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Improved quality of life and prolonged survival with add-on homeopathic treatment in patients with non-small cell lung cancer: a prospective, randomized, placebo-controlled, double-blind, three-arm, multicenter study.

BACKGROUND: Alongside conventional anticancer treatment, add-on homeopathy might help to alleviate adverse effects of conventional therapy. AIM: The aim of this study was to replicate previous studies on the effect of adjunctive homeopathy on quality of life (QoL) and survival in non-small cell lung cancer (NSCLC) patients. METHOD: In this prospective, randomized, placebo-controlled, double-blind, three-arm multicenter phase III study with quadruple-checked data analysis, we investigated the potential effects of an add-on homeopathic treatment compared to placebo in patients with stage IV NSCLC in terms of QoL. Ninety-eight received either individualized homeopathic medicinal products (HMPs; n&#x2009;=&#x2009;51) or placebo (n&#x2009;=&#x2009;47) in a double-blinded fashion. Fifty-two control patients without homeopathic treatment were only observed in terms of their survival rate. The ingredients of the various HMPs were mainly prepared of plant, mineral, or animal origin. The data entry and statistical analysis were subject to an exceptional quadruple-checked data analysis process. The analysis presented in this article was inspired by our earlier report of this trial published in The Oncologist in 2020, which was retracted by that journal in November 2025 after two corrections; a majority of the co-authors disagreed with this decision. The present article is based on the same trial dataset but was deliberately designed to highlight the unique research methodology: design and preparation by a lead statistician, data entry, data clearing and independent statistical evaluation were performed in four mutually independent steps, reporting follows the CONSORT statement, and the interpretation of the findings has been reframed conservatively. RESULTS: Global health status (QoL) was higher in the homeopathy group than in the placebo group after 9&#xa0;weeks and after 18&#xa0;weeks (p&#x2009;<&#x2009;0.001). With the exception of cognitive functioning at 9&#xa0;weeks and of pain, diarrhea and financial difficulties at 9&#xa0;weeks, all functional and symptom scales of the EORTC QLQ-C30 favored the homeopathy group (p&#x2009;<&#x2009;0.001 for the multivariate comparisons), with between-group differences exceeding the threshold of 10 points that is generally regarded as clinically meaningful. Median survival time over the 730-day observation period was 435&#xa0;days in the homeopathy group, 257&#xa0;days in the placebo group (p&#x2009;=&#x2009;0.010), and 228&#xa0;days in the non-randomized control group (p&#x2009;<&#x2009;0.001); the corresponding 2-year survival rates were 45.1%, 23.4%, and 13.5% (homeopathy vs. placebo p&#x2009;=&#x2009;0.020; homeopathy vs. control p&#x2009;<&#x2009;0.001). The difference between the placebo group and the non-randomized control group was not statistically significant (p&#x2009;=&#x2009;0.154). CONCLUSION: In this trial, add-on homeopathy was associated with better quality of life across most functional and symptom domains, with clinically meaningful effect sizes congruently to a previous open study. Survival time was significantly longer in the homeopathy group compared to both the placebo and control groups. Independent replication, ideally within contemporary immuno-oncological treatment regimens is required. TRIALS REGISTRATION: ClinicalTrials.gov; No.: NCT01509612; January 7, 2012.

Humans

Increasing gut short-chain fatty acids protects intestinal barrier function but does not spare muscle glycogen or impact aerobic performance.

Animal studies suggest gut microbiota-derived short-chain fatty acids (SCFA) provide an intestinal barrier-protecting, glycogen-sparing energy source that increases aerobic endurance performance, but confirmation in humans is needed. This study aimed to determine whether increasing colonic SCFA availability impacts intestinal barrier function, substrate metabolism, muscle glycogen and aerobic performance in healthy adults. Using a randomized, double-blind, crossover design 12 active men (age 18-30&#xa0;years;40.0&#xa0;&#xb1;&#xa0;7.1&#xa0;mL/kg/min) performed prescribed exercise and consumed a provided diet supplemented with acetylated and butyrylated high-amylose maize starch engineered to deliver SCFA to the colon (HAMS-A/B) or low-amylose maize starch (LAMS) for 7 days, separated by a 2 week washout. Indirect calorimetry, stable isotopes and blood, muscle and urine biomarkers were measured on intervention day 8 while participants completed 90&#xa0;min of steady-state cycle ergometry (ExSS; 60 &#xb1; 5%) followed by a 5&#xa0;km treadmill time trial. HAMS-A/B, relative to LAMS, increased faecal and serum SCFA. Multiple markers of intestinal barrier damage and permeability were lower, and the respiratory exchange ratio during ExSS was higher (0.02 [95% confidence interval (CI): 0.01, 0.03], Ptreatment&#xa0;<&#xa0;0.001) following HAMS-A/B versus LAMS. However no between-treatment difference in glucose turnover, muscle glycogen depletion (14&#xa0;&#xb5;mol/kg/g dry wt. [95% CI: -116, 143], Pinteractio n&#xa0;=&#xa0;0.613) or TT performance (5&#xa0;s [95%CI: -44, 54], Ptreatment&#xa0;=&#xa0;0.816) was observed. Increasing colonic and circulating SCFA modestly altered substrate oxidation and preserved intestinal barrier function during endurance exercise. However effects were not sufficient to spare muscle glycogen or increase aerobic endurance performance, leaving the practical relevance unclear and underscoring challenges inherent in translating promising preclinical findings to humans. KEY POINTS: Animal studies suggest gut microbiota-derived short-chain fatty acids (SCFA) provide an intestinal barrier-protecting, glycogen-sparing energy source that increases aerobic endurance performance, but confirmation in humans is lacking. A gut microbiota-targeted dietary supplementation strategy was used to deliver SCFA to the colon and successfully increased colonic and systemic SCFA concentrations in healthy, physically active adults before and during an endurance exercise bout and aerobic performance test. Increasing colonic and systemic SCFA availability preserved intestinal barrier function but did not impact glucose turnover, alter protein expression in muscle or spare muscle glycogen during endurance exercise. Increasing colonic and systemic SCFA availability did not impact aerobic endurance performance.

Humans

Eating Experiences During Cancer Treatment in Adolescents and Young Adults: A Systematic Literature Review and Meta-Synthesis.

Adolescents and young adults (AYAs) aged 15-39 with cancer face distinct challenges during treatment, with eating consistently emerging as one of the most distressing and underrecognized concerns. At a critical life stage, AYAs must navigate illness-related consequences that profoundly affect well-being. Eating reflects these broader challenges and is identified as a key issue requiring health care attention. To address this, we synthesized evidence on AYAs' eating experiences and well-being during mealtime-related activities to inform health care practice. Qualitative and mixed-method studies were identified through searches across CINAHL, Embase, PubMed, Scopus, and Web of Science for studies published up to May 2025, supplemented by snowball searches. Of 3214 records, 74 full-text articles were reviewed, and 18 met the inclusion criteria. These represented 302 AYAs, 73 relatives, and 88 health care professionals. Studies were analyzed using Joanna Briggs Institute review methods and GRADE-CERQual to support clinical interpretability. The meta-synthesis identified one core theme: "Eating as an embodied struggle and act of agency," with three subthemes: (a) living through physical and sensory disruption, (b) carrying the weight of new emotions and shifting relations, and (c) finding ways through gaps in support. Eating emerged as a disrupted, emotionally charged, yet agentic act requiring sensitive, individualized approaches. Thirteen evidence-informed recommendations were developed to guide clinical application. These emphasize early nutritional screening, dietetic support, flexible meal options, respectful family involvement, and psychosocially attuned care. Future research should codevelop and evaluate tailored interventions that address AYAs' embodied, emotional, and social needs to improve eating-related quality of life during cancer treatment.

Humans

Genomic science and the nurse educator's role: Promoting integration from curriculum to clinical practice.

BACKGROUND: Registered nurses and nurse educators play a critical role in preparing future clinicians to translate genomic discoveries into practice. However, emerging evidence suggests that both groups may lack sufficient knowledge and confidence in genomics, potentially limiting their ability to teach, mentor, and apply genomics in real-world settings. This gap is especially concerning in Aotearoa New Zealand, where the genomic literacy of nurse educators and clinicians remains underexplored. OBJECTIVE: This study aims to: (1) assess nurse educators' genomic literacy and confidence in teaching genomics; and (2) evaluate registered nurses' knowledge and confidence in applying and teaching genomics in clinical practice. DESIGN: Exploratory descriptive qualitative. SETTING: This study was conducted in the greater Auckland area. PARTICIPANTS: A total of 17 participants were recruited using purposive sampling to ensure a diverse range of perspectives across varying levels of teaching experience, disciplinary backgrounds, and exposure to genomic content. METHODS: Data were collected using semi-structured focus group interviews, a method well-suited for generating in-depth discussion and facilitating interaction among participants with shared professional interests. The collected data were analysed using thematic analysis methods. RESULTS: The findings offer insight into the preparedness of New Zealand's nursing workforce to engage with genomic-informed healthcare and inform strategies for integrating genomics into nursing curricula and continuing professional development. Given the interdisciplinary nature of genomic healthcare, these insights may also be relevant to other health professionals-including midwives, pharmacists, and allied health practitioners-who increasingly encounter genomic information in clinical practice and require foundational competencies to support patient care. CONCLUSION: Addressing this educational gap is critical to ensuring that nurses-key facilitators of patient care and public health-are equipped to deliver safe, equitable, and evidence-based genomic healthcare.

Humans

Assessing the Concurrent Validity of the Australian Treatment Outcomes Profile in a Methamphetamine Dependent Treatment-Seeking Population.

INTRODUCTION: The Australian Treatment Outcomes Profile (ATOP) is a brief clinical tool assessing substance use, health and well-being used in Australian alcohol and other drug treatment services. It is validated for use with clients using alcohol, opioids and cannabis, but not yet for clients who primarily use methamphetamine. METHODS: An embedded validation study was undertaken in treatment-seeking adults enrolled in a randomised double-blind placebo-controlled trial of lisdexamfetamine for methamphetamine dependence with sites in New South Wales, South Australia and Victoria. Participant demographics were collected during study screening. The ATOP and comparators (Time Line Follow Back, Opiate Treatment Index, Depression Anxiety Stress Scale, WHOQOL-BREF and Personal Wellbeing Index) were collected at baseline. Continuous ATOP items were analysed using Pearson's correlation coefficient, and dichotomous items were analysed using Fleiss's &#x3ba;. Agreement was rated as strong where measures were &#x2265;&#x2009;0.50, moderate where agreement was 0.30-0.49, and weak where <&#x2009;0.30. RESULTS: One hundred and eighteen study participants (2018-2020) had data for concurrent validity analysis. Strong validity was demonstrated for physical health, psychological health, quality of life, injecting drug use and crime items, and for days of use for amphetamines, alcohol, cannabis and cocaine. There was weak validity for days of use for benzodiazepines. Heroin use days and other opioid use days were endorsed by fewer than five participants and were therefore unable to be assessed. DISCUSSION AND CONCLUSIONS: The ATOP is valid for use in a treatment-seeking methamphetamine-dependent population, expanding the range of tools for assessment and standardised outcome monitoring across different settings and services.

Humans

Exploring Professional Experiences in Caring for Vulnerable Migrants in an Italian Rural Reception Centre: A Qualitative Study Using Multidimensional Textual Analysis-Professional Experiences in Rural Migrant Care.

AIM: This study aims to explore the experiences, strengths, challenges, and potential improvements for professionals in managing the complex needs of vulnerable migrants (VM) in an Italian rural reception centre. METHODS: A qualitative study using semi-structured interviews was conducted in April 2024. Data were analysed using the Automatic Analysis of Textual Data, based on Fraire's seven-step model for Exploratory Multidimensional Data Analysis. DATA SOURCES: Data were collected from 16 professionals working in a rural reception centre in southern Italy. Interviews were conducted and analysed using AATD in April 2024. FINDINGS: The analysis identified two main dimensions of professionals' roles: balancing systemic responsibilities with personal engagement and managing immediate needs versus long-term integration goals. Professionals face significant challenges, such as resource scarcity, bureaucratic inefficiencies, and emotional fatigue, which impact their well-being and the quality of care provided to migrants. Resilience, adaptability, and multidisciplinary collaboration were identified as key strengths. CONCLUSION: The study highlights the dual nature of professionals' work in reception centres, requiring them to balance operational tasks with emotional involvement in migrant care. Targeted interventions and systemic reforms are necessary to support professionals and enhance the quality of care for vulnerable migrants, particularly in resource-constrained rural settings. IMPLICATIONS FOR PRACTICE AND/OR PATIENT CARE: This study underscores the importance of providing targeted support to professionals working in reception centres, including training in intercultural competence, stress management, and coping strategies. Policies should address systemic challenges and provide resources to enhance healthcare delivery and social integration programs. REPORTING METHOD: This study adhered to the EQUATOR guidelines for reporting qualitative research (COREQ). The findings were reported in compliance with these guidelines, ensuring methodological rigour and transparency. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This study highlights the critical need for targeted support and training for professionals working in reception centres, particularly in rural settings. To improve care for vulnerable migrants, professionals should receive training in intercultural competence, stress management, and coping strategies to better navigate the complex challenges they face. Furthermore, systemic changes are necessary to alleviate the pressures on reception centres, such as streamlining bureaucratic processes and enhancing healthcare infrastructure, particularly in rural areas where resources are limited. By addressing these needs, we can improve the well-being of both the professionals and the migrants they serve, fostering more effective support systems and better care outcomes. Additionally, fostering multidisciplinary collaboration and community engagement can contribute to more comprehensive and sustainable care models. PROTOCOL REGISTRATION: The Ethics Committee of the University of Rome Tor Vergata approved this study on 07/07/2021 (protocol registration number 160.21).

Humans

Compliance With Ecological Momentary Assessment Among Patients With Cancer: Systematic Review and Meta-Analysis.

BACKGROUND: Patients with cancer often experience substantial fluctuations in psychological states during disease management. Traditional research tools are limited in capturing these dynamic changes in real time, constraining clinicians' understanding of patients' true conditions. Ecological momentary assessment (EMA) enables high-frequency, real-time data collection, providing patient-reported data with greater ecological validity. However, the effectiveness of EMA studies critically depends on patient compliance, and reported compliance rates vary widely, with a lack of systematic quantitative synthesis. OBJECTIVE: This study aims to systematically review and quantitatively analyze compliance with EMA among patients with cancer, and to examine whether EMA design characteristics were associated with compliance. METHODS: Web of Science, PubMed, Embase, Cochrane Library, CINAHL, PsycINFO, CNKI, and Wanfang databases were searched for literature published up to April 30, 2026. Compliance was defined as completed prompts divided by delivered prompts. Single-group proportions were pooled using logit transformation and random-effects models with the Hartung-Knapp-Sidik-Jonkman adjustment. Prediction intervals were calculated to describe the expected distribution of compliance in future comparable settings. Subgroup analyses, univariable meta-regressions, leave-one-out sensitivity analyses, and tests for small-study effects were performed. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data, methodological reporting quality was assessed using a modified Checklist for Reporting EMA Studies, and certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Twenty-three studies involving 13,565 participants were included. The pooled compliance rate was 78.55% (95% CI 73.48%-82.87%), with a prediction interval of 48.59%-93.41%. Subgroup analyses identified no robust differences across study characteristics. Although study length showed a statistically significant subgroup test, the result was not stable after excluding singleton categories. Meta-regression analyses similarly found no significant linear associations for study length, prompts per day, items per prompt, or assessment window. Leave-one-out analyses showed that no single study drove the pooled estimate. Regarding the risk of bias, 2 studies were judged as low, while 21 were judged as moderate risk. Quality scores ranged from 6.5 to 9.0, and the certainty of evidence for the pooled compliance rate was rated as very low according to the Grading of Recommendations Assessment, Development, and Evaluation approach. CONCLUSIONS: Overall compliance with EMA among patients with cancer was moderate to high, suggesting that repeated real-world assessment may be feasible in oncology research settings. Nevertheless, the very high heterogeneity, wide prediction interval, and very low certainty of evidence indicate that compliance is context-dependent. The pooled estimate should therefore be interpreted as an approximate benchmark rather than a universal expected rate. Future oncology EMA studies should use standardized compliance denominators, report missing prompts transparently, and prospectively evaluate patient-centered design strategies that reduce burden while preserving data quality.

Humans

Hypoxaemia and mortality in children with lower respiratory infection in low-income and middle-income countries: systematic review and meta-analysis.

BACKGROUND: Hypoxaemic lower respiratory infections (LRIs) are a leading cause of childhood mortality, with the highest burden in low-income and middle-income countries (LMICs). Hypoxaemia-low peripheral capillary oxyhaemoglobin saturation (SpO2)-is a marker of severity, and WHO recommends hospitalisation and oxygen administration for patients with SpO2 <90%. We aimed to update estimates from a 2015 systematic review and meta-analysis examining the association between hypoxaemia and mortality among children with LRIs in LMICs by incorporating studies published over the subsequent decade and evaluating mortality risk across multiple SpO2 thresholds. METHODS: We conducted a systematic review with meta-analysis by searching PubMed, Embase, LILACS, Global Index Medicus, Web of Science, and Scopus for peer-reviewed studies published between Jan 1, 2015, and June 18, 2025, with combined terms related to pneumonia, children, mortality, and LMICs. We also included selected earlier studies through citation checking. Eligible studies reported associations between hypoxaemia and mortality in children younger than 5 years with LRIs in LMICs. We excluded case reports and case series with fewer than five deaths, studies focused exclusively on the neonatal period, and those limited to children with specific comorbidities or to postoperative patients, for consistency with the original review. Two reviewers independently screened studies, extracted data, and assessed quality. Eligible studies were combined with those from the original review and analysed using random-effects models to estimate odds ratios (ORs) by hypoxaemia threshold subgroup. The protocol was registered on PROSPERO (CRD42023433946). FINDINGS: We identified 7734 records; 26 new studies met inclusion criteria and were combined with 18 from the original review. The 44 studies were published between 1993 and 2024 and were primarily from Africa (25 [57%] of 44) or Asia (19 [43%]); some studies spanned multiple locations. Data from 33 studies including 155&#x2009;633 participants were included in the primary meta-analysis. Hypoxaemia of any threshold was associated with higher odds of LRI mortality (OR 4&#xb7;36 [95% CI 3&#xb7;52-5&#xb7;39]) compared with no hypoxaemia. For SpO2 <90% versus 90-100%, OR for death was 4&#xb7;75 (95% CI 3&#xb7;42-6&#xb7;58). For SpO2 90-94% versus 95-100%, mortality risk was more than twice as high (OR 2&#xb7;27 [95% CI 1&#xb7;22-4&#xb7;25]). Heterogeneity was substantial (I2 64-85% across analyses), and eight (24%) of 33 studies in the primary meta-analysis had a high overall risk of bias; however, a sensitivity analysis restricted to studies with low or moderate risk of bias yielded similar results. INTERPRETATION: SpO2 <90% strongly predicts mortality in children with LRIs in LMICs. Children with SpO2 90-94% also have elevated risk, suggesting that paediatric LRI and pneumonia treatment algorithms should consider management at this hypoxaemia threshold. FUNDING: None.

Journal Article

Micro- and nanoplastics-induced neurotoxicity: a CNS-centered, evidence-graded adverse outcome pathway framework based on systematic weight-of-evidence assessment.

Micro- and nanoplastics (MPs/NPs) are ubiquitous anthropogenic particulate pollutants posing emerging threats to human neurological health. Severe heterogeneity in particle physicochemical properties, environmental aging status, exposure paradigms and experimental platforms has created persistent mechanistic uncertainties in MP/NP neurotoxicology, hindering reliable hazard characterization and risk translation. Here, we systematically consolidate empirical toxicological evidence and construct a dedicated central nervous system (CNS)-targeted adverse outcome pathway (AOP) network integrated with rigorous weight-of-evidence (WoE) grading to elucidate the hierarchical, particle-specific toxic cascades underlying MP/NP-induced neural injury. Our synthesis overturns the conventional linear toxicity paradigm, demonstrating that MPs/NPs trigger neurotoxicity via a complex multi-input mechanistic network. We definitively establish oxidative stress as a robust early convergent key event-rather than a universal molecular initiating event-orchestrating ROS overproduction, lipid peroxidation, mitochondrial dysfunction, and neuroinflammation to propagate neuronal damage. This core module is driven by five distinct particulate upstream triggers: particle-biomolecule interfacial perturbation, corona-facilitated cellular internalization, plastic-associated chemical leaching, aging-derived free radical reactivity, and gut-borne systemic neurotoxic signaling. Downstream pathogenic outcomes encompass glial overactivation, neurotransmitter dyshomeostasis, autophagy-lysosome dysfunction, metabolic reprogramming, regulated neuronal cell death, and behavioral impairments. Tiered WoE analysis confirms strong validation for early oxidative/inflammatory cascades, moderate support for gut-brain axis crosstalk and intracellular trafficking disruption, and nascent evidence for synaptic dysfunction and neurodegeneration-linked proteostatic defects. Extrapolation to human health risk remains constrained by the frequent use of high-dose exposure paradigms, limited validated data on internal dosimetry in the human brain, discrepancies between effective concentrations in experimental models and environmentally relevant human tissue burdens, and insufficient causal validation of distal adverse outcomes. We highlight key research priorities including aged mixed-particle exposure systems, leachate-controlled assays, quantitative internal dose evaluation, and mechanistic intervention verification. This evidence-stratified AOP framework resolves longstanding mechanistic ambiguities in particulate neurotoxicity, providing a standardized, causality-based foundation for future mechanistic exploration and health risk assessment of global plastic pollution.

Adverse outcome pathway

Rotavirus vaccine effectiveness against rotavirus and acute gastroenteritis mortality: an analysis of pooled case-control studies from the MNSSTER-V dataset.

BACKGROUND: Rotavirus accounts for an estimated 25% of diarrhoea deaths in children under 5 years globally, and more than 140 countries have included rotavirus vaccines in their routine national infant vaccination programmes. We aimed to calculate rotavirus vaccine effectiveness against rotavirus-positive and all-cause acute gastroenteritis deaths. METHODS: The Multi-National Subpopulations Study to Evaluate Rotavirus Vaccines (MNSSTER-V) dataset combines child-level data from test-negative case-control studies of rotavirus vaccine effectiveness that enrolled children under 5 years of age seeking care for acute gastroenteritis at hospitals or emergency departments in 24 countries between July 1, 2007, and Aug 24, 2023. Children were included in this study if they were: younger than 5 years, met the acute gastroenteritis case definition (had at least three episodes of diarrhoea in a 24-h period, had non-bloody and non-chronic diarrhoea, and were enrolled within 7 days of diarrhoea onset), met vaccine card quality metrics, had vaccine delivery dates if the child was reported to have received a rotavirus vaccine, and had a reported outcome of death or discharge. In-hospital acute gastroenteritis deaths were characterised, and rotavirus vaccine effectiveness against all-cause and rotavirus-positive acute gastroenteritis mortality was calculated using an unconditional logistic regression model with adjustment for national under-5 mortality strata and child's age. Vaccine effectiveness analyses against all-cause and rotavirus-positive acute gastroenteritis mortality were restricted to children aged at least 3 months who received any routine vaccines from countries reporting at least one acute gastroenteritis death. FINDINGS: From the MNSSTER-V dataset, we included 27&#x2008;252 children younger than 5 years enrolled from 22 countries; outcomes of patients were not available for two countries. At least one in-hospital acute gastroenteritis death was reported from 16 countries including 21&#x2008;522 children; in total, 183 all-cause acute gastroenteritis deaths and 25 rotavirus-positive deaths were reported. Among children aged at least 3 months who had received any routine vaccines, receiving at least one dose of a rotavirus vaccine had an adjusted vaccine effectiveness of 75&#xb7;8% (95% CI 28&#xb7;4 to 91&#xb7;8; n=13&#x2008;630) against rotavirus-positive acute gastroenteritis mortality and 20&#xb7;8% (-47&#xb7;0 to 57&#xb7;3; n=20&#x2008;005) against all-cause acute gastroenteritis mortality. INTERPRETATION: Rotavirus vaccines are effective in preventing rotavirus-positive acute gastroenteritis mortality. Continued efforts to improve vaccine delivery could help to reduce acute gastroenteritis mortality due to rotavirus worldwide. FUNDING: None.

Humans

A pragmatic randomized controlled trial of self-directed online writing interventions for posttraumatic stress symptoms in a real-world digital setting.

Background: Public health and other large-scale crises, such as the COVID-19 pandemic, have intensified the global mental health burden, creating unprecedented demand for accessible interventions for posttraumatic stress symptoms (PTSS).Objective: We evaluated the feasibility and effectiveness of two self-directed online writing interventions embedded within China's WeChat ecosystem during the COVID-19 pandemic through a pragmatic randomised controlled trial.Methods: Between December 2021 and August 2022, 1,526 adults were screened for PTSS via a Tencent Medinfo Mini-Program. Eligible participants (n&#x2009;=&#x2009;211) were randomised to Guided Narrative Technique-Writing (GNT-W, n&#x2009;=&#x2009;100) or Expressive Writing (EW, n&#x2009;=&#x2009;111). Both interventions comprised three self-directed daily writing sessions delivered entirely online without human support. Primary outcome was PTSD symptom severity (PTSD Checklist-Short), assessed at baseline, post-intervention, 2-week, and 1-month follow-ups.Results: While initial engagement followed typical digital health patterns (64.5% overall attrition), participants who initiated treatment showed strong adherence (77% completion). Both interventions were associated with significant within-group reductions in PTSS severity (GNT-W: b&#x2009;=&#x2009;-0.43, p&#x2009;=&#x2009;.023, d&#x2009;=&#x2009;-0.43; EW: b&#x2009;=&#x2009;-0.60, p&#x2009;=&#x2009;.001, d&#x2009;=&#x2009;-0.58), with no significant between-group difference (group &#xd7; time: b&#x2009;=&#x2009;0.18, p&#x2009;=&#x2009;.48). GNT-W did not confer additional benefit over EW protocol on PTSS severity.Conclusions: Both self-directed writing interventions were associated with within-group reductions in PTSS; without an inactive control condition, however, these changes cannot be firmly attributed to the interventions. GNT-W showed no advantage over the simpler EW protocol. These findings offer preliminary support for embedding scalable, low-barrier writing interventions in widely used digital platforms.Chinese Clinical Trial Registry: ChiCTR2000034836.

Humans

Risk of mortality and complications in people with depressive disorder and co-occurring diabetes mellitus: a systematic review and meta-analysis.

AIMS: People with depressive disorder have increased premature mortality and higher rates of diabetes mellitus than general population. Evidence shows that diabetes may further increase their risk of premature death from diabetes-related complications, especially cardiovascular diseases (CVDs). Earlier studies examining depression-associated outcomes in diabetes patients have shown mixed results and were hindered by important limitations, especially the use of self-reported questionnaires to ascertain depression, causing misclassification bias by identifying subclinical symptoms or diabetes distress. Associations of depression with specific diabetes complications have not been systematically evaluated. This meta-analysis aimed to investigate the risk of mortality and complications among patients with depression and co-occurring diabetes (depression-diabetes group) relative to patients with diabetes-only (diabetes-only group), on their all-cause mortality rates, and if applicable cause-specific mortality rates, and occurrence of specific diabetes complications. METHODS: We systematically reviewed and quantitatively synthesized diabetes-related outcomes in patients with depression by searching Embase, MEDLINE, PsycInfo and Web-of-Science from inception to 20&#xa0;December 2024, and included studies that examined mortality and complication outcomes in depression-diabetes group relative to diabetes-only group. Results were synthesized by random-effects meta-analytic models, with stratified-analyses (subgroup analyses and meta-regression) by study-level characteristics, including age, gender, study period, geographic region, follow-up duration and nature of diabetes sample. The study was registered with PROSPERO (CRD42024595145). RESULTS: Twenty-six studies were identified from nine geographic regions. Regarding mortality risk, depression-diabetes group exhibited increased risks of all-cause mortality (RR&#xa0;=&#xa0;1.30 [95% CI: 1.21-1.39]) and CVD-specific mortality (1.15 [1.02-1.29]) relative to diabetes-only group. Regarding complication risk, depression-diabetes group showed increased risk of complications (1.28 [1.18-1.40]) relative to diabetes-only group, especially in incident-diabetes sample signifying advanced disease stage upon presentation, with stratified-analyses showing higher risk of metabolic complications (1.63 [1.33-1.99]) and cardiovascular complications (1.20 [1.11-1.29]), and lower likelihood of retinopathy (0.84 [0.76-0.94]), albeit comparable rates of cerebrovascular complications (1.36 [0.99-1.87]), nephropathy (1.09 [0.93-1.27]) and peripheral-vascular complications (0.97 [0.79-1.18]). Both overall mortality and complication risks were present in various regions and persisted over time. Heterogeneities were noted and could not be entirely explained by stratified analyses. CONCLUSIONS: Our study demonstrated that patients with depression and co-occurring diabetes were associated with elevated overall mortality risk and complication risk (particularly metabolic and cardiovascular-complications) than non-depressed counterparts, suggesting an overall poorer glycemic control that might eventually drive their earlier death. Comprehensive and multipronged interventions are needed for individualized risk estimation of diabetes-related outcomes, with consequent early interventions to minimize the avoidable physical morbidity and premature mortality in this vulnerable population.

Humans

Biological mechanisms of atropine in myopia control (Review).

Myopia is now recognized as a progressive, potentially sight&#x2011;threatening disease rather than just a refractive error, with its prevalence rising rapidly worldwide due to its high occurrence, major vision losses and huge public health cost. The World Health Organization estimates that 2.6 billion individuals in the world were myopic in 2020 this figure is projected to increase to 3.364 billion by 2030. Although myopia may be better controlled in its early stages, it may not be completely reversed at this time. Of all of the methods for controlling myopia, atropine, a muscarinic receptor antagonist, remains an effective pharmacological option for slowing myopia progression in children. However, the mechanisms of action of atropine remain to be fully elucidated. This review provided a systematic review for myopia epidemiology, pathogenesis, the effects and side effects, as well as up&#x2011;to&#x2011;date possible mechanisms, in the hope of facilitating that researchers in this field elucidate its underlying mechanisms so that clinical ophthalmologists may be able to better control this disease.

Humans

Longitudinal comparison of treat-to-target states and clinical outcomes in patients with late-onset versus early-onset systemic lupus erythematosus.

OBJECTIVE: We compared demographic and clinical characteristics between patients with late-onset (LO) and early-onset (EO) systemic lupus erythematosus (SLE) and examined their longitudinal associations with treatment targets and long-term outcomes, irreversible organ damage accrual and health-related quality of life (HRQoL). METHODS: We analyzed prospectively collected data from patients enrolled in the Asia Pacific Lupus Collaboration cohort. Patients diagnosed with SLE at age >50 years were classified as LO-SLE and compared with those diagnosed at age &#x2264;50 years (EO-SLE). Longitudinal associations with treatment targets (LLDAS and DORIS remission), organ damage accrual (SLICC/ACR Damage Index), and HRQoL (SF36v2 physical and mental component summary (PCS and MCS) scores) were examined using multivariable multilevel logistic, recurrent-event survival, and linear mixed-effects models, respectively. Disease activity, flares, medication exposure, and other clinical characteristics were also compared between groups. RESULTS: Among 3,917 patients studied, 346 (8.8%) had LO-SLE. Compared with EO-SLE, patients with LO-SLE had lower disease activity, lower glucocorticoid and immunosuppressant exposure, and higher attainment of treatment targets; LO-SLE was associated with higher odds of attaining LLDAS (OR: 2.33 (1.66, 3.28)) and DORIS remission (OR: 2.22 (1.45, 3.38)). However, they were at a greater risk of damage accrual (HR:1.82 (1.50, 2.21)) and lower PCS scores, meaning poorer physical health (regression coefficient (RC) = -3.63 (-4.58, -2.68)) but not MCS (RC= 0.68 (-.50, 1.86)). CONCLUSION: Despite higher attainment of treatment targets, patients with LO-SLE experienced greater damage accrual and poorer physical health, suggesting that disease activity targets alone may not fully capture outcome risk in LO-SLE.

Journal Article

CanDo (Canadian Donor Milk) randomised controlled trial: pasteurised human donor milk supplementation in the well-baby unit - protocol.

INTRODUCTION: Mother's milk is the gold standard for feeding newborns. Despite lactation support while in hospital, supplementation rates remain high in Canadian well-baby units at 35-50%. When supplementation is needed, the choice between formula milk and pasteurised human donor milk (donor milk) remains uncertain with a lack of clinical trials to inform this practice. This study aims to compare the effect of supplementing mother's milk with donor milk versus formula in infants at higher risk for supplementation (infants of diabetic mothers, infants born small for gestational age or with a birth weight less than 2.5&#x2009;kg and late preterm infants born between 350/7 and 366/7 weeks gestation). METHODS AND ANALYSIS: This is an ongoing, open-label, single-centre, randomised controlled trial conducted at Mount Sinai Hospital, Toronto, Canada. A total of 112 infants (56 per group) will be randomised to receive donor milk or infant formula as a supplement to mother's milk during their initial hospital stay, when supplementation is deemed necessary by the family and/or healthcare team. The primary outcome is exclusive human milk feeding at 4 months of age. Secondary outcomes include any or exclusive human milk feeding at 1, 2 and 3 months; infant growth and health indicators and breastfeeding self-efficacy. Exploratory outcomes encompass infant temperament; parental mental health (assessed using the State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale); milk cortisol concentrations; and informal milk sharing comparing donor milk and formula supplementation. Follow-up includes monthly telephone assessments and a virtual or in-person visit at 4 months post partum. Data will be analysed using intention-to-treat principles. ETHICS AND DISSEMINATION: The CanDo trial has received ethics approval from the Mount Sinai Hospital Research Ethics Board and the University of Toronto. Results will be disseminated through peer-reviewed journals, conference presentations and stakeholder engagement with hospital and public health decision-makers. Findings will address a critical evidence gap regarding the use of donor milk supplementation in well-baby units and may inform future clinical practice and policy in newborn feeding. TRIAL REGISTRATION NUMBER: NCT06315127.

Humans

Feeding the disease: The impact of nutritional supplementation on Nosema (Vairimorpha) infection in honey bees (Apis mellifera).

Honey bees (Apis mellifera) experience variable colony losses across regions and years, with infectious diseases representing a key component of colony health challenges. Among the most prevalent pathogens are the microsporidian parasites Nosema apis and Nosema ceranae, whose impacts on host survival and transmission vary widely depending on context. While nutritional supplementation is commonly used to support honey bee health, its effects on Nosema infection outcomes remain unclear. Here, we experimentally tested whether dietary enrichment alters survival and infection intensity following exposure to a mixed Nosema inoculum. Newly emerged worker bees were challenged with Nosema spores and maintained on either a basic sucrose diet or the same diet supplemented with a commercial pollen substitute. Dietary enrichment significantly increased both mortality risk and infection intensity in Nosema-infected bees, while having no detectable effect on survival in uninfected controls. These results indicate that supplementation can, counter intuitively, exacerbate nosemosis by promoting parasite replication rather than enhancing host resistance. Our findings highlight the importance of distinguishing nutritional effects on host tolerance versus resistance, and caution that interventions intended to improve bee nutrition may inadvertently increase pathogen production and transmission potential under certain conditions.

Animals

Integrated Telehealth Rehabilitation and Quality of Life in Mechanically Ventilated Adults: A Randomized Clinical Trial.

IMPORTANCE: Whether integrated rehabilitation strategies spanning intensive care unit (ICU), hospital, and postdischarge phases improve quality of life after acute respiratory failure is uncertain. OBJECTIVE: To evaluate the effect of an integrated multicomponent telehealth-based rehabilitation intervention on health-related quality of life at 90 days after hospital discharge among adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation. DESIGN, SETTING, AND PARTICIPANTS: This stepped-wedge cluster randomized clinical trial in ICUs of 20 public hospitals in Brazil enrolled adults with acute hypoxemic respiratory failure requiring invasive mechanical ventilation between June 2024 and May 2025, with follow-up through September 2025. INTERVENTIONS: A multicomponent telehealth-based rehabilitation program integrating an ICU telehealth-based rehabilitation intervention focused on ventilator liberation; a ward telehealth-based rehabilitation intervention targeting risk stratification and initiation of individualized rehabilitation plans; and a postdischarge telehealth-based rehabilitation intervention consisting of a 2-month personalized centralized telerehabilitation program. MAIN OUTCOMES AND MEASURES: Health-related quality of life at 90 days after hospital discharge, measured using the EuroQol 5-Dimension 3-Level (EQ-5D-3L) utility score (range, -0.17 [worse than death] to 1 [best health state], with 0 representing death). RESULTS: Among 1916 enrolled patients (mean [SD] age, 60.6 [17.3] years; 43.6% female), 1063 were assigned to the intervention and 853 to usual care per local protocols. At 90 days after hospital discharge, mean (SD) EQ-5D-3L utility scores were higher in the intervention group than in the usual care group (0.16 [0.31] vs 0.12 [0.28]; adjusted difference, 0.049; 95% CI, 0.0002 to 0.098; P&#x2009;=&#x2009;.04) but did not differ among survivors (0.60 [0.32] vs 0.59 [0.32]; adjusted difference, -0.045; 95% CI, -0.138 to 0.045; P&#x2009;=&#x2009;.34). Compared with usual care, the intervention resulted in lower 90-day all-cause mortality (71.8% [676 of 941] vs 78.3% [584 of 746]; adjusted difference, -7.6%; 95% CI, -14.7% to -0.6%; P&#x2009;=&#x2009;.03) and shorter mean (SD) mechanical ventilation duration (9.9 [10.3] vs 15.5 [15.9] days; adjusted difference, -6.2 days; 95% CI, -8.5 to -3.9; P&#x2009;<&#x2009;.001). CONCLUSIONS AND RELEVANCE: In this study, an integrated telehealth-based rehabilitation strategy delivered across ICU, hospital, and postdischarge phases improved 90-day health-related quality of life, potentially influenced by reduced mortality. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06343545.

Humans

Are there any common effects in preclinical models of micro- and nanoplastic (MNP) exposure? A systematic review.

Micro- and nanoplastics (MNPs) are emerging contaminants detected in food sources and the marine food chain, raising concerns about human health. Although no causal relationship has been established between MNP exposure and specific diseases, growing evidence suggests adverse developmental, behavioral, cognitive and biochemical effects. This systematic review synthesized evidence from common preclinical neurotoxicology models, including C. elegans, D. rerio, D. melanogaster, in vitro systems and rodents, to identify convergent developmental, behavioral and biochemical outcomes. The protocol was preregistered in OSF, followed PRISMA-P guidelines, applied PICOS criteria, and assessed methodological quality using the European Commission's ToxRTool. Overall, 185 studies were included. Consistent findings showed impaired survival and disrupted development across all models. Behavioral alterations affecting anxiety, memory, learning, sociability and locomotor activity were also consistently reported. In addition, numerous studies identified disruptions in the serotonergic (5-HT) system, including changes in neurotransmitter levels, transporters and metabolic enzymes. Despite methodological heterogeneity, these findings indicate that MNP exposure produces reproducible neurodevelopmental and neurochemical alterations across experimental models. Future studies should improve methodological harmonization, strengthen cross-model comparability and identify robust biomarkers and key mechanisms underlying MNP-induced neurotoxicity, facilitating translation to human health risk assessment frameworks.

Animals