Men Are at Higher Risk of Screening Positive for Vascular Cognitive Impairment Compared to Women after Stroke and Transient Ischemic Attack.

While women have greater incidence of dementia, men have higher prevalence of vascular risk factors. This study examined sex differences in risk of screening positive for cognitive impairment after stroke. Ischemic stroke/TIA patients (N = 5969) participated in this prospective, multi-centered study, which screened for cognitive impairment using a validated brief screen. Men showed a higher risk of screening positive for cognitive impairment after adjusting for age, education, stroke severity, and vascular risk factors, suggesting that other factors may be contributing to increased risk among men (OR = 1.34, CI 95% [1.16, 1.55], p < 0.001). The effect of sex on cognitive impairment after stroke warrants further attention.

Multidisciplinary quality improvement initiative to optimize acute neurovascular imaging for transient ischemic attack or minor stroke.

BACKGROUND: Neurovascular imaging for patients with high-risk transient ischemic attack (TIA) or minor stroke in the emergency department (ED) with computed tomography angiography (CTA) of the head and neck is the guideline-recommended standard of care, but it is underutilized in routine practice. We conducted a quality initiative to improve adherence to guidelines. METHODS: Between January 2017 and March 2019, we implemented a decision support tool integrated into the electronic ordering system to guide ED physicians to order a CTA on patients with high-risk TIA or minor stroke defined as ongoing neurological deficits in the ED or resolved motor or speech deficits in the preceding 48 h. Data were collected retrospectively pre-intervention and prospectively post-intervention. We used an interrupted time-series analysis for the before-after comparison of the use of CTA among patients who met criteria (main process measure) and those who did not meet criteria (balancing measure). RESULTS: Among 861 patients with TIA or minor stroke, the proportion of patients with high-risk events imaged with a CTA in the ED increased from 12.0% pre-intervention to 77.0% post-intervention and this shift was sustained over 11 months. CTA use in those without high-risk events increased to a lesser extent (15.3% versus 42.9%). The interrupted time-series analysis showed a step change immediately post-intervention where the increase in CTA use in patients with high-risk events was 51.7% higher than its use in those without high-risk events (p < 0.001). Compared to pre-intervention, the median ED length of stay increased by 2 h and neurology consultation in the ED was more frequent (5.8% versus 19.5%) post-intervention. CONCLUSION: We provide a detailed framework that improved adherence to acute imaging guidelines for patients with TIA or minor stroke and anticipate that our approach could improve acute imaging for such patients in most EDs.

RéSUMé: CONTEXTE: L'imagerie neurovasculaire pour les patients présentant un risque élevé d'accident ischémique transitoire (AIT) ou d'accident vasculaire cérébral mineur aux services d'urgence, avec une angiographie par tomodensitométrie (CTA) de la tête et du cou, est la norme de soins recommandée par les directives, mais elle est sous-utilisée dans la pratique courante. Nous avons mené une initiative de qualité pour améliorer le respect des lignes directrices. MéTHODES: Entre janvier 2017 et mars 2019, nous avons mis en place un outil d'aide à la décision intégré au système de commande électronique pour guider les médecins du service d'urgence à prescrire un CTA sur des patients atteints d'un AIT à haut risque ou d'un AVC mineur défini comme des déficits neurologiques en cours au service des urgences ou une résolution de la motricité ou des troubles de la parole dans les 48 heures précédentes. Les données ont été recueillies rétrospectivement avant l'intervention et prospectivement après l'intervention. Nous avons utilisé une analyse de séries chronologiques interrompues pour la comparaison avant-après de l'utilisation du CTA chez les patients qui répondaient aux critères (mesure principale du processus) et ceux qui ne répondaient pas aux critères (mesure d'équilibrage). RéSULTATS: Parmi les 861 patients atteints d'un AIT ou d'un AVC mineur, la proportion de patients présentant des événements à haut risque imagés avec un CTA au service d'urgence est passé de 12,0 % avant l'intervention à 77,0 % après l'intervention et ce changement s'est maintenu pendant 11 mois. L'utilisation de CTA chez les personnes sans événements à haut risque a augmenté dans une moindre mesure (15,3 % contre 42,9 %). L'analyse des séries chronologiques interrompues a montré un changement d'étape immédiatement après l'intervention où l'augmentation de l'utilisation du CTA chez les patients présentant des événements à haut risque était 51,7 % plus élevée que son utilisation chez ceux sans événements à haut risque (p < 0,001). Par rapport à la pré-intervention, la durée médiane du séjour au SU a augmenté de deux heures et les consultations de neurologie au SU étaient plus fréquentes (5,8 % contre 19,5 %) après l'intervention. CONCLUSION: Nous fournissons un cadre détaillé qui a amélioré le respect des lignes directrices en matière d'imagerie aiguë pour les patients souffrant d'AIT ou d'AVC mineur et nous prévoyons que notre approche pourrait améliorer l'imagerie aiguë pour ces patients dans la plupart des urgences.

Younger Age and Depressive Symptoms Predict High Risk of Generalized Anxiety After Stroke and Transient Ischemic Attack.

Background and Purpose- Depression and anxiety are common after stroke/transient ischemic attack (TIA). These conditions are associated with poor functional outcome and worse quality of life. However, few studies have explored predictors of poststroke risk of generalized anxiety, especially in patients without comorbid depressive symptoms. We aimed to explore predictors of high risk of generalized anxiety after stroke/TIA. Methods- Consecutive stroke and TIA referrals to the Sunnybrook Stroke Prevention Clinic over a 2-year period (April 2012-April 2014) who spoke English, were not severely aphasic, and who consented to complete neuropsychological testing were included in this analysis. Generalized anxiety and depressive symptoms were assessed using the Generalized Anxiety Disorder 7-item scale and Center for Epidemiological Studies Depression Scale, respectively. Results- Two hundred and fifty-eight patients completed the Generalized Anxiety Disorder 7-item scale, of whom 56 (22%) were at high risk for generalized anxiety (scores ≥10). Younger age (odds ratio=0.96; 95% CI, 0.93-0.99; P=0.004) and greater depressive symptoms (odds ratio=1.20; 95% CI, 1.14-1.26; P≤0.001) were significant predictors of being at high risk for generalized anxiety after stroke/TIA. Younger patients (≤50 years) were significantly more likely to be at high risk for both depression and generalized anxiety than older patients (30% versus 12%, χ2 [1, N=258]=10.98, P=0.001). Our model explained 56% of the variance in risk of generalized anxiety after stroke. In patients without severe depressive symptoms (n=193, 75%), age and severity of depressive symptoms remained the only factors associated with risk of generalized anxiety. Conclusions- Anxiety is common after stroke/TIA and is highly correlated with poststroke depressive symptoms and age, even among those without severe depressive symptoms. Given the greater frequency of both generalized anxiety and depressive symptoms in young survivors, routine screening for depression and further evaluation of anxiety after stroke/TIA is warranted.

Nanoparticles targeting extra domain B of fibronectin-specific to the atherosclerotic lesion types III, IV, and V-enhance plaque detection and cargo delivery.

Extra domain B of fibronectin (FN-EDB) is upregulated in the extracellular matrix during tissue remodeling and has been postulated as a potential biomarker for atherosclerosis, yet no systematic test for FN-EDB in plaques has been reported. We hypothesized that FN-EDB expression would intensify in advanced plaques. Furthermore, engineering of FN-EDB-targeted nanoparticles (NPs) could enable imaging/diagnosis and local delivery of payloads to plaques. Methods: The amount of FN-EDB in human atherosclerotic and normal arteries (ages: 40 to 85 years) was assessed by histological staining and quantification using an FN-EDB-specific aptide (APTFN-EDB). FN-EDB-specific NPs that could serve as MRI beacons were constructed by immobilizing APTFN-EDB on the NP surface containing DTPA[Gd]. MRI visualized APTFN-EDB-[Gd]NPs administered to atherosclerotic apolipoprotein E-deficient mice in the brachiocephalic arteries. Analysis of the ascending-to-descending thoracic aortas and the aortic roots of the mice permitted quantitation of Gd, FN-EDB, and APTFN-EDB-[Gd]NPs. Cyanine, a model small molecule drug, was used to study the biodistribution and pharmacokinetics of APTFN-EDB-NPs to evaluate their utility for drug delivery. Results: Atherosclerotic tissues had significantly greater FN-EDB-positive areas than normal arteries (P < 0.001). This signal pertained particularly to Type III (P < 0.01), IV (P < 0.01), and V lesions (P < 0.001) rather than Type I and II lesions (AHA classification). FN-EDB expression was positively correlated with macrophage accumulation and neoangiogenesis. Quantitative analysis of T1-weighted images of atherosclerotic mice revealed substantial APTFN-EDB-[Gd]NPs accumulation in plaques compared to control NPs, conventional MRI contrast agent (Gd-DTPA) or accumulation in wild-type C57BL/6J mice. Additionally, the APTFN-EDB-NPs significantly prolonged the blood-circulation time (t1/2: ~ 6 h) of a model drug and increased its accumulation in plaques (6.9-fold higher accumulation vs. free drug). Conclusions: Our findings demonstrate augmented FN-EDB expression in Type III, IV, and V atheromata and that APTFN-EDB-NPs could serve as a platform for identifying and/or delivering agents locally to a subset of atherosclerotic plaques.

Targeted Nanotherapeutics Encapsulating Liver X Receptor Agonist GW3965 Enhance Antiatherogenic Effects without Adverse Effects on Hepatic Lipid Metabolism in Ldlr-/- Mice.

The pharmacological manipulation of liver X receptors (LXRs) has been an attractive therapeutic strategy for atherosclerosis treatment as they control reverse cholesterol transport and inflammatory response. This study presents the development and efficacy of nanoparticles (NPs) incorporating the synthetic LXR agonist GW3965 (GW) in targeting atherosclerotic lesions. Collagen IV (Col IV) targeting ligands are employed to functionalize the NPs to improve targeting to the atherosclerotic plaque, and formulation parameters such as the length of the polyethylene glycol (PEG) coating molecules are systematically optimized. In vitro studies indicate that the GW-encapsulated NPs upregulate the LXR target genes and downregulate proinflammatory mediator in macrophages. The Col IV-targeted NPs encapsulating GW (Col IV-GW-NPs) successfully reaches atherosclerotic lesions when administered for 5 weeks to mice with preexisting lesions, substantially reducing macrophage content (≈30%) compared to the PBS group, which is with greater efficacy versus nontargeting NPs encapsulating GW (GW-NPs) (≈18%). In addition, mice administered the Col IV-GW-NPs do not demonstrate increased hepatic lipid biosynthesis or hyperlipidemia during the treatment period, unlike mice injected with the free GW. These findings suggest a new form of LXR-based therapeutics capable of enhanced delivery of the LXR agonist to atherosclerotic lesions without altering hepatic lipid metabolism.