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OBJECTIVE: Etanercept is a soluble fusion protein designed to inhibit tumor necrosis factor (TNF). During the Wegener's Granulomatosis Etanercept Trial (WGET), a placebo-controlled trial of etanercept given in addition to standard therapy for remission induction and maintenance, more solid malignancies were observed in the etanercept group than in the group treated with standard therapy alone. This study was undertaken to further explore the potential association between anti-TNF therapy and the development of malignancy in these patients. METHODS: One hundred eighty patients with active WG were enrolled and followed up for a median of 27 months. At enrollment, disease characteristics, treatment history, specific medical history items, and information about previous WG treatments and risk factors for malignancy were recorded. During the trial, the occurrence of malignancies and other adverse events was recorded prospectively. RESULTS: All 6 solid malignancies observed during the WGET occurred in the etanercept group (P = 0.01 versus placebo group); based on a comparison of age- and sex-specific incidence rates, 1.92 solid malignancies would have been expected in this group. The solid malignancies included 2 cases of mucinous adenocarcinoma of the colon, 1 each of metastatic cholangiocarcinoma, renal cell carcinoma, and breast carcinoma, and 1 recurrent liposarcoma. There were no differences between the 2 treatment groups in sex distribution, disease severity, personal or family history of cancer, or tobacco and alcohol use. The etanercept group was older at baseline and less likely to be newly diagnosed with WG at the time of randomization. Patients who developed solid tumors were older than patients who did not. All etanercept-treated patients who developed solid tumors were also treated with cyclophosphamide during the trial. However, there were no differences between the groups in the amount of cyclophosphamide received during the trial or the percentage who had received cyclophosphamide before enrollment. There were also no differences in the mean duration of daily cyclophosphamide therapy or the maximum daily cyclophosphamide dosage before enrollment. CONCLUSION: Data from the WGET, the first substantial reported experience of the combined use of etanercept and cyclophosphamide in the treatment of WG, indicate that the combination of TNF inhibition and cyclophosphamide may heighten the risk of cancer beyond that observed with cyclophosphamide alone. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To analyze damage occurring in patients with Wegener's granulomatosis (WG) enrolled in the WG Etanercept Trial (WGET) and to correlate that damage with disease activity, adverse events, and quality of life. METHODS: The Vasculitis Damage Index (VDI) was applied to all 180 patients at trial entry and every 6 months throughout the trial. Items of damage were analyzed by presumed etiology (i.e., secondary to WG, to therapy, or both) and time of occurrence. Spearman's rank correlation coefficients were calculated between VDI scores and the Birmingham Vasculitis Activity Score for WG (BVAS/WG), frequency of flares, number of adverse events, and the patients' quality-of-life assessments. RESULTS: The mean VDI score was 1.3 at the study enrollment and 1.8 at the end of the trial. This increase was due to damage that occurred despite (or because of) therapy, including visual impairment, hearing loss, nasal blockade, pulmonary fibrosis, hypertension, renal insufficiency, peripheral neuropathy, gonadal failure, and diabetes mellitus. Only 11% of the enrolled patients had not sustained a single VDI item after 1 year of enrollment. When adjusted for baseline VDI, the baseline BVAS/WG correlated moderately well with the VDI score at 1 year (r = 0.20, P = 0.015). Increases in adjusted VDI scores also correlated with the number of adverse events, particularly among patients with limited WG (P = 0.06). CONCLUSION: Damage from both active disease and its treatment remain important problems for patients with WG. Despite the dramatic improvements in patient survival achieved over the last several decades, only a few patients with WG emerge from a period of active disease without sustaining some damage from the disease itself, its treatment, or both. An important measure of future therapeutic approaches will be their ability to reduce the damage accrued over time. [ABSTRACT FROM AUTHOR]

Intensive longitudinal research-including experience sampling and smartphone sensor monitoring-has potential for identifying proximal risk factors for psychopathology, including suicidal thoughts and behaviors (STB). Yet, missing data can complicate analysis and interpretation. This study aimed to address whether clinical and study design factors are associated with missing data and whether missingness predicts changes in symptom severity or STB. Adolescents ages 13- to 18 years old ( N = 179) reporting depressive, anxiety, and/or substance use disorders were enrolled; 65% reported current suicidal ideation and 29% indicated a past-year attempt. Passively acquired smartphone sensor data (e.g., global positioning system, accelerometer, and keyboard inputs), daily mood surveys, and weekly suicidal ideation surveys were collected during the 6-month study period using the effortless assessment research system smartphone app. First, acquisition of passive smartphone sensor data (with data on ∼80% of days across the whole sample) was strongly associated with survey data acquisition on the same day (∼44% of days). Second, STB and psychiatric symptoms were largely not associated with missing data. Rather, temporal features (e.g., length of time in study, weekends, and summer) explained more missingness of survey and passive smartphone sensor data. Last, within-participant changes in missing data over time neither followed nor predicted subsequent change in suicidal ideation and psychiatric symptoms. Findings indicate that considering technical and study design factors impacting missingness is critical and highlight several factors that should be addressed to maximize the validity of clinical interpretations in intensive longitudinal research. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Importance: It is well established that people of South Asian background have a high burden of atherosclerotic cardiovascular disease (ASCVD). However, few studies have comprehensively examined if South Asian adults in the United States (US) develop cardiovascular risk factors at younger ages than adults from other race and ethnic groups., Objective: To compare the prevalence and change in ASCVD risk factors across age strata by race and ethnic group., Design: We combined data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and the Multi-Ethnic Study of Atherosclerosis (MESA) cohort studies. Longitudinal data from all eligible participants at all available exam visits were used to estimate the prevalence of risk factors at ages 45 and 55 years for each race and ethnic group., Setting: Multicenter longitudinal cohort study in 7 field centers across the U.S., Participants: The baseline study sample included individuals free of clinical ASCVD; 554 South Asians, 796 White, 588 Black, 517 Hispanic/Latino, and 245 Chinese adults aged 45-55 years were included., Exposures: Self-identified race (Black, Chinese, South Asian, or White) or ethnic group (Hispanic/Latino)., Main Outcomes and Measures: Prevalence of clinical (prediabetes & diabetes, hypertension, dyslipidemia, BMI) and behavioral (diet quality, alcohol use, exercise) ASCVD risk factors at age 45 and age 55., Results: At age 45, South Asian men and women had the highest prevalence of pre-diabetes and diabetes and higher prevalence of hypertension compared to White, Chinese, and Hispanic/Latino men and women. South Asian men had a higher prevalence of dyslipidemia than White, Chinese, and Black men, and South Asian women had a higher prevalence than Chinese and Black women. All groups had worse diet quality than South Asian men and women at age 45, and most also had higher rates of alcohol use., Conclusions and Relevance: We observed significant differences in the prevalence of risk factors for South Asian adults compared to adults from other U.S. race and ethnic groups at age 45 years. Understanding trends and disparities in cardiovascular risk and protective factors across the life course can help equitably improve prevention and treatment strategies for US populations., Key Points: Question: Do South Asian adults have a higher burden of cardiovascular risk factors at age 45 years compared adults from other race and ethnic groups? Findings: In this study of 2754 adults from two cohort studies, the prevalence of prediabetes and diabetes at age 45 years was higher among South Asians than in Black, Chinese, Hispanic and White adults; hypertension prevalence was higher among South Asians than all groups except Black adults. Meaning: South Asian adults have a higher prevalence of several clinical cardiovascular risk factors at a younger age.

Background: Studying the association between blood pressure (BP) trajectories during young adulthood and subsequent cardiovascular disease (CVD) risk can provide insights into how long-term BP patterns in early life influence the development of CVD later in life., Methods: We pooled data from two US cohorts (CARDIA, FHS). We used latent growth curve models to identify distinct BP trajectory groups during ages 18-39 years. We then used Cox proportional hazards models to assess the associations between BP trajectories and CVD events (composite of coronary heart disease [CHD], stroke, and heart failure [HF]) after age 40 years., Results: We included 6,579 participants and identified four distinct systolic BP trajectory groups during young adulthood. During a median follow-up of 18.2 years after age 40 years, 213 CHD, 139 stroke, 120 HF, and 400 composite CVD events occurred. Individuals in an elevated-increasing vs. low-stable systolic BP trajectory during young adulthood was associated with a higher risk of CVD after adjusting for traditional CVD risk factors, with hazard ratios (95% CI) of 3.25 (1.63, 6.46) for CHD, 3.92 (1.63, 9.43) for stroke, 8.30 (2.97, 23.17) for HF, and 3.91 (2.38, 6.41) for composite CVD outcomes. Adding BP trajectory to BP at baseline improved model discrimination for all outcomes (changes in Harrell's C-index 0.0084 to 0.0192)., Conclusions: An elevated-increasing BP trajectory during young adulthood is associated with a higher risk of CVD later in life, highlighting the importance of maintaining a low-stable BP trajectory throughout the young adulthood period for prevention of CVD in later life., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Adolescence and early adulthood are pivotal stages for the onset of mental health disorders and the development of health behaviors. Digital behavioral activation interventions, with or without coaching support, hold promise for addressing risk factors for both mental and physical health problems by offering scalable approaches to expand access to evidence-based mental health support., Objective: This 2-arm pilot randomized controlled trial evaluated 2 versions of a digital behavioral health product, Vira (Ksana Health Inc), for their feasibility, acceptability, and preliminary effectiveness in improving mental health in young adults with depressive symptoms and obesity risk factors., Methods: A total of 73 participants recruited throughout the United States were randomly assigned to use Vira either as a self-guided product (Vira Self-Care) or with support from a health coach (Vira+Coaching) for 12 weeks. The Vira smartphone app used passive sensing of behavioral data related to mental health and obesity risk factors (ie, activity, sleep, mobility, and language patterns) and offered users personalized insights into patterns of behavior associated with their daily mood. Participants completed self-reported outcome measures at baseline and follow-up (12 weeks). All study procedures were completed via digital communications., Results: Both versions of Vira showed strong user engagement, acceptability, and evidence of effectiveness in improving mental health and stress. However, users receiving coaching exhibited more sustained engagement with the platform and reported greater reductions in depression (Cohen d=0.45, 95% CI 0.10-0.82) and anxiety (Cohen d=0.50, 95% CI 0.13-0.86) compared to self-care users. Both interventions also resulted in reduced stress (Vira+Coaching: Cohen d=-1.05, 95% CI -1.57 to --0.50; Vira Self-Care: Cohen d=-0.78, 95% CI -1.33 to -0.23) and were perceived as useful and easy to use. Coached users also reported reductions in sleep-related impairment (Cohen d=-0.51, 95% CI -1.00 to -0.01). Moreover, participants increased their motivation for and confidence in making behavioral changes, with greater improvements in confidence among coached users., Conclusions: An app-based intervention using passive mobile sensing to track behavior and deliver personalized insights into behavior-mood associations demonstrated feasibility, acceptability, and preliminary effectiveness for reducing depressive symptoms and other mental health problems in young adults. Future directions include (1) optimizing the interventions, (2) conducting a fully powered trial that includes an active control condition, and (3) testing mediators and moderators of outcome effects., Trial Registration: ClinicalTrials.gov NCT05638516; https://clinicaltrials.gov/study/NCT05638516., (©Lauren S Weiner, Ryann N Crowley, Lisa B Sheeber, Frank H Koegler, Jon F Davis, Megan Wells, Carter J Funkhouser, Randy P Auerbach, Nicholas B Allen. Originally published in JMIR Mental Health (https://mental.jmir.org), 19.09.2024.)

Background: The ability of a 1-time measurement of non-high-density lipoprotein cholesterol (non-HDL-C) or low-density lipoprotein cholesterol (LDL-C) to predict the cumulative exposure to these lipids during early adulthood (age 18-40 years) and the associated atherosclerotic cardiovascular disease (ASCVD) risk after age 40 years is not clear., Objectives: The objectives of this study were to evaluate whether a 1-time measurement of non-HDL-C or LDL-C in a young adult can predict cumulative exposure to these lipids during early adulthood, and to quantify the association between cumulative exposure to non-HDL-C or LDL-C during early adulthood and the risk of ASCVD after age 40 years., Methods: We included CARDIA (Coronary Artery Risk Development in Young Adults Study) participants who were free of cardiovascular disease before age 40 years, were not taking lipid-lowering medications, and had ≥3 measurements of LDL-C and non-HDL-C before age 40 years. First, we assessed the ability of a 1-time measurement of LDL-C or non-HDL-C obtained between age 18 and 30 years to predict the quartile of cumulative lipid exposure from ages 18 to 40 years. Second, we assessed the associations between quartiles of cumulative lipid exposure from ages 18 to 40 years with ASCVD events (fatal and nonfatal myocardial infarction and stroke) after age 40 years., Results: Of 4,104 CARDIA participants who had multiple lipid measurements before and after age 30 years, 3,995 participants met our inclusion criteria and were in the final analysis set. A 1-time measure of non-HDL-C and LDL-C had excellent discrimination for predicting membership in the top or bottom quartiles of cumulative exposure (AUC: 0.93 for the 4 models). The absolute values of non-HDL-C and LDL-C that predicted membership in the top quartiles with the highest simultaneous sensitivity and specificity (highest Youden's Index) were >135 mg/dL for non-HDL-C and >118 mg/dL for LDL-C; the values that predicted membership in the bottom quartiles were <107 mg/dL for non-HDL-C and <96 mg/dL for LDL-C. Individuals in the top quartile of non-HDL-C and LDL-C exposure had demographic-adjusted HRs of 4.6 (95% CI: 2.84-7.29) and 4.0 (95% CI: 2.50-6.33) for ASCVD events after age 40 years, respectively, when compared with each bottom quartile., Conclusions: Single measures of non-HDL-C and LDL-C obtained between ages 18 and 30 years are highly predictive of cumulative exposure before age 40 years, which in turn strongly predicts later-life ASCVD events., Competing Interests: Funding Support and Author Disclosures This work was supported by National Heart, Lung, and Blood Institute R01HL146844. Dr Wilkins has served as a consultant for 3M (nonmedical division) that is not relevant to the content of this manuscript. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background: Atherosclerotic cardiovascular disease (ASCVD) risk estimation based on the pooled cohort equation (PCE) overestimates in population-based cohorts. Whether it performs equally across disaggregated demographics in health care populations is less known., Objectives: The purpose of the study was to recalibrate PCE and rederive prevention thresholds in a contemporary health care system and evaluate its performance across sociodemographics., Methods: We retrospectively inspected electronic health records between 2010 to 2012 and 2020 to 2022 within Mass General Brigham health care in New England region. We compared performance of the original vs recalibrated PCE measured by calibration, discrimination, reclassification rate, and net benefit among 160,926 patients aged 40 to 79 years and without prior ASCVD or lipid-lowering medication., Results: Of the 160,926 patients (mean age: 54.6 ± 8.6 years; 61.4% female), 20,373 (12.7%) developed ASCVD over 10 years. The original PCE globally underestimated ASCVD risk (observed vs predicted incidence rate: 0.13 vs 0.05). Recalibration upclassified risk primarily among individuals with low-to-borderline risk by the original PCE and additionally identified 40% of patients who had undergone ASCVD events yet deemed statin-ineligible based on the original PCE. Treatment thresholds yielding the greatest net benefit were ≥24.0% for women (+23.3%) vs ≥26.0% for men (+18.7%), whereas ≥26.0% for White or other race (+24.7%) vs ≥14.0% Black or African American (+12.5%), respectively. Specifically, Hispanic or Latino and non-Hispanic Black patients conferred the greatest sensitivity improvement at ≥12.3% threshold compared to higher ≥23.6% among non-Hispanic Asian or Pacific Islanders. Generally, lower thresholds earlier in life were optimal., Conclusions: Recalibration and personalized treatment thresholds derived within a health system may improve prevention treatment allocation efficiency., Competing Interests: Dr Cho is supported by a grant of the Korea Health Technology R&D Project through the 10.13039/501100003710Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health and Welfare, Republic of Korea (grant no.: HI19C1330). Dr Paruchuri is supported in part by the Massachusetts General Hospital Executive Committee on Research Fund for Medical Discovery Population Healthcare Sciences Research Fellowship Award. Dr Honigberg is supported by grants from the 10.13039/100000050National Heart, Lung, and Blood Institute (K08HL166687) and the 10.13039/100000968American Heart Association (940166, 979465). Dr Natarajan is supported by grants from the 10.13039/100000050National Heart, Lung, and Blood Institute (R01HL142711, R01HL127564, R01HL148050, R01HL151283, R01HL148565, R01HL135242, and R01HL151152), the National Human Genetics Research Institute (U01HG011719), the 10.13039/100000062National Institute of Diabetes and Digestive and Kidney Diseases (R01DK125782), 10.13039/501100001674Fondation Leducq (TNE-18CVD04), and 10.13039/100005294Massachusetts General Hospital (Paul and Phyllis Fireman Endowed Chair in Vascular Medicine). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr Bhattacharya reports prior advisory relationship with Casana Care, Inc unrelated to the current work. Dr Paruchuri has received research support from Genetech, 10.13039/100004336Novartis, and Allelica, all unrelated to this work. Dr Honigberg has received consulting fees from CRISPR Therapeutics and Comanche Biopharma; advisory board service for Miga Health; and research support from Genetech, all unrelated to the present work. Dr Natarajan has received personal consulting fees from Allelica, Amgen, Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Genentech/Roche, Novartis, and TenSixteen Bio; investigator-initiated grants from Apple, 10.13039/100004325AstraZeneca, 10.13039/100002429Amgen, Genentech/Roche, 10.13039/100004336Novartis, and 10.13039/100008497Boston Scientific; is a co-founder of TenSixteen Bio, is a scientific advisory board member of Esperion Therapeutics, TenSixteen Bio, and geneXwell; and spousal employment at Vertex, all unrelated to the present work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Metabolic comorbidities, such as obesity and diabetes, are associated with subclinical alterations in both cardiac structure/function and natriuretic peptides prior to the onset of heart failure (HF). Despite this, the exact metabolic pathways of cardiac dysfunction which precede HF are not well-defined. Among older individuals without HF in the Multi-Ethnic Study of Atherosclerosis (MESA), we evaluated the associations of 47 circulating metabolites measured by 1 H-NMR with echocardiographic measures of cardiac structure and function. We then evaluated associations of significant metabolites with circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a separate cohort, we evaluated differences between top metabolites in patients with HF with preserved ejection fraction (HFpEF) and comorbidity-matched controls. Genetic variants associated with top metabolites (mQTLs) were then related to echocardiographic measures and NT-proBNP. Among 3440 individuals with metabolic and echocardiographic data in MESA (62 ± 10 years, 52% female, 38% White), 10 metabolites broadly reflective of glucose and amino acid metabolism were associated with at least 1 measure of cardiac structure or function. Of these 10 metabolites, 4 (myo-inositol, glucose, dimethylsulfone, carnitine) were associated with higher NT-proBNP and 2 (d-mannose, acetone) were associated with lower NT-proBNP. In a separate cohort, patients with HFpEF had higher circulating myo-inositol levels compared with comorbidity-matched controls. Genetic analyses revealed that 1 of 6 known myo-inositol mQTLs conferred risk of higher NT-proBNP. In conclusion, metabolomic profiling identifies several novel metabolites associated with cardiac dysfunction in a cohort at high risk for HF, revealing pathways potentially relevant to future HF risk., (© 2024. The Author(s).)

Background: Cardiovascular health (CVH) in young adulthood (YA) has been associated with cardiovascular outcomes in older age. However, little is known about the relationship between YA CVH and mid-life blood pressure (BP) trajectories., Methods: Baseline CVH (defined by 7 of the American Heart Association's [AHA] Life's Essential 8 [LE8] metrics, excluding BP) was measured in YA with individual metrics scored and averaged as a composite LE8 score. Categorical CVH status was defined as high, moderate, and low. Latent class analysis was used to identify trajectories of mid-BP (mean of systolic blood pressure [SBP] and diastolic blood pressure [DBP]) from average ages 35 to 55 years. Multinomial logistic regression was used to estimate the association of YA CVH status (continuously and categorically) with mid-life BP trajectory group membership., Results: There were 3,688 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study in YA with follow-up data for mid-life BP trajectories. We observed 3 BP trajectory groups, labeled as Persistently-Low, Middle, and High-Increasing. On average, each 10-points higher baseline LE8 score (mean [SD] of 73.5 [13.1]) in YA was associated with adjusted odds ratios of 0.78 (95% CI, 0.72-0.84) for membership in the Middle and 0.65 (0.57-0.73) for membership in the High-Increasing trajectory groups. Compared with categorical low CVH status at baseline, those with high CVH were significantly less likely to be in the Middle and High-Increasing BP trajectory groups., Conclusions: Moderate or low CVH status in YA is associated with elevated mid-life BP trajectory. These data suggest that young adult CVH promotion may be important for the primordial prevention of hypertension., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Youth screen media activity is a growing concern, though few studies include objective usage data. Through the longitudinal, U.S.-based Adolescent Brain Cognitive Development (ABCD) Study, youth (m age  = 14; n = 1415) self-reported their typical smartphone use and passively recorded three weeks of smartphone use via the ABCD-specific Effortless Assessment Research System (EARS) application. Here we describe and validate passively-sensed smartphone keyboard and app use measures, provide code to harmonize measures across operating systems, and describe trends in adolescent smartphone use. Keyboard and app-use measures were reliable and positively correlated with one another (r = 0.33) and with self-reported use (rs = 0.21-0.35). Participants recorded a mean of 5 h of daily smartphone use, which is two more hours than they self-reported. Further, females logged more smartphone use than males. Smartphone use was recorded at all hours, peaking on average from 8 to 10 PM and lowest from 3 to 5 AM. Social media and texting apps comprised nearly half of all use. Data are openly available to approved investigators ( https://nda.nih.gov/abcd/ ). Information herein can inform use of the ABCD dataset to longitudinally study health and neurodevelopmental correlates of adolescent smartphone use., (© 2024. The Author(s).)

Suicide is the second leading cause of death among adolescents, and rates of suicidal thoughts and behaviors (STBs) are climbing. 1 Promising interventions such as dialectical behavior therapy (DBT) are available to treat suicidal youth, and new approaches may facilitate greater intervention engagement, adherence, and effectiveness. 2 Digital tools (eg, personal smartphones) are a particularly promising avenue and could enhance existing, evidence-based interventions by providing new opportunities for assessment and intervention between sessions., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Adolescence is marked by an increasing risk of depression and is an optimal window for prevention and early intervention. Personalizing interventions may be one way to maximize therapeutic benefit, especially given the marked heterogeneity in depressive presentations. However, empirical evidence that can guide personalized intervention for youth is lacking. Identifying person-specific symptom drivers during adolescence could improve outcomes by accounting for both developmental and individual differences., Objective: This study leverages adolescents' everyday smartphone use to investigate person-specific drivers of depression and validate smartphone-based mobile sensing data against established ambulatory methods. We describe the methods of this study and provide an update on its status. After data collection is completed, we will address three specific aims: (1) identify idiographic drivers of dynamic variability in depressive symptoms, (2) test the validity of mobile sensing against ecological momentary assessment (EMA) and actigraphy for identifying these drivers, and (3) explore adolescent baseline characteristics as predictors of these drivers., Methods: A total of 50 adolescents with elevated symptoms of depression will participate in 28 days of (1) smartphone-based EMA assessing depressive symptoms, processes, affect, and sleep; (2) mobile sensing of mobility, physical activity, sleep, natural language use in typed interpersonal communication, screen-on time, and call frequency and duration using the Effortless Assessment of Risk States smartphone app; and (3) wrist actigraphy of physical activity and sleep. Adolescents and caregivers will complete developmental and clinical measures at baseline, as well as user feedback interviews at follow-up. Idiographic, within-subject networks of EMA symptoms will be modeled to identify each adolescent's person-specific drivers of depression. Correlations among EMA, mobile sensor, and actigraph measures of sleep, physical, and social activity will be used to assess the validity of mobile sensing for identifying person-specific drivers. Data-driven analyses of mobile sensor variables predicting core depressive symptoms (self-reported mood and anhedonia) will also be used to assess the validity of mobile sensing for identifying drivers. Finally, between-subject baseline characteristics will be explored as predictors of person-specific drivers., Results: As of October 2023, 84 families were screened as eligible, of whom 70% (n=59) provided informed consent and 46% (n=39) met all inclusion criteria after completing baseline assessment. Of the 39 included families, 85% (n=33) completed the 28-day smartphone and actigraph data collection period and follow-up study visit., Conclusions: This study leverages depressed adolescents' everyday smartphone use to identify person-specific drivers of adolescent depression and to assess the validity of mobile sensing for identifying these drivers. The findings are expected to offer novel insights into the structure and dynamics of depressive symptomatology during a sensitive period of development and to inform future development of a scalable, low-burden smartphone-based tool that can guide personalized treatment decisions for depressed adolescents., International Registered Report Identifier (irrid): DERR1-10.2196/43931., (©Mei Yi Ng, Jennifer A Frederick, Aaron J Fisher, Nicholas B Allen, Jeremy W Pettit, Dana L McMakin. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 16.07.2024.)

Sexual and gender minority (SGM) adolescents are at elevated risk for depression. This risk is especially pronounced among adolescents whose home environment is unsupportive or nonaffirming, as these adolescents may face familial rejection due to their identity. Therefore, it is critical to better understand the mechanisms underlying this risk by probing temporally sensitive associations between negative mood and time spent in potentially hostile home environments. The current study included adolescents ( N = 141; 43% SGM; 13-18 years old), oversampled for depression history, who completed clinical interviews assessing lifetime psychiatric history and depression severity as well as self-report measures of social support. Participants also installed an app on their personal smartphones, which assessed their daily mood and geolocation-determined mobility patterns over a 6-month follow-up period. Over the 6-month follow-up period, SGM adolescents reported elevated depression severity and lower daily mood relative to non-SGM youth. Interestingly, SGM adolescents who reported low family support experienced lower daily mood than non-SGM adolescents, particularly on days when they spent more time at home. Current findings reinforce evidence for disparities in depression severity among SGM adolescents and highlight family support as a key factor. Specifically, more time spent in home environments with low family support was associated with worse mood among SGM adolescents. These results underscore the need for clinical interventions to support SGM youth, particularly interventions that focus on familial relationships and social support within the home environment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Cross sectional studies have identified linguistic correlates of major depressive disorder (MDD) in smartphone communication. However, it is unclear whether monitoring these linguistic characteristics can detect when an individual is experiencing MDD, which would facilitate timely intervention., Methods: Approximately 1.2 million messages typed into smartphone social communication apps (e.g. texting, social media) were passively collected from 90 adolescents with a range of depression severity over a 12-month period. Sentiment (i.e. positive vs. negative valence of text), proportions of first-person singular pronouns (e.g. 'I'), and proportions of absolutist words (e.g. 'all') were computed for each message and converted to weekly aggregates temporally aligned with weekly MDD statuses obtained from retrospective interviews. Idiographic, multilevel logistic regression models tested whether within-person deviations in these linguistic features were associated with the probability of concurrently meeting threshold for MDD., Results: Using more first-person singular pronouns in smartphone communication relative to one's own average was associated with higher odds of meeting threshold for MDD in the concurrent week (OR = 1.29; p = .007). Sentiment (OR = 1.07; p = .54) and use of absolutist words (OR = 0.99; p = .90) were not related to weekly MDD., Conclusions: Passively monitoring use of first-person singular pronouns in adolescents' smartphone communication may help detect MDD, providing novel opportunities for early intervention., (© 2023 Association for Child and Adolescent Mental Health.)

Introduction: Higher levels of perceived stress are associated with adverse cardiovascular health. It is plausible that these associations are attenuated among individuals with positive psychological factors such as social support and health-enhancing behaviors. Therefore, this study examined longitudinal associations of chronic stress with cardiovascular disease (CVD) events, and whether social support and physical activity (PA) modify these associations., Methods: Data from 3,401 adults (mean age 40.2 years; 46.7% Black; 56.2% women) from the Coronary Artery Risk Development in Young Adults (CARDIA) study, with no prior CVD event in 2000-2001 were analyzed. Chronic stress lasting ≥6 months across 5 life domains (work, financial, relationships, health of self, and health of close other) was self-reported. Adjudicated CVD events (fatal/or nonfatal CVD event) were ascertained yearly through 2020. PA and social support were self-reported via questionnaires. Statistical analyses were conducted in 2023 using multivariable stepwise Accelerated Failure Time analysis to assess associations between key study variables., Results: The mean chronic stress score was 1.30±1.33 stressors and, by 2020, 220 participants had experienced a CVD event. Chronic stress was associated with lowered survival (time ratio: 0.92; 95% CI: 0.854-0.989), when adjusted for sociodemographic and lifestyle variables but no longer significant when adjusting for clinical factors. Neither PA nor social support were significant modifiers (all ps>0.05)., Conclusions: Chronic stress was associated with the risk of having a CVD event among middle-aged adults, due at least in part to clinical mediators. Studies should continue exploring positive psychosocial and behavioral factors that may modify this association., (Copyright © 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Combining pertinent data from multiple studies can increase the robustness of epidemiological investigations. Effective "pre-statistical" data harmonization is paramount to the streamlined conduct of collective, multi-study analysis. Harmonizing data and documenting decisions about the transformations of variables to a common set of categorical values and measurement scales are time consuming and can be error prone, particularly for numerous studies with large quantities of variables. The psHarmonize R package facilitates harmonization by combining multiple datasets, applying data transformation functions, and creating long and wide harmonized datasets. The user provides transformation instructions in a "harmonization sheet" that includes dataset names, variable names, and coding instructions and centrally tracks all decisions. The package performs harmonization, generates error logs as necessary, and creates summary reports of harmonized data. psHarmonize is poised to serve as a central feature of data preparation for the joint analysis of multiple studies., Competing Interests: N.B.A. receives funding from the National Institutes of Health and the American Heart Association. D.M.S. receives funding from the National Institutes of Health., (© 2024 The Authors.)

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.

Rationale: Chronic obstructive pulmonary disease (COPD) and emphysema are associated with endothelial damage and altered pulmonary microvascular perfusion. The molecular mechanisms underlying these changes are poorly understood in patients, in part because of the inaccessibility of the pulmonary vasculature. Peripheral blood mononuclear cells (PBMCs) interact with the pulmonary endothelium. Objectives: To test the association between gene expression in PBMCs and pulmonary microvascular perfusion in COPD. Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Study recruited two independent samples of COPD cases and controls with ⩾10 pack-years of smoking history. In both samples, pulmonary microvascular blood flow, pulmonary microvascular blood volume, and mean transit time were assessed on contrast-enhanced magnetic resonance imaging, and PBMC gene expression was assessed by microarray. Additional replication was performed in a third sample with pulmonary microvascular blood volume measures on contrast-enhanced dual-energy computed tomography. Differential expression analyses were adjusted for age, gender, race/ethnicity, educational attainment, height, weight, smoking status, and pack-years of smoking. Results: The 79 participants in the discovery sample had a mean age of 69 ± 6 years, 44% were female, 25% were non-White, 34% were current smokers, and 66% had COPD. There were large PBMC gene expression signatures associated with pulmonary microvascular perfusion traits, with several replicated in the replication sets with magnetic resonance imaging ( n  = 47) or dual-energy contrast-enhanced computed tomography ( n  = 157) measures. Many of the identified genes are involved in inflammatory processes, including nuclear factor-κB and chemokine signaling pathways. Conclusions: PBMC gene expression in nuclear factor-κB, inflammatory, and chemokine signaling pathways was associated with pulmonary microvascular perfusion in COPD, potentially offering new targetable candidates for novel therapies.

Background: The impact of digital device use on health and well-being is a pressing question. However, the scientific literature on this topic, to date, is marred by small and unrepresentative samples, poor measurement of core constructs, and a limited ability to address the psychological and behavioral mechanisms that may underlie the relationships between device use and well-being. Recent authoritative reviews have made urgent calls for future research projects to address these limitations. The critical role of research is to identify which patterns of use are associated with benefits versus risks and who is more vulnerable to harmful versus beneficial outcomes, so that we can pursue evidence-based product design, education, and regulation aimed at maximizing benefits and minimizing the risks of smartphones and other digital devices., Objective: The objective of this study is to provide normative data on objective patterns of smartphone use. We aim to (1) identify how patterns of smartphone use impact well-being and identify groups of individuals who show similar patterns of covariation between smartphone use and well-being measures across time; (2) examine sociodemographic and personality or mental health predictors and which patterns of smartphone use and well-being are associated with pre-post changes in mental health and functioning; (3) discover which nondevice behavior patterns mediate the association between device use and well-being; (4) identify and explore recruitment strategies to increase and improve the representation of traditionally underrepresented populations; and (5) provide a real-world baseline of observed stress, mood, insomnia, physical activity, and sleep across a representative population., Methods: This is a prospective, nonrandomized study to investigate the patterns and relationships among digital device use, sensor-based measures (including both behavioral and physiological signals), and self-reported measures of mental health and well-being. The study duration is 4 weeks per participant and includes passive sensing based on smartphone sensors, and optionally a wearable (Fitbit), for the complete study period. The smartphone device will provide activity, location, phone unlocks and app usage, and battery status information., Results: At the time of submission, the study infrastructure and app have been designed and built, the institutional review board of the University of Oregon has approved the study protocol, and data collection is underway. Data from 4182 enrolled and consented participants have been collected as of March 27, 2023. We have made many efforts to sample a study population that matches the general population, and the demographic breakdown we have been able to achieve, to date, is not a perfect match., Conclusions: The impact of digital devices on mental health and well-being raises important questions. The Digital Well-Being Study is designed to help answer questions about the association between patterns of smartphone use and well-being., International Registered Report Identifier (irrid): DERR1-10.2196/49189., (©Daniel McDuff, Andrew Barakat, Ari Winbush, Allen Jiang, Felicia Cordeiro, Ryann Crowley, Lauren E Kahn, John Hernandez, Nicholas B Allen. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 14.05.2024.)

Introduction: Emerging literature links fatherhood to men's health but lacks comprehensive assessment of health outcomes, especially among multiethnic populations. This study's objective was to evaluate the associations of fatherhood (age at onset and status) with cardiovascular health scores, incident cardiovascular disease, cardiovascular disease death, and all-cause mortality, examining differences by race/ethnicity., Methods: The study sample included men from Multi-Ethnic Study of Atherosclerosis, prospective cohort study that enrolled adults aged 45-84 years without known cardiovascular disease at baseline. Cardiovascular health was defined using the American Heart Association's Life's Essential 8 scores (0-100), excluding sleep (cardiovascular health score)., Results: In this sample of 2,814 men, mean age at cardiovascular health assessment was 62.2 years, 82% were fathers, 24% self-identified as Black, 13% self-identified Chinese, 22% self-identified Hispanic, and 41% self-identified White. Fathers who were aged <20 years and 20-24 years at their oldest child's birth had worse overall cardiovascular health than fathers who were aged >35 years (adjusted mean score of 61.1 vs 64.7 [ p =0.01] and 61.0 vs 64.7 [ p <0.001], respectively). Fathers had worse overall cardiovascular health (adjusted mean score of 63.2 vs 64.7, p =0.03) and more nicotine exposure (63.1 vs 66.6, p =0.04) than nonfathers. In age-adjusted models, fathers overall (hazard ratio=0.82; 95% CI=0.69, 0.98) and Black fathers (hazard ratio=0.73; 95% CI=0.53, 0.999) had a lower rate of all-cause mortality rate than nonfathers, but these associations were no longer significant in fully adjusted models., Conclusions: Fatherhood is a social determinant of health, and understanding its influence may provide opportunities to improve men's health, particularly among men of color., (© 2024 The Authors.)

Smaller mean airway tree caliber is associated with airflow obstruction and chronic obstructive pulmonary disease (COPD). We investigated whether airway tree caliber heterogeneity was associated with airflow obstruction and COPD. Two community-based cohorts (MESA Lung, CanCOLD) and a longitudinal case-control study of COPD (SPIROMICS) performed spirometry and computed tomography measurements of airway lumen diameters at standard anatomical locations (trachea-to-subsegments) and total lung volume. Percent-predicted airway lumen diameters were calculated using sex-specific reference equations accounting for age, height, and lung volume. The association of airway tree caliber heterogeneity, quantified as the standard deviation (SD) of percent-predicted airway lumen diameters, with baseline forced expired volume in 1-second (FEV 1 ), FEV 1 /forced vital capacity (FEV 1 /FVC) and COPD, as well as longitudinal spirometry, were assessed using regression models adjusted for age, sex, height, race-ethnicity, and mean airway tree caliber. Among 2,505 MESA Lung participants (means ± SD age: 69 ± 9 yr; 53% female, mean airway tree caliber: 99 ± 10% predicted, airway tree caliber heterogeneity: 14 ± 5%; median follow-up: 6.1 yr), participants in the highest quartile of airway tree caliber heterogeneity exhibited lower FEV 1 (adjusted mean difference: -125 mL, 95%CI: -171,-79), lower FEV 1 /FVC (adjusted mean difference: -0.01, 95%CI: -0.02,-0.01), and higher odds of COPD (adjusted odds ratio: 1.42, 95%CI: 1.01-2.02) when compared with the lowest quartile, whereas longitudinal changes in FEV 1 and FEV 1 /FVC did not differ significantly. Observations in CanCOLD and SPIROMICS were consistent. Among older adults, airway tree caliber heterogeneity was associated with airflow obstruction and COPD at baseline but was not associated with longitudinal changes in spirometry. NEW & NOTEWORTHY In this study, by leveraging two community-based samples and a case-control study of heavy smokers, we show that among older adults, airway tree caliber heterogeneity quantified by CT is associated with airflow obstruction and COPD independent of age, sex, height, race-ethnicity, and dysanapsis. These observations suggest that airway tree caliber heterogeneity is a structural trait associated with low baseline lung function and normal decline trajectory that is relevant to COPD.

Background: The American Heart Association recently launched updated cardiovascular health metrics, termed Life's Essential 8 (LE8). Compared with Life's Simple 7 (LS7), the new approach added sleep health as an eighth metric and updated the remaining 7 health factors and behaviors. The association of the updated LE8 score with long-term cardiovascular disease (CVD) outcomes and death is unknown., Methods: We pooled individual-level data from 6 contemporary US-based cohorts from the Cardiovascular Lifetime Risk Pooling Project. Total LE8 score (0-100 points), LE8 score without sleep (0-100 points), and prior LS7 scores (0-14 points) were calculated separately. We used multivariable-adjusted Cox models to evaluate the association of LE8 with CVD, CVD subtypes, and all-cause mortality among younger, middle, and older adult participants. Net reclassification improvement analysis was used to measure the improvement in CVD risk classification with the addition of LS7 and LE8 recategorization based on score quartile rankings., Results: Our sample consisted of 32 896 US adults (7836 [23.8%] Black; 14 941 [45.4%] men) followed for 642 000 person-years, of whom 9391 developed CVD events. Each 10-point higher overall LE8 score was associated with lower risk by 22% to 40% for CVD, 24% to 43% for congenital heart disease, 17% to 34% for stroke, 23% to 38% for heart failure, and 17% to 21% for all causes of mortality events across age strata. LE8 score provided more granular differentiation of the related CVD risk than LS7. Overall, 19.5% and 15.5% of the study participants were recategorized upward and downward based on LE8 versus LS7 categories, respectively, and the recategorization was significantly associated with CVD risk in addition to LS7 score. The addition of recategorization between LE8 and LS7 categories improved CVD risk reclassification across age groups (clinical net reclassification improvement, 0.06-0.12; P <0.01)., Conclusions: These findings support the improved utility of the LE8 algorithm for assessing overall cardiovascular health and future CVD risk., Competing Interests: Disclosures None.

Background: Suicide is a major public health crisis among youth. Several prominent theories, including the Interpersonal Theory of Suicide (IPTS), aim to characterize the factors leading from suicide ideation to action. These theories are largely based on findings in adults and require testing and elaboration in adolescents., Methods: Data were examined from high-risk 13-18-year-old adolescents (N = 167) participating in a multi-wave, longitudinal study; 63% of the sample exhibited current suicidal thoughts or recent behaviors (n = 105). The study included a 6-month follow-up period with clinical interviews and self-report measures at each of the four assessments as well as weekly smartphone-based assessments of suicidal thoughts and behaviors. Regression and structural equation models were used to probe hypotheses related to the core tenets of the IPTS., Results: Feelings of perceived burdensomeness were associated with more severe self-reported suicidal ideation (b = 0.58, t(158) = 7.64, p < .001). Similarly, burdensomeness was associated with more frequent ideation based on weekly smartphone ratings (b = 0.11, t(1460) = 3.41, p < .001). Contrary to IPTS hypotheses, neither feelings of thwarted belongingness, nor interactions between burdensomeness and thwarted belongingness were significantly associated with ideation (ps > .05). Only elevated depression severity was associated with greater odds of suicide events (i.e., suicide attempts, psychiatric hospitalizations, and/or emergency department visits for suicide concerns) during the follow-up period (OR = 1.83, t(158) = 2.44, p = .01). No effect of acquired capability was found., Conclusions: Perceptions of burdensomeness to others reflect a critical risk factor for suicidal ideation among high-risk adolescents. Null findings with other IPTS constructs may suggest a need to adopt more developmentally sensitive models or measures of interpersonal and acquired capability risk factors for youth. Refining methods and theoretical models of suicide risk may help improve the identification of high-risk cases and inform clinical intervention., (© 2023 Association for Child and Adolescent Mental Health.)

Background: Blood pressure (BP) trajectories from young adulthood through middle age are associated with cardiovascular risk. We examined the associations of hypertension risk factors with BP trajectories among a large diverse sample., Methods and Results: We analyzed data from young adults, aged 18 to 39 years, with untreated BP <140/90 mm Hg at baseline from Kaiser Permanente Southern California (N=355 324). We used latent growth curve models to identify 10-year BP trajectories and to assess the associations between characteristics in young adulthood and BP trajectories. We identified the following 5 distinct systolic BP trajectories, which appeared to be determined mainly by the baseline BP with progressively higher BP at each year: group 1 (lowest BP trajectory, 7.9%), group 2 (26.5%), group 3 (33.0%), group 4 (25.4%), and group 5 (highest BP trajectory, 7.3%). Older age (adjusted odds ratio for 30-39 versus 18-29 years, 1.23 [95% CI, 1.18-1.28]), male sex (13.38 [95% CI, 12.80-13.99]), obesity (body mass index ≥30 versus 18.5-24.9 kg/m 2 , 14.81 [95% CI, 14.03-15.64]), overweight (body mass index 25-29.9 versus 18.5-24.9 kg/m 2 , 3.16 [95% CI, 3.00-3.33]), current smoking (1.58 [95% CI, 1.48-1.67]), prediabetes (1.21 [95% CI, 1.13-1.29]), diabetes (1.60 [95% CI, 1.41-1.81]) and high low-density lipoprotein cholesterol (≥160 versus <100 mg/dL, 1.52 [95% CI, 1.37-1.68]) were associated with the highest BP trajectory (group 5) compared with the reference group (group 2)., Conclusions: Traditional hypertension risk factors including smoking, diabetes, and elevated lipids were associated with BP trajectories in young adults, with obesity having the strongest association with the highest BP trajectory group.

Background: Multimorbidity research has focused on the prevalence and consequences of multimorbidity in older populations. Less is known about the accumulation of chronic conditions earlier in the life course., Methods: We identified patterns of longitudinal multimorbidity accumulation using 30 years of data from in-person exams, annual follow-ups, and adjudicated end-points among 4,945 participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study. Chronic conditions included arthritis, asthma, atrial fibrillation, cancer, end stage renal disease, chronic obstructive pulmonary disease, coronary heart disease, diabetes, heart failure, hyperlipidemia, hypertension, and stroke. Trajectory patterns were identified using latent class growth curve models., Results: Mean age (SD) at baseline (1985-6) was 24.9 (3.6), 55% were female, and 51% were Black. The median follow-up was 30 years (interquartile range 25-30). We identified six trajectory classes characterized by when conditions began to accumulate and the rapidity of accumulation: (1) early-fifties, slow, (2) mid-forties, fast, (3) mid-thirties, fast, (4) late-twenties, slow, (5) mid-twenties, slow, and (6) mid-twenties, fast. Compared with participants in the early-fifties, slow trajectory class, participants in mid-twenties, fast were more likely to be female, Black, and currently smoking and had a higher baseline mean waist circumference (83.6 vs. 75.6 cm) and BMI (27.0 vs. 23.4 kg/m 2 ) and lower baseline physical activity (414.1 vs. 442.4 exercise units)., Conclusions: A life course approach that recognizes the heterogeneity in patterns of accumulation of chronic conditions from early adulthood into middle age could be helpful for identifying high risk subgroups and developing approaches to delay multimorbidity progression., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Youth use different forms of screen time (e.g., streaming, gaming) that may be related to body mass index (BMI). Screen time is non-independent from other behaviors, including physical activity and sleep duration. Statistical approaches such as isotemporal substitution or compositional data analysis (CoDA) can model associations between these non-independent behaviors and health outcomes. Few studies have examined different types of screen time, physical activity, and sleep duration simultaneously in relation to BMI., Methods: Data were baseline (2017-2018) and one-year follow-up (2018-2019) from the Adolescent Brain Cognitive Development Study, a multi-site study of a nationally representative sample of U.S. youth (N = 10,544, mean [SE] baseline age = 9.9 [0.03] years, 48.9% female, 45.4% non-White). Participants reported daily minutes of screen time (streaming, gaming, socializing), physical activity, and sleep. Sex-stratified models estimated the association between baseline behaviors and follow-up BMI z-score, controlling for demographic characteristics, internalizing symptoms, and BMI z-score at baseline., Results: In females, isotemporal substitution models estimated that replacing 30 min of socializing (β [95% CI] = -0.03 [-0.05, -0.002]), streaming (-0.03 [-0.05, -0.01]), or gaming (-0.03 [-0.06, -0.01]) with 30 min of physical activity was associated with a lower follow-up BMI z-score. In males, replacing 30 min of socializing (-0.03 [-0.05, -0.01]), streaming (-0.02 [-0.03, -0.01]), or gaming (-0.02 [-0.03, -0.01]) with 30 min of sleep was associated with a lower follow-up BMI z-score. In males, replacing 30 min of socializing with 30 min of gaming was associated with a lower follow-up BMI z-score (-0.01 [-0.03, -0.0001]). CoDA estimated that in males, a greater proportion of time spent in baseline socializing, relative to the remaining behaviors, was associated with a higher follow-up BMI z-score (0.05 [0.02, 0.08]). In females, no associations between screen time and BMI were observed using CoDA., Conclusions: One-year longitudinal associations between screen time and BMI may depend on form of screen time, what behavior it replaces (physical activity or sleep), and participant sex. The alternative statistical approaches yielded somewhat different results. Experimental manipulation of screen time and investigation of biopsychosocial mechanisms underlying the observed sex differences will allow for causal inference and can inform interventions., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: Given the high rates at which individuals with alcohol use disorder (AUD) utilize health care for co-existing conditions, health systems are promising venues for interventions that will facilitate access to AUD treatment. However, how individuals with AUD interact with such systems and, thus, how systems should intervene is unclear. In this study, we seek to identify patterns in how individuals diagnosed with AUD within an academic health system interacted with the system prior to diagnosis., Methods: We use electronic health records from a single academic health system in a major US metropolitan area to create a deidentified retrospective cohort including all individuals age 18+ diagnosed with AUD 2010-2019 (n = 26,899). Latent class analysis (LCA) identified subgroups defined by aspects of previous system interaction and health status, including having an in-system primary care provider, previous utilization of primary and specialty care, diagnosis setting, payer, and presence of other chronic conditions. We then assessed subgroup differences in demographics and associations with in-system AUD treatment receipt in the year following diagnosis, adjusting for demographics., Results: The population was on average 38.6 years old (standard deviation = 15.4) and predominantly male (66.1 %), White (64.5 %), and not of Hispanic/Latino ethnicity (87.8 %). Only 4.7 % received in-system treatment following diagnosis. We deemed the four-class model the optimal LCA model. This model identified subgroups that can be described as 1) average utilization (20.7 % of population), 2) low utilization (54.5 %), 3) high health burden and low utilization (14.2 %), and 4) high health burden and high utilization (10.6 %). Predicted membership in the high health burden and high utilization subgroup and low utilization subgroup were associated with higher and lower odds of treatment receipt, respectively, compared with predicted membership in the average utilization subgroup (odds ratio (OR) for high/high subgroup = 1.21, 95 % confidence interval (CI) = 1.01, 1.27; OR for low subgroup = 0.29 95 % CI = 0.24, 0.34)., Conclusion: Individuals diagnosed with AUD within a health system interact with that system in markedly different ways and are unlikely to benefit uniformly from system-based interventions to facilitate treatment. Group-tailored interventions are more likely to have impact and provide returns on investments for systems., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to report., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cartilage damage presents a significant clinical challenge due to its intrinsic avascular nature which limits self-repair. Addressing this, our study focuses on an alginate-based bioink, integrating human articular cartilage, for cartilage tissue engineering. This novel bioink was formulated by encapsulating C20A4 human articular chondrocytes in sodium alginate, polyvinyl alcohol, gum arabic, and cartilage extracellular matrix powder sourced from allograft femoral condyle shavings. Using a 3D bioprinter, constructs were biofabricated and cross-linked, followed by culture in standard medium. Evaluations were conducted on cellular viability and gene expression at various stages. Results indicated that the printed constructs maintained a porous structure conducive to cell growth. Cellular viability was 87% post printing, which decreased to 76% after seven days, and significantly recovered to 86% by day 14. There was also a notable upregulation of chondrogenic genes, COL2A1 ( p = 0.008) and SOX9 ( p = 0.021), suggesting an enhancement in cartilage formation. This study concludes that the innovative bioink shows promise for cartilage regeneration, demonstrating substantial viability and gene expression conducive to repair and suggesting its potential for future therapeutic applications in cartilage repair.

Objective: We provide proof-of-principle for a mental health risk calculator advancing clinical utility of the irritability construct for identification of young children at high risk for common, early onsetting syndromes., Method: Data were harmonized from two longitudinal early childhood subsamples (total N  = 403; 50.1% Male; 66.7% Nonwhite; M age  = 4.3 years). The independent subsamples were clinically enriched via disruptive behavior and violence (Subsample 1) and depression (Subsample 2). In longitudinal models, epidemiologic risk prediction methods for risk calculators were applied to test the utility of the transdiagnostic indicator, early childhood irritability, in the context of other developmental and social-ecological indicators to predict risk of internalizing/externalizing disorders at preadolescence (M age  = 9.9 years). Predictors were retained when they improved model discrimination (area under the receiver operating characteristic curve [AUC] and integrated discrimination index [IDI]) beyond the base demographic model., Results: Compared to the base model, the addition of early childhood irritability and adverse childhood experiences significantly improved the AUC (0.765) and IDI slope (0.192). Overall, 23% of preschoolers went on to develop a preadolescent internalizing/externalizing disorder. For preschoolers with both elevated irritability and adverse childhood experiences, the likelihood of an internalizing/externalizing disorder was 39-66%., Conclusions: Predictive analytic tools enable personalized prediction of psychopathological risk for irritable young children, holding transformative potential for clinical translation.

This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-S1 antibodies were measured from dried blood spots collected between February 2021-August 2022 using Luminex-based microsphere immunoassays. Of 6245 participants, mean age was 73 years (range, 21-100), 58% were female, and 76% were non-Hispanic White. Nearly 52% of participants received the BNT162b2 vaccine and 48% received the mRNA-1273 vaccine. Lower anti-S1 antibody levels are associated with age of 65 years or older, male sex, higher body mass index, smoking, diabetes, COPD and receipt of BNT16b2 vaccine (vs mRNA-1273). Participants with a prior infection, particularly those with a history of hospitalized illness, have higher anti-S1 antibody levels. These results suggest that adults with certain socio-demographic and clinical characteristics may have less robust antibody responses to COVID-19 vaccination and could be prioritized for more frequent re-vaccination., (© 2024. The Author(s).)

Objective: Psychosocial stress is associated with increased cardiovascular disease (CVD) risk. The relationship between financial strain, a toxic form of psychosocial stress, and ideal cardiovascular health (CVH) is not well established. We examined whether financial strain was associated with poorer CVH in a multi-ethnic cohort free of CVD at baseline., Methods: This was a cross-sectional analysis of 6,453 adults aged 45-84 years from the Multi-Ethnic Study of Atherosclerosis. Financial strain was assessed by questionnaire and responses were categorized as yes or no. CVH was measured from 7 metrics (smoking, body mass index, physical activity, diet, total cholesterol, blood glucose and blood pressure). A CVH score of 14 was calculated by assigning points to the categories of each metric (poor = 0 points, intermediate = 1 point, ideal = 2 points). Multinomial logistic regression was used to examine the association of financial strain with the CVH score (inadequate 0-8, average 9-10, and optimal 11-14 points) adjusting for sociodemographic factors, depression and anxiety., Results: The mean age (SD) was 62 (10) and 53 % were women. Financial strain was reported by 25 % of participants. Participants who reported financial strain had lower odds of average (OR, 0.82 [95 % CI, 0.71, 0.94]) and optimal (0.73 [0.62, 0.87]) CVH scores. However, in the fully adjusted model, the association was only significant for optimal CVH scores (0.81, [0.68, 0.97])., Conclusion: Financial strain was associated with poorer CVH. More research is needed to understand this relationship so the burden of CVD can be decreased, particularly among people experiencing financial hardship., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Background: Mean systolic and diastolic blood pressure (SBP and DBP) on ambulatory blood pressure (BP) monitoring (ABPM) are higher among Black compared with White adults. With 48 to 72 BP measurements obtained over 24 h, ABPM can generate parameters other than mean BP that are associated with increased risk for cardiovascular events. There are few data on race differences in ABPM parameters other than mean BP., Methods: To estimate differences between White and Black participants in ABPM parameters, we used pooled data from five US-based studies in which participants completed ABPM (n = 2580). We calculated measures of SBP and DBP level, including mean, load, peak, and measures of SBP and DBP variability, including average real variability (ARV) and peak increase., Results: There were 1513 (58.6%) Black and 1067 (41.4%) White participants with mean ages of 56.1 and 49.0 years, respectively. After multivariable adjustment, asleep SBP and DBP load were 5.7% (95% CI: 3.5-7.9%) and 2.7% (95% CI: 1.1-4.3%) higher, respectively, among Black compared with White participants. Black compared with White participants also had higher awake DBP ARV (0.3 [95%CI: 0.0-0.6] mmHg) and peak increase in DBP (0.4 [95% CI: 0.0-0.8] mmHg). There was no evidence of Black:White differences in awake measures of SBP level, asleep peak SBP or DBP, awake and asleep measures of SBP variability or asleep measures of DBP variability after multivariable adjustment., Conclusion: Asleep SBP load, awake DBP ARV and peak increase in awake DBP were higher in Black compared to White participants, independent of mean BP on ABPM., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Clinical cardiovascular health is a construct that includes 4 health factors-systolic and diastolic blood pressure, fasting glucose, total cholesterol, and body mass index-which together provide an evidence-based, more holistic view of cardiovascular health risk in adults than each component separately. Currently, no pediatric version of this construct exists. This study sought to develop sex-specific charts of clinical cardiovascular health for age to describe current patterns of clinical cardiovascular health throughout childhood., Methods: Data were used from children and adolescents aged 8-19 years in six pooled childhood cohorts (19,261 participants, collected between 1972 and 2010) to create reference standards for fasting glucose and total cholesterol. Using the models for glucose and cholesterol as well as previously published reference standards for body mass index and blood pressure, clinical cardiovascular health charts were developed. All models were estimated using sex-specific random-effects linear regression, and modeling was performed during 2020-2022., Results: Models were created to generate charts with smoothed means, percentiles, and standard deviations of clinical cardiovascular health for each year of childhood. For example, a 10-year-old girl with a body mass index of 16 kg/m 2 (30th percentile), blood pressure of 100/60 mm Hg (46th/50th), glucose of 80 mg/dL (31st), and total cholesterol of 160 mg/dL (46th) (lower implies better) would have a clinical cardiovascular health percentile of 62 (higher implies better)., Conclusions: Clinical cardiovascular health charts based on pediatric data offer a standardized approach to express clinical cardiovascular health as an age- and sex-standardized percentile for clinicians to assess cardiovascular health in childhood to consider preventive approaches at early ages and proactively optimize lifetime trajectories of cardiovascular health., (Copyright © 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

It is increasingly clear that longitudinal risk factor levels and trajectories are related to risk for atherosclerotic cardiovascular disease (ASCVD) above and beyond single measures. Currently used in clinical care, the Pooled Cohort Equations (PCE) are based on regression methods that predict ASCVD risk based on cross-sectional risk factor levels. Deep learning (DL) models have been developed to incorporate longitudinal data for risk prediction but its benefit for ASCVD risk prediction relative to the traditional Pooled Cohort Equations (PCE) remain unknown. Our study included 15,565 participants from four cardiovascular disease cohorts free of baseline ASCVD who were followed for adjudicated ASCVD. Ten-year ASCVD risk was calculated in the training set using our benchmark, the PCE, and a longitudinal DL model, Dynamic-DeepHit. Predictors included those incorporated in the PCE: sex, race, age, total cholesterol, high density lipid cholesterol, systolic and diastolic blood pressure, diabetes, hypertension treatment and smoking. The discrimination and calibration performance of the two models were evaluated in an overall hold-out testing dataset. Of the 15,565 participants in our dataset, 2170 (13.9%) developed ASCVD. The performance of the longitudinal DL model that incorporated 8 years of longitudinal risk factor data improved upon that of the PCE [AUROC: 0.815 (CI 0.782-0.844) vs 0.792 (CI 0.760-0.825)] and the net reclassification index was 0.385. The brier score for the DL model was 0.0514 compared with 0.0542 in the PCE. Incorporating longitudinal risk factors in ASCVD risk prediction using DL can improve model discrimination and calibration., (© 2024. The Author(s).)

Background: Social and psychosocial determinants are associated with cardiovascular health (CVH)., Objectives: To quantify the contributions of social and psychosocial factors to racial/ethnic differences in CVH., Methods: In the Multi-Ethnic Study of Atherosclerosis and Mediators of Atherosclerosis in South Asians Living in America cohorts, Kitagawa-Blinder-Oaxaca decomposition quantified the contributions of social and psychosocial factors to differences in mean CVH score (range 0-14) in Black, Chinese, Hispanic, or South Asian compared with White participants., Results: Among 7,978 adults (mean age 61 [SD 10] years, 52 % female), there were 1,892 Black (mean CVH score for decomposition analysis 7.96 [SD 2.1]), 804 Chinese (CVH 9.69 [1.8]), 1,496 Hispanic (CVH 8.00 [2.1]), 1,164 South Asian (CVH 9.16 [2.0]), and 2,622 White (CVH 8.91 [2.1]) participants. The factors that were associated with the largest magnitude of explained differences in mean CVH score were income for Black participants (if mean income in Black participants were equal to White participants, Black participants' mean CVH score would be 0.14 [SE 0.05] points higher); place of birth for Chinese participants (if proportion of US-born and foreign-born individuals among Chinese adults were equivalent to White participants, Chinese participants' mean CVH score would be 0.22 [0.10] points lower); and education for Hispanic and South Asian participants (if educational attainment were equivalent to White participants, Hispanic and South Asian participants' mean CVH score would be 0.55 [0.11] points higher and 0.37 [0.11] points lower, respectively)., Conclusions: In these multiethnic US cohorts, social and psychosocial factors were associated with racial/ethnic differences in CVH., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nilay S. Shah reports financial support was provided by National Heart Lung and Blood Institute. Alka M. Kanaya reports financial support was provided by National Heart Lung and Blood Institute. Alka M. Kanaya reports financial support was provided by National Center for Advancing Translational Sciences. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Objective: Changes in cardiovascular health (CVH) during the life course are associated with future cardiovascular disease (CVD). Longitudinal clustering analysis using subgraph augmented non-negative matrix factorization (SANMF) could create phenotypic risk profiles of clustered CVH metrics., Materials and Methods: Life's Essential 8 (LE8) variables, demographics, and CVD events were queried over 15 ears in 5060 CARDIA participants with 18 years of subsequent follow-up. LE8 subgraphs were mined and a SANMF algorithm was applied to cluster frequently occurring subgraphs. K-fold cross-validation and diagnostics were performed to determine cluster assignment. Cox proportional hazard models were fit for future CV event risk and logistic regression was performed for cluster phenotyping., Results: The cohort (54.6% female, 48.7% White) produced 3 clusters of CVH metrics: Healthy & Late Obesity (HLO) (29.0%), Healthy & Intermediate Sleep (HIS) (43.2%), and Unhealthy (27.8%). HLO had 5 ideal LE8 metrics between ages 18 and 39 years, until BMI increased at 40. HIS had 7 ideal LE8 metrics, except sleep. Unhealthy had poor levels of sleep, smoking, and diet but ideal glucose. Race and employment were significantly different by cluster (P < .001) but not sex (P = .734). For 301 incident CV events, multivariable hazard ratios (HRs) for HIS and Unhealthy were 0.73 (0.53-1.00, P = .052) and 2.00 (1.50-2.68, P < .001), respectively versus HLO. A 15-year event survival was 97.0% (HIS), 96.3% (HLO), and 90.4% (Unhealthy, P < .001)., Discussion and Conclusion: SANMF of LE8 metrics identified 3 unique clusters of CVH behavior patterns. Clustering of longitudinal LE8 variables via SANMF is a robust tool for phenotypic risk assessment for future adverse cardiovascular events., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: This study first examined how mothers with and without depression differ in neural activation in response to adolescents' affective faces. Second, it examined the extent to which these neural activation patterns are related to observed positive and aggressive parenting behavior., Methods: Mothers with and without depression (based on self-reported symptoms and treatment history; n = 77 and n = 64, respectively; mean age  = 40 years) from low-income families completed an interaction task with their adolescents (mean age  = 12.8 years), which was coded for parents' aggressive and positive affective behavior. During functional magnetic resonance imaging, mothers viewed blurry, happy, sad, and angry faces of unfamiliar adolescents, with an instruction to either label the emotion or determine the clarity of the image., Results: The depression group showed less activation in the posterior midcingulate than the control subject group while labeling happy faces. Higher activation in the insula and dorsomedial prefrontal cortex (PFC) was related to less positive parenting behavior. Ventrolateral PFC activation was most pronounced when labeling negative emotions, but stronger ventrolateral PFC response to happy faces was associated with more aggressive parenting behavior., Conclusions: This demonstrates the association between parents' neural responses to adolescent faces and their behavior during interactions with their own adolescents, with relatively low insula and dorsomedial PFC activation supporting positive parenting and affect-dependent response in the ventrolateral PFC as being important to limit aggressive behavior., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Importance: Education is a social determinant of health. Quantifying its association with lifetime cardiovascular disease (CVD) risk has public health importance., Objective: To calculate lifetime risk estimates of incident CVD and CVD subtypes and estimate years lived with and without CVD by education., Design, Setting, and Participants: Included community-based cohort studies with adjudicated cardiovascular events used pooled individual-level data from 1985 to 2015 of 6 prospective cohort studies. The study team assessed the association between education and lifetime CVD risk with modified Kaplan-Meier and Cox models accounting for competing risk of noncardiovascular death. The study team estimated years lived with and without CVD by education with the Irwin restricted mean and the utility of adding educational attainment to CVD risk assessment. Participants (baseline 40 to 59 years old and 60 to 79 years old) were without CVD at baseline and had complete education, cardiovascular risk factors, and prospective CVD outcomes data. Data were analyzed from January 2022 to September 2022., Exposures: Educational attainment (less than high school, high school completion, some college, or college graduate)., Main Outcome and Measures: Cardiovascular events (fatal and nonfatal coronary heart disease, heart failure, and stroke; CVD-related deaths; and total CVD encompassing any of these events)., Results: There were 40 998 participants (23 305 female [56.2%]) with a mean (SD) age of 58.1 (9.7) years for males and 58.3 (9.9) years for females. Compared with college graduates, those with less than high school or high school completion had higher lifetime CVD risks. Among middle-aged men, the competing hazard ratios (HRs) for a CVD event were 1.58 (95% CI, 1.38-1.80), 1.30 (95% CI, 1.10-1.46), and 1.16 (95% CI, 1.00-1.34) in those with less than high school, high school, and some college, respectively, compared with those with college completion. Among women, these competing HRs were 1.70 (95% CI, 1.49-1.95), 1.19 (95% CI, 1.05-1.35), and 0.98 (95% CI, 0.83-1.15). Individuals with higher education had longer duration of life prior to incident CVD. Education provided limited contribution toward enhancing CVD risk prediction., Conclusions and Relevance: Lower education was associated with lifetime CVD risk across adulthood; higher education translated to healthy longevity. Educational policy initiatives may associate with long-term health benefits.