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Importance: Overweight and obesity affect 340 million adolescents worldwide and constitute a risk factor for poor mental health. Understanding the association between body mass index (BMI) and mental health in adolescents may help to address rising mental health issues; however, existing studies lack comprehensive evaluations spanning diverse countries and periods., Objective: To estimate the association between BMI and mental health and examine changes over time from 2002 to 2018., Design, Setting, and Participants: This was a repeated multicountry cross-sectional study conducted between 2002 and 2018 and utilizing data from the Health Behaviour in School-aged Children (HBSC) survey in Europe and North America. The study population consisted of more than 1 million adolescents aged 11 to 15 years, with all surveyed children included in the analysis. Data were analyzed from October 2022 to March 2023., Main Outcomes and Measures: Mental health difficulties were measured by an 8-item scale for psychological concerns, scoring from 0 to 32, where a higher score reflects greater psychosomatic issues. BMI was calculated using weight divided by height squared and adjusted for age and sex. Data were fitted by multilevel generalized additive model. Confounders included sex, living with parents, sibling presence, academic pressure, the experience of being bullied, family affluence, screen time, and physical activity., Results: Our analysis of 1 036 869 adolescents surveyed from 2002 to 2018, with a mean (SD) age of 13.55 (1.64) years and comprising 527 585 girls (50.9%), revealed a consistent U-shaped association between BMI and mental health. After accounting for confounders, adolescents with low body mass and overweight or obesity had increased psychosomatic symptoms compared to those with healthy weight (unstandardized β, 0.14; 95% CI, 0.08 to 0.19; unstandardized β, 0.27; 95% CI, 0.24 to 0.30; and unstandardized β, 0.62; 95% CI, 0.56 to 0.67, respectively), while adolescents with underweight had fewer symptoms (unstandardized β, -0.18; 95% CI, -0.22 to -0.15). This association was observed across different years, sex, and grade, indicating a broad relevance to adolescent mental health. Compared to 2002, psychosomatic concerns increased significantly in 2006 (unstandardized β, 0.19; 95% CI, 0.11 to 0.26), 2010 (unstandardized β, 0.14; 95% CI, 0.07 to 0.22), 2014 (unstandardized β, 0.48; 95% CI, 0.40 to 0.56), and 2018 (unstandardized β, 0.82; 95% CI, 0.74 to 0.89). Girls reported significantly higher psychosomatic concerns than boys (unstandardized β, 2.27; 95% CI, 2.25 to 2.30). Compared to primary school, psychosomatic concerns rose significantly in middle school (unstandardized β, 1.15; 95% CI, 1.12 to 1.18) and in high school (unstandardized β, 2.12; 95% CI, 2.09 to 2.15)., Conclusions and Relevance: Our study revealed a U-shaped association between adolescent BMI and mental health, which was consistent across sex and grades and became stronger over time. These insights emphasize the need for targeted interventions addressing body image and mental health, and call for further research into underlying mechanisms.

Importance: In response to widespread concerns about social media's influence on adolescent mental health, most research has studied adolescents from the general population, overlooking clinical groups., Objective: To synthesize, quantify, and compare evidence on the association between social media use and internalizing symptoms in adolescent clinical and community samples., Data Sources: Peer-reviewed publications from MEDLINE, Web of Science, PsycInfo, and Scopus (initially reviewed in May 2022 and updated in October 2023) and preprints from Europe PubMed Central (February 2023) published in English between 2007 and 2023., Study Selection: Two blinded reviewers initially identified 14 211 cross-sectional and longitudinal studies quantifying the association between social media use and internalizing symptoms, excluding experimental studies and randomized clinical trials., Data Extraction and Synthesis: PRISMA and MOOSE guidelines were followed, pooling data using a random-effects model and robust variance estimation. The quality of evidence was assessed using the Quality of Survey Studies in Psychology Checklist., Main Outcomes and Measures: Articles were included if they reported at least 1 quantitative measure of social media use (time spent, active vs passive use, activity, content, user perception, and other) and internalizing symptoms (anxiety, depression, or both)., Results: The 143 studies reviewed included 1 094 890 adolescents and 886 effect sizes, 11% of which examined clinical samples. In these samples, a positive and significant meta-correlation was found between social media use and internalizing symptoms, both for time spent (n = 2893; r, 0.08; 95% CI, 0.01 to 0.15; P = .03; I2, 57.83) and user engagement (n = 859; r, 0.12; 95% CI, 0.09 to 0.15; P = .002; I2, 82.67). These associations mirrored those in community samples., Conclusions and Relevance: The findings in this study highlight a lack of research on clinical populations, a critical gap considering public concerns about the increase in adolescent mental health symptoms at clinical levels. This paucity of evidence not only restricts the generalizability of existing research but also hinders our ability to evaluate and compare the link between social media use and mental health in clinical vs nonclinical populations.

Importance: Coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) may contribute to the pathophysiologic characteristics of heart failure with preserved ejection fraction (HFpEF). However, the prevalence of CAD and CMD have not been systematically studied., Objective: To examine the prevalence of CAD and CMD in hospitalized patients with HFpEF., Design, Setting, and Participants: A total of 106 consecutive patients hospitalized with HFpEF were evaluated in this prospective, multicenter, cohort study conducted between January 2, 2017, and August 1, 2018; data analysis was performed from March 4 to September 6, 2019. Participants underwent coronary angiography with guidewire-based assessment of coronary flow reserve, index of microvascular resistance, and fractional flow reserve, followed by coronary vasoreactivity testing. Cardiac magnetic resonance imaging was performed with late gadolinium enhancement and assessment of extracellular volume. Myocardial perfusion was assessed qualitatively and semiquantitatively using the myocardial-perfusion reserve index., Main Outcomes and Measures: The prevalence of obstructive epicardial CAD, CMD, and myocardial ischemia, infarction, and fibrosis., Results: Of 106 participants enrolled (53 [50%] women; mean [SD] age, 72 [9] years), 75 had coronary angiography, 62 had assessment of coronary microvascular function, 41 underwent coronary vasoreactivity testing, and 52 received cardiac magnetic resonance imaging. Obstructive epicardial CAD was present in 38 of 75 participants (51%, 95% CI, 39%-62%); 19 of 38 (50%; 95% CI, 34%-66%) had no history of CAD. Endothelium-independent CMD (ie, coronary flow reserve <2.0 and/or index of microvascular resistance ≥25) was identified in 41 of 62 participants (66%; 95% CI, 53%-77%). Endothelium-dependent CMD (ie, abnormal coronary vasoreactivity) was identified in 10 of 41 participants (24%; 95% CI, 13%-40%). Overall, 45 of 53 participants (85%; 95% CI, 72%-92%) had evidence of CMD and 29 of 36 (81%; 95% CI, 64%-91%) of those without obstructive epicardial CAD had CMD. Cardiac magnetic resonance imaging findings included myocardial-perfusion reserve index less than or equal to 1.84 (ie, impaired global myocardial perfusion) in 29 of 41 patients (71%; 95% CI, 54%-83%), visual perfusion defect in 14 of 46 patients (30%; 95% CI, 19%-46%), ischemic late gadolinium enhancement (ie, myocardial infarction) in 14 of 52 patients (27%; 95% CI, 16%-41%), and extracellular volume greater than 30% (ie, diffuse myocardial fibrosis) in 20 of 48 patients (42%; 95% CI, 28%-56%). Patients with obstructive CAD had more adverse events during follow-up (28 [74%]) than those without obstructive CAD (17 [46%])., Conclusions and Relevance: In this cohort study, 91% of patients with HFpEF had evidence of epicardial CAD, CMD, or both. Of those without obstructive CAD, 81% had CMD. Obstructive epicardial CAD and CMD appear to be common and often unrecognized in hospitalized patients with HFpEF and may be therapeutic targets.

Importance: Microvascular obstruction commonly affects patients with acute ST-segment elevation myocardial infarction (STEMI) and is associated with adverse outcomes., Objective: To determine whether a therapeutic strategy involving low-dose intracoronary fibrinolytic therapy with alteplase infused early after coronary reperfusion will reduce microvascular obstruction., Design, Setting, and Participants: Between March 17, 2016, and December 21, 2017, 440 patients presenting at 11 hospitals in the United Kingdom within 6 hours of STEMI due to a proximal-mid-vessel occlusion of a major coronary artery were randomized in a 1:1:1 dose-ranging trial design. Patient follow-up to 3 months was completed on April 12, 2018., Interventions: Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145) by manual infusion over 5 to 10 minutes. The intervention was scheduled to occur early during the primary PCI procedure, after reperfusion of the infarct-related coronary artery and before stent implant., Main Outcomes and Measures: The primary outcome was the amount of microvascular obstruction (% left ventricular mass) demonstrated by contrast-enhanced cardiac magnetic resonance imaging (MRI) conducted from days 2 through 7 after enrollment. The primary comparison was the alteplase 20-mg group vs the placebo group; if not significant, the alteplase 10-mg group vs the placebo group was considered a secondary analysis., Results: Recruitment stopped on December 21, 2017, because conditional power for the primary outcome based on a prespecified analysis of the first 267 randomized participants was less than 30% in both treatment groups (futility criterion). Among the 440 patients randomized (mean age, 60.5 years; 15% women), the primary end point was achieved in 396 patients (90%), 17 (3.9%) withdrew, and all others were followed up to 3 months. In the primary analysis, the mean microvascular obstruction did not differ between the 20-mg alteplase and placebo groups (3.5% vs 2.3%; estimated difference, 1.16%; 95% CI, -0.08% to 2.41%; P = .32) nor in the analysis of 10-mg alteplase vs placebo groups (2.6% vs 2.3%; estimated difference, 0.29%; 95% CI, -0.76% to 1.35%; P = .74). Major adverse cardiac events (cardiac death, nonfatal MI, unplanned hospitalization for heart failure) occurred in 15 patients (10.1%) in the placebo group, 18 (12.9%) in the 10-mg alteplase group, and 12 (8.2%) in the 20-mg alteplase group., Conclusions and Relevance: Among patients with acute STEMI presenting within 6 hours of symptoms, adjunctive low-dose intracoronary alteplase given during the primary percutaneous intervention did not reduce microvascular obstruction. The study findings do not support this treatment., Trial Registration: ClinicalTrials.gov Identifier: NCT02257294.