Tag: pubmed

Environ Sci Pollut Res Int. 2025 Nov 12. doi: 10.1007/s11356-025-37134-4. Online ahead of print.

ABSTRACT

Per- and polyfluoroalkyl substances (PFASs) are persistent endocrine-disrupting chemicals widely detected in human serum. Epidemiological studies suggest that PFAS exposure may disrupt thyroid function by interfering with hormone production, transport, and metabolism; however, findings remain inconsistent, particularly regarding sex-specific effects. This study aimed to (1) examine associations between serum PFAS mixtures and thyroid hormone levels in adolescents and (2) identify mixture patterns and explore sex-specific associations using a nationally representative dataset. We investigated the association between serum PFAS mixtures and thyroid function markers-including thyroid-stimulating hormone (TSH), thyroid hormones, and thyroglobulin-among 12- to 20-year-olds in NHANES 2011-2012. Principal component analysis (PCA) identified three factors: Factor 1 (long-chain carboxylates: PFUnA, PFDA, PFNA), Factor 2 (sulfonates: PFHxS, PFOS, MeFOSAA, and PFOA), and Factor 3 (PFHpA). Multivariable linear regression estimated associations between PFAS factors and thyroid hormone concentrations. Higher exposure to Factor 1 was significantly positively associated with free T4 in males but negatively associated with total T4 in females. PFASs may alter hormone clearance or interfere with feedback regulation. Factor 2 exposure was negatively associated with total T4 and positively associated with TSH in males, with statistical significance. Greater exposure to Factor 3 was significantly associated with increased total T4 in males. Overall, exposure to Factors 1 and 2 was predominantly linked to lower thyroid hormone levels, whereas Factor 3 was positively associated with thyroid hormones. These findings highlight the importance of evaluating PFAS mixtures rather than individual compounds and suggest sex-specific thyroid hormone disruptions.

PMID:41222812 | DOI:10.1007/s11356-025-37134-4

Saudi Pharm J. 2025 Nov 12;33(6):43. doi: 10.1007/s44446-025-00042-2.

ABSTRACT

While several anti-tumor biosimilars have been approved in China, comprehensive nationwide analyses of their real-world utilization patterns remain limited, particularly regarding cross-regional adoption and indication-specific usage. We collected information on patients treated with bevacizumab, rituximab, trastuzumab and their biosimilars at 109 hospitals in nine Chinese cities from 2019 to 2023. Analysis of 264,527 prescriptions revealed rapid biosimilar adoption for bevacizumab (2023 originator share: 20.0%, -25.1%/year), moderate for rituximab (32.1%, -16.8%/year), and limited for trastuzumab (70.0%, -8.3%/year). Geographic variation was substantial (2023 city ranges: bevacizumab 2.3-43.0%; rituximab 6.7-70.3%; trastuzumab 42.4-92.4%). Tertiary hospitals showed faster biosimilar uptake than secondary hospitals (bevacizumab: + 23.7%). Free medical care patients preferred originators (bevacizumab: 64.1% vs 38-39% for other payers). Off-label use demonstrated significantly higher biosimilar adoption (bevacizumab: 69.0%; rituximab: 52.1%) versus approved indications (p < 0.00625). Cost distributions mirrored prescription trends but consistently favored originators. All trends were statistically significant (p < 0.05). The biosimilar market share showed steady annual growth, however the growth rates vary across different products. However, Patients with lower out-of-pocket costs remained more likely to choose original products. Enhanced regulatory oversight of both approved and off-label/extrapolated indications is needed to ensure appropriate biosimilar utilization.

PMID:41222808 | DOI:10.1007/s44446-025-00042-2

Clin Rheumatol. 2025 Nov 12. doi: 10.1007/s10067-025-07804-2. Online ahead of print.

ABSTRACT

BACKGROUND: Primary Sjögren’s syndrome (pSS), a systemic autoimmune disorder, is recognized by immune dysregulation and chronic inflammation. Though telomere attrition has been linked to various immune-related diseases, its relationship with pSS pathogenesis remains poorly understood. This research seeks to explore the relationship between peripheral blood leukocytes’ telomere length and the susceptibility to pSS, thereby offering insights into the potential role as a biomarker.

METHODS: 181 participants, comprising pSS patients (n = 87) and healthy controls (n = 94) were involved in this study. Relative length of leukocyte telomere (T/S ratio) was quantified by a validated quantitative PCR protocol. To define the independent effect of telomere length on pSS susceptibility, logistic regression analyses, including univariate and multivariable, were performed. In addition, generalized additive modeling (GAM) was applied to identify possible nonlinear dose-response patterns.

RESULTS: pSS patients demonstrated significantly shorter telomere lengths than healthy controls (mean T/S ratio: 0.8 ± 0.35 vs. 1.01 ± 0.49, P = 0.0019). Decreased length of telomere was strongly linked to a higher likelihood of pSS occurrence (OR = 0.31, 95% CI: 0.15-0.66, P = 0.0021). This relationship stayed statistically meaningful, albeit slightly weakened, after accounting for clinical characteristics and therapeutic variables. Moreover, nonlinear modeling suggested that progressive telomere shortening corresponded to a rising probability of developing pSS, implying a potential mechanistic contribution of telomere erosion to disease development.

CONCLUSION: This cross-sectional study indicates that reduced telomere length in peripheral blood leukocytes is linked to an elevated likelihood of developing pSS, suggesting that telomere dynamics could function as a promising biomarker for early detection and risk assessment. Future longitudinal studies are warranted to confirm causality and assess telomere-targeted interventions. Key Points • Leukocyte telomere shortening serves as a clinically relevant biomarker in pSS. • Nonlinear dynamics link telomere attrition to immune dysregulation. • Telomere length shows complex interaction with disease stage and therapeutics.

PMID:41222807 | DOI:10.1007/s10067-025-07804-2

Clin Rheumatol. 2025 Nov 12. doi: 10.1007/s10067-025-07768-3. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the clinical characteristics, associated factors, and outcomes of posterior reversible encephalopathy syndrome (PRES) in patients with systemic lupus erythematosus (SLE).

METHODS: This retrospective case-control study, conducted from 2009 to 2022, included 32 patients with SLE who developed PRES and 50 matched controls with neuropsychiatric SLE (NPSLE). Controls were matched for age, sex, and disease duration. Clinical characteristics, laboratory indices, neuroimaging findings, and treatment approaches were systematically evaluated. Multivariate logistic regression was performed to identify factors associated with PRES in patients with SLE. In addition, survival outcomes were compared according to different glucocorticoid (GC) dosing regimens.

RESULTS: Patients with SLE who developed PRES had significantly longer hospitalizations and a higher frequency of hypertension compared with NPSLE controls (P < 0.05). Laboratory findings showed elevated white blood cell (WBC) and neutrophil (NE) counts, as well as increased levels of creatinine (Cr), blood urea nitrogen (BUN), and C-reactive protein (CRP); in contrast, serum albumin (Alb) and magnesium levels were markedly lower before the onset of neurological symptoms in the PRES group (all p < 0.05). PRES patients also demonstrated higher rates of nephritis and hypomagnesemia compared with NPSLE controls without PRES (p < 0.05). At the time of neurological symptom onset, seizures, visual impairment, and vomiting were more common in the PRES group, whereas acute confusional state were less frequent (p < 0.05). Neuroimaging revealed that patients with PRES more often exhibited lesions involving the parietal, occipital, frontal, and temporal lobes (p < 0.05). Multivariate logistic regression analysis identified several factors associated with an increased risk of PRES in patients with SLE: hypertension (OR 38.419, 95% CI: 6.073-243.037, p < 0.001), hypomagnesemia (OR 8.360, 95% CI: 1.542-45.322, p = 0.014), nephritis (OR 10.362, 95% CI:1.246-86.156, p = 0.030) and treatment with very-high-dose GC (OR 14.352, 95% CI: 1.927-106.921, p = 0.009). Furthermore, among SLE patients with PRES, survival rates differed significantly across GC dosing regimens (p = 0.045, Fisher’s exact test), with rates of 50.00% (6/12) in the very-high-dose group, 88.24% (15/17) in the high-dose group, and 100.00% (3/3) in the low-medium-dose group. During follow-up (1-6 months), disease relapse occurred in three patients (9.38%).

CONCLUSION: Hypertension, hypomagnesemia, nephritis, and the use of very-high-dose GC may represent potential factors associated with the development of PRES in patients with SLE. Moreover, treatment approaches, especially GC dosing, may influence patient survival outcomes.It should be emphasized, however, that the observed association involving hypomagnesemia, though statistically significant in this cohort, remains preliminary and necessitates further validation in larger, prospectively designed studies. Key Points • This study represents the largest case-control analysis of SLE-associated PRES to date (32 cases vs. 50 NPSLE controls), identifying multiple associated factors linked to PRES. • Hypomagnesemia and treatment with very-high-dose GCs were identified as novel associated factors for PRES in SLE, reported here for the first time. • Disease activity (SLE disease activity index (SLEDAI)) was compared between the SLE-PRES cohort (before and during the episode) and the NPSLE cohort. • Survival outcomes in SLE-PRES patients varied significantly according to GC dosing intensity (p = 0.045), with the highest mortality (50.0%) observed in the very-high-dose group.

PMID:41222806 | DOI:10.1007/s10067-025-07768-3

Mol Biol Rep. 2025 Nov 12;53(1):69. doi: 10.1007/s11033-025-11217-4.

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) is a complex disease influenced by genetic and environmental factors. Polymorphisms in RAAS genes have been implicated in kidney disease, though their influence on disease susceptibility varies across studies. The AGT and AGTR1 are key candidate genes of the RAAS cascade, essential for kidney function.

METHODS AND RESULTS: This study investigated the association of AGT (rs699) and AGTR1 (rs5186) polymorphisms with susceptibility to CKD. A total of 380 participants were recruited in this hospital-based case-control study and genotyping was performed using PCR- RFLP method. Statistical analyses were conducted using SPSS Statistics version 26.0. Computational analysis was done to predict the pathogenicity of missense variant rs699 and its effect on structure and function of AGT; however, rs5186, a 3′ UTR non-coding variant of the AGTR1 gene was excluded. Our findings showed that the AGT (rs699) T allele was more frequent in controls (46.9%) than in CKD cases (35.3%), suggesting a potential protective role against CKD (p = 0.001). No significant associations were observed in AGTR1 (rs5186) and CKD (p > 0.05). Furthermore, the studied polymorphisms did not significantly affect serum creatinine, urea, or eGFR levels in CKD patients. In silico analysis predicted the AGT rs699 variant to be likely benign, with slightly decreased AGT protein stability and binding affinity to renin.

CONCLUSIONS: The results suggest a significant association of the AGT (rs699) polymorphism with CKD. Computational findings support a limited functional impact of the rs699 variant. Further research, including functional studies and investigations in larger cohorts, is warranted to assess the potential of these polymorphisms as biomarkers for CKD risk.

PMID:41222805 | DOI:10.1007/s11033-025-11217-4

HEC Forum. 2025 Nov 12. doi: 10.1007/s10730-025-09570-9. Online ahead of print.

ABSTRACT

Despite the existence of codified ethical standards in healthcare, their consistent application in clinical decision-making remains underexplored. This study quantitatively evaluates the knowledge, attitudes and practices of Moroccan healthcare professionals regarding medical ethics. Guided by a positivist epistemology and a hypothetico-deductive methodology, a validated questionnaire was administered to 200 practitioners from diverse medical backgrounds. Descriptive statistics revealed that 96% of respondents report disclosing medical errors, yet only 50% had formal exposure to medical ethics, and 51.5% were familiar with the national code of ethics. Correlation analysis indicated weak but positive associations between ethical training and disclosure practices (r ≈ 0.07). Multiple linear regression demonstrated that variables such as knowledge of ethics (β = 0.111) and training (β = 0.022) had modest, non-significant effects on ethical conduct (R² = 1.05%). Attitudinal factors, such as acceptance of placebo use (β = – 0.121, p = 0.094), showed marginal influence, while respect for patient autonomy and additional training did not significantly predict behavior. Sociodemographic variables (age, experience, rank) also lacked predictive power, though the main model constant (β ≈ 1.0, p < 0.001) suggests a generally strong ethical baseline. These findings show the importance of targeted ethics education and institutional reinforcement to strengthen ethical clinical behavior and promote transparency within the Moroccan healthcare system.

PMID:41222799 | DOI:10.1007/s10730-025-09570-9

Adv Ther. 2025 Nov 12. doi: 10.1007/s12325-025-03402-5. Online ahead of print.

ABSTRACT

INTRODUCTION: Immunoglobulin A (IgA) nephropathy is a rare renal condition associated with a high risk of kidney failure. However, conducting phase 3 clinical trials with kidney failure as a primary endpoint is generally not feasible because of sample size and protracted follow-up requirements. Hence, surrogate outcomes are necessary when assessing new treatments in randomized controlled trials. Previous meta-analyses have assessed the validity of early change in proteinuria as a surrogate endpoint, and the present research updates the analysis with additional patient-level data.

METHODS: The same methodology as two previously published individual patient-level meta-analyses was used, with additional data from the PROTECT study included. Early change in proteinuria was defined as change from baseline at 9 months, and the clinical endpoint was defined as the composite of doubling of serum creatinine level, kidney failure or death. The association of treatment effects was ascertained using individual patient data via a Bayesian mixed-effect regression model to relate treatment effects on the clinical outcome to treatment effects on proteinuria with study as the unit of analysis.

RESULTS: The updated individual patient-level meta-analysis including data from PROTECT resulted in an overall slope of 1.03 (95% Bayesian credible interval – 0.40 to 2.34) between treatment effects on early change in proteinuria versus longer-term treatment effects on the clinical outcome, with an R² of 0.80 (95% Bayesian credible interval 0.07 to1.00). This corroborates the use of early proteinuria as a valid surrogate endpoint for a treatment’s effect on progression to kidney failure in studies of IgA nephropathy.

CONCLUSIONS: The FDA and EMA have accepted proteinuria as a valid surrogate outcome for use in clinical trials of new interventions for the treatment of IgA nephropathy, and the present analysis provides further indications that interventions that reduce proteinuria in a short-term trial are likely to improve kidney outcomes over the long term.

PMID:41222790 | DOI:10.1007/s12325-025-03402-5

BJOG. 2025 Nov 12. doi: 10.1111/1471-0528.70080. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess whether Er:YAG laser is superior to sham in treating women with mild/moderate stress urinary incontinence (SUI).

DESIGN: A single blinded, multi-centre RCT comparing Er:YAG laser to sham in women with mild/moderate SUI with patients blinded to allocated treatment.

SETTING: Three urogynaecology departments in United Kingdom, Switzerland and Germany.

POPULATION OR SAMPLE: 79 participants were recruited with mild/moderate SUI.

METHODS: Participants were randomised (2 active: 1 sham) receiving 3 treatment sessions. Participants were assessed at baseline and 6 months post final treatment.

MAIN OUTCOME MEASURES: Primary outcome measure: cure defined as at least 50% reduction in 1 h pad weigh test (PWT) at 6 months compared to baseline (as per FDA guidelines).

SECONDARY OUTCOMES: Change in PWT, (ICIQ-UI SF), (PISQ-12), cough test standing and supine and visual analogue score for pain.

RESULTS: 32/51 patients (62.7%) of patients were defined as cured (per FDA guidelines) in the laser group compared with 4/23 (18.2%) cure in the sham group, p < 0.001, (OR 7.6, 2.2-25.8 95% CI). There was a statistically and clinically significant improvement in patients treated with laser in PWT, ICIQ-UI SF and PISQ-12 at 6 months (3 g, p = 0.002, 5 points, p < 0.001 and 6 points, p < 0.001, respectively). There was no evidence of statistically significant differences in the sham group.

CONCLUSIONS: This RCT demonstrates a beneficial effect of Er:YAG laser in women with mild/moderate SUI compared with sham.

TRIAL REGISTRATION: www.

CLINICALTRIALS: gov (NCT03996070).

PMID:41221700 | DOI:10.1111/1471-0528.70080

Am J Hum Biol. 2025 Nov;37(11):e70168. doi: 10.1002/ajhb.70168.

ABSTRACT

OBJECTIVES: This study investigates how marital and maternal statuses influenced female mortality in the Tang Dynasty (618-907 ce), China. It challenges the focus on reproductive risks by exploring both biological and social factors affecting female mortality in reproductive and post-reproductive years.

MATERIALS AND METHODS: Epitaph data were analyzed from four female groups: bureaucrats’ wives (married, reproductive), eunuchs’ wives (married, nonreproductive due to husband’s castration), never-married religious women (never married, nonreproductive), and widowed religious women (reproductive, later left marriage). Ages at death were illustrated using summary statistics and kernel density plots, analyzed using bootstrapped polynomial regression, pairwise comparisons with 9999 replicates, and Kaplan-Meier survival curves. Male bureaucrats and eunuchs were also included for contextual comparison.

RESULTS: Bureaucrats’ wives had a significantly lower adjusted mean age at death than nonreproductive groups, eunuchs’ wives (-7.43 years; p = 0.006), and never-married religious women (-7.07 years; p = 0.006). Survival curves support that reproductive risks shaped mortality. Among post-reproductive women, those who remained in marital roles had a significantly lower mean age at death than those who joined a religious order (-3.9 years; p = 0.003). The negative effects of remaining in marriage in later life were supported.

DISCUSSION: Female mortality resulted from a complex interplay of biological and social factors. Reproductive risks primarily affected females during younger ages. During post-reproductive years, remaining in marriage and widowhood negatively affected survival, while entering religious orders was protective.

PMID:41221699 | DOI:10.1002/ajhb.70168

J Pharm Pract. 2025 Nov 12:8971900251395191. doi: 10.1177/08971900251395191. Online ahead of print.

ABSTRACT

Background: Several strategies described in the literature regarding the role of pharmacist-led educational interventions to healthcare providers, however, evidence available on the role of education in the Emergency Department (ED) setting on discharge prescriptions is limited. The purpose of this study was to evaluate the impact of pharmacist-led education on antimicrobial prescribing at discharge from the ED. Objective: To determine whether pharmacist-led provider education improves patient outcomes by reducing medication-related errors in the ED when prescribing antimicrobials at discharge for skin and soft tissue infections (SSTIs), urinary tract infections (UTIs), and community-acquired pneumonia (CAP). Methods: This was a retrospective pre-vs post-intervention cohort study at Maimonides Medical Center (MMC). A total of 192 patients in the pre-intervention period and 181 patients in the post-intervention period were included. The primary endpoint was appropriateness of antimicrobial discharge prescriptions pre- and post-intervention. Results: In the pre-intervention period, 17.7% of patients had an SSTI, 47.4% had a UTI, and 34.9% had CAP. In the post-intervention period, 15.5% of patients had an SSTI, 51.4% had a UTI, and 33.1% had CAP. After implementation of pharmacist-led provider education, there was a statistically significant increase in the number of appropriate antimicrobial discharge prescriptions in the post-intervention period, 86.7% vs 75.5% respectively (P = .008). While there was no statistically significant difference in recurrent infections, there was a trend towards improvement in post-intervention period, 3.9% vs 5.7% respectively (P = .473). Conclusion: Pharmacist-led provider education significantly improved prescribing patterns for antimicrobial discharge prescriptions.

PMID:41221665 | DOI:10.1177/08971900251395191