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How can we improve stroke thrombolysis rates? A review of health system factors and approaches associated with thrombolysis administration rates in acute stroke care.

ABSTRACT: Thrombolysis using intravenous (IV) tissue plasminogen activator (tPA) is one of few evidence-based acute stroke treatments, yet achieving high rates of IV tPA delivery has been problematic. The 4.5-h treatment window, the complexity of determining eligibility criteria and the availability of expertise and required resources may impact on treatment rates, with barriers encountered at the levels of the individual clinician, the social context and the health system itself. The review aimed to describe health system factors associated with higher rates of IV tPA administration for ischemic stroke and to identify whether system-focussed interventions increased tPA rates for ischemic stroke.Published original English-language research from four electronic databases spanning 1997-2014 was examined. Observational studies of the association between health system factors and tPA rates were described separately from studies of system-focussed intervention strategies aiming to increase tPA rates. Where study outcomes were sufficiently similar, a pooled meta-analysis of outcomes was conducted.Forty-one articles met the inclusion criteria: 7 were methodologically rigorous interventions that met the Cochrane Collaboration Evidence for Practice and Organization of Care (EPOC) study design guidelines and 34 described observed associations between health system factors and rates of IV tPA. System-related factors generally associated with higher IV tPA rates were as follows: urban location, centralised or hub and spoke models, treatment by a neurologist/stroke nurse, in a neurology department/stroke unit or teaching hospital, being admitted by ambulance or mobile team and stroke-specific protocols. Results of the intervention studies suggest that telemedicine approaches did not consistently increase IV tPA rates. Quality improvement strategies appear able to provide modest increases in stroke thrombolysis (pooled odds ratio = 2.1, p = 0.05).In order to improve IV tPA rates in acute stroke care, specific health system factors need to be targeted. Multi-component quality improvement approaches can improve IV tPA rates for stroke, although more thoughtfully designed and well-reported trials are required to safely increase rates of IV tPA to eligible stroke patients.

SUBMITTER: Paul CL

PROVIDER: S-EPMC4825073 | biostudies-other | 2016 Apr

REPOSITORIES: biostudies-other

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Project description:Tenecteplase is a fibrinolytic drug with higher fibrin specificity and longer half-life than the standard stroke thrombolytic, alteplase, permitting the convenience of single bolus administration. Tenecteplase, at 0.5 mg/kg, has regulatory approval to treat ST-segment-elevation myocardial infarction, for which it has equivalent 30-day mortality and fewer systemic hemorrhages. Investigated as a thrombolytic for ischemic stroke over the past 15 years, tenecteplase is currently being studied in several phase 3 trials. Based on a systematic literature search, we provide a qualitative synthesis of published stroke clinical trials of tenecteplase that (1) performed randomized comparisons with alteplase, (2) compared different doses of tenecteplase, or (3) provided unique quantitative meta-analyses. Four phase 2 and one phase 3 study performed randomized comparisons with alteplase. These and other phase 2 studies compared different tenecteplase doses and effects on early outcomes of recanalization, reperfusion, and substantial neurological improvement, as well as symptomatic intracranial hemorrhage and 3-month disability on the modified Rankin Scale. Although no single trial prospectively demonstrated superiority or noninferiority of tenecteplase on clinical outcome, meta-analyses of these trials (1585 patients randomized) point to tenecteplase superiority in recanalization of large vessel occlusions and noninferiority in disability-free 3-month outcome, without increases in symptomatic intracranial hemorrhage or mortality. Doses of 0.25 and 0.4 mg/kg have been tested, but no advantage of the higher dose has been suggested by the results. Current clinical practice guidelines for stroke include intravenous tenecteplase at either dose as a second-tier option, with the 0.25 mg/kg dose recommended for large vessel occlusions, based on a phase 2 trial that demonstrated superior recanalization and improved 3-month outcome relative to alteplase. Ongoing randomized phase 3 trials may better define the comparative risks and benefits of tenecteplase and alteplase for stroke thrombolysis and answer questions of tenecteplase efficacy in the >4.5-hour time window, in wake-up stroke, and in combination with endovascular thrombectomy.

Project description:Background and purposeTime is brain: benefits of intravenous thrombolysis (IVT) in ischemic stroke last for 4.5 hours but rapidly decrease as time progresses following symptom onset. The goal of the Acute Brain Care (ABC) intervention study was to reduce the door-to-needle time (DNT) to ≤30 minutes by optimizing in-hospital stroke treatment.MethodsWe performed a single-centre before (pre-intervention period: 2000-2005) versus after (post-intervention period: 2006-2012) comparison in a cohort of consecutive patients treated with IVT. The intervention consisted of the implementation of a multidisciplinary stroke protocol combining simple strategies to reduce the DNT. Primary endpoint was the DNT, presented as proportion ≤30 minutes and median time. Secondary clinical endpoints were symptomatic intracranial hemorrhage (SICH), and favourable outcome defined as a modified Rankin scale (mRs) score of 0-2 at 3 months. Endpoints were additionally adjusted for baseline imbalances between the groups.ResultsIn the pre-intervention period, none (0.0%) of the 100 patients (mean age 63.8 years, median National Institutes of Health Stroke Scale [NIHSS] score 14) treated with IVT had a DNT ≤30 minutes compared to 234 (62.7%) of the 373 patients (mean age 66.7 years, median NIHSS score 10) in the post-intervention period (p<0.001). The median DNT decreased from 75 (IQR 60-105) to 28 minutes (IQR 20-37, p<0.001). SICH rate remained stable (3.0% versus 4.4%, OR 1.50, 95% CI 0.43─5.25; adjusted OR 5.47, 95% CI 0.69-42.12). The proportion of patients with a favourable outcome increased (38.9% versus 52.3%, OR 1.72, 95% CI 1.09-2.73) but lost statistical significance after adjustment (adjusted OR 1.46, 95% CI 0.82-2.61).ConclusionsImportant and sustained reduction of the DNT to 30 minutes or less can be safely achieved by optimizing in-hospital stroke treatment. With its simple strategies, the ABC-protocol is a pragmatic framework for increasing the therapeutic yield in time-dependent stroke treatment.

Project description:BACKGROUND AND PURPOSE:Mild stroke is the most common cause for thrombolysis exclusion in patients acutely presenting to the hospital. Thrombolysis administration in this subgroup is highly variable among different clinicians and institutions. We aim to study the predictors of thrombolysis in patients with mild ischemic stroke in the FL-PR CReSD registry (Florida-Puerto Rico Collaboration to Reduce Stroke Disparities). METHODS:Among 73?712 prospectively enrolled patients with a final diagnosis of ischemic stroke or TIA from January 2010 to April 2015, we identified 7746 cases with persistent neurological symptoms and National Institutes of Health Stroke Scale ?5 who arrived within 4 hours of symptom onset. Multilevel logistic regression analysis with generalized estimating equations was used to identify independent predictors of thrombolytic administration in the subgroup of patients without contraindications to thrombolysis. RESULTS:We included 6826 cases (final diagnosis mild stroke, 74.6% and TIA, 25.4%). Median age was 72 (interquartile range, 21); 52.7% men, 70.3% white, 12.9% black, 16.8% Hispanic; and median National Institutes of Health Stroke Scale, 2 (interquartile range, 3). Patients who received thrombolysis (n=1281, 18.7%) were younger (68 versus 72 years), had less vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia), had lower risk of prior vascular disease (myocardial infarction, peripheral vascular disease, and previous stroke), and had a higher presenting median National Institutes of Health Stroke Scale (4 versus 2). In the multilevel multivariable model, early hospital arrival (arrive by 0-2 hours versus ?3.5 hours; odds ratio [OR], 8.16; 95% confidence interval [CI], 4.76-13.98), higher National Institutes of Health Stroke Scale (OR, 1.87; 95% CI, 1.77-1.98), aphasia at presentation (OR, 1.35; 95% CI, 1.12-1.62), faster door-to-computed tomography time (OR, 1.81; 95% CI, 1.53-2.15), and presenting to an academic hospital (OR, 2.02; 95% CI, 1.39-2.95) were independent predictors of thrombolysis administration. CONCLUSIONS:Mild acutely presenting stroke patients are more likely to receive thrombolysis if they are young, white, or Hispanic and arrive early to the hospital with more severe neurological presentation. Identification of predictors of thrombolysis is important in design of future studies to assess the use of thrombolysis for mild stroke.

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How can we improve stroke thrombolysis rates? A review of health system factors and approaches associated with thrombolysis administration rates in acute stroke care.

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