Importance Denosumab reduces skeletal-related events in bone-metastatic prostate cancer but carries a cumulative risk of medication-related osteonecrosis of the jaw (ONJ). The treatment duration that best balances these risks has not been established in clinical settings. Objective To evaluate the association between duration of denosumab treatment and the 3-year cumulative incidence of ONJ and skeletal events. Design, Setting, and Participants This nationwide retrospective cohort study emulated a target trial using Korean Health Insurance Review and Assessment Service data from January 1, 2009, through August 31, 2024; patients were not randomized. A clone-censor-weight approach with inverse probability of censoring weighting estimated 3-year cumulative incidence and risk ratios (RRs), with death as a competing event. Men included in the analysis had bone-metastatic castration-resistant prostate cancer and initiated oncologic-dose denosumab therapy; men with castration-sensitive disease were excluded. Exposures Six strategies defined by 3 durations (≤6, 7-12, and ≥13 months), each as a schedule-flexible group and a schedule-adherent subgroup (intervals ≤12 weeks). Main Outcomes and Measures Three-year cumulative incidence of ONJ and skeletal events (pathologic fracture, spinal cord compression, and surgery to bone) was the primary outcome; a radiotherapy-inclusive conventional composite of skeletal-related events was assessed as a secondary outcome. Results Among 3307 men included in the analysis (mean [SD] age, 72.6 [8.6] years; median follow-up, 42.6 [IQR, 26.5-57.4] months), the overall 3-year cumulative incidence was 9.8% (95% CI, 8.7%-11.0%) for ONJ and 4.9% (95% CI, 4.2%-5.7%) for skeletal events. Relative to treatment for 6 months or less, treatment for 7 to 12 months showed a lower risk of skeletal events (3.82% [95% CI, 3.04%-4.80%] vs 5.76% [95% CI, 4.23%-7.79%]; RR, 0.66 [95% CI, 0.45-0.97]) and higher risk of ONJ (3.28% [95% CI, 2.41%-4.44%] vs 1.47% [95% CI, 0.86%-2.50%]; RR, 2.22 [95% CI, 1.21-4.11]). Compared with 7 to 12 months, treatment for 13 months or longer was associated with higher risk of ONJ (12.20% [95% CI, 10.86%-13.68%]; risk difference, 8.93 [95% CI, 7.16-10.64] percentage points), without further reduction in risk for skeletal events (3.99% [95% CI, 3.30%-4.82%]; risk difference, 0.17 [95% CI, −1.03 to 1.31] percentage points). Conclusions and Relevance In this cohort study of bone-metastatic castration-resistant prostate cancer, denosumab treatment for 7 to 12 months was associated with lower risk of skeletal events and a modest increase in ONJ, whereas treatment beyond 12 months was associated with markedly higher ONJ risk but no further reduction of skeletal events. These findings support individualized reassessment of denosumab treatment duration after approximately 1 year.
Importance Telephone consultations for acutely injured children receiving care in emergency departments (EDs) in nonpediatric trauma centers frequently exclude direct communication and informed decision-making with parents. The use of telemedicine to facilitate real-time expert consultation and parental communication with pediatric trauma specialists is underexplored and may improve family experience and support clinical decision-making. Objective To examine the impact of telemedicine on parent experience of care, parent distress, and transfer frequency for acutely injured children presenting to EDs in nonpediatric trauma centers. Design, Setting, and Participants This stepped-wedge cluster-randomized clinical trial recruited patients between November 30, 2020, and November 27, 2022. Participants included families of children younger than 18 years with acute physical trauma presenting to 1 of 10 nonpediatric trauma centers in northern California. Analyses were conducted between June 2023 and March 2026. Interventions EDs were randomized to use telemedicine following a standard telephone consultation or the standard of care (telephone consultation only) when consulting with pediatric trauma physicians. Main Outcomes and Measures Primary outcomes were parent experience of care and parent distress measured 3 days or more following the child's injury. Experience of care was measured using ED Consumer Assessment of Healthcare Providers and Systems (CAHPS) questions. Distress was measured using the State-Trait Anxiety Inventory Form Y survey. Modified intention-to-treat analyses were performed to evaluate outcomes. Results The study included 595 children with acute physical trauma with a mean (SD) age of 7.6 (5.1) years, of whom 369 (62.0%) were assigned to telemedicine and 226 (38.0%) to standard of care. Summary scores for parent experience of care 3 days post injury were similar between cohorts (adjusted mean difference [AMD], 0.041 [95% CI, −0.008 to 0.090; P = .10]), as were parent distress summary scores (AMD, −0.031 [95% CI, −0.297 to 0.235; P = .82]). The adjusted odds ratio for transfer of patients assigned to telemedicine was 0.59 (95% CI, 0.16 to 2.16; P = .43). Subscale analyses found significantly higher parental ED discharge and/or transfer experience ratings for patients assigned to telemedicine (AMD, 0.104 [95% CI, 0.023 to 0.186; P = .01]). Conclusions and Relevance In this randomized clinical trial, telemedicine consultations did not differ statistically significantly from standard care with respect to parent experience of care, distress, and transfer rates. Subscale analyses suggested a potential improvement with telemedicine consultations in parent experience related to ED discharge and interfacility transfers, highlighting a potential benefit in communication and preparation during care transitions. Trial Registration ClinicalTrials.gov Identifier: NCT04469036
Importance Population aging is contributing to rising multimorbidity across physical, psychological, and cognitive domains, yet global evidence integrating health and economic burdens in older adults remains limited. Objectives To quantify the global health and economic burden of multimorbidity among adults aged 60 years or older and to assess trends from 2000 to 2023. Design, Setting, and Participants This economic evaluation used observational modeling of Global Burden of Disease study 2023 estimates as health inputs and integrated them with macroeconomic, health expenditure, and population data from World Bank Open Data, the World Health Organization Global Health Expenditure Database, and United Nations population data. Health burden analyses covered adults aged 60 years or older in 204 countries and territories from 2000 to 2023, and economic burden analyses covered 180 countries and territories. Data analyses were performed from January 27 to July 22, 2026. Exposures Cross-domain multimorbidity spanning physical conditions, psychological disorders, and cognitive disorders, operationalized as 78 multimorbidity combinations. Main Outcomes and Measures The main outcomes were years lived with disability (YLDs) per 100 000 population and economic losses. All economic indicators are reported in 2021 international dollars (USD) adjusted for purchasing power parity. Joinpoint regression characterized 2000 to 2023 trends. Results From 2000 to 2023, total YLDs increased from 2367.81 (95% uncertainty interval [UI], 1067.67-4969.59) to 2941.68 (95% UI, 1252.99-6816.95) per 100 000 population, while economic losses increased from $80.10 billion (95% UI, $59.60-$104.69 billion) to $363.25 billion (95% UI, $264.04-$502.74 billion). The highest 2023 YLD rate was observed for osteoarthritis and Alzheimer disease and other dementias (369.87 [95% UI, 163.86-752.23] per 100 000 population), whereas the largest 2023 economic loss was observed for osteoarthritis and anxiety disorders ($48.51 billion [95% UI, $31.68-$76.57 billion]). The fastest-growing combination was diabetes, anxiety disorders, and Parkinson disease, with a YLD average annual percentage change (AAPC) of 3.94% (95% CI, 3.79%-4.08%) and an economic loss AAPC of 9.92% (95% CI, 9.69%-10.13%). Conclusions and Relevance In this economic evaluation of the global health and economic burden of multimorbidity among adults aged 60 years or older, multimorbidity burden increased worldwide, with economic losses growing faster than YLDs. Heterogeneity across sex, country income groups, and disease combinations, together with divergence between disability and economic burden, suggest that policy priorities for aging populations should consider both health burden and economic vulnerability.
This cross-sectional study surveys US neurology clinics on wait times and compares wait times by community population density and clinic specialization.
