Status-neutral community-based multilevel intervention to address intersectional stigma and discrimination, and increase HIV testing, PrEP, and ART uptake among YGBMSM in Ghanaian Slums: A clustered randomized control trial protocol.

Background: While GBMSM constitute less than 2% of Ghana's population, their HIV prevalence surpasses the national average by more than eightfold, emphasizing the critical need for targeted interventions to improve detection, care linkage, and reduce community transmission. This study seeks to increase HIV testing, Pre-Exposure Prophylaxis (PrEP), and Antiretroviral Therapy (ART) uptake (HPART) among YGBMSM through the adaptation of an evidence-based intervention (LAFIYA). Methodology: We will employ the ADAPTT-IT framework to adapt LAFIYA and evaluate its feasibility and effectiveness in addressing intersectional stigma and increasing HPART uptake among YGBMSM residing in Ghanaian slums. In aim 1, we will hold focus groups (n=5) and interviews (n=20) among YGBMSM and two FGDs among GBMSM-led organizations. At the HCF level, we will hold 6 FGDs and interviews (n=20) among nurses. In AIM 2, we will randomly assign 6 healthcare facilities (HCFs) to receive the LAFIYA (n=3) or wait-list control (n=3). Friend groups (cluster) of YGBMSM (N=240) will be assigned to receive LAFIYA (n=120) or a wait-list control (n=120). We will collect 3-, 6-, and 9-months post-intervention data among YGBMSM(n=240) and HCWs(n=300) to measure HPART adherence (primary outcomes), ISD reduction, HIV and status-neutral knowledge (secondary outcomes), and intervention acceptability, appropriateness, and feasibility (implementation outcomes). Conclusion: The intervention group will observe increased HPART adherence, reduced ISD, and enhanced HPART knowledge and efficacy relative to the wait-list control group. The findings will inform ISD reduction and HIV status-neutral implementation strategies - and place-based interventions that address access to HIV prevention and care among YGBMSM, slum and in different settings. Trail Registration: This study was registered on clinicalTrail.gov, with identifier number NCT06312514 on 03/14/2023. https://classic.clinicaltrials.gov/ct2/show/NCT06312514.

Heart failure in nursing homes: A scoping review of educational interventions for optimising care provision.

Background: Heart failure has an estimated global prevalence of 64.3 million cases, with an average age of a person living with heart failure at 75.2 years. Approximately 20% of residents living in nursing homes (a long-term residential care environment for some individuals) report living with heart failure. Residents living with heart failure in nursing home environments are often frail, have reduced quality of life, higher rates of rehospitalisation and mortality, and greater complications in heart failure management. Further, nursing home staff often lack the knowledge and skills required to provide the necessary care for those living with heart failure. Interventions for improving heart failure management in nursing homes have proven effective, yet there is a lack of understanding regarding interventions for optimising care provision. The aim of this review was to synthesise the current evidence on educational interventions to optimise care provided to people with heart failure in nursing homes. Methods: A scoping review with four databases searched: Medline, CINAHL, Web of Science, and EMBASE. Relevant reference lists were searched manually for additional records. Studies of nursing home staff or resident outcomes associated with changes in care provision (i.e., resident quality of life, staff knowledge of heart failure) were included. Results from the charting data process were collated into themes: intervention outcomes, changes to practice, and implementation and process evaluation. Results: Seven papers were deemed eligible for inclusion. Most studies (n=6) were comprised of nursing home staff only, with one comprised only of residents. Study aims were to improve heart failure knowledge, interprofessional communication, heart failure assessment and management. Positive changes in staff outcomes were observed, with improvements in knowledge, self-efficacy, and confidence in providing care reported. No difference was reported concerning nursing home resident outcomes. Interprofessional communication and staff ability to conduct heart failure assessments improved post-intervention. Changes to practice were mixed, with issues around sustainability reported. Nursing home staff highlighted their appreciation towards receiving education, recommending that videos, images, and humour could improve the intervention content. Conclusions: There is a paucity of evidence around educational interventions to support residents living with heart failure in nursing homes. However, available evidence suggests that educational interventions in nursing homes may improve care through improving staff self-efficacy and confidence in providing care, heart failure knowledge and interprofessional communication. The complexity of implementing educational interventions in the nursing home setting must be considered during the development process to improve implementation, effectiveness, and sustainability.

Study protocol: Examining sexual and reproductive health literacy in Mexican American young women using a positive deviance approach.

Health literacy is generally low in marginalized groups, leading to delays in accessing care, poor health outcomes, and health disparities. Yet, some individuals in these groups demonstrate higher health literacy and better health outcomes. These exceptional cases exemplify 'positive deviance' because they have found ways to be successful where others have not. Identifying the methods, practices, and resources that these individuals have used to gain health literacy and healthcare access may have generalized application to improve health literacy, access to care, and health outcomes. Using the Integrated Model of Health Literacy, the main objectives of this study are to (1) identify facilitators, barriers, and strategies to gain sexual and reproductive health literacy and healthcare access and (2) to explore each of the core domains of health literacy as they relate to successful access of sexual and reproductive healthcare services among individuals identified as positive deviants. For the purposes of this mixed methods community engaged study, positive deviants are defined as Mexican American young women aged 18-29 years old living in Rural Western New York who have accessed sexual and reproductive healthcare within the past year. A community advisory committee will be formed to provide community-engaged guidance and support for the recruitment of participants. Positive deviants will participate in a survey and semi-structured interview. Data collection and analysis will be simultaneous and iterative. Results will provide evidence of positive deviant methods, practices, and strategies to gain health literacy and access to sexual and reproductive healthcare. Findings may reveal characteristics and patterns in the relationship of health literacy and healthcare access that can inform interventions to improve health literacy and make healthcare more accessible for this demographic group and context.

Co-design and mixed methods evaluation of an interdisciplinary digital resource for undergraduate health profession students to improve the prevention, recognition, and management of delirium in Ireland: a study protocol.

BACKGROUND: Delirium is a common symptom of acute illness which is potentially avoidable with early recognition and intervention. Despite being a growing concern globally, delirium remains underdiagnosed and poorly reported, with limited understanding of effective delirium education for undergraduate health profession students. Digital resources could be an effective approach to improving professional knowledge of delirium, but studies utilising these with more than one profession are limited, and no evidence-based, interdisciplinary, digital delirium education resources are reported. This study aims to co-design and evaluate a digital resource for undergraduate health profession students across the island of Ireland to improve their ability to prevent, recognise, and manage delirium alongside interdisciplinary colleagues. METHODS: Utilising a logic model, three workstreams have been identified. Workstream 1 will comprise three phases: (1) a systematic review identifying the format, methods, and content of existing digital delirium education interventions for health profession students, and their effect on knowledge, self-efficacy, and behavioural change; (2) focus groups with health profession students to determine awareness and experiences of delirium care; and (3) a Delphi survey informed by findings from the systematic review, focus groups, and input from the research team and expert reference group to identify resource priorities. Workstream 2 will involve the co-design of the digital resource through workshops (n = 4) with key stakeholders, including health profession students, professionals, and individuals with lived experience of delirium. Lastly, Workstream 3 will involve a mixed methods evaluation of the digital resource. Outcomes include changes to delirium knowledge and self-efficacy towards delirium care, and health profession students experience of using the resource. DISCUSSION: Given the dearth of interdisciplinary educational resources on delirium for health profession students, a co-designed, interprofessional, digital education resource will be well-positioned to shape undergraduate delirium education. This research may enhance delirium education and the self-efficacy of future health professionals in providing delirium care, thereby improving practice and patients' experiences and outcomes. TRIAL REGISTRATION: Not applicable.

Heart Failure Nurses within the Primary Care Setting.

Cardiology services within primary care often focus on disease prevention, early identification of illness and prompt referral for diagnosis and specialist treatment. Due to advances in pharmaceuticals, implantable cardiac devices and surgical interventions, individuals with heart failure are living longer, which can place a significant strain on global healthcare resources. Heart failure nurses in a primary care setting offer a wealth of clinical knowledge and expertise across all phases of the heart failure trajectory and are able to support patients, family members and other community services, including general practitioners. This review examines the recently published evidence on the current and potential future practice of heart failure nurses within primary care.

Assessing understandings and perceptions of HIV cure among peer navigators and treatment officers in Australia.

HIV community peer navigators and treatment officers are important sources of information and guidance for people living with HIV. We conducted an anonymous online survey with members of the treatment outreach network of the Australian National Association of People Living with HIV. The survey explored understandings and acceptance of HIV cure research and was disseminated before and following an interactive workshop on HIV cure. We demonstrated an improvement in understandings of HIV cure science and increased willingness to participate in interventional clinical trials after the workshop. Concerns around interrupting HIV treatment and detrimental impacts on health were identified as barriers to participation. Altruism was a motivator to enrol in HIV cure trials, along with endorsement from a trusted member of community.

KDM3B inhibitors disrupt the oncogenic activity of PAX3-FOXO1 in fusion-positive rhabdomyosarcoma.

Fusion-positive rhabdomyosarcoma (FP-RMS) is an aggressive pediatric sarcoma driven primarily by the PAX3-FOXO1 fusion oncogene, for which therapies targeting PAX3-FOXO1 are lacking. Here, we screen 62,643 compounds using an engineered cell line that monitors PAX3-FOXO1 transcriptional activity identifying a hitherto uncharacterized compound, P3FI-63. RNA-seq, ATAC-seq, and docking analyses implicate histone lysine demethylases (KDMs) as its targets. Enzymatic assays confirm the inhibition of multiple KDMs with the highest selectivity for KDM3B. Structural similarity search of P3FI-63 identifies P3FI-90 with improved solubility and potency. Biophysical binding of P3FI-90 to KDM3B is demonstrated using NMR and SPR. P3FI-90 suppresses the growth of FP-RMS in vitro and in vivo through downregulating PAX3-FOXO1 activity, and combined knockdown of KDM3B and KDM1A phenocopies P3FI-90 effects. Thus, we report KDM inhibitors P3FI-63 and P3FI-90 with the highest specificity for KDM3B. Their potent suppression of PAX3-FOXO1 activity indicates a possible therapeutic approach for FP-RMS and other transcriptionally addicted cancers.

Experiences of People Living with Parkinson's Disease in Care Homes: A Qualitative Systematic Review.

BACKGROUND: Incidence of disability secondary to Parkinson's disease is increasing faster globally than any other neurological condition. The diverse appearance of symptomatology associated with Parkinson's, and the degenerative nature and subsequent functional decline, often increase dependence on caregivers for assistance with daily living, most commonly within a care home setting. Yet, primary literature and evidence synthesis surrounding these unique and complex care needs, challenges and the lived experiences of this population living in long-term nursing or residential facilities remains sparce. The aim of this review is to synthesize qualitative literature about the lived experience of people with Parkinson's disease living in care home settings. METHODS: A systematic search of the literature was conducted in October 2023 across six different databases (CINAHL, Medline, EMBASE, PsycINFO, Scopus and Cochrane Library). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) was used to guide this review. RESULTS: Five articles met the inclusion criteria. Four themes were identified following evidence synthesis: (1) Unique pharmacological challenges. (2) Transitioning and adapting to care home life and routines. (3) Dignified care within care homes. (4) Multidisciplinary care vacuum in care homes. CONCLUSION: This review revealed the significant and unique challenges for people with Parkinson's disease when transitioning into care homes. These are exacerbated by wider social care challenges such as staffing levels, skill mixes and attitudes as well as a lack of disease-specific knowledge surrounding symptomatology and pharmacology. The lack of multi-disciplinary working and risk-adverse practice inhibited person-centred care and autonomy and reduced the quality of life of people living with Parkinson's disease in care homes. Recommendations for practice highlight training gaps, the need for consistent and improved interdisciplinary working and better person-centred assessment and care delivery.

Exploring the Holistic Needs of People Living with Cancer in Care Homes: An Integrative Review.

Up to 26% of individuals residing in care homes are impacted by cancer. This underscores the importance of understanding the holistic needs of care home residents living with cancer to enhance the quality of their care. The primary objective of this integrative literature review was to consolidate the available evidence concerning the comprehensive needs of people living with cancer in care home settings, providing valuable insights into addressing their diverse needs. An integrative literature review was conducted using a systematic approach. Extensive searches were conducted in three databases, complemented by a thorough examination of grey literature and reference lists of relevant papers. The review focused on literature published between 2012 and 2022. The screening process involved two independent reviewers, with a third reviewer resolving any discrepancies. The review identified twenty research papers that met the eligibility criteria. These papers shed light on three primary themes related to the holistic needs of care home residents with cancer: physical, psychological, and end-of-life needs. Physical needs encompassed pain management, symptom control, and nutrition, while psychological needs involved social support, emotional well-being, and mental health care. End-of-life needs addressed end-of-life care and advance care planning. These themes highlight the multifaceted nature of cancer care in care homes and underscore the importance of addressing residents' holistic needs in a comprehensive and integrated manner. Improving care home education about cancer and integrating palliative and hospice services within this setting are vital for addressing the diverse needs of residents with cancer.

The APPRISE Virtual Biobank for Infectious Diseases.

The Australian Partnership for Preparedness Research on InfectiouS disease Emergencies (APPRISE) has developed a virtual biobank to support infectious disease research in Australia. The virtual biobank (https://apprise.biogrid.org.au) integrates access to existing distributed infectious disease biospecimen collections comprising multiple specimen types, including plasma, serum, and peripheral blood mononuclear cells. Through the development of a common data model, multiple collections can be searched simultaneously via a secure web portal. The portal enhances the visibility and searchability of existing collections within their current governance and custodianship arrangements. The portal is easily scalable for integration of additional collections.

Applying the Theoretical Domains Framework to identify police, fire, and paramedic preferences for accessing mental health care in a First Responder Operational Stress Injury Clinic: a qualitative study. / Application du cadre Theoretical Domains Framework pour cerner les préférences des policiers, des pompiers et des ambulanciers en matière d'accès aux soins de santé mentale dans une clinique de traitement des blessures de stress opérationnel pour les premiers répondants : une étude qualitative.

INTRODUCTION: First responders and other public safety personnel (PSP; e.g. correctional workers, firefighters, paramedics, police, public safety communicators) are often exposed to events that have the potential to be psychologically traumatizing. Such exposures may contribute to poor mental health outcomes and a greater need to seek mental health care. However, a theoretically driven, structured qualitative study of barriers and facilitators of help-seeking behaviours has not yet been undertaken in this population. This study used the Theoretical Domains Framework (TDF) to identify and better understand critical barriers and facilitators of help-seeking and accessing mental health care for a planned First Responder Operational Stress Injury (OSI) clinic. METHODS: We conducted face-to-face, one-on-one semistructured interviews with 24 first responders (11 firefighters, five paramedics, and eight police officers), recruited using purposive and snowball sampling. Interviews were analyzed using deductive content analysis. The TDF guided study design, interview content, data collection, and analysis. RESULTS: The most reported barriers included concerns regarding confidentiality, lack of trust, cultural competency of clinicians, lack of clarity about the availability and accessibility of services, and stigma within first responder organizations. Key themes influencing help-seeking were classified into six of the TDF's 14 theoretical domains: environmental context and resources; knowledge; social influences; social/professional role and identity; emotion; and beliefs about consequences. CONCLUSION: The results identified key actions that can be utilized to tailor interventions to encourage attendance at a First Responder OSI Clinic. Such approaches include providing transparency around confidentiality, policies to ensure greater cultural competency in all clinic staff, and clear descriptions of how to access care; routinely involving families; and addressing stigma.

Impact of a TLR9 agonist and broadly neutralizing antibodies on HIV-1 persistence: the randomized phase 2a TITAN trial.

Inducing antiretroviral therapy (ART)-free virological control is a critical step toward a human immunodeficiency virus type 1 (HIV-1) cure. In this phase 2a, placebo-controlled, double-blinded trial, 43 people (85% males) with HIV-1 on ART were randomized to (1) placebo/placebo, (2) lefitolimod (TLR9 agonist)/placebo, (3) placebo/broadly neutralizing anti-HIV-1 antibodies (bNAbs) or (4) lefitolimod/bNAb. ART interruption (ATI) started at week 3. Lefitolimod was administered once weekly for the first 8 weeks, and bNAbs were administered twice, 1 d before and 3 weeks after ATI. The primary endpoint was time to loss of virologic control after ATI. The median delay in time to loss of virologic control compared to the placebo/placebo group was 0.5 weeks (P = 0.49), 12.5 weeks (P = 0.003) and 9.5 weeks (P = 0.004) in the lefitolimod/placebo, placebo/bNAb and lefitolimod/bNAb groups, respectively. Among secondary endpoints, viral doubling time was slower for bNAb groups compared to non-bNAb groups, and the interventions were overall safe. We observed no added benefit of lefitolimod. Despite subtherapeutic plasma bNAb levels, 36% (4/11) in the placebo/bNAb group compared to 0% (0/10) in the placebo/placebo group maintained virologic control after the 25-week ATI. Although immunotherapy with lefitolimod did not lead to ART-free HIV-1 control, bNAbs may be important components in future HIV-1 curative strategies. ClinicalTrials.gov identifier: NCT03837756 .

Effect of high dose vitamin D3 on the HIV-1 reservoir: A pilot randomised controlled trial.

Introduction: Antiretroviral therapy for people living with HIV-1 must be taken lifelong due to the persistence of latent virus in long-lived and proliferating CD4+ T cells. Vitamin D3 is a steroidal gene transcription regulator which exerts diverse effects on immune and epithelial cells including reductions in CD4+ T cell proliferation and improvement in gut barrier integrity. We hypothesised that a high dose of vitamin D3 would reduce the size of the HIV-1 reservoir by reducing CD4+ T cell proliferation. Methods: We performed a randomised placebo-controlled trial evaluating the effect of 24 weeks of vitamin D3 (10,000 international units per day) on the HIV-1 reservoir and immunologic parameters in 30 adults on antiretroviral therapy; participants were followed for 12 weeks post-treatment. The primary endpoint was the effect on total HIV-1 DNA at week 24. Parameters were assessed using mixed-effects models. Results: We found no effect of vitamin D3 on the change in total HIV-1 DNA from week 0 to week 24 relative to placebo. There were also no changes in integrated HIV-1 DNA, 2-long-terminal repeat (2-LTR) circles or cell-associated HIV-1 RNA. Vitamin D3 induced a significant increase in the proportion of central memory CD4+ and CD8+ T cells, a reduction in the proportion of senescent CD8+ T cells and a reduction in the natural killer cell frequency at all time points including week 36, 12 weeks after the study drug cessation. At week 36, there was a significant reduction in total HIV-1 DNA relative to placebo and persistently elevated 25-hydroxyvitamin D levels. No significant safety issues were identified. Conclusions: Vitamin D3 administration had a significant impact on the T cell differentiation but overall effects on the HIV-1 reservoir were limited and a reduction in HIV-1 DNA was only seen following cessation of the study drug. Additional studies are required to determine whether the dose and duration of vitamin D3 can be optimised to promote a continued depletion of the HIV-1 reservoir over time. Trial registration: ClinicalTrials.gov NCT03426592.

Venetoclax, alone and in combination with the BH3 mimetic S63845, depletes HIV-1 latently infected cells and delays rebound in humanized mice.

HIV-1 persists indefinitely in people living with HIV (PLWH) on antiretroviral therapy (ART). If ART is stopped, the virus rapidly rebounds from long-lived latently infected cells. Using a humanized mouse model of HIV-1 infection and CD4+ T cells from PLWH on ART, we investigate whether antagonizing host pro-survival proteins can prime latent cells to die and facilitate HIV-1 clearance. Venetoclax, a pro-apoptotic inhibitor of Bcl-2, depletes total and intact HIV-1 DNA in CD4+ T cells from PLWH ex vivo. This venetoclax-sensitive population is enriched for cells with transcriptionally higher levels of pro-apoptotic BH3-only proteins. Furthermore, venetoclax delays viral rebound in a mouse model of persistent HIV-1 infection, and the combination of venetoclax with the Mcl-1 inhibitor S63845 achieves a longer delay in rebound compared with either intervention alone. Thus, selective inhibition of pro-survival proteins can induce death of HIV-1-infected cells that persist on ART, extending time to viral rebound.

Serological assays to measure dimeric IgA antibodies in SARS-CoV-2 infections.

Current serological tests cannot differentiate between total immunoglobulin A (IgA) and dimeric IgA (dIgA) associated with mucosal immunity. Here, we describe two new assays, dIgA-ELISA and dIgA-multiplex bead assay (MBA), that utilize the preferential binding of dIgA to a chimeric form of secretory component, allowing the differentiation between dIgA and monomeric IgA. dIgA responses elicited through severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were measured in (i) a longitudinal panel, consisting of 74 samples (n = 20 individuals) from hospitalized cases of coronavirus disease 2019 (COVID-19); (ii) a longitudinal panel, consisting of 96 samples (n = 10 individuals) from individuals with mild COVID-19; (iii) a cross-sectional panel with PCR-confirmed SARS-CoV-2 infection with mild COVID-19 (n = 199) and (iv) pre-COVID-19 samples (n = 200). The dIgA-ELISA and dIgA-MBA demonstrated a specificity for dIgA of 99% and 98.5%, respectively. Analysis of dIgA responses in the longitudinal panels revealed that 70% (ELISA) and 50% (MBA) of patients elicited a dIgA response by day 20 after PCR diagnosis with a SARS-CoV-2 infection. Individuals with mild COVID-19 displayed increased levels of dIgA within the first 3 weeks after diagnosis but responses appeared to be short lived, compared with sustained IgA levels. However, in samples from hospitalized patients with COVID-19 we observed high and sustained levels of dIgA, up to 245 days after PCR diagnosis. Our results suggest that severe COVID-19 infections are associated with sustained levels of plasma dIgA compared with mild cases.

Optimising quality of life for people living with heart failure in care homes: Protocol for the co-design and feasibility testing of a digital intervention.

BACKGROUND: Heart failure (HF) affects up to 64.3 million people globally. Advancements in pharmaceutical, device or surgical therapies, have led to patients living longer with HF. Heart failure affects 20% of care home residents, with these individuals presenting as older, frailer, and with more complex needs compared to those living at home. Thus, improving care home staff (e.g., registered nurse and care assistant) knowledge of HF has the potential to benefit patient care and reduce acute care utilization. Our aim is to co-design, and feasibility test, a digital intervention to improve care home staff knowledge of HF and optimise quality of life for those living with the condition in long-term residential care. METHODS: Using a logic model, three workstreams have been identified. Workstream 1 (WS1), comprised of three steps, will inform the 'inputs' of the model. First, qualitative interviews (n = 20) will be conducted with care home staff to identify facilitators and barriers in the provision of care to people with HF. Concurrently, a scoping review will be undertaken to synthesise current evidence of HF interventions within care homes. The last step will involve a Delphi study with 50-70 key stakeholders (for example care home staff, people with HF and their family and friends) to determine key education priorities related to HF. Using data from WS1, a digital intervention to improve care home staff knowledge and self-efficacy of HF will be co-designed in workstream 2 (WS2) alongside those living with HF or their carers, HF professionals, and care home staff. Lastly, workstream 3 (WS3) will involve mixed-methods feasibility testing of the digital intervention. Outcomes include staff knowledge on HF and self-efficacy in caring for HF residents, intervention usability, perceived benefits of the digital intervention on quality of life for care home residents, and care staff experience of implementing the intervention. DISCUSSION: As HF affects many care home residents, it is vital that care home staff are equipped to support people living with HF in these settings. With limited interventional research in this area, it is envisaged that the resulting digital intervention will have relevance for HF resident care both nationally and internationally.

Impact of H3K27 trimethylation loss in meningiomas: a meta-analysis.

Trimethylation of lysine 27 on histone 3 (H3K27me3) loss has been implicated in worse prognoses for patients with meningiomas. However, there have been challenges in measuring H3K27me3 loss, quantifying its impact, and interpreting its clinical utility. We conducted a systematic review across Pubmed, Embase, and Web of Science to identify studies examining H3K27me3 loss in meningioma. Clinical, histopathological, and immunohistochemistry (IHC) characteristics were aggregated. A meta-analysis was performed using a random-effects model to assess prevalence of H3K27me3 loss and meningioma recurrence risk. Study bias was characterized using the NIH Quality Assessment Tool and funnel plots. Nine publications met inclusion criteria with a total of 2376 meningioma cases. The prevalence of H3K27me3 loss was 16% (95% CI 0.09-0.27), with higher grade tumors associated with a significantly greater proportion of loss. H3K27me3 loss was more common in patients who were male, had recurrent meningiomas, or required adjuvant radiation therapy. Patients were 1.70 times more likely to have tumor recurrence with H3K27me3 loss (95% CI 1.35-2.15). The prevalence of H3K27me3 loss in WHO grade 2 and 3 meningiomas was found to be significantly greater in tissue samples less than five years old versus tissue of all ages and when a broader definition of IHC staining loss was applied. This analysis demonstrates that H3K27me3 loss significantly associates with more aggressive meningiomas. While differences in IHC and tumor tissue age have led to heterogeneity in studying H3K27me3 loss, a robust prognostic signal is present. Our findings suggest an opportunity to improve study design and standardize tissue processing to optimize clinical viability of this epigenetic marker.