Recruitment in Acute Stroke Trials: Challenges and Potential Solutions.

Randomized clinical trials of acute stroke have led to major advances in acute stroke therapy over the past decade. Despite these successes, recruitment in acute trials is often difficult. We outline challenges in recruitment for acute stroke trials and present potential solutions, which can increase the speed and decrease the cost of identifying new treatments for acute stroke. One of the largest opportunities to increase the speed of enrollment and make trials more generalizable is expansion of inclusion criteria whose impact on expected recruitment can be assessed by epidemiologic and registry databases. Another barrier to recruitment besides the number of eligible patients is availability of study investigators limited to business hours, which may be helped by financial support for after-hours call. The wider use of telemedicine has accelerated quicker stroke treatment at many hospitals and has the potential to accelerate research enrollment but requires training of clinical investigators who are often inexperienced with this approach. Other potential solutions to enhance recruitment include rapid prehospital notification of clinical investigators of potential patients, use of mobile stroke units, advances in the process of emergency informed consent, storage of study medication in the emergency department, simplification of study treatments and data collection, education of physicians to improve equipoise and enthusiasm for randomization of patients within a trial, and clear recruitment plans, and even potentially coenrollment, when there are competing trials at sites. Without successful recruitment, scientific advances and clinical benefit for acute stroke patients will lag.

Trends in Disparities in Advanced Neuroimaging Utilization in Acute Stroke: A Population-Based Study.

BACKGROUND: Our primary objective was to evaluate if disparities in race, sex, age, and socioeconomic status (SES) exist in utilization of advanced neuroimaging in year 2015 in a population-based study. Our secondary objective was to identify the disparity trends and overall imaging utilization as compared with years 2005 and 2010. METHODS: This was a retrospective, population-based study that utilized the GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study) data. Patients with stroke and transient ischemic attack were identified in the years 2005, 2010, and 2015 in a metropolitan population of 1.3 million. The proportion of imaging use within 2 days of stroke/transient ischemic attack onset or hospital admission date was computed. SES determined by the percentage below the poverty level within a given respondent's US census tract of residence was dichotomized. Multivariable logistic regression was used to determine the odds of advanced neuroimaging use (computed tomography angiogram/magnetic resonance imaging/magnetic resonance angiogram) for age, race, gender, and SES. RESULTS: There was a total of 10 526 stroke/transient ischemic attack events in the combined study year periods of 2005, 2010, and 2015. The utilization of advanced imaging progressively increased (48% in 2005, 63% in 2010, and 75% in 2015 [P<0.001]). In the combined study year multivariable model, advanced imaging was associated with age and SES. Younger patients (≤55 years) were more likely to have advanced imaging compared with older patients (adjusted odds ratio, 1.85 [95% CI, 1.62-2.12]; P<0.01), and low SES patients were less likely to have advanced imaging compared with high SES (adjusted odds ratio, 0.83 [95% CI, 0.75-0.93]; P<0.01). A significant interaction was found between age and race. Stratified by age, the adjusted odds of advanced imaging were higher for Black patients compared with White patients among older patients (>55 years; adjusted odds ratio, 1.34 [95% CI, 1.15-1.57]; P<0.01), but no racial differences among the young. CONCLUSIONS: Racial, age, and SES-related disparities exist in the utilization of advanced neuroimaging for patients with acute stroke. There was no evidence of a change in trend of these disparities between the study periods.

Using Epidemiological Data to Inform Clinical Trial Feasibility Assessments: A Case Study.

BACKGROUND: Clinical trial enrollment and completion is challenging, with nearly half of all trials not being completed or not completed on time. In 2014, the National Institutes of Health StrokeNet in collaboration with stroke epidemiologists from GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study) began providing proposed clinical trials with formal trial feasibility assessments. Herein, we describe the process of prospective feasibility analyses using epidemiological data that can be used to improve enrollment and increase the likelihood a trial is completed. METHODS: In 2014, DEFUSE 3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke 3) trialists, National Institutes of Health StrokeNet, and stroke epidemiologists from GCNKSS collaborated to evaluate the initial inclusion/exclusion criteria for the DEFUSE 3 study. Trial criteria were discussed and an assessment was completed to evaluate the percent of the stroke population that might be eligible for the study. The DEFUSE 3 trial was stopped early with the publication of DAWN (Thrombectomy 6 to 24 Hours After Stroke With a Mismatch Between Deficit and Infarct), and the Wilcoxon rank-sum statistic was used to analyze whether the trial would have been stopped had the proposed changes not been made, following the DEFUSE 3 statistical analysis plan. RESULTS: After initial epidemiological analysis, 2.4% of patients with acute stroke in the GCNKSS population would have been predicted to be eligible for the study. After discussion with primary investigators and modifying 4 key exclusion criteria (upper limit of age increased to 90 years, baseline modified Rankin Scale broadened to 0-2, time since last well expanded to 16 hours, and decreased lower limit of National Institutes of Health Stroke Scale score to <6), the number predicted to be eligible for the trial increased to 4%. At the time of trial conclusion, 57% of the enrolled patients qualified only by the modified criteria, and the trial was stopped at an interim analysis that demonstrated efficacy. We estimated that the Wilcoxon rank-sum value for the unadjusted predicted enrollment would not have crossed the threshold for efficacy and the trial not stopped. CONCLUSIONS: Objectively assessing trial inclusion/exclusion criteria using a population-based resource in a collaborative and iterative process including epidemiologists can lead to improved recruitment and can increase the likelihood of successful trial completion.

Acute Ischemic Stroke, Depressed Left Ventricular Ejection Fraction, and Sinus Rhythm: Prevalence and Practice Patterns.

BACKGROUND: There are limited data about the epidemiology and secondary stroke prevention strategies used for patients with depressed left ventricular ejection fraction (LVEF) and sinus rhythm following an acute ischemic stroke (AIS). We sought to describe the prevalence of LVEF ≤40% and sinus rhythm among patients with AIS and antithrombotic treatment practice in a multi-center cohort from 2002 to 2018. METHODS: This was a multi-center, retrospective cohort study comprised of patients with AIS hospitalized in the Greater Cincinnati Northern Kentucky Stroke Study and 4 academic, hospital-based cohorts in the United States. A 1-stage meta-analysis of proportions was undertaken to calculate a pooled prevalence. Univariate analyses and an adjusted multivariable logistic regression model were performed to identify demographic, clinical, and echocardiographic characteristics associated with being prescribed an anticoagulant upon AIS hospitalization discharge. RESULTS: Among 14 338 patients with AIS with documented LVEF during the stroke hospitalization, the weighted pooled prevalence of LVEF ≤40% and sinus rhythm was 5.0% (95% CI, 4.1-6.0%; I2, 84.4%). Of 524 patients with no cardiac thrombus and no prior indication for anticoagulant who survived postdischarge, 200 (38%) were discharged on anticoagulant, 289 (55%) were discharged on antiplatelet therapy only, and 35 (7%) on neither. There was heterogeneity by site in the proportion discharged with an anticoagulant (22% to 45%, P<0.0001). Cohort site and National Institutes of Health Stroke Severity scale >8 (odds ratio, 2.0 [95% CI, 1.1-3.8]) were significant, independent predictors of being discharged with an anticoagulant in an adjusted analysis. CONCLUSIONS: Nearly 5% of patients with AIS have a depressed LVEF and are in sinus rhythm. There is significant variation in the clinical practice of antithrombotic therapy prescription by site and stroke severity. Given this clinical equipoise, further study is needed to define optimal antithrombotic treatment regimens for secondary stroke prevention in this patient population.

Electronic health record-embedded decision support to reduce stroke risk in patients with atrial fibrillation - Study protocol.

BACKGROUND: Atrial fibrillation (AF) is the most common significant cardiac rhythm disorder and is a powerful common risk factor for stroke. Randomized trials have demonstrated that anticoagulation can reduce the risk of stroke in patients with AF. Yet, there continues to be widespread underutilization of this therapy. To address this practice gap locally and improve efforts to reduce the risk of stroke for patients with AF in our health system, we have designed a study to implement and evaluate the effectiveness of an Atrial Fibrillation Decision Support Tool (AFDST) embedded within our electronic health record. METHODS: Our intervention is provider-facing and focused on decision support. The clinical setting is ambulatory patients being seen by primary care physicians. Patients include those with both incident and prevalent AF. This randomized, prospective trial will enroll 800 patients in our University of Cincinnati Health System who are currently receiving less than optimal anticoagulation therapy as determined by the AFDST. Patients will be randomized to one of two arms - 1) usual care, in which the AFDST is available for use; 2) addition of a best practice advisory (BPA) to the AFDST notifying the clinician that their patient stands to gain a significant benefit from a change in their current thromboprophylactic therapy. RESULTS: The primary outcome is effectiveness of the BPA measured by change to "appropriate thromboprophylaxis" based on the AFDST recommendation at 3 months post randomization. Secondary endpoints include Reach and Adoption, from the RE-AIM framework for implementation studies. Sample size is based upon an improvement from inappropriate to appropriate anticoagulation therapy estimated at 4% in the usual care arm and ≥10% in the experimental arm. CONCLUSION: Our goal is to examine whether addition of a BPA to an AFDST focused on primary care physicians in an ambulatory care setting will improve "appropriate thromboprophylaxis" compared with usual care. Results will be examined at 3 months post randomization and at the end of the study to evaluate durability of changes. We expect to complete patient enrollment by the end of June 2022. TRIAL REGISTRATION: Clinicaltrials.gov NCT04099485.

Co-exposure to manganese and lead and pediatric neurocognition in East Liverpool, Ohio.

Exposure to metal mixtures may lead to health impacts greater than the effects associated with singular exposures. Two common childhood environmental exposures, manganese (Mn) and lead (Pb), are associated with similar adverse neurodevelopmental effects; however, the effects surrounding concurrent exposure to both metals remain unclear. We study the impact of joint exposure to Mn and Pb on cognitive performance in school-aged children participating in the Communities Actively Researching Exposure Study (CARES) based in East Liverpool, Ohio. Blood Pb levels were measured for each child (geometric mean (GM) = 1.13 µg/dL, range 0.30 µg/dL - 6.64 µg/dL). Mn was measured in participant blood, hair, and toenails with GMs of 10.1 µg/L, 360 ng/g, 0.974 µg/g, respectively. Trained team members administered the Wechsler Intelligence Scale for Children-IV (WISC-IV) to assess intelligence quotient (IQ). The WISC-IV provides scores for Full Scale IQ, Perceptual Reasoning, Processing Speed, Working Memory, and Verbal Comprehension. Interactions between blood Pb and all Mn biomarkers were tested in linear models adjusted for child sex, household income, and serum cotinine. Separate regression models were run for each of the Mn biomarkers. The cohort was comprised of 106 children with a mean age of 8.4 years. Interactions between blood Pb and hair Mn were significant (p < 0.05) for four out of the five IQ domains. The effect of blood Pb on IQ was more pronounced at higher levels of hair and toenail Mn. No significant associations were observed when characterizing the main effect of Mn using blood. Uncovering the health impacts associated with exposure mixtures is critical to understanding the impact of real-life conditions. Our findings suggest that joint exposure to Mn and Pb may produce heightened neurocognitive impacts even at blood Pb levels below the CDC reference concentration of 5 µg/dL.

Isolated Third Cranial Nerve Palsy in Pituitary Apoplexy: Case Report and Systematic Review.

OBJECTIVES: To report a case of isolated third nerve palsy from pituitary apoplexy and perform a systematic literature review. MATERIALS AND METHODS: MEDLINE/EMBASE databases were searched up to September 2020. INCLUSION CRITERIA: Age≥18, isolated third nerve palsy from pituitary apoplexy. EXCLUSION CRITERIA: Age<18, presence of other neurological findings, no hemorrhage or infarction of pituitary. RESULTS: Case report: A 76-year-old woman presented with headache and right-sided ptosis. Right-eye exam revealed complete ptosis, absent pupillary constriction and accommodation, depressed and abducted eye on primary gaze, and -1 impaired depression, adduction, elevation, without other neurological findings. Brain MRI was suggestive of pituitary apoplexy. Pathology after transsphenoidal resection revealed an infarcted pituitary adenoma. Third nerve palsy resolved completely in 21 days. Systematic review: Twenty-three studies reporting 35 patients were selected from 182 abstracts. Twenty-nine (83%) had complete isolated third nerve palsy. Headache was reported in 31 (97%). Thirty-one had hemorrhage and 1 had infarction of pituitary. Cavernous sinus invasion occurred in 14 (50%). Twenty-eight were managed surgically (80%) and 7 medically (20%). Nerve palsy resolved completely in 27 (82%) and partially in 4 (11%). CONCLUSIONS: Pituitary apoplexy is an important differential diagnosis in patients with isolated third nerve palsy. Isolated third nerve palsy in apoplexy appears to have favorable prognosis.

Effect of COVID-19 on Emergent Stroke Care: A Regional Experience.

BACKGROUND AND PURPOSE: Anecdotal evidence suggests that the coronavirus disease 2019 (COVID-19) pandemic mitigation efforts may inadvertently discourage patients from seeking treatment for stroke with resultant increased morbidity and mortality. Analysis of regional data, while hospital capacities for acute stroke care remained fully available, offers an opportunity to assess this. We report regional Stroke Team acute activations and reperfusion treatments during COVID-19 mitigation activities. METHODS: Using case log data prospectively collected by a Stroke Team exclusively serving ≈2 million inhabitants and 30 healthcare facilities, we retrospectively reviewed volumes of consultations and reperfusion treatments for acute ischemic stroke. We compared volumes before and after announcements of COVID-19 mitigation measures and the prior calendar year. RESULTS: Compared with the 10 weeks prior, stroke consultations declined by 39% (95% CI, 32%-46%) in the 5 weeks after announcement of statewide school and restaurant closures in Ohio, Kentucky, and Indiana. Results compared with the prior year and time trend analyses were consistent. Reperfusion treatments also appeared to decline by 31% (95% CI, 3%-51%), and specifically thrombolysis by 33% (95% CI, 4%-55%), but this finding had less precision. CONCLUSIONS: Upon the announcement of measures to mitigate COVID-19, regional acute stroke consultations declined significantly. Reperfusion treatment rates, particularly thrombolysis, also appeared to decline qualitatively, and this finding requires further study. Urgent public education is necessary to mitigate a possible crisis of avoiding essential emergency care due to COVID-19.

Temporal Trends in Stroke Incidence Over Time by Sex and Age in the GCNKSS.

Background and Purpose- Sex differences in stroke incidence over time were previously reported from the GCNKSS (Greater Cincinnati/Northern Kentucky Stroke Study). We aimed to determine whether these differences continued through 2015 and whether they were driven by particular age groups. Methods- Within the GCNKSS population of 1.3 million, incident (first ever) strokes among residents ≥20 years of age were ascertained at all local hospitals during 5 periods: July 1993 to June 1994 and calendar years 1999, 2005, 2010, and 2015. Out-of-hospital cases were sampled. Sex-specific incidence rates per 100 000 were adjusted for age and race and standardized to the 2010 US Census. Trends over time by sex were compared (overall and age stratified). Sex-specific case fatality rates were also reported. Bonferroni corrections were applied for multiple comparisons. Results- Over the 5 study periods, there were 9733 incident strokes (56.3% women). For women, there were 229 (95% CI, 215-242) per 100 000 incident strokes in 1993/1994 and 174 (95% CI, 163-185) in 2015 (P<0.05), compared with 282 (95% CI, 263-301) in 1993/1994 to 211 (95% CI, 198-225) in 2015 (P<0.05) in men. Incidence rates decreased between the first and last study periods in both sexes for IS but not for intracerebral hemorrhage or subarachnoid hemorrhage. Significant decreases in stroke incidence occurred between the first and last study periods for both sexes in the 65- to 84-year age group and men only in the ≥85-year age group; stroke incidence increased for men only in the 20- to 44-year age group. Conclusions- Overall stroke incidence decreased from the early 1990s to 2015 for both sexes. Future studies should continue close surveillance of sex differences in the 20- to 44-year and ≥85-year age groups, and future stroke prevention strategies should target strokes in the young- and middle-age groups, as well as intracerebral hemorrhage.

Potential Impact of C-STAT for Prehospital Stroke Triage up to 24 Hours on a Regional Stroke System.

Background and Purpose: Thrombectomy for large vessel occlusion acute ischemic stroke (AIS-LVO) may benefit patients up to 24 hour since last known normal (LKN). Prehospital tools, like the Cincinnati Stroke Triage Assessment Tool (C-STAT), are used to select hospital destination for suspected AIS-LVO patients. The objective of this study was to estimate the potential impact of the expanded thrombectomy time window on suspected AIS-LVO cases transported to the regional comprehensive stroke center (CSC). Methods: From June to November 2015, C-STAT was performed by prehospital providers following a positive prehospital Cincinnati Prehospital Stroke Scale (CPSS) stroke screen in suspected stroke/TIA patients. There was no preferential triage based on C-STAT results. Final diagnoses, including the presence of AIS-LVO was ascertained via medical record review. Impact of positive C-STAT cases on CSC volumes was estimated for up to 24 hours since LKN. Results: Of 158 patients with prehospital suspicion for stroke/TIA, 105 were CPSS positive within 24 hours of onset and had complete C-STAT and clinical data available for analysis. Forty-six percent (17/37) of C-STAT + were non-strokes. C-STAT sensitivity and specificity for LVO were 71% (95% CI 36-92) and 67% (95% CI 58-80), respectively. C-STAT triage would increase transport of prehospital suspected stroke cases to the CSC by 11% (12/105) within six hours and 21% (22/105) within 24 hours. Of 37 C-STAT + patients, only 5 (13.5%) had LVO as final diagnosis. Conclusions: Preferential triage of prehospital suspected stroke patients using C-STAT would increase the number of patients transported to the CSC by 11% within six hours and an additional 10% from six to 24 hours. For every patient with LVO as final diagnosis, approximately an additional 6 non-LVO patients would be triaged to a CSC.

Can non-contrast head CT and stroke severity be used for stroke triage? A population-based study.

BACKGROUND AND PURPOSE: Acute ischemic stroke (AIS) patients may benefit from endovascular thrombectomy (EVT) up to 24 h since last known normal (LKN). Advanced imaging is required for patient selection. Small or rural hospitals may not have sufficient CT technician and radiology support to rapidly acquire and interpret images. We estimated transfer rates using non-contrast head CT and stroke severity to select patients to be transferred to larger centers for evaluation. METHODS: We identified all AIS among residents of the study region in 2010. Only cases age ≥ 18 with baseline mRS 0-2 that presented to an ED were included. Among cases that presented between 6 and 24 h from LKN, those without evidence of acute infarct on head CT and with initial NIHSS ≥6 or ≥ 10 were identified. RESULTS: Of 1359 AIS cases, 448 (33.0%) presented between 6 and 24 h, of which 383 (85.5%) showed no evidence of acute infarct on CT. Of cases with no acute infarct on CT, 89/383 (23.2%) had NIHSS ≥6, of which 66 (74.2%) initially presented to a hospital without thrombectomy capabilities; and 51/383 (13.3%) had NIHSS ≥10, of which 40 (78.4%) presented to a non-thrombectomy hospital. CONCLUSIONS: In our population, 40-66 AIS patients annually (0.8-1.3/week, or 3-5 patients/100,000 persons/year) may present to non-thrombectomy hospitals and need to be transferred using non-contrast CT and stroke severity as screening tools. Such an approach may sufficiently mitigate the impact of delays in treatment on outcomes, without overburdening the referring nor accepting hospitals.

Paediatric clinical and social concerns identified by home visit nurses in the immediate postdischarge period.

AIM: To describe paediatric postdischarge concerns manifesting in the first 96 hr after hospital discharge. DESIGN: Analysis of nursing documentation generated as part of a randomized controlled trial evaluating the effect of a nurse home visit on healthcare re-use. METHODS: We analysed home visit records of 651 children (age <18) hospitalized at a large Midwestern children's hospital in 2015 and 2016 who were enrolled in the trial. Registered nurses documented concerns in structured fields and free-text notes in visit records. Descriptive statistics were used to summarize visit documentation. Free-text visit notes were reviewed and exemplars illustrative of quantitative findings were selected. RESULTS: Overall, nurses documented at least one concern in 56% (N = 367) of visits. Most commonly, they documented concerns about medication safety (15% or 91 visits). Specifically, in 11% (N = 58) of visits nurses were concerned that caregivers lacked a full understanding of medications and in 8% (N = 49) of visits families did not have prescribed discharge medications. Pain was documented as present in 9% of all visits (N = 56). Nurses completed referrals to other providers/services in 12% of visits (N = 78), most frequently to primary care providers. In 13% of visits (N = 85) nurses documented concerns considered beyond the immediate scope of the visit related to social needs such as housing and transportation. CONCLUSION: Inpatient and community nurses and physicians should be prepared to reconcile and manage discharge medications, assess families' medication administration practices and anticipate social needs after paediatric discharge. IMPACT: Little empirical data are available describing concerns manifesting immediately after paediatric hospital discharge. Concerns about medication safety were most frequent followed by concerns related to housing and general safety. The results are important for clinicians preparing children and families for discharge and for community clinicians caring for discharged children.

Blood Pressure after Endovascular Therapy for Ischemic Stroke (BEST): A Multicenter Prospective Cohort Study.

Background and Purpose- To identify the specific post-endovascular stroke therapy (EVT) peak systolic blood pressure (SBP) threshold that best discriminates good from bad functional outcomes (a priori hypothesized to be 160 mm Hg), we conducted a prospective, multicenter, cohort study with a prespecified analysis plan. Methods- Consecutive adult patients treated with EVT for an anterior ischemic stroke were enrolled from November 2017 to July 2018 at 12 comprehensive stroke centers accross the United States. All SBP values within 24 hours post-EVT were recorded. Using Youden index, the threshold of peak SBP that best discriminated primary outcome of dichotomized 90-day modified Rankin Scale score (0-2 versus 3-6) was identified. Association of this SBP threshold with the outcomes was quantified using multiple logistic regression. Results- Among 485 enrolled patients (median age, 69 [interquartile range, 57-79] years; 51% females), a peak SBP of 158 mm Hg was associated with the largest difference in the dichotomous modified Rankin Scale score (absolute risk reduction of 19%). Having a peak SBP >158 mm Hg resulted in an increased likelihood of modified Rankin Scale score 3 to 6 (odds ratio, 2.24 [1.52-3.29], P<0.01; adjusted odds ratio, 1.29 [0.81-2.06], P=0.28, after adjustment for prespecified variables). Conclusions- A peak post-EVT SBP of 158 mm Hg was prospectively identified to best discriminate good from bad functional outcome. Those with a peak SBP >158 had an increased likelihood of having a bad outcome in unadjusted, but not in adjusted analysis. The observed effect size was similar to prior studies. This finding should undergo further testing in a future randomized trial of goal-targeted post-EVT antihypertensive treatment.

Collateral Clock Is More Important Than Time Clock for Tissue Fate.

Background and Purpose- Although perfusion abnormality is an increasingly important therapeutic target, the natural history of tissue at risk without reperfusion treatment is understudied. Our objective was to determine how time affects penumbral salvage and infarct growth in untreated acute ischemic stroke patients and whether collateral status affects this relationship. Methods- We used a prospectively collected, multicenter acute stroke registry to assess acute stroke patients who were not treated with intravenous thrombolysis or endovascular treatment. We analyzed baseline computed tomography angiogram and computed tomography perfusion within 24 hours of stroke onset along with follow-up imaging and assessed time from stroke onset to baseline imaging, ASPECTS (Alberta Stroke Program Early CT Score), vessel occlusion, collaterals, ischemic core, and penumbra. Penumbral salvage and infarct growth were calculated. Correlations between time and penumbral salvage and infarct growth were evaluated with Spearman correlation. Penumbral salvage and infarct growth were compared between subjects with good versus poor collateral status using the Wilcoxon rank-sum test. Clinical and imaging factors affecting penumbral salvage and infarct growth were evaluated by linear regression. Results- Among 94 untreated stroke patients eligible for this analysis, the mean age was 65 years, median National Institutes of Health Stroke Scale score was 13, and median (range) time from stroke onset to baseline imaging was 2.9 (0.4-23) hours. There was no correlation between time and salvaged penumbra ( r=0.06; P=0.56) or infarct growth ( r=-0.05; P=0.61). Infarct growth was higher among those with poor collaterals versus those with good collaterals (median, 52.3 versus 0.9 cm3; P<0.01). Penumbral salvage was lower among those with poor collaterals compared with those with good collaterals (poor, 0 [0-0]; good, 5.9 cm3 [0-29.4]; P<0.01). Multivariable linear regression demonstrated that collaterals, but not time, were significantly associated with infarct growth and penumbral salvage. Conclusions- In this natural history study, penumbral salvage and infarct growth were less time dependent and more a measure of collateral flow.

Infant Weight and Length Growth Trajectories Modeled Using Superimposition by Translation and Rotation Are Differentially Associated with Body Composition Components at 3 and 7 Years of Age.

OBJECTIVE: To evaluate how infant weigh and length growth trajectories associate with body composition at 3 and 7 years because previous studies have noted that rapid infant weight gain increases risk for high body mass index (BMI) in children. STUDY DESIGN: There were 322 children enrolled at 3 years of age with dual x-ray absorptiometry body composition data and pediatrician growth data for 0-2 years of age who were included in analysis. Superimposition by translation and rotation modeling was used to characterize infant weight and length trajectories in terms of size, tempo and velocity measures. Associations of these measures with fat mass, lean mass, percent body fat, bone mineral content, BMI z-score, and overweight prevalence at 3 and 7 years of age were determined. RESULTS: Infant growth trajectories differed by sex, race, and breastfeeding status. Higher overall weight size and weight velocity from 0 to 2 years of age were associated positively with all age 3 body composition and anthropometry outcomes. However, longer length size from 0 to 2 years of age was associated independently with higher bone mineral content and lean mass, but lower percent body fat, BMI z-score, and a lower odds of overweight at 3 years of age. By 7 years of age, later than average infant weight tempo was also associated with lower fat mass, lean mass, and BMI z-score. CONCLUSIONS: Greater average weight size and greater weight velocity in infancy are markers for greater overall body size at 3 and 7 years of age. However, longer average lengths and later weight gain tempo between 0 and 2 years of age may help to establish a leaner body composition by 3 and 7 years of age.

Primary Care and Home Visiting Utilization Patterns among At-Risk Infants.

OBJECTIVE: To describe well child care (WCC) utilization in the first year of life among at-risk infants, and the relationship to home visiting enrollment. STUDY DESIGN: Retrospective cohort study using linked administrative data for infants ≥34 weeks' gestation from 2010 to 2014, within a regional, academic primary care system. Association between WCC visits and home visiting enrollment was evaluated using bivariate comparisons and multivariable Poisson regression. Latent class analysis further characterized longitudinal patterns of WCC attendance. Multivariable logistic regression tested the association between home visiting and pattern of timeliest adherence to recommended WCC. RESULTS: Of 11 936 infants, mean number of WCC visits was 4.1 in the first 12 months of life. Of 3910 infants eligible for home visiting, 28.5% were enrolled. Among enrolled infants, mean WCC visits was 4.7 vs 4.4 among eligible, nonenrolled infants, P value < .001. After multivariable adjustment, there was no significant association between enrollment and WCC visit count (adjusted incident rate ratio 1.03, 95% CI 0.99, 1.07). Using latent class analysis, 3 WCC classes were identified: infants in class 1 (77.7%) were most adherent to recommended WCC, class 2 (12.5% of cohort) had progressively declining WCC attendance over the first year of life, and class 3 (9.8%) maintained moderate attendance. In multivariable regression, home visiting was associated with class 1 membership, aOR 1.27, 95% CI 1.04, 1.57. CONCLUSIONS: A pattern of timely WCC attendance was more likely among infants in home visiting; however, most infants eligible for home visiting were not enrolled.

Prehospital neurological deterioration in stroke.

BACKGROUND AND PURPOSE: Patients with stroke can experience neurological deterioration in the prehospital setting. We evaluated patients with stroke to determine factors associated with prehospital neurological deterioration (PND). METHODS: Among the Greater Cincinnati/Northern Kentucky region (population ~1.3 million), we screened all 15 local hospitals' admissions from 2010 for acute stroke and included patients aged ≥20. The GCS was compared between emergency medical services (EMS) arrival and hospital arrival, with decrease ≥2 points considered PND. Data obtained retrospectively included demographics, medical history and medication use, stroke subtype (eg, ischaemic stroke (IS), intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH)) and IS subtype (eg, small vessel, large vessel, cardioembolic), seizure at onset, time intervals between symptom onset, EMS arrival and hospital arrival, EMS level of training, and blood pressure and serum glucose on EMS arrival. RESULTS: Of 2708 total patients who had a stroke, 1092 patients (median (IQR) age 74 (61-83) years; 56% women; 21% black) were analysed. PND occurred in 129 cases (12%), including 9% of IS, 24% of ICH and 16% of SAH. In multivariable analysis, black race, atrial fibrillation, haemorrhagic subtype and ALS level of transport were associated with PND. CONCLUSION: Haemorrhage and atrial fibrillation is associated with PND in stroke, and further investigation is needed to establish whether PND can be predicted. Further studies are also needed to assess whether preferential transport of patients with deterioration to hospitals equipped with higher levels of care is beneficial, identify why race is associated with deterioration and to test therapies targeting PND.

Estimated Impact of Emergency Medical Service Triage of Stroke Patients on Comprehensive Stroke Centers: An Urban Population-Based Study.

BACKGROUND AND PURPOSE: The American Stroke Association recommends that Emergency Medical Service bypass acute stroke-ready hospital (ASRH)/primary stroke center (PSC) for comprehensive stroke centers (CSCs) when transporting appropriate stroke patients, if the additional travel time is ≤15 minutes. However, data on additional transport time and the effect on hospital census remain unknown. METHODS: Stroke patients ≥20 years old who were transported from home to an ASRH/PSC or CSC via Emergency Medical Service in 2010 were identified in the Greater Cincinnati area population of 1.3 million. Addresses of all patients' residences and hospitals were geocoded, and estimated travel times were calculated. We estimated the mean differences between the travel time for patients taken to an ASRH/PSC and the theoretical time had they been transported directly to the region's CSC. RESULTS: Of 929 patients with geocoded addresses, 806 were transported via Emergency Medical Service directly to an ASRH/PSC. Mean additional travel time of direct transport to the CSC, compared with transport to an ASRH/PSC, was 7.9±6.8 minutes; 85% would have ≤15 minutes added transport time. Triage of all stroke patients to the CSC would have added 727 patients to the CSC's census in 2010. Limiting triage to the CSC to patients with National Institutes of Health Stroke Scale score of ≥10 within 6 hours of onset would have added 116 patients (2.2 per week) to the CSC's annual census. CONCLUSIONS: Emergency Medical Service triage to CSCs based on stroke severity and symptom duration may be feasible. The impact on stroke systems of care and patient outcomes remains to be determined and requires prospective evaluation.

Clinical Selection Strategies to Identify Ischemic Stroke Patients With Large Anterior Vessel Occlusion: Results From SITS-ISTR (Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Registry).

BACKGROUND AND PURPOSE: The National Institutes of Health Stroke Scale (NIHSS) correlates with presence of large anterior vessel occlusion (LAVO). However, the application of the full NIHSS in the prehospital setting to select patients eligible for treatment with thrombectomy is limited. Therefore, we aimed to evaluate the prognostic value of simple clinical selection strategies. METHODS: Data from the Safe Implementation of Thrombolysis in Stroke International Stroke Thrombolysis Registry (January 2012-May 2014) were analyzed retrospectively. Patients with complete breakdown of NIHSS scores and documented vessel status were included. We assessed the association of prehospital stroke scales and NIHSS symptom profiles with LAVO (internal carotid artery, carotid-terminus or M1-segment of the middle cerebral artery). RESULTS: Among 3505 patients, 23.6% (n=827) had LAVO. Pathological finding on the NIHSS item best gaze was strongly associated with LAVO (adjusted odds ratio 4.5, 95% confidence interval 3.8-5.3). All 3 face-arm-speech-time test (FAST) items identified LAVO with high sensitivity. Addition of the item gaze to the original FAST score (G-FAST) or high scores on other simplified stroke scales increased specificity. The NIHSS symptom profiles representing total anterior syndromes showed a 10-fold increased likelihood for LAVO compared with a nonspecific clinical profile. If compared with an NIHSS threshold of ≥6, the prehospital stroke scales performed similarly or even better without losing sensitivity. CONCLUSIONS: Simple modification of the face-arm-speech-time score or evaluating the NIHSS symptom profile may help to stratify patients' risk of LAVO and to identify individuals who deserve rapid transfer to comprehensive stroke centers. Prospective validation in the prehospital setting is required.

Prospective Prehospital Evaluation of the Cincinnati Stroke Triage Assessment Tool.

BACKGROUND AND PURPOSE: A simple, easily adoptable scale with good performance characteristics is needed for EMS providers to appropriately triage suspected stroke patients to comprehensive stroke centers (CSC). Many existing tools are complex, require substantial training, or have not been prospectively validated in the prehospital setting. We describe the feasibility and effectiveness of prehospital implementation of our previously retrospectively derived and validated Cincinnati Stroke Triage Assessment Tool (C-STAT) to identify subjects with severe stroke (NIHSS ≥15) among all prehospital patients with clinical suspicion of stroke/TIA. Secondarily, we evaluated the tool's ability to identify subjects with NIHSS ≥10, large vessel occlusion (LVO), or needing services available only at a CSC. METHODS: Without formalized training, Cincinnati Fire Department providers performed standard stroke screening ("face, arm, speech, time;" FAST) and C-STAT as part of their assessment of suspected stroke/TIA patients. Outcomes for patients brought to the region's only CSC or assessed by the regional stroke team were determined through structured chart review by a stroke team nurse. C-STAT test characteristics for each outcome were calculated with 95% confidence intervals. RESULTS: Complete prehospital and outcome data were available for 58 FAST-positive subjects among 158 subjects with prehospital suspicion for stroke/TIA. Subjects were excluded if FAST was negative (n = 22), FAST or C-STAT was incompletely documented (n = 24), if the patient was taken to a non-CSC and did not receive a stroke team consult (n = 48), or if outcome data were missing (n = 6). C-STAT sensitivity and specificity for each outcome were: NIHSS ≥ 15, 77% (95% CI 46-95) and 84% (95% CI 69-93); NIHSS ≥10, 64% (95% CI 41-83) and 91% (95% CI 76-98); LVO, 71% (95% CI 29-96) and 70% (95% CI 55-83); overall CSC need 57% (95% CI 34-78) and 79% (95% CI 61-91). CONCLUSION: In this pilot prospective evaluation performed in the prehospital setting by EMS providers without formalized training, C-STAT is comparable to other published tools in test characteristics and may inform appropriate CSC triage beyond LVO ascertainment alone.