Reduced Ejection Fraction in Elite Endurance Athletes: Clinical and Genetic Overlap With Dilated Cardiomyopathy.

BACKGROUND: Exercise-induced cardiac remodeling can be profound, resulting in clinical overlap with dilated cardiomyopathy, yet the significance of reduced ejection fraction (EF) in athletes is unclear. The aim is to assess the prevalence, clinical consequences, and genetic predisposition of reduced EF in athletes. METHODS: Young endurance athletes were recruited from elite training programs and underwent comprehensive cardiac phenotyping and genetic testing. Those with reduced EF using cardiac magnetic resonance imaging (defined as left ventricular EF <50%, or right ventricular EF <45%, or both) were compared with athletes with normal EF. A validated polygenic risk score for indexed left ventricular end-systolic volume (LVESVi-PRS), previously associated with dilated cardiomyopathy, was assessed. Clinical events were recorded over a mean of 4.4 years. RESULTS: Of the 281 elite endurance athletes (22±8 years, 79.7% male) undergoing comprehensive assessment, 44 of 281 (15.7%) had reduced left ventricular EF (N=12; 4.3%), right ventricular EF (N=14; 5.0%), or both (N=18; 6.4%). Reduced EF was associated with a higher burden of ventricular premature beats (13.6% versus 3.8% with >100 ventricular premature beats/24 h; P=0.008) and lower left ventricular global longitudinal strain (-17%±2% versus -19%±2%; P<0.001). Athletes with reduced EF had a higher mean LVESVi-PRS (0.57±0.13 versus 0.51±0.14; P=0.009) with athletes in the top decile of LVESVi-PRS having an 11-fold increase in the likelihood of reduced EF compared with those in the bottom decile (P=0.034). Male sex and higher LVESVi-PRS were the only significant predictors of reduced EF in a multivariate analysis that included age and fitness. During follow-up, no athletes developed symptomatic heart failure or arrhythmias. Two athletes died, 1 from trauma and 1 from sudden cardiac death, the latter having a reduced right ventricular EF and a LVESVi-PRS >95%. CONCLUSIONS: Reduced EF occurs in approximately 1 in 6 elite endurance athletes and is related to genetic predisposition in addition to exercise training. Genetic and imaging markers may help identify endurance athletes in whom scrutiny about long-term clinical outcomes may be appropriate. REGISTRATION: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374976&isReview=true; Unique identifier: ACTRN12618000716268.

Maryland opioid overdose deaths from 2018 to 2022: occupational patterns and their sociodemographic variations.

INTRODUCTION: We aimed to describe the occupational pattern of opioid overdose deaths in Maryland between 2018 and 2022 and determine the occupations at higher risk of opioid overdose death. METHODS: The sample included undetermined or unintentional opioid overdose deaths among those aged 16 years or older in Maryland, drawn from the State Unintentional Drug Overdose Reporting System. We calculated population-based incidence overdose rates by occupation, stratified by sex and race. We further calculated the incidence rate ratios (IRRs) comparing each occupation with all other groups combined and estimated the IRRs among males versus females and non-Hispanic whites versus other racial/ethnic groups. RESULTS: The pooled sample included 11 455 opioid overdose decedents (72% male and 55% non-Hispanic whites) of whom 80% were employed. The three occupation groups with the highest incidence rates were 'construction and extraction', 'transportation and material moving' and 'installation/maintenance and repair' with 291, 137 and 133 deaths per 100 000 workers in these respective occupational groups. Incidence rates were significantly higher in males than females in all categories except those 'Not in Labour Force' (IRR=0.51, p<0.001). Non-Hispanic whites relative to other racial/ethnic groups had a lower incidence of opioid overdose death in 'Military-Specific' occupations (IRR=0.53, p=0.031). CONCLUSION: Opioid overdose deaths vary by type of occupation and certain occupations are at higher risk of overdose death. The findings highlight the need for priority setting in the implementation and expansion of existing strategies to target the workers most impacted by opioid overdose.

Ratio of emergency department visits to deaths for opioid overdose.

BACKGROUND: Data on fatal and non-fatal overdose provide important information about the magnitude of the overdose crisis. We consider these metrics in tandem and estimated the ratio of opioid overdose-related emergency department (ED) visits to opioid overdose deaths. A lower ratio could indicate more fatal overdoses, fewer overdose reversals with naloxone or a combination of both. METHODS: Data are from the Maryland Vital Statistics Administration (opioid overdose deaths), the Health Services Cost Review Commission (non-fatal ED visits for opioid overdose). We generated 2020 annual rates of fatal and non-fatal opioid overdose deaths for the state of Maryland and its 24 jurisdictions and estimated the ratio of opioid overdose-related ED visits to deaths. RESULTS: The 2020 visit-to-death ratio for Maryland was 1.7, and ranged from 0.9 to 3.8 across jurisdictions. We identified five counties that had above-median rates of opioid overdose-related ED visits and deaths, and low visit-to-death ratios. CONCLUSIONS: Our findings indicate that there were nearly two ED visits for each opioid overdose death in Maryland, and there was substantial variation across counties. The visit-to-death ratio enables a better understanding of the relationship between fatal and non-fatal opioid overdose and is essential to averting deaths and evaluating overdose prevention efforts.

Psychosocial and pharmacologic interventions to reduce harmful alcohol use in low- and middle-income countries.

BACKGROUND: Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk factors for disease, disability and premature mortality globally. The burden of harmful alcohol use is increasing in low- and middle-income countries (LMICs) and there remains a large unmet need for indicated prevention and treatment interventions to reduce harmful alcohol use in these settings. Evidence regarding which interventions are effective and feasible for addressing harmful and other patterns of unhealthy alcohol use in LMICs is limited, which contributes to this gap in services. OBJECTIVES: To assess the efficacy and safety of psychosocial and pharmacologic treatment and indicated prevention interventions compared with control conditions (wait list, placebo, no treatment, standard care, or active control condition) aimed at reducing harmful alcohol use in LMICs. SEARCH METHODS: We searched for randomized controlled trials (RCTs) indexed in the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, the Cochrane Clinical Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, Embase, PsycINFO, CINAHL, and the Latin American and Caribbean Health Sciences Literature (LILACS) through 12 December 2021. We searched clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, Web of Science, and Opengrey database to identify unpublished or ongoing studies. We searched the reference lists of included studies and relevant review articles for eligible studies. SELECTION CRITERIA: All RCTs comparing an indicated prevention or treatment intervention (pharmacologic or psychosocial) versus a control condition for people with harmful alcohol use in LMICs were included. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 66 RCTs with 17,626 participants. Sixty-two of these trials contributed to the meta-analysis. Sixty-three studies were conducted in middle-income countries (MICs), and the remaining three studies were conducted in low-income countries (LICs). Twenty-five trials exclusively enrolled participants with alcohol use disorder. The remaining 51 trials enrolled participants with harmful alcohol use, some of which included both cases of alcohol use disorder and people reporting hazardous alcohol use patterns that did not meet criteria for disorder. Fifty-two RCTs assessed the efficacy of psychosocial interventions; 27 were brief interventions primarily based on motivational interviewing and were compared to brief advice, information, or assessment only. We are uncertain whether a reduction in harmful alcohol use is attributable to brief interventions given the high levels of heterogeneity among included studies (Studies reporting continuous outcomes: Tau² = 0.15, Q =139.64, df =16, P<.001, I² = 89%, 3913 participants, 17 trials, very low certainty; Studies reporting dichotomous outcomes: Tau²=0.18, Q=58.26, df=3, P<.001, I² =95%, 1349 participants, 4 trials, very low certainty). The other types of psychosocial interventions included a range of therapeutic approaches such as behavioral risk reduction, cognitive-behavioral therapy, contingency management, rational emotive therapy, and relapse prevention. These interventions were most commonly compared to usual care involving varying combinations of psychoeducation, counseling, and pharmacotherapy. We are uncertain whether a reduction in harmful alcohol use is attributable to psychosocial treatments due to high levels of heterogeneity among included studies (Heterogeneity: Tau² = 1.15; Q = 444.32, df = 11, P<.001; I²=98%, 2106 participants, 12 trials, very low certainty). Eight trials compared combined pharmacologic and psychosocial interventions with placebo, psychosocial intervention alone, or another pharmacologic treatment. The active pharmacologic study conditions included disulfiram, naltrexone, ondansetron, or topiramate. The psychosocial components of these interventions included counseling, encouragement to attend Alcoholics Anonymous, motivational interviewing, brief cognitive-behavioral therapy, or other psychotherapy (not specified). Analysis of studies comparing a combined pharmacologic and psychosocial intervention to psychosocial intervention alone found that the combined approach may be associated with a greater reduction in harmful alcohol use (standardized mean difference (standardized mean difference (SMD))=-0.43, 95% confidence interval (CI): -0.61 to -0.24; 475 participants; 4 trials; low certainty). Four trials compared pharmacologic intervention alone with placebo and three with another pharmacotherapy. Drugs assessed were: acamprosate, amitriptyline, baclofen disulfiram, gabapentin, mirtazapine, and naltrexone. None of these trials evaluated the primary clinical outcome of interest, harmful alcohol use.   Thirty-one trials reported rates of retention in the intervention. Meta-analyses revealed that rates of retention between study conditions did not differ in any of the comparisons (pharmacologic risk ratio (RR) = 1.13, 95% CI: 0.89 to 1.44, 247 participants, 3 trials, low certainty; pharmacologic in addition to psychosocial intervention: RR = 1.15, 95% CI: 0.95 to 1.40, 363 participants, 3 trials, moderate certainty). Due to high levels of heterogeneity, we did not calculate pooled estimates comparing retention in brief (Heterogeneity: Tau² = 0.00; Q = 172.59, df = 11, P<.001; I2 = 94%; 5380 participants; 12 trials, very low certainty) or other psychosocial interventions (Heterogeneity: Tau² = 0.01; Q = 34.07, df = 8, P<.001; I2 = 77%; 1664 participants; 9 trials, very low certainty). Two pharmacologic trials and three combined pharmacologic and psychosocial trials reported on side effects. These studies found more side effects attributable to amitriptyline relative to mirtazapine, naltrexone and topiramate relative to placebo, yet no differences in side effects between placebo and either acamprosate or ondansetron. Across all intervention types there was substantial risk of bias. Primary threats to validity included lack of blinding and differential/high rates of attrition. AUTHORS' CONCLUSIONS: In LMICs there is low-certainty evidence supporting the efficacy of combined psychosocial and pharmacologic interventions on reducing harmful alcohol use relative to psychosocial interventions alone. There is insufficient evidence to determine the efficacy of pharmacologic or psychosocial interventions on reducing harmful alcohol use largely due to the substantial heterogeneity in outcomes, comparisons, and interventions that precluded pooling of these data in meta-analyses. The majority of studies are brief interventions, primarily among men, and using measures that have not been validated in the target population. Confidence in these results is reduced by the risk of bias and significant heterogeneity among studies as well as the heterogeneity of results on different outcome measures within studies. More evidence on the efficacy of pharmacologic interventions, specific types of psychosocial interventions are needed to increase the certainty of these results.

Disparities in Prehospital Non-Traumatic Pain Management.

Introduction: While prior research has identified racial disparities in prehospital analgesia for traumatic pain, little is known about non-traumatic pain. Using a national prehospital dataset, we sought to evaluate for racial and ethnic disparities in analgesia given by EMS for non-traumatic pain.Methods: We analyzed the 2018 and 2019 data from the ESO Data Collaborative, a collection of de-identified prehospital electronic health records from nearly 1,300 participating EMS agencies in the US. We included all transported, adult, non-traumatic encounters with a primary or secondary impression of a pain complaint, and we stratified encounters based on race and ethnicity as recorded by the EMS clinicians. We performed a mixed model analysis, modeling EMS agency as a random intercept and adjusting for age, sex, pain location, level of service, location of incident, and highest pain score. With non-Hispanic White patients as the reference group, we then evaluated the association between race/ethnicity and receiving any pain medication (acetaminophen, non-steroidal anti-inflammatories, or opioids), receiving opioid pain medication, and receiving pain medication within 20 minutes of EMS arrival.Results: We included 1,035,486 patients; 67.5% non-Hispanic White, 26.8% Black, 4.9% Hispanic, 0.5% Asian, 0.1% Native Hawaiian or Other Pacific Islander, and 0.2% American Indian or Alaska Native patients. 4.7% of patients received pain medications. Compared to White patients (5.1%), Black patients were less likely to receive pain medication (3.3%, aOR 0.7; 95% CI 0.7-0.7) and Hispanics were more likely to receive pain medication (7.6%, aOR 1.5; 95% CI 1.4-1.6). Black patients were also less likely to receive opioids (1.8% for Black v 3.0% for White, aOR 0.7; 95% CI 0.6-0.7), while Hispanic patients were more likely to receive opioids (4.9%, aOR 1.4; 95% CI 1.3-1.5). The odds of receiving pain medication within 20 minutes was lower for Black patients (aOR 0.9; 95% CI 0.8-0.95) but no different for Hispanic patients (aOR 1.0; 95% CI 0.9-1.1), when compared to White patients.Conclusion: Pain medication administration is uncommon for non-traumatic pain complaints. While Black patients were less likely than White patients to receive pain medications and receive pain medication within 20 minutes, Hispanics were more likely to receive pain medications.

Utilizing an Online Communication Module With Baccalaureate Nursing Students to Teach Leadership in Team Meetings.

ABSTRACT: This article presents an online communication module for teaching nurse leadership in team meetings. Baccalaureate students ( n = 64) participated in a one-hour online module as part of a leadership course. The module included a quantitative pre-post assessment and qualitative open-ended responses to video-based scenarios of team meetings. Student responses to scenarios revealed high levels of content mastery and ability to apply module content (range, 89 percent to 90 percent across two scenarios). The module was effective in increasing the knowledge, attitude, and behaviors of students and is effective for facilitating student understanding of nurse leadership in team meetings.

Implementation of Overdose Prevention in Maryland: Implications for Resource Allocation, Program Scale-Up, and Evaluation.

Overdose mortality in the United States continues to climb, with Maryland being one of the hardest hit states. We summarized implementation of overdose prevention and response programs in Maryland and identified associations between opioid overdose deaths by jurisdiction in 2019 and implementation of overdose programs by 2021. Data on program implementation are from Maryland's Opioid Operational Command Center (OOCC) Program Inventory. OOCC coordinates the state's response to overdose, and their Program Inventory tracks implementation of 145 programs across 12 domains (e.g., public health, education, and judiciary), including 10 programs designed to broaden naloxone access. The level of program implementation was dichotomized as substantial implementation versus other levels (i.e., partial, planned, and none). We estimated associations between per capita opioid overdose deaths and substantial implementation of: all 145 programs in the Inventory, programs within each of 12 domains, and 10 naloxone programs. Data on program implementation and overdose mortality are summarized at the jurisdiction level. Across jurisdictions, the median proportion of programs with substantial implementation was 51% across all programs and 70% among naloxone programs. Overdose mortality was associated with subsequent substantial implementation of programs within the public health domain (p = .04), but not in the other 11 domains. We did not find evidence that per capita overdose deaths in 2019 spurred overdose program implementation by 2021, with the exception of public health programs. The OOCC Program Inventory is a novel way to track implementation across jurisdictions. Findings can inform the implementation and evaluation of overdose programs in other jurisdictions across the United States.

"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.

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 .

Evidence-Based Assessment of Genes in Dilated Cardiomyopathy.

BACKGROUND: Each of the cardiomyopathies, classically categorized as hypertrophic cardiomyopathy, dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy, has a signature genetic theme. Hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are largely understood as genetic diseases of sarcomere or desmosome proteins, respectively. In contrast, >250 genes spanning >10 gene ontologies have been implicated in DCM, representing a complex and diverse genetic architecture. To clarify this, a systematic curation of evidence to establish the relationship of genes with DCM was conducted. METHODS: An international panel with clinical and scientific expertise in DCM genetics evaluated evidence supporting monogenic relationships of genes with idiopathic DCM. The panel used the Clinical Genome Resource semiquantitative gene-disease clinical validity classification framework with modifications for DCM genetics to classify genes into categories on the basis of the strength of currently available evidence. Representation of DCM genes on clinically available genetic testing panels was evaluated. RESULTS: Fifty-one genes with human genetic evidence were curated. Twelve genes (23%) from 8 gene ontologies were classified as having definitive (BAG3, DES, FLNC, LMNA, MYH7, PLN, RBM20, SCN5A, TNNC1, TNNT2, TTN) or strong (DSP) evidence. Seven genes (14%; ACTC1, ACTN2, JPH2, NEXN, TNNI3, TPM1, VCL) including 2 additional ontologies were classified as moderate evidence; these genes are likely to emerge as strong or definitive with additional evidence. Of these 19 genes, 6 were similarly classified for hypertrophic cardiomyopathy and 3 for arrhythmogenic right ventricular cardiomyopathy. Of the remaining 32 genes (63%), 25 (49%) had limited evidence, 4 (8%) were disputed, 2 (4%) had no disease relationship, and 1 (2%) was supported by animal model data only. Of the 16 evaluated clinical genetic testing panels, most definitive genes were included, but panels also included numerous genes with minimal human evidence. CONCLUSIONS: In the curation of 51 genes, 19 had high evidence (12 definitive/strong, 7 moderate). It is notable that these 19 genes explain only a minority of cases, leaving the remainder of DCM genetic architecture incompletely addressed. Clinical genetic testing panels include most high-evidence genes; however, genes lacking robust evidence are also commonly included. We recommend that high-evidence DCM genes be used for clinical practice and that caution be exercised in the interpretation of variants in variable-evidence DCM genes.

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.

ISGylation is induced in neurons by demyelination driving ISG15-dependent microglial activation.

The causes of grey matter pathology and diffuse neuron injury in MS remain incompletely understood. Axonal stress signals arising from white matter lesions has been suggested to play a role in initiating this diffuse grey matter pathology. Therefore, to identify the most upstream transcriptional responses in neurons arising from demyelinated axons, we analyzed the transcriptome of actively translating neuronal transcripts in mouse models of demyelinating disease. Among the most upregulated genes, we identified transcripts associated with the ISGylation pathway. ISGylation refers to the covalent attachment of the ubiquitin-like molecule interferon stimulated gene (ISG) 15 to lysine residues on substrates targeted by E1 ISG15-activating enzyme, E2 ISG15-conjugating enzymes and E3 ISG15-protein ligases. We further confirmed that ISG15 expression is increased in MS cortical and deep gray matter. Upon investigating the functional impact of neuronal ISG15 upregulation, we noted that ISG15 expression was associated changes in neuronal extracellular vesicle protein and miRNA cargo. Specifically, extracellular vesicle-associated miRNAs were skewed toward increased frequency of proinflammatory and neurotoxic miRNAs and decreased frequency of anti-inflammatory and neuroprotective miRNAs. Furthermore, we found that ISG15 directly activated microglia in a CD11b-dependent manner and that microglial activation was potentiated by treatment with EVs from neurons expressing ISG15. Further study of the role of ISG15 and ISGylation in neurons in MS and neurodegenerative diseases is warranted.

Inflammatory monocytes and microglia play independent roles in inflammatory ictogenesis.

BACKGROUND: The pathogenic contribution of neuroinflammation to ictogenesis and epilepsy may provide a therapeutic target for reduction of seizure burden in patients that are currently underserved by traditional anti-seizure medications. The Theiler's murine encephalomyelitis virus (TMEV) model has provided important insights into the role of inflammation in ictogenesis, but questions remain regarding the relative contribution of microglia and inflammatory monocytes in this model. METHODS: Female C57BL/6 mice were inoculated by intracranial injection of 2 × 105, 5 × 104, 1.25 × 104, or 3.125 × 103 plaque-forming units (PFU) of the Daniel's strain of TMEV at 4-6 weeks of age. Infiltration of inflammatory monocytes, microglial activation, and cytokine production were measured at 24 h post-infection (hpi). Viral load, hippocampal injury, cognitive performance, and seizure burden were assessed at several timepoints. RESULTS: The intensity of inflammatory infiltration and the extent of hippocampal injury induced during TMEV encephalitis scaled with the amount of infectious virus in the initial inoculum. Cognitive performance was preserved in mice inoculated with 1.25 × 104 PFU TMEV relative to 2 × 105 PFU TMEV, but peak viral load at 72 hpi was equivalent between the inocula. CCL2 production in the brain was attenuated by 90% and TNFα and IL6 production was absent in mice inoculated with 1.25 × 104 PFU TMEV. Acute infiltration of inflammatory monocytes was attenuated by more than 80% in mice inoculated with 1.25 × 104 PFU TMEV relative to 2 × 105 PFU TMEV but microglial activation was equivalent between groups. Seizure burden was attenuated and the threshold to kainic acid-induced seizures was higher in mice inoculated with 1.25 × 104 PFU TMEV but low-level behavioral seizures persisted and the EEG exhibited reduced but detectable abnormalities. CONCLUSIONS: The size of the inflammatory monocyte response induced by TMEV scales with the amount of infectious virus in the initial inoculum, despite the development of equivalent peak infectious viral load. In contrast, the microglial response does not scale with the inoculum, as microglial hyper-ramification and increased Iba-1 expression were evident in mice inoculated with either 1.25 × 104 or 2 × 105 PFU TMEV. Inoculation conditions that drive inflammatory monocyte infiltration resulted in robust behavioral seizures and EEG abnormalities, but the low inoculum condition, associated with only microglial activation, drove a more subtle seizure and EEG phenotype.

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.

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.

Trajectories of Mental Distress Among U.S. Adults During the COVID-19 Pandemic.

BACKGROUND: Cross-sectional studies have found that the coronavirus disease 2019 (COVID-19) pandemic has negatively affected population-level mental health. Longitudinal studies are necessary to examine trajectories of change in mental health over time and identify sociodemographic groups at risk for persistent distress. PURPOSE: To examine the trajectories of mental distress between March 10 and August 4, 2020, a key period during the COVID-19 pandemic. METHODS: Participants included 6,901 adults from the nationally representative Understanding America Study, surveyed at baseline between March 10 and 31, 2020, with nine follow-up assessments between April 1 and August 4, 2020. Mixed-effects logistic regression was used to examine the association between date and self-reported mental distress (measured with the four-item Patient Health Questionnaire) among U.S. adults overall and among sociodemographic subgroups defined by sex, age, race/ethnicity, household structure, federal poverty line, and census region. RESULTS: Compared to March 11, the odds of mental distress among U.S. adults overall were 1.84 (95% confidence interval [CI] = 1.65-2.07) times higher on April 1 and 1.92 (95% CI = 1.62-2.28) times higher on May 1; by August 1, the odds of mental distress had returned to levels comparable to March 11 (odds ratio [OR] = 0.80, 95% CI = 0.66-0.96). Females experienced a sharper increase in mental distress between March and May compared to males (females: OR = 2.29, 95% CI = 1.85-2.82; males: OR = 1.53, 95% CI = 1.15-2.02). CONCLUSIONS: These findings highlight the trajectory of mental health symptoms during an unprecedented pandemic, including the identification of populations at risk for sustained mental distress.

Behavioral Intentions to Use Patient Portals to Disclose HIV and Other Sexually Transmitted Infection Testing Histories with Sexual Partners Among U.S. Sexual Minority Men.

Disclosure of HIV and other sexually transmitted infection (HIV/STI) testing history to sexual partners is low among gay, bisexual, and other U.S. sexual minority men (SMM). Patient portals (PP) could increase HIV/STI testing history disclosure. This study estimated the predictive validity of the Enhancing Dyadic Communication (EDC) latent construct for perceived behavioral intentions to use PP for HIV/STI test disclosures. A randomized subset of SMM completed the Patient Portal Sexual Health Instrument as part of the 2018 American Men's Internet Survey. Multivariable logistic regression models estimated associations between EDC and intentions to use PP for test disclosures. Among a sample of 1,509 SMM aged 15 to 77 years, EDC was associated with intentions to use PP to disclose test history with main partners (aOR 2.17; 95% CI 1.90 to 2.47) and non-main partners (aOR 2.39; 95%CI 2.07 to 2.76). Assessing EDC could be useful in clinical settings for interventions encouraging patients to communicate with partners about testing.

RESUMEN: La divulgación del historial de pruebas del VIH y otras infecciones de transmisión sexual (VIH / ITS) a las parejas sexuales es baja entre los homosexuales, bisexuales y otros hombres de minorías sexuales (SMM) de EE. UU. Los portales de pacientes (PP) podrían aumentar la divulgación del historial de pruebas de VIH / ITS. Este estudio estimó la validez predictiva del constructo latente Mejora de la comunicación diádica (EDC) para las intenciones conductuales percibidas de usar PP para las revelaciones de pruebas de VIH / ITS. Un subconjunto aleatorio de SMM completó el Instrumento de salud sexual del portal para pacientes como parte de la Encuesta de Internet de hombres estadounidenses de 2018. Los modelos de regresión logística multivariable estimaron asociaciones entre EDC e intenciones de usar PP para divulgaciones de pruebas. Entre una muestra de 1.509 SMM de entre 15 y 77 años, la EDC se asoció con las intenciones de utilizar PP para revelar el historial de pruebas con los socios principales (ORa = 2,17; IC del 95% = 1,90 a 2,47) y socios no principales (ORa = 2,39; IC del 95% = 2,07 a 2,76). La evaluación de EDC podría ser útil en entornos clínicos para intervenciones que alienten a los pacientes a comunicarse con sus socios sobre las pruebas.

Multisite medical record review of emergency department visits for unspecified injury of head following the ICD-10-CM coding transition.

INTRODUCTION: In 2016, a proposed International Classification of Diseases, Tenth Edition, Clinical Modification surveillance definition for traumatic brain injury (TBI) morbidity was introduced that excluded the unspecified injury of head (S09.90) diagnosis code. This study assessed emergency department (ED) medical records containing S09.90 for evidence of TBI based on medical documentation. METHODS: State health department representatives in Maryland, Kentucky, Colorado and Massachusetts reviewed a target of 385 randomly sampled ED records uniquely assigned the S09.90 diagnosis code (without proposed TBI codes), which were initial medical encounters among state residents discharged home during October 2015-December 2018. Using standardised abstraction procedures, reviewers recorded signs and symptoms of TBI, and head imaging results. A tiered case confirmation strategy was applied that assigned a level of certainty (high, medium, low, none) to each record based on the number and type of symptoms and imaging results present in the record. Positive predictive value (PPV) of S09.90 by level of TBI certainty was calculated by state. RESULTS: Wide variation in PPV of sampled ED records assigned S09.90: 36%-52% had medium or high evidence of TBI, while 48%-64% contained low or no evidence of a TBI. Loss of consciousness was mentioned in 8%-24% of sampled medical records. DISCUSSION: Exclusion of the S09.90 code in surveillance estimates may result in many missed TBI cases; inclusion may result in counting many false positives. Further, missed TBI cases influenced by incidence estimates, based on the TBI surveillance definition, may lead to inadequate allocation of public health resources.

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.

Correction: Using the Patient Portal Sexual Health Instrument in Surveys and Patient Questionnaires Among Sexual Minority Men in the United States: Cross-sectional Psychometric Validation Study.

[This corrects the article DOI: 10.2196/18750.].