An interpretable framework to identify responsive subgroups from clinical trials regarding treatment effects: Application to treatment of intracerebral hemorrhage.

Randomized Clinical trials (RCT) suffer from a high failure rate which could be caused by heterogeneous responses to treatment. Despite many models being developed to estimate heterogeneous treatment effects (HTE), there remains a lack of interpretable methods to identify responsive subgroups. This work aims to develop a framework to identify subgroups based on treatment effects that prioritize model interpretability. The proposed framework leverages an ensemble uplift tree method to generate descriptive decision rules that separate samples given estimated responses to the treatment. Subsequently, we select a complementary set of these decision rules and rank them using a sparse linear model. To address the trial's limited sample size problem, we proposed a data augmentation strategy by borrowing control patients from external studies and generating synthetic data. We apply the proposed framework to a failed randomized clinical trial for investigating an intracerebral hemorrhage therapy plan. The Qini-scores show that the proposed data augmentation strategy plan can boost the model's performance and the framework achieves greater interpretability by selecting complementary descriptive rules without compromising estimation quality. Our model derives clinically meaningful subgroups. Specifically, we find those patients with Diastolic Blood Pressure≥70 mm hg and Systolic Blood Pressure<215 mm hg benefit more from intensive blood pressure reduction therapy. The proposed interpretable HTE analysis framework offers a promising potential for extracting meaningful insight from RCTs with neutral treatment effects. By identifying responsive subgroups, our framework can contribute to developing personalized treatment strategies for patients more efficiently.

Door to needle time trends after transition to tenecteplase: A Multicenter Texas stroke registry.

BACKGROUND: Tenecteplase (TNK) is considered a promising option for the treatment of acute ischemic stroke (AIS) with the potential to decrease door-to-needle times (DTN). This study investigates DTN metrics and trends after transition to tenecteplase. METHODS: The Lone Star Stroke (LSS) Research Consortium TNK registry incorporated data from three Texas hospitals that transitioned to TNK. Subject data mapped to Get-With-the-Guidelines stroke variables from October 1, 2019 to March 31, 2023 were limited to patients who received either alteplase (ALT) or TNK within the 90 min DTN times. The dataset was stratified into ALT and TNK cohorts with univariate tables for each measured variable and further analyzed using descriptive statistics. Logistic regression models were constructed for both ALT and TNK to investigate trends in DTN times. RESULTS: In the overall cohort, the TNK cohort (n = 151) and ALT cohort (n = 161) exhibited comparable population demographics, differing only in a higher prevalence of White individuals in the TNK cohort. Both cohorts demonstrated similar clinical parameters, including mean NIHSS, blood glucose levels, and systolic blood pressure at admission. In the univariate analysis, no difference was observed in median DTN time within the 90 min time window compared to the ALT cohort [40 min (30-53) vs 45 min (35-55); P = .057]. In multivariable models, DTN times by thrombolytic did not significantly differ when adjusting for NIHSS, age (P = .133), or race and ethnicity (P = .092). Regression models for the overall cohort indicate no significant DTN temporal trends for TNK (P = .84) after transition; nonetheless, when stratified by hospital, a single subgroup demonstrated a significant DTN upward trend (P = 0.002). CONCLUSION: In the overall cohort, TNK and ALT exhibited comparable temporal trends and at least stable DTN times. This indicates that the shift to TNK did not have an adverse impact on the DTN stroke metrics. This seamless transition is likely attributed to the similarity of inclusion and exclusion criteria, as well as the administration processes for both medications. When stratified by hospital, the three subgroups demonstrated variable DTN time trends which highlight the potential for either fatigue or unpreparedness when switching to TNK. Because our study included a multi-ethnic cohort from multiple large Texas cities, the stable DTN times after transition to TNK is likely applicable to other healthcare systems.

Enhancing long-term survival prediction with two short-term events: Landmarking with a flexible varying coefficient model.

Patients with cardiovascular diseases who experience disease-related short-term events, such as hospitalizations, often exhibit diverse long-term survival outcomes compared to others. In this study, we aim to improve the prediction of long-term survival probability by incorporating two short-term events using a flexible varying coefficient landmark model. Our objective is to predict the long-term survival among patients who survived up to a pre-specified landmark time since the initial admission. Inverse probability weighting estimation equations are formed based on the information of the short-term outcomes before the landmark time. The kernel smoothing method with the use of cross-validation for bandwidth selection is employed to estimate the time-varying coefficients. The predictive performance of the proposed model is evaluated and compared using predictive measures: area under the receiver operating characteristic curve and Brier score. Simulation studies confirm that parameters under the landmark models can be estimated accurately and the predictive performance of the proposed method consistently outperforms existing methods that either do not incorporate or only partially incorporate information from two short-term events. We demonstrate the practical application of our model using a community-based cohort from the Atherosclerosis Risk in Communities (ARIC) study.

A Cross-sectional Survey of Comprehension and Satisfaction of Spanish-Reading Adults Regarding RÁPIDO as a Stroke Awareness Acronym.

ABSTRACT: BACKGROUND: Delay time to hospital arrival may be influenced by lack of recognition of stroke signs and the necessity to seek emergency medical, which in turn is influenced by language barriers to, a modifiable risk factor, stroke awareness education. The objective was to determine the comprehension and satisfaction of a Spanish stroke awareness acronym, RÁPIDO, among community-living, Hispanic and Latino, Spanish-reading adults. METHODS: A 33-item survey was completed by 166 adults. Data on sociodemographics, language preferences, stroke education, and comprehension and satisfaction with RÁPIDO were collected. Descriptive characteristics were calculated. Fisher exact tests were performed to determine whether reading language (group 1, only or predominantly reads in Spanish; group 2, reads in Spanish and English equally or reads predominately in English) influenced survey responses. Responses to open-ended questions were categorized. RESULTS: Sixty-nine percent of the participants were born outside of the United States, 82% currently resided in the United States, 34% read only or predominately in Spanish, and 7% had a stroke. Most participants thought RÁPIDO was informative, eye-catching, and easily remembered. Significant differences were found between reading language preference groups for correctly identifying RÁPIDO images for facial drooping (group 1, 80%; group 2, 95%; P ≤ .001) and dizziness/loss of balance (group 1, 54%; group 2, 73%; P = .027). Eighty percent or more of all participants were able to correctly interpret RÁPIDO images for facial drooping, blurry vision, impaired speech, and call emergency services. Adding "911" to the RÁPIDO image of the clock was a common suggestion. CONCLUSIONS: RÁPIDO was well received among the participants. Modifications to RÁPIDO images representing dizziness/loss of balance and arm weakness, and the addition of "911" may improve its usefulness. Obtaining more extensive feedback across the United States and testing the effect of RÁPIDO on increasing knowledge of stroke signs and retention of that knowledge are necessary next steps.

Experience with a hybrid recruitment approach of patient-facing web portal screening and subsequent phone and medical record review for a neurosurgical intervention trial for chronic ischemic stroke disability (PISCES III).

BACKGROUND: Recruitment of participants is the greatest risk to completion of most clinical trials, with 20-40% of trials failing to reach the targeted enrollment. This is particularly true of trials of central nervous system (CNS) therapies such as intervention for chronic stroke. The PISCES III trial was an invasive trial of stereotactically guided intracerebral injection of CTX0E03, a fetal derived neural stem cell line, in patients with chronic disability due to ischemic stroke. We report on the experience using a novel hybrid recruitment approach of a patient-facing portal to self-identify and perform an initial screen for general trial eligibility (tier 1), followed by phone screening and medical records review (tier 2) prior to a final in-person visit to confirm eligibility and consent. METHODS: Two tiers of screening were established: an initial screen of general eligibility using a patient-facing web portal (tier 1), followed by a more detailed screen that included phone survey and medical record review (tier 2). If potential participants passed the tier 2 screen, they were referred directly to visit 1 at a study site, where final in-person screening and consent were performed. Rates of screening were tracked during the period of trial recruitment and sources of referrals were noted. RESULTS: The approach to screening and recruitment resulted in 6125 tier 1 screens, leading to 1121 referrals to tier 2. The tier 2 screening resulted in 224 medical record requests and identification of 86 qualifying participants for referral to sites. The study attained a viable recruitment rate of 6 enrolled per month prior to being disrupted by COVID 19. CONCLUSIONS: A tiered approach to eligibility screening using a hybrid of web-based portals to self-identify and screen for general eligibility followed by a more detailed phone and medical record review allowed the study to use fewer sites and reduce cost. Despite the difficult and narrow population of patients suffering moderate chronic disability from stroke, this strategy produced a viable recruitment rate for this invasive study of intracranially injected neural stem cells. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03629275.

Comparing Stroke Risk Factors Among Sexual Minority Groups in Texas.

BACKGROUND: Knowledge gaps remain on stroke risk and disparities between sexual minority (SM) subgroups. In this study, stroke risk between SM subgroups, specifically gay/bisexual men and lesbian/bisexual women (G/BM and L/BW), was assessed. METHOD: Data were collected in June 2022 using a bilingual (English and Spanish) cross-sectional paper-and-pen survey distributed among 183 SM individuals attending the 2022 Houston Pride Parade and Festival, as well as across Texas via phone call or online format. Relevant sociodemographic and stroke risk factors were compared between G/BM and L/BW using chi-square (or Fisher's exact, when appropriate) and two-sample t-tests. Sexual orientation was used to predict stroke risk using multiple binomial logistic regression, adjusting for other sociodemographic determinants. RESULTS: While comparing the stroke risk factors between G/BW and L/BW, statistically significant differences were found in hypertension (p = 0.047), age (p < 0.001), smoking status (p = 0.043), cholesterol level (p < 0.001), and HIV (p = 0.038). G/BM were 2.79 times more likely to have a higher stroke risk compared to L/BW (aOR = 2.79; CI, 1.11-6.05, p = 0.032), after adjusting for other sociodemographic factors. CONCLUSION: This pilot study, conducted in Texas, adds to the existing scientific literature on stroke risk among the SM population and revealed that G/BM might have a higher stroke risk compared to L/BW. These findings can inform future research and intervention designs tailored to G/BM and L/BW communities and improve their overall health.

Autologous bone marrow mononuclear cells to treat severe traumatic brain injury in children.

Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood-brain barrier and diminish neuroinflammation, leading to structural CNS preservation with improved outcomes. We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at two children's hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083). Patients 5-17 years of age with severe traumatic brain injury (Glasgow Coma Scale score ≤ 8) were randomized to BMMNC or placebo (3:2). Bone marrow harvest, cell isolation and infusion were completed by 48 h post-injury. A Bayesian continuous reassessment method was used with cohorts of size 3 in the BMMNC group to choose the safest between two doses. Primary end points were quantitative brain volumes using MRI and microstructural integrity of the corpus callosum (diffusivity and oedema measurements) at 6 months and 12 months. Long-term functional outcomes and ventilator days, intracranial pressure monitoring days, intensive care unit days and therapeutic intensity measures were compared between groups. Forty-seven patients were randomized, with 37 completing 1-year follow-up (23 BMMNC, 14 placebo). BMMNC treatment was associated with an almost 3-day (23%) reduction in ventilator days, 1-day (16%) reduction in intracranial pressure monitoring days and 3-day (14%) reduction in intensive care unit (ICU) days. White matter volume at 1 year in the BMMNC group was significantly preserved compared to placebo [decrease of 19 891 versus 40 491, respectively; mean difference of -20 600, 95% confidence interval (CI): -35 868 to -5332; P = 0.01], and the number of corpus callosum streamlines was reduced more in placebo than BMMNC, supporting evidence of preserved corpus callosum connectivity in the treated groups (-431 streamlines placebo versus -37 streamlines BMMNC; mean difference of -394, 95% CI: -803 to 15; P = 0.055), but this did not reach statistical significance due to high variability. We conclude that autologous BMMNC infusion in children within 48 h after severe traumatic brain injury is safe and feasible. Our data show that BMMNC infusion led to: (i) shorter intensive care duration and decreased ICU intensity; (ii) white matter structural preservation; and (iii) enhanced corpus callosum connectivity and improved microstructural metrics.

Dynamic Imaging of Blood Coagulation Within the Hematoma of Patients With Acute Hemorrhagic Stroke.

BACKGROUND: The dynamics of blood clot (combination of Hb [hemoglobin], fibrin, and a higher concentration of aggregated red blood cells) formation within the hematoma of an intracerebral hemorrhage is not well understood. A quantitative neuroimaging method of localized coagulated blood volume/distribution within the hematoma might improve clinical decision-making. METHODS: The deoxyhemoglobin of aggregated red blood cells within extravasated blood exhibits a higher magnetic susceptibility due to unpaired heme iron electrons. We propose that coagulated blood, with higher aggregated red blood cell content, will exhibit (1) a higher positive susceptibility than noncoagulated blood and (2) increase in fibrin polymerization-restricted localized diffusion, which can be measured noninvasively using quantitative susceptibility mapping and diffusion tensor imaging. In this serial magnetic resonance imaging study, we enrolled 24 patients with acute intracerebral hemorrhage between October 2021 to May 2022 at a stroke center. Patients were 30 to 70 years of age and had a hematoma volume >15 cm3 and National Institutes of Health Stroke Scale score >1. The patients underwent imaging 3×: within 12 to 24 (T1), 36 to 48 (T2), and 60 to 72 (T3) hours of last seen well on a 3T magnetic resonance imaging system. Three-dimensional anatomic, multigradient echo and 2-dimensional diffusion tensor images were obtained. Hematoma and edema volumes were calculated, and the distribution of coagulation was measured by dynamic changes in the susceptibilities and fractional anisotropy within the hematoma. RESULTS: Using a coagulated blood phantom, we demonstrated a linear relationship between the percentage coagulation and susceptibility (R2=0.91) with a positive red blood cell stain of the clot. The quantitative susceptibility maps showed a significant increase in hematoma susceptibility (T1, 0.29±0.04 parts per millions; T2, 0.36±0.04 parts per millions; T3, 0.45±0.04 parts per millions; P<0.0001). A concomitant increase in fractional anisotropy was also observed with time (T1, 0.40±0.02; T2, 0.45±0.02; T3, 0.47±0.02; P<0.05). CONCLUSIONS: This quantitative neuroimaging study of coagulation within the hematoma has the potential to improve patient management, such as safe resumption of anticoagulants, the need for reversal agents, the administration of alteplase to resolve the clot, and the need for surgery.

Regression analysis of multivariate recurrent event data allowing time-varying dependence with application to stroke registry data.

In multivariate recurrent event data, each patient may repeatedly experience more than one type of event. Analysis of such data gets further complicated by the time-varying dependence structure among different types of recurrent events. The available literature regarding the joint modeling of multivariate recurrent events assumes a constant dependency over time, which is strict and often violated in practice. To close the knowledge gap, we propose a class of flexible shared random effects models for multivariate recurrent event data that allow for time-varying dependence to adequately capture complex correlation structures among different types of recurrent events. We developed an expectation-maximization algorithm for stable and efficient model fitting. Extensive simulation studies demonstrated that the estimators of the proposed approach have satisfactory finite sample performance. We applied the proposed model and the estimating method to data from a cohort of stroke patients identified in the University of Texas Houston Stroke Registry and evaluated the effects of risk factors and the dependence structure of different types of post-stroke readmission events.

Association Between Body Mass Index and Functional Outcomes in Patients With Intracerebral Hemorrhage.

BACKGROUND AND OBJECTIVES: Evidence of the so-called "obesity paradox," which refers to the protective effect and survival benefit of obesity in patients with spontaneous intracerebral hemorrhage (ICH), remains controversial. This study aims to determine the association between body mass index (BMI) and functional outcomes in patients with ICH and whether it is modified by race/ethnicity. METHODS: Included individuals were derived from the Ethnic/Racial Variations of Intracerebral Hemorrhage study, which prospectively recruited 1,000 non-Hispanic White, 1,000 non-Hispanic Black, and 1,000 Hispanic patients with spontaneous ICH. Only patients with available BMI were included. The primary outcome was 90-day mortality. Secondary outcomes were mortality at discharge, modified Rankin Scale (mRS), Barthel Index, and self-reported health status measures at 90 days. Associations between BMI and ICH outcomes were assessed using univariable and multivariable logistic, ordinal, and linear regression models, as appropriate. Sensitivity analyses after excluding frail patients and by patient race/ethnicity were performed. RESULTS: A total of 2,841 patients with ICH were included. The median age was 60 years (interquartile range 51-73). Most patients were overweight (n = 943; 33.2%) or obese (n = 1,032; 36.3%). After adjusting for covariates, 90-day mortality was significantly lower among overweight and obese patients than their normal weight counterparts (adjusted odds ratio [aOR] = 0.71 [0.52-0.98] and aOR = 0.70 [0.50-0.97], respectively). Compared with patients with BMI <25 kg/m2, those with BMI ≥25 kg/m2 had better 90-day mRS (aOR = 0.80 [CI 0.67-0.95]), EuroQoL Group 5-Dimension (EQ-5D) (aß = 0.05 [0.01-0.08]), and EQ-5D VAS (aß = 3.80 [0.80-6.98]) scores. These differences persisted after excluding withdrawal of care patients. There was an inverse relationship between BMI and 90-day mortality (aOR = 0.97 [0.96-0.99]). Although non-Hispanic White patients had significantly higher 90-day mortality than non-Hispanic Black and Hispanic (26.6% vs 19.5% vs 18.0%, respectively; p < 0.001), no significant interactions were found between BMI and race/ethnicity. No significant interactions between BMI and age or sex for 90-day mortality were found, whereas for 90-day mRS, there was a significant interaction with age (pinteraction = 0.004). CONCLUSION: We demonstrated that a higher BMI is associated with decreased mortality, improved functional outcomes, and better self-reported health status at 90 days, thus supporting the paradoxical role of obesity in patients with ICH. The beneficial effect of high BMI does not seem to be modified by race/ethnicity or sex, whereas age may play a significant role in patient functional outcomes.

Allogeneic Stem Cell Therapy for Acute Ischemic Stroke: The Phase 2/3 TREASURE Randomized Clinical Trial.

Importance: Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke. Objective: To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset. Design, Setting, and Participants: The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were age 20 years or older, presence of acute ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 8-20 at baseline), confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis (determined with diffusion-weighted magnetic resonance imaging), and a modified Rankin Scale (mRS) score of 0 or 1 before stroke onset. Data analysis was performed between May 9 and August 15, 2022. Exposure: Patients were randomly assigned to either intravenous MultiStem in 1 single unit of 1.2 billion cells or intravenous placebo within 18 to 36 hours of ischemic stroke onset. Main Outcomes and Measures: The primary end points were safety and excellent outcome at day 90, measured as a composite of a modified Rankin Scale (mRS) score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score of 95 or greater. The secondary end points were excellent outcome at day 365, mRS score distribution at days 90 and 365, and mRS score of 0 to 1 and 0 to 2 at day 90. Statistical analysis of efficacy was performed using the Cochran-Mantel-Haenszel test. Results: This study included 206 patients (104 received MultiStem and 102 received placebo). Their mean age was 76.5 (range, 35-95) years, and more than half of patients were men (112 [54.4%]). There were no between-group differences in primary and secondary end points. The proportion of excellent outcomes at day 90 did not differ significantly between the MultiStem and placebo groups (12 [11.5%] vs 10 [9.8%], P = .90; adjusted risk difference, 0.5% [95% CI, -7.3% to 8.3%]). The frequency of adverse events was similar between treatment groups. Conclusions and Relevance: In this randomized clinical trial, intravenous administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes. Further research is needed to determine whether MultiStem therapy for ischemic stroke has a beneficial effect in patients who meet specific criteria, as indicated by the exploratory analyses in this study. Trial Registration: ClinicalTrials.gov Identifier: NCT02961504.

Multicenter exploration of tenecteplase transition factors: A quantitative analysis.

BACKGROUND: Tenecteplase (TNK) is gaining recognition as a novel therapy for acute ischemic stroke (AIS). Despite TNK offering a longer half-life, time and cost saving benefits and comparable treatment and safety profiles to Alteplase (ALT), the adoption of TNK as a treatment for AIS presents challenges for hospital systems. OBJECTIVE: Identify barriers and facilitators of TNK implementation at acute care hospitals in Texas. METHODS: This prospective survey used open-ended questions and Likert statements generated from content experts and informed by qualitative research. Stroke clinicians and nurses working at 40 different hospitals in Texas were surveyed using a virtual platform. RESULTS: The 40 hospitals had a median of 34 (IQR 24.5-49) emergency department beds and 42.5 (IQR 23.5-64.5) inpatient stroke beds with 506.5 (IQR 350-797.5) annual stroke admissions. Fifty percent of the hospitals were Comprehensive Stroke Centers, and 18 (45 %) were solely using ALT for treatment of eligible AIS patients. Primary facilitators to TNK transition were team buy-in and a willingness of stroke physicians, nurses, and pharmacists to adopt TNK. Leading barriers were lack of clinical evidence supporting TNK safety profile inadequate evidence supporting TNK use and a lack of American Heart Association guidelines support for TNK administration in all AIS cases. CONCLUSION: Understanding common barriers and facilitators to TNK adoption can assist acute care hospitals deciding to implement TNK as a treatment for AIS. These findings will be used to design a TNK adoption Toolkit, utilizing implementation science techniques, to address identified obstacles and to leverage facilitators.

Feasibility and user-experience of a virtual environment for social connection and education after stroke: A pilot study.

OBJECTIVES: To evaluate the feasibility and usability of stroke survivor participation in an 8-week virtual environment intervention that provides opportunities for social support exchanges, social network interactions, and recovery education. MATERIALS AND METHODS: A single-group, pre- and post-test measure design was used. Descriptive statistics were used to examine enrollment and retention rates, proportion of questionnaires completed, and virtual environment process data (e.g., number of log-ins) and usability scores. Changes in pre- and post-intervention questionnaire (e.g., usability, social support, depression, anxiety, loneliness, and self-efficacy) scores were explored using Wilcoxon signed-rank tests and paired t-test. RESULTS: Fifteen (65 %) of the eligible stroke survivors enrolled (60 % white, 27 % black), 12 (80 %) had an ischemic stroke, ages ranged from 33 to 74 years (mean 44 years), and mean months since stroke was 33 ± 23. Retention and questionnaire completion rates were both 93 % (n = 14). Survivors logged into the virtual environment a total of 122 times, logged an average of 49 min/log-in, and 12 (80 %) attended support groups and social activities. Median usability score indicated lower than average usability. Improvement trends in social support, loneliness, and depressive symptoms were found, but significant changes in mean questionnaire scores were not found. CONCLUSIONS: Overall, the results suggest that using a virtual environment to foster social support exchanges, social network interactions, and recovery education after stroke is feasible. Similar to other chronic disease populations, stroke survivor adoption of a virtual environment likely requires ongoing technical assistance, repetition of instructions, and opportunities for practice to reinforce engagement. TRIAL REGISTRATION: NCT05487144.

A qualitative study of barriers and facilitators to using tenecteplase to treat acute ischemic stroke.

BACKGROUND: Tenecteplase (TNK) is emerging as an alternative to alteplase (ALT) for thrombolytic treatment of acute ischemic stroke (AIS). Compared to ALT, TNK has a longer half-life, shorter administration time, lower cost, and similarly high efficacy in treating large vessel occlusion. Nevertheless, there are barriers to adopting TNK as a treatment for AIS. This study aimed to identify thematic barriers and facilitators to adopting TNK as an alternative to ALT as a thrombolytic for eligible AIS patients. METHODS: Qualitative research methodology using hermeneutic cycling and purposive sampling was used to interview four stroke clinicians in Texas. Interviews were recorded and transcribed verbatim. Enrollment was complete when saturation was reached. All members of the research team participated in content analysis during each cycle and in thematic analysis after saturation. RESULTS: Interviews were conducted between November 2022 and February 2023 with stroke center representatives from centers that either had successfully adopted TNK, or had not yet adopted TNK. Three themes and eight sub-themes were identified. The theme "Evidence" had three sub-themes: Pro-Con Balance, Fundamental Knowledge, and Pharmacotherapeutics. The theme "Process Flow" had four subthemes: Proactive, Reflective self-doubt, Change Process Barriers, and Parameter Barriers. The theme "Consensus" had one sub-theme: Getting Buy-In. CONCLUSION: Clinicians experience remarkably similar barriers and facilitators to adopting TNK. The results lead to a hypothesis that providing evidence to support a practice change, and identifying key change processes, will help clinicians achieve consensus across teams that need to 'buy in' to adopting TNK for AIS treatment.

A retrospective examination of pain in acute stroke at hospital discharge.

OBJECTIVES: Pain is an overlooked sequela of stroke. Persistent pain after stroke is an underrecognized experience and significantly impacts survivors' function, ability to participate in rehabilitation, and quality of life. The aim of this retrospective, observational study is to examine the incidence of pain at the acute hospitalization period immediately after stroke, to identify the characteristics of those reporting pain at discharge, and to compare pain reporting between stroke and non-stroke hospital controls. MATERIALS AND METHODS: Using discharge diagnosis, this retrospective review examined self- reports of pain during acute hospitalization for stroke compared to those with COPD (control group) admitted during the same time in the same facilities. Variables of interest included age, gender, body mass index (BMI), length of stay, pain assessment score (numeric rating scale [NRS], behavior pain scale [BPS], and medication administration record pain score total [MAR]), smoking history, prevalence of hypertension and race. 821 subjects were included from a total of three campuses from one large hospital system. 772 subjects were included in the comparative analysis with COPD patients from the same facilities during the same time. RESULTS: 43% of patients diagnosed with stroke reported pain at discharge. For stroke survivors reporting pain at discharge, the average BMI was higher (p=0.009), average arrival NIHSS was higher (p=0.044), and mean hospital length of stay was longer (p<0.001). CONCLUSIONS: The evidence demonstrated in this study highlights the critical need for the implementation of targeted objective pain assessment and effective pain interventions for stroke survivors beginning at initial hospitalization.

Dietary Intake and Quality among Stroke Survivors: NHANES 1999-2018.

BACKGROUND: Nutrition is an important modifiable risk factor for prevention and treatment of stroke. However, examination of nutrient intake and diet quality in stroke survivors is limited. OBJECTIVES: The aim of the study was to estimate usual nutrient intake and diet quality in US adults with and without a history of self-reported stroke. METHODS: Using US National Health and Nutrition Examination Survey (NHANES) 1999-2018, we analyzed demographics, health history, and dietary intake data in 1626 individuals with a history of stroke matched for age, gender, and survey cycle to respective controls (n=1621) with no history of stroke. A minimum of one 24-h dietary recall was used to assess dietary intake. Diet quality was determined using Healthy Eating Index 2015 (HEI-2015) scores. Adult food security was assessed based on responses to the US Department of Agriculture Household Food Security Survey Module. Physical and mental limitations were assessed from responses to the NHANES Physical Functioning Questionnaire. Estimates were reported as mean (standard error). RESULTS: In comparison to controls, stroke survivors were more likely to be food insecure, experience poverty, and report physical and mental limitations (P < .001, all comparisons). Stroke survivors were more likely to report excessive (% > acceptable macronutrient distribution range) intake for total fat (50.9 [2.7]% vs. 40.4 [2.2]%, P < .001) and inadequate intake (% < estimated average requirement) for calcium (54.6 [1.8]% vs. 43.5 [2.4]%, P = .001) and magnesium (66 [1.8] vs. 53.6 [1.8]%, P < .001). In addition, stroke survivors reported lower HEI-2015 total scores than controls (49.8 vs. 51.9, P < .001). Finally, HEI-2015 total scores were lower in stroke survivors who were food insecure and those with a lower income-to-poverty ratio (< 185%) (P = .001). CONCLUSIONS: Dietary intake in stroke survivors was nutritionally poor, with suboptimal nutrient intake and lower overall diet quality compared with age- and gender-matched controls. Furthermore, poverty and food insecurity were more prevalent in stroke survivors and associated with worse diet quality.

Enhanced Cerebroprotection of Xenon-Loaded Liposomes in Combination with rtPA Thrombolysis for Embolic Ischemic Stroke.

Xenon (Xe) has shown great potential as a stroke treatment due to its exceptional ability to protect brain tissue without inducing side effects. We have previously developed Xe-loaded liposomes for the ultrasound-activated delivery of Xe into the cerebral region and demonstrated their therapeutic efficacy. At present, the sole FDA-approved thrombolytic agent for stroke treatment is recombinant tissue plasminogen activator (rtPA). In this study, we aimed to investigate the potential of combining Xe-liposomes with an intravenous rtPA treatment in a clinically relevant embolic rat stroke model. We evaluated the combinational effect using an in vitro clot lysis model and an in vivo embolic middle cerebral artery occlusion (eMCAO) rat model. The treatment groups received intravenous administration of Xe-liposomes (20 mg/kg) at 2 h post-stroke onset, followed by the administration of rtPA (10 mg/kg) at either 2 or 4 h after the onset. Three days after the stroke, behavioral tests were conducted, and brain sections were collected for triphenyltetrazolium chloride (TTC) and TUNEL staining. Infarct size was determined as normalized infarct volume (%). Both in vitro and in vivo clot lysis experiments demonstrated that Xe-liposomes in combination with rtPA resulted in effective clot lysis comparable to the treatment with free rtPA alone. Animals treated with Xe-liposomes in combination with rtPA showed reduced TUNEL-positive cells and demonstrated improved neurological recovery. Importantly, Xe-liposomes in combination with late rtPA treatment reduced rtPA-induced hemorrhage, attributing to the reduction of MMP9 immunoreactivity. This study demonstrates that the combined therapy of Xe-liposomes and rtPA provides enhanced therapeutic efficacy, leading to decreased neuronal cell death and a potential to mitigate hemorrhagic side effects associated with late rtPA treatment.

Non-invasive arterial blood pressure measurement and SpO2 estimation using PPG signal: a deep learning framework.

BACKGROUND: Monitoring blood pressure and peripheral capillary oxygen saturation plays a crucial role in healthcare management for patients with chronic diseases, especially hypertension and vascular disease. However, current blood pressure measurement methods have intrinsic limitations; for instance, arterial blood pressure is measured by inserting a catheter in the artery causing discomfort and infection. METHOD: Photoplethysmogram (PPG) signals can be collected via non-invasive devices, and therefore have stimulated researchers' interest in exploring blood pressure estimation using machine learning and PPG signals as a non-invasive alternative. In this paper, we propose a Transformer-based deep learning architecture that utilizes PPG signals to conduct a personalized estimation of arterial systolic blood pressure, arterial diastolic blood pressure, and oxygen saturation. RESULTS: The proposed method was evaluated with a subset of 1,732 subjects from the publicly available ICU dataset MIMIC III. The mean absolute error is 2.52 ± 2.43 mmHg for systolic blood pressure, 1.37 ± 1.89 mmHg for diastolic blood pressure, and 0.58 ± 0.79% for oxygen saturation, which satisfies the requirements of the Association of Advancement of Medical Instrumentation standard and achieve grades A for the British Hypertension Society standard. CONCLUSIONS: The results indicate that our model meets clinical standards and could potentially boost the accuracy of blood pressure and oxygen saturation measurement to deliver high-quality healthcare.

Hemostatic efficacy of four factor prothrombin complex concentrate in intracerebral hemorrhage patients receiving warfarin vs. factor Xa inhibitors.

INTRODUCTION: 4-F PCC is administered for reversal of factor Xa inhibitor-associated coagulopathy despite a lack of quality evidence demonstrating hemostatic efficacy. The aim of this study was to evaluate the hemostatic efficacy of 4-F PCC in intracerebral hemorrhage patients who received factor Xa inhibitors versus warfarin. MATERIALS AND METHODS: This was a multi-center, retrospective, observational cohort study at a large healthcare system. Patients taking warfarin received 4-F PCC 25-50 units/kg based on the presenting INR, while patients taking a factor Xa inhibitor received 35 units/kg. The primary outcome was the percentage of patients with good or excellent hemostatic efficacy as assessed by modified Sarode scale, with neurologic outcomes assessed as a secondary endpoint. Patients were included in the primary outcome population if they had a repeat CT scan within 24 h. RESULTS: One hundred fifty-seven patients were included in the primary outcome population; [warfarin (n = 76), factor Xa inhibitors (n = 81)]. Hemostatic efficacy was 83 % in the warfarin group versus 75 % in the factor Xa inhibitor group (p = 0.24). The hemostatic efficacy risk difference between the groups was 7.6 % (95 % CI 5.1 %, 20.2 %). Good neurologic outcome (mRS 0-2) at discharge was 17 % in warfarin patients versus 12 % in the factor Xa inhibitor patients (p = 0.40). CONCLUSIONS: There was no significant difference in hemostatic efficacy or clinical outcomes between patients taking warfarin or a factor Xa inhibitor following reversal with 4-F PCC. This study provides further support that 4-F PCC can be used for the reversal of factor Xa inhibitor-associated coagulopathy.