Digital mental health apps are increasingly available and used, yet the large majority lack clinical and economic evidence, limiting reimbursement support and the identification of high-value interventions. MindMySkin is a digital psychobehavioral mobile intervention co-designed with patients and guided by behavioral change frameworks to address the psychobehavioral determinants of symptom burden in chronic inflammatory skin diseases. The app comprises 74 modules targeting illness coherence, symptom management, and emotional and functional impairment and is currently being tested in a double-blind randomized controlled trial.

This protocol prespecifies an economic evaluation plan conducted as a secondary analysis alongside the trial to assess the cost-effectiveness of MindMySkin within Singapore's health care system.

The parent trial recruits English-speaking participants aged 16 years or older with psoriasis, eczema, or chronic urticaria across 3 sites in Singapore (target N=690; 2:1 allocation, 32-week follow-up). The active comparator is Healthy365, a general wellness app managed by the Singapore Health Promotion Board. The trial-based economic evaluation will adopt a health care system perspective as the primary analytic viewpoint. Resource costs will include intervention deployment and dermatology-related health care use. Indirect medical costs and work productivity losses will additionally be included in a sensitivity analysis conducted from a societal perspective. A cost-effectiveness analysis will use the Dermatology Life Quality Index, a dermatology-specific measure of health-related quality of life, while a cost-utility analysis will derive health utilities from the EQ-5D-5L to enable estimation of quality-adjusted life years. Incremental cost-effectiveness ratios and net monetary benefit will be estimated using intention-to-treat analyses with regression adjustment. Uncertainty will be explored using bootstrapping, deterministic sensitivity analyses, subgroup analyses, and scenario modeling. A Markov model-based extrapolation over 5 years will be undertaken if within-trial results suggest a high likelihood of cost-effectiveness.

Study funding is provided by the National Medical Research Council Clinical-Scientist Individual Research Grant New Investigator Grant (CS-IRG NIG; funded on June 5, 2024), and ethics approval has been obtained (2022/00751). Recruitment commenced in February 2026, and as of June 2026, a total of 46 participants have been enrolled. Economic data collection will be conducted concurrently with the parent trial, and the economic analysis is expected to commence following trial completion, which is anticipated in 2028.

By embedding a health economic evaluation within a randomized controlled design and incorporating condition-sensitive outcome measures, this study advances methodological standards for evaluating scalable psychobehavioral interventions. Demonstrating value through disability reduction rather than survival gain may strengthen the legitimacy of low-intensity digital therapeutics within health technology assessment frameworks and inform implementation decisions in resource-constrained health systems.

Tobacco use remains a major contributor to mortality and disability in India. This study assessed tobacco-attributable mortality and disability-adjusted life-years (DALYs) in India in 1990 and 2023, with comparisons by sex, age group and type of tobacco exposure.

Descriptive population-level analysis of secondary data from the Global Burden of Disease 2023 study.

India.

Tobacco-attributable deaths and DALYs were assessed by sex, age group and type of tobacco exposure, including smoking, chewing tobacco and secondhand smoke. Absolute numbers and age-standardised rates were compared between 1990 and 2023.

Tobacco-attributable deaths increased by 54.7%, from 745.74 thousand in 1990 to 1 153.98 thousand in 2023, while DALYs increased by 15.1%, from 27.3 to 31.4 million. In contrast, age-standardised death and DALY rates declined by 39.8% and 47.8%, respectively. Smoking remained the leading contributor (738.8 thousand deaths; 19.78 million DALYs in 2023), particularly among males. Chewing tobacco showed the largest increase (deaths +153.7%; DALYs +124.8%). Secondhand smoke remained substantial, particularly among females (325.63 thousand deaths), though its DALY burden declined by 10.8%. The burden shifted towards non-communicable diseases, with chronic obstructive pulmonary disease, ischaemic heart disease and stroke as leading contributors in 2023.

Despite declines in age-standardised rates, the overall burden of tobacco in India remains substantial. The differing patterns across smoking, chewing tobacco and secondhand smoke highlight the need for comprehensive and targeted tobacco-control strategies.

Optimizing sugar intake during early childhood is critical for preventing non-communicable diseases. Although international guidelines recommend limiting free sugar intake, Japan is yet to consolidate data on free sugar intake among children under 2 years of age. This study examined free sugar intake, dietary sources, and associated factors among Japanese children aged 18-23 months.

A cross-sectional study was conducted among children attending infant health checkups in Kama City, Japan. Caregivers recorded two non-weighed dietary records (one weekday and one Sunday). Free sugar intake, dietary sources, and related factors were analyzed.

Among 84 participants, the mean free sugar intake was 13.3 g/day, corresponding to 5.7% of estimated energy requirements. Overall, 44.0% of children exceeded the World Health Organization recommended level of <5% of energy from free sugar, and 16.7% exceeded the <10% threshold. Major sources included confectioneries (43.2%), fruits including 100% fruit juice (27.3%), dairy products (23.3%), and sweetened beverages (4.6%). Free sugar intake was 37% higher on Sundays than on weekdays. Multivariable analyses showed no significant associations between excessive free sugar intake and demographic or lifestyle characteristics.

A substantial proportion of Japanese infants aged 18-23 months consumed free sugar in excess of World Health Organization recommendations. These findings highlight the need to improve caregiver awareness of major free sugar sources, particularly 100% fruit juice, and support the development of age-specific dietary guidance and pediatric nutrition counseling in Japan.

Research output on the impacts of climate change and human health is growing rapidly. We aimed to synthesise peer-reviewed studies on this subject published between January 2000 and May 2024.

Scoping review.

Literature was collected from PubMed, Embase and Scopus on 11 November 2019, 25 June 2021 and 22 April 2024.

We included English language quantitative peer-reviewed primary research articles about the impacts of long-term climate change (ie, as opposed to effects of weather or single climatic events with the exception of attribution studies) on human health.

Two reviewers independently screened titles and abstracts. Full-texts were screened by single reviewers, although 23% of publications selected for full-text screening received an independent second-screening. Reported exposures and health outcomes were classified. Reported quantitative effects of long-term climate change on human health were coded as increasing, decreasing, variable or non-significant.

From 60 781 initial records we included 1223 quantitative publications in this scoping review. Health impacts of long-term climate change were studied most often in Europe, the Americas and the Western Pacific. Studies on temperature and on disease vectors, including the diseases they transmit, represented 39.3% and 30.9% of all included publications, respectively. Included results covered over 100 specific health outcomes. Diarrhoeal diseases, malaria, dengue, ischaemic heart disease and stroke were the most studied specific health outcomes. While infectious diseases were often studied in low- and middle-income countries, non-communicable diseases were rarely examined in this context. About 20% of included publications provided retrospective results, demonstrating that climate change is already impacting human health in variable ways globally. About 80% of included publications provided prospective results, projecting mostly variable or increasing impacts on human health over the coming decades.

Our scoping review provides a comprehensive overview of existing evidence about the impacts of long-term climate change on human health. Currently, differences in research methodologies make it difficult to directly compare study findings. The outcomes of this review can help to harmonise future climate change and health research and support evidence-based climate change adaptation.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease driven by genetic susceptibility and triggered by environmental cues. This review aims to systematically elaborate the full pathogenic cascade of T1DM involving the crosstalk among genetics, environment, immunity and pancreatic target cells, and summarize current preventive and therapeutic strategies together with outstanding unresolved questions.

We reviewed published literatures regarding T1DM pathogenesis, preclinical intervention and curative β cell replacement therapy, focusing on established immune mechanisms, controversial hypotheses and translational barriers.

Breakdown of immune tolerance leads to progressive destruction of pancreatic β cells mediated by autoreactive CD4⁺ and CD8⁺ T cells, resulting in absolute insulin deficiency and lifelong exogenous insulin dependence. Viral infection serves as a major disease trigger, while multiple pathways including β cell stress-related neoantigen formation, gut microbiota-intestinal barrier dysfunction, mechanosensing-dependent immune cell homing and epigenetic modification of memory T cells jointly drive disease progression. T1DM follows a 1-3 staging framework, providing an intervention window at preclinical stages. Current therapies can merely delay onset, and stem-cell-derived β cell transplantation is restricted by allogeneic rejection and recurrent autoimmunity.

Multiple intertwined genetic-environmental-immune events initiate and propagate T1DM. Novel strategies targeting key pathogenic nodes are urgently required to eliminate autoimmune memory, and further translational studies are needed to achieve curative treatment for T1DM.

To assess the clinical severity of dry eye disease and its association with tear film inflammatory biomarkers among adults in Northern Ethiopia.

Multicentre cross-sectional study.

Ophthalmic centres in Northern Ethiopia.

A total of 618 adults were included in the analysis, with a response rate of 97.17%.

Sociodemographic and clinical data were collected using a pretested structured questionnaire. Dry eye disease was assessed using the Ocular Surface Disease Index, tear break-up time, Schirmer I test and ocular surface staining. Tear samples were collected and analysed for interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α) and matrix metalloproteinase-9 (MMP-9) using standard laboratory procedures. Differences in biomarker concentrations across dry eye disease severity categories were assessed using one-way analysis of variance or appropriate non-parametric tests. Correlations between inflammatory biomarkers and clinical parameters were assessed using Pearson or Spearman correlation coefficients, as appropriate. Ordinal multivariable logistic regression was used to identify factors associated with increasing dry eye disease severity. Statistical significance was set at p<0.05.

The prevalence of dry eye disease was 44.01% (95% CI 40.8% to 48.1%). Concentrations of IL-1β, IL-6, TNF-α and MMP-9 increased significantly across dry eye disease severity categories. MMP-9 demonstrated the strongest correlations with clinical parameters of DED. Female sex (adjusted OR (AOR)=1.62, 95% CI 1.15 to 2.30), diabetes mellitus (AOR=2.18; 95% CI 1.34 to 3.55), screen exposure of ≥3 hours/day (AOR=2.12; 95% CI 1.48 to 3.04), bicycle or motorbike riding (AOR=1.69; 95% CI 1.16 to 2.46) and alcohol consumption (AOR=1.58; 95% CI 1.06 to 2.35) were independently associated with increasing dry eye disease severity.

Dry eye disease was common among adults attending ophthalmic centres in Northern Ethiopia, with inflammatory biomarker concentrations increasing with greater clinical severity. MMP-9 showed the strongest observed association with clinical measures of dry eye disease. These findings suggest that tear film inflammatory biomarkers may have relevance for understanding the biological processes underlying dry eye disease severity, while attention to modifiable associated factors may contribute to improved prevention and management.

Diabetic retinopathy (DR) is one of the leading causes of visual impairment among working-age adults worldwide. Existing artificial intelligence (AI) studies have mainly focused on automated diagnosis and grading of DR or diabetic macular oedema while relatively few studies have investigated long-term prediction of visual outcomes. In clinical practice, patients and clinicians are more concerned about whether future visual decline will occur rather than merely identifying the current presence of DR. This study aims to develop and validate a real-world prognostic model integrating AI-derived imaging scores, ophthalmic examinations and systemic clinical variables to predict 3-year visual decline in patients with diabetes.

This retrospective longitudinal cohort study will use routinely collected ophthalmic imaging and clinical data from Peking University Third Hospital for model development and internal validation, with independent external validation planned using data from Ningbo Eye Hospital, Wenzhou Medical University. The development cohort will cover the period from 1 January 2018 to 1 May 2026. Eligible eyes will have baseline colour fundus photography (CFP) and/or optical coherence tomography (OCT), baseline best-corrected visual acuity and at least one follow-up visual acuity record within 3 years after the index date. CFP-enhanced analyses will include eyes with eligible CFP, OCT-enhanced analyses will include eyes with eligible OCT and multimodal analyses will require eligible paired CFP and OCT. The primary outcome will be time to first visual decline within 3 years, defined as an increase in logarithm of the minimum angle of resolution (logMAR) best-corrected visual acuity of ≥0.2 from baseline in the same eye. Sustained visual decline, requiring confirmation of a ≥0.2-logMAR deterioration at a subsequent eligible visit, will be evaluated as a key secondary outcome. AI-derived imaging scores will be generated using prespecified modality-specific and multimodal retinal image models. Separate CFP and OCT models will generate continuous CFP-derived and OCT-derived imaging scores, while a prespecified multimodal model jointly integrating paired CFP and OCT information will generate a single continuous multimodal imaging score. These imaging scores will be incorporated separately into prespecified AI-enhanced prognostic models together with demographic, systemic and ophthalmic predictors. Cox regression, penalised Cox regression and exploratory machine learning survival models will be developed and internally validated and the final prognostic model will be externally evaluated in an independent cohort from Ningbo Eye Hospital. Performance will be evaluated using discrimination, calibration, Brier score and decision curve analysis.

This study has received ethical approval from the Ethics Committee of Peking University Third Hospital (approval number: IRB00006761-M20260399). All data will be de-identified before analysis. The findings of this study will be disseminated through peer-reviewed publications and conferences.

Diabetes-associated cognitive impairment (DACI) undermines diabetes self-management and is associated with increased morbidity and mortality. Although mind-body exercise may improve cognition, its benefits are often limited by the lack of timely, precise, individualised instruction and feedback in adults with cognitive impairment. Augmented reality (AR) systems can deliver performance-adaptive, visually anchored cues and auditory prompts in real-world settings, but their cognitive and metabolic benefits in DACI remain unknown. This trial will compare AR-assisted Tai Chi (iTaiChi), instructor-led Tai Chi (TaiChi) and standard care in adults with DACI and explore underlying metabolic and neurobiological mechanisms.

In this randomised controlled trial, 246 community-dwelling adults aged 45-75 years with DACI will be enrolled and randomly allocated in a 1:1:1 ratio to a TaiChi group, an iTaiChi group or a standard care group. All participants will receive standard care. In addition, participants assigned to the two exercise groups will undertake a standardised Yang-style 24-form Tai Chi programme three times weekly for 12 weeks. The primary outcome is the change in Montreal Cognitive Assessment Score. Secondary outcomes include physical health related parameters and brain health related parameters.

This study was approved by the Ethics Committee of Shanghai Sixth People's Hospital (Approval No. 2025-017). Dissemination of the findings will include peer-reviewed publications, conference presentations and media releases.

ChiCTR2500111614.

Dietary management is crucial for diabetes, yet the impact of macronutrient and energy intake on diabetic kidney disease (DKD) and all-cause mortality remains unclear. This study aimed to investigate these associations and to identify intake levels that were associated with the lowest odds of DKD and mortality.

Using combined cross-sectional and prospective data from NHANES (2011-2018), we analyzed 3066 diabetic adults (representing 30.3 million individuals in the USA). Weighted logistic regression was used to assess the prevalence of DKD, while Cox regression was employed to evaluate associations with all-cause mortality, incorporating dose-response analyses and mediation testing.

After multivariable adjustment, higher protein and dietary fiber intake showed significant inverse linear associations with DKD (P-trend <0.05). Compared with the lowest quartile (Q1), the highest quartile (Q4) had significantly lower DKD odds: protein (OR=0.41, 95% CI 0.21 to 0.79) and fiber (OR=0.50, 95% CI 0.31 to 0.82). The statistical inflection points associated with lower DKD odds were protein >74 g/day and fiber >14 g/day. Exploratory mediation analysis suggested that body mass index and hemoglobin partially explained the associations of proteins and fibers with DKD, respectively. Prospectively, after 48 months median follow-up (366 deaths, representing 3.36 million), only energy intake exhibited a significant U-shaped association with mortality risk (non-linear p<0.05). Mortality was lowest with daily energy intake between 1750 kcal and 1810 kcal.

In this observational analysis, higher protein (>74 g/day) and fiber intake (>14 g/day) were associated with lower DKD prevalence in diabetes, while maintaining daily energy within 1750-1810 kcal is associated with the lowest all-cause mortality risk. These findings suggest potential reference values for dietary patterns in diabetes management.