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Item Open Access Future-proofing integrity in the age of artificial intelligence and neurotechnology: prioritizing human rights, dignity, and equity(2024-11-12) Eaton, Sarah E.Abstract This article I argue for the prioritisation of human rights when developing and implementing misconduct policies. Existing approaches may be perpetuate inequities, particularly for individuals from marginalised groups. A human-rights-by-design approach, which centres human rights in policy development, revision, and implementation, ensuring that every individual is treated with dignity and respect. Recommendations for implementing a human-rights approach to misconduct investigations and case management are offered, covering areas such as procedural fairness, privacy, equity, and the right to education. Additional topics covered are the need to limit surveillance technologies, and the need to recognize that not all use of artificial intelligence tools automatically constitutes misconduct. I disentangle the differences between equity and equality and explain how both are important when considering ethics and integrity. A central argument of this paper is that a human-rights-by-design approach to integrity does not diminish standards but rather strengthens educational systems by cultivating ethical awareness and respect for personhood. I conclude with a call to action with a seven-point plan for institutions to adopt a human-rights-based approach to ethics and integrity. In the age of artificial intelligence and neurotechnology, insisting on human rights and dignity when we investigate and address misconduct allegations is an ethical imperative that has never been more important.Item Open Access Canada needs a national COVID-19 inquiry now(2024-11-15) Fisman, David; Horton, Jillian; Oliver, Matthew; Ungrin, Mark; Vipond, Joseph; Wright, Julia M.; Zoutman, DickAbstract Background We are now in the fifth year of an ongoing pandemic, and Canada continues to experience significant surges of COVID-19 infections. In addition to the acute impacts of deaths and hospitalizations, there is growing awareness of an accumulation of organ damage and disability which is building a “health debt” that will affect Canadians for decades to come. Calls in 2023 for an inquiry into the handling of the COVID-19 pandemic went unheeded, despite relevant precedent. Canada urgently needs a comprehensive review of its successes and failures to chart a better response in the near- and long-term. Main body While Canada fared better than many comparators in the early years of the COVID-19 pandemic, it is clearly still in a public health crisis. Infections are not only affecting Canadians’ daily lives but also eroding healthcare capacity. Post-COVID condition is having accumulating and profound individual, social, and economic consequences. An inquiry is needed to understand the current evidence underlying policy choices, identify a better course of action on various fronts, and build resilience. More must be done to reduce transmission, including a serious public education campaign to better inform Canadians about COVID and effective mitigations, especially the benefits of respirator masks. We need a national standard for indoor air quality to make indoor public spaces safer, particularly schools. Data collection must be more robust, especially to understand and mitigate the disproportionate impacts on under-served communities and high-risk populations. General confidence in public health must be rebuilt, with a focus on communication and transparency. In particular, the wide variation in provincial policies has sown mistrust: evidence-based policy should be consistent. Finally, Canada’s early success in vaccination has collapsed, and this development needs a careful post-mortem. Conclusions A complete investigation of Canada’s response to the pandemic is not yet possible because that response is still ongoing and, while we have learned much, there remain areas of dispute and uncertainty. However, an inquiry is needed to conduct a rapid assessment of the current evidence and policies and provide recommendations on how to improve in 2025 and beyond as well as guidance for future pandemics.Item Open Access Long-term effectiveness of aripiprazole once monthly on functioning and quality of life in schizophrenia: results of year 2 of the ReLiAM study(2024-11-14) Roy, Marc-André; Therrien, François; Boucher, Matthieu; Oluboka, OloruntobaAbstract Background Aripiprazole once-monthly (AOM) has proven effective in the treatment of schizophrenia, although little is known about its impact on global functioning and quality of life beyond 1 year. Here, we investigate the continued impact of AOM on the participants of the ReLiAM study during the second year of follow-up. Methods The participants who were evaluated at ≥ 1 time point during the second year of the ReLiAM study (months 15, 18, 21, and 24; year 1 completers) were assessed via the GAF scale. Secondary outcomes were reported on the SOFAS, CGI-S, and QLS. Results 109 (86%) completed at least 1 post-12-month visit and 33 (30.3%) patients completed the final assessment at month 24. The improvements observed in the year 1 completers in GAF total score were maintained through to year 2 completers. The improvements in CGI-S and SOFAS that were observed at the end of year 1 were also maintained through the end of the second year. Similar trends of sustained improvement in GAF total score, CGI-S score, and SOFAS were observed in the post-hoc analyses of the year 2 completers. Seventy-four percent (74.3%) of year 1 completers experienced mild treatment-emergent adverse events during the second year, the most frequently reported being weight gain, akathisia, and insomnia. Seventeen percent (17.4%) experienced serious adverse events. Similar findings regarding effectiveness and tolerability were reported in the year 1 completers and in year 2 completers. Conclusions These findings suggest that the favorable effectiveness, including tolerability observed during the first year following AOM initiation, are maintained and may even continue to improve during the second year of treatment. Trial registration ClinicalTrials.gov NCT02131415, first posted on May 6, 2014. Overall trial status: Terminated.Item Open Access Interventions employed to address vaccine hesitancy among Black populations outside of African and Caribbean countries: a scoping review(2024-11-13) Majekodunmi, Precious; Tulli-Shah, Mia; Kemei, Janet; Kayode, Ibukun; Maduforo, Aloysius N.; Salami, BukolaAbstract Background Black people are disproportionately affected by structural and social determinants of health, resulting in greater risks of exposure to and deaths from COVID-19. Structural and social determinants of health feed vaccine hesitancy and worsen health disparities. Objective This scoping review explored interventions that have been employed to address vaccine hesitancy among Black population outside of African and Caribbean countries. This review provides several strategies for addressing this deep-rooted public health problem. Methods The scoping review followed the five-step framework outlined by Arksey and O’Malley. It complies with reporting guidelines from the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Research studies that examined interventions utilized to promote vaccine confidence within Black populations living outside of African and Caribbean countries were reviewed. Findings A total of 20 articles met the inclusion criteria for this study: 17 were quantitative studies and three were mixed-method studies. This scoping review highlighted six themes: educational advancement, messaging, multi-component approaches, outreach efforts, enhancing healthcare access, and healthcare provider leadership. Conclusion The review identified effective interventions for addressing vaccine hesitancy among Black populations outside Africa and the Caribbean, emphasizing education, multidimensional approaches, and healthcare provider recommendations. It calls for more qualitative research and interventions in countries like Canada and the UK to enhance vaccine confidence and reduce mistrust.Item Open Access Experiences and perceptions of migrant populations in South Africa on COVID-19 immunization: an interpretative phenomenological analysis(2024-11-12) Mukumbang, Ferdinand C.; Ndlovu, Sibusiso; Adebiyi, Babatope O.Abstract Introduction Migrant populations (asylum seekers, permit holders, refugees, and undocumented migrants) living in South Africa face various individual, social, and physical circumstances that underpin their decisions, motivation, and ability to receive the COVID-19 vaccine. We conducted a qualitative study to explore the experiences and perceptions of migrant populations in South Africa on COVID-19 vaccines to inform recommendations for improved COVID-19 immunization. Methods We conducted an Interpretative Phenomenological Analysis (IPA) with 20 asylum seekers, permit holders, refugees, and undocumented migrants living in South Africa. We applied a maximum variation purposive sampling approach to capture all three categories of migrants in South Africa. Semi-structured interviews were conducted and recorded electronically with consent and permission from the study participants. The recordings were transcribed and analyzed thematically following the IPA using Atlas.ti version 9. Results Four major reflective themes emanated from the data analysis. (1) While some migrants perceived being excluded from the South African national immunization program at the level of advertisement and felt discriminated against at the immunization centers, others felt included in the program at all levels. (2) Skepticism, myths, and conspiracy theories around the origin of SARS-CoV-2 and the COVID-19 vaccine are pervasive among migrant populations in South Africa. (3) There is a continuum of COVID-19 vaccine acceptance/hesitancy ranging from being vaccinated through waiting for the chance to be vaccinated to refusal. (4) Accepting the vaccine or being hesitant follows the beliefs of the participant, knowledge of the vaccine’s benefits, and lessons learned from others already vaccinated. Conclusion COVID-19 vaccine inclusiveness, awareness, and uptake should be enhanced through migrant-aware policies and actions such as community mobilization, healthcare professional training, and mass media campaigns.Item Open Access Association of lifetime lactation and characteristics of menopause: a longitudinal cohort study(2024-11-11) Scime, Natalie V.; Huang, Beili; Brockway, Meredith M.; Brown, Hilary K.; Brennand, Erin A.Abstract Background Lactation has many established benefits for women’s long-term health; however, its influence on menopause is less clear. This study investigated the association between lifetime duration of lactation and the timing and type of menopause in midlife women. Methods We analyzed survey data on 19,783 parous women aged 40 to 65 years at enrollment in the Alberta’s Tomorrow Project (2000–2022), a prospective community-based cohort study in Alberta, Canada. Duration of lifetime lactation across all births was categorized as: <1 month (reference group; 19.8% of women), 1–3 months (12.1%), 4–6 months (11.7%), 7–12 months (18.8%), and ≥ 13 months (37.7%). Women were classified as premenopause, natural menopause (age at 1 year after the final menstrual period), surgical menopause (age at bilateral oophorectomy), or indeterminate menopause (age at premenopausal hysterectomy with ovarian preservation). Flexible parametric survival analysis and multinomial logistic regression were used to analyze menopause timing and type, respectively, according to lactation status and controlling for birth year, education, parity, hormonal contraceptive use, and smoking. Results In a dose-response manner, longer lactation was associated with reduced risk of natural menopause before age 50 (for ≥ 13 months of lactation, adjusted hazard ratio at age 45: 0.68, 95% CI 0.59–0.78), surgical menopause before age 55 (age 45: 0.56, 0.50–0.63), and indeterminate menopause before age 50 (age 45: 0.75, 0.69–0.82). Longer lactation was associated with lower odds of surgical (adjusted odds ratio 0.54, 95% CI 0.45–0.66) and indeterminate menopause (0.63, 0.55–0.73), compared to natural menopause. Conclusions Optimizing the timing of natural menopause and reducing risks of early surgical and indeterminate menopause may be novel maternal benefits of breastfeeding.Item Open Access The impact of co-occurring chronic pain and mental health symptoms on adolescent functioning, a cross-sectional survey(2024-11-06) Bateman, Sharon; Jordan, Abbie; Noel, Melanie; Loades, Maria; Caes, LineAbstract Adolescents who experience poor mental health may develop chronic pain. Similarly, those with chronic pain may develop mental health symptoms. Little is known concerning how these co-occurring symptoms are associated with adolescent functioning. Our online cross-sectional quantitative study compared the specific nature of challenges to psychosocial functioning, across 4 groups: (1) adolescents with co-occurring chronic pain and mental health symptoms; (2) adolescents who only experience chronic pain symptoms; (3) adolescents who only experience mental health symptoms, and (4) adolescents who do not report either symptom. Participants completed self-report questionnaires assessing pain experiences, mental health symptoms and psychosocial functioning. After controlling for pain intensity, findings revealed significant differences, in physical, social, and family functioning across all groups. Significantly worse physical functioning was reported by adolescents with co-occurring pain and mental health symptoms and those with pain-only symptoms compared with adolescents with mental health-only symptoms and those without symptoms. Social functioning was significantly worse for adolescents who experienced co-occurring chronic pain and mental health symptoms compared with adolescents who experienced pain-only symptoms, and those with no symptoms. Significantly worse family functioning was reported by adolescents with mental health-only symptoms compared with adolescents reporting pain-only symptoms and no symptoms. Results suggest the combined impact of pain and mental health symptoms mainly influences adolescent social functioning. Future research is needed to develop standardised assessment and treatment plans to facilitate a thorough understanding of symptoms presented by adolescents who experience co-occurring pain and mental health symptoms. This study identifies that the combined impact of pain and mental health symptoms influences adolescent social functioning when compared to adolescents who experience pain-only or those without symptoms. Research is needed to develop standardised assessment and treatment plans to fully understand the symptoms presented by adolescents with co-occurring symptoms.Item Open Access Exploring patient perspectives on the impact of resuming cost sharing: a qualitative analysis(2024-11-09) Tran, Sophia H. N.; Fletcher, Jane M.; McSweeney, Breanna; Saunders-Smith, Terry; Manns, Braden J.; Campbell, David J. T.Abstract Introduction The ACCESS trial showed that those who received a copayment elimination benefit had a modest improvement in their adherence to medications, but no improvement in clinical outcomes. This is consistent with other studies that have demonstrated that time-limited copayment elimination was welcomed by participants. However, the removal of such benefits can be problematic, as participants may have become accustomed to receiving the benefit, and made changes to their spending that would need to be reconsidered. We aimed to explore participants’ experience with resuming cost sharing for their medications at the end of the ACCESS trial and if this experience influenced their willingness to participate in future trials like ACCESS. Methods We conducted semi-structured interviews with 21 former participants of the ACCESS trial who were receiving the copayment elimination intervention, with discussions focused on the loss of the copayment elimination. The interviews were recorded, transcribed, and analyzed in duplicate using thematic analysis. Results Four primary themes emerged from the analysis, including emotionality regarding loss of benefits; notification of benefit termination, describing tangible losses from coverage ending, but resistance to acknowledging negative impacts; and acceptability of receiving a temporary financial benefit. Many participants described negative emotions around the loss of coverage and concern about affording care for their chronic diseases. Despite negative emotions about the end of their study benefit, participants generally had a positive view of the study and would participate again in a future study of this nature. Conclusion The positive tangible and emotional benefits of the copayment elimination over 3 years outweighed the negative emotions and impacts associated with having to become reaccustomed to life without it. Patient and public contribution Within the ACCESS trial, participants were involved in the design, modification, and implementation of the program using multiple focus groups. The current study aimed to engage patients to provide input on their experience and engagement with the copayment elimination program.Item Open Access Developing a question prompt tool to prevent and manage early cardiovascular disease after hypertensive pregnancy: qualitative interviews with women and clinicians(2024-11-07) Theodorlis, Madeline; Edmonds, Jessica; Sino, Sara; Lyons, Mavis S.; Ramlakhan, Jessica U.; Nerenberg, Kara; Gagliardi, Anna R.Abstract Background Persons (henceforth, women) who have hypertensive disorders of pregnancy (HDP) are at risk of premature cardiovascular disease (CVD). While largely preventable through lifestyle management, many women and clinicians are unaware of the risk. Based on prior research, we developed a question prompt tool (QPT) on preventing and managing CVD after HDP. The purpose of this study was to refine QPT design. Methods We recruited Canadian women who had HDP and clinicians who might care for them using multiple strategies, conducted telephone interviews with consenting participants, and used qualitative description and inductive content analysis to derive themes. Results We interviewed 21 women who varied in HDP type, CVD status, years since HDP pregnancy, age, geography and ethno-cultural group; and 21 clinicians who varied in specialty (midwife, nurse practitioner, family physician, internist, obstetrician, cardiologist), geography and years in practice. Participating women and clinicians agreed on needed improvements: more instructions, lay and gender-neutral language, links to additional information, more space for answers, graphic appeal, and both print and electronic format. Both groups identified similar barriers: clinicians lack time/willingness, and low language/health literacy and access to technology among women; enablers: translated, credible source/endorser, culturally relevant, organized by health trajectory stages; and likely benefits: raise awareness, empower women, encourage them to adopt healthy lifestyle. Women desired exposure to the QPT before or during pregnancy, while clinicians recommended waiting until postpartum to avoid overwhelming women. Similarly, most women said the QPT should be available through multiple avenues to empower them for health self-advocacy, while clinicians thought they should introduce the QPT to women, and decide when and which questions to address. To mitigate reluctance, clinicians recommended self-directed educational materials accompany the QPT. Conclusions We will use this information to refine QPT design and plan for future evaluation. If found to be effective and widely disseminated, the QPT could improve awareness and communication about this issue, and may reduce CVD risk in many women who have hypertensive pregnancies. Ongoing research is needed to more fully understand how QPTs support patient-clinician communication, and how to alert and prime both patients and clinicians to use QPTs.Item Open Access Landscape transcriptomic analysis of bovine follicular cells during key phases of ovarian follicular development(2024-10-28) Mogollón García, Henry D.; de Andrade Ferrazza, Rodrigo; Ochoa, Julian C.; de Athayde, Flávia F.; Vidigal, Pedro M. P.; Wiltbank, Milo; Kastelic, John P.; Sartori, Roberto; Ferreira, João C. P.Abstract Background There are many gaps in our understanding of the mechanisms involved in ovarian follicular development in cattle, particularly regarding follicular deviation, acquisition of ovulatory capacity, and preovulatory changes. Molecular evaluations of ovarian follicular cells during follicular development in cattle, especially serial transcriptomic analyses across key growth phases, have not been reported. This study aims to address this gap by analyzing gene expression using RNA-seq in granulosa and antral cells recovered from ovarian follicular fluid during critical phases of ovarian follicular development in Holstein cows. Results Integrated analysis of gene ontology (GO), gene set enrichment (GSEA), protein–protein interaction (PPI), and gene topology identified that differentially expressed genes (DEGs) in the largest ovarian follicles at deviation (Dev) were primarily involved in FSH-negative feedback, steroidogenesis, cell proliferation, apoptosis, and the prevention of early follicle rupture. In contrast, DEGs in the second largest follicles (DevF2) were mainly related to loss of cell viability, apoptosis, and immune cell invasion. In the dominant (PostDev) and preovulatory (PreOv) follicles, DEGs were associated with vascular changes and inflammatory responses. Conclusions The transcriptome of ovarian follicular fluid cells had a predominance of granulosa cells in the dominant follicle at deviation, with upregulation of genes involved in cell viability, steroidogenesis, and apoptosis prevention, whereas in the non-selected follicle there was upregulation of cell death-related transcripts. Immune cell transcripts increased significantly after deviation, particularly in preovulatory follicles, indicating strong intrafollicular chemotactic activity. We inferred that immune cell invasion occurred despite an intact basal lamina, contributing to follicular maturation. Graphical AbstractItem Open Access Fenebrutinib, a Bruton’s tyrosine kinase inhibitor, blocks distinct human microglial signaling pathways(2024-10-27) Langlois, Julie; Lange, Simona; Ebeling, Martin; Macnair, Will; Schmucki, Roland; Li, Cenxiao; DeGeer, Jonathan; Sudharshan, Tania J. J.; Yong, V. W.; Shen, Yun-An; Harp, Christopher; Collin, Ludovic; Keaney, JamesAbstract Background Bruton’s tyrosine kinase (BTK) is an intracellular signaling enzyme that regulates B-lymphocyte and myeloid cell functions. Due to its involvement in both innate and adaptive immune compartments, BTK inhibitors have emerged as a therapeutic option in autoimmune disorders such as multiple sclerosis (MS). Brain-penetrant, small-molecule BTK inhibitors may also address compartmentalized neuroinflammation, which is proposed to underlie MS disease progression. BTK is expressed by microglia, which are the resident innate immune cells of the brain; however, the precise roles of microglial BTK and impact of BTK inhibitors on microglial functions are still being elucidated. Research on the effects of BTK inhibitors has been limited to rodent disease models. This is the first study reporting effects in human microglia. Methods Here we characterize the pharmacological and functional properties of fenebrutinib, a potent, highly selective, noncovalent, reversible, brain-penetrant BTK inhibitor, in human microglia and complex human brain cell systems, including brain organoids. Results We find that fenebrutinib blocks the deleterious effects of microglial Fc gamma receptor (FcγR) activation, including cytokine and chemokine release, microglial clustering and neurite damage in diverse human brain cell systems. Gene expression analyses identified pathways linked to inflammation, matrix metalloproteinase production and cholesterol metabolism that were modulated by fenebrutinib treatment. In contrast, fenebrutinib had no significant impact on human microglial pathways linked to Toll-like receptor 4 (TLR4) and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) signaling or myelin phagocytosis. Conclusions Our study enhances the understanding of BTK functions in human microglial signaling that are relevant to MS pathogenesis and suggests that fenebrutinib could attenuate detrimental microglial activity associated with FcγR activation in people with MS.Item Open Access Association between SMOFlipid and impaired brain development on term-equivalent age brain magnetic resonance imaging in very preterm infants(2024-10-29) Al-Mouqdad, Mountasser M.; Alshaikh, Belal; Sumaily, Haider H.; Alodhaidan, Nabeel A.; AlMahmoud, Latifah; Almotiri, Ameen A.; Alkhourmi, Mousa A.; Abounassif, Mazen M.; Beh, Ahmed F.; Alawad, Mashael A.; Albraiki, Amani A.; Alqarni, Aziza A.; Al-Anazi, Maha R.; Basodan, Nadia A.; Assiri, Fuddah M.; Asfour, Suzan S.Abstract Soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOFlipid) is used without evidence of benefits. We investigated the relationship between lipid emulsions and brain injury in term-equivalent age magnetic resonance imaging (MRI) in 148 very preterm infants with a birth weight of < 1500 g at ≤ 32 gestational weeks in a neonatal intensive care unit. Infants who received soybean-based lipid emulsions between January 2015 and December 2018 were compared with those who received SMOFlipids between January 2019 and December 2022. A negative binomial generalized linear model was applied for bivariate analysis. Modified log-Poisson regression with generalized linear models and a robust variance estimator (Huber–White) were applied to adjust for potential confounders. The Kidokoro score was used to determine if lipid emulsion type would affect brain morphology and growth at term-equivalent age. Eighty-six (58.9%) received SMOFlipid. SMOFlipid was associated with lower focal signal abnormality, myelination delay, increased extracerebral space, and cerebellar volume reduction (P = 0.02, P = 0.007, P = 0.01, P = 0.02, respectively). SMOFlipidis are associated with brain insult, especially in white matter, cortical gray matter, and the cerebellum. Well-designed studies are needed to investigate the effect of lipid emulsions on the central nervous system.Item Open Access Clinical epidemiology and impact of Haemophilus influenzae airway infections in adults with cystic fibrosis(2024-10-27) Weyant, R. Benson; Waddell, Barbara J.; Acosta, Nicole; Izydorczyk, Conrad; Conly, John M.; Church, Deirdre L.; Surette, Michael G.; Rabin, Harvey R.; Thornton, Christina S.; Parkins, Michael D.Abstract Background Haemophilus influenzae is prevalent within the airways of persons with cystic fibrosis (pwCF). H. influenzae is often associated with pulmonary exacerbations (PEx) in pediatric cohorts, but in adults, studies have yielded conflicting reports around the impact(s) on clinical outcomes such as lung function decline. Accordingly, we sought to discern the prevalence, natural history, and clinical impact of H. influenzae in adult pwCF. Methods This single-centre retrospective cohort study reviewed all adult pwCF with H. influenzae sputum cultures between 2002 and 2016. From this cohort, persistently infected subjects (defined as: ≥2 samples with the same pulsotype and > 50% sputum culture-positive for H. influenzae in each year) were matched (1:2) to controls without H. influenzae. Demographic and clinical status (baseline health or during periods of PEx) were obtained at each visit that H. influenzae was cultured. Yearly biobank isolates were typed using pulsed-field gel electrophoresis (PFGE) to assess relatedness. Results Over the study period, 30% (n = 70/240) of pwCF were culture positive for H. influenzae, of which 38 (54%) were culture-positive on multiple occasions and 12 (17%) had persistent infection. One hundred and thirty-seven isolates underwent PFGE, with 94 unique pulsotypes identified. Two (1.5%) were serotype f with the rest non-typeable (98.5%). H. influenzae isolation was associated with an increased risk of PEx (RR = 1.61 [1.14–2.27], p = 0.006), however, this association was lost when we excluded those who irregularly produced sputum (i.e. only during a PEx). Annual lung function decline did not differ across cohorts. Conclusions Isolation of H. influenzae was common amongst adult pwCF but often transient. H. influenzae infection was not associated with acute PEx or chronic lung function decline.Item Open Access Harnessing the power of patient engagement in evaluating a novel brace for knee osteoarthritis: a co-produced commentary(2024-10-24) Bishop, Emily L.; Bonhomme, Justin; Baranec, Deb; Wamsley, Anita; Ronsky, Janet L.; Clark, Marcia L.Abstract Introduction Patient oriented research (POR) invites patients to partner with researchers, clinicians, and other stakeholders, incorporating diverse perspectives to generate scientific evidence meaningful to all parties involved. We adopted a POR approach for this study evaluating the feasibility of conducting a randomized control trial of a novel tri-compartment offloader brace for knee osteoarthritis. We involved patients as partners to enhance study design, implementation and interpretation of key outcomes. Approach Patient involvement consisted of two patient leaders and five patient advisors. Patients participated in 2 virtual focus groups to discuss study outcomes, protocol, results and knowledge translation. Patients were involved in all aspects of the research cycle. Outcomes Patient feedback resulted in changes to study design, documentation, participant recruitment, data collection, results interpretation and knowledge dissemination, improving the participant experience and aligning study outcomes with patient priorities. Study participants showed a high level of protocol adherence and follow-up rates were excellent. We experienced several unexpected benefits including genuine friendships, a deeper understanding of the patient experience, a more pragmatic approach to clinical research, and leadership opportunities for patients. Recommendations We agreed on POR “non-negotiables” to ensure a positive experience for everyone, including creating a safe and comfortable environment, being genuinely receptive to patient feedback, and providing appropriate supports for patients. We strongly recommend that researchers (1) involve patients as early as possible, (2) provide ample and equal opportunities for all patients to be involved, and (3) address system hierarchy by involving patients as equals and fully considering all patient ideas from the beginning of the project. Conclusions While POR is a learning process that is often more challenging than the traditional clinical research approach, the benefits are well worth the additional time and effort required to do it well. Over time, our team experienced a cultural shift and evolution from a top-down research approach to a more inclusive approach considering patient voices as equal to those of researchers. Patient involvement in all aspects of the research process, from question development to results interpretation and dissemination is integral to clinical research advancing equitably.Item Open Access Adult day programs and their effects on individuals with dementia and their caregivers (ADAPT-DemCare): a realist synthesis to develop program theories on the how and why(2024-10-23) Nguyen, Hung; Rahman, Atiqur; Ubell, Andrea; Goodarzi, Zahra; Maxwell, Colleen J.; Allana, Saleema; Tate, Kaitlyn; Symonds-Brown, Holly; Weeks, Lori; Caspar, Sienna; Mann, Jim; Hoben, MatthiasAbstract Background Adult day programs aim to facilitate aging in place by supporting the health and well-being of persons with dementia and providing respite to their caregivers. However, studies on the effects of day programs are inconclusive, and we especially lack insights into the context conditions and mechanisms of day programs that may produce different outcomes for different groups of persons with dementia and their caregivers. Our objective was to conduct a realist review, synthesizing research on day programs to develop program theories explaining how and why day programs do or do not produce positive or negative outcomes for different groups of persons with dementia, and caregivers. Methods We identified 14 literature reviews (including 329 references published between 1975 and 2021) on adult day programs. From this initial pool of studies, we will include those that focused on day program attendees with dementia or meaningful cognitive impairment, and/or their caregivers, and that report how day program contexts (C) and mechanisms (M) bring about outcomes (O) for attendees and caregivers. We will extract CMO statements (i.e., narratives that explain how and why day programs do or do not bring about certain outcomes for whom and under what circumstances). Using additional focused searches, citation mapping, citation tracking, and discussions with our researcher and expert team members, we will identify additional references. CMO statements will be synthesized, transformed into hypotheses, and linked and visualized to form program theories. Using focus groups and the James Lind Alliance Priority Setting Partnership method, we will discuss and prioritize our CMO statements and refine our program theories with 32 experts (older adults, caregivers, Alzheimer societies, caregiver organizations, day program staff and managers, and health system and policy decision makers). Discussion By identifying essential elements and processes of day programs and related knowledge gaps, this study will generate much-needed knowledge to leverage the full potential of day programs so they can provide appropriate care, preventing premature institutionalization, and unnecessary acute and primary care use. This will ultimately improve the quality of life of persons with dementia and their caregivers, alleviate caregiver burden, and reduce social costs. Systematic review registration PROSPERO CRD42024504030Item Open Access Surgical stabilization of rib fractures (SSRF): the WSES and CWIS position paper(2024-10-18) Sermonesi, Giacomo; Bertelli, Riccardo; Pieracci, Fredric M.; Balogh, Zsolt J.; Coimbra, Raul; Galante, Joseph M.; Hecker, Andreas; Weber, Dieter; Bauman, Zachary M.; Kartiko, Susan; Patel, Bhavik; Whitbeck, SarahAnn S.; White, Thomas W.; Harrell, Kevin N.; Perrina, Daniele; Rampini, Alessia; Tian, Brian; Amico, Francesco; Beka, Solomon G.; Bonavina, Luigi; Ceresoli, Marco; Cobianchi, Lorenzo; Coccolini, Federico; Cui, Yunfeng; Dal Mas, Francesca; De Simone, Belinda; Di Carlo, Isidoro; Di Saverio, Salomone; Dogjani, Agron; Fette, Andreas; Fraga, Gustavo P.; Gomes, Carlos A.; Khan, Jim S.; Kirkpatrick, Andrew W.; Kruger, Vitor F.; Leppäniemi, Ari; Litvin, Andrey; Mingoli, Andrea; Navarro, David C.; Passera, Eliseo; Pisano, Michele; Podda, Mauro; Russo, Emanuele; Sakakushev, Boris; Santonastaso, Domenico; Sartelli, Massimo; Shelat, Vishal G.; Tan, Edward; Wani, Imtiaz; Abu-Zidan, Fikri M.; Biffl, Walter L.; Civil, Ian; Latifi, Rifat; Marzi, Ingo; Picetti, Edoardo; Pikoulis, Manos; Agnoletti, Vanni; Bravi, Francesca; Vallicelli, Carlo; Ansaloni, Luca; Moore, Ernest E.; Catena, FaustoAbstract Background Rib fractures are one of the most common traumatic injuries and may result in significant morbidity and mortality. Despite growing evidence, technological advances and increasing acceptance, surgical stabilization of rib fractures (SSRF) remains not uniformly considered in trauma centers. Indications, contraindications, appropriate timing, surgical approaches and utilized implants are part of an ongoing debate. The present position paper, which is endorsed by the World Society of Emergency Surgery (WSES), and supported by the Chest Wall Injury Society, aims to provide a review of the literature investigating the use of SSRF in rib fracture management to develop graded position statements, providing an updated guide and reference for SSRF. Methods This position paper was developed according to the WSES methodology. A steering committee performed the literature review and drafted the position paper. An international panel of experts then critically revised the manuscript and discussed it in detail, to develop a consensus on the position statements. Results A total of 287 studies (systematic reviews, randomized clinical trial, prospective and retrospective comparative studies, case series, original articles) have been selected from an initial pool of 9928 studies. Thirty-nine graded position statements were put forward to address eight crucial aspects of SSRF: surgical indications, contraindications, optimal timing of surgery, preoperative imaging evaluation, rib fracture sites for surgical fixation, management of concurrent thoracic injuries, surgical approach, stabilization methods and material selection. Conclusion This consensus document addresses the key focus questions on surgical treatment of rib fractures. The expert recommendations clarify current evidences on SSRF indications, timing, operative planning, approaches and techniques, with the aim to guide clinicians in optimizing the management of rib fractures, to improve patient outcomes and direct future research.Item Open Access Colostrum-derived extracellular vesicles: potential multifunctional nanomedicine for alleviating mastitis(2024-10-16) Xiong, Yindi; Shen, Taiyu; Lou, Peng; Yang, Jingyue; Kastelic, John P.; Liu, Jingping; Xu, Chuang; Han, Bo; Gao, JianAbstract Bovine mastitis is an infectious disease that causes substantial economic losses to the dairy industry worldwide. Current antibiotic therapy faces issues of antibiotic misuse and antimicrobial resistance, which has aroused concerns for both veterinary and human medicine. Thus, this study explored the potential of Colo EVs (bovine colostrum-derived extracellular vesicles) to address mastitis. Using LPS-induced murine mammary epithelial cells (HC11), mouse monocyte macrophages (RAW 264.7), and a murine mastitis model with BALB/C mice, we evaluated the safety and efficacy of Colo EVs, in vivo and in vitro. Colo EVs had favorable biosafety profiles, promoting cell proliferation and migration without inducing pathological changes after injection into murine mammary glands. In LPS-induced murine mastitis, Colo EVs significantly reduced inflammation, improved inflammatory scores, and preserved tight junction proteins while protecting milk production. Additionally, in vitro experiments demonstrated that Colo EVs downregulated inflammatory cytokine expression, reduced inflammatory markers, and attenuated NF-κB pathway activation. In summary, we inferred that Colo EVs have promise as a therapeutic approach for mastitis treatment, owing to their anti-inflammatory properties, potentially mediated through the NF-κB signaling pathway modulation. Graphical AbstractItem Open Access The directors of resident support program: a program evaluation of a resident well-being and support innovation(2024-10-17) Ruzycki, Shannon M.; des Ordons, Amanda R.; Davis, Melinda; Steele, J. M.; Tutu, Kannin O.; Welikovitch, LisaAbstract Background Medical training can be a challenging time for residents both professionally and personally. Resident support programs must be able to address a range of potential experiences, be accessible and easy to navigate, and consider the unique context of residency. Rigorous evaluation of resident support programs is needed to determine whether these programs are meeting these goals. Methods The Directors of Resident Support (DRS) program, launched in January 2021 at the Cumming School of Medicine at the University of Calgary, is a near-peer support model consisting of three faculty physicians, trained in peer support, who receive contacts from residents needing support for any issue. DRS physicians provide empathetic listening, referral to existing resources, and peer support for residents. A multisource evaluation of the DRS program, including field notes, data collection forms, and surveys, was guided by the Donabedian framework. Results There were 62 total contacts in the 2-year evaluation period which required a median 2 h to address (range 5 min to more than 40 h). The most common topic for contact was to discuss feedback or evaluation (n = 10, 24.4%) and the most common response was listening and support (n = 29, 70.7%). Residents also contacted DRS to discuss experiences of racism, physical assault, sexual harassment, and mental health crises. Residents (n = 13) rated a median score of 74 out of possible 100 for usefulness (interquartile range [IQR] 1-100, with higher scores suggesting greater usefulness). Free text survey responses suggested that residents felt validated by contact with the program though some residents felt that additional follow-up would have been helpful. Conclusion The DRS program has been well-utilized by residents for a variety of issues. Postgraduate Medical Education offices seeking to create resident support programs may anticipate that about 3% of residents may use a similar program per year and that the typical interaction would last 2 h, with a wide range. Feedback suggested that similar programs should have a formal process for follow-up with residents to ensure their concern was addressed and that resident supporters should have diverse lived experiences.Item Open Access Refractive error and ocular alignment in school-aged children from low-income areas of São Paulo, Brazil(2024-10-15) Fernandes, Arthur G.; Vianna, Rodrigo G.; Gabriel, Debora C.; Ferreira, Bruna G.; Barbosa, Eduardo P.; Salomão, Solange R.; Campos, MauroAbstract Background Uncorrected refractive errors and amblyopia are reported as the two main causes of childhood visual impairment and blindness worldwide. Our purpose was to evaluate refractive status, ocular alignment and effective refractive error coverage (eREC) of school-aged children from low-income areas of Sao Paulo city, Brazil. Methods Data from the “Ver na Escola” Project were used for the current study. Children enrolled in the selected schools had an ophthalmic exam including eye alignment assessed by cover test, automatized and subjective dynamic and static refraction. The associations of demographic variables with occurrence and magnitude of refractive errors and eREC were investigated by multiple logistic regressions and multilevel mixed effect models. Results A total of 17,973 children (51.12% females) with mean ± sd age 8.24 ± 3.54 years old examined from July 2018 to July 2019, were included in the study. Most of the participants (73%) showed orthoposition of the visual axis for both distance and near. Heterophoria was found in about 25% of participants (N = 4,498), with 71.7% of them (N= 3,222) classified as exophoria. Less than 2% (N = 232) showed strabismus, most of them (N = 160) esotropia. Overall, 1,370 (7.70%) of participants had myopia and 577 (3.24%) had hyperopia. Age was found to be significantly associated with increasing static subjective refraction spherical equivalent (Coefficient: -0.18; 95% Confidence Interval (CI): -0.21 to -0.16; p < 0.001). Female sex (Odds Ratio (OR) = 1.13; 95%CI: 1.01–1.27; p = 0.027) and older age (OR = 1.17; 95%CI: 1.16–1.19; p < 0,001) were significantly associated with myopia diagnosis. Older age decreased the odds of hyperopia (OR = 0.95; 95%CI: 0.93–0.98; p < 0.001). The overall effective refractive coverage was 51.76% and was significantly associated with age group, ranging from 32.25% in children aged 3 to 7 years to 61.35% in children aged 8 to 12 years. Conclusions Most children have shown eye alignment for both distance and near assessments and no refractive error. Myopia was observed in 7.70% of the population and it was associated with older age and female sex. Hyperopia was observed in 3.24% and was associated with younger age. The overall eREC was 51.76%, significantly associated with age.Item Open Access A combination of calcium hydroxide and sodium hydrosulphate controls pathogens causing environmental mastitis in recycled manure solids(2024-10-08) Praveen, Selladurai; Kataktalware, Mukund A.; Meena, Priyanka; Lavanya, Maharajan; Patoliya, Priyanka; Jeyakumar, Sakthivel; Ravindra, Menon R.; Chauhan, Mamta; Ramesha, K. P.; Devi, G. L.; Kastelic, John P.; Dhali, ArindamAbstract Recycled manure solids (RMS) are dried cow dung processed using a manure dewatering machine and subsequently sun-dried to ~ 20% moisture. Benefits of RMS include abundant availability, low cost, and eco-friendliness, but its use as bedding material for cows is hindered by a moisture content that promotes microbial growth. This in vitro study evaluated impacts of calcium hydroxide (CH; 5 and 7.5%) and sodium hydrosulphate (SHS; 6 and 8%), independently and in combinations, at various depths of RMS, on physicochemical and microbial properties. The CH-treated groups had increased pH and reduced moisture on Day 0. Incorporating 7.5% CH + 6% SHS at 15–20 cm, and 7.5% CH + 8% SHS at all depths, effectively suppressed Escherichia coli and Klebsiella spp. Furthermore, a combination of 7.5% CH + 8% SHS at 20 cm inhibited coliform growth, whereas 7.5% CH with 6% SHS inhibited Streptococcus spp. In conclusion, a combination of 7.5% CH with either 6 or 8% SHS at a depth of 15 cm in RMS was particularly effective in controlling environmental mastitis-causing pathogens, specifically E. coli and Klebsiella spp. Graphical Abstract