Biomarkers of Coagulation and Inflammation in COVID-19-Associated Ischemic Stroke.

[Figure: see text].

Risk factors for intracerebral hemorrhage in patients with COVID-19.

Intracerebral hemorrhage (ICH) can be a devastating complication of coronavirus disease (COVID-19). We aimed to assess risk factors associated with ICH in this population. We performed a retrospective cohort study of adult patients admitted to NYU Langone Health system between March 1 and April 27 2020 with a positive nasopharyngeal swab polymerase chain reaction test result and presence of primary nontraumatic intracranial hemorrhage or hemorrhagic conversion of ischemic stroke on neuroimaging. Patients with intracranial procedures, malignancy, or vascular malformation were excluded. We used regression models to estimate odds ratios and 95% confidence intervals (OR, 95% CI) of the association between ICH and covariates. We also used regression models to determine association between ICH and mortality. Among 3824 patients admitted with COVID-19, 755 patients had neuroimaging and 416 patients were identified after exclusion criteria were applied. The mean (standard deviation) age was 69.3 (16.2), 35.8% were women, and 34.9% were on therapeutic anticoagulation. ICH occurred in 33 (7.9%) patients. Older age, non-Caucasian race, respiratory failure requiring mechanical ventilation, and therapeutic anticoagulation were associated with ICH on univariate analysis (p < 0.01 for each variable). In adjusted regression models, anticoagulation use was associated with a five-fold increased risk of ICH (OR 5.26, 95% CI 2.33-12.24, p < 0.001). ICH was associated with increased mortality (adjusted OR 2.6, 95 % CI 1.2-5.9). Anticoagulation use is associated with increased risk of ICH in patients with COVID-19. Further investigation is required to elucidate underlying mechanisms and prevention strategies in this population.

Risk of Ischemic Stroke in Patients With Atrial Fibrillation After Extracranial Hemorrhage.

BACKGROUND AND PURPOSE: Anticoagulation therapy not only reduces the risk of ischemic stroke in atrial fibrillation (AF) but also predisposes patients to hemorrhagic complications. There is limited knowledge on the risk of first-ever ischemic stroke in patients with AF after extracranial hemorrhage (ECH). METHODS: We conducted a retrospective study using the California State Inpatient Database including all nonfederal hospital admissions in California from 2005 to 2011. The exposure variable was hospitalization with a diagnosis of ECH with a previous diagnosis of AF. The outcome variable was a subsequent hospitalization with acute ischemic stroke. We excluded patients with stroke before or at the time of ECH diagnosis. We calculated adjusted hazard ratios for ischemic stroke during follow-up and at 6-month intervals using Cox regression models adjusted for pertinent demographics and comorbidities. In subgroup analyses, subjects were stratified by primary ECH diagnosis, severity/type of ECH, age, CHA2DS2-VASc score, or the presence/absence of a gastrointestinal or genitourinary cancer. RESULTS: We identified 764 257 patients with AF (mean age 75 years, 49% women) without a documented history of stroke. Of these, 98 647 (13%) had an ECH-associated hospitalization, and 22 748 patients (3%) developed an ischemic stroke during the study period. Compared to patients without ECH, subjects with ECH had ≈15% higher rate of ischemic stroke (overall adjusted hazard ratio, 1.15 [95% CI, 1.11-1.19]). The risk appeared to remain elevated for at least 18 months after the index ECH. In subgroup analyses, the risk was highest in subjects with a primary admission diagnosis of ECH, severe ECH, gastrointestinal-type ECH, with gastrointestinal or genitourinary cancer, and age ≥60 years. CONCLUSIONS: Patients with AF hospitalized with ECH may have a slightly elevated risk for future ischemic stroke. Particular consideration should be given to the optimal balance between the benefits and risks of anticoagulation therapy and the use of nonanticoagulant alternatives, such as left atrial appendage closure in this vulnerable population.

Prevalence and Impact of Hyponatremia in Patients With Coronavirus Disease 2019 in New York City.

OBJECTIVES: Hyponatremia occurs in up to 30% of patients with pneumonia and is associated with increased morbidity and mortality. The prevalence of hyponatremia associated with coronavirus disease 2019 and the impact on outcome is unknown. We aimed to identify the prevalence, predictors, and impact on outcome of mild, moderate, and severe admission hyponatremia compared with normonatremia among coronavirus disease 2019 patients. DESIGN: Retrospective, multicenter, observational cohort study. SETTING: Four New York City hospitals that are part of the same health network. PATIENTS: Hospitalized, laboratory-confirmed adult coronavirus disease 2019 patients admitted between March 1, 2020, and May 13, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hyponatremia was categorized as mild (sodium: 130-134 mmol/L), moderate (sodium: 121-129 mmol/L), or severe (sodium: ≤ 120 mmol/L) versus normonatremia (135-145 mmol/L). The primary outcome was the association of increasing severity of hyponatremia and in-hospital mortality assessed using multivariable logistic regression analysis. Secondary outcomes included encephalopathy, acute renal failure, mechanical ventilation, and discharge home compared across sodium levels using Kruskal-Wallis and chi-square tests. In exploratory analysis, the association of sodium levels and interleukin-6 levels (which has been linked to nonosmotic release of vasopressin) was assessed. Among 4,645 patient encounters, hyponatremia (sodium < 135 mmol/L) occurred in 1,373 (30%) and 374 of 1,373 (27%) required invasive mechanical ventilation. Mild, moderate, and severe hyponatremia occurred in 1,032 (22%), 305 (7%), and 36 (1%) patients, respectively. Each level of worsening hyponatremia conferred 43% increased odds of in-hospital death after adjusting for age, gender, race, body mass index, past medical history, admission laboratory abnormalities, admission Sequential Organ Failure Assessment score, renal failure, encephalopathy, and mechanical ventilation (adjusted odds ratio, 1.43; 95% CI, 1.08-1.88; p = 0.012). Increasing severity of hyponatremia was associated with encephalopathy, mechanical ventilation, and decreased probability of discharge home (all p < 0.001). Higher interleukin-6 levels correlated with lower sodium levels (p = 0.017). CONCLUSIONS: Hyponatremia occurred in nearly a third of coronavirus disease 2019 patients, was an independent predictor of in-hospital mortality, and was associated with increased risk of encephalopathy and mechanical ventilation.

Factors Associated With DNR Status After Nontraumatic Intracranial Hemorrhage.

BACKGROUND: We explored factors associated with admission and discharge code status after nontraumatic intracranial hemorrhage. METHODS: We extracted data from patients admitted to our institution between January 1, 2013, and March 1, 2016 with nontraumatic intracerebral hemorrhage or subarachnoid hemorrhage who had a discharge modified Rankin Scale (mRS) of 4 to 6. We reviewed data based on admission and discharge code status. RESULTS: Of 88 patients who met inclusion criteria, 6 (7%) were do not resuscitate (DNR) on admission (aDNR). Do not resuscitate on admission patients were significantly older than those who were full code on admission (P = 0.04). There was no significant difference between admission code status and sex, marital status, active cancer, premorbid mRS, admission Glasgow Coma scale (GCS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, or bleed severity. At discharge, 66 (75%) patients were full code (dFULL), 11 (13%) were DNR (dDNR), and 11 (13%) were comfort care. African American and Hispanic patients were significantly more likely to be dFULL than Asian or white patients (P = .01) and less likely to be seen by palliative care (P = .004). Patients with less aggressive code status had higher median APACHE II scores (P = .008) and were more likely to have active cancer (P = .06). There was no significant difference between discharge code status and sex, age, marital status, premorbid mRS, discharge GCS, or bleed severity. CONCLUSIONS: Limitation of code status after nontraumatic intracranial hemorrhage appears to be associated with older age, white race, worse APACHE II score, and active cancer. The role of palliative care after intracranial hemorrhage and the racial disparity in limitation and de-escalation of treatment deserves further exploration.

Post-traumatic Stress Disorder and Complicated Grief are Common in Caregivers of Neuro-ICU Patients.

BACKGROUND: To explore the effect of end of life and other palliative decision making scenarios on the mental health of family members of patients in the neuro-intensive care unit. METHODS: Decision makers of patients in the neuro-ICU at a large, urban, academic medical center meeting palliative care triggers were identified from November 10, 2014, to August 27, 2015. Interviews were conducted at 1 and 6 months post-enrollment. At 1 month, the Inventory of Complicated Grief-Revised (ICG-R), Impact of Events Scale-Revised (IES-R), and the Family Satisfaction-ICU (FS-ICU) were performed along with basic demographic questionnaires. At 6 months, only the ICG-R and IES-R were repeated. RESULTS: At 1 month, 9 (35%) subjects had significant symptoms in at least one of the three domains of traumatic response. Two (7.7%) subjects met full criteria for PTSD (IES-R ≥ 1.5). At 6 months, 5 (22%) subjects met criteria for PTSD and 5 (22%) for Complicated Grief (ICG-R ≥ 36). Fifteen (50%) had at least one domain of PTSD symptoms identified in follow-up. Time spent at bedside and lower household income were associated with PTSD at 1 and 6 months, respectively. In all, clinically significant psychological outcomes were identified in 9 (30%) of subjects. CONCLUSIONS: Clinically significant grief and stress reactions were identified in 30% of decision makers for severely ill neuro-ICU patients. Though factors including time at bedside during hospitalization and total household income may have some predictive value for these disorders, further evaluation is required to help identify family members at risk of psychopathology following neuro-ICU admissions.

Discharge educational strategies for reduction of vascular events (DESERVE): design and methods.

RATIONALE: Stroke and vascular risk factors disproportionately affect minority populations, with Blacks and Hispanics experiencing a 2·5- and 2·0-fold greater risk compared with whites, respectively. Patients with transient ischemic attacks and mild, nondisabling strokes tend to have short hospital stays, rapid discharges, and inaccurate perceptions of vascular risk. AIM: The primary aim of the Discharge Educational Strategies for Reduction of Vascular Events (DESERVE) trial is to evaluate the efficacy of a novel community health worker-based multilevel discharge intervention vs. standard discharge care on vascular risk reduction among racially/ethnically diverse transient ischemic attack/mild stroke patients at one-year postdischarge. We hypothesize that those randomized to the discharge intervention will have reduced modifiable vascular risk factors as determined by systolic blood pressure compared with those receiving usual care. SAMPLE SIZE ESTIMATES: Given 300 subjects per group and alpha of 0·05, the power to detect a 6 mmHg reduction in systolic blood pressure is 89%. DESIGN: DESERVE trial is a prospective, randomized, multicenter clinical trial of a novel discharge behavioral intervention. Patients with transient ischemic attack/mild stroke are randomized during hospitalization or emergency room visit to intervention or usual care. Intervention begins prior to discharge and continues postdischarge. STUDY OUTCOMES: The primary outcome is difference in systolic blood pressure reduction between groups at 12 months. Secondary outcomes include between-group differences in change in glycated hemoglobin, smoking rates, medication adherence, and recurrent stroke/transient ischemic attack at 12 months. DISCUSSION: DESERVE will evaluate whether a novel discharge education strategy leads to improved risk factor control in a racially diverse population.