The majority of response-adaptive randomization (RAR) designs in the literature rely on efficacy data to guide dynamic patient allocation. However, their applicability becomes limited in settings where efficacy outcomes, such as survival, are observed with a random delay. To address this limitation, we introduce SAFER, a novel RAR design that leverages early-emerging safety data to inform treatment allocation decisions, particularly in oncology trials. The design is broadly applicable to contexts where prioritizing the arm with superior safety is desirable. This is especially relevant in noninferiority trials, to demonstrate that an experimental treatment is not inferior to the standard of care, while potentially offering improved tolerability. In such trials, an unavoidable trade-off arises: maintaining statistical efficiency for the efficacy hypothesis while integrating safety-driven adaptations through RAR. The SAFER design addresses this trade-off by dynamically adjusting the allocation proportion based on the observed association between safety and efficacy endpoints. We illustrate the performance of SAFER through a simulation study inspired by the CAPP-IT Phase III oncology trial. Results show that SAFER preserves statistical power, reduces the adverse event rate, and offers flexible adaptation speed depending on the temporal alignment of the endpoints.

The COVID-19 pandemic affected healthcare worldwide. This study analysed age-standardised incidence rates (ASIR) of colorectal cancer (CRC) in Bavaria to assess the COVID-19 pandemic's impact. We modelled CRC ASIR, overall and in the subgroups (sex, age group, site and stage), in the pre-pandemic (01/2007 to 02/2020) and pandemic (03/2020 to 02/2022) periods using interrupted time-series analyses. Predictions for the third year of the pandemic (03/2022 to 02/2023) were compared to expected ASIR. Comparing expected and observed CRC ASIR during the first year of the pandemic showed a significant relative change of -8.8% (95% CI: -12.7% to -4.6%), improving to 1.4% (95% CI: -4.5% to 7.2%) in the third year of the pandemic. Likewise, ASIR significantly decreased across almost all subgroups during the first year of the pandemic, recovering during the second and the third year of the pandemic. Early stages showed a significant estimated reduction, persisting until the third year of the pandemic (-4.7%; 95% CI: -8.6% to -0.9%). In contrast, for women aged 70 years and above and women with colon cancer, ASIR experienced a significant excess. In the first year of the pandemic, estimated CRC ASIR experienced significant decline, returning to the expected rates during the third year of the pandemic, for most, but not all subgroups. The relative difference remained significantly negative for early stages. A significant catch-up effect occurred in the subgroups of women aged 70 years and above and women with colon cancer. Overall, estimations indicate a recovery of CRC ASIR.

Cancer survivorship often includes reproductive health concerns (e.g., fertility potential and treatment-related health problems) that elevate psychological distress. Partner support is a key, modifiable resource linked to better adjustment, yet its pathway of influence is not fully understood. To test whether partner support mediates and/or moderates the association between reproductive health concerns and psychological distress among female cancer survivors. A cross-sectional study was conducted with 202 married female cancer survivors (ages 20-49) attending the oncology departments of Tanta University Hospital, Egypt. Validated measures included the Reproductive Concerns after Cancer Scale, Partner Support Scale, and Kessler Psychological Distress Scale. Higher reproductive concerns related to greater distress (r = 0.517, p < 0.01). Partner support correlated negatively with reproductive concerns (r =  - 0.446, p < 0.01) and distress (r =  - 0.471, p < 0.01). Adding partner support improved prediction of distress (Model 2, R² = 0.345); partner support was a significant negative predictor (B =  - 0.364, p < 0.001). Mediation was supported: Reproductive Concerns after Cancer Scale → distress total effect B = 0.4212 (p < 0.001); direct effect B = 0.3124 (p < 0.001); indirect effect via partner support B = 0.1088, 95% CI [0.0617, 0.1613]. Moderation was not supported (interaction B≈0.000, p = 0.998). Conclusions: Reproductive concerns are associated with elevated psychological distress. Partner support partially mediates yet does not moderate this relationship, indicating a protective, indirect effect on distress. Implications for Practice: Integrate structured partner-involved education and counselling into survivorship care to reduce distress linked to reproductive concerns (confirmed need). Screen routinely for reproductive concerns and perceived partner support and refer dyads to targeted psychosocial interventions. Training for nurses should prioritize communication about fertility/health concerns and techniques to engage partners effectively.

Survivors of critical illness frequently experience persistent impairments in health-related quality of life (HRQoL), with psychological symptoms contributing substantially to this burden. The relative contribution of co-occurring depression, anxiety, and post traumatic stress symptoms remains insufficiently understood. To address this gap, we conducted a cross-sectional analysis of pre-randomization data from the PICTURE randomized controlled trial, a multicenter study of a brief primary care-based psychological intervention for post-traumatic stress disorder symptoms following critical illness, including 319 intensive care unit survivors. Clinical, demographic, and mental health assessments were obtained after ICU discharge. Latent profile analysis, random forest modeling, and quantile regression were applied to identify determinants of HRQoL measured by the EuroQol Five-Dimension Five-Level (EQ-5D-5L) index and visual analog scale (VAS). The mean EQ-5D-5L index was 0.71 (SD 0.27; median 0.81) and the mean EQ VAS score was 60.7 (SD 19.4; median 60.0), indicating considerable overall impairment. Depression, anxiety, and post-traumatic stress symptoms showed substantial overlap and formed four distinct symptom profiles associated with specific functional impairments. Screening positive for depression on the 2-item Patient Health Questionnaire (PHQ-2) with ≥ 3 points was associated with a median reduction of -0.13 (95% CI -0.19 to -0.07) on the EQ-5D-5L index and -12.45 points (95% CI -17.93 to -6.96) on the EQ VAS, exceeding clinical and demographic predictors. These findings indicate that depressive symptoms are a major determinant of impaired health related quality of life among intensive care survivors with psychological distress and support routine brief depression screening in post-intensive care follow up.Trial registration: ClinTrials.gov: NCT03315390 (Registration date: 2017-10-20); German Clinical Trials Register: DRKS-ID: DRKS00012589 (Registration date: 2017-10-17).

Orthorexia Nervosa (ON), the obsessive preoccupation with healthy eating, and Exercise Addiction (EA), the behavioral addiction to exercise, are controversially discussed as potential mental disorders. The unclear distinction between these conditions and disordered eating, especially regarding restrictive eating and instrumental exercise behaviors, contributes to this debate. The objective of the study was to ascertain whether latent profiles can be identified that support the independence of ON and EA from disordered eating. It was hypothesized that ON profiles would be characterized by stronger health orientation, EA profiles by greater fitness orientation, and disordered eating profiles by heightened preoccupation with overweight, appearance concerns, and lower self-esteem.

A total of 661 participants (77.2% women, age M ± SD = 26.74 ± 9.68) completed an online survey including the Düsseldorf Orthorexia Scale, Revised Exercise Addiction Inventory, Eating Disorder Examination-Questionnaire, Multidimensional Body Self-Relations Questionnaire, and Rosenberg Self-Esteem Scale. Latent profile analysis was used to identify distinct subgroups of ON, EA, and disordered eating, which were subsequently compared on self-esteem and body image measures using one-way ANOVAs.

The latent profile analysis yielded five distinct profiles: In addition to two "healthy" clusters - one characterized by non-pathological eating behaviors and the other by low commitment to both diet and exercise - three profiles were identified as being of potential clinical interest. These included: (I) disordered eating, ON and instrumental exercise; (II) disordered eating alone; and (III) EA. Notably, no profile was characterized exclusively by ON. Profile I - which exhibited the highest levels of ON, EA and disordered eating - was marked by the lowest self-esteem and the strongest concerns about appearance, overweight, fitness, and health. Conversely, profile III was characterized by only modestly elevated EA levels, favorable body image, and self-esteem.

These findings question the independence of ON, as it was closely intertwined with disordered eating pathology rather than forming a distinct behavioral pattern. Exercise addiction showed relatively low symptom severity in the absence of disordered eating, highlighting the risk of falsely identifying instrumental exercise as EA. Instrumental exercise and orthorexic tendencies may worsen negative body image in disordered eating by increasing pressure on appearance, fitness, and health of individuals.

Not applicable.

With the widespread implementation of antiretroviral therapy (ART), human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) has gradually transitioned from a highly fatal infectious disease to a manageable chronic condition. Simultaneously, global population aging has accelerated, making older adults with HIV (≥75 years) an increasingly important group in terms of disease burden. However, the epidemiological characteristics, disease spectrum, and long-term trends of this population-including key metrics such as incidence, mortality, prevalence, and disability-adjusted life years (DALYs)-remain inadequately assessed, particularly regarding epidemiological transitions and inter-country differences in this age group across G7 nations.

Data on HIV/AIDS and its subtypes from 1990 to 2021 were obtained from the Global Burden of Disease (GBD) 2021 database for G7 countries (Canada, France, Germany, Italy, Japan, the United Kingdom, and the United States) among individuals aged ≥75 years. Metrics included age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized prevalence rate (ASPR), and DALYs. Stratified analyses were performed by age groups (75-79, 80-84, 85-89, 90-94, ≥95 years), sex, and disease subtype. Long-term trends were assessed using Joinpoint regression, calculating the annual percent change (APC) and average annual percent change (AAPC).

Between 1990 and 2021, the incidence and mortality of HIV/AIDS in older adults declined continuously in most G7 countries, reflecting the effectiveness of ART and public health interventions. In contrast, prevalence and DALYs increased in some countries, indicating an asymmetric pattern of "decreasing incidence and mortality, but increasing survival and disability." Considerable heterogeneity existed among countries: the United States and several European countries exhibited a high burden among surviving individuals, whereas Japan showed a consistently increasing trend. Sex-specific analysis revealed a higher overall burden in males than females, although the sex gap narrowed in the oldest age groups. The disease spectrum shifted over time, with a declining burden of drug-susceptible tuberculosis and non-communicable chronic diseases (conditions associated with HIV/AIDS) emerging as the primary drivers of DALYs.

Older adults should be incorporated into HIV prevention, screening, and health management strategies, with particular attention to chronic disease management, functional maintenance, and multidisciplinary care to address the long-term health challenges posed by aging HIV cohorts.

The implementation of digital health technology (DHT) has not reached its full potential. Research on the factors influencing the acceptance and use of DHTs in low- and middle-income countries (LMICs) is fragmented and sparse. This study aimed to identify the facilitators and barriers to DHT acceptance and use in healthcare consumers.

The systematic review and meta-analysis were conducted using PubMed, Embase, and Web of Science from inception to July 1st, 2025. Facilitators and barriers to the acceptance and use of DHT were extracted, and a modified framework was developed based on the Unified Theory of Acceptance and Use of Technology. The strength of each pathway recorded in the framework was estimated through meta-analysis.

A total of 78 publications were included in the systematic review, comprising 64 quantitative studies and 14 qualitative studies. Twelve dimensions were summarized. Factors demonstrating the highest positive associations with intentions to use DHTs included attitude (r = 0.5644; 95% CI: 0.4498, 0.6607), trust (r = 0.5239; 95% CI: 0.4243, 0.6109), performance expectancy (r = 0.4851; 95% CI: 0.4335, 0.5335), technology self-efficacy (r = 0.4430; 95% CI: 0.2504, 0.6018), facilitating conditions (r = 0.4345; 95% CI: 0.3526, 0.5098), effort expectancy (r = 0.4171; 95% CI: 0.3508, 0.4793), and habit (r = 0.4213; 95% CI: 0.1684, 0.6222). Social influence was also positively associated (r = 0.3582; 95% CI: 0.2823, 0.4297), as well as hedonic motivation (r = 0.3963, 95% CI: 0.2280, 0.5416). Price value showed a near-null, imprecise association (r = 0.0304; 95% CI: -0.1483, 0.2072). Perceived risk to patient privacy, patient security and telemedicine systems security, showed a small negative but imprecise association with intentions (r = -0.0402; 95% CI: -0.2169, 0.1391). Anxiety showed a non-significant negative association (r = -0.2071; 95% CI: -0.5108, 0.1426).

The barriers identified in this analysis highlight the necessity of establishing and sustaining an integrated enabling environment as well as investing in digital health literacy to enhance healthcare consumers' self-efficacy. Findings of the study will facilitate the improvement of DHT implementation to address health concerns.

This study was funded by Noncommunicable Chronic Diseases-National Science and Technology Major Project (2024ZD0524500, 2024ZD0524501), National Natural Science Foundation of China (72274005 and 72304013), Beijing Nova Program (20230484284).

Noncommunicable diseases (NCDs) are a leading cause of morbidity and mortality globally, and the burden falls disproportionately on low- and middle-income countries. In Nigeria, hypertension and diabetes are among the most prevalent NCDs, yet diabetes screening coverage remains poorly characterised relative to blood pressure screening. This study quantifies missed opportunities for diabetes screening among adults who had already accessed blood pressure screening services and identifies the population subgroups most affected.

We conducted a secondary analysis of individual-level data from the 2023-2024 Nigeria Demographic and Health Survey (NDHS), a nationally representative survey of 39,050 women aged 15-49 years and 12,204 men aged 15-59 years. A missed opportunity was defined at the individual level as reporting a prior blood pressure measurement without a concurrent blood sugar measurement. The McNemar test compared the paired proportions of blood pressure and blood sugar screening within each sex, and multivariable logistic regression identified independent predictors of missed opportunity, adjusting for residence, education, wealth, and age.

Bloodpressure screening coverage was 52.2% among women and 35.0% among men, compared with 18.6% and 19.9% for blood sugar screening, respectively. The absolute gap was 33.6 percentage points in women (McNemar p < 0.001) and 15.1 percentage points in men (McNemar p < 0.001). Among bloodpressure-screened individuals, 65.9% of women and 46.5% of men had not received blood sugar screening. In logistic regression restricted to bloodpressure-screened individuals, higher education, greater wealth, and older age were each independently associated with lower odds of missing blood sugar screening in both sexes, while residence was not a significant predictor after adjustment.

Among Nigerian adults who had been screened for hypertension, nearly two-thirds of women and almost half of men had never been screened for diabetes. This reflects a system-level integration failure rather than a lack of health-system contact. Embedding diabetes screening into existing blood pressure screening encounters represents a practical and scalable strategy for improving early diabetes detection in Nigeria.

Southeast Asia (SEA) faces persistent gaps in regional understanding and control of ticks and tick-borne diseases (TBDs) despite recent advances (2023-2025). The second international symposium on ticks and TBDs in SEA (Singapore, August 2025), following the inaugural 2023 meeting in Cambodia, served as a catalyst for regional exchange that informed this perspective. SEA's ecological and host diversity supports complex tick-host-pathogen networks, yet evidence remains fragmented due to uneven sampling that has largely focused on livestock and peri-urban environments. Key constraints include limited taxonomic resolution driven by outdated or incomplete identification keys, under-sampling of soft ticks (Argasidae), and the absence of harmonized, open-access regional reference resources (including DNA barcodes and MALDI-TOF MS spectral databases). While MALDI-TOF MS, proteomics, AI-assisted identification, and next-generation sequencing/metagenomics are increasingly applied, their broader regional uptake is limited by the absence of harmonized, open-access reference resources (including DNA barcodes and MALDI-TOF MS spectral databases). Broad ecological surveys and integrated animal and human surveillance remain limited, and vector competence studies are constrained by the scarcity of SEA-derived tick colonies and cell lines. Regional data and recent findings (2024-2026) confirm circulation of multiple TBPs (including Anaplasma, Babesia, Borrelia, Coxiella, Ehrlichia, Rickettsia, and Theileria) and highlight emerging viral findings, including southward reports of Bandavirus dabieense. Human infestations and non-communicable tick bite outcomes (e.g., tick paralysis and alpha-gal syndrome) are recognized but remain under-reported due to low clinical awareness and limited diagnostics. Importantly, the diagnostic chain is further disrupted by missed/insufficient specimen collection at the point of care, and by constrained capacity to identify (especially immature) ticks to species level-limitations compounded by the absence of harmonized, open-access regional reference resources. The symposium identified six priorities: (1) full completion and regional validation of tick identification keys for adults (in progress) and immatures (to be initiated), plus an open-access DNA barcode library anchored by curated, voucher-based collections from all SEA countries; (2) harmonization of molecular and proteomic diagnostic platforms, including expansion of regional MALDI-TOF MS and NGS protocols and reference databases; (3) development of tick colonies and cell lines from locally prevalent species to support vector competence, vaccine, and acaricide testing; (4) expansion of One Health surveillance with enhanced ecological sampling at wildlife-livestock-human interfaces; (5) establishment of open-access, region-wide data platforms for integrated tick, TBP, and ecological metadata sharing; and (6) sustained investment in human resources, training, and policy advocacy to raise research and public health visibility of ticks and TBDs.

Background: Iron deficiency (ID) progresses through three stages: iron deficiency stores (IDS), iron deficiency erythropoiesis (IDE), and iron deficiency anemia (IDA). Neglecting subclinical ID may be harmful to school-aged children and increase the public health burden. Although diet is a key modifiable factor, most studies only focus on overall ID or merely the clinical IDA stage. This study combines a dietary index with pattern analysis to take advantage of their complementary strengths and explore their associations with ID progression. Methods: This cross-sectional study included 2493 participants from rural Guangzhou between June 2022 and May 2023. Demographic, lifestyle, anthropometric, and dietary data were collected via structured questionnaires. Blood samples were analyzed for iron status. Factor analysis identified dietary patterns, and the Chinese Dietary Guidelines Index for Children and Adolescents [CDGI(2021)-C] assessed dietary quality. We used ordinal logistic regression, multivariable logistic regression, and restricted cubic spline (RCS) models to examine dietary associations with ID stages. Results: IDS, IDE, and IDA proportions were 68.22%, 17.45%, and 14.33%, respectively. All four dietary patterns correlated positively with CDGI(2021)-C, most strongly for the fruit-vegetable (r_s = 0.552) and cereal-tuber-legume patterns (r_s = 0.386). Higher CDGI(2021)-C (OR = 0.852, 95% CI: 0.751-0.966, p-trend = 0.012), fruit-vegetable (OR = 0.866, 95%CI: 0.748-0.993, p-trend = 0.047), and meat-offal patterns (OR = 0.733, 95%CI: 0.611-0.868, p-trend < 0.001) were inversely associated with advancing ID stages, while the snack-fast food pattern was positively associated (OR = 1.233, 95% CI: 1.094-1.381, p-trend < 0.001). In IDS, higher adherence to CDGI(2021)-C, fruit-vegetable, and meat-offal patterns was associated with lower odds (all p-trend < 0.05). RCS showed nonlinear associations for the snack-fast food and cereal-tuber-legume patterns, with risk peaking at moderate-to-high adherence to these patterns (both p-nonlinear < 0.05). In IDE and IDA, the snack-fast food pattern risk rose steeply at moderate-to-high adherence (p-nonlinear = 0.036), whereas the cereal-tuber-legume pattern's ORs fluctuated near 1 (p-nonlinear = 0.020). Conclusions: Dietary pattern and index analyses showed consistent associations across ID stages. Adherence to dietary guidelines slows ID progression, especially in early subclinical stages. More fruits, vegetables, and heme-iron-rich foods, alongside less fast food and snacks, slow ID progression. Though dietary intervention effects weaken in later stages, reducing fast food and snacks confers long-term benefits. These findings inform targeted nutrition policies to prevent ID progression in children.