Cognitive Outcome after Acute Spontaneous Intracerebral Hemorrhage: Analysis of the iDEF Randomized Trial.

INTRODUCTION: The impact of intracerebral hemorrhage (ICH) on cognition and the determinants of cognitive recovery early after ICH remain elusive. In this post hoc analysis of the intracerebral hemorrhage deferoxamine (iDEF) trial, we examined the trajectories of cognitive impairment and the determinants of early cognitive recovery after ICH. METHODS: We examined baseline factors associated with a 90-day cognitive outcome and constructed generalized linear mixed models to examine the trajectory of cognitive function over time among iDEF participants. Cognition was measured by the Montreal Cognitive Assessment (MoCA) scores on days 7, 30, and 90. RESULTS: 291 were available for analysis under the trial's modified intention-to-treat definition (38% female, mean age 60.3 ± 12.0 years, median NIHSS 13, IQR 8-18). The median baseline ICH volume was 12.9 IQR (6.4-26.0) mL; 59 (20%) of the ICH cases were lobar, 120 (41%) had intraventricular extension. There was an overall significant increase in total MOCA score with time (p < 0.0001). Total MOCA score increased by an estimated 3.9 points (95% CI: 3.1, 4.7) between the day 7 and day 30 assessments and by an additional 2.9 points (95% CI: 2.2, 3.6) between the day 30 and day 90 assessments. Despite the overall improvement, 134 of 205 (65%) patients with an available 90-day MoCA score remained cognitively impaired with a score <26 on day 90. Older age, higher NIHSS score, baseline ICH volume, intraventricular hemorrhage, and perihematoma edema had an adjusted negative impact on cognitive recovery. CONCLUSIONS: Although ICH survivors exhibit significant improvement of cognitive status over the first 3 months, cognitive performance remains impaired in the majority of patients. Among factors independently associated with worse cognitive recovery, higher baseline ICH, intraventricular blood and perihematomal edema volumes, are potential therapeutic targets that merit further exploration.

Poor haemorrhagic stroke outcomes during the COVID-19 pandemic are driven by socioeconomic disparities: analysis of nationally representative data.

Background: Nationally representative studies evaluating the impact of the COVID-19 pandemic on haemorrhagic stroke outcomes are lacking. Methods: In this pooled cross-sectional analysis, we identified adults (≥18 years) with primary intracerebral haemorrhage (ICH) or subarachnoid haemorrhage (SAH) from the National Inpatient Sample (2016-2020). We evaluated differences in rates of in-hospital outcomes between the prepandemic (January 2016-February 2020) and pandemic (March-December 2020) periods using segmented logistic regression models. We used multivariable logistic regression to evaluate differences in mortality between patients admitted from April to December 2020, with and without COVID-19, and those admitted from April to December 2019. Stratified analyses were conducted among patients residing in low-income and high-income zip codes, as well as among patients with extreme loss of function (E-LoF) and those with minor to major loss of function (MM-LoF). Results: Overall, 309 965 patients with ICH (47% female, 56% low income) and 112 210 patients with SAH (62% female, 55% low income) were analysed. Prepandemic, ICH mortality decreased by ~1% per month (adjusted OR, 95% CI: 0.99 (0.99 to 1.00); p<0.001). However, during the pandemic, the overall ICH mortality rate increased, relative to prepandemic, by ~2% per month (1.02 (1.00 to 1.04), p<0.05) and ~4% per month (1.04 (1.01 to 1.07), p<0.001) among low-income patients. There was no significant change in trend among high-income patients with ICH (1.00 (0.97 to 1.03)). Patients with comorbid COVID-19 in 2020 had higher odds of mortality (versus 2019 cohort) only among patients with MM-LoF (ICH, 2.15 (1.12 to 4.16), and SAH, 5.77 (1.57 to 21.17)), but not among patients with E-LoF. Conclusion: Sustained efforts are needed to address socioeconomic disparities in healthcare access, quality and outcomes during public health emergencies.

The Influence of Social Determinants on Receiving Outpatient Treatment with Monoclonal Antibodies, Disease Risk, and Effectiveness for COVID-19.

BACKGROUND: Limited research has studied the influence of social determinants of health (SDoH) on the receipt, disease risk, and subsequent effectiveness of neutralizing monoclonal antibodies (nMAbs) for outpatient treatment of COVID-19. OBJECTIVE: To examine the influence of SDoH variables on receiving nMAb treatments and the risk of a poor COVID-19 outcome, as well as nMAb treatment effectiveness across SDoH subgroups. DESIGN: Retrospective observational study utilizing electronic health record data from four health systems. SDoH variables analyzed included race, ethnicity, insurance, marital status, Area Deprivation Index, and population density. PARTICIPANTS: COVID-19 patients who met at least one emergency use authorization criterion for nMAb treatment. MAIN MEASURE: We used binary logistic regression to examine the influence of SDoH variables on receiving nMAb treatments and risk of a poor outcome from COVID-19 and marginal structural models to study treatment effectiveness. RESULTS: The study population included 25,241 (15.1%) nMAb-treated and 141,942 (84.9%) non-treated patients. Black or African American patients were less likely to receive treatment than white non-Hispanic patients (adjusted odds ratio (OR) = 0.86; 95% CI = 0.82-0.91). Patients who were on Medicaid, divorced or widowed, living in rural areas, or living in areas with the highest Area Deprivation Index (most vulnerable) had lower odds of receiving nMAb treatment, but a higher risk of a poor outcome. For example, compared to patients on private insurance, Medicaid patients had 0.89 (95% CI = 0.84-0.93) times the odds of receiving nMAb treatment, but 1.18 (95% CI = 1.13-1.24) times the odds of a poor COVID-19 outcome. Age, comorbidities, and COVID-19 vaccination status had a stronger influence on risk of a poor outcome than SDoH variables. nMAb treatment benefited all SDoH subgroups with lower rates of 14-day hospitalization and 30-day mortality. CONCLUSION: Disparities existed in receiving nMAbs within SDoH subgroups despite the benefit of treatment across subgroups.

Minimally Invasive Surgery With Thrombolysis for Intracerebral Hemorrhage Evacuation: Bayesian Reanalysis of a Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Bayesian analysis of randomized controlled trials (RCTs) can extend the value of trial data beyond interpretations based on conventional p value-based binary cutoffs. We conducted an exploratory post hoc Bayesian reanalysis of the minimally invasive surgery with thrombolysis for intracerebral hemorrhage (ICH) evacuation (MISTIE-3) trial and derived probabilities of potential intervention effect on functional and survival outcomes. METHODS: MISTIE-3 was a multicenter phase 3 RCT designed to evaluate the efficacy and safety of the MISTIE intervention. Five hundred and six adults (18 years or older) with spontaneous, nontraumatic, supratentorial ICH of ≥30 mL were randomized to receive either the MISTIE intervention (n = 255) or standard medical care (n = 251). We provide Bayesian-derived estimates of the effect of the MISTIE intervention on achieving a good 365-day modified Rankin Scale score (mRS score 0-3) as relative risk (RR) and absolute risk difference (ARD), and the probabilities that these treatment effects are greater than prespecified thresholds. We used 2 sets of prior distributions: (1) reference priors, including minimally informative, enthusiastic, and skeptical priors, and (2) data-derived prior distribution, using a hierarchical random effects model. We additionally evaluated the potential effects of the MISTIE intervention on 180-day and 30-day mRS and 365-, 180-, and 30-day mortality using data-derived priors. RESULTS: The Bayesian-derived probability that MISTIE intervention has any beneficial effect (RR >1) on achieving a good 365-day mRS score was 70% using minimally informative prior, 87% with enthusiastic prior, 68% with skeptical prior, and 73% with data-derived prior. However, these probabilities were ≤55% for RR >1.10 and 0% for RR >1.52 across a range of priors. The probabilities of achieving RR >1 for 180- and 30-day mRS scores are 65% and 80%, respectively. Furthermore, the probabilities of achieving RR <1 for 365-, 180-, and 30-day mortality are 93%, 98%, and 99%, respectively. DISCUSSION: Our exploratory analyses indicate that across a range of priors, the Bayesian-derived probability of MISTIE intervention having any beneficial effect on 365-day mRS for patients with ICH is between 68% and 87%. These analyses do not change the frequentist-based interpretation of the trial. However, unlike the frequentist p values, which indirectly evaluate treatment effects and only provide an arbitrary binary cutoff (such as 0.05), the Bayesian framework directly estimates the probabilities of potential treatment effects. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov/ct2/show/NCT01827046. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that minimally invasive surgery (MIS) + recombinant tissue plasminogen activator (rt-PA) does not significantly improve functional outcome in patients with ICH. However, this study lacks the precision to exclude a potential benefit of MIS + rt-PA.

Cardiovascular disease in Filipino American men and women: A 2023 update.

With more than 4.2 million people, Filipino Americans are the third largest Asian group in the US and the largest Southeast Asian group in the country. Despite relatively favorable average socioeconomic indicators compared to the general US population, Filipino Americans face a significant burden of traditional cardiovascular risk factors, particularly among men. Moreover, Filipino Americans have high rates of cardiovascular death, often occurring at a younger age compared to other minority groups and Non-Hispanic White adults. In view of these trends, in 2010 the American Heart Association designated Filipino Americans as a high cardiovascular risk group. Despite this, in 2023, Filipino Americans remain underrepresented in landmark cardiovascular cohort studies and are often over looked as a group at increased cardiovascular risk. In this updated narrative review, we summarize the current state of knowledge about the burden of cardiovascular risk factors and diseases experienced by the Filipino American population. Our aim is to inform enhanced clinical, population, and policy-level prevention interventions and boost research in this space.

A Neuro-Informatics Pipeline for Cerebrovascular Disease: Research Registry Development.

BACKGROUND: Although stroke is well recognized as a critical disease, treatment options are often limited. Inpatient stroke encounters carry critical information regarding the mechanisms of stroke and patient outcomes; however, these data are typically formatted to support administrative functions instead of research. To support improvements in the care of patients with stroke, a substantive research data platform is needed. OBJECTIVE: To advance a stroke-oriented learning health care system, we sought to establish a comprehensive research repository of stroke data using the Houston Methodist electronic health record (EHR) system. METHODS: Dedicated processes were developed to import EHR data of patients with primary acute ischemic stroke, intracerebral hemorrhage (ICH), transient ischemic attack, and subarachnoid hemorrhage under a review board-approved protocol. Relevant patients were identified from discharge diagnosis codes and assigned registry patient identification numbers. For identified patients, extract, transform, and load processes imported EHR data of primary cerebrovascular disease admissions and available data from any previous or subsequent admissions. Data were loaded into patient-focused SQL objects to enable cross-sectional and longitudinal analyses. Primary data domains (admission details, comorbidities, laboratory data, medications, imaging data, and discharge characteristics) were loaded into separate relational tables unified by patient and encounter identification numbers. Computed tomography, magnetic resonance, and angiography images were retrieved. Imaging data from patients with ICH were assessed for hemorrhage characteristics and cerebral small vessel disease markers. Patient information needed to interface with other local and national databases was retained. Prospective patient outreach was established, with patients contacted via telephone to assess functional outcomes 30, 90, 180, and 365 days after discharge. Dashboards were constructed to provide investigators with data summaries to support access. RESULTS: The Registry of Neurological Endpoint Assessments among Patients with Ischemic and Hemorrhagic Stroke (REINAH) database was constructed as a series of relational category-specific SQL objects. Encounter summaries and dashboards were constructed to draw from these objects, providing visual data summaries for investigators seeking to build studies based on REINAH data. As of June 2022, the database contains 18,061 total patients, including 1809 (10.02%) with ICH, 13,444 (74.43%) with acute ischemic stroke, 1221 (6.76%) with subarachnoid hemorrhage, and 3165 (17.52%) with transient ischemic attack. Depending on the cohort, imaging data from computed tomography are available for 85.83% (1048/1221) to 98.4% (1780/1809) of patients, with magnetic resonance imaging available for 27.85% (340/1221) to 85.54% (11,500/13,444) of patients. Outcome assessment has successfully contacted 56.1% (240/428) of patients after ICH, with 71.3% (171/240) of responders providing consent for assessment. Responders reported a median modified Rankin Scale score of 3 at 90 days after discharge. CONCLUSIONS: A highly curated and clinically focused research platform for stroke data will establish a foundation for future research that may fundamentally improve poststroke patient care and outcomes.

Seasonal variation in the incidence of primary intracerebral hemorrhage: a 16-year nationwide analysis.

Introduction: Data on nationwide trends and seasonal variations in the incidence of Intracerebral Hemorrhage (ICH) in the United States (US) are lacking. Methods: We used the Nationwide Inpatient Sample (2004-2019) and Census Bureau data to calculate the quarterly (Q1:January-March; Q2:April-June; Q3:July-September; Q4:October-December) incidence rates (IR) of adult (≥18 years) ICH hospitalizations, aggregated across Q1-Q4 and Q2-Q3. We report adjusted incidence rate ratios (aIRR) and 95% confidence intervals (CI) for differences in the quarterly incidence of ICH, as compared to acute ischemic stroke (AIS), between Q1Q4 and Q2Q3 using a multivariable Poisson regression model. We additionally performed stratified analyses across the four US regions. Results: Among 822,143 (49.0% female) ICH and 6,266,234 (51.9% female) AIS hospitalizations, the average quarterly crude IR of ICH was consistently higher in Q1Q4 compared to Q2Q3 (5.6 vs. 5.2 per 100,000) (aIRR, CI: 1.09, 1.08-1.11)-this pattern was similar across all four US regions. However, a similar variation pattern was not observed for AIS incidence. The incidence (aIRR, CI) of both ICH (1.01, 1.00-1.02) and AIS (1.03, 1.02-1.03) is rising. Conclusion: Unlike AIS, ICH incidence is consistently higher in colder quarters, underscoring the need for evaluation and prevention of factors driving seasonal variations in ICH incidence.

Lifelong cerebrovascular disease burden among CADASIL patients: analysis from a global health research network.

Introduction: Data reporting on patients with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) within the United States population is limited. We sought to evaluate the overt cerebrovascular disease burden among patients with CADASIL. Methods: Harmonized electronic medical records were extracted from the TriNetX global health research network. CADASIL patients were identified using diagnostic codes and those with/without history of documented stroke sub-types (ischemic stroke [IS], intracerebral hemorrhage [ICH], subarachnoid hemorrhage [SAH] and transient ischemic attack [TIA]) were compared. Adjusted odds ratios (OR) and 95% confidence intervals (CI) of stroke incidence and mortality associated with sex were computed. Results: Between September 2018 and April 2020, 914 CADASIL patients were identified (median [IQR] age: 60 [50-69], 61.3% females); of whom 596 (65.2%) had documented cerebrovascular events (i.e., CADASIL-Stroke patients). Among CADASIL-Stroke patients, 89.4% experienced an IS, co-existing with TIAs in 27.7% and hemorrhagic strokes in 6.2%; initial stroke events occurred ≤65 years of age in 71% of patients. CADASIL-Stroke patients (vs. CADASIL-non-Stroke) had higher cardiovascular and neurological (migraines, cognitive impairment, epilepsy/seizures, mood disorders) burden. In age- and comorbidity-adjusted models, males had higher associated risk of stroke onset (OR: 1.37, CI: 1.01-1.86). Mortality risk was higher for males (OR: 2.72, CI: 1.53-4.84). Discussion: Early screening and targeted treatment strategies are warranted to help CADASIL patients with symptom management and risk mitigation.

Stroke severity mediates the effect of socioeconomic disadvantage on poor outcomes among patients with intracerebral hemorrhage.

Background: Socioeconomic deprivation drives poor functional outcomes after intracerebral hemorrhage (ICH). Stroke severity and background cerebral small vessel disease (CSVD) burden have each been linked to socioeconomic status and independently contribute to worse outcomes after ICH, providing distinct, plausible pathways for the effects of deprivation. We investigate whether admission stroke severity or cerebral small vessel disease (CSVD) mediates the effect of socioeconomic deprivation on 90-day functional outcomes. Methods: Electronic medical record data, including demographics, treatments, comorbidities, and physiological data, were analyzed. CSVD burden was graded from 0 to 4, with severe CSVD categorized as ≥3. High deprivation was assessed for patients in the top 30% of state-level area deprivation index scores. Severe disability or death was defined as a 90-day modified Rankin Scale score of 4-6. Stroke severity (NIH stroke scale (NIHSS)) was classified as: none (0), minor (1-4), moderate (5-15), moderate-severe (16-20), and severe (21+). Univariate and multivariate associations with severe disability or death were determined, with mediation evaluated through structural equation modelling. Results: A total of 677 patients were included (46.8% female; 43.9% White, 27.0% Black, 20.7% Hispanic, 6.1% Asian, 2.4% Other). In univariable modelling, high deprivation (odds ratio: 1.54; 95% confidence interval: [1.06-2.23]; p = 0.024), severe CSVD (2.14 [1.42-3.21]; p < 0.001), moderate (8.03 [2.76-17.15]; p < 0.001), moderate-severe (32.79 [11.52-93.29]; p < 0.001), and severe stroke (104.19 [37.66-288.12]; p < 0.001) were associated with severe disability or death. In multivariable modelling, severe CSVD (3.42 [1.75-6.69]; p < 0.001) and moderate (5.84 [2.27-15.01], p < 0.001), moderate-severe (27.59 [7.34-103.69], p < 0.001), and severe stroke (36.41 [9.90-133.85]; p < 0.001) independently increased odds of severe disability or death; high deprivation did not. Stroke severity mediated 94.1% of deprivation's effect on severe disability or death (p = 0.005), while CSVD accounted for 4.9% (p = 0.524). Conclusion: CSVD contributed to poor functional outcome independent of socioeconomic deprivation, while stroke severity mediated the effects of deprivation. Improving awareness and trust among disadvantaged communities may reduce admission stroke severity and improve outcomes.

Reducing psychiatric illness in the perinatal period: A review and commentary.

This brief overview highlights the global crisis of perinatal psychiatric illness (PPI). PPI is a major contributor to many adverse pregnancy, childbirth, and childhood development outcomes. It contributes to billions of dollars in spending worldwide each year and has a significant impact on the individual, their family, and their community. It is also highly preventable. Current recommendations for intervention and management of PPI are limited and vary considerably from country to country. Furthermore, there are several significant challenges asso-ciated with implementation of these recommendations. These challenges are magnified in number and consequence among women of color and/or minority populations, who experience persistent and negative health disparities during pregnancy and the postpartum period. This paper aims to provide a broad overview of the current state of recommendations and implementation challenges for PPI and layout a framework for overcoming these challenges. An equity-informed model of care that provides universal intervention for pregnant women may be one solution to address the preventable consequences of PPI on child and maternal health. Uniquely, this model emphasizes the importance of managing and eliminating known barriers to traditional health care models. Culturally and contextually specific challenges must be overcome to fully realize the impact of improved management of PPI.

Geographic Disparities in Case Fatality and Discharge Disposition Among Patients With Primary Intracerebral Hemorrhage.

Background We evaluate nationwide trends and urban-rural disparities in case fatality (in-hospital mortality) and discharge dispositions among patients with primary intracerebral hemorrhage (ICH). Methods and Results In this repeated cross-sectional study, we identified adult patients (≥18 years of age) with primary ICH from the National Inpatient Sample (2004-2018). Using a series of survey design Poisson regression models, with hospital location-time interaction, we report the adjusted risk ratio (aRR), 95% CI, and average marginal effect (AME) for factors associated with ICH case fatality and discharge dispositions. We performed a stratified analysis of each model among patients with extreme loss of function and minor to major loss of function. We identified 908 557 primary ICH hospitalizations (overall mean age [SD], 69.0 [15.0] years; 445 301 [49.0%] women; 49 884 [5.5%] rural ICH hospitalizations). The crude ICH case fatality rate was 25.3% (urban hospitals: 24.9%, rural hospitals:32.5%). Urban (versus rural) hospital patients had a lower likelihood of ICH case fatality (aRR, 0.86 [95% CI, 0.83-0.89]). ICH case fatality is declining over time; however, it is declining faster in urban hospitals (AME, -0.049 [95% CI, -0.051 to -0.047]) compared with rural hospitals (AME, -0.034 [95% CI, -0.040 to -0.027]). Conversely, home discharge is increasing significantly among urban hospitals (AME, 0.011 [95% CI, 0.008-0.014]) but not significantly changing in rural hospitals (AME, -0.001 [95% CI, -0.010 to 0.007]). Among patients with extreme loss of function, hospital location was not significantly associated with ICH case fatality or home discharge. Conclusions Improving access to neurocritical care resources, particularly in resource-limited communities, may reduce the ICH outcomes disparity gap.

Real-world effectiveness of COVID-19 vaccines and anti-SARS-CoV-2 monoclonal antibodies against postacute sequelae of SARS-CoV-2: analysis of a COVID-19 observational registry for a diverse US metropolitan population.

OBJECTIVES: We evaluated the effectiveness of COVID-19 vaccines and monoclonal antibodies (mAbs) against postacute sequelae of SARS-CoV-2 infection (PASC). DESIGN AND SETTING: A retrospective cohort study using a COVID-19 specific, electronic medical record-based surveillance and outcomes registry from an eight-hospital tertiary hospital system in the Houston metropolitan area. Analyses were replicated across a global research network database. PARTICIPANTS: We identified adult (≥18) patients with PASC. PASC was defined as experiencing constitutional (palpitations, malaise/fatigue, headache) or systemic (sleep disorder, shortness of breath, mood/anxiety disorders, cough and cognitive impairment) symptoms beyond the 28-day postinfection period. STATISTICAL ANALYSIS: We fit multivariable logistic regression models and report estimated likelihood of PASC associated with vaccination or mAb treatment as adjusted ORs with 95% CIs. RESULTS: Primary analyses included 53 239 subjects (54.9% female), of whom 5929, 11.1% (95% CI 10.9% to 11.4%), experienced PASC. Both vaccinated breakthrough cases (vs unvaccinated) and mAb-treated patients (vs untreated) had lower likelihoods for developing PASC, aOR (95% CI): 0.58 (0.52-0.66), and 0.77 (0.69-0.86), respectively. Vaccination was associated with decreased odds of developing all constitutional and systemic symptoms except for taste and smell changes. For all symptoms, vaccination was associated with lower likelihood of experiencing PASC compared with mAb treatment. Replication analysis found identical frequency of PASC (11.2%, 95% CI 11.1 to 11.3) and similar protective effects against PASC for the COVID-19 vaccine: 0.25 (0.21-0.30) and mAb treatment: 0.62 (0.59-0.66). CONCLUSION: Although both COVID-19 vaccines and mAbs decreased the likelihood of PASC, vaccination remains the most effective tool for the prevention of long-term consequences of COVID-19.

Neutralizing Monoclonal Antibody Use and COVID-19 Infection Outcomes.

Importance: Evidence on the effectiveness and safety of COVID-19 therapies across a diverse population with varied risk factors is needed to inform clinical practice. Objective: To assess the safety of neutralizing monoclonal antibodies (nMAbs) for the treatment of COVID-19 and their association with adverse outcomes. Design, Setting, and Participants: This retrospective cohort study included 167 183 patients from a consortium of 4 health care systems based in California, Minnesota, Texas, and Utah. The study included nonhospitalized patients 12 years and older with a positive COVID-19 laboratory test collected between November 9, 2020, and January 31, 2022, who met at least 1 emergency use authorization criterion for risk of a poor outcome. Exposure: Four nMAb products (bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab) administered in the outpatient setting. Main Outcomes and Measures: Clinical and SARS-CoV-2 genomic sequence data and propensity-adjusted marginal structural models were used to assess the association between treatment with nMAbs and 4 outcomes: all-cause emergency department (ED) visits, hospitalization, death, and a composite of hospitalization or death within 14 days and 30 days of the index date (defined as the date of the first positive COVID-19 test or the date of referral). Patient index dates were categorized into 4 variant epochs: pre-Delta (November 9, 2020, to June 30, 2021), Delta (July 1 to November 30, 2021), Delta and Omicron BA.1 (December 1 to 31, 2021), and Omicron BA.1 (January 1 to 31, 2022). Results: Among 167 183 patients, the mean (SD) age was 47.0 (18.5) years; 95 669 patients (57.2%) were female at birth, 139 379 (83.4%) were White, and 138 900 (83.1%) were non-Hispanic. A total of 25 241 patients received treatment with nMAbs. Treatment with nMAbs was associated with lower odds of ED visits within 14 days (odds ratio [OR], 0.76; 95% CI, 0.68-0.85), hospitalization within 14 days (OR, 0.52; 95% CI, 0.45-0.59), and death within 30 days (OR, 0.14; 95% CI, 0.10-0.20). The association between nMAbs and reduced risk of hospitalization was stronger in unvaccinated patients (14-day hospitalization: OR, 0.51; 95% CI, 0.44-0.59), and the associations with hospitalization and death were stronger in immunocompromised patients (hospitalization within 14 days: OR, 0.31 [95% CI, 0.24-0.41]; death within 30 days: OR, 0.13 [95% CI, 0.06-0.27]). The strength of associations of nMAbs increased incrementally among patients with a greater probability of poor outcomes; for example, the ORs for hospitalization within 14 days were 0.58 (95% CI, 0.48-0.72) among those in the third (moderate) risk stratum and 0.41 (95% CI, 0.32-0.53) among those in the fifth (highest) risk stratum. The association of nMAb treatment with reduced risk of hospitalizations within 14 days was strongest during the Delta variant epoch (OR, 0.37; 95% CI, 0.31-0.43) but not during the Omicron BA.1 epoch (OR, 1.29; 95% CI, 0.68-2.47). These findings were corroborated in the subset of patients with viral genomic data. Treatment with nMAbs was associated with a significant mortality benefit in all variant epochs (pre-Delta: OR, 0.16 [95% CI, 0.08-0.33]; Delta: OR, 0.14 [95% CI, 0.09-0.22]; Delta and Omicron BA.1: OR, 0.10 [95% CI, 0.03-0.35]; and Omicron BA.1: OR, 0.13 [95% CI, 0.02-0.93]). Potential adverse drug events were identified in 38 treated patients (0.2%). Conclusions and Relevance: In this study, nMAb treatment for COVID-19 was safe and associated with reductions in ED visits, hospitalization, and death, although it was not associated with reduced risk of hospitalization during the Omicron BA.1 epoch. These findings suggest that targeted risk stratification strategies may help optimize future nMAb treatment decisions.

Clinical and Economic Profile of Homeless Young Adults with Stroke in the United States, 2002-2017.

Homelessness is a major social determinant of health. We studied the clinical and economic profile of homeless young adults hospitalized with stroke. We studied the National Inpatient Sample database (2002-2017) to evaluate trends of stroke hospitalization, clinical outcomes, and health expenditure in homeless vs non-homeless young adults (<45 years). We identified 3134 homeless individuals out of 648,944 young adults. Homeless patients were more likely to be men, Black adults and had a higher prevalence of cardiometabolic risk factors and psychiatric disorders than non-homeless adults. Both homeless and non-homeless adults had a similar prevalence of ischemic and hemorrhagic stroke. Between 2002 and 2017, hospitalization rates per million increased for both non-homeless (295.8-416.8) and homeless adults (0.5-3.6) (P ≤ 0.01). Between 2003 and 2017, the decline in in-hospital mortality was limited to non-homeless adults (11%-9%), while it has increased in homeless adults (3%-11%) (P < 0.01). The prevalence of acute myocardial infarction (6.8% vs 3.3%, P < 0.01), and acute kidney injury (13.1% vs 9.4%, P < 0.01) was also higher in homeless vs. non-homeless adults. The length of stay and inflation-adjusted care cost were comparable between both study groups. Finally, a higher proportion of homeless patients left the hospital against medical advice than non-homeless adults. Homeless young stroke patients had significant comorbidities, increased hospitalization rates, and adverse clinical outcomes. Therefore, public health interventions should focus on multidisciplinary care to reduce health care disparities among young homeless adults.

An Intervention Mapping Approach to Developing a Stroke Literacy Video for Recent Stroke Survivors: Development and Usability Study.

BACKGROUND: Most vascular events after stroke may be prevented by modifying vascular risk factors through medical and behavioral interventions. Stroke literacy-an understanding of stroke symptoms, risk factors, and treatment-likely contributes to vascular risk factor control and in turn stroke recurrence risk. Stroke literacy is the lowest among adults belonging to racial and ethnic minority populations in the United States. Video-based interventions targeting stroke literacy may help acute stroke survivors understand stroke and subsequently reduce the risk of stroke recurrence. However, the failure of prior stroke literacy interventions may be due in part to the fact that the interventions were not theory-driven. Intervention mapping (IM) provides a framework for use in the development, implementation, and evaluation of evidence-informed, health-related interventions. OBJECTIVE: We aimed to develop a video-based educational intervention to improve stroke literacy in hospitalized patients with acute stroke. METHODS: The 6-step iterative process of IM was used to develop a video-based educational intervention and related implementation and evaluation plans. The six steps included a needs assessment, the identification of outcomes and change objectives, the selection of theory- and video-based intervention methods and practical applications, the development of a video-based stroke educational intervention, plans for implementation, and evaluation strategies. RESULTS: A 5-minute video-based educational intervention was developed. The IM approach led to successful intervention development by emphasizing stakeholder involvement, generation and adoption, and information retainment in the planning phase of the intervention. A planned approach to video adoption, implementation, and evaluation was also developed. CONCLUSIONS: An IM approach guided the development of a 5-minute video-based educational intervention to promote stroke literacy among acute stroke survivors. Future studies are needed to assess the use of technology and digital media to support widespread access and participation in video-based health literacy interventions for populations with acute and chronic stroke. Studies are needed to assess the impact of video-based educational interventions that are paired with stroke systems of care optimization to reduce the risk of stroke recurrence. Furthermore, studies on culturally and linguistically sensitive video-based stroke literacy interventions are needed to address known racial and ethnic disparities in stroke literacy. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1371/journal.pone.0171952.

Extraction of Radiological Characteristics From Free-Text Imaging Reports Using Natural Language Processing Among Patients With Ischemic and Hemorrhagic Stroke: Algorithm Development and Validation.

BACKGROUND: Neuroimaging is the gold-standard diagnostic modality for all patients suspected of stroke. However, the unstructured nature of imaging reports remains a major challenge to extracting useful information from electronic health records systems. Despite the increasing adoption of natural language processing (NLP) for radiology reports, information extraction for many stroke imaging features has not been systematically evaluated. OBJECTIVE: In this study, we propose an NLP pipeline, which adopts the state-of-the-art ClinicalBERT model with domain-specific pretraining and task-oriented fine-tuning to extract 13 stroke features from head computed tomography imaging notes. METHODS: We used the model to generate structured data sets with information on the presence or absence of common stroke features for 24,924 patients with strokes. We compared the survival characteristics of patients with and without features of severe stroke (eg, midline shift, perihematomal edema, or mass effect) using the Kaplan-Meier curve and log-rank tests. RESULTS: Pretrained on 82,073 head computed tomography notes with 13.7 million words and fine-tuned on 200 annotated notes, our HeadCT_BERT model achieved an average area under receiver operating characteristic curve of 0.9831, F1-score of 0.8683, and accuracy of 97%. Among patients with acute ischemic stroke, admissions with any severe stroke feature in initial imaging notes were associated with a lower probability of survival (P<.001). CONCLUSIONS: Our proposed NLP pipeline achieved high performance and has the potential to improve medical research and patient safety.

A Contemporary Review of Epidemiology, Risk Factors, Etiology, and Outcomes of Premature Stroke.

PURPOSE OF REVIEW: Recent data identifies increases in young ischemic and hemorrhagic strokes. We provide a contemporary overview of current literature on stroke among young patients or premature stroke along with directions for future investigation. RECENT FINDINGS: Strokes in the young are highly heterogenous and often cryptogenic. Sex distribution and risk factors shift from women among the youngest age groups (< 35) to men over the age of 45, with a coinciding rise in traditional vascular risk factors. Incidence is higher in minority and socioeconomically disadvantaged populations, and the impact of stroke among these communities may be exaggerated by disparities in symptom recognition and access to care. Special diagnostic work-up may be needed, and a lower threshold for diagnosis is warranted as potential misdiagnosis is a concern and may preclude necessary triage and management. Although "premature strokes" form a relatively small proportion of total incidence, they vary greatly across subgroups and present an outsized impact on quality of life and productivity.

SARS-CoV-2 and the central nervous system: Emerging insights into hemorrhage-associated neurological consequences and therapeutic considerations.

Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to impact our lives by causing widespread illness and death and poses a threat due to the possibility of emerging strains. SARS-CoV-2 targets angiotensin-converting enzyme 2 (ACE2) before entering vital organs of the body, including the brain. Studies have shown systemic inflammation, cellular senescence, and viral toxicity-mediated multi-organ failure occur during infectious periods. However, prognostic investigations suggest that both acute and long-term neurological complications, including predisposition to irreversible neurodegenerative diseases, can be a serious concern for COVID-19 survivors, especially the elderly population. As emerging studies reveal sites of SARS-CoV-2 infection in different parts of the brain, potential causes of chronic lesions including cerebral and deep-brain microbleeds and the likelihood of developing stroke-like pathologies increases, with critical long-term consequences, particularly for individuals with neuropathological and/or age-associated comorbid conditions. Our recent studies linking the blood degradation products to genome instability, leading to cellular senescence and ferroptosis, raise the possibility of similar neurovascular events as a result of SARS-CoV-2 infection. In this review, we discuss the neuropathological consequences of SARS-CoV-2 infection in COVID survivors, focusing on possible hemorrhagic damage in brain cells, its association to aging, and the future directions in developing mechanism-guided therapeutic strategies.

COVID-19 associated disruptions in routine health care of people with mild cognitive impairment or dementia.

Introduction: We report the COVID-19 pandemic's impact on health-care use disruption among people with mild cognitive impairment or Alzheimer's disease and related dementia (MCI/ADRD). Methods: We compared the pandemic-period health-care use between MCI/ADRD and matched non-MCI/ADRD patients. Using 4-year pre-pandemic data, we modeled three health-care use types (inpatient, outpatient, emergency encounters) to predict pandemic-period use, disaggregated for lockdown and post-lockdown periods. Observed health-care use was compared to the predicted. Proportional differences (confidence intervals) are reported. Results: Both MCI/ADRD and non-MCI/ADRD patients (n = 5479 each) experienced pandemic-related health-care use disruptions, which were significantly larger for the MCI/ADRD group for outpatient, -13.2% (-16.2%, -10.2%), and inpatient encounters, -12.8% (-18.4%, -7.3%). Large health-care disruptions during lockdown were similar for both groups. However, post-lockdown outpatient, -14.4% (-17.3%, -11.5%), and inpatient, -15.2% (-21.0%, -9.5%), disruptions were significantly greater for MCI/ADRD patients. Conclusion: MCI/ADRD patients experienced greater and sustained pandemic-related health-care use disruptions, highlighting the need for robust strategies to sustain their essential health care during pandemic-like catastrophes.

Sex differences in post-stroke cognitive decline: A population-based longitudinal study of nationally representative data.

BACKGROUND: Sex differences in post-stroke cognitive decline have not been systematically evaluated in a nationally representative cohort. We use a quasi-experimental design to investigate sex differences in rate of post-stroke cognitive decline. METHODS: Utilizing the event study design, we use the Health and Retirement Study (HRS) data (1996-2016) to evaluate the differences (percentage points [95% Confidence interval]) in the rate of change in cognitive function, measured using the modified version of the Telephone Interview for Cognitive Status (TICS-m) score, before and after incident stroke, and among patients with and without incident stroke. We estimated this event study model for the overall study population and separately fit the same model for male and female participants. RESULTS: Of 25,872 HRS participants included in our study, 14,459 (55.9%) were females with an overall mean age (SD) of 61.2 (9.3) years. Overall, 2,911 (11.3%) participants reported experiencing incident stroke. Participants with incident stroke (vs. no stroke) had lower baseline TICS-m score (15.6 vs. 16.1). Among participants with incident stroke, the mean pre-stroke TICS-m score was higher than the mean post-stroke TICS-m score (14.9 vs. 12.7). Event study revealed a significant short-term acceleration of cognitive decline for the overall population (4.2 [1.7-6.6] percentage points, p value = 0.001) and among female participants (5.0 [1.7-8.3] percentage points, p value = 0.003). We, however, found no evidence of long-term acceleration of cognitive decline after stroke. Moreover, among males, incident stroke was not associated with significant changes in rate of post-stroke cognitive decline. CONCLUSION: Females, in contrast to males, experience post-stroke cognitive deficits, particularly during early post-stroke period. Identifying the sex-specific stroke characteristics contributing to differences in post stroke cognitive decline may inform future strategies for reducing the burden of post-stroke cognitive impairment and dementia.