| 1. |
- Debette, Stéphanie, et al.
(författare)
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Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 47, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year)1. Minor cervical traumas, infection, migraine and hypertension are putative risk factors1–3, and inverse associations with obesity and hypercholesterolemia are described3,4. No confirmed genetic susceptibility factors have been identified using candidate gene approaches5. We performed genome-wide association studies (GWAS) in 1 1,393 CeAD cases and 1 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69–0.82; P = 4.46 × 1 10−10), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 1 × 1 10−3; combined P = 1 1.00 × 1 10−1111). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction6–9. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions.
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| 2. |
- Ederle, Joerg, et al.
(författare)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 3. |
- Nordanstig, Annika, 1974, et al.
(författare)
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EndoVAscular treatment and ThRombolysis for Ischemic Stroke Patients (EVA-TRISP) registry: basis and methodology of a pan-European prospective ischaemic stroke revascularisation treatment registry.
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- The Thrombolysis in Ischemic Stroke Patients (TRISP) collaboration was a concerted effort initiated in 2010 with the purpose to address relevant research questions about the effectiveness and safety of intravenous thrombolysis (IVT). The collaboration also aims to prospectively collect data on patients undergoing endovascular treatment (EVT) and hence the name of the collaboration was changed from TRISP to EVA-TRISP. The methodology of the former TRISP registry for patients treated with IVT has already been published. This paper focuses on describing the EVT part of the registry.All centres committed to collecting predefined variables on consecutive patients prospectively. We aim for accuracy and completeness of the data and to adapt local databases to investigate novel research questions. Herein, we introduce the methodology of a recently constructed academic investigator-initiated open collaboration EVT registry built as an extension of an existing IVT registry in patients with acute ischaemic stroke (AIS).Currently, the EVA-TRISP network includes 20 stroke centres with considerable expertise in EVT and maintenance of high-quality hospital-based registries. Following several successful randomised controlled trials (RCTs), many important clinical questions remain unanswered in the (EVT) field and some of them will unlikely be investigated in future RCTs. Prospective registries with high-quality data on EVT-treated patients may help answering some of these unanswered issues, especially on safety and efficacy of EVT in specific patient subgroups.This collaborative effort aims at addressing clinically important questions on safety and efficacy of EVT in conditions not covered by RCTs. The TRISP registry generated substantial novel data supporting stroke physicians in their daily decision making considering IVT candidate patients. While providing observational data on EVT in daily clinical practice, our future findings may likewise be hypothesis generating for future research as well as for quality improvement (on EVT). The collaboration welcomes participation of further centres willing to fulfill the commitment and the outlined requirements.
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| 4. |
- Nowak, Bartosch, et al.
(författare)
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Occurrence of No-Harm Incidents and Adverse Events in Hospitalized Patients with Ischemic Stroke or TIA : A Cohort Study Using Trigger Tool Methodology
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 19:5
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Tidskriftsartikel (refereegranskat)abstract
- Adverse events (AEs)-healthcare caused events leading to patient harm or even death-are common in healthcare. Although it is a frequently investigated topic, systematic knowledge on this phenomenon in stroke patients is limited. To determine cumulative incidence of no-harm incidents and AEs, including their severity and preventability, a cohort study using trigger tool methodology for retrospective record review was designed. The study was carried out in a stroke center at a university hospital in the German speaking part of Switzerland. Electronic records from 150 randomly selected patient admissions for transient ischemic attack (TIA) or ischemic stroke, with or without acute recanalization therapy, were used. In total, 170 events (108 AEs and 62 no-harm incidents) were identified, affecting 83 patients (55.3%; 95% CI 47 to 63.4), corresponding to an event rate of 113 events/100 admissions or 142 events/1000 patient days. The three most frequent AEs were ischemic strokes (n = 12, 7.1%), urinary tract infections (n = 11, 6.5%) and phlebitis (n = 10, 5.9%). The most frequent no-harm incidents were medication events (n = 37, 21.8%). Preventability ranged from 12.5% for allergic reactions to 100% for medication events and pressure ulcers. Most of the events found (142; 83.5%; 95% CI 76.9 to 88.6) occurred throughout the whole stroke care. The remaining 28 events (16.5%; 95% CI 11.4 to 23.1) were detected during stroke care but were related to care outside the stroke pathway. Trigger tool methodology allows detection of AEs and no-harm incidents, showing a frequent occurrence of both event types in stroke and TIA patients. Further investigations into events' relationships with organizational systems and processes will be needed, first to achieve a better understanding of these events' underlying mechanisms and risk factors, then to determine efforts needed to improve patient safety.
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| 5. |
- Pfeiffer, Dorothea, et al.
(författare)
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Genetic Imbalance Is Associated With Functional Outcome After Ischemic Stroke
- 2019
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Ingår i: Stroke. - 1524-4628. ; 50:2, s. 298-304
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose- We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods- Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of ≥3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs-a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results- The study sample comprised 816 CADISP patients (age 44.2±10.3 years) and 2498 SiGN/GISCOME patients (age 67.7±14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P=0.0007; odds ratio=0.89; 95% CI, 0.82-0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91-0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80-0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89-0.98) whereas imbalance without ohnologs lacked such an association. Conclusions- Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.
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| 6. |
- Traenka, Christopher, et al.
(författare)
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Artery occlusion independently predicts unfavorable outcome in cervical artery dissection.
- 2020
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Ingår i: Neurology. - 1526-632X. ; 94:2
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Tidskriftsartikel (refereegranskat)abstract
- To assess the impact of dissected artery occlusion (DAO) on functional outcome and complications in patients with cervical artery dissection (CeAD).We analyzed combined individual patient data from 3 multicenter cohorts of consecutive patients with CeAD (the Cervical Artery Dissection and Ischemic Stroke Patients [CADISP]-Plus consortium dataset). Patients with data on DAO and functional outcome were included. We compared patients with DAO to those without DAO. Primary outcome was favorable functional outcome (i.e., modified Rankin Scale [mRS] score 0-1) measured 3-6 months from baseline. Secondary outcomes included delayed cerebral ischemia, major hemorrhage, recurrent CeAD, and death. We performed univariate and multivariable binary logistic regression analyses and calculated odds ratios (OR) with 95% confidence intervals (CI), with adjustment for potential confounders.Of 2,148 patients (median age 45 years [interquartile range (IQR) 38-52], 43.6% women), 728 (33.9%) had DAO. Patients with DAO more frequently presented with cerebral ischemia (84.6% vs 58.5%, p < 0.001). Patients with DAO were less likely to have favorable outcome when compared to patients without DAO (mRS 0-1: 59.6% vs 80.1%, punadjusted < 0.001). After adjustment for age, sex, and initial stroke severity, DAO was independently associated with less favorable outcome (mRS 0-1: OR 0.65, CI 0.50-0.84, p = 0.001). Delayed cerebral ischemia occurred more frequently in patients with DAO than in patients without DAO (4.5% vs 2.9%, p = 0.059).DAO independently predicts less favorable functional outcome in patients with CeAD. Further research on vessel patency, collateral status and effects of revascularization therapies particularly in patients with DAO is warranted.
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| 7. |
- Traenka, Christopher, et al.
(författare)
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Cervical artery dissection in patients ≥60 years: Often painless, few mechanical triggers.
- 2017
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Ingår i: Neurology. - 1526-632X. ; 88:14, s. 1313-1320
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Tidskriftsartikel (refereegranskat)abstract
- In a cohort of patients diagnosed with cervical artery dissection (CeAD), to determine the proportion of patients aged ≥60 years and compare the frequency of characteristics (presenting symptoms, risk factors, and outcome) in patients aged <60 vs ≥60 years.We combined data from 3 large cohorts of consecutive patients diagnosed with CeAD (i.e., Cervical Artery Dissection and Ischemic Stroke Patients-Plus consortium). We dichotomized cases into 2 groups, age ≥60 and <60 years, and compared clinical characteristics, risk factors, vascular features, and 3-month outcome between the groups. First, we performed a combined analysis of pooled individual patient data. Secondary analyses were done within each cohort and across cohorts. Crude and adjusted odds ratios (OR [95% confidence interval]) were calculated.Among 2,391 patients diagnosed with CeAD, we identified 177 patients (7.4%) aged ≥60 years. In this age group, cervical pain (ORadjusted 0.47 [0.33-0.66]), headache (ORadjusted 0.58 [0.42-0.79]), mechanical trigger events (ORadjusted 0.53 [0.36-0.77]), and migraine (ORadjusted 0.58 [0.39-0.85]) were less frequent than in younger patients. In turn, hypercholesterolemia (ORadjusted 1.52 [1.1-2.10]) and hypertension (ORadjusted 3.08 [2.25-4.22]) were more frequent in older patients. Key differences between age groups were confirmed in secondary analyses. In multivariable, adjusted analyses, favorable outcome (i.e., modified Rankin Scale score 0-2) was less frequent in the older age group (ORadjusted 0.45 [0.25, 0.83]).In our study population of patients diagnosed with CeAD, 1 in 14 was aged ≥60 years. In these patients, pain and mechanical triggers might be missing, rendering the diagnosis more challenging and increasing the risk of missed CeAD diagnosis in older patients.
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