Lewis B. Morgenstern

Intensive blood pressure reduction in acute cerebral haemorrhage trial (INTERACT): a randomised pilot trial

BACKGROUND There is much uncertainty about the effects of early lowering of elevated blood pressure (BP) after acute intracerebral haemorrhage (ICH). Our aim was to assess the safety and efficiency of this treatment, as a run-in phase to a larger trial. METHODS Patients who had acute spontaneous ICH diagnosed by CT within 6 h of onset, elevated systolic BP (150-220 mm Hg), and no definite indication or contraindication to treatment were randomly assigned to early intensive lowering of BP (target systolic BP 140 mm Hg; n=203) or standard guideline-based management of BP (target systolic BP 180 mm Hg; n=201). The primary efficacy endpoint was proportional change in haematoma volume at 24 h; secondary efficacy outcomes included other measurements of haematoma volume. Safety and clinical outcomes were assessed for up to 90 days. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00226096. FINDINGS Baseline characteristics of patients were similar between groups, but mean haematoma volumes were smaller in the guideline group (12.7 mL, SD 11.6) than in the intensive group (14.2 mL, SD 14.5). From randomisation to 1 h, mean systolic BP was 153 mm Hg in the intensive group and 167 mm Hg in the guideline group (difference 13.3 mm Hg, 95% CI 8.9-17.6 mm Hg; p<0.0001); from 1 h to 24 h, BP was 146 mm Hg in the intensive group and 157 mm Hg in the guideline group (10.8 mm Hg, 95% CI 7.7-13.9 mm Hg; p<0.0001). Mean proportional haematoma growth was 36.3% in the guideline group and 13.7% in the intensive group (difference 22.6%, 95% CI 0.6-44.5%; p=0.04) at 24 h. After adjustment for initial haematoma volume and time from onset to CT, median haematoma growth differed between the groups with p=0.06; the absolute difference in volume between groups was 1.7 mL (95% CI -0.5 to 3.9, p=0.13). Relative risk of haematoma growth >or=33% or >or=12.5 mL was 36% lower (95% CI 0-59%, p=0.05) in the intensive group than in the guideline group. The absolute risk reduction was 8% (95% CI -1.0 to 17%, p=0.05). Intensive BP-lowering treatment did not alter the risks of adverse events or secondary clinical outcomes at 90 days. INTERPRETATION Early intensive BP-lowering treatment is clinically feasible, well tolerated, and seems to reduce haematoma growth in ICH. A large randomised trial is needed to define the effects on clinical outcomes across a broad range of patients with ICH. FUNDING National Health and Medical Research Council of Australia.

Stroke Among Patients With Dizziness, Vertigo, and Imbalance in the Emergency Department: A Population-Based Study

Background and Purpose— Dizziness, vertigo, and imbalance are common presenting symptoms in the emergency department. Stroke is a leading concern even when these symptoms occur in isolation. The objective of the present study was to determine the “real-world” proportion of stroke among patients presenting to the emergency department with these dizziness symptoms (DS). Methods— From a population-based study, patients >44 years of age presenting with DS to the emergency department, or directly admitted to the hospital, were identified. Demographics, the frequency of new cerebrovascular events, and the frequency of isolated DS (ie DS with no other stroke screening term or accompanying neurologic signs or symptoms) were assessed. Multivariable logistic regression was used to evaluate the association of age, gender, ethnicity, and isolated DS with stroke/transient ischemic attack (TIA). The association of the presenting symptoms with stroke/TIA was also assessed. Results— Stroke/TIA was diagnosed in 3.2% (53 of 1666) of all patients with DS. Only 0.7% (9 of 1297) of those with isolated DS had a stroke/TIA. Patients with stroke/TIA were slightly older than those without stroke/TIA (69.3±11.7 vs 65.3±12.9, P=0.02). Male gender was associated with stroke/TIA, whereas isolated DS was negatively associated with stroke/TIA. Patients with imbalance (dizziness as referent) were more likely to have stroke/TIA. Conclusions— The proportion of cerebrovascular events in patients presenting with dizziness, vertigo, or imbalance is very low. Isolated dizziness, vertigo, or imbalance strongly predicts a noncerebrovascular cause. The symptom of imbalance is a predictor of stroke/TIA.

Early care limitations independently predict mortality after intracerebral hemorrhage

Objective: Intracerebral hemorrhage (ICH) is associated with a high early mortality rate. We examined the impact of early do not resuscitate (DNR) orders and other limitations in aggressive care on mortality after ICH in a community-based study. Methods: Cases of spontaneous ICH from 2000 to 2003 were identified from the Brain Attack Surveillance in Corpus Christi (BASIC) project, with deaths ascertained through 2005. Charts were reviewed for early (<24 hours from presentation) DNR orders, withdrawal of care, or deferral of other life sustaining interventions, analyzed together as combined DNR (C-DNR). Multivariable Cox-proportional hazards models were used to examine the association between short- and long-term all-cause mortality and early C-DNR, adjusted for demographics and established predictors of mortality after ICH. Results: Of 18,393 subjects screened for cerebrovascular disease, 270 non-traumatic ICH cases were included. Cumulative mortality risk was 0.43 at 30 days and 0.55 over the study course. Early C-DNR was noted in 34% of cases and was associated with a doubling in the hazard of death both at 30 days (hazard ratio [HR] 2.17, 95% CI 1.38, 3.41) and at end of follow-up (HR 1.92, 95% CI 1.29, 2.87) despite adjustment for age, gender, ethnicity, Glasgow Coma Scale, ICH volume, intraventricular hemorrhage, and infratentorial hemorrhage. Conclusions: Early care limitations are independently associated with both short- and long-term all-cause mortality after intracerebral hemorrhage (ICH) despite adjustment for expected predictors of ICH mortality. Physicians should carefully consider the effect of early limitations in aggressive care to avoid limiting care for patients who may survive their acute illness.

Projected costs of ischemic stroke in the United States

Background: There are barriers to acute stroke care in minority groups as well as a higher incidence of ischemic stroke when compared with non-Hispanic whites. Objective: To estimate the future economic burden of stroke in non-Hispanic whites, Hispanics, and African Americans in the United States from 2005 to 2050. Methods: We used U.S. Census estimates of the race–ethnic group populations age 45 years and older. We obtained stroke epidemiology and service utilization data from the Northern Manhattan Stroke Study and the Brain Attack Surveillance in Corpus Christi project and other published data. We estimated costs directly from Medicare reimbursement or from studies that used Medicare reimbursement. Direct and indirect costs considered included ambulance services, initial hospitalization, rehabilitation, nursing home costs, outpatient clinic visits, drugs, informal caregiving, and potential lost earnings. Results: The total cost of stroke from 2005 to 2050, in 2005 dollars, is projected to be

Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm

1.52 trillion for non-Hispanic whites,

Headache in the emergency department

313 billion for Hispanics, and

Ambient air pollution and risk for ischemic stroke and transient ischemic attack

379 billion for African Americans. The per capita cost of stroke estimates are highest in African Americans (

Effects of Deferoxamine on Intracerebral Hemorrhage-Induced Brain Injury in Aged Rats

25,782), followed by Hispanics (

Platelet-oriented inhibition in new TIA and minor ischemic stroke (POINT) trial: rationale and design.

17,201), and non-Hispanic whites (

A Randomized, Controlled Trial to Teach Middle School Children to Recognize Stroke and Call 911 The Kids Identifying and Defeating Stroke Project

15,597). Loss of earnings is expected to be the highest cost contributor in each race–ethnic group. Conclusions: The economic burden of stroke in African Americans and Hispanics will be enormous over the next several decades. Further efforts to improve stroke prevention and treatment in these high stroke risk groups are necessary.