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  • Ovid Technologies (Wolters Kluwer Health)  (3)
  • 1
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 99, No. 16 ( 2022-10-18), p. e1738-e1754
    Abstract: Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. Methods We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18–59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. Results We observed genome-wide significant associations of EOS with 2 variants in ABO , a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85–0.91) in EOS vs 0.96 (95% CI: 0.92–1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11–1.21) for EOS vs 1.05 (0.99–1.11) in LOS; p -values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS ( p = 0.008). Discussion The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 3 ( 2023-03), p. 810-818
    Abstract: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20–1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01–1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59–0.67) to 0.65 (95% CI, 0.62–0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=−4.82×10 −3 per year [95% CI, −6.49×10 −3 to −3.14×10 −3 ]; P =1.82×10 −8 ), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86–0.98]; P =0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1467823-8
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  • 3
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 6, No. 11 ( 2017-11)
    Abstract: Mechanical cardiopulmonary resuscitation ( mCPR ) for patients with out‐of‐hospital cardiac arrest attending the emergency department has become more widespread in Japan. The objective of this study is to determine the association between the mCPR in the emergency department and clinical outcomes. Methods and Results In a prospective, multicenter, observational study, adult patients with out‐of‐hospital cardiac arrest with sustained circulatory arrest on hospital arrival were identified. The primary outcome was survival to hospital discharge. The secondary outcomes included a return of spontaneous circulation and successful hospital admission. Multivariate analyses adjusted for potential confounders and within‐institution clustering effects using a generalized estimation equation were used to analyze the association of the mCPR with outcomes. Between January 1, 2012 and March 31, 2013, 6537 patients with out‐of‐hospital cardiac arrest were eligible; this included 5619 patients (86.0%) in the manual CPR group and 918 patients (14.0%) in the mCPR group. Of those patients, 28.1% (1801/6419) showed return of spontaneous circulation in the emergency department, 20.4% (1175/5754) had hospital admission, 2.6% (168/6504) survived to hospital discharge, and 1.2% (75/6419) showed a favorable neurological outcome at 1 month after admission. Multivariate analyses revealed that mCPR was associated with a decreased likelihood of survival to hospital discharge (adjusted odds ratio, 0.40; 95% confidence interval, 0.20–0.78; P =0.005), return of spontaneous circulation (adjusted odds ratio, 0.71; 95% confidence interval, 0.53–0.94; P =0.018), and hospital admission (adjusted odds ratio, 0.57; 95% confidence interval, 0.40–0.80; P =0.001). Conclusions After accounting for potential confounders, the mCPR in the emergency department was associated with decreased likelihoods of good clinical outcomes after adult nontraumatic out‐of‐hospital cardiac arrest. Further studies are needed to clarify circumstances in which mCPR may benefit these patients.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2653953-6
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