Changes in anticoagulation practice in subjects admitted with stroke associated with atrial fibrillation, following introduction of direct oral anticoagulants over 2013-2021.

BACKGROUND: The adoption of direct oral anticoagulants (DOACs) has changed practice in prevention of stroke in atrial fibrillation (AF). We used Irish data national data on stroke and anticoagulation therapy over 9 years to investigate changes in anticoagulation practice and potential consequences on stroke prevalence and thrombolysis. METHODS: AF, anticoagulation, thrombolysis, and stroke data from the Irish National Audit of Stroke (INAS) 2013-2021 were reviewed. The proportion of patients with ischemic stroke (IS) and intracerebral hemorrhage (IH) with known AF admitted on anticoagulation was determined. Effects on age distribution in the population and thrombolysis practice were assessed. RESULTS: AF data were available on 34,630 of 35,241 individuals (98.3%) included in INAS; median age was 74 years and 56% were male. AF was found in 10,016 (28.9%, 9059 IS, 957 IH). 6313 had known AF prior to stroke (63.1%). The proportion all total IS due to AF decreased by 15.3% (31.3%-26.5%, chi-square = 24.6, p < 0.0001). The proportion of IH did not change significantly (21.6%-20.2%, chi-square = 1.8, p = 0.18). Over the 9 years, 3875 (38.6%) of the subjects with AF were recorded as receiving anticoagulants at admission. In 2013, 4.4% of AF-associated strokes were admitted on a DOAC and 21.4% on warfarin; by 2021, 44.1% were receiving a DOAC and 6.2% warfarin. There was a strong inverse correlation between the proportion of anticoagulated stroke patients and the total proportion of AF-associated strokes over time (r = -0.82, p = 0.006). In contrast, no correlation was found between increasing DOAC usage and IH (r = 0.14, p = 0.71). Increased anticoagulation usage correlated with a reduction in patients ⩾ 80 years (r = -0.83, p = 0.006) and also correlated with a relative reduction of 30.1% in subjects thrombolysed <4 h from onset (r = -0.89, p = 0.001). CONCLUSION: DOACs have led to increased use of anticoagulation, but warfarin use fell by two-thirds. There has been a reduction in the proportion of AF-associated IS without a noticeable increase in IH. Increased anticoagulation correlated with reduced numbers of strokes in those >80 years and in the proportion of patients thrombolysed.

A single-site retrospective review of in-hospital stroke.

BACKGROUND: In-hospital stroke refers to a stroke arising in a patient during hospital admission for another condition. Between 2 and 17% of all inpatient strokes are in-hospital strokes. AIM: To compare the outcomes and performance on quality-of-care stroke measures of in-hospital stroke cases with community-onset strokes. METHODS: Data collected for the Irish Annual Audit of Stroke from an Irish university teaching hospital was analysed for a 2-year period from 1st January 2020 to 31st December 2021. A retrospective cohort study was conducted to compare baseline characteristics, outcomes, and performance on standardised quality-of-care measures between the cohorts. RESULTS: The rate of IHS was 15.6%. Median age was 73 years and 72 years for in-hospital and community-onset strokes respectively. Amongst in-hospital strokes, COVID-19 co-diagnosis (9.1% versus 1.3%; p = .0004), admission to intensive care (52.3% versus 5.3%; p < .0001), discharge to long term care (6.8% versus 2.3%; p = .04), mortality (12.5% versus 7.6%; p = .13), and modified Rankin score of two or more at discharge (58.0% versus 38.1%; p = .001), were more likely compared to community-onset strokes. Thrombolysis rates were lower (7.3% versus 12.0%; p = .22) and thrombectomy rates higher (9.8% versus 6.6;% p = .32), albeit non-significantly. Median time to thrombolysis was slower amongst in-hospital strokes (105 min versus 66 min; p = .03) and they were less likely to be admitted to the stroke unit (43.2% versus 78.5%; p < .0001). CONCLUSIONS: When compared with community-onset stroke, in-hospital stroke represents a distinct stroke subgroup with poorer outcomes and delays to thrombolysis emphasising the need for standardised approaches to evaluation and management.

Clinical validation of in-hospital stroke diagnosis.

OBJECTIVE: In-hospital stroke cases occur during hospitalization for another diagnosis and reflect a clinically distinct cohort from community-onset stroke. The objective was to validate the diagnostic accuracy of in-hospital stroke identification in stroke audit data at a large teaching hospital. METHODS: A retrospective clinical validation of in-hospital stroke diagnoses from two linked data sources was completed for a 2-year period from January 1st 2020 to December 31st 2021. The linked data sources include the Hospital Inpatient Enquiry system which assigns coded stroke diagnoses at discharge and/or the local stroke audit coordinators who work clinically in stroke teams and input additional specific clinical data. Diagnostic sensitivity, specificity and the level of agreement using an unweighted Cohen's Kappa were calculated. RESULTS: There were 597 strokes admitted during the 2-year period. The median age was 72 years and 55% occurred in males. In total, 88 cases of in-hospital stroke were clinically validated yielding an in-hospital stroke rate of 15%. The clinical audit coordinator identified in-hospital stroke with higher sensitivity (86%; 95% CI 77%-93%) whereas the coding process was more specific at 96% (95% CI 85% to 99%). Levels of agreement with the clinically validated gold standard sample were moderate for the audit coordinator and coding process with κ = 0.57 and K = 0.42 respectively. When both data sources were combined the level of agreement was substantial (κ = 0.65; p < .000). CONCLUSIONS: Clinical validation studies are required to reinforce data quality within stroke registers. Combining clinical and administrative data sources improves diagnostic accuracy for in-hospital stroke identification.

Symptomatic Carotid Atheroma Inflammation Lumen-stenosis score compared with Oxford and Essen risk scores to predict recurrent stroke in symptomatic carotid stenosis.

BACKGROUND: The Oxford Carotid Stenosis tool (OCST) and Essen Stroke Risk Score (ESRS) are validated to predict recurrent stroke in patients with and without carotid stenosis. The Symptomatic Carotid Atheroma Inflammation Lumen stenosis (SCAIL) score combines stenosis and plaque inflammation on fluorodeoxyglucose positron-emission tomography (18FDG-PET). We compared SCAIL with OCST and ESRS to predict ipsilateral stroke recurrence in symptomatic carotid stenosis. PATIENTS AND METHODS: We pooled three prospective cohort studies of patients with recent (<30 days) non-severe ischaemic stroke/TIA and internal carotid artery stenosis (>50%). All patients had carotid 18FDG-PET/CT angiography and late follow-up, with censoring at carotid revascularisation. RESULTS: Of 212 included patients, 16 post-PET ipsilateral recurrent strokes occurred in 343 patient-years follow-up (median 42 days (IQR 13-815)).Baseline SCAIL predicted recurrent stroke (unadjusted hazard ratio [HR] 1.96, CI 1.20-3.22, p = 0.007, adjusted HR 2.37, CI 1.31-4.29, p = 0.004). The HR for OCST was 0.996 (CI 0.987-1.006, p = 0.49) and for ESRS was 1.26 (CI 0.87-1.82, p = 0.23) (all per 1-point score increase). C-statistics were: SCAIL 0.66 (CI 0.51-0.80), OCST 0.52 (CI 0.40-0.64), ESRS 0.61 (CI 0.48-0.74). Compared with ESRS, addition of plaque inflammation (SUVmax) to ESRS improved risk prediction when analysed continuously (HR 1.51, CI 1.05-2.16, p = 0.03) and categorically (ptrend = 0.005 for risk increase across groups; HR 3.31, CI 1.42-7.72, p = 0.006; net reclassification improvement 10%). Findings were unchanged by further addition of carotid stenosis. CONCLUSIONS: SCAIL predicted recurrent stroke, had discrimination better than chance, and improved the prognostic utility of ESRS, suggesting that measuring plaque inflammation may improve risk stratification in carotid stenosis.

Perspective: The Case for Acute Large Vessel Ischemic Stroke in COVID-19 Originating Within Thrombosed Pulmonary Venules.

The main burden of SARS-CoV-2 falls on the lungs but neurological manifestations, the most disabling of which are strokes and which correlate with disease severity, are common. We proffer a novel mechanism for acute COVID-19 stroke whereby pulmonary vein clots developing within the characteristic pulmonary intravascular thrombotic lesions can embolize to the brain. Appreciation of this mechanism requires an understanding of the tricompartmental model of lung parenchyma oxygenation (the alveolus, the bronchial artery, and the pulmonary artery), all of which are compromised in COVID-19. Of these 3 sources, the bronchial artery plays a crucial role in COVID-19 stroke because the unique collaterals from bronchial artery to pulmonary vein which exist under normal physiological conditions (and which maintain venous patency when the pulmonary artery is blocked by embolus) are occluded, thus leading to venular thrombosis in the presence of hypercoagulability. Dislodgement of clots from this source translocates the pathology to the brain and is a disease mechanism, formerly rare, which may account for many cases of large vessel occlusion stroke in COVID-19. This mechanism extends the concept of cardioembolic stroke from endocardium retrogradely into the pulmonary circulation with which the left cardiac chambers lie in direct continuity, and which is an accepted stroke mechanism under other circumstances such as lung lobectomy, where surgical ligation of the pulmonary vein creates a blind sac from which thrombi can embolize. The proposed model is supported by postmortem studies which have demonstrated venular thrombosis and by case reports of pulmonary vein thrombosis in COVID-19. This concept provides a more plausible cause for COVID-19 associated large vessel occlusion stroke than other putative mechanisms, such as cerebral endotheliitis, cytokine storm, and hypercoagulopathy, although it is acknowledged that the latter mechanism contributes to the genesis of pulmonary vein clots. Recognizing that extrapulmonary manifestations including stroke arise within thrombosed pulmonary veins is key to understanding of neurological manifestations of SARS-CoV-2 infection.

Association of Plaque Inflammation With Stroke Recurrence in Patients With Unproven Benefit From Carotid Revascularization.

BACKGROUND AND OBJECTIVES: In pooled analyses of endarterectomy trials for symptomatic carotid stenosis, several subgroups experienced no net benefit from revascularization. The validated symptomatic carotid atheroma inflammation lumen-stenosis (SCAIL) score includes stenosis severity and inflammation measured by PET and improves the identification of patients with recurrent stroke compared with lumen-stenosis alone. We investigated whether the SCAIL score improves the identification of recurrent stroke in subgroups with uncertain benefit from revascularization in endarterectomy trials. METHODS: We did an individual-participant data pooled analysis of 3 prospective cohort studies (Dublin Carotid Atherosclerosis Study [DUCASS], 2008-2011; Biomarkers and Imaging of Vulnerable Atherosclerosis in Symptomatic Carotid Artery Disease [BIOVASC], 2014-2018; Barcelona Plaque Study, 2015-2018). Eligible patients had a recent nonsevere (modified Rankin Scale score ≤3) anterior circulation ischemic stroke/TIA and ipsilateral mild carotid stenosis (<50%); ipsilateral moderate carotid stenosis (50%-69%) plus at least 1 of female sex, age <65 years, diabetes mellitus, TIA, or delay >14 days to revascularization; or monocular loss of vision. Patients underwent coregistered carotid 18F-fluorodeoxyglucosePET/CT angiography (≤7 days from inclusion). The primary outcome was 90-day ipsilateral ischemic stroke. Multivariable Cox regression modeling was performed. RESULTS: We included 135 patients. All patients started optimal modern-era medical treatment at admission, and 62 (45.9%) underwent carotid revascularization (36 within the first 14 days and 26 beyond). At 90 days, 18 (13.3%) patients had experienced at least 1 stroke recurrence. The risk of recurrence increased progressively according to the SCAIL score (0.0% in patients scoring 0-1, 15.1% scoring 2-3, and 26.7% scoring 4-5; p = 0.04). The adjusted (age, smoking, hypertension, diabetes, carotid revascularization, antiplatelets and statins) hazard ratio for ipsilateral recurrent stroke per 1-point SCAIL increase was 2.16 (95% CI 1.32-3.53; p = 0.002). A score ≥2 had a sensitivity of 100% for recurrence. DISCUSSION: The SCAIL score improved the identification of early recurrent stroke in subgroups who did not experience benefit in endarterectomy trials. Randomized trials are needed to test whether a combined stenosis-inflammation strategy will improve selection for carotid revascularization when benefit is currently uncertain. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, in patients with recent anterior circulation ischemic stroke who do not benefit from carotid revascularization, the SCAIL score accurately distinguishes those at risk for recurrent ipsilateral ischemic stroke.

Atrial fibrillation and acceleration of frailty: findings from the Irish Longitudinal Study on Ageing.

INTRODUCTION: both atrial fibrillation (AF) and frailty are increasingly prevalent with age. Cross-sectional studies have suggested a relationship between AF and frailty, but longitudinal data are lacking. We explored if the presence of AF was associated with accelerated progression of frailty over 8 years in community-dwelling older adults. METHODS: a longitudinal retrospective case-control study was conducted using data from Waves 1 and 5 of the Irish Longitudinal Study on Ageing (TILDA). Participants with electrocardiographically detected AF at Wave 1 were matched to controls without AF (1:2) based on age and gender. Frailty was assessed using both the frailty phenotype (FP) and a 31-item frailty index (FI). Change in cases' and controls' FP and FI scores from Waves 1 to 5 were modelled using repeated measures analysis of variance (RM-ANOVA). RESULTS: one hundred eighteen TILDA participants with AF at Wave 1 were matched to 236 controls. By FP, participants with AF were not significantly more frail than controls at Wave 1 (P = 0.166) but were at Wave 5 (P = 0.011), and RM-ANOVA suggested that frailty progressed more in participants with AF between Waves 1 and 5 compared with controls (P = 0.033). By FI, participants with AF were significantly more frail at Wave 1 (P < 0.001) and 5 (P = 0.010), and RM-ANOVA did not show a difference in frailty progression between groups (P = 0.955). CONCLUSION: AF may drive the development of the FP. The FP is a pre-disability syndrome and hence may be better than the FI as a focus for disability prevention in adults with AF.

Atrial Fibrillation and Dementia: A Report From the AF-SCREEN International Collaboration.

Growing evidence suggests a consistent association between atrial fibrillation (AF) and cognitive impairment and dementia that is independent of clinical stroke. This report from the AF-SCREEN International Collaboration summarizes the evidence linking AF to cognitive impairment and dementia. It provides guidance on the investigation and management of dementia in patients with AF on the basis of best available evidence. The document also addresses suspected pathophysiologic mechanisms and identifies knowledge gaps for future research. Whereas AF and dementia share numerous risk factors, the association appears to be independent of these variables. Nevertheless, the evidence remains inconclusive regarding a direct causal effect. Several pathophysiologic mechanisms have been proposed, some of which are potentially amenable to early intervention, including cerebral microinfarction, AF-related cerebral hypoperfusion, inflammation, microhemorrhage, brain atrophy, and systemic atherosclerotic vascular disease. The mitigating role of oral anticoagulation in specific subgroups (eg, low stroke risk, short duration or silent AF, after successful AF ablation, or atrial cardiopathy) and the effect of rhythm versus rate control strategies remain unknown. Likewise, screening for AF (in cognitively normal or cognitively impaired patients) and screening for cognitive impairment in patients with AF are debated. The pathophysiology of dementia and therapeutic strategies to reduce cognitive impairment warrant further investigation in individuals with AF. Cognition should be evaluated in future AF studies and integrated with patient-specific outcome priorities and patient preferences. Further large-scale prospective studies and randomized trials are needed to establish whether AF is a risk factor for cognitive impairment, to investigate strategies to prevent dementia, and to determine whether screening for unknown AF followed by targeted therapy might prevent or reduce cognitive impairment and dementia.

Carotid Plaque Inflammation Imaged by PET and Prediction of Recurrent Stroke at 5 Years.

BACKGROUND AND OBJECTIVES: To determine whether carotid plaque inflammation identified by 18F-fluorodeoxyglucose (18FDG)-PET is associated with late (5-year) recurrent stroke. METHODS: We did an individual-participant data pooled analysis of 3 prospective studies with near-identical study methods. Eligible patients had recent nonsevere (modified Rankin Scale score ≤3) ischemic stroke/TIA and ipsilateral carotid stenosis (50%-99%). Participants underwent carotid 18FDG-PET/CT angiography ≤14 days after recruitment. 18FDG uptake was expressed as maximum standardized uptake value (SUVmax) in the axial single hottest slice of symptomatic plaque. We calculated the previously validated Symptomatic Carotid Atheroma Inflammation Lumen-Stenosis (SCAIL) score, which incorporates a measure of stenosis severity and 18FDG uptake. The primary outcome was 5-year recurrent ipsilateral ischemic stroke after PET imaging. RESULTS: Of 183 eligible patients, 181 patients completed follow-up (98.9%). The median duration of follow-up was 4.9 years (interquartile range 3.3-6.4 years, cumulative follow-up period 901.8 patient-years). After PET imaging, 17 patients had a recurrent ipsilateral ischemic strokes at 5 years (recurrence rate 9.4%, 95% confidence interval [CI] 5.6%-14.6%). Baseline plaque SUVmax independently predicted 5-year ipsilateral recurrent stroke after adjustment for age, sex, carotid revascularization, stenosis severity, NIH Stroke Scale score, and diabetes mellitus (adjusted hazard ratio [HR] 1.98, 95% CI 1.10-3.56, p = 0.02 per 1-g/mL increase in SUVmax). On multivariable Cox regression, SCAIL score predicted 5-year ipsilateral stroke (adjusted HR 2.73 per 1-point increase, 95% CI 1.52-4.90, p = 0.001). DISCUSSION: Plaque inflammation-related 18FDG uptake improved identification of 5-year recurrent ipsilateral ischemic stroke. Addition of plaque inflammation to current selection strategies may target patients most likely to have late and early benefit from carotid revascularization. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in individuals with recent ischemic stroke/TIA and ipsilateral carotid stenosis, carotid plaque inflammation-related 18FDG uptake on PET/CT angiography was associated with 5-year recurrent ipsilateral stroke.

Progressive resistance training in a post-acute, older, inpatient setting: A randomised controlled feasibility study.

OBJECTIVES: Progressive resistance training can successfully target functional decline in healthy older community-dwelling adults. There are concerns about the safety and acceptance of its use in frail older populations. The aim of this study was to evaluate the feasibility of using progressive resistance training in an older, post-acute, inpatient setting. METHODS: A randomised controlled feasibility study was conducted. Appropriate older inpatients undergoing post-acute rehabilitation were recruited. Feasibility measures examined were safety, recruitment, outcome measurement, adherence and retention rates and satisfaction. A range of clinical measures were used to capture changes in body structure and function, activity and participation. Assessments were performed on admission to the study and six weeks later. RESULTS: A sample of 33 patients were included and randomised to the treatment group (n=16) or the control group (n=17). There were no serious adverse events, adherence rates were 63% and retention rates were 82%. While both groups improved between time 1 and 2, there were no significant differences in clinical measures between the groups. CONCLUSION: Progressive resistance training is a safe and acceptable intervention for use with this population. Further work on the effectiveness of progressive resistance training in this setting is now required.

von Willebrand Factor Antigen, von Willebrand Factor Propeptide, and ADAMTS13 in Carotid Stenosis and Their Relationship with Cerebral Microemboli.

BACKGROUND: The relationship between von Willebrand factor antigen (VWF:Ag), VWF propeptide (VWFpp), VWFpp/VWF:Ag ratio, ADAMTS13 activity, and microembolic signal (MES) status in carotid stenosis is unknown. METHODS: This prospective, multicenter study simultaneously assessed plasma VWF:Ag levels, VWFpp levels and ADAMTS13 activity, and their relationship with MES in asymptomatic versus symptomatic moderate-to-severe (≥50-99%) carotid stenosis patients. One-hour transcranial Doppler ultrasound of the middle cerebral arteries classified patients as MES+ve or MES-ve. RESULTS: Data from 34 asymptomatic patients were compared with 43 symptomatic patients in the "early phase" (≤4 weeks) and 37 patients in the "late phase" (≥3 months) after transient ischemic attack (TIA)/ischemic stroke. VWF:Ag levels were higher (p = 0.049) and VWFpp/VWF:Ag ratios lower (p = 0.006) in early symptomatic than in asymptomatic patients overall, and in early symptomatic versus asymptomatic MES-ve subgroups (p ≤0.02). There were no intergroup differences in VWFpp expression or ADAMTS13 activity (p ≥0.05). VWF:Ag levels and ADAMTS13 activity decreased (p ≤ 0.048) and VWFpp/VWF:Ag ratios increased (p = 0.03) in symptomatic patients followed up from the early to late phases after TIA/stroke. Although there were no differences in the proportions of symptomatic and asymptomatic patients with blood group O, a combined analysis of early symptomatic and asymptomatic patients revealed lower median VWF:Ag levels in patients with blood group O versus those without blood group O (9.59 vs. 12.32 µg/mL, p = 0.035). DISCUSSION: VWF:Ag expression, a marker of endothelial ± platelet activation, is enhanced in recently symptomatic versus asymptomatic carotid stenosis patients, including in MES-ve patients, and decreases with ADAMTS13 activity over time following atherosclerotic TIA/ischemic stroke.

Association Between 18-FDG Positron Emission Tomography and MRI Biomarkers of Plaque Vulnerability in Patients With Symptomatic Carotid Stenosis.

Purpose: Pathologic studies suggest that unstable plaque morphology and inflammation are associated with cerebrovascular events. 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) is a validated technique for non-invasive imaging of inflammation-related plaque metabolism, and MRI can identify morphologic features of plaque instability. The aim of this study was to investigate the association of selected imaging characteristics of plaque vulnerability measured with MRI and PET in patients with symptomatic carotid stenosis. Methods: Patients from the BIOVASC study were selected based on the following inclusion criteria: (1) age ≥ 50 years; (2) recent (<30 days) ischaemic stroke (modified Rankin scale ≤3) or motor/speech/vision TIA; (3) ipsilateral internal carotid artery stenosis (≥5 0% lumen-narrowing); (4) carotid PET/CTA and MRI completed. Semi-automated plaque analysis of MRI images was performed to quantify morphologic features of plaque instability. PET images were co-registered with CTA and inflammation-related metabolism expressed as maximum standardised uptake value (SUVmax). Results: Twenty-five patients met inclusion criteria (72% men, mean age 65 years). MRI-measured plaque volume was greater in men (1,708-1,286 mm3, p = 0.03), patients who qualified with stroke (1,856-1,440 mm3, p = 0.05), and non-statin users (1,325-1,797 mm3, p = 0.03). SUVmax was associated with MRI-measured plaque lipid-rich necrotic core (LRNC) in the corresponding axial slice (r s = 0.64, p < 0.001) and was inversely associated with whole-plaque fibrous cap thickness (r s = -0.4, p = 0.02) and calcium volume (r s = -0.4, p = 0.03). Conclusion: This study demonstrated novel correlations of non-invasive imaging biomarkers of inflammation-related plaque metabolism with morphological MRI markers of plaque instability. If replicated, our findings may support the application of combined MRI and PET to detect vulnerable plaque in future clinical practise and randomised trials.

Development of a national stroke audit in Ireland: scoping review protocol.

Introduction Recent advances in stroke management and care have resulted in improved survival and outcomes. However, providing equitable access to acute care, rehabilitation and longer-term stroke care is challenging. Recent Irish evidence indicates variation in stroke outcomes across hospitals, and a need for continuous audit of stroke care to support quality improvement. The aim of this project is to develop a core minimum dataset for use in the new Irish National Audit of Stroke (INAS), which aims to improve the standard of stroke care in Ireland. This paper outlines the protocol for conducting a scoping review of international practice and guidelines in auditing acute and non-acute stroke care. Objective Identify data items that are currently collected by stroke audits internationally, and identify audit guidelines that exist for recommending inclusion of content in stroke audit datasets. Methods and analysis This scoping review will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews extension for Scoping Reviews (PRISMA-ScR). We will search the following databases: Medline Ovid; Embase; CINAHL EBSCOHost. Grey literature will also be searched for relevant materials, as will relevant websites. Study selection and review will be carried out independently by two researchers, with discrepancies resolved by a third. Data charting and synthesis will involve sub-dividing relevant sources of evidence, and synthesising data into three categories: i) acute stroke care; ii) non-acute stroke care; and iii) audit data collection procedures and resourcing. Data will be charted using a standardised form specific to each category. Consultation with knowledge users will be conducted at all stages of the scoping review. Discussion This scoping review will contribute to a larger project aimed at developing an internationally benchmarked stroke audit tool that will be used prospectively to collect data on all stroke admissions in Ireland, encompassing both acute and non-acute data items.

Is there an association between orthostatic hypotension and cerebral white matter hyperintensities in older people? The Irish longitudinal study on ageing.

INTRODUCTION: Orthostatic Hypotension (OH) is an abnormal drop in blood pressure (BP) that occurs following orthostatic challenge. OH is associated with increased risk of falls, cognitive impairment and death. White Matter Hyperintensities (WMH) on MR Brain are associated with vascular risk factors such as hypertension, diabetes and age. We examined whether extent White matter intensities were associated with presence of OH detected in a community dwelling population of older people. METHODS: Individuals from the MR sub-study of the Irish Longitudinal Study of Ageing underwent a 3 Tesla MR Brain scan to assess WMH severity (Schelten's Score). The scans were performed during the Wave 3 TILDA health assessment phase when the subjects also underwent assessment for OH with an active stand protocol. Data was analysed for association between WMH and vascular risks and orthostatic change in BP 10 second intervals during the OH evaluation. RESULTS: 440 subjects were investigated; median age 72 years (65-92 years) and 228 (51.5%) female. Range of Scheltens' Scores was 0-32. Mean score was 9.72 (SD 5.87). OH was detected in 68.4% (301). On linear regression, positive associations were found between Scheltens' Score and age, hypertension, prior history of stroke and TIA, and with OH at 30, 70, 90 and 100 seconds following standing (p < 0.05, O.R. 1.9-2.5). CONCLUSION: WMD is associated with OH detected at multiple time points using active stand in community dwelling older subjects. Further research is necessary to evaluate the direction of this association.

Cohort profile: BIOVASC-late, a prospective multicentred study of imaging and blood biomarkers of carotid plaque inflammation and risk of late vascular recurrence after non-severe stroke in Ireland.

PURPOSE: Inflammation is important in stroke. Anti-inflammatory therapy reduces vascular events in coronary patients. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) identifies plaque inflammation-related metabolism. However, long-term prospective cohort studies investigating the association between carotid plaque inflammation, identified on 18F-FDG PET and the risk of recurrent vascular events, have not yet been undertaken in patients with stroke. PARTICIPANTS: The Biomarkers Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease (BIOVASC) study and Dublin Carotid Atherosclerosis Study (DUCASS) are two prospective multicentred observational cohort studies, employing near-identical methodologies, which recruited 285 patients between 2008 and 2016 with non-severe stroke/transient ischaemic attack and ipsilateral carotid stenosis (50%-99%). Patients underwent coregistered carotid 18F-FDG PET/CT angiography and phlebotomy for measurement of inflammatory cytokines. Plaque 18F-FDG-uptake is expressed as maximum standardised uptake value (SUVmax) and tissue-to-background ratio. The BIOVASC-Late study is a follow-up study (median 7 years) of patients recruited to the DUCASS/BIOVASC cohorts. FINDINGS TO DATE: We have reported that 18F-FDG-uptake in atherosclerotic plaques of patients with symptomatic carotid stenosis predicts early recurrent stroke, independent of luminal narrowing. The incorporation of 18F-FDG plaque uptake into a clinical prediction model also improves discrimination of early recurrent stroke, when compared with risk stratification by luminal stenosis alone. However, the relationship between 18F-FDG-uptake and late vascular events has not been investigated to date. FUTURE PLANS: The primary aim of BIOVASC-Late is to investigate the association between SUVmax in symptomatic 'culprit' carotid plaque (as a marker of systemic inflammatory atherosclerosis) and the composite outcome of any late major vascular event (recurrent ischaemic stroke, coronary event or vascular death). Secondary aims are to investigate associations between: (1) SUVmax in symptomatic plaque, and individual vascular endpoints (2) SUVmax in asymptomatic contralateral carotid plaque and SUVmax in ipsilateral symptomatic plaque (3) SUVmax in asymptomatic carotid plaque and major vascular events (4) inflammatory cytokines and vascular events.

A Risk Score Including Carotid Plaque Inflammation and Stenosis Severity Improves Identification of Recurrent Stroke.

Background and Purpose- In randomized trials of symptomatic carotid endarterectomy, only modest benefit occurred in patients with moderate stenosis and important subgroups experienced no benefit. Carotid plaque 18F-fluorodeoxyglucose uptake on positron emission tomography, reflecting inflammation, independently predicts recurrent stroke. We investigated if a risk score combining stenosis and plaque 18F-fluorodeoxyglucose would improve the identification of early recurrent stroke. Methods- We derived the score in a prospective cohort study of recent (<30 days) non-severe (modified Rankin Scale score ≤3) stroke/transient ischemic attack. We derived the SCAIL (symptomatic carotid atheroma inflammation lumen-stenosis) score (range, 0-5) including 18F-fluorodeoxyglucose standardized uptake values (SUVmax <2 g/mL, 0 points; SUVmax 2-2.99 g/mL, 1 point; SUVmax 3-3.99 g/mL, 2 points; SUVmax ≥4 g/mL, 3 points) and stenosis (<50%, 0 points; 50%-69%, 1 point; ≥70%, 2 points). We validated the score in an independent pooled cohort of 2 studies. In the pooled cohorts, we investigated the SCAIL score to discriminate recurrent stroke after the index stroke/transient ischemic attack, after positron emission tomography-imaging, and in mild or moderate stenosis. Results- In the derivation cohort (109 patients), recurrent stroke risk increased with increasing SCAIL score (P=0.002, C statistic 0.71 [95% CI, 0.56-0.86]). The adjusted (age, sex, smoking, hypertension, diabetes mellitus, antiplatelets, and statins) hazard ratio per 1-point SCAIL increase was 2.4 (95% CI, 1.2-4.5, P=0.01). Findings were confirmed in the validation cohort (87 patients, adjusted hazard ratio, 2.9 [95% CI, 1.9-5], P<0.001; C statistic 0.77 [95% CI, 0.67-0.87]). The SCAIL score independently predicted recurrent stroke after positron emission tomography-imaging (adjusted hazard ratio, 4.52 [95% CI, 1.58-12.93], P=0.005). Compared with stenosis severity (C statistic, 0.63 [95% CI, 0.46-0.80]), prediction of post-positron emission tomography stroke recurrence was improved with the SCAIL score (C statistic, 0.82 [95% CI, 0.66-0.97], P=0.04). Findings were confirmed in mild or moderate stenosis (adjusted hazard ratio, 2.74 [95% CI, 1.39-5.39], P=0.004). Conclusions- The SCAIL score improved the identification of early recurrent stroke. Randomized trials are needed to test if a combined stenosis-inflammation strategy improves selection for carotid revascularization where benefit is currently uncertain.

Online Resources Used by Medical Students, a Literature Review.

This article was migrated. The article was marked as recommended. Purpose: To summarise research pertaining to the use of online resources by medical students throughout the course of their studies in a literature review. Method: Twenty studies published between 2003-2017 were identified for inclusion in the review. All reviewed papers reported on medical students use of online resources for their studies, both in preclinical and clinical settings. Results: Of the studies initially identified, twenty studies focusing on medical students were included and reviewed. The online resources, most frequently mentioned were UpToDate (35%); Epocrates (35%); Medscape (25%), Google (25%); PubMed (20%); Micromedex (20%); Wikipedia (15%); PEPID (10%); Dynamed (10%). Fourteen studies linked the use of online resources to their accessibility and reliability. In nine studies students reported that online resource use enhanced clinical management and diagnostic accuracy. Conclusion: Research on the use of online resources by medical students is largely limited to their use in clinical settings. As technology and learning evolve there is an increased need for students to be able to access such resources online and have the required teaching to understand how best to utilise them.

Neuroimaging provides relevant clinical information in patients with burn injuries.

INTRODUCTION: Neurological assessment of patients with burn injuries may be complicated by a variety of factors including artificial ventilation and sedation, cerebral hypoxia and intoxication. Medically unstable intubated patients present logistical challenges for radiological imaging. The role of neuroimaging as an adjunct to clinical assessment of burn injured patients has not yet been determined. AIM: This study aims to investigate the indications, findings and outcomes of neuroimaging studies performed for burn injured patients. METHODS: A retrospective case series study of adult burn patients admitted over an 8 year period was completed in the National Burns Centre at St James's Hospital, Dublin. Neuroimaging studies carried out for patients admitted during the study period were reviewed by a Consultant Radiologist and Consultant Stroke Physician. Outcomes included neuroimaging findings, prevalence of white matter disease (Fazekas scale), length of stay, discharge destination, predicted and observed mortality. RESULTS: 1328 consecutive patients with burn injuries were admitted during the study period. 56 patients underwent neuroimaging studies with computerised tomography, magnetic resonance imaging or both. 46 out of 56 neuroimaged patients (82.1%) had significant radiological findings, including 14 patients (25%) with acute findings. There was a high prevalence of white matter disease (mean total Fazekas score: 3.59) and acute cerebral infarction (7 patients). Patients with radiological findings required additional in-patient rehabilitation and had increased length of stay (Median 47.0 days vs. 27.5 days, p < 0.027). Patients with resuscitation burns or associated inhalation injury were significantly more likely to undergo neuroimaging (p < 0.0001) and to have positive radiological findings. Predicted mortality was higher in patients with positive neuroimaging findings compared to patients with normal neuroimaging studies, although there was no significant difference in observed mortality between these two groups. CONCLUSION: Neuroimaging is used appropriately in patients admitted with burns and provides valuable applicable clinical information when indicated.

Simultaneous assessment of plaque morphology, cerebral micro-embolic signal status and platelet biomarkers in patients with recently symptomatic and asymptomatic carotid stenosis.

The relationship between plaque morphology, cerebral micro-embolic signals (MES) and platelet biomarkers in carotid stenosis patients warrants investigation.We combined data from two prospective, observational studies to assess carotid plaque morphology and relationship with cerebral MES and platelet biomarkers in patients with recently symptomatic (≤4 weeks of transient ischaemic attack (TIA)/ischaemic stroke) versus asymptomatic carotid stenosis. Plaque morphology on ultrasound was graded with Grey-Scale Median (GSM) and Gray-Weale (GW) scoring. Bilateral transcranial Doppler ultrasound classified patients as 'MES+ve' or 'MES-ve'. Full blood counts were analysed and flow cytometry quantified CD62P and CD63 expression, leucocyte-platelet complexes and reticulated platelets.Data from 42 recently symptomatic carotid stenosis patients were compared with those from 36 asymptomatic patients. There were no differences in median GSM scores between symptomatic and asymptomatic patients (25 vs. 30; P = 0.31) or between MES+ve vs. MES-ve symptomatic patients (36 vs. 25; P = 0.09). Symptomatic patients with GSM-echodense plaques (GSM ≥25) had higher platelet counts (228 vs. 191 × 109/L), neutrophil-platelet (3.3 vs. 2.7%), monocyte-platelet (6.3 vs. 4.55%) and lymphocyte-platelet complexes (2.91 vs. 2.53%) than 'asymptomatic patients with GSM-echodense plaques' (P ≤ 0.03).Recently, symptomatic carotid stenosis patients with 'GSM-echodense plaques' have enhanced platelet production/secretion/activation compared with their asymptomatic counterparts. Simultaneous assessment with neurovascular imaging and platelet biomarkers may aid risk-stratification in carotid stenosis.

Searching for Atrial Fibrillation Poststroke: A White Paper of the AF-SCREEN International Collaboration.

Cardiac thromboembolism attributed to atrial fibrillation (AF) is responsible for up to one-third of ischemic strokes. Stroke may be the first manifestation of previously undetected AF. Given the efficacy of oral anticoagulants in preventing AF-related ischemic strokes, strategies of searching for AF after a stroke using ECG monitoring followed by oral anticoagulation (OAC) treatment have been proposed to prevent recurrent cardioembolic strokes. This white paper by experts from the AF-SCREEN International Collaboration summarizes existing evidence and knowledge gaps on searching for AF after a stroke by using ECG monitoring. New AF can be detected by routine plus intensive ECG monitoring in approximately one-quarter of patients with ischemic stroke. It may be causal, a bystander, or neurogenically induced by the stroke. AF after a stroke is a risk factor for thromboembolism and a strong marker for atrial myopathy. After acute ischemic stroke, patients should undergo 72 hours of electrocardiographic monitoring to detect AF. The diagnosis requires an ECG of sufficient quality for confirmation by a health professional with ECG rhythm expertise. AF detection rate is a function of monitoring duration and quality of analysis, AF episode definition, interval from stroke to monitoring commencement, and patient characteristics including old age, certain ECG alterations, and stroke type. Markers of atrial myopathy (eg, imaging, atrial ectopy, natriuretic peptides) may increase AF yield from monitoring and could be used to guide patient selection for more intensive/prolonged poststroke ECG monitoring. Atrial myopathy without detected AF is not currently sufficient to initiate OAC. The concept of embolic stroke of unknown source is not proven to identify patients who have had a stroke benefitting from empiric OAC treatment. However, some embolic stroke of unknown source subgroups (eg, advanced age, atrial enlargement) might benefit more from non-vitamin K-dependent OAC therapy than aspirin. Fulfilling embolic stroke of unknown source criteria is an indication neither for empiric non-vitamin K-dependent OAC treatment nor for withholding prolonged ECG monitoring for AF. Clinically diagnosed AF after a stroke or a transient ischemic attack is associated with significantly increased risk of recurrent stroke or systemic embolism, in particular, with additional stroke risk factors, and requires OAC rather than antiplatelet therapy. The minimum subclinical AF duration required on ECG monitoring poststroke/transient ischemic attack to recommend OAC therapy is debated.