External electrical and pharmacological cardioversion for atrial fibrillation, atrial flutter or atrial tachycardias: a network meta-analysis.

BACKGROUND: Atrial fibrillation (AF) is the most frequent sustained arrhythmia. Cardioversion is a rhythm control strategy to restore normal/sinus rhythm, and can be achieved through drugs (pharmacological) or a synchronised electric shock (electrical cardioversion). OBJECTIVES: To assess the efficacy and safety of pharmacological and electrical cardioversion for atrial fibrillation (AF), atrial flutter and atrial tachycardias. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Conference Proceedings Citation Index-Science (CPCI-S) and three trials registers (ClinicalTrials.gov, WHO ICTRP and ISRCTN) on 14 February 2023. SELECTION CRITERIA: We included randomised controlled trials (RCTs) at the individual patient level. Patient populations were aged ≥ 18 years with AF of any type and duration, atrial flutter or other sustained related atrial arrhythmias, not occurring as a result of reversible causes. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology to collect data and performed a network meta-analysis using the standard frequentist graph-theoretical approach using the netmeta package in R. We used GRADE to assess the quality of the evidence which we presented in our summary of findings with a judgement on certainty. We calculated differences using risk ratios (RR) and 95% confidence intervals (CI) as well as ranking treatments using a P value. We assessed clinical and statistical heterogeneity and split the networks for the primary outcome and acute procedural success, due to concerns about violating the transitivity assumption. MAIN RESULTS: We included 112 RCTs (139 records), from which we pooled data from 15,968 patients. The average age ranged from 47 to 72 years and the proportion of male patients ranged from 38% to 92%. Seventy-nine trials were considered to be at high risk of bias for at least one domain, 32 had no high risk of bias domains, but had at least one domain classified as uncertain risk, and one study was considered at low risk for all domains. For paroxysmal AF (35 trials), when compared to placebo, anteroapical (AA)/anteroposterior (AP) biphasic truncated exponential waveform (BTE) cardioversion (RR: 2.42; 95% CI 1.65 to 3.56), quinidine (RR: 2.23; 95% CI 1.49 to 3.34), ibutilide (RR: 2.00; 95% CI 1.28 to 3.12), propafenone (RR: 1.98; 95% CI 1.67 to 2.34), amiodarone (RR: 1.69; 95% CI 1.42 to 2.02), sotalol (RR: 1.58; 95% CI 1.08 to 2.31) and procainamide (RR: 1.49; 95% CI 1.13 to 1.97) likely result in a large increase in maintenance of sinus rhythm until hospital discharge or end of study follow-up (certainty of evidence: moderate). The effect size was larger for AA/AP incremental and was progressively smaller for the subsequent interventions. Despite low certainty of evidence, antazoline may result in a large increase (RR: 28.60; 95% CI 1.77 to 461.30) in this outcome. Similarly, low-certainty evidence suggests a large increase in this outcome for flecainide (RR: 2.17; 95% CI 1.68 to 2.79), vernakalant (RR: 2.13; 95% CI 1.52 to 2.99), and magnesium (RR: 1.73; 95% CI 0.79 to 3.79). For persistent AF (26 trials), one network was created for electrical cardioversion and showed that, when compared to AP BTE incremental energy with patches, AP BTE maximum energy with patches (RR 1.35, 95% CI 1.17 to 1.55) likely results in a large increase, and active compression AP BTE incremental energy with patches (RR: 1.14, 95% CI 1.00 to 1.131) likely results in an increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: high). Use of AP BTE incremental with paddles (RR: 1.03, 95% CI 0.98 to 1.09; certainty of evidence: low) may lead to a slight increase, and AP MDS Incremental paddles (RR: 0.95, 95% CI 0.86 to 1.05; certainty of evidence: low) may lead to a slight decrease in efficacy. On the other hand, AP MDS incremental energy using patches (RR: 0.78, 95% CI 0.70 to 0.87), AA RBW incremental energy with patches (RR: 0.76, 95% CI 0.66 to 0.88), AP RBW incremental energy with patches (RR: 0.76, 95% CI 0.68 to 0.86), AA MDS incremental energy with patches (RR: 0.76, 95% CI 0.67 to 0.86) and AA MDS incremental energy with paddles (RR: 0.68, 95% CI 0.53 to 0.83) probably result in a decrease in this outcome when compared to AP BTE incremental energy with patches (certainty of evidence: moderate). The network for pharmacological cardioversion showed that bepridil (RR: 2.29, 95% CI 1.26 to 4.17) and quindine (RR: 1.53, (95% CI 1.01 to 2.32) probably result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up when compared to amiodarone (certainty of evidence: moderate). Dofetilide (RR: 0.79, 95% CI 0.56 to 1.44), sotalol (RR: 0.89, 95% CI 0.67 to 1.18), propafenone (RR: 0.79, 95% CI 0.50 to 1.25) and pilsicainide (RR: 0.39, 95% CI 0.02 to 7.01) may result in a reduction in this outcome when compared to amiodarone, but the certainty of evidence is low. For atrial flutter (14 trials), a network could be created only for antiarrhythmic drugs. Using placebo as the common comparator, ibutilide (RR: 21.45, 95% CI 4.41 to 104.37), propafenone (RR: 7.15, 95% CI 1.27 to 40.10), dofetilide (RR: 6.43, 95% CI 1.38 to 29.91), and sotalol (RR: 6.39, 95% CI 1.03 to 39.78) probably result in a large increase in the maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: moderate), and procainamide (RR: 4.29, 95% CI 0.63 to 29.03), flecainide (RR 3.57, 95% CI 0.24 to 52.30) and vernakalant (RR: 1.18, 95% CI 0.05 to 27.37) may result in a large increase in maintenance of sinus rhythm at hospital discharge or end of study follow-up (certainty of evidence: low). All tested electrical cardioversion strategies for atrial flutter had very high efficacy (97.9% to 100%). The rate of mortality (14 deaths) and stroke or systemic embolism (3 events) at 30 days was extremely low. Data on quality of life were scarce and of uncertain clinical significance. No information was available regarding heart failure readmissions. Data on duration of hospitalisation was scarce, of low quality, and could not be pooled. AUTHORS' CONCLUSIONS: Despite the low quality of evidence, this systematic review provides important information on electrical and pharmacological strategies to help patients and physicians deal with AF and atrial flutter. In the assessment of the patient comorbidity profile, antiarrhythmic drug onset of action and side effect profile versus the need for a physician with experience in sedation, or anaesthetics support for electrical cardioversion are key aspects when choosing the cardioversion method.

Individual patient data meta-analysis of the effects of fluoxetine on functional outcomes after acute stroke.

BACKGROUND: Three large randomized controlled trials of fluoxetine for stroke recovery have been performed. We performed an individual patient data meta-analysis (IPDM) on the combined data. METHODS: Fixed effects meta-analyses were performed on the combined data set, for the primary outcome (modified Rankin scale (mRS) at 6 months), and secondary outcomes common to the individual trials. As a sensitivity analysis, summary statistics from each trial were created and combined. FINDINGS: The three trials recruited a combined total of 5907 people (mean age 69.5 years (SD 12.3), 2256 (38%) females, 2-15 days post-stroke) from Australia, New Zealand, United Kingdom, Sweden, and Vietnam; and randomized them to fluoxetine 20 mg daily or matching placebo for 6 months. Data on 5833 (98.75%) were available at 6 months. The adjusted ordinal comparison of mRS was similar in the two groups (common OR 0.96, 95% CI 0.87 to 1.05, p = 0.37). There were no statistically significant interactions between the minimization variables (baseline probability of being alive and independent at 6 months, time to treatment, motor deficit, or aphasia) and pre-specified subgroups (including age, pathological type, inability to assess mood, proxy or patient consent, baseline depression, country). Fluoxetine increased seizure risk (2.64% vs 1.8%, p = 0.03), falls with injury (6.26% vs 4.51%, p = 0.03), fractures (3.15% vs 1.39%, p < 0.0001) and hyponatremia (1.22% vs 0.61%, p = 0.01) but reduced new depression (10.05% vs 13.42%, p < 0.0001). At 12 months, there was no difference in adjusted mRS (n = 5760; common OR 0.98, 95% CI 0.89 to 1.07). Sensitivity analyses gave the same results. INTERPRETATION: Fluoxetine 20 mg daily for 6 months did not improve functional recovery. It increased seizures, falls with injury, and bone fractures but reduced depression frequency at 6 months.

Shared decision making in older people after severe stroke.

Stroke is a major cause of death and lifelong disability. Although stroke treatments have improved, many patients are left with life-changing deficits. Shared decision making and consent are fundamental to good medical practice. This is challenging because stroke often causes mental incapacity, prior views might not be known and prognosis early after stroke is often uncertain. There are no large trials of shared decision making after severe stroke, so we need to rely on observational data to inform practice. Core ethical principles of autonomy, beneficence, non-maleficence and justice must underpin our decision making. 'Surrogate' decision makers will need to be involved if a patient lacks capacity, and prior expressed views and values and beliefs need to be taken into account in decision making. Patients and surrogates often feel shocked at the sudden nature of stroke, and experience grief including anticipatory grief. Health care professionals need to acknowledge these feelings and provide support, be clear about what decisions need to be made and provide sufficient information about the stroke, and the risks and benefits of treatments being considered. Shared decision making can be emotionally difficult for health care professionals and so working in a supportive environment with compassionate leadership is important. Further research is needed to better understand the nature of grief and what sort of psychological support would be most helpful. Large randomised trials of shared decision making are also needed.

Validation of general pain scores from multidomain assessment tools in stroke.

Purpose: We describe how well general pain reported in multidomain assessment tools correlated with pain-specific assessment tools; associations between general pain, activities of daily living and independence after stroke. Materials and methods: Analyses of individual participant data (IPD) from the Virtual International Stroke Trials Archive (VISTA) described correlation coefficients examining (i) direct comparisons of assessments from pain-specific and multidomain assessment tools that included pain, (ii) indirect comparisons of pain assessments with the Barthel Index (BI) and modified Rankin Scale (mRS), and (iii) whether pain identification could be enhanced by accounting for reported usual activities, self-care, mobility and anxiety/depression; factors associated with pain. Results: European Quality of Life 3- and 5-Level (EQ-5D-3L and EQ-5D-5L), RAND 36 Item Health Survey 1.0 (SF-36) or the 0-10 Numeric Pain Rating Scale (NPRS) were available from 10/94 studies (IPD = 10,002). The 0-10 NPRS was the only available pain-specific assessment tool and was a reference for comparison with other tools. Pearson correlation coefficients between the 0-10 NPRS and (A) the EQ-5D-3L and (B) EQ5D-5 L were r = 0.572 (n = 436) and r = 0.305 (n = 1,134), respectively. mRS was better aligned with pain by EQ-5D-3L (n = 8,966; r = 0.340) than by SF-36 (n = 623; r = 0.318). BI aligned better with pain by SF-36 (n = 623; r = -0.320). Creating a composite score using the EQ-5D 3 L and 5 L comprising pain, mobility, usual-activities, self-care and anxiety/depression did not improve correlation with the 0-10 NPRS. Discussion: The EQ-5D-3L pain domain aligned better than the EQ-5D-5L with the 0-10 NPRS and may inform general pain description where resources and assessment burden hinder use of additional, pain-specific assessments.

A roadmap for research in post-stroke fatigue: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

RATIONALE: Fatigue affects almost half of all people living with stroke. Stroke survivors rank understanding fatigue and how to reduce it as one of the highest research priorities. METHODS: We convened an interdisciplinary, international group of clinical and pre-clinical researchers and lived experience experts. We identified four priority areas: (1) best measurement tools for research, (2) clinical identification of fatigue and potentially modifiable causes, (3) promising interventions and recommendations for future trials, and (4) possible biological mechanisms of fatigue. Cross-cutting themes were aphasia and the voice of people with lived experience. Working parties were formed and structured consensus building processes were followed. RESULTS: We present 20 recommendations covering outcome measures for research, development, and testing of new interventions and priority areas for future research on the biology of post-stroke fatigue. We developed and recommend the use of the Stroke Fatigue Clinical Assessment Tool. CONCLUSIONS: By synthesizing current knowledge in post-stroke fatigue across clinical and pre-clinical fields, our work provides a roadmap for future research into post-stroke fatigue.

A roadmap for research in post-stroke fatigue: Consensus-based core recommendations from the third Stroke Recovery and Rehabilitation Roundtable.

RATIONALE: Fatigue affects almost half of all people living with stroke. Stroke survivors rank understanding fatigue and how to reduce it as one of the highest research priorities. METHODS: We convened an interdisciplinary, international group of clinical and pre-clinical researchers and lived experience experts. We identified four priority areas: (1) best measurement tools for research, (2) clinical identification of fatigue and potentially modifiable causes, (3) promising interventions and recommendations for future trials, and (4) possible biological mechanisms of fatigue. Cross-cutting themes were aphasia and the voice of people with lived experience. Working parties were formed and structured consensus building processes were followed. RESULTS: We present 20 recommendations covering outcome measures for research, development, and testing of new interventions and priority areas for future research on the biology of post-stroke fatigue. We developed and recommend the use of the Stroke Fatigue Clinical Assessment Tool. CONCLUSIONS: By synthesizing current knowledge in post-stroke fatigue across clinical and pre-clinical fields, our work provides a roadmap for future research into post-stroke fatigue.

Non-pharmacological interventions for the treatment of post-stroke fatigue: A systematic review.

BACKGROUND: Post-stroke fatigue (PSF) affects 50% of stroke survivors. Current guidance on management of this condition is limited. AIMS: This systematic review and meta-analysis aimed to identify and analyze all randomized clinical trials (RCTs) of non-pharmacological interventions for the treatment of PSF. SUMMARY OF REVIEW: Six electronic databases were searched from inception to January 2023 for English-language RCTs investigating the efficacy of non-pharmacological interventions versus passive controls in patients with PSF. The primary outcome was fatigue severity at the end of the intervention. The Cochrane risk-of-bias (ROB)2 tool was used to assess evidence quality. A total of 7990 records were retrieved, 333 studies were scrutinized, and 13 completed RCTs (484 participants) were included. Interventions included psychological therapies, physical therapies, and brain stimulation. Nine studies provided sufficient data for meta-analysis, of which seven also had follow-up data. Fatigue severity was lower in the intervention groups at the end of the intervention compared with control (participants = 310, standardized mean difference (SMD) = -0.57, 95% confidence intervals (CIs) (-0.87 to -0.28)) and at follow-up (participants = 112, SMD = -0.36, 95% CIs (-0.83 to 0.10)). Certainty in the effect estimate was downgraded to low for a serious ROB and imprecision. Subgroup analysis revealed significant benefits with physical therapy and brain stimulation but not psychological therapies, though sample sizes were low. CONCLUSION: Non-pharmacological interventions improved fatigue but the quality of evidence was low. Further RCTs are needed for PSF management.

Prevalence, Trajectory, and Predictors of Poststroke Pain: Retrospective Analysis of Pooled Clinical Trial Data Set.

BACKGROUND: Poststroke pain remains underdiagnosed and inadequately managed. To inform the optimum time to initiate interventions, we examined prevalence, trajectory, and participant factors associated with poststroke pain. METHODS: Eligible studies from the VISTA (Virtual International Stroke Trials Archives) included an assessment of pain. Analyses of individual participant data examined demography, pain, mobility, independence, language, anxiety/depression, and vitality. Pain assessments were standardized to the European Quality of Life Scale (European Quality of Life 5 Dimensions 3 Level) pain domain, describing no, moderate, or extreme pain. We described pain prevalence, associations between participant characteristics, and pain using multivariable models. RESULTS: From 94 studies (n>48 000 individual participant data) in VISTA, 10 (n=10 002 individual participant data) included a pain assessment. Median age was 70.0 years (interquartile range [59.0-77.1]), 5560 (55.6%) were male, baseline stroke severity was National Institutes of Health Stroke Scale score 10 (interquartile range [7-15]). Reports of extreme pain ranged between 3% and 9.5% and were highest beyond 2 years poststroke (31/328 [9.5%]); pain trajectory varied by study. Poorer independence was significantly associated with presence of moderate or extreme pain (5 weeks-3 months odds ratio [OR], 1.5 [95% CI, 1.4-1.6]; 4-6 months OR, 1.7 [95% CI, 1.3-2.1]; >6 months OR, 1.5 [95% CI, 1.2-2.0]), and increased severity of pain (5 weeks-3 months: OR, 1.2 [95% CI, 1.1-1.2]; 4-6 months OR, 1.1 [95% CI, 1.1-1.2]; >6 months, OR, 1.2 [95% CI, 1.1-1.2]), after adjusting for covariates. Anxiety/depression and lower vitality were each associated with pain severity. CONCLUSIONS: Between 3% and 9.5% of participants reported extreme poststroke pain; the presence and severity of pain were independently associated with dependence at each time point. Future studies could determine whether and when interventions may reduce the prevalence and severity of poststroke pain.

Systematic review: Pharmacological interventions for the treatment of post-stroke fatigue.

BACKGROUND: Post-stroke fatigue (PSF) affects around 50% of stroke survivors. Previous systematic reviews of randomized controlled trials found insufficient evidence to guide practice, but most excluded Chinese studies. Furthermore, their searches are now out-of-date. AIMS: To systematically review and perform a meta-analysis of randomized placebo-controlled trials of pharmacological interventions for treating PSF. METHODS: We screened Airitri, CNKI, VIP, CINAHL, ClinicalTrials.gov, CENTRAL, Cochrane Stroke Group Trial Register, EMBASE, EU Clinical Trial Register, ISRCTN, MEDLINE, PsycINFO, Wanfang, and WHO ICTRP up to 11 November 2022. Our primary outcome was fatigue severity. We conducted subgroup analysis by drug type and sensitivity analysis after excluding the trials at high risk of bias. Secondary outcomes included mood and quality of life. RESULTS: We screened 33,297 citations and identified 10 published completed trials, 6 unpublished completed trials, and 6 ongoing trials. Pharmacological treatments were associated with lower fatigue severity at the end of treatment (10 published completed trials, 600 participants, pooled standardized mean difference (SMD) = -0.80, 95% confidence interval (CI): -1.29 to -0.31; I2 = 86%, p < 0.00001), but not at follow-up (265 participants, pooled SMD = -0.14, 95% CI: -0.38 to 0.10; I2 = 0, p = 0.51). However, these trials were small and had considerable risk of bias. Beneficial effects were seen in trials with low risk of bias on randomization, missing outcome data, and reporting bias. There were insufficient data on secondary outcomes for meta-analysis, but six trials reported improved quality of life. CONCLUSION: There is insufficient evidence to support a particular pharmacological treatment for PSF, thus current clinical guidelines do not require amendment.

Intervention to reduce sedentary behaviour and improve outcomes after stroke (Get Set Go): a study protocol for the process evaluation of a pilot cluster randomised controlled trial (RECREATE).

INTRODUCTION: Stroke survivors spend long periods of time engaging in sedentary behaviour (SB) even when their functional recovery is good. In the RECREATE programme, an intervention aimed at reducing SB ('Get Set Go') will be implemented and evaluated in a pragmatic external pilot cluster randomised controlled trial with embedded process and economic evaluations. We report the protocol for the process evaluation which will address the following objectives: (1) describe and clarify causal assumptions about the intervention, and its mechanisms of impact; (2) assess implementation fidelity; (3) explore views, perceptions and acceptability of the intervention to staff, stroke survivors and their carers; (4) establish the contextual factors that influence implementation, intervention mechanisms and outcomes. METHODS AND ANALYSIS: This pilot trial will be conducted in 15 UK-based National Health Service stroke services. This process evaluation study, underpinned by the Medical Research Council guidance, will be undertaken in six of the randomised services (four intervention, two control). Data collection includes the following: observations of staff training sessions, non-participant observations in inpatient and community settings, semi-structured interviews with staff, patients and carers, and documentary analysis of key intervention components. Additional quantitative implementation data will be collected in all sites. Training observations and documentary analysis data will be summarised, with other observational and interview data analysed using thematic analysis. Relevant theories will be used to interpret the findings, including the theoretical domains framework, normalisation process theory and the theoretical framework of acceptability. Anticipated outputs include the following: recommendations for intervention refinements (both content and implementation); a revised implementation plan and a refined logic model. ETHICS AND DISSEMINATION: The study was approved by Yorkshire & The Humber - Bradford Leeds Research Ethics Committee (REC reference: 19/YH/0403). Findings will be disseminated via peer review publications, and national and international conference presentations. TRIAL REGISTRATION NUMBER: ISRCTN82280581.

RECREATE: a study protocol for a multicentre pilot cluster randomised controlled trial (cRCT) in UK stroke services evaluating an intervention to reduce sedentary behaviour in stroke survivors (Get Set Go) with embedded process and economic evaluations.

INTRODUCTION: Sedentary behaviour (sitting or lying during waking hours without being otherwise active) is strongly associated with adverse health outcomes, including all-cause, cancer and cardiovascular mortality in adults. Stroke survivors are consistently reported as being more sedentary than healthy age-matched controls, spending more hours sedentary daily and sustaining longer unbroken bouts of sedentary time. An evidence-based and clinically feasible intervention ('Get Set Go') was developed. A pragmatic definitive trial to evaluate Get Set Go was planned; however, due to the unprecedented effects of the COVID-19 pandemic on National Health Service (NHS) services this study was reduced in size and scope to become an external pilot trial. We report the protocol for this external pilot trial, which aims to undertake a preliminary exploration of whether Get Set Go is likely to improve ability to complete extended activities of daily living in the first year post-stroke and inform future trial designs in stroke rehabilitation. METHODS AND ANALYSIS: This study is a pragmatic, multicentre, two-arm, external pilot cluster randomised controlled trial with embedded process and economic evaluations. UK-based stroke services will be randomised 1:1 to the intervention (usual care plus Get Set Go) or control (usual care) arm. Fifteen stroke services will recruit 300-400 stroke inpatient and carer participants, with follow-up at 6, 12 and 24 months. The proposed primary endpoint is stroke survivor self-reported Nottingham Extended Activities of Daily Living scale at 12 months. Endpoint analyses will be exploratory and provide preliminary estimates of intervention effect. The process evaluation will provide valuable information on intervention fidelity, acceptability and how it can be optimised. ETHICS AND DISSEMINATION: The study has been approved by Yorkshire and The Humber - Bradford-Leeds Research Ethics Committee (Ref: 19/YH/0403). Results will be disseminated through journal publications and conference presentations. TRIAL REGISTRATION NUMBER: This trial was registered prospectively on 01 April 2020 (ISRCTN ref: ISRCTN82280581).

Neuroimaging correlates of post-stroke fatigue: A systematic review and meta-analysis.

BACKGROUND: Fatigue is a common and disabling symptom following stroke, but its underlying mechanisms are unknown. Associations with a number of imaging features have been proposed. AIMS: We aimed to assess whether neuroimaging parameters could better inform our understanding of possible causes of post-stroke fatigue (PSF) through systematic review and meta-analysis. METHODS: Using a predefined protocol registered with PROSPERO (ID: CRD42022303168), we searched EMBASE, MEDLINE, PubMed, and PsycInfo for studies assessing PSF and computerized tomography (CT), magnetic resonance (MR), positron emission tomography (PET) imaging, or diffusion tensor imaging (DTI). We extracted neuroimaging parameters and narratively analyzed study results to assess any association with PSF. Where there were 3+ similar studies, we carried out a meta-analysis using inverse-variance random-effects model to estimate the total association of each neuroimaging parameter on PSF. The risk of bias was assessed using the Newcastle and Ottawa Scale. RESULTS: We identified 46 studies (N = 6543); in many studies, associations with fatigue were secondary or subanalyses (28.3%). Imaging parameters were assessed across eight variables: lesion lateralization, lesion location, lesion volume, brain atrophy, infarct number, cerebral microbleeds, white matter hyperintensities (WMHs), and network measures. Most variables showed no conclusive evidence for any association with fatigue. Meta-analysis, where possible, showed no association of the following with PSF; left lesion lateralization (OR: 0.88, 95% CI (0.64, 1. 22) (p = 0.45)), infratentorial lesion location (OR: 1.83, 95% CI (0.63, 5.32) (p = 0.27)), and WMH (OR: 1.21, 95% CI (0.84, 1.75) (p = 0.29)). Many studies assessed lesion location with mixed findings; only one used voxel-symptom lesion-mapping (VSLM). Some small studies suggested an association between altered functional brain networks, namely frontal, fronto-striato-thalamic, and sensory processing networks, with PSF. CONCLUSION: There was little evidence for the association between any neuroimaging parameters and PSF. Future studies should utilize advanced imaging techniques to fully understand the role of lesion location in PSF, while the role of altered brain networks in mediating PSF merits further research.

A systematic review and synthesis of global stroke guidelines on behalf of the World Stroke Organization.

BACKGROUND: There are multiple stroke guidelines globally. To synthesize these and summarize what existing stroke guidelines recommend about the management of people with stroke, the World Stroke Organization (WSO) Guideline committee, under the auspices of the WSO, reviewed available guidelines. AIMS: To systematically review the literature to identify stroke guidelines (excluding primary stroke prevention and subarachnoid hemorrhage) since 1 January 2011, evaluate quality (The international Appraisal of Guidelines, Research and Evaluation (AGREE II)), tabulate strong recommendations, and judge applicability according to stroke care available (minimal, essential, advanced). SUMMARY OF REVIEW: Searches identified 15,400 titles; 911 texts were retrieved, 200 publications scrutinized by the three subgroups (acute, secondary prevention, rehabilitation), and recommendations extracted from most recent version of relevant guidelines. For acute treatment, there were more guidelines about ischemic stroke than intracerebral hemorrhage; recommendations addressed pre-hospital, emergency, and acute hospital care. Strong recommendations were made for reperfusion therapies for acute ischemic stroke. For secondary prevention, strong recommendations included establishing etiological diagnosis; management of hypertension, weight, diabetes, lipids, and lifestyle modification; and for ischemic stroke, management of atrial fibrillation, valvular heart disease, left ventricular and atrial thrombi, patent foramen ovale, atherosclerotic extracranial large vessel disease, intracranial atherosclerotic disease, and antithrombotics in non-cardioembolic stroke. For rehabilitation, there were strong recommendations for organized stroke unit care, multidisciplinary rehabilitation, task-specific training, fitness training, and specific interventions for post-stroke impairments. Most recommendations were from high-income countries, and most did not consider comorbidity, resource implications, and implementation. Patient and public involvement was limited. CONCLUSION: The review identified a number of areas of stroke care where there was strong consensus. However, there was extensive repetition and redundancy in guideline recommendations. Future guideline groups should consider closer collaboration to improve efficiency, include more people with lived experience in the development process, consider comorbidity, and advise on implementation.

Association of post-stroke fatigue with physical activity and physical fitness: A systematic review and meta-analysis.

BACKGROUND: It has been hypothesized that post-stroke fatigue (PSF) is associated with reduced physical activity (PA) and impaired physical fitness (fitness). Understanding associations between PSF and PA, and/or fitness could help guide the development of targeted exercise interventions to treat PSF. AIMS: Our systematic review and meta-analysis aimed to investigate PSF's associations with PA and fitness. SUMMARY OF REVIEW: Following a registered protocol, we included studies with cross-sectional or prospective observational designs, published in English or a Scandinavian language, which reported an association of PSF with PA and/or fitness in adult stroke survivors. We searched MEDLINE, Embase, AMED, CINAHL, PsycINFO, ClinicalTrials.gov, and World Health Organization's International Clinical Trials Registry Platform from inception to November 30, 2022. Risk of bias was assessed using Quality in Prognosis Studies. Thirty-two unique studies (total n = 4721 participants, 55% male), and three study protocols were included. We used random-effects meta-analysis to pool data for PA and fitness outcomes, and vote-counting of direction of association to synthesize data that could not be meta-analyzed. We found moderate-certainty evidence of a weak association between higher PSF and impaired fitness (meta r = -0.24; 95% confidence interval (CI) = -0.33, -0.15; n = 905, 7 studies), and very low-certainty evidence of no association between PSF and PA (meta r = -0.09; 95% CI = -0.34, 0.161; n = 430, 3 studies). Vote-counting showed a higher proportion of studies with associations between higher PSF and impaired fitness (pˆ = 0.83; 95% CI = 0.44, 0.97; p = 0.22, n = 298, 6 studies), and with associations between higher PSF and lower PA (pˆ = 0.75; 95% CI = 0.51, 0.90; p = 0.08, n = 2566, 16 studies). Very low- to moderate-certainty evidence reflects small study sample sizes, high risk of bias, and inconsistent results. CONCLUSIONS: The meta-analysis showed moderate-certainty evidence of an association between higher PSF and impaired fitness. These results indicate that fitness might protect against PSF. Larger prospective studies and randomized controlled trials evaluating the effect of exercise on PSF are needed to confirm these findings.

Predictors of post-stroke cognitive impairment using acute structural MRI neuroimaging: A systematic review and meta-analysis.

BACKGROUND: Stroke survivors are at an increased risk of developing post-stroke cognitive impairment and post-stroke dementia; those at risk could be identified by brain imaging routinely performed at stroke onset. AIM: This systematic review aimed to identify features which are associated with post-stroke cognitive impairment (including dementia) on magnetic resonance imaging (MRI) performed at stroke diagnosis. SUMMARY OF REVIEW: We searched the literature from inception to January 2022 and identified 10,284 records. We included studies that performed MRI at the time of stroke (0-30 days after a stroke) and assessed cognitive outcome at least 3 months after stroke. We synthesized findings from 26 papers, comprising 27 stroke-populations (N = 13,114, average age range = 40-80 years, 19-62% female). When data were available, we pooled unadjusted (ORu) and adjusted (ORa) odds ratios.We found associations between cognitive outcomes and presence of cerebral atrophy (three studies, N = 453, ORu = 2.48, 95% CI = 1.15-4.62), presence of microbleeds (two studies, N = 9151, ORa = 1.36, 95% CI = 1.08-1.70), and increasing severity of white matter hyperintensities (three studies, N = 704, ORa = 1.26, 95% CI = 1.06-1.49). Increasing cerebral small vessel disease score was associated with cognitive outcome following unadjusted analysis only (two studies, N = 499, ORu = 1.34, 95%CI = 1.12-1.61; three studies, N = 950, ORa = 1.23, 95% CI = 0.96-1.57). Associations remained after controlling for pre-stroke cognitive impairment. We did not find associations between other stroke features and cognitive outcome, or there were insufficient data. CONCLUSION: Acute stroke MRI features may enable healthcare professionals to identify patients at risk of post-stroke cognitive problems. However, there is still substantial uncertainty about the prognostic utility of acute MRI for this.

Repeated Measures of Modified Rankin Scale Scores to Assess Functional Recovery From Stroke: AFFINITY Study Findings.

Background Function after acute stroke using the modified Rankin Scale (mRS) is usually assessed at a point in time. The analytical implications of serial mRS measurements to evaluate functional recovery over time is not completely understood. We compare repeated-measures and single-measure analyses of the mRS from a randomized clinical trial. Methods and Results Serial mRS data from AFFINITY (Assessment of Fluoxetine in Stroke Recovery), a double-blind placebo randomized clinical trial of fluoxetine following stroke (n=1280) were analyzed to identify demographic and clinical associations with functional recovery (reduction in mRS) over 12 months. Associations were identified using single-measure (day 365) and repeated-measures (days 28, 90, 180, and 365) partial proportional odds logistic regression. Ninety-five percent of participants experienced a reduction in mRS after 12 months. Functional recovery was associated with age at stroke <70 years; no prestroke history of diabetes, coronary heart disease, or ischemic stroke; prestroke history of depression, a relationship partner, living with others, independence, or paid employment; no fluoxetine intervention; ischemic stroke (compared with hemorrhagic); stroke treatment in Vietnam (compared with Australia or New Zealand); longer time since current stroke; and lower baseline National Institutes of Health Stroke Scale & Patient Health Questionnaire-9 scores. Direction of associations was largely concordant between single-measure and repeated-measures models. Association strength and variance was generally smaller in the repeated-measures model compared with the single-measure model. Conclusions Repeated-measures may improve trial precision in identifying trial associations and effects. Further repeated-measures stroke analyses are required to prove methodological value. Registration URL: http://www.anzctr.org.au; Unique identifier: ACTRN12611000774921.

Post stroke intervention trial in fatigue (POSITIF): Randomised multicentre feasibility trial.

OBJECTIVE: To test the feasibility of a telephone delivered intervention, informed by cognitive behavioural principles, for post-stroke fatigue, and estimated its effect on fatigue and other outcomes. DESIGN: Randomised controlled parallel group trial. SETTING: Three Scottish stroke services. SUBJECTS: Stroke survivors with fatigue three months to two years post-stroke onset. INTERVENTIONS: Seven telephone calls (fortnightly then a 'booster session' at 16 weeks) of a manualised intervention, plus information about fatigue, versus information only. MAIN MEASURES: Feasibility of trial methods, and collected outcome measures (fatigue, mood, anxiety, social participation, quality of life, return to work) just before randomisation, at the end of treatment (four months after randomisation) and at six months after randomisation. RESULTS: Between October 2018 and January 2020, we invited 886 stroke survivors to participate in postal screening: 188/886 (21%) returned questionnaires and consented, of whom 76/188 (40%) were eligible and returned baseline forms; 64/76 (84%) returned six month follow-up questionnaires. Of the 39 allocated the intervention, 23 (59%) attended at least four sessions. At six months, there were no significant differences between the groups (adjusted mean differences in Fatigue Assessment Scale -0.619 (95% CI -4.9631, 3.694; p = 0.768), the Generalised Anxiety Disorder 7 -0.178 (95% CI -3.823, 3.467, p = 0.92), and the Patient Health Questionnaire -0.247 (95% CI -2.935, 2.442, p = 0.851). There were no between-group differences in quality of life, social participation or return to work. CONCLUSION: Patients can be recruited to a trial of this design. These data will inform the design of further trials in post-stroke fatigue.

Informing Patients with Acute Stroke About their Risk of Dementia: A Survey of UK Healthcare Professionals.

OBJECTIVES: Cognitive problems following stroke are of key concern to stroke survivors. Discussing risk of dementia at the time of stroke could have implications for follow-up care. However, informing someone who has just had a stroke about risk of dementia could cause distress. This survey explored healthcare professionals' views on discussing risk of post-stroke dementia at the time of stroke. MATERIALS AND METHODS: This online survey was aimed at all UK healthcare professionals who care for patients with stroke. The survey was distributed via the mailing lists of seven professional stroke-related organisations and Twitter. Descriptive statistics were used to summarise findings. RESULTS: Sixty healthcare professionals completed the survey. Healthcare professionals were aware of the main risk factors associated with post-stroke dementia (e.g. previous stroke, age). Most respondents (N=34/60, 57%) thought that patients with acute stroke would benefit from knowing if they are at high risk of dementia, and 75% (N=45/60) agreed that carers would benefit. Despite this, the majority of healthcare professionals (N=47/53, 89%) who cared for patients with acute stroke in the past year said they rarely/never discussed dementia with their patients. Most respondents (N=46/60, 77%) thought risk of dementia should be discussed 1-6 months post-stroke. CONCLUSION: Although healthcare professionals felt it would be helpful to discuss risk of post-stroke dementia, in practice, most said that they rarely or never discussed this with their patients. Stroke survivors could benefit from a healthcare system that offers appropriate follow-up care and support to patients at high risk of dementia.