Thrombolytic Treatment in Wake-Up Stroke: A Propensity Score-Matched Analysis of Treatment Effectiveness in the Norwegian Stroke Registry.

BACKGROUND: Previous clinical trials found improved outcome of thrombolytic treatment in patients with ischemic wake-up stroke (WUS) selected by advanced imaging techniques. The authors assessed the effectiveness of thrombolytic treatment in patients with WUS in a nationwide stroke registry. METHODS AND RESULTS: Using propensity score matching, the authors assessed the effectiveness and safety of thrombolytic treatment versus no thrombolytic treatment in 726 patients (363 matched pairs) with WUS in the Norwegian Stroke Registry in 2014 to 2019. Thrombolytic treatment in WUS versus known-onset stroke was compared in 730 patients (365 matched pairs). Functional outcomes were assessed by the modified Rankin Scale (mRS) at 3 months. A significant benefit of thrombolytic treatment in WUS was seen in ordinal analysis (odds ratio [OR], 1.48 [95% CI, 1.15-1.91]; P=0.003) and for mRS 0 to 2 (OR, 1.81 [95% CI, 1.29-2.52]; P=0.001) but not for mRS 0 or 1 (OR, 1.32 [95% CI, 1.00-1.74]; P=0.050). The proportion of patients with mRS 0 or 1 was lower in patients with WUS who underwent thrombolysis versus those with known-onset stroke (50.4% versus 59.5%; OR, 0.69 [95% CI, 0.52-0.93]; P=0.013), while outcomes were similar between groups for mRS 0 to 2 and ordinal analysis. Symptomatic intracranial hemorrhage after thrombolytic treatment occurred in 4.4% of patients with WUS and 3.9% of patients with known-onset stroke (OR, 1.14 [95% CI, 0.54-2.41]; P=0.726). CONCLUSIONS: Thrombolytic treatment in patients with WUS was associated with improved functional outcome compared with patients with no thrombolytic treatment and was not associated with increased rates of symptomatic intracranial hemorrhage compared with known-onset stroke. The results indicate that thrombolytic treatment is effective and safe in WUS in a real-life setting.

Reduced physical activity level was associated with poorer quality of life during the early phase of the COVID-19 pandemic: a sub-study of the last-long trial.

OBJECTIVES: To assess how physical activity levels changed in a stroke cohort during the COVID-19 (SARS-CoV-2) pandemic, and how these changes were associated with quality of life (QoL). METHODS: Between March and July 2021, 150 patients with stroke already included in the Life after Stroke (LAST-long) trial in Norway were invited to participate in this cross-sectional survey. Participants were asked to complete a questionnaire assessing changes in physical activity and self-reported health following the pandemic. Univariate and multivariate logistic regression analyses were used to explore the association between physical activity, loneliness, mental health, social activity and QoL. RESULTS: In all, 118 (79%) participants completed the questionnaire. A total of 80 (68%) reported less physical activity, 46 (39%) felt lonelier, and 43 (37%) reported worse mental health, while 50 (42%) reported reduced QoL compared with before the lockdown. In the univariate analyses less physical activity, feeling lonelier and changes in mental health were associated with reduced QoL. In the multivariate analysis only less physical activity odds ratio (OR) = 4.04 (95% confidence interval (95% CI) 1.44-11.34, p = 0.008) was significantly associated with reduced QoL. CONCLUSION: More than two-thirds of patients with stroke reported reduced physical activity during the COVID-19 pandemic, and less physical activity was strongly associated with reduced QoL.

Accelerometer-measured physical activity at 3 months as a predictor of symptoms of depression and anxiety 1 year after stroke: a multicentre prospective cohort study in central Norway.

OBJECTIVES: To study sedentary behaviour and physical activity at 3 months as predictors for symptoms of depression and anxiety at 1-year post-stroke. DESIGN: A prospective cohort study. PATIENTS: Patients with first-ever ischaemic stroke. METHODS: Mood was assessed 3- and 12-months post-stroke using the Hospital Anxiety and Depression Scale. Sedentary behaviour and physical activity were measured using accelerometry 3 months post-stroke. RESULTS: A total of 292 participants (116 (39.7%) females; mean age 71.7 (standard deviation 11.3) years) were included. At 12 months, 16.7% experienced depression and 19.5% anxiety, respectively. Adjusting for age and sex, regression analysis showed that comorbidity burden (ß 0.26; 95% confidence interval (95% CI) 0.02, 0.51; p = 0.038), stroke severity (ß 0.22; 95% CI 0.10, 0.35; p = 0.001), functional disability (ß 0.89, 95% CI 0.49, 1.30; p = 0.000), and global cognition (ß-0.15; 95% CI -0.25, -0.05; p = 0.004) predicted depression. Multi-adjusted analysis showed sedentary behaviour and physical activity did not significantly predict depression or anxiety (p > 0.05). CONCLUSION: Sedentary behaviour and physical activity did not significantly predict mood after stroke. Comorbidity burden, stroke severity, functional disability, and global cognition were identified as possible predictors of depression. More research is needed to determine the impact of physical activity on depression and anxiety symptoms.

Multimodal individualised intervention to prevent functional decline after stroke: protocol of a randomised controlled trial on long-term follow-up after stroke (LAST-long).

INTRODUCTION: Multimodal interventions have emerged as new approaches to provide more targeted intervention to reduce functional decline after stroke. Still, the evidence is contradictory. The main objective of the Life After Stroke (LAST)-long trial is to investigate if monthly meetings with a stroke coordinator who offers a multimodal approach to long-term follow-up can prevent functional decline after stroke. METHODS AND ANALYSIS: LAST-long is a pragmatic single-blinded, parallel-group randomised controlled trial recruiting participants living in six different municipalities, admitted to four hospitals in Norway. The patients are screened for inclusion and recruited into the trial 3 months after stroke. A total of 300 patients fulfilling the inclusion criteria will be randomised to an intervention group receiving monthly follow-up by a community-based stroke coordinator who identifies the participants' individual risk profile and sets up an action plan based on individual goals, or to a control group receiving standard care. All participants undergo blinded assessments at 6-month, 12-month and 18-month follow-up. Modified Rankin Scale at 18 months is primary outcome. Secondary outcomes are results of blood tests, blood pressure, adherence to secondary prophylaxis, measures of activities of daily living, cognitive function, physical function, physical activity, patient reported outcome measures, caregiver's burden, the use and costs of health services, safety measures and measures of adherence to the intervention. Mixed models will be used to evaluate differences between the intervention and control group for all endpoints across the four time points, with treatment group, time as categorical covariates and their interaction as fixed effects, and patient as random effect. ETHICS AND DISSEMINATION: This trial was approved by the Regional Committee of Medical and Health Research Ethics, REC no. 2018/1809. The main results will be published in international peer-reviewed open access scientific journals and to policy-makers and end users in relevant channels. TRIAL REGISTRATION NUMBER: ClincalTrials.gov Identifier: NCT03859063, registered on 1 March 2019.

A phase III, multi-arm multi-stage covariate-adjusted response-adaptive randomized trial to determine optimal early mobility training after stroke (AVERT DOSE).

RATIONALE: The evidence base for acute post-stroke rehabilitation is inadequate and global guideline recommendations vary. AIM: To define optimal early mobility intervention regimens for ischemic stroke patients of mild and moderate severity. HYPOTHESES: Compared with a prespecified reference arm, the optimal dose regimen(s) will result in more participants experiencing little or no disability (mRS 0-2) at 3 months post-stroke (primary), fewer deaths at 3 months, fewer and less severe complications during the intervention period, faster recovery of unassisted walking, and better quality of life at 3 months (secondary). We also hypothesize that these regimens will be more cost-effective. SAMPLE SIZE ESTIMATES: For the primary outcome, recruitment of 1300 mild and 1400 moderate participants will yield 80% power to detect a 10% risk difference. METHODS AND DESIGN: Multi-arm multi-stage covariate-adjusted response-adaptive randomized trial of mobility training commenced within 48 h of stroke in mild (NIHSS < 7) and moderate (NIHSS 8-16) stroke patient strata, with analysis of blinded outcomes at 3 (primary) and 6 months. Eligibility criteria are broad, while excluding those with severe premorbid disability (mRS > 2) and hemorrhagic stroke. With four arms per stratum (reference arm retained throughout), only the single treatment arm demonstrating the highest proportion of favorable outcomes at the first stage will proceed to the second stage in each stratum, resulting in a final comparison with the reference arm. Three prognostic covariates of age, geographic region and reperfusion interventions, as well as previously observed mRS 0-2 responses inform the adaptive randomization procedure. Participants randomized receive prespecified mobility training regimens (functional task-specific), provided by physiotherapists/nurses until discharge or 14 days. Interventions replace usual mobility training. Fifty hospitals in seven countries (Australia, Malaysia, United Kingdom, Ireland, India, Brazil, Singapore) are expected to participate. SUMMARY: Our novel adaptive trial design will evaluate a wider variety of mobility regimes than a traditional two-arm design. The data-driven adaptions during the trial will enable a more efficient evaluation to determine the optimal early mobility intervention for patients with mild and moderate ischemic stroke.

Safety and efficacy of tenecteplase in patients with wake-up stroke assessed by non-contrast CT (TWIST): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Current evidence supports the use of intravenous thrombolysis with alteplase in patients with wake-up stroke selected with MRI or perfusion imaging and is recommended in clinical guidelines. However, access to advanced imaging techniques is often scarce. We aimed to determine whether thrombolytic treatment with intravenous tenecteplase given within 4·5 h of awakening improves functional outcome in patients with ischaemic wake-up stroke selected using non-contrast CT. METHODS: TWIST was an investigator-initiated, multicentre, open-label, randomised controlled trial with blinded endpoint assessment, conducted at 77 hospitals in ten countries. We included patients aged 18 years or older with acute ischaemic stroke symptoms upon awakening, limb weakness, a National Institutes of Health Stroke Scale (NIHSS) score of 3 or higher or aphasia, a non-contrast CT examination of the head, and the ability to receive tenecteplase within 4·5 h of awakening. Patients were randomly assigned (1:1) to either a single intravenous bolus of tenecteplase 0·25 mg per kg of bodyweight (maximum 25 mg) or control (no thrombolysis) using a central, web-based, computer-generated randomisation schedule. Trained research personnel, who conducted telephone interviews at 90 days (follow-up), were masked to treatment allocation. Clinical assessments were performed on day 1 (at baseline) and day 7 of hospital admission (or at discharge, whichever occurred first). The primary outcome was functional outcome assessed by the modified Rankin Scale (mRS) at 90 days and analysed using ordinal logistic regression in the intention-to-treat population. This trial is registered with EudraCT (2014-000096-80), ClinicalTrials.gov (NCT03181360), and ISRCTN (10601890). FINDINGS: From June 12, 2017, to Sept 30, 2021, 578 of the required 600 patients were enrolled (288 randomly assigned to the tenecteplase group and 290 to the control group [intention-to-treat population]). The median age of participants was 73·7 years (IQR 65·9-81·1). 332 (57%) of 578 participants were male and 246 (43%) were female. Treatment with tenecteplase was not associated with better functional outcome, according to mRS score at 90 days (adjusted OR 1·18, 95% CI 0·88-1·58; p=0·27). Mortality at 90 days did not significantly differ between treatment groups (28 [10%] patients in the tenecteplase group and 23 [8%] in the control group; adjusted HR 1·29, 95% CI 0·74-2·26; p=0·37). Symptomatic intracranial haemorrhage occurred in six (2%) patients in the tenecteplase group versus three (1%) in the control group (adjusted OR 2·17, 95% CI 0·53-8·87; p=0·28), whereas any intracranial haemorrhage occurred in 33 (11%) versus 30 (10%) patients (adjusted OR 1·14, 0·67-1·94; p=0·64). INTERPRETATION: In patients with wake-up stroke selected with non-contrast CT, treatment with tenecteplase was not associated with better functional outcome at 90 days. The number of symptomatic haemorrhages and any intracranial haemorrhages in both treatment groups was similar to findings from previous trials of wake-up stroke patients selected using advanced imaging. Current evidence does not support treatment with tenecteplase in patients selected with non-contrast CT. FUNDING: Norwegian Clinical Research Therapy in the Specialist Health Services Programme, the Swiss Heart Foundation, the British Heart Foundation, and the Norwegian National Association for Public Health.

Self-reported cognitive and psychiatric symptoms at 3 months predict single-item measures of fatigue and daytime sleep 12 months after ischemic stroke.

Introduction: Post-stroke fatigue and increased need for daytime sleep are multidimensional and insufficiently understood sequelae. Our aim was to study the relationships of self-reported cognitive and psychiatric symptoms at 3 months with fatigue and daytime sleep at 12 months post-stroke. Methods: Ischemic stroke patients without reported history of dementia or depression completed postal surveys 3- and 12-months post-stroke. At 3 months, psychiatric symptoms were assessed with the Hospital Anxiety and Depression Scale (HADS), and self-reported changes in cognitive symptoms (concentration and memory) compared to pre-stroke were assessed using single-item measures. At 12 months, single-item questions about changes in self-reported difficulties sleeping at night, fatigue and daytime sleep were included. First, we studied whether self-reported cognitive and/or psychiatric symptoms at 3 months were associated with daytime sleep and fatigue at 12 months using multiple logistic regression. Second, we fitted 2 structural equation models (SEMs) predicting fatigue and 2 models predicting daytime sleep. We compared a model where only age, sex, stroke severity (National Institutes of Health Stroke Scale; NIHSS), and difficulties sleeping at night predicted fatigue and daytime sleep at 12 months to a model where mental distress (i.e., a latent variable built of cognitive and psychiatric symptoms) was included as an additional predictor of fatigue and daytime sleep at 12 months. Results: Of 156 patients (NIHSS within 24 hours after admission (mean ± SD) = 3.6 ± 4.3, age = 73.0 ± 10.8, 41% female) 37.9% reported increased daytime sleep and 50.0% fatigue at 12 months. Increased psychiatric symptoms and worsened cognitive symptoms were associated with fatigue and daytime sleep at 12 months, after controlling for NIHSS, age, sex, and difficulties sleeping at night. SEM models including mental distress as predictor showed adequate model fit across 3 fit measures (highest RMSEA = 0.063, lowest CFI and TLI, both 0.975). Models without mental distress were not supported. Conclusion: Self-reported cognitive and psychiatric symptoms at 3 months predict increased daytime sleep and fatigue at 12 months. This highlights the relevance of monitoring cognitive and psychiatric symptoms in the subacute phase post-stroke. However, future research using validated measures of self-reported symptoms are needed to further explore these relationships.

Wake-up stroke and unknown-onset stroke; occurrence and characteristics from the nationwide Norwegian Stroke Register.

Introduction: Population-based knowledge of the characteristics of wake-up stroke and unknown-onset stroke is limited. We compared occurrence and characteristics of ischaemic and haemorrhagic wake-up stroke, unknown-onset stroke and known-onset stroke in a nationwide register-based study. Patients and methods: We included patients registered in the Norwegian Stroke Register from 2012 through 2019. Age, sex, risk factors, clinical characteristics, acute stroke treatment and discharge destination were compared according to stroke type and time of onset. Results: Of the 60,320 patients included, 11,451 (19%) had wake-up stroke, 11,098 (18.4%) had unknown time of onset and 37,771 (62.6%) had known symptom onset. The proportion of haemorrhagic stroke was lower among wake-up stroke patients (1107/11,451, 9.7%, 95% CI: 9.1-10.2) than for known-onset stroke (5230/37,771, 13.8%, 95% CI: 13.5-14.2) and for unknown-onset stroke (1850/11,098, 16.7%, 95% CI: 16.0-17.4). Mild stroke (NIHSS <5) was more frequent in ischaemic wake-up stroke (5364/8308, 64.6%, 95% CI: 63.5-65.5) than in known-onset (16,417/26,746, 61.4%, 95% CI: 60.8-62.0) and unknown-onset stroke (3242/5853, 55.4%, 95% CI: 54.1-56.7), while baseline characteristics were otherwise similar to known-onset stroke. Unknown-onset stroke patients were more often female, lived alone and had more severe strokes compared to wake-up stroke and known-onset stroke patients. Unknown-onset stroke patients were more often in need of community-based health care on discharge and had a higher in-hospital mortality. Discussion and conclusions: Ischaemic wake-up strokes shared baseline characteristics with known-onset strokes, but tended to be milder. Ischaemic unknown-onset stroke patients differed significantly from wake-up stroke, emphasising the importance of considering them as separate entities.

Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST).

BACKGROUND: Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings. OBJECTIVE: To publish the detailed statistical analysis plan for TWIST prior to unblinding. METHODS: The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CONSORT) statement and provides clear and open reporting. DISCUSSION: Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses. TRIAL REGISTRATION: ClinicalTrials.gov NCT03181360 . EudraCT Number 2014-000096-80 . WHO ICRTP registry number ISRCTN10601890 .

Perceived Caregiver Strain, 3- and 18-Month Poststroke, in a Cohort of Caregivers from the Life after Stroke Trial (LAST).

Aim: To gain more knowledge of caregiver strain in the Life After Stroke Trial (LAST) population. Methods: This is a substudy of the LAST study, including all caregivers' reports of perceived Caregiver Strain Index (CSI) at inclusion and 18-month follow-up irrespective of group allocation. The checklist "STROBE Statement-Checklist of items that should be included in reports of cohort studies" was used. Caregivers to adults (age ≥18 years), here defined as the person living with, a patient with a first-ever or recurrent stroke, community dwelling, with modified Rankin Scale (mRS) <5 and no serious comorbidities, was invited to fill out the Caregiver Strain Index at three months (10-16 weeks) poststroke. Domains indicating differences of change in perceived strain in the total sample were analyzed in a linear regression analysis. Results: Caregiver strain (n = 147) varying from 5% to 27% was reported by the caregivers at baseline and between 2% to18% at 18-month follow-up. The items indicating the highest level of strain at baseline and 18 months were as follows: "Care giving is confining," "There have been changes in personal plans," "There have been emotional adjustments," and "I feel completely overwhelmed." The samples were divided into age groups 0-79 years and 80-100 years, indicating a higher strain on the caregiver for persons 80-100 years at 18 months. Conclusion: Caregiver strain was relatively low both at baseline and at 18-month follow-up. Main caregiver strains were reported in terms of a sense of confinement, a tendency of emotional strain, and the altering of plans at both time points. Depression was one of the main explanatory factors for the perceived caregiver strain. The perception of caregiver strain was higher in age groups 80-100 years than age groups 0-79 years.

The Relationship of Psychiatric Symptoms with Performance-Based and Self-Reported Cognitive Function After Ischemic Stroke.

OBJECTIVE: Findings on the relationship of psychiatric symptoms with performance-based and self-reported cognitive function post-stroke are inconclusive. We aimed to (1) study the relation of depression and anxiety to performance-based cognitive function and (2) explore a broader spectrum of psychiatric symptoms and their association with performance-based versus self-reported cognitive function. METHOD: Individuals with supratentorial ischemic stroke performed neuropsychological examination 3 months after stroke. For primary analyses, composite scores for memory and attention/executive function were calculated based on selected neuropsychological tests, and the Hospital Anxiety and Depression Scale (HADS) was used. Psychiatric symptoms and self-reported cognitive function for secondary aims were assessed using the Symptom-Checklist-90 - Revised (SCL-90-R). RESULTS: In a sample of 86 patients [mean (M) age: 64.6 ± 9.2; Mini-Mental State Examination (MMSE), 3-7 days post-stroke: M = 28.4 ± 1.7; National Institutes of Health Stroke Scale (NIHSS) after 3 months: M = 0.7 ± 1.6] depressive symptoms (HADS) were associated with poorer memory performance after controlling for age, sex, and education (p ≤ .01). In a subsample (n = 41; Age: M = 65.7 ± 8.1; MMSE: M = 28.4 ± 1.8; NIHSS: M = 1.0 ± 1.9), symptoms of phobic anxiety (SCL-90-R) were associated with poorer performance-based memory and attention/executive function, and symptoms of anxiety (SCL-90-R) with lower attention/executive function. Higher levels of self-reported cognitive difficulties were associated with higher scores in all psychiatric domains (p ≤ .05). CONCLUSION: Even in relatively well-functioning stroke patients, depressive symptoms are associated with poorer memory. The results also suggest that various psychiatric symptoms are more related to self-reported rather than to performance-based cognitive function. Screening for self-reported cognitive difficulties may not only help to identify patients with cognitive impairment, but also those who need psychological treatment.

Can functional walk tests add value to the prediction of cardiorespiratory fitness after stroke? A prospective cohort study.

BACKGROUND: Cardiorespiratory fitness is often impaired following stroke, and peak oxygen consumption (VO2peak) is an important prognostic value of all-cause mortality. The primary objective was to investigate whether functional walk tests assessed in the subacute phase after stroke added value in predicting VO2peak in chronic stroke, in addition to age, sex and functional dependency. Secondary objectives were to investigate associations between daily physical activity and functional walk tests, and with VO2peak in chronic stroke. METHODS: This prospective cohort study included eligible participants originally included in the randomized controlled trial Life After Stroke. Functional walk tests, i.e., six-minute walk test (6MWT) and maximal gait speed, were assessed at inclusion and 18 months later. VO2peak [ml/kg/min] was assessed by a cardiopulmonary exercise test on a treadmill 20 months after inclusion. Daily physical activity was measured by a uniaxial accelerometer (activPAL) at 18-month follow-up. RESULTS: Ninety-two community-dwelling individuals, with a mean (SD) age of 69.2 (10.6) years and 33 (35.9%) women, were included 3 months after stroke onset. Eighty-three (90.2%) participants had a modified Rankin Scale (mRS) score of 1 or 2, indicating functional independence. An overall assessment of four prediction models indicated the combination of age, sex, mRS and 6MWT as predictors to be the best fitted model in predicting VO2peak (adjusted R2 = 0.612). Secondary results showed statistically significant, but not clinically significant, associations between daily physical activity and functional walk tests, and with VO2peak. CONCLUSIONS: 6MWT add significant value to the prediction of mean VO2peak in the chronic phase in mild strokes, in combination with age, sex and functional dependency. This prediction model may facilitate clinical decisions and rehabilitation strategies for mildly affected stroke survivors in risk of low levels of VO2peak. Future studies should validate the model in various stages after stroke and in patients moderately and severely affected.

Effects of High-Intensity Interval Training After Stroke (The HIIT Stroke Study) on Physical and Cognitive Function: A Multicenter Randomized Controlled Trial.

OBJECTIVE: To assess the effects of high-intensity interval training (HIIT) on physical, mental, and cognitive functioning after stroke. DESIGN: The HIIT Stroke Study was a single-blind, multicenter, parallel-group randomized controlled trial. SETTING: Specialized rehabilitation units at 3 Norwegian hospitals. PARTICIPANTS: Adult stroke survivors (N=70) 3 months to 5 years after a first-ever stroke. Mean age was 57.6±9.2 years and 58.7±9.2 years in the intervention and control groups, respectively. INTERVENTIONS: Participants were randomized to standard care in combination with 4×4 minutes of treadmill HIIT at 85%-95% of peak heart rate or standard care only. OUTCOMES: Outcomes were measured using physical, mental, and cognitive tests and the FIM and Stroke Impact Scale. Linear mixed models were used to analyze differences between groups at posttest and 12-month follow-up. RESULTS: The intervention group showed a significant treatment effect (95% confidence interval [CI]) from baseline to posttest on a 6-minute walk test of 28.3 (CI, 2.80-53.77) meters (P=.030); Berg Balance Scale 1.27 (CI, 0.17-2.28) points (P=.025); and Trail Making Test Part B (TMT-B; -24.16 [CI, -46.35 to -1.98] s, P=.033). The intervention group showed significantly greater improvement on TMT-B at the 12-month follow-up (25.44 [CI, -49.01 to -1.87] s, P=.035). The control group showed significantly greater improvement in total Functional Independence Measure score with a treatment effect of -2.37 (CI, -4.30 to -0.44) points (P=.016) at 12-month follow-up. No significant differences were identified between groups on other outcomes at any time point. CONCLUSIONS: HIIT combined with standard care improved walking distance, balance, and executive function immediately after the intervention compared with standard care only. However, only TMT-B remained significant at the 12-month follow-up.

Post-stroke fatigue: an exploratory study with patients and health professionals to develop a patient-reported outcome measure.

BACKGROUND: Post-stroke fatigue (PSF) is commonly reported and described as disabling by patients recovering from stroke. However, a major challenge is how to accurately diagnose and assess PSF. Therefore, the aim of this study was to explore PSF as it is experienced by stroke survivors and described by health professionals to guide future development of a PSF-specific PROM. METHODS: Individual semi-structured interviews were conducted with stroke survivors experiencing PSF (n = 9) and three focus groups were conducted with health professionals (n = 16). Data were analyzed through inductive content analysis. RESULTS: The analysis revealed four themes illustrating the experience and descriptions of PSF: 1) PSF characteristics, 2) interfering and aggravating factors, 3) management, and 4) PSF awareness, which refers to stroke survivors first becoming aware of PSF after their initial hospital admission. CONCLUSION: This study highlights the complexity and multidimensionality of PSF. The results from this study will guide future development of a PSF-PROM and support its content validity.

ABCD3-I and ABCD2 Scores in a TIA Population with Low Stroke Risk.

OBJECTIVES: We aimed to evaluate the ABCD3-I score and compare it with the ABCD2 score in short- (1 week) and long-term (3 months; 1 year) stroke risk prediction in our post-TIA stroke risk study, MIDNOR TIA. MATERIALS AND METHODS: We performed a prospective, multicenter study in Central Norway from 2012 to 2015, enrolling 577 patients with TIA. In a subset of patients with complete data for both scores (n = 305), we calculated the AUC statistics of the ABCD3-I score and compared this with the ABCD2 score. A telephone follow-up and registry data were used for assessing stroke occurrence. RESULTS: Within 1 week, 3 months, and 1 year, 1.0% (n = 3), 3.3% (n = 10), and 5.2% (n = 16) experienced a stroke, respectively. The AUCs for the ABCD3-I score were 0.72 (95% CI, 0.54 to 0.89) at 1 week, 0.66 (95% CI, 0.53 to 0.80) at 3 months, and 0.68 (0.95% CI, 0.56 to 0.79) at 1 year. The corresponding AUCs for the ABCD2 score were 0.55 (95% CI, 0.24 to 0.86), 0.55 (95% CI, 0.42 to 0.68), and 0.63 (95% CI, 0.50 to 0.76). CONCLUSIONS: The ABCD3-I score had limited value in a short-term prediction of subsequent stroke after TIA and did not reliably discriminate between low- and high-risk patients in a long-term follow-up. The ABCD2 score did not predict subsequent stroke accurately at any time point. Since there is a generally lower stroke risk after TIA during the last years, the benefit of these clinical risk scores and their role in TIA management seems limited. Clinical Trial Registration. This trial is registered with NCT02038725 (retrospectively registered, January 16, 2014).

Tenecteplase in wake-up ischemic stroke trial: Protocol for a randomized-controlled trial.

BACKGROUND: Patients with wake-up ischemic stroke who have evidence of salvageable tissue on advanced imaging can benefit from intravenous thrombolysis. It is not known whether patients who do not fulfil such imaging criteria might benefit from treatment, but studies indicate that treatment based on non-contrast CT criteria may be safe. Tenecteplase has shown promising results in patients with acute ischemic stroke. The aim of the Tenecteplase in Wake-up Ischemic Stroke Trial (TWIST) is to compare the effect of thrombolytic treatment with tenecteplase and standard care versus standard care alone in patients with wake-up ischemic stroke selected by non-contrast CT. METHODS/DESIGN: TWIST is an international, investigator-initiated, multi-centre, prospective, randomized-controlled, open-label, blinded end-point trial of tenecteplase (n = 300) versus standard care (n = 300) in patients who wake up with an acute ischemic stroke and can be treated within 4.5 h upon awakening. Seventy-seven centres in 10 countries (Denmark, Estonia, Finland, Latvia, Lithuania, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom) participate. The primary outcome is the modified Rankin Scale on the ordinal scale (0-6) at three months. DISCUSSION: TWIST aims to determine the effect and safety of thrombolytic treatment with tenecteplase in patients with wake-up ischemic stroke selected by non-contrast CT. TRIAL REGISTRATION: ClinicalTrials.gov NCT03181360. EudraCT Number 2014-000096-80.

Fatigue and activity after stroke. Secondary results from the Life After Stroke study.

OBJECTIVES: The aim of this study was to describe how the prevalence of fatigue changed from the subacute phase to the chronic phase after stroke, and to investigate how activity was associated with fatigue among participants included in the randomized controlled multicentre-study Life After STroke (LAST). METHODS: The present study represents secondary analysis based on data from the LAST study. One-hundred-and-forty-five patients with mild and moderate stroke (mean (SD) age: 71.5 (10.5) years, 57.2% males) recruited from St. Olav's University Hospital were included. Fatigue was assessed by the Fatigue Severity Scale (FSS-7) at inclusion, 3 months after stroke, and at follow-up 18 months later. activPAL was used to measure activity at follow-up. RESULTS: A total of 46 (31.7%) participants reported fatigue at inclusion and 43 (29.7%) at follow-up (p = .736). In the univariable regression analysis, sedentary behaviour, walking and sedentary bouts were significantly associated with fatigue (p ≤ .015), whereas only time spent walking was significantly associated with fatigue in the multivariable regression analysis (p = .017). CONCLUSIONS: The present study showed that fatigue is a common symptom after stroke and that the prevalence of fatigue remained unchanged from the subacute to the chronic phase. The study also showed that increased time spent walking was strongly related to lower fatigue, while no such associations were found between the other activity categories and fatigue.

Factors contributing to post-stroke health care utilization and costs, secondary results from the life after stroke (LAST) study.

BACKGROUND: The result from the Life After Stroke (LAST) study showed that an 18-month follow up program as part of the primary health care, did not improve maintenance of motor function for stroke survivors. In this study we evaluated whether the follow-up program could lead to a reduction in the use of health care compared to standard care. Furthermore, we analyse to what extent differences in health care costs for stroke patients could be explained by individual need factors (such as physical disability, cognitive impairment, age, gender and marital status), and we tested whether a generic health related quality of life (HRQoL) is able to predict the utilisation of health care services for patients post-stroke as well as more disease specific indexes. METHODS: The Last study was a multicentre, pragmatic, single-blinded, randomized controlled trial. Adults (age ≥ 18 years) with first-ever or recurrent stroke, community dwelling, with modified Rankin Scale < 5. The study included 380 persons recruited 10 to 16 weeks post-stroke, randomly assigned to individualized coaching for 18 months (n = 186) or standard care (n = 194). Individual need was measured by the Motor assessment scale (MAS), Barthel Index, Hospital Anxiety and Depression Scale (HADS), modified Rankin Scale (mRS) and Gait speed. HRQoL was measured by EQ-5D-5 L. Health care costs were estimated for each person based on individual information of health care use. Multivariate regression analysis was used to analyse cost differences between the groups and the relationship between individual costs and determinants of health care utilisation. RESULTS: There were higher total costs in the intervention group. MAS, Gait speed, HADS and mRS were significant identifiers of costs post-stroke, as was EQ-5D-5 L. CONCLUSION: Long term, regular individualized coaching did not reduce health care costs compared to standard care. We found that MAS, Gait speed, HADS and mRS were significant predictors for future health care use. The generic EQ-5D-5 L performed equally well as the more detailed battery of outcome measures, suggesting that HRQoL measures may be a simple and efficient way of identifying patients in need of health care after stroke and targeting groups for interventions. TRIAL REGISTRATION: https://www.clinicaltrials.govNCT01467206. The trial was retrospectively registered after the first 6 participants were included.

Effects of High-Intensity Interval Training After Stroke (the HIIT-Stroke Study): A Multicenter Randomized Controlled Trial.

OBJECTIVE: To examine if 8 weeks of high-intensity interval training (HIIT) in addition to standard care would increase and maintain peak oxygen uptake (Vo2peak) more than standard care alone in patients with stroke. DESIGN: This was a single-blind, multicenter, parallel group, randomized controlled trial. SETTING: Specialized rehabilitation units at 3 Norwegian hospitals. PARTICIPANTS: Participants (N=70), 3 months to 5 years after first-ever stroke, were randomly assigned to the intervention group (n=36) or the control group (n=34); 42% were women, mean age was 57.6±9.3 years, mean time post stroke was 26.4±14.5 months. INTERVENTION: The intervention was 8 weeks: 3 times a week with HIIT treadmill training with work periods of 4 × 4 minutes at 85%-95% of peak heart rate interspersed with 3 minutes of active recovery at 50%-70% of peak heart rate. The control group received standard care according to national guidelines. OUTCOMES: The primary outcome, analyzed by intention-to-treat, was Vo2peak measured as liters per minute 12 months after inclusion. Secondary outcome measures were blood pressure and blood profile. RESULTS: Mean baseline Vo2peak was 2.63±1.08 L·min-1 vs 2.87±0.71 L·min-1, while at 12 months Vo2peak was 2.70±1.00 L·min-1 vs 2.67±0.76 L·min-1 (P=.068) in the intervention and control groups, respectively. There was a significant and greater improvement in the intervention group compared with the control group at 12 months in 3 of 6 secondary outcomes from the peak test but no significant differences for blood pressure or blood profile. CONCLUSIONS: The HIIT intervention, which was well-tolerated in this sample of well-functioning survivors of stroke, was not superior to standard care in improving and maintaining Vo2peak at the 12-month follow-up. However, secondary results from the peak test showed a significant improvement from before to immediately after the intervention.

Stroke in Norway 2015­16 ­ treatment and outcomes. / Hjerneslag i Norge 2015­16 ­ behandling og resultater.

BACKGROUND: Treatment of stroke in Norway is decentralised; patients with stroke are treated at 50 different hospitals. We have surveyed the treatment of stroke in these hospitals and collated this with data from the Norwegian Stroke Registry. We wished to investigate whether there was any variation in treatment interventions and treatment outcomes between university hospitals and local hospitals. MATERIAL AND METHOD: A questionnaire survey among all Norwegian hospitals examined treatment interventions and resource availability. Data from the Norwegian Stroke Registry in 2015-2016 (n = 17 183) were used to compare patient characteristics and treatment outcomes for patients in university hospitals (n = 5 312) and local hospitals (n = 11 871). Treatment quality was measured using the quality indicators in the Norwegian Stroke Registry. RESULTS: The median age in the university hospitals was 75 years (interquartile range 65-83), and 44.1% of the patients were women. The median age in the local hospitals was 76 years (interquartile range 67-85); 46.7% women. Goal achievement on five out of ten quality indicators was high; for example, more than 90% of the patients were treated in a stroke unit, irrespective of the type of hospital. At the university hospitals, 1 038 (19.0%) of patients received thrombolytic therapy, compared to 1 612 (17.2%) in the local hospitals. Adjusted for age and level of consciousness, the probability of being self-reliant three months after the stroke was higher in local hospitals (OR 1.15, CI 1.04-1.27). INTERPRETATION: The decentralised stroke treatment in Norway accomplishes high and moderate goal achievement on the Norwegian Stroke Registry's quality indicators. The quality of treatment in local hospitals appears to be equally good or better than that provided in university hospitals.