Tag: pubmed

Toxicol Sci. 2026 Feb 12:kfag011. doi: 10.1093/toxsci/kfag011. Online ahead of print.

ABSTRACT

Parental exposure to toxicants can affect progeny health. However, laboratory studies often employ exposures that result in loading of pollutants to gametes, or toxic effects to parents which could indirectly affect germ cell or gamete health. Here, we took advantage of the biology of Caenorhabditis elegans to carry out a study in which we minimized the potential for maternal loading of toxicants, and used an exposure paradigm that either did (high concentration) or did not (low concentration) significantly impact the health of the P0 generation. We hypothesized that parental exposure to mitochondrial toxicants during germ cell and gamete development, at levels not causing P0 toxicity, would result in altered mitochondria and organismal health in offspring. In the P0 generation, a high rotenone concentration altered growth, mitochondrial respiration, gene expression, induction of the mitochondrial unfolded protein response, and susceptibility to dopaminergic neurodegeneration induced by a chemical rechallenge later in life. However, we observed minor or no effects in P0 at a low concentration. In high-exposure F1 offspring, we observed altered embryo size, larval developmental stage distribution, spare respiratory capacity, heat shock protein expression, and dopaminergic neurodegeneration after a secondary rotenone challenge. The only effects observed in the F1 offspring of the low exposure were a 1.7% decrease in egg size (size later in development was normal), and moderate evidence of a slightly increased sensitivity to heat shock protein expression and dopaminergic neurodegeneration caused by a secondary later-in-life rotenone exposure. We recommend parental toxicity be carefully assessed to contextualize offspring outcomes.

PMID:41678270 | DOI:10.1093/toxsci/kfag011

Exp Clin Psychopharmacol. 2026 Feb 12. doi: 10.1037/pha0000832. Online ahead of print.

ABSTRACT

Cannabidiol (CBD), a nonintoxicating molecule derived from the cannabis plant, is garnering attention as a novel sleep aid despite a dearth of empirical literature supporting its efficacy for sleep-related indications. The present study aimed to address this gap. Participants were 63 individuals (M_age = 29.27; SD_age = 9.58) reporting elevated trait worry who were randomly assigned to take 300 mg CBD, 50 mg CBD, or placebo daily for 2 weeks. Results suggested 300 mg CBD decreased sleep disturbances and sleep quality significantly more than 50 mg CBD (B = -0.39, t = -2.59, p < .05, d = 0.08), but not placebo (B = -0.32, t = -2.09, p = .10, d = 0.07) with no effects on sedation or cognitive impairment. These data suggest 300 mg CBD showed significantly greater improvement than 50 mg CBD but did not show statistically significant improvement compared to placebo. More work is needed to assert strong conclusions regarding CBD’s effects on sleep-related indicators. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

PMID:41678223 | DOI:10.1037/pha0000832

Psychol Assess. 2026 Mar;38(3):253-265. doi: 10.1037/pas0001451.

ABSTRACT

We thank Stein et al. (2026) and Jenkins (2026) for their commentaries on our critical review of the Social Cognition and Object Relations Scale-Global system as applied to the Thematic Apperception Test (Sinclair et al., 2023) and appreciate the opportunity to respond in kind. Although we acknowledge the considerable effort put into these response articles (analytically and conceptually), both fall short in addressing the myriad serious methodological and procedural concerns we raised in 2023 and do little to move the needle in support of this assessment technique. This article will review the many ways these responses misinterpret and misrepresent our original review and the voluminous methodological problems with the “meta-analyses” that are presented by Stein et al.-and the various ways they are statistically confounded, confusing, and scientifically unsound. Further, this article will highlight the considerable number of logical inconsistencies that are inherent within Stein et al.’s core arguments, as well as the numerous contradictions between Stein et al. and Jenkins-all of which seriously undermine the methodology itself. Given the many ethical ambiguities that arise as a result, we conclude with a repeat calling for a moratorium on this methodology until these issues are sufficiently resolved. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

PMID:41678221 | DOI:10.1037/pas0001451

Clin Exp Rheumatol. 2026 Feb 6. doi: 10.55563/clinexprheumatol/itysdz. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to develop and validate a risk stratification scale for unfavourable outcomes in adult patients with IgA vasculitis nephritis (IgAVN).

METHODS: The derivation cohort in this study was constructed using the existing prognosis data from adult IgAVN cohorts. We extracted the risk factors and their hazard ratios. Only statistically significant risk factors were included in our final risk stratification scale. Then this study validated the risk stratification scale in an external cohort of Chinese patients. The performance of the risk stratification scale was evaluated by the receiver operating characteristic (ROC), calibration, decision, and Kaplan-Meier curves.

RESULTS: Ten cohorts involving 1,814 adult patients with IgAVN were included in this meta-analysis. Serum albumin (ALB), estimated glomerular filtration rate (eGFR), endocapillary hypercellularity (E1), and tubular atrophy/interstitial fibrosis (T1/2) were included in the risk stratification and scored according to their weightings (maximum score: 6.5). An external cohort comprising 133 patients was used to validate the risk stratification scale. The area under the curve (AUC) value of the scoring scale was 0.88 (95%CI: 0.78-0.99), with a sensitivity of 0.79 (95%CI: 0.49-0.95) and specificity of 0.89 (95%CI: 0.82-0.94), at a cut-off value of 3. The calibration, decision, and Kaplan-Meier curves further confirmed the robust performance of the risk stratification scale.

CONCLUSIONS: In this study, we established a simple and practical tool to identify adult IgAVN patients at high risk of unfavourable outcomes. Reasonable use of the risk stratification scale can help make early clinical decisions and facilitate the development of precision medicine.

PMID:41678202 | DOI:10.55563/clinexprheumatol/itysdz

JAMA Ophthalmol. 2026 Feb 12. doi: 10.1001/jamaophthalmol.2025.6262. Online ahead of print.

ABSTRACT

IMPORTANCE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are considered safe, effective medications for type 2 diabetes (T2D) and weight loss, used by millions worldwide. While their cardiometabolic benefits are well established, emerging observations suggest a potential association between GLP-1RA use and new-onset nonarteritic anterior ischemic optic neuropathy (NAION).

OBJECTIVE: To emulate a target trial evaluating the risk of NAION associated with initiation of semaglutide (GLP-1RA), compared with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) as second-line therapy for T2D in a nationwide cohort of US veterans.

DESIGN, SETTING, AND PARTICIPANTS: This study was conducted nationwide using data from the Veterans Health Administration health care system between March 1, 2018, and March 1, 2025. This active-comparator, new-user, target trial emulation used cause-specific hazard ratios (HRs) that were estimated using overlap weighting to account for confounding. Participants included US veterans with T2D, current metformin use, and no prior GLP-1RA or SGLT2i use. Data analysis was conducted from July 2025 through September 2025.

EXPOSURE: Initiation of semaglutide or any SGLT2i.

MAIN OUTCOME AND MEASURE: Incident NAION, identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision and Systematized Nomenclature of Medicine codes.

RESULTS: A total of 102 361 US veterans met inclusion criteria, including 11 478 initiators of semaglutide and 90 883 initiators of an SGLT2i. Baseline characteristics were well balanced between treatment groups after overlap weighting (mean [SD] age, 60.1 [11.7] years; body mass index, 37.8 [6.7]; hemoglobin A1c, 7.0% [1.4]; 85.5% male and 14.5% female; 20.7% Black, 8.1% Hispanic, and 61.9% non-Hispanic White). Over a maximum follow-up of 7.5 years, 173 total incident NAION events occurred. The incidence rate of NAION was 123 per 100 000 person-years among semaglutide initiators and 67 per 100 000 person-years among SGLT2i. In 2.1 years of median follow-up, semaglutide initiators had a 2.33-fold higher risk than SGLT2i initiators (hazard ratio, 2.33; 95% CI, 1.54-3.54; P < .001). The overlap weighted incidence rate of NAION was 0.29% for semaglutide initiators and 0.13% for SGLT2i initiators, with a corresponding average treatment effect of 0.16 percentage points.

CONCLUSIONS AND RELEVANCE: In this nationwide cohort of US veterans with T2D, semaglutide initiators had a 2-fold NAION risk than SGLT2i initiators, while the absolute risk was low. Clinicians and patients should be counseled on the rare but evident increased risk of NAION after semaglutide initiation.

PMID:41678180 | DOI:10.1001/jamaophthalmol.2025.6262

JAMA Oncol. 2026 Feb 12. doi: 10.1001/jamaoncol.2025.6448. Online ahead of print.

ABSTRACT

IMPORTANCE: Patients with recurrent prostate cancer after previous radiotherapy typically have poor survival. Those with recurrences prostate confined might be suitable for salvage focal therapy (sFT) or salvage radical prostatectomy (sRP). sFT may offer good cancer control with comparatively less toxic effects, but outcomes beyond 5 years have not been reported, and no study has compared sFT to sRP.

OBJECTIVE: To compare cancer control and perioperative complications among patients after sFT vs sRP.

DESIGN, SETTING, AND PARTICIPANTS: In this international, multicenter cohort study of matched comparison data, patients undergoing sFT were derived from the prospective UK HIFU (high-intensity focused ultrasound) Evaluation and Treatment and International Cryotherapy Evaluation registries (9 centers; 2006-2024) and the prospective UK Focal Recurrent Assessment and Salvage Treatment cohort study (6 centers; 2014-2018). Patients undergoing sRP were derived from an international retrospective registry (12 centers in 8 countries; 2000-2021). Patients with biopsy-confirmed, localized recurrent prostate cancer postradiotherapy, either external beam radiotherapy, brachytherapy, or both, were included. Data were analyzed from March to July 2025.

EXPOSURES: sFT using HIFU or cryotherapy vs sRP.

MAIN OUTCOMES AND MEASURES: The primary outcome was cancer-specific survival up to 10 years. Secondary outcomes were overall survival, any perioperative complications (Clavien-Dindo grades 1-5), and major perioperative complications (Clavien-Dindo grades 3-5). Comparisons were made on matched patients following 1:1 cardinality matching within individual multiply-imputed datasets. Matching variables used were radiotherapeutic treatment, years between primary and salvage treatments, European Association of Urology recurrence risk group, and presalvage age, prostate-specific antigen, prostate volume, grade group, T stage, and androgen-deprivation therapy use.

RESULTS: A total of 923 patients were eligible for matching (419 undergoing sFT and 504 undergoing sRP). Of the patients undergoing sFT, 325 (77.6%) underwent HIFU and the remainder cryotherapy, with 241 (57.5%) treated with quadrant ablation. Of patients treated with sRP, 376 (74.6%) underwent open surgery and the remainder robot-assisted surgery. For sFT vs sRP, 10-year cancer-specific survival was 92% (95% CI, 86%-98%) vs 99% (95% CI, 97%-100%), with no statistically significant difference (restricted mean time lost, -0.09 years; 95% CI, -0.22 to 0.03 years; P = .15; subdistribution hazard ratio, 0.45; 95% CI, 0.05-4.00; P = .47). There was no statistically significant difference in 10-year overall survival (restricted mean survival time, -0.13 years; 95% CI, -0.86 to 0.60 years; P = .72). Undergoing sRP was associated with statistically significant higher odds of any complication (adjusted odds ratio, 24.20; 95% CI, 12.94-45.27; P < .001) and major complication (adjusted odds ratio, 9.31; 95% CI, 3.42-25.36; P < .001).

CONCLUSIONS AND RELEVANCE: In this cohort study, sFT and sRP were effective for treating localized radiorecurrent prostate cancer, while sFT was associated with fewer perioperative complications. sFT may provide a favorable therapeutic ratio for many patients with localized radiorecurrent prostate cancer.

PMID:41678176 | DOI:10.1001/jamaoncol.2025.6448

Clin Exp Rheumatol. 2026 Jan 26. doi: 10.55563/clinexprheumatol/pg971k. Online ahead of print.

ABSTRACT

OBJECTIVES: Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome predominantly affecting women, suggesting possible links with reproductive and hormonal factors. Although reproductive history has been associated with various long-term health conditions, its role in FM remains insufficiently explored. This study aimed to investigate the association between parity, age at first pregnancy, and the presence of fibromyalgia among women of reproductive age.

METHODS: This cross-sectional observational study included 260 women aged 18-50 years with at least one prior live birth, recruited from Physical Medicine and Rehabilitation, Rheumatology, and Gynaecology Outpatient Clinics between March and December 2024. Demographic, clinical, and reproductive data were collected through structured interviews and medical records. FM diagnosis was based on the 2016 revised criteria of the American College of Rheumatology (ACR) using Widespread Pain Index (WPI) and Symptom Severity Scale (SSS) scores; the Global Symptom Score (GSS) was defined as their sum. Statistical analyses included independent-sample t-tests, chi-square tests, and multivariate logistic regression adjusting for age, body mass index, comorbidities, and educational level.

RESULTS: FM was diagnosed in 104 participants (40%). Women with three or more live births had a significantly higher prevalence of FM compared with those with fewer births (p=0.006). In multivariate analysis, grand multiparity remained independently associated with FM (adjusted OR = 2.46, 95% CI = 1.28-4.72, p=0.006). No significant association was found between age at first pregnancy and FM (p>0.05). FM-diagnosed participants reported significantly higher WPI, SSS, and GSS scores (p=0.001 for all), with strong correlations between WPI and both GSS (r=0.782) and SSS (r=0.472).

CONCLUSIONS: Grand multiparity was independently associated with fibromyalgia, suggesting that cumulative hormonal and physiological stress from multiple pregnancies may contribute to chronic pain susceptibility. No association was found between age at first pregnancy and FM. Larger, longitudinal studies are warranted to clarify causal pathways between reproductive history and FM pathogenesis.

PMID:41678172 | DOI:10.55563/clinexprheumatol/pg971k

Clin Exp Rheumatol. 2026 Jan 29. doi: 10.55563/clinexprheumatol/0yu9gm. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the clinical response of Janus kinase inhibitors (JAKi) across subtypes of idiopathic inflammatory myopathies (IIM) in a cohort of patients with refractory disease.

METHODS: We conducted a retrospective analysis of all adult IIM patients treated with JAKi at our centre. Treatment response was assessed based on changes in muscle strength, serum biomarkers of muscle damage and inflammation, pulmonary function, radiological evolution of interstitial lung disease (ILD) and corticosteroid dosage.

RESULTS: Ten IIM patients who were previously or currently receiving JAKi therapy were identified. Six patients were female and the mean age was 52.7 years (standard deviation [SD] 13.91). Anti-synthetase syndrome was the most common subtype (n=5, 50%). At baseline, median manual muscle test 8 score was 136 (interquartile range [IQR] 25.5) and, after therapy, was 147 (IQR 8), representing a statistically significant increase (p<0.05). Corticosteroid dose reduction was also statistically significant (p<0.05), with the median daily dose decreasing from 10mg to 2.5mg. Additionally, four patients were able to discontinue corticosteroid therapy. In six patients with ILD, diffusion capacity for carbon monoxide improved significantly (p<0.01), from 68.33% (IQR 19.31) to 93% (IQR 7.27). No significant changes were observed in serum inflammatory markers, creatine kinase, forced expiratory volume first second or forced vital capacity.

CONCLUSIONS: JAKi therapy appears to be clinically effective, well tolerated, and safe in patients with refractory IIM, with a particular benefit in ILD. The steroid sparing effect was also a major outcome. Future prospective and controlled studies are warranted to confirm these preliminary results and better define the therapeutic potential of JAKi in IIM.

PMID:41678164 | DOI:10.55563/clinexprheumatol/0yu9gm

Eur Geriatr Med. 2026 Feb 12. doi: 10.1007/s41999-025-01363-0. Online ahead of print.

ABSTRACT

PURPOSE: To deliver an effective training intervention to staff in temporary elder care institutions in municipalities.

SETTINGS: A geriatric department at a university hospital in collaboration with 6 surrounding municipalities.

INTERVENTION: The training intervention was planned using self-determination theory as framework. Important elements were relation building, giving nursing staff a choice concerning themes of teaching sessions (supports autonomy) and selection of cases, supporting competence development through case-based discussions. Study design and statistical approach: before and after the intervention, an electronic questionnaire was mailed to staff at care institutions in the municipalities. The questionnaire contained questions drawn from the Basic Psychological Need Satisfaction and Frustration Scale (BPNSFS). Differences concerning competences between before and after the intervention were assessed using Wilcoxon signed-rank test.

KEY FINDINGS: 55 persons answered the BPNSFS before and after the intervention. For all items in BPNSFS, the results after compared to before improved. However, the improvement was significant only for the sum of all items with a mean difference of 0.13, p = 0.05, and for one single item (I feel capable at what I do at work), with a mean difference of 0.15, p = 0.02.

CONCLUSIONS: We have shown that self-determination theory has the potential to provide a theoretical framework for planning training interventions among staff in temporary elder care institutions. It is possible to measure the effect using an instrument developed within the framework of self-determination theory (BPNSFS).

PMID:41678141 | DOI:10.1007/s41999-025-01363-0

Adv Ther. 2026 Feb 12. doi: 10.1007/s12325-026-03504-8. Online ahead of print.

ABSTRACT

INTRODUCTION: Delamanid (Deltyba®), a medicinal product with an orphan designation for the treatment of tuberculosis, received a conditional marketing authorisation in the European Union (EU) based on phase 2 data, while phase 3 trial was ongoing. The list of adverse drug reactions (ADRs) in the original Summary of Product Characteristics (SmPC) contained all adverse events (AEs) considered related by the investigator that were reported in at least one of the 321 patients receiving delamanid. The safety profile observed after completion of the phase 3 clinical trial, post-marketing studies and spontaneous reports from post-marketing appeared different from what the initial SmPC was indicating. A comprehensive analysis was undertaken aiming to provide evidence for identification of a well-substantiated and clinically useful delamanid safety profile.

METHODS: In support of the process of ADR identification, a statistical methodology of data from controlled clinical trials was introduced based on the estimation of risk difference and risk ratio for identification of a potential risk from delamanid in high and low incidence situations. Final medical assessment was supported by this statistical analysis of data from controlled clinical trials, any signal from all other Otsuka-sponsored clinical trials, along with data from post-marketing solicited and unsolicited sources.

RESULTS: ADRs were either retained, added to or removed from the ADR list with the same or modified frequency. Thus, the total number of ADRs listed in the original SmPC was significantly reduced.

CONCLUSION: A combination of statistical parameters and medical judgement should be considered for the selection of undesirable effects for the product label and for the safety risk classification.

PMID:41678139 | DOI:10.1007/s12325-026-03504-8