Andexanet alfa effectiveness and safety versus four-factor prothrombin complex concentrate (4F-PCC) in intracranial hemorrhage while on apixaban or rivaroxaban: A single-center, retrospective, matched cohort analysis.

BACKGROUND: There is limited information directly comparing andexanet alfa (AA) versus four-factor prothrombin complex concentrate (4F-PCC) in intracranial hemorrhage (ICH) on apixaban or rivaroxaban. OBJECTIVE: The objective of this study was to compare the effectiveness and safety of AA versus 4F-PCC in ICH on apixaban or rivaroxaban. METHODS: This retrospective, matched, cohort analysis was conducted at a single healthcare system. Patients were matched based on baseline ICH volume. The primary outcome was good or excellent ICH hemostasis, which was defined as a 35% or less increase in ICH volume within 24 h following AA or 4F-PCC administration. The secondary outcome was thrombotic events within 14 days following AA or 4F-PCC administration. RESULTS: In total, 26 AA and 26 4F-PCC patients were included in this matched cohort analysis. Both groups had comparable rates of good or excellent ICH hemostasis (AA: 92.3% vs. 4F-PCC: 88.5%, p = 1.000). Thrombotic events within 14-days were not significantly different (AA: 26.9% vs. 4F-PCC: 11.5%, p = 0.159). CONCLUSION AND RELEVANCE: This study found no significant differences in good or excellent ICH hemostasis within 24-h or new thrombotic events within 14-days in a cohort given AA or 4F-PCC for ICH while on apixaban or rivaroxaban. However, this single-center analysis is underpowered due to sample size constraints, therefore further high-quality research comparing AA safety and effectiveness versus 4F-PCC is needed.

Trends in age and sex-specific prevalence of cancer and cancer subtypes in acute ischemic stroke from 2007-2019.

OBJECTIVE: To describe age and sex-specific prevalence of cancer in acute ischemic stroke (AIS) hospitalizations in the United States over the last decade. METHODS: We conducted a retrospective serial cross-sectional study using all primary AIS discharges (weighted n=5,748,358) with and without cancer in the 2007-2019 National Inpatient Sample. Admissions with primary central nervous system cancers were excluded. Joinpoint regression was used to compute the average annualized percentage change (AAPC) in cancer prevalence over time. RESULTS: Across the study period, 12.7% of AIS admissions had previous/active cancer, while 4.4% had active cancer. Of these, 18.8% were hematologic cancers, 47.2% were solid cancers without metastasis and 34.0% were metastatic cancers of any type. Age-adjusted active cancer prevalence differed by sex (males:4.8%; females:4.0%) and increased with age up to age 70-79 years (30-39 years 1.4%; 70-79 years:5.7%). Amongst cancer admissions, lung (18.7%) and prostate (17.8%) were the most common solid cancers in men, while lung (19.6%) and breast (13.7%) were the most prevalent in women. Active cancer prevalence increased over time (AAPC 1.7%, p<0.05) but the pace of increase was significantly faster in women (AAPC 2.8%) compared to men (AAPC 1.1%) (p-comparison =0.003). Fastest pace of increased prevalence was seen for genitourinary cancers in women and for gastrointestinal cancers in both sexes. Genitourinary cancers in men declined over time (AAPC -2.5%, p<0.05). Lung cancer prevalence increased in women (AAPC 1.8%, p<0.05) but remained constant in men. Prevalence of head/neck, skin/bone, gastrointestinal, hematological and metastatic cancers increased over time at similar pace in both sexes. CONCLUSION: Prevalence of cancer in AIS admissions increased in the US over the last decade but the pace of this increase was faster in women compared to men. Gastrointestinal cancers in both sexes and genitourinary cancers in women are increasing at the fastest pace. Additional studies are needed to determine whether this increase is from co-occurrence or causation of AIS by cancer.

Ten-Year Trend in Age, Sex, and Racial Disparity in tPA (Alteplase) and Thrombectomy Use Following Stroke in the United States.

Background and Purpose: IV tPA (intravenous thrombolysis with alteplase) and mechanical thrombectomy (MT) utilization increased in acute ischemic stroke hospitalizations in the United States over the last decade. It is uncertain whether this increase occurred equally across all age, sex, and racial groups. Methods: Adult acute ischemic stroke hospitalizations (weighted n=4 442 657) contained in the 2008 to 2017 National Inpatient Sample were identified using International Classification of Diseases codes. Proportions of hospitalizations with IV tPA and MT were computed according to age, sex, and race. Joinpoint and multivariable-adjusted logistic regression models were used to evaluate trends over time. Results: Across this period, 32.4% of all hospitalizations were in patients ≥80 years, and 64.7% of these were women. IV tPA and MT use differed by age with highest proportion of utilization of both treatments in patients aged 18 to 39 years (IV tPA, 12.3%) and lowest percentage in patients aged ≥90 years (IV tPA, 7.9%). Utilization of both procedures increased over time in all age groups, but the pace of increase was faster in patients ≥90 years compared with patients aged 18 to 39 years (MT: odds ratio, 1.25 [95% CI, 1.20­1.35] per unit increase in year, P interaction <0.001). Frequency of utilization of IV tPA and MT was lower in Black patients compared with White patients in most age groups. Usage of both procedures increased over time in all races and after 2015, IV tPA utilization was >10% in all demographic subgroups except in Black patients 60 to 79 years and Black patients ≥80 years. Analysis of race-by-time interaction revealed the Black-vs-White treatment gaps for IV tPA (odds ratio, 1.02 [95% CI, 1.01­1.03]) and MT (odds ratio, 1.08 [95% CI,1.05­1.12]) declined over time (both P interaction <0.01). Sex-related differences in IV tPA use were noted, but this gap also declined over time. Conclusions: Age- and sex-related treatment gaps in IV tPA and MT reduced over the last decade. Racial disparity in IV tPA and MT utilization persists with particularly lower frequency of usage of both acute stroke treatments in Black patients compared with White patients, but race-associated treatment gaps also declined over time.

Correction to: 2019 Neurocritical Care Survey: Physician Compensation, Unit Staffing and Structure.

The original article had a typo in Table 2, the "N" for males and females should be switched. The corrected table is shown below.

Scoping Review and Commentary on Prognostication for Patients with Intracerebral Hemorrhage with Advances in Surgical Techniques.

INTRODUCTION: The intracerebral hemorrhage (ICH) score provides an estimate of 30-day mortality for patients with intracerebral hemorrhage in order to guide research protocols and clinical decision making. Several variations of such scoring systems have attempted to optimize its prognostic value. More recently, minimally invasive surgical techniques are increasingly being used with promising results. As more patients become candidates for surgical intervention, there is a need to re-discuss the best methods for predicting outcomes with or without surgical intervention. METHODS: We systematically performed a scoping review with a comprehensive literature search by two independent reviewers using the PubMed and Cochrane databases for articles pertaining to the "intracerebral hemorrhage score." Relevant articles were selected for analysis and discussion of potential modifications to account for increasing surgical indications. RESULTS: A total of 64 articles were reviewed in depth and identified 37 clinical grading scales for prognostication of spontaneous intracerebral hemorrhage. The original ICH score remains the most widely used and validated. Various authors proposed modifications for improved prognostic accuracy, though no single scale showed consistent superiority. Most recently, scales to account for advances in surgical techniques have been developed but lack external validation. CONCLUSION: We provide the most comprehensive review to date of prognostic grading scales for patients with intracerebral hemorrhage. Current prognostic tools for patients with intracerebral hemorrhage remain limited and may overestimate risk of a poor outcome. As minimally invasive surgical techniques are developed, prognostic scales should account for surgical candidacy and outcomes.

Cannabis, Cannabinoids, and Cerebral Metabolism: Potential Applications in Stroke and Disorders of the Central Nervous System.

No compound has generated more attention in both the scientific and recently in the political arena as much as cannabinoids. These diverse groups of compounds referred collectively as cannabinoids have both been vilified due to its dramatic and potentially harmful psychotropic effects and glorified due to its equally dramatic and potential application in a number of acute and chronic neurological conditions. Previously illegal to possess, cannabis, the plant where natural form of cannabinoids are derived, is now accepted in a growing number of states for medicinal purpose, and some even for recreational use, increasing opportunities for more scientific experimentation. The purpose of this review is to summarize the growing body of literature on cannabinoids and to present an overview of our current state of knowledge of the human endocannabinoid system in the hope of defining the future of cannabinoids and its potential applications in disorders of the central nervous system, focusing on stroke.

Plateauing atrial fibrillation burden in acute ischemic stroke admissions in the United States from 2010 to 2020.

BACKGROUND: Utilization of oral anticoagulants for acute ischemic stroke (AIS) prevention in patients with atrial fibrillation (AF) increased in the United States over the last decade. Whether this increase has been accompanied by any change in AF prevalence in AIS at the population level remains unknown. The aim of this study is to evaluate trends in AF prevalence in AIS hospitalizations in various age, sex, and racial subgroups over the last decade. METHODS: We used data contained in the 2010-2020 National Inpatient Sample to conduct a serial cross-sectional study. Primary AIS hospitalizations with and without comorbid AF were identified using International Classification of Diseases Codes. Joinpoint regression was used to compute annualized percentage change (APC) in prevalence and to identify points of change in prevalence over time. RESULTS: Of 5,190,148 weighted primary AIS hospitalizations over the study period, 25.1% had comorbid AF. The age- and sex-standardized prevalence of AF in AIS hospitalizations increased across the entire study period 2010-2020 (average APC: 1.3%, 95% confidence interval (CI): 0.8-1.7%). Joinpoint regression showed that prevalence increased in the period 2010-2015 (APC: 2.8%, 95% CI: 1.9-3.9%) but remained stable in the period 2015-2020 (APC: -0.3%, 95% CI: -1.0 to 1.9%). Upon stratification by age and sex, prevalence increased in all age/sex groups from 2010 to 2015 and continued to increase throughout the entire study period in hospitalizations in men 18-39 years (APC: 4.0%, 95% CI: 0.2-7.9%), men 40-59 years (APC: 3.4%, 95% CI: 1.9-4.9%) and women 40-59 years (APC: 4.4%, 95% CI: 2.0-6.8%). In contrast, prevalence declined in hospitalizations in women 60-79 (APC: -1.0%, 95% CI: -0.5 to -1.5%) and women ⩾ 80 years over the period 2015-2020 but plateaued in hospitalizations in similar-aged men over the same period. CONCLUSION: AF prevalence in AIS hospitalizations in the United States increased over the period 2010-2015, then plateaued over the period 2015-2020 due to declining prevalence in hospitalizations in women ⩾ 60 years and plateauing prevalence in hospitalizations in men ⩾ 60 years.

Age-specific trends in intravenous thrombolysis and mechanical thrombectomy utilization in acute ischemic stroke in children under age 18.

OBJECTIVES: To evaluate current trends in the utilization of intravenous thrombolysis (IV-tPA) and mechanical thrombectomy (MT) in acute ischemic stroke (AIS) in various age groups of children in the United States. METHODS: We conducted a serial cross-sectional study using primary AIS admissions in children ⩽ 17 years (weighted n = 2807) contained in the 2009-2019 KIDS Inpatient Database. Age-specific utilization frequency of IV-tPA and MT were calculated. Multivariable-adjusted models were used to evaluate demographic predictors of treatment. RESULTS: From 2009 to 2019, there were 2807 AIS admissions in children in the KID of which 55.9% were in boys and 29.9% were 15-17 years old.128 (4.6%) received IV-tPA. IV-tPA utilization differed by age (5-9 years: 3.1%, 15-17 years 8.1% p value < 0.001). Overall MT usage was 2.3% and this also varied by age (1-4 years: 0.9% and 15-17years 4.0%, p value = 0.006). IV-tPA utilization almost tripled across the study period (2.5% 2009 to 6.5% in 2019, p value = 0.001) while MT use more than doubled over time (1.2% in 2009 and 3.0% in 2019, p value = 0.048). Increased IV-tPA utilization was seen primarily in children 10-14 years (0.8% in 2009 to 7.2% 2019, p value = 0.005) and 15-17 years (5.4% in 2009 to 10.4% in 2019, p value = 0.045). Utilization in younger age groups remained unchanged over time. MT usage was very variable across various age groups over time. IV-tPA and MT utilization increased over time in nonchildren's hospitals (both p values < 0.05) but usage in designated children's hospitals did not change significantly over time. In multivariable models, there was no significant difference in odds of IV-tPA and MT use by sex, race or insurance status. CONCLUSION: IV-tPA and MT utilization in pediatric AIS increased in the United States over the past decade mainly in older children 10-17 years. Utilization increased mainly in patients hospitalized in nonchildren's hospitals. Usage in children's hospitals did not change significantly over time.

NSAID exposure and risk of nonunion: a meta-analysis of case-control and cohort studies.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used for postoperative pain control. However, concerns regarding the potential deleterious effects of NSAIDs on bone healing have compelled many physicians to avoid NSAIDs in patients with healing fractures, osteotomies, and fusions. We systematically reviewed and analyzed the best clinical evidence regarding the effects of NSAID exposure on bone healing. Medline, Embase, and Cochrane electronic databases were searched for prospective and retrospective clinical studies of fracture, osteotomy, and fusion studies of patients with NSAID exposure and nonunion as an outcome. Study quality was assessed using the Newcastle-Ottawa Scale. Data on study design, patient characteristics, and risk estimates were extracted. Pooled effect estimates were calculated. Subanalyses were performed by bone type and by NSAID dose, duration, and route of administration. In the initial analysis of 11 cohort and case-control studies, the pooled odds ratio for nonunion with NSAID exposure was 3.0 (95% confidence interval 1.6-5.6). A significant association between lower-quality studies and higher reported odds ratios for nonunion was observed. When only higher-quality studies were considered, seven spine fusion studies were analyzed, and no statistically significant association between NSAID exposure and nonunion was identified (odds ratio = 2.2, 95% confidence interval 0.8-6.3). There was no increased risk of nonunion with NSAID exposure when only the highest-quality studies were assessed. Randomized controlled trials assessing NSAID exposure in fracture, fusion, and osteotomy populations are warranted to confirm or refute the findings of this meta-analysis of observational studies.

Revascularization of Onyx induced intra-operative occlusion of vertebro-basilar artery using the Merci device.

INTRODUCTION: Endovascular embolization is an important modality in the treatment of cerebral arteriovenous malformations (AVMs). Onyx is an ethylene vinyl alcohol copolymer dissolved in dimethyl sulfoxide that is approved for use as an embolic agent for brain AVMs. CASE REPORT: We describe a case of revascularization of an occluded vertebro-basilar artery during embolization of an AVM with Onyx, by using the Merci device. CONCLUSION: Reflux embolization of patent vessels is a rare complication of using Onyx to treat AVMs. It can be successfully managed by retrieving the Onyx substance using mechanical retrieval devices like the Merci device.

Trends in incidence and epidemiologic characteristics of cerebral venous thrombosis in the United States.

OBJECTIVE: To test the hypothesis that race-, age-, and sex-specific incidence of cerebral venous thrombosis (CVT) has increased in the United States over the last decade. METHODS: In this retrospective cohort study, validated ICD codes were used to identify all new cases of CVT (n = 5,567) in the State Inpatients Databases (SIDs) of New York and Florida (2006-2016). A new CVT case was defined as first hospitalization for CVT in the SID without prior CVT hospitalization. CVT counts were combined with annual Census data to compute incidence. Joinpoint regression was used to evaluate trends in incidence over time. RESULTS: From 2006 to 2016, annual age- and sex-standardized incidence of CVT in cases per 1 million population ranged from 13.9 to 20.2, but incidence varied significantly by sex (women 20.3-26.9, men 6.8-16.8) and by age/sex (women 18-44 years of age 24.0-32.6, men 18-44 years of age 5.3-12.8). Incidence also differed by race (Blacks: 18.6-27.2; Whites: 14.3-18.5; Asians: 5.1-13.8). On joinpoint regression, incidence increased across 2006 to 2016, but most of this increase was driven by an increase in all age groups of men (combined annualized percentage change [APC] 9.2%, p < 0.001), women 45 to 64 years of age (APC 7.8%, p < 0.001), and women ≥65 years of age (APC 7.4%, p < 0.001). Incidence in women 18 to 44 years of age remained unchanged over time. CONCLUSION: CVT incidence is disproportionately higher in Blacks compared to other races. New CVT hospitalizations increased significantly over the last decade mainly in men and older women. Further studies are needed to determine whether this increase represents a true increase from changing risk factors or an artifactual increase from improved detection.

Effective glycemic control with aggressive hyperglycemia management is associated with improved outcome in aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Hyperglycemia strongly predicts poor outcome in patients with aneurysmal subarachnoid hemorrhage, but the effect of hyperglycemia management on outcome is unclear. We studied the impact of glycemic control on outcome of patients with aneurysmal subarachnoid hemorrhage. METHODS: A prospective intensive care unit database was used to identify 332 patients with hyperglycemic aneurysmal subarachnoid hemorrhage admitted between January 2000 and December 2006. Patients treated with an aggressive hyperglycemia management (AHM) protocol after 2003 (N=166) were compared with 166 patients treated using a standard hyperglycemia management before 2003. Within the AHM group, outcome was compared between patients who achieved good (mean glucose burden <1.1 mmol/L) and poor (mean glucose burden >or=1.1 mmol/L) glycemic control. Poor outcome was defined as modified Rankin scale >or=4 at 3 to 6 months. Multivariable logistic regression models correcting for temporal trend were used to quantify the effect of AHM on poor outcome. RESULTS: Poor outcome in AHM-treated patients was lower (28.31% versus 40.36%) but was not statistically significant after correcting for temporal trend. However, good glycemic control significantly reduced the incidence of poor outcome (OR, 0.25; 95% CI, 0.08 to 0.80; P=0.02) compared with patients with poor glycemic control within the AHM group. No difference in the rate of clinical vasospasm or the development of delayed ischemic neurological deficit was seen before and after AHM protocol implementation. CONCLUSIONS: AHM results in good glucose control and significantly reduces the odds for poor outcome after aneurysmal subarachnoid hemorrhage in glucose-controlled patients. Further studies are needed to confirm these results.

Outcomes after Early Anticonvulsant Discontinuation in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Empiric use of anticonvulsant (AED) for seizure prophylaxis in aneurysmal subarachnoid hemorrhage (SAH) remains controversial and may be associated with worse SAH outcome. We determined the safety and feasibility of early discontinuation of empiric AED in a select cohort of SAH patients. METHODS: In a cohort of 166 consecutive SAH patients, a subset underwent early AED discontinuation if they were awake and following commands after aneurysm treatment. We examined the effect of AED discontinuation on seizure incidence, mortality and functional outcome at discharge using logistic regression and validated results using 70%-30% data partition. RESULTS: Seventy-three subjects underwent AED discontinuation. Patient groups had similar gender, age, Fisher grade, incidence of craniotomy, vasospasm, ischemic infarct, intraventricular and intraparenchymal hemorrhages. Hunt-Hess (HH) grade were lower in AED-discontinuation group. Clinical or electrographic seizure occurred in 1/93 (1%) patients on AED and 0/73 patient in AED-discontinuation group. Crude mortality was 24% in patients on AED and 2.7% off AED. After adjusting for age, HH grade, vasospasm, ischemic infarct, intracerebral, and intraventricular hemorrhage, AED discontinuation remains independently associated with lower mortality and higher odds of discharge to home (p=0.0002). AED use is not associated with angiographic vasospasm on exploratory analysis. CONCLUSION: AED discontinuation in SAH patients who are awake and following commands post aneurysm treatment is safe, feasible, and associated with better outcome at hospital discharge. A larger, prospective study is necessary to determine if empiric AED use in SAH leads to poorer functional status.

Pearls and oy-sters: reversible Ondine's curse in a case of lateral medullary infarction.

Ondine's curse is an eponym that refers to central alveolar apnea/hypopnea observed among patients with acquired or congenital brainstem disorders. This condition results in loss of automatic and/or voluntary respiration with characteristic polysomnographic finding of impaired ventilator responses to hypercapnia and sleep apnea, which are more pronounced during non-REM sleep, less in REM sleep, and least during wakefulness.