IV tissue plasminogen activator use in acute stroke: experience from a statewide registry.

OBJECTIVE: To assess the use of IV recombinant tissue plasminogen activator (rt-PA) in a statewide hospital-based stroke registry and to identify factors associated with its use among eligible patients. METHODS: A modified stratified sampling scheme was used to obtain a representative sample of 16 hospitals. Prospective case ascertainment and data collection were used to identify all acute stroke admissions over a 6-month period. Subjects eligible for IV rt-PA were defined as those who arrived within 3 hours of onset, who had no evidence of hemorrhage on initial brain image, and who had no physician-documented reasons for non-treatment with IV rt-PA. Multivariate logistic regression was used to identify factors associated with IV rt-PA use. RESULTS: Of 2,566 stroke admissions, 330 (12.9%) met the eligibility criteria for rt-PA treatment, and of these 43 (13%) received IV rt-PA treatment. Among 2,236 admissions excluded from consideration, 21% had evidence of hemorrhage on initial imaging, 35% had unknown stroke onset times, 38% had an onset to arrival time >3 hours, and 6% had physician documented contraindications. Among eligible patients, being male, use of emergency medical services, and rapid presentation were associated with increased IV rt-PA use. CONCLUSIONS: Treatment with IV rt-PA was underutilized in this hospital-based stroke registry. The primary reason for nontreatment was delayed presentation. Reducing prehospital and in-hospital response times would help increase IV rt-PA use, as would greater emergency medical services use. Improving the documentation of onset times would help clarify the underlying causes of delayed presentation.

A national study of the quantity and cost of informal caregiving for the elderly with stroke.

BACKGROUND: As the US population ages, increased stroke incidence will result in higher stroke-associated costs. Although estimates of direct costs exist, little information is available regarding informal caregiving costs for stroke patients. OBJECTIVE: To determine a nationally representative estimate of the quantity and cost of informal caregiving for stroke. METHODS: The authors used data from the first wave of the Asset and Health Dynamics (AHEAD) Study, a longitudinal study of people over 70, to determine average weekly hours of informal caregiving. Two-part multivariable regression analyses were used to determine the likelihood of receiving informal care and the quantity of caregiving hours for those with stroke, after adjusting for important covariates. Average annual cost for informal caregiving was calculated. RESULTS: Of 7,443 respondents, 656 (8.8%) reported a history of stroke. Of those, 375 (57%) reported stroke-related health problems (SRHP). After adjusting for cormorbid conditions, potential caregiver networks, and sociodemographics, the proportion of persons receiving informal care increased with stroke severity, and there was an association of weekly caregiving hours with stroke +/- SRHP (p < 0.01). Using the median 1999 home health aide wage (8.20 dollars/hour) as the value for family caregiver time, the expected yearly caregiving cost per stroke ranged from 3,500 dollars to 8,200 dollars. Using conservative prevalence estimates from the AHEAD sample (750,000 US elderly patients with stroke but no SRHP and 1 million with stroke and SRHP), this would result in an annual cost of up to 6.1 billion dollars for stroke-related informal caregiving in the United States. CONCLUSIONS: Informal caregiving-associated costs are substantial and should be considered when estimating the cost of stroke treatment.

Acute stroke care in non-urban emergency departments.

OBJECTIVE: To evaluate the practice patterns for stroke care in rural emergency departments (ED). METHODS: The authors prospectively evaluated clinical practice decisions for all ED patients in two non-urban East Texas communities using active and passive surveillance methods. Data collected included demographics, risk factors, symptoms, and treatment. Data analysis consisted of descriptive statistics and logistic regression analysis. RESULTS: During the study period, 429 patients presented with validated strokes. Risk factors included hypertension (65%), previous stroke (41%), coronary artery disease (33%), diabetes (25%), current smoking (17%), and atrial fibrillation (11%). In the ED, neurology consultation occurred in 32%, head CT in 88%, and ECG in 85%. Heparin was used in 9%, and 5% received aspirin. Blood pressure was lowered in 19% from a mean high of 189(+/-38)/97(+/-26), average reduction 34 points (18%) systolic. Motor symptoms were more likely to prompt a neurology consultation (OR = 2.47). Heparin was used more commonly for patients with atrial fibrillation (OR = 2.93). Socioeconomic factors did not alter care. IV recombinant tissue plasminogen activator was used in 1.4% of ischemic stroke cases. CONCLUSIONS: Acute stroke care in this representative non-urban community frequently does not follow published guidelines or clinical trial results. Whereas a high percentage of patients receive CT, aggressive blood pressure treatment occurs commonly and at pressures below current recommendations. The use of heparin is common, more so than aspirin treatment. These facts argue for educational interventions aimed at non-urban physicians to improve evidence-based medical practice.

Hypothermia after cardiac arrest: feasibility and safety of an external cooling protocol.

BACKGROUND: No proven neuroprotective treatment exists for ischemic brain injury after cardiac arrest. Mild-to-moderate induced hypothermia (MIH) is effective in animal models. METHODS AND RESULTS: A safety and feasibility trial was designed to evaluate mild-to-moderate induced hypothermia by use of external cooling blankets after cardiac arrest. Inclusion criteria were return of spontaneous circulation within 60 minutes of advanced cardiac life support, hypothermia initiated within 90 minutes, persistent coma, and lack of acute myocardial infarction or unstable dysrhythmia. Hypothermia to 33 degrees C was maintained for 24 hours followed by passive rewarming. Nine patients were prospectively enrolled. Mean time from advanced cardiac life support to return of spontaneous circulation was 11 minutes (range 3 to 30); advanced cardiac life support to initiation of hypothermia was 78 minutes (range 40 to 109); achieving 33 degrees C took 301 minutes (range 90 to 690). Three patients completely recovered, and 1 had partial neurological recovery. One patient developed unstable cardiac dysrhythmia. No other unexpected complications occurred. CONCLUSIONS: Mild-to-moderate induced hypothermia after cardiac arrest is feasible and safe. However, external cooling is slow and imprecise. Efforts to speed the start of cooling and to improve the cooling process are needed.

Activation of emergency medical services for acute stroke in a nonurban population: the T.L.L. Temple Foundation Stroke Project.

BACKGROUND AND PURPOSE: Activating emergency medical services (EMS) is the most important factor in reducing delay times to hospital arrival for stroke patients. Determining who calls 911 for stroke would allow more efficient targeting of public health initiatives. METHODS: The T.L.L. Temple Foundation Stroke Project is an acute stroke surveillance and intervention project in nonurban East Texas. Prospective case ascertainment allowed chart abstraction and structured interviews for all hospitalized stroke patients to determine if EMS was activated, and if so, by whom. RESULTS: Of 429 validated strokes, 38.0% activated EMS by calling 911. Logistic regression analysis comparing those who called 911 with those who did not activate EMS found that individuals who were employed were 81% less likely to have EMS activated (OR 0.19, 95% CI 0.04 to 0.63). Of the 163 cases in which 911 was called, the person activating EMS was: self (patient), 4.3%; family member of significant other, 60. 1%; paid caregiver, 18.4%; and coworker or other, 12.9%. Significant associations between the variables age group (P=0.02), insurance status (P=0.007), and living alone (P=0.05) with who called 911 was found on chi(2) analysis. CONCLUSIONS: Educational efforts directed at patients themselves at risk for stroke may be of low yield. To increase the use of time dependent acute stroke therapy, interventions may wish to concentrate on family, caregivers, and coworkers of high-risk patients. Large employers may be good targets to increase utilization of EMS services for acute stroke.

Acute ischemic stroke therapy.

Acute ischemic stroke is a medical emergency that requires rapid evaluation and treatment. Prehospital and emergency department care can be streamlined to meet those goals. Intravenous rt-PA therapy improves outcome in selected patients with ischemic stroke if given within 3 hours of stroke onset, but offers no benefit beyond that time window. Intra-arterial thrombolytic therapy and intravenous defibrogenating agents may also be beneficial in selected patients. Newer thrombolytic agents such as aspirin and heparin in acute ischemic stroke treatment have been clarified by recent trials.

Nuclear factor-kappaB and cell death after experimental intracerebral hemorrhage in rats.

BACKGROUND AND PURPOSE: Nuclear factor-kappaB (NF-kappaB) is a ubiquitous transcription factor that, when activated, translocates to the nucleus, binds to DNA, and promotes transcription of many target genes. Its activation has been demonstrated in chronic inflammatory conditions, cerebral ischemia, and apoptotic cell death. The present study evaluated the presence and activation of NF-kappaB in relation to cell death surrounding intracerebral hemorrhage (ICH). METHODS: Striatal ICH was induced in rats by the double blood injection method. Animals were killed 2, 8, and 24 hours and 4 days after ICH. To examine changes in NF-kappaB protein, Western blot was performed on brain extract. We determined NF-kappaB activity using electrophoretic mobility shift assay (EMSA) and immunohistochemistry, using an antibody that only recognizes active NF-kappaB. DNA fragmentation was detected with terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) staining. RESULTS: Western blot analysis of the NF-kappaB p65 subunit showed that there was no difference in p65 protein levels in the control, 2-hour, 8-hour, or 24-hour groups. However, ipsilateral perilesional samples from the 4-day group revealed a 1.8- to 2.5-fold increase compared with the contralateral hemisphere. Western blotting showed no differences in the inhibitor of NF-kappaB, IkappaBalpha, in any group. EMSA showed 1.3-, 2.1-, and 3.6-fold increased NF-kappaB activation in the ipsilateral striatum from the 8-hour, 24-hour, and 4-day groups, respectively, compared with the contralateral hemisphere. Immunohistochemistry, in which an activation-dependent anti-NF-kappaB antibody was used, demonstrated perivascular NF-kappaB activation as early as 2 hours after ICH with more generalized activation at 8 hours, in agreement with the EMSA results. NF-kappaB activation colocalized to cells containing fragmented DNA measured by TUNEL. CONCLUSIONS: The present study suggests a relationship between NF-kappaB and the pathobiology of perilesional cell death after ICH.

Neuroprotective therapy.

The concept of neuroprotection relies on the principle that delayed neuronal injury occurs after ischemia. The phenomenon of the "ischemic cascade" has been described, and each step along this cascade provides a target for therapeutic intervention. In animal models of global and focal cerebral ischemia, numerous preclinical studies have demonstrated various agents to be neuroprotective at different steps along this cascade. A wide variety of drugs has also been studied in humans. Ten classes of neuroprotective agents have reached phase III efficacy trials but have shown mixed results. They include calcium channel antagonists, NMDA receptor antagonists, lubeluzole, CDP-choline, the free radical scavenger tirilizad, anti-intercellular adhesion molecule-1 (ICAM-1) antibody, GM-1 ganglioside, clomethiazole, the sodium channel antagonist fosphenytoin, and piracetam. In the future, clinicians may have an armamentarium of treatments for acute ischemic stroke at their disposal, with a combination of agents directed at different sites in the ischemic cascade being the ultimate goal.

Thrombolysis, stroke units and other strategies for reducing acute stroke costs.

Stroke is the leading cause of long term disability and the third leading cause of death in the US. Nearly $US40.9 billion (1997 values) are spent each year on direct and indirect stroke-related costs in the US alone. Length of hospital stay, hospital overheads and nursing-related and rehabilitation costs account for the majority of stroke-related expenditures. Intravenous recombinant tissue plasminogen activator (rt-PA) therapy for patients presenting within 3 hours from onset of ischaemic stroke was shown to improve outcome at 3 months by the National Institute of Neurological Disease and Stroke (NINDS) investigators using a dosage of 0.9 mg/kg. When the NINDS rt-PA Stroke Study results were examined using a Markov model, savings of $US4 to $US5 million (1996 values) per 1000 patients treated with rt-PA were projected. These savings were predicted to result from decreases in length of hospital stay, inpatient rehabilitation and nursing home costs, increases in the number of patients discharged directly to home and improvements in quality-adjusted life-years. Furthermore, a recent meta-analysis has documented that the institution of stroke units, consisting of multidisciplinary specialised stroke teams, also decreased length of hospital stay, death and dependency. Because only a minority of patients who have a stroke are currently eligible for thrombolysis, implementation of specialised and standardised stroke care may further enhance cost benefits and improve patient outcomes.