Are methodological quality and completeness of reporting associated with citation-based measures of publication impact? A secondary analysis of a systematic review of dementia biomarker studies

Objective: To determine whether methodological and reporting quality are associated with surrogate measures of publication impact in the field of dementia biomarker studies. Methods: We assessed dementia biomarker studies included in a previous systematic review in terms of methodological and reporting quality using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) and Standards for Reporting of Diagnostic Accuracy (STARD), respectively. We extracted additional study and journal-related data from each publication to account for factors shown to be associated with impact in previous research. We explored associations between potential determinants and measures of publication impact in univariable and stepwise multivariable linear regression analyses. Outcome measures: We aimed to collect data on four measures of publication impact: two traditional measures—average number of citations per year and 5-year impact factor of the publishing journal and two alternative measures—the Altmetric Attention Score and counts of electronic downloads. Results: The systematic review included 142 studies. Due to limited data, Altmetric Attention Scores and electronic downloads were excluded from the analysis, leaving traditional metrics as the only analysed outcome measures. We found no relationship between QUADAS and traditional metrics. Citation rates were independently associated with 5-year journal impact factor (β=0.42; p<0.001), journal subject area (β=0.39; p<0.001), number of years since publication (β=-0.29; p<0.001) and STARD (β=0.13; p<0.05). Independent determinants of 5-year journal impact factor were citation rates (β=0.45; p<0.001), statement on conflict of interest (β=0.22; p<0.01) and baseline sample size (β=0.15; p<0.05). Conclusions: Citation rates and 5-year journal impact factor appear to measure different dimensions of impact. Citation rates were weakly associated with completeness of reporting, while neither traditional metric was related to methodological rigour. Our results suggest that high publication usage and journal outlet is not a guarantee of quality and readers should critically appraise all papers regardless of presumed impact

Social engagement after stroke – is it relevant to cognitive function? A cross-sectional analysis of UK Biobank data

Background: Findings from studies in older adult populations suggest that measures of social engagement may be associated with health outcomes, including cognitive function. Plausibly the magnitude and direction of this association may differ in stroke. The disabling nature of stroke increases the likelihood of social isolation and stroke survivors are at high risk of cognitive decline. We assessed the association between social engagement and cognitive function in a sample of stroke survivors. Methods: We included available data from stroke survivors in the UK Biobank (N=8776; age range: 40-72; 57.4% male). In a series of regression models, we assessed cross-sectional associations between proxies of social engagement (frequency of family/friend visits, satisfaction with relationships, loneliness, opportunities to confide in someone, participation in social activities) and performance on domain specific cognitive tasks: reaction time, verbal-numerical reasoning, visual memory and prospective memory. We adjusted for demographics, health-, lifestyle-, and stroke-related factors. Accounting for multiple testing, we set our significance threshold at p<0.003. Results: After adjusting for covariates, we found independent associations between faster reaction times and monthly family visits as compared to no visit (standardised beta=-0.32, 99.7% CI: -0.61 to -0.03, N=4,930); slower reaction times and religious group participation (standardised beta=0.25, 99.7% CI 0.07 to 0.44, N=4,938); and poorer performance on both verbal-numerical reasoning and prospective memory tasks with loneliness (standardised beta=-0.19, 99.7% CI: -0.34 to -0.03, N=2,074; odds ratio=0.66, 99.7% CI: 0.46 to 0.94, N=2,188; respectively). In models where all proxies of social engagement were combined, no associations remained significant. Conclusions: We found limited task-specific associations between cognitive performance and proxies of social engagement, with only loneliness related to two tasks. Further studies are necessary to confirm and improve our understanding of these relationships and investigate the potential to target psychosocial factors to support cognitive function in stroke survivors

Thinking About the Future: A Review of Prognostic Scales Used in Acute Stroke

Background: There are many prognostic scales that aim to predict functional outcome following acute stroke. Despite considerable research interest, these scales have had limited impact in routine clinical practice. This may be due to perceived problems with internal validity (quality of research), as well as external validity (generalizability of results). We set out to collate information on exemplar stroke prognosis scales, giving particular attention to the scale content, derivation, and validation.Methods: We performed a focused literature search, designed to return high profile scales that use baseline clinical data to predict mortality or disability. We described prognostic utility and collated information on the content, development and validation of the tools. We critically appraised chosen scales based on the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modeling Studies (CHARMS).Results: We chose 10 primary scales that met our inclusion criteria, six of which had revised/modified versions. Most primary scales used 5 input variables (range: 4–13), with substantial overlap in the variables included. All scales included age, eight included a measure of stroke severity, while five scales incorporated pre-stroke level of function (often using modified Rankin Scale), comorbidities and classification of stroke type. Through our critical appraisal, we found issues relating to excluding patients with missing data from derivation studies, and basing the selection of model variable on significance in univariable analysis (in both cases noted for six studies). We identified separate external validation studies for all primary scales but one, with a total of 60 validation studies.Conclusions: Most acute stroke prognosis scales use similar variables to predict long-term outcomes and most have reasonable prognostic accuracy. While not all published scales followed best practice in development, most have been subsequently validated. Lack of clinical uptake may relate more to practical application of scales rather than validity. Impact studies are now necessary to investigate clinical usefulness of existing scales

Who is classified as untestable on brief cognitive screens in an acute stroke setting?

Full completion of cognitive screening tests can be problematic in the context of a stroke. Our aim was to examine the completion of various brief cognitive screens and explore reasons for untestability. Data were collected from consecutive stroke admissions (May 2016–August 2018). The cognitive assessment was attempted during the first week of admission. Patients were classified as partially untestable (≥1 test item was incomplete) and fully untestable (where assessment was not attempted, and/or no questions answered). We assessed univariate and multivariate associations of test completion with: age (years), sex, stroke severity (National Institutes of Health Stroke Scale (NIHSS)), stroke classification, pre-morbid disability (modified Rankin Scale (mRS)), previous stroke and previous dementia diagnosis. Of 703 patients admitted (mean age: 69.4), 119 (17%) were classified as fully untestable and 58 (8%) were partially untestable. The 4A-test had 100% completion and the clock-draw task had the lowest completion (533/703, 76%). Independent associations with fully untestable status had a higher NIHSS score (odds ratio (OR): 1.18, 95% CI: 1.11–1.26), higher pre-morbid mRS (OR: 1.28, 95% CI: 1.02–1.60) and pre-stroke dementia (OR: 3.35, 95% CI: 1.53–7.32). Overall, a quarter of patients were classified as untestable on the cognitive assessment, with test incompletion related to stroke and non-stroke factors. Clinicians and researchers would benefit from guidance on how to make the best use of incomplete test data

Cardiovascular risk factors indirectly affect acute post-stroke cognition through stroke severity and prior cognitive impairment: A moderated mediation analysis

Abstract: Background: Cognitive impairment is an important consequence of stroke and transient ischaemic attack, but its determinants are not fully understood. Simple univariable or multivariable models have not shown clinical utility for predicting cognitive impairment. Cardiovascular risk factors may influence cognition through multiple, direct, and indirect pathways, including effects on prior cognition and stroke severity. Understanding these complex relationships may help clinical teams plan intervention and follow-up strategies. Methods: We analysed clinical and demographic data from consecutive patients admitted to an acute stroke ward. Cognitive assessment comprised Abbreviated Mental Test and mini-Montreal Cognitive Assessment. We constructed bias-corrected confidence intervals to test indirect effects of cardiovascular risk factors (hypertension, vascular disease, atrial fibrillation, diabetes mellitus, previous stroke) on cognitive function, mediated through stroke severity and history of dementia, and we assessed moderation effects due to comorbidity. Results: From 594 eligible patients, we included 587 in the final analysis (age range 26–100; 45% female). Our model explained R2 = 62.10% of variance in cognitive test scores. We found evidence for an indirect effect of previous stroke that was associated with increased risk of prevalent dementia and in turn predicted poorer cognitive score (estimate = − 0.39; 95% bias-corrected CI, − 0.75 to − 0.13; p = 0.02). Atrial fibrillation was associated with greater stroke severity and in turn with a poorer cognitive score (estimate = − 0.27; 95% bias-corrected CI, − 0.49 to − 0.05; p = 0.02). Conversely, previous TIA predicted decreased stroke severity and, through that, lesser cognitive impairment (estimate = 0.38; 95% bias-corrected CI, 0.08 to 0.75; p = 0.02). Through an association with reduced stroke severity, vascular disease was associated with lesser cognitive impairment, conditional on presence of hypertension and absence of diabetes mellitus (estimate = 0.36; 95% bias-corrected CI, 0.03 to 0.68; p = 0.02), although the modelled interaction effects did not reach statistical significance. Conclusions: We have shown that relationships between cardiovascular risk factors and cognition are complex and simple multivariable models may be overly reductionist. Including direct and indirect effects of risk factors, we constructed a model that explained a substantial proportion of variation in cognitive test scores. Models that include multiple paths of influence and interactions could be used to create dementia prognostic tools for use in other healthcare settings

Prognostic rules for predicting cognitive syndromes following stroke: a systematic review

Purpose: Stroke survivors are at high risk of developing cognitive syndromes, such as delirium and dementia. Accurate prediction of future cognitive outcomes may aid timely diagnosis, intervention planning, and stratification in clinical trials. We aimed to identify, describe and appraise existing multivariable prognostic rules for prediction of post-stroke cognitive status. Method: We systematically searched four electronic databases from inception to November 2019 for publications describing a method to estimate individual probability of developing a cognitive syndrome following stroke. We extracted data from selected studies using a pre-specified proforma and applied the Prediction model Risk Of Bias Assessment Tool (PROBAST) for critical appraisal. Findings: Of 17,390 titles, we included 10 studies (3143 participants), presenting the development of 11 prognostic rules – 7 for post-stroke cognitive impairment and 4 for delirium. Most commonly incorporated predictors were: demographics, imaging findings, stroke type and symptom severity. Among studies assessing predictive discrimination, the area under the receiver operating characteristic (AUROC) in apparent validation ranged from 0.80 to 0.91. The overall risk of bias for each study was high. Only one prognostic rule had been externally validated. Discussion/conclusion: Research into the prognosis of cognitive outcomes following stroke is an expanding field, still at its early stages. Recommending use of specific prognostic rules is limited by the high risk of bias in all identified studies, and lack of supporting evidence from external validation. To ensure the quality of future research, investigators should adhere to current, endorsed best practice guidelines for conduct of prediction model studies

Long-term psychological outcomes following stroke: the OX-CHRONIC study

Background: Stroke survivors rate longer-term (> 2 years) psychological recovery as their top priority, but data on how frequently psychological consequences occur is lacking. Prevalence of cognitive impairment, depression/anxiety, fatigue, apathy and related psychological outcomes, and whether rates are stable in long-term stroke, is unknown. Methods: N = 105 long-term stroke survivors (M [SD] age = 72.92 [13.01]; M [SD] acute NIH Stroke Severity Score = 7.39 [6.25]; 59.0% Male; M [SD] years post-stroke = 4.57 [2.12]) were recruited (potential N = 208). Participants completed 3 remote assessments, including a comprehensive set of standardized cognitive neuropsychological tests comprising domains of memory, attention, language, and executive function, and questionnaires on emotional distress, fatigue, apathy and other psychological outcomes. Ninety participants were re-assessed one year later. Stability of outcomes was assessed by Cohen’s d effect size estimates and percent Minimal Clinically Important Difference changes between time points. Results: On the Montreal Cognitive Assessment 65.3% scored  Conclusion: Nearly half of participants > 2 years post-event exhibited psychological difficulties including domains of cognition, mood, and fatigue, which impact long-term quality of life. Stroke is a chronic condition with highly prevalent psychological needs, which require monitoring and intervention development

European Stroke Organisation and European Academy of Neurology joint guidelines on post-stroke cognitive impairment.

The optimal management of post-stroke cognitive impairment remains controversial. These joint European Stroke Organisation (ESO) and European Academy of Neurology (EAN) guidelines provide evidence-based recommendations to assist clinicians in decision making around prevention, diagnosis, treatment and prognosis. These guidelines were developed according to ESO standard operating procedure and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and, where possible, meta-analyses of the literature, assessed the quality of the available evidence and made specific recommendations. Expert consensus statements were provided where insufficient evidence was available to provide recommendations based on the GRADE approach. There was limited randomised controlled trial evidence regarding single or multicomponent interventions to prevent post-stroke cognitive decline. Interventions to improve lifestyle and treat vascular risk factors may have many health benefits but a beneficial effect on cognition is not proven. We found no evidence around routine cognitive screening following stroke but recognise the importance of targeted cognitive assessment. We described the accuracy of various cognitive screening tests but found no clearly superior approach to testing. There was insufficient evidence to make a recommendation for use of cholinesterase inhibitors, memantine nootropics or cognitive rehabilitation. There was limited evidence on the use of prediction tools for post-stroke cognitive syndromes (cognitive impairment, dementia and delirium). The association between post-stroke cognitive impairment and most acute structural brain imaging features was unclear, although the presence of substantial white matter hyperintensities of presumed vascular origin on acute MRI brain may help predict cognitive outcomes. These guidelines have highlighted fundamental areas where robust evidence is lacking. Further, definitive randomised controlled trials are needed, and we suggest priority areas for future research

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Stroke prediction and the future of prognosis research

In a new study of 1,102 patients, a multi-item prognostic tool has been developed and validated for use in acute stroke. Using a mix of clinical variables (age and stroke severity), a process variable (administration of thrombolysis) and a biomarker (plasma copeptin), the authors were able to predict 3-month disability