PubMed Health⌕ Search

Biomedical subjects

Chelsea S Kidwell

Publications and source records attributed to Chelsea S Kidwell.

At least 19 recordsLinked to original sources
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 A greater proportion of harmful outcomes in unpublished studies (n = 4) compared with published trials (0.75 vs 0.06, p 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

Imaging of the brain and cerebral vasculature in patients with suspected stroke: advantages and disadvantages of CT and MRI.

Although neuroimaging remains the foundation for the diagnosis of cerebrovascular disease, ongoing technologic advances have now opened up new frontiers for stroke evaluation and treatment. Neuroimaging studies can provide crucial information regarding tissue injury (size, location, and degree of reversibility of ischemic injury as well as presence of hemorrhage), vessel status (site and severity of stenoses and occlusions), and cerebral perfusion (size, location, and severity of hypoperfusion). This information can be combined to identify patients with salvageable penumbral tissue who may benefit most from acute therapies. The multimodal combinations of advanced imaging techniques, particularly in the realm of CT and MRI, have emerged as the most promising noninvasive approaches to acute stroke evaluation.

Brain↗
PubMed2005

Use of multimodal MRI and novel endovascular therapies in a patient ineligible for intravenous tissue plasminogen activator.

BACKGROUND AND PURPOSE: Options are limited for individuals who present to the ED within 3 hours of ischemic stroke onset, but who are deemed ineligible for intravenous thrombolysis. Multimodal MRI has been shown to be of great help in identifying stroke patients with large areas of at risk "penumbral tissue", who may gain from the use of novel endovascular therapies. We report a patient who twice benefited from this management approach, in the setting of hemorrhagic risk following successive ischemic strokes. CASE DESCRIPTION: The patient is a 78 year old male who experienced acute ischemic stroke on 2 separate occasions 5 months apart, and for whom perceived contraindications to appropriate thrombolytic therapy administration led to the successful use of different endovascular therapies at each encounter. Furthermore, following mechanical clot retrieval during the second encounter, the high intensity signal area noted on the baseline diffusion weighted imaging (DWI) in the posterior circulation territory, was almost completely resolved on the day 7 post-procedure MRI. CONCLUSIONS: To our knowledge, this is the first reported case of reversal of a DWI abnormality in the posterior circulation territory.

Aged↗
PubMed2005

Enhancing the development and approval of acute stroke therapies: Stroke Therapy Academic Industry roundtable.

BACKGROUND: Previous Stroke Therapy Academic Industry Roundtable (STAIR) meetings focused on preclinical evidence of drug efficacy and enhancing acute stroke trial design and performance. A fourth (STAIR-IV) was held to discuss relevant issues related to acute stroke drug development and regulatory approval. SUMMARY OF REVIEW: The STAIR-IV meeting had 3 main focus areas. The first topic was novel approaches to statistical design of acute stroke trials and appropriate outcome measures. The second focus was the need for better cooperation among participants in stroke therapy development that may be addressed through a national consortium of stroke trial centers in the United States and elsewhere. Lastly, regulatory issues related to the approval of novel mono and multiple acute stroke therapies were discussed. CONCLUSIONS: The development of additional acute stroke therapies represents a large unmet need with many remaining challenges and also opportunities to incorporate novel approaches to clinical trial design that will lead to regulatory approval. The STAIR-IV meeting explored new concepts of trial methodology and data analysis, initiatives for implementing a US clinical trialist consortium, and pertinent regulatory issues to expedite approval of novel therapies.

Brain Ischemia↗
PubMed2005

Safety and efficacy of mechanical embolectomy in acute ischemic stroke: results of the MERCI trial.

BACKGROUND AND PURPOSE: The only Food and Drug Administration (FDA)-approved treatment for acute ischemic stroke is tissue plasminogen activator (tPA) given intravenously within 3 hours of symptom onset. An alternative strategy for opening intracranial vessels during stroke is mechanical embolectomy, especially for patients ineligible for intravenous tPA. METHODS: We investigated the safety and efficacy of a novel embolectomy device (Merci Retriever) to open occluded intracranial large vessels within 8 hours of the onset of stroke symptoms in a prospective, nonrandomized, multicenter trial. All patients were ineligible for intravenous tPA. Primary outcomes were recanalization and safety, and secondary outcomes were neurological outcome at 90 days in recanalized versus nonrecanalized patients. RESULTS: Recanalization was achieved in 46% (69/151) of patients on intention to treat analysis, and in 48% (68/141) of patients in whom the device was deployed. This rate is significantly higher than that expected using an historical control of 18% (P<0.0001). Clinically significant procedural complications occurred in 10 of 141 (7.1%) patients. Symptomatic intracranial hemorrhages was observed in 11 of 141 (7.8%) patients. Good neurological outcomes (modified Rankin score < or =2) were more frequent at 90 days in patients with successful recanalization compared with patients with unsuccessful recanalization (46% versus 10%; relative risk [RR], 4.4; 95% CI, 2.1 to 9.3; P<0.0001), and mortality was less (32% versus 54%; RR, 0.59; 95% CI, 0.39 to 0.89; P=0.01). CONCLUSIONS: A novel endovascular embolectomy device can significantly restore vascular patency during acute ischemic stroke within 8 hours of stroke symptom onset and provides an alternative intervention for patients who are otherwise ineligible for thrombolytics.

Angiography↗
PubMed2005

Withdrawal of warfarin prior to a surgical procedure: time to follow the guidelines?

BACKGROUND AND OBJECTIVE: Patients with cardiogenic sources of embolism may be at increased risk of cerebral infarction when anticoagulation therapy is suspended for surgical procedures. The purpose of this study was to determine frequency of cardioembolic cerebral infarction during periprocedural warfarin withdrawal. METHODS: Retrospective analysis of prospective cerebral infarction registry data from two tertiary medical centers. RESULTS: Over a 12-month period, 14 cases of cardioembolic cerebral infarction occurring during the period of warfarin withdrawal for a medical procedure were observed, accounting for 7.1% of the 197 cardioembolic cerebral infarctions encountered. Across all patients, cerebral infarctions developed an average of 5.4 days after the last dose of warfarin (range 3-8). Among the 14 patients (8 males and 6 females) with warfarin cessation-related infarcts, age ranged from 54 to 91 years. Each had been on chronic anticoagulation with warfarin for more than 1 year. Retrospective analysis suggested that all these cerebral infarctions had been potentially preventable. In each case, either the planned procedure did not require discontinuation of warfarin or, when withdrawal was required, no bridging, parenteral anticoagulation was provided to lessen the risk during the warfarin-free period. CONCLUSION: Patients at high risk of cardioembolic cerebral infarction may benefit from more intensive management strategies to reduce cerebral infarction risk during periprocedural periods.

Aged↗
PubMed2005

Expanding indications for statins in cerebral ischemia: a quantitative study.

BACKGROUND: New US Food and Drug Administration labeling in 2003 recognizes stroke and evidence of cerebrovascular disease as indicator conditions for initiating statin (simvastatin) therapy, based on results of the Heart Protection Study, thereby extending the indications for statins in stroke beyond current US and European guidelines. OBJECTIVE: To assess the impact on clinical practice of broadening indications for statins in patients with stroke. DESIGN: Observational study. SETTING: University hospital stroke service. PATIENTS: One hundred consecutive patients with ischemic stroke and transient ischemic attack. INTERVENTIONS: Development and application of algorithms for initiating statin therapy in patients with stroke and transient ischemia abstracted from recent national and international guidelines (National Cholesterol Education Program Adult Treatment Panel III, European Joint Task Force II), Heart Protection Study entry criteria, and Heart Protection Study-based US Food and Drug Administration labeling. MAIN OUTCOME MEASURES: Percentages of patients who met clinical trial-validated and US Food and Drug Administration-approved criteria for initiation of statin therapy. RESULTS: Patient age averaged 74 years (range, 35-96 years); 64% were female, and 74% were white. Stroke subtype was large-vessel atherosclerosis in 24%, cardioembolic in 44%, small-vessel atherosclerosis in 22%, and other in 10%. Twenty of 100 patients were already taking statins on admission. Guidelines for definite initiation of statin treatment were met by 48% of patients for the National Cholesterol Education Program III, 38% for the European Joint Task Force II, 92% for the Heart Protection Study, and 100% for the Food and Drug Administration. CONCLUSIONS: Most clinically encountered patients with ischemic stroke meet clinical trial-validated criteria for initiation of statin therapy. Rigidly applying current national and international guidelines may deprive up to one half of these patients of advantages of statin therapy.

Adult↗
PubMed2005

Advanced MR imaging of acute stroke: the University of California at Los Angeles endovascular therapy experience.

Rapid implementation of multimodal MR imaging, including diffusion-perfusion imaging before and following endovascular therapies for treatment of acute ischemic stroke, has yielded novel observations and expanded contemporary knowledge of acute stroke pathophysiology. For more than a decade at the University of California at Los Angeles, an intensive imaging strategy has been used to establish stroke diagnosis, delineate early patterns of cerebral ischemia, and monitor response to various reperfusion techniques. Angiographic findings before thrombolysis have substantiated stroke subtype, and documentation of concomitant recanalization has provided considerable insight regarding the vascular and imaging correlates of intra-arterial therapies. MR imaging studies have progressively characterized the complex pathophysiology of acute ischemic stroke, providing imaging strategies and models that may be used to optimize acute stroke care. The ensuing review emphasizes salient aspects of these neuroimaging studies, addressing numerous facets of acute stroke pathophysiology.

Acute Disease↗
PubMed2004

MERCI 1: a phase 1 study of Mechanical Embolus Removal in Cerebral Ischemia.

BACKGROUND AND PURPOSE: To report the result of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) 1 study, a phase 1 trial to evaluate the safety and efficacy of mechanical embolectomy in the cerebral vasculature. METHODS: MERCI 1 enrolled 30 patients in 7 US centers. Main inclusion criteria were: National Institutes of Health Stroke Scale score (NIHSS) > or =10; treatment performed within 8 hours from symptoms onset and contra-indication to intravenous thrombolysis; no large hypodensity on computed tomography; and occlusion of a major cerebral artery on the angiogram. Safety was defined by the absence of vascular injury or symptomatic intracranial hemorrhage. Efficacy was assessed by recanalization rate and clinical outcome at 1 month. Significant recovery was defined as 30-day modified Rankin of 0 to 2 in patients with baseline NIHSS 10 to 20 and 30-day modified Rankin of 0 to 3 in patients with baseline NIHSS >20. The procedures were performed with the Merci Retrieval System, a system specially designed for intracranial embolectomy. RESULTS: Twenty-eight patients were treated. Median NIHSS was 22. Median time from onset to completion of treatment was 6 hours and 15 minutes. Successful recanalization with mechanical embolectomy only was achieved in 12 (43%) patients, and with additional intra-arterial tissue plasminogen activator in 18 (64%) patients. There was one procedure related technical complication, with no clinical consequence. Twelve asymptomatic and no symptomatic intracranial hemorrhages occurred. At 1 month, 9 of 8 revascularized patients and 0 of 10 nonrevascularized patients had achieved significant recovery. CONCLUSIONS: This phase 1 study shows that cerebral embolectomy with the Merci Retriever was safe and that successful recanalization could benefit a significant number of patients, even when performed in an extended 8-hour time window.

Adult↗
PubMed2004

In-hospital initiation of secondary stroke prevention therapies yields high rates of adherence at follow-up.

BACKGROUND AND PURPOSE: The Stroke PROTECT (Preventing Recurrence Of Thromboembolic Events through Coordinated Treatment) program systematically implements, at the time of acute transient ischemic attack (TIA) or ischemic stroke admission, 8 medication/behavioral secondary prevention measures known to improve outcome in patients with cerebrovascular disease. The objective of this study was to determine if the high utilization rates previously demonstrated at hospital discharge were maintained at 90 days after discharge. METHODS: Data were prospectively collected on consecutively encountered ischemic stroke and TIA patients admitted to a university hospital stroke service beginning September 1, 2002. PROTECT interventions were initiated before hospital discharge in all PROTECT-target (underlying stroke mechanism large vessel atherosclerosis or small vessel disease) and PROTECT-ACS (At-risk for Coronary Sequelae) patients. Adherence to program goals was assessed 3 months after discharge. RESULTS: During the period from September 2002 to August 2003, 144 individuals met criteria for PROTECT intervention. Of the 130 patients (90%) with available day 90 follow-up data, mean age was 72 (range, 37 to 95), and 63% were male. Adherence rates in patients without specific contraindications were 100% for antithrombotics, 99% for statins, 92% for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and 80% for thiazides. Awareness of the importance of calling 911 in response to stroke was 87%. Adherence to diet and exercise guidelines were 78% and 70%, respectively. Of the 24 smokers, tobacco cessation was maintained in 20 (83%). CONCLUSIONS: High rates of adherence to PROTECT therapies were maintained at 90 days after hospital discharge.

Adult↗
PubMed2004

Comparison of MRI and CT for detection of acute intracerebral hemorrhage.

CONTEXT: Noncontrast computed tomography (CT) is the standard brain imaging study for the initial evaluation of patients with acute stroke symptoms. Multimodal magnetic resonance imaging (MRI) has been proposed as an alternative to CT in the emergency stroke setting. However, the accuracy of MRI relative to CT for the detection of hyperacute intracerebral hemorrhage has not been demonstrated. OBJECTIVE: To compare the accuracy of MRI and CT for detection of acute intracerebral hemorrhage in patients presenting with acute focal stroke symptoms. DESIGN, SETTING, AND PATIENTS: A prospective, multicenter study was performed at 2 stroke centers (UCLA Medical Center and Suburban Hospital, Bethesda, Md), between October 2000 and February 2003. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain MRI followed by noncontrast CT. MAIN OUTCOME MEASURES: Acute intracerebral hemorrhage and any intracerebral hemorrhage diagnosed on gradient recalled echo (GRE) MRI and CT scans by a consensus of 4 blinded readers. RESULTS: The study was stopped early, after 200 patients were enrolled, when it became apparent at the time of an unplanned interim analysis that MRI was detecting cases of hemorrhagic transformation not detected by CT. For the diagnosis of any hemorrhage, MRI was positive in 71 patients with CT positive in 29 (P<.001). For the diagnosis of acute hemorrhage, MRI and CT were equivalent (96% concordance). Acute hemorrhage was diagnosed in 25 patients on both MRI and CT. In 4 other patients, acute hemorrhage was present on MRI but not on the corresponding CT--each of these 4 cases was interpreted as hemorrhagic transformation of an ischemic infarct. In 3 patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In 1 patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. In 49 patients, chronic hemorrhage, most often microbleeds, was visualized on MRI but not on CT. CONCLUSION: MRI may be as accurate as CT for the detection of acute hemorrhage in patients presenting with acute focal stroke symptoms and is more accurate than CT for the detection of chronic intracerebral hemorrhage.

Acute Disease↗
PubMed2004

Evolving paradigms in neuroimaging of the ischemic penumbra.

Identification of the ischemic penumbra in the acute stroke clinical setting is an important goal for stroke researchers and clinicians. Various models for imaging the penumbra with MRI have been proposed, including the pioneering diffusion-perfusion mismatch model and later multivariate approaches. A number of multicenter clinical trials are now under way to test these models and confirm the utility of MRI-based treatment decisions. Present knowledge about MRI visualization of the salvageable penumbra suggests a promising future in which MRI studies are performed routinely in the acute stroke setting and the data provided by these MRI studies assist in individualizing therapeutic decisions and identifying effective therapies that can be delivered at late time points.

Brain Ischemia↗
PubMed2004

Acute basilar artery occlusion: diffusion-perfusion MRI characterization of tissue salvage in patients receiving intra-arterial stroke therapies.

BACKGROUND AND PURPOSE: Diffusion-perfusion MRI in patients with anterior circulation occlusions has demonstrated salvage of threatened tissue after thrombolytic therapy. Similar studies have not been reported with posterior circulation occlusions. METHODS: Patients with acute basilar artery occlusion treated with intra-arterial thrombolytics were studied with multimodal MRI before treatment, several hours after treatment, and at day 7. RESULTS: Ten patients were studied (9 men, 1 woman). Mean age was 70 years, and median pretreatment National Institutes of Health Stroke Scale (NIHSS) score was 14. In 6 patients imaged before treatment and at day 7, mean pretreatment diffusion-weighted imaging (DWI) lesion volume was 11 cm(3), and day 7, lesion volume was 2.6 cm(3). Significant mismatch was visualized in all 5 patients with pretreatment perfusion-diffusion imaging (mean, 73%; range, 49% to 99%). Late imaging obtained in 4 of these 5 patients demonstrated that mean posttreatment DWI lesion volume (21 cm(3)) was less than the mean initial perfusion lesion volume (62 cm(3)). Although there was no direct correlation between pretreatment DWI volume and initial NIHSS (r=-0.113), there was good correlation between pretreatment perfusion-weighted imaging volume and initial NIHSS (r=0.72). CONCLUSIONS: In this first report of diffusion-perfusion MRI in patients with acute basilar artery occlusions treated with intra-arterial thrombolysis, significant mismatch was visualized on pretreatment studies, suggesting that large volumes of salvageable tissue were present. Final infarct volumes were smaller than pretreatment perfusion volumes, suggesting that substantial volumes of tissue were salvaged by thrombolytic reperfusion.

Acute Disease↗
PubMed2004

Predictors of apparent diffusion coefficient normalization in stroke patients.

BACKGROUND AND PURPOSE: We sought to describe the frequency of normalization of apparent diffusion coefficient (ADC) values that are decreased in hyperacute stroke and to identify characteristics of tissue demonstrating normalization. METHODS: Sixty-eight acute ischemic stroke patients underwent MRI examination (including diffusion/perfusion imaging and MR angiography) within 6 hours (mean, 2.8 hours) after symptom onset, after 24 hours, and again 4 to 7 days later. Lesion volumes with decreased ADC and delayed time to peak in perfusion imaging were determined. In patients showing ADC normalization, volumes with ADC decrease graded as <50%, 50% to 60%, 60% to 70%, and 70% to 80% of the contralateral value were determined by thresholding. Patients were categorized as normalizers (demonstrating ADC normalization in >5 mL tissue with initially decreased ADC) or nonnormalizers (demonstrating ADC normalization in <5 mL tissue). RESULTS: Fourteen patients (19.7%) were classified as normalizers. Eleven of 31 patients (35.5%) initially imaged <3 hours after stroke onset and 3 of 37 (7.5%) of those imaged 3 to 6 hours after onset were normalizers. ADC normalization occurred predominantly in the basal ganglia and white matter after thrombolytic therapy in patients with more distal vessel occlusions. All normalizers demonstrated at least partial tissue reperfusion. Tissue with more severe initial decrease in ADC was less likely to demonstrate normalization. CONCLUSIONS: ADC normalization is not a rare event in acute stroke after tissue reperfusion. Brain tissue with initially decreased ADC, especially within 3 hours after stroke onset, may include "tissue at risk."

Acute Disease↗
PubMed2003

Acute ischemic cerebrovascular syndrome: diagnostic criteria.

BACKGROUND: Existing diagnostic classification systems for cerebrovascular disease are based primarily on clinical impression of temporal features, clinical syndrome, inferred localization, or ischemic mechanism. Diagnostic certainty of the ischemic pathology based on supportive or refuting laboratory or radiological evidence has been of secondary importance. SUMMARY OF COMMENT: Acute ischemic cerebrovascular syndrome (AICS) describes a spectrum of clinical presentations that share a similar underlying pathophysiology: cerebral ischemia. Diagnostic criteria for AICS incorporate prior classification systems and currently available information provided by neuroimaging and laboratory data to define 4 categories ranging from "definite AICS" to "not AICS," which define the degree of diagnostic certainty. CONCLUSIONS: Clinical trials testing new treatments for acute ischemic stroke or secondary stroke prevention should limit enrollment to patients with "definite" AICS whenever feasible.

Acute Disease↗
PubMed2003

Validation of computed tomographic middle cerebral artery "dot"sign: an angiographic correlation study.

BACKGROUND AND PURPOSE: The middle cerebral artery (MCA) "dot" sign consists of hyperdensity of an arterial structure, seen as a dot in the sylvian fissure. The MCA dot sign has been proposed to indicate thrombosis of M2 or M3 MCA branches, analogous to the hyperdense middle cerebral artery (HMCA) sign indicating M1 thrombosis. The MCA dot sign has not been validated previously against the gold standard of conventional cerebral angiography. METHODS: Noncontrast CT scans and immediately subsequent cerebral angiograms from 54 acute stroke patients within 8 hours of symptom onset were analyzed. CT films were inspected for the MCA dot sign and HMCA sign. Vascular findings on CT were compared with findings at angiography. RESULTS: Mean patient age was 71 years; median National Institutes of Health Stroke Scale score was 16.5. Mean time from symptom onset to CT was 125 minutes, and that from CT to angiography was 117 minutes. All patients had arterial occlusion at angiography. Of the anterior circulation occlusions, M1 occlusions were noted in 28 patients, isolated M2 in 15, and isolated M3 in 4. One definite MCA dot sign was observed in 16.7% of patients, and an HMCA sign was observed in 13.9%. MCA dot sign performance in predicting the presence of M2 or M3 clot at angiography was as follows: sensitivity 38%, specificity 100%, positive predictive value 100%, negative predictive value 68%, and overall accuracy 73%. CONCLUSIONS: The MCA dot sign is a highly specific and moderately sensitive indicator of acute thrombus in the M2/M3 MCA branches, as validated by catheter angiography. The MCA dot sign is a useful additional acute stroke CT marker.

Acute Disease↗