Overview of stroke care in the United States and beyond.
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Benchmarking↗
Biomedical subjects
Joseph P Broderick
Publications and source records attributed to Joseph P Broderick.
ESPRIT trial.
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Anti-Inflammatory Agents, Non-Steroidal↗
Community socioeconomic status and prehospital times in acute stroke and transient ischemic attack: do poorer patients have longer delays from 911 call to the emergency department?
BACKGROUND AND PURPOSE: Timely access to medical treatment is critical for patients with acute stroke because acute therapies must be given very quickly after symptom onset. We examined the effect of socioeconomic status on prehospital delays in stroke and transient ischemic attack (TIA) patients within a large, biracial population. METHODS: By screening all local hospital ICD-9 codes 430 to 436, all stroke and TIA patients were identified during the calendar year of 1999. Cases must have used emergency medical services (EMS), lived at home, had their stroke at home, and had documented times of the 911 call and arrival to the emergency department. Socioeconomic status was estimated using economic data regarding the geocoded home residence census tract. RESULTS: Only 38% of stroke and TIA patients used EMS. There were 978 cases of stroke and TIA included in this analysis. The mean times were call to arrival on scene 6.5 minutes, on-scene time 14.1 minutes, and transport time 13.1 minutes. Lower community socioeconomic status was associated with all 3 EMS time intervals; however, all time differences were small: the largest difference was 5 minutes. CONCLUSIONS: Within our population, living in a poorer area does not appear to delay access to acute care for stroke in a clinically significant way. We did find small, statistically significant delays in prehospital times that were associated with poorer communities, black race, and increasing age. However, delays related to public recognition of stroke symptoms, and limited use of 911, are likely much more important than these small delays that occur with EMS systems.
Emergency Medical Services↗
Gene expression in blood changes rapidly in neutrophils and monocytes after ischemic stroke in humans: a microarray study.
Ischemic brain and peripheral white blood cells release cytokines, chemokines and other molecules that activate the peripheral white blood cells after stroke. To assess gene expression in these peripheral white blood cells, whole blood was examined using oligonucleotide microarrays in 15 patients at 2.4+/-0.5, 5 and 24 h after onset of ischemic stroke and compared with control blood samples. The 2.4-h blood samples were drawn before patients were treated either with tissue-type plasminogen activator (tPA) alone or with tPA plus Eptifibatide (the Combination approach to Lysis utilizing Eptifibatide And Recombinant tPA trial). Most genes induced in whole blood at 2 to 3 h were also induced at 5 and 24 h. Separate studies showed that the genes induced at 2 to 24 h after stroke were expressed mainly by polymorphonuclear leukocytes and to a lesser degree by monocytes. These genes included: matrix metalloproteinase 9; S100 calcium-binding proteins P, A12 and A9; coagulation factor V; arginase I; carbonic anhydrase IV; lymphocyte antigen 96 (cluster of differentiation (CD)96); monocarboxylic acid transporter (6); ets-2 (erythroblastosis virus E26 oncogene homolog 2); homeobox gene Hox 1.11; cytoskeleton-associated protein 4; N-formylpeptide receptor; ribonuclease-2; N-acetylneuraminate pyruvate lyase; BCL6; glycogen phosphorylase. The fold change of these genes varied from 1.6 to 6.8 and these 18 genes correctly classified 10/15 patients at 2.4 h, 13/15 patients at 5 h and 15/15 patients at 24 h after stroke. These data provide insights into the inflammatory responses after stroke in humans, and should be helpful in diagnosis, understanding etiology and pathogenesis, and guiding acute treatment and development of new treatments for stroke.
Adult↗
The Paul Coverdell National Acute Stroke Registry: initial results from four prototypes.
BACKGROUND: This paper summarizes the experiences of the Paul Coverdell National Acute Stroke Registry first four prototype registries in Georgia (GA), Massachusetts (MA), Michigan (MI), and Ohio (OH), and includes information on their sampling design, case ascertainment, and data collection methods, as well as some key findings. METHODS: Using a combination of different sampling methods, each prototype obtained a representative statewide sample of hospitals. Acute stroke admissions were identified through prospective (MA, MI) or retrospective (GA, OH) methods. A common set of case definitions and data elements were used by each registry. Weighted site-specific frequencies and 95% confidence intervals were generated for each outcome. A summary estimate, representing a weighted average of the four site-specific estimates, was also calculated. RESULTS: Of the total 6867 admissions, 1487 (21.6%) were from the GA registry, 1206 (17.6%) from MA, 2566 (37.4%) from MI, and 1608 (23.4%) from the OH prototype. Just less than 60% of admissions were ischemic strokes (site-specific estimates ranged from 52% to 70%), with transient ischemic attack (18.5%) and intracerebral hemorrhage (8.8%) making up most of the remainder. Twenty-one percent of patients admitted were younger than 60 years of age, and 55.3% were women. The proportion of black subjects varied from 7.1% (MI) to 30.6% (GA). Twenty-three percent of admissions arrived at the emergency department within 3 hours of onset. Overall 4.5% of ischemic stroke admissions were treated with recombinant tissue plasminogen activator; site-specific treatment rates were 3.0% (GA), 3.2% (OH), 3.4% (MI), and 8.5% (MA). Only a small minority of treated patients (range, 10.8% [OH] to 19.6% [MI]) received recombinant tissue plasminogen activator within the recommended 1 hour door-to-needle time. A minority of eligible subjects were screened for dysphagia (45.4%), underwent lipid testing (33.6%), or received smoking-cessation counseling (21.4%). In contrast, compliance with antithrombotic treatments at discharge was high (91.5%). CONCLUSIONS: A minority of acute stroke patients are treated according to established guidelines. Quality improvement interventions, targeted primarily at the healthcare systems level, are needed to improve acute stroke care in the United States.
Acute Disease↗
Temporal trends in the incidence and case fatality of stroke in children and adolescents.
A recent study reported that mortality from stroke in children and adolescents decreased by 58% from 1979 to 1998, although it wasn't clear if the case fatality or the incidence of stroke in this age group is decreasing. We report trends of stroke incidence and case fatality in children and adolescents within a large biracial population. The study involved collection of all strokes in the study population between January 1, 1988 and December 31, 1989, July 1, 1993 and June 30, 1994, and January 1, 1999 and December 31, 1999, at all of the regional hospitals serving the Greater Cincinnati/Northern Kentucky population (only the children's hospital in 1988). Study nurses reviewed the medical records of all inpatients with stroke-related discharge diagnoses and abstracted relevant data. A study physician reviewed each abstract to determine whether a stroke or transient ischemic attack had occurred. A total of 54 strokes occurred in children or adolescents younger than 20 years during the three study periods (30% African American, 70% Caucasian, and 56% female). The overall incidence rate of all strokes in children younger than 15 years was 6.4/100,000 in 1999, a nonsignificant increase when compared to 1988. The 30-day case-fatality rates were 18% in 1988-1989, 9% in 1993-1994, and 9% in 1999. We found that the incidence of strokes in children has been stable over the past 10 years. The previously reported nationwide decrease in overall stroke mortality in children might be due to decreasing case fatality after stroke and not decreasing stroke incidence. Based on our data, we conservatively estimated that approximately 3000 children less than 20 years old would have a stroke in the United States in 2004.
Adolescent↗
Potential applicability of recombinant factor VIIa for intracerebral hemorrhage.
BACKGROUND AND PURPOSE: To date, there are no proven, effective treatments for intracerebral hemorrhage (ICH) beyond supportive medical care. A recent randomized, blinded, placebo-controlled trial of recombinant factor VIIa (rFVIIa) administered intravenously within 4 hours of ICH onset reported a reduction in morbidity and mortality compared with placebo. We sought to determine the potential applicability of rFVIIa in a large, population-based cohort of ICH patients. METHODS: All of the patients age > or =18 years hospitalized with nontraumatic ICH in the Greater Cincinnati region were identified from May 1998 to July 2001 and August 2002 to April 2003. Patient demographics were compared with the inclusion and exclusion criteria from the rFVIIa trial to determine eligibility for treatment and reasons for exclusion. Mortality in the eligible patient group was compared with the placebo group in the rFVIIa trial. RESULTS: Over 4 calendar years, 1018 ICH patients were identified; of these, 133 (13.1%) had no exclusions and presented within the prescribed time window. An additional 45 patients (4.4%) may have been eligible but had uncertain onset or computed tomography scan times. The most common reasons for exclusion (not mutually exclusive) were late presentation (n=398), vaso-occlusive disease (n=369), deep coma (n=219), and prolonged international normalized ratio or partial thromboplastin time (n=200). Mortality at 90 days among potentially eligible patients was the same as for the placebo group in the rFVIIa trial (29% versus 29%; P=0.99). CONCLUSIONS: In this large, population-based ICH cohort, 13.1% to 17.5% of patients would have qualified for treatment with rFVIIa by trial criteria.
Aged↗
Revascularization end points in stroke interventional trials: recanalization versus reperfusion in IMS-I.
BACKGROUND AND PURPOSE: The acute stroke literature lacks a standard convention regarding the critical end point of revascularization. Two distinct parameters may be clinically important: (1) recanalization of the primary arterial occlusive lesion (AOL) and (2) global reperfusion of the distal vascular bed. We sought to determine their relationship in the Interventional Management of Stroke (IMS) Phase I trial of combined intravenous (IV) and intraarterial (IA) recombinant tissue plasminogen activator. METHODS: Sixty-one angiograms were reanalyzed using recanalization and reperfusion scores. The AOL Score was defined as: 0=no recanalization of the primary occlusion, I=incomplete or partial recanalization of the primary occlusion with no distal flow, II=incomplete or partial recanalization of the primary occlusion with distal flow, or III=complete recanalization of the primary occlusion with distal flow. The Thrombolysis in Myocardial Infarction (TIMI) Score was defined as: 0=no perfusion, 1=perfusion past the initial occlusion but no distal branch filling, 2=perfusion and incomplete or slow distal branch filling, or 3=full perfusion with filling of all distal branches. We compared the 2 scores with one another and with good clinical outcome (modified Rankin Score zero to 2). RESULTS: AOL and TIMI scores showed modest agreement (kappa, 0.30; confidence interval, 0.16 to 0.44). Good clinical outcome was seen in 49% of patients with AOL II/III scores (P=0.055) and 54% with TIMI 2/3 scores (P=0.019). The 2 methods did not significantly differ in predicting outcome (P=0.13). CONCLUSIONS: AOL recanalization and TIMI reperfusion scores comparably predict clinical outcome in this treatment paradigm. Other modalities may show different relationships between these 2 revascularization end points. Future studies should distinguish between these parameters semantically and methodologically.
Acute Disease↗
Major risk factors for intracerebral hemorrhage in the young are modifiable.
BACKGROUND AND PURPOSE: To identify risk factors for intracerebral hemorrhage (ICH), we examined data from the Hemorrhagic Stroke Project (HSP), a case-control study of hemorrhagic stroke among men and women aged 18 to 49 years. METHODS: Case subjects for the HSP were recruited from 44 hospitals in the United States. Eligibility criteria included an ICH within 30 days preceding enrollment, no history of stroke or known brain lesion. For this report, we focused on patients with primary ICH, defined as not associated with an aneurysm, arteriovenous malformation or other structural lesion. Two control subjects were sought for each case subject. A multivariate regression analysis was performed to determine risk factors for primary ICH. RESULTS: A total of 1714 patients with hemorrhagic stroke were identified for participation in the HSP. Of these, 217 cases met the criteria for primary ICH. Cases with primary ICH were matched to 419 controls. Independent risk factors for ICH included hypertension (adjusted odds ratio [OR], 5.71; 95% CI, 3.61 to 9.05), diabetes (adjusted OR, 2.40; 95% CI, 1.15 to 5.01), menopause (adjusted OR, 2.50; 95% CI, 1.06 to 5.88), current cigarette smoking (adjusted OR, 1.58; 95% CI, 1.02 to 2.44), alcoholic drinks> or =2/day (adjusted OR, 2.23; 95% CI, 1.16 to 4.32), caffeinated drinks> or =5/day (adjusted OR, 1.73; 95% CI, 1.08 to 2.79), and caffeine in drugs (adjusted OR, 3.55; 95% CI, 1.24 to 10.20). CONCLUSIONS: Among young men and women, the major risk factors for primary ICH can be modified, suggesting that this type of stroke may be preventable. Our findings for caffeine and menopause warrant further study.
Adolescent↗
The STICH trial: what does it tell us and where do we go from here?
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Cerebral Hemorrhage↗
Acute stroke care in the US: results from 4 pilot prototypes of the Paul Coverdell National Acute Stroke Registry.
BACKGROUND AND PURPOSE: The Paul Coverdell National Acute Stroke Registry is being developed to improve the quality of acute stroke care. This article describes key features of acute stroke care from 4 prototype registries in Georgia (Ga), Massachusetts (Mass), Michigan (Mich), and Ohio. METHODS: Each prototype developed its own sampling scheme to obtain a representative sample of hospitals. Acute stroke admissions were identified using prospective (Mass, Mich) or retrospective (Ga, Ohio) methods. All prototypes used a common set of case definitions and data elements. Weighted site-specific frequencies were generated for each outcome. RESULTS: A total of 6867 admissions from 98 hospitals were included; the majority were ischemic strokes (range, 52% to 70%) with transient ischemic attack and intracerebral hemorrhage comprising the bulk of the remainder. Between 19% and 26% of admissions were younger than age 60 years, and between 52% and 58% were female. Black subjects varied from 7.1% (Mich) to 30.6% (Ga). Between 20% and 25% of admissions arrived at the emergency department within 3 hours of onset. Treatment with recombinant tissue plasminogen activator (rtPA) was administered to between 3.0% (Ga) and 8.5% (Mass) of ischemic stroke admissions. Of 118 subjects treated with intravenous rtPA, <20% received it within 60 minutes of arrival. Compliance with secondary prevention practices was poorest for smoking cessation counseling and best for antithrombotics. CONCLUSIONS: A minority of acute stroke patients are treated according to established guidelines. Quality improvement interventions, targeted primarily at the health care systems level, are needed to improve acute stroke care in the United States.
Adolescent↗
The Familial Intracranial Aneurysm (FIA) study protocol.
BACKGROUND: Subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysms (IAs) occurs in about 20,000 people per year in the U.S. annually and nearly half of the affected persons are dead within the first 30 days. Survivors of ruptured IAs are often left with substantial disability. Thus, primary prevention of aneurysm formation and rupture is of paramount importance. Prior studies indicate that genetic factors are important in the formation and rupture of IAs. The long-term goal of the Familial Intracranial Aneurysm (FIA) Study is to identify genes that underlie the development and rupture of intracranial aneurysms (IA). METHODS/DESIGN: The FIA Study includes 26 clinical centers which have extensive experience in the clinical management and imaging of intracerebral aneurysms. 475 families with affected sib pairs or with multiple affected relatives will be enrolled through retrospective and prospective screening of potential subjects with an IA. After giving informed consent, the proband or their spokesperson invites other family members to participate. Each participant is interviewed using a standardized questionnaire which covers medical history, social history and demographic information. In addition blood is drawn from each participant for DNA isolation and immortalization of lymphocytes. High- risk family members without a previously diagnosed IA undergo magnetic resonance angiography (MRA) to identify asymptomatic unruptured aneurysms. A 10 cM genome screen will be performed to identify FIA susceptibility loci. Due to the significant mortality of affected individuals, novel approaches are employed to reconstruct the genotype of critical deceased individuals. These include the intensive recruitment of the spouse and children of deceased, affected individuals. DISCUSSION: A successful, adequately-powered genetic linkage study of IA is challenging given the very high, early mortality of ruptured IA. Design features in the FIA Study that address this challenge include recruitment at a large number of highly active clinical centers, comprehensive screening and recruitment techniques, non-invasive vascular imaging of high-risk subjects, genome reconstruction of dead affected individuals using marker data from closely related family members, and inclusion of environmental covariates in the statistical analysis.
Clinical Protocols↗
Racial variations in location and risk of intracerebral hemorrhage.
BACKGROUND AND PURPOSE: Risk factors for intracerebral hemorrhage (ICH) vary by location. Incidence rates of ICH are known to be higher in American blacks than whites, but how rates may differ by hemorrhage location is unknown. We sought to define incidence rates for different ICH locations in a biracial population. METHODS: All hospitalized patients age > or =20 years with spontaneous ICH were identified in the Greater Cincinnati/Northern Kentucky metropolitan area from May 1998 to July 2001 and August 2002 to April 2003. Incidence rates per 100,000 persons were age, sex, and race adjusted as appropriate to the 2000 US population. Risk ratios (RRs) with 95% CIs were calculated from unadjusted incidence rates. RESULTS: There were 1038 qualifying ICHs. Annual incidence rates per 100,000 persons > or =20 years of age were 48.9 for blacks and 26.6 for whites. Annual incidence rates per 100,000 blacks in lobar, deep cerebral, brain stem, and cerebellar locations were 15.2, 25.7, 5.1, and 2.9, respectively. Annual incidence rates per 100,000 whites in the same locations were 9.4, 13.0, 1.3, and 2.9. The greatest excess risk of ICH in blacks compared with whites was found among young to middle-aged (35 to 54 years) persons with brain stem (RR, 9.8; 95% CI, 4.2 to 23.0) and deep cerebral (RR, 4.5; 3.0 to 6.8) hemorrhage. CONCLUSIONS: The excess risk of ICH in American blacks is largely attributable to higher hemorrhage rates in young and middle-aged persons, particularly for deep cerebral and brain stem locations. Hypertension is the predominant risk factor for hemorrhages in these locations.
Adult↗
Incidence and short-term prognosis of transient ischemic attack in a population-based study.
BACKGROUND AND PURPOSE: Transient ischemic attacks (TIAs) have been shown to be a strong predictor of subsequent stroke and death. We present the incidence and short-term prognosis of TIA within a large population with a significant proportion of minorities with out-of-hospital TIA. METHODS: TIA cases were identified between July 1, 1993 and June 30, 1994 from the Greater Cincinnati/Northern Kentucky population of 1.3 million inhabitants by previously published surveillance methods, including inpatient and out-of-hospital events. Incidence rates were adjusted to the 1990 population, and life-table analyses were used for prognosis. RESULTS: The overall race, age, and gender-adjusted incidence rate for TIA within our population was 83 per 100,000, with age, race, and gender adjusted to the 1990 US population. Blacks and men had significantly higher rates of TIA than whites and women. Risk of stroke after TIA was 14.6% at 3 months, and risk of TIA/stroke/death was 25.2%. Age, race, and sex were not associated with recurrent TIA or subsequent stroke in our population, but age was associated with mortality. CONCLUSIONS: Using our incidence rates for TIA in blacks and whites, we conservatively estimate that approximately 240 000 TIAs occurred in 2002 in the United States. Our incidence rate of TIA is slightly higher than previously reported, which may be related to the inclusion of blacks and out-of-hospital events. There are racial and gender-related differences in the incidence of TIA. We found a striking risk of adverse events after TIA; however, there were no racial or gender differences predicting these events. Further study is warranted in interventions to prevent these adverse events after TIA.
Adult↗
A description of Canadian and United States physician reimbursement for thrombolytic therapy administration in acute ischemic stroke.
BACKGROUND AND PURPOSE: Acute ischemic stroke patients are infrequently treated with rtPA, despite its proven effectiveness. Poor physician reimbursement for acute stroke care is one possible explanation for the low frequency of use. We describe the physician reimbursement for thrombolytic therapy for the stroke team physicians serving the Greater Cincinnati/Northern Kentucky region (GCNK), and the Alberta region. METHODS: GCNK: billing logs were accessed for the study period of 7/01-12/02, and cross-matched to stroke call logs. University of Calgary (UC): treatment records of a single physician were reviewed from 4/02-3/04. A telephone survey of Canadian provinces was conducted regarding billing practices. RESULTS: GCNK: During the study period, 151 patients received rtPA. For treated pts. the average time spent was 2.6 hours, and average reimbursement received was 472 dollars (of those with insurance). The highest reimbursement was received by billing critical care codes. Reimbursement for critical care was similar to or lower than common office procedures for neurologists. UC: during the study period, 131 patients received rtPA. Average reimbursement for rtPA treated patients was 340 dollars US, not including on-call payments. Survey across Canada revealed many provinces with weekend/after hour premium stipends and on-call stipends. CONCLUSIONS: Physician reimbursement for the evaluation and treatment of acute stroke, when compared with other diagnoses commonly treated by neurologists, is relatively low in both the U.S. and Canada. Health policy decision-makers in the US and Canada should be made aware of the importance of providing a more balanced plan to provide medical care to stroke patients.
Alberta↗
Risk of thrombolysis-associated intracerebral hemorrhage: the need to compare apples with apples.
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Cerebral Hemorrhage↗
Epidemiology of ischemic stroke in patients with diabetes: the greater Cincinnati/Northern Kentucky Stroke Study.
OBJECTIVE: Diabetes is a well known risk factor for stroke, but the impact of diabetes on stroke incidence rates is not known. This study uses a population-based study to describe the epidemiology of ischemic stroke in diabetic patients. RESEARCH DESIGN AND METHODS: Hospitalized cases were ascertained by ICD-9 discharge codes, prospective screening of emergency department admission logs, and review of coroner's cases. A sampling scheme was used to ascertain cases in the out-of-hospital setting. All potential cases underwent detailed chart abstraction by study nurses followed by physician review. Diabetes-specific incidence rates, case fatality rates, and population-attributable risks were estimated. RESULTS: Ischemic stroke patients with diabetes are younger, more likely to be African American, and more likely to have hypertension, myocardial infarction, and high cholesterol than nondiabetic patients. Age-specific incidence rates and rate ratios show that diabetes increases ischemic stroke incidence at all ages, but this risk is most prominent before age 55 in African Americans and before age 65 in whites. One-year case fatality rates after ischemic stroke are not different between those patients with and without diabetes. CONCLUSIONS: Given the "epidemic" of diabetes, with substantially increasing diabetes prevalence each year across all age- and race/ethnicity groups, the significance of diabetes as a risk factor for stroke is becoming more evident. Diabetes is clearly one of the most important risk factors for ischemic stroke, especially in those patients less than 65 years of age. We estimate that 37-42% of all ischemic strokes in both African Americans and whites are attributable to the effects of diabetes alone or in combination with hypertension.
Adult↗
Advances in the treatment of hemorrhagic stroke: a possible new treatment.
Recombinant factor VIIa may be the first proven treatment for intracerebral hemorrhage (ICH); to be effective, it must be given soon after the onset of symptoms. Surgical removal of the hematoma by craniotomy at about 24 hours does not appear to offer much benefit compared with conservative therapy and delayed surgery, except possibly for superficial ICHs. Standardized management of medical complications remains important. New randomized treatment trials of recombinant factor VII and surgery are in progress or just beginning.
Cerebral Hemorrhage↗