Epidemiologic Features of Recovery From SARS-CoV-2 Infection.

Importance: Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden. Objective: To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days. Design, Setting, and Participants: For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection. Exposure: Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires. Main Outcomes and Measures: Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days. Results: Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections. Conclusions and Relevance: In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.

Diabetes mellitus and hard braking events in older adult drivers.

BACKGROUND: Diabetes mellitus (DM) can impair driving safety due to hypoglycemia, hyperglycemia, diabetic peripheral neuropathy, and diabetic eye diseases. However, few studies have examined the association between DM and driving safety in older adults based on naturalistic driving data. METHODS: Data for this study came from a multisite naturalistic driving study of drivers aged 65-79 years at baseline. Driving data for the study participants were recorded by in-vehicle recording devices for up to 44 months. We used multivariable negative binomial modeling to estimate adjusted incidence rate ratios (aIRRs) and 95% confidence intervals (CIs) of hard braking events (HBEs, defined as maneuvers with deceleration rates ≥ 0.4 g) associated with DM. RESULTS: Of the 2856 study participants eligible for this analysis, 482 (16.9%) reported having DM at baseline, including 354 (12.4%) insulin non-users and 128 (4.5%) insulin users. The incidence rates of HBEs per 1000 miles were 1.13 for drivers without DM, 1.15 for drivers with DM not using insulin, and 1.77 for drivers with DM using insulin. Compared to drivers without DM, the risk of HBEs was 48% higher for drivers with DM using insulin (aIRR 1.48; 95% CI: 1.43, 1.53). CONCLUSION: Older adult drivers with DM using insulin appear to be at increased proneness to vehicular crashes. Driving safety should be taken into consideration in DM care and management.

Examining the Impact of the Innovative Opioid Court Model on Treatment Access and Court Outcomes for Court Participants.

OBJECTIVE: The opioid intervention court (OIC) is an innovative, pre-plea treatment court to facilitate rapid linkage to medications for opioid use disorder (MOUD) for people at risk of overdose. This study compares participants in OIC and participants with opioid use problems in a traditional drug treatment court model on (i) initiation for any substance use (SU) treatment, (ii) initiation of MOUD, (iii) number of days to MOUD initiation, and (iv) retention in the OIC program/retention on MOUD. METHODS: We used administrative court records from n = 389 OIC and n = 229 drug court participants in 2 counties in New York State. Differences in outcomes by court were assessed using logistic, multinomial, or linear regressions. RESULTS: After adjusting for current charge severity, gender, race/ethnicity, age, and county, OIC participants were no more likely to initiate any SU treatment but were significantly more likely to initiate MOUD (81.2% OIC vs 45.9% drug court, P < 0.001) and were more quickly linked to any SU treatment (hazard ratio = 1.68, 95% confidence interval = 1.35-2.08) and MOUD (hazard ratio = 4.25, 95% confidence interval = 3.23-5.58) after starting the court. Retention in court/MOUD was higher among drug court participants and may speak to the immediate sanctions (eg, jail) for noncompliance with drug court directives as compared with opioid court, which does not carry such immediate sanctions for noncompliance. CONCLUSIONS: These analyses suggest that the new OIC model can more rapidly link participants to treatment, including MOUD, as compared with traditional drug court model, and may demonstrate improved ability to immediately stabilize and reduce overdose risk in court participants.

The Legacy of Redlining: Increasing Childhood Asthma Disparities Through Neighborhood Poverty.

RATIONALE: Identifying the root causes of racial disparities in childhood asthma is critical for health equity. OBJECTIVES: To determine if the 1930's racist policy of redlining led to present-day disparities in childhood asthma by increasing community-level poverty and decreasing neighborhood socioeconomic position (SEP). METHODS: We categorized census tracts at birth of participants from the Children's Respiratory and Environmental Workgroup birth cohort consortium into A, B, C, or D categories as defined by the Home Owners Loan Corporation (HOLC), with D being the highest perceived risk. Surrogates of present-day neighborhood-level SEP were determined for each tract including the percentage of low-income households, the CDC's social vulnerability index (SVI), and other tract-level variables. We performed causal mediation analysis, which, under the assumption of no unmeasured confounding, estimates the direct and mediated pathways by which redlining may cause asthma disparities through census tract-level mediators adjusting for individual-level covariates. MEASUREMENTS AND MAIN RESULTS: Of 4,849 children, the cumulative incidence of asthma through age 11 was 26.6% and 13.2% resided in census tracts with a HOLC grade of D. In mediation analyses, residing in grade D tracts (aOR = 1.03 [95%CI 1.01,1.05]) was significantly associated with childhood asthma, with 79% of this increased risk mediated by percentage of low-income households; results were similar for SVI and other tract-level variables. CONCLUSIONS: The historical structural racist policy of redlining led to present-day asthma disparities in part through decreased neighborhood SEP. Policies aimed at reversing the effects of structural racism should be considered to create more just, equitable, and healthy communities.

Sleep-wake behavior, perceived fatigability, and cognitive reserve in older adults.

INTRODUCTION: The effects of sleep-wake behavior on perceived fatigability and cognitive abilities when performing daily activities have not been investigated across levels of cognitive reserve (CR). METHODS: CR Index Questionnaire (CRIq) data were collected and subjected to moderated mediation analysis. RESULTS: In amnestic mild cognitive impairment (aMCI; n = 41), CR moderated sleep-related impairments (SRIs), and fatigability at low CR (CRIq < 105.8, p = 0.004) and mean CR (CRIq = 126.9, p = 0.03) but not high CR (CRIq > 145.9, p = 0.65) levels. SRI affected cognitive abilities mediated by fatigability at low CR (p < 0.001) and mean CR (p = 0.003) levels. In healthy controls (n = 13), SRI in fatigability did not alter cognitive abilities across CR levels; controls had higher leisure scores than patients with aMCI (p = 0.003, effect size = 0.93). DISCUSSION: SRI can amplify impaired cognitive abilities through exacerbation of fatigability in patients with aMCI with below-mean CR. Therefore, improving sleep-wake regulation and leisure activities may protect against fatigability and cognitive decline. HIGHLIGHTS: Clinical fatigue and fatigability cannot be alleviated by rest. Clinical fatigability disrupts daily activities during preclinical Alzheimer's. High cognitive reserve mitigates sleep-wake disturbance effects. High cognitive reserve attenuates clinical fatigability effects on daily functioning. Untreated obstructive sleep apnea potentiates Alzheimer's pathology in the brain.

Association between polypharmacy and hard braking events in older adult drivers.

BACKGROUND: Polypharmacy (i.e., simultaneous use of two or more medications) poses a serious safety concern for older drivers. This study assesses the association between polypharmacy and hard braking events in older adult drivers. METHODS: Data for this study came from a naturalistic driving study of 2990 older adults. Information about medications was collected through the "brown-bag review" method. Primary vehicles of the study participants were instrumented with data recording devices for up to 44 months. Multivariable negative binomial model was used to estimate the adjusted incidence rate ratios (aIRRs) and 95 % confidence intervals (CIs) of hard-braking events (i.e., maneuvers with linear deceleration rates ≥0.4 g) associated with polypharmacy. RESULTS: Of the 2990 participants, 2872 (96.1 %) were eligible for this analysis. At the time of enrollment, 157 (5.5 %) drivers were taking fewer than two medications, 904 (31.5 %) were taking 2-5 medications, 895 (31.2 %) were taking 6-9 medications, 571 (19.9 %) were taking 10-13 medications, and 345 (12.0 %) were taking 14 or more medications. Compared to drivers using fewer than two medications, the risk of hard-braking events increased 8 % (aIRR 1.08, 95 % CI 1.04, 1.13) for users of 2-5 medications, 12 % (aIRR 1.12, 95 % CI 1.08, 1.16) for users of 6-9 medications, 19 % (aIRR 1.19, 95 % CI 1.15, 1.24) for users of 10-13 medications, and 34 % (aIRR 1.34, 95 % CI 1.29, 1.40) for users of 14 or more medications. CONCLUSIONS: Polypharmacy in older adult drivers is associated with significantly increased incidence of hard-braking events in a dose-response fashion. Effective interventions to reduce polypharmacy use may help improve driving safety in older adults.

Frailty and poor physical functioning as risk factors for driving cessation.

Introduction: Frailty and low physical performance are modifiable factors and, therefore, targets for interventions aimed at delaying driving cessation (DC). The objective was to determine the impact of frailty and physical performance on DC. Methods: Multisite prospective cohort of older drivers. The key inclusion criteria are as follows: active driver age 65-79 years, possessing a valid driver's license, without significant cognitive impairment, and driving a 1996 car or a newer model car. Of the 2,990 enrolled participants, 2,986 (99.9%) had at least one frailty or Short Physical Performance Battery (SPPB) measure and were included in this study. In total, 42% of participants were aged 65-69 years, 86% were non-Hispanic white, 53% were female, 63% were married, and 41% had a high degree of education. The Fried Frailty Phenotype and the Expanded Short Physical Performance Battery (SPPB) from the National Health and Aging Trends Study were utilized. At each annual visit, DC was assessed by the participant notifying the study team or self-reporting after no driving activity for at least 30 days, verified via GPS. Cox proportional hazard models, including time-varying covariates, were used to examine the impact of the SPPB and frailty scores on time to DC. This assessment included examining interactions by sex. Results: Seventy-three participants (2.4%) stopped driving by the end of year 5. Among women with a fair SPPB score, the adjusted hazard ratio (HR) of DC was 0.26 (95% confidence interval (CI) 0.10-0.65) compared to those with a poor SPPB score. For those with a good SPPB score, the adjusted HR of DC had a p-value of <0.001. Among men with a fair SPPB score, the adjusted hazard ratio (HR) of DC was 0.45 (95% CI 0.25-0.81) compared to those with a poor SPPB score. For men with a good SPPB score, the adjusted HR of DC was 0.19 (95% CI 0.10-0.36). Sex was not an effect modifier between frailty and DC. For those who were categorized into pre-frail or frail, the adjusted ratio of HR to DC was 6.1 (95% CI 2.7-13.8) compared to those who were not frail. Conclusion and relevance: Frailty and poor physical functioning are major risk factors for driving cessation. Staying physically active may help older adults to extend their driving life expectancy and mobility.

Change in parental knowledge and beliefs about early childhood dental caries following a pragmatic community-based trial.

OBJECTIVES: To evaluate parent knowledge and belief changes following the MySmileBuddy (MSB) early childhood caries (ECC) intervention. METHODS: Pre- and post-intervention surveys were completed by 669 parents of children with visually-evident ECC from among 977 participants in a 6-12-month pragmatic community-based caries management trial administered by community health workers (CHWs). Six domains of knowledge about caries and motivating and facilitating determinants were assessed via 26 survey items. Principal components analysis and reliability testing reduced dataset dimensionality. Parent and CHW characteristics were analyzed as potential moderators. Paired T-tests measured pre-to-post-intervention changes. Generalized estimating equations accounted for within-participant correlation with significance set at p < 0.05. RESULTS: Twenty items consolidated into five factors (saliva, hygiene, diet, seriousness/susceptibility, and outcome expectations). Six additional items were evaluated individually. Positive post-intervention changes (p < 0.0001) were observed across all factors and all but one individual item (tooth decay is very common). Greatest knowledge increases related to caries as a bacterial disease in two measures, the saliva factor and a single caries belief item tooth decay is an infectious disease (0.59 unit increase, 95% CI [0.55, 0.64] and 0.46 unit increase, 95% CI [0.4, 0.51], respectively), and in the value of fluoridated water over bottled (0.46 unit increase, 95% CI [0.39-0.53]). Most parents improved knowledge of ECC salivary (72%) and dietary risks (57%), and preventative hygiene behaviors (59%). CONCLUSIONS: MSB enhanced knowledge and beliefs about caries and confirmed hypothesized mediators of behavior change among parents of high-risk children. Engaging peer-like CHW interventionists may have moderated intervention effects, warranting further exploration.

Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome.

INTRODUCTION: Virtually all people with Down syndrome (DS) develop neuropathology associated with Alzheimer's disease (AD). Atrophy of the hippocampus and entorhinal cortex (EC), as well as elevated plasma concentrations of neurofilament light chain (NfL) protein, are markers of neurodegeneration associated with late-onset AD. We hypothesized that hippocampus and EC gray matter loss and increased plasma NfL concentrations are associated with memory in adults with DS. METHODS: T1-weighted structural magnetic resonance imaging (MRI) data were collected from 101 participants with DS. Hippocampus and EC volume, as well as EC subregional cortical thickness, were derived. In a subset of participants, plasma NfL concentrations and modified Cued Recall Test scores were obtained. Partial correlation and mediation were used to test relationships between medial temporal lobe (MTL) atrophy, plasma NfL, and episodic memory. RESULTS: Hippocampus volume, left anterolateral EC (alEC) thickness, and plasma NfL were correlated with each other and were associated with memory. Plasma NfL mediated the relationship between left alEC thickness and memory as well as hippocampus volume and memory. DISCUSSION: The relationship between MTL gray matter and memory is mediated by plasma NfL levels, suggesting a link between neurodegenerative processes underlying axonal injury and frank gray matter loss in key structures supporting episodic memory in people with DS.

Early-Life Exposure to Air Pollution and Childhood Asthma Cumulative Incidence in the ECHO CREW Consortium.

Importance: Exposure to outdoor air pollution contributes to childhood asthma development, but many studies lack the geographic, racial and ethnic, and socioeconomic diversity to evaluate susceptibility by individual-level and community-level contextual factors. Objective: To examine early life exposure to fine particulate matter (PM2.5) and nitrogen oxide (NO2) air pollution and asthma risk by early and middle childhood, and whether individual and community-level characteristics modify associations between air pollution exposure and asthma. Design, Setting, and Participants: This cohort study included children enrolled in cohorts participating in the Children's Respiratory and Environmental Workgroup consortium. The birth cohorts were located throughout the US, recruited between 1987 and 2007, and followed up through age 11 years. The survival analysis was adjusted for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, neighborhood characteristics, and cohort. Statistical analysis was performed from February 2022 to December 2023. Exposure: Early-life exposures to PM2.5 and NO2 according to participants' birth address. Main Outcomes and Measures: Caregiver report of physician-diagnosed asthma through early (age 4 years) and middle (age 11 years) childhood. Results: Among 5279 children included, 1659 (31.4%) were Black, 835 (15.8%) were Hispanic, 2555 (48.4%) where White, and 229 (4.3%) were other race or ethnicity; 2721 (51.5%) were male and 2596 (49.2%) were female; 1305 children (24.7%) had asthma by 11 years of age and 954 (18.1%) had asthma by 4 years of age. Mean values of pollutants over the first 3 years of life were associated with asthma incidence. A 1 IQR increase in NO2 (6.1 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.25 [95% CI, 1.03-1.52]) and children younger than 11 years (HR, 1.22 [95% CI, 1.04-1.44]). A 1 IQR increase in PM2.5 (3.4 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.31 [95% CI, 1.04-1.66]) and children younger than 11 years (OR, 1.23 [95% CI, 1.01-1.50]). Associations of PM2.5 or NO2 with asthma were increased when mothers had less than a high school diploma, among Black children, in communities with fewer child opportunities, and in census tracts with higher percentage Black population and population density; for example, there was a significantly higher association between PM2.5 and asthma incidence by younger than 5 years of age in Black children (HR, 1.60 [95% CI, 1.15-2.22]) compared with White children (HR, 1.17 [95% CI, 0.90-1.52]). Conclusions and Relevance: In this cohort study, early life air pollution was associated with increased asthma incidence by early and middle childhood, with higher risk among minoritized families living in urban communities characterized by fewer opportunities and resources and multiple environmental coexposures. Reducing asthma risk in the US requires air pollution regulation and reduction combined with greater environmental, educational, and health equity at the community level.

Impact of driving cessation on health-related quality of life trajectories.

BACKGROUND: Trajectories of health-related quality of life (HRQoL) after driving cessation (DC) are thought to decline steeply, but for some, HRQoL may improve after DC. Our objective is to examine trajectories of HRQoL for individuals before and after DC. We hypothesize that for urban drivers, volunteers and those who access alternative transportation participants' health may remain unchanged or improve. METHODS: This study uses data from the AAA Longitudinal Research on Aging Drivers (LongROAD) study, a prospective cohort of 2,990 older drivers (ages 65-79 at enrollment). The LongROAD study is a five-year multisite study and data collection ended October 31, 2022. Participants were recruited using a convenience sample from the health centers roster. The number of participants approached were 40,806 with 7.3% enrolling in the study. Sixty-one participants stopped driving permanently by year five and had data before and after DC. The PROMIS®-29 Adult Profile was utilized and includes: 1) Depression, 2) Anxiety, 3) Ability to Participate in Social Roles and Activities, 4) Physical Function, 5) Fatigue, 6) Pain Interference, 7) Sleep Disturbance, and 8) Numeric Pain Rating Scale. Adjusted (age, education and gender) individual growth models with 2989 participants with up to six observations from baseline to year 5 in the models (ranging from n = 15,041 to 15,300) were utilized. RESULTS: Ability to participate in social roles and activities after DC improved overall. For those who volunteered, social roles and activities declined not supporting our hypothesis. For those who accessed alternative transportation, fatigue had an initial large increase immediately following DC thus not supporting our hypothesis. Urban residents had worse function and more symptoms after DC compared to rural residents (not supporting our hypothesis) except for social roles and activities that declined steeply (supporting our hypothesis). CONCLUSIONS: Educating older adults that utilizing alternative transportation may cause initial fatigue after DC is recommended. Accessing alternative transportation to maintain social roles and activities is paramount for rural older adults after DC especially for older adults who like to volunteer.

Periodontitis and brain magnetic resonance imaging markers of Alzheimer's disease and cognitive aging.

INTRODUCTION: We examined the association of clinical, microbiological, and host response features of periodontitis with MRI markers of atrophy/cerebrovascular disease in the Washington Heights Inwood Columbia Aging Project (WHICAP) Ancillary Study of Oral Health. METHODS: We analyzed 468 participants with clinical periodontal data, microbial plaque and serum samples, and brain MRIs. We tested the association of periodontitis features with MRI features, after adjusting for multiple risk factors for Alzheimer's disease/Alzheimer's disease-related dementia (AD/ADRD). RESULTS: In fully adjusted models, having more teeth was associated with lower odds for infarcts, lower white matter hyperintensity (WMH) volume, higher entorhinal cortex volume, and higher cortical thickness. Higher extent of periodontitis was associated with lower entorhinal cortex volume and lower cortical thickness. Differential associations emerged between colonization by specific bacteria/serum antibacterial IgG responses and MRI outcomes. DISCUSSION: In an elderly cohort, clinical, microbiological, and serological features of periodontitis were associated with MRI findings related to ADRD risk. Further investigation of causal associations is warranted.

Association of brain arterial diameters with demographic and anatomical factors in a multi-national pooled analysis of cohort studies.

BACKGROUND AND PURPOSE: Brain arterial diameters are markers of cerebrovascular disease. Demographic and anatomical factors may influence arterial diameters. We hypothesize that age, sex, height, total cranial volume (TCV), and persistent fetal posterior cerebral artery (fPCA) correlate with brain arterial diameters across populations. METHODS: Participants had a time-of-flight MRA from nine international cohorts. Arterial diameters of the cavernous internal carotid arteries (ICA), middle cerebral arteries (MCA), and basilar artery (BA) were measured using LAVA software. Regression models assessed the association between exposures and brain arterial diameters. RESULTS: We included 6,518 participants (mean age: 70 ± 9 years; 41% men). Unilateral fPCA was present in 13.2% and bilateral in 3.2%. Larger ICA, MCA, and BA diameters correlated with older age (Weighted average [WA] per 10 years: 0.18 mm, 0.11 mm, and 0.12 mm), male sex (WA: 0.24 mm, 0.13 mm, and 0.21 mm), and TCV (WA: for one TCV standard deviation: 0.24 mm, 0.29 mm, and 0.18 mm). Unilateral and bilateral fPCAs showed a positive correlation with ICA diameters (WA: 0.39 mm and 0.73 mm) and negative correlation with BA diameters (WA: -0.88 mm and -1.73 mm). Regression models including age, sex, TCV, and fPCA explained on average 15%, 13%, and 25% of the ICA, MCA, and BA diameter interindividual variation, respectively. Using height instead of TCV as a surrogate of head size decreased the R-squared by 3% on average. CONCLUSION: Brain arterial diameters correlated with age, sex, TCV, and fPCA. These factors should be considered when defining abnormal diameter cutoffs across populations.

Chromosome 10q24.32 Variants Associate With Brain Arterial Diameters in Diverse Populations: A Genome-Wide Association Study.

BACKGROUND: Brain arterial diameters (BADs) are novel imaging biomarkers of cerebrovascular disease, cognitive decline, and dementia. Traditional vascular risk factors have been associated with BADs, but whether there may be genetic determinants of BADs is unknown. METHODS AND RESULTS: The authors studied 4150 participants from 6 geographically diverse population-based cohorts (40% European, 14% African, 22% Hispanic, 24% Asian ancestries). Brain arterial diameters for 13 segments were measured and averaged to obtain a global measure of BADs as well as the posterior and anterior circulations. A genome-wide association study revealed 14 variants at one locus associated with global BAD at genome-wide significance (P<5×10-8) (top single-nucleotide polymorphism, rs7921574; ß=0.06 [P=1.54×10-8]). This locus mapped to an intron of CNNM2. A trans-ancestry genome-wide association study meta-analysis identified 2 more loci at NT5C2 (rs10748839; P=2.54×10-8) and AS3MT (rs10786721; P=4.97×10-8), associated with global BAD. In addition, 2 single-nucleotide polymorphisms colocalized with expression of CNNM2 (rs7897654; ß=0.12 [P=6.17×10-7]) and AL356608.1 (rs10786719; ß=-0.17 [P=6.60×10-6]) in brain tissue. For the posterior BAD, 2 variants at one locus mapped to an intron of TCF25 were identified (top single-nucleotide polymorphism, rs35994878; ß=0.11 [P=2.94×10-8]). For the anterior BAD, one locus at ADAP1 was identified in trans-ancestry genome-wide association analysis (rs34217249; P=3.11×10-8). CONCLUSIONS: The current study reveals 3 novel risk loci (CNNM2, NT5C2, and AS3MT) associated with BADs. These findings may help elucidate the mechanism by which BADs may influence cerebrovascular health.

Motor Vehicle Crash Risk in Older Adult Drivers With Attention-Deficit/Hyperactivity Disorder.

Importance: Symptoms of attention-deficit/hyperactivity disorder (ADHD), such as inattentiveness and impulsivity, could affect daily functioning and driving performance throughout the life span. Previous research on ADHD and driving safety is largely limited to adolescents and young adults. Objective: To examine the prevalence of ADHD and the association between ADHD and crash risk among older adult drivers. Design, Setting, and Participants: This prospective cohort study collected data from primary care clinics and residential communities in 5 US sites (Ann Arbor, Michigan; Baltimore, Maryland; Cooperstown, New York; Denver, Colorado; and San Diego, California) between July 6, 2015, and March 31, 2019. Participants were active drivers aged 65 to 79 years at baseline enrolled in the Longitudinal Research on Aging Drivers project who were studied for up to 44 months through in-vehicle data recording devices and annual assessments. The data analysis was performed between July 15, 2022, and August 14, 2023. Exposure: Lifetime ADHD based on an affirmative response to the question of whether the participant had ever had ADHD or had ever been told by a physician or other health professional that he or she had ADHD. Main Outcomes and Measures: The main outcomes were hard-braking events defined as maneuvers with deceleration rates of 0.4g or greater, self-reported traffic ticket events, and self-reported vehicular crashes. Multivariable negative binomial modeling was used to estimate adjusted incidence rate ratios (aIRRs) and 95% CIs of outcomes according to exposure status. Results: Of the 2832 drivers studied, 1500 (53.0%) were women and 1332 (47.0%) were men with a mean (SD) age of 71 (4) years. The lifetime prevalence of ADHD in the study sample was 2.6%. Older adult drivers with ADHD had significantly higher incidence rates of hard-braking events per 1000 miles than those without ADHD (1.35 [95% CI, 1.30-1.41] vs 1.15 [95% CI, 1.14-1.16]), as well as self-reported traffic ticket events per 1 million miles (22.47 [95% CI, 16.06-31.45] vs 9.74 [95% CI, 8.99-10.55]) and self-reported vehicular crashes per 1 million miles (27.10 [95% CI, 19.95-36.80] vs 13.50 [95% CI, 12.61-14.46]). With adjustment for baseline characteristics, ADHD was associated with a significant 7% increased risk of hard-braking events (aIRR, 1.07; 95% CI, 1.02-1.12), a 102% increased risk of self-reported traffic ticket events (aIRR, 2.02; 95% CI, 1.42-2.88), and a 74% increased risk of self-reported vehicular crashes (aIRR, 1.74; 95% CI, 1.26-2.40). Conclusions and Relevance: As observed in this prospective cohort study, older adult drivers with ADHD may be at a significantly elevated crash risk compared with their counterparts without ADHD. These findings suggest that effective interventions to improve the diagnosis and clinical management of ADHD among older adults are warranted to promote safe mobility and healthy aging.

Sensory Symptoms and Signs of Hyperarousal in Individuals with Fragile X Syndrome: Findings from the FORWARD Registry and Database Multisite Study.

This study was designed to increase our understanding about characteristics and the impact of sensory symptoms (SS) and signs of hyperarousal (HA) in individuals with fragile X syndrome (FXS) from childhood through early adulthood and by gender. Data derived from the Fragile X Online Registry With Accessible Research Database (FORWARD), a natural history study of FXS, were analyzed using descriptive statistics and multivariate linear and logistic regression models to examine SS and signs of HA, their impact on behavioral regulation and limitations on the subject/family. The sample (N = 933) consisted of 720 males and 213 females. More males were affected with SS (87% vs. 68%) and signs of HA (92% vs. 79%). Subjects who were endorsed as having a strong sensory response had more comorbidities, including behavioral problems. The predominant SS was difficulty with eye gaze that increased with age in both genders. As individuals age, there was less use of non-medication therapies, such as occupational therapy (OT)/physical therapy (PT), but there was more use of psychopharmacological medications and investigational drugs for behaviors. Multiple regression models suggested that endorsing SS and signs of HA was associated with statistically significantly increased ABC-C-I subscale scores and limited participation in everyday activities. This study improves our understanding of SS and signs of HA as well as their impact in FXS. It supports the need for more research regarding these clinical symptoms, especially to understand how they contribute to well-known behavioral concerns.

Longitudinal Impact of the COVID-19 Pandemic on Stress and Occupational Well-Being of Mental Health Professionals: An International Study.

BACKGROUND: Increased levels of occupational stress among health professionals during the COVID-19 pandemic have been documented. Few studies have examined the effects of the pandemic on mental health professionals despite the heightened demand for their services. METHOD: A multilingual, longitudinal, global survey was conducted at 3 time points during the pandemic among members of the World Health Organization's Global Clinical Practice Network. A total of 786 Global Clinical Practice Network members from 86 countries responded to surveys assessing occupational distress, well-being, and posttraumatic stress symptoms. RESULTS: On average, respondents' well-being deteriorated across time while their posttraumatic stress symptoms showed a modest improvement. Linear growth models indicated that being female, being younger, providing face-to-face health services to patients with COVID-19, having been a target of COVID-related violence, and living in a low- or middle-income country or a country with a higher COVID-19 death rate conveyed greater risk for poor well-being and higher level of stress symptoms over time. Growth mixed modeling identified trajectories of occupational well-being and stress symptoms. Most mental health professions demonstrated no impact to well-being; maintained moderate, nonclinical levels of stress symptoms; or showed improvements after an initial period of difficulty. However, some participant groups exhibited deteriorating well-being approaching the clinical threshold (25.8%) and persistently high and clinically significant levels of posttraumatic stress symptoms (19.6%) over time. CONCLUSIONS: This study indicates that although most mental health professionals exhibited stable, positive well-being and low stress symptoms during the pandemic, a substantial minority of an already burdened global mental health workforce experienced persistently poor or deteriorating psychological status over the course of the pandemic.

Interaction between benzodiazepines and prescription opioids on incidence of hard braking events in older drivers.

BACKGROUND: Polypharmacy use among older adults is of increasing concern for driving safety. This study assesses the individual and joint effects of benzodiazepines and prescription opioids on the incidence of hard braking events in older drivers. METHODS: Data for this study came from the Longitudinal Research on Aging Drivers project-a multisite, prospective cohort study of 2990 drivers aged 65-79 years at enrollment (2015-2017). Adjusted incidence rate ratios (aIRRs) and 95% confidence intervals (CIs) of hard braking events (defined as maneuvers with deceleration rates ≥0.4 g and commonly known as near-crashes) were estimated through multivariable negative binominal modeling. RESULTS: Of the 2929 drivers studied, 167 (5.7%) were taking benzodiazepines,  163 (5.6%) prescription opioids, and 23 (0.8%) both drugs at baseline. The incidence rates of hard braking events per 1000 miles driven were 1.14 (95% CI 1.10-1.18) for drivers using neither benzodiazepines nor prescription opioids, 1.25 (95% CI 1.07-1.43) for those using benzodiazepines only, 1.55 (95% CI 1.35-1.76) for those using prescription opioids only, and 1.63 (95% CI 1.11-2.16) for those using both medications. Multivariable modeling revealed that the use of prescription opioids was associated with a 19% increased risk of hard braking events (aIRR 1.19, 95% CI 1.03-1.36). There existed a positive interaction between the two drugs on the additive scale but not on the multiplicative scale. CONCLUSION: Concurrent use of benzodiazepines and prescription opioids by older drivers appears to affect driving safety through increased incidence of hard braking events.

Randomized double-blind personalized N-of-1 clinical trial to test the safety and potential efficacy of TJ-68 for treating muscle cramps in amyotrophic lateral sclerosis (ALS): study protocol for a TJ-68 trial.

INTRODUCTION/AIMS: Muscle cramps are a common and often disabling symptom in amyotrophic lateral sclerosis (ALS), a devastating and incurable neurodegenerative disorder. To date, there are no medications specifically approved for the treatment of muscle cramps. Ameliorating muscle cramps in ALS may improve and sustain quality of life. A widely prescribed traditional Japanese (Kampo) medicine against muscle cramps, shakuyakukanzoto (TJ-68), has been studied in advanced liver disease, spinal stenosis, kidney failure, and diabetic neuropathy. The Japanese ALS Management Guideline mentions TJ-68 for difficult muscle cramps in ALS. Therefore, the rationale of our trial is to investigate the safety and effectiveness of TJ-68 in treating painful and disabling muscle cramps in people with ALS outside of Japan. Accordingly, we are conducting a randomized clinical trial to test the safety and efficacy of TJ-68 in participants with ALS reporting frequent muscle cramps using an innovative, personalized N-of-1 design. If successful, TJ-68 may be used for muscle cramps in a broader population of people with ALS. METHODS: This is a two-site, double-blind, randomized personalized N-of-1 early clinical trial with TJ-68. At least 22 participants with ALS and daily muscle cramps will receive drug or placebo for 2 weeks (one treatment period) followed by a 1-week washout in a four-period cross-over design. While the primary objective is to evaluate the safety of TJ-68, the study has 85% power to detect a one-point shift on the Visual Analog Scale for Muscle Cramps Affecting Overall Daily Activity of the Columbia Muscle Cramp Scale (MCS). Secondary outcomes include the full MCS score, a Cramp Diary, Clinical Global Impression of Changes, Goal Attainment Scale, quality of life scale and ALS functional rating scale-revised (ALSFRS-R). DISCUSSION: The study is underway. A personalized N-of-1 trial design is an efficient approach to testing medications that alleviate muscle cramps in rare disorders. If TJ-68 proves safe and efficacious then it may be used to treat cramps in ALS, and help to improve and sustain quality of life. TRIAL REGISTRATION: This clinical trial has been registered with ClinicalTrials.gov (NCT04998305), 8/9/2021.