Psychometric evaluation of a newly developed measure of emotionalism after stroke (TEARS-Q)

Objective: To evaluate, psychometrically, a new measure of tearful emotionalism following stroke: Testing Emotionalism After Recent Stroke – Questionnaire (TEARS-Q). Setting: Acute stroke units based in nine Scottish hospitals, in the context of a longitudinal cohort study of post-stroke emotionalism. Subjects: A total of 224 clinically diagnosed stroke survivors recruited between October 1st 2015 and September 30th 2018, within 2 weeks of their stroke. Measures: The measure was the self-report questionnaire TEARS-Q, constructed based on post-stroke tearful emotionalism diagnostic criteria: (i) increased tearfulness, (ii) crying comes on suddenly, with no warning (iii) crying not under usual social control and (iv) crying episodes occur at least once weekly. The reference standard was presence/absence of emotionalism on a diagnostic, semi-structured post-stroke emotionalism interview, administered at the same assessment point. Stroke, mood, cognition and functional outcome measures were also completed by the subjects. Results: A total of 97 subjects were female, with a mean age 65.1 years. 205 subjects had sustained ischaemic stroke. 61 subjects were classified as mild stroke. TEARS-Q was internally consistent (Cronbach’s alpha 0.87). TEARS-Q scores readily discriminated the two groups, with a mean difference of −7.18, 95% CI (−8.07 to −6.29). A cut off score of 2 on TEARS-Q correctly identified 53 of the 61 stroke survivors with tearful emotionalism and 140 of the 156 stroke survivors without tearful emotionalism. One factor accounted for 57% of the item response variance, and all eight TEARS-Q items acceptably discriminated underlying emotionalism. Conclusion: TEARS-Q accurately diagnoses tearful emotionalism after stroke

Depression and anxiety symptoms post-stroke/TIA:prevalence and associations in cross-sectional data from a regional stroke registry

BACKGROUND: Mood disorders are commonly seen in those with cerebrovascular disease. Literature to-date has tended to focus on depression and on patients with stroke, with relatively little known about post-stroke anxiety or mood disorder in those with transient ischaemic attack (TIA). We aimed to describe prevalence of depression and anxiety symptoms in stroke and TIA cohorts and to explore association with clinical and socio-demographic factors. METHODS: We used a city wide primary care stroke registry (Glasgow Local Enhanced Service for Stroke - LES). All community dwelling stroke-survivors were included. We described cross-sectional prevalence of depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS). Data on clinical and demographic details was collected and univariable and multivariable analyses performed to describe associations with HADS scores. We examined those with a diagnosis of 'stroke' and 'TIA' as separate cohorts. RESULTS: From 13,283 potentially eligible stroke patients in the registry, we had full HADS data on 4,079. Of the 3,584 potentially eligible TIA patients, we had full HADS data on 1,247 patients. Across the stroke cohort, 1181 (29%) had HADS anxiety scores suggestive of probable or possible anxiety; 993 (24%) for depression. For TIA patients, 361 (29%) had anxiety and 254 (21%) had depression. Independent predictors of both depression and anxiety symptoms were female sex, younger age and higher socioeconomic deprivation score (all p < 0.001). CONCLUSION: Using HADS, we found a high prevalence of anxiety and depression symptoms in a community-based cohort of patients with cerebrovascular disease

Xanthine oxidase inhibition and white matter hyperintensity progression following ischaemic stroke and transient ischaemic attack (XILO-FIST): a multicentre, double-blinded, randomised, placebo-controlled trial

BACKGROUND: People who experience an ischaemic stroke are at risk of recurrent vascular events, progression of cerebrovascular disease, and cognitive decline. We assessed whether allopurinol, a xanthine oxidase inhibitor, reduced white matter hyperintensity (WMH) progression and blood pressure (BP) following ischaemic stroke or transient ischaemic attack (TIA). METHODS: In this multicentre, prospective, randomised, double-blinded, placebo-controlled trial conducted in 22 stroke units in the United Kingdom, we randomly assigned participants within 30-days of ischaemic stroke or TIA to receive oral allopurinol 300 mg twice daily or placebo for 104 weeks. All participants had brain MRI performed at baseline and week 104 and ambulatory blood pressure monitoring at baseline, week 4 and week 104. The primary outcome was the WMH Rotterdam Progression Score (RPS) at week 104. Analyses were by intention to treat. Participants who received at least one dose of allopurinol or placebo were included in the safety analysis. This trial is registered with ClinicalTrials.gov, NCT02122718. FINDINGS: Between 25th May 2015 and the 29th November 2018, 464 participants were enrolled (232 per group). A total of 372 (189 with placebo and 183 with allopurinol) attended for week 104 MRI and were included in analysis of the primary outcome. The RPS at week 104 was 1.3 (SD 1.8) with allopurinol and 1.5 (SD 1.9) with placebo (between group difference −0.17, 95% CI −0.52 to 0.17, p = 0.33). Serious adverse events were reported in 73 (32%) participants with allopurinol and in 64 (28%) with placebo. There was one potentially treatment related death in the allopurinol group. INTERPRETATION: Allopurinol use did not reduce WMH progression in people with recent ischaemic stroke or TIA and is unlikely to reduce the risk of stroke in unselected people. FUNDING: The British Heart Foundation and the UK Stroke Association

Behavioural activation therapy for depression after stroke (BEADS): a study protocol for a feasibility randomised controlled pilot trial of a psychological intervention for post-stroke depression

Background There is currently insufficient evidence for the clinical and cost-effectiveness of psychological therapies for treating post-stroke depression. Methods/Design BEADS is a parallel group feasibility multicentre randomised controlled trial with nested qualitative research and economic evaluation. The aim is to evaluate the feasibility of undertaking a full trial comparing behavioural activation (BA) to usual stroke care for 4 months for patients with post-stroke depression. We aim to recruit 72 patients with post-stroke depression over 12 months at three centres, with patients identified from the National Health Service (NHS) community and acute services and from the voluntary sector. They will be randomly allocated to receive behavioural activation in addition to usual care or usual care alone. Outcomes will be measured at 6 months after randomisation for both participants and their carers, to determine their effectiveness. The primary clinical outcome measure for the full trial will be the Patient Health Questionnaire-9 (PHQ-9). Rates of consent, recruitment and follow-up by centre and randomised group will be reported. The acceptability of the intervention to patients, their carers and therapists will also be assessed using qualitative interviews. The economic evaluation will be undertaken from the National Health Service and personal social service perspective, with a supplementary analysis from the societal perspective. A value of information analysis will be completed to identify the areas in which future research will be most valuable. Discussion The feasibility outcomes from this trial will provide the data needed to inform the design of a definitive multicentre randomised controlled trial evaluating the clinical and cost-effectiveness of behavioural activation for treating post-stroke depression

Cyclophosphamide Chemotherapy Sensitizes Tumor Cells to TRAIL-Dependent CD8 T Cell-Mediated Immune Attack Resulting in Suppression of Tumor Growth

Background: Anti-cancer chemotherapy can be simultaneously lymphodepleting and immunostimulatory. Pre-clinical models clearly demonstrate that chemotherapy can synergize with immunotherapy, raising the question how the immune system can be mobilized to generate anti-tumor immune responses in the context of chemotherapy. Methods and Findings: We used a mouse model of malignant mesothelioma, AB1-HA, to investigate T cell-dependent tumor resolution after chemotherapy. Established AB1-HA tumors were cured by a single dose of cyclophosphamide in a CD8 T cell- and NK cell-dependent manner. This treatment was associated with an IFN-α/β response and a profound negative impact on the anti-tumor and total CD8 T cell responses. Despite this negative effect, CD8 T cells were essential for curative responses. The important effector molecules used by the anti-tumor immune response included IFN-γ and TRAIL. The importance of TRAIL was supported by experiments in nude mice where the lack of functional T cells could be compensated by agonistic anti-TRAIL-receptor (DR5) antibodies. Conclusion: The data support a model in which chemotherapy sensitizes tumor cells for T cell-, and possibly NK cell-, mediated apoptosis. A key role of tumor cell sensitization to immune attack is supported by the role of TRAIL in tumor resolution and explains the paradox of successful CD8 T cell-dependent anti-tumor responses in the absence of CD8 T cell expansion

Stroke in women — from evidence to inequalities

Stroke is the second largest cause of disability-adjusted life-years lost worldwide. The prevalence of stroke in women is predicted to rise rapidly, owing to the increasing average age of the global female population. Vascular risk factors differ between women and men in terms of prevalence, and evidence increasingly supports the clinical importance of sex differences in stroke. The influence of some risk factors for stroke — including diabetes mellitus and atrial fibrillation — are stronger in women, and hypertensive disorders of pregnancy also affect the risk of stroke decades after pregnancy. However, in an era of evidence-based medicine, women are notably under-represented in clinical trials — despite governmental actions highlighting the need to include both men and women in clinical trials — resulting in a reduced generalizability of study results to women. The aim of this Review is to highlight new insights into specificities of stroke in women, to plan future research priorities, and to influence public health policies to decrease the worldwide burden of stroke in women

Covert and overt attention in trait anxiety: a cognitive psychophysiological analysis

The effect of threatening cues and anxiety upon attention within a Posner paradigm was investigated in two experiments. It was predicted anxious individuals would show a bias to threat-related material. Heart rate and eye movements were obtained to assess the attentional processes associated with this cognitive bias. Sixty and 40 participants were allocated respectively to groups based on self-reported scores of anxiety and repressive coping style. All participants were exposed to threat and non-threat cue words within a word based Posner cueing task. In the second study, spatial position of the target was manipulated, together with instructional set. Differential patterns of attentional disengagement to threat were found that were modulated by trait anxiety in study 2. A bias towards threat involving uninstructed eye movements was observed amongst anxious participants. Repressors made few such eye movements. Findings are discussed in relation to models of attentional deployment to threat

How does thought suppression impact upon beliefs about uncontrollability of worry?

According to Wells' metacognitive model of generalised anxiety disorder (GAD; [Wells, A. (1995). Meta-cognition and worry: A cognitive model of generalised anxiety disorder. Behavioural and Cognitive Psychotherapy, 23, 301-320]), GAD patients attempt to suppress intrusions that trigger worry. Wells postulates that these attempts are rarely effective and may increase the frequency of worry triggers. These apparent failures are interpreted as evidence for loss of mental control, thereby exacerbating beliefs about worry uncontrollability. The current study tested these predictions. Sixty-two high worriers completed a naturalistic experiment comprising two sessions separated by 1 week. In Session 1, participants recorded their beliefs about worry in general, including its uncontrollability. They then selected a current worry and recorded how often it came to mind over the following week. The Suppression group (N=32) suppressed their chosen worry during the week. The Mention group (N=30) simply monitored its occurrence. In Session 2, Session 1 measures were repeated. Contrary to prediction, the Suppression group reported a significant increase in worry controllability in general. No shift was demonstrated by the Mention group. In addition, relative to the Mention group, the Suppression group reported more success at suppressing their chosen worries, spent less time thinking about them, and found them more controllable and less distressing. Findings are discussed within the context of Wells' model

Examining the feed forward model of problem drinking and co-morbid panic disorder using a single case approach

Alcohol use and anxiety disorder frequently co-occur. Despite this, no research has satisfactorily examined the effect of alcoholism treatment on anxiety states. The effect of Relapse Prevention (RP) treatment on alcohol dependence and co-morbid panic disorder in a single case was therefore examined. RP reduced alcohol intake and anxiety levels, and eliminated panic attacks, although carrying alcohol to prevent panic attack remained. Belief change was achieved when this behaviour was eliminated. Results are consistent with a "feed-forward" model of co-morbidity. The need for further research exploring RP and co-morbid anxiety disorder is emphasized, as is work examining alcohol-related safety-seeking behaviour