EClinicalMedicine最新文献

Background: Non-communicable diseases (NCDs) are a major contributor to morbidity and mortality worldwide, yet their burden among adolescents and young adults in the Middle East and North Africa (MENA) region remains underexplored. Understanding age-, sex-, and country-specific patterns is critical in a region marked by conflict, demographic transition, and rapid urbanization.

Methods: We used estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to quantify mortality and disability due to NCDs among people aged 10-24 years across 21 MENA countries from 1990 to 2023. Causes were analyzed by three hierarchical levels of the GBD 2023 cause list. For each cause, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) with 95% uncertainty intervals (UIs) were extracted and stratified by sex, age group, and country. Temporal trends (1990-2023) and associations between Level 2 NCD DALY rates and each country's Socio-demographic Index (SDI) were assessed using correlation. Analyses were performed using R (version 2025.09.0) and Julia (version 1.10).

Findings: In 2023, NCDs accounted for 76.0% (95% UI 71.5-79.6) of all YLDs and 29.0% (27.0-32.3) of total deaths among young people aged 10-24 years in MENA. Among NCDs, cardiovascular diseases and neoplasms were the leading causes of mortality (9.64 [7.64-12.14] and 6.93 [6.05-7.78] per 100,000, respectively), whereas mental disorders were the main contributors to YLDs (2916.2 [2013.4-4165.8] per 100,000) and DALYs (2916.3 [2013.4-4165.9] per 100,000). NCD mortality was higher in males than females (37.9 vs 18.6 per 100,000), while females had slightly higher DALY rates (8970.4 vs 8221.6 per 100,000). From 1990 to 2023, mortality due to NCDs declined by 33.6% and YLLs by 34.2%, reflecting steady improvements until 2019 before plateauing during and after the COVID-19 period. Over the same timeframe, YLDs declined modestly until 2019 but increased thereafter (+8.6% [-3.4 to 21.9]), largely due to mental and metabolic disorders. The largest declines were seen for digestive (-60.9%) and cardiovascular diseases (-43.6%), whereas increases occurred in mental (128.4%) and substance-use disorders (12.9%). Countries with higher SDI scores had lower DALY rates for cardiovascular, digestive, neoplastic, and other NCDs.

Interpretation: Integrated, youth-responsive NCD and mental health services are needed to address rising disability and health loss among young people in the MENA region.

Funding: Khalifa University of Science and Technology.

[This retracts the article DOI: 10.1016/j.eclinm.2025.103681.].

[This corrects the article DOI: 10.1016/j.eclinm.2026.103764.].

Background: Optimizing nucleoside reverse transcriptase inhibitor (NRTI) backbones is vital for pediatric and adolescent HIV treatment, yet real-world comparative evidence is limited. This study assessed backbone regimen effectiveness and factors influencing viral suppression (VLS) in Uganda.

Methods: We conducted a retrospective cohort of 1033 children and adolescents (≤19 years) receiving HIV care in Uganda (2018-2023). Participants received Tenofovir Disoproxil Fumarate (TDF, 57.3%), Abacavir (ABC, 32.7%), or zidovudine (AZT, 10.0%). Viral load (VL) suppression was classified as suppressed (≤200 copies/mL), low-level viremia (201-999 copies/mL), and high-level viremia (≥1000 copies/mL). Outcomes were compared by χ² tests, and mixed-effects logistic regression identified factors associated with non-suppression over time.

Findings: Overall VLS was 83.5%. VLS was highest among TDF recipients (84.8%), followed by ABC (82.8%), and lowest with AZT (78.6%; p = 0.313). AZT recipients had the highest high-level viremia (19.4%) and greater odds of non-suppression compared with ABC (adjusted odds ratio [aOR] 2.02, 95% CI 1.20-3.40; p = 0.008). TDF was associated with lower odds of non-suppression in bivariable analysis (OR 0.71, 95% CI 0.53-0.95; p = 0.023 but was not significant after adjustment (p = 0.748). Increasing age reduced the odds of non-suppression by 8% per year (aOR 0.92, 95% CI 0.86-0.98; p = 0.006), while male sex increased odds of non-suppression (aOR 1.36, 95% CI 1.03-1.81; p = 0.033). Later VL testing time points were linked to improved suppression (aOR 0.95, 95% CI 0.91-1.00; p = 0.037).

Interpretation: Overall VLS exceeded 80% but fell short of the UNAIDS 95% target. TDF-backbones had the highest success, AZT the lowest. Younger age and male sex predicted poorer outcomes. These results highlight the need for optimized regimens, targeted adherence support, and strengthened programs to improve pediatric and adolescent HIV care.

Funding: National Institute for Health and Care Research (NIHR), United Kingdom through the Royal Society for Tropical Medicine and Hygiene Early Career Grants.

Background: Wearable digital health technologies offer a unique opportunity to assess gait at the stride level in real-world settings. Walking impairment is a major cause of disability in multiple sclerosis (MS), yet current clinical metrics lack sensitivity to early and progressive changes in mobility.

Methods: We conducted two studies (NCT04888689/NCT04882891) using a wearable device to develop and validate digital mobility outcome measures based on individual strides in patients with MS. First, we assessed technical performance in a controlled, single-center environment between September 12 and September 18, 2021. We then conducted a 12-month longitudinal study under daily living conditions across six sites between March 2021 and January 2024. The evaluated metrics included stride velocity 95th centile, walking distance 90th centile, and strides per hour.

Findings: The controlled and longitudinal studies included 21 and 78 participants, respectively. The device demonstrated high stride detection accuracy (precision: 0·99) and a mean absolute error in stride velocity of 0·019 m/s. In the longitudinal study, stride velocity 95th percentile showed excellent reliability (ICC (2,1) = 0·97, SEM = 0·06) and strong agreement with Expanded Disability Status Scale (Spearman's rho = 0·65, p < 0·001) and Timed 25-Foot Walk (Spearman's rho = -0·71, p < 0·001), sensitivity to 12-month progression in both relapsing-remitting and progressive MS (p = 0·049 and p = 0·006, respectively), outperforming the Expanded Disability Status Scale. Walking distance 90th percentile and strides per hour were reliable and valid but less sensitive to progression.

Interpretation: Stride velocity 95th percentile derived from real-world, stride-level data, provides a valid, reliable, and sensitive digital outcome for detecting MS progression. It may serve as an early indicator of progression and support the accelerated evaluation of treatments targeting progression.

Funding: This study was funded by F. Hoffmann-La Roche Ltd.

Background: Automated insulin delivery (AID) systems have demonstrated significant improvements in glycemic control in children and adults with type 1 diabetes, but long-term real-world data in preschool-aged children remain limited, particularly in Europe, where Control-IQ is not approved for children under 6 years. This study aimed to evaluate the long-term effectiveness and safety of the t:slim X2 insulin pump with Control-IQ technology in children aged 0.5-5 years compared with those aged 6-10 years in a real-world multicenter Italian cohort.

Methods: In this longitudinal, observational study conducted from 2020 to 2023, data were collected from 32 Italian centers on children <11 years diagnosed with type 1 diabetes for at least six months and using the t:slim X2 with Control-IQ technology (CIQ). Participants were grouped into 0.5-5 years or 6-10 years at CIQ initiation. Primary endpoints were the percentage of time spent in range (TIR, 70-180 mg/dL) and in tight range (TITR, 70-140 mg/dL) in the two age groups, evaluated according to children's demographic, socioeconomic, and clinical characteristics using mixed-effects models for repeated measures.

Findings: We evaluated 253 children with 18-month follow-up, 131 into the 0.5-5-year group and 122 in the 6-10-year group. In the 0.5-5-year group, TIR and TITR increased significantly from baseline to 6 months and were then maintained through 18 months. In the 6-10-year group, similar improvements were observed, with no statistically significant differences between age groups in the TIR or TITR trajectories. In the adjusted mixed-effects models, TIR increased from baseline to 6 months by 5.45% (95% CI 3.78-7.11) and TITR increased by 5.56% (95% CI 3.60-7.51), with stabilization thereafter. Children of parents with a high level of education had a significantly greater mean TIR. A longer interval between T1D diagnosis and CIQ initiation was associated with a lower mean TITR (-1.21%, 95% CI -2.32 to -0.10). During observation, there were no episodes of severe hypoglycemia in younger children and only one episode in a 6-10-year-old. One episode of DKA occurred after the start of CIQ in a younger child.

Interpretation: CIQ was associated with sustained improvements in glycemic outcomes, especially within the first six months. Adverse events were rare. These findings support potential supervised off-label use in young children.

Funding: No specific funds were received for this study.

Background: To date, studies of neuropsychiatric symptoms in systemic autoimmune rheumatic diseases (SARDs) have largely been cross-sectional. Our longitudinal study with patients with SARDs from the international INSPIRE cohort aimed to advance knowledge of changes in patient-reported neuropsychiatric symptoms and adapting over time.

Methods: We conducted an observational cohort study analysing longitudinal data from the international INSPIRE (Investigating Neuropsychiatric Symptom Prevalence and Impact in Rheumatology Patient Experiences) research project. Self-reported validated survey measures for anxiety (GAD-7), depression (PROMIS SF8), and memory (EMQ-R) were compared between baseline (2022) and follow-up surveys 2 years later (2024). We invited all participants who had provided their contact details and consented for the follow-up survey. Our co-produced "ADAPT" instrument was used to assess and compare changes in how people with SARDs adapt to living with their disease over time. T-tests, Kruskal-Wallis and Mann-Whitney U tests were used to assess differences across groups for changes in study measures. Sociodemographic and disease differences were controlled for by generalised linear modelling in adjusted analyses. Patients with polymyalgia rheumatica (PMR) made up the reference group because the Kruskal-Wallis test established no significant difference between the PMR and the control group for memory, depression and anxiety scores on the baseline dataset.

Findings: The modal within-person change between baseline (BL) and follow-up (FU) for the N = 742 participants was zero for all 3 validated tools. Significant improvements at group level over two years were identified for memory scores (BL:16.14 to FU: 13.96, p = 0.002), and all four ADAPT measures (p < 0.05), whereas mean depression (BL:16.61 to FU:16.21, p = 0.303) and anxiety (BL:5.83 to FU:5.36, p = 0.073) scores were unchanged over time. Significant improvements in memory scores were observed in SLE (p = 0.022) and RA/IA (p = 0.009), and in those diagnosed (at baseline) > 10 years (p = 0.016) and between 6 and 9 years (p = 0.020).

Interpretation: This study provides evidence against the expectation of progressive memory impairment in most cases in SARDs, including SLE. Lack of improvement in mean depression and anxiety scores over time suggests that many patients with SARDs may benefit from more proactive/assertive rheumatologic disease control, psychiatric intervention, and/or psychosocial support. Early and effective SARDs disease control is required, with timely psychiatric intervention and psychosocial support provided, particularly for the newly diagnosed.

Funding: This study was funded by The Lupus Trust.