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.

Macro- and microvascular contributions to cerebral structural alterations in patients with asymptomatic carotid artery stenosis.

Atherosclerosis can underly internal carotid artery stenosis (ICAS), a major risk factor for ischemic stroke, as well as small vessel disease (SVD). This study aimed to investigate hemodynamics and structural alterations associated with SVD in ICAS patients. 28 patients with unilateral asymptomatic ICAS and 30 age-matched controls underwent structural (T1-/T2-weighted and diffusion tensor imaging [DTI]) and hemodynamic (pseudo-continuous arterial spin labeling and dynamic susceptibility contrast) magnetic resonance imaging. SVD-related alterations were assessed using free water (FW), FW-corrected DTI, and peak-width of skeletonized mean diffusivity (PSMD). Furthermore, cortical thickness, cerebral blood flow (CBF), and capillary transit time heterogeneity (CTH) were analyzed. Ipsilateral to the stenosis, cortical thickness was significantly decreased in the posterior dorsal cingulate cortex (p = 0.024) and temporal pole (p = 0.028). ICAS patients exhibited elevated PSMD (p = 0.005), FW (p < 0.001), and contralateral alterations in FW-corrected DTI metrics. We found significantly lateralized CBF (p = 0.011) and a tendency for lateralized CTH (p = 0.067) in the white matter (WM) related to ICAS. Elevated PSMD and FW may indicate a link between SVD and WM changes. Contralateral alterations were seen in FW-corrected DTI, whereas hemodynamic and cortical changes were mainly ipsilateral, suggesting SVD might influence global brain changes concurrent with ICAS-related hemodynamic alterations.

Electronic informed consent: effects on enrolment, practical and economic benefits, challenges, and drawbacks-a systematic review of studies within randomized controlled trials.

BACKGROUND: Enrolment is one of the most challenging aspects of conducting clinical trials, preceded by the process of informed consent (IC). Different strategies to improve recruitment in clinical trials have been used, including electronic IC. During COVID-19 pandemic, barriers to enrolment have been evident. Although digital technologies were acknowledged as the future of clinical research and potential advantages were shown for recruitment, electronic informed consent (e-IC) has not yet been globally adopted. The purpose of this review is to investigate the effect of using e-IC on enrolment, practical and economic benefits, challenges, and drawbacks when compared to traditional informed consent, through a systematic review. METHODS: Embase, Global Health Library, Medline, and The Cochrane Library databases were searched. No limit was set for publication date, age, sex, or study design. We included all studies within a randomized controlled trial (RCT), published in English, Chinese or Spanish, evaluating the electronic consent process used in the parent RCT. Studies were included if any of the three components ((i) information provision, (ii) participant's comprehension, (iii) signature) of the IC process was designed as electronic, whether administered remotely or face-to-face. The primary outcome was the rate of enrolment to the parent trial. Secondary outcomes were summarized according to the various findings reported on the use of electronic consent. RESULTS: From a total of 9069 titles, 12 studies were included in the final analysis with a total of 8864 participants. Five studies of high heterogeneity and risk of bias showed mixed results on the efficacy of e-IC on enrolment. Data of included studies suggested e-IC could improve comprehension and recall of study-related information. Meta-analysis could not be conducted due to different study designs and outcome measures and the predominantly qualitative findings. CONCLUSION: Few published studies have investigated the impact of e-IC on enrolment and findings were mixed. e-IC may improve participant's comprehension and recall of information. High-quality studies are needed to evaluate the potential benefit of e-IC to increase clinical trial enrolment. TRIAL REGISTRATION: PROSPERO CRD42021231035 . Registration date: 19-Feb-2021.

Clinical Diagnosis and Magnetic Resonance Imaging in Patients With Transient and Minor Neurological Symptoms: A Prospective Cohort Study.

BACKGROUND: The utility of magnetic resonance imaging (MRI) brain in patients with transient or minor neurological symptoms is uncertain. We sought to determine the proportion of participants with transient or minor neurological symptoms who had MRI evidence of acute ischemia at different clinical probabilities of transient ischemic attack (TIA) or minor stroke. METHODS: Cohort of participants with transient or minor neurological symptoms from emergency and outpatient settings. Clinicians at different levels of training gave each participant a diagnostic probability (probable when TIA/stroke was the most likely differential diagnosis; possible when TIA/stroke was not the most likely differential diagnosis; or uncertain when diagnostic probability could not be given) before 1.5 or 3T brain MRI ≤5 days from onset. Post hoc, each clinical syndrome was defined blind to MRI findings as National Institute of Neurological Disorders and Stroke criteria TIA/stroke; International Headache Society criteria migraine aura; non-TIA focal symptoms; or nonfocal symptoms. MRI evidence of acute ischemia was defined by 2 reads of MRI. Stroke was ascertained for at least 90 days and up to 18 months after recruitment. RESULTS: Two hundred seventy-two participated (47% female, mean age 60, SD 14), 58% with MRI ≤2 days of onset. Most (92%) reported focal symptoms. MR evidence of acute ischemia was found, for stroke/TIA clinical probabilities of probable 23 out of 75 (31% [95% CI, 21%-42%]); possible 26 out of 151 (17% [12%-24%]); and uncertain 9 out of 43, (20% [10%-36%]). MRI evidence of acute ischemia was found in National Institute of Neurological Disorders and Stroke criteria TIA/stroke 40 out of 95 (42% [32%-53%]); migraine aura 4 out of 38 (11% [3%-25%]); non-TIA focal symptoms 16 out of 99 (16% [10%-25%]); and no focal features 1 out of 29 (3% [0%-18%]). After MRI, a further 14 (5% [95% CI, 3-8]) would be treated with an antiplatelet drug compared with treatment plan before MRI. By 18 months, a new ischemic stroke occurred in 9 out of 61 (18%) patients with MRI evidence of acute ischemia and 2 out of 211 (1%) without (age-adjusted hazard ratio, 13 [95% CI, 3-62]; P<0.0001). CONCLUSIONS: MRI evidence of acute brain ischemia was found in about 1 in 6 transient or minor neurological symptoms patients with a nonstroke/TIA initial diagnosis or uncertain diagnosis. Methods to determine the clinical and cost-effectiveness of MRI are needed in this population.

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.

18F-NaF PET/MRI for Detection of Carotid Atheroma in Acute Neurovascular Syndrome.

Background MRI and fluorine 18-labeled sodium fluoride (18F-NaF) PET can be used to identify features of plaque instability, rupture, and disease activity, but large studies have not been performed. Purpose To evaluate the association between 18F-NaF activity and culprit carotid plaque in acute neurovascular syndrome. Materials and Methods In this prospective observational cohort study (October 2017 to January 2020), participants underwent 18F-NaF PET/MRI. An experienced clinician determined the culprit carotid artery based on symptoms and record review. 18F-NaF uptake was quantified using standardized uptake values and tissue-to-background ratios. Statistical significance was assessed with the Welch, χ2, Wilcoxon, or Fisher test. Multivariable models were used to evaluate the relationship between the imaging markers and the culprit versus nonculprit vessel. Results A total of 110 participants were evaluated (mean age, 68 years ± 10 [SD]; 70 men and 40 women). Of the 110, 34 (32%) had prior cerebrovascular disease, and 26 (24%) presented with amaurosis fugax, 54 (49%) with transient ischemic attack, and 30 (27%) with stroke. Compared with nonculprit carotids, culprit carotids had greater stenoses (≥50% stenosis: 30% vs 15% [P = .02]; ≥70% stenosis: 25% vs 4.5% [P < .001]) and had increased prevalence of MRI-derived adverse plaque features, including intraplaque hemorrhage (42% vs 23%; P = .004), necrotic core (36% vs 18%; P = .004), thrombus (7.3% vs 0%; P = .01), ulceration (18% vs 3.6%; P = .001), and higher 18F-NaF uptake (maximum tissue-to-background ratio, 1.38 [IQR, 1.12-1.82] vs 1.26 [IQR, 0.99-1.66], respectively; P = .04). Higher 18F-NaF uptake was positively associated with necrosis, intraplaque hemorrhage, ulceration, and calcification and inversely associated with fibrosis (P = .04 to P < .001). In multivariable analysis, carotid stenosis at or over 70% (odds ratio, 5.72 [95% CI: 2.2, 18]) and MRI-derived adverse plaque characteristics (odds ratio, 2.16 [95% CI: 1.2, 3.9]) were both associated with the culprit versus nonculprit carotid vessel. Conclusion Fluorine 18-labeled sodium fluoride PET/MRI characteristics were associated with the culprit carotid vessel in study participants with acute neurovascular syndrome. Clinical trial registration no. NCT03215550 and NCT03215563 © RSNA, 2022 Online supplemental material is available for this article.

Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) might theoretically reduce post-stroke disability by direct effects on the brain. This Cochrane Review was first published in 2012 and last updated in 2019. OBJECTIVES: To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post-stroke, and to determine whether treatment with SSRIs is associated with adverse effects. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched 7 January 2021), Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, 7 January 2021), MEDLINE (1946 to 7 January 2021), Embase (1974 to 7 January 2021), CINAHL (1982 to 7 January 2021), PsycINFO (1985 to 7 January 2021), and AMED (1985 to 7 January 2021). PsycBITE had previously been searched (16 July 2018). We searched clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) recruiting stroke survivors within the first year. The intervention was any SSRI, at any dose, for any period, and for any indication. The comparator was usual care or placebo. Studies reporting at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, cognition, healthcare cost, death, adverse events and leaving the study early) were included in the meta-analysis. The primary analysis included studies at low risk of bias. DATA COLLECTION AND ANALYSIS: We extracted data on demographics, stroke type and, our pre-specified outcomes, and bias sources. Two review authors independently extracted data. We used mean difference (MD) or standardised mean differences (SMDs) for continuous variables, and risk ratios (RRs) for dichotomous variables, with 95% confidence intervals (CIs). We assessed bias risks and applied GRADE criteria. MAIN RESULTS: We identified 76 eligible studies (13,029 participants); 75 provided data at end of treatment, and of these two provided data at follow-up. Thirty-eight required participants to have depression to enter. The duration, drug, and dose varied. Six studies were at low risk of bias across all domains; all six studies did not need participants to have depression to enter, and all used fluoxetine. Of these six studies, there was little to no difference in disability between groups SMD -0.0; 95% CI -0.05 to 0.05; 5 studies, 5436 participants, high-quality evidence) or in independence (RR 0.98; 95% CI 0.93 to 1.03; 5 studies, 5926 participants; high-quality evidence) at the end of treatment. In the studies at low risk of bias across all domains, SSRIs slightly reduced the average depression score (SMD 0.14 lower, 95% CI 0.19 lower to 0.08 lower; 4 studies; 5356 participants, high-quality evidence) and there was a slight reduction in the proportion with depression (RR 0.75, 95% CI 0.65 to 0.86; 3 studies, 5907 participants, high-quality evidence). Cognition was slightly better in the control group (MD -1.22, 95% CI -2.37 to -0.07; 4 studies, 5373 participants, moderate-quality evidence). Only one study (n = 30) reported neurological deficit score (SMD -0.39, 95% CI -1.12 to 0.33; low-quality evidence). SSRIs resulted in little to no difference in motor deficit (SMD 0.03, -0.02 to 0.08; 6 studies, 5518 participants, moderate-quality evidence). SSRIs slightly increased the proportion leaving the study early (RR 1.57, 95% CI 1.03 to 2.40; 6 studies, 6090 participants, high-quality evidence). SSRIs slightly increased the outcome of a seizure (RR 1.40, 95% CI 1.00 to 1.98; 6 studies, 6080 participants, moderate-quality evidence) and a bone fracture (RR 2.35, 95% CI 1.62 to 3.41; 6 studies, 6080 participants, high-quality evidence). One study at low risk of bias across all domains reported gastrointestinal side effects (RR 1.71, 95% CI 0.33, to 8.83; 1 study, 30 participants). There was no difference in the total number of deaths between SSRI and placebo (RR 1.01, 95% CI 0.82 to 1.24; 6 studies, 6090 participants, moderate quality evidence). SSRIs probably result in little to no difference in fatigue (MD -0.06; 95% CI -1.24 to 1.11; 4 studies, 5524 participants, moderate-quality of evidence), nor in quality of life (MD 0.00; 95% CI -0.02 to 0.02, 3 studies, 5482 participants, high-quality evidence). When all studies, irrespective of risk of bias, were included, SSRIs reduced disability scores but not the proportion independent. There was insufficient data to perform a meta-analysis of outcomes at end of follow-up. Several small ongoing studies are unlikely to alter conclusions. AUTHORS' CONCLUSIONS: There is high-quality evidence that SSRIs do not make a difference to disability or independence after stroke compared to placebo or usual care, reduced the risk of future depression, increased bone fractures and probably increased seizure risk.

Effects of Fluoxetine on Outcomes at 12 Months After Acute Stroke: Results From EFFECTS, a Randomized Controlled Trial.

Background and Purpose: The EFFECTS (Efficacy of Fluoxetine­a Randomised Controlled Trial in Stroke) recently reported that 20 mg fluoxetine once daily for 6 months after acute stroke did not improve functional outcome but reduced depression and increased fractures and hyponatremia at 6 months. The purpose of this predefined secondary analysis was to identify if any effects of fluoxetine were maintained or delayed over 12 months. Methods: EFFECTS was an investigator-led, randomized, placebo-controlled, double-blind, parallel group trial in Sweden that enrolled adult patients with stroke. Patients were randomized to 20 mg oral fluoxetine or matching placebo for 6 months and followed for another 6 months. The primary outcome was functional outcome (modified Rankin Scale), at 6 months. Predefined secondary outcomes for these analyses included the modified Rankin Scale, health status, quality of life, fatigue, mood, and depression at 12 months. Results: One thousand five hundred patients were recruited from 35 centers in Sweden between 2014 and 2019; 750 were allocated fluoxetine and 750 placebo. At 12 months, modified Rankin Scale data were available in 715 (95%) patients allocated fluoxetine and 712 (95%) placebo. The distribution of modified Rankin Scale categories was similar in the 2 groups (adjusted common odds ratio, 0.92 [95% CI, 0.76­1.10]). Patients allocated fluoxetine scored worse on memory with a median value of 89 (interquartile range, 75­100) versus 93 (interquartile range, 82­100); P=0.0021 and communication 93 (interquartile range, 82­100) versus 96 (interquartile range, 86­100); P=0.024 domains of the Stroke Impact Scale compared with placebo. There were no other differences in secondary outcomes. Conclusions: Fluoxetine after acute stroke had no effect on functional outcome at 12 months. Patients allocated fluoxetine scored worse on memory and communication on the Stroke Impact Scale compared with placebo, but this is likely to be due to chance. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02683213.

Effects of Antiplatelet Therapy After Stroke Caused by Intracerebral Hemorrhage: Extended Follow-up of the RESTART Randomized Clinical Trial.

Importance: The Restart or Stop Antithrombotics Randomized Trial (RESTART) found that antiplatelet therapy appeared to be safe up to 5 years after intracerebral hemorrhage (ICH) that had occurred during antithrombotic (antiplatelet or anticoagulant) therapy. Objectives: To monitor adherence, increase duration of follow-up, and improve precision of estimates of the effects of antiplatelet therapy on recurrent ICH and major vascular events. Design, Setting and Participants: From May 22, 2013, through May 31, 2018, this prospective, open, blinded end point, parallel-group randomized clinical trial studied 537 participants at 122 hospitals in the UK. Participants were individuals 18 years or older who had taken antithrombotic therapy for the prevention of occlusive vascular disease when they developed ICH, discontinued antithrombotic therapy, and survived for 24 hours. After initial follow-up ended on November 30, 2018, annual follow-up was extended until November 30, 2020, for a median of 3.0 years (interquartile range [IQR], 2.0-5.0 years) for the trial cohort. Interventions: Computerized randomization that incorporated minimization allocated participants (1:1) to start or avoid antiplatelet therapy. Main Outcomes and Measures: Participants were followed up for the primary outcome (recurrent symptomatic ICH) and secondary outcomes (all major vascular events) for up to 7 years. Data from all randomized participants were analyzed using Cox proportional hazards regression, adjusted for minimization covariates. Results: A total of 537 patients (median age, 76.0 years; IQR, 69.0-82.0 years; 360 [67.0%] male; median time after ICH onset, 76.0 days; IQR, 29.0-146.0 days) were randomly allocated to start (n = 268) or avoid (n = 269 [1 withdrew]) antiplatelet therapy. The primary outcome of recurrent ICH affected 22 of 268 participants (8.2%) allocated to antiplatelet therapy compared with 25 of 268 participants (9.3%) allocated to avoid antiplatelet therapy (adjusted hazard ratio, 0.87; 95% CI, 0.49-1.55; P = .64). A major vascular event affected 72 participants (26.8%) allocated to antiplatelet therapy compared with 87 participants (32.5%) allocated to avoid antiplatelet therapy (hazard ratio, 0.79; 95% CI, 0.58-1.08; P = .14). Conclusions and Relevance: Among patients with ICH who had previously taken antithrombotic therapy, this study found no statistically significant effect of antiplatelet therapy on recurrent ICH or all major vascular events. These findings provide physicians with some reassurance about the use of antiplatelet therapy after ICH if indicated for secondary prevention of major vascular events. Trial Registration: isrctn.org Identifier: ISRCTN71907627.

Appearance of COVID-19 pneumonia on 1.5 T TrueFISP MRI.

OBJECTIVE: To evaluate the performance of 1.5 T true fast imaging with steady state precession (TrueFISP) magnetic resonance imaging (MRI) sequences for the detection and characterization of pulmonary abnormalities caused by coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: In this retrospective single-center study, computed tomography (CT) and MRI scans of 20 patients with COVID-19 pneumonia were evaluated with regard to the distribution, opacity, and appearance of pulmonary lesions, as well as bronchial changes, pleural effusion, and thoracic lymphadenopathy. McNemar's test was used in order to compare the COVID-19-associated alterations seen on CT with those seen on MRI. RESULTS: Ground-glass opacities were better visualized on CT than on MRI (p = 0.031). We found no statistically significant differences between CT and MRI regarding the visualization/characterization of the following: consolidations; interlobular/intralobular septal thickening; the distribution or appearance of pulmonary abnormalities; bronchial pathologies; pleural effusion; and thoracic lymphadenopathy. CONCLUSION: Pulmonary abnormalities caused by COVID-19 pneumonia can be detected on TrueFISP MRI sequences and correspond to the patterns known from CT. Especially during the current pandemic, the portions of the lungs imaged on cardiac or abdominal MRI should be carefully evaluated to promote the identification and isolation of unexpected cases of COVID-19, thereby curbing further spread of the disease.

OBJETIVO: Avaliar o desempenho da ressonância magnética (RM) de 1,5 T true fast imaging with steady state precession (TrueFISP) para detecção e caracterização de anormalidades pulmonares causadas por doença do coronavírus 2019 (COVID-19). MATERIAIS E MÉTODOS: Neste estudo retrospectivo unicêntrico, imagens de tomografia computadorizada (TC) e RM de 20 pacientes com pneumonia COVID-19 foram avaliadas em relação a distribuição, opacidade e forma das lesões pulmonares, anormalidades brônquicas, derrame pleural e linfadenopatia torácica. O teste de McNemar foi usado para comparar os achados associados à COVID-19 na TC e na RM. RESULTADOS: As opacidades em vidro fosco foram mais bem visualizadas na TC do que na RM (p = 0,031). Não foram encontradas diferenças estatisticamente significantes entre TC e RM em relação aos outros aspectos, ou seja, visualização de consolidações e espessamento septal interlobular/intralobular, distribuição ou forma de anormalidades pulmonares, doenças brônquicas, derrame pleural ou linfadenopatia torácica. CONCLUSÃO: As anomalias pulmonares causadas pela pneumonia por COVID-19 podem ser detectadas nas sequências TrueFISP e correspondem aos padrões conhecidos da TC. Especialmente em face da pandemia atual, as porções de imagem dos pulmões na RM cardíaca ou abdominal devem ser cuidadosamente avaliadas para apoiar a identificação e o isolamento de casos inesperados de COVID-19 e, assim, conter a disseminação.

European Stroke Organisation expedited recommendation for the use of short-term dual antiplatelet therapy early after minor stroke and high-risk TIA.

Prevention of early recurrent ischaemic stroke remains a priority in people with TIA or ischaemic stroke. A number of trials have recently been completed assessing the efficacy of short-term dual antiplatelet therapy (DAPT) versus single antiplatelet therapy early after minor or moderate stroke or high-risk TIA. We present an Expedited Recommendation for use of dual antiplatelet therapy early after ischaemic stroke and TIA on behalf of the ESO Guideline Board. We make a strong recommendation based on high quality of evidence for use of 21-days of dual antiplatelet therapy with aspirin and clopidogrel in people with a non-cardioembolic minor ischaemic stroke or high-risk TIA in the past 24 hours. We make a weak recommendation based on moderate quality evidence for 30-days of dual antiplatelet therapy with aspirin and ticagrelor in people with non-cardioembolic mild to moderate ischaemic stroke or high-risk TIA in the past 24 hours.

European Stroke Organisation (ESO) guidelines on management of transient ischaemic attack.

The aim of the present European Stroke Organisation Transient Ischaemic Attack (TIA) management guideline document is to provide clinically useful evidence-based recommendations on approaches to triage, investigation and secondary prevention, particularly in the acute phase following TIA. The guidelines were prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined TIA clinically and pragmatically for generalisability as transient neurological symptoms, likely to be due to focal cerebral or ocular ischaemia, which last less than 24 hours. High risk TIA was defined based on clinical features in patients seen early after their event or having other features suggesting a high early risk of stroke (e.g. ABCD2 score of 4 or greater, or weakness or speech disturbance for greater than five minutes, or recurrent events, or significant ipsilateral large artery disease e.g. carotid stenosis, intracranial stenosis). Overall, we strongly recommend using dual antiplatelet treatment with clopidogrel and aspirin short term, in high-risk non-cardioembolic TIA patients, with an ABCD2 score of 4 or greater, as defined in randomised controlled trials (RCTs). We further recommend specialist review within 24 hours after the onset of TIA symptoms. We suggest review in a specialist TIA clinic rather than conventional outpatients, if managed in an outpatient setting. We make a recommendation to use either MRA or CTA in TIA patients for additional confirmation of large artery stenosis of 50% or greater, in order to guide further management, such as clarifying degree of carotid stenosis detected with carotid duplex ultrasound. We make a recommendation against using prediction tools (eg ABCD2 score) alone to identify high risk patients or to make triage and treatment decisions in suspected TIA patients as due to limited sensitivity of the scores, those with score value of 3 or less may include significant numbers of individual patients at risk of recurrent stroke, who require early assessment and treatment. These recommendations aim to emphasise the importance of prompt acute assessment and relevant secondary prevention. There are no data from randomised controlled trials on prediction tool use and optimal imaging strategies in suspected TIA.

European Stroke Organisation expedited recommendation for the use of short-term dual antiplatelet therapy early after minor stroke and high-risk TIA.

Prevention of early recurrent ischaemic stroke remains a priority in people with TIA or ischaemic stroke. A number of trials have recently been completed assessing the efficacy of short-term dual antiplatelet therapy (DAPT) versus single antiplatelet therapy early after minor or moderate stroke or high-risk TIA. We present an Expedited Recommendation for use of dual antiplatelet therapy early after ischaemic stroke and TIA on behalf of the ESO Guideline Board. We make a strong recommendation based on high quality of evidence for use of 21-days of dual antiplatelet therapy with aspirin and clopidogrel in people with a non-cardioembolic minor ischaemic stroke or high-risk TIA in the past 24 hours. We make a weak recommendation based on moderate quality evidence for 30-days of dual antiplatelet therapy with aspirin and ticagrelor in people with non-cardioembolic mild to moderate ischaemic stroke or high-risk TIA in the past 24 hours.

European Stroke Organisation (ESO) guidelines on management of transient ischaemic attack.

The aim of the present European Stroke Organisation Transient Ischaemic Attack (TIA) management guideline document is to provide clinically useful evidence-based recommendations on approaches to triage, investigation and secondary prevention, particularly in the acute phase following TIA. The guidelines were prepared following the Standard Operational Procedure for a European Stroke Organisation guideline document and according to GRADE methodology. As a basic principle, we defined TIA clinically and pragmatically for generalisability as transient neurological symptoms, likely to be due to focal cerebral or ocular ischaemia, which last less than 24 hours. High risk TIA was defined based on clinical features in patients seen early after their event or having other features suggesting a high early risk of stroke (e.g. ABCD2 score of 4 or greater, or weakness or speech disturbance for greater than five minutes, or recurrent events, or significant ipsilateral large artery disease e.g. carotid stenosis, intracranial stenosis). Overall, we strongly recommend using dual antiplatelet treatment with clopidogrel and aspirin short term, in high-risk non-cardioembolic TIA patients, with an ABCD2 score of 4 or greater, as defined in randomised controlled trials (RCTs). We further recommend specialist review within 24 hours after the onset of TIA symptoms. We suggest review in a specialist TIA clinic rather than conventional outpatients, if managed in an outpatient setting. We make a recommendation to use either MRA or CTA in TIA patients for additional confirmation of large artery stenosis of 50% or greater, in order to guide further management, such as clarifying degree of carotid stenosis detected with carotid duplex ultrasound. We make a recommendation against using prediction tools (eg ABCD2 score) alone to identify high risk patients or to make triage and treatment decisions in suspected TIA patients as due to limited sensitivity of the scores, those with score value of 3 or less may include significant numbers of individual patients at risk of recurrent stroke, who require early assessment and treatment. These recommendations aim to emphasise the importance of prompt acute assessment and relevant secondary prevention. There are no data from randomised controlled trials on prediction tool use and optimal imaging strategies in suspected TIA.

Appearance of COVID-19 pneumonia on 1.5 T TrueFISP MRI / Aspectos da pneumonia por COVID-19 na ressonância magnética 1.5 T TrueFISP

Abstract Objective: To evaluate the performance of 1.5 T true fast imaging with steady state precession (TrueFISP) magnetic resonance imaging (MRI) sequences for the detection and characterization of pulmonary abnormalities caused by coronavirus disease 2019 (COVID-19). Materials and Methods: In this retrospective single-center study, computed tomography (CT) and MRI scans of 20 patients with COVID-19 pneumonia were evaluated with regard to the distribution, opacity, and appearance of pulmonary lesions, as well as bronchial changes, pleural effusion, and thoracic lymphadenopathy. McNemar's test was used in order to compare the COVID-19-associated alterations seen on CT with those seen on MRI. Results: Ground-glass opacities were better visualized on CT than on MRI (p = 0.031). We found no statistically significant differences between CT and MRI regarding the visualization/characterization of the following: consolidations; interlobular/intralobular septal thickening; the distribution or appearance of pulmonary abnormalities; bronchial pathologies; pleural effusion; and thoracic lymphadenopathy. Conclusion: Pulmonary abnormalities caused by COVID-19 pneumonia can be detected on TrueFISP MRI sequences and correspond to the patterns known from CT. Especially during the current pandemic, the portions of the lungs imaged on cardiac or abdominal MRI should be carefully evaluated to promote the identification and isolation of unexpected cases of COVID-19, thereby curbing further spread of the disease.

Resumo Objetivo: Avaliar o desempenho da ressonância magnética (RM) de 1,5 T true fast imaging with steady state precession (TrueFISP) para detecção e caracterização de anormalidades pulmonares causadas por doença do coronavírus 2019 (COVID-19). Materiais e Métodos: Neste estudo retrospectivo unicêntrico, imagens de tomografia computadorizada (TC) e RM de 20 pacientes com pneumonia COVID-19 foram avaliadas em relação a distribuição, opacidade e forma das lesões pulmonares, anormalidades brônquicas, derrame pleural e linfadenopatia torácica. O teste de McNemar foi usado para comparar os achados associados à COVID-19 na TC e na RM. Resultados: As opacidades em vidro fosco foram mais bem visualizadas na TC do que na RM (p = 0,031). Não foram encontradas diferenças estatisticamente significantes entre TC e RM em relação aos outros aspectos, ou seja, visualização de consolidações e espessamento septal interlobular/intralobular, distribuição ou forma de anormalidades pulmonares, doenças brônquicas, derrame pleural ou linfadenopatia torácica. Conclusão: As anomalias pulmonares causadas pela pneumonia por COVID-19 podem ser detectadas nas sequências TrueFISP e correspondem aos padrões conhecidos da TC. Especialmente em face da pandemia atual, as porções de imagem dos pulmões na RM cardíaca ou abdominal devem ser cuidadosamente avaliadas para apoiar a identificação e o isolamento de casos inesperados de COVID-19 e, assim, conter a disseminação.

Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration.

BACKGROUND AND PURPOSE: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. METHODS: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. RESULTS: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76-1.14]; P=0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P=0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P=0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P=0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P=0.64) at 12 months. CONCLUSIONS: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. Registration: URL: http://www.anzctr.org.au/; Unique identifier: ACTRN12611000774921.

Predicting specific abilities after disabling stroke: Development and validation of prognostic models.

BACKGROUND: Predicting specific abilities (e.g. walk and talk) to provide a functional profile six months after disabling stroke could help patients/families prepare for the consequences of stroke and facilitate involvement in treatment decision-making. AIM: To develop new statistical models to predict specific abilities six months after stroke and test their performance in an independent cohort of patients with disabling stroke. METHODS: We developed models to predict six specific abilities (to be independent, walk, talk, eat normally, live without major anxiety/depression, and to live at home) using data from seven large multicenter stroke trials with multivariable logistic regression. We included 13,117 participants recruited within three days of hospital admission. We assessed model discrimination and derived optimal cut-off values using four statistical methods. We validated the models in an independent single-center cohort of patients (n = 403) with disabling stroke. We assessed model discrimination and calibration and reported the performance of our models at the statistically derived cut-off values. RESULTS: All six models had good discrimination in external validation (AUC 0.78-0.84). Four models (predicting to walk, eat normally, live without major anxiety/depression, live at home) calibrated well. Models had sensitivities between 45.0 and 97.9% and specificities between 21.6 and 96.5%. CONCLUSIONS: We have developed statistical models to predict specific abilities and demonstrated that these models perform reasonably well in an independent cohort of disabling stroke patients. To aid decision-making regarding treatments, further evaluation of our models is required.

Feasibility of reporting results of large randomised controlled trials to participants: experience from the Fluoxetine Or Control Under Supervision (FOCUS) trial.

OBJECTIVES: Informing research participants of the results of studies in which they took part is viewed as an ethical imperative. However, there is little guidance in the literature about how to do this. The Fluoxetine Or Control Under Supervision trial randomised 3127 patients with a recent acute stroke to 6 months of fluoxetine or placebo and was published in the Lancet on 5 December 2018. The trial team decided to inform the participants of the results at exactly the same time as the Lancet publication, and also whether they had been allocated fluoxetine or placebo. In this report, we describe how we informed participants of the results. DESIGN: In the 6-month and 12-month follow-up questionnaires, we invited participants to provide an email address if they wished to be informed of the results of the trial. We re-opened our trial telephone helpline between 5 December 2018 and 31 March 2019. SETTING: UK stroke services. PARTICIPANTS: 3127 participants were randomised. 2847 returned 6-month follow-up forms and 2703 returned 12-month follow-up forms; the remaining participants had died (380), withdrawn consent or did not respond. RESULTS: Of those returning follow-up questionnaires, a total of 1845 email addresses were provided and a further 50 people requested results to be sent by post. Results were sent to all email and postal addresses provided; 309 emails were returned unrecognised. Seventeen people replied, of whom three called the helpline and the rest responded by email. CONCLUSION: It is feasible to disseminate results of large trials to research participants, though only around 60% of those randomised wanted to receive the results. The system we developed was efficient and required very little resource, and could be replicated by trialists in the future. TRIAL REGISTRATION NUMBER: ISRCTN83290762; Post-results.

Update to the FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke: statistical analysis plan for the trials and for the individual patient data meta-analysis.

BACKGROUND: Three large trials of fluoxetine for stroke recovery (FOCUS (fluoxetine or control under supervision), AFFINITY (the Assessment oF FluoxetINe In sTroke recovery) and EFFECTS (Efficacy oF Fluoxetine-a randomisEd Controlled Trial in Stroke)) have been collaboratively designed with the same basic protocol to facilitate an individual patient data analysis (IPDM). The statistical analysis plan for the three individual trials has already been reported in Trials, including a brief description of the IPDM. In this protocol, we describe in detail how we will perform the IPDM. METHODS/DESIGN: Data from EFFECTS and AFFINITY will be transferred securely to the FOCUS statistician, who will perform a one-stage IPDM and a two-stage IPDM. For the one-stage IPDM, data will be combined into a single data set and the same analyses performed as described for the individual trials. For the two-stage IPDM, the results for the three individual trials will be combined using fixed effects meta-analyses. The primary and secondary outcome domains for the IPDM are the same as for individual trials. We will also perform analyses according to several subgroups including country of recruitment, ethnicity and trial. We will also explore the effects of fluoxetine on our primary and secondary outcomes in subgroups defined by combinations of characteristics. We also describe additional research questions that will be addressed using the combined data set, and published subsequently, including predictors of important post-stroke problems such as seizures, low mood and bone fractures. DISCUSSION: An IPDM of our three large trials of fluoxetine for stroke recovery will allow us to provide the most precise estimates of any risks and benefits of fluoxetine vs placebo, to detect reliably a smaller overall effect size than those detectable by the individual trials, to better determine the effects of fluoxetine vs placebo in subgroups of patients and outcomes and to broaden the generalisability of the results. Also, we may identify differences in treatment effects between studies. TRIAL REGISTRATION: FOCUS: ISRCTN ISRCTN83290762 . Registered on 23 May 2012. EudraCT 2011-005616-29 . Registered on 3 February 2012. AFFINITY: Australian New Zealand Clinical Trials Registry ACTRN12611000774921 . Registered on 22 July 2011. EFFECTS: ISRCTN ISRCTN13020412 . Registered on 19 December 2014. ClinicalTrials.gov NCT02683213 . Registered on 2 February 2016. EudraCT 2011-006130-16 . Registered on 8 August 2014.

Reporting "specific abilities" after major stroke to better describe prognosis.

INTRODUCTION: If health professionals are to involve major stroke patients and their families in making decisions about treatments, they need to describe prognosis in terms that are easily understood. We suggest that referring to "specific abilities", such as ability to be independent, walk, talk, eat normally, be continent, live without severe pain, live without major anxiety or depression and to live at home may be more easily understood than terms such as disabled based on the modified Rankin scale (mRs). OBJECTIVE: We aimed to describe the "specific abilities" and quality of life of patients in each mRs level at six months after major stroke. PATIENTS AND METHODS: A longitudinal cohort study of patients admitted to hospital with major stroke with follow up at six months. RESULTS: We recruited 403 patients, mean age 77.5yrs. The number (%) in each mRs level at six months was 0 (no problems): 8(2%), 1: 45(11.2%), 2: 7(1.7%), 3: 149(37.1%), 4: 46(11.4%), 5: 36(9.0%) and 6(dead) 111(27.6%). Patients within each mRs level varied with respect to their "specific abilities" and quality of life. For example, of the 36(9%) patients with mRs 5, 30(83%) could talk, 14(39%) were continent, 33(92%) were not in severe pain, 22(61%) did not have major anxiety/depression and 5(14%) could live at home. Their median utility (derived from HRQoL) was -0.08 (range -0.35 to 0.43). DISCUSSION AND CONCLUSIONS: Describing prognosis with the mRs does not convey the variation in specific abilities and HRQoL amongst patients with major stroke. Therefore, describing prognosis in terms of "specific abilities" may be more appropriate.