Association of estimated pulse wave velocity with cognitive function in a multiethnic diverse population: The Northern Manhattan Study.

INTRODUCTION: Arterial stiffness is linked to age-related cognitive dysfunction. Estimated pulse wave velocity (ePWV) is associated with cerebrovascular disease. We sought to determine whether ePWV was associated with cognition in a multiethnic population. METHODS: We included 1257 participants enrolled in a Northern Manhattan Study magnetic resonance imaging MRI-cognitive study (mean age 64 ± 8 years, 61% women, 67% Hispanic, 18% non-Hispanic Black, 15% non-Hispanic white) and analyzed cognitive performance at two time points, at enrollment and on an average 5.0 ± 0.6 years later. ePWV was calculated using baseline age and blood pressure. Cognition and cognitive change scores were regressed on ePWV in multivariable linear regression models. RESULTS: In adjusted models, ePWV (mean 11 ± 2 m/s) was significantly associated with cognition (b = -0.100, 95% CI, -0.120, -0.080) and cognitive change over time (b = -0.063, 95% CI, -0.082, -0.045). Effect modification by race and sex was found. DISCUSSION: In this multiethnic population, the associations of ePWV with cognitive performance underline the role of vascular stiffness in age-related cognitive decline. HIGHLIGHTS: ePWV is a modest but independent predictor of cognitive function and cognitive decline among older individuals. After adjustment, the ePWV measure was inversely associated with performance and decline in global cognition, processing speed, episodic memory, executive function, and semantic memory. After adjustment, modification of the association between ePWV and change in episodic memory and executive function by race and ethnicity was suggested by a significant interaction term. The association between ePWV and episodic memory decline was stronger in females.

The Effect of 30-Day Adequate Transitions of Acute Stroke Care on 90-Day Readmission or Death.

OBJECTIVES: We explore patient-reported behaviors and activities within 30-days post-stroke hospitalization and their role in reducing death or readmissions within 90-days post-stroke. METHODS: We constructed the adequate transitions of care (ATOC) composite score, measuring patient-reported participation in eligible behaviors and activities (diet modification, weekly exercise, follow-up medical appointment attendance, medication adherence, therapy use, and toxic habit cessation) within 30 days post-stroke hospital discharge. We analyzed ATOC scores in ischemic and intracerebral hemorrhage stroke patients discharged from the hospital to home or rehabilitation facilities and enrolled in the NIH-funded Transitions of Care Stroke Disparities Study (TCSD-S). We utilized Cox regression analysis, with the progressive adjustment for sociodemographic variables, social determinants of health, and stroke risk factors, to determine the associations between ATOC score within 30-days and death or readmission within 90-days post-stroke. RESULTS: In our sample of 1239 stroke patients (mean age 64+/-14, 58% male, 22% Hispanic, 22% Black, 52% White, 76% discharged home), 13% experienced a readmission or death within 90 days (3 deaths, 160 readmissions, 3 readmissions with subsequent death). Seventy percent of participants accomplished a ≥75% ATOC score. A 25% increase in ATOC was associated with a respective 20% (95% CI 3%-33%) reduced risk of death or readmission within 90-days. CONCLUSION: ATOC represents modifiable behaviors and activities within 30-days post-stroke that are associated with reduced risk of death or readmission within 90-days post-stroke. The ATOC score should be validated in other populations, but it can serve as a tool for improving transitions of stroke care initiatives and interventions.

Sleep Duration Is Associated With Subclinical Carotid Plaque Burden.

BACKGROUND: Sleep duration is associated with stroke risk and is 1 of 8 essential components of cardiovascular health according to the American Heart Association. As stroke disproportionately burdens Black and Hispanic populations in the United States, we hypothesized that long and short sleep duration would be associated with greater subclinical carotid atherosclerosis, a precursor of stroke, in the racially and ethnically diverse NOMAS (Northern Manhattan Study). METHODS: NOMAS is a study of community-dwelling adults. Self-reported nightly sleep duration and daytime sleepiness were collected between 2006 and 2011. Carotid plaque presence, total plaque area, and intima-media thickness were measured by ultrasound between 1999 and 2008. Linear and logistic regression models examined the cross-sectional associations of sleep duration groups (primary exposure) or daytime sleepiness (secondary exposure) with measures of carotid atherosclerosis. Models adjusted for age, time between ultrasound and sleep data collection, sex, race and ethnicity, education, health insurance, smoking, alcohol use, physical activity, body mass index, hypertension, diabetes, hypercholesterolemia, and cardiac disease. RESULTS: The sample (n=1553) had a mean age of 64.7±8.5 years and was 61.9% female, 64.8% Hispanic, and 18.2% non-Hispanic Black. Of the sample, 55.6% had carotid plaque, 22.3% reported nightly short sleep (<7 hours), 66.6% intermediate sleep (≥7 and <9 hours), and 11.1% had long sleep (≥9 hours). Compared with intermediate sleep, long sleep was associated with greater odds of carotid plaque presence relative to plaque absence (odds ratio, 1.6 [95% CI, 1.1-2.4]) and larger total plaque area (odds ratio, 1.4 [95% CI, 1.0-1.9]) after full covariate adjustment. Short sleep and daytime sleepiness were not significantly associated with any carotid measures. CONCLUSIONS: The association between long sleep and subclinical carotid atherosclerosis may explain prior associations between long sleep and stroke.

Factors and Behaviors Related to Successful Transition of Care After Hospitalization for Ischemic Stroke.

BACKGROUND: Our objective is to describe adoption of the posthospitalization behaviors associated with successful transition of care and related baseline characteristics. METHODS: This study includes 550 participants in the Transition of Care Stroke Disparities Study, a prospective observational cohort derived from the Florida Stroke Registry. Participants had an ischemic stroke (2018-2021), discharged home or to rehabilitation, with modified Rankin Scale score=0-3 (44% women, 24% Black, 48% White, 26% Hispanic, 35% foreign-born). We collected baseline sociodemographic and clinical characteristics. A structured telephone interview at 30-day postdischarge evaluated outcomes including medication adherence, medical appointment attendance, outpatient therapy, exercise, diet modification, toxic habit cessation, and a calculated composite adequate transition of care measure. Multivariable analyses assessed the association of baseline characteristics with 30-day behaviors. RESULTS: At 30 days, medication adherence was achieved by 89%, medical appointments by 82%, outpatient therapy by 76%, exercise by 71%, diet modification by 68%, toxic habit cessation by 35%, and adequate transition of care measure by 67%. Successful adequate transition of care participants were more likely to be used full-time (42% versus 31%, P=0.02), live with a spouse (60% versus 47%, P=0.01), feel close to ≥3 individuals (84% versus 71%, P<0.01), have history of dyslipidemia (45 versus 34%, P=0.02), have thrombectomy (15% versus 8%, P=0.02), but less likely to have a history of smoking (17% versus 32%, P<0.001), coronary artery disease (14% versus 21%, P=0.04), and heart failure (3% versus 11%, P<0.01). Multivariable logistic regression analyses revealed that multiple socio-economic factors and prestroke comorbid diseases predicted fulfillment of transition of care measures. There was no difference in outcomes during the Covid-19 pandemic (2020-2021) compared with prepandemic years (2018-2019). CONCLUSIONS: One in 3 patients did not attain adequate 30-day transition of care behaviors. Their achievement varied substantially among different measures and was influenced by multiple socioeconomic and clinical factors. Interventions aimed at facilitating transition of care from hospital after stroke are needed. REGISTRATION: URL: https://clinicaltrials.gov/; Unique identifier: NCT03452813.

Impact of Time to Treatment on Endovascular Thrombectomy Outcomes in the Early Versus Late Treatment Time Windows.

BACKGROUND: The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows. METHODS: Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and categorized into early window treated (OTP ≤6 hours) and late window treated (OTP >6 and ≤24 hours). Association between OTP and favorable discharge outcomes (independent ambulation, discharge home and to acute rehabilitation facility) as well as symptomatic intracerebral hemorrhage and in-hospital mortality were examined using multilevel-multivariable analysis with generalized estimating equations. RESULTS: Among 8002 EVT patients (50.9% women; median age [±SD], 71.5 [±14.5] years; 61.7% White, 17.5% Black, and 21% Hispanic), 34.2% were treated in the late time window. Among all EVT patients, 32.4% were discharged home, 23.5% to rehabilitation facility, 33.7% ambulated independently at discharge, 5.1% had symptomatic intracerebral hemorrhage, and 9.2% died. As compared with the early window, treatment in the late window was associated with lower odds of independent ambulation (odds ratio [OR], 0.78 [0.67-0.90]) and discharge home (OR, 0.71 [0.63-0.80]). For every 60-minute increase in OTP, the odds of independent ambulation reduced by 8% (OR, 0.92 [0.87-0.97]; P<0.001) and 1% (OR, 0.99 [0.97-1.02]; P=0.5) and the odds of discharged home reduced by 10% (OR, 0.90 [0.87-0.93]; P<0.001) and 2% (OR, 0.98 [0.97-1.00]; P=0.11) in the early and late windows, respectively. CONCLUSIONS: In routine practice, just over one-third of EVT-treated patients independently ambulate at discharge and only half are discharged to home/rehabilitation facility. Increased time from symptom onset to treatment is significantly associated with lower chance of independent ambulation and ability to be discharged home after EVT in the early time window.

Determinants and Temporal Trends of Dual Antiplatelet Therapy After Mild Noncardioembolic Stroke.

BACKGROUND: Short-term dual antiplatelet therapy (DAPT) reduces early stroke recurrence after mild noncardioembolic ischemic stroke (NCIS). We aim to evaluate temporal trends and determinants of DAPT prescription after mild NCIS in the Florida Stroke Registry, a statewide registry across Get With The Guidelines-Stroke participating hospitals. METHODS: In this cross-sectional analysis of a cohort study, we included patients with mild NCIS (National Institutes of Health Stroke Scale score ≤3) who were potentially eligible for DAPT across 168 Florida Stroke Registry participating hospitals between January 2010 and September 2022. Using antiplatelet prescription as the dependent variable (DAPT versus single antiplatelet therapy), we fit logistic regression models adjusted for patient-related factors, hospital-related factors, clinical presentation, vascular risk factors, and ischemic stroke subtype, to obtain adjusted odds ratios (aORs) with 95% CIs. RESULTS: From 283 264 Florida Stroke Registry ischemic stroke patients during the study period, 109 655 NCIS were considered eligible. Among these, 37 058 patients with National Institutes of Health Stroke Scale score >3 were excluded, resulting in a sample of 72 597 mild NCIS (mean age 68±14 years; female 47.3%). Overall, 24 693 (34.0%) patients with mild NCIS were discharged on DAPT and 47 904 (66.0%) on single antiplatelet therapy. DAPT prescription increased from 25.7% in 2010 to 52.8% in 2022 (ß/year 2.5% [95% CI, 1.5%-3.4%]). Factors associated with DAPT prescription were premorbid antiplatelet therapy (aOR, 4.66 [95% CI, 2.20-9.88]), large-artery atherosclerosis (aOR, 1.68 [95% CI, 1.43-1.97]), diabetes (aOR, 1.29 [95% CI, 1.13-1.47]), and hyperlipidemia (aOR, 1.24 [95% CI, 1.10-1.39]), whereas female sex (aOR, 0.83 [95% CI, 0.75-0.93]), being non-Hispanic Black patients (compared with non-Hispanic White patients; aOR, 0.78 [95% CI, 0.68-0.90]), admission to a Thrombectomy-capable Stroke Center (compared with Comprehensive Stroke Center; aOR, 0.78 [95% CI, 0.66-0.92]), time-to-presentation 1 to 7 days from last seen well (compared with <24 h; aOR, 0.86 [95% CI, 0.76-0.96]), and small-vessel disease stroke (aOR, 0.81 [95% CI, 0.72-0.94]) were associated with not receiving DAPT at discharge. CONCLUSIONS: Despite a temporal trend increase in DAPT prescription after mild NCIS, we found substantial underutilization of evidence-based DAPT associated with significant disparities in stroke care.

Nationally Certified Stroke Centers Outperform Self-Attested Stroke Centers in the Florida Stroke Registry.

BACKGROUND: The Florida Stroke Act, signed into law in 2004, set criteria for Comprehensive Stroke Centers (CSC). For a set time period, Florida hospitals were permitted to either receive national certification (NC) or could self-attest (SA) as fulfilling CSC criteria. The aim of this project was to evaluate the quality of ischemic stroke care in NC versus SA stroke centers in Florida, using well-known, guideline-driven ischemic stroke outcome metrics. METHODS: A total of 37 CSCs (74% of Florida CSCs) in the Florida Stroke Registry from January 2013 through December 2018 were analyzed, including 19 SA CSCs and 18 NC (13 CSCs and 5 Thrombectomy-Capable Stroke Center). Hospital- and patient-level characteristics and stroke metrics were evaluated, adjusting for demographics, medical comorbidities, and stroke severity. RESULTS: A total of 78 424 acute ischemic stroke cases, 36 089 from SA CSCs and 42 335 from NC CSC/Thrombectomy-Capable Stroke Centers were analyzed. NC centers had older patients (73 [61-83] versus 71 [60-81]; P<0.001) with more severe strokes (median National Institutes of Health Stroke Scale score of 5 versus 4; P<0.001). NC had higher intravenous tissue-type plasminogen activator utilization (15% versus 13%; P<0.001), endovascular treatment (10% versus 7%; P<0.001) and faster median door-to-computed tomography (23 minutes [11-73] versus 31 [12-78]; P<0.001), door-to-needle (37 minutes [26-50] versus 45 [34-58]; P<0.001) and door-to-puncture times (77 minutes [50-113] versus 93 [62-140]; P<0.001). In adjusted analysis, patients arriving to NC hospitals by 3 hours were more likely to get intravenous tissue-type plasminogen activator in the 3- to 4.5-hour window (adjusted odds ratio, 1.87 [95% CI, 1.30-2.68]; P=0.001) and more likely to be treated with intravenous tissue-type plasminogen activator within 45 minutes (adjusted odds ratio, 1.61 [95% CI, 1.04-2.50]; P=0.04) compared with SA CSCs. CONCLUSIONS: Among Florida-Stroke Registry CSCs, acute ischemic stroke performance and treatment measures at NC centers are superior to SA CSCs. These findings have implications for stroke systems of care in Florida and support legislation updates requiring NC and removal of SA claims.

Osteopontin is associated with dementia in the presence of cerebral small vessel disease.

BACKGROUND: Osteopontin (OPN) is a proinflammatory cytokine that has been recently implicated in neuroinflammation and neurodegeneration. We hypothesized that an increase in plasma osteopontin is a deleterious neuroinflammatory marker in people with dementia and cerebral small vessel disease (CSVD). METHODS: A pilot study was conducted on participants in the Northern Manhattan Study (NOMAS). Three groups were selected based on their dementia status and evidence of subclinical CSVD and chosen to be similar in age, sex, and education attainment: No dementia/No CSVD (n=19), Dementia/No CSVD (n=22), and Dementia+CSVD (n=21). Dementia (any type) was diagnosed by consensus adjudication following a series of comprehensive neuropsychological assessments and a review of the medical history. CSVD was indicated by silent brain infarcts, enlarged perivascular spaces, cerebral microbleeds, and white matter hyperintensity volumes (WMHV) on MRI. Multinomial logistic regression was used to examine the difference in OPN levels across groups, adjusting for key determinants of CSVD and neurodegeneration. RESULTS: Plasma osteopontin levels were elevated in the Dementia+CSVD group (mean=70.69±39.00 ng/ml) but not in the Dementia/No CSVD group (mean=45.46±19.11 ng/ml) compared to the No dementia/No CSVD group (mean=36.43±15.72 ng/ml). Osteopontin was associated with Dementia+CSVD (Odds Ratio (OR) per ng/ml=1.06, 95%CI 1.02-1.11) after adjusting for covariates, including brain volume. OPN was strongly correlated with WMHV (Spearman's rank correlation =0.46, p=0.0001), but not with other components of CSVD. CONCLUSION: In this pilot, greater levels of plasma osteopontin were associated with dementia with evidence of CSVD. This link was predominately driven by the contribution of OPN to dementia through the burden of white matter lesions.

Preexisting Depression and Ambulatory Status After Stroke: Florida-Puerto Rico Collaboration to Reduce Stroke Disparities.

OBJECTIVE: Stroke is a global public health burden, and therefore it is critical to identify modifiable risk factors to reduce stroke incidence and improve outcomes. Depression is such a risk factor; however, the association between preexisting depression and stroke outcomes, such as independent ambulation, is not well studied, especially among racial-ethnic minority groups. To address this gap in the literature, effects of preexisting depression on ambulatory status at hospital discharge after stroke were evaluated among individuals participating in the racially and ethnically diverse Florida-Puerto Rico Collaboration to Reduce Stroke Disparities project. METHODS: Data were analyzed from a total of 42,031 ischemic stroke patients, who were independently ambulatory prior to their stroke, after discharge from 84 hospitals between 2014 and 2017. Preexisting depression was confirmed by medical history or antidepressant medication use. Multilevel multivariate logistic regression analyses were used to assess the association of preexisting depression with independent ambulation at hospital discharge. Effects of sex and race-ethnicity on this association were examined. RESULTS: Of 42,031 participants (mean±SD age=70.4±14.2 years; 48% were female; race-ethnicity: 16% Black, 12% Hispanic living in Florida, and 7% Hispanic living in Puerto Rico), 6,379 (15%) had preexisting depression. Compared with participants without depression, those with preexisting depression were older, were more likely to be female and non-Hispanic White, and had a greater burden of vascular risk factors or comorbid conditions. Independent ambulation at hospital discharge was less frequent among women, Black participants, and individuals with vascular risk factors or comorbid conditions. In multivariate models, preexisting depression decreased the likelihood of independent ambulation at discharge (odds ratio=0.88, 95% CI=0.81, 0.97). No interactions were found between preexisting depression and race-ethnicity or sex. CONCLUSIONS: Preexisting depression was independently associated with dependent ambulation at hospital discharge after stroke, regardless of sex and race-ethnicity. Treating depression may contribute to primary stroke prevention and could improve ambulatory status at discharge.

The effect of nutrition on stroke risk: A systematic review.

Background: An estimated 33% reduction in cardiovascular events can be achieved when incorporating whole grains, fruits, vegetables, poultry, nuts, and vegetable oils in the diet along with reduced consumption of refined carbohydrates, processed meats, and sugar sweetened beverages. We performed a systematic review to analyze the impact of nutritional intervention on stroke risk, as there is no current consensus concerning dietary recommendation for primary and secondary stroke prevention. Methods: A literature search of the PubMed database from January 2010 to June 2020 was performed using combinations of the following search terms: carotid disease, carotid artery disease, carotid stenosis, carotid intima-media thickness (CIMT), diet, nutrition, micronutrition, embolic stroke, and stroke. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 checklist. Results: 28 studies met our inclusion criteria. Multiple studies showed an inverse relationship between consumption of vegetables and fruits and stroke risk. Vitamin B12 or a combination of B Vitamins was the most common supplement studied in stroke prevention. Only one RCT showed the use of B12 (500 micrograms/day) correlated with lower CIMT at follow up in healthy vegetarians. Discussion: The key findings from this systematic review indicate that adopting a diet rich in fruits and vegetables earlier in life may lower stroke risk compared with meats and fat intake. B vitamins also appear to confer some protection against stroke. However, not enough data exists to support the use of multivitamins, calcium, soy products and other supplements for primary or secondary stroke prevention.

Mediterranean-style diet and intracranial large artery stenosis in the Northern Manhattan Study.

OBJECTIVES: Given Mediterranean-style diet (MeDi) reduces risk of cardiovascular events, we hypothesized MeDi may also be protective against intracranial large artery stenosis (ICAS), a common cause of stroke worldwide. METHODS: This cross-sectional study included stroke-free participants of the Northern Manhattan Study, a diverse population-based study of stroke risk factors. We represented MeDi continuously (range 0-8) based on enrollment food frequency questionnaires, excluding alcohol consumption. We evaluated ICAS both dichotomously at clinically relevant stenosis severities and continuously as a score (possible range 0-44), summated from stenosis severity scores of major intracranial arteries from time-of-flight magnetic resonance angiography. We used logistic or zero-inflated Poisson regression, adjusting for key confounders. RESULTS: Among 912 included participants (mean age 64±8 years, 59% female, 65% Hispanic, mean MeDi score 4±1.5), 5% and 8% of participants had ≥50% or ≥70% ICAS, respectively (score median [interquartile range]: 0 [0-2]). Increased MeDi score was inversely associated with ICAS, but did not reach statistical significance (≥50% stenosis odds ratio (OR) [95% confidence interval (CI)]: 0.89 [0.79-1.06]; ≥70% stenosis OR [95% CI]: 0.91 [0.74-1.13]; stenosis score ß-estimate [95% CI]: -0.02 [-0.06-0.01]). CONCLUSION: In this stroke-free subsample, we did not find a significant association between MeDi and ICAS. We may have been limited by statistical power.

Disparities in transitions of acute stroke care: The transitions of care stroke disparities study methodological report.

OBJECTIVE: The Transitions of Stroke Care Disparities Study (TCSD-S) is an observational study designed to determine race-ethnic and sex disparities in post-hospital discharge transitions of stroke care and stroke outcomes and to develop hospital-level initiatives to reduce these disparities to improve stroke outcomes. MATERIALS AND METHODS: Here, we present the study rationale, describe the methodology, report preliminary outcomes, and discuss a critical need for the development, implementation, and dissemination of interventions for successful post-hospital transition of stroke care. The preliminary outcomes describe the demographic, stroke risk factor, socioeconomic, and acute care characteristics of eligible participants by race-ethnicity and sex. We also report on all-cause and vascular-related death, readmissions, and hospital/emergency room representations at 30- and 90-days after hospital discharge. RESULTS: The preliminary sample included data from 1048 ischemic stroke and intracerebral hemorrhage discharged from 10 comprehensive stroke centers across the state of Florida. The overall sample was 45% female, 22% Non-Hispanic Black and 21% Hispanic participants, with an average age of 64 ± 14 years. All cause death, readmissions, or hospital/emergency room representations are 10% and 19% at 30 and 90 days, respectively. One in 5 outcomes was vascular-related. CONCLUSIONS: This study highlights the transition from stroke hospitalization as an area in need for considerable improvement in systems of care for stroke patients discharged from hospital. Results from our preliminary analysis highlight the importance of investigating race-ethnic and sex differences in post-stroke outcomes.

Radiographic Characteristics of Mild Ischemic Stroke Patients With Visible Intracranial Occlusion: The INTERRSeCT Study.

BACKGROUND AND PURPOSE: Early neurological deterioration occurs in one-third of mild strokes primarily due to the presence of a relevant intracranial occlusion. We studied vascular occlusive patterns, thrombus characteristics, and recanalization rates in these patients. METHODS: Among patients enrolled in INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography), a multicenter prospective study of acute ischemic strokes with a visible intracranial occlusion, we compared characteristics of mild (National Institutes of Health Stroke Scale score, ≤5) to moderate/severe strokes. RESULTS: Among 575 patients, 12.9% had a National Institutes of Health Stroke Scale score ≤5 (median age, 70.5 [63-79]; 58% male; median National Institutes of Health Stroke Scale score, 4 [2-4]). Demographics and vascular risk factors were similar between the two groups. As compared with those with a National Institutes of Health Stroke Scale score >5, mild patients had longer symptom onset to assessment times (onset to computed tomography [240 versus 167 minutes] and computed tomography angiography [246 versus 172 minutes]), more distal occlusions (M3, anterior cerebral artery and posterior cerebral artery; 22% versus 6%), higher clot burden score (median, 9 [6-9] versus 6 [4-9]), similar favorable thrombus permeability (residual flow grades I-II, 21% versus 19%), higher collateral flow (9.1 versus 7.6), and lower intravenous alteplase treatment rates (55% versus 85%). Mild patients were more likely to recanalize (revised arterial occlusion scale score 2b/3, 45%; 49% with alteplase) compared with moderate/severe strokes (26%; 29% with alteplase). In an adjusted model for sex, alteplase, residual flow, and time between the two vessel imagings, intravenous alteplase use (odds ratio, 3.80 [95% CI, 1.11-13.00]) and residual flow grade (odds ratio, 8.70 [95% CI, 1.26-60.13]) were associated with successful recanalization among mild patients. CONCLUSIONS: Mild strokes with visible intracranial occlusions have different vascular occlusive patterns but similar thrombus permeability compared with moderate/severe strokes. Higher thrombus permeability and alteplase use were associated with successful recanalization, although the majority do not recanalize. Randomized controlled trials are needed to assess the efficacy of new thrombolytics and endovascular therapy in this population.

Frequency and Prognostic Significance of Clinical Fluctuations Before Hospital Arrival in Stroke.

BACKGROUND AND PURPOSE: Clinical fluctuations in ischemic stroke symptoms are common, but fluctuations before hospital arrival have not been previously characterized. METHODS: A standardized qualitative assessment of fluctuations before hospital arrival was obtained in an observational study that enrolled patients with mild ischemic stroke symptoms (National Institutes of Health Stroke Scale [NIHSS] score of 0-5) present on arrival to hospital within 4.5 hours of onset, in a subset of 100 hospitals participating in the Get With The Guidelines-Stroke quality improvement program. The number of fluctuations, direction, and the overall improvement or worsening was recorded based on reports from the patient, family, or paramedics. Baseline NIHSS on arrival and at 72 hours (or discharge if before) and final diagnosis and stroke subtype were collected. Outcomes at 90 days included the modified Rankin Scale, Barthel Index, Stroke Impact Scale 16, and European Quality of Life. Prehospital fluctuations were examined in relation to hospital NIHSS change (admission to 72 hours or discharge) and 90-day outcomes. RESULTS: Among 1588 participants, prehospital fluctuations, consisting of improvement, worsening, or both were observed in 35.5%: 25.1% improved once, 5.3% worsened once, and 5.1% had more than 1 fluctuation. Those who improved were less likely and those who worsened were more likely to receive alteplase. Those who improved before hospital arrival had lower change in the hospital NIHSS than those who did not fluctuate. Better adjusted 90-day outcomes were noted in those with prehospital improvement compared to those without any fluctuations. CONCLUSIONS: Fluctuations in neurological symptoms and signs are common in the prehospital setting. Prehospital improvement was associated with better 90-day outcomes, controlling for admission NIHSS and alteplase treatment. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02072681.

Phthalate and bisphenol a exposures during pregnancy: Findings from the National Children's Study.

Maternal exposure to phthalates and bisphenol A (BPA) during pregnancy can result in many adverse offspring health outcomes. Exposure to phthalates and BPA can vary depending on consumption of certain foods, some of which may vary by race/ethnicity. This study relates urine phthalate and BPA concentrations to sociodemographic and diet data. Concentrations of bisphenol A (BPA) and 11 phthalate metabolites were measured from spot urine at the third trimester visit of a sample of 485 pregnant women from the National Children's Study Vanguard Study Pilot data from seven U.S. cities. At the same time, food frequency questionnaires (FFQ) using the Diet*Calc software were obtained from 313 (65%) participants to assess dietary behavior. Overall, phthalate metabolites were highest among Hispanic women, particularly mBP, miBP, and mECPP, and these disparities were not explained by diet. Participants who did not attend college had higher concentrations of mBP, mBzP, mEP, and miBP, and lower mCOP. These disparities were also not explained by diet. The causes for these disparities should be further studied to reduce potential negative health outcomes associated with phthalate exposure for children of Hispanic or non-college educated women.

Accuracy of transcranial Doppler in detecting intracranial stenosis in patients with sickle cell anemia when compared to magnetic resonance angiography.

BACKGROUND: Stroke, the most devastating consequence of sickle cell anemia (SCA), is associated with endothelial damage and intracranial artery stenosis. We aimed to assess transcranial Doppler (TCD) ultrasound accuracy in detecting intracranial stenosis when compared to magnetic resonance angiography (MRA). METHODS: Children with SCA and at least one TCD and MRA within 1 month were identified from a retrospectively collected database. Sensitivity and specificity were obtained to assess the overall accuracy of TCD mean flow velocity (mFV) ≥200 cm/s in detecting vessel stenosis of ≥50%. Multivariate analysis identified independent factors associated with MRA stenosis. RESULTS: Among 157 patients in the database, 64 had a TCD and MRA within 1 month (age 11.8 ± 5.3 years, 56% female, 20% with cerebral infarcts on MRI, 8 or 13% had mFV ≥200 cm/s and 20% or 21%, had intracranial stenosis ≥50% on MRA). TCD mFV ≥200 cm/s had a high specificity (95%) but low sensitivity (29%) to detecting intracranial stenosis. As a continuous variable, TCD mFV of 137.5 cm/s had maximal specificity (77%) and sensitivity (72%). After adjustment for age, hemoglobin level, transfusion status, hydroxyurea treatment, and vessel, for every increase in cm/sec on TCD, there was a 2% increase in the odds of ≥50% stenosis on MRA (p < 0.001). CONCLUSION: Our study reports TCD mFV is a positive predictor of MRA stenosis in SCA, independent of patient characteristics, including hemoglobin. A mFV ≥200 cm/s is highly specific but less sensitive in detecting stenosis ≥50%. Lower mFV cut points may be needed for the early detection of intracranial stenosis.

Thrombolysis in Mild Stroke: A Comparative Analysis of the PRISMS and MaRISS Studies.

Background and Purpose: Mild ischemic stroke patients enrolled in randomized controlled trials of thrombolysis may have a different symptom severity distribution than those treated in routine clinical practice. Methods: We compared the distribution of the National Institutes of Health Stroke Scale (NIHSS) scores, neurological symptoms/severity among patients enrolled in the PRISMS (Potential of r-tPA for Ischemic Strokes With Mild Symptoms) randomized controlled trial to those with NIHSS score ≤5 enrolled in the prospective MaRISS (Mild and Rapidly Improving Stroke Study) registry using global P values from χ2 analyses. Results: Among 1736 participants in MaRISS, 972 (56%) were treated with alteplase and 764 (44%) were not. These participants were compared with 313 patients randomized in PRISMS. The median NIHSS scores were 3 (2­4) in MaRISS alteplase-treated, 1 (1­3) in MaRISS non­alteplase-treated, and 2 (1­3) in PRISMS. The percentage with an NIHSS score of 0 to 2 was 36.3%, 73.3%, and 65.2% in the 3 groups, respectively (P<0.0001). The proportion of patients with a dominant neurological syndrome (≥1 NIHSS item score of ≥2) was higher in MaRISS alteplase-treated (32%) compared with MaRISS nonalteplase-treated (13.8%) and PRISMS (8.6%; P<0.0001). Conclusions: Patients randomized in PRISMS had comparable deficit and syndromic severity to patients not treated with alteplase in the MaRISS registry and lesser severity than patients treated with alteplase in MaRISS. The PRISMS trial cohort is representative of mild patients who do not receive alteplase in current broad clinical practice.

Predictors of Outcomes in Patients With Mild Ischemic Stroke Symptoms: MaRISS.

Background and Purpose: Although most strokes present with mild symptoms, these have been poorly represented in clinical trials. The objective of this study is to describe multidimensional outcomes, identify predictors of worse outcomes, and explore the effect of thrombolysis in this population. Methods: This prospective observational study included patients with ischemic stroke or transient ischemic attack, a baseline National Institutes of Health Stroke Scale (NIHSS) score 0 to 5, presenting within 4.5 hours from symptom onset. The primary outcome was a 90-day modified Rankin Scale score of 0 to 1; secondary outcomes included good outcomes in the Barthel Index, Stroke Impact Scale-16, and European Quality of Life. Multivariable models were created to determine predictors of outcomes and the effect of alteplase. Results: A total of 1765 participants were included from 100 Get With The Guidelines-Stroke participating hospitals (age, 65±14; 42% women; final diagnosis of ischemic stroke, 90%; transient ischemic attack, 10%; 57% received alteplase). At 90 days, 37% were disabled and 25% not independent. Worse outcomes were noted for older individuals, women, non-Hispanic Blacks and Hispanics, Medicaid recipients, smokers, those with diabetes, atrial fibrillation, prior stroke, higher baseline NIHSS, visual field defects, and extremity weakness. Similar outcomes were noted for the alteplase-treated and untreated groups. Alteplase-treated patients were younger (64±13 versus 67±1.4) with higher NIHSS (2.9±1.4 versus 1.7±1.4). After adjusting for age, sex, race/ethnicity, and baseline NIHSS, we did not identify an effect of alteplase on the primary outcome but did find an association with Stroke Impact Scale-16 in the restricted sample of baseline NIHSS score 3­5. Few symptomatic intracerebral hemorrhages were recorded (<1%). Conclusions: A large proportion of stroke patients presenting with low NIHSS have a disabled outcome. Baseline predictors of worse outcomes are described. An effect of alteplase on outcomes was not identified in the overall cohort, but a suggestion of efficacy was noted in the NIHSS 3­5 subgroup. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02072681.

Optimization of duplex velocity criteria for diagnosis of internal carotid artery (ICA) stenosis: A report of the Intersocietal Accreditation Commission (IAC) Vascular Testing Division Carotid Diagnostic Criteria Committee.

Diagnostic criteria to classify severity of internal carotid artery (ICA) stenosis vary across vascular laboratories. Consensus-based criteria, proposed by the Society of Radiologists in Ultrasound in 2003 (SRUCC), have been broadly implemented but have not been adequately validated. We conducted a multicentered, retrospective correlative imaging study of duplex ultrasound versus catheter angiography for evaluation of severity of ICA stenosis. Velocity data were abstracted from bilateral duplex studies performed between 1/1/2009 and 12/31/2015 and studies were interpreted using SRUCC. Percentage ICA stenosis was determined using North American Symptomatic Carotid Endarterectomy Trial (NASCET) methodology. Receiver operating characteristic analysis evaluated the performance of SRUCC parameters compared with angiography. Of 448 ICA sides (from 224 patients), 299 ICA sides (from 167 patients) were included. Agreement between duplex ultrasound and angiography was moderate (κ = 0.42), with overestimation of degree of stenosis for both moderate (50-69%) and severe (⩾ 70%) ICA lesions. The primary SRUCC parameter for ⩾ 50% ICA stenosis of peak-systolic velocity (PSV) of ⩾ 125 cm/sec did not meet prespecified thresholds for adequate sensitivity, specificity, and accuracy (sensitivity 97.8%, specificity 64.2%, accuracy 74.5%). Test performance was improved by raising the PSV threshold to ⩾ 180 cm/sec (sensitivity 93.3%, specificity 81.6%, accuracy 85.2%) or by adding the additional parameter of ICA/common carotid artery (CCA) PSV ratio ⩾ 2.0 (sensitivity 94.3%, specificity 84.3%, accuracy 87.4%). For ⩾ 70% ICA stenosis, analysis was limited by a low number of cases with angiographically severe disease. Interpretation of carotid duplex examinations using SRUCC resulted in significant overestimation of severity of ICA stenosis when compared with angiography; raising the PSV threshold for ⩾ 50% ICA stenosis to ⩾ 180 cm/sec as a single parameter or requiring the ICA/CCA PSV ratio ⩾ 2.0 in addition to PSV of ⩾ 125 cm/sec for laboratories using the SRUCC is recommended to improve the accuracy of carotid duplex examinations.

PFAS concentration during pregnancy in relation to cardiometabolic health and birth outcomes.

INTRODUCTION: Poly- and perfluoroalkyl substances (PFAS) are persistent organic pollutants with pervasive exposure and suspected associations with metabolic abnormalities and adverse pregnancy outcomes. The goal of the present study was to examine the relationship between serum-PFAS concentrations measured in late pregnancy with relevant outcomes. METHODS: The study sample included 433 pregnant women enrolled in the Vanguard Pilot Study of the National Children's Study. Six PFAS were measured in primarily third trimester serum, as well as fasting insulin, total cholesterol, and triglycerides. The PFAS were examined in quartiles in relation to serum biomarkers, gestational age at birth and birth weight standardized for gestational age using multivariable-adjusted regression models. RESULTS: Over 98% of the study population had detectable concentrations of four of the PFAS, and concentrations varied by race/ethnicity. Total cholesterol was positively associated with PFDA, PFNA, and PFOS, and triglycerides with PFDA, PFNA, PFOS, and PFOA, but PFAS were not associated with fasting insulin in adjusted models. Only PFNA was associated with an increased odds of birth at <37 weeks gestation. PFAS were generally not associated with birth weight, though PFHxS was associated with the first quartile of birth weight among males only. CONCLUSIONS: This study of pregnant U.S. women supports the ubiquitous exposure to PFAS and positive associations between PFAS exposure with serum-lipid concentrations. PFAS were largely unassociated with gestational age at birth and birth weight, though PFNA was associated with preterm birth. The results support the vulnerability to PFAS exposure of pregnancy.