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PubMed2026

Peripheral immune markers and choroid plexus volumes as predictors of change in depressive symptoms: Insights from the EMBARC study.

Changes in choroid plexus (ChP) volume and peripheral inflammation have been associated with Major Depressive Disorder (MDD), yet their individual and combined impact on depressive symptoms is unclear. This study investigated whether baseline immune markers and ChP volumes predict changes in depressive symptoms during the 8-week treatment period among Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study participants who received either sertraline or placebo. Adults (n = 222) with MDD with peripheral blood samples were included. Circulating chemokines and cytokines were examined using a 40-plex assay. Depressive symptoms were assessed over 8 weeks using the Hamilton Depression Rating Scale (HAMD-17). Principal component analysis (PCA) was used for dimension reduction. Mixed-effects models were used to examine whether immune profiles and ChP volumes, and their interaction predicted HAMD-17, adjusting for demographic/clinical covariates and baseline depression severity. PCA identified three immune profiles. One profile, characterized by higher levels of cytokines and chemokines including IL-6, TNF-α, and IL-1β, was associated with greater depression severity, higher BMI, age, and CRP at baseline. Higher levels of these immune markers were associated with less improvement in depressive symptoms at 8 weeks (estimate = 1.211, p = 0.018) in models adjusting for right and left ChP volume (right ChP model: estimate = 1.034, p = 0.005; left ChP model: estimate = 0.993, p = 0.007). Interactions between immune markers and ChP volumes were not significant. Future investigations are warranted to examine the relationships between immune markers and ChP volume beyond structural changes in the context of depression symptoms.

Adult↗

PubMed2026

Female genital mutilation knowledge, attitudes and training needs among health professionals in non-practicing countries: A literature review.

BACKGROUND: With increasing globalization and migration, the number of women affected by female genital mutilation who reside in countries where the practice is not traditionally performed is constantly increasing. Healthcare providers in these settings are required to address the complex health needs of this vulnerable population. We aimed to synthesize recent literature on their knowledge, preparedness, and educational background. METHODS: We conducted a systematic review across PubMed, Scopus and Embase, identifying papers published from January 2015 onwards, examining providers' knowledge, education and attitudes toward female genital mutilation in non-practicing countries. Both quantitative and qualitative observational studies were eligible. Given heterogeneity in study populations, outcome definitions, and assessment tools, findings were synthesized narratively. The review protocol was registered with the International Prospective Register of Systematic Reviews (CRD420251044761). FINDINGS: 1046 records were screened by title and abstract, and 140 full-text articles were assessed for eligibility. 31 studies met the inclusion criteria (23 quantitative, 8 qualitative). Many providers reported clinical experience with women affected by female genital mutilation, yet substantial variability was observed in knowledge, training, and attitudes. Gaps were particularly evident regarding legislation, World Health Organization classification, clinical guidelines, referral pathways, workplace protocols. Midwives and younger professionals tended to demonstrate higher knowledge levels. Training exposure ranged from 5% to 91%, and many participants perceived it as insufficient. Qualitative findings echoed these patterns, highlighting challenges in female genital mutilation classification, legal awareness, documentation systems, the impact of providers' cultural beliefs on care delivery. CONCLUSION: Considerable efforts are needed to equip healthcare providers to deliver high-quality, culturally competent care to women affected by female genital mutilation. Research should develop validated tools to assess preparedness, adopt mixed-methods strategies to capture patient and provider perspectives, and guide standardized, up-to-date training programs, strengthening knowledge in managing female genital mutilation.

Humans↗

PubMed2026

Potential Links Between Physiological and Perceptual Strain in High Heat Stress.

The physiological strain index (PhSI) is widely used to quantify thermoregulatory and cardiovascular strain during heat stress. However, direct physiological measurements may not always be feasible in occupational or athletic settings. Therefore, this study aimed to examine the relationship and agreement between perceptual strain and integrated physiological strain indices during high heat stress. Ten healthy, physically active, non-heat-acclimated males (29 (7) yr; 1.79 (0.11) m; 77.4 (9.3) kg) completed two randomized crossover exercise trials in hot-dry (HD) and warm-humid (WH) environments with equivalent wet-bulb globe temperatures. Heart rate, rectal temperature, skin temperature, rating of perceived exertion, and thermal sensation were measured at baseline and every 15 minutes during 60 minutes of cycling. Physiological strain index (PhSI), adaptive physiological strain index (aPhSI), and perceptual strain index (PeSI) were calculated using validated equations. Repeated-measures correlation analyses demonstrated very strong associations between PeSI and both PhSI and aPhSI under HD (Rrm = 0.940-0.943) and WH (Rrm = 0.980-0.982; all p < 0.001). Receiver operating characteristic analyses demonstrated good-to-excellent discrimination of physiological strain by PeSI (AUC = 0.895-0.969). Mixed-effects analyses showed that higher PeSI values were associated with increased PhSI (β = 1.325, p < 0.001) and aPhSI (β = 1.459, p < 0.001). However, Bland-Altman analyses demonstrated relatively small mean biases (0.4-0.9 AU) but wide limits of agreement (-2.8 to 4.2 AU), indicating that PeSI and physiological strain indices are not interchangeable. These findings suggest that PeSI may serve as a practical adjunctive or screening indicator of physiological strain when direct physiological measurements are unavailable.

Humans↗

PubMed2026

Cross-kingdom dynamics of the subgingival bacteriome and mycobiome: A pilot study on the effects of a novel HA-H₂O₂-Glycine formulation to treat periodontitis.

OBJECTIVES: Traditional periodontal therapy primarily focuses on bacterial biofilm control; however, recent evidence also suggests a critical role for the oral mycobiome. This study evaluated the clinical and ecological impact of a novel mouthwash formulation containing hyaluronic acid (HA), hydrogen peroxide (H2O2), and glycine on periodontal patients METHODS: This prospective, randomized split-mouth trial included 13 adult participants with periodontitis treated with HA-H2O2-glycine formula (BMG0703A) used twice a day for seven days. Subgingival plaque samples were collected from periodontal pocket and healthy control sites at baseline (T0) and one-week post-treatment (T1). Microbial and fungal communities were characterized using Next-Generation Sequencing (NGS) of the 16S rRNA and ITS2 regions. Linear Mixed Models (LMM) and Spearman correlation were used to assess taxonomic shifts and cross-kingdom relationships. RESULTS: Sequencing revealed a promising ecological shift: the bacteriome shifted from anaerobic dominance (Olsenella, Peptostreptococcus) toward a health-associated aerobic profile, with Rothia near-doubling (11.91% to 22.68%). The mycobiome underwent a "normalization" effect: Candida abundance decreased significantly (22.8% to 9.1%), while fungal Shannon diversity in pockets returned to healthy-site levels. Inter-kingdom analysis identified antagonistic relationships between expanding commensal bacteria and opportunistic fungi, suggesting that the intervention may help re-establish a protective bacterial niche. CONCLUSIONS: The HA-H2O2-glycine formulation seems to facilitate a rapid, cross-kingdom modulation of the subgingival niche. By reducing anaerobic pathogens and normalizing the mycobiome it appear to induce short-term changes, suggesting potential as adjunctive strategy in periodontal management. CLINICAL SIGNIFICANCE: The present work underlines the possible cross-Kingdom effects of a novel compound.

Humans↗

PubMed2026

Assessing the accuracy and efficiency of an electronic platform for managing childhood illnesses in rural China: A cluster randomized controlled trial.

OBJECTIVES: The Integrated Management of Childhood Illness (IMCI) faces challenges in capacity building and quality control. This trial aims to assess an electronic IMCI (eIMCI) platform in improving the effectiveness and efficiency in disease classification and management by community health workers (CHWs). DESIGN: Cluster randomized controlled trial. SETTING: Rural western China. PARTICIPANTS: 24 CHWs and 72 ill children aged 2 months to 5 years (3 children per CHW). CHWs were randomly assigned to intervention or control groups. INTERVENTIONS: The intervention CHWs received online training and performed disease management using the eIMCI platform featuring integrated training modules and decision-support tools. The control group received traditional face-to-face training and used paper-based IMCI protocols. MAIN OUTCOME MEASURES: Proportion of children correctly diagnosed or classified by CHWs, as determined by a pediatric specialist. Relative risk (RR) between groups was estimated using Poisson Generalized Linear Mixed Models incorporating a random intercept for CHW to account for clustering of children within individual CHWs and adjusting for key covariates at both the CHW and child levels. RESULTS: The intervention group (13 CHWs, 39 children) had a higher rate of correct classification (64.1%) compared to the control group (11 CHWs, 33 children) (39.4%, P = .056). Multivariable regression analysis confirmed this (RR = 2.1, 95% CI: 1.5-3.1; P < .001). No significant difference was found in correct treatment rates (38.5% vs. 27.3%, P = .316). Online training reduced time and costs by approximately 80%, though with a slight decrease in post-training evaluation scores. CONCLUSIONS: The eIMCI platform shows potential in enhancing IMCI implementation and significantly reducing the training burden in resource-limited settings. Trial registration: Chinese Clinical Trial Registry: ChiCTR2100042533, https://www.chictr.org.cn/showproj.html?proj=119995.

Humans↗

PubMed2026

Comparative evaluation of oxidative stress biomarkers F2-isoprostanes and 8-OHdG in Parkinson's disease and Type 2 Diabetes Mellitus: a systematic review and meta-analysis of human studies.

BACKGROUND: Oxidative stress is central to type 2 diabetes mellitus (T2DM) and Parkinson's disease (PD). However, the utility of biomarkers for lipid peroxidation (F2-isoprostanes) and DNA damage (8-OHdG) in the comorbidity of PD and T2DM remains unclear. METHODS: We conducted a systematic review and meta-analysis of 54 unique studies of human subjects aged ≥ 50 years (n = 7,521: 3,522 with T2DM, 722 with PD, and 3,277 controls), measuring biomarkers in serum, plasma, or leukocytes. Mixed-effects models quantified standardized differences (Hedges' g) across subgroups. RESULTS: In T2DM, F2-isoprostanes (g = 1.60, 95% CI: 0.95-2.25) and 8-OHdG (g = 2.64, 95% CI: 2.13-3.14) were markedly elevated (p < 0.001). Stronger effects were observed in younger cohorts and serum/plasma samples, with complications like nephropathy exhibiting extreme oxidative stress (g = 5.24). In PD, 8-OHdG was moderately elevated (g = 0.78, 95% CI: 0.18-1.39; p = 0.011), particularly in randomized controlled trials and plasma samples, whereas F2-isoprostanes were not significantly elevated (g = 0.47, 95% CI: -0.43-1.38). High heterogeneity in T2DM (I2 > 90%) reflected methodological variability. CONCLUSION: Distinct profiles - both markers elevated in T2DM but only 8-OHdG in PD - underscore 8-OHdG's potential in PD-T2DM comorbidity. Future research should focus on standardized assays, multi-compartmental or multi-modal sampling, and longitudinal studies to clarify mechanisms and therapeutic targets.

Humans↗

PubMed2026

Changes in sexual behavior among women in studies evaluating the dapivirine vaginal ring for HIV prevention.

BACKGROUND: Access to novel HIV prevention technologies often raise concerns of risk compensation. This analysis examined changes in the sexual behaviors of MTN 020/ASPIRE participants, a placebo controlled randomized control trial, who subsequently enrolled in MTN-025/HOPE, an open-label extension using the dapivirine vaginal ring. METHODS: Both studies enrolled healthy, sexually active, HIV-negative women from Malawi, South Africa, Uganda and Zimbabwe. Longitudinal data on participants' sexual behaviors, specifically sex with a nonprimary partner (past 3 months), and use of male or female condoms at the last vaginal sex act were compared between ASPIRE and HOPE. Conditional and mixed ordinal logistic regression models evaluated associations between study and sexual behaviors at enrollment, and quarterly over the first 12 months. RESULTS: Of the 2629 individuals enrolled in ASPIRE, 1456 (55%) participated in HOPE. At enrollment, the proportion of participants who reported sex with a nonprimary partner and condom use at last vaginal sex act did not differ by study. Across all quarterly follow-up visits, sex with a nonprimary partner was more common in HOPE (13.9-18.7%) than ASPIRE (10.7-12.6%); adjusted OR 1.47, 95% CI 1.24-1.75, P < 0.001. There was no difference in condom use at the last vaginal act across all quarterly follow-up visits between ASPIRE (36.5-42.7%) and HOPE (43.6-46.7%); adjusted OR 1.05, 95% CI 0.94-1.18. CONCLUSION: More women reported sex with nonprimary partners in HOPE, with little change in condom use over time between the two studies. Understanding behavior changes during PrEP use allows for tailored, holistic reproductive health programming.

Humans↗

PubMed2025

Effectiveness of physical activity intervention for depression, anxiety and comorbid symptoms during the perinatal period among Chinese primiparas.

BACKGROUND: To examine the effectiveness of a physical activity (PA) programme incorporating partner support and enjoyment in preventing perinatal depression, anxiety, and comorbid anxiety and depression (CAD) among Chinese primiparas. METHODS: A total of 120 eligible primiparas were randomised into intervention or control groups. The intervention group received the 13-week PA programme and the control group received the usual care. The outcomes were depression, anxiety, and CAD assessed at baseline, post-intervention, and 6 weeks after delivery. Differences were examined using generalised linear mixed models with intention-to-treat. RESULTS: A significant group × time interaction was observed for depression score, anxiety score, anxiety incidence, and CAD incidence (all p < 0.05). However, no significant interaction was found for depression incidence. Compared to the control, the intervention substantially reduced the scores of depression (MD: -2.67 (-4.16 to -1.17); -2.63 (-4.15 to -1.11)) and anxiety (MD: -4.95 (-9.23 to -0.67); -7.33 (-11.85 to -2.82)), as well as the rates of depression (OR: 0.40 (0.18 to 0.85); 0.44 (0.21 to 0.93)) and CAD (OR: 0.35 (0.14 to 0.87); 0.26 (0.11 to 0.62)) at post-intervention and 6-week postpartum. Notably, anxiety incidence showed significant reduction only at 6-week postpartum (OR: 0.34 (0.16 to 0.74)) (all p < 0.05). Within the intervention group, no significant changes occurred in most outcomes from baseline to post-intervention and 6-week postpartum, except depression scores (MD:-1.60 (-2.79 to -0.41); -1.23 (-2.44 to -0.03); p < 0.05). CONCLUSIONS: The PA programme (including partner support and enjoyment) may be effective in reducing perinatal depression, anxiety and CAD among primiparas.

Adult↗

PubMed2026

Cognitive-behavioral therapy for post COVID-19 condition: A pilot randomized controlled trial.

BACKGROUND: The post COVID-19 condition (PCC) is a disabling condition with urgent need for effective treatments. This pilot randomized controlled trial examined the feasibility and efficacy of a cognitive-behavioral therapy (CBT) for PCC in a parallel-group design. METHODS: N = 53 individuals with PCC were randomized to CBT (n = 27) or 16-week wait-list control (WLC) condition (n = 26). One participant allocated to WLC was excluded after randomization, resulting in an intention-to-treat (ITT) sample of N = 52 participants (CBT: n = 27, age: M = 48.59, SD = 11.52, 77.8% female; WLC: n = 25, Age: M = 48.44, SD = 9.81, 60% female). CBT comprised eight group and five individual sessions addressing cognitive and behavioral factors of symptom maintenance (treatment duration if completed: M = 14 weeks, SD = 1 week). Primary outcomes included fatigue (FSS), overall somatic symptom burden (PHQ-15), and respiratory and cardiovascular symptoms (SBQ™-LC "Breathing" and "Circulation"), assessed at pre-, post-assessment, and follow-up. RESULTS: Participants receiving CBT showed a significant medium-sized reduction in fatigue directly after treatment compared to the WLC condition (d = -0.58, p = .045), whereas the WLC group showed a significant increase in overall somatic symptoms (d = 0.60, p = .027). Results for respiratory symptoms were mixed, showing inconsistent patterns across analyses. Retrospectively assessed feasibility and treatment satisfaction were good, with few adverse effects reported. CONCLUSIONS: This pilot trial suggests the feasibility and preliminary efficacy of CBT for PCC. Larger RCTs with active control groups should confirm these findings.

Humans↗

PubMed2026

Association of hydroxyurea use and sickle cell retinopathy: A systematic review and meta-analysis.

Hydroxyurea (HU) is prescribed to reduce systemic complications of sickle cell disease; however, its association with sickle cell retinopathy (SCR) remains unclear. This meta-analysis (PROSPERO: CRD420251079006) evaluates the pooled association between HU use and SCR. In the primary analysis, HU use was not associated with a statistically significant reduction in SCR (OR = 0.90, 95% CI [0.41, 1.97], p = 0.79; I² = 77%). In a prespecified leave-one-out analysis, exclusion of the outlier study did not produce a statistically significant association, although the estimate shifted toward a stronger protective effect with reduced heterogeneity (OR = 0.70, 95% CI [0.39, 1.27], p = 0.25; I² = 67%). In a subgroup analysis excluding high-risk-of-bias studies, HU use was also not associated with a statistically significant reduction in SCR (OR = 0.84, 95% CI [0.39, 1.82], p = 0.66; I² = 77%). In post hoc analyses, HU use was not associated with a statistically significant reduction in SCR in non-adult populations (OR = 1.14, 95% CI [0.43, 3.05], p = 0.79; I² = 81%) or genotype-restricted analyses (OR = 1.22, 95% CI [0.81, 1.84], p = 0.35; I² = 0%). In post hoc analyses restricting studies to retinopathy phenotype, however, HU was associated with statistically significant lower odds of non-proliferative SCR (OR = 0.73, 95% CI [0.54, 0.98], p = 0.04; I² = 0%) and proliferative SCR (OR = 0.24, 95% CI [0.09, 0.60], p = 0.002; I² = 12%). Very low-certainty evidence suggests mixed associations between HU and SCR. Prospective studies are needed to clarify its role in SCR prevention.

Humans↗

PubMed2026

Co-Use of Some Substances Associated With Higher Doses in Adolescents: Findings From the Adolescent Brain Cognitive Development Study.

PURPOSE: Adolescence is a critical developmental period marked by heightened vulnerability to initiating substance use, with long-term implications for health and behavior. Nicotine, alcohol, and cannabis are the most commonly used substances among adolescents. Their use often co-occurs but few studies have described or quantified the patterns and doses of substance co-use in this vulnerable population. METHODS: We used data from six waves of the Adolescent Brain Cognitive Development study. Substance use was measured through a web-based timeline followback interview, and outcomes are operationalized into substance use quantity (in standard units), single use, and co-use (use of two substances on the same day) of alcohol, cannabis, and nicotine. Group differences of average dose in standard units between single use and co-use for each substance class were analyzed using linear mixed-effects modeling in years 4-6. RESULTS: The average dose of nicotine was significantly higher when co-used with alcohol (4.32; 95% confidence interval [CI]: 2.55-6.09; p < .001) or when co-used with cannabis (4.41; 95% CI: 2.76-6.05; p < .001) in year 6; nicotine trends were similar in years four and five. In year 6, the average dose of alcohol was higher when co-used with cannabis (1.87; 95% CI: 0.37-3.36; p = .004) or co-used with nicotine (1.64; 95% CI: 0.06-3.22; p = .03) compared to single use of alcohol. The average dose of cannabis was not significantly different when used singularly or co-used with either alcohol or nicotine in our study years. DISCUSSION: During adolescence, the co-use of substances (namely alcohol and nicotine) may lead to higher average doses compared to single-substance use.

Humans↗

PubMed2026

Discrimination, chronic stress, and multimorbidity in cohort of Black and Latina transgender women with HIV: Longitudinal findings from the LITE Plus study.

Black and Latina transgender women with HIV (BLTWH) are exposed to repeated, intersecting discrimination based on race, gender, and serostatus. Minority stress theory conceptualizes discrimination as minority-specific stressors that drive health inequities. Allostatic load theory posits a pathway between discrimination and chronic disease through multisystem physiological dysregulation caused by chronic stress. To test this pathway, a longitudinal cohort of 108 BLTWH, enrolled December 2020 - June 2022 in Boston, New York City, and Washington, DC, were followed for 24 months, with biomarkers measured at baseline, 12, and 24 months. Questionnaires administered every 6 months assessed anticipated discrimination, everyday discrimination, perceived stress, and other psychosocial factors. Multimorbidity was measured via self-reported non-HIV chronic conditions. In mixed-effects mediation models, allostatic load did not mediate relationships between multimorbidity outcomes and anticipated discrimination (β: -0.0004 [95% CI: -0.004, 0.003]) nor everyday discrimination (β: -0.002 [95%CI: -0.009, 0.003]). Perceived stress demonstrated indirect effects on multimorbidity in unadjusted models of anticipated discrimination (β: 0.024, [95% CI: 0.015, 0.081]) and everyday discrimination (β: 0.021 [95%CI: 0.016, 0.077]). Indirect effects remained significant, with attenuated effects (β: 0.020 for anticipated discrimination; β: 0.017 for everyday discrimination) after adjusting for social support, community connection, and resilient coping. Total effects were only significant for the adjusted model of everyday discrimination (β: 0.056 [0.014, 0.099]). Findings suggest discrimination impacted health through specific psychosocial pathways. Alongside efforts to eliminate intersectional discrimination, stress-lowering interventions and increased access to social support and community connection may be effective approaches to reducing multimorbidity in this highly marginalized group.

Humans↗

PubMed2026

Diabetic macular edema and GLP-1 receptor agonist use: a systematic review and meta-analysis.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type II diabetes and obesity because of their cardiometabolic benefits. However, concerns regarding potential ocular adverse effects, particularly diabetic macular edema (DME), have prompted the need to clarify their retinal safety. METHODS: A systematic review and meta-analysis study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements (PROSPERO registration: CRD420251176164). MEDLINE (Ovid), EMBASE (Ovid), CENTRAL (Ovid), Web of Science, and PubMed were searched from inception to October 24, 2025. Randomized trials and observational cohort or case-control studies, including individuals with diabetes without baseline DME and exposed to GLP-1RAs were eligible. Two reviewers independently screened studies, extracted data, and assessed risk of bias using ROBINS-I. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluation. Random-effects models were used to pool incidence proportions and hazard ratios (HRs). RESULTS: Thirteen retrospective cohort studies (2021-2025) using large real-world databases were included. Across 6 studies, the pooled proportion of incident DME among GLP-1RA users was 0.14 (95% CI: 0.07-0.23; I² = 99.8%). Compared with mixed antihyperglycemic therapies, GLP-1RA use was not associated with increased DME risk (pooled HR: 0.81, 95% CI: 0.52-1.26). GLP-1RAs were associated with a higher relative risk of DME compared with sodium-glucose cotransporter-2 inhibitors (HR: 1.50, 95% CI: 1.17-1.94) but not compared with dipeptidyl peptidase-4 inhibitors (HR: 0.90, 95% CI: 0.69-1.19). Evidence certainty was very low. CONCLUSION: Current low-certainty observational evidence does not support an overall increased risk of DME with GLP-1RA use. Prospective studies are needed to clarify comparative retinal safety.

Humans↗

PubMed2026

Incidence of Cirrhosis in Fibrotic Metabolic Dysfunction-Associated Steatohepatitis: A Meta-Analysis of Placebo Arms from Randomized Clinical Trials.

BACKGROUNDS AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH) with stage F2-F3 fibrosis represents the main target population for emerging pharmacotherapies. However, data on short-term progression to cirrhosis (F4) in this group remain limited. We aimed to evaluate the incidence of cirrhosis in placebo-treated patients with fibrotic MASH in randomized controlled trials (RCTs). METHODS: In this single-arm meta-analysis, we systematically searched PubMed and Cochrane Library from inception to December 13, 2024, for pharmacological Phase ≥ 2 RCTs reporting cirrhosis events (detected in liver biopsy or clinical signs) among patients with fibrotic MASH receiving placebo. Incidence rates were pooled using generalized linear mixed models with Clopper-Pearson confidence intervals (CIs). RESULTS: We identified a total of 11 RCTs, including 586 patients with fibrotic MASH. Total follow-up was 657.23 person-years (PYs), with 83 cirrhosis events reported. The pooled incidence rate was 13.09 per 100 PYs (95% CI 7.81 to 21.12, I2 = 75.6%, τ2 = 0.682). In subgroup analysis, the incidence of cirrhosis was 3.40 per 100 PYs in MASH F2 (95% CI 1.10 to 10.02, I2 = 0%, τ2 = 0) and 17.90 per 100 PYs (95% CI 10.63 to 28.55, I2 = 70.2%, τ2 = 0.561) in MASH F3, with significant differences between stages (p = 0.006). Sensitivity analyses showed consistent estimates. Most RCTs were judged to have a low risk of bias. CONCLUSIONS: This study provides stage-specific data on cirrhosis incidence in fibrotic MASH, highlighting the high short-term risk associated with MASH F3 in trial settings. These data may inform benchmarks to guide event expectations, enrichment strategies, sample size assumptions, and the interpretation of future MASH clinical trials.

Humans↗

PubMed2026

Safety and outcomes of dapagliflozin initiation in critically ill patients with acute kidney injury: A post-hoc analysis of the defender trial.

BACKGROUND: SGLT2 inhibitor use in acute kidney injury (AKI) is controversial due to concerns about hemodynamic instability. We evaluated dapagliflozin initiation in critically ill patients with AKI enrolled in the DEFENDER trial. METHODS: Among 212 patients with AKI at enrollment (100 dapagliflozin, 112 control), we compared 28-day mortality, kidney replacement therapy (KRT), and composite death/KRT. Adjusted risk differences were estimated controlling for age, sepsis, baseline vasopressor use, and creatinine. Physiological trajectories (creatinine, urine output, fluid balance, acid-base parameters) over days 1-5 were analyzed using mixed models. Likelihood ratios quantified compatibility with clinically meaningful harm or benefit. RESULTS: Event rates were similar: 28-day mortality 38% vs 40%, KRT 12% vs 18%, composite 41% vs 42% (dapagliflozin vs control). Adjusted risk differences were - 1.9% (95% CI -14.5 to 10.7) for death, -7.4% (-16.2 to 1.5) for KRT, and - 0.9% (-13.6 to 11.8) for the composite. Physiological trajectories showed no divergence suggestive of hemodynamic or metabolic instability. Likelihood ratios provided limited separation: at 5% absolute effect threshold, LR against harm was 1.47 and against benefit 1.19. CONCLUSIONS: Dapagliflozin initiation in critically ill patients with AKI was not associated with excess mortality, KRT, or physiological derangement. The near-neutral evidential profile indicates neither moderate harm nor benefit can be excluded, supporting feasibility of dedicated trials of SGLT2 inhibitors in AKI.

Humans↗

PubMed2026

Association between Kidney Tubular Secretory Clearance with Cognitive Function among Adults with CKD in the Systolic Blood Pressure Intervention Trial.

BACKGROUND: Persons with CKD are disproportionally affected with cognitive impairment, yet the pathophysiology linking the two conditions is unclear. Because kidney tubule secretion is essential for clearance of medications, uremic toxins, and metabolites, we hypothesized that worse tubular secretion would be associated with reduced cognitive function in CKD. METHODS: The Systolic Blood Pressure Intervention Trial tested a systolic blood pressure target <120 mmHg vs. <140 mmHg in hypertensive individuals at high cardiovascular risk. In paired blood and urine specimens from 1,937 participants with eGFR <60 ml/min/1.73m2, we measured 10 endogenous tubule-secreted metabolites and calculated a urine/plasma ratio for each, then averaged these to generate a summary secretion score. We used unadjusted and multivariable-adjusted linear regression and mixed models to evaluate cross-sectional and longitudinal associations of the secretion score with the Montreal Cognitive Assessment, Digit Symbol Coding, and Logical Memory immediate and delayed tests-measured at baseline and months 24 and 48 of follow-up. Multivariable Cox regression evaluated associations with incident probable dementia and mild cognitive impairment, adjudicated by prespecified criteria. RESULTS: Mean age was 73 ± 9 years, 41% were women, mean eGFR was 48.2 ± 11.4 ml/min/1.73m2, median albuminuria was 14.8 [7.1-48.6] mg/g. Lower secretion score was associated with a 0.06 higher adjusted logical memory delayed score (95% CI: 0.02, 0.11) but not with other cognitive tests at baseline or longitudinal cognitive decline. After a median 4.1 years of follow-up, 118 developed probable dementia and 187 developed mild cognitive impairment. Each 1-SD lower secretion score was associated with lower risk of probable dementia (HR 0.78, 95% CI: 0.63, 0.98) but not mild cognitive impairment. CONCLUSIONS: Among Systolic Blood Pressure Intervention Trial participants with CKD, lower estimated tubular secretion was not associated with worse cognition at baseline or during longitudinal follow-up.

Journal Article↗

PubMed2026

Premature closure underlies bias in medical diagnosis in students: A randomised controlled experiment.

OBJECTIVE: The purpose of the study reported in this article was to shed light on the cognitive mechanism mediating between biasing information and diagnostic error. The literature suggests at least two different hypotheses: premature closure leading biased participants to spend less time on diagnosis or increased competition between diagnostic hypotheses. The latter hypothesis predicts that biased participants would spend more time reaching a diagnosis. METHOD: Using the salient distracting findings (SDF) experimental paradigm, we biased 58 fourth-year medical students while diagnosing 12 clinical vignettes in a within-group incomplete block design under three conditions: cases presented without SDF, with SDF at the beginning and with SDF at the end. For each of these conditions, diagnostic accuracy, the number of SDF-related mistakes and time per word needed to process the case were recorded. The data were analysed using linear mixed modelling. Estimated marginal mean scores were reported. RESULTS: Participants confronted with salient distracting features (SDFs) at the beginning of a clinical case demonstrated significantly lower diagnostic accuracy (mean 0.11) compared with the No-SDF condition (0.27), representing a 61% reduction (F2,693 = 11.995, p < 0.001), and made more SDF-related mistakes (F2, 693 = 16.395, p < 0.001). When SDFs were presented at the end of the case, diagnostic accuracy was also reduced (mean 0.17; 36% reduction), but processing time did not differ from the No-SDF condition. Only early presentation of SDFs was associated with reduced processing time per word (F2,636 = 4.799, p < 0.01), consistent with premature closure. CONCLUSION: These findings demonstrate that biasing information increases diagnostic error in medical students and that only early bias is associated with reduced information processing. The data do not support the competition hypothesis for early bias, as processing time did not increase under biasing conditions. Premature closure can therefore be directly observed rather than inferred, inviting further research.

Humans↗

PubMed2026

Repeated low-level red-light therapy for improving asthenopic symptoms and accommodation in presbyopia.

BACKGROUND: To assess the short-term effectiveness of repeated low-level red light (RLRL) therapy in relieving asthenopia and enhancing accommodation in presbyopia. METHODS: This randomized, parallel-group, double-masked clinical trial enrolled adults with presbyopia and self-reported asthenopia. Participants were allocated using computer-generated randomization and randomly assigned at a 1:1 ratio to RLRL or sham groups. Blinding included participants, examiners, assessors, and statisticians. The primary outcome was the change from baseline in the Computer Vision Syndrome Questionnaire (CVS-Q) score at day 31. Secondary outcomes were the change in accommodative amplitude (AA), Near Activity Visual Questionnaire (NAVQ) score, habitual near visual acuity, near-addition power, accommodative facility, positive and negative relative accommodation, binocular cross-cylinder response, and accommodative convergence-to-accommodation ratio. Continuous outcomes were analyzed using linear mixed-effects models. RESULTS: Sixty-four of 66 randomized participants (aged 41-62 years) completed the 1-month trial. At day 31, RLRL showed greater improvement than sham in CVS-Q score (adjusted mean difference, -1.75 points; 95% CI, -3.10 to -0.39), binocular AA (1.09 D; 95% CI, 0.37 to 1.82), and NAVQ score (-8.07 points; 95% CI, -14.17 to -1.97). The effect on AA was most pronounced in a subgroup of eyes with baseline amplitude >2.0 D (adjusted mean difference 1.33 D; 95% CI 0.32-2.34). Other measures did not differ between groups at each visit. No treatment-related adverse events were reported. Adherence was similar between groups (mean compliance: 98.2% vs 97.5%). CONCLUSIONS: Short-term treatment with RLRL significantly reduced asthenopic symptoms and improved accommodative amplitude in individuals with presbyopia.Trial registration: NCT06745661 (registered December 8, 2024).

Humans↗