-
[show abstract]
[hide abstract]
ABSTRACT: Introduction: In patients with a transient ischemic attack (TIA) or ischemic stroke, the combination of focal and nonfocal symptoms has been associated with a higher risk of cardiovascular events. We hypothesized that nonfocal symptoms are more frequent in patients with symptomatic stenosis of a vertebral artery (VA) than of a carotid artery (CA). Therefore, we assessed the prevalence of nonfocal symptoms in patients with a recent TIA or nondisabling ischemic stroke and studied their relation with symptomatic CA or VA stenosis. Methods: We administered a standardized questionnaire on the occurrence of focal and nonfocal symptoms during the qualifying TIA or nondisabling ischemic stroke and in the preceding 6 months. We included 50 consecutive patients with a recently symptomatic CA stenosis ≥50%, 50 consecutive patients with a recently symptomatic VA stenosis ≥50%, 25 consecutive patients with an anterior circulation event without an ipsilateral CA stenosis ≥50%, and 25 consecutive patients with a posterior circulation event without a relevant VA stenosis ≥50%. Relative risks for the presence of nonfocal symptoms in relation to the presence of a symptomatic stenosis were calculated with univariate and multivariate Poisson regression. Adjustments were made for age, sex, stroke as the qualifying event, and cardiovascular risk factors. A subgroup analysis was performed for patients in whom the vascular territory of the event was confirmed on imaging. Results: During the qualifying ischemic event, focal symptoms were accompanied by nonfocal symptoms in 80 (53%) patients. Nonfocal symptoms occurred more frequently in patients with a VA stenosis (72%) than in patients with a CA stenosis [26%; adjusted relative risk (aRR), 2.9; 95% confidence interval (CI), 1.8-4.6]. A higher prevalence of nonfocal symptoms was found in patients with posterior circulation TIAs and strokes (73%) than in patients with anterior circulation TIAs and strokes (33%; aRR, 2.2; 95% CI, 1.6-3.1). During the preceding 6 months, 45% of patients with and 20% of patients without a symptomatic stenosis had had nonfocal symptoms (aRR, 2.4; 95% CI, 1.3-4.3). Subgroup analysis for the 89 (59%) patients with ischemia visible on imaging gave essentially the same results. Conclusions: More than half of the TIAs or nondisabling ischemic strokes were associated with nonfocal neurological symptoms. Nonfocal symptoms occurred more frequently in patients with a symptomatic VA stenosis than CA stenosis.
Cerebrovascular Diseases 04/2013; 35(4):378-384. · 2.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In patients with space-occupying hemispheric infarction, surgical decompression within 48 h after stroke onset increases the chance of a good functional outcome, but also the chance of survival with severe disability. Until now, cognitive outcome in these patients has not been reported in a consecutive series. Participants of the hemicraniectomy after middle cerebral artery infarction with life-threatening edema trial (HAMLET; ISRCTN94237756) underwent detailed neuropsychological examination at a median of 14.5 months after stroke onset. 'Global cognitive impairment' was defined as a score on the Cambridge cognitive examination (CAMCOG) ≤ 83. Impairment on an individual neuropsychological task was defined as a score below the 2.5th percentile or more than two standard deviations below standard norms. The association between cognitive and functional outcome was analysed with linear regression. Twenty patients were tested. Fifteen (75 %) had global cognitive impairment or such poor performance that assessment of global cognitive performance by the CAMCOG was not feasible. Five had only focal cognitive deficits. Still, detailed neuropsychological examination was feasible in 18 patients. Patients with aphasia performed worse than those without on both verbal and non-verbal tasks. Poorer cognitive performance was associated with worse functional outcome as assessed with the modified Rankin scale (β -0.4, 95 % CI -0.6 to -0.1). No differences were observed between operated and non-operated patients. The majority of survivors of space-occupying hemispheric infarction suffered from long-term global cognitive impairment. Isolated focal neuropsychological deficits were found in only a quarter. Impaired cognitive outcome was associated with worse functional outcome.
Journal of Neurology 01/2013; · 3.47 Impact Factor
-
Henrik Gensicke,
Thomas Zumbrunn,
Lisa M Jongen,
Paul J Nederkoorn,
Sumaira Macdonald,
Peter A Gaines,
Philippe A Lyrer,
Stephan G Wetzel,
Aad van der Lugt,
Willem P Th M Mali,
Martin M Brown, H Bart van der Worp,
Stefan T Engelter,
Leo H Bonati
[show abstract]
[hide abstract]
ABSTRACT: BACKGROUND AND PURPOSE: In a substudy of the International Carotid Stenting Study (ICSS), more patients had new ischemic brain lesions on diffusion-weighted magnetic resonance imaging (MRI) after stenting (CAS) than after endarterectomy (CEA). In the present analysis, we compared characteristics of diffusion-weighted MRI lesions. METHODS: Number, individual and total volumes, and location of new diffusion-weighted MRI lesions were compared in patients with symptomatic carotid stenosis randomized to CAS (n=124) or CEA (n=107) in the ICSS-MRI substudy. RESULTS: CAS patients had higher lesion numbers than CEA patients (1 lesion, 15% vs 8%; 2-5 lesions, 19% vs 5%; >5 lesions, 16% vs 4%). The overall risk ratio for the expected lesion count with CAS versus CEA was 8.8 (95% confidence interval, 4.4-17.5; P<0.0001) and significantly increased among patients with lower blood pressure at randomization, diabetes mellitus, stroke as the qualifying event, left-side stenosis, and if patients were treated at centers routinely using filter-type protection devices during CAS. Individual lesions were smaller in the CAS group than in the CEA group (P<0.0001). Total lesion volume per patient did not differ significantly. Lesions in the CAS group were more likely to occur in cortical areas and subjacent white matter supplied by leptomeningeal arteries than lesions in the CEA group (odds ratio, 4.2; 95% confidence interval, 1.7-10.2; P=0.002). CONCLUSIONS: Compared with patients undergoing CEA, patients treated with CAS had higher numbers of periprocedural ischemic brain lesions, and lesions were smaller and more likely to occur in cortical areas and subjacent white matter. These findings may reflect differences in underlying mechanisms of cerebral ischemia.Clinical Trial Registration-URL: http://www.isrctn.org. Unique identifier: ISRCTN25337470.
Stroke 12/2012; · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Arterial hypotension is more frequently observed early after carotid artery stenting (CAS) than after carotid endarterectomy (CEA), but their long-term effects on blood pressure (BP) are unclear. We compared the effects of CAS and CEA on BP up to 1 year after treatment in the International Carotid Stenting Study.
Patients with symptomatic carotid stenosis were randomly allocated to CAS or CEA. Systolic and diastolic BP were recorded at baseline, at discharge, and at 1, 6, and 12 months. Antihypertensive medication use was recorded. A per-protocol analysis was performed. Patients with missing BP records were excluded. Between-group BP changes were compared and adjusted for baseline covariates with linear regression. Within-group BP changes were compared with the paired t test.
CAS (N=587) and CEA (N=637) were both associated with a decrease in BP at discharge, which was greater after CAS (mean difference in systolic BP between groups, 10.3 mm Hg; 95% CI, 7.3-13.3; P<0.0001; in diastolic BP, 4.1 mm Hg; 95% CI, 2.4-5.7; P<0.0001). During follow-up, BP changes were not different between groups. Adjustment for differences in baseline characteristics did not change the results. Fewer patients undergoing CAS used antihypertensive medication during follow-up than patients undergoing CEA (relative risk at 12 months, 0.91; 95% CI, 0.85-0.97; P=0.0073).
CAS leads to a larger early decrease in BP than CEA, but this effect does not persist over time. CAS may lessen the requirement for antihypertensive medication more than CEA. Clinical Trial Registration- URL: www.controlled-trials.com. Unique identifier: ISRCTN25337470.
Stroke 12/2011; 42(12):3491-6. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Outcomes following treatment of brain arteriovenous malformations (AVMs) with microsurgery, embolization, stereotactic radiosurgery (SRS), or combinations vary greatly between studies.
To assess rates of case fatality, long-term risk of hemorrhage, complications, and successful obliteration of brain AVMs after interventional treatment and to assess determinants of these outcomes.
We searched PubMed and EMBASE to March 1, 2011, and hand-searched 6 journals from January 2000 until March 2011.
We identified studies fulfilling predefined inclusion criteria. We used Poisson regression analyses to explore associations of patient and study characteristics with case fatality, complications, long-term risk of hemorrhage, and successful brain AVM obliteration.
We identified 137 observational studies including 142 cohorts, totaling 13,698 patients and 46,314 patient-years of follow-up. Case fatality was 0.68 (95% CI, 0.61-0.76) per 100 person-years overall, 1.1 (95% CI, 0.87-1.3; n = 2549) after microsurgery, 0.50 (95% CI, 0.43-0.58; n = 9436) after SRS, and 0.96 (95% CI, 0.67-1.4; n = 1019) after embolization. Intracranial hemorrhage rates were 1.4 (95% CI, 1.3-1.5) per 100 person-years overall, 0.18 (95% CI, 0.10-0.30) after microsurgery, 1.7 (95% CI, 1.5-1.8) after SRS, and 1.7 (95% CI, 1.3-2.3) after embolization. More recent studies were associated with lower case-fatality rates (rate ratio [RR], 0.972; 95% CI, 0.955-0.989) but increased rates of hemorrhage (RR, 1.02; 95% CI, 1.00-1.03). Male sex (RR, 0.964; 95% CI, 0.945-0.984), small brain AVMs (RR, 0.988; 95% CI, 0.981-0.995), and those with strictly deep venous drainage (RR, 0.975; 95% CI, 0.960-0.990) were associated with lower case fatality. Lower hemorrhage rates were associated with male sex (RR, 0.976, 95% CI, 0.964-0.988), small brain AVMs (RR, 0.988, 95% CI, 0.980-0.996), and brain AVMs with deep venous drainage (0.982, 95% CI, 0.969-0.996). Complications leading to permanent neurological deficits or death occurred in a median 7.4% (range, 0%-40%) of patients after microsurgery, 5.1% (range, 0%-21%) after SRS, and 6.6% (range, 0%-28%) after embolization. Successful brain AVM obliteration was achieved in 96% (range, 0%-100%) of patients after microsurgery, 38% (range, 0%-75%) after SRS, and 13% (range, 0%-94%) after embolization.
Although case fatality after treatment has decreased over time, treatment of brain AVM remains associated with considerable risks and incomplete efficacy. Randomized controlled trials comparing different treatment modalities appear justified.
JAMA The Journal of the American Medical Association 11/2011; 306(18):2011-9. · 30.03 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Cerebral vascular reactivity assessment is typically performed with 2 perfusion measurements before and after a vasodilatory challenge. The aim of this study was to assess the time course of the vasodilatory effect in the brain-feeding arteries after a challenge with acetazolamide in patients with a stenosis of the internal carotid artery (ICA).
Twenty-one patients with a symptomatic ICA stenosis and 18 healthy control subjects underwent 2-dimensional phase-contrast MR angiography to repeatedly measure the blood flow (mL/min) in both ICAs at baseline and in 5-minute intervals for 30 minutes after intravenous administration of acetazolamide.
At baseline, the blood flow was significantly lower in the stenosed ICAs of patients (155 ± 17 mL/min) than in the contralateral ICAs (237 ± 21 mL/min, P<0.05) and the ICAs of healthy control subjects (249 ± 15 mL/min, P<0.05) and remained lower throughout the time course. The maximum vasodilatory effect in the stenosed ICAs was observed after 15.3 ± 0.9 minutes, which was significantly later than in the contralateral ICAs (within 12.9 ± 0.7 minutes, P<0.05) and healthy ICAs (within 12.8 ± 0.8 minutes, P<0.05).
The onset of the maximum vasodilatory effect after administration of acetazolamide is delayed in patients with a symptomatic ICA stenosis.
Stroke 11/2011; 43(2):553-6. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The risk of ischemic stroke in patients with asymptomatic vertebral artery stenosis is unknown. We examined the incidence of posterior circulation ischemic stroke in patients with asymptomatic stenosis of the vertebral artery origin (VAo).
We studied a hospital-based cohort of 3717 patients (median age, 60 years; interquartile range, 52 to 68 years) with atherosclerotic arterial disease enrolled in the Second Manifestations of ARTerial disease (SMART) study. We included patients in whom duplex ultrasound of the carotid artery and vertebral artery had been performed. Patients with symptomatic VAo stenosis or planned revascularization of the carotid artery or vertebral artery were excluded. Data were analyzed with Cox regression; hazard ratios were adjusted for age and vascular risk factors.
In 282 patients (7.6%), asymptomatic VAo stenosis>50% was diagnosed with duplex ultrasound. During a mean follow-up of 4.6 years (SD, 3.0), posterior circulation ischemic stroke occurred in 5 of the 282 patients with asymptomatic VAo stenosis at baseline (annual stroke rate, 0.4%) and in 12 of the 3435 patients without VAo stenosis (annual stroke rate, <0.1%). The risk of posterior circulation ischemic stroke was higher in patients with VAo stenosis than in patients without VAo stenosis (hazard ratio, 4.2; 95% CI, 1.4 to 13.1) and was further increased in patients with both VAo and carotid artery stenosis (hazard ratio, 10.5; 95% CI, 3.0 to 37.3). In multivariable analysis, this risk remained essentially the same.
Patients with atherosclerotic arterial disease and asymptomatic VAo stenosis have a higher risk of posterior circulation ischemic stroke than patients without such a stenosis, but the absolute risk remains low.
Stroke 08/2011; 42(10):2795-800. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The results of animal studies of human disease often do not translate at the level of randomized clinical trials, which has cast doubt on the usefulness of the relevant animal models. Translational failure has in part been explained by methodological flaws of preclinical studies, disparities between animal models and clinical trials, and publication bias favoring positive animal studies. The designing and reporting of each formal animal study testing the effectiveness of an intervention should therefore be performed in standards similar to those expected of clinical trials to ensure that decision making is based on high-quality and unbiased data. Recommendations for the reporting of aspects of study quality in publications of comparisons of treatment strategies in animal models of disease are provided in this article.
Journal of Molecular and Cellular Cardiology 04/2011; 51(4):449-50. · 5.17 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate the influence of internal carotid artery (ICA) stenosis on the distribution of blood flow to the caudate nucleus, lentiform nucleus, and thalamus.
We studied 18 healthy control subjects, 20 patients with a unilateral asymptomatic ICA stenosis, and 15 patients with a recently symptomatic unilateral ICA stenosis. The contribution of the ICAs and the basilar artery to the perfusion of the deep brain structures was assessed by perfusion territory selective arterial spin labeling (ASL) MRI. Differences were tested with a two-tailed Fishers' exact test.
The caudate nucleus was predominantly supplied with blood by the ipsilateral ICA in all groups. In 4 of the 15 (27%) the symptomatic patients, the caudate nucleus partially received blood from the contralateral ICA, compared to none of the 18 healthy control subjects (p = 0.03). The lentiform nucleus and the thalamus were predominantly supplied with blood by the ipsilateral ICA and basilar artery respectively in all groups.
In patients with a symptomatic ICA stenosis, the caudate nucleus may be supplied with blood by the contralateral ICA more often than in healthy controls.
European Radiology 04/2011; 21(4):875-81. · 3.22 Impact Factor
-
Stroke 03/2011; 42(3):845-6. · 5.73 Impact Factor
-
Practical Neurology 12/2010; 10(6):312-4.
-
[show abstract]
[hide abstract]
ABSTRACT: Subfebrile temperature or fever is present in about a third of patients on the first day after stroke onset and is associated with poor outcome. However, the temporal profile of this association is not well established. We aimed to assess the relationship between body temperature on admission as well as the change in body temperature from admission to 24 h thereafter and functional outcome and death. We analyzed data of 1,332 patients admitted within 12 h of stroke onset. The relation between body temperature on admission or the change in body temperature from admission to 24 h thereafter (adjusted for body temperature on admission) on the one hand and unfavorable outcome (death, or a modified Rankin Scale score >2) at 3 months on the other were expressed as odds ratio per 1.0°C increase in body temperature. Adjustments for potential confounders were made with a multiple logistic regression model. No relation was found between admission body temperature and poor outcome (aOR 1.06; 95% CI 0.85-1.32) and death (aOR 1.23; 95% CI 0.95-1.60). In contrast, increased body temperature in the first 24 h after stroke onset was associated with poor outcome (aOR 1.30; 95% CI 1.05-1.63) and death (aOR 1.51; 95% CI 1.15-1.98). An early rise in body temperature rather than high body temperature on admission is a risk factor for unfavorable outcome in patients with acute stroke.
Journal of Neurology 09/2010; 258(2):302-7. · 3.47 Impact Factor
-
Neurology 08/2010; 75(8):676-7. · 8.31 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: No single animal model is able to encompass all of the variables known to affect human ischemic stroke. This review highlights the major strengths and weaknesses of the most commonly used animal models of acute ischemic stroke in the context of matching model and experimental aim. Particular emphasis is placed on the relationships between outcome and underlying vascular variability, physiologic control, and use of models of comorbidity. The aim is to provide, for novice and expert alike, an overview of the key controllable determinants of experimental stroke outcome to help ensure the most effective application of animal models to translational research.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 08/2010; 30(8):1412-31. · 5.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To measure the cerebral autoregulatory status of the brain tissue supplied by the individual brain-feeding arteries in patients with symptomatic stenosis of the internal carotid artery (ICA) by using arterial spin-labeling (ASL) magnetic resonance (MR) imaging and to compare this status with that in healthy controls.
Institutional review board approval and informed consent were obtained. Twenty-three patients (mean age, 69.3 years +/- 8.0 [standard deviation]) with unilateral symptomatic stenosis of the ICA and 20 healthy controls (mean age, 66.8 years +/- 6.3 [standard deviation]) underwent perfusion and flow territory-selective ASL MR imaging before and after intravenous administration of acetazolamide. Cerebrovascular reactivity was measured throughout the brain in the gray matter that is supplied by the individual ICAs and the basilar artery. Data were analyzed with paired and unpaired t tests.
In patients with symptomatic stenosis of the ICA, the flow territory of the symptomatic ICA was smaller than that of the asymptomatic ICA. After administration of acetazolamide, a significant increase in cerebral blood flow at the brain tissue level was measured in both control subjects and patients in all perfusion territories. Mean cerebrovascular reactivity values were 35.9% +/- 3.0% (standard error) and 44.6% +/- 3.5% (standard error) in the flow territories of the patients with symptomatic ICAs and those with asymptomatic ICAs, respectively, and 47.9% +/- 3.1% (standard error) in the control subjects. Cerebrovascular reactivity was lower in the flow territory of the symptomatic ICA than in the arteries of control participants (mean difference, -12.0%; 95% confidence interval: -20.7%, -3.3%).
In patients with symptomatic stenosis of the ICA, vasodilatory capacity in the flow territories of the major cerebral arteries can be visualized and quantified at the brain tissue level with ASL MR imaging.
Radiology 07/2010; 256(1):201-8. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Patients with impaired perfusion in the hemisphere ipsilateral to a stenotic internal carotid artery may have a higher risk of cerebral ischemic complications than those with normal perfusion. We therefore studied whether the occurrence of new ischemic lesions after carotid artery stenting is related to cerebral perfusion.
In 45 patients with symptomatic carotid artery stenosis, CT perfusion and magnetic resonance diffusion-weighted imaging (DWI) were performed before carotid artery stenting; DWI was repeated within 2 days thereafter. Cerebral blood volume (CBV), mean transit time (MTT), and cerebral blood flow (CBF) were measured with CT perfusion in the cortical flow territory of the middle cerebral artery. Hyperintense lesions on postprocedural DWI not visible on baseline DWI were considered new cerebral ischemic lesions. The relation between CBF, CBV, and MTT and new ipsilateral ischemic lesions was tested with logistic regression.
In 11 of the 45 (24%) patients, new ischemic lesions were found in the ipsilateral hemisphere. The occurrence of these lesions was related to a lower CBF [adjusted odds ratio (aOR), 0.96; 95% confidence interval (CI), 0.92-1.00] and a longer MTT (aOR, 1.65; 95% CI, 1.02-2.66) compared with ipsilateral hemispheres without new lesions.
Patients with impaired cerebral perfusion are more prone to develop ischemic lesions during carotid artery stenting. This suggests that in ischemic stroke during or after carotid artery stenting, embolic and hemodynamic mechanisms act in concert.
Cerebrovascular Diseases 04/2010; 29(6):538-45. · 2.72 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Therapeutic hypothermia is a means of neuroprotection well established in the management of acute ischemic brain injuries such as anoxic encephalopathy after cardiac arrest and perinatal asphyxia. As such, it is the only neuroprotective strategy for which there is robust evidence for efficacy. Although there is overwhelming evidence from animal studies that cooling also improves outcome after focal cerebral ischemia, this has not been adequately tested in patients with acute ischemic stroke. There are still some uncertainties about crucial factors relating to the delivery of hypothermia, and the resolution of these would allow improvements in the design of phase III studies in these patients and improvements in the prospects for successful translation. In this study, we discuss critical issues relating first to the targets for therapy including the optimal depth and duration of cooling, second to practical issues including the methods of cooling and the management of shivering, and finally, of factors relating to the design of clinical trials. Consideration of these factors should inform the development of strategies to establish beyond doubt the place of hypothermia in the management of acute ischemic stroke.
Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 03/2010; 30(6):1079-93. · 5.46 Impact Factor
-
Leo H Bonati,
Lisa M Jongen,
Sven Haller,
H Zwenneke Flach,
Joanna Dobson,
Paul J Nederkoorn,
Sumaira Macdonald,
Peter A Gaines,
Annet Waaijer,
Annet Waajier,
Peter Stierli,
H Rolf Jäger,
Philippe A Lyrer,
L Jaap Kappelle,
Stephan G Wetzel,
Aad van der Lugt,
Willem P Mali,
Martin M Brown, H Bart van der Worp,
Stefan T Engelter
[show abstract]
[hide abstract]
ABSTRACT: The International Carotid Stenting Study (ICSS) of stenting and endarterectomy for symptomatic carotid stenosis found a higher incidence of stroke within 30 days of stenting compared with endarterectomy. We aimed to compare the rate of ischaemic brain injury detectable on MRI between the two groups.
Patients with recently symptomatic carotid artery stenosis enrolled in ICSS were randomly assigned in a 1:1 ratio to receive carotid artery stenting or endarterectomy. Of 50 centres in ICSS, seven took part in the MRI substudy. The protocol specified that MRI was done 1-7 days before treatment, 1-3 days after treatment (post-treatment scan), and 27-33 days after treatment. Scans were analysed by two or three investigators who were masked to treatment. The primary endpoint was the presence of at least one new ischaemic brain lesion on diffusion-weighted imaging (DWI) on the post-treatment scan. Analysis was per protocol. This is a substudy of a registered trial, ISRCTN 25337470.
231 patients (124 in the stenting group and 107 in the endarterectomy group) had MRI before and after treatment. 62 (50%) of 124 patients in the stenting group and 18 (17%) of 107 patients in the endarterectomy group had at least one new DWI lesion detected on post-treatment scans done a median of 1 day after treatment (adjusted odds ratio [OR] 5.21, 95% CI 2.78-9.79; p<0.0001). At 1 month, there were changes on fluid-attenuated inversion recovery sequences in 28 (33%) of 86 patients in the stenting group and six (8%) of 75 in the endarterectomy group (adjusted OR 5.93, 95% CI 2.25-15.62; p=0.0003). In patients treated at a centre with a policy of using cerebral protection devices, 37 (73%) of 51 in the stenting group and eight (17%) of 46 in the endarterectomy group had at least one new DWI lesion on post-treatment scans (adjusted OR 12.20, 95% CI 4.53-32.84), whereas in those treated at a centre with a policy of unprotected stenting, 25 (34%) of 73 patients in the stenting group and ten (16%) of 61 in the endarterectomy group had new lesions on DWI (adjusted OR 2.70, 1.16-6.24; interaction p=0.019).
About three times more patients in the stenting group than in the endarterectomy group had new ischaemic lesions on DWI on post-treatment scans. The difference in clinical stroke risk in ICSS is therefore unlikely to have been caused by ascertainment bias. Protection devices did not seem to be effective in preventing cerebral ischaemia during stenting. DWI might serve as a surrogate outcome measure in future trials of carotid interventions.
UK Medical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union, Netherlands Heart Foundation, and Mach-Gaensslen Foundation.
The Lancet Neurology 02/2010; 9(4):353-62. · 23.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The consolidation of scientific knowledge proceeds through the interpretation and then distillation of data presented in research reports, first in review articles and then in textbooks and undergraduate courses, until truths become accepted as such both amongst "experts" and in the public understanding. Where data are collected but remain unpublished, they cannot contribute to this distillation of knowledge. If these unpublished data differ substantially from published work, conclusions may not reflect adequately the underlying biological effects being described. The existence and any impact of such "publication bias" in the laboratory sciences have not been described. Using the CAMARADES (Collaborative Approach to Meta-analysis and Review of Animal Data in Experimental Studies) database we identified 16 systematic reviews of interventions tested in animal studies of acute ischaemic stroke involving 525 unique publications. Only ten publications (2%) reported no significant effects on infarct volume and only six (1.2%) did not report at least one significant finding. Egger regression and trim-and-fill analysis suggested that publication bias was highly prevalent (present in the literature for 16 and ten interventions, respectively) in animal studies modelling stroke. Trim-and-fill analysis suggested that publication bias might account for around one-third of the efficacy reported in systematic reviews, with reported efficacy falling from 31.3% to 23.8% after adjustment for publication bias. We estimate that a further 214 experiments (in addition to the 1,359 identified through rigorous systematic review; non publication rate 14%) have been conducted but not reported. It is probable that publication bias has an important impact in other animal disease models, and more broadly in the life sciences.
PLoS Biology 01/2010; 8(3):e1000344. · 11.45 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: H. Bart van der Worp and colleagues discuss the controversies and possibilities of translating the results of animal experiments into human clinical trials.
PLoS Medicine 01/2010; 7(3):e1000245. · 16.27 Impact Factor
