Comparing the frequency of variants of uncertain significance (VUS) between ancestry groups in a paediatric epilepsy cohort.

BACKGROUND: Studies indicate that variants of uncertain significance are more common in non-European populations due to lack of a diversity in population databases. This difference has not been explored in epilepsy, which is increasingly found to be genetic in paediatric populations, and has precision medicine applications. This study examines the differences in the frequency of uncertain next-generation sequencing (NGS) results among a paediatric epilepsy cohort between ancestral groups historically under-represented in biomedical research (UBR) and represented in biomedical research (RBR). METHODS: A retrospective chart review of patients with epilepsy seen at Columbia University Irving Medical Center (CUIMC). One hundred seventy-eight cases met the following criteria: (1) visited any provider within the Pediatric Neurology Clinic at CUIMC, (2) had an ICD code indicating a diagnosis of epilepsy, (3) underwent NGS testing after March 2015 and (4) had self-reported ancestry that fit into a single dichotomous category of either historically represented or under-represented in biomedical research. RESULTS: UBR cases had significantly higher rates of uncertain results when compared with RBR cases (79.2% UBR, 20.8% RBR; p value=0.002). This finding remained true after controlling for potential confounding factors, including sex, intellectual disability or developmental delay, epilepsy type, age of onset, number of genes tested and year of testing. CONCLUSION: Our results add to the literature that individuals who are of ancestries historically under-represented in genetics research are more likely to receive uncertain genetic results than those of represented majority ancestral groups and establishes this finding in an epilepsy cohort.

A randomized controlled trial of oral antipyretic treatment to reduce overheating during exercise in adults with multiple sclerosis.

BACKGROUND: Some people with multiple sclerosis (pwMS) avoid exercise due to overheating. Evidence from a variety of cooling treatments shows benefits for pwMS. OBJECTIVE: Conduct a randomized controlled trial of antipyretic treatment before exercise in pwMS. METHODS: Adults over age 18 diagnosed with relapsing-remitting MS reporting heat sensitivity during exercise were randomly assigned to one of six sequences counterbalancing aspirin, acetaminophen, placebo. At each of three study visits separated by ≥ one week, participants received 650-millograms of aspirin, acetaminophen, or placebo before completing a maximal exercise test. Primary outcomes were body temperature change and total time-to-exhaustion (TTE), secondary outcomes were physiological and patient-reported outcomes (PROs). RESULTS: Sixty participants were enrolled and assigned to treatment sequence; 37 completed ≥ one study visit. After controlling for order effects, we found that body temperature increase was reduced after aspirin (+ 0.006 ± 0.32 degrees Fahrenheit, p < 0.001) and after acetaminophen (+ 0.31 ± 0.35; p = 0.004) compared to placebo (+ 0.68 ± 0.35). TTE after aspirin (331.6 ± 76.6 s) and acetaminophen (578.2 ± 82.1) did not differ significantly from placebo (551.0 ± 78.4; p's > 0.05). Aspirin benefited all secondary outcomes compared to placebo (all p's < 0.001); acetaminophen showed broadly consistent benefits. CONCLUSION: These results support antipyretic treatment as effective for reducing overheating during exercise in pwMS and failed to support antipyretics for increasing TTE in the context of a maximal exercise test. Benefits were shown for physiological markers of exercise productivity and PROs of fatigue, pain, and perceived exertion.

2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.

BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2024 AHA Statistical Update is the product of a full year's worth of effort in 2023 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. The AHA strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional global data, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Neurocognitive Impairment in Ugandan Children with Sickle Cell Anemia Compared to Sibling Controls: A cross-sectional study.

Introduction: Neurocognitive function in Ugandan children aged 1-12 years with sickle cell anemia (SCA) were compared to their non-SCA siblings to identify risk factors for disease-associated impairment. Methods: This cross-sectional neurocognitive function study of children with SCA (N=242) and non-SCA siblings (N=127) used age- and linguistically-appropriate standardized tests of cognition, executive function and attention for children ages 1-4 and 5-12 years. Test scores were converted to locally derived age-normalized z-scores. The SCA group underwent standardized stroke examination for prior stroke and transcranial doppler ultrasound (TCD) to determine stroke risk by arterial flow velocity. Results: The SCA group was younger than siblings (mean ages 5.46±3.0 versus 7.11±3.51 years, respectively; p <.001), with lower hemoglobin concentration (7.32±1.02 vs. 12.06±1.42, p <.001). Overall cognitive SCA z-scores were lower: -0.73 ±0.98 vs. siblings -0.25 ±1.12 (p<.001), with comparable findings for executive function of -1.09±0.94 versus -0.84±1.26 (p=0.045), respectively. Attention z-scores for ages 5-12 for the SCA group and controls were similar: -0.37±1.4 vs. -0.11±0.17 (p=.09). Overall differences by SCA status were largely driven by the older age group, as z-scores in the younger sub-sample did not differ from controls. Analyses revealed the strongest predictors of poor neurocognitive outcomes among the SCA sample to be the disease, age and prior stroke (each p<.001). Impact from anemia and SCA were indistinguishable. Discussion: Neurocognitive testing in children with SCA compared to non-SCA siblings revealed poorer SCA-associated functioning in children older than age 4. Results indicate need for trials assessing impact from disease modification for children with SCA.

Measures of Aging Biology in Saliva and Blood as Novel Biomarkers for Stroke and Heart Disease in Older Adults.

BACKGROUND AND OBJECTIVES: The role of aging biology as a novel risk factor and biomarker for vascular outcomes in different accessible body tissues such as saliva and blood remain unclear. We aimed to (1) assess the role of aging biology as a risk factor of stroke and heart disease among individuals of same chronologic age and sex and (2) compare aging biology biomarkers measured in different accessible body tissues as novel biomarkers for stroke and heart disease in older adults. METHODS: This study included individuals who consented for blood and saliva draw in the Venous Blood Substudy and Telomere Length Study of the Health and Retirement Study (HRS). The HRS is a population-based, nationally representative longitudinal survey of individuals aged 50 years and older in the United States. Saliva-based measures included telomere length. Blood-based measures included DNA methylation and physiology biomarkers. Propensity scores-matched analyses and Cox regression models were conducted. RESULTS: This study included individuals aged 50 years and older, who consented for blood (N = 9,934) and saliva (N = 5,808) draw in the HRS. Blood-based biomarkers of aging biology showed strong associations with incident stroke as follows: compared with the lowest tertile of blood-based biomarkers of aging, biologically older individuals had significantly higher risk of stroke based on DNA methylation Grim Age clock (adjusted hazard ratio [aHR] = 2.64, 95% CI 1.90-3.66, p < 0.001) and Physiology-based Phenotypic Age clock (aHR = 1.75, 95% CI 1.27-2.42, p < 0.001). In secondary analysis, biologically older individuals had increased risk of heart disease as follows: DNA methylation Grim Age clock (aHR = 1.77, 95% CI 1.49-2.11, p < 0.001) and Physiology-based Phenotypic Age clock (aHR = 1.61, 95% CI 1.36-1.90, p < 0.001). DISCUSSION: Compared with saliva-based telomere length, blood-based aging physiology and some DNA methylation biomarkers are strongly associated with vascular disorders including stroke and are more precise and sensitive biomarkers of aging. Saliva-based telomere length and blood-based DNA methylation and physiology biomarkers likely represent different aspects of biological aging and accordingly vary in their precision as novel biomarkers for optimal vascular health.

Hospital-Acquired Infection at Time of Stroke and Cognitive Decline: The Cardiovascular Health Study.

Introduction Hospital-acquired infections (HAIs) after stroke are associated with additional morbidity and mortality, but whether HAIs increase long-term cognitive decline in stroke patients is unknown. We hypothesized that older adults with incident stroke with HAI experience faster cognitive decline than those having stroke without HAI and those without stroke. Methods We performed a longitudinal analysis in the population-based prospective Cardiovascular Health Study. Medicare-eligible participants aged >65 years with and without incident stroke had cognition assessed annually. HAIs were assessed by hospital discharge codes. Global cognitive function was assessed annually by Modified Mini-Mental State Examination (3MSE) and executive function by Digit Symbol Substitution Test (DSST). We used linear mixed models to estimate the mean decline and 95% confidence intervals (95% CI) for 3MSE and DSST scores by incident stroke and HAI status, adjusted for demographics and vascular risk factors. Results Among 5,443 participants >65 years without previous history of stroke, 393 participants had stroke with HAI (SI), 766 had a stroke only (SO), and 4,284 had no stroke (NS) throughout a maximum 9-year follow-up. For 3MSE, compared with NS participants, SO participants had a similar adjusted mean decline (additional 0.08 points/year, 95%CI -0.15, 0.31), while SI participants had a more rapid decline (additional 0.28 points/year, 95%CI 0.16, 0.40). Adjusted mean decline was 0.20 points/year faster (95%CI -0.05, 0.45) among SI than SO participants. For DSST, compared with NS participants, SO participants had a faster adjusted mean decline (additional 0.17 points/year (95%CI 0.003, 0.33), as did SI participants (additional 0.27 points/year (95%CI 0.19, 0.35). Conclusion Stroke, when accompanied by HAI, leads to a faster long-term decline in cognitive ability than in those without stroke. The clinical and public health implications of the effect of infection on post-stroke cognitive decline warrant further attention.

The association between temperature and alcohol- and substance-related disorder hospital visits in New York State.

BACKGROUND: Limited evidence exists on how temperature increases are associated with hospital visits from alcohol- and substance-related disorders, despite plausible behavioral and physiological pathways. METHODS: In the present study, we implemented a case-crossover design, which controls for seasonal patterns, long-term trends, and non- or slowly-varying confounders, with distributed lag non-linear temperature terms (0-6 days) to estimate associations between daily ZIP Code-level temperature and alcohol- and substance-related disorder hospital visit rates in New York State during 1995-2014. We also examined four substance-related disorder sub-causes (cannabis, cocaine, opioid, sedatives). RESULTS: Here we show that, for alcohol-related disorders, a daily increase in temperature from the daily minimum (-30.1 °C (-22.2 °F)) to the 75th percentile (18.8 °C (65.8 °F)) across 0-6 lag days is associated with a cumulative 24.6% (95%CI,14.6%-34.6%) increase in hospital visit rates, largely driven by increases on the day of and day before hospital visit, with an association larger outside New York City. For substance-related disorders, we find evidence of a positive association at temperatures from the daily minimum (-30.1 °C (-22.2 °F)) to the 50th percentile (10.4 °C (50.7 °F)) (37.7% (95%CI,27.2%-48.2%), but not at higher temperatures. Findings are consistent across age group, sex, and social vulnerability. CONCLUSIONS: Our work highlights how hospital visits from alcohol- and substance-related disorders are currently impacted by elevated temperatures and could be further affected by rising temperatures resulting from climate change. Enhanced social infrastructure and health system interventions could mitigate these impacts.

We investigated the relationship between temperature and hospital visits related to alcohol and other drugs including cannabis, cocaine, opioids, and sedatives in New York State. We found that higher temperatures resulted in more hospital visits for alcohol. For other drugs, higher temperatures also resulted in more hospital visits but only up to a certain temperature level. Our findings suggest that rising temperatures, including those caused by climate change, may influence hospital visits for alcohol and other drugs, emphasizing the need for appropriate and proportionate social and health interventions, as well as highlighting potential hidden burdens of climate change.

Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia.

Cerebrovascular injury frequently occurs in children with sickle cell anaemia (SCA). Limited access to magnetic resonance imaging and angiography (MRI-MRA) in sub-Saharan Africa impedes detection of clinically unapparent cerebrovascular injury. Blood-based brain biomarkers of cerebral infarcts have been identified in non-SCA adults. Using plasma samples from a well-characterized cross-sectional sample of Ugandan children with SCA, we explored relationships between biomarker levels and MRI-detected cerebral infarcts and transcranial Doppler (TCD) arterial velocity. Testing was performed using a 4-plex panel of brain injury biomarkers, including neurofilament light chain (NfL), a central nervous system neuron-specific protein. Mean biomarker levels from the SCA group (n = 81) were similar to those from non-SCA sibling controls (n = 54). Within the SCA group, NfL levels were significantly higher in those with MRI-detected infarcts compared to no infarcts, and higher with elevated TCD velocity versus normal velocity. Elevated NfL remained strongly associated with MRI-detected infarcts after adjusting for sex and age. All non-SCA controls and SCA participants lacking MRI-detected infarcts had low NfL levels. These data suggest potential utility of plasma-based NfL levels to identify children with SCA cerebrovascular injury. Replication and prospective studies are needed to confirm these novel findings and the clinical utility of NfL versus MRI imaging.

Concordance Between Active Partial Thromboplastin Time and Anti-Factor Xa Assays in Neurocritically Ill Patients Receiving Subcutaneous Heparin Prophylaxis.

Background: Laboratory monitoring is not recommended when subcutaneous unfractionated heparin (SQ-UFH) is administered at prophylactic doses. However, aPTT prolongation and associated hemorrhage has been reported in the neurocritically ill. At our institution, Neuroscience Intensive Care Unit (Neuro-ICU) patients with prolonged aPTT are further evaluated with a follow up aPTT and anti-factor Xa. Purpose: The purpose of this study was to describe concordance between aPTT and anti-factor Xa in neurocritically ill patients receiving prophylactic SQ-UFH with evidence of aPTT prolongation. Methods: A retrospective chart review of adult patients admitted to the Neuro-ICU from June 2017 to June 2019 was performed. Patients were included if they received SQ-UFH with aPTT levels and at least one anti-factor Xa level drawn within one hour of each other. Concordance between paired aPTT and anti-factor Xa was evaluated using Cohen's weighted kappa. Results: Forty two patients with 56 paired aPTT and anti-factor Xa levels were included. The most prescribed SQ-UFH regimen was 5000 units every 8 hours (60.7%) and anti-factor Xa levels were drawn a median (IQR) of 5.7 (3.1-10.7) hours after the SQ-UFH dose. Only 16 (28.6%) pairs were in concordance. The analysis showed a weighted kappa of .09; 95% CI [-.05 to .22] indicating poor agreement. Conclusions: In neurocritically ill patients receiving prophylactic SQ-UFH with aPTT prolongation, there was poor concordance between aPTT and anti-factor Xa. This suggests that aPTT prolongation may not be solely driven by heparin activity and further evaluation of mechanistic drivers for coagulopathy in this population is necessary.

Applying principal component pursuit to investigate the association between source-specific fine particulate matter and myocardial infarction hospitalizations in New York City.

The association between fine particulate matter (PM2.5) and cardiovascular outcomes is well established. To evaluate whether source-specific PM2.5 is differentially associated with cardiovascular disease in New York City (NYC), we identified PM2.5 sources and examined the association between source-specific PM2.5 exposure and risk of hospitalization for myocardial infarction (MI). Methods: We adapted principal component pursuit (PCP), a dimensionality-reduction technique previously used in computer vision, as a novel pattern recognition method for environmental mixtures to apportion speciated PM2.5 to its sources. We used data from the NY Department of Health Statewide Planning and Research Cooperative System of daily city-wide counts of MI admissions (2007-2015). We examined associations between same-day, lag 1, and lag 2 source-specific PM2.5 exposure and MI admissions in a time-series analysis, using a quasi-Poisson regression model adjusting for potential confounders. Results: We identified four sources of PM2.5 pollution: crustal, salt, traffic, and regional and detected three single-species factors: cadmium, chromium, and barium. In adjusted models, we observed a 0.40% (95% confidence interval [CI]: -0.21, 1.01%) increase in MI admission rates per 1 µg/m3 increase in traffic PM2.5, a 0.44% (95% CI: -0.04, 0.93%) increase per 1 µg/m3 increase in crustal PM2.5, and a 1.34% (95% CI: -0.46, 3.17%) increase per 1 µg/m3 increase in chromium-related PM2.5, on average. Conclusions: In our NYC study, we identified traffic, crustal dust, and chromium PM2.5 as potentially relevant sources for cardiovascular disease. We also demonstrated the potential utility of PCP as a pattern recognition method for environmental mixtures.

Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2023 Statistical Update is the product of a full year's worth of effort in 2022 by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. The American Heart Association strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional COVID-19 (coronavirus disease 2019) publications, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Epilepsy, Vascular Risk Factors, and Cognitive Decline in Older Adults: The Cardiovascular Health Study.

BACKGROUND AND OBJECTIVES: Recent studies have shown that global cognitive ability tends to decline faster over time in older adults (≥65 years) with epilepsy compared with older adults without epilepsy. Scarce data exist about the role of vascular risk factors (VRFs) on cognitive course in epilepsy. We assessed whether the associations of individual VRFs with cognitive trajectory differed depending on the presence of prevalent epilepsy. METHODS: The Cardiovascular Health Study is a population-based longitudinal cohort study of 5,888 US adults aged ≥65 years. Cognitive function was assessed annually with modified Mini-Mental State Examination (3MS; global cognitive ability) and Digit Symbol Substitution Test (DSST; information processing speed). We used linear mixed models to estimate the individual and joint associations of epilepsy and VRFs with cognitive decline by modeling epilepsy × VRF interactions one by one, each adjusted for all other VRFs considered, including demographics, health behaviors, clinical characteristics, and comorbid diagnoses. From these models, we estimated excess mean cognitive decline due to interaction of epilepsy with each VRF. RESULTS: We observed excess mean decline in global cognitive ability (3MS) due to interactions of epilepsy with hypertension (6.6 points greater mean 8-year decline than expected if no interaction; 95% CI 1.3-12.0) and with abstaining from alcohol (5.8 points greater than expected; 95% CI 0.3-11.3). We also observed excess mean decline in information processing speed (DSST) due to interactions of epilepsy with prior stroke (18.1 points greater mean 9-year decline than expected; 95% CI 7.6-28.5), with abstaining from alcohol (6.1 points greater than expected; 95% CI 2.5-9.8), and with higher triglyceride levels (2.4 points greater than expected per SD; 95% CI 0.4-4.3). DISCUSSION: Associations of some VRFs with cognitive decline in older adults are stronger in the presence of epilepsy, suggesting a need for greater attention to vascular protection for preserving brain health in older adults with epilepsy.

Individual and Joint Effects of Influenza-Like Illness and Vaccinations on Stroke in the Young: A Case-Control Study.

BACKGROUND: Influenza-like illness (ILI) is an acute trigger for stroke, although joint effects of vaccinations and ILI have not yet been explored. METHODS: Data for our case-control study was obtained from MarketScan Commercial Claims and Encounters between 2008 and 2014. Patients 18 to 65 years old who experienced a stroke were matched on age and admission date to a control, defined as patients with head trauma or ankle sprain at an inpatient or emergency department visit. Exposures were ILI in the prior 30 days, and any type of vaccination during the year prior. Our outcome was ischemic and intracerebral hemorrhagic strokes identified using International Classification of Diseases, Ninth Revision (ICD-9) codes. Logistic regression models estimated adjusted odds ratios (aORs) controlling for preventive care visits, diabetes, valvular heart disease, smoking, alcohol abuse, obesity, and hypertension. RESULTS: We identified and matched 24 103 cases 18 to 44 years old and 141 811 45 to 65 years old. Those aged 18 to 44 years had increased stroke risk 30 days after ILI (aOR, 1.68 [95% CI, 1.51-1.86]) and reduced risk with any vaccination in the year prior (aOR, 0.92 [95% CI, 0.87-0.99]). Joint effects indicate that ILI was associated with increased stroke risk among those with (aOR, 1.41 [95% CI, 1.08-1.85]) and without (aOR, 1.73 [95% CI, 1.55-1.94]) vaccinations in the prior year (Pinteraction=0.16). Among those aged 45 to 65 years, adjusted analyses indicate increased stroke risk for those with ILI (aOR, 1.32 [95% CI, 1.26-1.38]), although there was no effect of vaccinations (aOR, 1.00 [95% CI, 0.97-1.02]). Joint effects indicate that ILI was not associated with stroke among those with any vaccination (aOR, 1.07 [95% CI, 0.96-1.18]) but was associated with increased risk among those without vaccinations ([aOR, 1.39 [95% CI, 1.32-1.47]; Pinteraction<0.001). CONCLUSIONS: ILI was associated with increased stroke risk in the young and middle-aged, while vaccinations of any type were associated with decreased risk among the young. Joint effects of ILI and vaccinations indicate vaccinations can reduce the effect of ILI on stroke.

Amyloid, cerebrovascular disease, and neurodegeneration biomarkers are associated with cognitive trajectories in a racially and ethnically diverse, community-based sample.

We characterized the additive contribution of cerebrovascular biomarkers to amyloid and neurodegeneration biomarkers (AV(N)) when modeling prospective, longitudinal cognitive trajectories within 3 major racial/ethnic groups. Participants (n = 172; age = 69-96 years; 62% women; 31%/49%/20% Non-Hispanic White/Non-Hispanic Black/Hispanic) from the Washington Heights-Inwood Columbia Aging Project were assessed for amyloid (Florbetaben PET), neurodegeneration (cortical thickness, hippocampal volume), and cerebrovascular disease (white matter hyperintensity (WMH), infarcts). Neuropsychological assessments occurred every 2.3 ± 0.6 years for up to 6 visits (follow-up time: 4.2 ± 3.2 years). Linear mixed-effects models were stratified by race/ethnicity groups. Higher amyloid was associated with faster memory decline in all 3 racial/ethnic groups, but was related to faster cognitive decline beyond memory in minoritized racial/ethnic groups. Higher WMH was associated with faster language, processing speed/executive function, and visuospatial ability decline in Non-Hispanic Black participants, while infarcts were associated with faster processing speed/executive function decline in Non-Hispanic White participants. Complementary information from AD, neurodegenerative, and cerebrovascular biomarkers explain decline in multiple cognitive domains, which may differ within each racial/ethnic group. Importantly, treatment strategies exist to minimize vascular contributions to cognitive decline.

PM2.5 composition and disease aggravation in amyotrophic lateral sclerosis: An analysis of long-term exposure to components of fine particulate matter in New York State.

Long-term exposure to fine particulate matter (PM2.5) has been associated with disease aggravation in amyotrophic lateral sclerosis (ALS). In this study, we characterized long-term exposure to six major PM2.5 components and their individual association with disease aggravation in ALS. Methods: We leveraged 15 years of data from the New York Department of Health Statewide Planning and Research Cooperative System (2000-2014) to calculate annual ALS first hospitalizations in New York State. We used the first hospital admission as a surrogate of disease aggravation and a prediction model to estimate population-weighted annual black carbon, organic matter (OM), nitrate, sulfate, sea salt, and soil concentrations at the county level. We used a multi-pollutant mixed quasi-Poisson model with county-specific random intercepts to estimate rate ratios (RR) of 1-year exposure to each PM2.5 component and disease aggravation in ALS, adjusting for potential confounders. Results: We observed 5,655 first ALS-related hospitalizations. The annual average hospitalization count per county was 6.08 and the average PM2.5 total mass concentration per county was 8.1 µg/m3-below the United States' National Ambient Air Quality Standard of 12 µg/m3. We found a consistent positive association between ALS aggravation and OM (1.17, 95% confidence intervals [CI], 1.11, 1.24 per standard deviation [SD] increase) and a negative association with soil (RR = 0.91, 95% CI, 0.86, 0.97). Conclusion: Our findings suggest that PM2.5 composition may influence its effect on ALS. We found that annual increases in county-level particulate OM may be associated with disease aggravation in ALS, even at PM2.5 levels below current standards.

Prolonged Unconsciousness is Common in COVID-19 and Associated with Hypoxemia.

OBJECTIVE: The purpose of this study was to estimate the time to recovery of command-following and associations between hypoxemia with time to recovery of command-following. METHODS: In this multicenter, retrospective, cohort study during the initial surge of the United States' pandemic (March-July 2020) we estimate the time from intubation to recovery of command-following, using Kaplan Meier cumulative-incidence curves and Cox proportional hazard models. Patients were included if they were admitted to 1 of 3 hospitals because of severe coronavirus disease 2019 (COVID-19), required endotracheal intubation for at least 7 days, and experienced impairment of consciousness (Glasgow Coma Scale motor score <6). RESULTS: Five hundred seventy-one patients of the 795 patients recovered command-following. The median time to recovery of command-following was 30 days (95% confidence interval [CI] = 27-32 days). Median time to recovery of command-following increased by 16 days for patients with at least one episode of an arterial partial pressure of oxygen (PaO2 ) value ≤55 mmHg (p < 0.001), and 25% recovered ≥10 days after cessation of mechanical ventilation. The time to recovery of command-following  was associated with hypoxemia (PaO2 ≤55 mmHg hazard ratio [HR] = 0.56, 95% CI = 0.46-0.68; PaO2 ≤70 HR = 0.88, 95% CI = 0.85-0.91), and each additional day of hypoxemia decreased the likelihood of recovery, accounting for confounders including sedation. These findings were confirmed among patients without any imagining evidence of structural brain injury (n = 199), and in a non-overlapping second surge cohort (N = 427, October 2020 to April 2021). INTERPRETATION: Survivors of severe COVID-19 commonly recover consciousness weeks after cessation of mechanical ventilation. Long recovery periods are associated with more severe hypoxemia. This relationship is not explained by sedation or brain injury identified on clinical imaging and should inform decisions about life-sustaining therapies. ANN NEUROL 2022;91:740-755.

Brain Magnetic Resonance Imaging and Angiography in Children with Sickle Cell Anaemia in Uganda in a Cross-Sectional Sample.

OBJECTIVE: Children with sickle cell anaemia (SCA) are highly susceptible to cerebrovascular injury. We performed brain magnetic resonance imaging and angiography (MRI-MRA) in Ugandan children with SCA to identify structural cerebrovascular abnormalities and examine their relationship to standardized clinical assessments. METHODS: A sub-sample (n=81) was selected from a cross-sectional study of children attending SCA clinic, including 52 (64.2%) with and 29 (35.8%) without clinically detected abnormalities. Clinical evaluation included assessment for prior stroke, cognitive testing and cerebral arterial transcranial doppler (TCD) flow velocity. MRI-MRA scans were interpreted by at least two neuroradiologists. RESULTS: Mean age was 6.5±2.7 years, with 39 (48.1%) female. Mean haemoglobin was 7.3±0.9 g/dl. Overall, 13 (16.0%) were malnourished. Infarcts and/or stenoses were detected in 55 (67.9%) participants, with stenoses primarily in the anterior circulation. Infarcts were seen in those with normal 17/29 (58.6%) or abnormal 34/52 (65.4%) clinical testing (p=0.181). Neither abnormal MRI nor MRA was associated with age, sex, haemoglobin, or malnutrition. Abnormal MRA was highly associated with infarcts (p<0.0001). Participants with abnormal imaging had two-fold higher proportion of stroke on exam and/or impaired cognition. Stroke on exam was strongly associated with an imaging abnormality after adjusting for age, sex, malnutrition, and haemoglobin (OR 11.8, 95%CI 1.87-74.2). CONCLUSION: Over half of these SCA children had cerebrovascular infarcts and/or arterial stenoses. Cerebrovascular disease was frequently undetectable by clinical assessments. While rarely available in under-resourced settings, MRI-MRA brain imaging is an important tool for defining SCA cerebrovascular disease and for assessing impact of clinical intervention trials.

Rural-Urban Differences in Diagnosed Cervical Artery Dissection in New York State.

BACKGROUND: Cervical artery dissection (CeAD) is a leading cause of stroke in young adults. Incidence estimates may be limited by under- or overdiagnosis. OBJECTIVE: We aimed to investigate if CeAD diagnosis would be higher in urban centers compared to rural regions of New York State (NYS). METHODS: For this ecological study, administrative codes were used to identify CeAD discharges in the NYS Statewide Planning and Research Cooperative System (SPARCS) from 2009 to 2014. Rural Urban Commuting Area (RUCA) codes were taken from the US Department of Agriculture and included the classifications metropolitan, micropolitan, small town, and rural. Negative binomial models were used to calculate effect estimates and 95% confidence limits (eß; 95% CL) for the association between RUCA classification and the number of dissections per ZIP code. Models were further adjusted by population. RESULTS: Population information was obtained from the US Census Bureau on 1,797 NYS ZIP codes (70.7% of NYS ZIP codes), 826 of which had at least 1 CeAD-related discharge from 2009 to 2014. Nonrural ZIP codes were more likely to report more CeAD cases relative to rural areas even after adjusting for population (metropolitan effect = eß 5.00; 95% CI: 3.75-6.66; micropolitan effect 3.02; 95% CI: 2.16-4.23; small town effect 2.34; 95% CI: 1.58-3.47). CONCLUSIONS: CeAD diagnosis correlates with population density as defined by rural-urban status. Our results could be due to underdiagnosis in rural areas or overdiagnosis with increasing urbanicity.

Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2022 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population and an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, and the global burden of cardiovascular disease and healthy life expectancy. RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Disorders of Consciousness in Hospitalized Patients with COVID-19: The Role of the Systemic Inflammatory Response Syndrome.

BACKGROUND: Prevalence and etiology of unconsciousness are uncertain in hospitalized patients with coronavirus disease 2019 (COVID-19). We tested the hypothesis that increased inflammation in COVID-19 precedes coma, independent of medications, hypotension, and hypoxia. METHODS: We retrospectively assessed 3203 hospitalized patients with COVID-19 from March 2 through July 30, 2020, in New York City with the Glasgow Coma Scale and systemic inflammatory response syndrome (SIRS) scores. We applied hazard ratio (HR) modeling and mediation analysis to determine the risk of SIRS score elevation to precede coma, accounting for confounders. RESULTS: We obtained behavioral assessments in 3203 of 10,797 patients admitted to the hospital who tested positive for SARS-CoV-2. Of those patients, 1054 (32.9%) were comatose, which first developed on median hospital day 2 (interquartile range [IQR] 1-9). During their hospital stay, 1538 (48%) had a SIRS score of 2 or above at least once, and the median maximum SIRS score was 2 (IQR 1-2). A fivefold increased risk of coma (HR 5.05, 95% confidence interval 4.27-5.98) was seen for each day that patients with COVID-19 had elevated SIRS scores, independent of medication effects, hypotension, and hypoxia. The overall mortality in this population was 13.8% (n = 441). Coma was associated with death (odds ratio 7.77, 95% confidence interval 6.29-9.65) and increased length of stay (13 days [IQR 11.9-14.1] vs. 11 [IQR 9.6-12.4]), accounting for demographics. CONCLUSIONS: Disorders of consciousness are common in hospitalized patients with severe COVID-19 and are associated with increased mortality and length of hospitalization. The underlying etiology of disorders of consciousness in this population is uncertain but, in addition to medication effects, may in part be linked to systemic inflammation.