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1.
J Am Heart Assoc ; 13(14): e034308, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38958125

ABSTRACT

BACKGROUND: Stroke survivors believe neighborhood resources such as community centers are beneficial; however, little is known about the influence of these resources on stroke outcomes. We evaluated whether residing in neighborhoods with greater resource density is associated with favorable post-stroke outcomes. METHODS AND RESULTS: We included Mexican American and non-Hispanic White stroke survivors from the Brain Attack Surveillance in Corpus Christi project (2009-2019). The exposure was density of neighborhood resources (eg, community centers, restaurants, stores) within a residential census tract at stroke onset. Outcomes included time to death and recurrence, and at 3 months following stroke: disability (activities of daily living/instrumental activities of daily living), cognition (Modified Mini-Mental State Exam), depression (Patient Health Questionnaire-8), and quality of life (abbreviated Stroke-Specific Quality of Life scale). We fit multivariable Cox regression and mixed linear models. We considered interactions with stroke severity, ethnicity, and sex. Among 1786 stroke survivors, median age was 64 years (interquartile range, 56-73), 55% men, and 62% Mexican American. Resource density was not associated with death, recurrence, or depression. Greater resource density (75th versus 25th percentile) was associated with more favorable cognition (Modified Mini-Mental State Exam mean difference=0.838, 95% CI=0.092, 1.584) and among moderate-severe stroke survivors, with more favorable functioning (activities of daily living/instrumental activities of daily living=-0.156 [95% CI, -0.284 to 0.027]) and quality of life (abbreviated Stroke-Specific Quality of Life scale=0.194 [95% CI, 0.029-0.359]). CONCLUSIONS: We observed associations between greater resource density and cognition overall and with functioning and quality of life among moderate-severe stroke survivors. Further research is needed to confirm these findings and determine if neighborhood resources may be a tool for recovery.


Subject(s)
Activities of Daily Living , Mexican Americans , Quality of Life , Stroke , Humans , Male , Female , Middle Aged , Aged , Stroke/psychology , Neighborhood Characteristics , Cognition , Survivors/psychology , Recurrence , Texas/epidemiology , Depression/epidemiology , Depression/psychology , Time Factors , White People
2.
JMIR Mhealth Uhealth ; 12: e54946, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38889070

ABSTRACT

Background: Hypertension, a key modifiable risk factor for cardiovascular disease, is more prevalent among Black and low-income individuals. To address this health disparity, leveraging safety-net emergency departments for scalable mobile health (mHealth) interventions, specifically using text messaging for self-measured blood pressure (SMBP) monitoring, presents a promising strategy. This study investigates patterns of engagement, associated factors, and the impact of engagement on lowering blood pressure (BP) in an underserved population. Objective: We aimed to identify patterns of engagement with prompted SMBP monitoring with feedback, factors associated with engagement, and the association of engagement with lowered BP. Methods: This is a secondary analysis of data from Reach Out, an mHealth, factorial trial among 488 hypertensive patients recruited from a safety-net emergency department in Flint, Michigan. Reach Out participants were randomized to weekly or daily text message prompts to measure their BP and text in their responses. Engagement was defined as a BP response to the prompt. The k-means clustering algorithm and visualization were used to determine the pattern of SMBP engagement by SMBP prompt frequency-weekly or daily. BP was remotely measured at 12 months. For each prompt frequency group, logistic regression models were used to assess the univariate association of demographics, access to care, and comorbidities with high engagement. We then used linear mixed-effects models to explore the association between engagement and systolic BP at 12 months, estimated using average marginal effects. Results: For both SMBP prompt groups, the optimal number of engagement clusters was 2, which we defined as high and low engagement. Of the 241 weekly participants, 189 (78.4%) were low (response rate: mean 20%, SD 23.4) engagers, and 52 (21.6%) were high (response rate: mean 86%, SD 14.7) engagers. Of the 247 daily participants, 221 (89.5%) were low engagers (response rate: mean 9%, SD 12.2), and 26 (10.5%) were high (response rate: mean 67%, SD 8.7) engagers. Among weekly participants, those who were older (>65 years of age), attended some college (vs no college), married or lived with someone, had Medicare (vs Medicaid), were under the care of a primary care doctor, and took antihypertensive medication in the last 6 months had higher odds of high engagement. Participants who lacked transportation to appointments had lower odds of high engagement. In both prompt frequency groups, participants who were high engagers had a greater decline in BP compared to low engagers. Conclusions: Participants randomized to weekly SMBP monitoring prompts responded more frequently overall and were more likely to be classed as high engagers compared to participants who received daily prompts. High engagement was associated with a larger decrease in BP. New strategies to encourage engagement are needed for participants with lower access to care.


Subject(s)
Emergency Service, Hospital , Safety-net Providers , Telemedicine , Humans , Male , Female , Middle Aged , Telemedicine/statistics & numerical data , Telemedicine/standards , Emergency Service, Hospital/statistics & numerical data , Emergency Service, Hospital/organization & administration , Safety-net Providers/statistics & numerical data , Adult , Hypertension/therapy , Hypertension/psychology , Hypertension/epidemiology , Aged , Michigan/epidemiology , Text Messaging/instrumentation , Text Messaging/statistics & numerical data , Text Messaging/standards , Blood Pressure Determination/methods , Blood Pressure Determination/statistics & numerical data , Blood Pressure Determination/instrumentation
3.
Mol Ther Methods Clin Dev ; 32(2): 101254, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38745893

ABSTRACT

A major limitation of gene therapy for sickle cell disease (SCD) is the availability and access to a potentially curative one-time treatment, due to high treatment costs. We have developed a high-titer bifunctional lentiviral vector (LVV) in a vector backbone that has reduced size, high vector yields, and efficient gene transfer to human CD34+ hematopoietic stem and progenitor cells (HSPCs). This LVV contains locus control region cores expressing an anti-sickling ßAS3-globin gene and two microRNA-adapted short hairpin RNA simultaneously targeting BCL11A and ZNF410 transcripts to maximally induce fetal hemoglobin (HbF) expression. This LVV induces high levels of anti-sickling hemoglobins (HbAAS3 + HbF), while concurrently decreasing sickle hemoglobin (HbS). The decrease in HbS and increased anti-sickling hemoglobin impedes deoxygenated HbS polymerization and red blood cell sickling at low vector copy per cell in transduced SCD patient CD34+ cells differentiated into erythrocytes. The dual alterations in red cell hemoglobins ameliorated the SCD phenotype in the SCD Berkeley mouse model in vivo. With high titer and enhanced transduction of HSPC at a low multiplicity of infection, this LVV will increase the number of patient doses of vector from production lots to decrease costs and help improve accessibility to gene therapy for SCD.

4.
J Stroke Cerebrovasc Dis ; 33(6): 107701, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38561169

ABSTRACT

OBJECTIVES: Post-stroke fatigue (PSF) is common and often disabling. Sleep-disordered breathing (SDB) is highly prevalent among stroke survivors and can cause fatigue. We explored the relationship between SDB and PSF over time. MATERIALS AND METHODS: Ischemic stroke (IS) patients within the BASIC project were offered SDB screening with a well-validated cardiopulmonary sleep apnea test at 0, 3-, 6-, and 12-months post-stroke. The primary exposure was the respiratory event index (REI; sum of apneas plus hypopneas per hour). The primary outcome was PSF, measured by the SF-36 vitality scale. Associations between REI and PSF were evaluated using linear regression including time-by-REI interactions, allowing the effect of REI to vary over time. RESULTS: Of the 411 IS patients who completed at least one outcome interview, 44 % were female, 61 % Mexican American (MA), 26 % non-Hispanic white, with a mean age of 64 (SD 10). Averaged across timepoints, REI was not associated with PSF. In a time-varying model, higher REI was associated with greater PSF at 3-months (ß = 1.75, CI = 0.08, 3.43), but not at 6- or 12-months. Across timepoints, female sex, depressive symptoms, and comorbidity burden were associated with greater PSF, whereas MA ethnicity was associated with less PSF. CONCLUSIONS: Higher REI was associated with modestly greater PSF in the early post-stroke period, but no association was observed at 6 months and beyond. SDB may be a modest modifiable risk factor for early PSF, but its treatment is unlikely to have a substantial impact on long-term PSF. MA ethnicity seems to be protective against PSF.


Subject(s)
Fatigue , Ischemic Stroke , Sleep Apnea Syndromes , Humans , Female , Sleep Apnea Syndromes/diagnosis , Sleep Apnea Syndromes/epidemiology , Sleep Apnea Syndromes/physiopathology , Sleep Apnea Syndromes/ethnology , Male , Middle Aged , Aged , Fatigue/etiology , Fatigue/epidemiology , Fatigue/physiopathology , Fatigue/diagnosis , Fatigue/psychology , Ischemic Stroke/epidemiology , Ischemic Stroke/diagnosis , Ischemic Stroke/ethnology , Risk Factors , Time Factors , Risk Assessment , Sleep , Respiration , Prognosis
5.
Stroke ; 55(3): e61-e76, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38235581

ABSTRACT

Accumulating evidence supports a link between sleep disorders, disturbed sleep, and adverse brain health, ranging from stroke to subclinical cerebrovascular disease to cognitive outcomes, including the development of Alzheimer disease and Alzheimer disease-related dementias. Sleep disorders such as sleep-disordered breathing (eg, obstructive sleep apnea), and other sleep disturbances, as well, some of which are also considered sleep disorders (eg, insomnia, sleep fragmentation, circadian rhythm disorders, and extreme sleep duration), have been associated with adverse brain health. Understanding the causal role of sleep disorders and disturbances in the development of adverse brain health is complicated by the common development of sleep disorders among individuals with neurodegenerative disease. In addition to the role of sleep disorders in stroke and cerebrovascular injury, mechanistic hypotheses linking sleep with brain health and biomarker data (blood-based, cerebrospinal fluid-based, and imaging) suggest direct links to Alzheimer disease-specific pathology. These potential mechanisms and the increasing understanding of the "glymphatic system," and the recognition of the importance of sleep in poststroke recovery, as well, support a biological basis for the indirect (through the worsening of vascular disease) and direct (through specific effects on neuropathology) connections between sleep disorders and brain health. Given promising evidence for the benefits of treatment and prevention, sleep disorders and disturbances represent potential targets for early treatment that may improve brain health more broadly. In this scientific statement, we discuss the evidence supporting an association between sleep disorders and disturbances and poor brain health ranging from stroke to dementia and opportunities for prevention and early treatment.


Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Sleep Wake Disorders , Stroke , Humans , Alzheimer Disease/complications , American Heart Association , Sleep , Brain/pathology , Stroke/complications , Sleep Wake Disorders/complications
6.
Sleep Med ; 113: 116-130, 2024 01.
Article in English | MEDLINE | ID: mdl-38011808

ABSTRACT

OBJECTIVE/BACKGROUND: Standard measures of sleep-disordered breathing (SDB) that rely on count data may not sufficiently capture SDB severity or reflect downstream consequences of SDB. We hypothesized that novel metrics derived from pulse rate, oxygen saturation, and nasal pressure would be associated with stroke outcomes. PATIENTS/METHODS: Shortly after ischemic stroke, participants in a population-based study were offered ApneaLink Plus testing. Signal analysis was used to generate 166 metrics from the nasal pressure cannula and finger probe, categorized as: autonomic (based on pulse rate variability), oximetry-derived, nasal pressure-derived, and mixed oxygen and nasal pressure-derived measures. Three-month outcome assessments included functional and cognitive outcomes and stroke recurrence. Tobit regression and Cox proportional hazards models were used to examine associations between each sleep apnea metric and the three outcomes, unadjusted and adjusted for multiple potential confounders. Models were adjusted for multiple comparisons. RESULTS: Of the 530 participants, the median age was 65 (IQR: 57, 73), 49 % were female, and 64 % were Mexican American. Without covariate adjustment, 23 of 166 variables were associated with functional outcome, 43 were associated with cognitive outcome, and 1 was associated with stroke recurrence. After adjustment, 7 mixed, oximetry, or nasal pressure-based metrics and 1 autonomic metric were associated with functional outcome, but none was associated with cognitive outcome or stroke recurrence. CONCLUSIONS: Many novel metrics of SDB were associated with important stroke outcomes, and 8 novel metrics were associated with functional outcome in adjusted models. This raises hypotheses about pathways by which SDB may negatively impact stroke outcomes.


Subject(s)
Ischemic Stroke , Sleep Apnea Syndromes , Stroke , Humans , Female , Aged , Male , Ischemic Stroke/complications , Sleep Apnea Syndromes/complications , Stroke/complications , Oximetry , Oxygen
8.
Stroke ; 54(10): 2583-2592, 2023 10.
Article in English | MEDLINE | ID: mdl-37706339

ABSTRACT

BACKGROUND: Higher neighborhood socioeconomic status has been favorably associated with stroke outcomes. This may be due to these areas having more beneficial resources such as recreational centers. We aimed to determine if neighborhood density of recreation centers is favorably associated with stroke outcomes. METHODS: We conducted analyses of data from the Brain Attack Surveillance in Corpus Christi project, a cohort of stroke survivors ≥45 years of age residing in Nueces County, TX (2009-2020). We included non-Hispanic White and Mexican American incident stroke survivors, who were not institutionalized prestroke and completed baseline and follow-up assessments (N=1392). We calculated the density of fitness and recreational sports centers within their residential census tract during the year of their stroke. Outcomes included function (self-ratings on activities of daily living and instrumental activities of daily living), cognition (modified mini-mental state exam), depression (Patient Health Questionnaire-8), and quality of life (abbreviated Stroke-Specific Quality of Life Scale). We fit confounder-adjusted gamma-distributed mixed generalized linear models with a log link for each outcome and considered interaction with stroke severity. RESULTS: On average, participants were 65 years old, 53% male, and 63% Mexican American. Median recreational centers were 1.60 per square mile (interquartile range, 0.41-3.06). Among moderate-severe stroke survivors, greater density of recreation centers (75th versus 25th percentile) was associated with more favorable function and possibly quality of life (activities of daily living/instrumental activities of daily living, 4.8% change [95% CI, -0.11% to -9.27%]; Stroke-Specific Quality of Life Scale, 3.7% change [95% CI, -0.7% to 8.2%]). Minimal nonsignificant differences were observed among the overall stroke population and those with mild stroke. CONCLUSIONS: The availability of recreation centers may be beneficial for poststroke function and quality of life among those with moderate-severe stroke. If further research confirms recreation centers to be beneficial, this could inform rehabilitation following stroke.


Subject(s)
Activities of Daily Living , Stroke , Humans , Male , Aged , Female , Quality of Life , Census Tract , Stroke/epidemiology , Recreation
9.
JAMA Netw Open ; 6(7): e2321558, 2023 07 03.
Article in English | MEDLINE | ID: mdl-37399011

ABSTRACT

Importance: Acute stroke treatment rates in the US lag behind those in other high-income nations. Objective: To assess whether a hospital emergency department (ED) and community intervention was associated with an increased proportion of patients with stroke receiving thrombolysis. Design, Setting, and Participants: This nonrandomized controlled trial of the Stroke Ready intervention took place in Flint, Michigan, from October 2017 to March 2020. Participants included adults living in the community. Data analysis was completed from July 2022 to May 2023. Intervention: Stroke Ready combined implementation science and community-based participatory research approaches. Acute stroke care was optimized in a safety-net ED, and then a community-wide, theory-based health behavior intervention, including peer-led workshops, mailers, and social media, was conducted. Main Outcomes and Measures: The prespecified primary outcome was the proportion of patients hospitalized with ischemic stroke or transient ischemic attack from Flint who received thrombolysis before and after the intervention. The association between thrombolysis and the Stroke Ready combined intervention, including the ED and community components, was estimated using logistic regression models, clustering at the hospital level and adjusting for time and stroke type. In prespecified secondary analyses, the ED and community intervention were explored separately, adjusting for hospital, time, and stroke type. Results: In total, 5970 people received in-person stroke preparedness workshops, corresponding to 9.7% of the adult population in Flint. There were 3327 ischemic stroke and TIA visits (1848 women [55.6%]; 1747 Black individuals [52.5%]; mean [SD] age, 67.8 [14.5] years) among patients from Flint seen in the relevant EDs, including 2305 in the preintervention period from July 2010 to September 2017 and 1022 in the postintervention period from October 2017 to March 2020. The proportion of thrombolysis usage increased from 4% in 2010 to 14% in 2020. The combined Stroke Ready intervention was not associated with thrombolysis use (adjusted odds ratio [OR], 1.13; 95% CI, 0.74-1.70; P = .58). The ED component was associated with an increase in thrombolysis use (adjusted OR, 1.63; 95% CI, 1.04-2.56; P = .03), but the community component was not (adjusted OR, 0.99; 95% CI, 0.96-1.01; P = .30). Conclusions and Relevance: This nonrandomized controlled trial found that a multilevel ED and community stroke preparedness intervention was not associated with increased thrombolysis treatments. The ED intervention was associated with increased thrombolysis usage, suggesting that implementation strategies in partnership with safety-net hospitals may increase thrombolysis usage. Trial Registration: ClinicalTrials.gov Identifier: NCT036455900.


Subject(s)
Ischemic Stroke , Stroke , Adult , Humans , Female , Aged , Michigan/epidemiology , Community-Based Participatory Research , Incidence , Stroke/drug therapy , Stroke/epidemiology , Thrombolytic Therapy
10.
Stroke ; 54(9): 2356-2365, 2023 09.
Article in English | MEDLINE | ID: mdl-37485665

ABSTRACT

BACKGROUND: The aim of this study was to characterize change in sleep-disordered breathing severity in the year following stroke, overall, and by ethnicity, within the population-based Brain Attack Surveillance in Corpus Christi Project. METHODS: First-ever ischemic strokes (n=414) were ascertained by active and passive surveillance and validated by stroke-trained physicians. Patients with stroke were invited to participate in portable sleep apnea testing (ApneaLink Plus) at baseline and 3, 6, and 12 months poststroke. Sleep-disordered breathing severity was assessed by the respiratory event index (apneas and hypopneas/hour of recording). The component obstructive apnea index and central apnea index were also assessed. Time and ethnicity effects on outcomes, as well as ethnic differences in time effects, were analyzed using generalized estimating equations with multivariable adjustment for confounding factors. RESULTS: Mean age (n=414) was 63.9 years (SD=10.9); 68.4% were Mexican American. Baseline mean respiratory event index, obstructive apnea index, and central apnea index were 21.3 (SD=16.6), 8.6 (SD=11.5), and 1.5 (SD=3.2), respectively. There was no time effect on respiratory event index (P=0.35) but obstructive apnea index increased over time (P<0.01). Averaged over follow-up, respiratory event index and obstructive apnea index were significantly higher in Mexican American than non-Hispanic White persons. No ethnic difference in the time effect was found for either outcome. For central apnea index, there was an ethnicity-time interaction (P=0.01) such that central apnea index increased in non-Hispanic White but did not change in Mexican American persons. CONCLUSIONS: Sleep-disordered breathing severity was significant and stable for most individuals in the year after stroke. These results do not confirm previous reports of diminishing sleep-disordered breathing severity over time after stroke and would support early assessment and treatment where indicated.


Subject(s)
Sleep Apnea Syndromes , Sleep Apnea, Central , Stroke , Humans , Middle Aged , Risk Factors , Stroke/complications , Stroke/epidemiology , Sleep Apnea Syndromes/diagnosis , Sleep Apnea Syndromes/epidemiology , Sleep Apnea Syndromes/etiology , Ethnicity
11.
Circ Cardiovasc Qual Outcomes ; 16(5): e009606, 2023 05.
Article in English | MEDLINE | ID: mdl-37192282

ABSTRACT

BACKGROUND: Mobile health (mHealth) strategies initiated in safety-net Emergency Departments may be one approach to address the US hypertension epidemic, but the optimal mHealth components or dose are unknown. METHODS: Reach Out is an mHealth, health theory-based, 2×2×2 factorial trial among hypertensive patients evaluated in a safety-net Emergency Department in Flint, Michigan. Reach Out consisted of 3 mHealth components, each with 2 doses: (1) healthy behavior text messaging (yes versus no), (2) prompted self-measured blood pressure (BP) monitoring and feedback (weekly versus daily), and (3) facilitated primary care provider appointment scheduling and transportation (yes versus no). The primary outcome was a change in systolic BP from baseline to 12 months. In a complete case analysis, we fit a linear regression model and accounted for age, sex, race, and prior BP medications to explore the association between systolic BP and each mHealth component. RESULTS: Among 488 randomized participants, 211 (43%) completed follow-up. Mean age was 45.5 years, 61% were women, 54% were Black people, 22% did not have a primary care doctor, 21% lacked transportation, and 51% were not taking antihypertensive medications. Overall, systolic BP declined after 6 months (-9.2 mm Hg [95% CI, -12.2 to -6.3]) and 12 months (-6.6 mm Hg, -9.3 to -3.8), without a difference across the 8 treatment arms. The higher dose of mHealth components were not associated with a greater change in systolic BP; healthy behavior text messages (point estimate, mmHG=-0.5 [95% CI, -6.0 to 5]; P=0.86), daily self-measured BP monitoring (point estimate, mmHG=1.9 [95% CI, -3.7 to 7.5]; P=0.50), and facilitated primary care provider scheduling and transportation (point estimate, mmHG=0 [95% CI, -5.5 to 5.6]; P=0.99). CONCLUSIONS: Among participants with elevated BP recruited from an urban safety-net Emergency Department, BP declined over the 12-month intervention period. There was no difference in change in systolic BP among the 3 mHealth components. Reach Out demonstrated the feasibility of reaching medically underserved people with high BP cared for at a safety-net Emergency Departments, yet the efficacy of the Reach Out mHealth intervention components requires further study. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03422718.


Subject(s)
Hypertension , Telemedicine , Humans , Female , Middle Aged , Male , Blood Pressure , Hypertension/diagnosis , Hypertension/drug therapy , Antihypertensive Agents/adverse effects , Health Behavior
12.
Sleep Med ; 107: 26-30, 2023 07.
Article in English | MEDLINE | ID: mdl-37099917

ABSTRACT

OBJECTIVE/BACKGROUND: Sleep-disordered breathing (SDB) is very common after ischemic stroke, and its treatment may have a positive impact on recovery from stroke and on secondary stroke prevention. This study sought to determine the prevalence of positive airway pressure (PAP) use after stroke. PATIENTS/METHODS: Participants in the Brain Attack Surveillance in Corpus Christi (BASIC) project underwent a home sleep apnea test shortly after ischemic stroke. Demographics and co-morbidities were ascertained from the medical record. Self-reported PAP use (present vs absent) was assessed at 3, 6, and 12 months after stroke. Fisher exact tests and t-tests were used to compare PAP users versus non-users. RESULTS: Of 328 participants who were found to have SDB after stroke, only 20 (6.1%) indicated using PAP at any point during the 12-month follow up period. High pre-stroke sleep apnea risk based on Berlin Questionnaire score, neck circumference, and co-morbid atrial fibrillation were associated with any self-reported PAP use; race/ethnicity, insurance status and other demographic variables were not associated with PAP use. CONCLUSIONS: Only a small proportion of individuals with ischemic stroke and SDB received treatment with PAP during the initial year after stroke among participants in this population-based cohort study in Nueces County, Texas. Closing the substantial treatment gap for SDB after stroke might improve sleepiness and neurologic recovery.


Subject(s)
Positive-Pressure Respiration , Sleep Apnea Syndromes , Stroke Rehabilitation , Stroke , Stroke/complications , Positive-Pressure Respiration/statistics & numerical data , Sleep Apnea Syndromes/etiology , Sleep Apnea Syndromes/therapy , Humans , Male , Female , Middle Aged , Aged , Self Report
13.
J Am Coll Health ; 71(6): 1643-1645, 2023.
Article in English | MEDLINE | ID: mdl-34398692

ABSTRACT

OBJECTIVE: We examined clinical trial knowledge and attitudes, and their relationship with willingness to participate in COVID-19 vaccine trials, and willingness to accept a COVID-19 vaccine among college students. PARTICIPANTS: 331 undergraduates: mean age 25; 72% women; and 78% white. METHODS: We administered an online, anonymous survey to undergraduate students in July, 2020, during the COVID-19 pandemic. RESULTS: The mean clinical trial knowledge score was 65% (SD = 16) correct. The mean attitudes toward clinical trials score (1 most negative: 5 most positive) was 3.3 (SD = 0.5). Attitudes toward clinical trials were associated with likelihood of COVID-19 trial participation (positive 76% vs. negative 35%, p = 0.001) and a trend toward likelihood of accepting a COVID-19 vaccine if available (positive 89% vs. negative 67%, p = 0.066). CONCLUSIONS: General clinical trial knowledge and attitudes appear to be important targets for educational interventions. Furthermore, fostering positive attitudes may lead to improved COVID-19 trial participation and vaccine uptake.

14.
Blood ; 141(9): 1007-1022, 2023 03 02.
Article in English | MEDLINE | ID: mdl-36332160

ABSTRACT

X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency caused by mutations in the CYBB gene, resulting in the inability of phagocytic cells to eliminate infections. To design a lentiviral vector (LV) capable of recapitulating the endogenous regulation and expression of CYBB, a bioinformatics-guided approach was used to elucidate the cognate enhancer elements regulating the native CYBB gene. Using this approach, we analyzed a 600-kilobase topologically associated domain of the CYBB gene and identified endogenous enhancer elements to supplement the CYBB promoter to develop MyeloVec, a physiologically regulated LV for the treatment of X-CGD. When compared with an LV currently in clinical trials for X-CGD, MyeloVec showed improved expression, superior gene transfer to hematopoietic stem and progenitor cells (HSPCs), corrected an X-CGD mouse model leading to complete protection against Burkholderia cepacia infection, and restored healthy donor levels of antimicrobial oxidase activity in neutrophils derived from HSPCs from patients with X-CGD. Our findings validate the bioinformatics-guided design approach and have yielded a novel LV with clinical promise for the treatment of X-CGD.


Subject(s)
Granulomatous Disease, Chronic , Animals , Mice , Granulomatous Disease, Chronic/genetics , Granulomatous Disease, Chronic/therapy , NADPH Oxidases/genetics , NADPH Oxidases/metabolism , NADPH Oxidase 2/genetics , Genetic Therapy/methods , Mutation
15.
Ann Neurol ; 93(2): 348-356, 2023 02.
Article in English | MEDLINE | ID: mdl-36134521

ABSTRACT

OBJECTIVE: To investigate stroke outcomes at 3, 6, and 12 months post-stroke overall and by ethnicity in a population-based, longitudinal study. METHODS: First-ever ischemic strokes (2014-2019, n = 1,332) among Mexican American persons (n = 807) and non-Hispanic white persons (n = 525) were identified from the Brain Attack Surveillance in Corpus Christi Project. Data were collected from patient or proxy interviews (baseline, 3, 6, and 12 months post-stroke) and medical records, including functional (activities of daily living/instrumental activities of daily living score), neurological (National Institutes of Health Stroke Scale), cognitive (Modified Mini-Mental State Examination), and quality of life (QOL) outcomes (12-domain Stroke-specific Quality of Life scale). Outcome trajectories were analyzed using multivariable adjusted linear models, with generalized estimating equations to account for within-subject correlations; interactions between ethnicity and time were included to investigate ethnic differences in outcomes. RESULTS: The median age was 67 years (interquartile range 58,78), 48.5% were women, and 60.6% were Mexican American persons. For all outcomes, significant improvement was seen between 3 and 6 months (p < 0.05 for all), with stability between 6 and 12 months. Mexican American persons had significantly worse outcomes compared with non-Hispanic white persons at all time points (3, 6, and 12 months), with the exception of the National Institutes of Health Stroke Scale, which did not differ by ethnicity at 6 and 12 months, and the average change in outcomes did not vary significantly by ethnicity. INTERPRETATION: Outcomes were at their worst at 3 months post-stroke, and ethnic disparities were already present, suggesting the need for early assessment and strategies to improve outcomes and possibly reduce disparities. ANN NEUROL 2023;93:348-356.


Subject(s)
Ischemic Stroke , Stroke , Humans , Female , Aged , Male , Ethnicity , Quality of Life , Activities of Daily Living , Longitudinal Studies , Mexican Americans , Risk Factors
16.
J Stroke Cerebrovasc Dis ; 31(12): 106822, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36244278

ABSTRACT

OBJECTIVE: We sought to characterize racial and ethnic differences in pre- and post-stroke sleep-disordered breathing (SDB) and pre-stroke sleep duration. METHODS: Within the Brain Attack Surveillance in Corpus Christi cohort of patients with ischemic stroke (8/26/2010-1/31/2020), pre-stroke SDB risk was assessed retrospectively using the Berlin Questionnaire. Post-stroke SDB was defined by prospective collection of the respiratory event index (REI) using the ApneaLink Plus performed shortly after stroke. Pre-stroke sleep duration was self-reported. We used separate regression models to evaluate the association between race/ethnicity and each outcome (pre-stroke SDB, post-stroke SDB, and pre-stroke sleep duration), without and with adjustment for potential confounders. RESULTS: There was no difference in pre-stroke risk of SDB between Black and non-Hispanic white (NHW) participants (odds ratio (OR) 1.07, 95% CI 0.77-1.49), whereas MA (Mexican American), compared to NHW, participants had a higher risk of SDB before adjusting for demographic and clinical variables (OR 1.26, 95% CI 1.08-1.47). Post-stroke SDB risk was higher in MA (estimate 1.16, 95% CI 1.06-1.28) but lower in Black (estimate 0.79, 95% CI 0.65-0.96) compared to NHW participants; although, only the ethnic difference remained after adjustment. MA and Black participants had shorter sleep duration than NHW participants (OR 0.83, 95% CI 0.72-0.96 for MA; OR 0.67, 95% CI 0.49-0.91 for Black participants) before but not after adjustment. CONCLUSIONS: Racial/ethnic differences appear likely to exist in pre- and post-stroke SDB and pre-stroke sleep duration. Such differences might contribute to racial/ethnic disparities in stroke incidence and outcomes.


Subject(s)
Sleep Apnea Syndromes , Stroke , Humans , Prospective Studies , Retrospective Studies , Prevalence , Stroke/epidemiology , Sleep Apnea Syndromes/diagnosis , Sleep Apnea Syndromes/epidemiology , Sleep , Risk Factors
18.
Sleep Med ; 100: 219-224, 2022 12.
Article in English | MEDLINE | ID: mdl-36115141

ABSTRACT

OBJECTIVE/BACKGROUND: To examine the association between ethnicity and 90-day post-stroke subjective sleepiness, an important determinant of quality of life, as measured by the Epworth Sleepiness Scale (ESS), among ischemic stroke survivors. PATIENTS/METHODS: Mexican American (MA) and non-Hispanic white (NHW) recent ischemic stroke patients were identified from the population-based Brain Attack Surveillance in Corpus Christi Project (2010-2016). Subjects completed a baseline interview and 90-day outcome assessment that included the ESS. Excessive daytime sleepiness was defined as an ESS >10. Tobit regression models were used to assess associations between ethnicity and ESS unadjusted and adjusted for multiple potential confounders. RESULTS: Among 1,181 (62.5% MA) subjects, mean ESS at 90 days was 8.9 (SD 6.0) among MA and 7.4 (SD 4.9) among NHW subjects: 1.45 (95% CI: 0.75, 2.15) points higher among MA than NHW subjects. After adjustment, mean ESS at 90 days was 1.16 (95% CI: 0.38, 1.94) points higher among MAs than NHWs. The prevalence of excessive daytime sleepiness was 39% among MA and 30% among NHW subjects (p = 0.0013). CONCLUSIONS: Ninety days after stroke, sleepiness is worse in MAs compared to NHWs, even after accounting for potential confounding variables. Further studies should address ways to reduce this disparity.


Subject(s)
Disorders of Excessive Somnolence , Ischemic Stroke , Stroke , Humans , Sleepiness , Quality of Life , Risk Factors , Stroke/epidemiology , Disorders of Excessive Somnolence/etiology
19.
Sleep Med ; 97: 43-46, 2022 09.
Article in English | MEDLINE | ID: mdl-35716543

ABSTRACT

OBJECTIVE/BACKGROUND: Continuous positive airway pressure (CPAP) for the treatment of sleep apnea may improve stroke recovery but is limited by poor adherence. We evaluated baseline features and psychosocial factors associated with CPAP adherence among stroke patients enrolled in a pilot study of an intensive CPAP adherence protocol initiated during inpatient rehabilitation. PATIENTS/METHODS: In a retrospective analysis of a prospective cohort study, we compared participants adherent to CPAP (≥4 h for ≥70% of nights over 3 months) to non-adherent participants. Using mixed methods, we quantitatively compared baseline demographic and stroke-related factors associated with adherence and qualitatively compared facilitators and barriers to adherence. RESULTS: There were 32 adherent and 20 non-adherent participants. Quantitative analysis revealed more severe stroke, aphasia and white race were associated with adherence. Adherent compared to non-adherent participants also had fewer early CPAP complaints, especially claustrophobia. In a thematic qualitative analysis, facilitators of adherence included improvement in sleep and stroke symptoms, confidence in CPAP use, and positive treatment expectations. Conversely, barriers to adherence included both potentially modifiable factors (lack of confidence in CPAP use, discomfort with a new health technology, and common CPAP-related complaints), and less modifiable factors (social stressors, sleep disturbance, and lack of home social support). DISCUSSION: Adherence programs for CPAP use after stroke should address modifiable barriers, with early desensitization to improve CPAP-related complaints and claustrophobia, and training to address perceived self-efficacy with CPAP. Future studies should explore individual goals and barriers associated with CPAP use among stroke survivors to improve long-term CPAP adherence. CLINICAL TRIAL REGISTRATION NUMBER: NCT02809430.


Subject(s)
Sleep Apnea, Obstructive , Stroke Rehabilitation , Stroke , Continuous Positive Airway Pressure/methods , Humans , Patient Compliance/psychology , Pilot Projects , Prospective Studies , Retrospective Studies , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/therapy , Stroke/complications , Stroke Rehabilitation/methods
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