Validation of two risk-prediction models for recurrent falls in the first year after stroke: a prospective cohort study.

Background: several multivariable models have been derived to predict post-stroke falls. These require validation before integration into clinical practice. The aim of this study was to externally validate two prediction models for recurrent falls in the first year post-stroke using an Irish prospective cohort study. Methodology: stroke patients with planned home-discharges from five hospitals were recruited. Falls were recorded with monthly diaries and interviews 6 and 12 months post-discharge. Predictors for falls included in two risk-prediction models were assessed at discharge. Participants were classified into risk groups using these models. Model 1, incorporating inpatient falls history and balance, had a 6-month outcome. Model 2, incorporating inpatient near-falls history and upper limb function, had a 12-month outcome. Measures of calibration, discrimination (area under the curve (AUC)) and clinical utility (sensitivity/specificity) were calculated. Results: 128 participants (mean age = 68.6 years, SD = 13.3) were recruited. The fall status of 117 and 110 participants was available at 6 and 12 months, respectively. Seventeen and 28 participants experienced recurrent falls by these respective time points. Model 1 achieved an AUC = 0.56 (95% CI 0.46-0.67), sensitivity = 18.8% and specificity = 93.6%. Model 2 achieved AUC = 0.55 (95% CI 0.44-0.66), sensitivity = 51.9% and specificity = 58.7%. Model 1 showed no significant difference between predicted and observed events (risk ratio (RR) = 0.87, 95% CI 0.16-4.62). In contrast, model 2 significantly over-predicted fall events in the validation cohort (RR = 1.61, 95% CI 1.04-2.48). Conclusions: both models showed poor discrimination for predicting recurrent falls. A further large prospective cohort study would be required to derive a clinically useful falls-risk prediction model for a similar population.

Plaque inflammation and unstable morphology are associated with early stroke recurrence in symptomatic carotid stenosis.

BACKGROUND AND PURPOSE: Although symptomatic carotid stenosis is associated with 3-fold increased risk of early stroke recurrence, the pathophysiologic mechanisms of high early stroke risk have not been established. We aimed to investigate the relationship between early stroke recurrence after initial symptoms and histological features of plaque inflammation and instability in resected carotid plaque. METHODS: Carotid endarterectomy tissue from consecutive patients with ipsilateral stenosis≥50% and recent symptoms were analyzed using a validated histopathologic algorithm (Oxford Plaque Study [OPS] system). Nonprocedural stroke recurrence before carotid endarterectomy was ascertained at 7, 28, and 90 days after initial symptoms. RESULTS: Among 44 patients meeting eligibility criteria, 27.3% (12/44) had stroke recurrence after initial stroke/transient ischemic attack but before carotid endarterectomy. Compared with patients without recurrence, stroke recurrence was associated with dense macrophage infiltration (OPS grade≥3; 91.7% versus 37.5%; P=0.002), extensive (>25%) fibrous cap disruption (90.9% versus 37%; P=0.004), neovascularization (OPS grade≥2; 83.3% versus 43.8%; P=0.04), and low plaque fibrous content (OPS grade<2; 50% versus 6.3%; P=0.003). Early recurrence rates were 82.3% (confidence interval, 49.2%-98.8%) in patients with extensive plaque macrophage infiltration (OPS grade≥3) compared with 22.2% (confidence interval, 3.5%-83.4%) in those with OPS grade<3 (log-rank P=0.009). On multivariable Cox regression, including OPS macrophage grade (≥3 or <3), age, and severity of stenosis (50%-69% or ≥70%), plaque inflammation was the only variable independently predicting stroke recurrence (adjusted hazard ratio, 9; confidence interval, 1.1-70.6; P=0.04). CONCLUSIONS: Plaque inflammation and other vulnerability features were associated with highest risk of stroke recurrence and may represent therapeutic targets for future stroke prevention trials.

Carotid plaque inflammation on 18F-fluorodeoxyglucose positron emission tomography predicts early stroke recurrence.

OBJECTIVE: Symptomatic carotid stenosis is associated with a 3-fold risk of early stroke recurrence compared to other stroke subtypes. Current carotid imaging techniques rely on estimating plaque-related lumen narrowing but do not evaluate intraplaque inflammation, a key mediator of plaque rupture and thromboembolism. Using combined (18) F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography, we investigated the relation between inflammation-related FDG uptake and stroke recurrence. METHODS: Consecutive patients with a recent (median, 6.5 days; interquartile range, 4-8) stroke, transient ischemic attack (TIA), or retinal embolism and ipsilateral carotid stenosis (≥50%) were included. FDG uptake was quantified as mean standardized uptake values (SUVs, g/ml). Patients were followed prospectively for stroke recurrence. RESULTS: Sixty patients were included (25 stroke, 29 TIA, 6 retinal embolism). Twenty-two percent (13 of 60) had stroke recurrence within 90 days. FDG uptake in ipsilateral carotid plaque was greater in patients with early recurrent stroke (mean SUV, 1.85 g/ml; standard deviation [SD], 0.44 vs 1.58 g/ml; SD, 0.32, p = 0.02). On life-table analysis, 90-day recurrence rates with mean SUV greater than a 2.14 g/ml threshold were 80% (95% confidence interval [CI], 41.8-99.2) versus 22.9% (95% CI, 12.3-40.3) with SUV ≤2.14 g/ml (log-rank, p < 0.0001). In a Cox regression model including age and degree of stenosis (50-69% or ≥70%), mean plaque FDG uptake was the only independent predictor of stroke recurrence (adjusted hazard ratio, 6.1; 95% CI, 1.3-28.8; p = 0.02). INTERPRETATION: In recently symptomatic carotid stenosis, inflammation-related FDG uptake was associated with early stroke recurrence, independent of the degree of stenosis. Plaque FDG-PET may identify patients at highest risk for stroke recurrence, who may be selected for immediate revascularization or intensive medical treatment.

'Not another UTI ... '.

Malaria includes a global disease burden with approximately 300-500 million cases worldwide annually. Varied symptomatology creates a diagnostic challenge. This is a case report of a stroke rehabilitation facility resident who developed Plasmodium ovale infection, several months post-exposure. Physicians should maintain a broad list of differential diagnoses, thinking beyond the range of common diagnoses.

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.

The experience of recurrent fallers in the first year after stroke.

PURPOSE: Understanding the experiences of fallers after stroke could inform falls-prevention interventions, which have not yet shown effectiveness in this population. The aim of this study was to explore the experience of recurrent fallers post-stroke in relation to recovery and living with falls. METHODS: Participants who had more than one fall in the first year after stroke were identified from a prospective cohort study. The methods of grounded theory informed data collection and analysis. Semi-structured interviews were conducted, audio-recorded and transcribed. Coding was conducted and categories were developed inductively. RESULTS: Nine stroke survivors aged 53-85 were interviewed 18-22 months post-discharge. Participants had experienced between 2 and 9 falls and one participant suffered a fracture. Three inter-linked categories were identified: (i) Judging the importance of falls by exploring cause and consequence, (ii) getting back up, and (iii) being careful. CONCLUSIONS: Stroke survivors' assessment of their own falls-risk and their individual priorities contribute to their decisions around activity participation. "Being careful" could be described as a form of self-managing falls-risk. The inclusion of self-management principles, peer-educators, and education to rise from the floor in falls-management programmes warrants investigation. Not all falls were considered equally important by participants. This could be considered when defining falls-related outcomes. Implications for Rehabilitation Healthcare professionals may be able to offer an increased sense of control to stroke survivors through education about how to avoid particular causes and consequences of falls. Falls-related advice should be specific, relevant to the individual, and respectful of their sense of identity. Being able to rise from the floor appears to be important for coping with falls and falls-risk. Professionals should be cognisant of the potential differences of opinion between stroke survivors and their families around management of falls-risk.

First year post-stroke healthcare costs and fall-status among those discharged to the community.

INTRODUCTION: Falls are common post-stroke events but their relationship with healthcare costs is unclear. The aim of this study was to examine the relationship between healthcare costs in the first year after stroke and falls among survivors discharged to the community. PATIENTS AND METHODS: Survivors of acute stroke with planned home discharges from five large hospitals in Ireland were recruited. Falls and healthcare utilisation data were recorded using inpatient records, monthly calendars and post-discharge interviews. Cost of stroke was estimated for each participant from hospital admission for one year. The association of fall-status with overall cost was tested with multivariable linear regression analysis adjusting for pre-stroke function, stroke severity, age and living situation. RESULTS: A total of 109 stroke survivors with complete follow-up data (mean age = 68.5 years (SD = 13.5 years)) were included. Fifty-three participants (49%) fell following stroke, of whom 28 (26%) had recurrent falls. Estimated mean total healthcare cost was €20,244 (SD=€23,456). The experience of one fall and recurrent falls was independently associated with higher costs of care (p = 0.02 and p < 0.01, respectively). DISCUSSION: The observed relationship between falls and cost is likely to be underestimated as aids and adaptions, productivity losses, and nursing home care were not included. CONCLUSION: This study points at differences across fall-status in several healthcare costs categories, namely the index admission, secondary/tertiary care (including inpatient re-admissions) and allied healthcare. Future research could compare the cost-effectiveness of inpatient versus community-based fall-prevention after stroke. Further studies are also required to inform post-stroke bone-health management and fracture-risk reduction.

Falls-Related EvEnts in the first year after StrokE in Ireland: Results of the multi-centre prospective FREESE cohort study.

INTRODUCTION: Falls are common post-stroke adverse events. This study aimed to describe the first-year falls incidence, circumstances and consequences among persons discharged home after stroke in Ireland, and to examine the association between potential risk factors and recurrent falls. PATIENTS AND METHODS: Patients with acute stroke and planned home-discharge were recruited consecutively from five hospitals. Variables recorded pre-discharge included: age, stroke severity, co-morbidities, fall history, prescribed medications, hemi-neglect, cognition and functional independence (Barthel index). Falls were recorded with monthly diaries, and 6 and 12-month interviews. The association of pre-discharge factors with recurrent falls (>1 fall) was examined using univariable logistic regression. RESULTS: A total of 128 participants (mean age = 68.6, SD = 13.3) were recruited; 110 completed the 12-month follow-up. The first-year falls incidence was 44.5% (95% CI = 35.1-53.6) with 25.6% falling repeatedly (95% CI = 18.5-34.4). Fallers experienced 1-18 falls (median = 2) and five reported fractures; 47% of fallers experienced at least one fall outdoors. Only 10% of recurrent fallers had bone health medication prescribed at discharge. Lower Barthel index scores (<75/100, RR = 4.38, 1.64-11.72) and psychotropic medication prescription (RR = 2.10, 1.13-3.91) were associated with recurrent falls. DISCUSSION: This study presents prospectively collected information about falls circumstances. It was not powered for multivariable analysis of risk factors. CONCLUSION: One-quarter of stroke survivors discharged to the community fall repeatedly and mostly indoors in the first year. Specific attention may be required for individuals with poor functional independence or those on psychotropic medication. Future falls-management research in this population should explore falls in younger individuals, outdoor as well as indoor falls and post-stroke bone health status.

Antithrombotic treatment at onset of stroke with atrial fibrillation, functional outcome, and fatality: a systematic review and meta-analysis.

BACKGROUND: In atrial fibrillation-associated stroke, conflicting data exist regarding association between therapeutic vitamin K-antagonist anticoagulation (International Normalized Ratio 2-3) and early death and functional outcome, and few data exist relating to late outcome in ischemic and haemorrhagic atrial fibrillation-stroke. AIM: We performed a systematic review and meta-analysis of oral anticoagulation at stroke onset, death and functional outcome. METHODS: We performed a systematic review, searching multiple sources. Studies were included if outcomes in atrial fibrillation-associated stroke were reported stratified by pre-stroke antithrombotic status, with documented International Normalized Ratio at onset. Outcomes were survival and good functional outcome (modified Rankin score 0-2) at discharge/30 days, and at one-year. RESULTS: Of eight studies (3552 patients) in ischemic stroke, International Normalized Ratio ≥ 2 compared with other treatments (International Normalized Ratio < 2, antiplatelet, or no antithrombotic) was associated with good outcome [pooled odds ratio 1·9 (95% confidence interval) 1·5-2·5, P < 0·001] and improved survival at 30 days discharge (pooled odds ratio for death 0·4, confidence interval 0·2-0·5, P < 0·001). The net benefit remained after inclusion of haemorrhagic stroke (odds ratio for good outcome 1·89, confidence interval 1·45-2·46, P < 0·001). At one-year, improved functional outcome for International Normalized Ratio ≥ 2 (pooled odds ratio 1·7, confidence interval 1·0-2·7, P = 0·04) and survival (odds ratio for death 0·5, confidence interval 0·4-0·8, P = 0·001) were also observed. CONCLUSIONS: Therapeutic International Normalized Ratio at stroke onset was associated with early and late improved survival and functional recovery suggesting sustained benefit for warfarin anticoagulation for stroke outcome in atrial fibrillation patients. Long-term outcome data following stroke in patients taking new oral anticoagulants is required.

Serum lipids associated with inflammation-related PET-FDG uptake in symptomatic carotid plaque.

OBJECTIVE: We hypothesized that serum lipids, which experimental data suggest may be key initiators of carotid plaque inflammation, would be associated with plaque inflammation on (18)fluorodeoxyglucose (FDG)-PET in patients with acutely symptomatic carotid stenosis. METHODS: In this cohort study, consecutive patients with acute symptomatic internal carotid artery (ICA) stenosis (≥50%) underwent carotid PET-CT. We quantified plaque FDG uptake as follows: (1) average maximum standardized uptake values (SUVmax) across 10 regions of interest (ROI); (2) highest single ROI SUV measure (SUVROImax); (3) averaged mean SUV across 10 ROIs (SUVmean). RESULTS: Sixty-one patients were included. Plaque inflammatory FDG SUVmax was associated with increasing tertiles of low-density lipoprotein (LDL) (trend p = 0.004), total cholesterol (p = 0.009), and triglycerides (p = 0.01), and with lower high-density lipoprotein (HDL) (p = 0.005). When analyzed as a continuous variable, LDL was associated with symptomatic ICA SUVmean (Spearman rho 0.44, p = 0.009), SUVROImax (rho 0.33, p = 0.01), and SUVmax (rho 0.35, p = 0.06). Total cholesterol was associated with SUVmean (rho 0.33, p = 0.009), with trends for SUVmax (rho 0.24, p = 0.059) and SUVROImax (rho 0.23, p = 0.08). Triglycerides were associated with SUVmax (rho 0.32, p = 0.01) and SUVROImax (rho 0.35, p = 0.005). HDL was associated with lower SUVmax (rho -0.37, p = 0.004) and SUVROImax (rho -0.44, p = 0.0004). On multivariable linear regression analysis adjusting for age, sex, degree of carotid stenosis, statins, and smoking, LDL (p = 0.008) and total cholesterol (p = 0.04) were independently associated with SUVmax. CONCLUSION: Serum LDL and total cholesterol were associated with acutely symptomatic carotid plaque FDG uptake, supporting experimental data suggesting lipids may promote plaque inflammation, mediating rupture and clinical events.