Abstract
BACKGROUND: Adverse effects of medical treatment (AEMT) pose critical global health challenges, yet comprehensive analyses of their long-term burden across socio-demographic contexts remain limited. This study evaluates 30-year trends (1990-2021) in AEMT-related mortality, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) across 204 countries using Global Burden of Disease (GBD) 2021 data. METHODS: Age-standardized rates (ASRs) were stratified by sociodemographic index (SDI) quintiles. Frontier efficiency analysis quantified health loss boundaries relative to SDI, while concentration (C) and slope indices of inequality (SII) assessed health inequities. Predictive models projected trends to 2035. RESULTS: Global age-standardized mortality rates (ASDR) declined by 36.3%, with low-SDI countries achieving the steepest reductions (5.31 to 3.71/100,000) but remaining 3.9-fold higher than high-SDI nations. DALYs decreased by 39.7% (106.49 to 64.19/100,000), driven by infectious disease control in low-SDI regions. High-SDI countries experienced post-2010 mortality rebounds (0.86 to 0.95/100,000), linked to aging and complex interventions. YLLs declined by 40.3% (104.87 to 62.66/100,000), while YLDs peaked transiently (2010: 1.95/100,000). Frontier analysis revealed low-SDI countries lagged furthest from optimal health outcomes, and inequality indices highlighted entrenched disparities (C: -0.34 for premature mortality). Projections suggest continued declines in ASDR, DALYs, and YLLs by 2035, contingent on addressing antimicrobial resistance and surgical overuse. CONCLUSIONS: SDI-driven inequities necessitate tailored interventions: low-SDI regions require strengthened infection control and primary care, while high-SDI systems must mitigate overmedicalization risks. Hybrid strategies integrating digital health and cross-sector collaboration are critical for equitable burden reduction.