TURN Score Predicts 24-Hour Cerebral Edema After IV Thrombolysis.

BACKGROUND AND PURPOSE: Cerebral edema is associated with poor outcome after IV thrombolysis. We recently described the TURN score (Thrombolysis risk Using mRS and NIHSS), a predictor of severe outcome after IV thrombolysis. Our purpose was to evaluate its ability to predict 24-h cerebral edema. METHODS: We retrospectively analyzed data from 303 patients who received IV rt-PA during the NINDS rt-PA trial. Measures of brain swelling included edema, mass effect and midline shift assessed at baseline, at 24 h and new onset at 24 h. Outcome was assessed using intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), 90-day severe outcome, and 90-day mortality. Statistical associations were assessed by logistic regression reporting odds ratios (OR) and by areas under the receiver operating characteristic curves (AUROC). RESULTS: Baseline brain swelling did not predict poor outcome; however, 24-h brain swelling predicted ICH (OR 5.69, P < 0.001), sICH (OR 9.50, P = 0.01), 90-day severe outcome (OR 7.10, P < 0.001), and 90-day mortality (OR 5.65, P = 0.01). Similar results were seen for new brain swelling at 24 h. TURN predicted 24-hour brain swelling (OR 2.5, P < 0.001; AUROC 0.69, 95 % CI 0.63-0.75) and new brain swelling at 24 h (OR 2.1, P < 0.001; AUROC 0.67, 95 % CI 0.61-0.73). CONCLUSIONS: Cerebral edema at 24 h is associated with poor outcome and 90-day mortality. TURN predicts ischemic stroke patients who will develop 24-h cerebral edema after IV thrombolysis.

On- versus Off-Hour Patient Cohorts at a Primary Stroke Center: Onset-to-Treatment Duration and Clinical Outcomes after IV Thrombolysis.

BACKGROUND: The symptom onset-to-treatment (OTT) duration predicts symptomatic intracerebral hemorrhage (sICH) and adverse outcomes after ischemic stroke. Previous studies found disparities in OTT durations and clinical outcomes between stroke patients with symptom onset during on-hours versus off-hours, which led to the initiation of nationwide efforts to provide consistent 24-hour stroke care. GOAL: Our objective is to compare OTT durations and clinical outcomes in ischemic stroke patients whose symptoms originated during on- versus off-hours at a primary stroke center. METHODS: We analyzed clinical data from 210 consecutive patients receiving intravenous recombinant tissue plasminogen activator therapy between January 2009 and December 2013 at Yale-New Haven Stroke Center, a primary stroke center. Stroke severity was assessed by baseline National Institutes of Health Stroke Scale (NIHSS) scores. Clinical outcomes were assessed by presence of sICH and by stroke-related fatalities. OTT durations and clinical outcomes were compared using Mann-Whitney tests, 2-sample tests of proportions, and 2-sample t-tests after testing for equal variance. FINDINGS: We found no significant differences in OTT durations between on-hour and off-hour patient cohorts (137 minutes versus 145 minutes, P = .53). There were also no differences in stroke severity (mean NIHSS score 12.4 versus 11.3, P = .27), sICH rates (4.6% versus 6.5%, P = .56), or stroke fatality rates (9.2% versus 9.8%, P = .89) between the 2 cohorts. CONCLUSIONS: Our results represent progress in emergency response and acute stroke care, and reinforce ongoing nationwide efforts to increase stroke awareness and provide consistent quality care for patients with acute stroke.

TURN Score Predicts 90-day Outcome in Acute Ischemic Stroke Patients After IV Thrombolysis.

BACKGROUND AND PURPOSE: We developed the TURN score for predicting symptomatic intracerebral hemorrhage (sICH) after IV thrombolysis. Our purpose was to evaluate its ability to predict 90-day outcome. METHODS: We retrospectively analyzed data from 303 patients who received IV rt-PA during the NINDS rt-PA trial. Severe outcome was defined as 90-day modified Rankin scale (mRS) scores ≥5, 90-day Barthel index (BI) scores <60 and 90-day Glasgow Outcome Scale (GOS) scores >2. Excellent outcome was defined as 90-day mRS scores ≤1, 90-day BI scores ≥95 and 90-day GOS scores = 1. Agreement between TURN and 90-day outcome was assessed by univariate logistic regression reporting odds ratios (OR) and by areas under the receiver operating characteristic curves (AUROC). TURN was also compared with 6 other scores for predicting sICH or severe outcome. RESULTS: TURN predicted 90-day mRS ≥5 with OR 5.73, 95% confidence interval (3.60, 9.10), P < 0.001 and AUROC 0.83, 95% confidence interval (0.77, 0.89). TURN also predicted 90-day mRS ≤1 with OR 5.24, 95% confidence interval (3.43, 7.99), P < 0.001 and AUROC 0.80, 95% confidence interval (0.74, 0.85). TURN predicted 90-day mRS ≥5 with OR significantly higher than DRAGON (2.30, P = 0.01), ASTRAL (1.18, P < 0.001), HAT (2.89, P = 0.05) and SEDAN (2.16, P = 0.01), and with AUROC significantly higher than SPAN-100 (0.64, P < 0.001) and SEDAN (0.71, P = 0.01). Likewise, TURN predicted 90-day mRS ≤1 with OR significantly higher than Stroke-TPI (2.89, P = 0.05), DRAGON (2.29, P = 0.01), ASTRAL (1.15, P < 0.001), HAT (2.71, P = 0.04) and SEDAN (2.15, P = 0.01), and with AUROC significantly higher than SPAN-100 (0.58, P < 0.001) and SEDAN (0.70, P = 0.01). Similar results were obtained using 90-day BI and 90-day GOS scores. CONCLUSIONS: TURN predicted 90-day outcome with comparable or better accuracy compared to several existing clinical scores.

Comparison of 8 scores for predicting symptomatic intracerebral hemorrhage after IV thrombolysis.

BACKGROUND: Intracerebral hemorrhage is a feared complication of IV thrombolytic (rt-PA) therapy. In recent years, at least 8 clinical scores have been proposed to predict either adverse outcome or symptomatic intracerebral hemorrhage (sICH) in patients undergoing rt-PA therapy. The purpose of this study was to evaluate the ability of these 8 scores to predict sICH in an independent clinical dataset. METHODS: Clinical data was analyzed from consecutive patients (n = 210) receiving IV rt-PA therapy from January 2009 to December 2013 at Yale-New Haven Hospital. Eight scores were calculated for each patient: Stroke-TPI, DRAGON, SPAN-100, ASTRAL, PRS, HAT, SEDAN, and SITS-ICH. sICH was defined according to the NINDS study criteria. Univariate logistic regression was performed using each score as an independent variable and sICH as the dependent variable. Goodness of fit was tested by Receiver operating characteristic (ROC) analysis and by Hosmer-Lemeshow statistics. RESULTS: sICH occurred in 12 patients (5.71 %) after IV rt-PA treatment. Only 4 scores predicted sICH with good accuracy (ROC area >0.7): DRAGON 0.76 (0.63, 0.89); Stroke-TPI 0.74 (0.61, 0.87); ASTRAL 0.72 (0.59, 0.86); and HAT 0.70 (0.55, 0.85), with odds ratios as follows: Stroke-TPI, 1.91 (1.26, 2.90); HAT, 1.67 (1.06, 2.62); DRAGON, 1.66 (1.21, 2.30); and ASTRAL, 1.10 (1.03, 1.16). CONCLUSIONS: Three scores showed good agreement with sICH: DRAGON, Stroke-TPI, and HAT with odds ratios substantially greater than 1. Stroke-TPI and HAT additionally benefited from low computational complexity and therefore performed best overall. Our results demonstrate the utility of clinical scores as predictors of sICH in acute ischemic stroke patients undergoing IV thrombolytic therapy.

TURN: A Simple Predictor of Symptomatic Intracerebral Hemorrhage After IV Thrombolysis.

BACKGROUND: IV Thrombolysis (rt-PA) for ischemic stroke treatment carries a substantial risk for symptomatic intracerebral hemorrhage (sICH). Our purpose was to develop a computationally simple and accurate sICH predictor METHODS : Our derivation dataset consisted of 210 ischemic stroke patients receiving IV rt-PA from January 2009 until July 2013 at Yale-New Haven Hospital. Our validation dataset included 303 patients who received IV rt-PA during the NINDS rt-PA trial. Independent sICH predictors were identified by logistic regression and combined to form the TURN score. Predictive ability and goodness of fit were quantified by odds ratios (OR) and areas under the receiver operating characteristic curve (AUROC). RESULTS: 3 out of 17 clinical parameters were identified as independent predictors of sICH: prestroke mRS score (OR 1.54, P = 0.02), baseline NIHSS score (OR 1.13, P = 0.002), and platelet count (OR 0.99, P = 0.04). We combined these three parameters to form the TURNP score. For added simplicity, prestroke mRS score and baseline NIHSS score alone were also combined to form the TURN score, and predicted sICH without a significant drop in OR or AUROC. CONCLUSIONS: We developed a new score for predicting sICH after IV thrombolysis. Our score is simple and with acceptable accuracy, making it ideal for use in the hyperacute stroke setting.

Cohort-Based Identification of Predictors of Symptomatic Intracerebral Hemorrhage After IV Thrombolysis.

INTRODUCTION: Symptomatic intracranial hemorrhage (sICH) is a serious complication of IV rt-PA therapy after acute ischemic stroke. Independent sICH predictors have been previously derived using case-control studies. Here we utilized a novel cohort-based comparison to identify additional independent predictors of sICH. METHODS: We included 210 patients receiving IV rt-PA therapy from January 2009 through December 2013 at the Yale-New Haven Stroke Center. Clinical parameters were compared using Mann-Whitney tests, two-sample tests of proportions and two-sample t tests. Logistic regression was performed using sICH as the dependent variable. Predictive ability was assessed using areas under the receiver operating characteristic (ROC) curve. RESULTS: sICH rates were lowest from 2010 to 2012 and comprised the low sICH cohort (2.0 % sICH), compared to the high sICH cohort from 2009 to 2013 (9.2 % sICH, P = 0.025). Patients in the low sICH cohort had significantly more visual field deficits (38.6 vs. 24.8 %, P = 0.03) and decreased levels of consciousness (62.4 vs. 39.4 %, P < 0.001), but fewer hyperdense MCA signs (5 vs. 13.8 %, P = 0.03) and early CT hypodensities (14.9 vs. 29.4 %, P = 0.01). These four parameters together predicted sICH modestly (area under ROC curve 0.66, odds ratio 2.72, P = 0.03) CONCLUSIONS: Using a novel cohort-based approach, we identified two new independent predictors of sICH after IV rt-PA therapy: the presence of the hyperdense MCA sign and early CT hypodensities. Novel methods are needed to reduce the risk of sICH for patients receiving antithrombolytic therapy for ischemic stroke.

Modest association between the discharge modified Rankin Scale score and symptomatic intracerebral hemorrhage after intravenous thrombolysis.

BACKGROUND: Thirty- and 90-day modified Rankin Scale (mRS) scores are used to monitor adverse outcome or symptomatic intracerebral hemorrhage (sICH) in ischemic stroke patients after intravenous (IV) thrombolytic therapy. Discharge mRS scores are more readily available and could serve as a proxy for 30- or 90-day mRS data. Our goal was to evaluate agreement between the discharge mRS score and sICH. Additionally, we tested for correlations between the discharge mRS score and 8 clinical scores developed to predict sICH or adverse outcomes based on 90-day mRS data. METHODS: Clinical data were analyzed from 210 patients receiving IV thrombolysis from January 2009 till December 2013 at the Yale New Haven Hospital. Agreement between sICH and the discharge mRS score was assessed using linear kappa. Eight clinical scores were calculated for each patient and compared with the discharge mRS score by univariate logistic regression. Goodness of fit was tested by receiver operating characteristic (ROC) analysis and by Hosmer-Lemeshow statistics. RESULTS: We found only modest agreement between sICH and unfavorable discharge mRS scores (mRS ≥ 5), with kappa .22, P = .0001. All 8 clinical scores tested showed good agreement with discharge mRS score of 5 or more (ROC area >.7). CONCLUSIONS: The discharge mRS score shows only modest agreement with sICH and therefore cannot be recommended as a proxy for 30- or 90-day mRS data. However, the discharge mRS score correlates strongly with clinical scores predicting long-term adverse outcome; therefore, assessment of discharge mRS scores may be of some clinical benefit.

Missed opportunities for recognition of ischemic stroke in the emergency department.

INTRODUCTION: Evidence suggests that a significant number of patients discharged from the hospital with a diagnosis of ischemic stroke are not identified as having a stroke on admission. Those presenting with "nontraditional" stroke symptoms may be less likely to be diagnosed correctly. We aimed to establish whether there was an association between symptom presentation and diagnostic accuracy and to identify the type and frequency of nontraditional symptoms that resulted in a missed diagnosis in the emergency department. METHODS: We reviewed the medical records of 189 patients discharged with a diagnosis of ischemic stroke from Yale-New Haven Hospital. We performed χ(2) analysis to determine whether an association existed between symptom presentation and diagnostic accuracy. Descriptive statistics allowed us to identify symptom type and frequency in patients with a missed diagnosis. RESULTS: A diagnosis of suspected stroke was missed in 15.3% of patients who presented to the emergency department. We found a strong association (P < 0.0001) between symptom presentation and diagnostic accuracy. Of the patients presenting with any "traditional" symptom, 4% were missed. Of those presenting with only nontraditional symptoms, 64% were missed (odds ratio, 43.4; 95% confidence interval, 15.0-125.4). Nontraditional symptoms included generalized weakness, altered mental status, altered gait, and dizziness. DISCUSSION: In order to facilitate appropriate management of patients with ischemic stroke, emergency nurses must be aware that symptom presentation is highly variable. Patients presenting with nontraditional symptoms may benefit from an immediate and comprehensive neurological evaluation.

Sustained In-Vivo Release of Triptorelin Acetate from a Biodegradable Silica Depot: Comparison to Pamorelin® LA.

Triptorelin acetate was encapsulated into silica microparticles by spray-drying a mixture of colloidal silica sol and triptorelin acetate solution. The resulting microparticles were then combined with another silica sol containing silica nanoparticles, which together formed an injectable silica-triptorelin acetate depot. The particle size and surface morphology of the silica-triptorelin acetate microparticles were characterized together with the in vitro release of triptorelin, injectability and rheology of the final injectable silica-triptorelin acetate depot. In vivo pharmacokinetics and pharmacodynamics of the silica-triptorelin acetate depot and Pamorelin® were evaluated and compared in Sprague-Dawley male rats after subcutaneous administration. Serum samples up to 91 days were collected and the plasma concentrations of triptorelin and testosterone were analyzed with ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In vivo pharmacokinetics showed that injections of the silica-triptorelin acetate depot gave 5-fold lower Cmax values than the corresponding Pamorelin® injections. The depot also showed a comparable sustained triptorelin release and equivalent pharmacodynamic effect as the Pamorelin® injections. Detectable triptorelin plasma concentrations were seen with the depot after the 91-day study period and testosterone plasma concentrations remained below the human castration limit for the same period.

Risk rtPA: An iOS mobile application based on TURN for predicting 90-day outcome after IV thrombolysis.

OBJECTIVE: We recently developed Thrombolysis risk Using mRS and NIHSS (TURN), a simple score using only prestroke mRS scores and admission NIHSS scores to predict 90-day outcome after IV thrombolysis in ischemic stroke patients. Our purpose was to develop and test a mobile application for utilization of TURN at the bedside. METHODS: We developed Risk rtPA, an iOS mobile application based on TURN for prediction of 90-day excellent and severe outcome after IV thrombolysis. Excellent outcome was defined as 90-day mRS≤1. Severe outcome was defined as 90-day mRS≥5. Predictors for excellent and severe outcome were calculated using the inverse logit of -TURN and TURN respectively. We retrospectively validated our mobile application using data from 303 patients who received IV rt-PA during the NINDS rt-PA trial. Sensitivity and specificity analyses were performed using receiver operating characteristic (ROC) curves. RESULTS: Prediction of excellent and severe outcome using Risk rtPA followed an S-shaped curve as expected. We confirmed this finding using data from the NINDS trial. Cutoffs selected after ROC analysis predicted severe outcome with sensitivity of 94.4% and specificity of 52.2%, and excellent outcome with specificity of 83.9% and sensitivity of 61.2%. CONCLUSION: The Risk rtPA mobile application predicted 90-day excellent and severe outcome in most clinically relevant cases. This mobile application brings the TURN score to the bedside for prediction of 90-day outcome in ischemic stroke patients being evaluated for IV thrombolysis.

Validation of TURN, a simple predictor of symptomatic intracerebral hemorrhage after IV thrombolysis.

OBJECTIVE: We recently described TURN (Thrombolysis risk Using mRS and NIHSS), a computationally simple tool for predicting symptomatic intracerebral hemorrhage (sICH) after IV thrombolysis (rt-PA). Our objective was to compare TURN to existing scores for predicting sICH. METHODS: Our internal dataset consisted of 210 ischemic stroke patients receiving IV rt-PA from January 2009 until July 2013 at Yale New Haven Hospital. Our external dataset included 303 patients who received IV rt-PA during the NINDS rt-PA trial. Predictive ability and goodness of fit were quantified by odds ratios (OR) and areas under the receiver operating characteristic curve (AUROC), and compared using unequal variance two-sample t-tests. RESULTS: TURN predicted sICH with a higher OR than ASTRAL in the internal dataset (2.72 versus 1.10, P=0.05). We found no other significant differences in OR or AUROC between TURN and other scores in both datasets. CONCLUSION: Despite its computational simplicity, TURN predicts sICH with accuracy comparable to existing scores.