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.

Association between sleep-disordered breathing and post-stroke fatigue in patients with ischemic stroke.

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.

Long-Term Psychological Distress Among Surrogate Decision Makers for Mexican American and Non-Hispanic White Patients With Severe Stroke.

BACKGROUND AND OBJECTIVES: During acute hospitalizations, physicians often focus on the stroke patient and not family who may be traumatized by this sudden change to their loved one. We investigated long-term psychological distress among family surrogate decision makers for Mexican American (MA) and non-Hispanic White (NHW) severe stroke patients. Previous work in other diseases suggested worse psychological outcomes in MA than NHW caregivers. METHODS: This was a population-based, prospective cohort study in Nueces County, TX. Stroke patient participants and their surrogate decision makers were enrolled soon after any stroke between April, 2016, and October, 2020, if surrogates had made decisions about life-sustaining treatments. Surrogates completed validated measures of posttraumatic stress, National Stressful Events Survey for Posttraumatic Stress Disorder Short Scale; anxiety, Generalized Anxiety Disorder-7; and depression, Patient Health Questionnaire-8 at discharge, 3, 6, and 12 months. Ethnic differences were assessed with multilevel linear mixed models, sequentially adjusted for prespecified patient and surrogate demographic, socioeconomic, and clinical covariates. RESULTS: There were 301 family surrogates for 241 severe stroke patients. The mean follow-up was 315 days. High scores on measures of psychological distress ranged between 17% and 28% of surrogates. One or more high levels of the psychological outcomes were found in 17%-43% of surrogates; 2 or more were found in 12%-27%; and all 3 were found in 5%-16% of surrogates. All psychological outcomes were worse among MAs on unadjusted analyses. In fully adjusted models, posttraumatic stress remained worse among MAs (0.36, 95% CI 0.17-0.56); ethnic differences were attenuated and no longer significant in the final model for anxiety (0.59, 95% CI -0.55 to 1.74) and depression (0.97, 95% CI -0.25 to 2.19). The trajectory for depression did differ by ethnicity (interaction p = 0.03), with depression score improving more rapidly over time among NHWs than MAs. Advance care plans did not seem to confound any ethnic differences. DISCUSSION: Psychological distress is common among family surrogate decision makers in the year after stroke and may be worse among MAs. Efforts are needed to support family members of all ethnic groups after severe stroke.

Differential Impact of Stroke on Cognitive Impairment in Mexican Americans and Non-Hispanic White Americans.

BACKGROUND: The association between stroke and dementia is well established. Less is known about this association in underrepresented ethnic groups. In a large ethnically diverse cohort, we examined whether history of stroke was associated with cognitive impairment, and whether this relationship differed by ethnicity (Mexican American [MA] versus non-Hispanic White). METHODS: This was a population-based cohort study conducted in Nueces County, TX, a biethnic community with a large and primarily nonimmigrant MA population. Residents aged ≥65 were recruited door-to-door or by telephone between May 2018 and December 2021. The primary exposure was history of stroke, obtained by self-report. Demographic, medical, and educational histories were also obtained. The primary outcome was the Montreal Cognitive Assessment (MoCA), a scale that evaluates multiple domains of cognitive performance. Scores were divided into 3 ordinal categories, roughly corresponding to normal cognition (MoCA 26-30), mild cognitive impairment (MoCA 20-25), or probable dementia (MoCA 0-19). RESULTS: One thousand eight hundred one participants completed MoCA screening (55% female; 50% MA, 44% Non-Hispanic White, 6% other), of whom 12.4% reported history of stroke. Stroke prevalence was similar across ethnicities (X2 2.1; P=0.34). In a multivariable cumulative logit regression model for the ordinal cognition outcome, a stroke by ethnicity interaction was observed (P=0.01). Models stratified by ethnicity revealed that stroke was associated with cognitive impairment across ethnicities, but had greater impact on cognition in non-Hispanic Whites (cumulative odds ratio=3.81 [95% CI, 2.37-6.12]) than in MAs (cumulative odds ratio=1.58 [95% CI, 1.04-2.41]). Increased age and lower educational attainment were also associated with cognitive impairment, regardless of ethnicity. CONCLUSIONS: History of stroke was associated with increased odds of cognitive impairment after controlling for other factors in both MA and Non-Hispanic White participants. The magnitude of the impact of stroke on cognition was less in MA than in Non-Hispanic White participants.

Declining use of neurological eponyms in cases where a non-eponymous alternative exists.

Eponyms are common in neurology, but their use is controversial. Recent studies have demonstrated increasing eponym use over time in the scientific literature, but it is unclear whether this is a result of authors choosing to use eponyms more frequently, or is merely a product of increasing rates of scientific publication. Our goal was to explore trends in decision-making pertaining to eponym usage. We identified cases where an eponym and a corresponding non-eponymous term existed, and assessed temporal trends in the relative usage of these terms using Google's n-gram viewer for each decade from 1900-2019. Relative to corresponding non-eponymous terms, the use of eponyms increased across the 20th century, peaking in the decade from 1980 to 1989, before sharply declining after the turn of the 21st century. This indicates that when faced with a choice between using an eponym and non-eponymous term, contemporary authors increasingly chose the non-eponymous term. This recent trend may reflect increased awareness of the limitations of eponyms, greater attention to the personal and political lives of namesakes, and a cultural shift toward viewing scientific advances as the result of collective and collaborative efforts rather than the solitary achievements of eminent individuals.

Human Posterior Insula Functional Connectivity Differs Between Electrical Pain and the Resting State.

The objective in this study was to directly compare MRI-based functional connectivity between conditions of rest and painful electrical nerve stimulation for key regions involved in pain processing: the anterior and posterior insula and the anterior cingulate cortex. Electric nerve stimulation, rated 7/10 for pain, was delivered to the right index finger of 14 healthy pain-free adult volunteers in four 30-sec blocks and continuously for 2 min. Functional connectivity maps obtained at rest and during both pain tasks were compared using seed time courses from the left anterior and posterior insula and anterior cingulate. Significant Pain versus Rest connectivity differences were consistently shown for the posterior insula, notably to the posterior cingulate and precuneus, while minimal and inconsistent differences were observed for the anterior insula and anterior cingulate. This study reinforces the known differences that can occur with changes in seed region selection in functional connectivity analysis. It also presents preliminary evidence that functional connectivity for the left posterior insula can potentially differentiate the presence of acute right-sided electrical pain from the nonpainful resting state.

Optimizing and Interpreting Insular Functional Connectivity Maps Obtained During Acute Experimental Pain: The Effects of Global Signal and Task Paradigm Regression.

The insula is uniquely located between the temporal and parietal cortices, making it anatomically well-positioned to act as an integrating center between the sensory and affective domains for the processing of painful stimulation. This can be studied through resting-state functional connectivity (fcMRI) imaging; however, the lack of a clear methodology for the analysis of fcMRI complicates the interpretation of these data during acute pain. Detected connectivity changes may reflect actual alterations in low-frequency synchronous neuronal activity related to pain, may be due to changes in global cerebral blood flow or the superimposed task-induced neuronal activity. The primary goal of this study was to investigate the effects of global signal regression (GSR) and task paradigm regression (TPR) on the changes in functional connectivity of the left (contralateral) insula in healthy subjects at rest and during acute painful electric nerve stimulation of the right hand. The use of GSR reduced the size and statistical significance of connectivity clusters and created negative correlation coefficients for some connectivity clusters. TPR with cyclic stimulation gave task versus rest connectivity differences similar to those with a constant task, suggesting that analysis which includes TPR is more accurately reflective of low-frequency neuronal activity. Both GSR and TPR have been inconsistently applied to fcMRI analysis. Based on these results, investigators need to consider the impact GSR and TPR have on connectivity during task performance when attempting to synthesize the literature.

Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors.

Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.

Synthesis and biological evaluation of phosphonate derivatives as autotaxin (ATX) inhibitors.

Autotaxin (ATX) is an autocrine motility factor that promotes cancer cell invasion, cell migration, and angiogenesis. ATX, originally discovered as a nucleotide phosphodiesterase, is known now to be responsible for the lysophospholipid-preferring phospholipase D activity in plasma. As such, it catalyzes the production of lysophosphatidic acid (LPA) from lysophophatidylcholine (LPC). ATX is thus an attractive drug target; small molecular inhibitors might be efficacious in slowing the spread of cancers. With this study we have generated a series of beta-keto and beta-hydroxy phosphonate derivatives of LPA, some of which are potent ATX inhibitors.

Design and operation of the National Survey of Children with Special Health Care Needs, 2001.

OBJECTIVES: This report presents the development, plan, and operation of the National Survey of Children with Special Health Care Needs (CSHCN), a module of the State and Local Area Integrated Telephone Survey, conducted by the National Center for Health Statistics, Centers for Disease Control and Prevention. This survey was designed to produce national and State-specific prevalence estimates of CSHCN, describe the types of services that they need and use, and assess aspects of the system of care for CSHCN. This study included two additional modules to provide health care coverage estimates for all children and to collect data on the reasons that low-income uninsured children lack health care coverage. Primary funding for this survey was provided by the Maternal and Child Health Bureau, Health Resources and Services Administration. METHODS: A random-digit-dial sample of households with children under 18 years of age was selected from each of the 50 States and the District of Columbia. Depending on the health care needs of the children in each household, a detailed interview was conducted for one randomly selected child with special needs and a brief health insurance interview was conducted for one randomly selected child without special needs. The respondent was the parent or guardian who knew the most about the child's health and health care. RESULTS: A total of 196,888 household screening interviews were completed from October 2000 to April 2002. This resulted in 38,866 completed special-needs interviews and 176,296 completed health insurance interviews for children without special needs. The weighted overall response rate for special-needs interviews was 61.0%.