Thromboembolism : A Cost-Effectiveness Study.

Clinical practice guidelines recommend indefinite anticoagulation for a first unprovoked venous thromboembolism (VTE). To estimate the benefit-harm tradeoffs of indefinite anticoagulation in patients with a first unprovoked VTE. Markov modeling study. Systematic reviews and meta-analyses for the long-term risks and case-fatality rates of recurrent VTE and major bleeding. Published literature for costs, quality of life, and other clinical events. Patients with a first unprovoked VTE who have completed 3 to 6 months of initial anticoagulant treatment. Lifetime. Canadian health care public payer. Indefinite anticoagulation with direct oral anticoagulants. Recurrent VTE events, major bleeding events, costs in 2022 Canadian dollars (CAD), and quality-adjusted life-years (QALYs). When compared with discontinuing anticoagulation after initial treatment in a hypothetical cohort of 1000 patients aged 55 years, indefinite anticoagulation prevented 368 recurrent VTE events, which included 14 fatal pulmonary emboli, but induced an additional 114 major bleeding events, which included 30 intracranial hemorrhages and 11 deaths from bleeding. Indefinite anticoagulation cost CAD $16 014 more per person and did not increase QALYs (-0.075 per person). Model results were most sensitive to the case-fatality rate of major bleeding and the annual risk for major bleeding during extended anticoagulation. The model assumed that risks for recurrent VTE and major bleeding measured in clinical trials at 1 year remained constant during extended anticoagulation. Clinicians should use shared decision making to incorporate individual patient preferences and values when considering treatment duration for unprovoked VTE. Canadian Institutes of Health Research.

624-P: Portrayal of Perceived Stigma across Ages in Type 1 Diabetes—A BETTER Registry Analysis

Background: People with type 1 diabetes (PWT1D) perceiving high diabetes-related stigma are less likely to report in-target A1c levels. We hypothesized that people with higher levels of stigma have suboptimal psychosocial outcomes and that stigma would be perceived differently across age groups. Methods: Cross-sectional analysis of 709 PWT1D aged ≥14 years in the BETTER T1D registry (Quebec, Canada) who completed the T1D Stigma Assessment Scale (DSAS-1). The DSAS-1 (/95) includes 3 subscales; Blame & Judgment (6 items), Identity Concern (7 items), and Treated Differently (6 items). Individuals who perceived more stigma compared to the total cohort (DSAS-1 mean score +1 standard deviation), were stratified into groups by age to determine associations with diabetes self-management behaviours and outcomes. Results: Across groups, youth (n=105; 14-24 years) had the highest stigma perception (20%), followed by 18% in middle-aged adults (n=401; 35-64 years), then 15% for both young adults (n=130; 25-34 years) and seniors (n=73; 65+ years). The majority of youth, young and middle-aged adults, and seniors perceived stigma as Blame & Judgment (51%, 44%, 33%, and 19%, respectively). Stigma related to Identity Concern was highest among seniors (15%). In an age- and diabetes duration-adjusted models, 40% of adjusted variance in stigma score was explained by increased diabetes distress (p<0.001), depression (p=0.005), hyperglycemia avoidance behaviours (p<0.001), fear of hypoglycemia (p<0.001) and decreased social support (p<0.001). Conclusion: Interventions targeting diabetes-related stigma need to be tailored for different age groups to target suboptimal diabetes self-management behaviours and improve psychosocial outcomes. Disclosure A.Housni: None. A.Katz: None. J.C.Kichler: None. M.Nakhla: None. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé. Funding JDRF (4-SRA-2018-651-Q-R); Canadian Institutes of Health Research (JT1-157204)

564-P: The Need for Mentorship in Diabetes Is Now

Background: Mentorship for health care professionals is used to offer guidance, knowledge, and transfer experience. Clinical Dietitians (CD) play a key role in diabetes care. Offering mentorship might help build their confidence levels (CL) and grow the profession with the goal of improving outcomes and experiences for people living with diabetes (PWD). The objectives are, in CD (1) to assess the need for mentorship in diabetes and (2) to gather opinions on the structure and content for appropriate mentorship. Methods: A 28-question online survey was developed, piloted with 8 CD through cognitive interviewing, and shared with CD across the province of Quebec (Canada). Descriptive analysis was used to determine the proportions (%) in survey responses, stratified by years of clinical experience (CE). Results: From the 284 participants (97% women, mean age 31+/-10 years), 275 (97%) of CD identified a need for mentorship in diabetes. Desire to participate and in what function (mentee, mentor or both) was dependent on the years of CE. Formal mentorship was preferred by 41%, 30% informal and 29% a combination of both which was independent of the years of CE. Finally, 93.5% believe their confidence level in providing care for PWD would increase if they participated in mentorship. Conclusion: Mentorship in diabetes was perceived as needed to increase Clinical Dietitians confidence level in caring for PWD and for interprofessional collaboration. Disclosure S.Blunden: Employee; Dexcom, Inc. A.Roy-fleming: None. C.South: None. C.Gillis: None. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé.

3-OR: Severe Hypoglycemia among Older Adults with Diabetes (iNPHORM, USA)

Despite an aging US diabetes population, little is known about the real-world frequency of iatrogenic severe hypoglycemia (SH) among older adults. We analyzed iNPHORM data to address this gap. People ≥60-year-old with T1DM or T2DM on insulin and/or secretagogues were recruited from a probability-based internet panel. Data on SH were obtained via a screener, baseline, and 12 monthly follow-ups. Crude SH incidence rates (IRs) and proportions (IPs) were calculated overall, and by diabetes type, medication type, and mode of SH recovery. N=307 were analyzed (T1DM: 8.5%; age: 67.5 [SD:5.5] years; male: 54.1%; retention rate: 81.8%). Among T2DM respondents, 39.9% used insulin without secretagogues, 50.2% secretagogues without insulin, and 10.0% insulin and secretagogues. The overall IP of SH was 19.9 (95%CI: 15.8-24.7)%, and the IR was 0.89 (95%CI: 0.62-1.27) events per person-year (EPPY). People with T1DM had a higher total IP (42.3 [95%CI: 25.5-61.1]%) and IR (2.07 [95%CI: 0.98-4.38] EPPY) than those with T2DM (IP: 17.8 [95%CI: 13.8-22.7]%; IR: 0.78 [95%CI: 0.52-1.15] EPPY), including insulin without secretagogue users (1.09 [95%CI: 0.66-1.80] vs. 0.61 [95%CI: 0.26 to 1.45] [insulin with secretagogues] and 0.50 [95%CI: 0.23 to 1.05] [secretagogues without insulin] EPPY). Emergency care and hospitalization constituted 3.6% (T1DM: 0%; T2DM: 6.7%) and 1.8% (T1DM: 0%; T2DM: 2.2%) of SH (n=224), respectively. Paramedical/hospital-based SH was more common in T2DM (0.06 [95%CI: 0.02-0.19]) than T1DM (0 EPPY) with IRs highest among insulin without secretagogue users (0.11 [95%CI: 0.03-0.47] EPPY). This is the first US prospective study on SH frequency in older adults with diabetes. Most (96.4%) events occurred at-home, underscoring the need for self-reported SH capture. Overall IPs and IRs were greater in T1DM than T2DM; but those with T2DM had more healthcare-based events. To mitigate undue health and economic costs, it is imperative clinicians remain vigilant to preventing SH in this vulnerable and growing population. Disclosure A.Ratzki-leewing: Consultant; Novo Nordisk, Eli Lilly and Company, Research Support; Sanofi. J.E.Black: None. G.Zou: None. B.L.Ryan: None. S.B.Harris: Advisory Panel; Bayer Inc., AstraZeneca, Eli Lilly and Company, Dexcom, Inc., Novo Nordisk A/S, Novo Nordisk Canada Inc., Sanofi, Consultant; Abbott Diabetes, Janssen Pharmaceuticals, Inc., Other Relationship; American Diabetes Association, Research Support; Abvance Therapeutics, Canadian Institutes of Health Research. Funding Sanofi Global

221-LB: Identification of PAM as Novel Monogenic Diabetes Gene

Background/Objectives: Various biological mechanisms involved in type 2 diabetes (T2D) have been unveiled through converging evidence in common variants from Genome wide association studies (GWAS) and rare or low frequency variants (RV/LFV) from Exome wide association studies (EXWAS). We hypothesized that a two-pronged approach interrogating both RV/LFV and common variants could yield identification of new pathways involved in T2D. Methods: Protein-altering RV/LFV burden was tested for T2D association in an EXWAS of 11,731 cases and 149,613 controls in the UKBiobank. Significant encoded proteins were then investigated using 2-sample Mendelian randomization for causal association with T2D and related variables. Protein quantitative trait loci were estimated in the Prospective Urban and Rural Epidemiological study (N=11,020) and tested against GWAS-summary statistics of T2D and related traits from 10 consortia. Results: At the EXWAS significance threshold (P=0.05/19,589=2.55×10-6), we identified loss-of-function RV/LFV in GCK and PAM, which encode the proteins glucokinase and peptidylgycine α-amidating monooxygenase respectively, to be associated with T2D risk. Deleterious mutations in the PAM gene were associated with an 29% increase in T2D risk (OR per RV/LFV=1.29; 95%CI=1.17-1.43; P=7.17×10-7). This association was driven by a low frequency variant, rs78408340-G present in 2.6% of T2D cases and only in 1.8% of controls. MR analyses confirmed that 1 SD decrease in PAM circulating levels was consistently associated with increased T2D risk (OR=1.16; 95%CI=1.14-1.19; P=9.54×10-52) and HbA1c (%) (β=0.0047; 95%CI= 0.00051-0.0090; P=0.028), and decreased post-prandial insulin (mU/L) secretion (β=-0.060; 95% CI=-0.083(-)-0.036; P=8.32×10-7). Conclusion: We identified PAM variants as a novel cause of monogenic diabetes and demonstrated a strong causal effect of circulating PAM levels on T2D risk and post-prandial insulin secretion. This supports further investigation of PAM as a therapeutic T2D target. Disclosure J. Feiner: None. N. Perrot: None. M. Chong: Research Support; Bayer Inc. R. Lali: None. R. Morton: None. P. Mohammadi-Shemirani: None. S. Yusuf: None. H. C. Gerstein: Advisory Panel; Abbott Diagnostics, Eli Lilly and Company, Sanofi. Research Support; Novo Nordisk. Advisory Panel; Novo Nordisk. Research Support; Eli Lilly and Company, Sanofi. Advisory Panel; Kowa Company, Ltd., Hanmi Pharm. Co., Ltd. Other Relationship; Zuellig Pharma Holdings Pte. Ltd., DKSH, AstraZeneca. G. Pare: Research Support; Bayer Inc. Advisory Panel; Bayer Inc., Amgen Inc., Novartis AG. M. Pigeyre: None. Funding Bayer; Canadian Institutes of Health Research

1615-P: The Peripheral and Central Cross Talk Mediated by Adipose MIF—A Novel Mechanism of Hyperphagia following Olanzapine Treatment

Olanzapine is one of the first-line antipsychotic medications but it usually induces metabolic side effects, characterized by obesity. We previously indicated that olanzapine leads to hyperphagia through the effects of a proinflammatory cytokine, macrophage migration inhibitory factor (MIF) in the hypothalamus. However, whether olanzapine's upregulated peripheral MIF could affect the central mechanism is currently unknown. Our present study found that olanzapine increases ectopic expression of dopamine receptor 1 (DRD1) in adipocytes which relatively upregulates MIF expression and release through a PKA/CREB signaling pathway. In global MIF knockout mice, MIF accumulation appears in the hypothalamus following peripheral injection of recombinant MIF proteins, suggesting that peripheral MIF indeed travels to the hypothalamus. Mif Lung Tg mice (MIF overexpression in the lung) with increased circulating MIF levels had hyperphagia and activation of the CaMKKβ/AMPK/AgRP signaling pathway in the hypothalamus. Overall, our study for the first time proved that adipose-derived MIF is a crucial factor in regulating metabolic side effects induced by olanzapine. Disclosure X.Chen: None. Y.Huang: None. Y.Qi: None. L.Chen: None. L.Li: None. P.Gao: None. D.Cui: None. D.Qi: None. Funding National Sciences and Engineering Research Council of Canada (RGPIN-2017-04542); Canadian Institutes of Health Research (PJT-156116); China Scholarship Council (202106230212)

387-P: High Incidences of Level 3 Severe Hypoglycemia Reported by T2DM Secretagogue-Users (iNPHORM, USA)

In the US, >90% of people with T2DM on oral antihyperglycemics use secretagogues. The present analysis is the first to quantify the real-world, US frequency of Level 3 severe hypoglycaemia (SH) in this population. Longitudinal, prospective data were leveraged from the iNPHORM study. Adults (≥18 years old) with secretagogue-treated T2DM (not on insulin) were recruited from a US-wide, probability-based internet panel. Data on participant characteristics and Level 3 SH occurrence were captured across a screener, baseline and 12 monthly follow-ups. Multivariable negative binomial regression with cluster bootstrapping for repeated measures modelled the annualized rate of SH for individuals completing ≥1 follow-up(s). A repeated lasso regression ‘voting’ procedure selected all risk factors. Multiple imputation addressed missingness. Of the 353 respondents (male: 51.1%; age: 54.6 [SD: 13.2] years; diabetes duration: 10 [IQR: 12] years; retention rate: 84.4%), the incidence proportion of SH over follow-up was 21.8 (95% CI: 17.8-26.3)%, and the rate was 3.8 (95% CI: 2.5-5.7) events per person-year. Our final model included age, continuous/flash glucose monitoring use, corticosteroid use, number of healthcare visits, fear of hypoglycemia, number of past-year SH requiring hospital care, retinopathy, and other diabetes complications. The rate of annualized Level 3 SH statistically increased with younger age, more frequent healthcare visits, greater fear of hypoglycemia, higher number of past-year healthcare-related SH, and presence of retinopathy. Our results indicate disturbingly high incidences of Level 3 SH among secretagogue users. Whenever logical and feasible, clinicians should prioritize one of the many other available antihyperglycemics that confer little to no hypoglycemia risk. Else, other hypoglycemia prevention strategies—risk-tailored to this ubiquitous T2DM population—are urgently warranted. Disclosure A.Ratzki-leewing: Consultant; Novo Nordisk, Eli Lilly and Company, Research Support; Sanofi. J.E.Black: None. G.Zou: None. B.L.Ryan: None. S.B.Harris: Advisory Panel; Bayer Inc., AstraZeneca, Eli Lilly and Company, Dexcom, Inc., Novo Nordisk A/S, Novo Nordisk Canada Inc., Sanofi, Consultant; Abbott Diabetes, Janssen Pharmaceuticals, Inc., Other Relationship; American Diabetes Association, Research Support; Abvance Therapeutics, Canadian Institutes of Health Research. Funding Sanofi Global

691-P: Characteristics of People with Type 1 Diabetes Who Consider Fear of Hypoglycemia a Barrier to Their Diabetes Management

Hypoglycemia is a common side effect of insulin therapy, the constant threat of hypoglycemia symptoms and consequences may lead people with type 1 diabetes (T1D) to develop fear of hypoglycemia (FOH). This analysis aims to explore the characteristics of people who consider FOH as a barrier to managing diabetes. Methods: Self-reported data from an online T1D registry were analyzed to compare participants who consider FOH a barrier to those who do not (a registry-specific yes/no question) using χ2 test for categorical variables (gender, diabetes technology use, and hypoglycemia history) and the Mann-Whitney Test for age, T1D duration, Hypoglycemia Fear Survey (HFS-II), Hypoglycemia Confidence Survey (HCS), and Diabetes Distress Scale (DDS) scores. Results: Among 780 adults, 65% women, aged 44±15 years, had T1D for 25±15 years, 35% reported HbA1c≤ 7%, and 45% perceived FOH as a barrier. The prevalence of FOH as a barrier was higher in women, participants with history of symptomatic nocturnal or level 3 hypoglycemia, higher HbA1c, higher HFS and DDS scores, and lower HCS scores (Table 1). Conclusion: A significant proportion of adults, in particular women and those with a challenging T1D management (high HbA1c, history of hypoglycemia, diabetes distress, and low hypoglycemia confidence), consider FOH to be a barrier in T1D management, thus it needs to be considered as part of clinical follow-up. Disclosure M.K.Talbo: None. C.Leroux: None. L.Hill: None. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé.

382-P: Comparison of Intranasal and Injectable Glucagon Administration among Pediatric Population Responders

Context: Intranasal glucagon (INg) might improve the management of severe hypoglycemia (SH) at school in children with type 1 diabetes (T1D), which is a major concern of our patient partners. Objectives: We compared the performance of parents of children with T1D & school workers (SW) for INg and injectable glucagon (IJg) administration. We also assessed the enablers and barriers associated with each glucagon and preferred teaching methods. Methods: After watching a video on glucagon administration, Patients and SW (30/group) administered both glucagon in random order in 2 simulated scenarios, followed by an individual interview. Performance was rated by a direct observer: completion time, successful execution of predefined key steps and critical steps. Results: Both groups had a better performance with INg than IJg (Fig 1). The majority preferred INg for its ease of use, safety in the pediatric context and better acceptability by SW. Some participants thought that IJg is more effective and useful for off-label smaller doses to prevent SH. Preferred teaching methods were videos and workshops, but only videos could be sufficient for INg. Conclusions: INg is faster and more likely to be successfully administered than IJg by. Implementing mandatory video-based trainings for SW could improve SH management and the involvement of SW. Disclosure Y.Wang: None. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation. C.Gagnon: Advisory Panel; Novo Nordisk, Other Relationship; Ascendis Pharma A/S, Research Support; Novo Nordisk. F.Bernatchez: None. S.Chouinard-castonguay: None. M.Tremblay: None. A.Vanasse: None. M.Megalli: None. M.Millette: Advisory Panel; Novo Nordisk Canada Inc., Pfizer Inc. G.Boulet: Other Relationship; Dexcom, Inc. M.Henderson: None. Funding Canadian Institutes of Health Research (157204); JDRF (2018651)

380-P: Towards Prevention of Nonsevere Hypoglycemia in Type 1 Diabetes with Oral Glucose at a Higher Blood Glucose Threshold—The REVERSIBLE Trial

Background: Current guidelines recommend initiating the treatment of non-severe (NS) hypoglycemia with 15g of carbohydrates (CHO) at 15 minutes intervals when blood glucose (BG) reaches <72 mg/dl. Despite this recommendation, NS hypoglycemia management remains challenging for people living with type 1 diabetes (pwT1D) and more optimal treatment strategies are required. We aim to assess the efficacy of 15g of CHO at higher treatment thresholds. Methods: The REVERSIBLE Trial is an open-label, randomized, three interventions x three periods cross-over study. Following inpatient insulin-induced decrease in BG, 16g of oral carbohydrates is administered at a plasma glucose threshold of <72 mg/dl, ≤81 mg/dl or ≤90 mg/dl. The primary outcome is the time (in minutes) spent in hypoglycemia (<72 mg/dl) after the initial correction. Results: Participants (n=29) characteristics are 52% male, 46.8±16.3 years old, BMI of 26.4±3.9 kg/m2, diabetes duration of 26.2±15.9 years, A1c of 53.4±15.5 mmol/mol and 62% insulin pump users. When comparing <72 mg/dl (control) to ≤81 mg/dl and ≤90 mg/dl treatment thresholds, 100% vs. 86% (p=0.1201) vs. 34% (p<0.0001) of participants had hypoglycemia. These hypoglycemic events lasted 26.0±12.6 vs. 17.9±14.7 (p=0.026) vs. 7.1±11.8 (p=0.002) minutes, with a blood glucose nadir of 56.5±9.9 vs. 63.5±7.9 (p=0.008) vs. 73.4±9.7 mg/dl (p=0.002) respectively. In the control group, 69% of participants required more than one treatment to reach or maintain normoglycemia (≥ 72 mg/dl) compared to 52% in the ≤81 mg/dl group and 31% in the ≤90 mg/dl group with no significant rebound hyperglycemia (>180mg/dl) within the first hour. Conclusion: Compared with <72 mg/dl, consuming 16g of oral carbohydrates at ≤81 mg/dl and ≤90 mg/dl shortened the time spent in hypoglycemia, lessened the glucose nadir and reduced the need for repetitive treatments. For some NS episodes, pwT1D could benefit from CHO intake at a higher BG threshold. Disclosure R.Cheng: None. N.Taleb: Consultant; Viatris Inc. Z.Wu: Other Relationship; Eli Lilly and Company. V.Messier: None. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation. Funding JDRF (4-SRA-2018-651-Q-R); Canadian Institutes of Health Research (JT1-157204)

1332-P: Comparison of Clinical Characteristics of People Living with Latent Autoimmune Diabetes of the Adult (LADA) and Type 1 Diabetes (T1D) in the Canadian BETTER Registry

Introduction: LADA is known for a slow progression of autoimmune destruction of beta-cells with cases that span a spectrum between classic T1D and T2D phenotypes. To date, lacking a good understanding of LADA has prohibited the release of specific clinical practice guidelines and subsequently an optimal management. Methodology: Cross-sectional analysis of online clinical questionnaires in the Canadian BETTER registry; participants can specify having received a diagnosis of LADA or T1D. Data was analyzed for the first 1464 participants; 131 (9%) reported LADA and 1333 (91%) T1D. Results: At registration; LADA vs T1D were 49 ± 13 y.o. vs 42 ± 15 y.o; 61% vs. 62% females; diabetes duration 10 ± 9 vs. 24 ± 15 years. LADA vs. T1D were older at diagnosis (39 ± 12 vs. 18 ± 12 years old; p<0.001), only half started insulin in first year of diagnosis (52 vs. 97%; p<0.001), more often reported a family history of T1D (46 vs. 32%; p=0.001). For comparable glycemic control (HbA1c < 8.6 mmol/l, <7%, 38 vs. 32%), fewer cases with LADA reported at least an episode in last month of level II hypoglycemia <54 mg/dL (3.0mmol/L) 63% vs. 77%; p= 0.004, severe hypoglycemia rates were 8% vs. 12%, p=0.15. Diabetes related hospitalizations were 10% in LADA vs. 6%, p=0.11, insulin pumps and glucagon were less used in LADA. In a matched analysis for diabetes duration and gender (1:1), glycemic control was still statistically comparable in LADA vs. T1D (HbA1c <7%: 38 vs 35%, p=0.12) as well as rates of nephropathy (6% vs. 11%, p=0.22), neuropathy (12% vs. 7%, p=0.23) and retinopathy (6% vs. 9%, p=0.07) yet with more cardiovascular disease (5% vs. 2%; p=0.02) and less coeliac disease (3 vs. 5%; p=0.001). Data analysis of 3000 participants is ongoing in early 2023. Conclusion: Reported differences may impact LADA management. This study sets the stage for building a prospective Canadian cohort of LADA to undergo deep phenotyping, genotyping and interventional trials. Disclosure M.Issa: None. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé. S.Haag: Other Relationship; Omnipod. A.Roy-fleming: None. V.Messier: None. N.Taleb: Consultant; Viatris Inc.

1194-P: Impact of COVID-19 on Gestational Diabetes Mellitus (GDM) Screening and Outcomes

Background: To minimize COVID-19 exposure, a modified 1-step strategy (MS) option was offered in addition to the standard (SS) GDM screening strategies (definitions in Fig 1A). Objectives: To assess the use of, and obstetrical and neonatal outcomes associated with, modified GDM screening during COVID-19. Methods: Primiparous pregnancies in Alberta, Canada (N=35,836; Jan 1, 2020 to Dec 31, 2021) were categorized by GDM screening status. Results: 87.4% underwent SS, 10.1% MS, and 2.5% had no GDM screening. MS use was highest in 2020-Q3 (second wave; Fig 1B). There was no difference in GDM rates between SS (11.1%) and MS (12.7%). MS screened women with GDM had worse outcomes than those screened using SS (Table). Conclusions: GDM screening rates were not impacted by COVID-19. The uptake of MS was low to modest and appeared to identify higher-risk GDM women. Disclosure V.Liyanage: None. O.Barrett: None. D.P.Ngwezi: None. A.Savu: None. R.O.Yeung: Research Support; Novo Nordisk Foundation, Abbott, Canadian Institutes of Health Research, Alberta Agriculture and Forestry, Alberta Canola. S.Butalia: None. P.Kaul: None.

274-OR: Do-It-Yourself Automated Insulin Delivery (AID) Systems Are Noninferior to Commercial AID Systems in Glucose Management among Adults with Type 1 Diabetes

AIM: We aim to compare commercial automated insulin delivery (C-AID) systems with open-source do-it-yourself (DIY)-AID systems for glucose management among adults with type 1 diabetes (T1D) in real-life conditions. METHODS: A prospective observational, non-inferiority, parallel-cohort study involving 77 adults with T1D, having used an AID for ≥3 months and living in Canada (25 DIY-AID and 52 C-AID users): 59.7% females, mean age 44.0 ± 14.7 years old with mean diabetes duration of 26.9 ± 14.5 years and HbA1c of 6.7 ± 0.7%. A total of 30 days’ data from an additional blinded CGM (Dexcom G6) was used to assess effectiveness [Primary outcome: 24h time in range% (TIR%) for 30 days]. RESULTS: DIY-AIDs were non-inferior to C-AIDs regarding the TIR% [78.3±11.0% vs. 71.2±10.9%, mean difference 7.2% [95% CI 1.9% to 12.5%], P<0.001 for non-inferiority (non-inferiority margin 5%)], even after adjusting for various confounding factors (age, sex, auto-mode%, duration of AID use, annual household income, and educational level). The percentage of time in hypoglycemia (<70 mg/dL) was higher with DIY-AID (3.9±3.1%) than with C-AID (1.8±1.3%) but still below recommended threshold (Table). Differences between both systems are more pronounced during daytime. CONCLUSION: DIY-AIDs are non-inferior to C-AIDs for TIR% among adults with T1D in real-world settings. Disclosure Z.Wu: Other Relationship; Eli Lilly and Company. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation. M.Lebbar: None. A.Bonhoure: Consultant; Dexcom, Inc. M.Raffray: None. M.Devaux: None. C.Grou: None. V.Messier: None. V.Boudreau: None. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé. Funding Canadian Institutes of Health Research (148464)

526-P: Increasing the Confidence of Health Care Professionals Treating Patients Living with Type 1 Diabetes through the Support-Pro Online Education Platform

Introduction: Support-Pro is a comprehensive online platform that was developed for healthcare professionals (HCP) and covers all technological, treatment and lifestyle needs for type 1 diabetes (T1D) management in short, practical modules. It was developed as studies have demonstrated that HCPs who work in healthcare not specific to T1D, find it difficult to keep up-to-date with new developments that could improve T1D care and management. However, specialized online resources, such as Support-Pro, could help rectify this problem. The objective of the study is to assess whether Support-Pro can increase HCPs confidence in treating and supporting people with T1D (PWT1D) and their satisfaction with the platform. Methods: Open-label, non-randomized, 3-month trial with 142 HCPs who had access to Support-Pro, and 66 who completed 3 months on the platform (NCT04859205). Results: On average, the 66 participants (years of practice: 14±10; 90% women; 71% Caucasian; 44% dietitians, 30% nurses, 23% pharmacists, 3% physician or resident physician) reported at 3 months, an average 10% improvement in their confidence (total score 58% to 68%; p<0.0001) and a median satisfaction score of 76%. HCPs most valued features that supported knowledge gain, such as downloadable PDF documents (72%) and case studies (44%). The platform was most used in first month of access (page views 1st month: 50 [5;135] vs. 3rd month: 0 [0;18]). Conclusions: HCPs who completed 3 months on Support-Pro platform reported increased confidence in treating PWT1D and high appreciation of learning content and modalities. This platform could improve the support and advice provided to PWT1D followed-up outside specialized clinics. Disclosure A.Katz: None. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation. M.K.Talbo: None. A.Housni: None. L.Hill: None. A.Roy-fleming: None. S.Haag: Other Relationship; Omnipod. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé. Funding Strategy Patient-Oriented Research (JT1-157204); JDRF (4-SRA-2018-651-Q-R)

900-P: Patient-Reported Outcomes of Adults with Type 1 Diabetes Using Do-It-Yourself Compared with Commercial Automated Insulin Delivery Systems

Introduction: We aim to assess the difference between open-source do-it-yourself (DIY) and commercial automated insulin delivery (AID) systems in patient-reported outcomes (PRO) of adults with type 1 diabetes (T1D). Methods: Analysis from a prospective, non-inferiority, non-randomized, parallel-cohort study involving 78 non-pregnant adults with T1D, AID users ≥3 months and living in Canada. Participants (25 DIYAID and 53 commercial AID users, 60.3% females, mean age 41.2±14.6 years, mean T1D duration 27.0±14.7 years, median [Q1, Q3] duration of AID use 15.6 [7.8, 27, 4] months, mean HbA1c 6.7±0.7%, median time in range [TIR 70-180 mg/dl] 74.3% [66.8, 81.0]) completed the following validated PRO questionnaires: Diabetes Distress Scale (DDS, high distress level defined as >2.0), Diabetes Treatment Satisfaction Questionnaire (DTS-Q), An Audit of Diabetes-Dependent Quality of Life (ADD-QoL), Hypoglycemia Fear Score II (HFS-II, fear of hypoglycemia defined as scoring ≥3 in any worry subscale item), Pittsburgh Sleep Quality Index (PSQI, poor sleep defined as >5), Clarke and Gold score (hypoglycemia unawareness defined as either score ≥4). Results: DIYAID users reported better sleep quality (66.7% vs 33.3%, p=0.02) and lower HFS-II worry subscale score (28.2 vs 33.2, p=0.03) than commercial AID users, but results did not remain significant after adjusting for sex, age, level of education, T1D and AID use duration, HbA1c, and TIR. The two groups were otherwise comparable in other PROs. Overall, one third of participants reported diabetes distress, 88.3% reported poor sleep, 20.8% reported impaired hypoglycemia awareness and 80.5% reported fear of hypoglycemia. Conclusion: Similar broad QoL and other PROs were observed between DIYAID and commercial AID users, with a persistent and significant diabetes burden for all, despite advanced diabetes technology use and optimal glycemic management. Disclosure M.Lebbar: None. Z.Wu: Other Relationship; Eli Lilly and Company. A.C.Bonhoure: Consultant; Dexcom, Inc. V.Messier: None. A.Brazeau: Other Relationship; Dexcom, Inc., Diabète québec, Ordre des diététistes nutritionnistes du Québec, Research Support; Canadian Institutes of Health Research, Fonds de recherche du Québec en Santé. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation. Funding Canadian Institutes of Health Research (148464)

Emerging Circuits in Anesthesia: Following the Mesolimbic Pathway.

From the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts; and Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts. Accepted for publication March 15, 2023. Funding: This work was supported in part by grants K99-AG076877 from the National Institutes of Health (Bethesda, MD), and BPF-180179 from the Canadian Institutes of Health Research (Ottawa, ON, Canada). The author declares no conflicts of interest. Address correspondence to Kathleen F. Vincent, PhD, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 149 13th St, Room 4.010, Charlestown, MA 02129. Address e-mail to [email protected]

Are we moving the dial? Canadian health research funding trends for women’s health, 2S/LGBTQ + health, sex, or gender considerations

BackgroundSex and gender impacts health outcomes and disease risk throughout life. The health of women and members of the Two-Spirit, Lesbian, Gay, Bisexual, Transgender, Queer or Questioning (2S/LGBTQ +) community is often compromised as they experience delays in diagnosis. Distinct knowledge gaps in the health of these populations have prompted funding agencies to mandate incorporation of sex and gender into research. Sex- and gender-informed research perspectives and methodology increases rigor, promotes discovery, and expands the relevance of health research. Thus, the Canadian Institutes of Health Research (CIHR) implemented a sex and gender-based analysis (SGBA) framework recommending the inclusion of SGBA in project proposals in 2010 and then mandating the incorporation of SGBA into grant proposals in 2019. To examine whether this mandate resulted in increased mention of sex or gender in funded research abstracts, we searched the publicly available database of grant abstracts funded by CIHR to analyze the percentage of abstracts that mentioned sex or gender of the population to be studied in the funded research. To better understand broader health equity issues we also examined whether the funded grant abstracts mentioned either female-specific health research or research within the 2S/LGBTQ + community.ResultsWe categorized a total of 8,964 Project and Operating grant abstracts awarded from 2009 to 2020 based on their study of female-specific or a 2S/LGBTQ + populations or their mention of sex or gender. Overall, under 3% of grant abstracts funded by CIHR explicitly mentioned sex and/or gender, as 1.94% of grant abstracts mentioned sex, and 0.66% mentioned gender. As one of the goals of SGBA is to inform on health equity and understudied populations with respect to SGBA, we also found that 5.92% of grant abstracts mentioned female-specific outcomes, and 0.35% of grant abstracts focused on the 2S/LGBTQ + community.ConclusionsAlthough there was an increased number of funded grants with abstracts that mentioned sex and 2S/LGBTQ + health across time, these increases were less than 2% between 2009 and 2020. The percentage of funded grants with abstracts mentioning female-specific health or gender differences did not change significantly over time. The percentage of funding dollars allocated to grants in which the abstracts mentioned sex or gender also did not change substantially from 2009 to 2020, with grant abstracts mentioning sex or female-specific research increasing by 1.26% and 3.47%, respectively, funding allocated to research mentioning gender decreasing by 0.49% and no change for 2S/LGBTQ +-specific health. Our findings suggest more work needs to be done to ensure the public can evaluate what populations will be examined with the funded research with respect to sex and gender to advance awareness and health equity in research.

Association between the timing of childhood adversity and epigenetic patterns across childhood and adolescence: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort

Childhood adversity is a potent determinant of health across development and is associated with altered DNA methylation signatures, which might be more common in children exposed during sensitive periods in development. However, it remains unclear whether adversity has persistent epigenetic associations across childhood and adolescence. We aimed to examine the relationship between time-varying adversity (defined through sensitive period, accumulation of risk, and recency life course hypotheses) and genome-wide DNA methylation, measured three times from birth to adolescence, using data from a prospective, longitudinal cohort study. We first investigated the relationship between the timing of exposure to childhood adversity between birth and 11 years and blood DNA methylation at age 15 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort study. Our analytic sample included ALSPAC participants with DNA methylation data and complete childhood adversity data between birth and 11 years. We analysed seven types of adversity (caregiver physical or emotional abuse, sexual or physical abuse [by anyone], maternal psychopathology, one-adult households, family instability, financial hardship, and neighbourhood disadvantage) reported by mothers five to eight times between birth and 11 years. We used the structured life course modelling approach (SLCMA) to identify time-varying associations between childhood adversity and adolescent DNA methylation. Top loci were identified using an R2 threshold of 0·035 (ie, ≥3·5% of DNA methylation variance explained by adversity). We attempted to replicate these associations using data from the Raine Study and Future of Families and Child Wellbeing Study (FFCWS). We also assessed the persistence of adversity-DNA methylation associations we previously identified from age 7 blood DNA methylation into adolescence and the influence of adversity on DNA methylation trajectories from ages 0-15 years. Of 13 988 children in the ALSPAC cohort, 609-665 children (311-337 [50-51%] boys and 298-332 [49-50%] girls) had complete data available for at least one of the seven childhood adversities and DNA methylation at 15 years. Exposure to adversity was associated with differences in DNA methylation at 15 years for 41 loci (R2 ≥0·035). Sensitive periods were the most often selected life course hypothesis by the SLCMA. 20 (49%) of 41 loci were associated with adversities occurring between age 3 and 5 years. Exposure to one-adult households was associated with differences in DNA methylation at 20 [49%] of 41 loci, exposure to financial hardship was associated with changes at nine (22%) loci, and physical or sexual abuse was associated with changes at four (10%) loci. We replicated the direction of associations for 18 (90%) of 20 loci associated with exposure to one-adult household using adolescent blood DNA methylation from the Raine Study and 18 (64%) of 28 loci using saliva DNA methylation from the FFCWS. The directions of effects for 11 one-adult household loci were replicated in both cohorts. Differences in DNA methylation at 15 years were not present at 7 years and differences identified at 7 years were no longer apparent by 15 years. We also identified six distinct DNA methylation trajectories from these patterns of stability and persistence. These findings highlight the time-varying effect of childhood adversity on DNA methylation profiles across development, which might link exposure to adversity to potential adverse health outcomes in children and adolescents. If replicated, these epigenetic signatures could ultimately serve as biological indicators or early warning signs of initiated disease processes, helping identify people at greater risk for the adverse health consequences of childhood adversity. Canadian Institutes of Health Research, Cohort and Longitudinal Studies Enhancement Resources, EU's Horizon 2020, US National Institute of Mental Health.

Gender disparity in Canadian Institutes of Health Research grant funding decisions among recipients from dermatology departments: a retrospective study.

We investigated the extent of gender disparity among dermatologists awarded Canadian Institutes of Health Research (CIHR) grants. Our results indicate that, between 2008 and 2022, CIHR grant recipients were disproportionately male, thereby substantiating the influence of system-level barriers during research funding decision-making.