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Biomedical subjects

Jeffrey L Saver

Publications and source records attributed to Jeffrey L Saver.

At least 19 recordsLinked to original sources
PubMed2026

Effect of Baseline ASPECTS on Tenecteplase Efficacy Before Thrombectomy in Acute Large-Vessel Occlusion Stroke: A Post Hoc Analysis of the BRIDGE-TNK Randomized Trial.

BACKGROUND AND OBJECTIVES: The impact of ischemic extent on the efficacy and safety of intravenous thrombolysis before thrombectomy remains uncertain. The aim of this study was to evaluate whether the baseline ischemic extent, measured by the Alberta Stroke Program Early Computed Tomography Score (ASPECTS), modifies outcomes of intravenous tenecteplase administered before endovascular thrombectomy. METHODS: This was a post hoc analysis of the BRIDGE-TNK (thrombectomy with vs without rhTNK-tPA in stroke) trial, conducted across China from May 2022 to September 2024. We compared the efficacy and safety of intravenous tenecteplase plus thrombectomy vs thrombectomy alone in acute large-vessel occlusion stroke patients within 4.5 hours of last known well, stratified by baseline ASPECTS (<8 vs 8-10). The outcomes included 90-day functional independence (modified Rankin Scale score of 0-2), 48-hour symptomatic intracranial hemorrhage (sICH), and 90-day mortality. Regression models incorporating a treatment-by-ASPECTS interaction term were used for analysis. RESULTS: Among 550 patients, 241 (43.8%) had ASPECTS <8 (median [interquartile range, IQR] age, 69 [61-77] years; 56.4% male) and 309 had ASPECTS 8-10 (median [IQR] age, 70 [61-77] years; 59.5% male). The rate of functional independence was significantly higher in the tenecteplase plus thrombectomy group than in the thrombectomy-alone group in the ASPECTS <8 subgroup (adjusted risk ratio [aRR], 1.67; 95% CI 1.18-2.35), but not in the ASPECTS 8-10 subgroup (aRR, 0.99; 95% CI 0.84-1.17; pinteraction = 0.007). Rates of sICH did not differ significantly between treatment groups in either ASPECTS subgroups (ASPECTS <8: 10.0% vs 11.2%; ASPECTS 8-10: 7.5% vs 2.8%; pinteraction = 0.11). Ninety-day mortality was comparable between treatment groups in the ASPECTS <8 subgroup, but numerically higher with tenecteplase plus thrombectomy in the ASPECTS 8-10 subgroup (aRR = 1.89, 95% CI 0.99-3.61, pinteraction = 0.04). DISCUSSION: In this exploratory post hoc analysis, a signal of benefit was observed in patients with ASPECTS <8 who received intravenous tenecteplase before thrombectomy, whereas no functional improvement and possible safety concerns were seen in those with ASPECTS 8-10. Prospective confirmation in randomized trials is required before practice change. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov; Unique identifier: NCT04733742.

Humans↗
PubMed2006

Evidence of publication bias in reporting acute stroke clinical trials.

OBJECTIVE: To ascertain the extent of publication bias in the reporting of acute stroke clinical trials. METHODS: We identified controlled acute ischemic stroke clinical trials reported in English over a 45-year period from 1955 to 1999 through systematic search of MEDLINE, the Cochrane Controlled Stroke Trials Register, and additional databases. We analyzed trial methodology, quality, outcome, study sponsorship, and timing of publication to identify various forms of publication bias, including nonpublication bias, abbreviated publication bias, and time-lag bias. RESULTS: One hundred seventy-eight acute ischemic stroke trials, enrolling 73,949 subjects, evaluated 75 agents or nonpharmacologic interventions. A greater proportion of harmful outcomes in unpublished studies (n = 4) compared with published trials (0.75 vs 0.06, p < 0.0001) and underreporting of smaller, nonbeneficial studies in acute stroke suggest nonpublication bias. Although a definite time-lag bias was not evident, nonbeneficial studies were slower to proceed from enrollment completion to publication (2.3 vs 2.0 years, p = 0.207), with an even longer delay for nonbeneficial corporate pharmaceutical sponsored trials (2.8 vs 2.1 years, p = 0.086), despite superior trial report quality scores for corporate-sponsored studies when compared with nonprofit/governmental studies (mean 69.2 +/- 95% CI 3.9 vs 53.4 +/- 95% CI 9.2, p < 0.005). CONCLUSION: Publication bias is evident in the acute stroke research literature, supporting the need for prospective trial registration.

Chi-Square Distribution↗
PubMed2006

Leukoaraiosis is a risk factor for symptomatic intracerebral hemorrhage after thrombolysis for acute stroke.

BACKGROUND AND PURPOSE: The aim of the study was to evaluate whether leukoaraiosis (LA) is a risk factor for symptomatic intracerebral hemorrhage (sICH) in patients treated with thrombolysis for acute stroke. METHODS: In this retrospective, multicenter analysis, we evaluated data from acute anterior circulation stroke patients (n=449; <6 hours after symptom onset) treated with thrombolysis. All patients had received standard magnetic resonance imaging evaluation before thrombolysis, including a high-quality T2-weighted sequence. For the analysis, LA in the deep white matter was dichotomized into absent or mild versus moderate or severe (corresponding to Fazekas scores of 0 to 1 versus 2 to 3). RESULTS: The rate of sICH was significantly more frequent in patients with moderate to severe LA of the deep white matter (n=12 of 114; 10.5%) than in patients without relevant LA (n=13 of 335; 3.8%), corresponding to an odds ratio of 2.9 (95% CI, 1.29 to 6.59; P=0.015). In a logistic-regression analysis (including age, National Institutes of Health Stroke Scale score at presentation, and type of thrombolytic treatment), LA remained a significant independent risk factor (odds ratio, 2.9; P=0.03). CONCLUSIONS: LA of the deep white matter is an independent risk factor for sICH after thrombolytic treatment for acute stroke.

Aged↗
PubMed2006

Frequency and determinants of nonpublication of research in the stroke literature.

BACKGROUND AND PURPOSE: Selective nonpublication will yield publication bias and a published literature imperfectly representative of the full range of scientific findings. We evaluated the proportion of research abstracts presented at the leading United States research meeting in stroke, the International Stroke Conference (ISC), which were subsequently published as full-length articles and investigated the factors associated with full manuscript publication. METHODS: Features of all abstracts presented at the annual ISC meeting in February 2000 were analyzed. Search of the National Library of Medicine PubMed database and written communication with abstract authors was performed to determine conversion of abstracts to fully published manuscripts over the subsequent 5 years. RESULTS: Among the 353 abstracts presented at the 2000 International Stroke Conference, 108 were oral presentations and 245 posters. Overall, 202/353 (62.3%) resulted in full-length publications, with a median time to publication of 15 months. In multivariate analysis, factors increasing likelihood of full-length publication were: platform rather than poster presentations (odds ratio [OR] 3.0, 95% CI, 1.6 to 5.5), authors with a university affiliation (OR 2.2, 95% CI, 1.2 to 4.1), and European region of origin (OR 2.2, 95% CI, 1.1 to 4.4), whereas topic concerning community/risk factors decreased the likelihood of publication (OR 0.3, 95% CI, 0.16 to 0.74). Positive results, multicenter collaboration and industry sponsorship did not affect publication rate. CONCLUSIONS: Approximately 1 of every 3 abstracts presented at an international stroke meeting was not published as a full manuscript within 5 years. Poster abstracts were less likely to be published in full manuscript form than oral presentations.

Abstracting and Indexing↗
PubMed2006

Predictors of cerebral microbleeds in acute ischemic stroke and TIA patients.

BACKGROUND: Cerebral microbleeds (CMB) detected on gradient-echo T2*-weighted MRI have been associated with cognitive impairment and the potential for increased risk of intracranial hemorrhage. We evaluated risk factors for these microangiopathic lesions in a cohort of stroke and transient ischemic attack patients. METHODS: Presence and number of CMB in consecutive acute stroke patients admitted to a university hospital stroke service over an 18-month period were rated. Multivariate models were generated to determine the contribution of 21 demographic and clinical variables to the frequency and number of CMB. RESULTS: Of 164 patients (mean age 71 years, 52% female), 57 (35%) had CMB evident on gradient-echo T2*-weighted MRI. CMB were more commonly noted among patients with small vessel disease ischemic stroke mechanism (47%) than large vessel atherothromboembolic (12%) or cardioembolic (18%, p = 0.0001). In univariate analysis, patients with CMB were older, (p = 0.008), more likely to have been on >1 antihypertensive prior to admission (p = 0.024) than those without CMB. In multivariate logistic regression analyses, presumed small vessel stroke subtype, history of atrial fibrillation, being on >1 antihypertensive prior to admission, and smoking were independent factors increasing the risk of CMB. Logistic regression analysis by number of CMB showed almost similar findings. CONCLUSIONS: CMB are more frequently noted in hospitalized stroke and transient ischemic attack patients with small vessel ischemia, as well as those with important modifiable vascular risk factors like atrial fibrillation and smoking.

Adult↗
PubMed2006

Analysis of thrombi retrieved from cerebral arteries of patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Information regarding the histological structure of thromboemboli that cause acute stroke provides insight into pathogenesis and clinical management. METHODS: This report describes the histological analysis of thromboemboli retrieved by endovascular mechanical extraction from the middle cerebral artery (MCA) and intracranial carotid artery (ICA) of 25 patients with acute ischemic stroke. RESULTS: The large majority (75%) of thromboemboli shared architectural features of random fibrin:platelet deposits interspersed with linear collections of nucleated cells (monocytes and neutrophils) and confined erythrocyte-rich regions. This histology was prevalent with both cardioembolic and atherosclerotic sources of embolism. "Red" clots composed uniquely of erythrocytes were uncommon and observed only with incomplete extractions, and cholesterol crystals were notably absent. The histology of thromboemboli that could not be retrieved from 29 concurrent patients may be different. No thrombus >3 mm wide caused stroke limited to the MCA, and no thrombus >5 mm wide was removed from the ICA. A mycotic embolus was successfully removed in 1 case, and a small atheroma and attached intima were removed without clinical consequence from another. CONCLUSIONS: Thromboemboli retrieved from the MCA or intracranial ICA of patients with acute ischemic stroke have similar histological components, whether derived from cardiac or arterial sources. Embolus size determines ultimate destination, those >5 mm wide likely bypassing the cerebral vessels entirely. The fibrin:platelet pattern that dominates thromboembolic structure provides a foundation for both antiplatelet and anticoagulant treatment strategies in stroke prevention.

Adolescent↗
PubMed2006

Cerebral white matter hyperintensities on MRI: Current concepts and therapeutic implications.

BACKGROUND: White matter hyperintensities (WMH) are commonly observed MRI abnormalities in the elderly, which generally reflect covert vascular brain injury. WMH cumulatively produce substantial neurologic, psychiatric, and medical morbidity. This review provides an overview of current knowledge on vascular WMH, and describes some pharmacological agents that may have a role in mitigating this condition. SUMMARY OF REVIEW: This review has two main focus areas. The first is a discussion of currently available knowledge regarding the public health burden, pathogenesis, and various risk factors associated with the presence of vascular white matter lesions noted on brain MRI. The second section of the article details the mechanistic and clinical basis for promising pharmacological treatment modalities that could potentially prevent progression of ischemic cerebral white matter brain injury. Many of these therapies are already of proven efficacy in preventing recurrent stroke. CONCLUSIONS: Individuals with vascular white matter lesions on MRI may represent a potential target population likely to benefit from secondary stroke prevention therapies.

Age Factors↗
PubMed2006

Impact of metabolic syndrome on prognosis of symptomatic intracranial atherostenosis.

BACKGROUND: The metabolic syndrome (MetS) is a cluster of risk factors linked to insulin resistance that increase an individual's risk of atherosclerotic vascular disease. The authors evaluated the prevalence and prognosis of the MetS among individuals with symptomatic intracranial arterial stenosis. METHODS: Patients enrolled in the Warfarin-Aspirin Symptomatic Intracranial Disease trial were evaluated in this post-hoc analysis. Baseline characteristics and outcome were compared in patients with the MetS vs patients without the MetS. RESULTS: Among 476 patients, the prevalence of the MetS was 43%. MetS patients were more likely to be younger, female, and white. During a mean follow-up period of 1.8 years, time to the first of ischemic stroke, myocardial infarction, or vascular death was shorter among patients with the MetS with a hazard ratio (syndrome/no syndrome) of 1.6 (95% CI = 1.1 to 2.4, p = 0.0097). Time to ischemic stroke alone was also shorter among patients with the MetS with a hazard ratio (syndrome/no syndrome) of 1.7 (95% CI = 1.1 to 2.6, p = 0.012). When controlling for individual factors of the definition, MetS was not significant (combined outcome: p = 0.14; ischemic stroke: p = 0.074). CONCLUSIONS: The metabolic syndrome is present in about half of individuals with symptomatic intracranial atherosclerotic disease and is associated with a substantially higher risk of major vascular events. The metabolic syndrome may not provide additional ability to predict outcomes beyond the individual factors for patients with intracranial stenosis.

Aged↗
PubMed2006

Secondary-prevention drug prescription in the very elderly after ischemic stroke or TIA.

BACKGROUND: An age bias may exist in the prescription of important secondary-preventive therapies in the elderly. OBJECTIVE: To evaluate patterns of drug prescription for cardiovascular prevention in the very elderly following hospitalization for an acute ischemic stroke or TIA. METHODS: The authors compared subjects ages > or = 80 with those < 80 in the California Acute Stroke Prototype Registry to evaluate the impact of age on receipt of secondary-prevention medications at the time of hospital discharge. Prespecified secondary-prevention drug classes studied were antithrombotics, lipid-lowering agents, and antihypertensives. RESULTS: Overall, there were 260 patients age > or = 80 and 534 age < 80 admitted with stroke or TIA during the study period. Patients > or = 80 years were less likely to receive actual treatment with antithrombotic medications (p = 0.002) and lipid-lowering medications (p = 0.005) but were more likely to receive antihypertensive medications (p = 0.0007) than their younger counterparts. With regard to optimal treatment (defined as receipt of, or a valid contraindication to, treatment in each category), those > or = 80 were equally likely to receive antithrombotic medications and lipid therapy but remained more likely to receive antihypertensive treatment (77.7 vs 67.0%; p = 0.0007). There were no differences in receipt of optimal combination therapy (defined as optimal treatment in all three therapeutic classes) between patient age groups, even when adjusted for medical history. CONCLUSION: After hospitalization for stroke or TIA, no differences in overall optimal treatment prescription of secondary-prevention medications between patients ages > or = 80 and their younger counterparts were observed.

Age Factors↗
PubMed2006

Effect of smoking status on outcome after acute ischemic stroke.

BACKGROUND: The status of smoking as a risk factor for the occurrence of stroke is well established. However, there is a paucity of data on the relationship between smoking status and acute stroke outcomes. We evaluated the role of recent smoking as a prognostic factor following acute ischemic stroke. METHODS: We analyzed data from patients enrolled in the Intravenous Magnesium Efficacy in Stroke (IMAGES) trial. Outcome measures studied included change in IMAGES stroke score, poor functional outcomes at day 30 and 90 (defined as Rankin Scale >1 and Barthel Index <95), and survival over the first 3 months after stroke. The independent effect of smoking status (subjects who had smoked in the past year) on outcome was evaluated by logistic regression analysis and Cox's proportional hazards model, adjusting for variables known to predict outcome after ischemic stroke. RESULTS: There were 2,386 subjects in the IMAGES efficacy dataset, including 615 recent or current smokers and 1,771 nonsmokers, among whom smokers were younger (p < 0.0001). After adjusting for covariates, smokers had increased odds of poor 90-day functional outcome independently of other statistically significant predictor variables, as assessed by Rankin Scale (odds ratio 1.38; 95% confidence interval 1.09-1.75) and Barthel Index (odds ratio 1.42; 95% confidence interval 1.13-1.79) at day 90. Smoking status did not affect survival at day 90. CONCLUSIONS: Current or recent smokers experience poorer functional outcomes than nonsmokers 3 months after acute ischemic stroke.

Aged↗
PubMed2006

Achieving target cholesterol goals after stroke: is in-hospital statin initiation the key?

BACKGROUND: National advisories recommend statin therapy as an element of secondary prevention for patients with ischemic stroke or transient ischemic attack of atherosclerotic origin. Statins are of proven benefit in persons at high risk of vascular disease. OBJECTIVES: To evaluate the effects of in-hospital initiation of statins on 3-month treatment adherence rates and achievement of national guideline target cholesterol goals. METHODS: Data were collected in consecutively encountered patients with ischemic stroke or transient ischemic attack admitted to a university hospital stroke service beginning September 1, 2002. Patients were included in the study if they were not receiving a statin before admission and had an indication for statin therapy. Adherence to statin treatment and achievement of national guideline target cholesterol goals were assessed 3 months after discharge. RESULTS: From September 1, 2002, through April 30, 2005, 92 (17%) of 552 individuals met the study criteria. Hospital initiation of statin therapy yielded high rates of adherence (93% [86/92]), lowered mean low-density lipoprotein cholesterol levels from 120 to 78 mg/dL (3.1 to 2.0 mmol/L; P<.001), and increased the proportion of patients with low-density lipoprotein cholesterol levels lower than 100 mg/dL (2.6 mmol/L) from 36% to 88% (P<.001) at 3 months. CONCLUSIONS: Statin initiation during hospitalization for an ischemic cerebrovascular event is associated with high rates of adherence to treatment, lowering of low-density lipoprotein cholesterol levels, and higher rates of achieving national cholesterol guidelines.

Adult↗
PubMed2006

Lipid assessment and treatment patterns in hospitalized TIA and ischemic stroke patients.

BACKGROUND: Identification of dyslipidemia and treatment with lipid-lowering agents are established targets for quality performance during hospitalization for ischemic stroke and transient ischemic attack (TIA). We aimed to study the frequency and predictors of lipid assessment and discharge utilization of lipid-lowering therapies among patients hospitalized for stroke and TIA. METHODS: Demographics, clinical findings, and laboratory data were documented as part of the California Acute Stroke Prototype Registry (CASPR). Frequency of low-density lipoprotein cholesterol (LDL-C) testing and the frequency and appropriate use of lipid-lowering treatment according to national cholesterol guidelines were determined. Multivariate models were generated to determine the contribution of clinical variables to LDL testing and prescription of lipid-lowering medications at discharge. RESULTS: Data were collected on 764 consecutive patients with ischemic stroke or TIA treated at 11 hospitals over a 2-year period. LDL-C measurements were performed in only 50.1% during hospitalization. Measurement of LDL-C was most strongly and independently associated with diagnosis of ischemic stroke (vs. TIA, P = .02) and history of dyslipidemia (P = .05). Overall, 48.4% of the CASPR cohort received lipid-lowering medications at discharge. Independent predictors for being prescribed lipid-lowering agents at discharge were diagnosis of ischemic stroke (P = .0009), LDL-C testing (P = .0002), high risk of future coronary events according to national guidelines (P = .02), and history of dyslipidemia (P< .0001). Only 59% of patients at high risk for future coronary events were discharged on a lipid-lowering medication. CONCLUSIONS: Serum cholesterol testing and treatment are underutilized during hospitalization for ischemic stroke or TIA.

Aged↗