Allopurinol and blood pressure variability following ischemic stroke and transient ischemic attack: a secondary analysis of XILO-FIST.

Blood Pressure Variability (BPV) is associated with cardiovascular risk and serum uric acid level. We investigated whether BPV was lowered by allopurinol and whether it was related to neuroimaging markers of cerebral small vessel disease (CSVD) and cognition. We used data from a randomised, double-blind, placebo-controlled trial of two years allopurinol treatment after recent ischemic stroke or transient ischemic attack. Visit-to-visit BPV was assessed using brachial blood pressure (BP) recordings. Short-term BPV was assessed using ambulatory BP monitoring (ABPM) performed at 4 weeks and 2 years. Brain MRI was performed at baseline and 2 years. BPV measures were compared between the allopurinol and placebo groups, and with CSVD and cognition. 409 participants (205 allopurinol; 204 placebo) were included in the visit-to-visit BPV analyses. There were no significant differences found between placebo and allopurinol groups for any measure of visit-to-visit BPV. 196 participants were included in analyses of short-term BPV at week 4. Two measures were reduced by allopurinol: the standard deviation (SD) of systolic BP (by 1.30 mmHg (95% confidence interval (CI) 0.18-2.42, p = 0.023)); and the average real variability (ARV) of systolic BP (by 1.31 mmHg (95% CI 0.31-2.32, p = 0.011)). There were no differences in other measures at week 4 or in any measure at 2 years, and BPV was not associated with CSVD or cognition. Allopurinol treatment did not affect visit-to-visit BPV in people with recent ischemic stroke or TIA. Two BPV measures were reduced at week 4 by allopurinol but not at 2 years.

Two Novel Adenoviruses in Free-Living British lizards.

In this study, we describe two novel adenoviruses isolated from (i) a common lizard (Zootoca vivipara) found dead and examined post-mortem and (ii) pooled samples from free-living sand lizards (Lacerta agilis agilis). Sequencing indicated the two were closely related atadenovirus strains which were distinct from previously recorded adenoviruses in lizards. Adenoviruses are not always associated with disease in squamates, but morbidity and mortality have been reported. These are the first known cases of adenovirus infection in free-living native British lizards, and further monitoring will be necessary to elucidate the implications of these possible pathogens for vulnerable populations of native reptiles.

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

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

Strangled by Dr Strangelove? Anarchic hand following a posterior cerebral artery territory ischemic stroke.

Anarchic hand is a rare condition where the complex movements of one hand appear to be goal directed and smoothly executed and yet are unintended and unwanted. Unlike alien hand syndrome, the patients recognise that the affected hand is part of their own body. They know the hand is theirs, but they deny having control over its actions. The syndrome has been reported after surgery on the corpus callosum and with brain tumours, aneurysms, degenerative diseases of the brain and uncommonly with stroke. We present a case of a 74-year-old man who developed an anarchic right hand following thrombolysis for a posterior cerebral artery territory ischemic stroke.

Development of a novel method to measure material surface staining by cigarette, e-cigarette or tobacco heating product aerosols.

Tobacco smoke (CS) may visually stain indoor surfaces including ceilings, walls and soft furnishings over time. Potentially reduced risk products (PRRPs) such as e-cigarettes (EC) and tobacco heating products (THP) produce chemically less complex aerosols with significantly reduced levels of toxicants, particles and odour. However, the potential effects of EC and THP aerosols on the staining of indoor surfaces are currently unknown. In this study, an exposure chamber was developed as a model system to enable the accelerated staining of wallpaper and cotton samples by a scientific reference cigarette (3R4F), three THP (glo™, glo™ pro, glo™ sens) and an e-cigarette (iSwitch Maxx). Exposure to 3R4F reference cigarettes caused the greatest level of staining, which was significantly higher than glo™, glo™ pro, glo™ sens or iSwitch Maxx aerosols, all of which showed relatively little colour change. Exposure to 200-1000 puffs of 3R4F cigarette smoke resulted in a visible dose response effect to wallpaper and cotton samples which was not observed following exposure to glo™, glo™ pro, glo™ sens or iSwitch Maxx aerosols. Aging of the samples for 4 weeks post-exposure resulted in changes to the staining levels, however PRRP staining levels were minimal and significantly lower than 3R4F exposed samples. For the first time, diverse PRRPs across the tobacco and nicotine products risk continuum have been assessed in vitro for their impact on surface staining. CS exposure significantly increased the level of wallpaper and cotton staining, whereas exposure to glo™, glo™ pro, glo™ sens or iSwitch Maxx aerosols resulted in significantly reduced levels of staining, staining levels were also comparable to untreated control samples.

Assessment of enamel discoloration in vitro following exposure to cigarette smoke and emissions from novel vapor and tobacco heating products.

PURPOSE: To evaluate in vitro enamel sample discoloration following exposure to a scientific reference cigarette (3R4F) or emissions from next generation tobacco and nicotine products (NGPs) such as electronic cigarettes (EC) and tobacco heating products (THP). METHODS: Bovine enamel blocks (6.5 × 6.5 mm) were prepared and pre-incubated with human or artificial saliva, to form a pellicle layer before exposure to either particulate matter (PM) or whole aerosols. PM was prepared by capturing 3R4F cigarette smoke (CS), a commercial THP (THP1.0) or a novel vapor product (NVP)/next generation e-cigarette aerosols on Cambridge filter pads followed by elution with dimethyl sulfoxide (DMSO). Ten enamel samples were exposed to each PM for 14 days. For aerosol exposure, 12 enamel samples were exposed (200 puffs per day, for 5 consecutive days) to 3R4F CS or THP1.0 and NVP aerosols. Control samples were incubated with DMSO (PM study) or phosphate buffered saline (PBS, aerosol study). Individual enamel sample color readings (L*, a*, b*) were measured at baseline and on each exposure day. Mean ΔL*, Δa*, Δb* and ΔE values were calculated for each product or control. A one-way ANOVA was used to assess the differences between the products and controls. The Tukey procedure for pairwise comparisons was also used. RESULTS: At all timepoints, 3R4F PM and CS induced enamel discoloration that was statistically significant (< 0.0001) when compared to THP1.0 or NVP. After 14-day PM exposure, mean ΔE values were 29.4± 3.6, 10.5 ± 2.3, 10.7 ± 2.6 and 12.6 ± 2.0 for 3R4F, THP1.0, NVP and DMSO control respectively. After 5-day CS or aerosol exposure, mean ΔE values were 26.2 ± 3.2, 3.6 ± 1.9, 3.4 ± 1.3, 5.3 ± 0.8 for 3R4F CS, THP1.0, NVP or PBS control, respectively. Both exposure methods demonstrated that THP1.0 and NVP induced minimal staining, mean ΔL* , Δa* , Δb* and ΔE values were comparable to DMSO or PBS controls. CLINICAL SIGNIFICANCE: For the first time, diverse NGPs across the risk continuum were assessed in vitro for their impact on enamel staining. CS exposure significantly increased the level of bovine enamel sample discoloration, whereas THP1.0 or NVP exposure resulted in values comparable to the controls.

Outcomes, experiences and palliative care in major stroke: a multicentre, mixed-method, longitudinal study.

BACKGROUND: Case fatality after total anterior circulation stroke is high. Our objective was to describe the experiences and needs of patients and caregivers, and to explore whether, and how, palliative care should be integrated into stroke care. METHODS: From 3 stroke services in Scotland, we recruited a purposive sample of people with total anterior circulation stroke, and conducted serial, qualitative interviews with them and their informal and professional caregivers at 6 weeks, 6 months and 1 year. Interviews were transcribed for thematic and narrative analysis. The Palliative Care Outcome Scale, EuroQol-5D-5L and Caregiver Strain Index questionnaires were completed after interviews. We also conducted a data linkage study of all patients with anterior circulation stroke admitted to the 3 services over 6 months, which included case fatality, place of death and readmissions. RESULTS: Data linkage (n = 219) showed that 57% of patients with total anterior circulation stroke died within 6 months. The questionnaires recorded that the patients experienced immediate and persistent emotional distress and poor quality of life. We conducted 99 interviews with 34 patients and their informal and professional careers. We identified several major themes. Patients and caregivers faced death or a life not worth living. Those who survived felt grief for a former life. Professionals focused on physical rehabilitation rather than preparation for death or limited recovery. Future planning was challenging. "Palliative care" had connotations of treatment withdrawal and imminent death. INTERPRETATION: Major stroke brings likelihood of death but little preparation. Realistic planning with patients and informal caregivers should be offered, raising the possibility of death or survival with disability. Practising the principles of palliative care is needed, but the term "palliative care" should be avoided or reframed.

Prognostic value of blood interleukin-6 in the prediction of functional outcome after stroke: a systematic review and meta-analysis.

We aimed to quantify the association of blood interleukin-6 (IL-6) concentrations with poor outcome after stroke and its added predictive value over clinical information. Meta-analysis of 24 studies confirmed this association with a weighted mean difference of 3.443 (1.592-5.294) pg/mL, despite high heterogeneity and publication bias. Individual participant data including 4112 stroke patients showed standardized IL-6 levels in the 4th quartile were independently associated with poor outcome (OR=2.346 (1.814-3.033), p<0.0001). However, the additional predictive value of IL-6 was moderate (IDI=1.5%, NRI=5.35%). Overall these results indicate an unlikely translation of IL-6 into clinical practice for this purpose.

Associations of inflammatory and haemostatic biomarkers with poor outcome in acute ischaemic stroke.

BACKGROUND: Many inflammatory and haemostatic biomarkers show associations with acute ischaemic stroke outcome, but few studies compare a large range of markers. METHODS: We assessed clinical status and 16 biomarkers within 24 h of onset in 180 consecutive acute ischaemic stroke patients. RESULTS: A total of 94 patients had a poor outcome (dead or dependent at 30 days). C-reactive protein (CRP), IL-6, and fibrin D-dimer showed the strongest univariate associations with poor outcome (>2-fold increase; p < 0.01). When all biomarkers were included with clinical variables in a multivariable model, only D-dimer (OR 1.54; 95% CI 1.09-2.17), CRP (OR 1.31; 95% CI 1.03-1.68) and Scandinavian Stroke Scale (OR 0.91; 95% CI 0.88-0.95) were associated with poor outcome. CONCLUSIONS: D-dimer and CRP are independently associated with poor outcome in acute ischaemic stroke. More data is required to expand our understanding of these potential relationships with outcome.

PI3K and RAC signalling in leukocyte and cancer cell migration.

Leukocytes and amoeboid-stage cancer cells migrate in a similar manner. Key signalling molecules regulating leukocyte and cancer cell migration are phosphoinositide 3-kinase (PI3K) and the Rho family of small GTPases. While PI3K activity defines the leading edge of the cell, Rho family GTPases regulate the cytoskeletal remodelling during polarisation and migration. We review here briefly the roles of PI3K, of the Rho-family GTPase Rac, and of the guanine-nucleotide exchange factors that activate Rac, in leukocyte and cancer cell migration.