A Machine Learning Approach to Predict Post-stroke Fatigue. The Nor-COAST study.

OBJECTIVE: This study aimed to predict fatigue 18 months post-stroke by utilizing comprehensive data from the acute and sub-acute phases after stroke in a machine-learning set-up. DESIGN: A prospective multicenter cohort-study with 18-month follow-up. SETTING: Outpatient clinics at 3 university hospitals and 2 local hospitals. PARTICIPANTS: 474 participants with the diagnosis of acute stroke (mean ± SD age; 70.5 (11.3), 59% male; N=474). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The primary outcome, fatigue at 18 months, was assessed using the Fatigue Severity Scale (FSS-7). FSS-7≥5 was defined as fatigue. In total, 45 prediction variables were collected, at initial hospital-stay and 3-month post-stroke. RESULTS: The best performing model, random forest, predicted 69% of all subjects with fatigue correctly with a sensitivity of 0.69 (95% CI: 0.50, 0.86), a specificity of 0.74 (95% CI: 0.66, 0.83), and an Area under the Receiver Operator Characteristic curve of 0.79 (95% CI: 0.69, 0.87) in new unseen data. The proportion of subjects predicted to suffer from fatigue, who truly suffered from fatigue at 18-months was estimated to 0.41 (95% CI: 0.26, 0.57). The proportion of subjects predicted to be free from fatigue who truly did not have fatigue at 18-months was estimated to 0.90 (95% CI: 0.83, 0.96). CONCLUSIONS: Our findings indicate that the model has satisfactory ability to predict fatigue in the chronic phase post-stroke and may be applicable in clinical settings.

Changes in sedentary behavior in the chronic phase following stroke.

BACKGROUND: Sedentary behavior increases risk for cardiovascular diseases. Little is known about sedentary behavior through the chronic phase after stroke. We aimed to describe how long and short bouts of sedentary behavior changed over the first three years after stroke and if cognition at baseline was an independent risk factor for sedentary behavior. METHODS: This is a sub-study of the Norwegian cognitive impairment after stroke (Nor-COAST) study, a multicenter study recruiting patients with acute stroke. Sedentary behavior was monitored with a thigh-worn sensor (ActivPal3®), at three-, 18- and 36-months post stroke. Stroke severity was assessed by National Institutes of Health Stroke Scale (NIHSS) and cognition by Montreal cognitive assessment (MoCA). Mixed model analysis with mean number of sedentary minutes accumulated daily as the dependent variable was repeated for all four zones (<30min, 30-60min, 60-90min, >90min) and for total sedentary time. RESULTS: The number of included participants was 528 (mean age 71.4, NIHSS on day 1, 2.7). The total amount of sedentary time accumulated between 08.00-22.00 increased significantly from about 9.8 hours at three months to 10.1 hours at 36 months post stroke (p=0.002). Patient characteristics associated with prolonged duration of the sedentary bouts and sedentary time were age, high BMI, comorbidities, and impaired physical function. No significant associations between MoCA score and sedentary time were found. CONCLUSION: The participants became increasingly sedentary and had fewer breaks in sedentary time from three to 36 months after stroke. Baseline cognition was not related to later sedentary behavior.

Plasma Inflammatory Biomarkers Are Associated With Poststroke Cognitive Impairment: The Nor-COAST Study.

BACKGROUND: Inflammation is proposed to be involved in the pathogenesis of poststroke cognitive impairment. The aim of this study was to investigate associations between concentrations of systemic inflammatory biomarkers after ischemic stroke and poststroke cognitive impairment. METHODS: The Nor-COAST study (Norwegian Cognitive Impairment After Stroke) is a prospective observational multicenter cohort study, including patients hospitalized with acute stroke between 2015 and 2017. Inflammatory biomarkers, including the TCC (terminal C5b-9 complement complex) and 20 cytokines, were analyzed in plasma, collected at baseline, 3-, and 18 months poststroke, using ELISA and a multiplex assay. Global cognitive outcome was assessed with the Montreal Cognitive Assessment (MoCA) scale. We investigated the associations between plasma inflammatory biomarkers at baseline and MoCA score at 3-, 18-, and 36-month follow-ups; the associations between inflammatory biomarkers at 3 months and MoCA score at 18- and 36-month follow-ups; and the association between these biomarkers at 18 months and MoCA score at 36-month follow-up. We used mixed linear regression adjusted for age and sex. RESULTS: We included 455 survivors of ischemic stroke. Higher concentrations of 7 baseline biomarkers were significantly associated with lower MoCA score at 36 months; TCC, IL (interleukin)-6, and MIP (macrophage inflammatory protein)-1α were associated with MoCA at 3, 18, and 36 months (P<0.01). No biomarker at 3 months was significantly associated with MoCA score at either 18 or 36 months, whereas higher concentrations of 3 biomarkers at 18 months were associated with lower MoCA score at 36 months (P<0.01). TCC at baseline and IL-6 and MIP-1α measured both at baseline and 18 months were particularly strongly associated with MoCA (P<0.01). CONCLUSIONS: Higher concentrations of plasma inflammatory biomarkers were associated with lower MoCA scores up to 36 months poststroke. This was most pronounced for inflammatory biomarkers measured in the acute phase following stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02650531.

Reasons and predictors of non-thrombolysis in patients with acute ischemic stroke admitted within 4.5 h.

OBJECTIVES: Thrombolytic treatment in acute ischemic stroke (AIS) reduces stroke-related disability. Nearly 40% of all patients with AIS (<4.5 h) receive thrombolysis, but there is a large variation in the use between hospitals. Little is known about reasons and predictors for not giving thrombolytic treatment. Therefore, we aimed to investigate reasons for non-thrombolysis in patients admitted within 4.5 h. METHODS: All patients with AIS (<4.5 h) admitted to Akershus University Hospital, Norway, between January 2015 and December 2017 were examined. Patient characteristics and reasons for not giving thrombolysis were registered. Descriptive statistics and logistic regression analyses were performed. RESULTS: Of 535 patients admitted with AIS (<4.5 h), 250 (47%) did not receive thrombolysis and of these only 26% had an absolute contraindication to treatment. Among the 74% with relative contraindications, the most common reasons given were mild and improving symptoms. Previous stroke (OR 3.32, 95%CI 1.99-5.52), arriving between 3 h and 4.5 h after onset (OR 7.76, 95%CI 3.73-16.11) or having mild symptoms (OR 2.33, 95%CI 1.56-3.49) were all significant predictors of not receiving thrombolytic treatment in the multivariable logistic regression model. CONCLUSION: A large proportion of patients with AIS do not receive thrombolysis. This study highlights up-to-date findings that arriving late in the time window, mild symptoms, and previous stroke are strong predictors of non-treatment. It is uncertain whether there is an underuse of thrombolysis in AIS. Increasing the utility of thrombolysis in the 4.5 h time window must be weighed against possible harms.

Physical Performance and Cognition as Predictors of Instrumental Activities of Daily Living After Stroke: A Prospective Multicenter Cohort Study.

OBJECTIVE: To investigate whether cognition and physical performance, both separately and combined, 3 months post stroke predict change in instrumental activities of daily living (IADL) up to 18 months and whether different paths of IADL could be identified by different scenarios, defined by combinations of high and low scores on physical performance and cognition. DESIGN: The study is part of the Norwegian Cognitive Impairment After Stroke study, a prospective multicenter cohort study including patients with acute stroke. SETTING: Stroke outpatient clinics at 3 university hospitals and 2 local hospitals. PARTICIPANTS: Adult survivors of stroke (N=544) were followed up at 3 and 18 months after stroke. Participants' mean ± SD age was 72.6±11.8 years, and 235 (43.2 %) were female. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The primary outcome was IADL as measured by Nottingham Extended Activities of Daily Living. At 3 months, Short Physical Performance Battery (SPPB) and Montreal Cognitive Assessment (MoCA) were used to assess physical performance and cognition, respectively. RESULTS: Mixed-effects linear regression analyses showed that the regression coefficient (95% CI) for the interaction with time was significant for MoCA, 0.238 (CI, 0.030-0.445; P=.025) but not for SPPB. The model combining SPPB and MoCA was significantly better than separate models (likelihood ratio P<.001). Overall, there was no improvement in IADL over time. A combination of SPPB and MoCA score in the upper quartile at 3 months was associated with improved IADL of 1.396 (CI, 0.252-2.540; P=.017) over time. CONCLUSIONS: Combining measures of cognition and physical performance gave the best prediction of change in IADL. Function at 3 months seems to be predictive for long-term IADL status, which highlights the importance of targeted rehabilitation in the early and subacute phases after stroke.

Association between in-hospital frailty and health-related quality of life after stroke: the Nor-COAST study.

BACKGROUND: Stroke survivors are known to have poorer health-related quality of life (HRQoL) than the general population, but less is known about characteristics associated with HRQoL decreasing through time following a stroke. This study aims to examine how in-hospital frailty is related to HRQoL from 3 to 18 months post stroke. METHOD: Six hundred twenty-five participants hospitalised with stroke were included and followed up at 3 and/or 18 months post stroke. Stroke severity was assessed the day after admission with the National Institutes of Health Stroke Scale (NIHSS). A modified Fried phenotype was used to assess in-hospital frailty; measures of exhaustion, physical activity, and weight loss were based on pre-stroke status, while gait speed and grip strength were measured during hospital stay. HRQoL at 3- and 18-months follow-up were assessed using the five-level version of the EuroQol five-dimensional descriptive system (EQ-5D-5L) and the EuroQol visual analogue scale (EQ-5D VAS). We conducted linear mixed effect regression analyses unadjusted and adjusted for sex, age, and stroke severity to investigate the association between in-hospital frailty and post-stroke HRQoL. RESULTS: Mean (SD) age was 71.7 years (11.6); mean NIHSS score was 2.8 (4.0), and 263 (42.1%) were female. Frailty prevalence was 10.4%, while 58.6% were pre-frail. The robust group had EQ-5D-5L index and EQ-5D VAS scores at 3 and 18 months comparable to the general population. Also at 3 and 18 months, the pre-frail and frail groups had significantly lower EQ-5D-5L indices than the robust group (p <  0.001), and the frail group showed a larger decrease from 3 to 18 months in the EQ-5D-5L index score compared to the robust group (- 0.056; 95% CI - 0.104 to - 0.009; p = 0.021). There were no significant differences in change in EQ-5D VAS scores between the groups. CONCLUSION: This study on participants mainly diagnosed with mild strokes suggests that robust stroke patients have fairly good and stable post-stroke HRQoL, while post-stroke HRQoL is impaired and continues to deteriorate among patients with in-hospital frailty. This emphasises the importance of a greater focus on frailty in stroke units. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02650531 ).

Investigating novel biomarkers of immune activation and modulation in the context of sedentary behaviour: a multicentre prospective ischemic stroke cohort study.

BACKGROUND: Sedentary behaviour is associated with disease, but the molecular mechanisms are not understood. Valid biomarkers with predictive and explanatory properties are required. Therefore, we have investigated traditional and novel biomarkers of inflammation and immune modulation and their association to objectively measured sedentary behaviour in an ischemic stroke population. METHODS: Patients admitted to hospital with acute ischemic stroke were included in the multicentre Norwegian Cognitive Impairment After Stroke (Nor-COAST) study (n = 815). For this sub-study (n = 257), sedentary behaviour was registered 3 months after stroke using position transition data from the body-worn sensor, ActivPal®. Blood samples were analysed for high sensitive C-reactive protein (hsCRP), the cytokines interleukin-6 (IL-6) and 10 (IL-10), neopterin, tryptophan (Trp), kynurenine (kyn), kynurenic acid (KA), and three B6 vitamers, pyridoxal 5'-phosphate (PLP), pyridoxal (PL), and pyridoxic acid (PA). The kynurenine/tryptophan ratio (KTR) and the pyridoxic acid ratio index (PAr = PA: PL + PLP) were calculated. RESULTS: Of the 815 patients included in the main study, 700 attended the three-month follow-up, and 257 fulfilled the inclusion criteria for this study. Sedentary time was significantly associated with levels of hsCRP, IL-6, neopterin, PAr-index, and KA adjusted for age, sex, waist circumference, and creatinine. In a fully adjusted model including all the significant biomarkers except hsCRP (because of missing values), sedentary time was independently positively associated with the PAr-index and negatively with KA. We did not find an association between sedentary behaviour, IL-10, and KTR. CONCLUSIONS: The PAr-index is known to capture several modes of inflammation and has previously shown predictive abilities for future stroke. This novel result indicates that the PAr-index could be a useful biomarker in future studies on sedentary behaviour and disease progression. KA is an important modulator of inflammation, and this finding opens new and exciting pathways to understand the hazards of sedentary behaviour. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov ( NCT02650531 ). First posted 08/01/2016.

Neopterin and kynurenic acid as predictors of stroke recurrence and mortality: a multicentre prospective cohort study on biomarkers of inflammation measured three months after ischemic stroke.

BACKGROUND: Chronic low-grade inflammation is associated with both ischemic stroke and sedentary behaviour. The aim of this study was to investigate the predictive abilities of biomarkers of inflammation and immune modulation associated with sedentary behaviour for ischemic stroke recurrence and mortality in a stroke population. METHODS: Patients admitted to hospital for acute stroke were recruited to the prospective multicentre cohort study, the Norwegian Cognitive Impairment After Stroke (Nor-COAST) study, from May 2015 until March 2017. Patients with ischemic stroke, blood samples available from the three-month follow-up, and no stroke recurrence before the three-month follow-up were included. Serum was analysed for C-reactive protein (CRP) with high-sensitive technique, and plasma for interleukin-6 (IL-6), neopterin, pyridoxic acid ratio index (PAr-index: 4-pyridoxic acid: [pyrioxal+pyridoxal-5'-phosphate]) and kynurenic acid (KA). Ischemic stroke recurrence and death were identified by the Norwegian Stroke Registry and the Cause of Death Registry until 31 December 2018. RESULTS: The study included 354 patients, 57% male, mean age 73 (SD 11) years, mean observation time 2.5 (SD 0.6) years, and median National Institute of Health Stroke Scale of 0 (IQR 1) at three months. CRP was associated with mortality (HR 1.40, CI 1.01, 1.96, p = 0.046), and neopterin was associated with the combined endpoint (recurrent ischemic stroke or death) (HR 1.52, CI 1.06, 2.20, p = 0.023), adjusted for age, sex, prior cerebrovascular disease, modified Rankin Scale, and creatinine. When adding neopterin and KA to the same model, KA was negatively associated (HR 0.57, CI 0.33, 0.97, p = 0.038), and neopterin was positively associated (HR 1.61, CI 1.02, 2.54, p = 0.040) with mortality. Patients with cardioembolic stroke at baseline had higher levels of inflammation at three months. CONCLUSION: Neopterin might be a valuable prognostic biomarker in stroke patients. The use of KA as a measure of anti-inflammatory capacity should be investigated further. TRIAL REGISTRATION: The study was registered at Clinicaltrials.gov ( NCT02650531 ). First posted on 08/01/2016.

An Exploration of Sedentary Behavior Patterns in Community-Dwelling People With Stroke: A Cluster-Based Analysis.

BACKGROUND AND PURPOSE: Long periods of daily sedentary time, particularly accumulated in long uninterrupted bouts, are a risk factor for cardiovascular disease. People with stroke are at high risk of recurrent events and prolonged sedentary time may increase this risk. We aimed to explore how people with stroke distribute their periods of sedentary behavior, which factors influence this distribution, and whether sedentary behavior clusters can be distinguished? METHODS: This was a secondary analysis of original accelerometry data from adults with stroke living in the community. We conducted data-driven clustering analyses to identify unique accumulation patterns of sedentary time across participants, followed by multinomial logistical regression to determine the association between the clusters, and the total amount of sedentary time, age, gender, body mass index (BMI), walking speed, and wake time. RESULTS: Participants in the highest quartile of total sedentary time accumulated a significantly higher proportion of their sedentary time in prolonged bouts (P < 0.001). Six unique accumulation patterns were identified, all of which were characterized by high sedentary time. Total sedentary time, age, gender, BMI, and walking speed were significantly associated with the probability of a person being in a specific accumulation pattern cluster, P < 0.001 - P = 0.002. DISCUSSION AND CONCLUSIONS: Although unique accumulation patterns were identified, there is not just one accumulation pattern for high sedentary time. This suggests that interventions to reduce sedentary time must be individually tailored.Video Abstract available for more insight from the authors (see the Video Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A343).

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.

Pre-stroke cognitive impairment is associated with vascular imaging pathology: a prospective observational study.

BACKGROUND: Chronic brain pathology and pre-stroke cognitive impairment (PCI) is predictive of post-stroke dementia. The aim of the current study was to measure pre-stroke neurodegenerative and vascular disease burden found on brain MRI and to assess the association between pre-stroke imaging pathology and PCI, whilst also looking for potential sex differences. METHODS: This prospective brain MRI cohort is part of the multicentre Norwegian cognitive impairment after stroke (Nor-COAST) study. Patients hospitalized with acute ischemic or hemorrhagic stroke were included from five participating stroke units. Visual rating scales were used to categorize baseline MRIs (N = 410) as vascular, neurodegenerative, mixed, or normal, based on the presence of pathological imaging findings. Pre-stroke cognition was assessed by interviews of patients or caregivers using the Global Deterioration Scale (GDS). Stroke severity was assessed with the National Institute of Health Stroke Scale (NIHSS). Univariate and multiple logistic regression analyses were performed to investigate the association between imaging markers, PCI, and sex. RESULTS: Patients' (N = 410) mean (SD) age was 73.6 (±11) years; 182 (44%) participants were female, the mean (SD) NIHSS at admittance was 4.1 (±5). In 68% of the participants, at least one pathological imaging marker was found. Medial temporal lobe atrophy (MTA) was present in 30% of patients, white matter hyperintensities (WMH) in 38% of patients and lacunes in 35% of patients. PCI was found in 30% of the patients. PCI was associated with cerebrovascular pathology (OR 2.5; CI = 1.4 to 4.5, p = 0.001) and mixed pathology (OR 3.4; CI = 1.9 to 6.1, p = 0.001) but was not associated with neurodegeneration (OR 1.0; CI = 0.5 to 2.2; p = 0.973). Pathological MRI markers, including MTA and lacunes, were more prevalent among men, as was a history of clinical stroke prior to the index stroke. The OR of PCI for women was not significantly increased (OR 1.2; CI = 0.8 to 1.9; p = 0.3). CONCLUSIONS: Pre-stroke chronic brain pathology is common in stroke patients, with a higher prevalence in men. Vascular pathology and mixed pathology are associated with PCI. There were no significant sex differences for the risk of PCI. TRIAL REGISTRATION: NCT02650531 , date of registration: 08.01.2016.

Associations between post-stroke motor and cognitive function: a cross-sectional study.

BACKGROUND: Motor and cognitive impairments are frequently observed following stroke, but are often managed as distinct entities, and there is little evidence regarding how they are related. The aim of this study was to describe the prevalence of concurrent motor and cognitive impairments 3 months after stroke and to examine how motor performance was associated with memory, executive function and global cognition. METHODS: The Norwegian Cognitive Impairment After Stroke (Nor-COAST) study is a prospective multicentre cohort study including patients hospitalized with acute stroke between May 2015 and March 2017. The National Institutes of Health Stroke Scale (NIHSS) was used to measure stroke severity at admission. Level of disability was assessed by the Modified Rankin Scale (mRS). Motor and cognitive functions were assessed 3 months post-stroke using the Montreal Cognitive Assessment (MoCA), Trail Making Test Part B (TMT-B), 10-Word List Recall (10WLR), Short Physical Performance Battery (SPPB), dual-task cost (DTC) and grip strength (Jamar®). Cut-offs were set according to current recommendations. Associations were examined using linear regression with cognitive tests as dependent variables and motor domains as covariates, adjusted for age, sex, education and stroke severity. RESULTS: Of 567 participants included, 242 (43%) were women, mean (SD) age was 72.2 (11.7) years, 416 (75%) had an NIHSS score ≤ 4 and 475 (84%) had an mRS score of ≤2. Prevalence of concurrent motor and cognitive impairment ranged from 9.5% for DTC and 10WLR to 22.9% for grip strength and TMT-B. SPPB was associated with MoCA (regression coefficient B = 0.465, 95%CI [0.352, 0.578]), TMT-B (B = -9.494, 95%CI [- 11.726, - 7.925]) and 10WLR (B = 0.132, 95%CI [0.054, 0.211]). Grip strength was associated with MoCA (B = 0.075, 95%CI [0.039, 0.112]), TMT-B (B = -1.972, 95%CI [- 2.672, - 1.272]) and 10WLR (B = 0.041, 95%CI [0.016, 0.066]). Higher DTC was associated with more time needed to complete TMT-B (B = 0.475, 95%CI [0.075, 0.875]) but not with MoCA or 10WLR. CONCLUSION: Three months after suffering mainly minor strokes, 30-40% of participants had motor or cognitive impairments, while 20% had concurrent impairments. Motor performance was associated with memory, executive function and global cognition. The identification of concurrent impairments could be relevant for preventing functional decline. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02650531 .

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.

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.

Correction to: Time spent lying, sitting, and upright during hospitalization after stroke: a prospective observation study.

The original version of this article.

Associations Between Adherence to the Physical Activity and Exercise Program Applied in the LAST Study and Functional Recovery After Stroke.

OBJECTIVE: To investigate the associations between participants' adherence to a physical activity and exercise program after stroke and functional recovery 18 months after inclusion. DESIGN: Secondary analyses of the intervention arm in the multisite randomized controlled trial Life After Stroke (LAST). SETTING: Primary health care services in 3 Norwegian municipalities. PARTICIPANTS: Of the participants enrolled (N=380), 186 (48.9%) were randomized to the intervention. The study sample comprised community dwelling individuals included 3 months after stroke, with mean age of 71.7 ± 11.9 years and 82 (44.1%) women. According to the National Institutes of Health Stroke Scale, 97.3% were diagnosed as having mild (National Institutes of Health Stroke Scale<8) and 2.7% with moderate (8-16 on the National Institutes of Health Stroke Scale) stroke. INTERVENTION: Monthly coaching by physiotherapists encouraging participants to adhere to 30 minutes of daily physical activity and 45-60 minutes of weekly exercise. MAIN OUTCOME MEASURES: The primary outcome was Motor Assessment Scale (MAS). Secondary outcome measures were 6-minute walk test, Timed Up and Go (TUG), Berg Balance Scale (BBS), and the physical domains of the Stroke Impact Scale (SIS). Adherence was assessed by combining participants' training diaries and physiotherapists' reports. RESULTS: The relationship between adherence and functional recovery was analyzed with simple and multiple linear regression models. Adjusted for age, sex, dependency, and cognition, results showed statistically significant associations between adherence and functional outcomes after 18 months, as measured by MAS, TUG, BBS, and SIS (P≤.026). CONCLUSIONS: Increased adherence to physical activity and exercise was associated with improved functional recovery after mild to moderate stroke. This emphasizes the importance of developing adherence-enhancing interventions. Dose-response studies are recommended for future research.

A physical activity program is no more effective than standard care at maintaining upper limb activity in community-dwelling people with stroke: secondary outcomes from a randomized trial.

OBJECTIVE: To evaluate whether an 18-month, physical activity coaching program is more effective than standard care in terms of upper-limb activity. DESIGN: A prospective, randomized controlled trial. SETTING: Three municipalities in Norway. POPULATION: A total of 380 persons with stroke. INTERVENTION: The intervention group received follow-up visits and coaching on physical activity and exercise each month for 18 months after inclusion, by a physiotherapist. The control group received standard care. MAIN MEASURES: The primary outcome, in this secondary analysis, was Motor Assessment Scale items 6, 7, and 8. Secondary outcomes were National Institute of Health Stroke Scale item 5, the Stroke Impact Scale domain 7, and the Modified Ashworth Scale in flexion/extension of the elbow. RESULTS: In total, 380 persons with stroke were recruited, with mean (SD) age 72 (11) years, and baseline scores total National Institute of Health Stroke Scale was 1.4 (2.2)/1.6 (2.4) and Motor Assessment Scale items 6, 7 and 8 in the intervention/control group was 5.5 (1.2)/5.5 (1.2), 5.4 (1.4)/5.4 (1.3), and 3.6 (2)/3.5 (2), respectively. There was no significant difference between groups in terms of upper limb function in any of the Motor Assessment Scale items. In this population with minor stroke, upper-limb activity was good at three months post-stroke (74% of the maximum) and remained good 18 months later (77% of maximum). CONCLUSION: After intervention, there was no difference between the groups in terms of upper-limb activity.

Efficacy and Safety of Individualized Coaching After Stroke: the LAST Study (Life After Stroke): A Pragmatic Randomized Controlled Trial.

BACKGROUND AND PURPOSE: The evidence for interventions to prevent functional decline in the long term after stroke is lacking. The aim of this trial was to evaluate the efficacy and safety of an 18-month follow-up program of individualized regular coaching on physical activity and exercise. METHODS: This 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, and no serious comorbidities were included 10 to 16 weeks poststroke. The intervention group received individualized regular coaching on physical activity and exercise every month for 18 consecutive months. The control group received standard care. Primary outcome was the Motor Assessment Scale at end of intervention (18-month follow-up). Secondary measures were Barthel index, modified Rankin Scale, item 14 from Berg Balance Scale, Timed Up and Go test, gait speed, 6-minute walk test, and Stroke Impact Scale. Other outcomes were adverse events and compliance to the intervention assessed by training diaries and the International Physical Activity Questionnaire. RESULTS: Three hundred and eighty consenting participants were randomly assigned to individualized coaching (n=186) or standard care (n=194). The mean estimated difference on Motor Assessment Scale in favor of control group was -0.70 points (95% confidence interval, -2.80, 1.39), P=0.512. There were no differences between the groups on Barthel index, modified Rankin Scale, or Berg Balance Scale. The frequency of adverse events was low in both groups. Results from International Physical Activity Questionnaire and training diaries showed increased activity levels but low intensity of the exercise in the intervention group. CONCLUSIONS: The regular individualized coaching did not improve maintenance of motor function or the secondary outcomes compared with standard care. The intervention should be regarded as safe. Despite the neutral results, the health costs related to the intervention should be investigated. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01467206.

Time spent lying, sitting, and upright during hospitalization after stroke: a prospective observation study.

BACKGROUND: Early mobilization has been an important part of acute stroke unit treatment. However, early and intense mobilization within the first 24 h post stroke may cause an unfavorable outcome. Recently, objective measurements using body-worn sensors have been applied, enabling continuous monitoring of physical activity in the hospital setting. This study aimed to use body-worn sensors to quantify the amount of physical activity and how activity levels changed over time during hospitalization in patients with acute stroke. We also wanted to investigate which factors were associated with upright and sitting activity. METHODS: This was a prospective study including patients admitted to hospital within seven days after onset of stroke. Physical activity was measured by two sensors (ActivPALs from PAL Technologies Ltd., Glasgow, UK), one attached on sternum and one on the thigh of the unaffected side, monitoring continuously from inclusion until discharge. Data were processed in Matlab R 2015B and provided information about daily time in lying, sitting, and upright positions, and daily average duration of sitting and upright bouts. A linear mixed model was used to analyze changes over time. RESULTS: 58 patients were included (31 women, mean (SD) age; 75.1 (12.0)). Patients were hospitalized for 12.1 (7.6) days and had a mean score on the National Institute of Health Stroke Scale of 6.2 (5.5) points. Time spent sitting and time spent upright increased per day during hospitalization by 22.10 min (95% Confidence interval (CI): 14.96, 29.24) and 3.75 min (95% CI: 1.70, 5.80) respectively. Increased time upright was associated with improved Modified Rankin Scale scores (- 38.09 min, 95% CI: -61.88, - 14.29) and higher Short Physical Performance Battery scores (6.97 min, 95% CI: 1.99, 11.95), while prolonged bouts of sitting were associated with more severe stroke (4.50 min, 95% CI: 0.80, 8.19), and older age (1.72 min, 95% CI: 0.20, 3.26). CONCLUSIONS: Patients increased their daily time spent sitting and upright during the initial hospital stay after stroke. Prolonged bouts of sitting were associated with older age and more severe strokes. Hence future research should investigate the benefit of interventions aimed at breaking up sitting time after stroke.

The Norwegian Cognitive impairment after stroke study (Nor-COAST): study protocol of a multicentre, prospective cohort study.

BACKGROUND: Early and late onset post-stroke cognitive impairment (PCI) contributes substantially to disability following stroke, and is a high priority within stroke research. The aetiology for PCI is complex and related to the stroke itself, brain resilience, comorbid brain diseases, prestroke vulnerability and complications during the hospital stay. The aim of the Norwegian Cognitive Impairment After Stroke study (Nor-COAST) is to quantify and measure levels of cognitive impairments in a general Norwegian stroke population and to identify biological and clinical markers associated with prognosis for cognitive disorders following incident stroke. The study will be organised within five work packages: 1) Incidence and trajectories 2) Pathological mechanisms 3) Development of a risk score 4) Impact of physical activity and 5) Adherence to secondary prevention. METHODS: Nor-COAST is an ongoing multicentre (five participating hospitals), prospective, cohort study with consecutive inclusion during the acute phase and with follow-up at three and 18 months, and at three years. Inclusion criteria are stroke defined according to the WHO criteria. During the recruitment period from 18.05.2015 to 31.03.2017, 816 participants have been included. Cognitive impairment will be classified according to the DSM-5 criteria using a consensus group. Cognitive function is assessed by a standardised neuropsychological test battery, the Montreal Cognitive Assessment, Trail making A and B, ten-word immediate and delayed recall test, the Controlled Oral Word Association, Global Deterioration Scale and proxy based information by and the Ascertain Dementia 8 item informant questionnaire. Biomarkers include magnetic resonance imaging, routine blood samples and bio-banking. Clinical assessments include characteristics of the stroke, comorbidity, delirium, frailty and tests for cognitive and physical function, sensor based activity monitoring and adherence to secondary prophylaxis. DISCUSSION: Nor-COAST is the first Norwegian multicentre study to quantify burden of PCI that will provide reliable estimates in a general stroke population. A multidisciplinary approach aiming to identify biomarkers and clinical markers of overall prognosis will add new knowledge about risk profiles, including pre-stroke vulnerability and modifiable factors such as physical activity and secondary prophylaxis of relevance for clinical practice and later intervention studies. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02650531 . Retrospectively registered January 8, 2016. First participant included May 18, 2015.