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.

Depression, Anxiety, and Suicide After Stroke: A Narrative Review of the Best Available Evidence.

Depression and anxiety each affect around 1 in 3 people during the first year after a stroke. Suicide causes the death of about 3 to 4/1000 stroke survivors during the first 5 years. This narrative review describes the best available evidence for the epidemiology of depression, anxiety, and suicide; their prevention; and the treatment of anxiety and depression. We conclude with directions for future research.

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.

Core Outcome Measures for Palliative and End-of-Life Research After Severe Stroke: Mixed-Method Delphi Study.

Background and Purpose: Stroke is the second commonest cause of death worldwide and a leading cause of severe disability, yet there are no published trials of palliative care in stroke. To design and evaluate palliative care interventions for people with stroke, researchers need to know what measurable outcomes matter most to patients and families, stroke professionals, and other service providers. Methods: A multidisciplinary steering group of professionals and laypeople managed the study. We synthesized recommendations from respected United Kingdom and international consensus documents to generate a list of outcome domains and then performed a rapid scoping literature review to identify potential outcome measures for use in future trials of palliative care after stroke. We then completed a 3-round, online Delphi survey of professionals, and service users to build consensus about outcome domains and outcome measures. Finally, we held a stakeholder workshop to review and finalize this consensus. Results: We generated a list of 36 different outcome domains from 4 key policy documents. The rapid scoping review identified 43 potential outcome measures that were used to create a shortlist of 16 measures. The 36 outcome domains and 16 measures were presented to a Delphi panel of diverse healthcare professionals and lay service users. Of 48 panelists invited to take part, 28 completed all 3 rounds. Shared decision-making and quality of life were selected as the most important outcome domains for future trials of palliative care in stroke. Additional comments highlighted the need for outcomes to be feasible, measurable, and relevant beyond the initial, acute phase of stroke. The stakeholder workshop endorsed these results. Conclusions: Future trials of palliative care after stroke should include pragmatic outcome measures, applicable to the evolving patient and family experiences after stroke and be inclusive of shared decision-making and quality of life.

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.

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.

Interventions for reducing sedentary behaviour in people with stroke.

BACKGROUND: Stroke survivors are often physically inactive as well as sedentary,and may sit for long periods of time each day. This increases cardiometabolic risk and has impacts on physical and other functions. Interventions to reduce or interrupt periods of sedentary time, as well as to increase physical activity after stroke, could reduce the risk of secondary cardiovascular events and mortality during life after stroke. OBJECTIVES: To determine whether interventions designed to reduce sedentary behaviour after stroke, or interventions with the potential to do so, can reduce the risk of death or secondary vascular events, modify cardiovascular risk, and reduce sedentary behaviour. SEARCH METHODS: In December 2019, we searched the Cochrane Stroke Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, Conference Proceedings Citation Index, and PEDro. We also searched registers of ongoing trials, screened reference lists, and contacted experts in the field. SELECTION CRITERIA: Randomised trials comparing interventions to reduce sedentary time with usual care, no intervention, or waiting-list control, attention control, sham intervention or adjunct intervention. We also included interventions intended to fragment or interrupt periods of sedentary behaviour. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and performed 'Risk of bias' assessments. We analyzed data using random-effects meta-analyses and assessed the certainty of the evidence with the GRADE approach. MAIN RESULTS: We included 10 studies with 753 people with stroke. Five studies used physical activity interventions, four studies used a multicomponent lifestyle intervention, and one study used an intervention to reduce and interrupt sedentary behaviour. In all studies, the risk of bias was high or unclear in two or more domains. Nine studies had high risk of bias in at least one domain. The interventions did not increase or reduce deaths (risk difference (RD) 0.00, 95% confidence interval (CI) -0.02 to 0.03; 10 studies, 753 participants; low-certainty evidence), the incidence of recurrent cardiovascular or cerebrovascular events (RD -0.01, 95% CI -0.04 to 0.01; 10 studies, 753 participants; low-certainty evidence), the incidence of falls (and injuries) (RD 0.00, 95% CI -0.02 to 0.02; 10 studies, 753 participants; low-certainty evidence), or incidence of other adverse events (moderate-certainty evidence). Interventions did not increase or reduce the amount of sedentary behaviour time (mean difference (MD) +0.13 hours/day, 95% CI -0.42 to 0.68; 7 studies, 300 participants; very low-certainty evidence). There were too few data to examine effects on patterns of sedentary behaviour. The effect of interventions on cardiometabolic risk factors allowed very limited meta-analysis. AUTHORS' CONCLUSIONS: Sedentary behaviour research in stroke seems important, yet the evidence is currently incomplete, and we found no evidence for beneficial effects. Current World Health Organization (WHO) guidelines recommend reducing the amount of sedentary time in people with disabilities, in general. The evidence is currently not strong enough to guide practice on how best to reduce sedentariness specifically in people with stroke. More high-quality randomised trials are needed, particularly involving participants with mobility limitations. Trials should include longer-term interventions specifically targeted at reducing time spent sedentary, risk factor outcomes, objective measures of sedentary behaviour (and physical activity), and long-term follow-up.

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.

Telemedicine Cognitive Behavioral Therapy for Anxiety After Stroke: Proof-of-Concept Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Disabling anxiety affects a quarter of stroke survivors but access to treatment is poor. We developed a telemedicine model for delivering guided self-help cognitive behavioral therapy (CBT) for anxiety after stroke (TASK-CBT). We aimed to evaluate the feasibility of TASK-CBT in a randomized controlled trial workflow that enabled all trial procedures to be carried out remotely. In addition, we explored the feasibility of wrist-worn actigraphy sensor as a way of measuring objective outcomes in this clinical trial. METHODS: We recruited adult community-based stroke patients (n=27) and randomly allocated them to TASK-CBT (n=14) or relaxation therapy (TASK-Relax), an active comparator (n=13). RESULTS: In our sample (mean age 65 [±10]; 56% men; 63% stroke, 37% transient ischemic attacks), remote self-enrolment, electronic signature, intervention delivery, and automated follow-up were feasible. All participants completed all TASK-CBT sessions (14/14). Lower levels of anxiety were observed in TASK-CBT when compared with TASK-Relax at both weeks 6 and 20. Mean actigraphy sensor wearing-time was 33 days (±15). CONCLUSIONS: Our preliminary feasibility data from the current study support a larger definitive clinical trial and the use of wrist-worn actigraphy sensor in anxious stroke survivors. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03439813.

Cluster-Randomized, Crossover Trial of Head Positioning in Acute Stroke.

BACKGROUND: The role of supine positioning after acute stroke in improving cerebral blood flow and the countervailing risk of aspiration pneumonia have led to variation in head positioning in clinical practice. We wanted to determine whether outcomes in patients with acute ischemic stroke could be improved by positioning the patient to be lying flat (i.e., fully supine with the back horizontal and the face upwards) during treatment to increase cerebral perfusion. METHODS: In a pragmatic, cluster-randomized, crossover trial conducted in nine countries, we assigned 11,093 patients with acute stroke (85% of the strokes were ischemic) to receive care in either a lying-flat position or a sitting-up position with the head elevated to at least 30 degrees, according to the randomization assignment of the hospital to which they were admitted; the designated position was initiated soon after hospital admission and was maintained for 24 hours. The primary outcome was degree of disability at 90 days, as assessed with the use of the modified Rankin scale (scores range from 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death). RESULTS: The median interval between the onset of stroke symptoms and the initiation of the assigned position was 14 hours (interquartile range, 5 to 35). Patients in the lying-flat group were less likely than patients in the sitting-up group to maintain the position for 24 hours (87% vs. 95%, P<0.001). In a proportional-odds model, there was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the lying-flat group and patients in the sitting-up group (unadjusted odds ratio for a difference in the distribution of scores on the modified Rankin scale in the lying-flat group, 1.01; 95% confidence interval, 0.92 to 1.10; P=0.84). Mortality within 90 days was 7.3% among the patients in the lying-flat group and 7.4% among the patients in the sitting-up group (P=0.83). There were no significant between-group differences in the rates of serious adverse events, including pneumonia. CONCLUSIONS: Disability outcomes after acute stroke did not differ significantly between patients assigned to a lying-flat position for 24 hours and patients assigned to a sitting-up position with the head elevated to at least 30 degrees for 24 hours. (Funded by the National Health and Medical Research Council of Australia; HeadPoST ClinicalTrials.gov number, NCT02162017 .).

Physical fitness training for stroke patients.

BACKGROUND: Levels of physical activity and physical fitness are low after stroke. Interventions to increase physical fitness could reduce mortality and reduce disability through increased function. OBJECTIVES: The primary objectives of this updated review were to determine whether fitness training after stroke reduces death, death or dependence, and disability. The secondary objectives were to determine the effects of training on adverse events, risk factors, physical fitness, mobility, physical function, health status and quality of life, mood, and cognitive function. SEARCH METHODS: In July 2018 we searched the Cochrane Stroke Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, SPORTDiscus, PsycINFO, and four additional databases. We also searched ongoing trials registers and conference proceedings, screened reference lists, and contacted experts in the field. SELECTION CRITERIA: Randomised trials comparing either cardiorespiratory training or resistance training, or both (mixed training), with usual care, no intervention, or a non-exercise intervention in stroke survivors. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed quality and risk of bias, and extracted data. We analysed data using random-effects meta-analyses and assessed the quality of the evidence using the GRADE approach. Diverse outcome measures limited the intended analyses. MAIN RESULTS: We included 75 studies, involving 3017 mostly ambulatory participants, which comprised cardiorespiratory (32 studies, 1631 participants), resistance (20 studies, 779 participants), and mixed training interventions (23 studies, 1207 participants). Death was not influenced by any intervention; risk differences were all 0.00 (low-certainty evidence). There were few deaths overall (19/3017 at end of intervention and 19/1469 at end of follow-up). None of the studies assessed death or dependence as a composite outcome. Disability scores were improved at end of intervention by cardiorespiratory training (standardised mean difference (SMD) 0.52, 95% CI 0.19 to 0.84; 8 studies, 462 participants; P = 0.002; moderate-certainty evidence) and mixed training (SMD 0.23, 95% CI 0.03 to 0.42; 9 studies, 604 participants; P = 0.02; low-certainty evidence). There were too few data to assess the effects of resistance training on disability. Secondary outcomes showed multiple benefits for physical fitness (VO2 peak and strength), mobility (walking speed) and physical function (balance). These physical effects tended to be intervention-specific with the evidence mostly low or moderate certainty. Risk factor data were limited or showed no effects apart from cardiorespiratory fitness (VO2 peak), which increased after cardiorespiratory training (mean difference (MD) 3.40 mL/kg/min, 95% CI 2.98 to 3.83; 9 studies, 438 participants; moderate-certainty evidence). There was no evidence of any serious adverse events. Lack of data prevents conclusions about effects of training on mood, quality of life, and cognition. Lack of data also meant benefits at follow-up (i.e. after training had stopped) were unclear but some mobility benefits did persist. Risk of bias varied across studies but imbalanced amounts of exposure in control and intervention groups was a common issue affecting many comparisons. AUTHORS' CONCLUSIONS: Few deaths overall suggest exercise is a safe intervention but means we cannot determine whether exercise reduces mortality or the chance of death or dependency. Cardiorespiratory training and, to a lesser extent mixed training, reduce disability during or after usual stroke care; this could be mediated by improved mobility and balance. There is sufficient evidence to incorporate cardiorespiratory and mixed training, involving walking, within post-stroke rehabilitation programmes to improve fitness, balance and the speed and capacity of walking. The magnitude of VO2 peak increase after cardiorespiratory training has been suggested to reduce risk of stroke hospitalisation by ˜7%. Cognitive function is under-investigated despite being a key outcome of interest for patients. Further well-designed randomised trials are needed to determine the optimal exercise prescription, the range of benefits and any long-term benefits.

Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.

BACKGROUND: Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. The 2012 Cochrane Review of SSRIs for stroke recovery demonstrated positive effects on recovery, even in people who were not depressed at randomisation. A large trial of fluoxetine for stroke recovery (fluoxetine versus placebo under supervision) has recently been published, and it is now appropriate to update the evidence. 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: For this update, we searched the Cochrane Stroke Group Trials Register (last searched 16 July 2018), the Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, July 2018), MEDLINE (1946 to July 2018), Embase (1974 to July 2018), CINAHL (1982 July 2018), PsycINFO (1985 to July 2018), AMED (1985 to July 2018), and PsycBITE March 2012 to July 2018). We also searched grey literature and clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that recruited ischaemic or haemorrhagic stroke survivors at any time within the first year. The intervention was any SSRI, given at any dose, for any period, and for any indication. We excluded drugs with mixed pharmacological effects. The comparator was usual care or placebo. To be included, trials had to collect data on at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, healthcare cost, death, adverse events and leaving the trial early). DATA COLLECTION AND ANALYSIS: We extracted data on demographics, type of stroke, time since stroke, our primary and secondary outcomes, and sources of bias. Two review authors independently extracted data from each trial. We used standardised mean differences (SMDs) to estimate treatment effects for continuous variables, and risk ratios (RRs) for dichotomous effects, with their 95% confidence intervals (CIs). We assessed risks of bias and applied GRADE criteria. MAIN RESULTS: We identified a total of 63 eligible trials recruiting 9168 participants, most of which provided data only at end of treatment and not at follow-up. There was a wide age range. About half the trials required participants to have depression to enter the trial. The duration, drug, and dose varied between trials. Only three of the included trials were at low risk of bias across the key 'Risk of bias' domains. A meta-analysis of these three trials found little or no effect of SSRI on either disability score: SMD -0.01 (95% CI -0.09 to 0.06; P = 0.75; 2 studies, 2829 participants; moderate-quality evidence) or independence: RR 1.00 (95% CI 0.91 to 1.09; P = 0.99; 3 studies, 3249 participants; moderate-quality evidence). We downgraded both these outcomes for imprecision. SSRIs reduced the average depression score (SMD 0.11 lower, 0.19 lower to 0.04 lower; 2 trials, 2861 participants; moderate-quality evidence), but there was a higher observed number of gastrointestinal side effects among participants treated with SSRIs compared to placebo (RR 2.19, 95% CI 1.00 to 4.76; P = 0.05; 2 studies, 148 participants; moderate-quality evidence), with no evidence of heterogeneity (I2 = 0%). For seizures there was no evidence of a substantial difference. When we included all trials in a sensitivity analysis, irrespective of risk of bias, SSRIs appeared to reduce disability scores but not dependence. One large trial (FOCUS) dominated the results. We identified several ongoing trials, including two large trials that together will recruit more than 3000 participants. AUTHORS' CONCLUSIONS: We found no reliable evidence that SSRIs should be used routinely to promote recovery after stroke. Meta-analysis of the trials at low risk of bias indicate that SSRIs do not improve recovery from stroke. We identified potential improvements in disability only in the analyses which included trials at high risk of bias. A further meta-analysis of large ongoing trials will be required to determine the generalisability of these findings.

Anxiety After Stroke: The Importance of Subtyping.

BACKGROUND AND PURPOSE: Anxiety after stroke is common and disabling. Stroke trialists have treated anxiety as a homogenous condition, and intervention studies have followed suit, neglecting the different treatment approaches for phobic and generalized anxiety. Using diagnostic psychiatric interviews, we aimed to report the frequency of phobic and generalized anxiety, phobic avoidance, predictors of anxiety, and patient outcomes at 3 months poststroke/transient ischemic attack. METHODS: We followed prospectively a cohort of new diagnosis of stroke/transient ischemic attack at 3 months with a telephone semistructured psychiatric interview, Fear Questionnaire, modified Rankin Scale, EuroQol-5D5L, and Work and Social Adjustment Scale. RESULTS: Anxiety disorder was common (any anxiety disorder, 38 of 175 [22%]). Phobic disorder was the predominant anxiety subtype: phobic disorder only, 18 of 175 (10%); phobic and generalized anxiety disorder, 13 of 175 (7%); and generalized anxiety disorder only, 7 of 175 (4%). Participants with anxiety disorder reported higher level of phobic avoidance across all situations on the Fear Questionnaire. Younger age (per decade increase in odds ratio, 0.64; 95% confidence interval, 0.45-0.91) and having previous anxiety/depression (odds ratio, 4.38; 95% confidence interval, 1.94-9.89) were predictors for anxiety poststroke/transient ischemic attack. Participants with anxiety disorder were more dependent (modified Rankin Scale score 3-5, [anxiety] 55% versus [no anxiety] 29%; P<0.0005), had poorer quality of life on EQ-5D5L, and restricted participation (Work and Social Adjustment Scale: median, interquartile range, [anxiety] 19.5, 10-27 versus [no anxiety] 0, 0-5; P<0.001). CONCLUSIONS: Anxiety after stroke/transient ischemic attack is predominantly phobic and is associated with poorer patient outcomes. Trials of anxiety intervention in stroke should consider the different treatment approaches needed for phobic and generalized anxiety.

Poststroke Fatigue: Emerging Evidence and Approaches to Management: A Scientific Statement for Healthcare Professionals From the American Heart Association.

At least half of all stroke survivors experience fatigue; thus, it is a common cause of concern for patients, caregivers, and clinicians after stroke. This scientific statement provides an international perspective on the emerging evidence surrounding the incidence, prevalence, quality of life, and complex pathogenesis of poststroke fatigue. Evidence for pharmacological and nonpharmacological interventions for management are reviewed, as well as the effects of poststroke fatigue on both stroke survivors and caregivers.

WITHDRAWN: Pharmacological cardioversion for atrial fibrillation and flutter.

BACKGROUND: Atrial fibrillation is the commonest cardiac dysrhythmia. It is associated with significant morbidity and mortality. There are two approaches to the management of atrial fibrillation: controlling the ventricular rate or converting to sinus rhythm in the expectation that this would abolish its adverse effects. OBJECTIVES: To assess the effects of pharmacological cardioversion of atrial fibrillation in adults on the annual risk of stroke, peripheral embolism, and mortality. SEARCH METHODS: We searched the Cochrane Controlled Trials Register (Issue 3, 2002), MEDLINE (2000 to 2002), EMBASE (1998 to 2002), CINAHL (1982 to 2002), Web of Science (1981 to 2002). We hand searched the following journals: Circulation (1997 to 2002), Heart (1997 to 2002), European Heart Journal (1997-2002), Journal of the American College of Cardiology (1997-2002) and selected abstracts published on the web site of the North American Society of Pacing and Electrophysiology (2001, 2002). SELECTION CRITERIA: Randomised controlled trials or controlled clinical trials of pharmacological cardioversion versus rate control in adults (>18 years) with acute, paroxysmal or sustained atrial fibrillation or atrial flutter, of any duration and of any aetiology. DATA COLLECTION AND ANALYSIS: One reviewer applied the inclusion criteria and extracted the data. Trial quality was assessed and the data were entered into RevMan. MAIN RESULTS: We identified two completed studies AFFIRM (n=4060) and PIAF (n=252). We found no difference in mortality between rhythm control and rate control relative risk 1.14 (95% confidence interval 1.00 to 1.31).Both studies show significantly higher rates of hospitalisation and adverse events in the rhythm control group and no difference in quality of life between the two treatment groups.In AFFIRM there was a similar incidence of ischaemic stroke, bleeding and systemic embolism in the two groups. Certain malignant dysrhythmias were significantly more likely to occur in the rhythm control group. There were similar scores of cognitive assessment.In PIAF, cardioverted patients enjoyed an improved exercise tolerance but there was no overall benefit in terms of symptom control or quality of life. AUTHORS' CONCLUSIONS: There is no evidence that pharmacological cardioversion of atrial fibrillation to sinus rhythm is superior to rate control. Rhythm control is associated with more adverse effects and increased hospitalisation. It does not reduce the risk of stroke. The conclusions cannot be generalised to all people with atrial fibrillation. Most of the patients included in these studies were relatively older (>60 years) with significant cardiovascular risk factors.

WITHDRAWN: Electrical cardioversion for atrial fibrillation and flutter.

BACKGROUND: Atrial fibrillation increases stroke risk and adversely affects cardiovascular haemodynamics. Electrical cardioversion may, by restoring sinus rhythm, improve cardiovascular haemodynamics, reduce the risk of stroke, and obviate the need for long-term anticoagulation. OBJECTIVES: To assess the effects of electrical cardioversion of atrial fibrillation or flutter on the risk of thromboembolic events, strokes and mortality (primary outcomes), the rate of cognitive decline, quality of life, the use of anticoagulants and the risk of re-hospitalisation (secondary outcomes) in adults (>18 years). SEARCH METHODS: We searched the Cochrane CENTRAL Register of Controlled Trials (1967 to May 2004), MEDLINE (1966 to May 2004), Embase (1980 to May 2004), CINAHL (1982 to May 2004), proceedings of the American College of Cardiology (published in Journal of the American College of Cardiology 1983 to 2003), www.trialscentral.org, www.controlled-trials.com and reference lists of articles. We hand-searched the indexes of the Proceedings of the British Cardiac Society published in British Heart Journal (1980 to 1995) and in Heart (1995 to 2002); proceedings of the European Congress of Cardiology and meetings of the Joint Working Groups of the European Society of Cardiology (published in European Heart Journal 1983-2003); scientific sessions of the American Heart Association (published in Circulation 1990-2003). Personal contact was made with experts. SELECTION CRITERIA: Randomised controlled trial or controlled clinical trials of electrical cardioversion plus 'usual care' versus 'usual care' only, where 'usual care' included any combination of anticoagulants, antiplatelet drugs and drugs for 'rate control'. We excluded trials which used pharmacological cardioversion as the first intervention, and trials of new onset atrial fibrillation after cardiac surgery. There were no language restrictions. DATA COLLECTION AND ANALYSIS: For dichotomous data, odds ratios were calculated; and for continuous data, the weighted mean difference was calculated. MAIN RESULTS: We found three completed trials of electrical cardioversion (rhythm control) versus rate control, recruiting a total of 927 participants (Hot Cafe; RACE; STAF) and one ongoing trial (J-RHYTHM). There was no difference in mortality between the two strategies (OR 0.83; CI 0.48 to 1.43). There was a trend towards more strokes in the rhythm control group (OR 1.9; 95% CI 0.99 to 3.64). At follow up, three domains of quality of life (physical functioning, physical role function and vitality) were significantly better in the rhythm control group (RACE 2002; STAF 2003). AUTHORS' CONCLUSIONS: Electrical cardioversion (rhythm control) led to a non-significant increase in stroke risk but improved three domains of quality of life.

The Nottingham Fatigue after Stroke (NotFAST) study: factors associated with severity of fatigue in stroke patients without depression.

OBJECTIVE: To identify factors associated with post-stroke fatigue in a sample of stroke survivors without depression. DESIGN: Cross-sectional cohort study. SETTING: Recruitment was from four stroke units in the UK. SUBJECTS: Participants were assessed within four to six weeks of first stroke; those with high levels of depressive symptoms (score ⩾7 Brief Assessment Schedule Depression Cards) were excluded. MAIN MEASURES: Participants were assessed after stroke on the Fatigue Severity Scale of the Fatigue Assessment Inventory, the Rivermead Mobility Index, Nottingham Extended Activities of Daily Living scale, Beck Anxiety Index, Sleep Hygiene Index, 6m walk test, and measures of cognitive ability. RESULTS: Of the 371 participants recruited, 103 were excluded and 268 were assessed. Of the latter, the mean age was 67.7 years (SD 13.5) and 168 (63%) were men. The National Institutes of Health Stroke Scale mean score was 4.96 (SD 4.12). Post-stroke fatigue was reported by 115 (43%) of participants, with 71 (62%) reporting this to be a new symptom since their stroke. Multivariate analysis using the Fatigue Severity Scale as the outcome variable found pre-stroke fatigue, having a spouse/partner, lower Rivermead Mobility Index score, and higher scores on both the Brief Assessment Schedule Depression Cards and Beck Anxiety Index were independently associated with post-stroke fatigue, accounting for approximately 47% of the variance in Fatigue Severity Scale scores. CONCLUSIONS: Pre-stroke fatigue, lower mood, and poorer mobility were associated with post-stroke fatigue.

The effect of treatment with selective serotonin reuptake inhibitors in comparison to placebo in the progression of dementia: a systematic review and meta-analysis.

BACKGROUND: selective serotonin reuptake inhibitors (SSRIs) may affect the neurodegenerative process of dementia, enhancing cognition. This systematic review aims to determine whether SSRIs influence cognitive performance, mood and function in people with any type of dementia. METHOD: randomised placebo-controlled studies of SSRIs in people with dementia, which recorded cognitive outcomes, were identified in ALOIS (ALzheimer's and cOgnitive Improvement Studies register) in April 2013 and updated in January 2015. Data were extracted on cognition, agitation, mood, activities of daily living (ADLs) and adverse events. End of treatment statistics were calculated. RESULTS: twelve studies met inclusion criteria (1,174 participants), of which seven studies (710 participants) provided data for meta-analysis on cognition. There was no difference in MMSE score at end of treatment; mean difference (MD) was 0.28 (95% CI -0.83 to 1.39) (six studies, 470 participants). For change in MMSE scores, there was a small improvement; MD was 0.53 (95%CI -0.07 to 1.14) (three studies, 352 participants). The remaining studies showed no improvement in cognition. There was no statistically significant benefit of SSRIs on mood (four studies, 317 participants); standard mean difference (SMD) -0.10 (95% CI -0.39 to 0.2), agitation (three studies, 189 participants); SMD -0.01(95% CI -0.86 to 0.83), or ADLs at end of treatment (four studies, 336 participants); SMD -0.15(95% CI -0.45 to 0.15). There was no difference in mortality between the two groups. Study quality was mixed with concerns over incomplete data. CONCLUSION: a small number of relatively low-powered studies showed no benefit or harm from SSRIs in terms of cognition, mood, agitation or ADLs. Large, methodologically robust studies are needed.

Physical fitness training for stroke patients.

BACKGROUND: Levels of physical fitness are low after stroke. It is unknown whether improving physical fitness after stroke reduces disability. OBJECTIVES: To determine whether fitness training after stroke reduces death, dependence, and disability and to assess the effects of training with regard to adverse events, risk factors, physical fitness, mobility, physical function, quality of life, mood, and cognitive function. Interventions to improve cognitive function have attracted increased attention after being identified as the highest rated research priority for life after stroke. Therefore we have added this class of outcomes to this updated review. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched February 2015), the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 1: searched February 2015), MEDLINE (1966 to February 2015), EMBASE (1980 to February 2015), CINAHL (1982 to February 2015), SPORTDiscus (1949 to February 2015), and five additional databases (February 2015). We also searched ongoing trials registers, handsearched relevant journals and conference proceedings, screened reference lists, and contacted experts in the field. SELECTION CRITERIA: Randomised trials comparing either cardiorespiratory training or resistance training, or both (mixed training), with usual care, no intervention, or a non-exercise intervention in stroke survivors. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed quality and risk of bias, and extracted data. We analysed data using random-effects meta-analyses. Diverse outcome measures limited the intended analyses. MAIN RESULTS: We included 58 trials, involving 2797 participants, which comprised cardiorespiratory interventions (28 trials, 1408 participants), resistance interventions (13 trials, 432 participants), and mixed training interventions (17 trials, 957 participants). Thirteen deaths occurred before the end of the intervention and a further nine before the end of follow-up. No dependence data were reported. Diverse outcome measures restricted pooling of data. Global indices of disability show moderate improvement after cardiorespiratory training (standardised mean difference (SMD) 0.52, 95% confidence interval (CI) 0.19 to 0.84; P value = 0.002) and by a small amount after mixed training (SMD 0.26, 95% CI 0.04 to 0.49; P value = 0.02); benefits at follow-up (i.e. after training had stopped) were unclear. There were too few data to assess the effects of resistance training.Cardiorespiratory training involving walking improved maximum walking speed (mean difference (MD) 6.71 metres per minute, 95% CI 2.73 to 10.69), preferred gait speed (MD 4.28 metres per minute, 95% CI 1.71 to 6.84), and walking capacity (MD 30.29 metres in six minutes, 95% CI 16.19 to 44.39) at the end of the intervention. Mixed training, involving walking, increased preferred walking speed (MD 4.54 metres per minute, 95% CI 0.95 to 8.14), and walking capacity (MD 41.60 metres per six minutes, 95% CI 25.25 to 57.95). Balance scores improved slightly after mixed training (SMD 0.27, 95% CI 0.07 to 0.47). Some mobility benefits also persisted at the end of follow-up. The variability, quality of the included trials, and lack of data prevents conclusions about other outcomes and limits generalisability of the observed results. AUTHORS' CONCLUSIONS: Cardiorespiratory training and, to a lesser extent, mixed training reduce disability during or after usual stroke care; this could be mediated by improved mobility and balance. There is sufficient evidence to incorporate cardiorespiratory and mixed training, involving walking, within post-stroke rehabilitation programmes to improve the speed and tolerance of walking; some improvement in balance could also occur. There is insufficient evidence to support the use of resistance training. The effects of training on death and dependence after stroke are still unclear but these outcomes are rarely observed in physical fitness training trials. Cognitive function is under-investigated despite being a key outcome of interest for patients. Further well-designed randomised trials are needed to determine the optimal exercise prescription and identify long-term benefits.