Search

Endothelial progenitor cells (EPCs), expressing markers for stemness (CD34), immaturity (CD133) and endothelial maturity (KDR), may determine the extent of post-stroke vascular repair. Given the prevalence of stroke in elderly, this study explored whether variations in plasmatic availability of certain EPC subtypes could predict the severity and outcome of disease in older patients. Blood samples were collected from eighty-one consented patients (≥ 65 years) at admission and days 7, 30 and 90 post-stroke. EPCs were counted with flow cytometry. Stroke severity and outcome were assessed using the National Institutes of Health Stroke Scale, Barthel Index and modified Rankin Scale. The levels of key elements known to affect EPC characteristics were measured by ELISA. Diminished total antioxidant capacity and CD34 + KDR + and CD133 + KDR + counts in early phases of stroke were associated with disease severity and worse functional outcome at day 90 post-stroke. Baseline levels of angiogenic agent PDGF-BB, but not VEGF, positively correlated with CD34 + KDR + numbers at day 90. Baseline LDL-cholesterol levels were inversely correlated with CD34 + KDR+, CD133 + KDR + and CD34 + CD133 + KDR + numbers at day 90. Close correlation between baseline CD34 + KDR + and CD133 + KDR + counts and the outcome of stroke proposes these particular EPC subtypes as potential prognostic markers for ischaemic stroke. [ABSTRACT FROM AUTHOR]

Ageing impairs endothelial function and predisposes the person to ischaemic stroke (IS). Endothelial progenitor cells (EPCs) repair endothelial damage and induce post-ischaemic neovascularisation. Given the prevalence of IS in older population, this study explored whether changes in EPC number and function may reliably predict the type or outcome of stroke in patients ≥ 65 years of age. For this, blood samples were collected once from healthy volunteers (HVs, n = 40) and four times (admission and days 7, 30 and 90 post-stroke) from participants with lacunar (n = 38) or cortical (n = 43) stroke. EPCs were counted with flow cytometry and defined as non-haematopoietic cells (CD45-) expressing markers for stemness (CD34 +), immaturity (CD133 +) and endothelial maturity (KDR +). Clonogenesis, tubulogenesis, migration and proliferation assays were performed as measures of EPC functionality. Biochemical profile of plasma inflammatory and angiogenic agents were studied using specific ELISAs. Primary outcome was disability or dependence on day 90 post-stroke, assessed by the modified Rankin Scale (mRS). Compared to HVs, EPC numbers were higher in stroke patients at all time points studied, reaching significance at baseline and day 30. No differences in EPC counts and functionality were observed between lacunar and cortical stroke groups at any time. Plasma endostatin, PDGF-BB, TNF-α and VEGF levels were higher in stroke patients vs HVs. Patient outcome, evaluated by mRS on day 90 post-stroke, did not correlate with EPC count or functionality. Baseline EPC counts may serve as a diagnostic marker for stroke but fail to distinguish between different stroke subtypes and predict post-stroke outcome. [ABSTRACT FROM AUTHOR]

Background The effectiveness and safety of endovascular thrombectomy (EVT) in the late window (6--24 hours) for acute ischemic stroke (AIS) patients selected without advanced imaging is undetermined. We aimed to assess clinical outcomes and the relationship with time-to-EVT treatment beyond 6 hours of stroke onset without advanced neuroimaging. Methods Patients who underwent EVT selected with non-contrast CT/CT angiography (without CT perfusion or MR imaging), between October 2015 and March 2020, were included from a national stroke registry. Functional and safety outcomes were assessed in both early (<6 hours) and late windows with time analyzed as a continuous variable. Results Among 3278 patients, 2610 (79.6%) and 668 (20.4%) patients were included in the early and late windows, respectively. In the late window, for every hour delay, there was no significant association with shift towards poorer functional outcome (modified Rankin Scale (mRS)) at discharge (adjusted common OR 0.98, 95% CI 0.94 to 1.01, p=0.27) or change in predicted functional independence (mRS ≤2) (24.5% to 23.3% from 6 to 24 hours; aOR 0.99, 95% CI0.94 to 1.04, p=0.85). In contrast, predicted functional independence was time sensitive in the early window: 5.2% reduction per-hour delay (49.4% to 23.5% from 1 to 6 hours, p=0.0001). There were similar rates of symptomatic intracranial hemorrhage (sICH) (3.4% vs 4.6%, p=0.54) and in-hospital mortality (12.9% vs 14.6%, p=0.33) in the early and late windows, respectively, without a significant association with time. Conclusion In this real-world study, there was minimal change in functional disability, sICH and in-hospital mortality within and across the late window. While confirmatory randomized trials are needed, these findings suggest that EVT remains feasible and safe when performed in AIS patients selected without advanced neuroimaging between 6--24 hours from stroke onset. [ABSTRACT FROM AUTHOR]

Objectives: The primary objective was to gain insight into the lived experiences of using day-to-day strategies to manage post-stroke fatigue. Design: Qualitative, descriptive study. Setting: Community telephone interviews. Participants: A purposive sample of 20 stroke survivors with current, or previous, post-stroke fatigue, and 8 caregivers, who provided informal care or support, were recruited. Main Measures: Semi-structured telephone interviews were undertaken. Data were analysed using a framework approach. Results: Most participants had found their own ways of coping and their personal strategies included acceptance of having fatigue; 'pacing' (spreading activities out and interspersing with rest periods); keeping a diary in order to plan activities and to identify 'trigger' activities which induced fatigue; talking to (and educating) others about having fatigue; using relaxation; and accessing professional advice and support. The burden placed on caregivers was considerable and they often had to oversee the post-stroke fatigue management strategies used. Conclusions: Post-stroke fatigue is managed in different ways and there was not one particular strategy that seemed effective for everyone. Most people in our study had had to devise their own ways of coping practically. Given the scale of this problem, which profoundly impacts the lives of both stroke survivors and caregivers, the management of post-stroke fatigue merits more attention and evaluation. However, this must be directly informed by those with lived experience. [ABSTRACT FROM AUTHOR]

To examine how patients spend their time in stroke rehabilitation units in England. We recruited 144 patients within a month after stroke from four stroke rehabilitation units and observed their activity type, interactions and location. Each participant was observed for 1 min every 10-minutes, for a total of 20 h, over three consecutive days. Multilevel modelling was performed to assess differences across sites. Across the four sites a total of 12,248 observations were performed. Patients spent on average 37% of the observed time inactive and 60% alone. A health care professional was present for 18% of the observations and patients' most frequent contact was with family members (19%). Patients were mainly physically active in the presence of therapists, but they practiced self-care activities of daily living most frequently in the presence of nursing staff. There were limited opportunities for activity away from the bedside. Significant differences were found between the units, including patients' level of contact with rehabilitation assistants and nursing staff, but not in their time with occupational therapists and physiotherapists. Stroke patients in England spend a large proportion of their day inactive and alone. Opportunities to promote a rehabilitation focused environment may include: a) enhancing the role of rehabilitation assistants, b) supporting nursing staff in maximising opportunities for the practice of activities of daily living and c) involving family members in the rehabilitation process. Clinicians need to consider stroke patients' activity levels and rehabilitation experience outside formal therapy. The role of rehabilitation assistants and nursing staff can be key in promoting patient activity and practice of self-care ADL tasks. Pragmatic strategies to encourage family involvement in the rehabilitation process need to be developed. [ABSTRACT FROM AUTHOR]

Introduction: Post-stroke fatigue is common and is one of the most distressing symptoms after stroke. It has a negative impact on physical, social and psychological functioning; it is also associated with poor outcomes and increased mortality. The effective management of post-stroke fatigue is therefore regarded as a clinical priority. Method: This study will use a mixed-methods design with three overlapping phases. Phase 1 will be a survey of existing fatigue management within the United Kingdom. In phase 2, interviews and focus groups will be conducted with stroke survivors with fatigue, carers and clinicians to determine strategies used to manage fatigue successfully. In phase 3, data from phases 1 and 2 will contribute to the co-design of a fatigue management programme with the NotFAST2 study Patient and Public Involvement group. This will be further refined through subsequent focus groups, which will include those with fatigue associated with other health conditions. Results: Survey data will be analysed using descriptive statistics. Interview and focus group data will be analysed using a framework approach. Conclusion: Post-stroke fatigue requires a comprehensive management programme necessitating input from key stakeholders. A post-stroke fatigue programme will be developed which will be tested in a future randomised controlled trial. [ABSTRACT FROM AUTHOR]

Background: Thrombolysis, with or without thrombectomy, for acute ischaemic stroke is associated with an increased risk of intracranial bleeding. We assessed whether treatment with glyceryl trinitrate (GTN), a nitric oxide donor, may influence the associated bleeding risk. Methods: We searched for completed randomized controlled trials of GTN vs. no GTN in acute ischaemic stroke with data on reperfusion treatments (thrombolysis and/or thrombectomy). The primary efficacy outcome was functional status as assessed by the modified Rankin Scale (mRS) at day 90; the primary safety outcome was intracranial bleeding. Secondary safety outcomes included symptomatic intracranial hemorrhage and haemorrhagic transformation of infarction. Individual patient data were pooled and meta-analysis performed using ordinal or binary logistic regression with adjustment for trial and prognostic variables both overall and in those randomized within 6 h of symptom onset. Results: Three trials met the eligibility criteria. Of 715 patients with ischaemic stroke who underwent thrombolysis (709, >99%) or thrombectomy (24, 3.4%), 357 (49.9%) received GTN and 358 (50.1%) received no GTN. Overall, there was no difference in the distribution of the mRS at day 90 between GTN vs. no GTN (OR 0.94, 95% CI 0.72–1.23; p = 0.65); similarly, there was no difference in intracranial hemorrhage rates between treatment groups (OR 0.90, 95% CI 0.43–1.89; p = 0.77). In those randomized to GTN vs. no GTN within 6 h of symptom onset, there were numerically fewer bleeding events, but these analyses did not reach statistical significance. Conclusions: In ischaemic stroke patients treated predominantly with thrombolysis, transdermal GTN was safe, but did not influence functional outcome at 90 days. [ABSTRACT FROM AUTHOR]

Objective: To determine the feasibility of recruiting to and delivering a biopsychosocial intervention for carers of stroke survivors. Design: Feasibility randomised controlled study with nested qualitative interview study. Setting: The intervention was delivered in the community in either a group or one-to-one format. Subjects: Carers and stroke survivors within one year of stroke onset. Interventions: A carer targeted intervention delivered by a research psychologist in six structured two-hour sessions or usual care control. The intervention combined education about the biological, psychological and social effects of stroke with strategies and techniques focussing on adjustment to stroke and caregiving. Stroke survivors in both groups received baseline and follow-up assessment but no intervention. Main Outcome: Recruitment rate, study attrition, fidelity of intervention delivery, acceptability and sensitivity of outcome measures used (health related quality of life, anxiety and depression and carer burden six months after randomisation). Results: Of the 257 carers approached, 41 consented. Six withdrew before randomisation. Eighteen participants were randomised to receive the intervention and 17 to usual care. Attendance at sessions was greater when treated one-to-one. Feedback interviews suggested that participants found the intervention acceptable and peer support particularly helpful in normalising their feelings. Thirty participants were assessed at follow-up with improvements from baseline on all health measures for both groups. Conclusions: Our results suggest that a biopsychosocial intervention was acceptable to carers and can be delivered in group and one-to-one formats. Timing of approach and mode of intervention delivery is critical and requires tailoring to the carers individual needs. [ABSTRACT FROM AUTHOR]

The main purpose was to evaluate, using the Think-Aloud method, a version of the Illness Perception Questionnaire–Revised for stroke survivors. Six stroke survivors (mean age = 58.8 years, range = 31–78 years, standard deviation = 18.9 years) took part in Think-Aloud interviews, analysed according to established guidelines. Overall, 179 problems emerged. The most noteworthy was missing or insufficient Think-Aloud data generated, where participants did not think out loud. Others included complex and negative item wording, and items on the treatment control sub-scale. Questionnaire length, simpler wording and verbal probing are important considerations in further development of an Illness Perception Questionnaire–Revised for stroke survivors. [ABSTRACT FROM AUTHOR]

Objective: To establish feasibility of initiating electrical stimulation treatment of wrist extensors and flexors in patients early after stroke to prevent muscle contractures and pain. Design: Feasibility randomized controlled trial with economic evaluation. Setting: A specialist stroke unit in Nottinghamshire. Subjects: A total of 40 patients recruited within 72 hours post-stroke with arm hemiparesis. Interventions: Participants were randomized to receive usual care or usual care and electrical stimulation to wrist flexors and extensors for 30 minutes, twice a day, five days a week for three months. Initial treatment was delivered by an occupational therapist or physiotherapist who trained participants to self-manage subsequent treatments. Measures: Measures of feasibility included recruitment and attrition rates, completion of treatment, and successful data collection. Outcome data on wrist range of motion, pain, arm function, independence, quality of life, and resource use were measured at 3-, 6-, and 12-months post-randomization. Results: A total of 40 participants (of 215 potentially eligible) were recruited in 15 months (20 men; mean age: 72 (SD: 13.0)). Half the participants lacked mental capacity and were recruited by consultee consent. Attrition at three-month follow-up was 12.5% (death (n = 2), end-of-life care (n = 2), and unable to contact (n = 1)). Compliance varied (mean: 65 (SD: 53)) and ranged from 10 to 166 treatments per patient (target dosage was 120). Data for a valid economic analysis can be adequately collected. Conclusion: Early initiation of electrical stimulation was acceptable and feasible. Data collection methods used were feasible and acceptable to participants. A large definitive study is needed to determine if electrical stimulation is efficacious and cost effective. [ABSTRACT FROM AUTHOR]

Background: Randomized controlled trials provide high-level evidence, but the necessity to include selected patients may limit the generalisability of their results. Methods: Comparisons were made of baseline and outcome data between patients with acute ischemic stroke (AIS) recruited into the alteplase-dose arm of the international, multi-center, Enhanced Control of Hypertension and Thrombolysis Stroke study (ENCHANTED) in the United Kingdom (UK), and alteplase-treated AIS patients registered in the UK Sentinel Stroke National Audit Programme (SSNAP) registry, over the study period June 2012 to October 2015. Results: There were 770 AIS patients (41.2% female; mean age 72 years) included in ENCHANTED at sites in England and Wales, which was 19.5% of alteplase-treated AIS patients registered in the SSNAP registry. Trial participants were significantly older, had lower baseline neurological severity, less likely Asian, and had more premorbid symptoms, hypertension and atrial fibrillation. Although ENCHANTED participants had higher rates of symptomatic intracerebral hemorrhage than those in SSNAP, there were no differences in onset-to-treatment time, levels of disability (assessed by the modified Rankin scale) at hospital discharge, and mortality over 90 days between groups. Conclusions: Despite the high level of participation, equipoise over the dose of alteplase among UK clinician investigators favored the inclusion of older, frailer, milder AIS patients in the ENCHANTED trial. Clinical trial registration: Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616 [ABSTRACT FROM AUTHOR]

Background and purpose: Although poor prognosis after intracerebral hemorrhage relates to risk factors and hematoma characteristics, there is limited evidence for the effect of race-ethnicity. Methods: Data from 1011 patients with intracerebral hemorrhage enrolled into hyperacute trials and randomized to control were obtained from the Virtual International Stroke Trials Archive and Efficacy of Nitric Oxide in Stroke Trial. Clinical characteristics and functional outcome were compared among three racial groups - Asians, Blacks, and Caucasians. Results: The majority of patients were Caucasian (78.1%) followed by Asians (14.5%) and Blacks (5.5%). At baseline, Caucasians were older and had larger hematoma volumes; Blacks had lower Glasgow Coma Scale and higher systolic blood pressure (all p<0.05). Although the primary outcome of modified Rankin Scale did not differ at 90 days (p=0.14), there were significant differences in mortality (p<0.0001) and quality of life (EQ-5D p<0.0001; EQ-VAS p 0.015). In test of multiple comparisons, Caucasians were more likely to die (p=0.0003) and had worse quality of life (EQ-5D p=0.003; EQ-VAS p<0.0001) as compared to Asians. Conclusion: Race-ethnicity appears to explain some of the variation in clinical characteristics and outcomes after acute intracerebral hemorrhage. Factors that explain this variation need to be identified. [ABSTRACT FROM AUTHOR]

Background: Stroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial. Methods: In a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125–170 mmHg were assigned randomly to at least 6 months of intensive (target SBP <125 mmHg) or guideline (target SBP <140 mmHg) BP lowering. The subset of patients with ischaemic stroke and total cholesterol 3.0–8.0 mmol/l were also assigned randomly to intensive (target LDL-cholesterol <1.3 mmol/l) or guideline (target LDL-c <3.0 mmol/l) lipid lowering. The primary outcome was the Addenbrooke’s Cognitive Examination-Revised (ACE-R). Results: We enrolled 83 patients, mean age 74.0 (6.8) years, and median 4.5 months after stroke. The median follow-up was 24 months (range 1–48). Mean BP was significantly reduced with intensive compared to guideline treatment (difference –10·6/–5·5 mmHg; p<0·01), as was total/LDL-cholesterol with intensive lipid lowering compared to guideline (difference –0·54/–0·44 mmol/l; p<0·01). The ACE-R score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6 (95% CI -9.7 to 2.4), and lipid lowering 4.4 (95% CI -2.1 to 10.9). However, intensive lipid lowering therapy was significantly associated with improved scores for ACE-R at 6 months, trail making A, modified Rankin Scale and Euro-Qol Visual Analogue Scale. There was no difference in rates of dementia or serious adverse events for either comparison. Conclusion: In patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe, but did not alter cognition over two years. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted. Trial Registration: ISRCTN [ABSTRACT FROM AUTHOR]

Background: Granulocyte-colony stimulating factor (G-CSF) mobilises endogenous haematopoietic stem cells and enhances recovery in experimental stroke. Recovery may also be dependent on an enriched environment and physical activity. G-CSF may have the potential to enhance recovery when used in combination with physiotherapy, in patients with disability late after stroke. Methods: A pilot 2 x 2 factorial randomised (1:1) placebo-controlled trial of G-CSF (double-blind), and/or a 6 week course of physiotherapy, in 60 participants with disability (mRS >1), at least 3 months after stroke. Primary outcome was feasibility, acceptability and tolerability. Secondary outcomes included death, dependency, motor function and quality of life measured 90 and 365 days after enrolment. Results: Recruitment to the trial was feasible and acceptable; of 118 screened patients, 92 were eligible and 32 declined to participate. 60 patients were recruited between November 2011 and July 2013. All participants received some allocated treatment. Although 29 out of 30 participants received all 5 G-CSF/placebo injections, only 7 of 30 participants received all 18 therapy sessions. G-CSF was well tolerated but associated with a tendency to more adverse events than placebo (16 vs 10 patients, p = 0.12) and serious adverse events (SAE) (9 vs 3, p = 0.10). On average, patients received 14 (out of 18 planned) therapy sessions, interquartile range [, ]. Only a minority (23%) of participants completed all physiotherapy sessions, a large proportion of sessions (114 of 540, 21%) were cancelled due to patient (94, 17%) and therapist factors (20, 4%). No significant differences in functional outcomes were detected in either the G-CSF or physiotherapy group at day 90 or 365. Conclusions: Delivery of G-CSF is feasible in chronic stroke. However, the study failed to demonstrate feasibility for delivering additional physiotherapy sessions late after stroke therefore a definitive study using this trial design is not supported. Future work should occur earlier after stroke, alongside on-going clinical rehabilitation. Trial Registration: ISRCTN.com [ABSTRACT FROM AUTHOR]

Background and purpose: Current evidence suggests that the time lag from the publication of randomised clinical trial results to changes in prescribing behaviour for drugs is gradually reducing. However, the effect of results of clinical trials of devices and nonpharmacological interventions on clinical practice is less clear. Methods; Prospective data from the ongoing international 'Efficacy of Nitric Oxide Stroke' (ENOS) trial were analysed to assess the use of graduated compression stockings (GCS) for deep vein thrombus (DVT) prophylaxis in acute stroke patients before and after publication of the large 'Clots in Legs Or sTockings after Stroke' (CLOTS-1) trial. Results; Data on GCS use were available for 1971 patients with acute stroke enrolled into ENOS from February 2003 to April 2011; of these, 498 (25.3%) wore GCS. Prior to publication of CLOTS-1, GCS use was common (>50%) in the UK, Australasia and Canada but infrequent in Asia and the rest of Europe. After publication of CLOTS-1, use of GCS in the UK declined from 398/656 (61%) to 20/567 (4%) (p<0.001) but not elsewhere (eg, in Australasia (57% before publication vs 70% after publication, p=0.24, but based on small numbers). Practice change was apparent within 3 months of the study publication and was sustained thereafter. There was no change in DVT rates before and after CLOTS-1 (0.8% vs 1.0%). Conclusions: GCS use declined dramatically following the reporting of the CLOTS-1 trial. The results support the notion that a neutral trial of a device can influence clinical practice rapidly, which is important with a widely used and moderately expensive (time and finance) intervention. [ABSTRACT FROM AUTHOR]

Keywords: bleeding; glyceryl trinitrate; ischaemic stroke; reperfusion; thrombolysis; thrombectomy; meta-analysis EN bleeding glyceryl trinitrate ischaemic stroke reperfusion thrombolysis thrombectomy meta-analysis N.PAG N.PAG 2 11/30/20 20201126 NES 201126 Joanna M. Wardlaw was not included as an author in the published article. Author Contributions JA performed the literature search, pooled analyses, statistical analysis and interpretation, manuscript drafting, and editing. Bleeding, glyceryl trinitrate, ischaemic stroke, reperfusion, thrombolysis, thrombectomy, meta-analysis. [Extracted from the article]