Recent innovations in long-term care coverage and financing: a rapid scoping review.

OBJECTIVES: To identify, chart and analyse the literature on recent initiatives to improve long-term care (LTC) coverage, financial protection and financial sustainability for persons aged 60 and older. DESIGN: Rapid scoping review. DATA SOURCES: Four databases and four sources of grey literature were searched for reports published between 2017 and 2022. After using a supervised machine learning tool to rank titles and abstracts, two reviewers independently screened sources against inclusion criteria. ELIGIBILITY CRITERIA: Studies published from 2017-2022 in any language that captured recent LTC initiatives for people aged 60 and older, involved evaluation and directly addressed financing were included. DATA EXTRACTION AND ANALYSIS: Data were extracted using a form designed to answer the review questions and analysed using descriptive qualitative content analysis, with data categorised according to a prespecified framework to capture the outcomes of interest. RESULTS: Of 24 reports, 22 were published in peer-reviewed journals, and two were grey literature sources. Study designs included quasi-experimental study, policy analysis or comparison, qualitative description, comparative case study, cross-sectional study, systematic literature review, economic evaluation and survey. Studies addressed coverage based on the level of disability, income, rural/urban residence, employment and citizenship. Studies also addressed financial protection, including out-of-pocket (OOP) expenditures, copayments and risk of poverty related to costs of care. The reports addressed challenges to financial sustainability such as lack of service coordination and system integration, insufficient economic development and inadequate funding models. CONCLUSIONS: Initiatives where LTC insurance is mandatory and accompanied by commensurate funding are situated to facilitate ageing in place. Efforts to expand population coverage are common across the initiatives, with the potential for wider economic benefits. Initiatives that enable older people to access the services needed while avoiding OOP-induced poverty contribute to improved health and well-being. Preserving health in older people longer may alleviate downstream costs and contribute to financial sustainability.

Social Vulnerability and Frailty in Hospitalized Older Adults.

Background: Social vulnerability is the accumulation of disadvantageous social circumstances resulting in susceptibility to adverse health outcomes. Associated with increased mortality, cognitive decline, and disability, social vulnerability has primarily been studied in large population databases rather than frail hospitalized individuals. We examined how social vulnerability contributes to hospital outcomes and use of hospital resources for older adults presenting to the Emergency Department. Methods: We analyzed patients 65 years of age or older admitted through the Emergency Department and consulted to internal medicine or geriatrics at a Canadian tertiary care hospital from July 2009 to September 2020. A 20-item social vulnerability index (SVI) and a 57-item frailty index (FI) were calculated, using a deficit accumulation approach. Outcomes were length of stay (LOS), extended hospital LOS designation, alternative level of care (ALC) designation, in-hospital mortality, and discharge to long-term care (LTC). Results: In 1,146 patients (mean age 80.5±8.3, 54.0% female), mean SVI was 0.40±0.16 and FI was 0.44±0.14. The SVI scores were not associated with admission to hospital. Amongst those admitted, for every 0.1 unit increase in SVI, LOS increased by 1.15 days (p<.001) after adjusting for age, sex and FI. SVI was associated with staying over the expected LOS (aOR: 1.19, 1.05-1.34, p=.009) and ALC status (aOR 1.39, 1.12-1.74, p<.004). SVI was not associated with in-hospital mortality, but was associated with incident discharge to LTC (aOR 1.03, 1.02-1.04, p<.001). Conclusion: Independent of frailty, being socially vulnerable was associated with increased LOS, designation as ALC, and being discharged to LTC from hospital. Consideration of social vulnerability's influence on prolonged hospitalization and long-term care needs has implications for screening and hospital resources.

Pilot randomized controlled trial of a brief strategy to prevent suicide after discharge from residential addiction treatment.

INTRODUCTION: Veterans are at greater risk for suicide and veterans with substance use disorder (SUD) have an even greater risk. Little research has looked into brief interventions to prevent suicide in this population in residential substance use treatment programs. METHOD: We conducted a pilot, randomized controlled trial of a brief suicide prevention strategy called Veterans Affairs Brief Intervention and Contact Program (VA BIC) in patients participating in the Residential Recovery Center (RRC) SUD 28-day program and deemed at risk for suicide. We measured changes in symptoms at 1-, 3-, and 6-months. We looked at social connectedness, suicidal ideation, hopelessness, thwarted belongingness, perceived burdensomeness, and treatment engagement. RESULTS: The study enrolled twenty patients. One participant withdrew immediately after baseline. We found that adherence to VA BIC components was high, as 100 % of patients (N = 10) completed 70 % or more of the VA BIC visits. Furthermore, 80 % of intervention group patients (N = 8) completed all VA BIC components. During the six-month follow-up, suicidal ideation improved in patients assigned to VA BIC, while it worsened in the standard care arm. Similarly, patients assigned to VA BIC reported a reduction in perceived burdensomeness over the six-month follow-up period while it worsened in the standard care arm. Additionally, VA BIC may modestly improve treatment engagement in the first month postdischarge. CONCLUSION: We were able to recruit and enroll patients from a residential SUD treatment program into a clinical trial of the VA BIC intervention. Our preliminary results suggest that VA BIC may be useful in reducing suicidal ideation and perceived burdensomeness in patients who are discharged from residential SUD treatment programs and increasing treatment engagement. Future trials of VA BIC should determine whether VA BIC can reduce the risk of suicide in patients who are discharged from residential SUD treatment programs.

Do Interventions Reducing Social Vulnerability Improve Health in Community Dwelling Older Adults? A Systematic Review.

Background: Social vulnerability occurs when individuals have been relatively disadvantaged by the social determinants of health. Complex interventions that reduce social vulnerability have the potential to improve health in older adults but robust evidence is lacking. Objective: To identify, appraise and synthesize evidence on the effectiveness of complex interventions targeting reduction in social vulnerability for improving health related outcomes (mortality, function, cognition, subjective health and healthcare use) in older adults living in the community. Methods: A mixed methods systematic review was conducted. Five databases and targeted grey literature were searched for primary studies of all study types according to predetermined criteria. Data were extracted from each distinct intervention and quality was assessed using the Mixed Methods Appraisal Tool. Effectiveness data were synthesized using vote counting by direction of effect, combining p values and Albatross plots. Results: Across 38 included studies, there were 34 distinct interventions categorized as strengthening social supports and communities, helping older adults and their caregivers navigate health and social services, enhancing neighbourhood and built environments, promoting education and providing economic stability. There was evidence to support positive influences on function, cognition, subjective health, and reduced hospital utilization. The evidence was mixed for non-hospital healthcare utilization and insufficient to determine effect on mortality. Conclusion: Despite high heterogeneity and varying quality of studies, attention to reducing an older adult's social vulnerability assists in improving older adults' health.

Spreading a Strategy to Prevent Suicide After Psychiatric Hospitalization: Results of a Quality Improvement Spread Initiative.

BACKGROUND: Suicide after psychiatric hospitalization is a major concern. Poor treatment engagement may contribute to risk. The World Health Organization Brief Intervention and Contact (BIC) Program is an evidence-based practice shown to prevent suicide after psychiatric discharge in international trials. There have been no efforts to implement BIC into routine practice in US populations. METHODS: The authors conducted a 12-month quality improvement (QI) collaborative at six US Department of Veterans Affairs (VA) medical centers serving a large rural population. Sites had low to moderate performance on a VA quality measure of mental health postdischarge care; a measure assessing the proportion of discharged patients who achieve the required number of visits ≤ 30 days. Sites received programmatic support to implement BIC locally. Implementation was assessed using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) framework. RESULTS: Overall, teams had high participation in programmatic activities and enrolled 85% of eligible patients that they approached. Among 70 enrolled patients, 81.4% achieved the VA quality measure of mental health postdischarge care, suggesting good treatment engagement. On average, patients rated BIC as excellent. Team members agreed that BIC was easy to use, implementable, possible, and doable. Factors facilitating implementation included standardized operating procedures to standardize processes. Barriers included insufficient staffing and loss to follow-up. Most sites plan to continue to enroll patients and to expand BIC to other areas. CONCLUSION: A QI collaborative can facilitate implementation of BIC in six VA facilities that provide inpatient psychiatric treatment. BIC may appeal to patients and providers and may improve treatment engagement.

A multi-stage process to develop quality indicators for community-based palliative care using interRAI data.

BACKGROUND: Individuals receiving palliative care (PC) are generally thought to prefer to receive care and die in their homes, yet little research has assessed the quality of home- and community-based PC. This project developed a set of valid and reliable quality indicators (QIs) that can be generated using data that are already gathered with interRAI assessments-an internationally validated set of tools commonly used in North America for home care clients. The QIs can serve as decision-support measures to assist providers and decision makers in delivering optimal care to individuals and their families. METHODS: The development efforts took part in multiple stages, between 2017-2021, including a workshop with clinicians and decision-makers working in PC, qualitative interviews with individuals receiving PC, families and decision makers and a modified Delphi panel, based on the RAND/ULCA appropriateness method. RESULTS: Based on the workshop results, and qualitative interviews, a set of 27 candidate QIs were defined. They capture issues such as caregiver burden, pain, breathlessness, falls, constipation, nausea/vomiting and loneliness. These QIs were further evaluated by clinicians/decision makers working in PC, through the modified Delphi panel, and five were removed from further consideration, resulting in 22 QIs. CONCLUSIONS: Through in-depth and multiple-stakeholder consultations we developed a set of QIs generated with data already collected with interRAI assessments. These indicators provide a feasible basis for quality benchmarking and improvement systems for care providers aiming to optimize PC to individuals and their families.

Identification and Characterization of Small-Molecule IRF3-Dependent Immune Activators for Pharmaceutical Development.

We sought to develop a small-molecule activator of interferon regulatory factor 3 (IRF3), an essential innate immune transcription factor, which could potentially be used therapeutically in multiple disease settings. Using a high-throughput screen, we identified small-molecule entities that activate a type I interferon response, with minimal off-target NFκB activation. We identified 399 compounds at a hit rate of 0.24% from singlicate primary screening. Secondary screening included the primary hits and additional compounds with similar chemical structures obtained from other library sources and resulted in 142 candidate compounds. The hit compounds were sorted and ranked to identify compound groups with activity in both human and mouse backgrounds to facilitate animal model engagement for translational development. Chemical modifications within two groups of small molecules produced leads with improved activity over original hits. Furthermore, these leads demonstrated activity in ex vivo cytokine release assays from human blood- and mouse bone marrow-derived macrophages. Dependence on IRF3 was demonstrated using bone marrow-derived macrophages from IRF3-deficient mice, which were not responsive to the molecules. To identify the upstream pathway leading to IRF3 activation, we used a library of CRISPR knockout cell lines to test the key innate immune adaptor and receptor molecules. These studies indicated a surprising toll-interleukin-1 receptor-domain-containing-adapter-inducing interferon-ß-dependent but TLR3/4-independent mechanism of IRF3 activation.

A virtual, pilot randomized trial of a brief intervention to prevent suicide in an integrated healthcare setting.

OBJECTIVE: Patients who die by suicide are often seen in primary care settings in the weeks leading to their death. There has been little study of brief interventions to prevent suicide in these settings. METHOD: We conducted a virtual, pilot, randomized controlled trial of a brief suicide prevention strategy called Veterans Affairs Brief Intervention and Contact Program (VA BIC) in patients who presented to a primary care mental health walk-in clinic for a new mental health intake appointment and were at risk for suicide. Our primary aim was to assess feasibility. We measured our ability to recruit 20 patients. We measured the proportion of enrolled patients who completed all study assessments. We assessed adherence among patients assigned to VA BIC. RESULTS: Twenty patients were enrolled and 95% (N = 19) completed all study assessments. Among the 10 patients assigned to VA BIC, 90% (N = 9) of patients completed all required intervention visits, and 100% (N = 10) completed ≥70% of the required interventions visits. CONCLUSION: It is feasible to conduct a virtual trial of VA BIC in an integrated care setting. Future research should clarify the role of VA BIC as a suicide prevention strategy in integrated care settings using an adequately powered design. CLINICAL TRIAL REGISTRATION: NCT04054947.

Hospital to Home: Supporting the Transition From Hospital to Home for Older Adults.

BACKGROUND: An increasing proportion of older adults experience avoidable hospitalizations, and some are potentially entering long-term care homes earlier and often unnecessarily. Older adults often lack adequate support to transition from hospital to home, without access to appropriate health services when they are needed in the community and resources to live safely at home. PURPOSE: This study collaborated with an existing enhanced home care program called Home Again in Nova Scotia, to identify factors that contribute to older adult patients being assessed as requiring long-term care when they could potentially return home with enhanced supports. METHODS: Using a case study design, this study examined in-depth experiences of multiple stakeholders, from December 2019 to February 2020, through analysis of nine interviews for three focal patient cases including older adult patients, their family or friend caregivers, and healthcare professionals. RESULTS: Findings indicate home care services for older adults are being sought too late, after hospital readmission, or a rapid decline in health status when family caregivers are already experiencing caregiver burnout. Limitations in home care services led to barriers preventing family caregivers from continuing to care for older adults at home. CONCLUSIONS: This study contributes knowledge about gaps within home care and transitional care services, highlighting the importance of investing in additional home care services for rehabilitation and prevention of rapidly deteriorating health.

A Pilot Randomized Trial of a Brief Intervention to Prevent Suicide After Inpatient Psychiatric Discharge.

OBJECTIVE: Risk for suicide is high after psychiatric hospitalization. The World Health Organization's Brief Intervention and Contact (BIC) program has shown efficacy in preventing suicide. A version adapted for the U.S. Department of Veterans Affairs (VA) was studied to determine preliminary effects. METHODS: Patients receiving psychiatric hospitalization because of acute risk for self-harm were randomly assigned to the VA BIC or standard care alone. Effect sizes (Hedges' g) for suicidal ideation (primary outcome), social connectedness (measured as thwarted belongingness and perceived burdensomeness), hopelessness, and engagement were calculated at 1 and 3 months. RESULTS: Patients were randomly assigned to the VA BIC (N=10) or standard care (N=9). The VA BIC had a medium or large effect on most measures at 1 month (suicidal ideation, g=0.45). Effects diminished at 3 months, except for thwarted belongingness (g=0.81). CONCLUSIONS: The VA BIC had meaningful effects on suicide-related outcomes. The largest effect was seen in the first month.

Social factors influencing utilization of home care in community-dwelling older adults: a scoping review.

BACKGROUND: Older adults want to live at home as long as possible, even in the face of circumstances that limit their autonomy. Home care services reflect this emergent preference, allowing older adults to 'age in place' in familiar settings rather than receiving care for chronic health conditions or ageing needs in an institutionalized setting. Numerous social factors, generally studied in isolation, have been associated with home care utilization. Even so, social circumstances are complex and how these factors collectively influence home care use patterns remains unclear. OBJECTIVES: To provide a broad and comprehensive overview of the social factors influencing home care utilization; and to evaluate the influence of discrete social factors on patterns of home care utilization in community-dwelling older adults in high-income countries. METHODS: A scoping review was conducted of six electronic databases for records published between 2010 and 2020; additional records were obtained from hand searching review articles, reference lists of included studies and documents from international organisations. A narrative synthesis was presented, complemented by vote counting per social factor, harvest plots and an evaluation of aggregated findings to determine consistency across studies. RESULTS: A total of 2,365 records were identified, of which 66 met inclusion criteria. There were 35 discrete social factors grouped into four levels of influence using a socio-ecological model (individual, relationship, community and societal levels) and grouped according to outcome of interest (home care propensity and intensity). Across all studies, social factors consistently showing any association (positive, negative, or equivocal in pattern) with home care propensity were: age, ethnicity/race, self-assessed health, insurance, housing ownership, housing problems, marital status, household income, children, informal caregiving, social networks and urban/rural area. Age, education, personal finances, living arrangements and housing ownership were associated with home care intensity, also with variable patterns in utilization. Additional community and societal level factors were identified as relevant but lacking consistency across the literature; these included rurality, availability of community services, methods of financing home care systems, and cultural determinants. CONCLUSION: This is the first literature review bringing together a wide range of reported social factors that influence home care utilization. It confirms social factors do influence home care utilization in complex interactions, distinguishes level of influences at which these factors affect patterns of use and discusses policy implications for home care reform.

CpG preconditioning reduces accumulation of lysophosphatidylcholine in ischemic brain tissue after middle cerebral artery occlusion.

Ischemic stroke is one of the major causes of death and permanent disability in the world. However, the molecular mechanisms surrounding tissue damage are complex and further studies are needed to gain insights necessary for development of treatment. Prophylactic treatment by administration of cytosine-guanine (CpG) oligodeoxynucleotides has been shown to provide neuroprotection against anticipated ischemic injury. CpG binds to Toll-like receptor 9 (TLR9) causing initialization of an inflammatory response that limits visible ischemic damages upon subsequent stroke. Here, we use nanospray desorption electrospray ionization (nano-DESI) mass spectrometry imaging (MSI) to characterize molecular effects of CpG preconditioning prior to middle cerebral artery occlusion (MCAO) and reperfusion. By doping the nano-DESI solvent with appropriate internal standards, we can study and compare distributions of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) in the ischemic hemisphere of the brain despite the large changes in alkali metal abundances. Our results show that CpG preconditioning not only reduces the infarct size but it also decreases the degradation of PC and accumulation of LPC species, which indicates reduced cell membrane breakdown and overall ischemic damage. Our findings show that molecular mechanisms of PC degradation are intact despite CpG preconditioning but that these are limited due to the initialized inflammatory response.

Longitudinal Examination of COVID-19 Public Health Measures on Mental Health for Rural Patients With Serious Mental Illness.

INTRODUCTION: There is emerging evidence to support that the COVID-19 pandemic and related public health measures may be associated with negative mental health sequelae. Rural populations in particular may fair worse because they share many unique characteristics that may put them at higher risk for adverse outcomes with the pandemic. Yet, rural populations may also be more resilient due to increased sense of community. Little is known about the impact of the pandemic on the mental health and well-being of a rural population pre- and post-pandemic, especially those with serious mental illness. MATERIAL AND METHODS: We conducted a longitudinal, mixed-methods study with assessments preceding the pandemic (between October 2019 and March 2020) and during the stay-at-home orders (between April 23, 2020, and May 4, 2020). Changes in hopelessness, suicidal ideation, connectedness, and treatment engagement were assessed using a repeated-measures ANOVA or Friedman test. RESULTS: Among 17 eligible participants, 11 people were interviewed. Overall, there were no notable changes in any symptom scale in the first 3-5 months before the pandemic or during the stay-at-home orders. The few patients who reported worse symptoms were significantly older (mean age: 71.7 years, SD: 4.0). Most patients denied disruptions to treatment, and some perceived telepsychiatry as beneficial. CONCLUSIONS: Rural patients with serious mental illness may be fairly resilient in the face of the COVID-19 pandemic when they have access to treatment and supports. Longer-term outcomes are needed in rural patients with serious mental illness to better understand the impact of the pandemic on this population.

Remdesivir for the Treatment of COVID-19: A Systematic Review of the Literature.

In March 2020, the World Health Organization declared the spread of SARS-CoV-2 a global pandemic. To date, coronavirus disease-2019 (COVID-19) has spread to over 200 countries, leading to over 1.6 million cases and over 99,000 deaths. Given that there is neither a vaccine nor proven treatment for COVID-19, there is currently an urgent need for effective pharmacotherapy. To address the need for an effective treatment of SARS-CoV-2 during the worldwide pandemic, this systematic review of intravenous (IV) remdesivir was performed. Remdesivir, an anti-viral prodrug originally developed to treat Ebola virus disease, has shown broad spectrum activity against the Coronavirus family. A recent case report reported improvement of clinical symptoms with remdesivir in a patient with COVID-19. After conducting a systematic search of 18 clinical trial registries and three large scientific databases, we identified 86 potentially eligible items. Following removal of duplicates (n = 21), eligible studies were reviewed independently by two authors. After the first round of screening, inter-rater agreement was 98.5% (κ = 0.925). After the second round of full-text screening, inter-rater agreement was 100%. A total of seven ongoing and recruiting clinical trials of remdesivir (100-200 milligrams, intravenous [IV]) were included. We identified the following primary outcomes: patients discharged (n = 2); time to clinical status improvement (n = 2); improved O2 saturation (n = 2); body temperature normalization (n = 2); and clinical status (n = 1). Secondary outcomes in all identified studies included documentation of adverse events. Phase 3 trials are expected to be completed between April 2020-2023. Therefore, despite supportive data from in vitro and in vivo studies, the clinical effectiveness of IV remdesivir for treatment of COVID-19 and potential side effects remain incompletely defined in the human population.

Home care clients: a research protocol for studying their pathways.

BACKGROUND: Enhancing non-clinical home care supports and services for older adults to live well is a strategic priority in developed countries, including Canada. Underpinning these supports and services are structures of care that are reflected in home care policies, programs and practices within jurisdictions. These approaches to care exist at multiple levels and inform interactions, perceptions, and care assessment, planning and provision, ultimately shaping the supports that are delivered. Jurisdictional differences in approaches to care mean that pathways through home care systems may differ, depending on where one lives. The goal of this study is to understand how approaches to care shape the pathways of older adult home care clients with chronic and long term conditions in two Canadian health jurisdictions. METHODS: This longitudinal mixed-methods study has three interrelated research streams informed by aspects of the socio-ecological framework. We will examine client pathways using a retrospective analysis of home care assessment data (Resident Assessment Instrument- Home Care) in two health authorities (Client/Service Data Stream). We will analyze interview data from older adult home care clients and a cluster of each client's family or friend caregiver(s), home support worker(s), care/case coordinator(s) and potentially other professionals at up to three points over 18 months using a prospective qualitative comparative case study design (Constellation Data Stream). We will review home care policies relevant to both health authorities and interview key informants regarding the creation and implementation of policies (Policy Stream). Our study will apply an integrated knowledge translation (iKT) approach that engages knowledge users in research design, analysis and interpretation to facilitate relevancy of results. DISCUSSION: Applying a mixed-method research design to understand approaches to care within and between two jurisdictions will contribute to the evidence base on older adult home care client pathways. Study results will identify how potential differences are experienced by clients and their families. An understanding of the policies will help to contextualize these findings. The iKT model will ensure that findings are useful for strategic planning and decision-making, and supporting changes in care practice.

Understanding the mental health impact of human trafficking.

The purpose of this report was to review the mental health consequences related to human trafficking and the important role of health care providers, particularly advanced practice nurses, nurse practitioners (NPs), and psychiatric mental health NPs in identifying and responding to trafficking victims. The framework was based on a biopsychosocial model for assessment and a trauma-informed approach to care. An integrative review of the literature was conducted to offer a comprehensive overview of the mental health consequences. Deleterious mental health consequences are common in individuals who have experienced trafficking, and symptoms suffered by individuals were assessed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria for posttraumatic stress disorder, as well as additional guidelines specific to a trauma-informed approach. Mental health sequelae experienced by trafficking survivors must be understood using a comprehensive trauma-informed framework for assessment and treatment.

Preconditioning in the Rhesus Macaque Induces a Proteomic Signature Following Cerebral Ischemia that Is Associated with Neuroprotection.

Each year, thousands of patients are at risk of cerebral ischemic injury, due to iatrogenic responses to surgical procedures. Prophylactic treatment of these patients as standard care could minimize potential neurological complications. We have shown that protection of brain tissue, in a non-human primate model of cerebral ischemic injury, is possible through pharmacological preconditioning using the immune activator D192935. We postulate that preconditioning with D192935 results in neuroprotective reprogramming that is evident in the brain following experimentally induced cerebral ischemia. We performed quantitative proteomic analysis of cerebral spinal fluid (CSF) collected post-stroke from our previously published efficacy study to determine whether CSF protein profiles correlated with induced protection. Four groups of animals were examined: naïve animals (no treatment or stroke); animals treated with vehicle prior to stroke; D192935 treated and stroked animals, further delineated into two groups, ones that were protected (small infarcts) and those that were not protected (large infarcts). We found that distinct protein clusters defined the protected and non-protected animal groups, with a 16-member cluster of proteins induced exclusively in D192935 protected animals. Seventy percent of the proteins induced in the protected animals have functions that would enhance neuroprotection and tissue repair, including several members associated with M2 macrophages, a macrophage phenotype shown to contribute to neuroprotection and repair during ischemic injury. These studies highlight the translational importance of CSF biomarkers in defining mechanism and monitoring responses to treatment in development of stroke therapeutics.

Preclinical Development of a Prophylactic Neuroprotective Therapy for the Preventive Treatment of Anticipated Ischemia-Reperfusion Injury.

Ischemia-reperfusion brain injury can be iatrogenically induced secondary to life-saving procedures. Prophylactic treatment of these patients offers a promising prevention for lifelong complications. We postulate that a cytosine-guanine (CpG) oligodeoxynucleotide (ODN) can provide robust antecedent protection against cerebral ischemic injury with minimal release of pro-inflammatory cytokines, making it an ideal candidate for further clinical development. Mouse and nonhuman primate (NHP) models of cerebral ischemic injury were used to test whether an A-type CpG ODN, which induces minimal systemic inflammatory cytokine responses, can provide prophylactic protection. Extent of injury in the mouse was measured by histological staining of live tissue. In the NHP, injury was assessed 2 and 7 days post-occlusion from T2-weighted magnetic resonance images and neurological and motor deficits were cataloged daily. Plasma cytokine levels were measured using species-specific Luminex assays. Prophylactic administration of an A-type CpG ODN provided robust protection against cerebral ischemic injury in the mouse with minimal systemic inflammation. Rhesus macaques treated with D192935, a mixture of human optimized A-type CpG ODNs, had smaller infarcts and demonstrated significantly less neurological and motor deficits following ischemic injury. Our findings demonstrate the translational potential of D192935 as a prophylactic treatment for patients at risk of cerebral ischemic injury.