Nontraumatic Intracranial Hemorrhage Research Articles

The efficacy and application of tranexamic acid in emergency medicine: Emergency Medicine Association of Türkiye clinical policy- 2024

Abstract The clinical policy of the Emergency Medicine Association of Türkiye (EMAT) provides guidance on the use of tranexamic acid (TXA) in emergency settings. TXA, an antifibrinolytic drug, is used to control bleeding by inhibiting plasminogen. Its applications have expanded from hemophilia and severe menstrual bleeding to include various forms of trauma and surgery-related bleeding. Despite its potential benefits, the use of TXA in emergency settings must be carefully evaluated due to its associated risks, including venous thromboembolism. This policy aimed to offer evidence-based recommendations on the indications and contraindications of TXA in different clinical scenarios encountered in the emergency departments. The guidelines were developed using the “Grading of Recommendations, Assessment, Development, and Evaluations” approach, incorporating systematic literature reviews, and expert consensus from the EMAT Research Committee. This document focuses on critical clinical questions regarding the efficacy and safety of TXA in situations such as gastrointestinal bleeding, multitrauma, traumatic brain injury, nontraumatic intracranial hemorrhage, hemoptysis, and epistaxis. By addressing these issues, the policy seeks to assist emergency physicians in making informed decisions about the use of TXA, ultimately aiming to improve the patient outcomes.

Is Ventilator-associated Event Algorithm Ideal for Surveillance? – Experience from a Neurosurgery Intensive Care Unit in Kerala

ABSTRACT Background: The ventilator-associated event (VAE) surveillance algorithm was brought in to replace the clinical ventilator-associated pneumonia (VAP) surveillance by NHSN in January 2013. This study intends to find the correlation of these surveillance criteria with the clinical VAP rates in a neurosurgery intensive care unit (ICU). Materials and Methods: This was a retrospective analysis of records of patients undergoing invasive mechanical ventilation in a neurosurgery ICU during a 3-month period. Results: Thirty-seven patients underwent invasive mechanical ventilation. The mean age was 56 years. Hypertension was the most common comorbidity among 22 (59.4%) patients. The neurological diagnosis was traumatic brain injury in 19 cases, nontraumatic intracranial hemorrhage in 12 cases, and ischemic stroke in 6 cases. Twenty-one patients had respiratory sample culture positivity and 14 were clinical VAP. The total ventilator days assessed were 82. The clinical VAP rate was 170.7, and the probable VAP (PVAP) rate for the same period was 12.19. Among the 14 patients who developed clinical VAP, 13 (88%) were hospital acquired and caused by multidrug-resistant pathogens. Six patients died during their ICU stay. ICU stay of more than 7 days was significantly associated with a clinical VAP. Conclusions: VAE was found to correlate poorly with a clinical diagnosis of VAP. When used as a surveillance tool in an ICU, it was found to miss important infection-related events in ventilated patients.

Клинический случай фокальной эпилепсии вследствие внутричерепного нетравматического кровоизлияния

Epilepsy is a multifactorial disease, the important role in the emergence and development of which is played by hereditary factors, exogenous causes, combined effects of the exogenous causes and congenital or acquired susceptibility. Perinatal (antenatal, natal, and early postnatal) damage to the central nervous system is a common etiological factor of epilepsy in children. The paper reports the clinical case of the patient having structural focal epilepsy with bilateral tonic seizures, cramps resulting from the non-traumatic intracranial hemorrhage.

Relationship between plasma brain-derived neurotrophic factor levels and neurological disorders: An investigation using Mendelian randomisation

BackgroundAltered brain-derived neurotrophic factor (BDNF) concentrations have been detected in the central nervous system tissues and peripheral blood. These alterations are associated with a series of neurological disorders. ObjectiveTo investigate the potential causal relationships between genetically determined plasma BDNF levels and various neurological diseases using a two-sample Mendelian randomisation study. MethodsWe selected single nucleotide polymorphisms strongly related to plasma BDNF levels as instrumental variables. Within the Mendelian randomisation framework, we used summary-level statistics for exposure (plasma BDNF levels) and outcomes (neurological disorders). ResultsWe observed suggestive evidence of a relation between higher plasma BDNF levels and less risk of nontraumatic intracranial haemorrhage (nITH) (odds ratio [OR] = 0.861, 95 % confidence interval [CI]: 0.774–0.958, P = 0.006, PFDR = 0.078), epilepsy (OR = 0.927, 95 % CI: 0.880–0.976, P = 0.004, PFDR = 0.078), focal epilepsy (OR = 0.928, 95 % CI: 0.874–0.986, P = 0.016, PFDR = 0.139), and non-lesional focal epilepsy (OR = 0.981, 95 % CI: 0.964–0.999, P = 0.041, PFDR = 0.267). Combined with the UK Biobank dataset, the association of plasma BDNF levels with nITH remained significant (OR = 0.88, 95 % CI: 0.81–0.96, P < 0.01). The combined analysis of three consortium datasets demonstrated a considerable impact of plasma BDNF on epilepsy (OR = 0.94, 95 % CI: 0.90–0.98, P < 0.01) and a suggestive impact on focal epilepsy (OR = 0.94, 95 % CI: 0.89–0.99, P = 0.02). However, there was no apparent correlation between plasma BDNF levels and other neurological disorders or related subtypes. ConclusionsOur study supports a possible causal relationship between elevated plasma BDNF levels and a reduced risk of nITH, epilepsy, and focal epilepsy.

873 Code Brain Ultra-Early Clinical Pathway for Patient Identification and Management in Spontaneous Non-traumatic Intracranial Hemorrhage Single-Institution Study

INTRODUCTION: Spontaneous non-traumatic intracranial hemorrhage causes high morbidity and mortality. Clinical pathways for the management of acute ischemic stroke are well established but fall short in identifying intracranial hemorrhage, preventing early therapy. METHODS: Using Class 1 recommendations from the AHA/ASA Spontaneous Intracranial Hemorrhage Guidelines, our multi-disciplinary stroke team developed a hyper-acute clinical pathway. Once the hemorrhagic stroke patient was identified, protocolized measures were immediately initiated to lower systolic blood pressure to 140 mmHg, institute factor replacement therapies in coagulopathic patients and anti-platelet reversal when appropriate. Key performance indicators and quality metrics were established to compare post-intervention groups to the baseline cohort. RESULTS: Of 180 patients, 113 and 67 patients were treated pre- and post-protocol, respectively. From pre- to post-protocol, diagnosis of hemorrhagic stroke using the alert increased from 59% to 81%. Anti-hypertensive initiation within 60 minutes increased from 79.5% to 88.7%, with the average time from CT result decreasing from 32.7 to 21.7 minutes. Time to reversal agent decreased from 53 to 23 minutes for pro-coagulation agents and 106 to 55 minutes for DDAVP. Reversal agent initiation within 60 minutes of CT result increased from 66.6% to 100% for pro-coagulation agents and 28.5% to 84.6% for DDAVP. CONCLUSIONS: The initiation of this management protocol for hemorrhagic stroke resulted in a higher proportion of patients being rapidly identified and earlier initiation of anti-hypertensive and hemostatic therapies. These processes are the key to important interventions designed to reduce injury extension associated with intracranial hemorrhage, like “time to thrombolysis” measures for acute ischemic stroke.

The Short- and Long-Term Risk of Mortality in Intracranial Hemorrhage Patients with Tranexamic Acid Treatment in a Population-Based Cohort Study.

Background: The mortality rate associated with nontraumatic intracranial hemorrhage (NTICrH) remains consistently high under the current care modality. The effectiveness of tranexamic acid (TXA) as a treatment option is still a subject of debate. This study aims to assess the association between TXA administration and both short-term and long-term mortality rates in patients with NTICrH. Methods: We conducted a retrospective cohort study using data from the Taiwan National Health Insurance Research Database (NHIRD) spanning from January 2000 to December 2017. The study population consists of NTICrH patients admitted to the ICU, divided into two groups: patients who were treated with TXA and those who were not. Propensity score matching (PSM) was conducted to balance the baseline characteristics of the two groups. Cox proportional hazard analysis was conducted to estimate the hazard ratio (HR) for the all-cause mortality. Sensitivity analyses were performed using the inverse probability of treatment-weighted hazard ratio (IPTW-HR). To assess the timing of TXA use, we compared the risk of all-cause mortality within 180 days between patients receiving early TXA treatment and those receiving late TXA treatment. Results: There was no significant difference in 180-day all-cause mortality between the groups; the hazard ratio was 1.07 (95% CI: 0.96-1.20) in patients treated with TXA compared to those without TXA treatment. Within 7 days of admission, patients treated with TXA had a lower hazard ratio of 0.81 (95% CI: 0.74-0.90) for all-cause mortality. Conclusions: Lower mortality within the first 7 days was observed in patients with NTICrH who received TXA.

Emergency Department Volume and Delayed Diagnosis of Serious Pediatric Conditions

Diagnostic delays are common in the emergency department (ED) and may predispose to worse outcomes. To evaluate the association of annual pediatric volume in the ED with delayed diagnosis. This retrospective cohort study included all children younger than 18 years treated at 954 EDs in 8 states with a first-time diagnosis of any of 23 acute, serious conditions: bacterial meningitis, compartment syndrome, complicated pneumonia, craniospinal abscess, deep neck infection, ectopic pregnancy, encephalitis, intussusception, Kawasaki disease, mastoiditis, myocarditis, necrotizing fasciitis, nontraumatic intracranial hemorrhage, orbital cellulitis, osteomyelitis, ovarian torsion, pulmonary embolism, pyloric stenosis, septic arthritis, sinus venous thrombosis, slipped capital femoral epiphysis, stroke, or testicular torsion. Patients were identified using the Healthcare Cost and Utilization Project State ED and Inpatient Databases. Data were collected from January 2015 to December 2019, and data were analyzed from July to December 2023. Annual volume of children at the first ED visited. Possible delayed diagnosis, defined as a patient with an ED discharge within 7 days prior to diagnosis. A secondary outcome was condition-specific complications. Rates of possible delayed diagnosis and complications were determined. The association of volume with delayed diagnosis across conditions was evaluated using conditional logistic regression matching on condition, age, and medical complexity. Condition-specific volume-delay associations were tested using hierarchical logistic models with log volume as the exposure, adjusting for age, sex, payer, medical complexity, and hospital urbanicity. The association of delayed diagnosis with complications by condition was then examined using logistic regressions. Of 58 998 included children, 37 211 (63.1%) were male, and the mean (SD) age was 7.1 (5.8) years. A total of 6709 (11.4%) had a complex chronic condition. Delayed diagnosis occurred in 9296 (15.8%; 95% CI, 15.5-16.1). Each 2-fold increase in annual pediatric volume was associated with a 26.7% (95% CI, 22.5-30.7) decrease in possible delayed diagnosis. For 21 of 23 conditions (all except ectopic pregnancy and sinus venous thrombosis), there were decreased rates of possible delayed diagnosis with increasing ED volume. Condition-specific complications were 11.2% (95% CI, 3.1-20.0) more likely among patients with a possible delayed diagnosis compared with those without. EDs with fewer pediatric encounters had more possible delayed diagnoses across 23 serious conditions. Tools to support timely diagnosis in low-volume EDs are needed.

Cerebrovascular Disease Hospitalization Rates in End-Stage Kidney Disease Patients with Kidney Transplant and Peripheral Vascular Disease: Analysis Using the National Inpatient Sample (2005-2019).

Individuals with end-stage kidney disease (ESKD) face higher cerebrovascular risk. Yet, the impact of peripheral vascular disease (PVD) and kidney transplantation (KTx) on hospitalization rates for cerebral infarction and hemorrhage remains underexplored. Analyzing 2,713,194 ESKD hospitalizations (2005-2019) using the National Inpatient Sample, we investigated hospitalization rates for ischemic and hemorrhagic cerebrovascular diseases concerning ESKD, PVD, KTx, or their combinations. Patients hospitalized with cerebral infarction due to thrombosis/embolism/occlusion (CITO) or artery occlusion resulting in cerebral ischemia (AOSI) had higher rates of comorbid ESKD and PVD (4.17% and 7.29%, respectively) versus non-CITO or AOSI hospitalizations (2.34%, p < 0.001; 2.29%, p < 0.001). Conversely, patients hospitalized with nontraumatic intracranial hemorrhage (NIH) had significantly lower rates of ESKD and PVD (1.64%) compared to non-NIH hospitalizations (2.34%, p < 0.001). Furthermore, hospitalizations for CITO or AOSI exhibited higher rates of KTx and PVD (0.17%, 0.09%, respectively) compared to non-CITO or AOSI hospitalizations (0.05%, p = 0.033; 0.05%, p = 0.002). Patients hospitalized with NIH showed similar rates of KTx and PVD (0.04%) versus non-NIH hospitalizations (0.05%, p = 0.34). This nationwide analysis reveals that PVD in ESKD patients is associated with increased hospitalization rates with cerebral ischemic events and reduced NIH events. Among KTx recipients, PVD correlated with increased hospitalizations for ischemic events, without affecting NIH. This highlights management concerns for patients with KTx and PVD.

Neonatal Outcomes After COVID-19 Vaccination in Pregnancy

Better knowledge about neonatal adverse events after COVID-19 vaccination during pregnancy could help address concerns about vaccine safety. To evaluate the risks of neonatal adverse events after exposure to COVID-19 vaccination during pregnancy. Population-based cohort study including all infants in Sweden and Norway born from June 2021 to January 2023. Unique personal identity numbers were used to link individual information from different national registers. Administration of any mRNA vaccine against COVID-19 during pregnancy, irrespective of previous vaccination, number of doses during pregnancy, or vaccine manufacturer. Outcomes were neonatal conditions with bleeding/thrombosis or inflammation/infection; disorders of the central nervous system; circulatory, respiratory, or gastrointestinal problems; and neonatal mortality. Statistical methods included logistic regression adjusted for characteristics of the pregnant individuals, with additional restricted and stratified analyses. Of 196 470 newborn infants included (51.3% male, 93.8% born at term, 62.5% born in Sweden), 94 303 (48.0%) were exposed to COVID-19 vaccination during pregnancy. Exposed infants exhibited no increased odds of adverse neonatal outcomes, and they exhibited lower odds for neonatal nontraumatic intracranial hemorrhage (event rate, 1.7 vs 3.2/1000; adjusted odds ratio [aOR], 0.78 [95% CI, 0.61-0.99]), hypoxic-ischemic encephalopathy (1.8 vs 2.7/1000; aOR, 0.73 [95% CI, 0.55-0.96]), and neonatal mortality (0.9 vs 1.8/1000; aOR, 0.68 [95% CI, 0.50-0.91]). Subgroup analyses found a similar association between vaccination during pregnancy and lower neonatal mortality; subgroups were restricted to infants delivered by individuals unvaccinated before pregnancy, individuals vaccinated before pregnancy, individuals vaccinated after a general recommendation of vaccination during pregnancy was issued, and individuals without COVID-19 infection during pregnancy. Analyses restricted to term infants, singleton births, or infants without birth defects yielded similar results. Stratifying the analysis by vaccine manufacturer did not attenuate the association between vaccination and low neonatal mortality. In this large population-based study, vaccination of pregnant individuals with mRNA COVID-19 vaccines was not associated with increased risks of neonatal adverse events in their infants.

Prediction of prognosis in patients with nontraumatic intracranial hemorrhage using blood urea nitrogen-to-creatinine ratio on admission: a retrospective cohort study based on data from the medical information Mart for intensive care-IV database.

The blood urea nitrogen-to-creatinine ratio (BUNCR) has been proposed as a potential biomarker for critical illness-induced catabolism. However, its specific relevance and significance in the context of non-traumatic intracranial hemorrhage (NTIH) remains unclear. As such, the primary objective of this study was to determine the role of BUNCR in the prognosis of patients with NTIH. All data were sourced from the Medical Information Mart for Intensive Care-IV 2.0 (MIMIC-IV) database. Study outcomes included 30-day and 1-year mortality rates. Univariate and multivariate logistic regression analyses were used to calculate adjusted odds ratio with corresponding 95% confidence interval, and generalized additive model were used to identify both linear and non-linear relationships between BUNCR and mortality rates. A two-piecewise regression model was performed to calculate the saturation effect. Subgroup analyses were performed to evaluate outcome stability in various groups. A retrospective study of 3,069 patients with NTIH revealed a U-shaped relationship between BUNCR levels and 30-day/1-year mortality. The two-piecewise regression model showed that the inflection points for 30-day and 1-year mortality were 10.455 and 16.25, respectively. On the left side of the inflection point, the 30-day and 1-year mortality rate decreased by 17.7% (OR = 0.823, 95%CI: 0.705-0.960; p = 0.013) and 5.3% (OR = 0.947, 95%CI: 0.899-0.999; p = 0.046), respectively, per 1 unit increment of BUNCR. On the right side of the inflection point, the 30-day and 1-year mortality rate increased by 1.6% (OR = 1.016, 95%CI: 1.000-1.031; p = 0.046) and 3.6% (OR = 1.036, 95%CI:1.019-1.054; p < 0.001) per 1 unit decrement of BUNCR. Subgroup analyses revealed consistent results across different strata. This study identified a nonlinear relationship between BUNCR and mortality in patients with NTIH, indicating that BUNCR may be valuable prognostic marker for early identification and proactive management.

Panic disorder in epilepsy

A 51-year-old woman showed structural epilepsy following an atypical, nontraumatic intracranial hemorrhage in the right frontal area. Despite successful seizure control with lamotrigine, she developed severe morning anxiety and panic attacks, leading to agoraphobia, social withdrawal, and psychogenic nonepileptic seizures. Neuropsychiatric and psychological assessments confirmed an anxiety disorder with no significant symptoms of depression. The patient received various psychopharmacological treatments with limited success. This case report illustrates that managing panic disorder in patients with structural epilepsy requires a comprehensive treatment approach that includes pharmacotherapy and psychotherapy. Differential diagnosis and accurate treatment are crucial because of the symptom overlap between panic attacks and peri-ictal fear. Screenings instruments such as the Panic and Agoraphobia Scale (PAS) can aid in assessing anxiety-related symptoms. First-line pharmacotherapy with selective serotonin reuptake inhibitors, especially sertraline, or venlafaxine can effectively reduce panic attacks and can be recommended in patients with epilepsy. Psychotherapy, particularly cognitive-behavioral therapy, is the treatment of choice. Referral to a psychiatrist is indicated when symptoms are severe or refractory to treatment.

The causal effects between gut microbiota and hemorrhagic stroke: a bidirectional two-sample Mendelian randomization study.

Recent studies have suggested that the composition of gut microbiota (GM) may change after intracerebral hemorrhage. However, the causal inference of GM and hemorrhagic stroke is unknown. Mendelian Randomization (MR) is an effective research method that removes confounding factors and investigates the causal relationship between exposure and outcome. This study intends to explore the causal relationship between GM and hemorrhagic stroke with the help of MR. Univariable and multivariable MR analyses were performed using summary statistics of the GM (n = 18,340) in the MiBioGen consortium vs. the FinnGen consortium R9 summary statistics (intracerebral hemorrhage, subarachnoid hemorrhage, and nontraumatic intracranial hemorrhage). Causal associations between gut microbiota and hemorrhagic stroke were analyzed using inverse variance weighted, MR-Egger regression, weighted median, weighted mode, simple mode, and MR-PRESSO. Cochran's Q statistic, MR-Egger regression, and leave-one-out analysis were used to test for multiplicity and heterogeneity of instrumental variables. Separate reverse MR analyses were performed for microbiota found to be causally associated with hemorrhagic stroke in the forward MR analysis. Also, multivariate MR analyses were conducted after incorporating common confounders. Based on the results of univariable and multivariate MR analyses, Actinobacteria (phylum) (OR, 0.80; 95%CI, 0.66-0.97; p = 0.025) had a protective effect against hemorrhagic stroke, while Rikenellaceae RC9 gut group (genus) (OR, 0.81; 95%CI, 0.67-0.99; p = 0.039) had a potential protective effect. Furthermore, Dorea (genus) (OR, 1.77; 95%CI, 1.27-2.46; p = 0.001), Eisenbergiella (genus) (OR, 1.24; 95%CI, 1.05-1.48; p = 0.013) and Lachnospiraceae UCG008 (genus) (OR, 1.28; 95%CI, 1.01-1.62; p = 0.041) acted as potential risk factors for hemorrhagic stroke. The abundance of Dorea (genus) (β, 0.05; 95%CI, 0.002 ~ 0.101; p = 0.041) may increase, and that of Eisenbergiella (genus) (β, -0.072; 95%CI, -0.137 ~ -0.007; p = 0.030) decreased after hemorrhagic stroke according to the results of reverse MR analysis. No significant pleiotropy or heterogeneity was detected in any of the MR analyses. There is a significant causal relationship between GM and hemorrhagic stroke. The prevention, monitoring, and treatment of hemorrhagic stroke through GM represent a promising avenue and contribute to a deeper understanding of the mechanisms underlying hemorrhagic stroke.

Stroke and Bleeding in Patients with Atrial Fibrillation and End-Stage Renal Disease Treated with Apixaban Versus Warfarin

Introduction: Treating patients with atrial fibrillation (AF) in patients with advanced chronic kidney disease (CKD) can be particularly challenging as CKD is associated with higher risk of both thrombotic and bleeding events. Direct oral anticoagulants (DOACs) are partially eliminated through the kidneys to varying extents and initial trials validating their effectiveness excluded individuals with advanced kidney disease (creatinine clearance &amp;lt;25). Among the DOACs, apixaban undergoes the least renal excretion, making it a preferred choice for numerous physicians when it comes to stroke prevention in dialysis patients with AF who are either unable or unwilling to take warfarin for any reason. Hence, in this study, we aim to describe the clinical outcomes and safety of apixaban therapy compared to warfarin among patients with end-stage renal disease (ESRD) and AF. Methods: We conducted a retrospective cohort study through population data collected and analyzed through the multicentric platform TriNetX, across 75 health care organizations (HCOs). Using International Classification of Diseases, tenth revision (ICD-10) codes, we identified patients diagnosed with ESRD (N18.6 and Z99.2) and AF (I48.0, I48.1, I48.91) after the year 2000. Over the period of 5 years, the incidence of ischemic embolic stroke, nontraumatic intracranial bleeding, gastrointestinal (GI) bleeding, and hemorrhage were compared among patients treated with warfarin versus those treated with apixaban. Results: Our search yielded 23447 patients that had been started on warfarin and 21466 that had been started on apixaban. After propensity score matching of demographics, 10037 patients remained in each group. The average age in our population was 69 years-old with a standard deviation of 12 years, 62% males and 38% females: 62% white, 22% black, 13% unknown, and 2% Asian. Compared with patients who were treated with warfarin over a 5-year period, patients with ESRD and AF treated with apixaban had a decreased risk of nontraumatic intracranial bleeding (161 events vs 205 events, risk ratio 0.777, confidence interval 0.633 to 0.953, p&amp;lt;0.05) and a decreased risk of hemorrhage (212 events vs 293 events, risk ratio 0.711, confidence interval 0.597 to 0.847, p&amp;lt;0.01). No significant difference was observed in the risk of ischemic embolic stroke (57 events vs 56 events, risk ratio 1.01, confidence interval 0.699 to 1.459, p=0.9567) or in the risk of GI bleed (705 events vs 723 events, risk ratio 0.935, confidence interval 0.847 to 1.033, p=0.1846). Conclusions: Patients with ESRD are at an increased risk of bleeding and thrombotic events. In patients with ESRD and AF, the use of apixaban was associated with a slight reduction in the risk of intracranial bleeding and hemorrhage. Meanwhile, no significant difference was observed in the risk of ischemic stroke or GI bleed. Notably, bleeding events were far more common compared to stroke events in our study. However, the evidence comparing the safety profiles of these two anticoagulants remains limited, particularly concerning randomized double-blind prospective data. Recent studies, such as the RENAL-AF trial showed similar rates of bleeding and strokes in both drugs, however, the study stopped prematurely because of enrollment challenges in the End-stage renal disease (ESRD) population. These findings warrant further investigation in a controlled prospective trial.

Joblessness, decreased income, and disability in intensive care unit survivors of nontraumatic intracranial hemorrhage in South Korea

ObjectivesTo examine the proportions of unemployment, decreased household income, and newly acquired disability, and their impact on long-term mortality after intensive care unit (ICU) admission due to nontraumatic intracranial hemorrhage (IH). Materials and methodsThis nationwide population-based retrospective cohort study enrolled adult patients admitted to the ICU because of nontraumatic IH between 2010 and 2018 in South Korea. Patients who were alive ≥365 days after ICU admission were defined as nontraumatic IH survivors. ResultsIn total, 104,086 nontraumatic IH survivors were included in the final analysis. Among them, 7,225 (6.9 %) experienced job loss, 25,709 (24.7 %) experienced decreased household income, and 20,938 (20.1 %) had newly acquired disabilities, of whom 14,188 (13.6 %) had newly acquired brain disabilities. Male sex, increased duration of intensive care unit stay, comorbid status, hospital admission through the emergency room, nontraumatic intracerebral hemorrhage, receipt of surgery, mechanical ventilatory support, and increased total cost of hospitalization were associated with job loss, decreased household income, and newly acquired disabilities. However, these changes were not significantly associated with 2-year all-cause mortality (adjusted hazard ratio: 1.00, 95 % confidence interval: 0.95, 1.06; P = 0.997). ConclusionsMany nontraumatic IH survivors experienced unemployment, decreased household income, and newly acquired disability one year after ICU admission in South Korea. Some factors were potential risk factors for these changes, but the changes were not associated with 2-year all-cause mortality.

PB0474 Anticoagulant Management and Outcomes in Non-Traumatic Intracranial Hemorrhage Complicated by Venous Thromboembolism

PB0474 Anticoagulant Management and Outcomes in Non-Traumatic Intracranial Hemorrhage Complicated by Venous Thromboembolism

Therapeutic review: The role of tranexamic acid in management of traumatic brain injury, nontraumatic intracranial hemorrhage, and aneurysmal subarachnoid hemorrhage.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. To summarize current literature evaluating tranexamic acid in the management of intracranial bleeding associated with traumatic and nontraumatic brain injuries and implications for clinical practice. Intracranial hemorrhage, regardless of etiology, is associated with high morbidity and mortality. Tranexamic acid is an antifibrinolytic with anti-inflammatory properties shown to reduce mortality in trauma patients with extracranial injuries. In traumatic brain injury, a large randomized trial found no difference in outcomes when tranexamic acid was compared to placebo; however, subgroup analyses suggested that it may reduce head injury-related mortality in the context of mild-to-moderate injury if treatment occurs within 1 hour of symptom onset. More recent out-of-hospital data have disputed these findings and even suggested harm in severely injured patients. In spontaneous, nontraumatic intracranial hemorrhage, treatment with tranexamic acid did not result in a difference in functional status; however, rates of hematoma expansion, even though modest, were significantly reduced. In aneurysmal subarachnoid hemorrhage, tranexamic acid may prevent rebleeding, but has not led to improved outcomes or reduced mortality, and there is concern for increased incidence of delayed cerebral ischemia. Overall, tranexamic acid has not been shown to result in increased risk of thromboembolic complications across these classes of brain injury. Despite its favorable safety profile overall, tranexamic acid does not seem to improve functional outcomes and cannot be routinely recommended. More data are needed to determine which head injury subpopulations are most likely to benefit from tranexamic acid and which patients are at increased risk for harm.

Differential Effect of Stroke Types on Cerebral White Matter Disease Progression (S45.001)

<h3>Objective:</h3> To determine the annual rate of WMD progression and cognition by stroke types in a cohort of real-world patients hospitalized for cerebrovascular diseases. <h3>Background:</h3> White matter disease (WMD) of presumed vascular origin is a type of cerebral small vessel disease associated with cognitive impairment. Studies have suggested that stroke may accelerate the progression of WMD, yet little is known on the potential differential effect of stroke types on WMD progression and cognition. <h3>Design/Methods:</h3> Consecutive patients with two brain MRI scans at least one year apart from a single-center cerebrovascular registry were included. Stroke types were categorized as ischemic stroke, non-traumatic intracranial hemorrhage (ICH) and aneurysmal subarachnoid hemorrhage (aSAH). Non-stroke served as control. SPM-lesion predictive algorithm was used to quantify WMD volume with primary outcome measured as annual change in WMD volume (cm³/year). Rate of WMD progression were compared across stroke types. <h3>Results:</h3> Of the 207 patients, mean age was 60±16 years, 54.6% were women, and median time between MRI brain scans was 4.3 (1.3–11.8) years. Of the stroke types, 65.8% had AIS, 11.1% had ICH, 3.4% had aSAH and 19.8% were non-stroke control. The rate of WMD progression was fastest in patients with ICH (1.63 cc/yr, IQR 0.0–4.14 cc/yr), followed by ischemic stroke (1.43 cc/yr, IQR 0.24–3.51 cc/yr), aSAH (0.53 cc/yr, IQR 0.13–0.79 cc/yr) and non-stroke control (0.32 cc/yr, IQR −0.01–1.35 cc/yr). In terms of cognition, median MMSE was lowest in ICH (22.5), followed by aSAH (23.2), ischemic stroke (24.8) and non-stroke control (28.7) (trend-p=0.002). <h3>Conclusions:</h3> Our study showed differential effects of stroke types on the rate of WMD progression and post-stroke cognition. Patients with ICH had greater risk for WMD progression and cognitive impairment compared to other stroke types. Larger longitudinal study is needed to better test this observation. <b>Disclosure:</b> Dr. Elkhair has nothing to disclose. Mr. Youssef has nothing to disclose. Dr. Anisetti has nothing to disclose. Mr. Salem has nothing to disclose. Mr. Mateti has nothing to disclose. Dr. Lin has nothing to disclose.

Clinical Performance Measures for Emergency Department Care for Adults With Intracranial Hemorrhage

Though select inpatient-based performance measures exist for the care of patients with nontraumatic intracranial hemorrhage, emergency departments lack measurement instruments designed to support and improve care processes in the hyperacute phase. To address this, we propose a set of measures applying a syndromic (rather than diagnosis-based) approach informed by performance data from a national sample of community EDs participating in the Emergency Quality Network Stroke Initiative. To develop the measure set, we convened a workgroup of experts in acute neurologic emergencies. The group considered the appropriate use case for each proposed measure: internal quality improvement, benchmarking, or accountability, and examined data from Emergency Quality Network Stroke Initiative-participating EDs to consider the validity and feasibility of proposed measures for quality measurement and improvement applications. The initially conceived set included 14 measure concepts, of which 7 were selected for inclusion in the measure set after a review of data and further deliberation. Proposed measures include 2 for quality improvement, benchmarking, and accountability (Last 2 Recorded Systolic Blood Pressure Measurements Under 150 and Platelet Avoidance), 3 for quality improvement and benchmarking (Proportion of Patients on Oral Anticoagulants Receiving Hemostatic Medications, Median ED Length of Stay for admitted patients, and Median Length of Stay for transferred patients), and 2 for quality improvement only (Severity Assessment in the ED and Computed Tomography Angiography Performance). The proposed measure set warrants further development and validation to support broader implementation and advance national health care quality goals. Ultimately, applying these measures may help identify opportunities for improvement and focus quality improvement resources on evidence-based targets.

Anticoagulation medication in nontraumatic intracranial hemorrhage survivors with atrial fibrillation.

The relative effectiveness of anticoagulation agents in patients with atrial fibrillation (AF) who survive an intracranial hemorrhage (ICH) is unknown. This study was performed to examine the comparative effectiveness of different oral anticoagulation (OAC) on clinical outcomes in this group of patients. We performed a Bayesian network meta-analysis of randomized controlled trials (RCTs) and observational studies comparing different OAC (direct oral anticoagulant [DOAC] and warfarin) for the treatment of patients with AF who sustained ICH. Outcomes included repeat ICH, thromboembolic events, and all-cause mortality. The values derived from the surface under the cumulative ranking curve were obtained to rank the treatment hierarchy. We identified 12 studies (two RCTs and ten observational studies) involving 23,265 patients; 346 patients were treated with any OAC agents; 5,006 received DOAC; 5,271 received warfarin; 12,007 received antiplatelet or no therapy, and 635 did not received relevant therapy. Both DOAC and warfarin (RR, 0.58; 95% CI, 0.45-0.74; RR, 0.83; 95% CI, 0.69-0.98) were superior to antiplatelet or no therapy in preventing thromboembolic events. Moreover, DOAC also showed superiority in preventing thromboembolic events (RR, 0.70; 95% CI, 0.58-0.83), repeat ICH (RR, 0.52; 95% CI, 0.40-0.67), and all-cause mortality (RR, 0.51; 95% CI, 0.46-0.56) than warfarin. Our study suggests DOACs may be a reasonable alternative to anti-platelet therapy and warfarin for patients with AF who experienced ICH. However, given the available evidence is primarily observational, further validation by ongoing trials directly comparing these two classes of drugs are needed.

Twenty-three medication-taking traits and stroke: A comprehensive Mendelian randomization study.

Certain medication categories may increase the risk of stroke. Nonetheless, the evidence regarding the causal relationship of medication-taking in promoting stroke and subtypes is deficient. We evaluated the causal effect of a genetic predisposition for certain medication categories on stroke and subtypes (ischemic and hemorrhagic categories) by a two-sample Mendelian randomization (MR) analysis. Data for 23 medication categories were gathered from a genome-wide association study (GWAS) involving 318,177 patients. The Medical Research Council Integrative Epidemiology Unit Open GWAS database and the FinnGen consortium were used to gather GWAS data for stroke and subtypes. Inverse variance weighted, MR-Egger, and weighted median were used for the estimation of causal effects. Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis were used for sensitivity analyses. Ten medication categories were linked to a high stroke risk. Nine categories were linked to a high-risk ischemic stroke. Five categories were associated with small vessel ischemic stroke. Nine categories were positively associated with large artery atherosclerotic ischemic stroke. Three categories causally increased the possibility of cardioembolic ischemic stroke. Four categories were associated with intracerebral hemorrhage. Four categories were associated with nontraumatic intracranial hemorrhage. Three categories were causally associated with subarachnoid hemorrhage (SAH). Four categories were associated with the combination of SAH, unruptured cerebral aneurysm, and aneurysm operations SAH. This study confirms that some medication categories lead to a greater risk of strokes. Meanwhile, it has an implication for stroke screening as well as direct clinical significance in the design of conduction of future randomized controlled trials.