Stroke Study Research Articles

Changes in the prognosis of CADASIL over time: a 23-year study in 555 individuals

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and is associated with early-onset stroke and dementia. Whether its clinical phenotype...

Abstract 4129036: Air pollution and Cardiovascular Disease Incidence in a Pooled Analysis of 6 U.S. Cohorts

Introduction/Background: Long term air pollution is associated with cardiovascular disease (CVD) incidence, however the effects at low levels in the US are unknown. Research Questions/Hypothesis: To assess the effect of long-term exposure to ambient air pollution CVD incidence (myocardial infarction [MI], stroke, and all CVD) in a pooled analysis of epidemiological cohorts. Materials and Methods: We harmonized data from six cohorts (Cardiovascular Health Study, Nurses’ Health Study II, Multi-Ethnic Study of Atherosclerosis, and Reasons for Geographic And Racial Differences in Stroke Study, Sister Study, and Women’s Health Initiative) with both CVD incidence data and extensive covariate information. We predicted time-varying two-year average concentrations of particulate matter <2.5 microns (PM 2.5 ) and nitrogen dioxide (NO 2 ) from 1990-2019 at participant residential addresses using validated regionalized spatio-temporal models, combining spatio-temporal universal kriging and partial least squares regression with inputs from monitoring data from regulatory and researcher-deployed networks, satellite remote-sensing data and chemical transport modeling. Cox proportional hazards regression models adjusted for individual and area-level information, including smoking status, socio-economic factors, anthropometry, blood pressure, cholesterol, and other clinical variables. Results: Our analysis included over 300,000 participants and 10,229 incident CVD events. The median residential concentration of PM 2.5 was 10.1 µg/m 3 and NO 2 was 9.3 ppb. A 5 µg/m 3 increase in PM 2.5 was not significantly associated with a higher hazard ratio for all outcomes: 1.03 (95%CI: 0.96, 1.10) for CVD incidence, 1.03 (95%CI 0.93, 1.15) for MI, and 1.00 (95%CI 0.90, 1.10) for stroke. We found that a 10ppb increase in NO 2 was associated with a 1.06 (95%CI: 1.01, 1.11) higher hazard ratio for CVD, 1.07 (95%CI: 1.01, 1.11) for MI, and 1.02 (95%CI 0.96, 1.09) for stroke. Conclusions: In this analysis of a large, pooled cohort with excellent exposure, outcome, and covariate information, we found an association of NO 2 exposure—considered a surrogate for traffic-related air pollution—with CVD incidence and MI. Associations with particulate matter were not statistically significant, but could not exclude a small increased risk. We are extending this analysis to include 6 additional cohorts and an additional 700,000 participants to allow for generation of a highly resolved concentration-response function.

How Can Graph Theory Inform the Dual-stream Model of Speech Processing? A Resting-state Functional Magnetic Resonance Imaging Study of Stroke and Aphasia Symptomology.

The dual-stream model of speech processing describes a cortical network involved in speech processing. However, it is not yet known if the dual-stream model represents actual intrinsic functional brain networks. Furthermore, it is unclear how disruptions after a stroke to the functional connectivity of the dual-stream model's regions are related to speech production and comprehension impairments seen in aphasia. To address these questions, in the present study, we examined two independent resting-state fMRI data sets: (1) 28 neurotypical matched controls and (2) 28 chronic left-hemisphere stroke survivors collected at another site. We successfully identified an intrinsic functional network among the dual-stream model's regions in the control group using functional connectivity. We then used both standard functional connectivity analyses and graph theory approaches to determine how this connectivity may predict performance on clinical aphasia assessments. Our findings provide evidence that the dual-stream model of speech processing is an intrinsic network as measured via resting-state MRI and that functional connectivity of the hub nodes of the dual-stream network defined by graph theory methods, but not overall average network connectivity, is weaker in the stroke group than in the control participants. In addition, the functional connectivity of the hub nodes predicted linguistic impairments on clinical assessments. In particular, the relative strength of connectivity of the right hemisphere's homologues of the left dorsal stream hubs to the left dorsal hubs, versus to the right ventral stream hubs, is a particularly strong predictor of poststroke aphasia severity and symptomology.

Genome-wide association studies of ischemic stroke based on interpretable machine learning

Despite the identification of several dozen genetic loci associated with ischemic stroke (IS), the genetic bases of this disease remain largely unexplored. In this research we present the results of genome-wide association studies (GWAS) based on classical statistical testing and machine learning algorithms (logistic regression, gradient boosting on decision trees, and tabular deep learning model TabNet). To build a consensus on the results obtained by different techniques, the Pareto-Optimal solution was proposed and applied. These methods were applied to real genotypic data of sick and healthy individuals of European ancestry obtained from the Database of Genotypes and Phenotypes (5,581 individuals, 883,749 single nucleotide polymorphisms). Finally, 131 genes were identified as candidates for association with the onset of IS. UBQLN1, TRPS1, and MUSK were previously described as associated with the course of IS in model animals. ACOT11 taking part in metabolism of fatty acids was shown for the first time to be associated with IS. The identified genes were compared with genes from the Illuminating Druggable Genome project. The product of GPR26 representing the G-coupled protein receptor can be considered as a therapeutic target for stroke prevention. The approaches presented in this research can be used to reprocess GWAS datasets from other diseases.

Unraveling the Influences of Hemodynamic Lag and Intrinsic Cerebrovascular Reactivity on Functional Metrics in Ischemic Stroke

Resting-state functional magnetic resonance imaging (rs-fMRI) is a prominent tool for investigating functional deficits in stroke patients. However, the extent to which the hemodynamic lags (LAG) and the intrinsic cerebrovascular reactivity (iCVR) may affect the rs-fMRI metrics in different scales needs to be clarified for ischemic stroke. In this study, 73 ischemic stroke patients and 74 healthy controls (HC) were recruited to investigate how the correction of the LAG and/or iCVR would influence resting-state functional magnetic resonance imaging (rs-fMRI) metrics of three different spatial scales (local-scale, meso-scale and global-scale) in ischemic stroke. The analysis revealed that the Stroke pattern of all functional metrics using different correction strategies resembled the HC pattern. The highest overlap was observed in the Stroke pattern with correction for both LAG and iCVR, while the pattern without correction showed the lowest overlap. Most functional metrics after correction showed higher sensitivity in detecting between-group differences than those without correction. Moreover, our results were generally reproducible in an independent dataset. Collectively, these findings emphasize the necessity of considering LAG and iCVR effects to investigate stroke-related functional alterations, and highlight the significance of correction strategies for accurately interpreting the findings in rs-fMRI study of ischemic stroke.

Comparing the properties of traditional and novel approaches to the modified Rankin scale: Systematic review and meta-analysis.

The Modified Rankin Scale (mRS) is the most commonly used functional measure in stroke research but is limited by inter-rater reliability (IRR). Various interventions to improve mRS application have been described. We aimed to compare properties of differing approaches to mRS assessment. Multidisciplinary databases (MEDLINE, EMBASE, Health and Psychosocial Instruments [OVID], CINAHL, PsycINFO [EBSCO]) were searched for adult human stroke studies describing psychometric properties of mRS. Two researchers independently screened 20% titles and abstracts, reviewed all full studies, extracted data, and conducted risk of bias (ROB) analysis. Primary outcomes for random-effects meta-analysis were IRR measured by kappa (K) and weighted kappa (KW). Validity and inter-modality reliability measures (Spearman's rho, KW) were also summarised. From 897 titles, 46 studies were eligible, including twelve differing approaches to mRS, 8608 participants. There was high ROB in 14 (30.4%) studies. Overall, reliability was substantial (n = 29 studies, K = 0.65, 95% CI: 0.58-0.71) but IRR was higher for novel approaches to mRS, for example, the Rankin Focussed Assessment (n = 2 studies, K = 0.94, 95% CI: 0.90-0.98) than standard mRS (n = 13 studies, K = 0.55, 95%CI:0.46-0.64). Reliability improved following the introduction of mRS training (K = 0.56, 95% CI: 0.44-0.67; vs K = 0.69, 95% CI: 0.62-0.77). Validity ranged from poor to excellent, with an excellent overall concurrent validity of novel scales (n = 6 studies, KW = 0.86, 95% CI: 0.75-0.97). The agreement between face-to-face and telephone administration was substantial (n = 5 studies, KW = 0.80, 95% CI: 0.74-0.87). The mRS is a valid measure of function but IRR remains an issue. The present findings are limited by a high ROB and possible publication bias. Interventions to improve mRS reliability (training, structured interview, adjudication) seem to be beneficial, but single interventions do not completely remove reliability concerns.

Mild intracerebral bleeding does not adversely affect survival and neurological outcome of surgical therapy for left-sided infective endocarditis

Abstract Background Intracerebral bleeding (IB) is a serious condition that requires increased attention and has implications for treatment options. For patients with infective endocarditis (IE), current guidelines recommend postponing surgery if IB is present. IB can be classified into four relevant groups (following European Cooperative Acute Stroke Study and Heidelberger Bleeding classification): hemorrhagic transformation (HT) 1 and 2, and parenchymal hemorrhage (PH) 1 and 2. PH2 is the only IB with neurological deterioration. These classifications were originally introduced for stroke patients following thrombolysis but without IE. The hypothesis tested in our study is that IB may influence IE treatment and thus outcome. Method Patients were retrospectively identifyied who were operated for left-sided IE, neuroradiologists re-evaluated and classified preoperative cerebral imaging for any IB. Outcome was quantified using the modified Rankin score (mRS), and mRS were extracted from the patients’ hospital chart at admission and by follow-up telephone call (FU), also including mortality. To ensure that the influence of IB was comparable, patients with IB (IB+) were propensity matched (EuroScore 2, Charlson Comorbidity Index, C-reactive protein; nearest neighbor match) to patients without IB (IB-) who also received surgical IE therapy. All IB+ patients underwent a careful risk-benefit analysis before therapy. Results Of 286 consecutive patients (January 2015 - November 2022) operated for left-sided IE, 36 had IB (65±13 years, 26% female): 11 with HT1, 9 with HT2, 8 with PH1, and 8 with PH2. These patients were matched with 36 operated IB- patients. Survival analysis showed no overall effect of IB+ vs. IB- (p = 0.112, 95% CI of hazard ratio was 0.246-1.243 vs. 0.709-3.572). Although there was no effect of IB on survival in the mild IB subgroup (HT1/2, Figure A), there was a difference in patients with severe IB (PH1/2) with less survival in IB+ (Figure B). Neurological outcome (ΔmRS) showed an effect of IB grade in the two-way ANOVA analysis (p = 0.029). Intergroup comparison showed a significantly better outcome for IB- (vs. IB+) in the PH2 subgroup (p = 0.034), but not in other subgroups. For all groups, the mean ΔmRS for IB+ was 1.1±1.6 vs. 0.70±1.4 for IB- (p = 0.256). The mean FU time was 2.6±2.1 years. Conclusion In patients operated for left-sided IE, mild IB did not affect survival or neurological outcome. In the more severe forms of IB, i.e. PH1 and PH2, survival was less favorable compared to matched controls. Furthermore, we observed a difference in neurological outcome in patients with severe IB. Thus, surgical therapy of left-sided IE should be avoided in patients with severe IB, whereas we can add evidence to the safety of surgical therapy in mild IB. Therefore, we recommend regular assessment of the degree of IB in such patients.Figure

Stroke is Not an Accident: An Integrative Review on the Use of the Term 'Cerebrovascular Accident'.

Cerebrovascular accident (CVA) is an outdated term for describing stroke as it implies stroke is an accident. We conducted an integrative review to determine use of CVA in terms of 1) frequency in major medical journals over time; 2) associated publication characteristics (e.g., number of authors, senior author country, topic); and 3) frequency in medical records. We searched Google Scholar for publications in leading neurology and vascular journals (Quartile 1) across two 5-year periods (1998-2002 and 2018-2022) using the terms "cerebrovascular accident" or "CVA." Two reviewers independently reviewed full-text publications and recorded the frequency of CVA use. Rates of use (per 1,000 articles/year) were calculated for each journal and time period. Associations of publication characteristics with CVA use were determined using multivariable logistic regression models. In addition, admission and discharge forms in the Auckland Regional Community Stroke Study (ARCOS V) were audited for frequency of use of the term CVA. Of the 1,643 publications retrieved, 1,539 were reviewed in full. Of these, CVA was used ≥1 time in 676 publications, and ≥2 times in 276 publications (129 in 1998-2002; 147 in 2018-2022). The terms CVA and stroke both appeared in 57% of publications where CVA was used ≥2 times in 1998-2002, compared to 65% in 2018-2022. Majority of publications were on the topic of stroke (22% in 1998-2002; 20% in 2018-2022). There were no associations between publication characteristics and the use of CVA. The highest rate of CVA use in 2018-2022 was in Circulation, and increased over time from 1.3 uses per 1,000 publications in 1998-2002 to 1.8 uses per 1,000 publications in 2018-2022. The largest reduction the use of CVA was in Neuroepidemiology (2.0 uses per 1,000 publications in 1998-2002 to 0 uses in 2018-2022). The term CVA was identified in 0.2% of stroke admission and discharge forms audited (17/7808). We found evidence of changes in the use of CVA in the scientific literature over the past two decades. Editors, authors and clinicians should avoid the use of the term CVA as it perpetuates the use of a non-specific, non-diagnostic, and non-scientific term.

Automated Extraction of Stroke Severity From Unstructured Electronic Health Records Using Natural Language Processing.

Multicenter electronic health records can support quality improvement and comparative effectiveness research in stroke. However, limitations of electronic health record-based research include challenges in abstracting key clinical variables, including stroke severity, along with missing data. We developed a natural language processing model that reads electronic health record notes to directly extract the National Institutes of Health Stroke Scale score when documented and predict the score from clinical documentation when missing. The study included notes from patients with acute stroke (aged ≥18 years) admitted to Massachusetts General Hospital (2015-2022). The Massachusetts General Hospital data were divided into training/holdout test (70%/30%) sets. We developed a 2-stage model to predict the admission National Institutes of Health Stroke Scale, obtained from the GWTG (Get With The Guidelines) stroke registry. We trained a model with the least absolute shrinkage and selection operator. For test notes with documented National Institutes of Health Stroke Scale, scores were extracted using regular expressions (stage 1); when not documented, least absolute shrinkage and selection operator was used for prediction (stage 2). The 2-stage model was tested on the holdout test set and validated in the Medical Information Mart for Intensive Care (2001-2012) version 1.4, using root mean squared error and Spearman correlation. We included 4163 patients (Massachusetts General Hospital, 3876; Medical Information Mart for Intensive Care, 287); average age, 69 (SD, 15) years; 53% men, and 72% White individuals. The model achieved a root mean squared error of 2.89 (95% CI, 2.62-3.19) and Spearman correlation of 0.92 (95% CI, 0.91-0.93) in the Massachusetts General Hospital test set, and 2.20 (95% CI, 1.69-2.66) and 0.96 (95% CI, 0.94-0.97) in the MIMIC validation set, respectively. The automatic natural language processing-based model can enable large-scale stroke severity phenotyping from the electronic health record and support real-world quality improvement and comparative effectiveness studies in stroke.

Association of Adherence to a MIND-Style Diet With the Risk of Cognitive Impairment and Decline in the REGARDS Cohort.

Diet may influence the development of cognitive impairment and affect cognitive decline, but whether this relationship varies between Black American and White American people is unclear. This study examined the association of Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) and incident cognitive impairment and cognitive trajectories in a biracial prospective cohort study. Using data derived from the Food Frequency Questionnaire in the REasons for Geographic and Racial Differences in Stroke study, we compared MIND diet adherence with incident cognitive impairment and cognitive trajectory in Black participants and White participants. Logistic regression was used to model MIND diet score (continuous variable and using tertiles) and incident cognitive impairment after adjusting for age, sex, race, region, education, income, total energy, hypertension history, dyslipidemia, diabetes, estimated glomerular filtration rate, ischemic heart conditions, atrial fibrillation, and lifestyle factors including sedentary, obesity, and smoking. Mixed-effects models were used to examine the association between cognitive trajectory and MIND diet adherence. Dietary data to calculate the MIND diet score and cognitive data were available on 14,145 participants with a mean age of 64 years (SD 9.0 years) that was 56.7% female. Greater MIND diet adherence was associated with a decreased incidence of cognitive impairment (odds ratio [OR] 0.96, 95% CI 0.93-0.99, p = 0.02) after adjusting for all covariates. In the fully adjusted model, greater MIND diet adherence was associated with decreased risk of cognitive impairment in female participants (OR 0.92, 95% CI 0.89-0.96, p < 0.001) but not in male participants (OR 1.01, 95% CI 0.97-1.06, p = 0.64). In all models, greater MIND diet adherence was associated with decreased risk of cognitive decline. MIND diet adherence was a better predictor of cognitive decline in Black participants (β = 0.04, SE = 0.007, p < 0.001) than in White participants (β = 0.03, SE = 0.004, p < 0.001). Greater MIND diet adherence was associated with decreased risk of cognitive impairment in female participants but not male participants, with no difference between Black participants and White participants. However, MIND diet adherence was a better predictor of cognitive trajectory in Black participants than in White participants.

Causal relationship between uric acid and stroke: a two-sample mendelian randomization study.

Many previous observational studies have disputed whether there is a link between uric acid and stroke. And the causal relationship between uric acid and stroke is unclear. To determine whether there is a causal relationship between uric acid and stroke by using mendelian randomization (MR). Uric acid dataset was obtained from Anna Kottgen et al, with a sample size of 110,347 people, including 2450,548 single nucleotide polymorphisms (SNPs). Stroke pooled data from Malik R et al, publicly available in MEGASTROKE genome-wide association study, included meta-analysis data from 40,585 stroke patients and 406,111 control patients, totaling 8211,693 SNPs. The summary data of genome-wide association study of uric acid and stroke were collected from publicly available online databases. Inverse variance weighting was used to determine the causal relationship between uric acid and stroke. MR-Egger and weighted median model were used for supplementary analysis. Results were then analyzed for heterogeneity, pleiotropy, and sensitivity to ensure no statistical pleiotropy and to reduce bias. A total of 27 SNPs were included in this study after the disequilibrium instrumental variables were excluded. Check the PhenoScanner database for SNPs associated with confounders. In the end, a total of 8 SNPs were excluded. Two SNPs were excluded because the correction direction was the same. Since the F statistic is >10, rs10761587 and rs1825043 are excluded. Finally, 15 SNPs were selected as uric acid instrumental variables. Inverse variance weighting-fixed effect model suggested that there was no causal relationship between uric acid and stroke (odds ratio = 1.004, 95% confidence interval = 0.940, 1.072). MR-Egger and weighted median model also showed the same result. In addition, the results of this study were robust without heterogeneity and pleiotropy. This MR study suggests no support of a causal relationship between uric acid and stroke.

Enhancing Blood-Brain Barrier Integrity in Patients With Acute Ischemic Stroke Via Normobaric Hyperoxia.

Recent advancements in animal studies have demonstrated the potential of normobaric hyperoxia (NBO) as a promising intervention for preserving the integrity of the blood-brain barrier (BBB). However, there is still limited understanding of the effects of NBO on BBB function in patients with clinical stroke. Therefore, the objective of this study was to investigate the efficacy of NBO therapy in attenuating BBB damage and reducing brain injury in individuals undergoing endovascular treatment (EVT) for acute stroke. This study enrolled patients from the OPENS-1 (Normobaric Hyperoxia Combined With Reperfusion for Acute Ischemic Stroke) study, with 43 patients receiving NBO combined with EVT and 43 patients receiving EVT alone. The main outcome measures included serum levels of occludin, MMP-9 (matrix metalloproteinase-9), NSE (neuron-specific enolase), and S100b at 24 hours and 7 days, as well as the intracranial extravasation rate at 24 hours. Serum markers were assessed using ELISA, and intracranial contrast extravasation was visualized using dual-energy computed tomography scan. We analyzed a total of 86 patients and found that the 24-hour serum markers levels of BBB damage and brain injury were significantly lower in the group receiving NBO therapy combined with EVT compared with the group receiving EVT alone. Similarly, at 7 days, the levels of occludin, MMP-9, and NSE were lower in the NBO+EVT group. We also found that the 24-hour serum levels of occludin and MMP-9 were correlated with intracranial contrast extravasation. Additionally, the incidence of intracranial contrast extravasation was lower in the NBO+EVT group compared with the EVT group (35.9% versus 60.5%, P=0.031). This study offers valuable insights into the positive impact of NBO on maintaining BBB integrity and reducing brain injury in patients with acute stroke undergoing EVT.

Factors Influencing the Association of 24-hour National Institutes of Health Stroke Scale & 90-day Modified Rankin Score.

The modified Rankin Scale (mRS) at 90days is the primary outcome in most acute stroke studies, but the long follow-up period has disadvantages. The National Institutes of Health Stroke Scale (NIHSS) at 24 h shows astrong, but imperfect, association with 90-day mRS. This study examines the association between 24-hour NIHSS and 90-day mRS and reasons for discrepancies. Data are from the ESCAPE-NA1 thrombectomy patients. To address the non-normality distribution of the NIHSS and include deceased patients, a7-point ordinal score was generated by grouping 24-hour NIHSS. The association of ordinal 24-hour NIHSS and 90-day mRS was assessed with adjusted ordinal logistic regression. Differences in baseline and treatment/post-treatment variables were compared between patients with discordant and concordant outcomes. One-thousand-seventy-six patients with available 24-hour NIHSS and 90-day mRS were included (median 24-hour NIHSS6[IQR: 2-14], median 90-day mRS2[IQR: 1-4]). Ordinal 24-hour NIHSS was associated with 90-day mRS (adjusted cOR 2.53 [95%CI 2.33-2.74]). Forty-eight (4.5%) patients had discordant outcomes. Of those, 19(1.8%) had 24-hour NIHSS < 6 and 90-day mRS5-6; all of which had ≥ 1 severe adverse event, most commonly pneumonia (6[31.6%]) or recurrent stroke (4[21.1%]). Twenty-nine patients (2.7%) had 24-hour NIHSS > 14 and 90-day mRS 0-2. In these patients, baseline NIHSS and ASPECTS was lower, and collateral status was worse. An ordinal NIHSS score that includes death at 24 h shows astrong association with 90-day mRS, suggesting that it could be used as an alternative outcome. Patients with discrepant outcomes differed from the remaining patients regarding their baseline NIHSS, ASPECTS, collateral status, and post-stroke complications.

Age differences in the change in cognition after stroke

ObjectiveTo compare changes in cognitive trajectories after stroke between younger (18-64) and older (65+) adults, accounting for pre-stroke cognitive trajectories. Materials and methodsPooled cohort study using individual participant data from 3 US cohorts (1971-2019), the Atherosclerosis Risk In Communities Study (ARIC), Framingham Offspring Study (FOS), and REasons for Geographic And Racial Differences in Stroke Study (REGARDS). Linear mixed effect models evaluated the association between age and the initial change (intercept) and rate of change (slope) in cognition after compared to before stroke. Outcomes were global cognition (primary), memory and executive function. ResultsWe included 1,292 participants with stroke; 197 younger (47.2 % female, 32.5 % Black race) and 1,095 older (50.2 % female, 46.4 % Black race). Median (IQR) age at stroke was 59.7 (56.6-61.7) (younger group) and 75.2 (70.5-80.2) years (older group). Compared to the young, older participants had greater declines in global cognition (-1.69 point [95 % CI, -2.82 to -0.55] greater), memory (-1.05 point [95 % CI, -1.92 to -0.17] greater), and executive function (-3.72 point [95 % CI, -5.23 to -2.21] greater) initially after stroke. Older age was associated with faster declines in global cognition (-0.18 points per year [95 % CI, -0.36 to -0.01] faster) and executive function (-0.16 [95 % CI, -0.26 to -0.06] points per year for every 10 years of higher age), but not memory (-0.006 [95 % CI, -0.15 to 0.14]), after compared to before stroke. ConclusionOlder age was associated with greater post-stroke cognitive declines, accounting for differences in pre-stroke cognitive trajectories between the old and the young.

Stroke Research Using Administrative Claims Database in Japan: A Narrative Review.

Although administrative claims databases have recently been used for clinical research in Japan, no detailed description of their utilization in stroke research is available. We reviewed stroke studies using the Diagnosis Procedure Combination (DPC), the National Database of Health Insurance Claims and Specific Health Checkups (NDB), and several commercial databases sourced from social health insurance associations, focusing on their applications and limitations. Original articles on stroke published by April 2024 using the DPC, NDB, and commercial databases were identified in Ovid MEDLINE. The characteristics of each database were compared in terms of comprehensiveness, traceability, baseline information, and outcome assessment in stroke research. A total of 114 studies were included (83 for DPC, 6 for NDB, and 25 for commercial databases). The number of stroke studies using administrative databases in Japan is still approximately 10 per year, although there is a slowly increasing trend. The DPC database was utilized for short-term outcome studies because of its detailed baseline and outcome information, although the inability to track patients once they changed facilities limits their use in long-term studies. The NDB database is potentially useful for long-term studies because of its comprehensiveness and traceability, but difficulties in data access restrict its usage. The most commonly used commercial database utilizes baseline information on lifestyle and blood test data, although the lack of coverage for those over 75 years old may limit its generalizability. Administrative claims databases are beginning to be used in stroke research in Japan but are not yet fully utilized. Researchers need to understand their applications and limitations.

Carbonated Beverage, Fruit Drink, and Water Consumption and Risk of Acute Stroke: the INTERSTROKE Case-Control Study.

Cold beverage intake (carbonated drinks, fruit juice/drinks, and water) may be important population-level exposures relevant to stroke risk and prevention. We sought to explore the association between intake of these beverages and stroke. INTERSTROKE is an international matched case-control study of first stroke. Participants reported beverage intake using food frequency questionnaires or were asked "How many cups do you drink each day of water?" Multivariable conditional logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for associations with stroke. We include 13,462 cases and 13,488 controls; mean age was 61.7±13.4 years and 59.6% (n=16,010) were male. After multivariable adjustment, carbonated beverages were linearly associated with ischemic stroke (OR 2.39 [95% CI 1.64-3.49]); only consumption once/day was associated with intracerebral hemorrhage (ICH) (OR 1.58 [95% CI 1.23-2.03]). There was no association between fruit juice/drinks and ischemic stroke, but increased odds of ICH for once/day (OR 1.37 [95% CI 1.08-1.75)] or twice/day (OR 3.18 [95% CI 1.69-5.97]). High water intake (>7 cups/day) was associated ischemic stroke (OR 0.82 [95% CI 0.68-0.99]) but not ICH. Associations differed by Eugeographical region-increased odds for carbonated beverages in some regions only; opposing directions of association of fruit juices/drinks with stroke in selected regions. Carbonated beverages were associated with increased odds of ischemic stroke and ICH, fruit juice/drinks were associated with increased odds of ICH, and high water consumption was associated with reduced odds of ischemic stroke, with important regional differences. Our findings suggest optimizing water intake, minimizing fruit juice/drinks, and avoiding carbonated beverages.

The Adaptive Physical Activity Study for Stroke: A Feasibility Sequential Multiple Assignment Randomized Trial

Abstract Background Between 1990 and 2017, stroke cases nearly doubled, ranking as the second leading cause of death and disability globally. Inadequate physical activity (PA) is a leading risk factor. Recent guidelines advise stroke survivors to follow population-based PA guidelines. Given stroke heterogeneity personalised PA interventions are recommended. Therefore, this study used a Sequential Multiple-Assignment Randomized Trial (SMART) design to develop an adaptive mHealth intervention to improve PA post-stroke. Methods This SMART is in progress, with recruitment completed and follow-up data ending November 2024. A 12-week intervention programme was developed incorporating public patient involvement (PPI), empirical evidence and behavioural change theory to increase participation in Structured Exercise (SE), Lifestyle Physical Activity (LPA), or both. The study enrolled 54 ambulatory, community-dwelling people who were randomly assigned to either SE or LPA treatment groups. Participants used Fitbit Inspire 2 devices to monitor step counts and set personalized weekly step goals. At six weeks post-randomisation, participants were evaluated and classified as responders or non-responders based on their step count target achievement. Non-responders were re-randomized to switch treatments or augment their current regime with an additional intervention. Responders maintained their original treatment protocol. Primary outcomes address recruitment, retention and adherence rates. Secondary outcomes encompass overall health. Results Preliminary results include 54 participants (56% male) aged 51.58 (± 15.12) with Ischaemic (44%), Haemorrhagic (28%) or unknown (28%) stroke type at baseline. The mean weekly step was 7046 (±3797) while the mean Fatigue Severity Scale score was 38.02 (± 14.60). Participants had a mean Hospital Anxiety and Depression Scale score of 12.33 (± 6.98). Additionally, the mean Stroke Specific Quality of Life was 155.04 (58.84). Conclusion This is the first trial to use a SMART to design an adaptive intervention post-stroke internationally. Findings will inform the development of a PA intervention and subsequently will be evaluated against treatment as usual in a definitive trial.

HTLV1 infection and long term association with liver function and lipid indices; 10 years’ follow-up

BackgroundHuman T-cell leukemia virus type 1 (HTLV-1) is a well-known retrovirus, particularly prevalent in northeastern Iran, where it is associated with a range of disorders, including liver dysfunction. Previous studies have demonstrated that HTLV-1 infection can alter lipid profiles, yet no research has examined lipid indices and liver function tests in these patients in the long term.MethodsThis data is part of the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study. A total of 1116 participants were randomly selected, including 837 healthy individuals and 279 HTLV-1-infected patients. Following a 10-year follow-up period, Serum levels of liver enzymes were measured. Lipid indices such as the Atherogenic Index of Plasma (AIP), Body Adiposity Index (BAC), Castelli risk index (CRI-I, CRI-II), Lipid Accumulation Product (LAP), Visceral Adiposity Index (VAI), Triglyceride-glucose index (TyG), and Triglyceride and HDL-C Ratio (THR) were calculated.ResultsMultivariable-adjusted regression analysis demonstrated a significant coefficient for the Visceral Adiposity Index (VAI) in HTLV-infected patients compared to healthy controls (B: -0.014, 95% CI: -0.02, 0.00, p = 0.046). However, no significant differences were observed in other lipid indices between HTLV-infected patients and healthy individuals. Regarding liver enzymes, significant variations were noted in HTLV-infected patients compared to healthy controls: Aspartate Aminotransferase (AST) (B: 2.978, 95% CI: 1.34, 4.61, p < 0.001), Alanine Aminotransferase (ALT) (B: 3.687, 95% CI: 1.59, 5.78, p = 0.001), Alkaline Phosphatase (ALP) (B: 18.232, 95% CI: 6.81, 29.65, p = 0.002), and Gamma-Glutamyl Transferase (GGT) (B: 3.714, 95% CI: 0.18, 7.24, p = 0.039).ConclusionIndividuals with HTLV-1 infection exhibit reduced VAI but elevated levels of liver enzymes such as AST, ALT, ALP, and GGT, indicating liver damage. These findings emphasize the virus’s involvement in liver pathology. Also, HTLV-I is associated with reduced visceral fat tissue.

Causal Associations of Sleep Apnea With Alzheimer Disease and Cardiovascular Disease: A Bidirectional Mendelian Randomization Analysis.

Sleep apnea (SA) has been linked to an increased risk of dementia in numerous observational studies; whether this is driven by neurodegenerative, vascular, or other mechanisms is not clear. We sought to examine the bidirectional causal relationships between SA, Alzheimer disease (AD), coronary artery disease (CAD), and ischemic stroke using Mendelian randomization. Using summary statistics from 4 recent, large genome-wide association studies of SA (n=523 366), AD (n=94 437), CAD (n=1 165 690), and stroke (n=1 308 460), we conducted bidirectional 2-sample Mendelian randomization analyses. Our primary analytic method was fixed-effects inverse variance-weighted (IVW) Mendelian randomization; diagnostics tests and sensitivity analyses were conducted to verify the robustness of the results. We identified a significant causal effect of SA on the risk of CAD (odds ratio [ORIVW]=1.35 per log-odds increase in SA liability [95% CI=1.25-1.47]) and stroke (ORIVW=1.13 [95% CI=1.01-1.25]). These associations were somewhat attenuated after excluding single-nucleotide polymorphisms associated with body mass index (ORIVW=1.26 [95% CI=1.15-1.39] for CAD risk; ORIVW=1.08 [95% CI=0.96-1.22] for stroke risk). SA was not causally associated with a higher risk of AD (ORIVW=1.14 [95% CI=0.91-1.43]). We did not find causal effects of AD, CAD, or stroke on risk of SA. These results suggest that SA increased the risk of CAD, and the identified causal association with stroke risk may be confounded by body mass index. Moreover, no causal effect of SA on AD risk was found. Future studies are warranted to investigate cardiovascular pathways between sleep disorders, including SA, and dementia.

Twenty-Four-Hour Post-Thrombolysis NIHSS Score As the Strongest Prognostic Predictor After Acute Ischemic Stroke: ENCHANTED Study.

This study was conducted to determine optimal predictive ability of National Institutes of Health Stroke Scale (NIHSS) measurements at baseline, 24 hours, and change from baseline to 24 hours after thrombolysis on functional recovery in patients with acute ischemic stroke who participated in the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). ENCHANTED was an international, multicenter, 2×2 quasifactorial, prospective, randomized open trial of low-dose versus standard-dose intravenous alteplase and intensive versus guideline-recommended blood pressure lowering in thrombolysis-eligible patients with acute ischemic stroke. Absolute (baseline minus 24 hours) and percentage (absolute change/baseline × 100) changes in NIHSS scores were calculated. Receiver operating characteristic curve analyses assessed performance of different NIHSS measurements on 90-day favorable functional recovery (modified Rankin Scale [mRS] score 0-2) and excellent functional recovery (mRS score 0-1). Youden index was used to identify optimal predictor cutoff points. A total of 4410 patients in the ENCHANTED trial were enrolled. The 24-hour NIHSS score had the highest discriminative ability for predicting favorable 90-day functional recovery (mRS score 0-2; area under the curve 0.866 versus 0.755, 0.689, 0.764; P<0.001) than baseline, absolute, and percentage change of NIHSS score, respectively. The optimal cutoff point of 24-hour NIHSS score for predicting favorable functional recovery was ≤4 (sensitivity 66.5%, specificity 87.1%, adjusted odds ratio, 9.44 [95% CI, 7.77-11.48]). The 24-hour NIHSS score (≤3) was the best predictor of 90-day excellent functional recovery (mRS score 0-1). Findings were consistent across subgroups, including sex, race, baseline NIHSS score, stroke subtype, and age. In thrombolysis-eligible patients with acute ischemic stroke, 24-hour NIHSS score (optimal cutpoint of 4) is the strongest predictor of 90-day functional recovery over baseline and early change of NIHSS score. URL: https://clinicaltrials.gov. Unique Identifier: NCT01422616.