Multi-omics data integration shines a light on the renal medulla.

The renal medulla maintains salt and water balance and is prone to dysregulation because of high oxygen demand. Challenges in obtaining high-quality tissue have limited characterization of molecular programs regulating the medulla. Haug et al. leveraged gene expression, chromatin accessibility, long-range chromosomal interactions, and spatial transcriptomics to build a reference set of medullary tissue marker genes to define the medullary role in kidney function, exemplifying the strength and utility of multi-omic data integration.

Benchmarking splice variant prediction algorithms using massively parallel splicing assays.

BACKGROUND: Variants that disrupt mRNA splicing account for a sizable fraction of the pathogenic burden in many genetic disorders, but identifying splice-disruptive variants (SDVs) beyond the essential splice site dinucleotides remains difficult. Computational predictors are often discordant, compounding the challenge of variant interpretation. Because they are primarily validated using clinical variant sets heavily biased to known canonical splice site mutations, it remains unclear how well their performance generalizes. RESULTS: We benchmark eight widely used splicing effect prediction algorithms, leveraging massively parallel splicing assays (MPSAs) as a source of experimentally determined ground-truth. MPSAs simultaneously assay many variants to nominate candidate SDVs. We compare experimentally measured splicing outcomes with bioinformatic predictions for 3,616 variants in five genes. Algorithms' concordance with MPSA measurements, and with each other, is lower for exonic than intronic variants, underscoring the difficulty of identifying missense or synonymous SDVs. Deep learning-based predictors trained on gene model annotations achieve the best overall performance at distinguishing disruptive and neutral variants, and controlling for overall call rate genome-wide, SpliceAI and Pangolin have superior sensitivity. Finally, our results highlight two practical considerations when scoring variants genome-wide: finding an optimal score cutoff, and the substantial variability introduced by differences in gene model annotation, and we suggest strategies for optimal splice effect prediction in the face of these issues. CONCLUSION: SpliceAI and Pangolin show the best overall performance among predictors tested, however, improvements in splice effect prediction are still needed especially within exons.

High-Throughput Splicing Assays Identify Known and Novel WT1 Exon 9 Variants in Nephrotic Syndrome.

Introduction: Frasier syndrome (FS) is a rare Mendelian form of nephrotic syndrome (NS) caused by variants which disrupt the proper splicing of WT1. This key transcription factor gene is alternatively spliced at exon 9 to produce 2 isoforms ("KTS+" and "KTS-"), which are normally expressed in the kidney at a ∼2:1 (KTS+:KTS-) ratio. FS results from variants that reduce this ratio by disrupting the splice donor of the KTS+ isoform. FS is extremely rare, and it is unclear whether any variants beyond the 8 already known could cause FS. Methods: To prospectively identify other splicing-disruptive variants, we leveraged a massively parallel splicing assay. We tested every possible single nucleotide variant (n = 519) in and around WT1 exon 9 for effects upon exon inclusion and KTS+/- ratio. Results: Splice disruptive variants (SDVs) made up 11% of the tested point variants overall and were tightly concentrated near the canonical acceptor and the KTS+/- alternate donors. Our map successfully identified all 8 known FS or focal segmental glomerulosclerosis (FSGS) variants and 16 additional novel variants which were comparably disruptive to these known pathogenic variants. We also identified 19 variants that, conversely, increased the KTS+/KTS- ratio, of which 2 are observed in unrelated individuals with 46,XX ovotesticular disorder of sex development (46,XX OTDSD). Conclusion: This splicing effect map can serve as functional evidence to guide the clinical interpretation of newly observed variants in and around WT1 exon 9.

Prevalence and risk factors of ischemic monocular vision loss and concurrent brain ischemia.

INTRODUCTION: We performed a retrospective cohort study to identify predictors of concurrent asymptomatic brain ischemia in patients with ischemic monocular vision loss. PATIENTS AND METHODS: An inpatient database research of admissions to the Helios University Hospital Wuppertal, Germany between 01/2016 and 12/2020 was conducted. Inclusion criteria were confirmed diagnosis of transient monocular vision loss (MVL), retinal artery occlusion (RAO), and magnetic resonance imaging (MRI) of the brain within 10 days of MVL. Silent brain ischemia (SBI) was defined as diffusion restrictions with corresponding reduced apparent diffusion coefficient in MRI and an absence of neurological deficits besides those complying with MVL in clinical examination. The prevalence and cardiovascular predictors of SBI were analyzed with logistic regression and an artificial neural network. RESULTS: One hundred fourteen out of 475 patients treated with monocular vision loss were included in this study. The mean age was 67.7 ± 13.6 years. 48.2% were male and 47.4% had RAO. MRI scan of the brain was performed after 3.9 ± 2.3 days and detected SBI in 17%. Age ⩾67 years, cardiac etiology of MVL, and cerebral ischemia in medical history were revealed as predictors of SBI in MRI. CONCLUSIONS: Patients older than 66 years, with a suspected cardiac embolism as the cause of RAO and previous cerebral ischemia, are more likely to present SBI in cerebral MRI. Therefore, MR imaging, particularly in these patients, can be useful.

Consequences of Exposure to War Violence: Discriminating Those with Heightened Risk for Aggression from Those with Heightened Risk for Post-Traumatic Stress Symptoms.

Chronic exposure to ethnic-political and war violence has deleterious effects throughout childhood. Some youths exposed to war violence are more likely to act aggressively afterwards, and some are more likely to experience post-traumatic stress symptoms (PTS symptoms). However, the concordance of these two outcomes is not strong, and it is unclear what discriminates between those who are at more risk for one or the other. Drawing on prior research on desensitization and arousal and on recent social-cognitive theorizing about how high anxious arousal to violence can inhibit aggression, we hypothesized that those who characteristically experience higher anxious arousal when exposed to violence should display a lower increase in aggression after exposure to war violence but the same or a higher increase in PTS symptoms compared to those low in anxious arousal. To test this hypothesis, we analyzed data from our 4-wave longitudinal interview study of 1051 Israeli and Palestinian youths (ages at Wave 1 ranged from 8 to 14, and at Wave 4 from 15-22). We used the 4 waves of data on aggression, PTS symptoms, and exposure to war violence, along with additional data collected during Wave 4 on the anxious arousal participants experienced while watching a very violent film unrelated to war violence (N = 337). Longitudinal analyses revealed that exposure to war violence significantly increased both the risk of subsequent aggression and PTS symptoms. However, anxious arousal in response to seeing the unrelated violent film (measured from skin conductance and self-reports of anxiety) moderated the relation between exposure to war violence and subsequent psychological and behavioral outcomes. Those who experienced greater anxious arousal while watching the violent film showed a weaker positive relation between amount of exposure to war violence and aggression toward their peers but a stronger positive relation between amount of exposure to war violence and PTS symptoms.

Benchmarking splice variant prediction algorithms using massively parallel splicing assays.

Background: Variants that disrupt mRNA splicing account for a sizable fraction of the pathogenic burden in many genetic disorders, but identifying splice-disruptive variants (SDVs) beyond the essential splice site dinucleotides remains difficult. Computational predictors are often discordant, compounding the challenge of variant interpretation. Because they are primarily validated using clinical variant sets heavily biased to known canonical splice site mutations, it remains unclear how well their performance generalizes. Results: We benchmarked eight widely used splicing effect prediction algorithms, leveraging massively parallel splicing assays (MPSAs) as a source of experimentally determined ground-truth. MPSAs simultaneously assay many variants to nominate candidate SDVs. We compared experimentally measured splicing outcomes with bioinformatic predictions for 3,616 variants in five genes. Algorithms' concordance with MPSA measurements, and with each other, was lower for exonic than intronic variants, underscoring the difficulty of identifying missense or synonymous SDVs. Deep learning-based predictors trained on gene model annotations achieved the best overall performance at distinguishing disruptive and neutral variants. Controlling for overall call rate genome-wide, SpliceAI and Pangolin also showed superior overall sensitivity for identifying SDVs. Finally, our results highlight two practical considerations when scoring variants genome-wide: finding an optimal score cutoff, and the substantial variability introduced by differences in gene model annotation, and we suggest strategies for optimal splice effect prediction in the face of these issues. Conclusion: SpliceAI and Pangolin showed the best overall performance among predictors tested, however, improvements in splice effect prediction are still needed especially within exons.

Effectiveness of training before unsedated MRI scans in young children: a randomized control trial.

BACKGROUND: Young children requiring clinical magnetic resonance imaging (MRI) may be given general anesthesia. General anesthesia has potential side effects, is costly, and introduces logistical challenges. Thus, methods that allow children to undergo awake MRI scans are desirable. OBJECTIVES: To compare the effectiveness of mock scanner training with a child life specialist, play-based training with a child life specialist, and home book and video preparation by parents to allow non-sedated clinical MRI scanning in children aged 3-7 years. MATERIALS AND METHODS: Children (3-7 years, n=122) undergoing clinical MRI scans at the Alberta Children's Hospital were invited to participate and randomized to one of three groups: home-based preparation materials, training with a child life specialist (no mock MRI), or training in a mock MRI with a child life specialist. Training occurred a few days prior to their MRI. Self- and parent-reported functioning (PedsQL VAS) were assessed pre/post-training (for the two training groups) and pre/post-MRI. Scan success was determined by a pediatric radiologist. RESULTS: Overall, 91% (111/122) of children successfully completed an awake MRI. There were no significant differences between the mock scanner (89%, 32/36), child life (88%, 34/39), and at-home (96%, 45/47) groups (P=0.34). Total functioning scores were similar across groups; however, the mock scanner group had significantly lower self-reported fear (F=3.2, P=0.04), parent-reported sadness (F=3.3, P=0.04), and worry (F=3.5, P=0.03) prior to MRI. Children with unsuccessful scans were younger (4.5 vs. 5.7 years, P<0.001). CONCLUSIONS: Most young children can tolerate awake MRI scans and do not need to be routinely anesthetized. All preparation methods tested, including at-home materials, were effective.

Video Conferencing With Residents and Families for Care Planning During COVID-19: Experiences in Canadian Long-Term Care.

BACKGROUND AND OBJECTIVES: Government-mandated health and safety restrictions to mitigate the effects of coronavirus disease 2019 (COVID-19) intensified challenges in caring for older adults in long-term care (LTC) without family/care partners. This article describes the experiences of a multidisciplinary research team in implementing an evidence-based intervention for family-centered, team-based, virtual care planning-PIECESTM approach-into clinical practice. We highlight challenges and considerations for implementation science to support care practices for older adults in LTC, their families, and the workforce. RESEARCH DESIGN AND METHODS: A qualitative descriptive design was used. Data included meetings with LTC directors and Registered Practical Nurses (i.e., licensed nurse who graduated with a 2-year diploma program that allows them to provide basic nursing care); one-on-one interviews with family/care partners, residents, Registered Practical Nurses, and PIECES mentors; and reflections of the academic team. The Consolidated Framework for Implementation Research provided sensitizing constructs for deductive coding, while an inductive approach also allowed themes to emerge. RESULTS: Findings highlighted how aspects related to planning, engagement, execution, reflection, and evaluation influenced the implementation process from the perspectives of stakeholders. Involving expert partners on the research team to bridge research and practice, developing relationships from a distance, empowering frontline champions, and adapting to challenging circumstances led to shared commitments for intervention success. DISCUSSION AND IMPLICATIONS: Lessons learned include the significance of stakeholder involvement throughout all research activities, the importance of clarity around expectations of all team members, and the consequence of readiness for implementation with respect to circumstances (e.g., COVID-19) and capacity for change.

Gene amplification acts as a molecular foothold to facilitate cross-species adaptation and evasion of multiple antiviral pathways.

Cross-species spillover events are responsible for many of the pandemics in human history including COVID-19; however, the evolutionary mechanisms that enable these events are poorly understood. We have previously modeled this process using a chimeric vaccinia virus expressing the rhesus cytomegalovirus-derived protein kinase R (PKR) antagonist RhTRS1 in place of its native PKR antagonists: E3L and K3L (VACVΔEΔK + RhTRS1). Using this virus, we demonstrated that gene amplification of rhtrs1 occurred early during experimental evolution and was sufficient to fully rescue virus replication in partially resistant African green monkey (AGM) fibroblasts. Notably, this rapid gene amplification also allowed limited virus replication in otherwise completely non-permissive human fibroblasts, suggesting that gene amplification may act as a 'molecular foothold' to facilitate viral adaptation to multiple species. In this study, we demonstrate that there are multiple barriers to VACVΔEΔK + RhTRS1 replication in human cells, mediated by both PKR and ribonuclease L (RNase L). We experimentally evolved three AGM-adapted virus populations in human fibroblasts. Each population adapted to human cells bimodally, via an initial 10-fold increase in replication after only two passages followed by a second 10-fold increase in replication by passage 9. Using our Illumina-based pipeline, we found that some single nucleotide polymorphisms (SNPs) which had evolved during the prior AGM adaptation were rapidly lost, while thirteen single-base substitutions and short indels increased over time, including two SNPs unique to human foreskin fibroblast (HFF)-adapted populations. Many of these changes were associated with components of the viral RNA polymerase, although no variant was shared between all three populations. Taken together, our results demonstrate that rhtrs1 amplification was sufficient to increase viral tropism after passage in an 'intermediate species' and subsequently enabled the virus to adopt different, species-specific adaptive mechanisms to overcome distinct barriers to viral replication in AGM and human cells.

Saturation-scale functional evidence supports clinical variant interpretation in Lynch syndrome.

BACKGROUND: Lynch syndrome (LS) is a cancer predisposition syndrome affecting more than 1 in every 300 individuals worldwide. Clinical genetic testing for LS can be life-saving but is complicated by the heavy burden of variants of uncertain significance (VUS), especially missense changes. RESULT: To address this challenge, we leverage a multiplexed analysis of variant effect (MAVE) map covering >94% of the 17,746 possible missense variants in the key LS gene MSH2. To establish this map's utility in large-scale variant reclassification, we overlay it on clinical databases of >15,000 individuals with LS gene variants uncovered during clinical genetic testing. We validate these functional measurements in a cohort of individuals with paired tumor-normal test results and find that MAVE-based function scores agree with the clinical interpretation for every one of the MSH2 missense variants with an available classification. We use these scores to attempt reclassification for 682 unique missense VUS, among which 34 scored as deleterious by our function map, in line with previously published rates for other cancer predisposition genes. Combining functional data and other evidence, ten missense VUS are reclassified as pathogenic/likely pathogenic, and another 497 could be moved to benign/likely benign. Finally, we apply these functional scores to paired tumor-normal genetic tests and identify a subset of patients with biallelic somatic loss of function, reflecting a sporadic Lynch-like Syndrome with distinct implications for treatment and relatives' risk. CONCLUSION: This study demonstrates how high-throughput functional assays can empower scalable VUS resolution and prospectively generate strong evidence for variant classification.

Nurse-Led Virtual Delivery of PIECES in Canadian Long-Term Care Homes to Support the Care of Older Adults Experiencing Responsive Behaviors During COVID-19: Qualitative Descriptive Study.

BACKGROUND: Worldwide, the COVID-19 pandemic has resulted in profound loss of life among older adults living in long-term care (LTC) homes. As a pandemic response, LTC homes enforced infection control processes, including isolating older adults in their rooms, canceling therapeutic programs, and restricting family member visits. Social isolation negatively impacts older adults in LTC, which may result in increased rates of anxiety, depression, physical and cognitive decline, disorientation, fear, apathy, and premature death. Isolation of older adults can also cause an increase in responsive behaviors (eg, yelling, hitting, calling out) to express frustration, fear, restricted movement, and boredom. To respond to the challenges in LTC and support frontline staff, older adults, and family members, a novel registered practical nurse (RPN)-led delivery of the PIECES approach for addressing responsive behaviors among older adults with dementia using virtual training/mentoring was implemented in Canadian LTC homes. PIECES employs a person- and family/care partner-centered collaborative team-based approach to provide education and capacity-building for nurses; engages families as active participants in care; and embeds evidence-informed practices to provide person- and family-centered care to older adults with complex needs, including dementia. OBJECTIVE: The aim of this study was to describe the experiences of LTC staff, family/care partners, and older adult research partners with implementation of a novel RPN-led virtual adaptation of the PIECES care-planning approach for responsive behaviors in two Canadian LTC homes during the COVID-19 pandemic. METHODS: Using a qualitative descriptive design, two focus groups were held with three to four staff members (eg, RPNs, managers) per LTC home in Ontario. A third focus group was held with three PIECES mentors. Individual semistructured interviews were conducted with RPN champions, family/care partners, and older adult research partners. Research team meeting notes provided an additional source of data. Content analysis was performed. RESULTS: A total of 22 participants took part in a focus group (n=11) or an in-depth individual interview (n=11). Participant experiences suggest that implementation of RPN-led virtual PIECES fostered individualized care, included family as partners in care, increased interdisciplinary collaboration, and improved staff practices. However, virtual PIECES, as delivered, lacked opportunities for family member feedback on older adult outcomes. Implementation facilitators included the provision of mentorship and leadership at all levels of implementation and suitable technological infrastructure. Barriers were related to availability and use of virtual communication technology (family members) and older adults became upset due to lack of comprehension during virtual care conferences. CONCLUSIONS: These findings offer promising support to adopting virtual PIECES, a team approach to gather valuable family input and engagement to address residents' unmet needs and responsive behaviors in LTC. Future research should investigate a hybridized communication format to foster sustainable person- and family-centered care-planning practices to include active collaboration of families in individualized care plans.

Lidocaine Ineffectiveness Suggests New Psychopharmacology Drug Target.

Objectives: The mechanism of many neuropsychiatric disorders remains unknown, but the ineffectiveness of the sodium channel blocker lidocaine has been suggested to be a biomarker for Attention Deficit Hyperactivity Disorder (ADHD) and a severe form of Premenstrual Syndrome (PMS) that is considered psychiatric. We conducted single-arm double-blind clinical trials to test whether lidocaine ineffectiveness can be used as a biomarker to identify people with these conditions and provide a clue as to the molecular mechanism and potential psychopharmacological intervention. Experimental Design: We developed a noninvasive taste test for lidocaine ineffectiveness, validated by comparing lidocaine injections to pain testing in 12 subjects, and assessed it in individuals with ADHD and PMS. Principal Observations: Lidocaine ineffectiveness had a strong association in women with ADHD + PMS in a sample of 53 subjects and controls (p < 0.001). Conclusions: These results suggest the possibility of the biological understanding of the combination of ADHD and PMS that is characteristic of the psychiatric disorder Premenstrual Dysphoric Disorder (PMDD). These results and comparison to family pedigrees of a neuromuscular channelopathy with overlapping symptoms suggest the possibility that the clinical phenotype in PMDD is produced by sensory overstimulation, and amenable to molecular understanding and treatment.

Gene amplification acts as a molecular foothold to facilitate cross-species adaptation and evasion of multiple antiviral pathways.

Cross-species spillover events are responsible for many of the pandemics in human history including COVID-19; however, the evolutionary mechanisms that enable these events are poorly understood. We have previously modeled this process using a chimeric vaccinia virus expressing the rhesus cytomegalovirus-derived PKR antagonist RhTRS1 in place of its native PKR antagonists; E3L and K3L (VACVΔEΔK+RhTRS1). Using this virus, we demonstrated that gene amplification of rhtrs1 occurred early during experimental evolution and was sufficient to fully rescue virus replication in partially resistant African green monkey (AGM) fibroblasts. Notably, this rapid gene amplification also allowed limited virus replication in otherwise completely non-permissive human fibroblasts, suggesting that gene amplification may act as a "molecular foothold" to facilitate viral adaptation to multiple species. In this study, we demonstrate that there are multiple barriers to VACVΔEΔK+RhTRS1 replication in human cells, mediated by both PKR and RNase L. We experimentally evolved three AGM-adapted virus populations in human fibroblasts. Each population adapted to human cells bimodally, via an initial 10-fold increase in replication after only two passages followed by a second 10-fold increase in replication by passage nine. Using our Illumina-based pipeline, we found that some SNPs which had evolved during the prior AGM adaptation were rapidly lost, while 13 single-base substitutions and short indels increased over time, including two SNPs unique to HFF adapted populations. Many of these changes were associated with components of the viral RNA polymerase, although no variant was shared between all three populations. Taken together, our results demonstrate that rhtrs1 amplification was sufficient to increase viral tropism after passage in an "intermediate species" and subsequently enabled the virus to adopt different, species-specific adaptive mechanisms to overcome distinct barriers to viral replication in AGM and human cells.

High-throughput splicing assays identify missense and silent splice-disruptive POU1F1 variants underlying pituitary hormone deficiency.

Pituitary hormone deficiency occurs in ∼1:4,000 live births. Approximately 3% of the cases are due to mutations in the alpha isoform of POU1F1, a pituitary-specific transcriptional activator. We found four separate heterozygous missense variants in unrelated individuals with hypopituitarism that were predicted to affect a minor isoform, POU1F1 beta, which can act as a transcriptional repressor. These variants retain repressor activity, but they shift splicing to favor the expression of the beta isoform, resulting in dominant-negative loss of function. Using a high-throughput splicing reporter assay, we tested 1,070 single-nucleotide variants in POU1F1. We identified 96 splice-disruptive variants, including 14 synonymous variants. In separate cohorts, we found two additional synonymous variants nominated by this screen that co-segregate with hypopituitarism. This study underlines the importance of evaluating the impact of variants on splicing and provides a catalog for interpretation of variants of unknown significance in POU1F1.

Social media strategies to affect vaccine acceptance: a systematic literature review.

Introduction: Vaccine hesitancy, defined as a delay in the acceptance or the refusal of vaccines despite their availability, is a growing global threat. More individuals are turning to social media for health information, including vaccine information. As such, there is an opportunity to leverage online platforms as a means to disseminate and persuade individuals toward vaccine acceptance. We sought to review literature focused on the influence of exposure to social media content on vaccine acceptance or hesitancy.Areas covered: This review focused on social networking sites (e.g. Facebook) and content communities (e.g. YouTube), to understand how exposure to vaccine information affected vaccine knowledge, attitudes, and intentions/behaviors. We searched PubMed, CINAHL, Scopus, and Inspec. We included English-language materials published from 2004 to 2020 and included interventional studies, observational studies, and impacts of policies. We excluded systematic reviews, protocols, editorials, letters, case reports, case studies, commentaries, opinion pieces, narrative reviews, and clinical guidelines.Expert opinion: Social media interventions to affect vaccine acceptance is a new but growing area of study. How a communication message is framed, who delivers the message, and network structure are critical for affecting the vaccine decision-making process. Social media should be leveraged to impact vaccine uptake.

Longitudinal predictions of young adults' weapons use and criminal behavior from their childhood exposure to violence.

In this study, we examine whether youth who are exposed to more weapons violence are subsequently more likely to behave violently with weapons. We use data collected with a 3-cohort, 4-wave, 10-year longitudinal study of 426 high-risk youth from Flint, Michigan, who were second, fourth, or ninth-graders in 2006-2007. The data were obtained from individual interviews with the youth, their parents, and their teachers, from archival school and criminal justice records, and from geo-coded criminal offense data. These data show that early exposure to weapons violence significantly correlates at modest levels with weapon carrying, weapon use or threats-to-use, arrests for weapons use, and criminally violent acts 10 years later. Multiple regression analyses, controlling for children's initial aggressiveness, intellectual achievement, and parents' income, education, and aggression, reveal statistically significant independent 10-year effects: (1) more early exposure to weapon use within the family predicts more using or threatening to use a gun; (2) more cumulative early violent video game playing predicts more gun using or threatening to use weapons, and normative beliefs that gun use is acceptable; (3) more cumulative early exposure to neighborhood gun violence predicts more arrests for a weapons crime; and (4) more cumulative early exposure to movie violence predicts more weapon carrying. We argue that youth who observe violence with weapons, whether in the family, among peers, or through the media or video games, are likely to be infected from exposure with a social-cognitive-emotional disease that increases their own risk of behaving violently with weapons later in life.

Collaborative framework for working with older simulated participants (SP).

Introduction: As the global population ages, healthcare providers must prepare for the complexities associated with caring for older adults, defined according to the WHO, as being over the age of 60. Simulation-based education in healthcare allows caregivers to practice and master skills and competencies associated with care of older adults. Simulated patients/participants (SP), well people trained to portray other individuals, are an effective choice when training behavioural skills (eg, communication). When working with older SPs, it is important to recognise unique considerations and requirements related to physiological changes, in physical, cognitive and sensory systems associated with normal ageing. Method: SP educators from two different countries, with diverse backgrounds and contexts, collaborated through an iterative, consensus-based process to create a framework for working with older SPs. Results: A practical three-phase framework with specific strategies was developed that synthesised elements of best practices related to simulation methodology with relevant clinical evidence. Discussion: Effective collaboration with older SPs is achievable through investing resources in preparing, training and ensuring their well-being. Through faculty development of healthcare simulation educators, we can ensure that older SPs and simulation communities have the right tools and support to safely and effectively contribute to simulation-based education.

"Please let me know when I do not realize it myself": a qualitative analysis of senior simulated patients' experiences.

BACKGROUND: Simulated patients (SPs), defined as being over 65 years old, are valuable partners in the training of health professionals related to the care of our aging population. Many senior SPs have been long-time members of SP programs. As SPs age, shifts in their abilities may be observed that, in turn, can affect the overall quality and effectiveness of their participation. It can be challenging and distressing for both the SP educator and the SP to acknowledge these changes and to respond in a compassionate, respectful, and ethical manner that ensures the safe and effective delivery of a simulation for all stakeholders. SP educators are looking for guidance. The aim of this study was to ask SPs from two countries (Switzerland and Canada) to identify the benefits and challenges of working as SPs as they age and to offer strategies to SP educators to accommodate and facilitate their participation. METHOD: A qualitative thematic analysis research design was implemented to address the study aims. A semi-structured approach with a topic guide was used to individually interview 16 SPs (9 in Switzerland; 7 in Canada). Researchers iteratively compared their results until consensus was reached in terms of identifying the themes and subthemes. RESULTS: Three main themes, with corresponding subthemes, were identified: giving and receiving value as senior SPs, recognizing challenges when working as a senior SP, and fostering meaningful involvement for senior SPs. Meaningful involvement focused on creating a sense of security, adapting to changing abilities, acknowledging contributions, and providing opportunities to stay connected to the program. CONCLUSION: This study illustrates the importance of SP educators working with SPs to co-create a safe and effective work environment. Studies like this can serve as a model to provide practical strategies. Through this study, we have learned from senior SPs how we can best support them in their important work.