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Real-World Safety and Effectiveness of 24-Hour Foslevodopa/Foscarbidopa in Parkinson's Disease: ROSSINI Study 6-Month Interim Results
(2026-05-07) Jost, Wolfgang H.; Bergquist, Filip; Evans, Andrew; Hassin-Baer, Sharon; Hauser, Robert A.; Henriksen, Tove; Malaty, Irene A.; Mestre, Tiago A.; Mir, Pablo; Rodriguez, Ramon; Schwingenschuh, Petra; Simu, Mihaela; Bergmann, Lars; Zhou, Teresa T.; Caughlin, Sarah; Gopalkrishnan, Mallika; Kukreja, Pavnit; O’Meara, Marie; Parra, Juan C.; Shah, Megha B.; Aldred, Jason
Abstract Introduction Foslevodopa/foscarbidopa (LDp/CDp) is a nonsurgical 24-h continuous subcutaneous infusion for patients with advanced Parkinson’s disease (aPD) and motor fluctuations uncontrolled on oral medications. We present the first multicountry real-world data from routine clinical practice. Methods ROSSINI (NCT06107426) is an ongoing 3-year multicountry, prospective, observational study of adults with aPD who are LDp/CDp-naïve (cohort A) or transitioning from LDp/CDp open-label extension studies (NCT04379050/NCT04750226, cohort B). For this interim analysis, the primary endpoint was change from baseline to 6 months in OFF time [Movement Disorder Society Unified Parkinson’s Disease Rating Scale Part IV (MDS-UPDRS-IV) modified item 4.3]. Safety was assessed by monitoring adverse events (AEs). Interim results for 105 cohort A patients enrolled ≥ 6 months by March 24, 2025 are presented only; cohort B results were limited (n = 5). Mixed-effects models for repeated measurements (continuous outcomes) were utilized, adjusted for country. Results Cohort A patients had a mean (SD) age of 68.5 (9.5) years, PD duration of 12.1 (5.3) years, and least squares mean (SE) OFF time of 5.2 (0.6) h at baseline. Patients on LDp/CDp showed statistically significant reductions (95% CI) in OFF time [(− 2.8 h (− 3.6, − 1.9), P ≤ .001, n = 47/40 at baseline/month 6], dyskinesia time [− 1.8 h (− 2.6, − 0.9), P ≤ 0.001], MDS-UPDRS-III [− 5.0 (− 8.2, − 1.9), P = 0.002], Parkinson’s Disease Sleep Scale-2 [− 5.2 (− 8.0, − 2.4), P ≤ .001], and 39-item Parkinson’s Disease Questionnaire [PDQ-39, − 5.6 (− 9.2, − 2.0), P = .002] from baseline to month 6. Freezing of Gait Questionnaire, Gastrointestinal Dysfunction Scale in PD, and King’s PD Pain Scale likewise showed statistically significant decreases (P < .05). Overall, 58 (55.2%) reported ≥ 1 AE, primarily nonserious and mild-to-moderate (12.4% serious, 17.1% severe), with hallucinations and infusion site events the most frequently reported events (5.7% each). Conclusions ROSSINI demonstrates reductions in motor fluctuations and nonmotor symptoms, and increased quality of life in patients with aPD after 6 months of LDp/CDp treatment. The safety profile was consistent with clinical trials. Trial registration ClinicalTrials.gov identifier, NCT06107426.
Association between neurofilament light chain concentrations and outcomes in patients with moderate to severe traumatic brain injury: a systematic review and meta-analysis
(2026-05-04) Bouras, Marwan; Pageau, Mathieu; Gagnon, Marc-Aurèle; Costerousse, Olivier; Demers, Karolane; Grenier-Gagnon, Anouk; Isaac, Chartelin J.; Torkomyan, Tomas H.; Lauzier, François; Zarychanski, Ryan; Francoeur, Charles L.; Gerges, Peter; Abiala, Godwill; Moore, Lynne; Englis, Shane W.; Turgeon, Alexis F.
Abstract Background Moderate to severe traumatic brain injury (TBI) is associated with high rates of mortality and long-term disability. Accurate biomarkers are needed to predict longterm neurological outcomes and guide decision-making early after TBI. Neurofilament light chain (NfL), a structural protein of neurons, has emerged as a promising candidate, but its association with outcomes in this population remains uncertain. Methods We conducted a systematic review and meta-analysis to assess the association between blood or cerebrospinal fluid NfL concentrations and outcomes in adults with moderate to severe TBI. We searched MEDLINE, Embase, Cochrane CENTRAL and Web of Science from inception to October 2025. Eligible studies included cohort studies or randomized controlled trials reporting NfL levels measured during the acute phase and reporting at least one outcome of interest. Our primary outcome was long-term neurological function, defined as the latest available Glasgow Outcome Scale (GOS) or Glasgow Outcome Scale–Extended (GOS-E) score, dichotomized into unfavorable (GOS ≤ 3 or GOS-E ≤ 4) and favorable (GOS > 3 or GOS-E > 4). Mortality, at any time point, was a secondary outcome. Risk of bias was assessed using an adapted scale from the QUADAS-2 tool, and certainty of evidence was evaluated using GRADE criteria. Results Fourteen studies (2,905 participants) were included, with ten (n = 1,648) contributing to the meta-analysis for our primary outcome. Higher NfL concentrations were associated with unfavorable neurological outcomes, with moderately higher levels in patients with poor outcomes compared with those with favorable outcomes (SMD 0.45, 95% CI 0.33–0.56; I² = 12%). Six studies (n = 483) assessed mortality; higher NfL concentrations were associated with increased mortality (SMD 0.71, 95% CI 0.04–1.39; I² = 82%), with a more consistent association when NfL was measured within 24 h after injury (I² = 0%). The certainty of evidence was graded as very low for both outcomes, reflecting risk of bias and, for mortality, additional inconsistency and imprecision. Conclusions Higher NfL concentrations were associated with unfavorable neurological outcomes after moderate-to-severe TBI. The association with mortality was more uncertain and should be interpreted with caution given the substantial heterogeneity across studies. Its incremental prognostic value beyond known predictors remains uncertain. Trial registration PROSPERO CRD42022332110, 22 May 2022.
Monitoring and evaluation strategies for surgical task-shifting and task-sharing interventions: a scoping review
(2026-03-26) Binda, Catherine; Livergant, Rachel; Tersago, Jamie; Jami, Zainab; Chen, Le Q.; Birch, Leah; Blackman, Chloe; Chin, Esther; Wild, Hannah; Joos, Emilie; Joharifard, Shahrzad
Abstract Background Task shifting and task sharing (TS/S) redistribute responsibilities across cadres to expand access to healthcare, particularly in underserved areas. TS/S addresses workforce shortages and improves the availability of essential surgical procedures. The scope and geographical distribution of surgical TS/S programs are well documented, less is known about how TS/S initiatives are monitored and evaluated, especially with respect to trainee, program, and health systems outcomes. This review describes existing approaches to evaluation within surgical TS/S initiatives. Methods We searched nine electronic databases (MEDLINE [Ovid], Embase [Ovid], CINAHL [EBSCO], Scopus, CABI Digital Library, Clarivate Web of Science, Evidence Aid, Global Index Medicus, and Eldis) on 31 January 2024 and 12 March 2025, using MeSH terms and keywords related to “Task Sharing” AND “Surgery”. All patient populations, practice settings, surgical skills, and study designs were eligible. No language or time restrictions were utilized. Publications that did not describe the evaluation of surgical skills, or that focused on skills within a practitioner’s typical scope of practice, were excluded. Two reviewers independently screened and extracted data. Risk of bias was assessed with MINORS. Findings were synthesized using inductive content analysis. Results were tabulated and presented graphically. Results Of 2483 identified records, 1609 unique publications were screened, 452 underwent full-text review, and 228 were included in the review. Most studies reported surgical TS/S in low-income countries (41.7%, 95/228). Obstetric and gynaecological procedures were most commonly taught (61.4%, 140/228). In total, 1753 examples of evaluation metrics were extracted from the 228 included publications. The evaluation metrics were sorted into three themes, including metrics that evaluated TS/S providers (72.6%, 1272/1753), training programs (7.5%, 132/1753), and systems (19.9%, 349/1753). Conclusion This scoping review comprehensively describes existing evaluation strategies. While evaluation of surgical TS/S initiatives remains heterogeneous, limiting the generalizability of any single approach, we successfully grouped monitoring and evaluation metrics into three key domains: provider, program, and health systems. Future work should focus on proposing a comprehensive but adaptable monitoring and evaluation framework that can be used by surgical TS/S programs across the globe.
Development of an infant and early childhood mental health service at a tertiary care pediatric hospital: a needs assessment, community case study and logic model creation
(2026-03-26) M Matheson, Katherine; de Schaetzen, Constance; Sheridan, Nicole; Holahan, Anne-Lise; Vloet, Melissa; Gray, Sarah; Carstens, Jenny; Postl, Lara; Deren, Barbara; Pajer, Kathleen
Abstract Introduction Early attachment relationships and positive childhood experiences are foundational to lifelong mental health, yet specialized services for children under six remain critically scarce. This study sought to characterize the service gap in infant and early childhood mental health (IECMH) in Eastern Ontario, Canada, as a first step in developing a logic model to inform creation of a program to support this population. Methods We completed a regional estimation model of IECMH concerns, conducted a semi-structured focus group with community mental health agencies, and administered a survey to pediatric physicians at a regional children’s hospital. Findings from the aforementioned evaluations informed the development of a logic model for a new, responsive, tertiary-level IECMH service. Results Disruptive behaviours emerged as the most frequently encountered IECMH concern, and respondents identified multiple systemic barriers to accessing care, including insufficient specialist services, prolonged wait times, limited inter-agency collaboration, and a lack of provider awareness and resources. These findings underscored the urgent need to use the logic model to develop a dedicated IECMH clinic, tailored to the unique needs of this vulnerable population. Discussion While developed within a Canadian regional context, this framework may serve as a flexible template for other jurisdictions seeking to establish or strengthen tertiary-level IECMH services. Adaptation to local service structures, workforce capacity, and population needs will be essential to ensure feasibility and sustainability. Future evaluation will be necessary to assess implementation outcomes, service utilization, and impact on child and family trajectories.
Optimizing future Telehealth mental health programs: a secondary analysis of a prospective cohort study to identify key predictors of intervention response in the Telehealth intervention program for older adults (TIP-OA)
(2026-03-31) Rigas, Christina; Lavin, Paola; Su, Chien-Lin; Hassan, Mahdi; Cinalioglu, Karin; Vacaflor, Blanca; Dikaios, Elena; Goodman, Allana; Ibrahim, Marim; Gruber, Johanna; Se, Jade; Sasi, Neeti; Nazar, Rim; Bodenstein, Katie; Elbaz, Sasha; Fajzel, Hannah; Berkani, Sonia; Hanganu, Cezara; Noble, Helen; Looper, Karl; Bouchard, Stephane; Seitz, Dallas; Kumar, Sanjeev; Beauchet, Olivier; Launay, Cyrille; McDonald, Emily; Khoury, Bassam; Ryder, Andrew; Battistini, Bruno; Fallavollita, Pascal; Vahia, Ipsit; Sekhon, Harmehr; Bukhari, Syeda; Rej, Soham
Abstract Background The Telehealth Intervention Program for Older Adults (TIP-OA) was a volunteer-based phone support program for to older adults during the COVID-19 pandemic. While volunteer-based phone programs can be effective in providing mental health support, there is limited data on the predictors of response to such interventions. This study aimed to examine clinical and demographic predictors of response to the TIP-OA intervention among older adults. Methods This secondary analysis of a prospective cohort study included 82 TIP-OA users who expressed interest in the program’s research component, met inclusion criteria, and provided informed consent. Participants completed both baseline and 8-week assessments or had 4-week data carried forward using the last observation carried forward (LOCF) method. The intervention consisted of weekly supportive phone calls over eight weeks. Baseline mental health risk level was assessed by clinicians during intake and categorized as low, medium, or high based on symptom severity within specific symptom categories. Associations between baseline risk level and changes in stress (primary outcome), depression, and anxiety (secondary outcomes) were examined. The primary outcome was measured by the Perceived Stress Scale (PSS; scores ranging from 0 (never) to 4 (very often)). Secondary outcomes were measured by the Patient Health Questionnaire-9 (PHQ-9; scores ranging from 0 (not at all) to 3 (nearly every day)), and the Generalized Anxiety Disorder-7 scale (GAD-7; scores can range from 0 (not at all sure) to 3 (nearly every day)). Results At 8 -week follow-up assessment, participants with higher baseline risk levels showed greater reductions in stress (mean difference in Perceived Stress Scale reduction by 2.13, (F(1,77) = 2.82, p = 0.09, 95% CI [−0.46, 5.56]) and depression (t(73) = −1.92, p = 0.059; Std. beta = −0.43, 95% CI [−0.87, 0.02]). Additionally, not identifying as a visible minority predicted lower stress scores, while male gender and a university education level were associated with greater reductions in depression scores. Conclusion TIP-OA participants with higher baseline mental health risk appeared to benefit more in terms of reductions in stress and depression. Non-minority status, male gender, and university education were also associated with better post-intervention outcomes in depression. Future studies should explore predictors of response in similar intervention programs through larger confirmatory studies. Trial registration Registered on clinicaltrials.gov (clinical trial no.: #NCT04523610) on 16/07/2020.
Defining and measuring implementation climate: a scoping review and concept analysis
(2026-03-19) Elakpa, Daniel N.; Thomas, Aliki; Lambert, Sylvie; Fontaine, Guillaume
Abstract Background Implementation climate is a key organizational determinant of whether evidence-based interventions (EBIs) are adopted, delivered with fidelity, and sustained in healthcare. Despite its importance, the concept is inconsistently defined, often conflated with culture or readiness, and assessed with measures of unclear scope. We aimed to clarify how implementation climate is defined and used in healthcare, identify its defining attributes, antecedents, and consequences, delineate boundaries with related constructs, and synthesize quantitative and qualitative approaches to measurement. Methods We combined a Joanna Briggs Institute (JBI) scoping review with Walker and Avant’s eight-step concept analysis method. CINAHL, Embase, MEDLINE, and PsycINFO were searched in November 2024, supplemented by citation tracking and grey literature searching. Empirical and theoretical articles that defined, discussed or measured implementation climate in healthcare were eligible. Data were charted in Excel and synthesised inductively to derive definitions, attributes, antecedents, consequences, conceptual boundaries, and measurement indicators; attributes were mapped to the Consolidated Framework for Implementation Research (CFIR). Results We included 39 sources (24 quantitative, 7 qualitative, 5 theoretical/review, 3 mixed-methods). We propose a synthesized definition: implementation climate is the shared perception among staff that using a specific EBI is an organizational priority, actively supported through resources and HR processes, reinforced by incentives or recognition, and aligned with everyday values and workflows. Seven recurring attributes emerged: clear expectations for EBI use; tangible organizational support (e.g., protected time, training, leadership); incentives and recognition; compatibility with workflow and values; high relative priority; tension for change; and HR practices that select and socialize staff for EBI openness. Transformational leadership and deliberate resource allocation surfaced as dominant antecedents. Stronger implementation climates were associated with improved implementation outcomes (e.g., reach and fidelity) and workforce outcomes (e.g., retention, lower burnout). Measurement options include the Implementation Climate Scale (ICS), the briefer Implementation Climate Measure (ICM), the Equity-Oriented Implementation Climate tool, and qualitative assessments. Conclusion Implementation climate is a modifiable, measurable organizational lever for strengthening quality improvement and implementation efforts. Leaders can strengthen it by clarifying expectations, protecting time and training, aligning incentives, and ensuring workflow fit. Researchers should refine and adapt measures across contexts and test objective indicators alongside staff perceptions.
Frailty and long-term mortality in cardiogenic shock: a binational multicentre cohort study
(2026-03-25) Ling, Ryan R.; Lim, Shir L.; Kaye, David M.; Lim, Oliver; Low, Christopher J. W.; MacLaren, Graeme; McIsaac, Daniel I.; Shekar, Kiran; Ueno, Ryo; Pilcher, David; Ramanathan, Kollengode; Subramaniam, Ashwin
Abstract Background Frailty is increasingly recognised as a prognostic marker in cardiovascular disease, but its role in cardiogenic shock is less defined. Methods In this retrospective cohort study across 188 intensive care units (ICUs), we analysed data from the Australia and New Zealand Intensive Care Society Adult Patient Database on adults (≥ 16 years) with admitted with cardiogenic shock between 2017–2023, and a documented Clinical Frailty Scale (CFS). The primary outcome was death at up to four years using an adjusted Cox proportional hazards model, which we also assessed using a time-varying model. We conducted subgroup analyses based on age, sex, aetiology of cardiogenic shock, and a landmark survival analysis at ICU discharge. Results We included 71,359 patients (median age 68.6 years, 70.0% males); 11,087 had frailty. Frailty was associated with a higher hazard of death (adjusted Hazard ratio [aHR]: 2.27, 95% confidence interval [CI]: 2.05–2.51) in a non-linear incremental fashion; this was consistent across sensitivity analyses. Time-varying analysis found that frailty demonstrated the highest hazard for death at approximately six months post-ICU admission (HR: 3.71, 95%-CI: 3.29–4.18). Frailty was more strongly associated with death in patients with ischaemic than non-ischaemic cardiogenic shock, and in males more than females. Frailty was also associated with death in a landmark survival analysis at ICU discharge (aHR: 3.13, 95%-CI: 2.82–3.48). Conclusions Frailty is associated with mortality beyond ICU discharge in cardiogenic shock in a non-linear, stepwise fashion. These findings support the integration of frailty assessment into ICU risk stratification and post-discharge care planning.
Baseline disease duration of chronic spontaneous urticaria participants in phase III clinical trials
(2026-03-25) Gupta, Sana; Rao, Vinesh; Xiong, Grace; Abu-Hilal, Mohannad
Abstract Chronic spontaneous urticaria often follows a prolonged and variable course, yet baseline disease duration is inconsistently reported in clinical trials, limiting interpretation of treatment outcomes. Accordingly, this systematic review aimed to evaluate baseline disease duration and reporting practices in phase-III trials for chronic spontaneous urticaria. Of 36 trials identified, only 16 (44.4%) reported baseline disease duration (mean: 5.30 ± 1.81 years). Differences in average disease duration were observed by publication date and intervention of interest. Definitions of disease duration were frequently unspecified, and no trials examined efficacy stratified by disease duration. This review ultimately highlights a gap in disease duration reporting, underscoring the need for standardization and transparency in clinical trial design.
Theory and behaviour change techniques informing strategies to improve recruitment to clinical trials: a systematic review of randomised evaluations
(2026-03-25) Hudek, Natasha; Carroll, Kelly; Semchishen, Seana N.; Presseau, Justin; Gillies, Katie; Grimshaw, Jeremy; Fergusson, Dean A.; Graham, Ian D.; Taljaard, Monica; Brehaut, Jamie C.
Abstract Introduction Efficiently meeting recruitment targets is foundational to clinical trial success. Past reviews on improving recruitment efficiency have highlighted only a few evidence-supported strategies; some of which may be context-specific, infeasible, or unsustainable. Re-framing research participation as a behaviour subject to the same forces as other human behaviours allows us to consider whether knowledge about behaviour change in other contexts can be applied to trial recruitment, potentially leading to more efficient theory-informed strategies. This study assessed randomised evaluations of recruitment interventions regarding (1) whether and how they reported using theory and (2) the extent behaviour change techniques (BCTs) were identifiable within recruitment methods and interventions. Methods We examined reports of randomised evaluations of recruitment interventions from a Cochrane review of trials evaluating strategies to improve recruitment, and the online resource for research in clinical trials database. To be eligible, studies had to include recruitment or willingness-to-participate outcomes. First, we assessed how and to what extent authors reported using theories, models, or frameworks in any part of their trial. Second, we extracted use of BCTs from study recruitment methods guided by the BCT taxonomy. Results We included 122 recruitment intervention studies. Few (n = 23, 19%) explicitly reported theory, model, or framework use; most often, theory was used to inform the intervention design (n = 15, 12%) or justification (n = 14, 11%). The most frequently cited theories included the theory of planned behaviour (n = 7, 6%) and prospect theory (n = 3, 3%). Studies contained anywhere from one identifiable BCT (n = 43, 35%) up to seven (n = 2, 2%); these typically included providing information about health consequences (e.g. side effects; n = 25, 21%), information about social and environmental consequences (e.g. helping society; n = 30, 25%), and prompts/cues (e.g. reminders; n = 25, 21%). Many studies did not report any codable BCTs (n = 35, 29%). Conclusions Studies evaluating recruitment interventions often fail to report any consideration of theories, models, or frameworks, and many well-understood behaviour change techniques are generally not reported. Future research that frames clinical trial participation as one or more behaviours may broaden the range of empirically based strategies available to support participation and lead to more productive evaluations of theory-guided, elemental, and empirically supported recruitment strategies.
Development and application of a scoring and visualization approach for 24-hour movement behaviours: an example based on social-emotional development in early years children
(2026-03-24) Zahran, Samah; Dumuid, Dorothea; Tremblay, Mark S.; Cliff, Dylan P.; Antczak, Devan; Aadland, Eivind; Anam, Emad A.; Aadland, Katrine N.; Christian, Hayley; Burley, Jade; Draper, Catherine E.; Silva, Diego A. S.; van Sluijs, Esther M.; Olds, Timothy S.; Stanford, Ty; Santos, Rute; Zhang, Zhiguang; Janssen, Ian
Abstract Background Current methods for assessing the healthfulness of 24-hour movement behaviours (sleep, sedentary time, light physical activity, moderate-to-vigorous physical activity) use binary classifications that fail to capture their continuous and compositional nature. This study introduces a percentile-based scoring and visualization approach to evaluate the healthfulness of movement behaviour time-use compositions, using social-emotional development in early childhood as an example. Methods This cross-sectional study includes 560 children aged 1.2–2.9 years and 1,500 children aged 3.0-4.9 years from Sleep and Activity Database for the Early Years (SADEY), an international accelerometer repository of young children’s movement behaviours. Sedentary time, light physical activity, and moderate-to-vigorous physical activity were measured using accelerometers. Sleep duration was parent-reported. Social-emotional development was assessed using age- and sex-normalized scores from the Strengths and Difficulties Questionnaire. Linear regression models with compositional covariates were used to model associations between movement behaviours and Strengths and Difficulties Questionnaire scores. Representative grids containing all possible time-use compositions (in 5 min/d increments) of sleep, sedentary time, light physical activity, and moderate-to-vigorous physical activity were developed. The regression models were applied to each time-use composition in the grid, and the predicted scores were ranked to create percentile scores for different movement behaviour time-use compositions. Results The 24-hour movement behaviour composition was associated with all five Strengths and Difficulties Questionnaire scores in both age groups (p ≤ 0.01). The grids contained 17,577 and 16,535 possible time-use compositions for 1–2 and 3–4-year-olds, respectively. Time-use compositions ranked at the 0th percentile had the least sleep and highest sedentary time, while those ranked at the 100th percentile had the most sleep and least sedentary time. Across the central range of the percentile score distribution (e.g., rankings between the 25th to 75th percentiles), some very different time-use compositions had the same percentile score. Interactive visualization tools were presented to enable real-time exploration of percentile scores for various movement behaviour time-use compositions. Conclusions This study introduces a novel approach to evaluate the health benefits of movement behaviours. This approach moves beyond traditional binary cutoffs to recognize the gradual improvements in health that occur with small changes in behaviours, and that there are multiple pathways to achieving the same health benefits.
Canadian mines, global issues: examining health impacts, demanding action
(2026-03-26) Spitzer, Denise L.; Castro-Palaganas, Erlinda; Simons, Penelope; Dzhusupov, Kenesh; Wittlin, Flavio; Grassman, Jean; Baker, Janelle; Labonté, Ronald
Abstract Background While a global player in the mining and metals sector, there is little regulatory oversight by Canada of Canadian mining companies in relation to their transnational activities. Much mineral exploration and mining take place in remote and rural areas inhabited by Indigenous and other minoritized and/or marginalized communities, and has been linked to worsening health, social, and environmental conditions. Few effective legal mechanisms exist to monitor, investigate, and provide effective remedies for their harmful impacts. Methods Three focal mining communities representing different mining life stages were studied: exploratory phase (Philippines), midlife (Brazil), and a transitioning to end-stage that has now been reinvigorated post-nationalization (Kyrgyz Republic). A qualitative approach based on locale-specific community consultations was employed with analysis informed by a theoretical framework based on the commercial, political, and social determinants of health, environmental justice, and their interactive and embodied impacts. Results and discussion The community consultations yielded the following notable findings: a failure to acknowledge Indigenous rights (all sites); intimidation and harassment of local residents raising objections (Brazil and Philippines); the centrality of mines entrench social and economic inequities —including pre-existing ones (all sites); prior experience and knowledge of harms linked to extractive resource industries affect perception and resistance to mines (Brazil and Philippines) and the presence of widespread illness and disease among miners (Brazil and Kyrgyz Republic). Participants expressed support for community-driven mining and health studies documenting long-term occupational and environmental health impacts, particularly respiratory and water-borne illnesses. Conclusions Despite the lethargy, obfuscation, and refusal of the Canadian government to take action on the global interests and actions of its corporations operating abroad, local efforts to resist the experienced and potential harms of transnational Canadian mining operations are noteworthy. Canada must comply with its binding international human rights obligations and move beyond its failed policy approach to addressing the harmful impacts of these endeavours. Future research must be conducted with and be accountable to local communities. Clinical trial number Not applicable.
Digenic inheritance of mutations in SPG7 and AFG3L2 causes motor neuron and cerebellar disorders
(2026-03-24) Estiar, Mehrdad A.; Yu, Eric; Varghaei, Parizad; Ross, Jay P.; Ashtiani, Setareh; Bayne, Andrew N.; Coarelli, Giulia; Timmann, Dagmar; Klockgether, Thomas; Beijer, Danique; Mengel, David; Coutelier, Marie; Dion, Patrick A.; Suchowersky, Oksana; Ewenczyk, Claire; Goizet, Cyril; Stevanin, Giovanni; Van Damme, Philip; Al-Chalabi, Ammar; Zuchner, Stephan; Synofzik, Matthis; Veldink, Jan H.; Trempe, Jean-Francois; Durr, Alexandra; Rouleau, Guy A.; Gan-Or, Ziv
Abstract Background Biallelic SPG7 mutations cause one of the most common forms of hereditary spastic paraplegia (HSP). Several reports have suggested that heterozygous SPG7 variants may also play a role in HSP, but also in amyotrophic lateral sclerosis (ALS). However, it remains controversial whether heterozygous SPG7 mutations are pathogenic on their own, or if other mechanisms are at play. We recently provided evidence for non-Mendelian inheritance in spastic paraplegia 7 (SPG7), as heterozygous carriers of SPG7 mutations often also carried mutations in other disease-related genes, including AFG3L2, more frequently than expected by chance. Given that SPG7 and AFG3L2 encode interacting subunits of the mitochondrial m-AAA protease complex, we hypothesized that combined heterozygous mutations in these genes may act synergistically to disrupt mitochondrial function and contribute to disease. In this study, we aimed to examine whether digenic heterozygous mutations in SPG7 and AFG3L2 can lead to a spectrum of neurodegenerative disorders. Methods We first analyzed genome and exome sequencing data of 6644 unrelated individuals including 4817 motor neuron disorder (MND) and ataxia patients and 1827 controls. We next analyzed an additional 18,748 exome data from rare disease cohorts to further examine the occurrence of variants in SPG7 and AFG3L2. Results Among the first 4817 MND and ataxia patients, we identified a total of 6 patients, 4 of whom were unrelated, who carried potentially pathogenic variants in both SPG7 and AFG3L2, in contrast to none in 1827 unrelated controls. Further analysis of the 18,748 additional patients with rare disease, as well as a comprehensive literature review, identified 6 more patients, 5 of whom were unrelated, who had digenic mutations in SPG7 and AFG3L2. In the two families we identified, digenic mutations in SPG7 and AFG3L2 perfectly segregated with the disease. The 12 patients reported here exhibited predominant signs of motor neuron and cerebellar involvement. Conclusions Our findings demonstrate that digenic inheritance of concurrent heterozygous mutations in SPG7 and AFG3L2 may cause motor neuron and cerebellar disorders. Screening of the entire SPG7 and AFG3L2 genes in genetically undiagnosed cases of MND and spastic ataxia may help to increase the diagnostic yield.
Associations between maternal race, socioeconomic status and shoulder dystocia: a population-based retrospective cohort study in Ontario Canada
(2026-03-21) Miao, Qun; Guo, Yanfang; Maxwell, Cynthia; Wen, Shi W.; St. Hill, Alicia; Dingwall-Harvey, Alysha; Kuepfer, Tammy; Walker, Mark
Abstract Background Shoulder dystocia is a severe and emergent adverse perinatal complication. Existing literature suggests that the risk of shoulder dystocia varies by race and socioeconomic status, but research in this area is lacking in Canada. Objectives To examine variations of shoulder dystocia by maternal race and maternal socioeconomic status and evaluate the interaction between race and macrosomia on the occurrence of shoulder dystocia. Study design We conducted a population-based retrospective cohort study including White and Black pregnant people who participated in prenatal screening and had singleton stillbirths or live hospital births, excluding those with no-labour caesarean deliveries, from January 1, 2013 to March 31, 2021 in Ontario, Canada. The BORN Information System and Canadian Institute for Health Information databases were linked for analysis. We used multivariable Poisson regression with robust error variance models to examine the association between maternal race, neighbourhood household median income and educational level, and shoulder dystocia, while adjusting for maternal age, parity, previous caesarean section, obesity, substance use, pre-existing physical and mental health conditions, gestational diabetes, obstetrician in antenatal care team, hospital level of maternal care, gestational age, infant sex and rural residence. The interaction between maternal race and fetal macrosomia on the outcome of shoulder dystocia was evaluated. Results Among the total cohort of 422,580 pregnant individuals, 10.2% were Black individuals and 89.8% were White individuals. The incidence of shoulder dystocia was 4.4% (N = 18,592) among the entire cohort, 4.4% (N = 16,739) among White individuals and 4.3% (N = 1,853) among Black individuals. There was a statistically significant interaction (P < 0.001) between maternal race and infant macrosomia on shoulder dystocia. Among the sub-cohort of pregnant individuals giving birth to infants with macrosomia, Black individuals had a 17% higher risk of experiencing shoulder dystocia (aRR: 1.17, 95% CI: 1.08–1.28) than White individuals. Individuals living in the lowest-income and least educated neighborhoods had a 19% and 25% higher risk of experiencing shoulder dystocia, respectively, compared to those in the wealthiest or most educated neighborhoods. However, no significant racial or household income differences on shoulder dystocia were observed among those giving birth to non-macrosomic infants. Conclusion The higher risk of shoulder dystocia among birthing individuals in lower socioeconomic status neighborhoods, coupled with the elevated risk for Black individuals at the same socioeconomic status level, suggests a double burden faced by Black individuals under Ontario’s universal healthcare system. The relationships between race, socioeconomic status, and macrosomia in shoulder dystocia are complex, highlighting the need for further studies to investigate potential racial disparities and discrimination. There is a need for policies and interventions that specifically address these inequities among Black communities to improve healthcare in Ontario.
A meta-review of patient engagement, shared decision-making, and factors influencing equity-deserving populations’ participation in clinical trials
(2026-03-16) Morgan, Tamara L.; Carroll, Kelly; Waqar, Anosha; Hudek, Natasha; Mosa, Meena; Richards, Dawn P.; Meeking, Kim; Granieri, Marisa; Smith, Maureen; Walz, Murray; Etherington, Cole; Marlin, Susan; Gillies, Katie; Presseau, Justin; Brehaut, Jamie C.
Abstract Background Many equity-deserving populations, including those facing structural health inequities, lack support to participate in clinical trials while facing barriers to participation. Two approaches—patient engagement (PE) and shared decision-making (SDM)—can help trialists better understand and address such barriers. PE can improve the relevance of trials to silenced communities while SDM can align participation decisions among socially disadvantaged groups with their values, needs, and preferences, which may help overcome health inequities. Further, Indigenous community engagement is vital to address the effects of colonialism and promote Indigenous self-determination and health equity. The extent to which existing reviews have identified common barriers, enablers, and strategies across equity-deserving groups and discussed PE and SDM concepts is unclear. Purpose (1) To describe which equity-deserving populations have been the focus of reviews on clinical trial participation and which barriers, enablers, and strategies are relevant to them (2) to explore the extent to which PE and SDM are discussed in these reviews. Methods We searched for English-language reviews (including any study design) summarizing trial participation barriers, enablers, and/or strategies among equity-deserving populations in five peer-reviewed databases. We coded data on the (1) equity-deserving population(s) of focus, (2) barriers, enablers, or interventions/strategies mentioned, (3) PE reported, (4) Indigenous community engagement reported, and (5) SDM outcomes discussed. Results Findings from 100 reviews showed that some equity-deserving populations have been represented more than others (e.g., 76% on racially, ethnically, culturally, or linguistically diverse populations; 29% on sex and gender populations; 2% on educationally disadvantaged populations). More reviews described barriers (84%) than enablers (31%) or strategies to improve participation (69%). Forty-five reviews (45%) reported PE while 11 (11%) reported Indigenous community engagement. Many reviews (74%) mentioned SDM outcomes (i.e., 9/11 [81.8%] outcomes from Gillies et al.’s internationally agreed core outcome set); however, few reviews (29%) discussed SDM outcomes in detail. Conclusions Our findings suggest that PE and SDM could be more broadly applied among multiple equity-deserving groups to better serve disadvantaged communities. We advocate for an expanded focus on less-researched equity-deserving groups, improved PE reporting, prioritization of patient outcomes, and engagement with patients and Indigenous communities.
ASSeTS: a systematic review and development of the World Health Organization’s classification system for social isolation and loneliness interventions
(2026-03-15) Surkalim, D. L.; Farzana, A.; Choo, W. Y.; Hussein, S.; Hébert, P. C.; Welch, V.; Tanjong Ghogomu, E.; Mikton, C.
Abstract Background Social isolation and loneliness (SIL) have emerged as critical population health concerns linked to various adverse health outcomes, including cardiovascular disease, stroke, dementia, depression, and premature mortality. However, the absence of a standard categorization for interventions aimed at reducing SIL has impeded consistent comparison, evaluation, and the accumulation of knowledge, affecting evidence-based policy decisions. To address this gap, we developed and empirically evaluated the ASSeTS (Access, Skills, Social engagement, Therapeutic and psychological, Systemic) classification system, a standardized approach for categorizing SIL interventions. Methods We conducted a systematic review to identify and evaluate existing classification systems used for SIL interventions. Seventeen databases were searched from inception to September 2023, with no language restrictions. Inclusion criteria encompassed established and widely used reviews with clear intervention categorizations and broad applicability to general population groups. Expert consultations supplemented the systematic review, providing iterative feedback and additional relevant literature missed from the literature search, to inform the development of the ASSeTS classification framework. The developed ASSeTS system was empirically tested by independent experts for clarity, applicability, and reliability, with inter-rater agreement assessed using Fleiss’ kappa. Results The review identified 11 studies covering a range of SIL intervention categorization approaches. Based on synthesis and expert feedback, the ASSeTS system was structured into five main categories: Access, Skills, Social engagement, Therapeutic and psychological, and Systemic interventions. Empirical testing yielded moderate inter-rater reliability (κ = 0.419), indicating acceptable usability among expert raters. Higher agreement was found for categories such as therapeutic and psychological interventions, whereas systemic interventions showed lower reliability, suggesting opportunities for future refinement. Conclusion The ASSeTS classification system provides a much-needed standardized framework for categorizing SIL interventions, facilitating comparability, rigorous evaluation, cumulative knowledge, and evidence-based policy decisions. Future work should focus on refining less reliable categories, validating ASSeTS across various contexts, and integrating it into global policy frameworks to more effectively address the public health implications of SIL.
A cognitive accessibility review of national palliative care resources with people with cognitive disabilities
(2026-03-14) Er-raji, Niima; Tahir, Munazza; Martin, Lynn
Abstract Background People with cognitive disabilities (including developmental disabilities and dementia) face significant inequities in accessing palliative care information and services. Accessible communication plays a critical role in enabling meaningful participation in care, yet few national palliative care resources are evaluated with direct input from people with lived experience. Methods A qualitative descriptive study engaged eight individuals with lived experience of cognitive disabilities as cognitive accessibility experts. These individuals reviewed three palliative care resources (in English or French) and participated in semi structured virtual interviews. Data were analyzed to identify accessibility challenges, strengths of resources, and actionable recommendations. Results The analysis revealed challenges such as dense vocabulary, abstract phrasing, and inconsistent sequencing. At the same time, cognitive accessibility experts by experience identified strengths, including plain-language sections, clear segmentation, simple visual layouts, and useful questions to ask healthcare providers. In particular, their comments praised the organization, straightforwardness, and readability. Based on these insights, cognitive accessibility experts by experience recommended simplifying language, improving clarity and structure, adding concrete examples, and incorporating more direct communication prompts. Health Canada has already begun revising the resources in response to these recommendations, demonstrating real-world impact. Conclusions Cognitive accessibility depends on how the information is designed, not on the person reading it. Involving people with cognitive disabilities as research partners strengthens both the ethical foundation and practical utility of palliative care communication. Co-designed, cognitively accessible resources are essential to support autonomy, shared decision-making, and equitable palliative care access for all.
Fracture table vs. lateral positioning for intramedullary fixation of femur fractures (The FLiP Trial): the feasibility of a cluster randomized crossover trial
(2026-03-13) Axelrod, Daniel E.; Sprague, Sheila; Guerra-Farfan, Ernesto; Garcia-Sanchez, Yaiza; Meulenkamp, Brad; Dodd-Moher, Melanie; Bzovsky, Sofia; Shibu, Christy; Del Fabbro, Gina; Gallant, Jodi L.; Mammen, Thomas; Johal, Herman
Abstract Background Femoral shaft fractures are common severe injuries that carry an elevated risk of operative complications, including femoral malrotation, neurologic, and vascular injuries. There is no definitive research comparing two commonly used surgical tables and patient positions in aiding with both reduction and fixation of femoral shaft fractures. The objective of this pilot trial was to test the feasibility of a cluster randomized crossover trial that assesses the comparative effectiveness of supine positioning on a fracture table versus lateral positioning on a radiolucent table for antegrade intramedullary fixation of femoral shaft fractures. Methods Three orthopaedic trauma centres participated in this pilot trial. Each clinical site was randomized to a starting position, crossed over to the other treatment after 2 months, and alternated treatments in this fashion for the length of the trial. During the enrolment phase, we assessed compliance, enrolment rates, participant follow-up, and accurate documentation of the primary clinical outcome. The feasibility success criteria were: (1) 90% enrolment of eligible participants during enrolment phases; (2) 90% compliance with the trial interventions as per the cluster randomization crossover scheme; (3) timely collection of primary outcome data (i.e., within 6 weeks of fracture) in 95% of participants, (4) 90% completion of participant follow-up data; and (5) definition of the primary outcome as a categorical variable with an appropriate threshold value. Feasibility outcomes were summarized using descriptive statistics reported as means (standard deviation) or medians (first quartile, third quartile) for continuous variables depending on their distribution and counts (percentage) for categorical variables. Results All five of the criteria for feasibility were met. Of the 110 eligible patients identified at the three clinical sites, 101 (91.8%) were enroled over a 2.5-year period and 95/101 (94.1%) received the correct cluster-assigned treatment. The primary outcome (malrotation measured on the CT) was accurately documented within 6 weeks of fracture for 98% of participants (99/101) with 93 participants completing the final follow-up (92.0%). Lastly, the trial data informed an appropriate threshold, a malrotation cut off of 15°, for the primary outcome in the definitive trial. Conclusions These results confirm the feasibility of a definitive trial comparing patient positioning during intramedullary fixation of femoral shaft fractures using a cluster randomized crossover trial design. However, due to funding limitations, a slower than anticipated enrolment, and concerns with surgical equipoise, this trial did not proceed to the definitive phase. Trial registration ClincialTrials.gov NCT03868280.
TaIlored ManagEment of Sleep (TIMES) for people with dementia and mild cognitive impairment in primary care in England: protocol for a feasibility cluster-randomised controlled trial
(2026-03-07) van Horik, Jayden; Allan, Louise; Aryankhesal, Aidin; Broomfield, Niall; Greenstreet, Peter; Hilton, Andrea; Killett, Anne; Khondoker, Mizanur; Livingston, Gill; Loke, Yoon; Maidment, Ian; Medina-Lara, Antonieta; Palmer-Welsh, Adam; Reeve, Joanne; Scott, Sion; Shepstone, Lee; Warren, Fiona C.; Wong, Geoff; Fox, Chris
Abstract Background People living with dementia (PLWD) and mild cognitive impairment (MCI), and their family carers, often experience sleep disturbance which can impair daily living and care. There are limited options for effective long-term pharmacological management of sleep disturbance, yet recent advances in non-pharmacological approaches offer promising alternatives. TIMES is a novel, complex intervention, which aims to improve wellbeing for PLWD/MCI and their carers in primary care, by developing whole-person, tailored care plans that optimise management of sleep disturbance in context. Methods Two-arm cluster-randomised (1:1), single-blinded, feasibility trial in 10 general practice sites in England, recruiting 64 patient–carer dyad participants (32 intervention + 32 treatment as usual). Co-primary objectives are to assess the feasibility and acceptability of conducting a subsequent definitive cluster-randomised controlled trial (cRCT) of the TIMES intervention. Secondary objectives include assessing the ability to collect data to address putative primary and secondary outcomes of a definitive cRCT. We will collect participant demographics at screening, and the following outcome measures at baseline, 9 and 15 week follow-ups: Sleep Disorders Inventory (SDI); Epworth Sleepiness Scale (ESS); Activities of Daily Living assessed with the Disability Assessment for Dementia (ADL DAD); Dementia Quality of Life Measure (DEMQOL); EQ-5D 5 level (EQ-5D-5L); ICEpop Capability measure for older people aged ≥ 65 (ICECAP-O); Neuropsychiatric Inventory Questionnaire (NPI-Q); Client Service Receipt Inventory (CSRI); Telephone Montreal Cognitive Assessment (T-MoCA); patient medical records review; patient serious adverse events (SAEs). We will conduct Process Evaluation interviews and Discrete Choice Experiments to inform refinement of the intervention content and delivery. Discussion Our findings will inform the refinement and delivery of a subsequent definitive cRCT that tests the clinical and cost-effectiveness of the TIMES intervention compared with usual care. Trial registration This study received approval from the Health Research Authority (HRA) and London–Harrow Research Ethics Committee (Reference: 24/LO/0123), and is sponsored by the University of Exeter (Reference: 2021–22-38). Trial registration: ISRCTN, ISRCTN54051676, registered 20 March 2024, https://www.isrctn.com/ISRCTN54051676 .
Risk of adverse maternal outcomes among pregnancies with gestational diabetes mellitus in Ontario, Canada, 2012–2020: a retrospective cohort study
(2026-03-07) Luo, Rong; Fell, Deshayne B.; Corsi, Daniel J.; Taljaard, Monica; Wen, Shi W.; Walker, Mark C.
Abstract Background The rate of gestational diabetes mellitus (GDM) has increased over the past decades, but it’s unclear whether associations with maternal outcomes have changed. We aimed to describe rates of adverse maternal outcomes following deliveries with and without GDM over time and assess risks in these outcomes for GDM by delivery period. Methods This population-based retrospective cohort study was conducted using provincial birth registry linked with health administrative databases in Ontario, Canada. All singleton hospital deliveries between April 1, 2012 and March 31, 2020 were included. We assessed the trends of adverse maternal outcomes among GDM and non-GDM pregnancies and used modified Poisson regression to estimate associations between GDM and adverse maternal outcomes, using crude and adjusted relative risk (aRR) and risk difference (aRD) with 95% confidence intervals (CIs). Outcome measures included labour induction, caesarean section (CS), assisted vaginal delivery, gestational hypertension/preeclampsia, and maternal morbidity or mortality. Results Among 1 044 258 deliveries, 82 896 (7.9%) had GDM. The age-adjusted rate of GDM increased from 6.2 (95% CI 6.1–6.4) to 10.2 (95% CI 10.0-10.4) per 100 deliveries from fiscal year 2012/13 to 2019/20. Overall, GDM were at a higher risk (aRR [95% CI]) of induction (1.61 [1.59, 1.62]), CS (1.08 [1.06, 1.09]) and gestational hypertension/preeclampsia (1.35 [1.32, 1.38]). The risk of gestational hypertension/preeclampsia for GDM, compared to no GDM, attenuated from an aRR of 1.45 (1.41, 1.49) in 2012/13-2015/16 to an aRR of 1.29 (1.25, 1.32) in 2016/17-2019/20. The strength of the association between GDM and induction (1.62 [1.60, 1.64] vs. 1.60 [1.59, 1.62]), CS (1.10 [1.08, 1,12] vs. 1.07 [1.05, 1.08]), assisted vaginal delivery (0.96 [0.92, 1.00] vs. 0.94 [0.90, 0.98]), and maternal morbidity and mortality (0.93 [0.78, 1.08] vs. 1.09 [0.97, 1.20]) remained stable over time. Conclusions In this large population-based study of singleton hospital deliveries in Ontario, Canada, GDM was associated with higher risks of certain maternal adverse outcomes; however, these risks did not increase despite the increasing rate of GDM over the 8-year period, except for postpartum hemorrhage with interventions. Future large prospective studies should prioritize investigation into the risks of maternal outcomes across different glycemic diagnostic thresholds to inform cost-effective health care resource allocation for GDM pregnancies.
A scoping review of statistical methods for the analysis of method comparison studies with repeated measurements of clinical data
(2026-03-11) Brousseau, Karine; Ivankovic, Victoria; Lenet, Tori; McIsaac, Daniel I.; Ramsay, Tim; Fergusson, Dean A.; Martel, Guillaume
Abstract Background Method comparison studies are conducted to examine the level of agreement between two instruments measuring physiological continuous parameters. The inclusion of repeated measurements in such studies poses additional challenges. The Bland & Altman limits of agreement (LOA) approach has been adapted to account for the correlation between repeated measurements and is widely used in method comparison studies. Alternate statistical methods are not always appropriate for the analysis of such data, and there is a paucity of evidence and guidelines pertaining to statistical methods that inform the analysis of method comparison studies that include repeated measurements. This scoping review aimed to identify methodological publications that propose statistical methods to inform the analysis of method comparison studies that include repeated measurements of continuous clinical data and that may be compared with the LOA method. Methods Six online databases were searched from inception to November 2022 using a peer-reviewed search strategy. Searching of grey literature and books, as well as backward citation searching were performed to identify additional sources of evidence. Screening and data abstraction were done by two independent reviewers. Results were synthesized narratively. Results Twenty-nine publications were included in this review. Thirty-two independent statistical methods were identified from the included publications, including variants of the LOA method. Four included publications compared findings from different versions of the LOA method. Four different approaches to handling repeated measurements in the context of method comparison studies were identified and were used to group findings from the included publications. Reported strengths and limitations of the LOA method were summarized. Conclusion This scoping review provides a synthesis of existing statistical approaches to inform the analysis of method comparison studies with repeated measurements of clinical data, as well as how the various statistical methods perform when compared with various version of the LOA method. Based on the findings, it is generally advisable to consider using adjusted LOAs or modified mixed-effect LOAs in analyzing method comparison studies with repeated measurements. Trial registration The protocol was registered on Open Science Framework ( https://osf.io/4p8ut ).

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