What is the benefit of a high-intensive exercise program on health-related quality of life and depression after stroke? A randomized controlled trial

The aim of the study was to evaluate the impact of a high-intensive exercise program containing high-intensive functional exercises implemented to real-life situations together with group discussions on falls and security aspects in stroke subjects with risk of falls. This was a pre-specified secondary outcome for this study. For evaluation, Short Form-36 (SF-36) health-related quality of life (HRQoL) and the Geriatric Depression Scale-15 (GDS-15) were used. This was a single-center, single-blinded, randomized, controlled trial. Consecutive >55 years old stroke patients with risk of falls at 3–6 months after first or recurrent stroke were randomized to the intervention group (IG, n = 15) or to the control group (CG, n = 19) who received group discussion with focus on hidden dysfunctions but no physical fitness training. The 5-week high-intensive exercise program was related to an improvement in the CG in the SF-36 Mental Component Scale and the Mental Health subscale at 3 months follow-up compared with baseline values while no improvement was seen in the IG at this time. For the SF-36 Physical Component Scale, there was an improvement in the whole study group at 3 and 6 months follow-up compared with baseline values without any significant changes between the IG and CG. The GDS-15 was unchanged throughout the follow-up period for both groups. Based on these data, it is concluded that high-intensive functional exercises implemented in real-life situations should also include education on hidden dysfunctions after stroke instead of solely focus on falls and safety aspects to have a favorable impact on HRQoL

Antithrombotic treatment after intracerebral hemorrhage: Surveys among stroke physicians in Scandinavia and the United Kingdom

BACKGROUND AND AIMS: It is unclear whether patients with previous intracerebral hemorrhage (ICH) should receive antithrombotic treatment to prevent ischemic events. We assessed stroke physicians' opinions about this, and their views on randomizing patients in trials assessing this question. METHODS: We conducted three web‐based surveys among stroke physicians in Scandinavia and the United Kingdom. RESULTS: Eighty‐nine of 205 stroke physicians (43%) responded to the Scandinavian survey, 161 of 180 (89%) to the UK antiplatelet survey, and 153 of 289 (53%) to the UK anticoagulant survey. In Scandinavia, 19 (21%) stroke physicians were uncertain about antiplatelet treatment after ICH for ischemic stroke or transient ischemic attack (TIA) and 21 (24%) for prior myocardial infarction. In the United Kingdom, 116 (77%) were uncertain for ischemic stroke or TIA and 115 (717%) for ischemic heart disease. In Scandinavia, 32 (36%) were uncertain about anticoagulant treatment after ICH for atrial fibrillation, and 26 (29%) for recurrent deep vein thrombosis or pulmonary embolism. In the United Kingdom, 145 (95%) were uncertain about anticoagulants after ICH in at least some cases. In both regions combined, 191 of 250 (76%) would consider randomizing ICH survivors in a trial of starting versus avoiding antiplatelets, and 176 of 242 (73%) in a trial of starting versus avoiding anticoagulants. CONCLUSION: Considerable proportions of stroke physicians in Scandinavia and the United Kingdom were uncertain about antithrombotic treatment after ICH. A clear majority would consider randomizing patients in trials assessing this question. These findings support the need for such trials

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 Fluoxetine—a 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, 0.76–1.10]). Patients allocated fluoxetine scored worse on memory with a median value of 89 (interquartile range, 75–100) versus 93 (interquartile range, 82–100); P =0.0021 and communication 93 (interquartile range, 82–100) versus 96 (interquartile range, 86–100); 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

Update on the EFFECTS study of fluoxetine for stroke recovery: a randomised controlled trial in Sweden

Studies have suggested that fluoxetine might improve neurological recovery after stroke, but the results remain inconclusive. The EFFECTS (Efficacy oF Fluoxetine – a randomisEd Controlled Trial in Stroke) reached its recruitment target of 1500 patients in June 2019. The purpose of this article is to present all amendments to the protocol and describe how we formed the EFFECTS trial collaboration in Sweden. Methods In this investigator-led, multicentre, parallel-group, randomised, placebo-controlled trial, we enrolled non-depressed stroke patients aged 18 years or older between 2 and 15 days after stroke onset. The patients had a clinical diagnosis of stroke (ischaemic or intracerebral haemorrhage) with persisting focal neurological deficits. Patients were randomised to fluoxetine 20 mg or matching placebo capsules once daily for 6 months. Results Seven amendments were made and included clarification of drug interaction between fluoxetine and metoprolol and the use of metoprolol for severe heart failure as an exclusion criterion, inclusion of data from central Swedish registries and the Swedish Stroke Register, changes in informed consent from patients, and clarification of design of some sub-studies. EFFECTS recruited 1500 patients at 35 centres in Sweden between 20 October 2014 and 28 June 2019. We plan to unblind the data in January 2020 and report the primary outcome in May 2020. Conclusion EFFECTS will provide data on the safety and efficacy of 6 months of treatment with fluoxetine after stroke in a Swedish health system setting. The data from EFFECTS will also contribute to an individual patient data meta-analysis

Image Analysis Based Grading of Bladder Carcinoma. Comparison of Object, Texture and Graph Based Methods and Their Reproducibility

The possibility that computerized image analysis could increase the reproducibility of grading of bladder carcinoma as compared to conventional subjective grading made by pathologists was investigated. Object, texture and graph based analysis were carried out from Feulgen stained histological tissue sections. The object based features were extracted from gray scale images, binary images obtained by thresholding the nuclei and several other images derived through image processing operations. The textural features were based on the spatial gray‐tone co‐occurrence probability matrices and the graph based features were extracted from the minimum spanning trees connecting all nuclei. The large numbers of extracted features were evaluated in relation to subjective grading and to factors related to prognosis using multivariate statistical methods and multilayer backpropagation neural networks. All the methods were originally developed and tested on material from one patient and then tested for reproducibility on entirely different patient material. The results indicate reasonably good reproducibility for the best sets of features. In addition, image analysis based grading showed almost identical correlation to mitotic density and expression of p53 protein as subjective grading. It should thus be possible to use this kind of image analysis as a prognostic tool for bladder carcinoma

STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage (STATICH): Protocol for a randomised controlled trial

Background and aims: Many patients with prior intracerebral haemorrhage have indications for antithrombotic treatment with antiplatelet or anticoagulant drugs for prevention of ischaemic events, but it is uncertain whether such treatment is beneficial after intracerebral haemorrhage. STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage will assess (i) the effects of long-term antithrombotic treatment on the risk of recurrent intracerebral haemorrhage and occlusive vascular events after intracerebral haemorrhage and (ii) whether imaging findings, like cerebral microbleeds, modify these effects. Methods: STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage is a multicentre, randomised controlled, open trial of starting versus avoiding antithrombotic treatment after non-traumatic intracerebral haemorrhage, in patients with an indication for antithrombotic treatment. Participants with vascular disease as an indication for antiplatelet treatment are randomly allocated to antiplatelet treatment or no antithrombotic treatment. Participants with atrial fibrillation as an indication for anticoagulant treatment are randomly allocated to anticoagulant treatment or no anticoagulant treatment. Cerebral CT or MRI is performed before randomisation. Duration of follow-up is at least two years. The primary outcome is recurrent intracerebral haemorrhage. Secondary outcomes include occlusive vascular events and death. Assessment of clinical outcomes is performed blinded to treatment allocation. Target recruitment is 500 participants. Trial status: Recruitment to STudy of Antithrombotic Treatment after IntraCerebral Haemorrhage is on-going. On 30 April 2020, 44 participants had been enrolled in 31 participating hospitals. An individual patient-data meta-analysis is planned with similar randomised trials

A global view of protein expression in human cells, tissues, and organs

Defining the protein profiles of tissues and organs is critical to understanding the unique characteristics of the various cell types in the human body. In this study, we report on an anatomically comprehensive analysis of 4842 protein profiles in 48 human tissues and 45 human cell lines. A detailed analysis of over 2 million manually annotated, high-resolution, immunohistochemistry-based images showed a high fraction (>65%) of expressed proteins in most cells and tissues, with very few proteins (<2%) detected in any single cell type. Similarly, confocal microscopy in three human cell lines detected expression of more than 70% of the analyzed proteins. Despite this ubiquitous expression, hierarchical clustering analysis, based on global protein expression patterns, shows that the analyzed cells can be still subdivided into groups according to the current concepts of histology and cellular differentiation. This study suggests that tissue specificity is achieved by precise regulation of protein levels in space and time, and that different tissues in the body acquire their unique characteristics by controlling not which proteins are expressed but how much of each is produced

Carotid bruits as predictor for carotid stenoses detected by ultrasonography: an observational study

<p>Abstract</p> <p>Background</p> <p>Carotid surgery in asymptomatic subjects with carotid stenosis is effective to prevent ischemic stroke. There is, however, uncertainty how to find such persons at risk, because mass screening with carotid artery ultrasonography (US) is not cost-effective. Signs of carotid bruits corresponding to the carotid arteries may serve as a tool to select subjects for further investigation. This study is thus aimed at determining the usefulness of carotid bruits in the screening of carotid stenoses.</p> <p>Methods</p> <p>1555 consecutive carotid ultrasonography investigations from 1486 cases done between January 2004 and March 2006 at Norrlands University Hospital, Sweden, were examined. 356 subjects, medium age 69 (27–88) years, had a significant (≥ 50%) US-verified carotid stenosis uni- or bilaterally, 291 had been examined for signs of carotid bruits. The likelihood ratios for carotid bruits to predict US-verified carotid stenoses were calculated and expressed as likelihood percentages.</p> <p>Results</p> <p>Thirty-one out of 100 persons (31%) with carotid bruit as an indication to perform carotid US had a significant (≥ 50%) carotid stenosis. 281 of the 356 (79%) cases with significant carotid stenoses were found among patients with cerebrovascular disease (CVD). 145 of 226 (64%) CVD patients with a significant carotid stenosis had a carotid bruit. In patients with 50–99% carotid stenoses carotid bruits had an accuracy of 75% (436/582), a sensitivity of 71% (236/334), a specificity of 81% (200/248), a positive likelihood ratio at 3.65 and a negative likelihood at 0.36. Patients with 70–99% stenoses had the highest sensitivity at 77% (183/238). In patients with 100% carotid stenoses, carotid bruits had a sensitivity of 26% (15/57) and a specificity of 49% (256/525).</p> <p>Conclusion</p> <p>Although carotid bruits are not accurate to confirm or to exclude significant carotid stenoses, these signs are appropriate for directed screening for further investigation with carotid US if the patient lacks contraindications for surgery. Lack of carotid bruits in CVD patients does not exclude a carotid stenosis.</p