Cost-Effectiveness of an Individualised Management Program after Stroke: A Trial-Based Economic Evaluation.

INTRODUCTION: Evidence on the cost-effectiveness of comprehensive post-stroke programs is limited. We assessed the cost-effectiveness of an individualised management program (IMP) for stroke or transient ischaemic attack (TIA). METHODS: A cost-utility analysis alongside a randomised controlled trial with a 24-month follow-up, from both societal and health system perspectives, was conducted. Adults with stroke/TIA discharged from hospitals were randomised by primary care practice to receive either usual care (UC) or an IMP in addition to UC (intervention). An IMP included stroke-specific nurse-led education and a specialist review of care plans at baseline, 3 months, and 12 months, and telephone reviews by nurses at 6 months and 18 months. Costs were expressed in 2021 Australian dollars (AUD). Costs and quality-adjusted life years (QALYs) beyond 12 months were discounted by 5%. The probability of cost-effectiveness of the intervention was determined by quantifying 10,000 bootstrapped iterations of incremental costs and QALYs below the threshold of AUD 50,000/QALY. RESULTS: Among the 502 participants (65% male, median age 69 years), 251 (50%) were in the intervention group. From a health system perspective, the incremental cost per QALY gained was AUD 53,175 in the intervention compared to the UC group, and the intervention was cost-effective in 46.7% of iterations. From a societal perspective, the intervention was dominant in 52.7% of iterations, with mean per-person costs of AUD 49,045 and 1.352 QALYs compared to mean per-person costs of AUD 51,394 and 1.324 QALYs in the UC group. The probability of the cost-effectiveness of the intervention, from a societal perspective, was 60.5%. CONCLUSIONS: Care for people with stroke/TIA using an IMP was cost-effective from a societal perspective over 24 months. Economic evaluations of prevention programs need sufficient time horizons and consideration of costs beyond direct healthcare utilisation to demonstrate their value to society.

Acute vestibular neuritis may provoke atrial fibrillation.

BACKGROUND: Exclusion of stroke is the focus of guidelines in the emergency department assessment of acute vertigo, especially with new-onset atrial fibrillation (AF). Early diagnosis of vestibular neuritis (VN) is also important but may be deferred awaiting brain magnetic resonance imaging (MRI) for exclusion of stroke. This may delay potentially beneficial corticosteroid therapy. AIMS: To highlight that VN can provoke acute AF. METHODS: In the course of a prospective study of acute vertigo in patients assessable within 24 h of admission, we encountered three patients with acute onset transient AF associated with VN. We performed a detailed neurological examination and quantitated the vestibulo-ocular reflex (VOR) gain with video-oculography. Brain MRI was performed in all patients. RESULTS: There were two men and one woman, aged 58-66 (mean 61) years. All patients had typical non-direction-changing rotatory nystagmus and positive head impulse tests. The horizontal VOR gains ranged 0.38-0.62 (mean 0.47). Diffusion-weighted MRI within 36 h was normal in all. AF reverted in all three within 24 h. CONCLUSIONS: Acute AF can be precipitated by vertigo such as in VN. In VN, the concurrence of acute AF may distract from the correct neurological diagnosis, delaying potentially beneficial corticosteroid therapy, especially if exclusion of stroke is dependent on MRI, which may be delayed.

Quality of life after stroke: a longitudinal analysis of a cluster randomized trial.

PURPOSE: Health-related quality of life (QoL) is poor after stroke, but may be improved with comprehensive care plans. We aimed to determine the effects of an individualized management program on QoL in people with stroke or transient ischemic attack (TIA), describe changes in QoL over time, and identify variables associated with QoL. METHODS: This was a multicenter, cluster randomized controlled trial with blinded assessment of outcomes and intention-to-treat analysis. Patients with stroke or TIA aged ≥ 18 years were randomized by general practice to receive usual care or an intervention comprising a tailored chronic disease management plan and education. QoL was assessed at baseline and 3, 12, and 24 months after baseline using the Assessment of Quality of Life instrument. Patient responses were converted to utility scores ranging from - 0.04 (worse than death) to 1.00 (good health). Mixed-effects models were used for analyses. RESULTS: Among 563 participants recruited (mean age 68.4 years, 64.5% male), median utility scores ranged from 0.700 to 0.772 at different time points, with no difference observed between intervention and usual care groups. QoL improved significantly from baseline to 3 months (ß = 0.019; P = 0.015) and 12 months (ß = 0.033; P < 0.001), but not from baseline to 24 months (ß = 0.013; P = 0.140) in both groups combined. Older age, females, lower educational attainment, greater handicap, anxiety and depression were longitudinally associated with poor QoL. CONCLUSION: An individualized management program did not improve QoL over 24 months. Those who are older, female, with lower educational attainment, greater anxiety, depression and handicap may require greater support. CLINICAL TRIAL REGISTRATION: https://www.anzctr.org.au . Unique identifier: ACTRN12608000166370.

Effectiveness of an Intervention to Improve Risk Factor Knowledge in Patients With Stroke: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Despite the benefit of risk awareness in secondary prevention, survivors of stroke are often unaware of their risk factors. We determined whether a nurse-led intervention improved knowledge of risk factors in people with stroke or transient ischemic attack. METHODS: Prospective study nested within a randomized controlled trial of risk factor management in survivors of stroke or transient ischemic attack. INTERVENTION: 3 nurse education visits and specialist review of care plans. OUTCOME: unprompted knowledge of risk factors of stroke or transient ischemic attack at 24 months. Effect of intervention on knowledge and factors associated with knowledge were determined using multivariable regression models. RESULTS: Knowledge was assessed in 268 consecutive participants from the main trial, 128 in usual care and 140 in the intervention. Overall, 34% of participants were unable to name any risk factor. In adjusted analyses, the intervention group had better overall knowledge than controls (incidence risk ratio, 1.26; 95% confidence interval, 1.00-1.58). Greater functional ability and polypharmacy were associated with better knowledge and older age and having more comorbidities associated with poorer knowledge. CONCLUSIONS: Overall knowledge of risk factors of stroke or transient ischemic attack was better in the intervention group than controls. However, knowledge was generally poor. New and more effective strategies are required, especially in subgroups identified as having poor knowledge. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Unique identifier: ACTRN12608000166370.

Community-Based Intervention to Improve Cardiometabolic Targets in Patients With Stroke: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Many guidelines for secondary prevention of stroke focus on controlling cardiometabolic risk factors. We investigated the effectiveness of a management program for attaining cardiometabolic targets in survivors of stroke/transient ischemic attack. METHODS: Randomized controlled trial of survivors of stroke/transient ischemic attack aged ≥18 years. General practices were randomized to usual care (control) or an intervention comprising specialist review of care plans and nurse education in addition to usual care. The outcome is attainment of pre-defined cardiometabolic targets based on Australian guidelines. Multivariable regression was undertaken to determine efficacy and identify factors associated with attaining targets. RESULTS: Overall, 283 subjects were randomized to the intervention and 280 to controls. Although we found no between-group difference in overall cardiometabolic targets achieved at 12 months, the intervention group more often achieved control of low-density lipoprotein cholesterol (odds ratio, 1.97; 95% confidence interval, 1.18-3.29) than controls. At 24 months, no between-group differences were observed. Medication adherence was ≥80% at follow-up, but uptake of lifestyle/behavioral habits was poor. Older age, being male, being married/living with partner, and having greater functional ability or a history of diabetes mellitus were associated with attaining targets. CONCLUSIONS: The intervention in this largely negative trial only had a detectable effect on attaining target for lipids but not for other factors at 12 months or any factor at 24 months. This limited effect may be attributable to inadequate uptake of behavioral/lifestyle interventions, highlighting the need for new or better approaches to achieve meaningful behavioral change. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: ACTRN12608000166370.

Maximizing Patient Recruitment and Retention in a Secondary Stroke Prevention Clinical Trial: Lessons Learned from the STAND FIRM Study.

BACKGROUND: Recruitment and retention of patients in a clinical trial is important for generalizability and robustness of findings. We aimed to investigate features of a study design that were associated with recruitment and retention in a Phase II and Phase III trial of a secondary prevention program for stroke. METHODS: Following informed consent in hospital, Phase II participants were randomized to intervention or usual care. Baseline clinical assessments were conducted at home approximately 3 months after discharge. In Phase III study, informed consent was obtained at home. We compared the characteristics of participants recruited and retained to 12 months for both phases. Interviews with study nurses were undertaken in order to ascertain their opinions of features of study design. Triangulation was used to identify the features of study design that nurses thought had improved recruitment and retention. RESULTS: All 24 eligible participants were recruited to the Phase II pilot study (100% recruitment), with 67% retention at 12 months. In Phase III study, 570 participants were recruited, and 93% of these participants had reached their 12-month assessment (n = 532) and were still participating. Consistent with the greater patient retention in Phase III study, nurses reported that patients' willingness to participate was greater when consent was obtained at home. CONCLUSION: Following a change in the consent process from hospital to home, more participants continued participation to 12 months. Pilot studies can provide important data to improve study design and better understand potential barriers to recruitment and retention.

Cerebral amyloid angiopathy: Review of clinico-radiological features and mimics.

Cerebral amyloid angiopathy (CAA) is an important cause of lobar intracerebral haemorrhage (ICH) in the elderly, but has other clinico-radiological manifestations. In the last two decades, certain magnetic resonance imaging (MRI) sequences, namely gradient-recalled echo imaging and the newer and more sensitive susceptibility-weighted imaging, have been utilised to detect susceptibility-sensitive lesions such as cerebral microbleeds and cortical superficial siderosis. These can be utilised sensitively and specifically by the Modified Boston Criteria to make a diagnosis of CAA without the need for 'gold-standard' histopathology from biopsy. However, recently, other promising MRI biomarkers of CAA have been described which may further increase precision of radiological diagnosis, namely chronic white matter ischaemia, cerebral microinfarcts and lobar lacunes, cortical atrophy, and increased dilated perivascular spaces in the centrum semiovale. However, the radiological manifestations of CAA, as well as their clinical correlates, may have other aetiologies and mimics. It is important for the radiologist to be aware of these clinico-radiological features and mimics to accurately diagnose CAA. This is increasingly important in a patient demographic that has a high prevalence for use of antiplatelet and antithrombotic medications for other comorbidities which inherently carries an increased risk of ICH in patients with CAA.

Long-term unmet needs and associated factors in stroke or TIA survivors: An observational study.

OBJECTIVE: To extensively investigate long-term unmet needs in survivors of stroke or TIA and to identify factors associated with these unmet needs. METHODS: Community-dwelling adults were invited to participate in a survey ≥2 years after discharge for stroke/TIA. Unmet needs were assessed across 5 domains: activities and participation, environmental factors, body functions, post-acute care, and secondary prevention. Factors associated with unmet needs were determined with multivariable negative binomial regression. RESULTS: Of 485 participants invited to complete the survey, 391 (81%) responded (median age 73 years, 67% male). Most responders (87%) reported unmet needs in ≥1 of the measured domains, particularly in secondary prevention (71%). Factors associated with fewer unmet needs included older age (incident rate ratio [IRR] 0.62, 95% confidence interval [CI] 0.50-0.77), greater functional ability (IRR 0.33, 95% CI 0.17-0.67), and reporting that the general practitioner was the most important in care (IRR 0.69, 95% CI 0.57-0.84). Being depressed (IRR 1.61, 95% CI 1.23-2.10) and receiving community services after stroke (IRR 1.45, 95% CI 1.16-1.82) were associated with more unmet needs. CONCLUSIONS: Survivors of stroke/TIA reported considerable unmet needs ≥2 years after discharge, particularly in secondary prevention. The factors associated with unmet needs could help guide policy decisions, particularly for tailoring care and support services provided after discharge.

Nurse-Led Intervention to Improve Knowledge of Medications in Survivors of Stroke or Transient Ischemic Attack: A Cluster Randomized Controlled Trial.

INTRODUCTION: Limited evidence exists on effective interventions to improve knowledge of preventive medications in patients with chronic diseases, such as stroke. We investigated the effectiveness of a nurse-led intervention, where a component was to improve knowledge of prevention medications, in patients with stroke or transient ischemic attack (TIA). METHODS: Prospective sub-study of the Shared Team Approach between Nurses and Doctors for Improved Risk Factor Management, a randomized controlled trial of risk factor management. We recruited patients aged ≥18 years and hospitalized for stroke/TIA. The intervention comprised an individualized management program, involving nurse-led education, and management plan with medical specialist oversight. The outcome, participants' knowledge of secondary prevention medications at 12 months, was assessed using questionnaires. A score of ≥5 was considered as good knowledge. Effectiveness of the intervention on knowledge of medications was determined using logistic regression. RESULTS: Between May 2014 and January 2015, 142 consecutive participants from the main trial were included in this sub-study, 64 to usual care and 78 to the intervention (median age 68.9 years, 68% males, and 79% ischemic stroke). In multivariable analyses, we found no significant difference between intervention groups in knowledge of medications. Factors independently associated with good knowledge (score ≥5) at 12 months included higher socioeconomic position (OR 4.79, 95% CI 1.76, 13.07), greater functional ability (OR 1.69, 95% CI 1.17, 2.45), being married/living with a partner (OR 3.12, 95% CI 1.10, 8.87), and using instructions on pill bottle/package as an administration aid (OR 4.82, 95% CI 1.76, 13.22). Being aged ≥65 years was associated with poorer knowledge of medications (OR 0.24, 95% CI 0.08, 0.71), while knowledge was worse among those taking three medications (OR 0.15, 95% CI 0.03, 0.66) or ≥4 medications (OR 0.09, 95% CI 0.02, 0.44), when compared to participants taking fewer (≤2) prevention medications. CONCLUSION: There was no evidence that the nurse-led intervention was effective for improving knowledge of secondary prevention medications in patients with stroke/TIA at 12 months. However, older patients and those taking more medications should be particularly targeted for more intensive education. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12688000166370).

Importance of spontaneous nystagmus detection in the differential diagnosis of acute vertigo.

Vertigo is a common cause of emergency department attendance. Detection of spontaneous nystagmus may be a useful sign in distinguishing vestibular neuritis from other vestibular diagnoses. We aimed to assess the contribution of spontaneous nystagmus in the diagnosis of acute vertigo. We enrolled consecutive consenting patients arriving at a single emergency department with acute vertigo. There was no declared protocol for the emergency department staff. A standardized history and examination was conducted by the investigators. Observation for spontaneous nystagmus, its response to visual fixation, and testing the vestibulo-ocular reflex with the horizontal head impulse test were the chief examination components. MRI was obtained within 24 hours. Clinical criteria and MRI were used to reach the final diagnosis. The investigators' physical findings and final neurological diagnosis were compared with the initial emergency department examination findings and the referral diagnosis. There were 28 patients, 15 with vestibular neuritis, six with benign paroxysmal positional vertigo, one with stroke, suspected clinically, and three with migraine. In three the diagnosis remained uncertain. Spontaneous nystagmus was seen in all 15 patients with vestibular neuritis, fixation-suppressed in eight of 11 tested for this. The head impulse test was positive in 12 of 15 with vestibular neuritis. The emergency department referral diagnosis was correct in six of 23 patients. The ability to detect spontaneous nystagmus is useful in vestibular diagnosis, both in support of a diagnosis of vestibular neuritis and in avoiding false positive diagnoses of benign paroxysmal positional vertigo.

Examining the lacunar hypothesis with diffusion and perfusion magnetic resonance imaging.

BACKGROUND: The clinical diagnosis of subcortical cerebral infarction is inaccurate for lesion location and pathogenesis. Clinically suspected small perforating artery occlusions may be embolic infarcts, with important implications for investigation and treatment. New MRI techniques may allow more accurate determination of the stroke mechanism soon after admission. METHODS: In a prospective series of 106 patients evaluated with acute diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) within 24 hours of stroke, we enrolled 19 with a lacunar syndrome. On the basis of the topography, DWI and PWI findings, and outcome T2 MRI, we determined whether the mechanism of infarction was single perforating vessel occlusion or large artery embolism. RESULTS: Thirteen patients had pure motor stroke, 2 had ataxic hemiparesis, and 4 had sensorimotor stroke. Six patients had lacunes on MRI, none with PWI lesions. Four patients had subcortical and distal cortical infarcts on DWI. Nine had solitary restricted striatocapsular infarcts. Seven of these 9 had PWI studies, 5 with PWI lesions. The presence of a PWI lesion reliably differentiated striatocapsular from lacunar infarction for solitary small subcortical infarcts (P=0.03). CONCLUSION: DWI and PWI altered the final diagnosis of infarct pathogenesis from small perforating artery occlusion to large artery embolism in 13 of 19 patients presenting with lacunar syndromes. Lacunes cannot be reliably diagnosed on clinical grounds.

Cognitive dysfunction follows left heart catheterisation but is not related to microembolic count.

BACKGROUND: Left heart catheterisation with coronary angiography (CA) may lead to cognitive dysfunction, as a result of neurological injury. The aim was to assess the incidence of cognitive dysfunction in elderly patients three months after CA and investigate any association between cognitive dysfunction and microembolic count during CA. METHODS: This was a prospective observational study with a control cohort. Cognitive testing was undertaken at baseline and at 3 months using a battery of 8 neuropsychological tests. Subjects comprised 51 CA patients, aged ≥ 50 years, with normal baseline cognition, and 31 community control participants. Microemboli were measured by Transcranial Doppler throughout the procedure. All patients underwent trans-femoral CA with aortography and ventriculography. Cognitive dysfunction was defined in an individual when their reliable change index score was less than -1.96 on 2 or more tests and/or their combined z score was less than -1.96. Microembolic count was assessed by off-line manual counting and automatic software was also used to count and differentiate gaseous from solid microemboli. RESULTS: Cognitive dysfunction was identified in 15.7% of patients at 3 months. Microemboli were detected in all patients, predominantly during aortography and ventriculography. The median total embolic count was 365 (IQR 192, 574), the majority being gaseous (84%). There was no multivariable association between cognitive dysfunction at 3 months and microembolic count. CONCLUSIONS: This study demonstrated that cognitive dysfunction following CA is not associated with microembolic load. Cognitive dysfunction occurs in 15.7% of patients at 3 months. This is reassuring for the proceduralist and suggests that other perioperative elements are involved.

Risk factor management in survivors of stroke: a double-blind, cluster-randomized, controlled trial.

BACKGROUND: Comprehensive community care has the potential to improve risk factor management of patients with stroke or transient ischaemic attack. AIM: The primary aim is to determine the effectiveness of an individualized management program on risk factor management for patients discharged from hospital after stroke. DESIGN: Multicentre, cluster-randomized, controlled trial, with clusters by general practice. Participants are randomized to receive intervention or control after a baseline assessment undertaken after discharge from hospital. The general practice they attend is marked as an intervention or control accordingly. All subsequent participants attending those practices are automatically assigned as intervention or control. Baseline and all outcome assessments, including an analysis of risk factors, are undertaken by assessors blinded to patient randomization. INTERVENTION DETAILS: Based on the results of blinded assessments, the individualized management program group will receive targeted advice on how to manage their risk factors using a standardized, evidence-based template to communicate 'ideal' management with their general practitioner. In addition, patients randomized to the individualized management program group will receive counselling and education about stroke risk factor management by an intervention study nurse. Individualized management programs will be reviewed at three-months, six-months, 12 months, and 18 months after stroke, at which times they will be modified if appropriate. Stroke risk management will be evaluated using changes in the Framingham cardiovascular risk score. Analysis will be on an intention-to-treat basis using analysis of covariance or generalized linear model to adjust for baseline risk score and other relevant confounding factors.

National survey of management of transient ischaemic attack in Australia: take immediate action.

OBJECTIVE: To understand the current organisation of services for people with transient ischaemic attack (TIA) and the processes of assessment and management across Australian hospitals. DESIGN AND SETTING: Cross-sectional survey in 2008 of 134 Australian hospitals, mostly urban centres that treat large numbers of stroke patients. MAIN OUTCOME MEASURES: Survey questions covered assessment, early management and follow-up practices, as well as organisation of services for TIA. RESULTS: Seventy-four hospitals (55%) responded: 47 (64%) reported access to a stroke unit, and 19 (26%) to a specialist clinic for TIA. Initial assessment included blood tests, electrocardiogram and brain computed tomography at most sites (92%-94%), and carotid imaging at more than half (65%), but magnetic resonance imaging at only 3% of sites. A tool to stratify the risk of subsequent stroke was used at 38 sites (51%), more commonly in hospitals with a stroke unit than in those without such a unit (64% v 30%; P = 0.005). Treatment was initiated at the initial assessment at 42 sites (58%), more commonly at stroke unit than non-stroke unit sites (68% v 37%; P = 0.007). Formalised policies for management of TIA patients were used at 38 sites (54%), with clear differences between sites with a stroke unit and those without (70% v 25%; P < 0.001). CONCLUSION: Access to rapid assessment and management services for TIA varies considerably between Australian hospitals. The presence of organised stroke care at a hospital leads to improved processes of care for patients presenting with TIA.

Clinical diagnosis of subcortical cerebral infarction.

Clinical diagnosis of subcortical infarction, chiefly lacunar stroke, has been considered important for arriving at the most rational stroke diagnosis and treatment strategy. This review focuses on the lacunar hypothesis and potential inaccuracy of clinical diagnosis and computed tomography in subcortical stroke. Modern magnetic resonance imaging techniques have increased sensitivity and specificity for subcortical infarcts and may help in determining the pathogenesis in individual patients. Full investigation is now favored for all stroke patients regardless of the clinical diagnosis. Acute stroke and secondary prevention treatments are discussed in reference to a diagnosis of subcortical infarction.

Diffusion- and perfusion-weighted MRI response to thrombolysis in stroke.

Diffusion- and perfusion-weighted magnetic resonance imaging provides important pathophysiological information in acute brain ischemia. We performed a prospective study in 19 sub-6-hour stroke patients using serial diffusion- and perfusion-weighted imaging before intravenous thrombolysis, with repeat studies, both subacutely and at outcome. For comparison of ischemic lesion evolution and clinical outcome, we used a historical control group of 21 sub-6-hour ischemic stroke patients studied serially with diffusion- and perfusion-weighted imaging. The two groups were well matched for the baseline National Institutes of Health Stroke Scale and magnetic resonance parameters. Perfusion-weighted imaging-diffusion-weighted imaging mismatch was present in 16 of 19 patients treated with tissue plasminogen activator, and 16 of 21 controls. Perfusion-weighted imaging-diffusion-weighted imaging mismatch patients treated with tissue plaminogen activator had higher recanalization rates and enhanced reperfusion at day 3 (81% vs 47% in controls), and a greater proportion of severely hypoperfused acute mismatch tissue not progressing to infarction (82% vs -25% in controls). Despite similar baseline diffusion-weighted imaging lesions, infarct expansion was less in the recombinant tissue plaminogen activator group (14cm(3) vs 56cm(3) in controls). The positive effect of thrombolysis on lesion growth in mismatch patients translated into a greater improvement in baseline to outcome National Institutes of Health Stroke Scale in the group treated with recombinant tissue plaminogen activator, and a significantly larger proportion of patients treated with recombinant tissue plaminogen activator having a clinically meaningful improvement in National Institutes of Health Stroke Scale of > or = 7 points. The natural evolution of acute perfusion-weighted imaging-diffusion-weighted imaging mismatch tissue may be altered by thrombolysis, with improved stroke outcome. This has implications for the use of diffusion- and perfusion-weighted imaging in selecting and monitoring patients for thrombolytic therapy.