Cerebral Microbleeds and the Effect of Intensive Blood Pressure Reduction on Hematoma Expansion and Functional Outcomes: A Secondary Analysis of the ATACH-2 Randomized Clinical Trial.

Importance: Response to intensive blood pressure (BP) lowering in acute intracerebral hemorrhage (ICH) might vary with the degree of underlying cerebral small vessel disease. Objectives: To characterize cerebral microbleeds (CMBs) in acute ICH and to assess the potential for interaction between underlying small vessel disease (as indicated by CMB number and location) and assignment to acute intensive BP targeting for functional outcomes and hematoma expansion. Design, Setting, and Participants: Preplanned subgroup analyses in the Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 (ATACH-2) trial were performed. The ATACH-2 was an open-label international randomized clinical trial that investigated optimal acute BP lowering in 1000 patients with acute ICH. Analyses followed the intent-to-treat paradigm. Participants were enrolled between May 2011 and September 2015 and followed up for 3 months. Eligible participants were aged at least 18 years with ICH volumes less than 60 mL on computed tomography (CT) and a Glasgow Coma Scale score of at least 5 on initial assessment, in whom study drug could be initiated within 4.5 hours of symptom onset. Eight hundred thirty-three participants were excluded, leaving 167 who had an interpretable axial T2*-weighted gradient-recalled echo sequence on magnetic resonance imaging to assess CMBs for inclusion in these subgroup analyses. Main Outcomes and Measures: The primary outcome of interest was death or disability (modified Ranking Scale score, 4-6) at 3 months. The secondary outcome of interest was hematoma volume expansion of at least 33% on a CT scan obtained 24 hours after randomization compared with the entry scan. Results: A total of 167 patients were included; their mean (SD) age was 61.9 (13.2) years, and 98 (58.7%) were male. Cerebral microbleeds were present in 120 patients. Forty-six of 157 (29.3%) patients had poor outcome (modified Ranking Scale score, ≥4), and hematoma expansion was observed in 29 of 144 (20.1%) patients. Risk of poor outcome was similar for those assigned to intensive vs standard acute BP lowering among patients with CMBs (relative risk, 1.19; 95% CI, 0.61-2.33; P = .61) and those without CMBs (relative risk, 1.42; 95% CI, 0.43-4.70; P = .57), and no significant interaction was observed (interaction coefficient, 0.18; 95% CI, -1.20 to 1.55; P = .80). Risk of hematoma expansion was also similar, and no significant interaction between treatment and CMBs was observed (interaction coefficient, 0.62; 95% CI, -1.08 to 2.31; P = .48). Conclusions and Relevance: Cerebral microbleeds are highly prevalent among patients with ICH but do not seem to influence response to acute intensive BP treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT01176565.

A New Risk Index for Predicting Outcomes among Patients Undergoing Carotid Endarterectomy in Large Administrative Data Sets.

BACKGROUND: We developed and validated a new index to provide risk adjustment and to predict in-hospital patient mortality and other outcomes in patients undergoing carotid endarterectomy (CEA). METHODS: The primary endpoint was occurrence of stroke, cardiac complications, or death during hospitalization for CEA derived from the Nationwide Inpatient Sample. Multivariate logistic regression was performed to identify the effect of clinical and demographic factors on occurrence of the primary endpoint. Data from 2005 to 2006 (study period 1) were used to derive risk index score whereas data from 2007 to 2009 (study period 2) were used for validation of the risk index. RESULTS: A total of 120,633 patients with mean age in years [ ±SD] of 71.1[ ±9.5] (42.4% women) underwent CEA during the derivation period. The rate of occurrence of composite endpoint during study period 1 was 3.1%. Predictors of the composite endpoint were (odds ratio [OR], P value) as follows: age 70 years or older (1.15, .013 assigned 1 point), atrial fibrillation (3.18, <.0001 assigned 3 points), Congestive Heart Failure (CHF) (1.81, <.0001 assigned 2 points), cigarette smoking (1.64, <.0001 assigned 2 points), symptomatic status (1.87, <.001 assigned 2 points), and chronic renal failure (1.64, <.0001 assigned 2 points). When applied to the validation cohort (n = 71,222), patients with scores 0-1 (OR 1.6, 95% confidence interval [CI] 1.5-1.8), scores 2-3 (OR 4.0, 95% CI 3.8-4.3), scores 4-5 (OR 7.5, 95% CI 6.8-8.2), and scores greater than 5 (OR 10.9, 95% CI 9.8-12.2) had composite rates of endpoint. The receiver operating characteristic curve of the risk index was 68.5% [±SE 0.5%]. CONCLUSION: New risk index will assist in risk adjustment for analyses of outcomes in large administrative data sets for comparative studies involving patients undergoing CEA.

Rates of Adverse Events and Outcomes among Stroke Patients Admitted to Primary Stroke Centers.

BACKGROUND AND PURPOSE: To identify the beneficial effects of primary stroke centers (PSCs) certification by Joint Commission (JC), we compared the rates of in-hospital adverse events and discharge outcomes among ischemic stroke patients admitted to PSCs and those admitted to non-PSC hospitals in the United States. METHODS: We obtained the data from the Nationwide Inpatient Sample from 2010 and 2011. The analysis was limited to states that publicly reported hospital identity. PSCs were identified by matching the Nationwide Inpatient Sample hospital files with the list provided by JC. The analysis was limited to patients (age ≥18 years) discharged with a principal diagnosis of ischemic stroke (International Classification of Disease, 9th Revision, codes 433.x1, 434.x1). RESULTS: We identified a total of 123,131 ischemic stroke patients from 28 states. A total of 72,982 (59.3%) patients were admitted to PSCs. After adjusting for age, gender, race or ethnicity, comorbidities, All Patients Refined Diagnosis Related Groups (APR-DRG)-based disease severity, and hospital teaching status, patients admitted to PSCs were at lower risk of in-hospital adverse events complications: pneumonia (odds ratio [OR], .8; 95% confidence interval [CI], .7-.8) and sepsis (OR, .7; 95% CI, .6-.8). Patients admitted to PSCs were more likely to receive thrombolysis (OR, 1.6; 95% CI, 1.5-1.7). The mean cost of hospitalization (95% CI) of the patients was significantly higher in patients admitted at PSCs compared with those admitted at non PSC hospitals $47621 (47099-48144) vs. $35229 (34803-35654), P < .0001). The patients admitted to PSCs had lower inpatient mortality (OR, .8; 95% CI, .8-.9) and were more likely to be discharged with none to minimal disability (OR, 1.1; 95% CI, 1.0-1.1). CONCLUSIONS: Compared with non-PSC admissions, patients admitted to PSCs are less likely to experience hospital adverse events and more likely to experience better discharge outcomes.

A Population-Based Study of the Incidence and Case Fatality of Intracerebral Hemorrhage of Undetermined Etiology.

BACKGROUND: There is a paucity of reliable recent data regarding epidemiology of intracerebral hemorrhage (ICH) of undetermined etiology in population-based studies. OBJECTIVES: To determine the incidence and case fatality of ICH of undetermined etiology using a population-based design. METHODS: Medical records and neuroimaging data of all patients with ICH from Stearns and Benton Counties, Minnesota, between June 1st, 2012 and June 30th, 2014 were reviewed. Patients with a first-time diagnosis of ICH were categorized as of undetermined etiology if ICH was without features typical of hypertensive etiology with normal or no magnetic resonance imaging (MRI)/angiograms. We calculated the incidences of [1] probable and possible hypertensive ICH; [2] related to arteriovenous malformation, cavernous malformation, or aneurysmal rupture (angiographic or MRI diagnoses); [3] secondary to anticoagulation; and [4] of undetermined etiology adjusted for age and sex based on the 2010 US census. RESULTS: Of the 50 identified ICHs among 136,654 resident populations, seven were true incident cases of ICH of undetermined etiology in this population-based study. The age- and sex-adjusted incidence of ICH of undetermined etiology was 2.6 [95% confidence interval (CI) 0.7-4.9] per 100, 000 person-years, which was lower than probable and possible hypertensive ICH incidence of 12.8 [95% CI 8.4-17.2] per 100,000 person-years. The age-adjusted case fatality rate at 1 month was 8.14 and 0.4 per 100,000 persons for probable and possible hypertensive ICHs and ICHs of undetermined etiology, respectively. CONCLUSIONS: Our results should prompt further studies into identification of causes in ICH patients presently classified as ICH of undetermined etiology to reduce the incidence and case fatality of such ICHs.

Clinical trials of cardiac repair with adult bone marrow- derived cells.

The past decade has witnessed a marked increase in the number of clinical trials of cardiac repair with adult bone marrow cells (BMCs). These trials included patients with acute myocardial infarction (MI) as well as chronic ischemic heart disease (IHD) and utilized different types of BMCs with variable numbers, routes of administration, and timings after MI. Given these differences in methods, the outcomes from these trials have been often disparate and controversial. However, analysis of pooled data suggests that BMC injection enhances left ventricular function, reduces infarct scar size, and improves remodeling in patients with acute MI as well as chronic IHD. BMC therapy also improves clinical outcomes during follow-up without any increase in adverse effects. Although the underlying mechanisms of heart repair are difficult to elucidate in human studies, valuable insights may be gleaned from subgroup analysis of key variables. This information may be utilized to design future randomized controlled trials to carefully determine the long-term safety and benefits of BMC therapy.

Rates and factors associated with admission in patients presenting to the ED with TIA in the United States-2006 to 2008.

BACKGROUND: The estimates of patients who present with transient ischemic attacks (TIA) in the emergency departments (EDs) of United States and their disposition and factors that determine hospital admission are not well understood. OBJECTIVE: We used a nationally representative database to determine the rate and predictors of admission in TIA patients presenting to EDs. METHODS: We analyzed data from the National Emergency Department Sample (2006-2008) for all patients presenting with a primary diagnosis of TIA in the United States. Samples were weighted to provide national estimates of TIA hospitalizations and identify factors that increase the odds of hospital admission including age, sex, type of insurance, median household income, and hospital type (urban teaching, urban nonteaching, and nonurban). Multivariate logistic regression analysis was used to identify independent predictors of hospital admission. RESULTS: There were 812908 ED visits for primary diagnosis of TIA; mean age (±SD), 70.3 ± 14.9 years; and 57.9% were women from 2006 to 2008. Of these ED visits, 516837 (63.5%) were admitted to the hospital, whereas 296071 (36.5%) were discharged from the ED to home. In the multivariate logistic regression analysis adjusting age, sex, and medical comorbidities, independent factors associated with hospital admissions were median household income $64000 or higher (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.22-1.44; P = .003), Medicare insurance type (OR, 1.19; 95% CI, 1.14-1.26; P < .0001), and metropolitan teaching hospital ED (OR, 2.17; 95% CI, 1.90-2.48; P < .0001). CONCLUSION: From 2006 to 2008, approximately 64% of all patients presenting with TIAs to the EDs within United States were admitted to the hospital. Factors unrelated to patients' condition such as median household income, insurance status, and ED affiliated hospital type play an important role in the decision to admit TIA patients to the hospitals.