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.

Post Stroke Outcome: Global Insight into Persisting Sequelae Using the Post Stroke Checklist.

BACKGROUND: Following stroke, individuals commonly experience persisting loss of function. Whilst long-term care should involve continued support for ongoing stroke sequelae, this is often not routinely practiced globally. The Post Stroke Checklist was designed to standardise the process of detecting persisting treatable problems following stroke. AIMS: This cross-sectional study aimed to identify the long-term problems reported in Australian and Chinese participants at six months post stroke using the Post Stroke Checklist. It also aimed to provide global insight into poststroke sequelae by comparing the study results to previously published studies which administered the Post Stroke Checklist in other countries. METHODS: Participants were recruited from two hospitals in Australia and one hospital in China. The Post Stroke Checklist consists of 11 problem areas commonly experienced after stroke. This study follows a sequence of studies which have applied the checklist to monitor long-term outcomes after stroke in Germany, Italy, Singapore, Sweden and the United Kingdom. RESULTS: Comparisons between Australia (n = 112) and China (n = 97) demonstrated statistically significant differences on the Post Stroke Checklist items. Across all seven countries, collectively the most common persisting difficulties post-stroke related to: cognition, life after stroke, mood, mobility and activities of daily living. An analysis of means procedure compared individual countries for each checklist item against the overall group mean (all countries combined). CONCLUSIONS: Globally, individuals report persisting functional difficulties following stroke. There appear to be differences in the proportions affected across the various countries, and healthcare systems may benefit from geographically tailoring post-stroke care.

Fatal and non-fatal events within 14 days after early, intensive mobilization post stroke.

OBJECTIVE: This tertiary analysis from AVERT examined fatal and non-fatal Serious Adverse Events (SAEs) at 14 days. METHOD: AVERT was a prospective, parallel group, assessor blinded, randomized international clinical trial comparing mobility training commenced <24 hours post stroke, termed very early mobilization (VEM) to usual care (UC). Primary outcome was assessed at 3 months. Included: Patients with ischaemic and haemorrhagic stroke within 24 hours of onset. Treatment with thrombolytics allowed. Excluded: Patients with severe premorbid disability and/or comorbidities. Interventions continued for 14 days or hospital discharge if less. The primary early safety outcome was fatal SAEs within 14 days. Secondary outcomes were non-fatal SAEs classified as neurologic, immobility-related, and other. Mortality influences were assessed using binary logistic regression adjusted for baseline stroke severity (NIHSS) and age. RESULTS: 2,104 participants were randomized to VEM (n = 1,054) or UC (n = 1,050) with a median age of 72 years (IQR 63-80) and NIHSS 7 (IQR 4-12). By 14 days, 48 had died in VEM, 32 in UC, age and stroke severity adjusted Odds Ratio of 1.76 (95% CI 1.06-2.92, p = 0.029). Stroke progression was more common in VEM. Exploratory subgroup analyses showed higher odds of death in intracerebral haemorrhage and >80 years subgroups, but there was no significant treatment by subgroup interaction. No difference in non-fatal SAEs found. CONCLUSION: While the overall case fatality at 14 days post-stroke was only 3.8%, mortality adjusted for age and stroke severity was increased with high dose, intensive training compared to usual care. Stroke progression was more common in VEM. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that very early mobilization increases mortality at 14 days post stroke. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12606000185561.

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.

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.

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.

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).

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.

Isolated asymptomatic pulmonary arteriovenous malformation presenting with ischaemic stroke.

Young onset stroke is uncommon, and may be due to conditions other than traditional vascular risk factors. A 42-year-old woman with an ischaemic stroke was found to have left atrial bubble study positivity on transthoracic echocardiogram (TTE) suggestive of patent foramen ovale, however she also had low peripheral oxygen saturation. Investigation revealed an isolated pulmonary arteriovenous malformation (PAVM), visible on admission chest radiograph. This can cause embolic stroke and is an alternate cause of the TTE findings. The PAVM was able to be closed via endovascular intervention, removing the shunt and therefore removing her risk of recurrent stroke events. This is a rare cause of embolic stroke in young people which can be easily missed on investigation yet is amenable to treatment.

Transient ischaemic attack clinic: an evaluation of diagnoses and clinical decision making.

The diagnosis of transient ischaemic attack (TIA) is based largely on the patient's symptom recall and clinical judgement. This decision-making process is highly subjective and the inter-observer reliability of TIA diagnosis is at best moderate, even among neurologists. The aim of this study is to examine the presenting features and final diagnoses of referrals to a TIA clinic and to evaluate characteristics that favoured the diagnosis of TIA over other TIA "mimics". Consecutive new referrals to a tertiary metropolitan hospital TIA clinic over a 9month period were examined. Characteristics between TIA and non-TIA diagnoses were compared and analysed. Eighty-two patients were recruited. Eighteen (22%) were given a final diagnosis of TIA or stroke. Major alternative diagnoses included migraine (n=17, 21%), presyncope/syncope (n=13, 16%) and anxiety (n=7, 9%). Four (5%) patients had unclassifiable symptoms with no clear final diagnosis. Mean age was 67±a standard deviation of 17years and patients diagnosed with TIA/stroke were on average older than those with non-TIA diagnoses (77±10 versus 64±17years, p=0.003). A diagnosis of TIA/stroke was favoured in the presence of moderate to severe weakness (p=0.032), dysphasia (p=0.037) or dysarthria (p=0.005). Unclassifiable symptoms (for example, palpitations, confusion, headache) were reported in 27 patients (33%) and their presence favoured non-TIA diagnoses (p=0.0003). TIA constituted a minority of the referrals to our clinic. Accurate clinical diagnosis of TIA facilitates early stroke prevention and avoids unnecessary investigations and prescriptions. Attempts to improve diagnostic accuracy of TIA should target improving the education and awareness of frontline medical practitioners.

Fatal ischemic stroke complicating acute multifocal placoid pigment epitheliopathy: histopathological findings.

A previously healthy 29-year-old man was admitted to a tertiary referral center with acute left hemiparesis followed shortly by de novo convulsive status epilepticus. This was in the context of a 2-month history of flu-like symptoms, severe headaches, and retinopathy recently diagnosed as acute multifocal placoid pigment epitheliopathy. Neuroimaging demonstrated bilateral, multiple territory cerebral infarction. Despite intravenous methylprednisolone and craniotomy for the management of raised intracranial pressure, the patient deteriorated and died 14 days later. At autopsy, multiple infarcts of varying ages within a 10-day period were seen in association with a segmental giant cell vasculopathy of meningeal arteries.

Accuracy of national mortality codes in identifying adjudicated cardiovascular deaths.

OBJECTIVE: This study investigated the sensitivity and specificity of the national mortality codes in identifying cardiovascular disease (CVD) deaths and documents methods of verification. METHODS: A 12-year retrospective case ascertainment of all ICD-coded CVD deaths was performed for deaths between 1990 and 2002 in the Melbourne Collaborative Cohort Study, comprising 41,528 subjects. Categories of non-CVD codes were also examined. Stratified samples of 750 deaths were adjudicated from a total of 2,230 deaths. Expert panels of cardiologists and neurologists adjudicated deaths. RESULTS: Of the 750 deaths adjudicated, 582 were verified as CVD [392 coronary heart disease (CHD) and 92 stroke] and 168 non-CVD. Estimated sensitivity and specificity of national mortality codes for identifying specific causes of death were: CHD 74.2% (95% CI: 69.8-78.5%) and 97.6% (96.0-99.2%), respectively; myocardial infarction 59.9% (50.9-69.0%) and 94.2% (92.4-96.0%), respectively; haemorrhagic stroke 58.9% (46.0-71.7%) and 99.8% (99.4-100.0%), respectively and; ischaemic stroke 38.7% (20.5-56.9%) and 99.9% (99.6-100.0%), respectively. Misclassification was most common for deaths with primary ICD codes for endocrine-metabolic and genito-urinary diseases. CONCLUSIONS: National mortality coding under-estimated the true proportion of CHD and stroke deaths in the cohort by 13.6% and 50.8%, respectively. IMPLICATIONS: Misclassification of cause of death may have implications for conclusions drawn from epidemiological research.

Management of cholesterol to reduce the burden of stroke in Asia: consensus statement.

Stroke is a major cause of morbidity and mortality in Asia, and its pattern is changing. The incidence of haemorrhagic stroke is declining while the incidence of ischaemic stroke caused by large artery atherothromboembolism is increasing secondary to an increase in the prevalence of hypercholesterolaemia. The Working Group on Stroke and Lipids Management in Asia Consensus Panel assembled leading experts from the region to reach a consensus on how to address this challenge. The group discussed the observational epidemiology of the relationship between cholesterol and risk of stroke, the clinical trial evidence base for cholesterol-lowering for stroke prevention, and issues specific to stroke and lipid management for Asian doctors and patients. Stroke guidelines from many of the Asian countries have recently recommended consideration of statins for recurrent stroke prevention in patients with previous ischaemic stroke or transient ischaemic attack. However, because these recommendations have yet to be implemented widely, there is a need to educate Asian physicians and patients about the importance of adequate control of hypercholesterolaemia. Further trials of statins in Asian patients are also needed, particularly in those with intracranial stenosis.

Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial.

BACKGROUND: Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3-6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI). METHODS: We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3-6 h after onset of ischaemic stroke. PWI and DWI were done before and 3-5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00238537. FINDINGS: We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71.6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1.24 with alteplase and 1.78 with placebo (ratio 0.69, 95% CI 0.38-1.28; Student's t test p=0.239); the median relative infarct growth was 1.18 with alteplase and 1.79 with placebo (ratio 0.66, 0.36-0.92; Wilcoxon's test p=0.054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0.001), better neurological outcome (p<0.0001), and better functional outcome (p=0.010) than was no reperfusion. INTERPRETATION: Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted.

Emergency administration of abciximab for treatment of patients with acute ischemic stroke: results of an international phase III trial: Abciximab in Emergency Treatment of Stroke Trial (AbESTT-II).

BACKGROUND AND PURPOSE: A previous randomized, placebo-controlled, double-blind study suggested that abciximab may be safe and effective in treatment of acute ischemic stroke. The current phase 3 study was planned to test the relative efficacy and safety of abciximab in patients with acute ischemic stroke with planned treatment within 5 hours since symptoms onset. METHODS: An international, randomized, placebo-controlled, double-blind phase 3 trial tested intravenous administration of abciximab in 2 study cohorts using stratification variables of time since onset and stroke severity. The planned enrollment was 1800 patients. The primary cohort enrolled those patients who could be treated within 5 hours of onset of stroke. A companion cohort enrolled patients that were treated 5 to 6 hours after stroke as well as a smaller cohort of patients who could be treated within 3 hours of stroke present on awakening. The primary efficacy measure was the dichotomous modified Rankin Scale score at 3 months as adjusted to the baseline severity of stroke among subjects in the primary cohort. The primary safety outcome was the rate of symptomatic or fatal intracranial hemorrhage that occurred within 5 days of stroke. RESULTS: The trial was terminated prematurely after 808 patients in all cohorts were enrolled by recommendation of an independent safety and efficacy monitoring board due to an unfavorable benefit-risk profile. At 3 months, approximately 33% of patients assigned placebo (72/218) and 32% of patients assigned abciximab (71/221; P=0.944) in the primary cohort were judged to have a favorable response to treatment. The distributions of outcomes on the modified Rankin Scale were similar between the treated and control groups. Within 5 days of enrollment, approximately 5.5% of abciximab-treated and 0.5% of placebo-treated patients in the primary cohort had symptomatic or fatal intracranial hemorrhage (P=0.002). The trial also did not demonstrate an improvement in outcomes with abciximab among patients in the companion and wake-up cohorts. Although the number of patients was small, an increased rate of hemorrhage was noted within 5 days among patients in the wake-up population who received abciximab (13.6% versus 5% for placebo). CONCLUSIONS: This trial did not demonstrate either safety or efficacy of intravenous administration of abciximab for the treatment of patients with acute ischemic stroke regardless of end point or population studied. There was an increased rate of symptomatic or fatal intracranial hemorrhage in the primary and wake-up cohorts.