Open Access Publications
Permanent URI for this collection
Browse
Recent Submissions
Item Open Access Metabolomic in severe traumatic brain injury: exploring primary, secondary injuries, diagnosis, and severity(2025-01-15) Banoei, Mohammad M.; Hutchison, James; Panenka, William; Wong, Andy; Wishart, David S.; Winston, Brent W.Abstract Background Traumatic brain injury (TBI) is a major public health concern worldwide, contributing to high rates of injury-related death and disability. Severe traumatic brain injury (sTBI), although it accounts for only 10% of all TBI cases, results in a mortality rate of 30–40% and a significant burden of disability in those that survive. This study explored the potential of metabolomics in the diagnosis of sTBI and explored the potential of metabolomics to examine probable primary and secondary brain injury in sTBI. Methods Serum samples from 59 adult patients with sTBI and 35 age- and sex-matched orthopedic injury controls were subjected to quantitative metabolomics, including proton nuclear magnetic resonance (1H-NMR) and direct infusion/liquid chromatography-tandem mass spectrometry (DI/LC–MS/MS), to identify and quantify metabolites on days 1 and 4 post-injury. In addition, we used advanced analytical methods to discover metabo-patterns associated with sTBI diagnosis and those related to probable primary and secondary brain injury. Results Our results showed different serum metabolic profiles between sTBI and orthopedic injury (OI) controls, with significant changes in measured metabolites on day 1 and day 4 post-brain injury. The number of altered metabolites and the extent of their change were more pronounced on day 4 as compared to day 1 post-injury, suggesting an evolution of mechanisms from primary to secondary brain injury. Data showed high sensitivity and specificity in separating sTBI from OI controls for diagnosis. Energy-related metabolites such as glucose, pyruvate, lactate, mannose, and polyamine metabolism metabolites (spermine and putrescine), as well as increased acylcarnitines and sphingomyelins, occurred mainly on day 1 post-injury. Metabolites of neurotransmission, catecholamine, and excitotoxicity mechanisms such as glutamate, phenylalanine, tyrosine, and branched-chain amino acids (BCAAs) increased to a greater degree on day 4. Further, there was an association of multiple metabolites, including acylcarnitines (ACs), lysophosphatidylcholines (LysoPCs), glutamate, and phenylalanine, with injury severity at day 4, while lactate, glucose, and pyruvate correlated with injury severity on day 1. Conclusion The results demonstrate that serum metabolomics has diagnostic potential for sTBI and may reflect molecular mechanisms of primary and secondary brain injuries when comparing metabolite profiles between day 1 and day 4 post-injury. These early changes in serum metabolites may provide insight into molecular pathways or mechanisms of primary injury and ongoing secondary injuries, revealing potential therapeutic targets for sTBI. This work also highlights the need for further research and validation of sTBI metabolite biomarkers in a larger cohort.Item Open Access Validation of the Maslach burnout inventory-general survey 9-item short version (MBI-GS9) among care aides in Canadian nursing homes(2025-01-16) Wang, Anni; Duan, Yinfei; Saeidzadeh, Seyedehtanaz; Norton, Peter G.; Estabrooks, Carole A.Abstract Background The Maslach Burnout Inventory-General Survey (MBI-GS) is the leading measure of burnout for all occupations. The MBI-GS9, the 9-item version of the MBI-GS, was formulated based on the MBI-GS and has been used for several years. However, very few studies have systematically tested its psychometric properties, and none have focused on care aides working in nursing homes who are susceptible to burnout. Methods Following the Standards for Educational and Psychological Testing, this study validated the MBI-GS9 among 3,765 care aides from 91 Canadian nursing homes, using data collected between September 2019 and February 2020 by the Translating Research in Elder Care (TREC) program. Results The Exhaustion subscale had good reliability with coefficients around 0.66–0.74. The Cynicism subscale had medium reliability with coefficients around 0.60–0.66, and the Efficacy subscale also had medium reliability with coefficients around 0.51–0.58. The MBI-GS9 was significantly correlated with various conceptually related constructs, such as health status, working environment, job satisfaction, psychological empowerment, work engagement, and organizational citizenship behaviors. The MBI-GS9 had a three-factor structure in the full sample and showed equivalent factor structure, factor loadings, latent values, factor variance and error variance across different sex and age groups. Care aides with English as their first language showed higher latent values of the Exhaustion subscale compared to those with English as a second language. Conclusion Overall, the MBI-GS9 exhibited acceptable psychometric properties, but medium reliability of cynicism and efficacy subscales, for measuring burnout among care aides in nursing homes, demonstrating equivalence across sex and gender groups. When comparing across different languages or racial or ethnic groups among care aides, it is important to consider inequivalent latent values on Exhaustion before comparing scores on the measure.Item Open Access Persistent NK cell deficiency associated with pulmonary cryptococcosis(2025-01-18) Martinot, Martin; Li, Shu S.; Farnarier, Catherine; Dubrou, Cléa; Piperoglou, Christelle; Mody, Christopher H.; Vely, FredericAbstract We describe pulmonary cryptococcosis in a 28-year-old previously healthy man. Exhaustive immunological investigations revealed a primary NK cell deficiency associated with a secondary impaired anti-Cryptococcus CD8 lymphocyte response and the expansion of a CD8Vβ14 + T cell clone. This case illustrates the potential role of NK cells in immunity against Cryptococcus.Item Open Access Inter-rater agreement and characterization of pleural line and subpleural fields in canine lung ultrasound: a comparative pilot study between high-frequency linear and curvilinear transducers using B- and M-mode ultrasonographic profiles(2025-01-13) Granger, Kyle L.; Guieu, Liz; Boysen, Søren R.Abstract Background Lung ultrasound (LUS) is increasingly utilized in veterinary medicine to assess pulmonary conditions. However, the characterization of pleural line and subpleural fields using different ultrasound transducers, specifically high-frequency linear ultrasound transducers (HFLUT) and curvilinear transducers (CUT), remains underexplored in canine patients. This study aimed to evaluate inter-rater agreement in the characterization of pleural line and subpleural fields using B- and M-mode ultrasonography in dogs with and without respiratory distress. Results Eighty-eight ultrasound clips from nine dogs were analyzed. HFLUT demonstrated strong inter-rater agreement in B-mode (κ = 0.89) and near-perfect agreement in M-mode (κ = 1.00) for pleural line homogeneity. In contrast, CUT showed minimal agreement in both B-mode (κ = 0.34) and M-mode (κ = 0.37). Homogeneous pleural lines were predominantly observed in control dogs or those with cardiogenic pulmonary edema (CPE), while non-homogeneous pleural lines were more common in dogs with non-cardiogenic alveolar-interstitial syndrome (NCAIS). Vertical subpleural fields identified in M-mode were associated with both CPE and NCAIS, whereas horizontal fields were more often observed in control dogs. Conclusions HFLUT offers superior inter-rater reliability for characterizing pleural and subpleural features in canine LUS compared to CUT, particularly in M-mode. These findings suggest HFLUT may enhance diagnostic accuracy for pulmonary conditions in dogs. Further studies are needed to explore the diagnostic potential of LUS in differentiating vertical artifact (e.g., B-lines) etiologies in veterinary patients.Item Open Access Aura phenomenon: a proposal for an etiology-based clinical classification(2025-01-13) Pensato, Umberto; Demchuk, Andrew M.; Dreier, Jens P.; Brennan, Kevin C.; Sacco, Simona; Romoli, MicheleAbstract Background The term “aura” refers to a well-defined pattern of usually positive, progressive, and reversible neurological symptoms, with spreading depolarization as the underlying mechanism. While commonly associated with migraine, aura can also occur in other neurological disorders (i.e., cerebrovascular disorders). However, current terminology inadequately describes its different underlying clinical etiologies. Main body We propose the following terminology and etiology-based clinical classification for the aura phenomenon: (i) Migrainous Aura (when the etiology is migraine), (ii) Non-migrainous Aura (when there is an alternative etiology), (iii) Aura of uncertain clinical etiology (when etiology is unclear), and (iv) Migrainous Infarction (a typical migrainous aura in a patient with migraine with aura associated with an infarction in a corresponding anatomical brain region). Conclusion This nuanced classification aims to aid in the diagnostic evaluation and phenotyping of aura phenomenon, ultimately improving the diagnosis and management of the different associated neurological conditions. Moreover, it could promote effective communication and translational mechanistic research.Item Open Access Outcomes of intravitreal dexamethasone implant (Ozurdex®) in patients with post-surgical macular edema – a real-world scenario(2025-01-10) de Oliveira Júnior, Elder O.; Ahn, Isabel; Fernandes, Rodrigo A. B.; Fernandes, Arthur G.Abstract Background Clinically significant macular edema (CME) is the leading cause of visual loss after ophthalmologic surgery due to the release of inflammatory mediators promoted by the procedures. We aimed to evaluate the outcomes of intravitreal Ozurdex® (700 µg dexamethasone) implants as a primary therapeutical option for post-surgical macular edema cases. Methods Patients with post-surgical macular edema diagnosed by optical coherence tomography (Cirrus SD-OCT) and treated with Ozudex were selected for the current study. Data was retrospectively collected from medical records from January 2020 to December 2022 and included sex, age, laterality, and timeline of treatment (i.e. implant alone or at the time of silicon oil removal in cases requiring vitreorretinal surgery). Complications associated with treatment were also noted as well as the need of further treatments. The structural analysis focused on measuring central macular thickness (CMT—average thickness within the 1 mm circle of the ETDRS) from the internal limiting membrane to the Bruch’s membrane complex, as well as the average total macular thickness including parafoveal and perifoveal regions determined by the device (CAT). The functional evaluation was based on the best-corrected visual acuity (VA) measured in logMAR. Results A total of 46 participants were included (56.2% males, mean age: 60.9 ± 11.2 years old). A statistically significant change was observed in the postoperative versus the preoperative period for all parameters (p < 0.05). The mean VA difference was − 0.17 ± 0.24; CMT was − 109.22 ± 124.85 and CAT was − 14.76 ± 58.95. We observed a significant effect of the moment of Ozurdex implantation on VA improvement, so that cases with implantation at the time of oil removal showed lower improvement than cases with implantation at a distinct timing (Coef. 0.19, 95%CI: 0.02 to 0.36, p = 0.027). Eleven cases (23.9%) required further treatment such as new Ozurdex implantation (8 cases) or surgery (3 cases). Only one case (2.17%) showed increased intraocular pressure and underwent glaucoma surgery. Conclusions Intravitreal Ozurdex implants significantly improved functional and structural aspects in post-surgical macular edema. The timing of implantation influenced VA improvement, with a distinct step approach showing better outcomes than at the time of oil removal.Item Open Access Aggressive Subtypes of Laryngeal Chondrosarcoma and their Clinical Behavior: A Systematic Review(2025-01-05) Piazza, Cesare; Montenegro, Claudia; Tomasoni, Michele; Leivo, Ilmo; Stenman, Göran; Agaimy, Abbas; Simpson, Roderick H. W.; Zidar, Nina; Ferlito, AlfioAbstract Introduction Laryngeal chondrosarcoma (CS) is a rare indolent malignant tumor. High-grade (G3), dedifferentiated (DD), and myxoid (MY) CSs are considered more aggressive subtypes due to their metastatic potential and relatively poor outcomes. The aim of this systematic review is to evaluate treatment modalities and survival outcomes in patients affected by these rarer CS subtypes. Methods Papers published from January 1, 2000, to August 25, 2024, describing cases of laryngeal G3, DD, and MY CS were included. Results A total of 38 patients (15 G3, 13 DD, and 10 MY) were selected. Cricoid cartilage was the most common site of origin. Total laryngectomy (TL) was often performed. Primary conservative approaches in 42.8% of patients were followed by loco-regional recurrence. Conclusions Aggressive subtypes of CS require a radical approach because of the higher rate of loco-regional and distant recurrences compared to low-grade CS. TL with radical intent is the most common treatment, and adjuvant therapy should be considered after careful multidisciplinary discussion.Item Open Access Development and usability testing of a multifaceted intervention to reduce low-value injury care(2025-01-07) Bérubé, Mélanie; Lapierre, Alexandra; Sykes, Michael; Grimshaw, Jeremy; Turgeon, Alexis F.; Lauzier, François; Taljaard, Monica; Stelfox, Henry T.; Witteman, Holly; Berthelot, Simon; Mercier, Éric; Gonthier, Catherine; Paquet, Jérôme; Fowler, Robert; Yanchar, Natalie; Haas, Barbara; Lessard-Bonaventure, Paule; Archambault, Patrick; Gabbe, Belinda; Guertin, Jason R.; Ouyang, Yougdong; Moore, LynneAbstract Background Multifaceted interventions that address barriers and facilitators have been shown to be most effective for increasing the adoption of high-value care, but there is a knowledge gap on this type of intervention for the de-implementation of low-value care. Trauma is a high-risk setting for low-value care, such as unnecessary diagnostic imaging and the use of specialized resources. The aim of our study was to develop and assess the usability of a multifaceted intervention to reduce low-value injury care. Methods We used the Consolidated Framework for Implementation Research and the Expert Recommendations for Implementing Change tool as theoretical foundations to identify barriers and facilitators, and strategies for the reduction of low-value practices. We designed an initial prototype of the intervention using the items of the Template for Intervention Description and Replication. The prototype’s usability was iteratively tested through four focus groups and four think-aloud sessions with trauma decision-makers (n = 18) from seven Level I to Level III trauma centers. We conducted an inductive analysis of the audio-recorded sessions to identify usability issues and other barriers and facilitators to refine the intervention. Results We identified barriers and facilitators related to individual characteristics, including knowledge and beliefs about low-value practices and the de-implementation process, such as the complexity of changing practices and difficulty accessing performance feedback. Accordingly, the following intervention strategies were selected: involving governing structures and leaders, distributing audit & feedback reports on performance, and providing educational materials, de-implementation support tools and educational/facilitation visits. A total of 61 issues were identified during the usability testing, of which eight were critical, 33 were moderately important, and 18 were minor. These issues led to numerous improvements, including the addition of information on the drivers and benefits of reducing low-value practices, changes in the definition of these practices, the addition of proposed strategies to facilitate de-implementation, and the tailoring of educational/facilitation visits. Conclusions We designed and refined a multifaceted intervention to reduce low-value injury care using a process that increases the likelihood of its acceptability and sustainability. The next step will be to evaluate the effectiveness of implementing this intervention using a pragmatic cluster randomized controlled trial. Trial registration This protocol has been registered on ClinicalTrials.gov (February 24th 2023, #NCT05744154, https://clinicaltrials.gov/ct2/show/NCT05744154 ).Item Open Access Examining factorial validity and internal consistency of Professional Quality of Life (ProQoL-9) among care aides working in Long-term Care (LTC)(2025-01-02) Saeidzadeh, Seyedehtanaz; Wang, Anni; Duan, Yinfei; Hipel, Isaiah; Norton, Peter G.; Estabrooks, Carole A.Abstract Background The ProQoL (30 items) is a widely used instrument of work-related quality of life for health care workers. Recently, a shorter 9-item version of the ProQoL was developed and validated among palliative care workers. The ProQoL-9 consists of three subscales: compassion satisfaction (CS), burnout (BO), and compassion fatigue (CF). Care aides (personal support workers, nursing assistants) are an understudied population in terms of their professional quality of life. It is critical to use validated instruments to measure their experiences. The purpose of this study was to examine the internal consistency and factorial structure of the ProQoL-9 among care aides working in LTC. Methods We used surveys collected by the Translating Research in Elder Care (TREC), a pan-Canadian program that collects longitudinal surveys from the healthcare workforce in the LTC. We used TREC surveys containing information on demographics, characteristics of LTC homes (e.g., ownership model), and the ProQoL-9. Our sample included all care aides who completed TREC surveys in the province of Alberta, Canada, from 2020–2021. We examined internal consistency via alpha and omega coefficients. To examine the factorial structure, we conducted confirmatory factor analysis (CFA) testing one factor, two factors (CF and BO together & CS), and three factor models (CF, BO, and CS). Results N = 760 care aides completed the surveys in Alberta. The majority were female (90.79%) and worked in general LTC units (55.29%). The Cronbach’s alpha results showed an overall α = 0.56 for the whole scale and adequate reliability of the subscales (α = 0.73 for CS, α = 0.68 for CF, and α = 0.75 for BO). The omega reliability results for all the subscales were ≥ 0.70, reflecting good internal consistency (BO = 0.77, CS = 0.73, and CF = 0.70). The three-factor model had the best goodness of fit values, reflecting an adequate goodness of fit (X2 = 165.82, DF = 24, X2/DF = 6.9, P < .0001, RMSEA = 0.08, CFI = 0.92, TLI = 0.89). Conclusions The ProQoL-9 is a valid and reliable instrument among care aides in LTC. The factorial structure shows that this shorter version of the ProQoL is rigorously designed and can be utilized by health service researchers in LTC.Item Open Access Approaches and outcomes of adalimumab discontinuation in patients with well-controlled inflammatory arthritis: a systematic search and review(2024-12-30) Balay-Dustrude, Erin; Fennell, Jessica; Baszis, Kevin; Goh, Y. I.; Horton, Daniel B.; Lee, Tzielan; Rotman, Chloe; Sutton, Anna; Twilt, Marinka; Halyabar, OlhaAbstract Objective This systematic search and review aimed to evaluate the available literature on discontinuation of adalimumab and other tumor necrosis factor inhibitors (TNFi) for patients with well-controlled chronic inflammatory arthritides. Methods We conducted a publication search on adalimumab discontinuation from 2000–2023 using PubMed, CINAHL, EMBASE, and Cochrane Library. Included studies evaluated adalimumab discontinuation approaches, tapering schemes, and outcomes including successful discontinuation and recapture after flare, in patients with well-controlled disease. Studies included evaluated rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and juvenile idiopathic arthritis (JIA). Results Forty-nine studies were included. Studies evaluating adalimumab alone were limited, and many reported TNFi outcomes as a single entity. Studies on rheumatoid arthritis (RA) (32, 8 RCTs) reported flare rates from 33–87%. Flares with medication tapering were slightly lower than with abrupt stop, and successful recapture was generally high (80–100%). Studies on spondyloarthropathy (12, 4 RCTs), focused on tapering, noting lower flare rates in tapering rather than abruptly stopping, and high recapture rates (~ 90%). Studies on JIA (5) were observational and demonstrated modestly lower flare rates with tapering (17–63%) versus abrupt stopping (28–82%). There was notable variability in study design, follow-up duration, specificity for TNFi results, and controlled pediatric studies. Conclusion The literature evaluating adalimumab and other TNFi discontinuation, flare rates, and recapture success within the inflammatory arthritis population demonstrated less flare when medications were tapered, over abrupt stop in the RA, spondyloarthropathy, and JIA populations. When medications were restarted after flare, recapture of well-controlled disease was generally high in RA and spondyloarthropathy, and generally favorable in JIA.Item Open Access Identification of progressive pulmonary fibrosis: consensus findings from a modified Delphi study(2024-12-31) Wells, Athol U.; Walsh, Simon L. F.; Adegunsoye, Ayodeji; Cottin, Vincent; Danoff, Sonye K.; Devaraj, Anand; Flaherty, Kevin R.; George, Peter M.; Johannson, Kerri A.; Kolb, Martin; Kondoh, Yasuhiro; Nicholson, Andrew G.; Tomassetti, Sara; Volkmann, Elizabeth R.; Brown, Kevin K.Abstract Background We sought consensus among practising respiratory physicians on the prediction, identification and monitoring of progression in patients with fibrosing interstitial lung disease (ILD) using a modified Delphi process. Methods Following a literature review, statements on the prediction, identification and monitoring of progression of ILD were developed by a panel of physicians with specialist expertise. Practising respiratory physicians were sent a survey asking them to indicate their level of agreement with these statements on a binary scale or 7-point Likert scale (− 3 to 3), or to select answers from a list. Consensus was considered to be achieved if ≥ 70% of respondents selected the same answer, or, for responses on a Likert scale, the median score was ≤ –2 (disagree/not important) or ≥ 2 (agree/important) with an interquartile range ≤ 1. There were three rounds of the survey. Results Surveys 1, 2 and 3 were completed by 207, 131 and 94 physicians, respectively, between March 2022 and July 2023. Decline in forced vital capacity (FVC), decline in diffusing capacity of the lungs for carbon monoxide, and increased fibrosis on high-resolution computed tomography (HRCT) were ranked as the most important endpoints for determining progression. Consensus was reached that progression on HRCT or a decline in FVC ≥ 10% from baseline is sufficient to determine progression, and that small declines in multiple endpoints indicates progression. Consensus was reached that a histological pattern of usual interstitial pneumonia (UIP) is a risk factor for progression of ILD, but that a biopsy to look for a UIP pattern should not be performed solely for prognostic reasons. Consensus was not reached on the time period over which progression should be defined. There was consensus that appropriate management of ILD depends on the type of ILD, and that ‘despite adequate management’ or ‘despite usual management’ should be included in the definition of progression. Conclusions This modified Delphi process provided consensus statements on the identification of ILD progression that were supported by a broad group of clinicians and may help to inform clinical practice until robust evidence-based guidelines are available.Item Open Access Therapeutic reduction of neurocan in murine intracerebral hemorrhage lesions promotes oligodendrogenesis and functional recovery(2025-01-04) Li, Hongmin; Ghorbani, Samira; Oladosu, Olayinka; Zhang, Ping; Visser, Frank; Dunn, Jeff; Zhang, Yunyan; Ling, Chang-Chun; Yong, V. W.; Xue, MengzhouAbstract Background Intracerebral hemorrhage (ICH) causes prominent deposition of extracellular matrix molecules, particularly the chondroitin sulphate proteoglycan (CSPG) member neurocan. In tissue culture, neurocan impedes the properties of oligodendrocytes. Whether therapeutic reduction of neurocan promotes oligodendrogenesis and functional recovery in ICH is unknown. Methods Mice were retro-orbitally injected with adeno-associated virus (AAV-CRISPR/Cas9) to reduce neurocan deposition after ICH induction by collagenase. Other groups of ICH mice were treated with vehicle or a drug that reduces CSPG synthesis, 4-4-difluoro-N-acetylglucosamine (difluorosamine). Rota-rod and grip strength behavioral tests were conducted over 7 or 14 days. Brain tissues were investigated for expression of neurocan by immunofluorescence microscopy and western blot analysis. Brain cryosections were also stained for microglia/macrophage phenotype, oligodendrocyte lineage cells and neuroblasts by immunofluorescence microscopy. Tissue structural changes were assessed using brain magnetic resonance imaging (MRI). Results The adeno-associated virus (AAV)-reduction of neurocan increased oligodendrocyte numbers and functional recovery in ICH. The small molecule inhibitor of CSPG synthesis, difluorosamine, lowered neurocan levels in lesions and elevated numbers of oligodendrocyte precursor cells, mature oligodendrocytes, and SOX2+ nestin+ neuroblasts in the perihematomal area. Difluorosamine shifted the degeneration-associated functional state of microglia/macrophages in ICH towards a regulatory phenotype. MRI analyses showed better fiber tract integrity in the penumbra of difluorosamine mice. These beneficial difluorosamine results were achieved with delayed (2 or 3 days) treatment after ICH. Conclusion Reducing neurocan deposition following ICH injury is a therapeutic approach to promote histological and behavioral recovery from the devastating stroke.Item Open Access Built environment change for injury prevention: insights from public health professionals across public health units in Ontario, Canada(2025-01-03) McCullogh, Emily; Macpherson, Alison; Harrington, Daniel W.; Pike, Ian; Hagel, Brent; Buchan, Claire; Fuselli, Pamela; Richmond, Sarah A.Abstract Background Road-related injuries and deaths are among the most significant and avoidable public health problems in Canada. Modifications to the built environment (BE) can reduce injury rates for vulnerable road users (VRUs) and other priority populations who experience disproportionate risk. This paper highlights public health professionals’ experiences working in injury prevention across Ontario public health units (PHUs) navigating barriers and facilitators to BE change. Their perspectives offer valuable insights that can support future BE change work in the Ontario public health context, thus illustrating the importance of including practitioners’ voices in injury prevention research. Methods Qualitative data were collected for a larger pan-Canadian study examining barriers and facilitators to BE change from the perspectives of injury prevention and transport professionals working across a variety of sectors, including public health, using key informant interviews (KI) and virtual focus groups (VFGs). Participants (n = 9) from four PHUs are included in this present study: Peel Region; York Region; Peterborough; and Ottawa. Thematic analysis was used to organize and code the data in relation to the guiding principles of the Ontario Public Health Standards (OPHS), situating our results within the broader context of public health and road-related injury prevention in Ontario. Results Major barriers included motor vehicle prioritization and decision-making structures. Facilitators included partnerships and collaboration, champions and advocates, and access to data. Lastly, participants highlighted the important role of public health in BE change discussions and decision-making for road-related injury prevention. Conclusion Public health professionals’ insights about barriers and facilitators show that some of their work aligns with the existing OPHS. Needs of local populations are clearly identified, while local data illustrating the impact of public health interventions are lacking. There are limits to PHU’s capacities, as well as the capacities of communities, which can be strengthened through the work of champions and advocates. Partnerships, collaboration, and engagement are also significant facilitators to BE change, aligning with the OPHS, but PHUs need to be involved more in BE change processes in order to prioritize the safety needs of VRUs in local communities.Item Open Access Ca2+ signaling in vascular smooth muscle and endothelial cells in blood vessel remodeling: a review(2024-12-27) Suzuki, Yoshiaki; Giles, Wayne R.; Zamponi, Gerald W.; Kondo, Rubii; Imaizumi, Yuji; Yamamura, HisaoAbstract Vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) act together to regulate blood pressure and systemic blood flow by appropriately adjusting blood vessel diameter in response to biochemical or biomechanical stimuli. Ion channels that are expressed in these cells regulate membrane potential and cytosolic Ca2+ concentration ([Ca2+]cyt) in response to such stimuli. The subsets of these ion channels involved in Ca2+ signaling often form molecular complexes with intracellular molecules via scaffolding proteins. This allows Ca2+ signaling to be tightly controlled in localized areas within the cell, resulting in a balanced vascular tone. When hypertensive stimuli are applied to blood vessels for extended periods, gene expression in these vascular cells can change dramatically. For example, alteration in ion channel expression often induces electrical remodeling that produces a depolarization of the membrane potential and elevated [Ca2+]cyt. Coupled with endothelial dysfunction blood vessels undergo functional remodeling characterized by enhanced vasoconstriction. In addition, pathological challenges to vascular cells can induce inflammatory gene products that may promote leukocyte infiltration, in part through Ca2+-dependent pathways. Macrophages accumulating in the vascular adventitia promote fibrosis through extracellular matrix turnover, and cause structural remodeling of blood vessels. This functional and structural remodeling often leads to chronic hypertension affecting not only blood vessels, but also multiple organs including the brain, kidneys, and heart, thus increasing the risk of severe cardiovascular events. In this review, we outline recent advances in multidisciplinary research concerning Ca2+ signaling in VSMCs and ECs, with an emphasis on the mechanisms underlying functional and structural vascular remodeling.Item Open Access Towards a histological diagnosis of childhood small vessel CNS vasculitis(2024-12-28) Nouri, Maryam N.; Dropol, Anastasia; Tyrrell, Pascal N.; Sheikh, Sheila; Twilt, Marinka; Michaud, Jean; Ellezam, Benjamin; Sarnat, Harvey B.; Dunham, Christopher; Schutz, Peter W.; Keith, Julia; Munoz, David G.; Vinters, Harry V.; Hawkins, Cynthia; Benseler, Susanne M.Abstract Background Primary small vessel CNS vasculitis (sv-cPACNS) is a challenging inflammatory brain disease in children. Brain biopsy is mandatory to confirm the diagnosis. This study aims to develop and validate a histological scoring tool for diagnosing small vessel CNS vasculitis. Methods A standardized brain biopsy scoring instrument was developed and applied to consecutive full-thickness brain biopsies of pediatric cases and controls at a single center. Stains included immunohistochemistry and Hematoxylin & Eosin. Nine North American neuropathologists, blinded to patients’ presentation, diagnosis, and therapy, scored de-identified biopsies independently. Results A total of 31 brain biopsy specimens from children with sv-cPACNS, 11 with epilepsy, and 11 with non-vasculitic inflammatory brain disease controls were included. Angiocentric inflammation in the cortex or white matter increases the likelihood of sv-cPACNS, with odds ratios (ORs) of 3.231 (95CI: 0.914–11.420, p = 0.067) and 3.923 (95CI: 1.13–13.6, p = 0.031). Moderate to severe inflammation in these regions is associated with a higher probability of sv-cPACNS, with ORs of 5.56 (95CI: 1.02–29.47, p = 0.046) in the cortex and 6.76 (95CI: 1.26–36.11, p = 0.025) in white matter. CD3, CD4, CD8, and CD20 cells predominated the inflammatory infiltrate. Reactive endothelium was strongly associated with sv-cPACNS, with an OR of 8.93 (p = 0.001). Features reported in adult sv-PACNS, including granulomas, necrosis, or fibrin deposits, were absent in all biopsies. The presence of leptomeningeal inflammation in isolation was non-diagnostic. Conclusion Distinct histological features were identified in sv-cPACNS biopsies, including moderate to severe angiocentric inflammatory infiltrates in the cortex or white matter, consisting of CD3, CD4, CD8, and CD20 cells, alongside reactive endothelium with specificity of 95%. In the first study of its kind proposing histological criteria for evaluating brain biopsies, we aim to precisely characterize the type and severity of the inflammatory response in patients with sv-cPACNS; this can enable consolidation of this population to assess outcomes and treatment methodologies comprehensively.Item Open Access Assessing the impact of the iPeer2Peer program for adolescents with juvenile idiopathic arthritis: a mixed-methods randomized controlled trial(2024-12-27) Nishat, Fareha; Kelenc, Lauren; Berard, Roberta; Duffy, Ciaran; Feldman, Brian; Forgeron, Paula; Huber, Adam M.; Luca, Nadia; Schmeling, Heinrike; Spiegel, Lynn; Tucker, Lori; Watanabe-Duffy, Karen; Killackey, Tieghan; Lalloo, Chitra; Wiles, Brittany; Nair, Anya; Olaizola, Sofia; McDermott, Brenna; Tavangar, Farideh; Kohut, Sara A.; Stinson, Jennifer N.Abstract Background Juvenile Idiopathic Arthritis (JIA) is a chronic pediatric illness, whereby youth experience physical, emotional and psychosocial challenges that result in reduced health related quality of life (HRQL). Peer mentoring has been shown to improve disease self-management in adults with chronic conditions, with mixed results in younger populations. Building on our pilot work – which supported the feasibility and initial effectiveness of the iPeer2Peer program – the objective of this study was to assess the clinical effectiveness of the program in youth with JIA through a waitlist randomized controlled trial. Methods Eighty-one youth (aged 12–18) were randomized to the intervention group and matched with trained peer mentors (18–25 years; successfully managing their JIA), completing of up to ten 30-min video calls over a 15-week period. Eighty-three youth in the control group received standard care. Outcome assessments occurred at enrollment, 15 weeks post randomization and 6-months post randomization. The primary outcome was self-management, measured using the TRANSITION-Q. Secondary outcomes were HRQL, pain, emotional distress, disease knowledge, self-efficacy, and perceived social support. These were assessed using linear mixed effects models. Content analysis of semi-structured interviews and focus groups was used to assess satisfaction with the program with mentors and mentees upon study completion. Results In total, 164 youth (mean age 14.4 ± 1.9 years, 78% female) were randomized to the study. The proposed sample size was not reached due to challenges in recruitment, likely impacted by the COVID-19 pandemic. The iPeer2Peer program did not show significant improvement in self-management (p = 0.7), or any of the secondary outcomes. Three key categories emerged from content analysis: (1) Fulfillment and Support Through Shared Experience, (2) Enhancing Program Delivery and (3) Strategies to Boost Engagement. These findings highlight that mentees valued the ability to converse with mentors who empathized with their disease experience, while mentors found it fulfilling to support mentees, and noted that they could have benefited from this type of support themselves. Conclusion While the iPeer2Peer did not result insignificant changes in clinical outcomes, both mentors and mentees were satisfied with the program and felt that mentorship provided real-world benefits for disease management and overall wellbeing. Trial registration ClinicalTrials.gov, NCT03116763. Registered 31, March 2017, https://www.clinicaltrials.gov/study/NCT03116763Item Open Access Extending the Calgary Audit and Feedback Framework into the virtual environment: a process evaluation and empiric evidence(2024-12-18) Woodhouse, Douglas; Duncan, Diane; Ferrie, Leah; Omodon, Onyebuchi; Mehta, Ashi; Pokharel, Surakshya; Ambasta, AnshulaAbstract Background The Calgary Audit and Feedback Framework (CAFF) is a pragmatic, evidence-based approach for the design and implementation of in-person social learning interventions using Audit and Group Feedback (AGF). This report describes extension of CAFF into the virtual environment as part of a multifaceted intervention bundle to reduce redundant daily laboratory testing in hospitals. We evaluate the process of extending CAFF in the virtual environment and share resulting evidence of participant engagement with planning for practice change. Methods We describe an innovative virtually facilitated AGF intervention based on the CAFF. The AGF intervention was part of an intervention bundle which included individual physician laboratory test utilization reports and educational tools to reduce redundant daily laboratory testing in hospitals. We used data from recorded and transcribed virtual AGF sessions, post AGF session surveys and detailed field notes maintained by project team members. We used simple descriptive statistics for quantitative data and analyzed qualitative data according to the elements of CAFF. Results Eighty-three physicians participated over twelve virtual AGF sessions conducted across four tertiary care hospitals during the study period. We demonstrate that all prerequisite activities for CAFF (relationship building, question choice and data representation) were present in every virtual AGF session. Virtual facilitation was effective in supporting the transition of participants through different steps of CAFF in each session to lead to change talk and planning. All participants contributed to discussion during the AGF sessions. The post AGF session surveys were filled by 66% of participants (55/83), with over 90% of respondents reporting that the session helped them improve practice. 46% of participants (38/83) completed personal commitment to change forms at the end of the sessions. Conclusions Virtual AGF sessions, developed and implemented with fidelity to the CAFF approach, successfully engaged physicians in a group learning environment that led to change planning. Further studies are needed to determine the generalizability of our findings and to add to the literature on evidence-based virtual facilitation techniques.Item Open Access PEARLS debriefing for social justice and equity: integrating health advocacy in simulation-based education(2024-12-18) Soilis, Niki; Kinsella, Elizabeth A.; Eppich, Walter; Cheng, Adam; Beavers, Lindsay; Bhanji, FarhanAbstract Addressing health inequities in health professions education is essential for preparing healthcare workers to meet the demands of diverse communities. While simulation has become a widely recognized and effective method for providing safe and authentic clinical learning experiences, there has been limited attention towards the power of simulation in preparing health practitioners to work with groups who experience health disparities due to systems of inequality. Balancing technical proficiency with educational approaches that foster critical reflection and inform action oriented towards social accountability is essential. Transformational learning promotes the development of critical consciousness through critical reflection. Debriefing plays a crucial role in fostering learning in this direction by providing a structured opportunity to critically reflect on taken for granted assumptions, examine power and privilege embedded within systems and structures, and empower learners to take action toward changing those conditions. Building on the Promoting Excellence and Reflective Learning in Simulation (PEARLS) Healthcare Debriefing Tool, we propose a PEARLS Debriefing for Social Justice and Equity (DSJE) Tool that specifically directs attention to systems of inequality that contribute to health disparities for vulnerable groups across a range of simulation scenarios. This approach has two aims: (a) to transform debriefings into a critically reflective space by engaging learners in dialogue about social and structural determinants of health that may create or perpetuate inequities and (b) to foster critical reflection on what actions can be taken to improve the health and well-being of identified at risk and vulnerable groups. From this perspective, we can use the adapted PEARLS Tool to incorporate conversations about systems of inequality, equity, diversity, and inclusion (EDI) into our existing educational practices, and make concentrated efforts towards community-driven and socially conscious simulation-based education (SBE).Item Open Access When common cognitive biases impact debriefing conversations(2024-12-18) Meguerdichian, Michael J.; Trottier, Dana G.; Campbell-Taylor, Kimberly; Bentley, Suzanne; Bryant, Kellie; Kolbe, Michaela; Grant, Vincent; Cheng, AdamAbstract Healthcare debriefing is a cognitively demanding conversation after a simulation or clinical experience that promotes reflection, underpinned by psychological safety and attention to learner needs. The process of debriefing requires mental processing that engages both “fast” or unconscious thinking and “slow” intentional thinking to be able to navigate the conversation. “Fast” thinking has the potential to surface cognitive biases that impact reflection and may negatively influence debriefer behaviors, debriefing strategies, and debriefing foundations. As a result, negative cognitive biases risk undermining learning outcomes from debriefing conversations. As the use of healthcare simulation is expanding, the need for faculty development specific to the roles bias plays is imperative. In this article, we hope to build awareness about common cognitive biases that may present in debriefing conversations so debriefers have the chance to begin the hard work of identifying and attending to their potential detrimental impacts.Item Open Access From ‘publish or perish’ to ‘publish with purpose’: perspectives from young adults with lived and living experience on transforming academic publishing in patient-oriented research(2024-12-20) Rao, Sandy; Jardine, Rae; Suthakaran, Abitha; Satam, Laetitia; Todorova, Antoaneta A.; Tumaneng, Ysabelle; Quickstad, JulienAbstract Background This commentary article critically assesses the inclusion and recognition of young adults with lived and living experiences (YALLE) in academic publishing. Stemming from our involvement in a health research study, this analysis interrogates the disparity between the stated importance of YALLE contributions in health research and their actual recognition, specifically in academic publications, which serve as the principal “currency” in research. This tokenism limits the potential for their unique insights to substantially enrich the discourse and dissemination of knowledge. Set against a backdrop of systemic biases and structural barriers, this discussion underscores the persistent minoritization of YALLE, despite increasing nominal recognition within academic and health research communities. Main text The commentary begins by placing the engagement of young adults in health research within its current context, showing that this inclusion often remains superficial, serving more as a symbolic gesture toward inclusivity rather than fostering genuine participatory research. It critiques the implicit biases within institutional frameworks that continue to shape research culture detrimentally, thus stifling the transformative potential of research led and partnered by young adults. The core of the narrative addresses the complex challenges faced by YALLE, including discrimination, underrecognition, and inadequate participatory roles in research processes. These issues are magnified by the prevalent “publish or perish” culture in academia, which prioritizes the quantity of scholarly output over the quality and inclusivity of research contributions. Conclusions The commentary advocates for a crucial shift in academic publishing to genuinely appreciate and integrate the contributions of young adults. We call for a transition from a “publish or perish” model to a “publish with purpose” approach, which necessitates rethinking what is considered valuable knowledge and who is acknowledged as its creators. This shift aims to cultivate an academic culture where knowledge is treated as a communal resource, and publications are used as tools to advance societal understanding and progress.