| 1. |
- Hinwood, M., et al.
(författare)
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Do P2Y12 receptor inhibitors prescribed poststroke modify the risk of cognitive disorder or dementia? Protocol for a target trial using multiple national Swedish registries
- 2022
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Ingår i: Bmj Open. - : BMJ. - 2044-6055. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction The target of a class of antiplatelet medicines, P2Y12R inhibitors, exists both on platelets and on brain immune cells (microglia). This protocol aims to describe a causal (based on a counterfactual model) approach for analysing whether P2Y12R inhibitors prescribed for secondary prevention poststroke may increase the risk of cognitive disorder or dementia via their actions on microglia, using real-world evidence. Methods and analysis This will be a cohort study nested within the Swedish National Health and Medical Registers, including all people with incident stroke from 2006 to 2016. We developed directed acyclic graphs to operationalise the causal research question considering potential time-independent and time-dependent confounding, using input from several experts. We developed a study protocol following the components of the target trial approach described by Hernan et al and describe the data structure that would be required in order to make a causal inference. We also describe the statistical approach required to derive the causal estimand associated with this important clinical question; that is, a time-to-event analysis for the development of cognitive disorder or dementia at 1, 2 and 5-year follow-up, based on approaches for competing events to account for the risk of all-cause mortality. Causal effect estimates and the precision in these estimates will be quantified. Ethics and dissemination This study has been approved by the Ethics Committee of the University of Gothenburg and Confidentiality Clearance at Statistics Sweden with Dnr 937-18, and an approved addendum with Dnr 2019-0157. The analysis and interpretation of the results will be heavily reliant on the structure, quality and potential for bias of the databases used. When we implement the protocol, we will consider and document any biases specific to the dataset and conduct appropriate sensitivity analyses. Findings will be disseminated to local stakeholders via conferences, and published in appropriate scientific journals.
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| 2. |
- Jones, K. A., et al.
(författare)
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Chronic stress exacerbates neuronal loss associated with secondary neurodegeneration and suppresses microglial-like cells following focal motor cortex ischemia in the mouse
- 2015
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Ingår i: Brain Behavior and Immunity. - : Elsevier BV. - 0889-1591. ; 48, s. 57-67
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Tidskriftsartikel (refereegranskat)abstract
- Post-stroke patients describe suffering from persistent and unremitting levels of distress. Using an experimental model of focal cortical ischemia in adult male C57BL/6 mice, we examined whether exposure to chronic stress could modify the development of secondary thalamic neurodegeneration (STND), which is commonly reported to be associated with impaired functional recovery. We were particularly focused on the modulatory role of microglia-like cells, as several clinical studies have linked microglial activation to the development of STND. One month following the induction of cortical ischemia we identified that numbers of microglial-like cells, as well as putative markers of microglial structural reorganization (Iba-1), complement processing (CD11b), phagocytosis (CD68), and antigen presentation (MHC-II) were all significantly elevated in response to occlusion. We further identified that these changes co-occurred with a decrease in the numbers of mature neurons within the thalamus. Occluded animals that were also exposed to chronic stress exhibited significantly lower levels of Iba-1 positive cells and a reduced expression of Iba-1 and CD11b compared to the 'occlusion-alone' group. Interestingly, the dampened expression of microglial/monocyte markers observed in stressed animals was associated with significant additional loss of neurons. These findings indicate that the process of STND can be negatively modified, potentially in a microglial dependent manner, by exposure to chronic stress. (C) 2015 Elsevier Inc. All rights reserved.
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| 3. |
- Bhaskar, S., et al.
(författare)
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The influence of initial stroke severity on mortality, overall functional outcome and in-hospital placement at 90 days following acute ischemic stroke: A tertiary hospital stroke register study
- 2017
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Ingår i: Neurology India. - : Medknow. - 0028-3886. ; 65:6, s. 1252-1259
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: Epidemiological studies on the extent of the interaction and/or influence of stroke severity on clinical outcomes are important. The aim of the present study was to investigate the putative (and degree of) impact of initial stroke severity in predicting the overall functional outcome, in-hospital placement, and mortality in acute ischemic stroke (AIS) in comparison with age, admission to the stroke unit and thrombolytic treatment. Materials and Methods: The John Hunter Hospital acute stroke register was used to collect a retrospective cohort of AIS patients being assessed for reperfusion therapy and admitted between January 2006 and December 2013. Univariate and multivariate logistic regression and receiver operating characteristics analyses were used to assess associations with functional outcome, in-hospital placement, and mortality at 90 days. Results: 608 AIS patients with complete datasets were included in the study. On univariate analysis, initial stroke severity showed the strongest independent association to the risk of death within 90 days (Odds ratio (OR) = 1.15; P < 0.001; 95% confidence interval (CI) = [1.11, 1.18]); age was a less significant independent influence (OR = 1.02; P = 0.049; 95% CI = [1.00, 1.03]). Multivariate logistic regression analysis demonstrated that initial stroke severity independently predicted the 90 day mortality (OR = 1.16; 95% CI = [1.12, 1.2]; P < 0.0001) and unfavorable outcome (OR = 1.16; 95% CI = [1.13, 1.2]; P < 0.0001). Higher National Institute of Health Stroke Scale at admission was significantly associated with longer in-hospital placement (P < 0.0001). Conclusions: In this acute stroke cohort, initial stroke severity had a major impact on the likelihood of death following an AIS and appears to be the dominant influence on the overall stroke outcome and in-hospital placement.
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| 4. |
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| 5. |
- Harris, Simon R., et al.
(författare)
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Whole-genome analysis of diverse Chlamydia trachomatis strains identifies phylogenetic relationships masked by current clinical typing
- 2012
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 44:4, s. 413-419
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Tidskriftsartikel (refereegranskat)abstract
- Chlamydia trachomatis is responsible for both trachoma and sexually transmitted infections, causing substantial morbidity and economic cost globally. Despite this, our knowledge of its population and evolutionary genetics is limited. Here we present a detailed phylogeny based on whole-genome sequencing of representative strains of C. trachomatis from both trachoma and lymphogranuloma venereum (LGV) biovars from temporally and geographically diverse sources. Our analysis shows that predicting phylogenetic structure using ompA, which is traditionally used to classify Chlamydia, is misleading because extensive recombination in this region masks any true relationships present. We show that in many instances, ompA is a chimera that can be exchanged in part or as a whole both within and between biovars. We also provide evidence for exchange of, and recombination within, the cryptic plasmid, which is another key diagnostic target. We used our phylogenetic framework to show how genetic exchange has manifested itself in ocular, urogenital and LGV C. trachomatis strains, including the epidemic LGV serotype L2b.
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| 6. |
- Holm, Niels R, et al.
(författare)
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OCT or Angiography Guidance for PCI in Complex Bifurcation Lesions.
- 2023
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Ingår i: The New England journal of medicine. - 1533-4406. ; 389:16, s. 1477-1487
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Tidskriftsartikel (refereegranskat)abstract
- Imaging-guided percutaneous coronary intervention (PCI) is associated with better clinical outcomes than angiography-guided PCI. Whether routine optical coherence tomography (OCT) guidance in PCI of lesions involving coronary-artery branch points (bifurcations) improves clinical outcomes as compared with angiographic guidance is uncertain.We conducted a multicenter, randomized, open-label trial at 38 centers in Europe. Patients with a clinical indication for PCI and a complex bifurcation lesion identified by means of coronary angiography were randomly assigned in a 1:1 ratio to OCT-guided PCI or angiography-guided PCI. The primary end point was a composite of major adverse cardiac events (MACE), defined as death from a cardiac cause, target-lesion myocardial infarction, or ischemia-driven target-lesion revascularization at a median follow-up of 2 years.We assigned 1201 patients to OCT-guided PCI (600 patients) or angiography-guided PCI (601 patients). A total of 111 patients (18.5%) in the OCT-guided PCI group and 116 (19.3%) in the angiography-guided PCI group had a bifurcation lesion involving the left main coronary artery. At 2 years, a primary end-point event had occurred in 59 patients (10.1%) in the OCT-guided PCI group and in 83 patients (14.1%) in the angiography-guided PCI group (hazard ratio, 0.70; 95% confidence interval, 0.50 to 0.98; P=0.035). Procedure-related complications occurred in 41 patients (6.8%) in the OCT-guided PCI group and 34 patients (5.7%) in the angiography-guided PCI group.Among patients with complex coronary-artery bifurcation lesions, OCT-guided PCI was associated with a lower incidence of MACE at 2 years than angiography-guided PCI. (Funded by Abbott Vascular and others; OCTOBER ClinicalTrials.gov number, NCT03171311.).
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| 7. |
- Janssen, H., et al.
(författare)
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Translating the use of an enriched environment poststroke from bench to bedside: study design and protocol used to test the feasibility of environmental enrichment on stroke patients in rehabilitation
- 2012
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Ingår i: International Journal of Stroke. - : SAGE Publications. - 1747-4930 .- 1747-4949. ; 7:6, s. 521-526
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Tidskriftsartikel (refereegranskat)abstract
- Rationale Environmental enrichment, a paradigm investigated extensively in animal models, is an intervention, which by design facilitates motor, sensory, social, and cognitive activity. It has been shown to improve poststroke motor and cognitive function in animal models of stroke. This is the first study to attempt to translate this intervention from the laboratory to the clinical setting. Aims The overall aim of this pilot study is to test the feasibility of using environmental enrichment with stroke patients in a rehabilitation setting. The aim is to enrich the environment of stroke survivors in a rehabilitation ward and measure changes in their activity (physical, cognitive, and social activity). Design Prospective nonrandomized block design intervention study. Study In the control phase we will determine the change in activity levels of patients treated in a usual rehabilitation environment over time. In the intervention phase structured observational techniques (behavioural mapping) will be used to quantify the change in activity levels of patients exposed to environmental enrichment. Outcomes The primary outcome is change in activity level. Additional data collected on entry to and exit from the study will include: cognitive function using a battery of cognitive tests, general function using the Functional Independence Measure, mood using the Patient Health Questionnaire 9 and boredom using the Stroke Rehabilitation Boredom Survey. Quality of life will be assessed using the Assessment of Quality of Life 1 month postdischarge from rehabilitation. Australian New Zealand Clinical Trials Registry# ACTRN12611000629932.
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| 8. |
- Lillicrap, T., et al.
(författare)
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Growth Hormone Deficiency Is Frequent After Recent Stroke
- 2018
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The incidence of pituitary dysfunction after severe ischemic stroke is unknown, however given the increasing attention to pituitary dysfunction after neurological injuries such as traumatic brain injury, this may represent a novel area of research in stroke. Methods: We perform an arginine and human growth hormone releasing hormone challenge on ischemic stroke patients within a week of symptom onset. Results: Over the study period, 13 patients were successfully tested within a week of stroke (baseline NIHSS 10, range 7-16). Overall, 9(69%) patients had a poor response, with 7(54%) of these patients meeting the criteria for had human growth hormone deficiency. Other measures of pituitary function were within normal ranges. Conclusion: After major ischemic stroke, low GH levels are common and may play a role in stroke recovery.
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