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BACKGROUND: Depression is an important morbidity associated with stroke that impacts on recovery, yet is often undetected or inadequately treated. OBJECTIVES: To evaluate the benefits and harms of pharmacological intervention, non-invasive brain stimulation, psychological therapy, or combinations of these to treat depression after stroke. SEARCH METHODS: This is a living systematic review. We search for new evidence every two months and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review. We searched the Specialised Registers of Cochrane Stroke, and Cochrane Depression Anxiety and Neurosis, CENTRAL, MEDLINE, Embase, five other databases, two clinical trials registers, reference lists and conference proceedings (February 2022). We contacted study authors. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing: 1) pharmacological interventions with placebo; 2) non-invasive brain stimulation with sham stimulation or usual care; 3) psychological therapy with usual care or attention control; 4) pharmacological intervention and psychological therapy with pharmacological intervention and usual care or attention control; 5) pharmacological intervention and non-invasive brain stimulation with pharmacological intervention and sham stimulation or usual care; 6) non-invasive brain stimulation and psychological therapy versus sham brain stimulation or usual care and psychological therapy; 7) pharmacological intervention and psychological therapy with placebo and psychological therapy; 8) pharmacological intervention and non-invasive brain stimulation with placebo and non-invasive brain stimulation; and 9) non-invasive brain stimulation and psychological therapy versus non-invasive brain stimulation and usual care or attention control, with the intention of treating depression after stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studi

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.

INTRODUCTION: Despite digital health tools being popular for supporting self-management of chronic diseases, little research has been undertaken on stroke. We developed and pilot tested, using a randomized controlled design, a multicomponent digital health programme, known as Inspiring Virtual Enabled Resources following Vascular Events (iVERVE), to improve self-management after stroke. The 4-week trial incorporated facilitated person-centred goal setting, with those in the intervention group receiving electronic messages aligned to their goals, versus limited administrative messages for the control group. In this paper, we describe the participant experience of the various components involved with the iVERVE trial. METHODS: Mixed method design: satisfaction surveys (control and intervention) and a focus group interview (purposively selected intervention participants). Experiences relating to goal setting and overall trial satisfaction were obtained from intervention and control participants, with feedback on the electronic message component from intervention participants. Inductive thematic analysis was used for interview data and open-text responses, and closed questions were summarized descriptively. Triangulation of data allowed participants' perceptions to be explored in depth. RESULTS: Overall, 27/54 trial participants completed the survey (13 intervention: 52%; 14 control: 48%); and 5/8 invited participants in the intervention group attended the focus group. Goal setting: The approach was considered comprehensive, with the involvement of health professionals in the process helpful in developing realistic, meaningful and person-centred goals. Electronic messages (intervention): Messages were perceived as easy to understand (92%), and the frequency of receipt was considered appropriate (11/13 survey; 4/5 focus group). The content of messages was considered motivational (62%) and assisted participants to achieve their goals (77%). Some participants described the

BACKGROUND: Antidepressants may be useful in the treatment of abnormal crying associated with stroke. This is an update of a Cochrane Review first published in 2004 and last updated in 2019. OBJECTIVES: To evaluate the benefits and harms of pharmaceutical treatment in people with emotionalism after stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Register, CENTRAL, MEDLINE, Embase, four other databases, and three trials registers (May 2022). SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing psychotropic medication to placebo in people with stroke and emotionalism (also known as emotional lability, pathological crying or laughing, emotional incontinence, involuntary emotional expression disorder, and pseudobulbar affect). DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed risk of bias, extracted data from all included trials, and used GRADE to assess the certainty of the body of evidence. We calculated the mean difference (MD) or standardised mean difference (SMD) for continuous data and the risk ratio (RR) for dichotomous data, with 95% confidence intervals (CIs). We assessed heterogeneity using the I2 statistic. The primary emotionalism measures were the proportion of participants achieving at least a 50% reduction in abnormal emotional behaviour at the end of treatment, improved score on the Center for Neurologic Study - Lability Scale (CNS-LS) or Clinician Interview-Based Impression of Change (CIBIC), or diminished tearfulness. MAIN RESULTS: We did not identify any new trials for this update. We included seven trials with a total of 239 participants. Two trials had a cross-over design, but outcome data were not available from the first phase (precross-over) in an appropriate format for inclusion as a parallel randomised controlled trial (RCT). Thus, the results of the review are based on five trials with a total of 213 participants. It is uncertain whether fluoxetine inc

Objective: In this systematic review and meta-analysis, we aimed to quantify the effects of text messaging interventions to reduce depressive symptoms and identify variables that might influence the effectiveness of the intervention. Design: Electronic databases including EMBASE, CENTRAL, MEDLINE, CINAHL, PsycINFO and SCOPUS, as well as Clinicaltrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) were searched for randomised controlled trials that sent one or more text messages with health-related content to adults who had been identified by a healthcare provider. Results: Seven trials (nine comparisons), with 1,918 participants, were included in the review, and the pooled analysis revealed a borderline statistically significant reduction in depressive symptom scores between the text messaging intervention and control groups (standardised mean difference [SMD], −0.27; 95% confidence interval [CI], −0.54 to 0.00; p =.00) favouring intervention at the end. Statistically significant reductions were shown in important subgroups, for example, where the primary aim of the messages was to reduce depressive symptoms; in those using the Beck Depression Inventory (BDI) or 9-item Patient Health Questionnaire (PHQ-9) questionnaires; where text message content was targeted at mental well-being, mood improvement and cognitive behavioural therapy information; and when the message frequency was ⩾2 times per week. Conclusion: Text messaging has potential to reduce depressive symptoms. The results of this review should be interpreted with caution, however, due to the methodological limitations of included trials. More research is required before recommendations can be made about the routine use of text messaging for the management of depressive symptoms.

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 effec

Objective: Uncertainty exists over the prognostic significance of low arterial oxygen saturation (SaO2) in acute stroke. We aimed to determine the strength of association of SaO2 and adverse outcomes among participants of the international Head Positioning in acute Stroke Trial (HeadPoST). Methods: Post-hoc analyzes of HeadPoST, a pragmatic cluster-crossover randomized trial of lying flat versus sitting up head positioning in 11,093 patients (age ≥18 years) with acute stroke at 114 hospitals in 9 countries during 2015–2016. Associations of the lowest recorded SaO2 level, as a continuous measure and as a cut-point for desaturation (SaO2 <93%), in the first 24 h and clinical outcomes of death or dependency (modified Rankin scale [mRS] scores 3–6) and any serious adverse event (SAE) at 90 days, were assessed in generalized linear mixed models adjusted for baseline and in-hospital management confounders. Results: There was an inverse J-shaped association between SaO2 and death or dependency, with a nadir for optimal outcome at 96–97%. Patients with SaO2 desaturation were older, and had greater neurological impairment, premorbid disability and cardiorespiratory disease. Desaturation was not clearly associated with death or dependency (adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 0.95–1.48) but was with SAEs (aOR 1.34, 95% CI 1.07–1.68), without heterogeneity by head position, cardiac-respiratory comorbidity, or other pre-specified subgroups. Conclusions: Any change in SaO2 outside of 96–97% is associated with poorer outcome after acute stroke. Clinical trial registration: HeadPoST is registered at ClinicalTrials.gov (NCT02162017).

Objective: As uncertainties exist over underlying causes, we aimed to define the characteristics and prognostic significance of low blood pressure (BP) early after the onset of acute stroke. Methods: Post hoc analyzes of the international Head Positioning in acute Stroke Trial (HeadPoST), a pragmatic cluster-crossover randomized trial of lying flat versus sitting up in stroke patients from nine countries during 2015- 2016. Associations of baseline BP and death or dependency [modified Rankin scale (mRS) scores 3-6] and serious adverse events (SAEs) at 90 days were assessed in generalized linear mixed models with adjustment for multiple confounders. SBP and DBP was analysed as continuous measures fitted with a cubic spline, and as categorical measures with low (<10th percentile) and high (-140 and -90 mmHg, respectively) levels compared with a normal range (-10th percentile; 120-139 and 70- 89 mmHg, respectively). Results: Among 11 083 patients (mean age 68 years, 39.9% women) with baseline BP values, 7.2 and 11.7% had low SBP (<120 mmHg) and DBP (<70 mmHg), respectively. Patients with low SBP were more likely to have preexisting cardiac and ischemic stroke and functional impairment, and to present earlier with more severe neurological impairment than other patients. Nonlinear 'Jshaped' relationships of BP and poor outcome were apparent: Compared with normal SBP, those with low SBP had worse functional outcome (adjusted odds ratio 1.27, 95% confidence interval 1.02-1.58) and more SAEs, particularly cardiac events, with adjustment for potential confounders to minimize reverse causation. The findings were consistent for DBP and were stronger for ischemic rather than hemorrhagic stroke. Conclusion: The prognostic significance of low BP on poor outcomes in acute stroke was not explained by reverse causality from preexisting cardiovascular disease, and propensity towards greater neurological deficits and cardiac events. These findings provide support for the hypothesis tha

Background and aims: The structured, simplified modified Rankin scale questionnaire (smRSq) may increase reliability over the interrogative approach to scoring the modified Rankin scale (mRS) in acute stroke research and practice. During the conduct of the alteplase-dose arm of the international ENhanced Control of Hypertension ANd Thrombolysis StrokE stuDy (ENCHANTED), we had an opportunity to compare each of these approaches to outcome measurement. Methods: Baseline demographic data were recorded together with the National Institutes of Health Stroke Scale (NIHSS). Follow-up measures obtained at 90 days included mRS, smRSq, and the 5-Dimension European Quality of life scale (EQ-5D). Agreements between smRSq and mRS were assessed with the Kappa statistic. Multiple logistic regression was used to identify baseline predictors of Day 90 smRSq and mRS scores. Treatment effects, based on Day 90 smRSq/mRS scores, were tested in logistic and ordinal logistic regression models. Results: SmRSq and mRS scores had good agreement (weighted Kappa 0.79, 95% confidence interval (CI) 0.78–0.81), while variables of age, atrial fibrillation, diabetes mellitus, pre-morbid mRS (1 vs. 0), baseline NIHSS scores, and imaging signs of cerebral ischemia, similarly predicted their scores. Odds ratios for death or disability, and ordinal shift, 90-day mRS scores using smRSq were 1.05 (95% CI 0.91–1.20; one-sided P = 0.23 for non-inferiority) and 0.98 (95% CI 0.87–1.11; P = 0.02 for non-inferiority), similar to those using mRS. Conclusions: This study demonstrates the utility of the smRSq in a large, ethnically diverse clinical trial population. Scoring of the smRSq shows adequate agreement with the standard mRS, thus confirming it is a reliable, valid, and useful alternative measure of functional status after acute ischemic stroke. Clinical Trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616.

Background: An indwelling urinary catheter (IUC) is often inserted to manage bladder dysfunction, but its impact on prognosis is uncertain. We aimed to determine the association of IUC use on clinical outcomes after acute stroke in the international, multi-center, cluster crossover, Head Positioning in Acute Stroke Trial (HeadPoST). Methods: Data were analyzed on HeadPoST participants (n = 11,093) randomly allocated to the lying-flat or sitting-up head position. Binomial, logistic regression, hierarchical mixed models were used to determine associations of early insertion of IUC within seven days post-randomization and outcomes of death or disability (defined as “poor outcome,” scores 3–6 on the modified Rankin scale) and any urinary tract infection at 90 days with adjustment of baseline and post-randomization management covariates. Results: Overall, 1167 (12%) patients had an IUC, but the frequency and duration of use varied widely across patients in different regions. IUC use was more frequent in older patients, and those with vascular comorbidity, greater initial neurological impairment (on the National Institutes of Health Stroke Scale), and intracerebral hemorrhage as the underlying stroke type. IUC use was independently associated with poor outcome (adjusted odds ratio (aOR): 1.40, 95% confidence interval (CI): 1.13–1.74), but not with urinary tract infection after adjustment for antibiotic treatment and stroke severity at hospital separation (aOR: 1.13, 95% CI: 0.59–2.18). The number exposed to IUC for poor outcome was 13. Conclusions: IUC use is associated with a poor outcome after acute stroke. Further studies are required to inform appropriate use of IUC.

OBJECTIVE: To determine any differential efficacy and safety of low- vs standard-dose IV alteplase for lacunar vs nonlacunar acute ischemic stroke (AIS), we performed post hoc analyzes from the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED) alteplase dose arm. METHODS: In a cohort of 3,297 ENCHANTED participants, we identified those with lacunar or nonlacunar AIS with different levels of confidence (definite/according to prespecified definitions based on clinical and adjudicated imaging findings. Logistic regression models were used to determine associations of lacunar AIS with 90-day outcomes (primary, modified Rankin Scale [mRS] scores 2-6; secondary, other mRS scores, intracerebral hemorrhage [ICH], and early neurologic deterioration or death) and treatment effects of low- vs standard-dose alteplase across lacunar and nonlacunar AIS with adjustment for baseline covariables. RESULTS: Of 2,588 participants with available imaging and clinical data, we classified cases as definite/probable lacunar (n = 490) or nonlacunar AIS (n = 2,098) for primary analyses. Regardless of alteplase dose received, lacunar AIS participants had favorable functional (mRS 2-6, adjusted odds ratio [95% confidence interval] 0.60 [0.47-0.77]) and other clinical or safety outcomes compared to participants with nonlacunar AIS. Low-dose alteplase (versus standard) had no differential effect on functional outcomes (mRS 2-6, 1.04 [0.87-1.24]) but reduced the risk of symptomatic ICH in all included participants. There were no differential treatment effects of low- vs standard-dose alteplase on all outcomes across lacunar and nonlacunar AIS (all pinteraction ≥0.07). CONCLUSIONS: We found no evidence from the ENCHANTED trial that low-dose alteplase had any advantages over standard dose for definite/probable lacunar AIS. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with lacunar AIS, low-dose alteplase had no additional benefit or safe

Background & Purpose: Anxiety and depression are common among stroke survivors, and their effect on long-term outcome remains unknown in those under 65 years of age. We investigated the association between early anxiety/depression after stroke and 12-month disability, and whether this is modified by sex. Methods: The Psychosocial Outcomes In StrokE (POISE) study was a prospective observational cohort study that recruited 441 younger (< 65 years) stroke survivors ≤28 days of acute stroke. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale, and disability using the World Health Organization Disability Assessment Scale version II (WHODAS-II). Associations between baseline anxiety/depression, and disability at 12-months was tested using analysis of covariance. Subgroup analysis was conducted using interaction term. Results: 92 (25%) had anxiety and 53 (14%) depression at baseline. Multivariable models showed significant association between baseline anxiety and 12-month disability (WHODAS-II score 15.24 vs. 11.49, p < .05). Those with anxiety had more impairment in ‘cognition’ (WHODAS-II score 18.26 vs. 8.71, p < .001), ‘getting along’ (WHODAS-II score 11.87 vs. 7.42, p < .05) and ‘participation’ (WHODAS-II score 22.37 vs. 15.92, p < .005) WHODAS-II. No significant relationship was found between baseline depression and long-term disability. There was no differential effect of anxiety by sex found in this study. Conclusions: Post-stroke anxiety has an adverse effect on disability at one year among young stroke survivors.

Objective: To determine the course of sleep distrurbance (insomnia symptoms and short sleep duration) after a diagnosis of epilepsy and their associations with seizure control, mood, disability, and quality of life. Patients and methods: One hundred and sixty-nine adults were drawn from the Sydney Epilepsy Incidence Study to Measure Illness Consequences (SEISMIC), a prospective, multicenter, community-wide study in Sydney, Australia. Socio-demographic, psychosocial, clinical characteristics, and information on sleep disturbance were obtained early (median 48 [IQR15-113] days) after a diagnosis of epilepsy, and at 12 months. Logistic regression models were used to determine associations between patterns of sleep disturbance with outcomes at 12 months. Results: Insomnia symptoms and/or short sleep duration were present in 18-23% of participants at both time points, with over half (54-61%) showing a chronic pattern. There was no association of sleep disturbance pattern with recurrent seizures, medication use or disability. Chronic insomnia symptoms and short sleep duration were strongly associated with worse mental health (aOR 3.76, 95% CI 1.28-11.06; and aOR 5.41, 95% CI 1.86-15.79) and poorer quality of life at 12 months (aOR 3.02, 95% CI 1.03-8.84; and aOR 3.11, 95% CI 1.10-8.82), after adjusting for clinical features of epilepsy and comorbidity. Those whose sleep disturbance remitted had no adverse outcomes. Conclusions: Insomnia symptoms and short sleep duration are less common in people with recently-diagnosed than chronic epilepsy. The temporal association with poor psycholosocial outcomes supports specific interventions addressing sleep disturbance.

Background: Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods: AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings: Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, p

Background and Purpose: The influence of specific brain lesions on health-related quality of life (HRQoL) after acute ischemic stroke (AIS) is uncertain. We aimed to identify imaging predictors of poor HRQoL in alteplase-treated participants of the alteplase dose arm of the Enhanced Control of Hypertension and Thrombolysis Stroke Study (ENCHANTED). Methods: ENCHANTED was an international trial of low- versus standard-dose intravenous alteplase in AIS patients, with functional outcome (modified Rankin scale [mRS]) and HRQoL on the 5-dimension European Quality of Life Scale (EQ-5D) assessed at 90 days post-randomization. Brain images were analyzed centrally by trained assessors. Multivariable logistic regression was undertaken in the study population randomly divided (2:1) into training (development) and validation (performance) groups, with age (per 10-year increase), ethnicity, baseline National Institutes of Health Stroke Scale (NIHSS) score, diabetes mellitus, premorbid function (mRS score 0 or 1), and proxy respondent, forced into all models. Data are presented with odds ratios (ORs) and 95% confidence intervals (CIs). Results: Eight prediction models were developed and validated in 2,526 AIS patients (median age 67.5 years; 38.4% female; 61.7% Asian) with complete brain imaging and 90-day EQ-5D utility score data. The best performance model included acute ischemic changes in the right (OR 1.69, 95% CI: 1.24-2.29) and deep (OR 1.50, 95% CI: 1.03-2.19) middle cerebral artery (MCA) regions. Several background features of brain frailty - atrophy, white matter change, and old infarcts - were significantly associated with adverse physical but not emotional HRQoL domains. Conclusions: In thrombolysed AIS patients, right-sided and deep ischemia within the MCA territory predict poor overall HRQoL, whilst features of old cerebral ischemia are associated with reduced physical HRQoL.

Objective: Access to acute stroke unit (ASU) care is known to vary worldwide. We aimed to quantify regional variations in the various components of ASU care. Method: Secondary analysis of the Head Positioning in acute Stroke Trial (HeadPoST), an international, multicentre, cluster crossover trial of head-up versus head-down positioning in 11,093 acute stroke patients at 114 hospitals in 9 countries. Patients characteristics and 11 standard components of processes of care were described according to ASU admission within and across four economically-defined regional groups (Australia/UK, China [includes Taiwan], India/Sri Lanka, and South America [Brazil/Chile/Colombia]). Variations in process of ASU care estimates were obtained in hierarchical mixed models, with adjustment for study design and potential patient- and hospital-level confounders. Results: Of 11,086 patients included in analyses, 59.7% (n = 6620) had an ASU admission. In China, India/Sri Lanka and South America, ASU patients were older, had greater neurological severity and more premorbid conditions than non-ASU patients. ASU patients were more likely to receive reperfusion therapy and multidisciplinary care within regions, but the components of care varied across regions. With Australia/UK as reference, patients in other regions had a lower probability of receiving reperfusion therapy, especially in India/Sri Lanka (adjusted odds ratio [aOR] 0.27, 95% confidence interval [CI] 0.12–0.63) and multidisciplinary care (mainly in formal dysphagia assessment, physiotherapy and occupational therapy). Conclusion: There is significant variation in the components of stroke care across economically-defined regions of the world. Ongoing efforts are required to reduce disparities and optimise health outcomes, especially in resource poor areas. Clinical trial registration: HeadPoST is registered at ClinicalTrials.gov (NCT02162017).

Background and Purpose-Patient-centered outcomes are important. We aimed to determine predictors of health-related quality of life (HRQoL) and develop utility-weighted modified Rankin Scale (mRS) scores in thrombolyzed acute ischemic stroke patients from both arms of ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). Methods-ENCHANTED was an international quasi-factorial clinical trial of different doses of intravenous alteplase and intensities of blood pressure control in acute ischemic stroke patients, with outcomes on the 5-Dimensional European Quality of Life Scale and mRS assessed at 90 days post-randomization. Logistic regression models were used to identify baseline predictors of poor HRQoL (≤mean 5-Dimensional European Quality of Life Scale utility scores). Ordinary least squares regression derived utility-weighted mRS scores. Results-In 4016 acute ischemic stroke patients with complete 5-Dimensional European Quality of Life Scale and mRS data, independent predictors of poor HRQoL were older age (odds ratio, 1.19 [95% CI, 1.12-1.27], per 10-year increase), non-Asian ethnicity (1.91 [1.61-2.27]), greater stroke severity on the National Institutes of Health Stroke Scale (1.11 [1.09-1.12]), diabetes mellitus (1.41 [1.18-1.69]), premorbid disability (mRS score 1 versus 0; 1.62 [1.33-1.97]), large vessel atheromatous pathogenesis (1.32 [1.12-1.54]), and proxy respondent (2.35 [2.01-2.74]). Sensitivity analyses indicate the ethnicity influence on HRQoL was driven by the high proportion of Chinese (62.9% of Asian) participants with better HRQoL compared with non-Chinese or other Asian groups. Derived utility values across mRS scores 0 to 5 were 0.977, 0.885, 0.748, 0.576, 0.194, and-0.174, respectively. Correlations between mRS and 5-Dimensional European Quality of Life Scale scores were stronger in Asians. Conclusions-HRQoL is worse after thrombolyzed acute ischemic stroke in the elderly, non-Asians, with greater initial severity, diabetes

Background: Electronic communication is used in various populations to achieve health goals, but evidence in stroke is lacking. We pilot tested the feasibility and potential effectiveness of a novel personalised electronic self-management intervention to support person-centred goal attainment and secondary prevention after stroke. Methods: A phase I, prospective, randomised controlled pilot trial (1:1 allocation) with assessor blinding, intention-to-treat analysis, and a process evaluation. Community-based survivors of stroke were recruited from participants in the Australian Stroke Clinical Registry (AuSCR) who had indicated their willingness to be contacted for research studies. Inclusion criteria include 1–2 years following hospital admission for stroke and living within 50 km of Monash University (Melbourne). Person-centred goals were set with facilitation by a clinician using a standardised template. The intervention group received electronic support messages aligned to their goals over 4 weeks. The control group received only 2–3 electronic administrative messages. Primary outcomes were study retention, goal attainment (assessed using Goal Attainment Scaling method) and satisfaction. Secondary outcomes were self-management (Health Education Impact Questionnaire: 8 domains), quality of life, mood and acceptability. Results: Of 340 invitations sent from AuSCR, 73 responded, 68 were eligible and 57 (84%) completed the baseline assessment. At the goal-setting stage, 54/68 (79%) were randomised (median 16 months after stroke): 25 to intervention (median age 69 years; 40% female) and 29 to control (median age 68 years; 38% female). Forty-five (83%) participants completed the outcome follow-up assessment. At follow-up, goal attainment (mean GAS-T score ≥ 50) in the intervention group was achieved for goals related to function, participation and environment (control: environment only). Most intervention participants provided positive feedback and reported that the iVE

Following publication of the original article [1], we were notified that one of the corresponding author's affiliations was omitted. Affiliation no. 2 is now added to for Prof. Erik Lundstrom.

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 o

Background: Studies have suggested that fluoxetine could improve neurological recovery after stroke. The Efficacy oF Fluoxetine—a randomisEd Controlled Trial in Stroke (EFFECTS) trial aimed to assess whether administration of oral fluoxetine for 6 months after acute stroke improves functional outcome. Methods: EFFECTS was an investigator-led, multicentre, randomised, placebo-controlled, double-blind, parallel group trial that enrolled patients aged 18 years or older between 2 and 15 days after stroke onset in 35 stroke and rehabilitation centres in Sweden. Eligible patients had a clinical diagnosis of ischaemic or intracerebral haemorrhage, brain imaging that was consistent with intracerebral haemorrhage or ischaemic stroke, and had at least one persisting focal neurological deficit. A web-based randomisation system that incorporated a minimisation algorithm was used to randomly assign (1:1) participants to receive oral fluoxetine 20 mg once daily or matching placebo capsules for 6 months. Patients, care providers, investigators, and outcomes assessors were masked to the allocation. The primary outcome was functional status, measured with the modified Rankin Scale (mRS) at 6 months, analysed in all patients with available mRS data at the 6-month follow-up; we did an ordinal analysis adjusted for the minimisation variables used in the randomisation. This trial is registered with EudraCT, 2011-006130-16; ISRCTN, 13020412; and ClinicalTrials.gov, NCT02683213. Findings: Between Oct 20, 2014, and June 28, 2019, 1500 patients were enrolled, of whom 750 were randomly assigned to fluoxetine and 750 were randomly assigned to placebo. At 6 months, mRS data were available for 737 (98%) patients in the fluoxetine group and 742 (99%) patients in the placebo group. There was no effect of fluoxetine on the primary outcome—distribution across mRS score categories—compared with placebo (adjusted common odds ratio 0·94 [95% CI 0·78 to 1·13]; p=0·42). The proportion of patients with a

Background: Depression is an important morbidity associated with stroke that impacts on recovery yet often undetected or inadequately treated. This is an update and expansion of a Cochrane Review first published in 2004 and updated in 2008. Objectives: Primary objective. • To determine whether pharmacological therapy, non-invasive brain stimulation, psychological therapy, or combinations of these interventions reduce the prevalence of diagnosable depression after stroke. Secondary objectives. • To determine whether pharmacological therapy, non-invasive brain stimulation, psychological therapy, or combinations of these interventions reduce levels of depressive symptoms, improve physical and neurological function and health-related quality of life, and reduce dependency after stroke. • To assess the safety of and adherence to such treatments. Search methods: We searched the Specialised Registers of Cochrane Stroke and Cochrane Depression Anxiety and Neurosis (last searched August 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1), in the Cochrane Library, MEDLINE (1966 to August 2018), Embase (1980 to August 2018), the Cumulative Index to Nursing and Alllied Health Literature (CINAHL) (1982 to August 2018), PsycINFO (1967 to August 2018), and Web of Science (2002 to August 2018). We also searched reference lists, clinical trial registers (World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) to August 2018; ClinicalTrials.gov to August 2018), and conference proceedings, and we contacted study authors. Selection criteria: Randomised controlled trials comparing (1) pharmacological interventions with placebo; (2) one of various forms of non-invasive brain stimulation with sham stimulation or usual care; (3) one of various forms of psychological therapy with usual care and/or attention control; (4) pharmacological intervention and various forms of psychological therapy with pharmacological intervention and us

BACKGROUND:Depression is an important consequence of stroke that influences recovery yet often is not detected, or is inadequately treated. This is an update and expansion of a Cochrane Review first published in 2004 and previously updated in 2008. OBJECTIVES:The primary objective is to test the hypothesis that pharmacological, psychological therapy, non-invasive brain stimulation, or combinations of these interventions reduce the incidence of diagnosable depression after stroke. Secondary objectives are to test the hypothesis that pharmacological, psychological therapy, non-invasive brain stimulation or combinations of these interventions reduce levels of depressive symptoms and dependency, and improve physical functioning after stroke. We also aim to determine the safety of, and adherence to, the interventions. SEARCH METHODS:We searched the Specialised Register of Cochrane Stroke and the Cochrane Depression Anxiety and Neurosis (last searched August 2018). In addition, we searched the following databases; Cochrane Central Register of Controlled Trials, CENTRAL (the Cochrane Library, 2018, Issue 8), MEDLINE (1966 to August 2018), Embase (1980 to August 2018), PsycINFO (1967 to August 2018), CINAHL (1982 to August 2018) and three Web of Science indexes (2002 to August 2018). We also searched reference lists, clinical trial registers (World Health Organization International Clinical Trials Registry Platform (WHO ICTRP); to August 2018 and ClinicalTrials.gov; to August 2018), conference proceedings; we also contacted study authors. SELECTION CRITERIA:Randomised controlled trials (RCTs) comparing: 1) pharmacological interventions with placebo; 2) one of various forms of psychological therapy with usual care and/or attention control; 3) one of various forms of non-invasive brain stimulation with sham stimulation or usual care; 4) a pharmacological intervention and one of various forms of psychological therapy with a pharmacological intervention and usual care and/or at

Background: Post-stroke pneumonia and other infectious complications are serious conditions whose frequency varies widely across studies. Aims: We conducted a systematic review to estimate the frequency of post-stroke pneumonia and other types of major infection. Summary of review: MEDLINE, EMBASE, CINAHL, and PsycINFO databases were searched for prospective studies with consecutive recruitment of stroke patients. The primary outcome was post-stroke pneumonia. Secondary outcomes were any infection and urinary tract infection. Quality assessment was done using Newcastle Ottawa scale. Heterogeneity of estimates across study populations was calculated using Cochran's Q (heterogeneity χ 2 ) and I 2 statistics. A total of 47 studies (139,432 patients) with 48 sample populations were eligible for inclusion. Mean age of patients was 68.3 years and their mean National Institute of Health Stroke Scale score was 8.2. The pooled frequency of post-stroke pneumonia was 12.3% (95% confidence interval [CI] 11%–13.6%; I 2 = 98%). The pooled frequency from 2011 to 2017 was 13.5% (95% CI 11.8%–15.3%; I 2 = 98%) and comparable with earlier periods (P interaction = 0.31). The pooled frequency in studies in stroke units was 8% (95% CI 7.1%–9%; I 2 = 78%) and significantly lower than other locations (P interaction = 0.001). The pooled frequency of post-stroke infection was 21% (95% CI 13%–29.3%; I 2 = 99%) and of post-stroke urinary tract infection was 7.9% (95% CI 6.7%–9.3%; I 2 = 96%). Conclusion: Approximately 1 in 10 stroke patients experience pneumonia during the acute period of hospital care. The frequency of post-stroke pneumonia has remained stable in recent decades but is lower in patients receiving stroke unit care compared to management in other ward settings.

Background: Training family carers to provide evidence-based rehabilitation to stroke patients could address the recognized deficiency of access to stroke rehabilitation in low-resource settings. However, our randomized controlled trial in India (ATTEND) found that this model of care was not superior to usual care alone. Aims: This process evaluation aimed to better understand trial outcomes through assessing trial implementation and exploring patients’, carers’, and providers’ perspectives. Methods: Our mixed methods study included process, healthcare use data and patient demographics from all sites; observations and semi-structured interviews with participants (22 patients, 22 carers, and 28 health providers) from six sampled sites. Results: Intervention fidelity and adherence to the trial protocol was high across the 14 sites; however, early supported discharge (an intervention component) was not implemented. Within both randomized groups, some form of rehabilitation was widely accessed. ATTEND stroke coordinators provided counseling and perceived that sustaining patients’ motivation to continue with rehabilitation in the face of significant emotional and financial stress as a key challenge. The intervention was perceived as an acceptable community-based package with education as an important component in raising the poor awareness of stroke. Many participants viewed family-led rehabilitation as a necessary model of care for poor and rural populations who could not access rehabilitation. Conclusion: Difficulty in sustaining patient and carer motivation for rehabilitation without ongoing support, and greater than anticipated access to routine rehabilitation may explain the lack of benefit in the trial. Nonetheless, family-led rehabilitation was seen as a concept worthy of further development.

Background and Purpose- The FOCUS trial (Fluoxetine or Control Under Supervision) showed that fluoxetine did not improve modified Rankin Scale scores (mRS) but increased the risk of fractures. We aimed to describe the fractures, their impact on mRS and factors associated with fracture risk. Methods- A United Kingdom, multicenter, parallel-group, randomized, placebo-controlled trial. Patients ≥18 years with a clinical stroke and persisting deficit assessed 2 to 15 days after onset were eligible. Consenting patients were allocated fluoxetine 20 mg or matching placebo for 6 months. The primary outcome was the mRS at 6 months and secondary outcomes included fractures. Results- Sixty-five of 3127 (2.1%) patients had 67 fractures within 6 months of randomization; 43 assigned fluoxetine and 22 placebo. Fifty-nine (90.8%) had fallen and 26 (40%) had fractured their neck of femur. The effect of fluoxetine on mRS (common odds ratio =0.951) was not significantly altered by excluding fracture patients (common odds ratio =0.961). Cox proportional hazards modeling showed that only age >70 year (hazard ratio =1.97; 95% CI, 1.13-3.45; P=0.017), female sex (hazard ratio =2.13; 95% CI, 1.29-3.51; P=0.003), and fluoxetine (hazard ratio =2.00; 95% CI, 1.20-3.34; P=0.008) were independently associated with fractures. Conclusions- Most fractures resulted from falls. Although many fractures were serious, and likely to impair patients' function, the increased fracture risk did not explain the lack of observed effect of fluoxetine on mRS. Only increasing age, female sex, and fluoxetine were independent predictors of fractures. Clinical Trial Registration- URL: http://www.controlled-trials.com. Unique identifier: ISRCTN83290762.

Objectives: To determine the validity, sensitivity, specificity and acceptability of the culturally adapted nine-item Patient Health Questionnaire (aPHQ-9) as a screening tool for depression in Aboriginal and Torres Strait Islander people. Design: Prospective observational validation study, 25 March 2015 – 2 November 2016. Setting, participants: 500 adults (18 years or older) who identified as Aboriginal or Torres Strait Islander people and attended one of ten primary health care services or service events in urban, rural and remote Australia that predominantly serve Indigenous Australians, and were able to communicate sufficiently to respond to questionnaire and interview questions. Main outcome measures: Criterion validity of the aPHQ-9, with the depression module of the Mini-International Neuropsychiatric Interview (MINI) 6.0.0 as the criterion standard. Results: 108 of 500 participants (22%; 95% CI, 18–25%) had a current episode of major depression according to the MINI criterion. The sensitivity of the aPHQ-9 algorithm for diagnosing a current major depressive episode was 54% (95% CI, 40–68%), its specificity was 91% (95% CI, 88–94%), with a positive predictive value of 64%. For screening for a current major depressive episode, the area under the receiver operator characteristic curve was 0.88 (95% CI, 0.85–0.92); with a cut-point of 10 points its sensitivity was 84% (95% CI, 74–91%) and its specificity 77% (95% CI, 71–83%). The aPHQ-9 was deemed acceptable by more than 80% of participants. Conclusions: Indigenous Australians found the aPHQ-9 acceptable as a screening tool for depression. Applying a cut-point of 10 points, the performance characteristics of the aPHQ were good.

Background: Whether continuous positive airway pressure (CPAP) treatment can improve depression or anxiety symptoms in obstructive sleep apnoea (OSA) patients remains uncertain. Methods: Secondary analysis of the Sleep Apnea Cardiovascular Endpoints (SAVE) trial, combined with a systematic review of randomised evidence. The SAVE secondary analyses involved 2410 patients with co-existing moderate–severe OSA and established cardiovascular disease randomly allocated to CPAP treatment plus usual care or usual care alone and followed up for 3·7 (SD 1·6) years. We evaluated the effect of CPAP treatment on depression and anxiety caseness (scores ≥ 8 on the Hospital Anxiety and Depression Scale depression and anxiety subscales [HADS-D and HADS-A]) for OSA patients. Findings: CPAP treatment was associated with reduced odds of depression caseness (adjusted odds ratio [OR] 0·80, 95% confidence interval [CI] 0·65–0·98, P = 0·031) compared to usual care in the SAVE trial and the treatment effect was greater in those with pre-existing depression symptoms. A systematic review of 20 randomised trials including 4255 participants confirmed a benefit of CPAP in reducing depression symptoms in OSA patients: the overall effect (standardised mean difference) was − 0·18 (95% CI − 0·24 to − 0·12). No effect of CPAP treatment on anxiety caseness was found both in patients of the SAVE study (adjusted OR 0·98, 95% CI 0·78–1·24, P = 0·89) and the systematic review. Interpretation: CPAP reduces depression symptoms in patients with co-existing OSA and CVD independently of improvements in sleepiness.

Background The uptake of proven stroke treatments varies widely. We aimed to determine the association of evidence-based processes of care for acute ischemic stroke (AIS) and clinical outcome of patients who participated in the HEADPOST (Head Positioning in Acute Stroke Trial), a multicenter cluster crossover trial of lying flat versus sitting up, head positioning in acute stroke. Methods and Results Use of 8 AIS processes of care were considered: Reperfusion therapy in eligible patients; acute stroke unit care; antihypertensive, antiplatelet, statin, and anticoagulation for atrial fibrillation; dysphagia assessment; and physiotherapist review. Hierarchical, mixed, logistic regression models were performed to determine associations with good outcome (modified Rankin Scale scores 0-2) at 90 days, adjusted for patient and hospital variables. Among 9485 patients with AIS, implementation of all processes of care in eligible patients, or “defect-free” care, was associated with improved outcome (odds ratio, 1.40; 95% CI, 1.18-1.65) and better survival (odds ratio, 2.23; 95% CI, 1.62-3.09). Defect-free stroke care was also significantly associated with excellent outcome (modified Rankin Scale score 0-1) (odds ratio, 1.22; 95% CI, 1.04-1.43). No hospital characteristic was independently predictive of outcome. Only 1445 (15%) of eligible patients with AIS received all processes of care, with significant regional variations in overall and individual rates. Conclusions Use of evidence-based care is associated with improved clinical outcome in AIS. Strategies are required to address regional variation in the use of proven AIS treatments.

Introduction: Epilepsy influences the ability to drive. We aimed to systematically summarize factors associated with driving, holding a driver's license, and traffic accidents among people with seizures. Material and methods: Eight databases were searched (from their inception to 27 June 2018). We included all published observational studies, except for case reports and studies with fewer than 50 participants. Pooled mean differences and pooled risk ratios (pRRs) with corresponding confidence intervals (CIs) were calculated using random effects. Results: Data were available from 18 studies, reporting a wide range of factors. There were frequent biases associated with cross-sectional study designs, selection bias, poor statistical quality, small samples, and lack of validation of models. The following six variables were consistently associated with driving: male gender (pRR: 1.42; 95% CI: 1.23 to 1.64), being in paid work (pRR: 1.72; 95% CI: 1.46 to 2.03), married (pRR: 1.26; 95% CI: 1.01 to 1.57), older age at seizure onset or diagnosis (pooled mean difference: 4.83; 95% CI: 0.48 to 9.18 years), less frequent seizures (fewer than monthly, pRR: 1.32; 95% CI: 1.12 to 1.56), and taking one or no antiepileptic drug (pRR: 1.34; 95% CI: 1.09 to 1.63). Lower seizure frequency was also protective for avoiding traffic accidents (pRR: 0.26; 95% CI: 0.10 to 0.66). Discussion: Stable multivariate models to predict driving or traffic accidents among people with seizures have not yet been developed. Current evidence shows that the likelihood of driving is associated with demographic and epilepsy-related factors, while the risk of traffic accidents is associated with seizure frequency.

Objective: To determine the patterns and predictors of disability over the first 12 months after a diagnosis of epilepsy. Patients and methods: The Sydney Epilepsy Incidence Study to Measure Illness Consequences (SEISMIC) was a prospective, multicenter, community-based study of people with newly diagnosed epilepsy in Sydney, Australia. Disability was assessed using the World Health Organization's, Disability Assessment Schedule (WHODAS) 2.0 12-item version, at baseline (i.e. within 28 days of diagnosis) and 12 months post-diagnosis. Demographic, socioeconomic, clinical and epilepsy-related data, obtained through structured interviews, were entered into multivariable linear regression and shift analysis to determine predictors of greater disability. Results: Of 259 adults (≥18 years), 190 (73%) had complete WHODAS at baseline (mean ± SD scores 4 ± 6) and follow-up (4 ± 8). After adjustment for age, sex and co-morbidity, greater overall disability at 12 months was associated with lower education (P = 0.05), economic hardship (P = 0.004), multiple antiepileptic medications (P = 0.02) and greater disability (P < 0.001) at the time of diagnosis; these variables explained 38.3% of the variance. Among the 12 WHODAS items, “being emotionally affected by health problems” was the most frequent disability problem identified at both time points (all P < 0.0001). The proportion of participants without problems in that domain improved over 12 months (from 24% to 50%, P < 0.0001), whereas the other 11 items remained relatively stable. Independent baseline predictors of a worse emotional outcome at 12 months were severe/extreme emotional distress (odds ratio [OR] 4.52, 95% confidence intervals [CI] 1.67–12.24), economic hardship (OR 2.30, 95% CI 1.24–4.25) and perceived stigma (OR 2.02, 95% CI 1.03–3.93). Conclusion: Most people report problems with emotional health after a diagnosis of epilepsy but many recover over the next 12 months. Services addressing the social and psychologi

Background Antidepressants may be useful in the treatment of abnormal crying associated with stroke. This is an update of a Cochrane Review first published in 2004 and last updated in 2010. Objectives To determine whether pharmaceutical treatment reduces the frequency of emotional displays in people with emotionalism after stroke. Search methods We searched the trial register of Cochrane Stroke (last searchedMay 2018). In addition, we searched the Cochrane Central Register of Controlled Trials (CENTRAL; to May 2018), MEDLINE (1966 to 14 May 2018), Embase (1980 to 14 May 2018), CINAHL (1982 to 14 May 2018), PsycINFO (1967 to 14 May 2018), BIOSIS Previews (2002 to 14 May 2018), Web of Science (2002 to 14 May 2018), WHO ICTRP (to 14 May 2018), ClinicalTrials.gov (to 14 May 2018), and ProQuest Dissertations and Theses Database (to 14 May 2018). Selection criteria Randomised controlled trials (RCTs) and quasi-RCTs comparing psychotropic medication to placebo in people with stroke and emotionalism (also known as emotional lability, pathological crying or laughing, emotional incontinence, involuntary emotional expression disorder, and pseudobulbar affect). Data collection and analysis Two review authors independently selected studies, assessed risk of bias, extracted data from all included studies, and used GRADE to assess the quality of the body of evidence.We calculated mean difference (MD) or standardised mean difference (SMD) for continuous data and risk ratio (RR) for dichotomous data with 95% confidence intervals (CIs). We assessed heterogeneity using the I2 statistic. The primary emotionalism measures were the proportion of participants achieving at least a 50% reduction in abnormal emotional behaviour at the end of treatment, improved score on Center for Neurologic Study-Lability Scale (CNS-LS), Clinician Interview-Based Impression of Change (CIBIC) or diminished tearfulness. Main results We included seven trials with a total of 239 participants. Two trials were of

Objective We aimed to evaluate the effects on depression scores of a lifestyle-focused cardiac support programme delivered via mobile phone text messaging among patients with coronary heart disease (CHD). Design Substudy and secondary analysis of a parallel-group, single-blind randomised controlled trial of patients with CHD. Setting A tertiary hospital in Sydney, Australia. Intervention The Tobacco, Exercise and dieT MEssages programme comprised four text messages per week for 6 months that provided education, motivation and support on diet, physical activity, general cardiac education and smoking, if relevant. The programme did not have any specific mental health component. Outcomes Depression scores at 6 months measured using the Patient Health Questionnaire-9 (PHQ-9). Treatment effect across subgroups was measured using log-binomial regression model for the binary outcome (depressed/not depressed, where depressed is any score of PHQ-9 ≥5) with treatment, subgroup and treatment by subgroup interaction as fixed effects. Results Depression scores at 6 months were lower in the intervention group compared with the control group, mean difference 1.9 (95% CI 1.5 to 2.4, p<0.0001). The frequency of mild or greater depressive symptoms (PHQ-9 scores≥5) at 6 months was 21/333 (6.3%) in the intervention group and 86/350 (24.6%) in the control group (relative risk (RR) 0.26, 95% CI 0.16 to 0.40, p<0.001). This proportional reduction in depressive symptoms was similar across groups defined by age, sex, education, body mass index, physical activity, current smoking, current drinking and history of depression, diabetes and hypertension. In particular, the rates of PHQ-9 ≥5 among people with a history of depression were 4/44 (9.1%) vs 29/62 (46.8%) in intervention vs control (RR 0.19, 95% CI 0.07 to 0.51, p<0.001), and were 17/289 (5.9%) vs 57/288 (19.8%) among others (RR 0.30, 95% CI 0.18 to 0.50, p<0.001). Conclusions Among people with CHD, a cardiac support programme delivere

ObjectiveTo explore the sex differences in outcomes and management after stroke using a large sample with high-quality international trial data.MethodsIndividual participant data were obtained from 5 acute stroke randomized controlled trials. Data were obtained on demographics, medication use, in-hospital treatment, and functional outcome. Study-specific crude and adjusted models were used to estimate sex differences in outcomes and management, and then pooled using random-effects meta-analysis.ResultsThere were 19,652 participants, of whom 7,721 (40%) were women. After multivariable adjustments, women with ischemic stroke had higher survival at 3-6 months (odds ratio [OR] 0.82, 95% confidence interval [CI] 0.70-0.97), higher likelihood of disability (OR 1.20, 95% CI 1.06-1.36), and worse quality of life (weighted mean difference -0.07, 95% CI -0.09 to 0.04). For management, women were more likely to be admitted to an acute stroke unit (OR 1.17, 95% CI 1.01-1.34), but less likely to be intubated (OR 0.58, 95% CI 0.36-0.93), treated for fever (OR 0.82, 95% CI 0.70-0.95), or admitted to an intensive care unit (OR 0.83, 95% CI 0.74-0.93). For preadmission medications, women had higher odds of being prescribed antihypertensive agents (OR 1.22, 95% CI 1.13-1.31) and lower odds of being prescribed antiplatelets (OR 0.86, 95% CI 0.79-0.93), glucose-lowering agents (OR 0.86, 95% CI 0.78-0.94), or lipid-lowering agents (OR 0.85, 95% CI 0.77-0.94).ConclusionsThis analysis suggests that women who had ischemic stroke had better survival but were also more disabled and had poorer quality of life. Variations in hospital and out-of-hospital management may partly explain the disparities.

The Head Positioning in Acute Stroke Trial (HeadPoST) is a pragmatic, international, cluster crossover randomized trial of 11,093 patients with acute stroke assigned to a lying-flat (0°) or sitting-up (head elevated ≥30°) position. This post hoc analysis aimed to determine the association between blood pressure variability (BPV) and outcomes for patients from a wide range of international clinical settings and how the association was modified by randomized head position. BPV was defined according to the standard criteria, with the key parameter considered the coefficient of variation (CV) of systolic BP (SBP) over 24 h. Outcome was ordinal 90-day Modified Rankin Scale (mRS) score. The association was analyzed by ordinal, logistic regression, hierarchical, mixed models with fixed intervention (lying flat vs. sitting up), and fixed period, random cluster, and random cluster-period, effects. Nine thousand one hundred and fifty six (8324 acute ischemic stroke and 817 intracerebral hemorrhage; mean age 68.1 years; 39.2% women) were included in the analysis. CV of SBP had a significant linear association with unfavorable shift of mRS at 90 days (adjusted odds ratio 1.06, 95% confidence interval 1.02–1.11; P = 0.01). There was no heterogeneity of the association by randomized head positioning. In addition, CV of diastolic BP (DBP) (1.08, 1.03–1.12; P = 0.001) over 24 h post stroke was significantly associated with 3-month poor outcome. The association was more apparent in sitting-up position (1.12, 1.06–1.19) compared with lying-flat position (1.03, 0.98–1.09) (P interaction = 0.005). BPV was associated with adverse stroke outcome, and the magnitude of the association was greater with sitting-up head positioning in terms of DBP variability.

BACKGROUND: Research can inform culturally-appropriate care to strengthen social and emotional wellbeing (SEWB) among Aboriginal and Torres Strait Islander (hereafter, the term 'Indigenous Peoples' is respectfully used and refers to all Aboriginal and/or Torres Strait Islander Peoples of Australia). We acknowledge the cultural diversity of Australia's Indigenous First Peoples and they do not represent a homogenous group.) (hereafter Indigenous) Peoples. We explore the perspectives of primary healthcare staff and Indigenous patients about their willingness to and experiences participating in SEWB research. METHOD: Process evaluation using grounded theory approaches of Getting it Right: The validation study, a national validation designed Indigenous SEWB research project (N = 500). Primary healthcare staff (n = 36) and community members (n = 4) from nine of ten primary healthcare services involved with the research project completed qualitative semi-structured interviews. Interview data were triangulated with participant feedback (responses to structured questions and free-text feedback collected during Getting it Right), study administrative data (participant screening logs, communication logs, study protocol, deviation logs and ethics correspondence) and interviewer field notes. RESULTS: Three themes about staff, patient and community perspectives concerning research participation developed: (1) considering the needs, risk, preferences and impact of participation in research for staff, patients and community; (2) building staff confidence speaking to patients about research and SEWB problems and (3) patients speaking openly about their SEWB. Some staff described pressure to ensure patients had a positive experience with the research, to respond appropriately if patients became upset or SEWB problems were identified during interviews, or due to their dual role as community member and researcher. Patients and staff reported that patients were more likely to participat

Background: Pneumonia is a common complication after stroke which increases morbidity and mortality. This systematic review was conducted to evaluate the efficacy and safety of antibiotics for the prevention of pneumonia after acute stroke. Methods: Medline, EMBASE, and Cochrane databases were searched for randomized controlled trials comparing preventive antibiotics to placebo or no antibiotics after acute stroke. The primary outcome was poststroke pneumonia. Secondary outcomes were all infections, urinary tract infections, death, dependency, length of hospital stay, and adverse events. Treatment effects were summarized using random effects metaanalysis. Results: Six trials (4111 patients) were eligible for inclusion. The median National Institute of Health Stroke Scale score in included trials ranged from 5 to 16.5. The proportion of dysphagia ranged from 26% to 100%. Preventive antibiotics were commenced within 48 hours after acute stroke. Compared to control, preventive antibiotics reduced the risk of poststroke pneumonia (RR.75, 95%CI ·.57-.99), and all infections (RR.58, 95%CI.48-.69). There was no significant difference in the risks of dependency (RR 0.99, 95%CI 0·80-1·11), or mortality (RR.96, 95%CI.78-1.19) between the preventive antibiotics and control groups. Preventive antibiotics did not increase the risk of elevated liver enzymes (RR 1.20, 95% CI.97-1.49). Preventive antibiotics had uncertain effects on the risks of other adverse events. Conclusion: Preventive antibiotics reduced the risk of post-stroke pneumonia. However, there is insufficient evidence to currently recommend routine use of preventive antibiotics after acute stroke.

Objective Depression after stroke and myocardial infarction (MI) is common but often assumed to be undertreated without reliable evidence being available. Thus, we aimed to determine treatment rates and investigate the application of guidelines in these conditions. Methods Databases MEDLINE, EMBASE, PsycInfo, Web of Science, CINAHL, and Scopus were systematically searched without language restriction from inception to June 30, 2017. Prospective observational studies with consecutive recruitment reporting any antidepressant treatment in adults with depression after stroke or MI were included. Random-effects models were used to calculate pooled estimates of treatment rates. Results Fifty-five studies reported 32 stroke cohorts (n = 8938; pooled frequency of depression = 34%, 95% confidence interval [CI] = 29%-38%) and 17 MI cohorts (n = 10,767; pooled frequency of depression = 24%, 95% CI = 20%-28%). In 29 stroke cohorts, 24% (95% CI = 20%-27%) of 2280 depressed people used antidepressant medication. In 15 MI cohorts, 14% (95% CI = 8%-19%) of 2381 depressed people used antidepressant medication indicating a lower treatment rate than in stroke. Two studies reported use of psychosocial interventions, indicating that less than 10% of participants were treated. Conclusions Despite the high frequency of depression after stroke and MI and the existence of efficacious treatment strategies, people often remain untreated. Innovative strategies are needed to increase the use of effective antidepressive interventions in patients with cardiovascular disease.