Abstract TMP5: Secondary Analysis of Eptifibatide Plus Full Dose rt-PA in Ischemic Stroke

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Opeolu Adeoye ◽  
Heidi Sucharew ◽  
Jane Khoury ◽  
Pamela Schmit ◽  
Joseph Broderick ◽  
...  

Background: The Phase 2 Combined approach to Lysis utilizing Eptifibatide And Rt-PA in Acute Ischemic Stroke - Full Dose Regimen (CLEAR-FDR) trial was a single arm trial that demonstrated the safety of full dose (0.9mg/kg) rt-PA plus eptifibatide in AIS patients treated with rt-PA within three hours of symptom onset. Interventional Management of Stroke (IMS) III randomized AIS patients to rt-PA plus endovascular therapy versus standard r-tPA. Albumin in Acute Stroke (ALIAS) Part 2 randomized patients to albumin±rt-PA versus saline±rt-PA. We compared outcomes in CLEAR-FDR patients to propensity score-matched rt-PA only subjects in ALIAS Part 2 and IMS. Methods: All datasets were restricted to subjects with baseline modified Rankin score (mRS) of 0 or 1. Controls were selected using propensity score matching of CLEAR-FDR subjects and rt-PA only subjects from both IMS III and ALIAS. Age, gender, race, baseline mRS, baseline NIHSS score, and time from stroke onset to rt-PA were included in the logistic model used to generate a propensity score for each subject. The greedy matching algorithm was then used to match 1:3. The primary outcome was 90-day severity-adjusted mRS dichotomization based on baseline NIHSS. Secondary outcomes were 90-day mRS dichotomized as excellent (mRS 0-1); favorable (mRS 0-2); and, nonparametric analysis of the ordinal mRS. Results: Eighteen CLEAR-FDR subjects were matched with 52 controls. Median age in CLEAR-FDR and control subjects was 67 and 68 years respectively. Median NIHSS in both CLEAR-FDR and control subjects was 11. At 90 days, CLEAR-FDR subjects had a nonsignificant greater proportion of patients with a favorable primary outcome (61% versus 38%; unadjusted RR 1.59; 95%CI 0.96-2.63; P=0.10). Secondary outcomes also favored CLEAR-FDR subjects: excellent outcomes - 67% versus 38% (RR 1.73; 95%CI 1.08-2.79; P=0.04); favorable outcomes - 67% versus 58% (RR 1.16; 95%CI 0.77-1.73; P=0.50); and ordinal Cochran-Mantel-Haenszel, P=0.13. Conclusion: The outcomes for combination of full dose rt-PA plus eptifibatide showed a consistent direction of effect in favor of the combination over rt-PA alone. A trial to establish the efficacy of rt-PA plus eptifibatide for improving AIS outcomes is warranted and in the planning stages.

2021 ◽  
pp. 37-43
Author(s):  
Hediyeh Baradaran ◽  
Alen Delic ◽  
Ka-Ho Wong ◽  
Nazanin Sheibani ◽  
Matthew Alexander ◽  
...  

Introduction: Current ischemic stroke risk prediction is primarily based on clinical factors, rather than imaging or laboratory markers. We examined the relationship between baseline ultrasound and inflammation measurements and subsequent primary ischemic stroke risk. Methods: In this secondary analysis of the Multi-Ethnic Study of Atherosclerosis (MESA), the primary outcome is the incident ischemic stroke during follow-up. The predictor variables are 9 carotid ultrasound-derived measurements and 6 serum inflammation measurements from the baseline study visit. We fit Cox regression models to the outcome of ischemic stroke. The baseline model included patient age, hypertension, diabetes, total cholesterol, smoking, and systolic blood pressure. Goodness-of-fit statistics were assessed to compare the baseline model to a model with ultrasound and inflammation predictor variables that remained significant when added to the baseline model. Results: We included 5,918 participants. The primary outcome of ischemic stroke was seen in 105 patients with a mean follow-up time of 7.7 years. In the Cox models, we found that carotid distensibility (CD), carotid stenosis (CS), and serum interleukin-6 (IL-6) were associated with incident stroke. Adding tertiles of CD, IL-6, and categories of CS to a baseline model that included traditional clinical vascular risk factors resulted in a better model fit than traditional risk factors alone as indicated by goodness-of-fit statistics. Conclusions: In a multiethnic cohort of patients without cerebrovascular disease at baseline, we found that CD, CS, and IL-6 helped predict the occurrence of primary ischemic stroke. Future research could evaluate if these basic ultrasound and serum measurements have implications for primary prevention efforts or clinical trial inclusion criteria.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Adam H de Havenon ◽  
Ka-Ho Wong ◽  
J Scott McNally ◽  
Jennifer Majersik

Background: The Multi-Ethnic Study of Atherosclerosis (MESA) is a large prospective epidemiologic study of the clinical factors that can predict transition from asymptomatic to symptomatic cardiovascular disease. Although prior studies have looked at ischemic stroke, they have not systematically examined the relationship between baseline ultrasound and inflammation measurements and subsequent primary stroke risk. Methods: The primary outcome is incident ischemic stroke during follow-up. The predictors are 9 ultrasound-derived measurements and 5 serum measurements related to inflammation. We fit Cox models to ischemic stroke and adjusted for patient age, hypertension, diabetes, total cholesterol, and smoking. Using DeLong’s method, we compared the AUC of the baseline adjusted model to the AUC of the model with predictor variables that were significant in the Cox models, to determine if they improved stroke prediction. Results: We included 6,095 patients with an average age of 61.9 years. The primary outcome of ischemic stroke was seen in 107 patients (1.8%) and the mean follow-up time was 7.7 years. In the Cox models, we found that small artery elasticity (SAE), carotid distensibility (CD), carotid stenosis (CS), and interleukin-6 (IL6) were associated with incident stroke. The AUC of the baseline model to predict stroke, which included patient age, hypertension, diabetes, total cholesterol, and smoking, was 0.745. When we added tertiles of SAE, CD, IL6 and categories of CS, the AUC improved to 0.765 (p=0.021 for difference). Conclusions: In a multiethnic cohort of patients without CVD at baseline, we found several ultrasound measurements and a serum marker of inflammation which predicted the occurrence of a primary ischemic stroke. Adding these basic ultrasound and serum measurements significantly improved the prediction of stroke, which could have implications for primary prevention efforts.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Cecilia Peterson ◽  
Ka-Ho Wong ◽  
Michael Dela Cruz ◽  
Kirby Taylor ◽  
Jennifer J Majersik ◽  
...  

Introduction: Antianxiety and antidepressant medications have shown some neuroprotective effects following stroke. However, the effect of premorbid use of these medications remains unclear. Hypothesis: Pre-morbid exposure to antianxiety or antidepressant medications will negatively impact recovery from acute ischemic stroke, measured by modified Rankin scale (mRS) at 90 days after stroke onset. Methods: This is a secondary analysis of the Albumin in Acute Ischemic Stroke (ALIAS) 2 trial. The primary outcome is 90-day mRS 0-1. The exposure is premorbid antidepressant or antianxiety medication. We fit univariate and multivariate logistic regression models to our outcome, with covariates chosen using a stepwise backwards interactive selection. Results: We included 806 patients with a mean (SD) age of 64.4 (12.8) years. The median (IQR) NIH Stroke Scale was 11 (8, 17) and 54.3% were male, 75.6% were Caucasian, 88.8% received tPA, 72.5% had hypertension, and 20.3% had diabetes. A total of 140/806 (17.4%) of patients took either an antidepressant or antianxiety medication, of which 91 took an antidepressant, 34 took an antianxiety medication, and 15 took both. The median (IQR) mRS Scale was one point higher in patients on antidepressant or antianxiety medication pre-stroke (3 vs. 2, p=0.019). The primary outcome of mRS 0-1 was seen in 37.7% of all patients. Taking an antidepressant or antianxiety medication was associated with lower odds of a good outcome in univariate (OR 0.61, 95% CI 0.41-0.91, p=0.015) and multivariate models (aOR 0.62, 95% CI 0.40-0.95, p=0.027) (Table 1). Conclusion: Pre-morbid exposure to antianxiety or antidepressant medications is associated with a worse outcome after acute ischemic stroke. This may be due to a negative impact of pre-stroke anxiety and depression that outweigh any neuroprotective factors of these medications.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Youfeng Zhu ◽  
Haiyan Yin ◽  
Rui Zhang ◽  
Xiaoling Ye ◽  
Jianrui Wei

Abstract Background The use of dobutamine in patients with sepsis is questionable currently. As the benefit of dobutamine in septic patients is unclear, we aimed to evaluate whether the use of dobutamine was associated with decreased hospital mortality in sepsis patients. Methods Based on the analysis of MIMIC III public database, we performed a big-data, real world study. According to the use of dobutamine or not, patients were categorized as the dobutamine group or non dobutamine group.We used propensity score matched (PSM) analysis to adjust for confoundings. The primary outcome was hospital mortality. Results In the present study, after screening 38,605 patients, 2826 patients with sepsis were included. 121 patients were in dobutamine group and 2165 patients were in non dobutamine group. Compared with patients in non-dobutamine group, patients in dobutamine group had a lower MAP, higher HR, higher RR, higher severity of illness scores. 72 of 121 patients (59.5%) in the dobutamine group and 754 of 2165 patients (34.8%) in the non-dobutamine group died in the hospital, which resulted in a significant between-group difference (OR 1.56, 95% CI 1.01–2.40; P = 0.000). For the secondary outcomes, patients in dobutamine group received more MV use, more renal replacement therapy use, had longer ICU stay durations and more cardiac arrhythmias than those in non-dobutamine group. After adjusting for confoundings between groups by PSM analysis, hospital mortality was consistently higher in dobutamine group than that in non-dobutamine group (60.2% vs. 49.4%, OR 1.55, 95% CI 1.01–2.37; P = 0.044). Conclusions Among patients with sepsis, our study showed that the use of dobutamine was not associated with decreased hospital mortality. Further large scale, randomized controlled studies are warrented to confirm our findings.


2015 ◽  
Vol 33 (2) ◽  
pp. 121-128 ◽  
Author(s):  
Hui Zheng ◽  
Wenjing Huang ◽  
Juan Li ◽  
Qianhua Zheng ◽  
Ying Li ◽  
...  

Objective To study whether a higher expectation of acupuncture measured at baseline and after acupuncture is associated with better outcome improvements in patients with migraine. Methods We performed a secondary analysis of a previous published trial in which 476 patients with migraine were randomly allocated to three real acupuncture groups and one sham acupuncture control group. All the participants received 20 sessions of acupuncture over a 4-week period. The primary outcome was the number of days with a migraine attack (NDMA) assessed at 5–8 weeks after randomisation. The secondary outcomes were visual analogue scale, headache intensity and quality of life assessed at 4, 8 and 16 weeks after randomisation. Expectations of the acupuncture effect were assessed at baseline and at the end of treatment and categorised into five levels, with 0% the lowest and 100% the highest. Outcome improvement was first compared among the participants with different expectation levels using an analysis of variance model. The association between expectations of treatment and outcome improvement was then calculated using a logistic regression model. Results Patients with 100% baseline expectations did not report significantly fewer NDMA than those with 0% baseline expectations after adjusting for the covariates (at 5–8 weeks, 1.7 vs 3.9 days, p=0.987). High baseline expectations had no significant impact on improvement of the primary outcome (100% vs 0%: OR 8.50, 95% CI 0.89 to 191.65, p=0.682). However, patients with 100% post-treatment expectations reported fewer NDMA than those with 0% expectations (primary outcome: 1.3 vs 5.0 days, p<0.001) and were more likely to have a favourable response (100% vs 0%: OR 68.87, 95% CI 6.26 to 1449.73, p=0.002). Similar results were found when analysing the impact of expectation on the secondary outcomes. Conclusions A high level of expectation after acupuncture treatment rather than at baseline was associated with better long-term outcome improvements in patients with migraine. Clinical Trial Number NCT00599586.


Stroke ◽  
2013 ◽  
Vol 44 (10) ◽  
pp. 2755-2759 ◽  
Author(s):  
Gustavo Saposnik ◽  
Mathew J. Reeves ◽  
S. Claiborne Johnston ◽  
Philip M.W. Bath ◽  
Bruce Ovbiagele

Background and Purpose— The ischemic stroke risk score (iScore) is a validated tool developed to estimate the risk of death and functional outcomes early after an acute ischemic stroke. Our goal was to determine the ability of the iScore to estimate clinical outcomes after intravenous thrombolysis tissue-type plasminogen activator (tPA) in the Virtual International Stroke Trials Archive (VISTA). Methods— We applied the iScore ( www.sorcan.ca/iscore ) to patients with an acute ischemic stroke within the VISTA collaboration to examine the effect of tPA. We explored the association between the iScore (<200 and ≥200) and the primary outcome of favorable outcome at 3 months defined as a modified Rankin scale score of 0 to 2. Secondary outcomes included death at 3 months, catastrophic outcomes (modified Rankin scale, 4–6), and Barthel index >90 at 3 months. Results— Among 7140 patients with an acute ischemic stroke, 2732 (38.5%) received tPA and 711 (10%) had an iScore ≥200. Overall, tPA treatment was associated with a significant improvement in the primary outcome among patients with an iScore <200 (38.9% non-tPA versus 47.5% tPA; P <0.001) but was not associated with a favorable outcome among patients with an iScore ≥200 (5.5% non-tPA versus 7.6% tPA; P =0.45). In the multivariable analysis after adjusting for age, baseline National Institutes of Health Stroke Scale, and onset-to-treatment time, there was a significant interaction between tPA administration and iScore; tPA administration was associated with 47% higher odds of a favorable outcome at 3 months among patients with an iScore <200 (odds ratio, 1.47; 95% confidence interval, 1.30–1.67), whereas the association between tPA and favorable outcome among those with an iScore ≥200 remained nonsignificant (odds ratio, 0.80; 95% confidence interval, 0.45–1.42). A similar pattern of benefit with tPA among patients with an iScore <200, but not ≥200, was observed for secondary outcomes including death. Conclusions— The iScore is a useful and validated tool that helps clinicians estimate stroke outcomes. In stroke patients participating in VISTA, an iScore <200 was associated with better outcomes at 3 months after tPA.


Author(s):  
Lara Shipley ◽  
Aarti Mistry ◽  
Don Sharkey

ObjectiveTherapeutic hypothermia (TH) for neonatal hypoxic-ischaemic encephalopathy (HIE), delivered mainly in tertiary cooling centres (CCs), reduces mortality and neurodisability. It is unknown if birth in a non-cooling centre (non-CC), without active TH, impacts short-term outcomes.DesignRetrospective cohort study using National Neonatal Research Database and propensity score-matching.SettingUK neonatal units.PatientsInfants ≥36 weeks gestational age with moderate or severe HIE admitted 2011–2016.InterventionsBirth in non-CC compared with CC.Main outcome measuresPrimary outcome was survival to discharge without recorded seizures. Secondary outcomes were recorded seizures, mortality and temperature on arrival at CCs following transfer.Results5059 infants were included with 2364 (46.7%) born in non-CCs. Birth in a CC was associated with improved survival without seizures (35.1% vs 31.8%; OR 1.15, 95% CI 1.02 to 1.31; p=0.02), fewer seizures (60.7% vs 64.6%; OR 0.84, 95% CI 0.75 to 0.95, p=0.007) and similar mortality (15.8% vs 14.4%; OR 1.11, 95% CI 0.93 to 1.31, p=0.20) compared with birth in a non-CC. Matched infants from level 2 centres only had similar results, and birth in CCs was associated with greater seizure-free survival compared with non-CCs. Following transfer from a non-CC to a CC (n=2027), 1362 (67.1%) infants arrived with a recorded optimal therapeutic temperature but only 259 (12.7%) of these arrived within 6 hours of birth.ConclusionsAlmost half of UK infants with HIE were born in a non-CC, which was associated with suboptimal hypothermic treatment and reduced seizure-free survival. Provision of active TH in non-CC hospitals prior to upward transfer warrants consideration.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3471-3471 ◽  
Author(s):  
Ang Li ◽  
Robert S Makar ◽  
Shelley Hurwitz ◽  
Lynne Uhl ◽  
Richard M. Kaufman ◽  
...  

Abstract Introduction: Thrombotic microangiopathies (TMA) are a group of uncommon disorders characterized clinically by the presence of thrombocytopenia and microangiopathic hemolytic anemia (MAHA). Therapeutic plasma exchange (TPE) is a proven treatment for cases of autoimmune thrombotic thrombocytopenic purpura (TTP) characterized by an ADAMTS13 activity level of ≤10%, but the efficacy of TPE in TMA with an ADAMTS13 activity level of >10% remains controversial. Methods: We conducted a retrospective cohort study of 186 adult patients included in the Harvard TMA Research Collaborative registry who presented with MAHA and thrombocytopenia concerning for TTP but an ADAMTS13 activity level of >10%. A propensity score (PS) logistic regression model was constructed based on 11 clinically relevant confounding variables: age; sex; ethnicity; Charlson Comorbidity Index (CCI); history of prior solid organ or bone marrow transplant; the presence of neurologic symptoms; the presence of sepsis, shock, or multiorgan failure (MOF); platelet count; creatinine; LDH; and INR. Matching was performed using a 1:1 nearest neighbor method without replacement within a set caliper distance. Standardized differences were used to assess the quality of matching and ensure balance of baseline characteristics. The primary outcome was 90-day survival. Secondary outcomes included in-hospital mortality, percent of patients experiencing platelet count recovery, time to platelet count recovery, and hospital length of stay (LOS). Results: Prior to matching, patients treated with TPE (N=71) had a lower acuity of illness compared to untreated patients (N=115) as reflected by a lower mean CCI (2.3 vs. 3.4, P = 0.003), lower mean INR (1.1 vs. 1.3, P = 0.02), and lower incidence of sepsis, shock or MOF (23% vs. 36%, P = 0.06). Consistent with this confounding, TPE in the pre-matched cohort appeared to be associated with reduced mortality at 90 days (HR 0.51, P = 0.01). The PS match was performed to address these imbalances and resulted in 59 TPE-treated patients paired to 59 untreated controls. After matching, baseline characteristics of the treated and untreated groups were well balanced, with a standardized difference of ≤11% in all PS variables (see Figure). In contrast to the unmatched cohort, Cox regression analysis stratified by matched pairs showed no significant difference in the primary outcome of 90-day survival between the treated and untreated groups (HR 0.88, 95% CI 0.44-1.8, P = 0.72) (see Table). We performed subgroup analyses by age, diagnostic category, and ADAMTS13 activity level and again did not observe any benefit to TPE. With regard to secondary outcomes, in-hospital mortality (OR 0.77, P = 0.53), percent of patients with platelet count recovery (OR 1.6, P = 0.21), median time to platelet count recovery (6 vs. 6 days, P = 0.99), and median hospital LOS (14 vs. 18 days, P = 0.93) did not differ significantly between the two groups. Conclusions: In the absence of a randomized controlled trial, PS matching represents a rigorous statistical approach to study the effect of treatment while adjusting for differences in baseline characteristics across groups of patients. Here we have used PS matching to assess the efficacy of TPE in the management of TMA associated with an ADAMTS13 activity level of >10%. Our data indicate that there is no benefit from TPE for this diverse group of TMA patients without severe ADAMTS13 deficiency. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures No relevant conflicts of interest to declare.


2017 ◽  
Vol 35 (05) ◽  
pp. 421-426
Author(s):  
Methodius Tuuli ◽  
Molly Stout ◽  
Candice Woolfolk ◽  
Kimberly Roehl ◽  
George Macones ◽  
...  

Objective The objective of this study was to estimate epidural timing's impact on fetal station during active labor. Study Design This secondary analysis of a single-institution prospective cohort study included all term singleton pregnancies, stratified by parity. Those with early epidurals (placed at <6 cm) were compared with those with late epidurals (placed at ≥6 cm). The primary outcome was median fetal station from 6 to 10 cm. Secondary outcomes included rate of prolonged first or second stage of labor (>95%). Multivariable logistic regression adjusted for labor type. Results Among 7,647 women, 3,434 were nulliparous (2,983 with early epidurals and 451 with late epidurals) and 4,213 multiparous (3,141 with early epidurals and 1,072 with late epidurals). Interquartile ranges (IQRs) suggested fetal station at 6 cm was likely lower among those with early epidurals (nulliparous: median head station −1 [IQR: −1 to 0] for early epidural vs. −1 [IQR: −2 to 0] for late epidural, p < 0.01; multiparous: −1 (IQR: −2 to 0] for early epidural vs. −1 [IQR: −3 to −1] for late epidural, p < 0.01). Early epidurals were not associated with increased risk of prolonged first stage, but among nulliparous were associated with decreased risk of prolonged second stage (adjusted odds ratio: 0.66 [95% confidence interval: 0.44–0.99]). Conclusion Early epidurals were associated with lower fetal station in active labor but not prolonged first stage.


2020 ◽  
Vol 41 (Supplement_1) ◽  
pp. S13-S14
Author(s):  
Rebecca Coffey ◽  
Richard V Zhelezny ◽  
Kyle Porter ◽  
Charles Zhang ◽  
Claire V Murphy

Abstract Introduction Based on the National Burn Repository Data (2002–2011), the incidence of diabetes is increasing among adult patients with burn injury. Diabetes has been associated with increased morbidity and mortality following burn injury. There is limited data related to prediabetes in burn injury, and no studies to date have compared clinical outcomes in patients without diabetes, with prediabetes, and with diabetes. Therefore, this study aimed to compare the impact of diabetes status, defined as no diabetes (ND), prediabetes (PD), or diabetes (DM), on clinical outcomes after burn injury. Methods A single-center, retrospective cohort study of adult patients admitted for initial management of burn injury between January 1, 2009 and February 28, 2019 who had a hemoglobin A1c (HbA1c) upon admission was performed. Patients with chemical or electrical injury, isolated smoke inhalation injury, total body surface area (TBSA) burn injury &lt; 1%, patients who expired or transitioned to comfort care within 24 hours of admission, or were incarcerated or pregnant were excluded. Patients were categorized as ND, PD, or DM based on their past medical history and admission HbA1c. The primary outcome was LOS/%TBSA burn. Secondary outcomes included mortality, LOS, discharge disposition, re-grafting of same site, and amputations. Propensity score methods were used to account for imbalance between groups. Separate propensity score weights were calculated for analysis of DM versus ND and DM versus PD. The primary outcome LOS/%TBSA burn was compared between groups using weighted linear models. Since the outcome was right-skewed, LOS/%TBSA burn was log-transformed for analysis, yielding estimates of the ratio of geometric means. Results A total of 1137 patients were included (710 ND, 191 PD, 236 DM). Patients were predominately male (70.3% ND, 67.4% PD, 70.2% DM) and Caucasian (85.5% ND, 73.8% PD, 82.1% DM). The mean BMI was highest in DM (31.8 kg/m2) and lowest in ND (27.8 kg/m2). After inverse probability weighing to adjust for potentially confounding factors, DM had longer LOS/%TBSA burn than patients with ND (ratio of geometric means (95% CI) = 1.61 (1.21, 2.15), p = 0.001) or PD (ratio (95% CI) = 1.53 (1.14, 2.05), p =0.01). No differences in secondary outcomes were observed between the DM and ND groups and between DM and PD groups with the exception of amputations (2.8% DM vs. 0.7% ND, p=0.06; 2.6% DM vs. 0% PD, p=0.04). Conclusions Diabetes in the burn patient significantly increases LOS/%TBSA index and amputation rates compared to both PD and ND. Applicability of Research to Practice Diabetes may contribute to increased cost of care in burn injury. Early identification of diabetes status may aid management of this patient population.


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