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Abstract This study aims to analyze the trends in the burden of depression among adolescents aged 10 to 24 years globally from 1990 to 2021, with a focus on the impact of COVID-19 on adolescent depression and health inequalities. Using data from the 2021 Global Burden of Disease Study, we examined age-standardized prevalence, incidence, and disability-adjusted life years (DALYs) for depression among adolescents aged 10–24 years. Estimated annual percentage change (EAPC) was used to assess temporal trends. Age-period-cohort (APC) analysis estimated age, period, and cohort effects. Bayesian APC (BAPC) analysis projected future trends. Decomposition analysis further explored drivers of changes in depression burden. Slope Index of Inequality (SII) and Concentration Index (CI) were calculated to assess health inequalities across regions and countries. From 1990 to 2021, the global incidence, prevalence and DALY rates of adolescent depression remained stable. Depression incidence and prevalence increased with age, with the 20–24 age group showing the highest rates. The burden of depression was higher in females than in males. The COVID-19 pandemic significantly impacted adolescent depression, with reported prevalence, incidence, and DALY rates in 2020 and 2021 far exceeding predicted values, and the burden of depression is expected to continue rising. Health inequalities between adolescents in high- and low-income regions have widened, particularly following the pandemic. The COVID-19 pandemic significantly exacerbated the burden of depression and intensified health inequalities.

ABSTRACT Background 7‐Hydroxymethotrexate (7‐OHMTX) is the main metabolite in plasma following high‐dose MTX (HD‐MTX), which may result in activity and toxicity of the MTX. Moreover, 7‐OHMTX could produce crystalline‐like deposits within the renal tubules under acidic conditions or induce renal inflammation, oxidative stress, and cell apoptosis through various signaling pathways, ultimately leading to kidney damage. The objectives of this study were thus to explore the exposure–safety relationship of two compounds and search the most reliable marker for predicting HDMTX nephrotoxicity. Method A total of 280 plasma concentration data (140 for MTX and 140 for 7‐OHMTX) for 60 pediatric patients with non‐Hodgkin lymphoma (NHL) were prospectively collected. Plasma MTX and 7‐OHMTX concentrations were determined using a high‐performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS) method. A nonlinear mixed effect model approach was used to build a joint population pharmacokinetic (PopPK) model. After validation, the model estimated the peak concentration (Cmax) and area under the curve within the initial 48 h (AUC0‐48h) of the patients after drug administration by Bayesian feedback. The receiver operating characteristic (ROC) curves were generated to identify an exposure threshold associated with nephrotoxicity. Results A three‐compartment chain model (central and peripheral compartments for MTX and central compartment 7‐OHMTX) with the first‐order elimination adequately characterized the in vivo process of MTX and 7‐OHMTX. The covariate analysis identified that the aspartate aminotransferase (AST) was strongly associated with the peripheral volume of distribution of MTX. Moreover, the Cmax of MTX and 7‐OHMTX showed significant differences (p