External validation of the SI2NCAL2C score for outcomes following cerebral venous thrombosis.

OBJECTIVES: Prognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI2NCAL2C score in an international cohort. MATERIALS AND METHODS: The SI2NCAL2C score was originally developed to predict poor outcome (modified Rankin Scale (mRS) 3-6) at 6 months, and mortality at 30 days and 1 year using data from the International CVT Consortium. The SI2NCAL2C score uses 9 variables: the absence of any female-sex-specific risk factors, intracerebral hemorrhage, central nervous system infection, focal neurological deficits, coma, age, lower level of hemoglobin, higher level of glucose, and cancer. The ACTION-CVT study was an international retrospective study that enrolled consecutive patients across 27 centers. The poor outcome score was validated using 90-day mRS due to lack of follow-up at the 6-month time-point in the ACTION-CVT cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations. RESULTS: Mortality data were available for 950 patients and poor outcome data were available for 587 of 1,025 patients enrolled in ACTION-CVT. Compared to the International CVT Consortium, the ACTION-CVT cohort was older, less often female, and with milder clinical presentation. Mortality was 2.5% by 30 days and 6.0% by one year. At 90-days, 16.7% had a poor outcome. The SI2NCAL2C score had an AUC of 0.74 [95% CI 0.69-0.79] for 90-day poor outcome, 0.72 [0.60-0.82] for mortality by 30 days, and 0.82 [0.76-0.88] for mortality by one year. CONCLUSIONS: The SI2NCAL2C score had acceptable to good performance in an international external validation cohort. The SI2NCAL2C score warrants additional validation studies in diverse populations and clinical implementation studies.

Association of Neighborhood Socioeconomic Status With Withdrawal of Life-Sustaining Therapies After Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: Mortality after intracerebral hemorrhage (ICH) is common. Neighborhood socioeconomic status (nSES) is an important social determinant of health (SDoH) that can affect clinical outcome. We hypothesize that SDoH, including nSES, contribute to differences in withdrawal of life-sustaining therapies (WLSTs) and mortality in patients with ICH. METHODS: We performed a retrospective study of patients with ICH at 3 tertiary care hospitals between January 2017 and December 2022 identified through the Get with the Guidelines Database. We collected data on age, clinical severity, race/ethnicity, median household income, insurance, marital status, religion, mortality before discharge, and WLST from the electronic medical record. We assessed for associations between SDoH and WLST, mortality, and poor discharge mRS using Mann-Whitney U tests and χ2 tests. We performed multivariable analysis using backward stepwise logistic regression. RESULTS: We identified 868 patients (median age 67 [interquartile range (IQR) 55-78] years; 43% female) with ICH. Of them, 16% were Black non-Hispanic, 17% were Asian, and 15% were of Hispanic ethnicity; 50% were on Medicare and 22% on Medicaid, and the median (IQR) household income was $81,857 ($58,669-$122,078). Mortality occurred in 17% of patients, and of them, 84% of patients had WLST. Patients from zip codes with higher median household incomes had higher incidence of WLST and mortality (p < 0.01). Black non-Hispanic race was associated with lower WLST and discharge mortality (p ≤ 0.01 for both). In multivariable analysis adjusting for age and clinical severity scores, patients who lived in zip codes with high-income levels were more likely to have WLST (adjusted odds ratio [aOR] 1.88; 95% CI 1.29-2.74) and mortality before discharge (aOR 1.5; 95% CI 1.06-2.13). DISCUSSION: SDoH, including nSES, are associated with WLST after ICH. This has important implications for the care and management of patients with ICH.

Bacterial endocarditis with AACEK (HACEK) organisms.

INTRODUCTION: Gram-negative organisms of the AACEK group, formerly known as HACEK, rarely cause endocarditis. CASE SERIES: We present three cases of bacterial endocarditis, involving native and prosthetic valves, caused by AACEK organisms. In two patients, Cardiobacterium hominis was the responsible organism, and in a third, Aggregatibacter aphrophilus was implicated. A dental source of infection was identified in two patients, and in all three patients, the presentation of endocarditis was subacute. DISCUSSION: This case series highlights the indolent nature of infection with the AACEK organisms. It also demonstrates the crucial role of multimodality imaging, especially transesophageal echocardiography, in the diagnosis of AACEk endocarditis of both native and prosthetic valves, and in delineating the extent of abscess in those with prosthetic valve infection.

Predictors of Recurrent Venous Thrombosis After Cerebral Venous Thrombosis: Analysis of the ACTION-CVT Study.

BACKGROUND AND OBJECTIVE: Cerebral venous thrombosis (CVT) is a rare cause of stroke carrying a nearly 4% risk of recurrence after 1 year. There are limited data on predictors of recurrent venous thrombosis in patients with CVT. In this study, we aim to identify those predictors. METHODS: This is a secondary analysis of the ACTION-CVT study which is a multicenter international study of consecutive patients hospitalized with a diagnosis of CVT over a 6-year period. Patients with cancer-associated CVT, CVT during pregnancy, or CVT in the setting of known antiphospholipid antibody syndrome were excluded per the ACTION-CVT protocol. The study outcome was recurrent venous thrombosis defined as recurrent venous thromboembolism (VTE) or de novo CVT. We compared characteristics between patients with vs without recurrent venous thrombosis during follow-up and performed adjusted Cox regression analyses to determine important predictors of recurrent venous thrombosis. RESULTS: Nine hundred forty-seven patients were included with a mean age of 45.2 years, 63.9% were women, and 83.6% had at least 3 months of follow-up. During a median follow-up of 308 (interquartile range 120-700) days, there were 5.05 recurrent venous thromboses (37 VTE and 24 de novo CVT) per 100 patient-years. Predictors of recurrent venous thrombosis were Black race (adjusted hazard ratio [aHR] 2.13, 95% CI 1.14-3.98, p = 0.018), history of VTE (aHR 3.40, 95% CI 1.80-6.42, p < 0.001), and the presence of one or more positive antiphospholipid antibodies (aHR 3.85, 95% CI 1.97-7.50, p < 0.001). Sensitivity analyses including events only occurring on oral anticoagulation yielded similar findings. DISCUSSION: Black race, history of VTE, and the presence of one or more antiphospholipid antibodies are associated with recurrent venous thrombosis among patients with CVT. Future studies are needed to validate our findings to better understand mechanisms and treatment strategies in patients with CVT.

Association of Chronic Kidney Disease With Risk of Intracerebral Hemorrhage.

Importance: The evidence linking chronic kidney disease (CKD) to spontaneous intracerebral hemorrhage (ICH) is inconclusive owing to possible confounding by comorbidities that frequently coexist in patients with these 2 diseases. Objective: To determine whether there is an association between CKD and ICH risk. Design, Setting, and Participants: A 3-stage study that combined observational and genetic analyses was conducted. First, the association between CKD and ICH risk was tested in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, a multicenter case-control study in the US. All participants with available data on CKD from ERICH were included. Second, this analysis was replicated in the UK Biobank (UKB), an ongoing population study in the UK. All participants in the UKB were included in this study. Third, mendelian randomization analyses were implemented in the UKB using 27 CKD-related genetic variants to test for genetic associations. ERICH was conducted from August 1, 2010, to August 1, 2017, and observed participants for 1 year. The UKB enrolled participants between 2006 and 2010 and will continue to observe them for 30 years. Data analysis was performed from November 11, 2019, to May 10, 2022. Exposures: CKD stages 1 to 5. Main Outcomes and Measures: The outcome of interest was ICH, ascertained in ERICH via expert review of neuroimages and in the UKB via a combination of self-reported data and International Statistical Classification of Diseases, Tenth Revision, codes. Results: In the ERICH study, a total of 2914 participants with ICH and 2954 controls who had available data on CKD were evaluated (mean [SD] age, 61.6 [14.0] years; 2433 female participants [41.5%]; 3435 male participants [58.5%]); CKD was found to be independently associated with higher risk of ICH (odds ratio [OR], 1.95; 95% CI, 1.35-2.89; P < .001). This association was not modified by race and ethnicity. Replication in the UKB with 1341 participants with ICH and 501 195 controls (mean [SD] age, 56.5 [8.1] years; 273 402 female participants [54.4%]; 229 134 male participants [45.6%]) confirmed this association (OR, 1.28; 95% CI, 1.01-1.62; P = .04). Mendelian randomization analyses indicated that genetically determined CKD was associated with ICH risk (OR, 1.56; 95% CI, 1.13-2.16; P = .007). Conclusions and Relevance: In this 3-stage study that combined observational and genetic analyses among study participants enrolled in 2 large observational studies with different characteristics and study designs, CKD was consistently associated with higher risk of ICH. Mendelian randomization analyses suggest that this association was causal. Further studies are needed to identify the specific biological pathways that mediate this association.

Development and Validation of a Model to Identify Critical Brain Injuries Using Natural Language Processing of Text Computed Tomography Reports.

Importance: Clinical text reports from head computed tomography (CT) represent rich, incompletely utilized information regarding acute brain injuries and neurologic outcomes. CT reports are unstructured; thus, extracting information at scale requires automated natural language processing (NLP). However, designing new NLP algorithms for each individual injury category is an unwieldy proposition. An NLP tool that summarizes all injuries in head CT reports would facilitate exploration of large data sets for clinical significance of neuroradiological findings. Objective: To automatically extract acute brain pathological data and their features from head CT reports. Design, Setting, and Participants: This diagnostic study developed a 2-part named entity recognition (NER) NLP model to extract and summarize data on acute brain injuries from head CT reports. The model, termed BrainNERD, extracts and summarizes detailed brain injury information for research applications. Model development included building and comparing 2 NER models using a custom dictionary of terms, including lesion type, location, size, and age, then designing a rule-based decoder using NER outputs to evaluate for the presence or absence of injury subtypes. BrainNERD was evaluated against independent test data sets of manually classified reports, including 2 external validation sets. The model was trained on head CT reports from 1152 patients generated by neuroradiologists at the Yale Acute Brain Injury Biorepository. External validation was conducted using reports from 2 outside institutions. Analyses were conducted from May 2020 to December 2021. Main Outcomes and Measures: Performance of the BrainNERD model was evaluated using precision, recall, and F1 scores based on manually labeled independent test data sets. Results: A total of 1152 patients (mean [SD] age, 67.6 [16.1] years; 586 [52%] men), were included in the training set. NER training using transformer architecture and bidirectional encoder representations from transformers was significantly faster than spaCy. For all metrics, the 10-fold cross-validation performance was 93% to 99%. The final test performance metrics for the NER test data set were 98.82% (95% CI, 98.37%-98.93%) for precision, 98.81% (95% CI, 98.46%-99.06%) for recall, and 98.81% (95% CI, 98.40%-98.94%) for the F score. The expert review comparison metrics were 99.06% (95% CI, 97.89%-99.13%) for precision, 98.10% (95% CI, 97.93%-98.77%) for recall, and 98.57% (95% CI, 97.78%-99.10%) for the F score. The decoder test set metrics were 96.06% (95% CI, 95.01%-97.16%) for precision, 96.42% (95% CI, 94.50%-97.87%) for recall, and 96.18% (95% CI, 95.151%-97.16%) for the F score. Performance in external institution report validation including 1053 head CR reports was greater than 96%. Conclusions and Relevance: These findings suggest that the BrainNERD model accurately extracted acute brain injury terms and their properties from head CT text reports. This freely available new tool could advance clinical research by integrating information in easily gathered head CT reports to expand knowledge of acute brain injury radiographic phenotypes.

Early Deterioration, Hematoma Expansion, and Outcomes in Deep Versus Lobar Intracerebral Hemorrhage: The FAST Trial.

BACKGROUND: In patients with intracerebral hemorrhage (ICH), it is unclear whether early neurological deterioration, hematoma expansion (HE), and outcome vary by supratentorial ICH location (deep versus lobar). Herein, we assessed these relationships in a clinical trial cohort that underwent brain imaging early after symptom onset. We hypothesized that HE would occur more frequently, and outcome would be worse in patients with deep ICH. METHODS: We performed a post hoc analysis of the FAST (Factor-VII-for-Acute-Hemorrhagic-Stroke-Treatment) trial including all patients with supratentorial hemorrhage. Enrolled patients underwent brain imaging within 3 hours of symptom onset and 24 hours after randomization. Multivariable regression was used to test the association between ICH location and 3 outcomes: HE (increase of ≥33% or 6mL), early neurological deterioration (decrease in Glasgow Coma Scale score ≥2 points or increase in National Institutes of Health Stroke Scale ≥4 points within 24 hours of admission), and 90-day outcome (modified Rankin Scale). RESULTS: Of 841 FAST trial patients, we included 728 (mean age 64 years, 38% women) with supratentorial hemorrhages (deep n=623, lobar n=105). HE (44 versus 27%, P=0.001) and early neurological deterioration (31 versus 17%, P=0.001) were more common in lobar hemorrhages. Deep hemorrhages were smaller than lobar hemorrhages at baseline (12 versus 35mL, P<0.001) and 24 hours (14 versus 38mL, P<0.001). Unadjusted 90-day outcome was worse in lobar compared with deep ICH (median modified Rankin Scale score 5 versus 4, P=0.03). However, when adjusting for variables included in the ICH score including ICH volume, deep location was associated with worse and lobar location with better outcome (odds ratio lobar location, 0.58 [95% CI, 0.38-0.89]; P=0.01). CONCLUSIONS: In this secondary analysis of randomized trial patients, lobar ICH location was associated with larger ICH volume, more HE and early neurological deterioration, and worse outcome than deep ICH. After adjustment for prognostic variables, however, deep ICH was associated with worse outcome, likely due to their proximity to eloquent brain structures.

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study.

BACKGROUND: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. METHODS: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. RESULTS: Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140-720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51-1.73]; P=0.84), death (aHR, 0.78 [95% CI, 0.22-2.76]; P=0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48-1.73]; P=0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15-0.82]; P=0.02). CONCLUSIONS: In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.

High altitude modulates concussion incidence, severity, and recovery in young athletes.

BACKGROUND: High altitude may affect concussion, but prior studies are limited . We tested whether high altitude affects sport-related concussion (SRC) incidence, severity, and recovery. METHODS: Twenty-five thousand eight hundred fifteen baseline and post-injury Immediate Post-Concussion Assessment and Cognitive Testing results were compiled from Florida and Colorado, low (27 m or 62 m) and high (1,640 m or 1,991 m) altitude locations, respectively. Incidence, severity, and recovery of injury were compared between altitudes. RESULTS: High altitude was associated with increased suspected concussion incidence (adjusted OR, 2.04 [95% CI, 1.86 to 2.24];P < .0001). However, high altitude was associated with lower concussion severity measured by Severity Index (SI) (adjusted OR, 0.42 [95% CI, 0.37 to 0.49];P < .0001). High altitude was associated with decreased recovery from post-concussive symptoms in the migraine (ß, -2.72 [95% CI, -3.31 to -2.13]; P < .0001), cognitive (ß, -1.88 [95% CI, -2.40 to -1.36]; P < .0001), and sleep symptom clusters (ß, -0.30 [95% CI, -0.52 to -0.08]; P = .007). Athletes with initial SI≥8 showed prolonged neurocognitive dysfunction at high altitude (HR, 1.38 [95% CI, 1.06 to 1.81]; P = .02). CONCLUSIONS: High altitude was associated with increased suspected concussions and prolonged recovery but less severe initial injury.

Hospital Revisits for Post-Ischemic Stroke Epilepsy after Acute Stroke Interventions.

OBJECTIVES: Improvements in acute stroke care have led to an increase in ischemic stroke survivors, who are at risk for development of post-ischemic stroke epilepsy (PISE). The impact of therapies such as thrombectomy and thrombolysis on risk of hospital revisits for PISE is unclear. We utilized administrative data to investigate the association between stroke treatment and PISE-related visits. MATERIALS AND METHODS: Using claims data from California, New York, and Florida, we performed a retrospective analysis of adult survivors of acute ischemic strokes. Patients with history of epilepsy, trauma, infections, or tumors were excluded. Included patients were followed for a primary outcome of revisits for seizures or epilepsy. Cox proportional hazards regression was used to identify covariates associated with PISE. RESULTS: In 595,545 included patients (median age 74 [IQR 21], 52% female), the 6-year cumulative rate of PISE-related revisit was 2.20% (95% CI 2.16-2.24). In multivariable models adjusting for demographics, comorbidities, and indicators of stroke severity, IV-tPA (HR 1.42, 95% CI 1.31-1.54, p<0.001) but not MT (HR 1.62, 95% CI 0.90-1.50, p=0.2) was associated with PISE-related revisit. Patients who underwent decompressive craniectomy experienced a 2-fold increase in odds for returning with PISE (HR 2.35, 95% CI 1.69-3.26, p<0.001). In-hospital seizures (HR 4.06, 95% CI 3.76-4.39, p<0.001) also elevated risk for PISE. SIGNIFICANCE: We demonstrate that ischemic stroke survivors who received IV-tPA, underwent decompressive craniectomy, or experienced acute seizures were at increased risk PISE-related revisit. Close attention should be paid to these patients with increased potential for long-term development of and re-hospitalization for PISE.

Antiplatelet Use and Ischemic Stroke Risk in Minor Stroke or Transient Ischemic Attack: A Post Hoc Analysis of the POINT Trial.

BACKGROUND AND PURPOSE: Dual antiplatelet therapy has been shown to reduce the risk of recurrent stroke in patients with minor stroke or transient ischemic attack. However, whether the effect of dual antiplatelet therapy is modified by pretreatment antiplatelet status is unclear. METHODS: This is a post hoc analysis of the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke). Patients were divided into 2 groups based on pretreatment antiplatelet use. The primary outcome was ischemic stroke within 90 days of randomization. RESULTS: We included 4881 patients of whom 41% belonged to the no pretreatment antiplatelet. Ischemic stroke occurred in 6% and 5% in the antiplatelet pretreatment and no antiplatelet pretreatment, respectively. Antiplatelet pretreatment was not associated with the risk of ischemic stroke (adjusted hazard ratio, 1.05 [95% CI, 0.81-137]) or risk of major hemorrhage (hazard ratio, 1.10 [95% CI, 0.55-2.21]; P=0.794). The effect of dual antiplatelet therapy on recurrent ischemic stroke risk was not different in patients who were on antiplatelet before randomization (adjusted hazard ratio, 0.69 [95% CI, 0.50-0.94]) as opposed to those who were not (adjusted hazard ratio, 0.75 [95% CI, 0.50-1.12]), P for interaction = 0.685. CONCLUSIONS: In patients with minor stroke and high-risk transient ischemic attack, dual antiplatelet therapy reduces the risk of ischemic stroke regardless of premorbid antiplatelet use.

Sex-Related Differences in the Incidence, Severity, and Recovery of Concussion in Adolescent Student-Athletes Between 2009 and 2019.

BACKGROUND: The sex of an athlete is thought to modulate concussion incidence; however, the effects of sex on concussion severity and recovery are less clear. PURPOSE: To evaluate sex differences in concussion severity and recovery using a large, heterogeneous sample of young student-athletes with the goal of understanding how sex affects concussion outcomes in young athletes. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The Immediate Post-Concussion Assessment and Cognitive Testing results of 11,563 baseline and 5216 postinjury tests were used to calculate the incidence of concussion of adolescent male and female student-athletes ages 12 to 22 years (median, 15 years). The postinjury tests of 3465 male and 1751 female student-athletes evaluated for concussion or head trauma were used to assess differences in the Severity Index (SI) and recovery. Chi-square tests and t tests were used to compare differences in demographic characteristics, incidence, and SI between the 2 cohorts. Multivariable linear, logistic, and Cox proportional hazards regressions were used to control for differences between cohorts in analyses of incidence, SI, and recovery. RESULTS: When we controlled for demographic differences, female participants had higher odds of concussion (odds ratio, 1.62; 95% CI, 1.40-1.86; P < .0001) and higher SI after concussion (ß = 0.67; 95% CI, 0.02-1.32; P = .04). This discrepancy in SI was a result of differences in Symptom (2.40 vs 2.94; P < .0001) and Processing Speed (0.91 vs 1.06; P = .01) composite scores between male and female participants, respectively. We found no effect of sex on time to recovery when controlling for initial concussion SI (hazard ratio, 0.94; 95% CI, 0.78-1.12; P = .48). CONCLUSION: Using large, multisport cohorts, this study provides evidence that female athletes are at higher risk for more concussions and these concussions are more severe, but male and female athletes have similar recovery times when the analysis controls for initial concussion SI.

Association of Serum IL-6 (Interleukin 6) With Functional Outcome After Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: IL-6 (interleukin 6) is a proinflammatory cytokine and an established biomarker in acute brain injury. We sought to determine whether admission IL-6 levels are associated with severity and functional outcome after spontaneous intracerebral hemorrhage (ICH). METHODS: We performed an exploratory analysis of the recombinant activated FAST trial (Factor VII for Acute ICH). Patients with admission serum IL-6 levels were included. Regression analyses were used to assess the associations between IL-6 and 90-day modified Rankin Scale. In secondary analyses, we used linear regression to evaluate the association between IL-6 and baseline ICH and perihematomal edema volumes. RESULTS: Of 841 enrolled patients, we included 552 (66%) with available admission IL-6 levels (mean age 64 [SD 13], female sex 203 [37%]). IL-6 was associated with poor outcome (modified Rankin Scale, 4-6; per additional 1 ng/L, odds ratio, 1.30 [95% CI, 1.04-1.63]; P=0.02) after adjustment for known predictors of outcome after ICH and treatment group. IL-6 was associated with ICH volume after adjustment for age, sex, and ICH location, and this association was modified by location (multivariable interaction, P=0.002), with a stronger association seen in lobar (ß, 12.51 [95% CI, 6.47-18.55], P<0.001) versus nonlobar (ß 5.32 [95% CI, 3.36-7.28], P<0.001) location. IL-6 was associated with perihematomal edema volume after adjustment for age, sex, ICH volume, and ICH location (ß 1.22 [95% CI, 0.15-2.29], P=0.03). Treatment group was not associated with IL-6 levels or outcome. CONCLUSIONS: In the FAST trial population, higher admission IL-6 levels were associated with worse 90-day functional outcome and larger ICH and perihematomal edema volumes.

Policy Interventions, Social Distancing, and SARS-CoV-2 Transmission in the United States: A Retrospective State-level Analysis.

BACKGROUND: Various non-pharmaceutical interventions (NPIs) such as stay-at-home orders and school closures have been employed to limit the spread of Coronavirus disease (COVID-19). This study measures the impact of social distancing policies on COVID-19 transmission in US states during the early outbreak phase to assess which policies were most effective. METHODS: To measure transmissibility, we analyze the average effective reproductive number (Rt) in each state the week following its 500th case and doubling time from 500 to 1000 cases. Linear and logistic regressions were performed to assess the impact of various NPIs while controlling for population density, GDP, and certain health metrics. This analysis was repeated for deaths with doubling time to 100 deaths with several healthcare infrastructure control variables. RESULTS: States with stay-at-home orders in place at the time of their 500th case were associated with lower average Rt the following week compared to states without them (p<0.001) and significantly less likely to have an Rt>1 (OR 0.07, 95% CI 0.01-0.37, p = 0.004). These states also experienced longer doubling time from 500 to 1000 cases (HR 0.35, 95% CI 0.17-0.72, p = 0.004). States in the highest quartile of average time spent at home were also slower to reach 1000 cases than those in the lowest quartile (HR 0.18, 95% CI 0.06-0.53, p = 0.002). CONCLUSIONS: Stay-at-home orders had the largest effect of any policy analyzed. Multivariate analyses with cellphone tracking data suggest social distancing adherence drives these effects. States that plan to scale back such measures should carefully monitor transmission metrics.

Admission Hemoglobin Levels Are Associated With Functional Outcome in Spontaneous Intracerebral Hemorrhage.

OBJECTIVES: To test the hypothesis that admission hemoglobin levels are associated with outcome in primary, nontraumatic intracerebral hemorrhage. DESIGN: Individual patient data meta-analysis of three studies of intracerebral hemorrhage. SETTING: Two randomized clinical trials and one multiethnic observational study. PATIENTS: Patients with spontaneous, nontraumatic intracerebral hemorrhage. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Our exposure of interest was admission hemoglobin levels and the primary outcome was 3-month postintracerebral hemorrhage-dichotomized modified Rankin Scale (0-3 vs 4-6). Intermediate outcomes were admission hematoma volume and hematoma expansion defined as 6 mL or 33% increase in hemorrhage size on repeat CT. A total of 4,172 intracerebral hemorrhage patients were included in the study (mean age 63 [sd = 14]; female sex 1,668 [40%]). Each additional g/dL of admission hemoglobin was associated with 14% (odds ratio, 0.86; 95% CI, 0.82-0.91) and 7% (odds ratio, 0.93; 95% CI, 0.88-0.98) reductions in the risk of poor outcome in unadjusted and adjusted analyses, respectively. Dose-response analyses indicated a linear relationship between admission hemoglobin levels and poor outcome across the entire evaluated range (test-for-trend p < 0.001). No consistent associations were found between the admission hemoglobin levels and hematoma volume or hematoma expansion. CONCLUSIONS: Higher hemoglobin levels are associated with better outcome in intracerebral hemorrhage. Further research is needed to evaluate admission hemoglobin levels as both a therapeutic target and predictor of outcome.

Excess Cerebrovascular Mortality in the United States During the COVID-19 Pandemic.

BACKGROUND AND PURPOSE: The magnitude and drivers of excess cerebrovascular-specific mortality during the coronavirus disease 2019 (COVID-19) pandemic are unknown. We aim to quantify excess stroke-related deaths and characterize its association with social distancing behavior and COVID-19-related vascular pathology. METHODS: United States and state-level excess cerebrovascular deaths from January to May 2020 were quantified using National Center for Health Statistic data and Poisson regression models. Excess cerebrovascular deaths were analyzed as a function of time-varying stroke-related emergency medical service (EMS) calls and cumulative COVID-19 deaths using linear regression. A state-level regression analysis was performed to determine the association between excess cerebrovascular deaths and time spent in residences, measured by Google Community Mobility Reports, during the height of the pandemic after the first COVID-19 death (February 29). RESULTS: Forty states and New York City were included. Excess cerebrovascular mortality occurred nationally from the weeks ending March 28 to May 2, 2020, up to a 7.8% increase above expected levels during the week of April 18. Decreased stroke-related EMS calls were associated with excess stroke deaths one (70 deaths per 1000 fewer EMS calls [95% CI, 20-118]) and 2 weeks (85 deaths per 1000 fewer EMS calls [95% CI, 37-133]) later. Twenty-three states and New York City experienced excess cerebrovascular mortality during the pandemic height. A 10% increase in time spent at home was associated with a 4.3% increase in stroke deaths (incidence rate ratio, 1.043 [95% CI, 1.001-1.085]) after adjusting for COVID-19 deaths. CONCLUSIONS: Excess US cerebrovascular deaths during the COVID-19 pandemic were observed and associated with decreases in stroke-related EMS calls nationally and mobility at the state level. Public health measures are needed to identify and counter the reticence to seeking medical care for acute stroke during the COVID-19 pandemic.

Association of race and ethnicity to incident epilepsy, or epileptogenesis, after subdural hematoma.

OBJECTIVE: To determine whether race is associated with the development of epilepsy after subdural hematoma (SDH), we identified adult survivors of SDH in a statewide administrative dataset and followed them up for at least 1 year for revisits associated with epilepsy. METHODS: We performed a retrospective cohort study using claims data on all discharges from emergency departments (EDs) and hospitals in California. We identified adults (age ≥18 years) admitted from 2005 to 2011 with first-time traumatic and nontraumatic SDH. We used validated diagnosis codes to identify a primary outcome of ED or inpatient revisit for epilepsy. We used multivariable Cox regression for survival analysis to identify demographic and medical risk factors for epilepsy. RESULTS: We identified 29,342 survivors of SDH (mean age 71.2 [SD 16.4] years, female sex 11,954 [41.1%]). Three thousand two hundred thirty (11.0%) patients had revisits to EDs or hospitals with a diagnosis of epilepsy during the study period. Black patients (n = 1,684 [5.7%]) had significantly increased risk compared to White patients (n = 16,945 [57.7%]; hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.28-1.64, p < 0.001). Status epilepticus during the index SDH admission, although infrequent (n = 94 [0.3%]), was associated with a nearly 4-fold risk of epilepsy (HR 3.75, 95% CI 2.80-5.03, p < 0.001). Alcohol use, drug use, smoking, renal disease, and markers of injury severity (i.e., intubation, surgical intervention, length of stay, disposition other than home) were also associated with epilepsy (all p < 0.05). CONCLUSIONS: We found an association between Black race and ED and hospital revisits for epilepsy after SDH, establishing the presence of a racial subgroup that is particularly vulnerable to post-SDH epileptogenesis.

Cause of death in spontaneous intracerebral hemorrhage survivors: Multistate longitudinal study.

OBJECTIVE: To determine the leading causes of death in intracerebral hemorrhage (ICH) survivors, we used administrative data from 3 large US states to identify adult survivors of a first-time spontaneous ICH and track all hospital readmissions resulting in death. METHODS: We performed a longitudinal analysis of prospectively collected claims data from hospitalizations in California (2005-2011), New York (2005-2014), and Florida (2005-2014). Adult residents admitted with a nontraumatic ICH who survived to discharge were included. Patients were followed for a primary outcome of any readmission resulting in death. The cause of death was defined as the primary diagnosis assigned at discharge. Multivariable Cox proportional hazards and multinomial logistic regression were used to determine factors associated with the risk for and cause of death. RESULTS: Of 72,432 ICH survivors (mean age 68 years [SD 16], 48% female), 12,753 (18%) died during a median follow-up period of 4.0 years (interquartile range 2.3-6.3). The leading causes of death were infection (34%), recurrent intracranial hemorrhage (14%), cardiac disease (8%), respiratory failure (8%), and ischemic stroke (5%). Death in patients with atrial fibrillation (AF) was more likely to be caused by ischemic stroke (odds ratio [OR] 2.4, 95% confidence interval [CI] 1.9-2.9, p < 0.001) and less likely to be caused by recurrent intracranial hemorrhage (OR 0.7, 95% CI 0.6-0.8, p < 0.001) compared to patients without AF. CONCLUSIONS: Infection is the leading cause of death in all ICH survivors. Survivors with AF were at increased risk for death from ischemic stroke. These findings will help prioritize interventions aimed to improve long-term survival and recovery in ICH survivors.