Approach to Acute Dizziness/Vertigo in the Emergency Department: Selected Controversies Regarding Specialty Consultation.

Acute dizziness and vertigo are common emergency department presentations (≈4% of annual visits) and sometimes, a life-threatening diagnosis like stroke is missed. Recent literature reviews the challenges in evaluation of these symptoms and offers guidelines for diagnostic approaches. Strong evidence indicates that when well-trained providers perform a high-quality bedside neurovestibular examination, accurate diagnosis of peripheral vestibular disorders and stroke increases. However, it is less clear who can and should be performing these assessments on a routine basis. This article offers a focused debate for and against routine specialty consultation for patients with acute dizziness or vertigo in the emergency department as well as a potential path forward utilizing new portable technologies to quantify eye movements.

Code-ICH: A New Paradigm for Emergency Intervention.

PURPOSE OF REVIEW: Intracerebral hemorrhage (ICH) is the most devastating type of stroke, causing widespread disability and mortality. Unfortunately, the acute care of ICH has lagged behind that of ischemic stroke. There is an increasing body of evidence supporting the importance of early interventions including aggressive control of blood pressure and reversal of anticoagulation in the initial minutes to hours of presentation. This review highlights scientific evidence behind a new paradigm to care for these patients called Code-ICH. RECENT FINDINGS: While numerous trials aimed at decreasing hematoma expansion through single interventions had failed to show statistically significant effects on primary outcomes, time-sensitive, multifaceted, bundled care approaches have recently shown substantial promise in improving functional outcomes in patients with ICH. The concept of Code-ICH can serve as a structural platform for the practice of acute care neurology to continuously measure its performance, reflect on best practices, advance care, and address disparities.

Vitamin K Antagonist Reversal for Urgent Surgery Using 4-Factor Prothrombin Complex Concentrates: A Randomized Clinical Trial.

Importance: Millions of people take vitamin K antagonists (VKAs). Some people who need urgent surgical procedures require rapid VKA reversal to prevent excessive intraoperative bleeding. Objective: To evaluate the hemostatic noninferiority of an investigational 4-factor prothrombin complex concentrate (4F-PCC) to a control 4F-PCC for rapid VKA reversal before urgent surgery. Design, Setting, and Participants: This phase 3, double-blind, noninferiority randomized clinical trial (LEX-209) was conducted in 24 hospitals in the US, Russia, Georgia, Belarus, Ukraine, and Romania from June 7, 2017, through November 8, 2021; the study was stopped in February 2022. Participants were adult patients taking VKA who had an international normalized ratio (INR) of 2 or higher and needed urgent surgery with a substantial bleeding risk (≥50 mL). Patients were randomized 1:1 to a single infusion of either the investigational 4F-PCC or the control 4F-PCC. Data analysis followed intention-to-treat and per-protocol approaches. Interventions: Single intravenous infusion was dosed by body weight and baseline INR. A dose of 25, 35, or 50 IU/kg of investigational 4F-PCC or control 4F-PCC was administered for baseline INR of 2 to less than 4, 4 to 6, or over 6, respectively. Main Outcome and Measure: The primary end point was hemostatic efficacy at surgery end. An independent adjudication board, blinded to the 4F-PCC treatment allocation, assessed hemostatic efficacy using an objective 4-point scale. Results: A total of 208 patients (median [range] age, 67.5 [31-92] years; 118 males [56.7%]) received the investigational (n = 105) or the control (n = 103) 4F-PCC. The median (range) dose was 25 (16-50) IU/kg in the investigational group and 25 (15-50) IU/kg in the control group, with a median (range) infusion time of 12 (8-50) minutes and 13 (7-30) minutes and a median (range) time from infusion to surgery start of 1.42 (0.25-15.25) hours and 1.50 (0.42-18.50) hours, respectively. Baseline median (range) INR was 3.05 (1.97-21.10) in the investigational group and 3.00 (2.00-11.30) in the control group. In the intention-to-treat analysis, the investigational 4F-PCC was noninferior to the control 4F-PCC, resulting in effective hemostasis in 94.3% of patients vs 94.2% of patients (proportion difference, 0.001; 95% CI, -0.080 to 0.082; P < .001), meeting the prespecified noninferiority margin of 0.15. An INR of 1.5 or lower at 30 minutes after infusion occurred in 78.1% of patients in the investigational group vs 71.8% of patients in the control group (proportion difference, 0.063; 95% CI, -0.056 to 0.181). Thrombotic events (2.9% vs 0%, respectively) and mortality (4.8% vs 1.0%, respectively) were no different than expected for 4F-PCC use. One patient in each treatment group discontinued due to adverse events (cardiac disorders unrelated to 4F-PCC). Conclusions and Relevance: This randomized clinical trial found that the investigational 4F-PCC was hemostatically noninferior to the control 4F-PCC for rapid VKA reversal in patients needing urgent surgery with considerable bleeding risk; the safety profile of these two 4F-PCCs was similar. These results support the investigational 4F-PCC as a therapeutic option for surgical patients requiring rapid VKA reversal. Trial Registration: ClinicalTrials.gov Identifier: NCT02740335.

Impact of COVID-19 on Characteristics and Funding of U.S. Healthcare Startups: Retrospective Review.

BACKGROUND: The rise of telehealth and telemedicine during the pandemic allowed patients and providers to develop a sense of comfort with telehealth, which may have increased the demand for virtual-first care solutions with spillover effects into venture capital funding. OBJECTIVE: We aimed to understand the size and type of digital health investments occurring in the prepandemic and pandemic periods. METHODS: We examined health care companies founded from March 14, 2019, to March 14, 2020 (prepandemic) versus those founded from March 15, 2020, to March 14, 2022, after pandemic onset. Data were obtained from Crunchbase, a publicly available database that catalogs information about venture capital investments for companies. We also compared companies founded prepandemic to those founded after the first year of the pandemic (pandemic steady-state). We performed a Wilcoxon rank sum test to compare median funding amounts. We compared the 2 groups of companies according to the type of funding round raised, geography, health care subcategory, total amount of funding per year since founding, and number of founders. RESULTS: There were 2714 and 2218 companies founded prepandemic and during the pandemic, respectively. The companies were similarly distributed across geographies in the prepandemic and pandemic periods (P=.46) with no significant differences in the number of founders (P=.32). There was a significant difference in total funding per year since founding between prepandemic and pandemic companies (US $10.8 million vs US $20.9 million; P<.001). The distribution of funding rounds differed significantly for companies founded in prepandemic and pandemic periods (P<.001). On excluding data from the first year of the pandemic, there were 581 companies founded in the pandemic steady-state period from March 14, 2021, to March 14, 2022. Companies founded prepandemic had a significantly greater mean number of founders than those founded during the pandemic (P=.02). There was no significant difference in total funding per year since founding between prepandemic and steady-state pandemic companies (US $10.8 million vs US $14.4 million; P=.34). The most common types of health care companies included wellness, biotech/biopharma, and software companies. Distributions of companies across health care subcategories were not significantly different before and during the pandemic. However, significant differences were identified when data from the first year of the pandemic were excluded (P<.001). Companies founded during the steady-state pandemic period were significantly more likely to be classified as artificial intelligence (7.3% vs 4.7%; P=.005), software (17.3% vs 12.7%; P=.002), and insurance (3.3% vs 1.7%; P=.003), and were significantly less likely to be classified as health care diagnostics (2.4% vs 5.1%; P=.002). CONCLUSIONS: We demonstrate no significant changes in the types of health care companies founded before versus during the pandemic, although significant differences emerge when comparing prepandemic companies to those founded after the first year of the pandemic.

Reaching Structurally Vulnerable Populations Using Low-Barrier COVID-19 Testing Clinics Co-Created with Community-Based Organizations.

BACKGROUND: The COVID-19 pandemic disproportionately affected people from structurally vulnerable communities. There was a need to improve COVID-19 testing in these communities to reduce viral spread and connect to treatment. OBJECTIVE: We created a partnership between an academic medical center and three community-based organizations (CBOs) to offer low-barrier COVID-19 walk-up testing clinics in Portland, Maine. Our objective was to examine whether the co-created testing clinics reached structurally vulnerable populations. DESIGN: The clinics offered COVID-19 rapid antigen tests three times a week outside CBO sites from January 2022 to May 2023. Clinic staff administered a brief survey on reason for testing and then instructed participants on how to self-swab. While staff processed the test, participants were invited to complete an additional survey about their demographics and testing perceptions. PARTICIPANTS: Adults seeking COVID-19 testing with specific outreach to people who are unhoused, immigrants, and low-income and/or uninsured. MAIN MEASURES: Number of tests conducted and result, reasons for testing, and testing perceptions. KEY RESULTS: Of 246 completed tests, 18 were positive for COVID-19 (7%). Participants sought testing for a variety of reasons, including symptoms (60%), close contact exposure (29%), and/or need for a negative test result to access services or an activity (33%). Overall, people primarily tested due to symptoms with only 7% testing due to close contact exposure alone. The clinics reached vulnerable populations. Among the 130 people completing the participant survey, 39% were unhoused, 22% spoke a language other than English at home, 23% were uninsured, and 46% earned less than $20,000 in 2019. Qualitative field notes captured key elements of clinics that influenced reach, and how this collaboration with CBOs helped build trust with our target populations. CONCLUSIONS: Providing low-barrier walk-up clinics partnering with trusted CBOs was observed to be helpful in reaching structurally vulnerable populations for COVID-19 testing.

Diffusion-Weighted Imaging Fluid-Attenuated Inversion Recovery Mismatch on Portable, Low-Field Magnetic Resonance Imaging Among Acute Stroke Patients.

OBJECTIVE: For stroke patients with unknown time of onset, mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) can guide thrombolytic intervention. However, access to MRI for hyperacute stroke is limited. Here, we sought to evaluate whether a portable, low-field (LF)-MRI scanner can identify DWI-FLAIR mismatch in acute ischemic stroke. METHODS: Eligible patients with a diagnosis of acute ischemic stroke underwent LF-MRI acquisition on a 0.064-T scanner within 24 h of last known well. Qualitative and quantitative metrics were evaluated. Two trained assessors determined the visibility of stroke lesions on LF-FLAIR. An image coregistration pipeline was developed, and the LF-FLAIR signal intensity ratio (SIR) was derived. RESULTS: The study included 71 patients aged 71 ± 14 years and a National Institutes of Health Stroke Scale of 6 (interquartile range 3-14). The interobserver agreement for identifying visible FLAIR hyperintensities was high (κ = 0.85, 95% CI 0.70-0.99). Visual DWI-FLAIR mismatch had a 60% sensitivity and 82% specificity for stroke patients <4.5 h, with a negative predictive value of 93%. LF-FLAIR SIR had a mean value of 1.18 ± 0.18 <4.5 h, 1.24 ± 0.39 4.5-6 h, and 1.40 ± 0.23 >6 h of stroke onset. The optimal cut-point for LF-FLAIR SIR was 1.15, with 85% sensitivity and 70% specificity. A cut-point of 6.6 h was established for a FLAIR SIR <1.15, with an 89% sensitivity and 62% specificity. INTERPRETATION: A 0.064-T portable LF-MRI can identify DWI-FLAIR mismatch among patients with acute ischemic stroke. Future research is needed to prospectively validate thresholds and evaluate a role of LF-MRI in guiding thrombolysis among stroke patients with uncertain time of onset. ANN NEUROL 2024;96:321-331.

2024 AHA/ASA Performance and Quality Measures for Spontaneous Intracerebral Hemorrhage: A Report From the American Heart Association/American Stroke Association.

The American Heart Association/American Stroke Association released a revised spontaneous intracerebral hemorrhage guideline in 2022. A working group of stroke experts reviewed this guideline and identified a subset of recommendations that were deemed suitable for creating performance measures. These 15 performance measures encompass a wide spectrum of intracerebral hemorrhage patient care, from prehospital to posthospital settings, highlighting the importance of timely interventions. The measures also include 5 quality measures and address potential challenges in data collection, with the aim of future improvements.

The Formal Demography of Peak Population.

When will the human population peak? In this article, we build on classical results by Ansley Coale, who showed that when fertility declines steadily, births reach their maximum before fertility reaches replacement level, and the decline in total population size does not occur until several decades after fertility has reached that level. We extend Coale's results by modeling longevity increases, net immigration, and a slowdown in fertility decline that resembles current projections. With these extensions, our models predict a typical lag between replacement-level fertility and population decline of about 35 to 40 years, consistent with projections by the United Nations and about 15 years longer than the lag predicted by Coale. Our analysis helps reveal underlying factors in the timing of peak population.

Long-Term Outcomes in Patients With Spontaneous Cerebellar Hemorrhage: An International Cohort Study.

BACKGROUND: Spontaneous intracerebral hemorrhage (ICH) in the cerebellum has a poor short-term prognosis, whereas data on the long-term case fatality and recurrent vascular events are sparse. Herewith, we aimed to assess the long-term case fatality and recurrence rate of vascular events after a first cerebellar ICH. METHODS: In this international cohort study, we included patients from 10 hospitals (the United States and Europe from 1997 to 2017) aged ≥18 years with a first spontaneous cerebellar ICH who were discharged alive. Data on long-term case fatality and recurrence of vascular events (recurrent ICH [supratentoria or infratentorial], ischemic stroke, myocardial infarction, or major vascular surgery) were collected for survival analysis and absolute event rate calculation. RESULTS: We included 405 patients with cerebellar ICH (mean age [SD], 72 [13] years, 49% female). The median survival time was 67 months (interquartile range, 23-100 months), with a cumulative survival rate of 34% at 10-year follow-up (median follow-up time per center ranged: 15-80 months). In the 347 patients with data on vascular events 92 events occurred in 78 patients, after initial cerebellar ICH: 31 (8.9%) patients had a recurrent ICH (absolute event rate, 1.8 per 100 patient-years [95% CI, 1.2-2.6]), 39 (11%) had an ischemic stroke (absolute event rate, 2.3 [95% CI, 1.6-3.2]), 13 (3.7%) had a myocardial infarction (absolute event rate, 0.8 [95% CI, 0.4-1.3]), and 5 (1.4%) underwent major vascular surgery (absolute event rate, 0.3 [95% CI, 0.1-0.7]). The median time to a first vascular event during follow-up was 27 months (interquartile range, 8.7-50 months), with a cumulative hazard of 47% at 10 years. CONCLUSIONS: The long-term prognosis of patients who survive a first spontaneous cerebellar ICH is poor and comparable to that of patients who survive a first supratentorial ICH. Further identification of patients at high risk of vascular events following the initial cerebellar ICH is needed. Including patients with cerebellar ICH in randomized controlled trials on secondary prevention of patients with ICH is warranted.

Association Between Hematoma Volume and Risk of Subsequent Ischemic Stroke: A MISTIE III and ATACH-2 Analysis.

BACKGROUND: Nontraumatic intracerebral hemorrhage (ICH) is independently associated with a long-term increased risk of major arterial ischemic events. While the relationship between ICH location and ischemic risk has been studied, whether hematoma volume influences this risk is poorly understood. METHODS: We pooled individual patient data from the MISTIE III (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase 3) and the ATACH-2 (Antihypertensive Treatment of Acute Cerebral Hemorrhage-2) trials. The exposure was hematoma volume, treated as a continuous measure in the primary analysis, and dichotomized by the median in the secondary analyses. The outcome was a symptomatic, clinically overt ischemic stroke, adjudicated centrally within each trial. We evaluated the association between hematoma volume and the risk of an ischemic stroke using Cox regression analyses after adjustment for demographics, vascular comorbidities, and ICH characteristics. RESULTS: Of 1470 patients with ICH, the mean age was 61.7 (SD, 12.8) years, and 574 (38.3%) were female. The median hematoma volume was 17.3 mL (interquartile range, 7.2-35.7). During a median follow-up of 107 days (interquartile range, 91-140), a total of 30 ischemic strokes occurred, of which 22 were in patients with a median ICH volume of ≥17.3 mL and a cumulative incidence of 4.6% (95% CI, 3.1-7.1). Among patients with a median ICH volume <17.3 mL, there were 8 ischemic strokes with a cumulative incidence of 3.1% (95% CI, 1.7-6.0). In primary analyses using adjusted Cox regression models, ICH volume was associated with an increased risk of ischemic stroke (hazard ratio, 1.02 per mL increase [95% CI, 1.01-1.04]). In secondary analyses, ICH volume of ≥17.3 mL was associated with an increased risk of ischemic stroke (hazard ratio, 2.5 [95% CI, 1.1-7.2]), compared with those with an ICH volume <17.3 mL. CONCLUSIONS: In a heterogeneous cohort of patients with ICH, initial hematoma volume was associated with a heightened short-term risk of ischemic stroke.

Time to Anticoagulation Reversal and Outcomes After Intracerebral Hemorrhage.

Importance: Intracerebral hemorrhage (ICH) is the deadliest stroke subtype, and mortality rates are especially high in anticoagulation-associated ICH. Recently, specific anticoagulation reversal strategies have been developed, but it is not clear whether there is a time-dependent treatment effect for door-to-treatment (DTT) times in clinical practice. Objective: To evaluate whether DTT time is associated with outcome among patients with anticoagulation-associated ICH treated with reversal interventions. Design, Setting, and Participants: This cohort study used data from the American Heart Association Get With The Guidelines-Stroke quality improvement registry. Patients with ICH who presented within 24 hours of symptom onset across 465 US hospitals from 2015 to 2021 were included. Data were analyzed from January to September 2023. Exposures: Anticoagulation-associated ICH. Main Outcomes and Measures: DTT times and outcomes were analyzed using logistic regression modeling, adjusted for demographic, history, baseline, and hospital characteristics, with hospital-specific random intercepts to account for clustering by site. The primary outcome of interest was the composite inpatient mortality and discharge to hospice. Additional prespecified secondary outcomes, including functional outcome (discharge modified Rankin Scale score, ambulatory status, and discharge venue), were also examined. Results: Of 9492 patients with anticoagulation-associated ICH and documented reversal intervention status, 4232 (44.6%) were female, and the median (IQR) age was 77 (68-84) years. A total of 7469 (78.7%) received reversal therapy, including 4616 of 5429 (85.0%) taking warfarin and 2856 of 4069 (70.2%) taking a non-vitamin K antagonist oral anticoagulant. For the 5224 patients taking a reversal intervention with documented workflow times, the median (IQR) onset-to-treatment time was 232 (142-482) minutes and the median (IQR) DTT time was 82 (58-117) minutes, with a DTT time of 60 minutes or less in 1449 (27.7%). A DTT time of 60 minutes or less was associated with decreased mortality and discharge to hospice (adjusted odds ratio, 0.82; 95% CI, 0.69-0.99) but no difference in functional outcome (ie, a modified Rankin Scale score of 0 to 3; adjusted odds ratio, 0.91; 95% CI, 0.67-1.24). Factors associated with a DTT time of 60 minutes or less included White race, higher systolic blood pressure, and lower stroke severity. Conclusions and Relevance: In US hospitals participating in Get With The Guidelines-Stroke, earlier anticoagulation reversal was associated with improved survival for patients with ICH. These findings support intensive efforts to accelerate evaluation and treatment for patients with this devastating form of stroke.

Hypotension During Vasopressor Infusion Occurs in Predictable Clusters: A Multicenter Analysis.

Background: Published evidence indicates that mean arterial pressure (MAP) below a goal range (hypotension) is associated with worse outcomes, though MAP management failures are common. We sought to characterize hypotension occurrences in ICUs and consider the implications for MAP management. Methods: Retrospective analysis of 3 hospitals' cohorts of adult ICU patients during continuous vasopressor infusion. Two cohorts were general, mixed ICU patients and one was exclusively acute spinal cord injury patients. "Hypotension-clusters" were defined where there were ≥10 min of cumulative hypotension over a 60-min period and "constant hypotension" was ≥10 continuous minutes. Trend analysis was performed (predicting future MAP using 14 min of preceding MAP data) to understand which hypotension-clusters could likely have been predicted by clinician awareness of MAP trends. Results: In cohorts of 155, 66, and 16 ICU stays, respectively, the majority of hypotension occurred within the hypotension-clusters. Failures to keep MAP above the hypotension threshold were notable in the bottom quartiles of each cohort, with hypotension durations of 436, 167, and 468 min, respectively, occurring within hypotension-clusters per day. Mean arterial pressure trend analysis identified most hypotension-clusters before any constant hypotension occurred (81.2%-93.6% sensitivity, range). The positive predictive value of hypotension predictions ranged from 51.4% to 72.9%. Conclusions: Across 3 cohorts, most hypotension occurred in temporal clusters of hypotension that were usually predictable from extrapolation of MAP trends.

Entropy removal of medical diagnostics.

Shannon entropy is a core concept in machine learning and information theory, particularly in decision tree modeling. To date, no studies have extensively and quantitatively applied Shannon entropy in a systematic way to quantify the entropy of clinical situations using diagnostic variables (true and false positives and negatives, respectively). Decision tree representations of medical decision-making tools can be generated using diagnostic variables found in literature and entropy removal can be calculated for these tools. This concept of clinical entropy removal has significant potential for further use to bring forth healthcare innovation, such as quantifying the impact of clinical guidelines and value of care and applications to Emergency Medicine scenarios where diagnostic accuracy in a limited time window is paramount. This analysis was done for 623 diagnostic tools and provided unique insights into their utility. For studies that provided detailed data on medical decision-making algorithms, bootstrapped datasets were generated from source data to perform comprehensive machine learning analysis on these algorithms and their constituent steps, which revealed a novel and thorough evaluation of medical diagnostic algorithms.

Acute care bundles should be used for patients with intracerebral haemorrhage: An expert consensus statement.

PURPOSE: Intracerebral haemorrhage (ICH) is the most devastating form of stroke and a major cause of disability. Clinical trials of individual therapies have failed to definitively establish a specific beneficial treatment. However, clinical trials of introducing care bundles, with multiple therapies provided in parallel, appear to clearly reduce morbidity and mortality. Currently, not enough patients receive these interventions in the acute phase. METHODS: We convened an expert group to discuss best practices in ICH and to develop recommendations for bundled care that can be delivered in all settings that treat acute ICH, with a focus on European healthcare systems. FINDINGS: In this consensus paper, we argue for widespread implementation of formalised care bundles in ICH, including specific metrics for time to treatment and criteria for the consideration of neurosurgical therapy. DISCUSSION: There is an extraordinary opportunity to improve clinical care and clinical outcomes in this devastating disease. Substantial evidence already exists for a range of therapies that can and should be implemented now.

Code ICH: A Call to Action.

Intracerebral hemorrhage is the most serious type of stroke, leading to high rates of severe disability and mortality. Hematoma expansion is an independent predictor of poor functional outcome and is a compelling target for intervention. For decades, randomized trials aimed at decreasing hematoma expansion through single interventions have failed to meet their primary outcomes of statistically significant improvement in neurological outcomes. A wide range of evidence suggests that ultra-early bundled care, with multiple simultaneous interventions in the acute phase, offers the best hope of limiting hematoma expansion and improving functional recovery. Patients with intracerebral hemorrhage who fail to receive early aggressive care have worse outcomes, suggesting that an important treatment opportunity exists. This consensus statement puts forth a call to action to establish a protocol for Code ICH, similar to current strategies used for the management of acute ischemic stroke, through which early intervention, bundled care, and time-based metrics have substantially improved neurological outcomes. Based on current evidence, we advocate for the widespread adoption of an early bundle of care for patients with intracerebral hemorrhage focused on time-based metrics for blood pressure control and emergency reversal of anticoagulation, with the goal of optimizing the benefit of these already widely used interventions. We hope Code ICH will endure as a structural platform for continued innovation, standardization of best practices, and ongoing quality improvement for years to come.

Cerebral small vessel disease modifies outcomes after minimally invasive surgery for intracerebral haemorrhage.

BACKGROUND: Minimally invasive surgery (MIS) for spontaneous supratentorial intracerebral haemorrhage (ICH) is controversial but may be beneficial if end-of-treatment (EOT) haematoma volume is reduced to ≤15 mL. We explored whether MRI findings of cerebral small vessel disease (CSVD) modify the effect of MIS on long-term outcomes. METHODS: Prespecified blinded subgroup analysis of 288 subjects with qualified imaging sequences from the phase 3 Minimally Invasive Surgery Plus Alteplase for Intracerebral Haemorrhage Evacuation (MISTIE) trial. We tested for heterogeneity in the effects of MIS and MIS+EOT volume ≤15 mL on the trial's primary outcome of good versus poor function at 1 year by the presence of single CSVD features and CSVD scores using multivariable models. RESULTS: Of 499 patients enrolled in MISTIE III, 288 patients had MRI, 149 (51.7%) randomised to MIS and 139 (48.3%) to standard medical care (SMC). Median (IQR) ICH volume was 42 (30-53) mL. In the full MRI cohort, there was no statistically significant heterogeneity in the effects of MIS versus SMC on 1-year outcomes by any specific CSVD feature or by CSVD scores (all Pinteraction >0.05). In 94 MIS patients with EOT ICH volume ≤15 mL, significant reduction in odds of poor outcome was found with cerebral amyloid angiopathy score <2 (OR, 0.14 (0.05-0.42); Pinteraction=0.006), absence of lacunes (OR, 0.37 (0.18-0.80); Pinteraction=0.02) and absence of severe white matter hyperintensities (WMHs) (OR, 0.22 (0.08-0.58); Pinteraction=0.03). CONCLUSIONS: Following successful haematoma reduction by MIS, we found significantly lower odds of poor functional outcome with lower total burden of CSVD in addition to absence of lacunes and severe WMHs. CSVD features may have utility for prognostication and patient selection in clinical trials of MIS.

Dilated optic nerve sheath by ultrasound predicts mortality among patients with acute intracerebral hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) is a deadly disease and increased intracranial pressure (ICP) is associated with worse outcomes in this context. OBJECTIVE: We evaluated whether dilated optic nerve sheath diameter (ONSD) depicted by optic nerve ultrasound (ONUS) at hospital admission has prognostic value as a predictor of mortality at 90 days. METHODS: Prospective multicenter study of acute supratentorial primary ICH patients consecutively recruited from two tertiary stroke centers. Optic nerve ultrasound and cranial computed tomography (CT) scans were performed at hospital admission and blindly reviewed. The primary outcome was mortality at 90-days. Multivariate logistic regression, ROC curve, and C-statistics were used to identify independent predictors of mortality. RESULTS: Between July 2014 and July 2016, 57 patients were evaluated. Among those, 13 were excluded and 44 were recruited into the trial. Their mean age was 62.3 ± 13.1 years and 12 (27.3%) were female. On univariate analysis, ICH volume on cranial CT scan, ICH ipsilateral ONSD, Glasgow coma scale, National Institute of Health Stroke Scale (NIHSS) and glucose on admission, and also diabetes mellitus and current nonsmoking were predictors of mortality. After multivariate analysis, ipsilateral ONSD (odds ratio [OR]: 6.24; 95% confidence interval [CI]: 1.18-33.01; p = 0.03) was an independent predictor of mortality, even after adjustment for other relevant prognostic factors. The best ipsilateral ONSD cutoff was 5.6mm (sensitivity 72% and specificity 83%) with an AUC of 0.71 (p = 0.02) for predicting mortality at 90 days. CONCLUSION: Optic nerve ultrasound is a noninvasive, bedside, low-cost technique that can be used to identify increased ICP in acute supratentorial primary ICH patients. Among these patients, dilated ONSD is an independent predictor of mortality at 90 days.

ANTECEDENTES: A hemorragia intraparenquimatosa (HIP) aguda apresenta elevada morbimortalidade e a presença de hipertensão intracraniana (HIC) confere um pior prognóstico. OBJETIVO: Avaliamos se a dilatação do diâmetro da bainha do nervo óptico (DBNO) através do ultrassom do nervo óptico (USNO) na admissão hospitalar seria preditora de mortalidade. MéTODOS: Estudo multicêntrico e prospectivo de pacientes consecutivos com HIP supratentorial primária aguda admitidos em dois centros terciários. Ultrassom do nervo óptico e tomografia computadorizada (TC) de crânio foram realizados na admissão e revisados de forma cega. O desfecho primário do estudo foi a mortalidade em 3 meses. Análises de regressão logística, curva de característica de operação do receptor (ROC, na sigla em inglês) e estatística-C foram utilizadas para identificação dos preditores independentes de mortalidade. RESULTADOS: Entre julho de 2014 e julho de 2016, 44 pacientes foram incluídos. A idade média foi 62,3 (±13,1) anos e 12 (27,3%) eram mulheres. Na análise univariada, o volume da HIP na TC de crânio, DBNO ipsilateral à HIP, glicemia, escala de coma de Glasgow (ECG) e NIHSS na admissão hospitalar, e também diabetes mellitus e não-tabagista foram preditores de mortalidade. Após análise multivariada, o DBNO ipsilateral à HIP permaneceu como preditor independente de mortalidade (odds ratio [OR]: 6,24; intervalo de confiança [IC] de 95%: 1,18­33,01; p = 0,03). O melhor ponto de corte do DBNO ipsilateral como preditor de mortalidade em 3 meses foi 5,6mm (sensibilidade 72% e especificidade 83%) e área sob a curva (AUC, na sigla em inglês) 0,71 (p = 0,02). CONCLUSãO: O USNO é um método não-invasivo, beira-leito, de baixo custo, que pode ser empregado para estimar a presença de HIC em pacientes com HIP supratentorial primária aguda. A presença de DBNO dilatada é um preditor independente de mortalidade em 3 meses nesses pacientes.

CenSoc: Public Linked Administrative Mortality Records for Individual-level Research.

In the United States, much has been learned about the determinants of longevity from survey data and aggregated tabulations. However, the lack of large-scale, individual-level administrative mortality records has proven to be a barrier to further progress. We introduce the CenSoc datasets, which link the complete-count 1940 U.S. Census to Social Security mortality records. These datasets-CenSoc-DMF (N = 4.7 million) and CenSoc-Numident (N = 7.0 million)-primarily cover deaths among individuals aged 65 and older. The size and richness of CenSoc allows investigators to make new discoveries into geographic, racial, and class-based disparities in old-age mortality in the United States. This article gives an overview of the technical steps taken to construct these datasets, validates them using external aggregate mortality data, and discusses best practices for working with these datasets. The CenSoc datasets are publicly available, enabling new avenues of research into the determinants of mortality disparities in the United States.

Intensive Blood Pressure Reduction is Associated with Reduced Hematoma Growth in Fast Bleeding Intracerebral Hemorrhage.

OBJECTIVE: Patients with spontaneous intracerebral hemorrhage (ICH) at the highest risk of hematoma growth are those with the most potential to benefit from anti-expansion treatment. Large clinical trials have not definitively shown a clear benefit of blood pressure (BP) reduction. We aim to determine whether intensive blood pressure reduction could benefit patients with fast bleeding ICH. METHODS: An exploratory analysis of data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) randomized controlled trial was performed. In order to capture not just early bleeding (even if a small amount), but the rate of bleeding (ml/hour), we restricted the study to "Fast bleeding ICH," defined as an ICH volume/onset to computed tomography (CT) time >5 ml/hr. Hematoma growth, as defined as an increase of hematoma volume > 33% between baseline and 24 hours. RESULTS: A total of 940 patients were included (mean age = 62.1 years, 61.5% men), of whom 214 (22.8%) experienced hematoma expansion. Of these, 567 (60.3%) met the definition of "fast bleeding" with baseline ICH volume/time to presentation of at least 5 ml/hr. Intensive BP reduction was associated with a significantly lower rate of hematoma growth in fast bleeding patients (20.6% vs 31.0%, p = 0.005). In a subgroup of 266 (46.9%) fast-bleeding patients who received treatment within 2 hours after symptom onset, intensive BP lowering was associated with improved functional independence (odds ratio [OR] = 1.98, 95% confidence interval [CI] = 1.06-3.69, p = 0.031). INTERPRETATION: Our results suggest that early use of intensive BP reduction may reduce hematoma growth and improve outcome in fast bleeding patients. ANN NEUROL 2023.

Stroke-Related Visceral Alterations: A Voxel-Based Neuroanatomic Localization Study.

OBJECTIVE: Functional and morphologic changes in extracranial organs can occur after acute brain injury. The neuroanatomic correlates of such changes are not fully known. Herein, we tested the hypothesis that brain infarcts are associated with cardiac and systemic abnormalities (CSAs) in a regionally specific manner. METHODS: We generated voxelwise p value maps of brain infarcts for poststroke plasma cardiac troponin T (cTnT) elevation, QTc prolongation, in-hospital infection, and acute stress hyperglycemia (ASH) in 1,208 acute ischemic stroke patients prospectively recruited into the Heart-Brain Interactions Study. We examined the relationship between infarct location and CSAs using a permutation-based approach and identified clusters of contiguous voxels associated with p < 0.05. RESULTS: cTnT elevation not attributable to a known cardiac reason was detected in 5.5%, QTc prolongation in the absence of a known provoker in 21.2%, ASH in 33.9%, and poststroke infection in 13.6%. We identified significant, spatially segregated voxel clusters for each CSA. The clusters for troponin elevation and QTc prolongation mapped to the right hemisphere. There were 3 clusters for ASH, the largest of which was in the left hemisphere. We found 2 clusters for poststroke infection, one associated with pneumonia in the left and one with urinary tract infection in the right hemisphere. The relationship between infarct location and CSAs persisted after adjusting for infarct volume. INTERPRETATION: Our results show that there are discrete regions of brain infarcts associated with CSAs. This information could be used to bootstrap toward new markers for better differentiation between neurogenic and non-neurogenic mechanisms of poststroke CSAs. ANN NEUROL 2023;94:1155-1163.