Opeolu Adeoye

Recombinant Tissue-Type Plasminogen Activator Use for Ischemic Stroke in the United States A Doubling of Treatment Rates Over the Course of 5 Years

Background and Purpose— Recombinant tissue-type plasminogen activator (rtPA) is the only approved therapy for acute ischemic stroke (AIS). In 2004, 1.8% to 2.1% of AIS patients in the United States received rtPA. Given incentives from regulatory agencies and payors to increase rtPA use, we hypothesized that rtPA use in the United States would increase from 2005 to 2009. Methods— AIS cases were defined by exclusion of hemorrhagic stroke and transient ischemic attack International Classification of Diseases 9th revision codes (430, 431, 432, and 435) from diagnosis-related groups 14, 15, 524, and 559 discharges. Patients receiving thrombolytics were identified using International Classification of Diseases 9th revision code 99.10 (Medicare Provider and Analysis Review and Premier databases) and pharmacy billing records (Premier). Change over time and differences between databases were tested using negative binomial regression. Results— Within Medicare Provider and Analysis Review, thrombolytic use increased from 1.1% in 2005 to 3.4% in 2009 (P<0.001 for trend). Within Premier, thrombolytic use increased from 1.4% in 2005 to 3.7% in 2009 for all cases (P<0.001). Analysis of pharmacy billing records in Premier for 50-mg or 100-mg doses of rtPA showed that 3.4% of AIS cases were treated in 2009. Inclusion of patients with transient ischemic attack or hemorrhagic stroke International Classification of Diseases 9th revision codes who received any thrombolytic as “ischemic stroke patients receiving rtPA” changed the rate of thrombolysis to 5.2%. Conclusions— In 2009, 3.4% to 5.2% of AIS patients in the United States received thrombolytics, approximately double the rate of treatment in 2005. Rapid recognition and transport and quick treatment in the emergency department remain goals for further improving treatment rates.

Age at stroke: Temporal trends in stroke incidence in a large, biracial population

Objectives: We describe temporal trends in stroke incidence stratified by age from our population-based stroke epidemiology study. We hypothesized that stroke incidence in younger adults (age 20–54) increased over time, most notably between 1999 and 2005. Methods: The Greater Cincinnati/Northern Kentucky region includes an estimated population of 1.3 million. Strokes were ascertained in the population between July 1, 1993, and June 30, 1994, and in calendar years 1999 and 2005. Age-, race-, and gender-specific incidence rates with 95 confidence intervals were calculated assuming a Poisson distribution. We tested for differences in age trends over time using a mixed-model approach, with appropriate link functions. Results: The mean age at stroke significantly decreased from 71.2 years in 1993/1994 to 69.2 years in 2005 (p < 0.0001). The proportion of all strokes under age 55 increased from 12.9% in 1993/1994 to 18.6% in 2005. Regression modeling showed a significant change over time (p = 0.002), characterized as a shift to younger strokes in 2005 compared with earlier study periods. Stroke incidence rates in those 20–54 years of age were significantly increased in both black and white patients in 2005 compared to earlier periods. Conclusions: We found trends toward increasing stroke incidence at younger ages. This is of great public health significance because strokes in younger patients carry the potential for greater lifetime burden of disability and because some potential contributors identified for this trend are modifiable.

Scientific Rationale for the Inclusion and Exclusion Criteria for Intravenous Alteplase in Acute Ischemic Stroke A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

Purpose— To critically review and evaluate the science behind individual eligibility criteria (indication/inclusion and contraindications/exclusion criteria) for intravenous recombinant tissue-type plasminogen activator (alteplase) treatment in acute ischemic stroke. This will allow us to better inform stroke providers of quantitative and qualitative risks associated with alteplase administration under selected commonly and uncommonly encountered clinical circumstances and to identify future research priorities concerning these eligibility criteria, which could potentially expand the safe and judicious use of alteplase and improve outcomes after stroke. Methods— Writing group members were nominated by the committee chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association Stroke Council’s Scientific Statement Oversight Committee and the American Heart Association’s Manuscript Oversight Committee. The writers used systematic literature reviews, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and to indicate gaps in current knowledge and, when appropriate, formulated recommendations using standard American Heart Association criteria. All members of the writing group had the opportunity to comment on and approved the final version of this document. The document underwent extensive American Heart Association internal peer review, Stroke Council Leadership review, and Scientific Statements Oversight Committee review before consideration and approval by the American Heart Association Science Advisory and Coordinating Committee. Results— After a review of the current literature, it was clearly evident that the levels of evidence supporting individual exclusion criteria for intravenous alteplase vary widely. Several exclusionary criteria have already undergone extensive scientific study such as the clear benefit of alteplase treatment in elderly stroke patients, those with severe stroke, those with diabetes mellitus and hyperglycemia, and those with minor early ischemic changes evident on computed tomography. Some exclusions such as recent intracranial surgery are likely based on common sense and sound judgment and are unlikely to ever be subjected to a randomized, clinical trial to evaluate safety. Most other contraindications or warnings range somewhere in between. However, the differential impact of each exclusion criterion varies not only with the evidence base behind it but also with the frequency of the exclusion within the stroke population, the probability of coexistence of multiple exclusion factors in a single patient, and the variation in practice among treating clinicians.

Stroke Incidence is Decreasing in Whites, but Not in Blacks: A Population-Based Estimate of Temporal Trends in Stroke Incidence from the Greater Cincinnati/Northern Kentucky Stroke Study

Background and Purpose— Although other studies (in largely white populations) have found that stroke incidence declined during the 1990s, we previously reported that stroke incidence in our population (18% of which was black) did not change during that decade and that incidence rates in blacks were significantly higher than in whites. We sought to update temporal trends in stroke incidence by adding new data obtained from our large, biracial population in 2005. The objective of this study was to examine temporal trends in stroke incidence and case-fatality within a large biracial population over time by comparing stroke incidence rates from 1993 to 1994, 1999, and 2005. Methods— Within the Greater Cincinnati/Northern Kentucky population of 1.3 million, all strokes among area residents were ascertained at all local hospitals during July 1993 to June 19/94 and calendar years 1999 and 2005. A sampling scheme was used to ascertain cases in the out-of-hospital setting. Only first-ever strokes were included in this analysis. Race-specific incidence rates, standardized to the 2000 US Census population, and case-fatality rates were calculated. Results— The number of physician-confirmed first-ever strokes in patients ≥20 years of age was 1942 in 1993 to 1994, 2041 in 1999, and 1921 in 2005. In all study periods, blacks had higher stroke incidence than whites, and case-fatality rates were similar between races. In contrast to previous study periods, we found a significant decrease in overall stroke incidence in 2005. When stratified by race and stroke subtype, this change was driven by a decrease in ischemic stroke incidence among whites, whereas ischemic stroke incidence in blacks was unchanged. Hemorrhagic stroke incidence was unchanged in both races. Conclusions— For the first time, we report a significant decrease in stroke incidence within our population, which is consistent with other reports in the literature. This decrease was found only among whites, which suggests a worsening of the racial disparity in stroke incidence.

US Geographic Distribution of rt-PA Utilization by Hospital for Acute Ischemic Stroke

Background and Purpose— Previously, we have estimated US national rates of recombinant tissue plasminogen activator (rt-PA) use to be 1.8% to 3.0% of all ischemic stroke patients. However, we hypothesized that the rate of rt-PA use may vary widely depending on regional variation, and that a large percentage of the US population likely does not have access to hospitals using rt-PA regularly. We describe the US geographic distribution of hospitals using rt-PA for acute ischemic stroke. Method— This analysis used the MEDPAR database, which is a claims-based dataset that contains every fee-for-service Medicare-eligible hospital discharge in the US. Cases potentially eligible for rt-PA treatment based on diagnosis were defined as those with a hospital DRG code of 14, 15, or 559, and that also had an ICD-9 code of 433, 434, or 436. Thrombolysis use was defined as an ICD-9 code of 99.1. Study interval was July 1, 2005 to June 30, 2007. Hospital locations were mapped using ArcView software; population densities and regions of the US are based on US Census 2000. Results— There were 4750 hospitals in the MEDPAR database, which included 495 186 ischemic stroke admissions during the study period. Of these hospitals, 64% had no reported treatments with rt-PA for ischemic stroke, and 0.9% reported >10% treatment rates within the MEDPAR dataset. Bed size, rural or underserved designation, and population density were significantly associated with reported rt-PA treatment rates, and remained significant in the multivariable regression. Approximately 162 million US citizens reside in counties containing a hospital reporting a ≥2.4% treatment rate within the MEDPAR dataset. Conclusion— We report the first description of US hospital rt-PA treatment rates by hospital. Unfortunately, we found that 64% of US hospitals did not report giving rt-PA at all within the MEDPAR database within a 2-year period. These tended to be hospitals that were smaller (average bed size of 95), located in less densely populated areas, or located in the South or Midwest. In addition, 40% of the US population resides in counties without a hospital that administered rt-PA to at least 2.4% of ischemic stroke patients, although distinguishing transferred patients is problematic within administrative datasets. Such national-based resource-utilization data is important for planning at the local and national level, especially for such initiatives as telemedicine, to reach underserved areas.

Lack of Evidence for an Association Between Hemodynamic Variables and Hematoma Growth in Spontaneous Intracerebral Hemorrhage

Background and Purpose— Early hematoma expansion in spontaneous intracerebral hemorrhage (ICH) is associated with worse clinical outcome. We hypothesized that hemodynamic parameters are associated with the increase in hematoma volume owing to their relationship to blood vessel wall stresses. Methods— We performed a post hoc analysis of clinical and computed tomography (CT) data from patients enrolled in a prospective observational study of ICH patients presenting within 3 hours from symptom onset. Hematoma volumes were measured at hospital arrival and at 1 and 20 hours from presentation. Blood pressure and heart rate, recorded at 19 time points between presentation and 20 hours, were used to derive hemodynamic variables. Multivariable logistic-regression models were constructed to assess the relation between hemodynamic parameters and hematoma growth, adjusted for clinical covariates. Results— From the original study, 98 patients underwent baseline and 1-hour CT scans; of these, 65 had 20-hour CT scans. Substantial hematoma growth was observed in 28% within the first hour. Of the 65 patients not undergoing surgery within 20 hours, 37% experienced hematoma growth by 20 hours. Neither baseline or peak hemodynamic parameters nor changes in hemodynamic parameters were significantly associated with hematoma growth at either 1 or 20 hours. Conclusions— We found no blood pressure or heart rate parameters, individually or in combination, that were associated with hematoma growth. Our data suggest the influence of hemodynamic parameters on vessel wall stress to be an unlikely target for intervention in reducing the risk of early hematoma growth in ICH.

Part 11: Adult Stroke 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care

Advances in stroke care will have the greatest effect on stroke outcome if care is delivered within a regional stroke system designed to improve both efficiency and effectiveness. The ultimate goal of stroke care is to minimize ongoing injury, emergently recanalize acute vascular occlusions, and begin secondary measures to maximize functional recovery. These efforts will provide stroke patients with the greatest opportunity for a return to previous quality of life and decrease the overall societal burden of stroke.

Design and Validation of a Prehospital Scale to Predict Stroke Severity: Cincinnati Prehospital Stroke Severity Scale

Background and Purpose— We derived and validated the Cincinnati Prehospital Stroke Severity Scale (CPSSS) to identify patients with severe strokes and large vessel occlusion (LVO). Methods— CPSSS was developed with regression tree analysis, objectivity, anticipated ease in administration by emergency medical services personnel and the presence of cortical signs. We derived and validated the tool using the 2 National Institute of Neurological Disorders and Stroke (NINDS) tissue-type plasminogen activator Stroke Study trials and Interventional Management of Stroke III (IMS III) Trial cohorts, respectively, to predict severe stroke (National Institutes of Health Stroke Scale [NIHSS] ≥15) and LVO. Standard test characteristics were determined and receiver operator curves were generated and summarized by the area under the curve. Results— CPSSS score ranges from 0 to 4; composed and scored by individual NIHSS items: 2 points for presence of conjugate gaze (NIHSS ≥1); 1 point for presence of arm weakness (NIHSS ≥2); and 1 point for presence abnormal level of consciousness commands and questions (NIHSS level of consciousness ≥1 each). In the derivation set, CPSSS had an area under the curve of 0.89; score ≥2 was 89% sensitive and 73% specific in identifying NIHSS ≥15. Validation results were similar with an area under the curve of 0.83; score ≥2 was 92% sensitive, 51% specific, a positive likelihood ratio of 3.3, and a negative likelihood ratio of 0.15 in predicting severe stroke. For 222 of 303 IMS III subjects with LVO, CPSSS had an area under the curve of 0.67; a score ≥2 was 83% sensitive, 40% specific, positive likelihood ratio of 1.4, and negative likelihood ratio of 0.4 in predicting LVO. Conclusions— CPSSS can identify stroke patients with NIHSS ≥15 and LVO. Prospective prehospital validation is warranted.

Advances in the management of intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a major public-health problem worldwide. No proven treatments are available for this condition, which is associated with high rates of morbidity and mortality. Only 20% of individuals who survive ICH are independent at 6 months. Hypertension, cerebral amyloid angiopathy (CAA) and anticoagulation are known to be associated with such hemorrhages. No effective preventive therapies exist specifically for CAA-related ICH. The incidence of hypertension-related ICH might be decreasing in some populations with improvements in the treatment of hypertension; however, the incidence of anticoagulant-related ICH is increasing, as the use of anticoagulants rises. Many questions remain unanswered regarding the clinical management of ICH, although in the past 10 years completed medical and surgical clinical trials—examining hemostatic therapy, blood pressure control and/or hematoma evacuation—have refined our understanding of the goals of such management. Ongoing clinical trials, which have built on the lessons of past studies, hold promise for the development of effective, scientifically proven treatments for ICH. In this Review, we discuss clinical trials for ICH that have been completed in the past 10 years, the contributions of these studies to the clinical management of ICH, and the ongoing trials that might further improve clinical care.

Decompressive hemicraniectomy for malignant middle cerebral artery territory infarction: is life worth living?

OBJECT Although decompressive hemicraniectomy has been shown to reduce death and improve functional outcome following malignant middle cerebral artery territory infarction, there is ongoing debate as to whether surgery should be routinely performed, considering the very high rates of disability and functional dependence in survivors. Through a systematic review of the literature, the authors sought to determine the outcome from a patients perspective. METHODS In September 2010, a MEDLINE search of the English-language literature was performed using various combinations of 12 key words. A total of 16 papers were reviewed and individual study data were extracted. RESULTS There was significant variability in study design, patient eligibility criteria, timing of surgery, and methods of outcome assessment. There were 382 patients (59% male, 41% female) with a mean age of 50 years, 25% with dominant-hemisphere infarction. The mortality rate was 24% and the mean follow-up in survivors was 19 months (range 3-114 months). Of 156 survivors with available modified Rankin Scale (mRS) scores, 41% had favorable functional outcome (mRS Score ≤ 3), whereas 47% had moderately severe disability (mRS Score 4). Among 157 survivors with quality of life assessment, the mean overall reduction was 45%: 67% for physical aspect and 37% for psychosocial aspect. Of 114 screened survivors, depression affected 56% and was moderate or severe in 25%. Most patients and/or caregivers (77% of the 209 interviewed) were satisfied and would give consent again for the procedure. CONCLUSIONS Despite high rates of physical disability and depression, the vast majority of patients are satisfied with life and do not regret having undergone surgery.