Received Tissue Plasminogen Activator Research Articles

REACH MUSC: A Telemedicine Facilitated Network for Stroke: Initial Operational Experience

REACH Medical University of South Carolina (MUSC) provides stroke consults via the internet in South Carolina. From May 2008 to April 2011 231 patients were treated with intravenous (IV) thrombolysis and 369 were transferred to MUSC including 42 for intra-arterial revascularization [with or without IV tissue plasminogen activator (tPA)]. Medical outcomes and hemorrhage rates, reported elsewhere, were good (Lazaridis et al., 2011). Here we report operational features of REACH MUSC which covers 15 sites with 2,482 beds and 471,875 Emergency Department (ED) visits per year. Eight Academic Faculty from MUSC worked with 165 different physicians and 325 different nurses in the conduct of 1085 consults. For the 231 who received tPA, time milestones (in minutes) were: Onset to Door: 62 (mean), 50 (median); Door to REACH Consult: 43 and 33, Consult Request to Consult Start: was 9 and 7, Consult Start to tPA Decision: 31 and 25; Decision to Infusion: 20 and 14, and total Door to Needle: 98 and 87. The comparable times for the 854 not receiving tPA were: Onset to Door: 140 and 75; Door to REACH Consult: 61 and 41; Consult Request to Consult Start: 9 and 7, Consult Start to tPA Decision: 27 and 23. While the consultants respond to consult requests in <10, there is a long delay between arrival and Consult request. Tracking of operations indicates if we target shortening Door to Call time and time from tPA decision to start of drug infusion we may be able to improve Door to Needle times to target of <60. The large number of individuals involved in the care of these patients, most of whom had no training in REACH usage, will require novel approaches to staff education in ED based operations where turnover is high. Despite these challenges, this robust system delivered tPA safely and in a high fraction of patients evaluated using the REACH MUSC system.

A Person with Factitious Disorder Presenting with Acute Stroke-Like Symptoms and Receiving Thrombolytic Therapy Twice

One of the challenges in acute stroke management is accurately differentiating between actual ischemic events and other conditions that mimic stroke. In a cohort of 821 consecutive patients admitted to an acute stroke unit, 13% were incorrectly diagnosed as stroke [1]. In another cohort of 411 patients, it was estimated that 19% of patients presenting to the emergency department with stroke-like symptoms ultimately have other diagnoses such as a postictal state, metabolic disturbances, and systemic infections [2]. Regardless of the actual percentage, it is clear that not all cases of acute stroke-like symptoms are true strokes and other mimics should be considered. One such mimic is factitious disorder. Factitious disorder is a psychiatric condition in which afflicted individuals exaggerate symptoms and even endorse medical illness, or psychological trauma in order to draw attention or sympathy to themselves. The DSM-IV criteria for this disorder are: 1) Intentional production or feigning of physical or psychological signs or symptoms; 2) The motivation for the behavior is to assume the sick role; and 3) External incentives for the behavior such as economic gain or avoiding legal responsibility as seen in malingering, are absent [3]. Here, we present a case of a patient who was diagnosed with factitious disorder after he presented to two different institutions with acute stroke-like symptoms and received tissue plasminogen activator (t-PA) twice within the span of 3 weeks.

FASTER (Face, Arm, Speech, Time, Emergency Response): Experience of Central Coast Stroke Services implementation of a pre-hospital notification system for expedient management of acute stroke

Despite benefit in acute ischaemic stroke, less than 3% of patients receive tissue plasminogen activator (tPA) in Australia. The FASTER (Face, Arm, Speech, Time, Emergency Response) protocol was constructed to reduce pre-hospital and Emergency Department (ED) delays and improve access to thrombolysis. This study aimed to determine if introduction of the FASTER protocol increases use of tPA using a prospective pre- and post-intervention cohort design in a metropolitan hospital. A pre-hospital assessment tool was used by ambulance services to screen potential tPA candidates. The acute stroke team was contacted, hospital bypass allowed, triage and CT radiology alerted, and the patient rapidly assessed on arrival to ED. Data were collected prospectively during the first 6 months of the new pathway and compared to a 6-month period 12 months prior to protocol initiation. In the 6 months following protocol introduction, 115 patients presented within 24 hours of onset of an ischaemic stroke: 22 (19%) received thrombolysis, significantly greater than five (7%) of 67 patients over the control period, p = 0.03. Overall, 42 patients were referred via the FASTER pathway, with 21 of these receiving tPA (50%). One inpatient stroke was also treated. Only two referrals (<5%) were stroke mimics. Introduction of the FASTER pathway also significantly reduced time to thrombolysis and time to admission to the stroke unit. Therefore, fast-track referral of potential tPA patients involving the ambulance services and streamlined hospital assessment is effective and efficient in improving patient access to thrombolysis.

Fluid-Attenuated Inversion Recovery Hyperintensity in Acute Ischemic Stroke May Not Predict Hemorrhagic Transformation

Background: Fluid-attenuated inversion recovery (FLAIR) hyperintensity within an acute cerebral infarct may reflect delayed onset time and increased risk of hemorrhage after thrombolysis. Given the important implications for clinical practice, we examined the prevalence of FLAIR hyperintensity in patients 3–6 h from stroke onset and its relationship to parenchymal hematoma (PH). Methods: Baseline DWI and FLAIR imaging with subsequent hemorrhage detection (ECASS criteria) were prospectively obtained in patients 3–6 h after stroke onset from the pooled EPITHET and DEFUSE trials. FLAIR hyperintensity within the region of the acute DWI lesion was rated qualitatively (dichotomized as visually obvious or subtle (i.e. only visible after careful windowing)) and quantitatively (using relative signal intensity (RSI)). The association of FLAIR hyperintensity with hemorrhage was then tested alongside established predictors (very low cerebral blood volume (VLCBV) and diffusion (DWI) lesion volume) in logistic regression analysis. Results: There were 49 patients with pre-treatment FLAIR imaging (38 received tissue plasminogen activator (tPA), 5 developed PH). FLAIR hyperintensity within the region of acute DWI lesion occurred in 48/49 (98%) patients, was obvious in 18/49 (37%) and subtle in 30/49 (61%). Inter-rater agreement was 92% (ĸ = 0.82). The prevalence of obvious FLAIR hyperintensity did not differ between studies obtained in the 3–4.5 h and 4.5–6 h time periods (40% vs. 33%, p = 0.77). PH was poorly predicted by obvious FLAIR hyperintensity (sensitivity 40%, specificity 64%, positive predictive value 11%). In univariate logistic regression, VLCBV (p = 0.02) and DWI lesion volume (p = 0.03) predicted PH but FLAIR lesion volume (p = 0.87) and RSI (p = 0.11) did not. In ordinal logistic regression for hemorrhage grade adjusted for age and baseline stroke severity (NIHSS), increased VLCBV (p = 0.002) and DWI lesion volume (p = 0.003) were associated with hemorrhage but FLAIR lesion volume (p = 0.66) and RSI (p = 0.35) were not. Conclusions: Visible FLAIR hyperintensity is almost universal 3–6 h after stroke onset and did not predict subsequent hemorrhage in this dataset. Our findings question the value of excluding patients with FLAIR hyperintensity from reperfusion therapies. Larger studies are required to clarify what implications FLAIR-positive lesions have for patient selection.

Late Night Activity regarding Stroke Codes: Lunar Strokes

There is diurnal variation for cardiac arrest and sudden cardiac death. Stroke may show a similar pattern. We assessed whether strokes presenting during a particular time of day or night are more likely of vascular etiology. To compare emergency department stroke codes arriving between 22:00 and 8:00 hours (LuNAR strokes) vs. others (n-LuNAR strokes). The purpose was to determine if late night strokes are more likely to be true strokes or warrant acute tissue plasminogen activator evaluations. We reviewed prospectively collected cases in the University of California, San Diego Stroke Team database gathered over a four-year period. Stroke codes at six emergency departments were classified based on arrival time. Those arriving between 22:00 and 8:00 hours were classified as LuNAR stroke codes, the remainder were classified as 'n-LuNAR'. Patients were further classified as intracerebral hemorrhage, acute ischemic stroke not receiving tissue plasminogen activator, acute ischemic stroke receiving tissue plasminogen activator, transient ischemic attack, and nonstroke. Categorical outcomes were compared using Fisher's Exact test. Continuous outcomes were compared using Wilcoxon's Rank-sum test. A total of 1607 patients were included in our study, of which, 299 (19%) were LuNAR code strokes. The overall median NIHSS was five, higher in the LuNAR group (n-LuNAR 5, LuNAR 7; P=0·022). There was no overall differences in patient diagnoses between LuNAR and n-LuNAR strokes (P=0·169) or diagnosis of acute ischemic stroke receiving tissue plasminogen activator (n-LuNAR 191 (14·6%), LuNAR 42 (14·0%); P=0·86). Mean arrival to computed tomography scan time was longer during LuNAR hours (n-LuNAR 54·9±76·3 min, LuNAR 62·5±87·7 min; P=0·027). There was no significant difference in 90-day mortality (n-LuNAR 15·0%, LuNAR 13·2%; P=0·45). Our stroke center experience showed no difference in diagnosis of acute ischemic stroke between day and night stroke codes. This similarity was further supported in similar rates of tissue plasminogen activator administration. Late night strokes may warrant a more rapid stroke specialist evaluation due to the longer time elapsed from symptom onset and the longer time to computed tomography scan.

Outcomes in Acute Ischemic Strokes Presenting with Disabling Neurologic Deficits without Intracranial Vascular Occlusion

Patients with moderate to severe acute ischemic stroke without intracranial vessel occlusion are an intriguing subset of stroke patients. They pose diagnostic and therapeutic challenges to the physician. We sought to study these patients with an emphasis on their radiological and clinical outcomes. This is a retrospective cohort study of ischemic stroke patients (NIHSS≥6), with no intracranial vessel occlusion on computed tomography angiography within six-hours of symptom onset. Follow-up imaging - either computed tomography brain or magnetic resonance imaging - was performed within one- to seven-days. The primary outcome was modified Rankin Scale score≤2 at three-months. In a database of 1308 patients, we identified 99 (7·6%) patients with NIHSS≥6 and no intracranial vessel occlusion on computed tomography angiography. The mean age was 67·8 ± 15·4 years and 60 (60·6%) were men. The median baseline NIHSS was nine (6-28). The initial computed tomography head was normal in 79 (79·8%) patients. Dramatic early clinical improvement at 24 h (NIHSS score ≤2 at 24 h or change between baseline and 24 h NIHSS score ≥15 points) was seen in 38 (38·4%) patients. Follow-up scans showed infarcts in 66 (66·7%) patients. Fifty (50·5%) patients received tissue plasminogen activator; one (2%) tissue plasminogen activator-treated patient developed symptomatic intracranial hemorrhage. At three-months; 59 (59·6%) patients were independent (modified Rankin Scale≤2), 34 (34·3%) patients were dependent (modified Rankin Scale 3-5), and six (6·1%) were dead. The factors associated with the unlikelihood of good outcome were higher initial NIHSS (odds ratio 0·86 per additional point, 95% confidence interval 0·77-0·95, P=0·003), and older age (odds ratio 0·95 per additional year, 95% confidence interval 0·92-0·98, P=0·004). Stroke without intracranial occlusions are not a benign entity. Factors that are independently associated with decreased likelihood of a good outcome are higher baseline NIHSS, and older age. Treatment with tissue plasminogen activator is not a predictor of outcome.

Enhancing Recovery After Acute Ischemic Stroke with Donepezil as an Adjuvant Therapy to Standard Medical Care: Results of a Phase IIa Clinical Trial

Our aim was to assess the safety, tolerability, and efficacy signal of early donepezil administration with regard to enhancing recovery in a diverse acute ischemic stroke population. This was a multicenter, single-arm, National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator trial-controlled, modified 2-stage adaptive clinical trial set in 2 tertiary care hospitals in the United States. Adults with ischemic stroke treated within 24 hours after onset of symptoms were included. The intervention studied was donepezil 5 mg/day for 30 days, followed by an increase to 10 mg/day for 60 days. Our main outcome measures included treatment-related adverse events and side effects. The primary favorable outcome was a 90-day National Institutes of Health Stroke Scale (NIHSS) score ≤1. Neurologic, cognitive, functional, and psychological outcomes were assessed longitudinally. Thirty-three adults (median age 66 years; 59% female; 39% received tissue plasminogen activator) initiated treatment with donepezil. There were no treatment-related serious adverse events. Three participants (9%) discontinued donepezil because of side effects and 3 participants (9%) required a reduction to 5 mg/day after titration to 10 mg/day. Fifteen participants (45%) had a favorable outcome (NIHSS score ≤1 at day 90), and the study met prespecified criteria for continuing to a randomized trial (P < .10). Statistically significant improvements from baseline were observed with several secondary cognitive measures, including the Trail Making Tests and Mini-Mental State Exam (P < .01 for both). Adjuvant donepezil therapy initiated within 24 hours of acute ischemic stroke was safe and tolerated at 5 mg/day to 10 mg/day. The study met a priori criteria to move forward with a randomized clinical trial.

Infection Stops Here

Infection Stops Here

Influence of thrombolytic therapy on early and long term leftventricular systolic function in patients with ST-segment elevation myocardial infarction

Background and objectives: Left ventricular systolic dysfunction complicating acute myocardial infarction are responsible for significant morbidity and mortality. This study to assess the effect of thrombolytic therapy on the left ventricular systolic function during the first week and a year after ST- elevation myocardial infarction. Methods: In a study of 56 patients with first ST-Segment elevation myocardial infarction (42 men and 14 women; age range, 42-89 years (mean, 61 ± 10 ), who had been admitted to the Coronary Care Unit at Hawler Teaching Hospital from May 2008 to May 2009. study done to assess the left ventricular systolic function during the first week and first year after ST-elevation myocardial infarction. Twenty one patients received tissue plasminogen activator (Alteplase) 12 hour after the onset of symptoms labeled as group-I, the remaining patients (35), had no chance to receive thrombolytic therapy labeled as group II. Results: In group I the mean ejection fraction improved significantly from 51.6±9.4 during the first week to 55.14±11, P=0.034, at first year after acute myocardial infarction, while in group II there was no significant difference of mean ejection fraction during the first week (45.97±12.2) and first year of acute myocardial infarction (46.1±13.2),P=0.5. Conclusions: Thrombolytic therapy has a beneficial effect on left ventricular systolic function detected by echocardiography at the end of the first year of ST-elevation myocardial infarction

Clinical Outcomes among Stroke Patients Receiving Tissue Plasminogen Activator Therapy Beyond the 3-hour Time Window

Tissue plasminogen activator therapy (t-PA) is associated with improved neurologic outcomes and reduced disability from ischemic stroke. The current guidelines stipulate that patients receive t-PA within 3 hours of symptom onset. However, actual practice patterns vary, and little is known about patient outcomes when t-PA is received outside of the recommended time window. We examined mean length of hospital stay, t-PA-related complications, and in-hospital death by time of t-PA administration in North Carolina Stroke Care Collaborative (NCSCC) patients. The NCSCC includes 53 hospitals that enroll patients presenting with stroke-like symptoms. Of 40,907 patients enrolled between January 2005 and February 2010, 1070 (2.6%) received t-PA. Of these, 88.2% received t-PA within 3 hours of symptom onset ("early") and 30.3% received t-PA between 3 and 6 hours after symptom onset ("late"). Unadjusted mean length of stay (days) was longer among early patients (5.0 days; 95% confidence interval [CI], 4.7-5.3) than late patients (3.6 days; 95% CI, 3.1-4.2). t-PA-related complications were similar among early (7.0%; 55/781) and late patients (6.7%; 7/102; P = .89). The proportion of in-hospital deaths was similar among late (10.5%) and early patients (12.0%). We used multivariable logistic regression to estimate odds ratios (ORs) and 95% CIs for the associations between late t-PA status and patient outcomes. In models controlling for age, race, sex, arrival mode, and ambulatory status on admission, late t-PA was not associated with increased odds of complications or in-hospital deaths (OR, 0.89; 95% CI, 0.49-1.62). The risks and benefits of expansion of the t-PA time window in stroke patients merit further investigation.

Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L)

Induced hypothermia is a promising neuroprotective therapy. We studied the feasibility and safety of hypothermia and thrombolysis after acute ischemic stroke. Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L) was a randomized, multicenter trial of hypothermia and intravenous tissue plasminogen activator in patients treated within 6 hours after ischemic stroke. Enrollment was stratified to the treatment time windows 0 to 3 and 3 to 6 hours. Patients presenting within 3 hours of symptom onset received standard dose intravenous alteplase and were randomized to undergo 24 hours of endovascular cooling to 33°C followed by 12 hours of controlled rewarming or normothermia treatment. Patients presenting between 3 and 6 hours were randomized twice: to receive tissue plasminogen activator or not and to receive hypothermia or not. Results- In total, 59 patients were enrolled. One patient was enrolled but not treated when pneumonia was discovered just before treatment. All 44 patients enrolled within 3 hours and 4 of 14 patients enrolled between 3 to 6 hours received tissue plasminogen activator. Overall, 28 patients randomized to receive hypothermia (HY) and 30 to normothermia (NT). Baseline demographics and risk factors were similar between groups. Mean age was 65.5±12.1 years and baseline National Institutes of Health Stroke Scale score was 14.0±5.0; 32 (55%) were male. Cooling was achieved in all patients except 2 in whom there were technical difficulties. The median time to target temperature after catheter placement was 67 minutes (Quartile 1 57.3 to Quartile 3 99.4). At 3 months, 18% of patients treated with hypothermia had a modified Rankin Scale score of 0 or 1 versus 24% in the normothermia groups (nonsignificant). Symptomatic intracranial hemorrhage occurred in 4 patients (68); all were treated with tissue plasminogen activator <3 hours (1 received hypothermia). Six patients in the hypothermia and 5 in the normothermia groups died within 90 days (nonsignificant). Pneumonia occurred in 14 patients in the hypothermia and in 3 of the normothermia groups (P=0.001). The pneumonia rate did not significantly adversely affect 3 month modified Rankin Scale score (P=0.32). This study demonstrates the feasibility and preliminary safety of combining endovascular hypothermia after stroke with intravenous thrombolysis. Pneumonia was more frequent after hypothermia, but further studies are needed to determine its effect on patient outcome and whether it can be prevented. A definitive efficacy trial is necessary to evaluate the efficacy of therapeutic hypothermia for acute stroke.

Minocycline to improve neurologic outcome in stroke (MINOS): a dose-finding study.

Minocycline is a promising anti-inflammatory and protease inhibitor that is effective in multiple preclinical stroke models. We conducted an early phase trial of intravenous minocycline in acute ischemic stroke. Following an open-label, dose-escalation design, minocycline was administered intravenously within 6 hours of stroke symptom onset in preset dose tiers of 3, 4.5, 6, or 10 mg/kg daily over 72 hours. Minocycline concentrations for pharmacokinetic analysis were measured in a subset of patients. Subjects were followed for 90 days. Sixty patients were enrolled, 41 at the highest dose tier of 10 mg/kg. Overall age (65±13.7 years), race (83% white), and sex (47% female) were consistent across the doses. The mean baseline National Institutes of Health Stroke Scale score was 8.5±5.8 and 60% received tissue plasminogen activator. Minocycline infusion was well tolerated with only 1 dose limiting toxicity at the 10-mg/kg dose. No severe hemorrhages occurred in tissue plasminogen activator-treated patients. Pharmacokinetic analysis (n=22) revealed a half-life of approximately 24 hours and linearity of parameters over doses. Minocycline is safe and well tolerated up to doses of 10 mg/kg intravenously alone and in combination with tissue plasminogen activator. The half-life of minocycline is approximately 24 hours, allowing every 24-hour dosing. Minocycline may be an ideal agent to use with tissue plasminogen activator.

Risk of Thrombolytic Therapy for Acute Ischemic Stroke in Patients With Current Malignancy

Little is known about the risk of thrombolysis in patients with malignancy, because these patients have been excluded from most clinical trials. We reviewed our acute ischemic stroke (AIS) database for clinical outcomes and complications in patients with current malignancy (CM) who received thrombolytic therapy. Consecutive AIS patients receiving thrombolysis between January 2003 and December 2006 were retrospectively abstracted in accordance with the American Stroke Association's Get With the Guidelines-Stroke definitions and charts were reviewed for history of malignancy. Patients with brain metastases did not receive tissue plasminogen activator (tPA). Stepwise logistic regression was used to identify independent predictors of in-hospital mortality. Of 308 AIS patients treated with thrombolytic therapy, 210 (68%) received intravenous (IV) tPA only, 41 (13%) received IV tPA plus intra-arterial therapy (IAT), and 57 (18%) received IAT only. Eighteen patients (5.8%) had a CM, and 26 patients (8.4%) had a remote history of malignancy. Patients with CM had a higher in-hospital mortality (38.9% vs 19.7 %; P=.05) and were more likely to have died due to worsening medical comorbidity (71.4% vs 9.6%; P < .001). The rate of symptomatic intracranial hemorrhage (ICH) was similar in the 2 groups (5.6% vs 2.7%; P=.47). In multivariate analysis, the only independent predictors of mortality were National Institutes of Health Stroke Scale score, history of hypertension, and smoking. CM was not independently associated with increased in-hospital mortality following thrombolysis. Mortality was attributable largely to medical comorbidities, not to symptomatic ICH. Our data suggest that thrombolysis may be a reasonable option for patients with malignancy who have acceptable medical comorbidities and performance status. Further research is warranted.

Effective Post-insult Neuroprotection by a Novel Ca2+/ Calmodulin-dependent Protein Kinase II (CaMKII) Inhibitor

Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) is a major mediator of physiological glutamate signaling involved in higher brain functions. Here, we show CaMKII involvement in pathological glutamate signaling relevant in stroke. The novel inhibitor tatCN21 was neuroprotective even when added hours after glutamate insults. By contrast, the "traditional" inhibitor KN93 attenuated excitotoxicity only when present during the insult. Both inhibitors efficiently blocked Ca(2+)/CaM-stimulated CaMKII activity, CaMKII interaction with NR2B and aggregation of CaMKII holoenzymes. However, only tatCN21 but not KN93 blocked the Ca(2+)-independent "autonomous" activity generated by Thr-286 autophosphorylation, the hallmark feature of CaMKII regulation. Mutational analysis further validated autonomous CaMKII activity as the drug target crucial for post-insult neuroprotection. Overexpression of CaMKII wild type but not the autonomy-deficient T286A mutant significantly increased glutamate-induced neuronal death. Maybe most importantly, tatCN21 also significantly reduced infarct size in a mouse stroke model (middle cerebral arterial occlusion) when injected (1 mg/kg intravenously) 1 h after onset of arterial occlusion. Together, these data demonstrate that inhibition of autonomous CaMKII activity provides a promising therapeutic avenue for post-insult neuro-protection after stroke.

Hospitalized Stroke Surveillance in the Community of Durango, Mexico

Vascular conditions are becoming the greatest cause of morbidity and mortality in developing countries. Few studies exist in Latin America. We aimed to perform a rigorous stroke surveillance study in Durango, Mexico. Active and passive surveillance were used to identify all patients with potential stroke presenting to Durango Municipality hospitals from August 2007 to July 2008. Exclusion criteria were subjects younger than 25 years old, stroke attributable to head trauma, and non-Durango Municipality residents. Brain Attack Surveillance in Durango-trained neurologists validated cases as stroke using source documentation. Stroke hospitalization rates were defined to include patients examined in the emergency department or admitted to the hospital. Abstractors identified 435 potential cases; 309 (71%) were validated as stroke. Of the validated stroke cases, the median age was 71 and 49% were female. Subtypes were 61.5% ischemic stroke, 20.7% intracerebral hemorrhage, 7.4% subarachnoid hemorrhage, and 10.4% undetermined. Overall initial NIHSS was a median of 11 (interquartile range, 7-17); in-hospital mortality was 39%. When adjusted to the world population, the age-adjusted hospitalization rate of first-ever stroke was 118.2 per 100 000; rates by type were: ischemic stroke, 69.1 (95% CI, 57.5-80.7); intracerebral hemorrhage, 26.7 (95% CI, 19.6-33.8); subarachnoid hemorrhage, 9.5 (95% CI, 5.3-13.8); and unknown, 12.3 (95% CI, 7.4-17.3). Of 190 patients with validated ischemic stroke, 44.2% received lipid testing and 7.4% received carotid imaging and echocardiography; 1.1% received tissue plasminogen activator. To our knowledge, this is the first estimate of stroke hospitalization rates in a Mexican community and it provides information important for design of interventions to prevent and treat stroke. This information is critical to reduce Mexico's stroke burden.

A Review of Barriers to Thrombolytic Therapy

Despite stroke being the third leading cause of death and a leading cause of disability in the United States, less than 7% of stroke survivors receive tissue plasminogen activator (tPA) in the treatment of acute stroke. The purpose of this review was to determine what research is available on barriers to tPA use and to determine gaps in the literature. A search of the literature was conducted using Medline, Cumulative Index to Nursing and Allied Health Literature, Embase, and PubMed. Keywords were stroke, emergency, nursing, thrombolytics, cerebrovascular accident, ischemia, intervention, tPA, and barriers. Pertinent references from articles obtained were searched as well. The search yielded 45 articles for review. Barriers to tPA use were found in both prehospital and in-hospital settings. Prehospital delays were related to contacting primary care physicians, mode of arrival to the hospital, and survivors' lack of knowledge regarding stroke. Sources of in-hospital delays included non-stroke center status, lack of training of emergency department staff, delays in computed tomography scans, and poor understanding regarding priority stroke treatment (e.g., mild or improving symptoms and disparities related to age, gender, and race). Future research to evaluate the impact of nursing care and attitudes toward stroke patients on the administration of tPA is recommended.

Hospital Care for Patients Experiencing Weekend vs Weekday Stroke

We examined the quality and aggressiveness of care for the treatment of acute ischemic stroke (AIS) on weekends vs weekdays. Acute ischemic stroke is a leading cause of death and disability in the United States, and aggressive treatment must be provided within 3 hours for optimal patient outcomes. Because of this short treatment window for the administration of tissue plasminogen activator, patients need around-the-clock access to high-quality and aggressive care. To determine whether there is a difference in the quality or aggressiveness of care for patients experiencing AIS on weekends vs weekdays. Retrospective study. Academic research. Patients We conducted a retrospective study of patients with AIS in Virginia. Two logistic regression analyses assessed the relationship between weekend admission and quality and aggressiveness of care, while controlling for appropriate patient-level and hospital-level control variables. A propensity score stratification approach controlled for selection bias. Treatment with tissue plasminogen activator and in-hospital mortality. Patients with AIS admitted on weekends are more likely to receive tissue plasminogen activator than those admitted on weekdays (P < .05). No statistically significant difference was noted in patient mortality based on day of admission (P >or= .05). We detected no difference in the likelihood to seek hospital care on weekends between patients with AIS vs patients with hemorrhagic stroke. Patients experiencing AIS are more likely to receive tissue plasminogen activator on weekends than on weekdays. Patients experiencing AIS who are admitted on weekends are no more likely to die than those who are admitted on weekdays. Further research is necessary to understand differences in weekend vs weekday care.

Adjunctive treatment with ticagrelor, but not clopidogrel, added to tPA enables sustained coronary artery recanalisation with recovery of myocardium perfusion in a canine coronary thrombosis model

Reperfusion therapy for myocardial infarction is limited by significant re-occlusion rates and less-than-optimal myocardial tissue perfusion. It was the objective of this study to assess and compare the effect of ticagrelor, the first reversibly binding oral P2Y12 receptor antagonist, with that of clopidogrel, in conjunction with thrombolytic therapy, on platelet aggregation, thrombus formation, and myocardial perfusion in a canine model. Thrombus formation was induced by electrolytic injury and blood flow was measured with a Doppler ultrasonic flowmeter. All animals received tissue plasminogen activator (tPA) (1 mg/kg over 20 min); 10 animals received clopidogrel (10 mg/kg IV bolus over 5 min), 10 animals received ticagrelor initiated with a 1-min bolus (75 microg/kg/min), followed by continuous infusion (10 microg/kg/min) for 2 h, and 10 animals received IV saline. Re-occlusion rate and cyclic flow variation decreased with ticagrelor compared to saline groups (p<0.05). Adenosine phosphate (ADP)-induced platelet aggregation decreased with ticagrelor (1.9% +/- 2.67) and clopidogrel (1.11% +/- 2.0) vs. saline (26.3% +/- 23.5, p<0.05) at the end of adjunctive therapy. Bleeding time increased in the clopidogrel compared to the ticagrelor group (p=0.01). Infarct size was reduced with ticagrelor compared to the clopidogrel and saline groups (p<0.05). Blood flow remained significantly below baseline values at 20 min after tPA administration in the saline and clopidogrel groups but not in the ticagrelor group. In conclusion, in a dog coronary thrombosis model, ticagrelor blocks ADP-induced platelet activation and aggregation; prevents platelet-mediated thrombosis; prolongs reperfusion time and reduces re-occlusion and cyclic flow variation; and significantly decreases infarct size and rapidly restores myocardial tissue perfusion.

Case files of the medical toxicology fellowship at banner good samaritan medical center in Phoenix, AZ: A non-warfarin anticoagulant overdose

A 50-year-old man presented to the emergency department (ED) following an overdose of his "blood thinners." The patient had become increasingly depressed over financial concerns, prompting a suicide attempt. He declined to provide any details regarding his current medications or his past medical history. A review of the computerized medical record, however, revealed he had a Factor V Leiden mutation with multiple venothromboembolic events. He previously had an inferior vena cava filter placed, and had received tissue plasminogen activator (tPA) for a cerebrovascular accident. A toxicology consult was obtained in the ED.

Spontaneous splenic rupture in a patient receiving thrombolytic therapy

We describe the case of a 67-year-old female patient with a history of femoral-distal bypass graft with sudden onset of unremitting leg pain, who had recently received tissue plasminogen activator (t-PA). The patient reported non-compliance with her warfarin regimen. Angiography revealed occlusion of the bypass graft. Infusion of t-PA was performed via a right femoral artery approach. On hospital day two, the patient developed nausea and abdominal pain with associated hypotension. A CT scan showed a massive intra-abdominal and pelvic free fluid consistent with blood. The spleen was enlarged and fluid noted around the liver. At laparotomy, a grade III splenic laceration at the hilum was identified and a splenectomy performed. The patient recovered completely. Although rare, spontaneous splenic rupture should be considered in the differential diagnosis of patients undergoing thrombolytic therapy who develop signs of hemodynamic instability.