Association between Current Substance Use, Healthy Behaviors, and Depression among Ukrainian College Students.

Depression is a pervasive issue among college students worldwide, yet there is a significant gap in the literature regarding its prevalence and coping strategies in the Ukrainian context. The present study aims to fill this gap by investigating how substance use and health-promoting behaviors relate to depressive symptoms among Ukrainian college students. Health-promoting behaviors are an important strategy to prevent depression, whereas substance use can contribute to depression or make it harder to manage. Given the substantial psychosocial problems and stressors related to the ongoing war in Ukraine and the limited availability of mental health services for college students, it is important to understand how we can encourage college students to keep themselves mentally healthy. A cross-sectional study was conducted among college students on 10 campuses in 2018. Almost 16% of participants met a cut-off for depression. Female students and those who were older reported significantly higher depressive symptoms. Participants were more likely to report depressive symptoms if they were more often involved with alcohol and cannabis use, were older, and engaged in fewer health-promoting behaviors. Tobacco use was not significantly associated with depressive symptoms. Our findings suggest a moderate prevalence of depressive symptoms in our study population. We recommend implementing balanced public health interventions that address risk factors (such as substance use) while also promoting protective behaviors and can be tailored to the specific cultural and environmental context of the region.

Polysubstance Use among Maryland High School Students: Variations across County-Level School Districts.

BACKGROUND: Polysubstance use is a highly prevalent public health issue, particularly among adolescents, and decisions on prevention programming and policies are often made at the local level. While there is a growing literature examining patterns of polysubstance use among adolescents, little is known about differences in those patterns across geographic regions. METHODS: Using a large, representative sample of high school students from the state of Maryland (n = 41,091) from the 2018 Maryland Youth Risk Behavior Survey, we conducted a latent class analysis (LCA) of adolescent substance use along nine binary indicators, including past 30-day combustible tobacco, e-cigarette, alcohol, and cannabis use, as well as lifetime use of prescription opioids, cocaine, heroin, methamphetamine, and injection drug use. Measurement invariance across counties was examined using the Multiple Indicators and Multiple Causes (MIMIC) procedure. RESULTS: The results of the LCA show three classes of adolescent substance use for the total sample: (1) low substance use, (2) commonly used substances (i.e., e-cigarette, alcohol, and cannabis use), and (3) polysubstance use. The results from the MIMIC procedure demonstrated geographic differences in students' endorsement of specific indicators and their class membership. CONCLUSIONS: These differences demonstrate the need for an examination of local trends in adolescent polysubstance use to inform multi-tiered prevention programming and policy.

"I've smoked weed with my daughter": Cannabis Use within Families Affected by Parental Opioid Misuse.

Youth with parents who use opioids are more likely to engage in early substance use, especially cannabis use. The purpose of this study was to describe the context of cannabis use among families affected by parental opioid misuse. We conducted 25 in-depth interviews with families affected by parental opioid misuse. Participants were parents with a history of opioid misuse and young adults (ages 18-24) who had parents with a history of opioid misuse. Interviews were digitally recorded and professionally transcribed. Data were analyzed inductively using a qualitative content analytic approach. Familial cannabis use was common among young people and their parents. Participants described familial cannabis use as a bonding activity that felt safe and lightened the mood. Additional research is needed to understand the complex role that cannabis use may play in families affected by opioid misuse. Strategies for intergenerational substance use prevention are discussed.

Risks of Ventricular Arrhythmia and Heart Failure in Carriers of RBM20 Variants.

BACKGROUND: Variants in RBM20 are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in RBM20 variant carriers and the impact of sex on outcomes. METHODS: Consecutive probands and relatives carrying RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and men and women compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. RBM20 variant carriers with left ventricular systolic dysfunction (RBM20LVSD) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction. RESULTS: Longitudinal follow-up data were available for 143 RBM20 variant carriers (71 men; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between men and women (log-rank P=0.07 and P=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 men and 3 women; log-rank P<0.001). Four of 10 variant carriers with available LVEF contemporary to MVA had an LVEF >35%. At 5 years, 15 of 67 (22.4%) RBM20LVSD versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank P<0.001). RBM20 variant carriage conferred a 6.0-fold increase in risk of the primary end point. CONCLUSIONS: RBM20 variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female RBM20 variant carriers is similar, but male sex is strongly associated with ESHF.

Classification of Students by Race and Hispanic/Latino/a/x Ethnicity Impacts Estimates of the Prevalence of Substance Use.

Multiracial and Hispanic/Latino/a/x youth are rapidly growing populations in the United States. When considered in substance use studies, they are often treated as homogeneous groups despite important demographic and cultural differences. The current study explores how substance use prevalence may differ depending on how precisely race and ethnicity groups are categorized. Data are from the 2018 High School Maryland Youth Risk Behavior Survey (n = 41,091, 48.4% female). We estimate prevalence of past 30-day substance use (i.e., alcohol, combustible tobacco, e-cigarettes, and marijuana) for all combinations of race and Hispanic/Latino/a/x ethnicity. Substance use prevalence across the specific Multiracial and Hispanic/Latino/a/x categories showed a wider range of estimates than within the traditional CDC racial and ethnic categories. Findings from this study suggest that state- and national-level surveillance of adolescent risk behavior should add further measures of race and ethnic identity to improve researchers' ability to increase precision of substance use prevalence estimates.

Multicenter clinical and functional evidence reclassifies a recurrent noncanonical filamin C splice-altering variant.

BACKGROUND: Truncating variants in filamin C (FLNC) can cause arrhythmogenic cardiomyopathy (ACM) through haploinsufficiency. Noncanonical splice-altering variants may contribute to this phenotype. OBJECTIVE: The purpose of this study was to investigate the clinical and functional consequences of a recurrent FLNC intronic variant of uncertain significance (VUS), c.970-4A>G. METHODS: Clinical data in 9 variant heterozygotes from 4 kindreds were obtained from 5 tertiary health care centers. We used in silico predictors and functional studies with peripheral blood and patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Isolated RNA was studied by reverse transcription polymerase chain reaction. iPSC-CMs were further characterized at baseline and after nonsense-mediated decay (NMD) inhibition, using quantitative polymerase chain reaction (qPCR), RNA-sequencing, and cellular electrophysiology. American College of Medical Genetics and Genomics (ACMG) criteria were used to adjudicate variant pathogenicity. RESULTS: Variant heterozygotes displayed a spectrum of disease phenotypes, spanning from mild ventricular dysfunction with palpitations to severe ventricular arrhythmias requiring device shocks or progressive cardiomyopathy requiring heart transplantation. Consistent with in silico predictors, the c.970-4A>G FLNC variant activated a cryptic splice acceptor site, introducing a 3-bp insertion containing a premature termination codon. NMD inhibition upregulated aberrantly spliced transcripts by qPCR and RNA-sequencing. Patch clamp studies revealed irregular spontaneous action potentials, increased action potential duration, and increased sodium late current in proband-derived iPSC-CMs. These findings fulfilled multiple ACMG criteria for pathogenicity. CONCLUSION: Clinical, in silico, and functional evidence support the prediction that the intronic c.970-4A>G VUS disrupts splicing and drives ACM, enabling reclassification from VUS to pathogenic.

Drug-resistant seizures associated with hyperinflammatory monocytes in FIRES.

OBJECTIVE: Therapeutic strategies for patients with febrile infection-related epilepsy syndrome (FIRES) are limited, ad hoc, and frequently ineffective. Based on evidence that inflammation drives pathogenesis in FIRES, we used ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) to characterize the monocytic response profile before and after therapy in a child successfully treated with dexamethasone delivered intrathecally six times between hospital Day 23 and 40 at 0.25 mg/kg/dose. METHODS: PBMCs were isolated from serial blood draws acquired during refractory status epilepticus (RSE) and following resolution associated with intrathecal dexamethasone therapy in a previously healthy 9-year-old male that presented with seizures following Streptococcal pharyngitis. Cells were stimulated with bacterial or viral ligands and cytokine release was measured and compared to responses in age-matched healthy control PBMCs. Levels of inflammatory factors in the blood and CSF were also measured and compared to pediatric healthy control ranges. RESULTS: During RSE, serum levels of IL6, CXCL8, HMGB1, S100A8/A9, and CRP were significantly elevated. IL6 was elevated in CSF. Ex vivo stimulation of PBMCs collected during RSE revealed hyperinflammatory release of IL6 and CXCL8 in response to bacterial stimulation. Following intrathecal dexamethasone, RSE resolved, inflammatory levels normalized in serum and CSF, and the PBMC hyperinflammatory response renormalized. SIGNIFICANCE: FIRES may be associated with a hyperinflammatory monocytic response to normally banal bacterial pathogens. This hyperinflammatory response may induce a profound neutrophil burden and the consequent release of factors that further exacerbate inflammation and drive neuroinflammation. Intrathecal dexamethasone may resolve RSE by resetting this inflammatory feedback loop.

"What Do You Consider Use?" Perspectives of Black Youth on Cannabis Use.

PURPOSE: Adolescent health surveillance systems are critical for understanding patterns of cannabis use; however, their limitations underscore the need for studies that generate new insights, particularly from individuals who are most impacted by negative outcomes. Our objectives were to learn about youths' cannabis use and their perceptions of their peers' cannabis use; their perspectives about trajectories of cannabis use over time and factors that influence trajectories; and perceived risks and benefits associated with cannabis use. METHODS: A group model building approach was used to gather data about cannabis use from a sample of urban, Black youth. Information about participants' cannabis use was assessed on eligibility screener, enrollment survey, and through structured activities over the course of four group model building workshops. RESULTS: Participants [(n = 20) mean age 18; 35% male and 95% Black] exclusively used the terms weed and blunts for cannabis. Youth who consume peers' blunts would not characterize themselves as cannabis users. Collectively, youth estimated the majority of Baltimore youth used cannabis by age 16 and that most used daily. Youth described cannabis as more beneficial than harmful. There were no gender differences in prevalence of use, but there were gender dynamics to shared use. DISCUSSION: Participatory research with urban, Black youth suggests youths' perceptions are misaligned with the ways that researchers conceptualize cannabis use. To better understand the scope of youth cannabis use and its harms, it is critical to leverage input from youth with lived experience to ensure survey tools adequately capture the way youth see themselves using cannabis.

Trends in heroin use and injection drug use among high school students in five urban school districts in the US (2005-2017).

Background. We describe the prevalence of and changes in heroin use and injection drug use (IDU) among high school students in five large, urban school districts in the US (2005-2017); nearly three-fourths of the students were Black and/or Hispanic/Latino.Methods. Data are from the Centers for Disease Control and Prevention's "Youth Risk Behavior Survey" program, which includes biennial surveys in urban school districts. We pooled data across districts and survey years, and then generated weighted prevalence estimates (and 95% CIs) for any lifetime heroin use and IDU. Joinpoint regression modeling was used to estimate changes in prevalence over the study period.Results. Biennial prevalence estimates (2005-2017) for heroin use and IDU were above 1.8% for all seven timepoints. In 2017, prevalence of heroin use and IDU were 2.9% and 2.5%, respectively. Both heroin use and IDU were higher among boys than girls. There were statistically significant increases in heroin use and IDU among girls from 2005-2009, whereas changes over time were stable among boys.Conclusions. High school students in large, urban school districts may have higher rates of heroin use and IDU than US high school students in general, and there is little evidence of increases since 2009. This study suggests that adolescence may be a critical period for initiation of heroin use among adolescents in large urban school districts, the majority of whom are Black and/or Latino.Supplemental data for this article is available online at https://doi.org/10.1080/15332640.2021.1992327 .

Rejuvenation of the aged brain immune cell landscape in mice through p16-positive senescent cell clearance.

Cellular senescence is a plausible mediator of inflammation-related tissue dysfunction. In the aged brain, senescent cell identities and the mechanisms by which they exert adverse influence are unclear. Here we used high-dimensional molecular profiling, coupled with mechanistic experiments, to study the properties of senescent cells in the aged mouse brain. We show that senescence and inflammatory expression profiles increase with age and are brain region- and sex-specific. p16-positive myeloid cells exhibiting senescent and disease-associated activation signatures, including upregulation of chemoattractant factors, accumulate in the aged mouse brain. Senescent brain myeloid cells promote peripheral immune cell chemotaxis in vitro. Activated resident and infiltrating immune cells increase in the aged brain and are partially restored to youthful levels through p16-positive senescent cell clearance in female p16-InkAttac mice, which is associated with preservation of cognitive function. Our study reveals dynamic remodeling of the brain immune cell landscape in aging and suggests senescent cell targeting as a strategy to counter inflammatory changes and cognitive decline.

Area-level deprivation and adverse childhood experiences among high school students in Maryland.

BACKGROUND: Nearly one-half of Americans have been exposed to at least one adverse childhood experience (ACE) before turning 18, contributing to a broad array of problems spanning physical health, mental and behavioral health, and psychosocial functioning. METHODS: This was a cross-sectional, survey research study, using 2018 data from a state adolescent health surveillance system, i.e., Maryland Youth Risk Behavior Survey/Youth Tobacco Survey. The population-based sample of Maryland high school students (n = 41,091) is representative at the state and county levels. The outcome variables included five binary measures of ACEs (i.e., food insecurity, parental substance use/gambling, parental mental illness, family member in jail/prison, and caregiver verbal abuse), and number of ACEs. The main exposure variable, area-level socioeconomic disadvantage, was assessed at the county level using a continuous measure of the area deprivation index (ADI). Additional covariates included: rural county status, age, race/ethnicity, sex, and sexual or gender minority (SGM) status. We used mixed-effect multivariate logistic regression to estimate the odds of ACEs in association with socioeconomic deprivation. Models were adjusted for all covariates. RESULTS: County-level ADI was associated with 3 of the 5 ACES [i.e., food insecurity (OR = 1.10, 95% CI: 1.07-1.13), parental substance use/gambling (OR = 1.05, 95% CI: 1.02-1.07), and incarceration of a family member (OR = 1.14, 95% CI: 1.09-1.19)]; and with having at least one ACE (i.e., OR = 1.08, 95% CI: 1.05-1.10). Odds of reporting at least one ACE were higher among girls, older adolescents (i.e., aged 16 and ≥ 17 relative to those aged ≤ 14 years), and among SGM, Black, and Latinx students (all ORs > 1.20). CONCLUSIONS: ACEs greatly increase risk for adolescent risk behaviors. We observed an increased likelihood of adversity among youth in more deprived counties and among Black, Latinx, or SGM youth, suggesting that social and structural factors play a role in determining the adversity that youth face. Therefore, efforts to address structural factors (e.g., food access, family financial support, imprisonment as a sanction for criminal behavior) could be a critical strategy for primary prevention of ACEs and promoting adolescent health.

Teriflunomide shifts the astrocytic bioenergetic profile from oxidative metabolism to glycolysis and attenuates TNFα-induced inflammatory responses.

Astrocytes utilize both glycolytic and mitochondrial pathways to power cellular processes that are vital to maintaining normal CNS functions. These cells also mount inflammatory and acute phase reactive programs in response to diverse stimuli. While the metabolic functions of astrocytes under homeostatic conditions are well-studied, the role of cellular bioenergetics in astrocyte reactivity is poorly understood. Teriflunomide exerts immunomodulatory effects in diseases such as multiple sclerosis by metabolically reprogramming lymphocytes and myeloid cells. We hypothesized that teriflunomide would constrain astrocytic inflammatory responses. Purified murine astrocytes were grown under serum-free conditions to prevent acquisition of a spontaneous reactive state. Stimulation with TNFα activated NFκB and increased secretion of Lcn2. TNFα stimulation increased basal respiration, maximal respiration, and ATP production in astrocytes, as assessed by oxygen consumption rate. TNFα also increased glycolytic reserve and glycolytic capacity of astrocytes but did not change the basal glycolytic rate, as assessed by measuring the extracellular acidification rate. TNFα specifically increased mitochondrial ATP production and secretion of Lcn2 required ATP generated by oxidative phosphorylation. Inhibition of dihydroorotate dehydrogenase via teriflunomide transiently increased both oxidative phosphorylation and glycolysis in quiescent astrocytes, but only the increased glycolytic ATP production was sustained over time, resulting in a bias away from mitochondrial ATP production even at doses down to 1 µM. Preconditioning with teriflunomide prevented the TNFα-induced skew toward oxidative phosphorylation, reduced mitochondrial ATP production, and reduced astrocytic inflammatory responses, suggesting that this drug may limit neuroinflammation by acting as a metabolomodulator.

Racial/Ethnic Inequities in Adverse Childhood Experiences and Selected Health-Related Behaviors and Problems Among Maryland Adolescents.

We examined racial/ethnic inequities in the prevalence of adverse childhood experiences (ACEs) and examined the association between ACEs and selected health-related behaviors and problems. Data for this cross-sectional study come from the 2018 Maryland Youth Risk Behavior Survey/Youth Tobacco Survey, a statewide survey of high school students (n = 40,188). ACEs included caregiver verbal abuse and household food insecurity, substance use or gambling, mental illness, and involvement with the criminal justice system. We estimated the prevalence of ACEs overall and by race/ethnicity, and then used multiple logistic regression to determine associations between ACEs and emotional/behavioral problems, adjusting for race/ethnicity. Outcome variables included emotional distress, poor school performance, suicidal ideation, fighting, alcohol use, and marijuana use. More than one fifth of students reported each individual ACE. Differences in the prevalence of ACEs by race/ethnicity were statistically significant (p < .001). More than one fourth (25.8%) reported one of the five ACEs, 15.1% reported two, and 15.4% reported three or more. For each ACE, reporting having experienced it (vs. not) was associated with a >30% higher prevalence for each of the outcome variables. Among students who reported three or more ACEs (relative to none), the odds of emotional distress and suicidal ideation were more than 8 times greater. Among Maryland adolescents, ACEs are common, are inequitably distributed by race/ethnicity, and are strongly linked to behavioral health. Findings suggest the need to monitor ACEs as a routine component of adolescent health surveillance and to refocus assessment and intervention toward "upstream" factors that shape adolescent health.

Phenotypic Expression, Natural History, and Risk Stratification of Cardiomyopathy Caused by Filamin C Truncating Variants.

BACKGROUND: Filamin C truncating variants (FLNCtv) cause a form of arrhythmogenic cardiomyopathy: the mode of presentation, natural history, and risk stratification of FLNCtv remain incompletely explored. We aimed to develop a risk profile for refractory heart failure and life-threatening arrhythmias in a multicenter cohort of FLNCtv carriers. METHODS: FLNCtv carriers were identified from 10 tertiary care centers for genetic cardiomyopathies. Clinical and outcome data were compiled. Composite outcomes were all-cause mortality/heart transplantation/left ventricle assist device (D/HT/LVAD), nonarrhythmic death/HT/LVAD, and sudden cardiac death/major ventricular arrhythmias. Previously established cohorts of 46 patients with LMNA and 60 with DSP-related arrhythmogenic cardiomyopathies were used for prognostic comparison. RESULTS: Eighty-five patients carrying FLNCtv were included (42±15 years, 53% men, 45% probands). Phenotypes were heterogeneous at presentation: 49% dilated cardiomyopathy, 25% arrhythmogenic left dominant cardiomyopathy, 3% arrhythmogenic right ventricular cardiomyopathy. Left ventricular ejection fraction was <50% in 64% of carriers and 34% had right ventricular fractional area changes (RVFAC=(right ventricular end-diastolic area - right ventricular end-systolic area)/right ventricular end-diastolic area) <35%. During follow-up (median time 61 months), 19 (22%) carriers experienced D/HT/LVAD, 13 (15%) experienced nonarrhythmic death/HT/LVAD, and 23 (27%) experienced sudden cardiac death/major ventricular arrhythmias. The sudden cardiac death/major ventricular arrhythmias incidence of FLNCtv carriers did not significantly differ from LMNA carriers and DSP carriers. In FLNCtv carriers, left ventricular ejection fraction was associated with the risk of D/HT/LVAD and nonarrhythmic death/HT/LVAD. CONCLUSIONS: Among patients referred to tertiary referral centers, FLNCtv arrhythmogenic cardiomyopathy is phenotypically heterogeneous and characterized by a high risk of life-threatening arrhythmias, which does not seem to be associated with the severity of left ventricular dysfunction.

Electronic cigarette and cannabis use: results from the 2018 Maryland Youth Risk Behavior Survey.

OBJECTIVE: To determine the relationship between lifetime e-cigarette use and current cannabis use among youth. Our analyses accounted for county variability, in addition to student-level covariates. METHODS: This study examined responses from high school students on a state-level population survey, the 2018 Maryland Youth Risk Behavior Survey/Youth Tobacco Survey, a cross-sectional, complex survey sample. Of participating students, final analyses included an unweighted sample of 41,091 9th to 12th grade students who provided complete reports for measured variables. Analyses with survey weights were conducted between August 2019 and May 2020. A multivariable logistic regression was conducted to investigate the association between lifetime e-cigarette use and current (past 30-day) cannabis use, after controlling for county, lifetime cigarette use, current (past 30-day) alcohol use, emotional distress, and demographics. RESULTS: Lifetime e-cigarette use significantly increased the odds of current cannabis use among Maryland high school students (aOR = 6.04; 95% CI 5.27, 6.93). Other significant risk factors for current cannabis use included lifetime cigarette use (aOR 2.23, 95% CI 1.86, 2.68) and current alcohol use (aOR 5.21, 95% CI 4.42, 6.14). Significantly higher odds of current cannabis use were also found among older high school students, males, non-Hispanic Blacks and students identifying as other race, and those reporting emotional distress. CONCLUSIONS: Lifetime e-cigarette use among Maryland high school students is strongly associated with current cannabis use when including counties as a covariate. Non-significant county differences, however, suggest smaller geographical units may be required to control for variability. Efforts should focus on reducing youth e-cigarette use to decrease cannabis use. Maryland's recent implementation of Tobacco 21 and a ban on flavored e-cigarettes will be of interest for future evaluations.

Medical marijuana laws (MMLs) and dispensary provisions not associated with higher odds of adolescent marijuana or heavy marijuana use: A 46 State Analysis, 1991-2015.

Background: States are rapidly moving to reverse marijuana prohibition, most frequently through legalization of medical marijuana laws (MMLs), and there is concern that marijuana legalization may affect adolescent marijuana use. Methods: This natural-experimental study used state Youth Risk Behavior Survey (YRBS) data collected from participants in grades 9-12 from 1991 to 2015 in 46 states (N = 1,091,723). Taking advantage of heterogeneity across states in MML status and MML dispensary design, difference-in-difference estimates compared states with enacted MMLs/dispensaries to non-MML/dispensaries states. Multivariable logistic regression modeling was used to adjust for state and year effects, and student demographics. The main outcome assessed was past 30-day adolescent marijuana use ["any" and "heavy" (≥20)]. Results: In the overall sample, the adjusted odds of adolescents reporting any past 30-day marijuana use was lower in states that enacted MMLs at any time during the study period (OR 0.94, 95% CI 0.89 to 0.99; p < .05), and in states with operational dispensaries in 2015 (OR 0.93, 95% CI 0.88 to 0.99; p < .05). Among grade cohorts, only 9th graders showed a significant effect, with lower odds of use with MML enactment. We found no effects on heavy marijuana use. Conclusions: This study found no evidence between 1991 and 2015 of increases in adolescents reporting past 30-day marijuana use or heavy marijuana use associated with state MML enactment or operational MML dispensaries. In a constantly evolving marijuana policy landscape, continued monitoring of adolescent marijuana use is important for assessing policy effects.

Effect of a Coordinated Community and Chronic Care Model Team Intervention vs Usual Care on Systolic Blood Pressure in Patients With Stroke or Transient Ischemic Attack: The SUCCEED Randomized Clinical Trial.

Importance: Few stroke survivors meet recommended cardiovascular goals, particularly among racial/ethnic minority populations, such as Black or Hispanic individuals, or socioeconomically disadvantaged populations. Objective: To determine if a chronic care model-based, community health worker (CHW), advanced practice clinician (APC; including nurse practitioners or physician assistants), and physician team intervention improves risk factor control after stroke in a safety-net setting (ie, health care setting where all individuals receive care, regardless of health insurance status or ability to pay). Design, Setting, and Participants: This randomized clinical trial included participants recruited from 5 hospitals serving low-income populations in Los Angeles County, California, as part of the Secondary Stroke Prevention by Uniting Community and Chronic Care Model Teams Early to End Disparities (SUCCEED) clinical trial. Inclusion criteria were age 40 years or older; experience of ischemic or hemorrhagic stroke or transient ischemic attack (TIA) no more than 90 days prior; systolic blood pressure (BP) of 130 mm Hg or greater or 120 to 130 mm Hg with history of hypertension or using hypertensive medications; and English or Spanish language proficiency. The exclusion criterion was inability to consent. Among 887 individuals screened for eligibility, 542 individuals were eligible, and 487 individuals were enrolled and randomized, stratified by stroke type (ischemic or TIA vs hemorrhagic), language (English vs Spanish), and site to usual care vs intervention in a 1:1 fashion. The study was conducted from February 2014 to September 2018, and data were analyzed from October 2018 to November 2020. Interventions: Participants randomized to intervention were offered a multimodal coordinated care intervention, including hypothesized core components (ie, ≥3 APC clinic visits, ≥3 CHW home visits, and Chronic Disease Self-Management Program workshops), and additional telephone visits, protocol-driven risk factor management, culturally and linguistically tailored education materials, and self-management tools. Participants randomized to the control group received usual care, which varied by site but frequently included a free BP monitor, self-management tools, and linguistically tailored information materials. Main Outcomes and Measures: The primary outcome was change in systolic BP at 12 months. Secondary outcomes were non-high density lipoprotein cholesterol, hemoglobin A1c, and C-reactive protein (CRP) levels, body mass index, antithrombotic adherence, physical activity level, diet, and smoking status at 12 months. Potential mediators assessed included access to care, health and stroke literacy, self-efficacy, perceptions of care, and BP monitor use. Results: Among 487 participants included, the mean (SD) age was 57.1 (8.9) years; 317 (65.1%) were men, and 347 participants (71.3%) were Hispanic, 87 participants (18.3%) were Black, and 30 participants (6.3%) were Asian. A total of 246 participants were randomized to usual care, and 241 participants were randomized to the intervention. Mean (SD) systolic BP improved from 143 (17) mm Hg at baseline to 133 (20) mm Hg at 12 months in the intervention group and from 146 (19) mm Hg at baseline to 137 (22) mm Hg at 12 months in the usual care group, with no significant differences in the change between groups. Compared with the control group, participants in the intervention group had greater improvements in self-reported salt intake (difference, 15.4 [95% CI, 4.4 to 26.0]; P = .004) and serum CRP level (difference in log CRP, -0.4 [95% CI, -0.7 to -0.1] mg/dL; P = .003); there were no differences in other secondary outcomes. Although 216 participants (89.6%) in the intervention group received some of the 3 core components, only 35 participants (14.5%) received the intended full dose. Conclusions and Relevance: This randomized clinical trial of a complex multilevel, multimodal intervention did not find vascular risk factor improvements beyond that of usual care; however, further studies may consider testing the SUCCEED intervention with modifications to enhance implementation and participant engagement. Trial Registration: ClinicalTrials.gov Identifier: NCT01763203.

Polytobacco use among a nationally-representative sample of black high school students.

BACKGROUND: Studies of the patterns of polytobacco use have increased. However, understanding the patterns of using multiple tobacco products among Black adolescents is minimal. This study identified the patterns of polytobacco use among U.S. Black adolescents. METHODS: Latent class analysis (LCA) was used to identify patterns of adolescent polytobacco use among a representative sample of Black youth from the 2017 Youth Risk Behavior Survey (n = 2782). Ever and recent (past 30 day) use of cigarettes, electronic cigarettes, cigars, and dip or chewing tobacco were used as latent class indicators. Multinomial regression was conducted to identify the association if smoking adjusting for sex, age, grade, and marijuana use. RESULTS: Most students were in the 9th grade (29%), e-cigarette users (21%) and were current marijuana users (25%). Three profiles of tobacco use were identified: Class 1: Non-smokers (81%), Class 2: E-cigarette Users (14%), and Class 3: Polytobacco Users (5%). Black adolescent Polytobacco users were the smallest class, but had the highest conditional probabilities of recent cigarette use, e-cigarette use, ever smoking cigars or chewing tobacco. Ever and current use of marijuana were associated with increased odds of being in the e-cigarette user versus non-smoker group, and current marijuana use was associated with increased odds of polytobacco use (aOR = 24.61, CI = 6.95-87.11). CONCLUSIONS: Findings suggests the need for targeted interventions for reducing tobacco use and examining the unique effects of polytobacco use on Black adolescents. Findings confirm a significant association of marijuana use with tobacco use.

Mental Distress in the United States at the Beginning of the COVID-19 Pandemic.

Objectives. To assess the impact of the COVID-19 pandemic on mental distress in US adults.Methods. Participants were 5065 adults from the Understanding America Study, a probability-based Internet panel representative of the US adult population. The main exposure was survey completion date (March 10-16, 2020). The outcome was mental distress measured via the 4-item version of the Patient Health Questionnaire.Results. Among states with 50 or more COVID-19 cases as of March 10, each additional day was significantly associated with an 11% increase in the odds of moving up a category of distress (odds ratio = 1.11; 95% confidence interval = 1.01, 1.21; P = .02). Perceptions about the likelihood of getting infected, death from the virus, and steps taken to avoid infecting others were associated with increased mental distress in the model that included all states. Individuals with higher consumption of alcohol or cannabis or with history of depressive symptoms were at significantly higher risk for mental distress.Conclusions. These data suggest that as the COVID-19 pandemic continues, mental distress may continue to increase and should be regularly monitored. Specific populations are at high risk for mental distress, particularly those with preexisting depressive symptoms.

Clinical Phenotypes and Prognosis of Dilated Cardiomyopathy Caused by Truncating Variants in the TTN Gene.

BACKGROUND: Truncating variants in the TTN gene (TTNtv) are the commonest cause of heritable dilated cardiomyopathy. This study aimed to study the phenotypes and outcomes of TTNtv carriers. METHODS: Five hundred thirty-seven individuals (61% men; 317 probands) with TTNtv were recruited in 14 centers (372 [69%] with baseline left ventricular systolic dysfunction [LVSD]). Baseline and longitudinal clinical data were obtained. The primary end point was a composite of malignant ventricular arrhythmia and end-stage heart failure. The secondary end point was left ventricular reverse remodeling (left ventricular ejection fraction increase by ≥10% or normalization to ≥50%). RESULTS: Median follow-up was 49 (18-105) months. Men developed LVSD more frequently and earlier than women (45±14 versus 49±16 years, respectively; P=0.04). By final evaluation, 31%, 45%, and 56% had atrial fibrillation, frequent ventricular ectopy, and nonsustained ventricular tachycardia, respectively. Seventy-six (14.2%) individuals reached the primary end point (52 [68%] end-stage heart failure events, 24 [32%] malignant ventricular arrhythmia events). Malignant ventricular arrhythmia end points most commonly occurred in patients with severe LVSD. Male sex (hazard ratio, 1.89 [95% CI, 1.04-3.44]; P=0.04) and left ventricular ejection fraction (per 10% decrement from left ventricular ejection fraction, 50%; hazard ratio, 1.63 [95% CI, 1.30-2.04]; P<0.001) were independent predictors of the primary end point. Two hundred seven of 300 (69%) patients with LVSD had evidence of left ventricular reverse remodeling. In a subgroup of 29 of 74 (39%) patients with initial left ventricular reverse remodeling, there was a subsequent left ventricular ejection fraction decrement. TTNtv location was not associated with statistically significant differences in baseline clinical characteristics, left ventricular reverse remodeling, or outcomes on multivariable analysis (P=0.07). CONCLUSIONS: TTNtv is characterized by frequent arrhythmia, but malignant ventricular arrhythmias are most commonly associated with severe LVSD. Male sex and LVSD are independent predictors of outcomes. Mutation location does not impact clinical phenotype or outcomes.