Canadian Institute Research Articles

The one-week prevalence of neck pain and low back pain in post-secondary students at two Canadian institutions

BackgroundLow back and neck pain are common in the general population, but the prevalence among Canadian post-secondary students is not well known. We aimed to determine the one-week prevalence of neck pain (NP) and low back pain (LBP) among postsecondary students in Canada.MethodsWe conducted a cross-sectional study of students enrolled in the Faculty of Health Sciences and Faculty of Education at Ontario Tech University, and the Canadian Memorial Chiropractic College (CMCC) in the Fall of 2017. Neck and low back pain intensity in the past week were measured with the 11-point numerical rating scale. We report the cumulative, gender- and institution-specific one-week prevalence (95% CI) of any pain (1–10/10) and moderate to severe pain (≥ 3/10).ResultsThe one-week prevalence of any neck pain ranged from 45.4% (95% CI: 38.4, 52.4) in the Faculty of Education to 76.9% (95% CI: 72.9, 80.4) at CMCC. The one-week prevalence of neck pain ≥3/10 ranged from 44.4% (95% CI: 37.5, 51.4) in the Faculty of Education to 58.4% (95% CI: 54.0, 62.7) at CMCC. The one-week prevalence of any low back pain ranged from 60.9% (95% CI: 53.8, 67.5) in the Faculty of Education to 69.0% (95% CI: 64.8, 73.0) at CMCC, and the one-week prevalence of low back pain ≥ 3/10 ranged from 47.8% (95% CI: 43.4, 52.2) at CMCC to 55.1% (95% CI: 51.2, 58.9) in the Faculty of Health Sciences. The prevalence of any back or neck pain and pain ≥ 3/10 was consistently higher in females than males, with the largest difference seen for neck pain at CMCC.ConclusionMost post-secondary students in our samples experienced LBP and NP in the past week. Overall, the one-week prevalence of NP and LBP was higher among chiropractic students and among females. This study should draw attention to school administrators about the burden of NP and LBP in post-secondary students.

Role of sex and gender in concussion outcome differences among patients presenting to the emergency department: a systematic review

ObjectiveThis systematic review aimed to identify research involving adults presenting to the emergency department (ED) with a concussion to document the reporting of sex and/or gender according to the Canadian...

Modelling the impact of a high-uptake bivalent booster scenario on the COVID-19 burden and healthcare costs in New York City

Uptake of the COVID-19 bivalent booster vaccine (targeting the original SARS-CoV-2 strain and subvariants BA.4 and BA.5 of the Omicron variant) among eligible residents of New York City (NYC) has been modest and declining. Assessing the impact of improved population-level booster coverage with bivalent vaccines in NYC can help inform investment towards vaccination and potential cost-savings. We calibrated an agent-based model of disease transmission to confirmed and probable cases of COVID-19 in NYC and simulated it to project outcomes under two scenarios. In the base case scenario, we assumed that vaccination continued with the average daily rate of 92 vaccine doses per 100,000 administered during December 2022. In the counterfactual scenario, we modeled a high-uptake scenario between January 1, 2023 and March 31, 2023, with an average daily rate of 296 vaccine doses per 100,000 population that increased bivalent coverage in NYC to match the age-specific influenza vaccine coverage of the 2020-2021 season. Vaccination rate outside the campaign duration remained the same as the base case scenario. Compared to the base case, the high-uptake scenario averted 88,274 (95% Confidence Interval [CI]: 77,097-100,342) cases, and prevented 2,917 (95% CI: 2,557-3,267) hospitalizations between January 1 through the end of June 2023. Averted outcomes resulted in net savings of $217.2 (95% CI: 190.0-242.2) million in direct healthcare costs. We estimated that the high-uptake scenario would avert 72,879 (95% CI: 63,894-82,228) days of student absenteeism from schools due to COVID-19 illness. Our results illustrate the continued benefits of COVID-19 vaccines in preventing severe health outcomes, averting healthcare costs, and maintaining educational continuity in NYC. The Canadian Institutes of Health Research, The Natural Sciences and Engineering Research Council of Canada, NIH, Centers for Disease Control and Prevention (CDC), NSF, The Commonwealth Fund, and The Notsew Orm Sands Foundation.

Patterns of patient-reported symptoms and association with sociodemographic and systemic sclerosis disease characteristics: a scleroderma Patient-centered Intervention Network (SPIN) Cohort cross-sectional study

Systemic sclerosis is a heterogenous disease in which little is known about patterns of patient-reported symptom clusters. We aimed to identify classes of individuals with similar anxiety, depression, fatigue, sleep disturbance, and pain symptoms and to evaluate associated sociodemographic and disease-related characteristics. This multi-centre cross-sectional study used baseline data from Scleroderma Patient-centered Intervention Network Cohort participants enrolled from 2014 to 2020. Eligible participants completed the PROMIS-29 v2.0 measure. Latent profile analysis was used to identify homogeneous classes of participants based on patterns of anxiety, depression, fatigue, sleep disturbance, and pain scores. Sociodemographic and disease-related characteristics were compared across classes. Among 2212 participants, we identified five classes, including four classes with "Low" (565 participants, 26%), "Normal" (651 participants, 29%), "High" (569 participants, 26%), or "Very High" (193 participants, 9%) symptom levels across all symptoms. Participants in a fifth class, "High Fatigue/Sleep/Pain and Low Anxiety/Depression" (234 participants, 11%) had similar levels of fatigue, sleep disturbance, and pain as in the "High" class but low anxiety and depression symptoms. There were significant and substantive trends in sociodemographic characteristics (age, education, race or ethnicity, marital or partner status) and increasing disease severity (diffuse disease, tendon friction rubs, joint contractures, gastrointestinal symptoms) across severity-based classes. Disease severity and sociodemographic characteristics of "High Fatigue/Sleep/Pain and Low Anxiety/Depression" class participants were similar to the "High" severity class. Most people with systemic sclerosis can be classified by levels of patient-reported symptoms, which are consistent across symptoms and highly associated with sociodemographic and disease-related variables, except for one group which reports low mental health symptoms despite high levels of other symptoms and substantial disease burden. Studies are needed to better understand resilience in systemic sclerosis and to identify and facilitate implementation of cognitive and behavioural strategies to improve coping and overall quality of life. National Institute of Nursing Research (F31NR019007), Canadian Institutes of Health Research, Arthritis Society Canada, the Lady Davis Institute for Medical Research, the Jewish General Hospital Foundation, McGill University, Scleroderma Society of Ontario, Scleroderma Canada, Sclérodermie Québec, Scleroderma Manitoba, Scleroderma Atlantic, Scleroderma Association of BC, Scleroderma SASK, Scleroderma Australia, Scleroderma New South Wales, Scleroderma Victoria, and Scleroderma Queensland.

Association of infertility with type and timing of menopause: a prospective cohort study.

What is the association between past infertility and the type and timing of menopause in midlife women? Women with a history of infertility were more likely to experience surgical menopause overall and had elevated risk of earlier surgical menopause until age 43 years but experienced no differences in the timing of natural menopause. Infertility is experienced by 12-25% of women and is thought to reveal a propensity for poor health outcomes, such as chronic illness, later in life. However, little is known about whether infertility is linked with characteristics of the menopausal transition as women age, despite possible shared underlying pathways involving ovarian function and gynecologic disease. Secondary analysis of a prospective cohort study of 13 243 midlife females recruited in Phase 1 of the Alberta's Tomorrow Project (Alberta, Canada) and followed approximately every 4 years (2000-2022). Data were collected through standardized self-report questionnaires. History of infertility, defined as ever trying to become pregnant for more than 1 year without conceiving, was measured at baseline. Menopause characteristics were measured at each study follow-up. Menopause type was defined as premenopause, natural menopause, surgical menopause (bilateral oophorectomy), or indeterminate menopause (premenopausal hysterectomy with ovarian conservation). Timing of natural menopause was defined as the age at 1 full year after the final menstrual period, and timing of surgical and indeterminate menopause was defined as the age at the time of surgery. We used flexible parametric survival analysis for the outcome of menopause timing with age as the underlying time scale and multinomial logistic regression for the outcome of menopause type. Multivariable models controlled for race/ethnicity, education, parity, previous pregnancy loss, and smoking. Sensitivity analyses additionally accounted for birth history, menopausal hormone therapy, body mass index, chronic medical conditions, and age at baseline. Overall, 18.2% of women reported a history of infertility. Past infertility was associated with earlier timing of surgical menopause exclusively before age 43 years (age 35: adjusted hazard ratio 3.13, 95% CI 1.95-5.02; age 40: adjusted hazard ratio 1.83, 95% CI 1.40-2.40; age 45: adjusted hazard ratio 1.13, 95% CI 0.87-1.46) as well as greater odds of experiencing surgical menopause compared to natural menopause (adjusted odds ratio 1.40, 95% CI 1.18-1.66). Infertility was not associated with the timing of natural or indeterminate menopause. Information on the underlying cause of infertility and related interventions was not collected, which precluded us from disentangling whether associations differed by infertility cause and treatment. Residual confounding is possible given that some covariates were measured at baseline and may not have temporally preceded infertility. Women with a history of infertility were more likely to experience early surgical menopause and may therefore benefit from preemptive screening and treatment for gynecologic diseases to reduce bilateral oophorectomy, where clinically appropriate, and its associated health risks in midlife. Moreover, the lack of association between infertility and timing of natural menopause adds to the emerging knowledge that diminishing ovarian reserve does not appear to be a primary biological mechanism of infertility nor its downstream implications for women's health. Alberta's Tomorrow Project is only possible due to the commitment of its research participants, its staff and its funders: Alberta Health, Alberta Cancer Foundation, Canadian Partnership Against Cancer and Health Canada, and substantial in-kind funding from Alberta Health Services. The views expressed herein represent the views of the author(s) and not of Alberta's Tomorrow Project or any of its funders. This secondary analysis is funded by Project Grant Priority Funding in Women's Health Research from the Canadian Institutes of Health Research (Grant no. 491439). N.V.S. is supported by a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research. H.K.B. is supported by the Canada Research Chairs Program. E.A.B. is supported by an Early Career Investigator Award in Maternal, Reproductive, Child and Youth Health from the Canadian Institutes of Health Research. A.K.S. has received honoraria from Pfizer, Lupin, Bio-Syent, and Eisai and has received grant funding from Pfizer. N.V.S., H.K.B., and E.A.B. have no conflicts of interest to report. N/A.

Equity, Diversity, and Inclusion from the Perspective of International Community College Students

With changing demographics, Canadian institutions of higher education are under pressure to address the challenges of student, faculty, and staff diversity. Despite growing numbers of international students at Canada’s community colleges, this group has historically been underrepresented. The intersectionality of their minority-status characteristics makes their experience complex. This qualitative study of 35 international students and graduates from 15 countries uses critical theory to explore their experiences through the lens of equity, diversity, and inclusion. Despite a high degree of cultural diversity, some of them experienced stereotyping. Moreover, they tended to engage less in classroom discussions, and many of them were unaware of college resources and services. Consequently, they had difficulty adjusting to life at college and life in Canada.

Trends in HIV testing, the treatment cascade, and HIV incidence among men who have sex with men in Africa: a systematic review and meta-analysis

Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV. In Africa, MSM face structural barriers to HIV prevention and treatment that increase their vulnerability to HIV acquisition and transmission, and undermine the HIV response. In this systematic review, we aimed to explore progress towards increases in HIV testing, improving engagement in the HIV treatment cascade, and HIV incidence reductions among MSM in Africa. We searched Embase, MEDLINE, Global Health, Scopus, and Web of Science for cross-sectional and longitudinal studies reporting HIV testing, knowledge of status, care, antiretroviral therapy (ART) use, viral suppression, and HIV incidence among MSM in Africa published between Jan 1, 1980, and March 3, 2023. We pooled surveys using Bayesian generalised linear mixed-effects models, used meta-regression to assess time trends, and compared HIV incidence estimates among MSM with those of all men. Of 9278 articles identified, we included 152 unique studies published in 2005-23. In 2020, we estimate that 73% (95% credible interval [CrI] 62-87) of MSM had ever tested for HIV. HIV testing in the past 12 months increased over time in central, western, eastern, and southern Africa (odds ratio per year [ORyear] 1·23, 95% CrI 1·01-1·51, n=46) and in 2020 an estimated 82% (70-91) had tested in the past 12 months, but only 51% (30-72) of MSM living with HIV knew their HIV status. Current ART use increased over time in central and western (ORyear 1·41, 1·08-1·93, n=9) and eastern and southern Africa (ORyear 1·37, 1·04-1·84, n=17). We estimated that, in 2020, 73% (47-88) of all MSM living with HIV in Africa were currently on ART. Nevertheless, we did not find strong evidence to suggest that viral suppression increased, with only 69% (38-89) of MSM living with HIV estimated to be virally suppressed in 2020. We found insufficient evidence of a decrease in HIV incidence over time (incidence ratio per year 0·96, 95% CrI 0·63-1·50, n=39), and HIV incidence remained high in 2020 (6·9 per 100 person-years, 95% CrI 3·1-27·6) and substantially higher (27-199 times higher) than among all men. HIV incidence remains high, and might not be decreasing among MSM in Africa over time, despite some increases in HIV testing and ART use. Achieving the UNAIDS 95-95-95 targets for diagnosis, treatment, and viral suppression equitably for all requires renewed focus on this key population. Combination interventions for MSM are urgently required to reduce disparities in HIV incidence and tackle the social, structural, and behavioural factors that make MSM vulnerable to HIV acquisition. US National Institutes of Health, UK Medical Research Council, Canadian Institutes of Health Research, and Fonds de Recherche du Québec-Santé. For the French translation of the abstract see Supplementary Materials section.

Efficacy and safety of envafolimab in the treatment of advanced dMMR/MSI‑H solid tumors: A single‑arm meta‑analysis.

In November 2021, the National Medical Products Administration (China) approved the marketing of envafolimab injection for the treatment of advanced defective mismatch repair (dMMR)/high microsatellite instability (MSI-H) solid tumors. Envafolimab became the first domestic PD-L1 inhibitor approved in China and the first worldwide approved subcutaneously injectable PD-L1 inhibitor. To the best of our knowledge, there are no reports of systematic analyses regarding the use of envafolimab in the treatment of advanced dMMR/MSI-H solid tumors. The present study was a single-arm meta-analysis performed on data systematically searched and retrieved from literature published on PubMed, Web of Science, Cochrane Library, China National Knowledge Infra-structure and Wan Fang databases on 1 October 2022. Quality assessment using the 20 items developed by the Canadian Institute of Health Economics. Data heterogenicity was evaluated using the I2 statistics. For datasets with I2>50%, the cumulative incidence and 95% CI for the outcomes of interests were calculated using the random effects model, whereas for I2<50% the fixed effects model was used. The current meta-analysis included four studies enrolling 181 patients with advanced dMMR/MSI-H solid tumors. The pooled objective remission rate was 29.53% (95% CI, 8.61-50.45%). The pooled disease control rate was 60.58% (95% CI, 31.79-89.38%). The pooled median progression-free survival was 4.89 months (95% CI, 1.86-7.93 months). The pooled overall survival (OS) rate was 73.38% (95% CI, 65.76-80.99%). The pooled 6-month and 12-month OS rates were 75.80% (95% CI, 57.02-94.58%) and 69.32% (95% CI, 51.92-86.72%), respectively. The combined data on the incidence of treatment-emergent adverse events (TEAEs) of any grade from all the studies was 77.19% (95% CI, 63.15-91.23%). Most of the adverse reactions were mild and the rate of 3/4 grade TEAE was 10.37% (95% CI, 6.14-14.60%). Gevokizumab was effective and safe in the treatment of patients with advanced dMMR/MSI-H solid tumors and its convenience could significantly improve patient compliance; therefore, the clinical application of envafolimab is promising.

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.

Exploring communication by public health leaders and organizations during the pandemic: a content analysis of COVID-related tweets.

Health communication is an essential competency in public health practice. The increasing use of social media and the connectivity between the general public and public health leaders present a unique opportunity to explore how digital communications tools were leveraged in the COVID-19 pandemic. This study explores Twitter-based communications from public health leaders and organizations across Canada and compares them with those from the World Health Organization (WHO). This research aimed to understand Twitter communications strategies to address the COVID-19 pandemic, other public health emergencies, and non-emergency public health issues. A content analysis of COVID-related Twitter content during the first wave of the pandemic (January 1-August 31, 2020) was performed. The Canadian Institute for Health Information (CIHI) Policy Intervention Scan was used as a framework to analyze messaging from public health leaders and the WHO. Findings demonstrate that most tweets from public health leaders and organizations in Canada and the WHO focused on case management and public information. Gaps and areas of weakness identified include the lack of Twitter participation by some public health leaders and a narrow range of policy intervention topics, limiting the breadth and depth of public health messages. Strengthening communications can serve to improve information sharing in future pandemics or public health crises. Further research should assess how public health leaders and organizations applied communication best practices on all social media platforms and across different policy interventions.

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

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 &amp; 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 &amp; 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&amp;lt;0.001), depression (p=0.005), hyperglycemia avoidance behaviours (p&amp;lt;0.001), fear of hypoglycemia (p&amp;lt;0.001) and decreased social support (p&amp;lt;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)

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.

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

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

In the US, &amp;gt;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

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)

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 &amp; 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)