Canadian Institute Research Articles

Gender disparity in Canadian Institutes of Health Research funding within neurology

BackgroundDespite efforts to advance equity, diversity and inclusion, women face gender-based barriers in research, including in neurology. Compared with men, women are less likely to hold leadership positions and be...

EPID-30. THE COST OF HOSPITAL-BASED CARE AMONG CANADIAN PATIENTS WITH MALIGNANT CENTRAL NERVOUS SYSTEM TUMOURS IN COMPARISON TO THOSE WITH LUNG AND COLORECTAL CANCERS IN THE YEAR PRECEDING THEIR CANCER DIAGNOSIS

Abstract BACKGROUND Approximately 12% of the Canadian GDP was spent on healthcare in 2023. While hospital-based care (HC) constitutes a significant portion of this expenditure, the costs may vary depending on the cancer type. We investigate the HC cost of patients with malignant central nervous system tumours (CNS cancer) and compare it to patients with common cancers in Canadian provinces. METHODS We obtained data between 2010 and 2014 from the Canadian Institute for Health Information’s in-patient and ambulatory care datasets. HC cost was estimated using a 12-month look back period prior to diagnosis date for each patient, including cost related to cancer diagnosis and general healthcare. Choosing colorectal (CRC) and lung (LC) cancers to be the common cancers, patients who were 15 years of age or older and had a diagnosis of one of these cancers were included. We used quantile regression to investigate the factors associated with HC cost. RESULTS A total of 4,498 (CNS), 41,028 (CRC) and 29,747 (LC) patients were included from Alberta and Ontario, Canada. Encounter type (in-patient/out-patient), province (AB/ON), and comorbidities (Yes/No) were the top three factors contributing to HC cost. Adjusting for encounter type, comorbidities and age, the HC costs for CNS patients were $0.7k and $2.4k higher than CRC patients at 50th and 90th percentile, respectively, and $1.0k higher than LC patients at 90th percentile in Ontario. While in Alberta, HC costs for CNS patients were $0.2k and $0.8k higher than CRC patients at 50th and 90th percentile, respectively, and $1.0k lower than LC patients at both 50th and 90th percentiles. CONCLUSIONS We compared HC cost among Canadian patients with different cancer types; significant HC cost differences between patients with CNS and common cancer were observed. Further investigations are warranted to understand drivers of the cost differences.

Encouraging movement opportunities through theory-informed video education among undergraduate students: the MOVE study

Objective: To explore the impact of a theory-informed educational video on undergraduates’: motivational readiness, self-efficacy, and decisional balance about changing sedentary time; sedentary time; and perceptions of sedentarism over time and compared to a control. Participants: Undergraduates (N = 160) from a Canadian institution. Methods: A single-blind randomized controlled trial using an intervention (sedentary video) and control (sleep video) group. Participants completed two validated questionnaires at baseline, immediate post-intervention, and one-month follow-up plus open-ended questions. Linear mixed models and content analysis were used. Results: No significant differences were observed between groups. Increases in self-efficacy (p = .016; d = 0.27) and decisional balance (p = .008; d = 0.31) were observed within intervention participants from baseline to post-intervention, and decreases in sedentary time at post-intervention (p = .032; d = −0.40) and follow-up (p = .006; d = −0.46). Conclusions: This theory-informed sedentary time video shows promise regarding undergraduates’ sedentarism.

Temporal and regional trends in Canada for the epidemiology and management of diabetic foot ulcers.

Diabetic foot ulcers (DFUs) are a common downstream consequence of diabetes and pose significant concern to the health of affected individuals. There are currently limited data available that detail the epidemiology and inpatient burden of DFUs in Canada. This study aims to provide updated data on the epidemiological and economic burden of DFUs in Canada between 2015 and 2019. Using the Canadian Institute for Health Information Patient Cost Estimator the authors estimated, as the primary outcome, the number of DFU inpatient cases in Canada, the associated financial burden of these admissions on the Canadian healthcare system, physician compensation, and average patient length of hospitalisation. This analysis covered 12 Canadian jurisdictions and was stratified by age, sex, province and geographical region. The secondary outcome was to highlight temporal trends in the public health burden of DFUs by computing the average annual percentage change (AAPC; the weighted average of several annual percentage changes over multiple years) using Joinpoint (Surveillance Research Program National Cancer Institute, US) regression analysis. The total number of cases, average length of hospitalisation and physician costs across Canada were highest for patients over ≥60 years of age. By region, the total number of cases and standardised physician costs were highest in Central Canada, followed by Western Canada, and subsequently Eastern and Northern Canada. In 2019, there were >1800 patients with DFUs admitted to Canadian acute care hospitals. Despite having the lowest number of inpatient admissions, Northern Canada had the highest associated inpatient costs, followed by Central, then Western and, lastly, Eastern Canada. Overall, mean inpatient costs remained stable over time across all age groups (AAPC 0.61; 95% confidence interval: -1.87-3.15), with an average cost of >$10,000 CAD per case. Average physician cost across all jurisdictions was approximately $1000 CAD per case, with the mean hospitalisation time being nine days. The findings of this study emphasise the dynamic nature of the economic and epidemiological DFU burden in Canada, underscoring the need for targeted interventions, multidisciplinary care and evidence-based resource allocation for the optimal management of diabetes and DFUs.

Burden of infant group B Streptococcus disease and impact of maternal screening and antibiotic prophylaxis in Ontario, Canada: a population-based cohort study

Group B Streptococcus (GBS) significantly contributes to neonatal sepsis and meningitis, with varying disease rates reported globally and limited population-based data. We estimated infant GBS disease burden in Ontario, Canada and assessed the association of maternal GBS screening (35-37 weeks' gestation) and intrapartum antibiotic prophylaxis (IAP) provision with infant disease rates. Our population-based cohort study included pregnant individuals and their offspring from April 2012 to March 2018, utilising the provincial birth registry linked to health administrative data. GBS cases were ascertained through culture results and diagnostic codes. We calculated incidence rates for early-onset disease (EOD: 0-6 days), late-onset disease (LOD: 7-89 days), and ultra-LOD (ULOD: 90-365 days). Adjusted incidence rate ratios (aIRR) were derived via log-binomial regression to compare infant GBS rates according to screening and IAP-receipt. Among 776,148 liveborn infants, we identified 803 with GBS, with multiples exhibiting a threefold incidence increase. Incidence rates of EOD, LOD and ULOD were 0.49, 0.46 and 0.07 per 1000 livebirths, respectively. Of eligible pregnancies, 94% were screened; 23% screened positive, and 81% of them received IAP. Nearly 12% of term EOD infants had mothers who missed IAP despite screening positive. Maternal screening was associated with lower rates of any infant GBS disease (aIRR: 0.60; 95% CI: 0.45, 0.80). Among screen-positive births, IAP-receipt was associated with reduced rates of EOD (aIRR: 0.72, 95% CI: 0.48, 1.29) and LOD/ULOD (aIRR: 0.69; 95% CI: 0.46, 1.05), but confidence intervals included 1.0. Our study, the largest Canadian investigation into infant GBS disease, highlights both widespread adoption and ongoing challenges of the current prevention strategy. Canadian Institutes of Health Research.

Identification of late-stage tau accumulation using plasma phospho-tau217

Blood-based disease staging across the Alzheimer's disease (AD) continuum holds the promise to identify individuals that profit from disease-modifying therapies. We set out to identify Braak V+ (Braak V and/or VI) tau PET-positive individuals within amyloid-β (Aβ)-positive individuals using plasma biomarkers. In this cross-sectional study, we assessed 289 individuals from the TRIAD cohort and 306 individuals from the WRAP study across the AD continuum. The participants were evaluated by amyloid-PET with [18F]AZD4694 or [11C]PiB and tau-PET with [18F]MK6240 and measured plasma levels included total tau, phospho-tau isoforms (pTau) pTau-181, pTau-217, pTau-231, and N-terminal tau (NTA-tau). We evaluated the performances of plasma biomarkers using different analytic platforms to predict Braak V+ positivity in Aβ+ individuals. Highest associations with Braak V+ tau positivity in Aβ+ individuals were found for plasma pTau-217+Janssen (AUC [CI95%]=0.97 [0.94, 1.0]) and ALZpath pTau-217 (AUC [CI95%]=0.93 [0.86, 1.0]) in TRIAD. Plasma ALZpath pTau-217 separated Braak V+ tau PET-positive individuals in the WRAP longitudinal study (AUC [CI95%]=0.97 [0.94,1.0]). Thus, we demonstrate that using adjusted cut-offs, plasma pTau-217 identifies individuals with later Braak stage tau accumulation which will be helpful to stratify patients for treatments and clinical studies. This research is supported by the Weston Brain Institute, Canadian Institutes of Health Research (CIHR) [MOP-11-51-31; RFN 152985, 159815, 162303], Canadian Consortium of Neurodegeneration and Aging (CCNA; MOP-11-51-31 -team 1), the Alzheimer's Association [NIRG-12-92090, NIRP-12-259245], Brain Canada Foundation (CFI Project 34874; 33397), the Fonds de Recherche du Québec-Santé (FRQS; Chercheur Boursier, 2020-VICO-279314). P.R-N and SG are members of the CIHR-CCNA Canadian Consortium of Neurodegeneration in Aging. Colin J. Adair Charitable Foundation.

Effects of a coal to clean heating policy on acute myocardial infarction in Beijing: a difference-in-differences analysis

In 2015, the Chinese Government launched the coal to clean heating policy (CHP), designed to improve air quality and health in China. The CHP banned household coal burning and provided subsidies for clean electric or gas-powered heating for millions of peri-urban and rural households. We aimed to investigate whether the CHP affected the incidence of acute myocardial infarction in Beijing townships. In this quasi-experimental study, we obtained township data on acute myocardial infarction hospital admissions and deaths, exposure to the CHP (yes vs no), and a range of covariates for periods before (Jan 1, 2013, to Dec 31, 2014) and after the CHP began (Jan 1, 2016, to Dec 31, 2017; and Jan 1, 2018, to Dec 31, 2019). The policy was gradually rolled out across villages, and townships in our study were considered exposed to the policy in periods when more than 50% of their villages were assigned into the CHP. We estimated the effect of the CHP on township incidence of acute myocardial infarction for all adults (aged ≥35 years) and separately for sex and older adults (aged ≥65 years) using a difference-in-differences approach that accommodates the progressive roll-out of the policy. Of 307 townships in Beijing, we excluded 156 (51%) urban townships where most villages had central heating and were thus ineligible for the CHP. Of the 151 peri-urban and rural Beijing townships considered eligible for the CHP, 75 (50%) townships were exposed to the CHP by the end of 2017 and 92 (61%) by the end of 2019. We estimated an overall reduction of 6·6% (95% CI -12·3 to -0·8) in the incidence of acute myocardial infarction from before to after roll-out of the CHP in exposed townships relative to those not exposed to the policy, with some evidence of larger effects in women (-11·7% [-19·0 to -4·1%]), older adults (-10·7% [-17·4 to -3·6%]), and in townships exposed for longer (-3·5% [-9·5 to 2·8%] after <2 years and -9·7% [-18·3 to -0·5%] after 2-4 years). Our results provide among the first empirical evidence of possible cardiovascular benefits from a household clean energy policy, and support efforts to implement and assess such policies in China and globally. Wellcome Trust, the Canadian Institutes for Health Research, and the National Natural Science Foundation of China.

How Do Scholars Conceptualize and Conduct Health and Digital Health Literacy Research? Survey of Federally Funded Scholars.

The concept of health literacy (HL) is constantly evolving, and social determinants of health (SDoH) have been receiving considerable attention in public health scholarship. Since a 1-size-fits-all approach for HL fails to account for multiple contextual factors and as a result poses challenges in improving literacy levels, there is a need to develop a deeper understanding of the current state of HL and digital health literacy (DHL) research. This study examined scholars' conceptualization and scope of work focused on HL and DHL. Using a search string, investigators (N=2042) focusing on HL, DHL, or both were identified from the grantee websites of the National Institutes of Health RePORTER (RePORT Expenditures and Results) and the Canadian Institutes of Health Research. The investigators were emailed a survey via Qualtrics. Survey questions examined the focus of work; whether the investigators studied HL/DHL in combination with other SDoH; the frameworks, definitions, and approaches used; and research settings. We analyzed survey data using SPSS Statistics version 28 and descriptive analysis, including frequencies and percentages, was conducted. Chi-square tests were performed to explore the association between the focus of work, settings, and age groups included in the investigators' research. A total of 193 (9.5%) of 2042 investigators responded to the online survey. Most investigators (76/153, 49.7%) were from public health, 83/193 (43%) reported their research focused on HL alone, 46/193 (23.8%) mentioned DHL, and 64/193 (33.2%) mentioned both. The majority (133/153, 86.9%) studied HL/DHL in combination with other SDoH, 106/135 (78.5%) conducted HL/DHL work in a community setting, and 100/156 (64.1%) reported not using any specific definition to guide their work. Digital tools (89/135, 65.9%), plain-language materials (82/135, 60.7%), and visual guides (56/135, 41.5%) were the top 3 approaches used. Most worked with adults (131/139, 94.2%) and all races and ethnicities (47/121, 38.8%). HL and DHL research largely considered SDoH. Multiple HL tools and approaches were used that support the examination and improvement of literacy and communication surrounding health care issues.

Challenges of remote working, perceived peer support, mental health and well-being of WIL students

PurposeThis study explored the relationship between perceived peer support, mental health and the well-being of students enrolled in work-integrated learning (WIL) at a Canadian institute of higher education, who were completing remote work experiences.Design/methodology/approachAn online survey and virtual semi-structured interviews were used to collect data. The online survey captured demographic information as well as measures of perceived peer support, loneliness, positive mental health (PMH) and stressors associated with the on-going pandemic. The interviews captured narratives regarding peer support, attitudes surrounding remote work, mental health and well-being.FindingsWIL students completing remote work terms experienced only moderate levels of peer support, moderate loneliness, below-average PMH and all the stressors associated with the on-going pandemic. Data also revealed that completing a remote work term negatively impacted work communications, opportunities to build connections with colleagues and overall motivation. On the other hand, WIL students appreciated the flexibility and comfort of working from home, as well as reduced work-related expenses.Originality/valueWith remote work experiences increasing globally and now a reality for many WIL students, the potential negative effects emphasize the importance of providing social and mental health support and resources, especially during stressful times.

Strengthening Equity, Diversity, and Inclusion in medical education via an intersectional approach

Abstract Background In the wake of COVID-19, equity, diversity, and inclusion (EDI) policies have been taken up in the health field, yet the actual impact of these initiatives, particularly for multiply marginalized individuals, is debated. Despite progress in areas such as diversity promotion, EDI has been critiqued as superficial and as failing to challenge the drivers of health inequity. This presentation discusses how an intersectionality-informed approach can help harness the transformative potential of EDI. Methods This research is informed by a literature review of EDI initiatives in the health field, and is an offshoot of a 4.5 year international project funded by the Canadian Institutes for Health Research focused on evaluating and strengthening intersectionality-informed policy guidance. Results There is a disconnect between EDI commitments and substantive action on health inequities and an intersectional approach can help bridge this divide. We demonstrate this with a case example which brings an intersectional approach to EDI initiatives in medical education - including bias trainings, courses on the social determinants of health, and the engagement of community groups. Drawing on promising equity promoting work across these areas, we show how intersectionality can harness the potential of EDI by bringing to the fore what has often been missing, including the promotion of health stakeholder reflexivity, attention to interacting systems and structures shaping health, and meaningful engagement with underrepresented communities. Conclusions An intersectionality-informed approach to EDI has the potential to enhance the health equity impacts of initiatives within medical education and the broader health field. Key messages • EDI initiatives in health often have limited impact on health inequities. • An intersectionality-informed approach to EDI can help health stakeholders drive transformative action on health inequities.

2.X.1. Sleep Health Disparities across the life-course: from research to public health policy

Abstract Poor sleep health is a recognized common problem across the life cycle, globally. Factors that contribute to this problem include the demands of a “Western” lifestyle (urgency, productivity), economic stressors, social and environmental determinants of health, and global crises including international conflicts, political tensions, and climate change. There is a growing consensus that optimizing sleep health should be a public health priority because poor sleep patterns are a modifiable risk factor for myriad health outcomes, such as cardiovascular disease, diabetes, cancer, cognitive decline, mental illness, and early mortality. In Canada, a nationwide sleep consortium funded by the Canadian Institutes of Health Research (CIHR) was recently formed with a mandate to generate new knowledge that will inform clinical practice and support public health initiatives to deliver resources where they are most needed. The proposed workshop organized by the Chronic Disease EPH section will start with a general overview of the impact of sleep health disparities across the life-course, from childhood to older age, as well as discuss evidence-based public health approaches to promote sleep hygiene and mitigate the risk of adverse health outcomes, including chronic disease (Saverio Stranges). It will be followed by three presentations to address the root causes of sleep health disparities and their impact on chronic disease (Dayna Johnson); participatory research with families and care providers on infant sleep intervention development (Elizabeth Keys), and strategies to address common sleep disorders among middle-aged and older adults (Tetyana Kendzerska). Key messages • Sleep health disparities are a neglected public health issue. • Optimizing sleep health is both a clinical and public health priority, as sleep patterns represent a modifiable risk factor for a range of adverse health outcomes.

04 Care for adolescents with substance use: A national survey of paediatric hospitals

Abstract Background Substance use is a recognized Paediatric health care issue. More than 9 in 10 individuals receiving treatment for substance use disorders report that their first use of substances occurred by young adulthood. The Canadian Institute for Health Information reported that 5% of hospital stays among Canadian youth in 2017-2018 were related to harmful substance use. In a study of youth with a first-time emergency department visit for a mental health problem between 2010 and 2014, most visits were due to substance related disorders. Despite this, little is known about practices relating to substance use in children's hospitals. Objectives 1. To describe how adolescents who present to Paediatric hospitals with substance use disorders or substance-related health issues are identified, assessed, and treated. 2. To identify best-practices that can inform national standards of care. Design/Methods An online questionnaire was utilized to obtain information on: 1. Clinical practices in the emergency department, inpatient services and ICU; 2. Hospital policies and practice guidelines; and 3. Hospital and community programs and resources. Recruitment emails were sent to hospital leaders (CEO or equivalent) at all 13 Paediatric hospitals. Leaders were asked to identify one individual to complete the survey on behalf of their hospital with input from relevant stakeholders in the various clinical areas. The survey was developed iteratively by a national group of 9 adolescent medicine clinicians and 2 Paediatric trainees. The survey was piloted at a single Paediatric hospital and refined. The survey was administered via RedCap technology. Results Survey response rate was 70% (9/13 hospitals). The mean number of contributors to each survey was 9 (range of 1-35). Overall, few hospitals utilized best practices consistently. There was inconsistency in the use of validated screening tools, use of clinical practice guidelines for monitoring and ongoing care and prescribing of nicotine replacement therapy and opioid agonist therapy. These inconsistencies were noted within each clinical setting (emergency department, inpatient services, and ICU), across services in each hospital, and between hospitals. With respect to hospital services, 5/9 had some type of consult team related to substance use (e.g., adolescent medicine), 4/9 had specialized substance use outpatient services, and 2/9 offered partial hospitalization/day treatment for patients with substance use issues. Local community-based substance use resources were identified as insufficient to address needs by 8/9 hospitals. Conclusion Inconsistencies in the care of adolescents with substance use disorders or substance-related health issues highlights the need for national guidelines for Paediatric hospital-based assessment and care, and enhanced coordination between services and systems of care for this patient population.

Geographical disparities in temporal trends of low birth weight in Saskatchewan from 2002/2003 to 2021/2022: insights from a joinpoint regression analysis.

Low birth weight (LBW) is an important public health indicator that is associated with various negative health outcomes in infants. To effectively implement interventions that would improve health outcomes in children, it is important to understand both the historical trends and current levels of LBW rates. In this study, trends and regional differences in LBW rates in Saskatchewan from 2002/2003 to 2021/2022 were assessed. A joinpoint regression analysis was conducted using historical LBW rates, obtained from the Canadian Institute for Health Information database. Data were analysed using average percent change and average annual percent change. Spatial patterns and trends were identified using a choropleth map. From a provincial and national rate of 5.2% in 2002/2003, the LBW rate in Saskatchewan increased to 6.5% in 2021/2022, approaching the national rate of 6.8%. Over the 20-year period, average annual changes for Canada were 1.4% and 1.0% for Saskatchewan. There was a turning point in the study: 2004/2005 for Canada and 2011/2012 for Saskatchewan. Initially, Saskatchewan had stable LBW rates, increasing yearly by 0.1%, while the national rate was 5.7%. However, in recent years, Saskatchewan's rate increased to 1.8% annually, surpassing the national rate of 0.9%. Geographical differences were also observed within Saskatchewan, with the Far North region having the highest LBW rate (9.2%), and the Central West region having the lowest rate (4.3%) in 2021/2022. The Central East, Regina Qu'Appelle, and southern Saskatchewan saw significant upwards trends in LBW rates between 2015/2016 and 2021/2022. There is an increasing trend in LBW rates in Canada and Saskatchewan, as well as geographical disparities within the province. The geographical disparities in LBW rates underscore the need for tailored interventions in high-risk regions in the province.

Mortality Following Childbirth in Ontario: A 20-Year Analysis of Temporal Trends and Causes

ObjectivesMaternal death during or after pregnancy is often preventable and accurate surveillance is key to prevention. We examined the number and causes of maternal death in Ontario over 20 years. MethodsRetrospective cohort study including all hospital livebirths and stillbirths from 2002–2022 in the Canadian Institute for Health Information Discharge Abstracts (for hospitalizations) and National Ambulatory Care System (for emergency department encounters) linked to the Better Outcomes and Registry and Network births. Death was ascertained from childbirth to 365 days thereafter; all deaths were reviewed by at least 3 clinicians. ResultsThere were 485 deaths among 2 764 214 live and stillbirths over 20 years—a maternal mortality ratio (MMR) of 17.5 per 100 000 (95% CI 16.0–19.2). There were 222 (45.8%) early deaths within 42 days of birth (MMR of 8.0 per 100 000; 95% CI 7.0–9.2), and 263 (54.2%) late deaths from 43 to 365 days after birth (MMR 9.5 per 100 000; 95% CI 8.4–10.7). Death was pregnancy-related in 169/485 cases (34.8%). Early death causes were predominantly hemorrhage, infection, preeclampsia, and pulmonary embolism. The top causes of 263 late deaths were cancer, injury, and cardiac arrest, or unknown. ConclusionsMost deaths within 1 year of childbirth are not related to obstetrical factors; however, pregnancy complications factor in early deaths. Causes of early and late deaths differ, but examining late deaths is equally important to identify factors not regularly examined in maternal mortality. As death in early pregnancy or outside hospitals is not reported, mortality is likely higher.

Validation of Preterm Birth Related Perinatal and Neonatal Data in the Canadian Discharge Abstract Database to Facilitate Long-term Outcomes Research of Individuals Born Preterm

IntroductionThe Canadian Institute of Health Information's (CIHI) Discharge Abstract Database (DAD) contains standardised administrative data on all hospitalisations in Canada, excluding Quebec. ObjectivesWe aimed to validate preterm birth related perinatal and neonatal data in DAD by assessing its accuracy against the reference standard of the Canadian Neonatal Network (CNN) database. MethodsWe linked birth hospitalization data between the DAD and CNN databases for all neonates born $&lt;$33 weeks gestational age (GA) admitted to the Neonatal Intensive Care Units in Winnipeg, Canada, between 2010 and 2022. A comprehensive list of maternal and neonatal variables relevant to preterm birth was chosen \textit{a priori} for validation. For categorical variables, we measured correlation using Cohen's weighted kappa (k) and for continuous variables, we measured agreement using Lin's concordance correlation coefficient (LCCC). Results2084 neonates were included (mean GA 29.4 ± 2.4 weeks; birth weight 1430 ± 461g). Baseline continuous maternal and neonatal variables showed excellent accuracy in DAD [Maternal age: LCCC = 0.99 (0.99, 0.99); GA: LCCC = 0.95 (0.95, 0.96); birth weight: LCCC = 0.97 (0.96, 0.97); sex: k = 0.99 (0.98-0.99)]. In contrast, the accuracy of the maternal baseline categorical variables and neonatal outcomes and interventions ranged from very good to poor [e.g., Caesarean section: k = 0.91 (0.89-0.93), pre-gestational diabetes: k = 0.04 (0.03-0.05), neonatal sepsis: k = 0.37 (0.31-0.42), bronchopulmonary dysplasia: k = 0.26 (0.19-0.33), neonatal laparotomy: k = 0.55 (0.43-067)]. ConclusionNeonatal variables such as gestational age and birth weight had high accuracy in DAD, while the accuracy of maternal and neonatal morbidities and interventions were variable, with some being poor. Reasons for the inaccuracy of these variables should be identified and measures taken to improve them.

6811 RESTORE: a Real-World Study of Setmelanotide in Patients With MC4R Pathway Diseases

Abstract Disclosure: C. Huber: Employee; Self; Rhythm Pharmaceuticals, Inc.. Stock Owner; Self; Rhythm Pharmaceuticals, Inc. B. Sweeney: Consulting Fee; Self; Rhythm Pharmaceuticals, Inc., Novo Nordisk. Research Investigator; Self; Rhythm Pharmaceuticals, Inc.. Speaker; Self; Rhythm Pharmaceuticals, Inc. J. Pomeroy: Research Investigator; Self; Rhythm Pharmaceuticals, Inc. U. Mallya: Employee; Self; Rhythm Pharmaceuticals, Inc.. Stock Owner; Self; Rhythm Pharmaceuticals, Inc. S. Zhang: Other; Self; Employer received funding from Rhythm Pharmaceuticals, Inc. to support this research. M. Yang: Other; Self; Employer received funding from Rhythm Pharmaceuticals, Inc. to support this research. S. Malhotra: Employee; Self; Rhythm Pharmaceuticals, Inc.. Stock Owner; Self; Rhythm Pharmaceuticals, Inc. A.M. Haqq: Advisory Board Member; Self; Rhythm Pharmaceuticals, Inc., Novo Nordisk, Foundation for Prader-Willi Research USA. Grant Recipient; Self; Weston Family Microbiome Initiative and Canadian Institutes of Health Research. Background: Setmelanotide has demonstrated efficacy in clinical trials of patients with obesity due to rare melanocortin-4 receptor pathway diseases. Real-world evidence can provide a greater understanding of patient outcomes, such as hyperphagia and quality of life, in a clinical practice setting. Real-world Evidence of SeTmelanotide fOr Hyperphagia and ChRonic Weight ManagEment (RESTORE) is a prospective, observational, longitudinal study aimed at assessing patient- and caregiver-reported real-world effectiveness of setmelanotide among patients with Bardet-Biedl syndrome and proopiomelanocortin, proprotein convertase subtilisin/kexin type 1, or leptin receptor deficiency and their caregivers. Methods: Patients aged ≥6 years and caregivers aged ≥18 years who are able to respond to a survey in English and consented to the Rhythm Intune Program are eligible for the study. Patients must have been prescribed, but not yet initiated, setmelanotide, not have been previously treated with setmelanotide, and not have previously participated in or be currently enrolled in any clinical trial, including setmelanotide trials. Caregivers must be confirmed legal guardians of patients without prior exposure to setmelanotide, have cared for their patient for ≥6 months, and not be paid professional caregivers. Participants will complete secure online surveys at baseline (ie, before treatment) and at 6 posttreatment time points over a 1-year study period. Patient surveys collect information on hyperphagia-related signs and symptoms, medical history, treatment adherence, weight management programs and treatment, comorbidities/complications, comedications, disease impact on psychological well-being and health-related quality of life, treatment satisfaction, work/school/activity status, and patient global assessment. Caregiver surveys include assessments on psychological well-being, treatment satisfaction, and impact on activities of daily living, work status, and family dynamics. A subset of study patients will be invited to receive a wearable device (CentrePoint® Insight Watch) to assess activity and sleep patterns. Treatments and outcomes among patients will be described and compared with baseline for all post-treatment initiation assessment time points. Current status: RESTORE is the first study to assess the real-world effectiveness of setmelanotide, has been IRB approved, and is actively enrolling. Presentation: 6/3/2024

Meeting Report: Controlled Human Influenza Virus Infection Model Studies: Current Status and Future Directions for Innovation.

On November 13-14, 2023, the National Institute of Allergy and Infectious Diseases (NIAID) in partnership with the Task Force for Global Health, Flu Lab, the Canadian Institutes of Health Research, and the Centers for Disease Control and Prevention convened a meeting on controlled human influenza virus infection model (CHIVIM) studies to review the current research landscape of CHIVIM studies and to generate actionable next steps. Presentations and panel discussions highlighted CHIVIM use cases, regulatory and ethical considerations, innovations, networks and standardization, and the utility of using CHIVIM in vaccine development. This report summarizes the presentations, discussions, key takeaways, and future directions for innovations in CHIVIMs. Experts agreed that CHIVIM studies can be valuable for the study of influenza infection, immune response, and transmission. Furthermore, they may have utility in the development of vaccines and other medical countermeasures; however, the use of CHIVIMs to de-risk clinical development of investigational vaccines should employ a cautious approach. Endpoints in CHIVIM studies should be tailored to the specific use case. CHIVIM studies can provide useful supporting data for vaccine licensure but are not required and do not obviate the need for the conduct of field efficacy trials. Future directions in this field include the continued expansion of capacity to conduct CHIVIM studies, development of a broad panel of challenge viruses and assay reagents and standards that can be shared, streamlining of manufacturing processes, the exploration of targeted delivery of virus to the lower respiratory tract, efforts to more closely replicate natural influenza disease in CHIVIM, alignment on a definition of breadth to facilitate development of more broadly protective/universal vaccine approaches, and continued collaboration between stakeholders.

Modelling vaccination approaches for mpox containment and mitigation in the Democratic Republic of the Congo.

Mpox was first identified in the Democratic Republic of the Congo (DRC) in 1970. In 2023, a historic outbreak of mpox occurred in the country, continuing into 2024. Over 14 000 cases and 600 deaths were reported in 2023 alone, representing a major increase from previous outbreaks. The modified vaccinia Ankara vaccine (brand names JYNNEOS, Imvamune, and Imvanex) was used in the 2022 mpox outbreak in the USA and Europe. However, at the time of the study, vaccination had not been made available in the DRC. We aimed to inform policy and decision makers on the potential benefits of, and resources needed, for mpox vaccination campaigns in the DRC by providing counterfactual scenarios evaluating the short-term effects of various vaccination strategies on mpox cases and deaths, if such a vaccination campaign had been undertaken before the 2023-24 outbreak. A dynamic transmission model was used to simulate mpox transmission in the DRC, stratified by age (<5, 5-15, and >15 years) and province. The model was used to simulate potential vaccination strategies, varying by age and region (endemic provinces, non-endemic provinces with historic cases, and all provinces) assessing the effect the strategies would have on deaths and cases in an epidemic year similar to 2023. In addition, we estimated the number of vaccine doses needed to implement each strategy. Without vaccination, our model predicted 14 700 cases and 700 deaths from mpox over 365 days. Vaccinating 80% of all children younger than 5 years in endemic regions led to a 27% overall reduction in cases and a 43% reduction in deaths, requiring 10·5 million vaccine doses. Vaccinating 80% of all children younger than 5 years in all regions led to a 29% reduction in cases and a 43% reduction in deaths, requiring 33·1 million doses. Vaccinating 80% of children aged 15 years or younger in endemic provinces led to a 54% reduction in cases and a 71% reduction in deaths, requiring 26·6 million doses. When resources are limited, vaccinating children aged 15 years or younger, or younger than 5 years, in endemic regions of the DRC would be the most efficient use of vaccines. Further research is needed to explore long-term effects of a one-time or recurrent vaccination campaign. Canadian Institutes of Health Research, Canadian International Development Research Centre, US Department of Defense (Defense Threat Reduction Agency, Mpox Threat Reduction Network), Global Affairs Canada (Weapons Threat Reduction Program), US Department for Agriculture (Agriculture Research Service, Non-Assistance Cooperative Agreement).

Safety and immunogenicity of a delayed booster dose of the rVSVΔG-ZEBOV-GP vaccine for prevention of Ebola virus disease: a multicentre, open-label, phase 2 randomised controlled trial

rVSVΔG-ZEBOV-GP is the first approved vaccine with clinical efficacy against Ebola virus disease. Although a seroprotective threshold has not been defined for those at occupational risk of exposure, the current vaccine strategy is to attain a sustained high level of antibody titres. The aim of this trial was to explore the effects of delayed boosting upon both the height and duration of antibody titres following primary immunisation. In this open-label phase 2 randomised controlled trial, we compared antibody titres at month 36in participants who had received a homologous booster dose at month 18following primary immunisation with those who had received no booster. From Oct 25, 2016, to Jan 29, 2020, healthy adults aged 18years or older deemed at occupational risk of exposure to Ebola virus due to laboratory work, clinical duties, or travel to an active endemic region were recruited from four hospital clinics in the USA and one hospital clinic in Canada and received primary vaccination with 2×107 plaque-forming unit per mL of VSVΔG-ZEBOV-GP. 18months later, individuals who consented and were still eligible were randomly assigned 1:1 to receive either a homologous booster dose or no booster. Study visits for safety and serial blood collections for antibody titres were done on enrolled participants at months 0, 1, 3, 6, 12, 18, 19, 24, 30, and 36. Through July, 2021, a web-based application was used for randomisation, including assignments with schedules for each of the five sites using mixed permuted blocks. The trial was not masked to participants or site staff. The primary endpoint was a comparison of geometric mean titres (GMTs) of anti-Ebola virus glycoprotein IgG antibody at month 36 (ie, 18months after randomisation) for all randomly assigned participants who completed the 36months of follow-up (primary analysis cohort). Investigators were aware of antibody titres from baseline (enrolment) through month 18but were masked to summary data by randomisation group after month 18. This study is registered with ClinicalTrials.gov (NCT02788227). Of the 248participants who enrolled and received their primary immunisation, 114proceeded to the randomisation step at month 18. The two randomisation groups were balanced: 57participants (24 [42%] of whom were female; median age was 42years [IQR 35-50]) were randomly assigned to the booster group and 57 (24 [42%] of whom were female; median age was 42years [IQR 36-51]) to the no-booster group. Of those randomly assigned, 92participants (45 in the booster group and 47in the no-booster group) completed 36months of follow-up. At 18months after primary immunisation, GMTs in the no-booster group increased from a baseline of 10ELISA units (EU)/mL (95% CI 7-14) to 1451EU/mL (1118-1882); GMTs in the booster group increased from 9EU/mL (6-16) to 1769EU/mL (1348-2321). At month 19, GMTs were 31 408EU/mL (23 181-42 554) for the booster group and 1406EU/mL (1078-1833) for the no-booster group; at month 36, GMTs were 10 146EU/mL (7960-12 933) for the booster group and 1240EU/mL (984-1563) for the no-booster group. Accordingly, the geometric mean ratio (GMR) of antibody titres had increased almost 21-fold more in the booster versus no-booster group at 1month after booster administration (GMR 20·6; 95% CI 18·2-23·0; p<0·0001) and was still over 7-fold higher at month 36 (GMR 7·8; 95% CI 5·5-10·2; p<0·0001). Consistent with previous reports of this vaccine's side-effects, transient mono-articular or oligo-articular arthritis was diagnosed in 18 (9%) of 207primary vaccination recipients; after randomisation, arthritis was diagnosed in one (2%)of 57participants in the no-booster group. No new cases of arthritis developed after booster administration. Four serious adverse events occurred following randomisation: one (epistaxis) in the booster group and three (gastrointestinal haemorrhage, prostate cancer, and tachyarrhythmia) in the no-booster group. None of the serious adverse events was judged attributable to the booster vaccination assignment. In addition to no new safety concerns and in marked contrast to earlier trials evaluating short-term boosting, delaying a rVSVΔG-ZEBOV-GP booster until month 18resulted in an increase in GMT that remained several-fold above the no-booster group GMT for at least 18months. These findings could have implications for defining the optimal timing of booster doses as pre-exposure prophylaxis in populations at ongoing risk for Ebola virus exposure. The Division of Intramural Research and the Division of Clinical Research of the National Institute of Allergyand Infectious Diseases at the US National Institutes of Health, Canadian Immunization Research Network through the Public Health Agency of Canada, Canadian Institutes of Health Research, and the US Defense Threat Reduction Agency.

CEST conversation with Prof. Marc A. Rosen: Evolving responsibilities and contributions in science and engineering for global carbon neutrality transitions

Prof. Marc A. Rosen is a Professor of Mechanical &amp; Manufacturing Engineering at Ontario Tech University (formally University of Ontario Institute of Technology) in Oshawa, Canada, where he served as founding Dean of the Faculty of Engineering and Applied Science. Prof. Rosen has served as President of the Engineering Institute of Canada and of the Canadian Society for Mechanical Engineering. He has received numerous awards and honors, including an Award of Excellence in Research and Technology Development from the Ontario Ministry of Environment and Energy, the Engineering Institute of Canada Smith Medal for achievement in the development of Canada, and the Canadian Society for Mechanical Engineering Angus Medal for outstanding contributions to the management and practice of mechanical engineering. Prof. Rosen received a distinguished scholar award from Toronto Metropolitan University (formerly Ryerson University) and a Mid-Career Award from University of Toronto. He is a fellow of the Royal Society of Canada, the Engineering Institute of Canada, the Canadian Academy of Engineering, the Canadian Society for Mechanical Engineering, the American Society of Mechanical Engineers and the International Energy Foundation.