Participation in daily life activities at two months after stroke predicts long-term health-related quality of life.

BACKGROUND: After stroke, many patients experience problems with participation in daily activities. Improving participation is the main goal in stroke rehabilitation. However, the longitudinal relationship between participation and health-related quality of life (HRQoL) remains unclear. OBJECTIVES: This study aimed to examine (1) the predictive value of participation at two months on long-term HRQoL and (2) the longitudinal relationship between participation and HRQoL. METHODS: In this multicenter, prospective cohort study, patients were assessed at two and 12 months after stroke. Participation was measured with the Restriction subscale of the Utrecht Scale for Evaluation of Rehabilitation - Participation. HRQoL was assessed with the three-level version of the EuroQoL five dimensions questionnaire index score. RESULTS: This study included 291 patients. Mean age was 66.6 ± 12.4 years, 64.3% were male and mean National Institutes of Health Stroke Scale (NIHSS) was 2.5 ± 2.9. Multivariable linear regression, adjusted for demographic characteristics, stroke characteristics, physical and cognitive impairment, showed that a higher level of participation at two months correlated with a higher HRQoL at one year (B = .004; 95% CI =.002-.005). Patients whose participation improved had a greater increase in HRQoL, compared to patients without improvement (0.080 ± .21 versus -.054 ± .21; p < .001). CONCLUSIONS: The level of participation at two months post-stroke predicts HRQoL at one year. Improvement in participation during the first year after stroke is associated with improvement in HRQoL. We recommend including the assessment of participation in daily activities at follow-up visits.

Effects of a 1 year aerobic and strength training on cognitive functioning after transient ischemic attack or minor stroke: A randomized controlled trial.

OBJECTIVES: Patients who have recently suffered a transient ischemic attack (TIA) or minor ischemic stroke are at increased risk of cognitive impairment. In the present study, we aimed to investigate the effect of a 1-year exercise intervention on cognitive functioning up to 2 years post intervention. MATERIAL AND METHODS: We conducted a single-blind randomized controlled trial to investigate the effect of an exercise intervention on cognitive functioning, compared with usual care, for up to 2 years. Patients with a TIA or minor stroke were randomly allocated to an intervention group receiving the 1-year exercise intervention (n = 60) or to usual care (n = 59). Outcome measures were assessed at baseline and after 1 and 2 years. We measured cognition with neuropsychological tests on three domains: (1) executive functioning, (2) attention-psychomotor speed, and (3) memory. Linear mixed models were used for longitudinal data to determine the effect of the exercise intervention on cognitive functioning. Statistical analyses were performed using IBM SPSS software 24.0. RESULTS: We found that over the two years study period -and corrected for age, sex, and educational level- the intervention group on average improved significantly more in executive functioning than the control group (ß = 0.13; 95 % CI [0.02 to 0.25]; p = 0.03). No significant intervention effects were found on either memory or attention-psychomotor speed. CONCLUSIONS: Our data show that a 1-year exercise intervention significantly improved executive functioning over time, compared to usual care. We recommend that health care professionals consider broadening standard secondary stroke prevention treatment in patients with TIA/minor stroke by adding exercise and physical activity.

Is Cardiorespiratory Fitness Independently Associated with Fatigue in Patients with Transient Ischemic Attack or Minor Stroke?

Fatigue is a common complaint and a disabling symptom among patients following transient ischemic attack (TIA) or minor stroke. In patients with stroke, decreased cardiorespiratory fitness (CRF) is believed to be related to increased severity of post-stroke fatigue (PSF). However, this association between PSF and CRF in patients with TIA or minor stroke has been less investigated, and currently there is no proven treatment for PSF. We aimed to determine the association between PSF and CRF in patients with TIA or minor stroke and to find out whether this association was distorted by confounders. A cross-sectional association study was conducted among a total of 119 patients with TIA or minor stroke. PSF was measured by the Fatigue Severity Scale (FSS) and CRF was quantified by maximal exercise capacity (V̇O2max). The FSS showed a significant association with V̇O2max (ß = -0.061, SE: 0.022; p = 0.007). This association was confounded by anxiety (ß = -0.044, SE: 0.020; p = 0.028) and depression (ß = -0.030, SE: 0.022; p = 0.177) as measured by the subscales of the Hospital Anxiety and Depression Scale (HADS). After controlling for HADS scores on depression and anxiety, the univariate relationship between V̇O2max and FSS was no longer significant. These results suggest that the association between PSF and CRF in patients with TIA or minor stroke is weak and significantly confounded by the factors of depression and anxiety.

Tranexamic Acid After Aneurysmal Subarachnoid Hemorrhage: Post-Hoc Analysis of the ULTRA Trial.

BACKGROUND AND OBJECTIVES: The ULTRA-trial showed that ultra-early and short-term tranexamic acid treatment after subarachnoid hemorrhage did not improve clinical outcome at six months. An expected proportion of the included patients had non-aneurysmal subarachnoid hemorrhage In this post-hoc study, we will investigate whether ultra-early and short-term tranexamic acid treatment in patients with aneurysmal subarachnoid hemorrhage improves clinical outcome at six months. METHODS: The ULTRA-trial is a multicenter, prospective, randomized, controlled, open-label trial with blinded outcome assessment, conducted between July 24, 2013 and January 20, 2020. After confirmation of subarachnoid hemorrhage on non-contrast computer tomography, patients were allocated to either ultra-early and short-term tranexamic acid treatment with usual care, or usual care only. In this post-hoc analysis, we included all ULTRA-participants with a confirmed aneurysm on CT angiography and/or digital subtraction angiography. The primary endpoint was clinical outcome at six months, assessed by the modified Rankin Scale, dichotomized into good (0-3) and poor (4-6) outcome. RESULTS: Of the 813 ULTRA-trial patients who had an aneurysmal subarachnoid hemorrhage, 409 (50%) were assigned to the tranexamic acid group and 404 (50%) to the control group. In the intention-to-treat analysis, 233 of 405 (58%) patients in the tranexamic acid group and 238 of 399 (60%) patients in the control group had a good clinical outcome (adjusted odds ratio (aOR) 0·92; 95% confidence interval (C.I.) 0·69 to 1·24). None of the secondary outcomes showed significant differences between the treatment groups: excellent clinical outcome (mRS 0-2) aOR 0.76, 95% C.I. 0.57-1.03, all-cause mortality at 30 days aOR 0.91, 95% C.I. 0.65-1.28), all-cause mortality at six months aOR 1.10 (95% C.I. 0.80-1.52). DISCUSSION: Ultra-early and short-term tranexamic acid treatment did not improve clinical outcome at six months in patients with aneurysmal subarachnoid hemorrhage and therefore, cannot be recommended. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02684812; submission date February 18, 2016, first patient enrollment on July 24th, 2013). CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that tranexamic acid does not improve outcomes in patients presenting with aneurysmal subarachnoid hemorrhage.

Effect of an exercise intervention on global cognition after transient ischemic attack or minor stroke: the MoveIT randomized controlled trial.

BACKGROUND: Patients with a transient ischemic attack (TIA) or ischemic stroke are at increased risk of developing cognitive impairment in the subacute phase. At present, the effects of exercise on cognitive functioning following a TIA or stroke are not fully known. The purpose of this trial was to investigate the effect of exercise on global cognition. METHODS: The MoveIT trial is a single-centre, observer-blinded, randomized controlled trial involving a 1-year exercise intervention consisting of a 12-week group exercise program, combined with three counselling visits to the physiotherapists over a 9-month period. The control group received standard care. The primary outcome was global cognitive functioning, assessed at one year, using the Montreal Cognitive Assessment (MoCA). Secondary outcomes included cardiorespiratory fitness, the cardiovascular profile, and attainment of secondary prevention targets, anxiety, depression and fatigue at one and two years. RESULTS: The experimental group consisted of 60 patients, while the control group consisted of 59 patients. The mean age was 64.3 years and 41% were female. No between-group differences were found on global cognitive functioning (MD, 0.7 out of 30, 95% CI, - 0.2 to 1.6) or on secondary outcome measures at 12 months. The only significant between-group difference was found for fatigue, in favour of the experimental group at 12 months (MD, 0.6 out of 63, 95% CI, 0.1 to 1.1). CONCLUSIONS: No benefit of this exercise intervention was found regarding global cognition. Future studies need to focus on optimizing rehabilitation strategies for this vulnerable group of patients. TRIAL REGISTRATION: http://www.trialregister.nl . Unique identifier: NL3721 . Date first registration: 06-03-2013.

Effectiveness and implementation of SHared decision-making supported by OUTcome information among patients with breast cancer, stroke and advanced kidney disease: SHOUT study protocol of multiple interrupted time series.

INTRODUCTION: Within the value-based healthcare framework, outcome data can be used to inform patients about (treatment) options, and empower them to make shared decisions with their health care professional. To facilitate shared decision-making (SDM) supported by outcome data, a multicomponent intervention has been designed, including patient decision aids on the organisation of post-treatment surveillance (breast cancer); discharge location (stroke) and treatment modality (advanced kidney disease), and training on SDM for health care professionals. The SHared decision-making supported by OUTcome information (SHOUT) study will examine the effectiveness of the intervention and its implementation in clinical practice. METHODS AND ANALYSIS: Multiple interrupted time series will be used to stepwise implement the intervention. Patients diagnosed with either breast cancer (N=630), stroke (N=630) or advanced kidney disease (N=473) will be included. Measurements will be performed at baseline, three (stroke), six and twelve (breast cancer and advanced kidney disease) months. Trends on outcomes will be measured over a period of 20 months. The primary outcome will be patients' perceived level of involvement in decision-making. Secondary outcomes regarding effectiveness will include patient-reported SDM, decisional conflict, role in decision-making, knowledge, quality of life, preferred and chosen care, satisfaction with the intervention, healthcare utilisation and health outcomes. Outcomes regarding implementation will include the implementation rate and a questionnaire on the health care professionals' perspective on the implementation process. ETHICS AND DISSEMINATION: The Medical research Ethics Committees United in Nieuwegein, the Netherlands, has confirmed that the Medical Research Involving Human Subjects Act does not apply to this study. Bureau Onderzoek & Innovatie of Santeon, the Netherlands, approved this study. The results will contribute to insight in and knowledge on the use of outcome data for SDM, and can stimulate sustainable implementation of SDM. TRIAL REGISTRATION NUMBER: NL8374, NL8375 and NL8376.

Practice variation in the informed consent procedure for thrombolysis in acute ischemic stroke: a survey among neurologists and neurology residents.

BACKGROUND: Obtaining informed consent for intravenous thrombolysis in acute ischemic stroke can be challenging, and little is known about if and how the informed consent procedure is performed by neurologists in clinical practice. This study examines the procedure of informed consent for intravenous thrombolysis in acute ischemic stroke in high-volume stroke centers in the Netherlands. METHODS: In four high volume stroke centers, neurology residents and attending neurologists received an online questionnaire concerning informed consent for thrombolysis with tissue-type plasminogen activator (tPA). The respondents were asked to report their usual informed consent practice for tPA treatment and their considerations on whether informed consent should be obtained. RESULTS: From the 203 invited clinicians, 50% (n = 101) completed the questionnaire. One-third of the neurology residents (n = 21) and 21% of the neurologists (n = 8) reported that they always obtain informed consent for tPA treatment. If a patient is not capable of providing informed consent, 30% of the residents (n = 19) reported that they start tPA treatment without informed consent. In these circumstances, 53% of the neurologists (n = 20) reported that the resident under their supervision would start tPA treatment without informed consent. Most neurologists (n = 21; 55%) and neurology residents (n = 45; 72%) obtained informed consent within one minute. None of the respondents used more than five minutes for informed consent. Important themes regarding obtaining informed consent for treatment were patients' capacity, and medical, ethical and legal considerations. CONCLUSION: The current practice of informed consent for thrombolysis in acute ischemic stroke varies among neurologists and neurology residents. If informed consent is obtained, most clinicians stated to obtain informed consent within one minute. In the future, a shortened information provision process may be applied, making a shift from informed consent to informed refusal, while still considering the patient's capacity, stroke severity, and possible treatment delays.

Patient-Reported Experience Measures in Stroke Care: A Systematic Review.

BACKGROUND AND PURPOSE: Patient-reported experience measures (PREMs) assess patients' perception of health care. We aimed to identify all reported PREMs for stroke care and critically appraise psychometric properties of PREMs validated for patients with stroke. METHODS: Studies on the development, validation, or utilization of PREMs for adult patients with stroke were systematically identified. The Consensus-Based Standards for the Selection of Health Measurement Instruments criteria were used to appraise psychometric performance. RESULTS: We included 18 studies, examining 13 PREMs. Two PREMs had been developed for stroke care: Consumer Quality Index: Cerebrovascular Accident and Riksstroke. Consumer Quality Index: Cerebrovascular Accident was given a positive psychometric assessment, but its length and limited language applicability impede clinical implementation. Riksstroke was appraised as doubtful. Eleven PREMs were generic. The psychometric performance of 5 generic PREMS, validated for patients with stroke, received conflicting assessments. Six generic PREMs had not been validated in patients with stroke and were therefore not assessed for instrument performance. CONCLUSIONS: Thirteen PREMs have been published for use in stroke care. The stroke-specific Consumer Quality Index: Cerebrovascular Accident has favorable psychometric performance but lacks practical feasibility. Other PREMs have inadequate or unknown psychometric properties. This indicates the need for developing stroke-specific PREMs to support quality improvement and enhance patient-centered care.

The association between computed tomography angiography timing and workflow times in patients with acute ischemic stroke.

BACKGROUND: In most hospitals, computed tomography angiography (CTA) is nowadays routinely performed in patients with acute ischemic stroke. However, it is unclear whether CTA is best performed before or after start of intravenous thrombolysis (IVT), since acquisition of CTA before IVT may prolong door-to-needle times, while acquisition after IVT may prolong door-to-groin times in patients undergoing endovascular treatment. METHODS: We performed a before-versus-after study (CTA following IVT, period I and CTA prior to IVT, period II), consisting of two periods of one year each. This study is based on a prospective registry of consecutive patients treated with IVT in two collaborating high-volume stroke centers; one primary stroke center and one comprehensive stroke center. The primary outcome was door-to-needle times. Secondary outcomes included door-to-groin times. Quantile regression analyses were performed to evaluate the association between timing of CTA and workflow times, adjusted for prognostic factors. RESULTS: A total of 519 patients received IVT during the study period (246 in period I, 273 in period II). In the adjusted analysis, we found a nonsignificant 1.13 min median difference in door-to-needle times (95% confidence interval: 1.03-3.29). Door-to-groin times was significantly shorter in period II in both unadjusted and adjusted analysis with the latter showing a 19.16 min median difference (95% confidence interval: 3.08-35.24). CONCLUSIONS: CTA acquisition prior to start of IVT did not adversely affect door-to-needle times. However, a significantly shorter door-to-groin times was observed in endovascular treatment eligible patients. Performing CTA prior to start of IVT seems the preferred strategy.

Ultra-early tranexamic acid after subarachnoid haemorrhage (ULTRA): a randomised controlled trial.

BACKGROUND: In patients with aneurysmal subarachnoid haemorrhage, short-term antifibrinolytic therapy with tranexamic acid has been shown to reduce the risk of rebleeding. However, whether this treatment improves clinical outcome is unclear. We investigated whether ultra-early, short-term treatment with tranexamic acid improves clinical outcome at 6 months. METHODS: In this multicentre prospective, randomised, controlled, open-label trial with masked outcome assessment, adult patients with spontaneous CT-proven subarachnoid haemorrhage in eight treatment centres and 16 referring hospitals in the Netherlands were randomly assigned to treatment with tranexamic acid in addition to care as usual (tranexamic acid group) or care as usual only (control group). Tranexamic acid was started immediately after diagnosis in the presenting hospital (1 g bolus, followed by continuous infusion of 1 g every 8 h, terminated immediately before aneurysm treatment, or 24 h after start of the medication, whichever came first). The primary endpoint was clinical outcome at 6 months, assessed by the modified Rankin Scale, dichotomised into a good (0-3) or poor (4-6) clinical outcome. Both primary and safety analyses were according to intention to treat. This trial is registered at ClinicalTrials.gov, NCT02684812. FINDINGS: Between July 24, 2013, and July 29, 2019, we enrolled 955 patients; 480 patients were randomly assigned to tranexamic acid and 475 patients to the control group. In the intention-to-treat analysis, good clinical outcome was observed in 287 (60%) of 475 patients in the tranexamic acid group, and 300 (64%) of 470 patients in the control group (treatment centre adjusted odds ratio 0·86, 95% CI 0·66-1·12). Rebleeding after randomisation and before aneurysm treatment occurred in 49 (10%) patients in the tranexamic acid and in 66 (14%) patients in the control group (odds ratio 0·71, 95% CI 0·48-1·04). Other serious adverse events were comparable between groups. INTERPRETATION: In patients with CT-proven subarachnoid haemorrhage, presumably caused by a ruptured aneurysm, ultra-early, short-term tranexamic acid treatment did not improve clinical outcome at 6 months, as measured by the modified Rankin Scale. FUNDING: Fonds NutsOhra.

Early cognitive and emotional outcome after stroke is independent of discharge destination.

BACKGROUND AND PURPOSE: Cognitive and emotional problems occur frequently after stroke. Patients with minor stroke are more likely to be discharged home. This paper compares early cognitive and emotional outcomes in patients discharged home after stroke versus patients discharged to inpatient rehabilitation, and examines the effect of cognitive and emotional outcomes on long-term participation. METHODS: In this multicenter prospective cohort study, patients with stroke were assessed at two months with the Hospital Anxiety and Depression Scale (HADS), the Checklist for Cognitive and Emotional Consequences following Stroke (CLCE-24) and the Montreal Cognitive Assessment (MoCA). One year post stroke, participation was assessed with the Restriction subscale of the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P Restriction). RESULTS: The study included 332 patients. Two months post stroke, anxiety and cognitive problems were equally prevalent among patients discharged home (n = 243; 73%) and patients discharged to inpatient rehabilitation (n = 89; 27%) (HADS-A = 4.8 ± 3.9 versus 4.6 ± 4.0, p = 0.747; MoCA < 26: 66.7% versus 70.8%, p = 0.477; CLCE-cognition = 3.0 ± 2.9 versus 3.3 ± 2.8, p = 0.499). Depressive symptoms were less severe in patients discharged home (HADS-D = 4.3 ± 3.9 versus 5.5 ± 3.8, p = 0.010). In patients discharged home, cognitive complaints were predictive of long-term participation (B = - 2.03; 95% CI - 3.15, - 0.90), while cognitive or emotional outcomes were not predictive in patients discharged to inpatient rehabilitation. CONCLUSIONS: Cognitive and emotional problems at two months post stroke were comparable between patients discharged home and those discharged to inpatient rehabilitation. For patients discharged home, cognitive complaints were predictive of long-term participation.

Determinants of extended door-to-needle time in acute ischemic stroke and its influence on in-hospital mortality: results of a nationwide Dutch clinical audit.

BACKGROUND: Intravenous thrombolysis (IVT) plays a prominent role in the treatment of acute ischemic stroke (AIS). The sooner IVT is administered, the higher the odds of a good outcome. Therefore, registering the in-hospital time to treatment with IVT, i.e. the door-to-needle time (DNT), is a powerful way to measure quality improvement. The aim of this study was to identify determinants that are associated with extended DNT. METHODS: Patients receiving IVT in 2015 and 2016 registered in the Dutch Acute Stroke Audit were included. DNT and onset-to-door time (ODT) were dichotomized using the median (i.e. extended DNT) and the 90th percentile (i.e. severely extended DNT). Logistic regression was performed to identify determinants associated with (severely) extended DNT/ODT and its effect on in-hospital mortality. A linear model with natural spline was used to investigate the association between ODT and DNT. RESULTS: Included were 9518 IVT treated patients from 75 hospitals. Median DNT was 26 min (IQR 20-37). Determinants associated with a higher likelihood of extended DNT were female sex (OR 1.17, 95% CI 1.05-1.31) and admission during off-hours (OR 1.12, 95% CI 1.01-1.25). Short ODT correlated with longer DNT, whereas longer ODT correlated with shorter DNT. Young age (OR 1.38, 95% CI 1.07-1.76) and admission to a comprehensive stroke center (OR 1.26, 1.10-1.45) were associated with severely extended DNT, which was associated with in-hospital mortality (OR 1.54, 95%CI 1.19-1.98). CONCLUSIONS: Even though DNT in the Netherlands is short compared to other countries, lowering the DNT may be achievable by focusing on specific subgroups.

Nonfocal Transient Neurological Attacks Are Associated With Cerebral Small Vessel Disease.

Background and Purpose- Nonfocal transient neurological attacks (TNAs), such as unsteadiness, bilateral weakness, or confusion, are associated with an increased risk of stroke and dementia. Cerebral ischemia plays a role in their pathogenesis, but the precise mechanisms are unknown. We hypothesized that cerebral small vessel disease is involved in the pathogenesis of TNAs and assessed the relation between TNAs and manifestations of cerebral small vessel disease on magnetic resonance imaging. Methods- We included participants from the HBC (Heart-Brain Connection) study. In this study, hemodynamic and cardiovascular contributions to cognitive impairment have been studied in patients with heart failure, carotid artery occlusion, or possible vascular cognitive impairment, as well as in a reference group. We excluded participants with a history of stroke or transient ischemic attacks. The occurrence of the following 8 TNAs was assessed with a standardized interview: unconsciousness, confusion, amnesia, unsteadiness, bilateral leg weakness, blurred vision, nonrotatory dizziness, and paresthesias. The occurrence of TNAs was related to the presence of lacunes or white matter hyperintensities (Fazekas score, ≥2; early confluent or confluent lesions) in logistic regression analysis, adjusted for age, sex, and hypertension. Results- Of 304 participants (60% men; mean age, 67±9 years), 63 participants (21%) experienced ≥1 TNAs. Lacunes and early confluent or confluent white matter hyperintensities were more common in participants with TNAs than in participants without TNAs (35% versus 20%; adjusted odds ratio, 2.32 [95% CI, 1.22-4.40] and 48% versus 27%; adjusted odds ratio, 2.65 [95% CI, 1.44-4.90], respectively). Conclusions- In our study, TNAs are associated with the presence of lacunes and early confluent or confluent white matter hyperintensities of presumed vascular origin, which indicates that cerebral small vessel disease might play a role in the pathogenesis of TNAs.

Cerebral Perfusion and the Occurrence of Nonfocal Transient Neurological Attacks.

INTRODUCTION: Nonfocal transient neurological attacks (TNAs) are associated with an increased risk of cardiac events, stroke and dementia. Their etiology is still unknown. Global cerebral hypoperfusion has been suggested to play a role in their etiology, but this has not been investigated. We assessed whether lower total brain perfusion is associated with a higher occurrence of TNAs. METHODS: Between 2015 and 2018, patients with heart failure were included in the Heart Brain Connection study. Patients underwent brain magnetic resonance imaging, including quantitative magnetic resonance angiography (QMRA) to measure cerebral blood flow (CBF). We calculated total brain perfusion of each participant by dividing total CBF by brain volume. Patients were interviewed with a standardized questionnaire on the occurrence of TNAs by physicians who were blinded to QMRA flow status. We assessed the relation between total brain perfusion and the occurrence of TNAs with Poisson regression analysis. RESULTS: Of 136 patients (mean age 70 years, 68% men), 29 (21%) experienced ≥1 TNAs. Nonrotatory dizziness was the most common subtype of TNA. Patients with TNAs were more often female and more often had angina pectoris than patients without TNAs, but total CBF and total brain perfusion were not different between both groups. Total brain perfusion was not associated with the occurrence of TNAs (adjusted risk ratio 1.12, 95% CI 0.88-1.42). CONCLUSION: We found no association between total brain perfusion and the occurrence of TNAs in patients with heart failure.

The Dutch Acute Stroke Audit: Benchmarking acute stroke care in the Netherlands.

INTRODUCTION: In the nationwide Dutch Acute Stroke Audit (DASA), consecutive patients with acute ischaemic stroke (AIS) and intracranial haemorrhage (ICH) are prospectively registered. Acute stroke care is a rapidly evolving field in which intravenous thrombolysis (IVT) and intra-arterial thrombectomy (IAT) play a crucial role in increasing odds of favourable outcome. The DASA can be used to assess the variation in care between hospitals and develop 'best practice' in acute stroke care. Patients and methods: We describe the initiation and design of the DASA as well as the results from 2015 and 2016. RESULTS: In 2015 and 2016, 55,854 patients with AIS and 7727 patients with ICH were registered in the DASA. Treatment with IVT was administered to 10,637 patients (with an increase of 1.3% in 2016) and 1740 patients underwent IAT (with an increase of 1% in 2016). Median door-to-needle time for IVT and median door-to-groin time for IAT have decreased from 27 to 25 min and 66 to 64 min, respectively. Mortality during admission was 4.9% in patients with AIS, whereas 26% of patients with ICH died. Modified Rankin Scale score at three months was registered in 49% of AIS patients and 45% of ICH patients. DISCUSSION: During the nationwide DASA, time to treatment is reduced for IVT as well as IAT. With the rapidly evolving treatment of acute stroke care, the DASA can be used to monitor the quality provided on patient- and hospital level. CONCLUSION: Increasing completeness of registration of the outcome, in combination with adjustment for patient-related factors, is necessary to define and further improve the quality of the acute stroke care.

Physical Activity and Characteristics of the Carotid Artery Wall in High-Risk Patients-The SMART (Second Manifestations of Arterial Disease) Study.

BACKGROUND: Physical activity reduces the risk of vascular disease. This benefit is not entirely explained through an effect on vascular risk factors. We examined the relationship of physical activity and characteristics of the carotid artery wall in patients with vascular disease or risk factors. METHODS AND RESULTS: Cross-sectional analyses were performed in 9578 patients from the SMART (Second Manifestations of Arterial Disease) study, a prospective cohort study among patients with vascular disease or risk factors. Physical activity was assessed using questionnaires. Carotid intima-media thickness and carotid artery stenosis of both common carotid arteries was measured. In a subset of 3165 participants carotid diastolic diameter and distension were assessed. Carotid stiffness was expressed as the distensibility coefficient and Young's elastic modulus. Regression analyses adjusted for vascular risk factors showed that physical activity was inversely associated with diastolic diameter (fifth versus first quintile B=-0.13 mm; 95% CI, -0.21 to -0.05) and decreased risk of carotid artery stenosis (relative risk, 0.58; 95% CI, 0.48-0.69). A light level of physical activity was associated with less carotid stiffness (second versus first quintile; Young's elastic modulus B=-0.11 kPa-1×10-3; 95% CI, -0.16 to -0.06; distensibility coefficient B=0.93 kPa×103; 95% CI, 0.34-1.51), but there was no additional benefit with increasing levels of physical activity. In patients with vascular disease, physical activity was inversely associated with common carotid intima-media thickness, but not in patients with vascular risk factors. CONCLUSIONS: In patients with vascular disease or risk factors, increased physical activity was associated with smaller carotid diastolic diameter, decreased risk of carotid artery stenosis, and less carotid stiffness, but it only showed benefits on carotid intima-media thickness in patients with vascular disease.

Cardiorespiratory fitness, cognition and brain structure after TIA or minor ischemic stroke.

Background It is not known whether cardiorespiratory fitness is associated with better cognitive performance and brain structure in patients with a TIA or minor ischemic stroke. Aims To examine the association between cardiorespiratory fitness, cognition and brain structure in patients with a TIA and minor stroke. Methods The study population consisted of patients with a TIA or minor stroke with a baseline measurement of the peak oxygen consumption, a MRI scan of brain and neuropsychological assessment. Composite z-scores were calculated for the cognitive domains attention, memory and executive functioning. White matter hyperintensities, microbleeds and lacunes were rated visually. The mean apparent diffusion coefficient was measured in regions of interest in frontal and occipital white matter and in the centrum semiovale as a marker of white matter structure. Normalized brain volumes were estimated by use of Statistical Parametric Mapping. Results In 84 included patients, linear regression analysis adjusted for age, sex and education showed that a higher peak oxygen consumption was associated with higher cognitive z-scores, a larger grey matter volume (B = 0.15 (95% CI 0.05; 0.26)) and a lower mean apparent diffusion coefficient (B = -.004 (95% CI -.007; -.001)). We found no association between the peak oxygen consumption and severe white matter hyperintensities, microbleeds, lacunes and total brain volume. Conclusions These data suggest that cardiorespiratory fitness is associated with better cognitive performance, greater grey matter volume and greater integrity of the white matter in patients with a TIA or minor ischemic stroke. Further prospective trials are necessary to define the effect of cardiorespiratory fitness on cognition and brain structure in patients with TIA or minor stroke.

PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2): Results of a Randomized, Double-Blind Placebo-Controlled Clinical Trial.

BACKGROUND AND PURPOSE: Subfebrile body temperature and fever in the first days after stroke are strongly associated with unfavorable outcome. A subgroup analysis of a previous trial suggested that early treatment with paracetamol may improve functional outcome in patients with acute stroke and a body temperature of ≥36.5°C. In the present trial, we aimed to confirm this finding. METHODS: PAIS 2 (Paracetamol [Acetaminophen] in Stroke 2) was a multicenter, randomized, double-blind, placebo-controlled clinical trial. We aimed to include 1500 patients with acute ischemic stroke or intracerebral hemorrhage within 12 hours of symptom onset. Patients were treated with paracetamol in a daily dose of 6 g or matching placebo for 3 consecutive days. The primary outcome was functional outcome at 3 months, assessed with the modified Rankin Scale and analyzed with multivariable ordinal logistic regression. Because of slow recruitment and lack of funding, the study was stopped prematurely. RESULTS: Between December 2011 and October 2015, we included 256 patients, of whom 136 (53%) were allocated to paracetamol. In this small sample, paracetamol had no effect on functional outcome (adjusted common odds ratio, 1.15; 95% confidence interval, 0.74-1.79). There was no difference in the number of serious adverse events (paracetamol n=35 [26%] versus placebo n=28 [24%]). CONCLUSIONS: Treatment with high-dose paracetamol seemed to be safe. The effect of high-dose paracetamol on functional outcome remains uncertain. Therefore, a large trial of early treatment with high-dose paracetamol is still needed. CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR2365.

Cardiorespiratory Fitness after Transient Ischemic Attack and Minor Ischemic Stroke: Baseline Data of the MoveIT Study.

BACKGROUND: Cardiorespiratory fitness (CRF) is reduced in patients with stroke. It is unclear whether it is also reduced in patients with a transient ischemic attack (TIA) or minor stroke. We investigated the CRF in patients with a recent TIA or minor stroke and explored which determinants are associated with a lower fitness. METHODS: In 113 patients with a recent TIA or minor ischemic stroke (64 (SD = 10) years of age; 49 (IQR 27-86) days post TIA or stroke), the peak oxygen consumption (VO2peak) was determined in a symptom-limited ramp exercise test. Physical activity level, vascular risk factors, history of vascular or pulmonary disease, and stroke characteristics were recorded at inclusion and related to the VO2peak. RESULTS: Mean VO2peak was 22 mL/kg/min (SD = 6), which is the fifth percentile of age- and sex-related normative values. Increasing age and female sex were associated with a lower VO2peak (B (95% CI): per 10 years -2.57 mL/kg/min (-3.75; -1.40) and female sex -5.84 mL/kg/min (-8.06; -3.62)). Age- and sex-adjusted linear regression analyses showed that a history of cardiovascular disease and pulmonary disease was associated with a lower VO2peak. In addition, a lower level of physical activity, hypertension, smoking, and overweight were associated with a lower VO2peak. History of stroke and stroke characteristics were not related to VO2peak. CONCLUSION: The majority of patients with a recent TIA or minor ischemic stroke have a poor CRF. Our findings suggest that premorbid cardiovascular and pulmonary disease and vascular risk factors, but not TIA- or stroke-related factors, contribute to a reduced CRF.

Lifestyle Interventions to Prevent Cardiovascular Events After Stroke and Transient Ischemic Attack: Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Patients with a transient ischemic attack or ischemic stroke have an increased risk of subsequent cardiovascular events. The purpose of this systematic review and meta-analysis was to determine whether lifestyle interventions focusing on behaviorally modifiable risk factors with or without an exercise program are effective in terms of (1) preventing recurrent cardiovascular events, (2) reducing mortality, and (3) improving modifiable risk factors associated with cardiovascular disease in patients after a transient ischemic attack or ischemic stroke. METHODS: For this systematic review and meta-analysis, we systematically searched PubMed, Embase, PsycInfo, and the Cochrane Library from the start of the database to May 7, 2015. Subgroup analyses were conducted to explore the influence of therapy-related factors. RESULTS: Twenty-two randomized controlled trials were identified with a total of 2574 patients. Pooling showed a significant reduction in systolic blood pressure by the lifestyle interventions applied, compared with usual care (mean difference, -3.6 mm Hg; 95% confidence interval, -5.6 to -1.6, I2=33%). No significant effect was found on cardiovascular events, mortality, diastolic blood pressure, or cholesterol. In the subgroup analyses, the trials with cardiovascular fitness interventions, trials with an intervention that lasted longer than 4 months, and interventions that used >3 behavior change techniques were more effective in reducing systolic blood pressure. CONCLUSIONS: We found that lifestyle interventions are effective in lowering systolic blood pressure. About other end points, this systematic review found no effect of lifestyle interventions on cardiovascular event rate mortality, diastolic blood pressure, or total cholesterol.