Racial Disparities in Blood Pressure at Time of Acute Ischemic Stroke Presentation: A Population Study.

BACKGROUND: Hypertension is a stroke risk factor with known disparities in prevalence and management between Black and White patients. We sought to identify if racial differences in presenting blood pressure (BP) during acute ischemic stroke exist. METHODS AND RESULTS: Adults with acute ischemic stroke presenting to an emergency department within 24 hours of last known normal during study epochs 2005, 2010, and 2015 within the Greater Cincinnati/Northern Kentucky Stroke Study were included. Demographics, histories, arrival BP, National Institutes of Health Stroke Scale score, and time from last known normal were collected. Multivariable linear regression was used to determine differences in mean BP between Black and White patients, adjusting for age, sex, National Institutes of Health Stroke Scale score, history of hypertension, hyperlipidemia, smoking, stroke, body mass index, and study epoch. Of 4048 patients, 853 Black and 3195 White patients were included. In adjusted analysis, Black patients had higher presenting systolic BP (161 mm Hg [95% CI, 159-164] versus 158 mm Hg [95% CI, 157-159], P<0.01), diastolic BP (86 mm Hg [95% CI, 85-88] versus 83 mm Hg [95% CI, 82-84], P<0.01), and mean arterial pressure (111 mm Hg [95% CI, 110-113] versus 108 mm Hg [95% CI, 107-109], P<0.01) compared with White patients. In adjusted subanalysis of patients <4.5 hours from last known normal, diastolic BP (88 mm Hg [95% CI, 86-90] versus 83 mm Hg [95% CI, 82-84], P<0.01) and mean arterial pressure (112 mm Hg [95% CI, 110-114] versus 108 mm Hg [95% CI, 107-109], P<0.01) were also higher in Black patients. CONCLUSIONS: This population-based study suggests differences in presenting BP between Black and White patients during acute ischemic stroke. Further study is needed to determine whether these differences influence clinical decision-making, outcome, or clinical trial eligibility.

Child and Adolescent Manganese Biomarkers and Adolescent Postural Balance in Marietta CARES Cohort Participants.

BACKGROUND: Manganese (Mn) plays a significant role in both human health and global industries. Epidemiological studies of exposed populations demonstrate a dose-dependent association between Mn and neuromotor effects ranging from subclinical effects to a clinically defined syndrome. However, little is known about the relationship between early life Mn biomarkers and adolescent postural balance. OBJECTIVES: This study investigated the associations between childhood and adolescent Mn biomarkers and adolescent postural balance in participants from the longitudinal Marietta Communities Actively Researching Exposures Study (CARES) cohort. METHODS: Participants were recruited into CARES when they were 7-9 y old, and reenrolled at 13-18 years of age. At both time points, participants provided samples of blood, hair, and toenails that were analyzed for blood Mn and lead (Pb), serum cotinine, hair Mn, and toenail Mn. In adolescence, participants completed a postural balance assessment. Greater sway indicates postural instability (harmful effect), whereas lesser sway indicates postural stability (beneficial effect). Multivariable linear regression models were conducted to investigate the associations between childhood and adolescent Mn biomarkers and adolescent postural balance adjusted for age, sex, height-weight ratio, parent/caregiver intelligence quotient, socioeconomic status, blood Pb, and serum cotinine. RESULTS: CARES participants who completed the adolescent postural balance assessment (n=123) were 98% White and 54% female and had a mean age of 16 y (range: 13-18 y). In both childhood and adolescence, higher Mn biomarker concentrations were significantly associated with greater adolescent sway measures. Supplemental analyses revealed sex-specific associations; higher childhood Mn biomarker concentrations were significantly associated with greater sway in females compared with males. DISCUSSION: This study found childhood and adolescent Mn biomarkers were associated with subclinical neuromotor effects in adolescence. This study demonstrates postural balance as a sensitive measure to assess the association between Mn biomarkers and neuromotor function. https://doi.org/10.1289/EHP13381.

Impact of Poverty on Stroke Recurrence: A Population-Based Study.

BACKGROUND AND OBJECTIVES: Poverty is associated with greater stroke incidence. The relationship between poverty and stroke recurrence is less clear. METHODS: In this population-based study, incident strokes within the Greater Cincinnati/Northern Kentucky region were ascertained during the 2015 study period and followed up for recurrence until December 31, 2018. The primary exposure was neighborhood socioeconomic status (nSES), defined by the percentage of households below the federal poverty line in each census tract in 4 categories (≤5%, >5%-10%, >10%-25%, >25%). Poisson regression models provided recurrence rate estimates per 100,000 residents using population data from the 2015 5-year American Community Survey, adjusting for age, sex, and race. In a secondary analysis, Cox models allowed for the inclusion of vascular risk factors in the assessment of recurrence risk by nSES among those with incident stroke. RESULTS: Of 2,125 patients with incident stroke, 245 had a recurrent stroke during the study period. Poorer nSES was associated with increased stroke recurrence, with rates of 12.5, 17.5, 25.4, and 29.9 per 100,000 in census tracts with ≤5%, >5%-10%, >10%-25%, and >25% below the poverty line, respectively (p < 0.01). The relative risk (95% CI) for recurrent stroke among Black vs White individuals was 2.54 (1.91-3.37) before adjusting for nSES, and 2.00 (1.47-2.74) after adjusting for nSES, a 35.1% decrease. In the secondary analysis, poorer nSES (HR 1.74, 95% CI 1.10-2.76 for lowest vs highest category) and Black race (HR 1.31, 95% CI 1.01-1.70) were both independently associated with recurrence risk, though neither retained significance after full adjustment. Age, diabetes, and left ventricular hypertrophy were associated with increased recurrence risk in fully adjusted models. DISCUSSION: Residents of poorer neighborhoods had a dose-dependent increase in stroke recurrence risk, and neighborhood poverty accounted for approximately one-third of the excess risk among Black individuals. These results highlight the importance of poverty, race, and the intersection of the 2 as potent drivers of stroke recurrence.

Factors Associated With Premature Termination of Hyperacute Stroke Trials: A Review.

BACKGROUND: We performed a review of acute stroke trials to determine features associated with premature termination of trial enrollment, defined by the authors as not meeting preplanned sample size. METHODS AND RESULTS: MEDLINE was searched for randomized clinical stroke trials published in 9 major clinical journals between 2013 and 2022. We included randomized clinical trials that were phase 2 or 3 with a preplanned sample size ≥100 and a time-to-treatment within 24 hours of onset for transient ischemic attack, ischemic stroke, or intracerebral hemorrhage. Data were abstracted on trial features including trial design, inclusion criteria, imaging, location and number of sites, masking, treatment complexity, control group (standard therapy, placebo), industry involvement, and preplanned stopping rules (futility and efficacy). Least absolute shrinkage and selection operator regression was used to select the most important factors associated with premature termination; then, a multivariable logistic regression was fit including only the least absolute shrinkage and selection operator selected variables. Of 1475 studies assessed, 98 trials met eligibility criteria. Forty-five (46%) trials were prematurely terminated, of which 27% were stopped for benefit/efficacy, 20% for lack of money/slow enrollment, 18% for futility, 16% for newly available evidence, 17% for other reasons, and 4% due to harm. Complex trials (adjusted odds ratio [aOR], 2.76 [95% CI, 1.13-7.49]), presence of a futility rule (aOR, 4.43 [95% CI, 1.62-17.91]), and exclusion of prestroke dependency (none/slight disability only; aOR, 2.19 [95% CI, 0.84-6.72] versus dependency allowed) were identified as the strongest predictors. CONCLUSIONS: Nearly half of acute stroke trials were terminated prematurely. Broadening inclusion criteria and simplifying trial design may decrease the likelihood of unplanned termination, whereas planned futility analyses may appropriately terminate trials early, saving money and resources.

Can a best practice advisory improve anticoagulation prescribing to reduce stroke risk in patients with atrial fibrillation?

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac rhythm disorder and a risk factor for stroke. Randomized trials have demonstrated that anticoagulation can reduce strokes in AF patients. Yet, widespread underutilization of this therapy continues. To address this practice gap, we designed a study to implement and evaluate the effectiveness of a best practice advisory (BPA) for an Atrial Fibrillation Decision Support Tool (AFDST) embedded within our electronic health record. METHODS: Our intervention is provider-facing, focused on decision support. Clinical setting is ambulatory patients being seen by primary care physicians. We prospectively enrolled 608 patients in our health system who are currently receiving less than optimal anticoagulation therapy as determined by the AFDST and randomized them to one of two arms - 1) usual care, in which the AFDST is available for use; or 2) addition of a BPA to the AFDST notifying clinicians that their patient stands to gain significant benefit from a change in current therapy. Primary outcome was effectiveness of the BPA measured by change to "appropriate thromboprophylaxis" based on the AFDST recommendation at 3 months post-enrollment. Secondary endpoints included Reach and Adoption from the RE-AIM (Reach, Effectiveness, Adoption, Implementation, & Maintenance) framework for implementation studies. RESULTS: Among 562 patients with a minimum follow-up of 3 months, addition of a BPA to the AFDST resulted in significant improvement in anticoagulation therapy, 5 % (12/248) versus 11 % (33/314) p = 0.02, odds ratio 2.31 (95 % CI, 1.17-4.87). CONCLUSIONS: A BPA added to an AF decision support tool improved anticoagulation therapy among AF patients in a primary care academic health system setting.

Insufficiencies in sensory systems reweighting is associated with walking impairment severity in chronic stroke: an observational cohort study.

Background: Walking and balance impairment are common sequelae of stroke and significantly impact functional independence, morbidity, and mortality. Adequate postural stability is needed for walking, which requires sufficient integration of sensory information between the visual, somatosensory, and vestibular centers. "Sensory reweighting" describes the normal physiologic response needed to maintain postural stability in the absence of sufficient visual or somatosensory information and is believed to play a critical role in preserving postural stability after stroke. However, the extent to which sensory reweighting successfully maintains postural stability in the chronic stages of stroke and its potential impact on walking function remains understudied. Methods: In this cross-sectional study, fifty-eight community-dwelling ambulatory chronic stroke survivors underwent baseline postural stability testing during quiet stance using the modified Clinical test of Sensory Interaction in Balance (mCTSIB) and assessment of spatiotemporal gait parameters. Results: Seventy-six percent (45/58) of participants showed sufficient sensory reweighting with visual and somatosensory deprivation for maintaining postural stability, albeit with greater postural sway velocity indices than normative data. In contrast, survivors with insufficient reweighting demonstrated markedly slower overground walking speeds, greater spatiotemporal asymmetry, and limited acceleration potential. Conclusion: Adequate sensory system reweighting is essential for chronic stroke survivors' postural stability and walking independence. Greater emphasis should be placed on rehabilitation strategies incorporating multisensory system integration testing and strengthening as part of walking rehabilitation protocols. Given its potential impact on outcomes, walking rehabilitation trials may benefit from incorporating formal postural stability testing in design and group stratification.

High Caregiver Adverse Childhood Experiences Are Associated With Pediatric Influenza and COVID-19 Vaccination Uptake.

BACKGROUND: Factors surrounding vaccine uptake are complex. Although anxiety, which could influence vaccination decisions, has been associated with adverse childhood experiences (ACEs), little is known about links between caregiver ACEs and pediatric vaccine uptake. We evaluated associations between caregivers' ACEs and decisions to vaccinate their children with influenza and coronavirus disease (COVID-19) vaccines. METHODS: A cross-sectional study of caregivers of patients ≥6 months at one pediatric primary care center (PPCC) was performed. Caregivers completed a 19-question survey examining caregiver ACEs, influenza vaccine acceptance and beliefs, and intention to vaccinate their child with the COVID-19 vaccine. Demographic characteristics, social risks (eg, housing and food insecurity), and vaccination data for children present with each caregiver were extracted from the electronic health record (EHR). Statistical analyses included χ2 tests for categorical variables and t-tests for continuous variables. RESULTS: A total of 240 caregivers participated, representing 283 children (mean age of 5.9 years, 47% male). Twenty-four percent (n = 58) had high ACEs (≥4). Of those with high ACEs, 55% accepted pediatric influenza vaccination compared with 38% with low ACEs (P = .02). Those with high ACEs had more positive attitudes toward influenza vaccine safety and efficacy (P ≤ .02). Those with high, compared with low, ACEs were also more likely to accept COVID-19 vaccination (38% vs 24%; P = .04). CONCLUSIONS: Pediatric influenza vaccination rates and intention to vaccinate children against COVID-19 differed between caregivers with high and low ACEs: those with more ACEs were more likely to vaccinate. Further studies assessing the role of caregiver ACEs on vaccine decision-making are warranted.

Garnering effective telehealth to help optimize multidisciplinary team engagement (GET2HOME) for children with medical complexity: Protocol for a pragmatic randomized control trial.

BACKGROUND: Children and young adults with medical complexity (CMC) experience high rates of healthcare reutilization following hospital discharge. Prior studies have identified common hospital-to-home transition failures that may increase the risk for reutilization, including medication, technology and equipment issues, financial concerns, and confusion about which providers can help with posthospitalization needs. Few interventions have been developed and evaluated for CMC during this transition period. OBJECTIVE: We will compare the effectiveness of the garnering effective telehealth 2 help optimize multidisciplinary team engagement (GET2HOME) transition bundle intervention to the standard hospital-based care coordination discharge process by assessing healthcare reutilization and patient- and family-centered outcomes. DESIGNS, SETTINGS, AND PARTICIPANTS: We will conduct a pragmatic 2-arm randomized controlled trial (RCT) comparing the GET2HOME bundle intervention to the standard hospital-based care discharge process on CMC hospitalized and discharged from hospital medicine at two sites of our pediatric medical center between November 2022 and February 2025. CMC of any age will be identified as having complex chronic disease using the Pediatric Medical Complexity Algorithm tool. We will exclude CMC who live independently, live in skilled nursing facilities, are in custody of the county, or are hospitalized for suicidal ideation or end-of-life care. INTERVENTION: We will randomize participants to the bundle intervention or standard hospital-based care coordination discharge process. The bundle intervention includes (1) predischarge telehealth huddle with inpatient providers, outpatient providers, patients, and their families; (2) care management discharge task tracker; and (3) postdischarge telehealth huddle with similar participants within 7 days of discharge. As part of the pragmatic design, families will choose if they want to complete the postdischarge huddle. The standard hospital-based discharge process includes a pharmacist, social worker, and care management support when consulted by the inpatient team but does not include huddles between providers and families. MAIN OUTCOME AND MEASURES: Primary outcome will be 30-day urgent healthcare reutilization (unplanned readmission, emergency department, and urgent care visits). Secondary outcomes include 7-day urgent healthcare reutilization, patient- and family-reported transition quality, quality of life, and time to return to baseline using electronic health record and surveys at 7, 30, 60, and 90 days following discharge. We will also evaluate heterogeneity of treatment effect for the intervention across levels of financial strain and for CMC with high-intensity neurologic impairment. The primary analysis will follow the intention-to-treat principle with logistic regression used to study reutilization outcomes and generalized linear mixed modeling to study repeated measures of patient- and family-reported outcomes over time. RESULTS: This pragmatic RCT is designed to evaluate the effectiveness of enhanced discharge transition support, including telehealth huddles and a care management discharge tool, for CMC and their families. Enrollment began in November 2022 and is projected to complete in February 2025. Primary analysis completion is anticipated in July 2025 with reporting of results following.

Impact of a Remote Virtual Reality Curriculum Pilot on Clinician Conflict Communication Skills.

OBJECTIVES: Conflict management skills are essential for interprofessional team functioning, however existing trainings are time and resource intensive. We hypothesized that a curriculum incorporating virtual reality (VR) simulations would enhance providers' interprofessional conflict communication skills and increase self-efficacy. METHODS: We conducted a randomized controlled pilot study of the Conflict Instruction through Virtual Immersive Cases (CIVIC) curriculum among inpatient clinicians at a pediatric satellite campus. Participants viewed a 30-minute didactic presentation on conflict management and subsequently completed CIVIC (intervention group) or an alternative VR curriculum on vaccine counseling (control group), both of which allowed for verbal interactions with screen-based avatars. Three months following VR training, all clinicians participated in a unique VR simulation focused on conflict management that was recorded and scored using a rubric of observable conflict management behaviors and a Global Entrustment Scale (GES). Differences between groups were evaluated using generalized linear models. Self-efficacy was also assessed immediately pre, post, and 3 months postcurriculum. Differences within and between groups were assessed with paired independent and 2-sample t-tests, respectively. RESULTS: Forty of 51 participants (78%) completed this study. The intervention group (n = 17) demonstrated better performance on the GES (P = .003) and specific evidence-based conflict management behaviors, including summarizing team member's concerns (P = .02) and checking for acceptance of the plan (P = .02), as well as statistical improvements in 5 self-efficacy measures compared with controls. CONCLUSIONS: Participants exposed to CIVIC demonstrated enhanced conflict communication skills and reported increased self-efficacy compared with controls. VR may be an effective method of conflict communication training.

Training parameters and longitudinal adaptations that most strongly mediate walking capacity gains from high-intensity interval training post-stroke.

Background: Locomotor high-intensity interval training (HIIT) has been shown to improve walking capacity more than moderate-intensity aerobic training (MAT) after stroke, but it is unclear which training parameter(s) should be prioritized (e.g. speed, heart rate, blood lactate, step count) and to what extent walking capacity gains are the result of neuromotor versus cardiorespiratory adaptations. Objective: Assess which training parameters and longitudinal adaptations most strongly mediate 6-minute walk distance (6MWD) gains from post-stroke HIIT. Methods: The HIT-Stroke Trial randomized 55 persons with chronic stroke and persistent walking limitations to HIIT or MAT and collected detailed training data. Blinded outcomes included 6MWD, plus measures of neuromotor gait function (e.g. fastest 10-meter gait speed) and aerobic capacity (e.g. ventilatory threshold). This ancillary analysis used structural equation models to compare mediating effects of different training parameters and longitudinal adaptations on 6MWD. Results: Net gains in 6MWD from HIIT versus MAT were primarily mediated by faster training speeds and longitudinal adaptations in neuromotor gait function. Training step count was also positively associated with 6MWD gains, but was lower with HIIT versus MAT, which decreased the net 6MWD gain. HIIT generated higher training heart rate and lactate than MAT, but aerobic capacity gains were similar between groups, and 6MWD changes were not associated with training heart rate, training lactate, or aerobic adaptations. Conclusions: To increase walking capacity with post-stroke HIIT, training speed and step count appear to be the most important parameters to prioritize.

Early-life exposure to a mixture of organophosphate esters and child behavior.

Organophosphate esters (OPEs), widely used as flame retardants and plasticizers for commercial and residential purposes, are suspected of being neurotoxic. We aimed to assess exposure to an OPE mixture in early life and its relationship to parent-reported child behavior. We measured urinary concentrations of three OPE metabolites, bis-2-chloroethyl phosphate (BCEP), bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), and diphenyl phosphate (DPHP), at pregnancy (16 and 26 weeks of gestation and delivery) and postnatal time points (ages 1, 2, 3, and 5 years) in the Health Outcomes and Measures of the Environment Study, a longitudinal pregnancy and birth cohort in Cincinnati, Ohio, USA (enrolled 2003-2006, n = 219). We used latent variable analysis in structural equations models and quantile g-computation to investigate associations of a mixture of the three OPE metabolites with parent-reported child behaviors at 3 and 8 years, measured using the Behavioral Assessment System for Children, Second Edition. Higher log-transformed urinary OPE latent variable values at 16 weeks were associated with fewer externalizing problem behaviors (ß = -5.74; 95% CI = -11.24, -0.24) and fewer overall behavioral problems at age 3 years (ß = -5.26; 95% CI = -10.33, -0.19), whereas having higher OPEs at delivery was associated with poorer overall behavioral problems at age 3 years (ß = 2.87; 95% CI = 0.13, 5.61). OPE latent variable values at 16 weeks, 26 weeks, and delivery were not associated with child behavior at 8 years. However, higher OPE latent variable values at 3 years were associated with fewer externalizing behaviors at 8 years (ß = -2.62; 95% CI = -5.13, -0.12). The quantile g-computation estimates had directions largely consistent with the latent variable analysis results. Pregnancy and postnatal urinary OPE metabolite mixtures were associated with child internalizing, externalizing, and overall negative behaviors at 3 and 8 years, but we did not identify a consistent pattern in terms of the direction of the effects or a particularly sensitive time point.

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.

Optimal Intensity and Duration of Walking Rehabilitation in Patients With Chronic Stroke: A Randomized Clinical Trial.

Importance: For walking rehabilitation after stroke, training intensity and duration are critical dosing parameters that lack optimization. Objective: To assess the optimal training intensity (vigorous vs moderate) and minimum training duration (4, 8, or 12 weeks) needed to maximize immediate improvement in walking capacity in patients with chronic stroke. Design, Setting, and Participants: This multicenter randomized clinical trial using an intent-to-treat analysis was conducted from January 2019 to April 2022 at rehabilitation and exercise research laboratories. Survivors of a single stroke who were aged 40 to 80 years and had persistent walking limitations 6 months or more after the stroke were enrolled. Interventions: Participants were randomized 1:1 to high-intensity interval training (HIIT) or moderate-intensity aerobic training (MAT), each involving 45 minutes of walking practice 3 times per week for 12 weeks. The HIIT protocol used repeated 30-second bursts of walking at maximum safe speed, alternated with 30- to 60-second rest periods, targeting a mean aerobic intensity above 60% of the heart rate reserve (HRR). The MAT protocol used continuous walking with speed adjusted to maintain an initial target of 40% of the HRR, progressing up to 60% of the HRR as tolerated. Main Outcomes and Measures: The main outcome was 6-minute walk test distance. Outcomes were assessed by blinded raters after 4, 8, and 12 weeks of training. Results: Of 55 participants (mean [SD] age, 63 [10] years; 36 male [65.5%]), 27 were randomized to HIIT and 28 to MAT. The mean (SD) time since stroke was 2.5 (1.3) years, and mean (SD) 6-minute walk test distance at baseline was 239 (132) m. Participants attended 1675 of 1980 planned treatment visits (84.6%) and 197 of 220 planned testing visits (89.5%). No serious adverse events related to study procedures occurred. Groups had similar 6-minute walk test distance changes after 4 weeks (HIIT, 27 m [95% CI, 6-48 m]; MAT, 12 m [95% CI, -9 to 33 m]; mean difference, 15 m [95% CI, -13 to 42 m]; P = .28), but HIIT elicited greater gains after 8 weeks (58 m [95% CI, 39-76 m] vs 29 m [95% CI, 9-48 m]; mean difference, 29 m [95% CI, 5-54 m]; P = .02) and 12 weeks (71 m [95% CI, 49-94 m] vs 27 m [95% CI, 3-50 m]; mean difference, 44 m [95% CI, 14-74 m]; P = .005) of training; HIIT also showed greater improvements than MAT on some secondary measures of gait speed and fatigue. Conclusions and Relevance: These findings show proof of concept that vigorous training intensity is a critical dosing parameter for walking rehabilitation. In patients with chronic stroke, vigorous walking exercise produced significant and meaningful gains in walking capacity with only 4 weeks of training, but at least 12 weeks were needed to maximize immediate gains. Trial Registration: ClinicalTrials.gov Identifier: NCT03760016.

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.

Beta-Lactam Allergy Association with Surgical Site Infections in Pediatric Procedures: A Matched Cohort Study.

BACKGROUND: Little is known about surgical site infection (SSI) risk among pediatric patients with reported beta-lactam allergy (BLA). METHODS: We performed a retrospective cohort study at a quaternary children's hospital and compared procedures in patients ages 1-19 years old with and without BLA that required antimicrobial prophylaxis (AMP) during 2010-2017. Procedures were matched 1:1 by patient age, complex chronic conditions, year of surgery, and National Surgical Quality Improvement Program current procedural terminology category. The primary outcome was SSI as defined by National Healthcare Safety Network. The secondary outcome was AMP protocol compliance as per American Society of Health-System Pharmacists. RESULTS: Of the 11 878 procedures identified, 1021 (9%) had a reported BLA. There were 35 (1.8%) SSIs in the matched cohort of 1944 procedures with no significant difference in SSI rates in BLA procedures (1.8%) compared to no-BLA (1.9%) procedures. Tier 3 AMP was chosen more frequently among BLA procedures (P < .01). Unmatched analysis of all procedures showed that 23.7% of BLA procedures received beta-lactam-AMP (vs. 93.7% of procedures without BLA). There were no major differences in SSI on sensitivity analysis of BLA procedures that did not receive beta-lactam AMP (1.4%) compared to no-BLA procedures with beta-lactam AMP (1.6%). CONCLUSIONS: Our retrospective matched analysis of 1944 pediatric procedures found no increase in SSIs in procedures with reported BLA, which differs from studies in adults. We observed that the choice of beta-lactam-AMP was common, even in BLA procedures. More data are needed to delineate an association between non-beta-lactam AMP and SSI in children.

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.

Declining influenza vaccination rates in an underserved pediatric primary care center during the COVID-19 pandemic.

BACKGROUND: Influenza vaccination rates are decreasing in the United States. Disinformation surrounding COVID-related public health protections and SARS-CoV-2 vaccine roll-out may have unintended consequences impacting pediatric influenza vaccination.We assessed influenza vaccination rates before and during the COVID-19 pandemic in one pediatric primary care center, serving a minoritized population. METHODS: A cross-sectional study assessed influenza vaccination rates for children aged 6 months to 12 years over the following influenza seasons (September-May): 1) 2018-19 and 2019-20 (pre-pandemic), and 2) 2020-21 and 2021-22 (intra-pandemic). Demographics and responses to social risk questionnaires were extracted from electronic health records. Total tetanus vaccinations across influenza seasons served as approximations of general vaccination rates. Generalized linear regression models with robust standard errors evaluated differences in demographics, social risks, and influenza vaccination rates by season. Multivariable logistic regression with robust standard errors evaluated associations between influenza season, demographics, social risks, and influenza vaccination. RESULTS: Most patients were young (mean age âˆ¼ 6 years), non-Hispanic Black (∼80%), and publicly insured (∼90%). Forty-two percent of patients eligible to receive the influenza vaccine who were seen in 2019-20 influenza season received the influenza vaccine, compared to 30% in 2021-22. Influenza and tetanus vaccination rates decreased during the COVID-19 pandemic (p < 0.01). The 2020-21 and 2021-22 influenza seasons, older age, Black race, and self-pay were associated with decreased influenza vaccine administration (p < 0.05). CONCLUSIONS: Influenza vaccination rates within one pediatric primary care center decreased during the COVID-19 pandemic and have not rebounded, particularly for older children, those identifying as Black, and those without insurance.

Racial Disparities in Stroke Recurrence: A Population-Based Study.

BACKGROUND AND OBJECTIVE: There are significant racial disparities in stroke in the United States, with Black individuals having a higher risk of incident stroke even when adjusted for traditional stroke risk factors. It is unknown whether Black individuals are also at a higher risk of recurrent stroke. METHODS: Over an 18-month period spanning 2014-2015, we ascertained index stroke cases within the Greater Cincinnati/Northern Kentucky population of 1.3 million. We then followed up all patients for 3 years and determined the risk of recurrence. Multivariable survival analysis was performed to determine the effect of Black race on recurrence. RESULTS: There were 3,816 patients with index stroke/TIA events in our study period, and 476 patients had a recurrent event within 3 years. The Kaplan-Meier estimate of 3-year recurrence rate was 15.4%. Age-adjusted and sex-adjusted stroke recurrence rate was higher in Black individuals (HR 1.34, 95% CI 1.1-1.6; p = 0.003); however, when adjusted for traditional stroke risk factors including hypertension, diabetes, smoking status, age, and left ventricular hypertrophy, the association between Black race and recurrence was significantly attenuated and became nonsignificant (HR 1.1, 95% CI 0.9-1.36, p = 0.32). At younger ages, Black race was more strongly associated with recurrence, and this effect may not be fully attenuated by traditional stroke risk factors. DISCUSSION: Recurrent stroke was more common among Black individuals, but the magnitude of the racial difference was substantially attenuated and became nonsignificant when adjusted for traditional stroke risk factors. Interventions targeting these risk factors could reduce disparities in stroke recurrence.

Serial Backward Locomotor Treadmill Training Improves Bidirectional Walking Performance in Chronic Stroke.

Background and Research Question: Walking impairment remains a major limitation to functional independence after stroke. Yet, comprehensive and effective strategies to improve walking function after stroke are presently limited. Backward Locomotor Treadmill Training (BLTT) is a promising training approach for improving walking function; however, little is known about its mechanism of effect or the relationship between backward walking training and resulting overground forward walking performance. This study aims to determine the effects of serial BLTT on spatial aspects of backward and forward walking in chronic post-stroke individuals with residual walking impairment. Methods: Thirty-nine adults (>6 months post-stroke) underwent 6 days of BLTT (3 × /week) over 2 weeks. Outcome measures included PRE-POST changes in backward and forward walking speeds, paretic and non-paretic step lengths, and single-support center of pressure distances. To determine the association between BLTT and overground walking, correlation analyses comparing training-related changes in these variables were performed. Results: We report an overall improvement in BLTT and overground walking speeds, bilateral step lengths, and single-support center of pressure distances over six training sessions. Further, there were weak positive associations between PRE-POST changes in BLTT speed, BLTT paretic step length, and overground forward walking speed. Conclusion and Significance: Our findings suggest that individuals with chronic post-stroke walking impairment experience improvements in spatial walking measures during BLTT and overground. Therefore, BLTT may be a potential adjunctive training approach for post-stroke walking rehabilitation.