Nevin Manimala

Int J Cancer. 2025 Oct 29. doi: 10.1002/ijc.70211. Online ahead of print.

ABSTRACT

The combination of two immune checkpoint inhibitors (CPI) or a CPI with a tyrosine kinase inhibitor (TKI) has expanded the therapeutic options for advanced/metastatic renal cell carcinoma (aRCC) beyond TKI monotherapy. In the absence of head-to-head randomized trials comparing these strategies, we estimate their real-world effectiveness by emulating a hypothetical randomized trial. A total of 936 patients with aRCC from the prospective, observational, multicenter clinical registry CARAT (NCT03374267) starting first-line treatment after January 15, 2019, were included. Inverse probability of treatment weighting (IPTW) was used to compare first-line CPI + TKI (n = 447), CPI + CPI (n = 257), and TKI monotherapy (n = 166). Real-world progression-free survival (rwPFS), overall survival (OS), and time-to-deterioration (TTD) of health-related quality of life (HRQoL) were analyzed, also stratified by patients’ prognostic risk according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model. IPTW-adjusted median rwPFS and OS independent of IMDC risk were 12.3 [10.4-15.6] and 29.0 months [25.6-36.3] for TKI + CPI, 8.3 [6.5-10.9] and 21.9 months [16.3-34.5] for CPI + CPI, and 8.5 [6.4-10.0] and 31.7 months [21.0-40.0] for TKI monotherapy. Compared to CPI + TKI, survival tended to be worse for CPI + CPI (rwPFS: hazard ratio (HR) 1.25 [1.00-1.58]; OS: HR 1.25 [0.95, 1.63]). This finding was more pronounced for rwPFS in patients at intermediate risk. Median TTD of HRQoL did not substantially differ between the strategies. Despite the lack of statistically significant HR differences in rwPFS and OS, there was a trend toward superior survival with first-line CPI + TKI compared to CPI + CPI. TKI monotherapy may remain a viable first-line treatment option in selected patient populations. Further analyses, preferentially randomized clinical trials, are warranted.

PMID:41159297 | DOI:10.1002/ijc.70211

J Helminthol. 2025 Oct 29;99:e118. doi: 10.1017/S0022149X25100850.

ABSTRACT

This study presents data on helminth communities from 93 Hooded Crows (Corvus cornix). The dataset includes historical and contemporary records from three localities in Ukraine with different levels of urbanisation: Kyiv, the Middle Dnipro River, and Polissya. Thirty-two helminth species were identified, including 14 trematodes, six cestodes, 11 nematodes, and one acanthocephalan. The nematodes Eufilariella delicata and Hadjelia truncata are documented in Hooded Crows for the first time. During the statistical analysis, it was revealed that the used dataset is insufficient for robust inference regarding the impact of urbanisation on helminth communities due to its temporal and spatial biases. Despite the limitation, the data offer information for future research on the influence of urbanisation on helminth biodiversity in avian hosts.

PMID:41159293 | DOI:10.1017/S0022149X25100850

Microbiologyopen. 2025 Dec;14(6):e70072. doi: 10.1002/mbo3.70072.

ABSTRACT

This study aimed to optimize culture media to enhance vancomycin production by Amycolatopsis orientalis. Using a combination of one-variable-at-a-time (OVAT) analysis, nutrient screening, and knockout experiments, we identified critical factors influencing biomass formation and antibiotic yield. Among tested carbon sources, maltodextrin significantly increased vancomycin production (bioassay zone: 13.33 mm), while glycerol favored biomass growth but had minimal impact on antibiotic synthesis. For nitrogen sources, soybean meal and soya flour optimally supported both biomass and vancomycin yield. Salt supplementation revealed that CaCO₃ and MgSO₄ improved mycelial growth, whereas knockout studies demonstrated that dextrose and soya peptone were essential for vancomycin production. Notably, omitting phosphate (K₂HPO₄) enhanced both biomass and antibiotic yield, suggesting phosphate repression of secondary metabolism. Seed media trials identified SS-6 and SS-10 + A as optimal for mycelial growth, highlighting the importance of early-stage culture conditions for fermentation outcomes. These findings provide a cost-effective, scalable strategy for maximizing vancomycin production, with potential for further optimization using statistical or metabolic flux approaches.

PMID:41159273 | DOI:10.1002/mbo3.70072

Am J Hosp Palliat Care. 2025 Oct 29:10499091251391420. doi: 10.1177/10499091251391420. Online ahead of print.

ABSTRACT

BackgroundMalignant bowel obstruction (MBO) is a complex clinical entity and there remains a relative lack of high-quality comparative trials on surgical management, in part due to a heterogeneous patient population and different treatment modalities which contribute to challenges in trial design and completion. SWOG S1316 is the only prospective randomized trial evaluating surgical vs non-surgical management of MBO and involved a trial framework in which patients were recruited for a randomization pathway as well as a patient choice pathway. Importantly, successful completion of S1316 required numerous amendment modifications to the trial during its course. We aimed to highlight aspects of S1316 trial design, execution, and modification that potentially contributed to trial completion.MethodsIterative qualitative content analysis of trial modification amendments through the course of the trial from 2015 to 2020.Results133 unique amendments were made to S1316 from 2015 to 2020. We found four dominant domains for the amendments: Accrual Barriers, Study Design Changes, Data Collection Issues, and Clarifications. Accrual amendments were essential to completing the trial and included increasing participating sites from six to 30 (including international sites) and the inclusion of Spanish-speaking participants (11% of final study population).ConclusionsContent analysis of S1316 trial amendments highlighted that Accrual amendments were important in trial completion. Future investigators may benefit from better anticipating trial modifications as they design their studies. It is likely that rapid initiation of trial amendments can lead to improved accrual and study completion.

PMID:41159270 | DOI:10.1177/10499091251391420

Andrology. 2025 Oct 29. doi: 10.1111/andr.70131. Online ahead of print.

ABSTRACT

BACKGROUND: Epidemiological studies have reported an association between advanced paternal age at conception and an increased risk of neurodevelopmental disorders in offspring, such as autism spectrum disorder. Evidence suggests that DNA methylation alterations in spermatozoa of older men may be transmitted to the feto-placental unit and associated with offspring brain development and behavioral differences later in childhood.

OBJECTIVE: We aimed to assess the association of advanced paternal age with DNA methylation alterations in the human placenta and compare the results to previous findings in spermatozoa.

METHODS: For this study, 64 placenta samples from the Design, Develop, and Discover (3D) prospective birth cohort study were categorized based on paternal age at conception. DNA methylation of the placenta was interrogated using the Illumina 850K array. There were no differentially methylated sites found to be statistically significant after correction for multiple comparisons, therefore sites with significant nominal p values < 0.05 were assessed and used to define differentially methylated regions (DMRs) associated with genes.

RESULTS: Advanced paternal age was associated with DNA methylation alterations in the placenta at up to 688 genes, with a predominance of hypomethylation (65%), including at eight imprinted loci. About 7% of genes with age-associated DNA methylation changes in placenta overlapped with genes previously reported to show altered DNA methylation in spermatozoa of older men; seven genes common to placenta and spermatozoa had previously been identified in association with susceptibility to autism spectrum disorder. Among loci most affected, we found evidence of sex-specific hypermethylation at genes linked to neurodevelopment (GRM7, EBF3, FOXG1).

CONCLUSION: Our findings suggest that advanced paternal age at conception correlates with altered DNA methylation at a small number of loci in the human placenta, notably affecting genes involved in neurodevelopment. This study highlights the use of the placenta DNA methylome as a surrogate marker for the potential impact of advanced paternal age on the child.

PMID:41159265 | DOI:10.1111/andr.70131

Hypertension. 2025 Oct 29. doi: 10.1161/HYPERTENSIONAHA.125.25202. Online ahead of print.

ABSTRACT

BACKGROUND: Midlife hypertension is linked to white matter injury and dementia, partly through cerebral small vessel disease. We examined how age and systolic blood pressure (SBP) affect progression of 2 cerebral small vessel disease markers, white matter hyperintensity volume (WMHv), and peak width of skeletonized mean diffusivity, in the SPRINT (Systolic Blood Pressure Intervention) and ACCORD (Action to Control Cardiovascular Risk in Diabetes) trials.

METHODS: We assessed age modification of intensive (<120 mm Hg) versus standard (<140 mm Hg) SBP treatment on peak width of skeletonized mean diffusivity (n=440) and asinh transformed WMHv (n=449) progression using linear mixed models in SPRINT using age as a continuous variable and by age group (≤65, 66-75, and >75 years). We performed similar analyses in ACCORD (n=172) on WMHv progression, continuously and in 2 age groups (≤65, 65-79 years).

RESULTS: In SPRINT, the overall interaction between age and SBP on WMHv change was not statistically significant (P=0.18). However, intensive SBP treatment demonstrated a stepwise greater longitudinal WMHv reduction with younger age ≤65 years (-0.19 [95% CI, -0.28 to -0.11]), 66 to 75 years (-0.11 [95% CI, -0.19 to -0.02]), >75 years (-0.06 [95% CI, -0.20 to 0.09]), corresponding to respective reductions of 75%, 34%, and 19%. Intensive treatment produced a similar pattern in peak width of skeletonized mean diffusivity progression, with a significant treatment effect in those ≤65 only (P=0.15 for overall treatment by age interaction). In ACCORD, intensive SBP-lowering was associated with reduced WMHv progression in the younger (≤65) compared with the older age group (P=0.038).

CONCLUSIONS: Intensive SBP control may be more effective in reducing white matter injury at younger compared with older ages.

PMID:41159258 | DOI:10.1161/HYPERTENSIONAHA.125.25202

Curr Med Res Opin. 2025 Oct 29:1-10. doi: 10.1080/03007995.2025.2580031. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare healthcare utilization and costs in RSV- and influenza-vaccinated vs unvaccinated and influenza-only vaccinated older, US adults in 2023.

METHODS: We used a retrospective, cohort study design and the Humana Healthcare Research database to identify individuals enrolled in a Medicare Advantage Prescription drug plan who received RSV vaccination from August 1, 2023 to December 31, 2023. Six-month follow-up through June 30, 2024 was indexed hierarchically on RSV vaccination, influenza vaccination (adults without RSV vaccination), or a primary care visit (adults without RSV and influenza vaccination). We used propensity score matching to adjust for baseline differences and generalized linear regression models to estimate difference-in-difference measures of all-cause inpatient stays, ED visits, outpatient visits, and healthcare costs in the 6 months following index compared with the 12-month baseline period.

RESULTS: RSV- and influenza-vaccinated individuals had lower ED utilization (16.1% vs 18.6%), fewer inpatient stays (5.1% vs 6.6%), and lower Per Person Per Month (PPPM) medical costs (-13.5%) compared with unvaccinated individuals. RSV- and influenza-vaccinated individuals had lower ED utilization (15.6% vs 16.6%), fewer inpatient stays (4.9% vs 5.4%), and lower PPPM medical costs (-4.7%) compared with those who were vaccinated against influenza only. All results were statistically significant at the p < 0.001 level.

CONCLUSIONS: At 6 months following RSV and influenza vaccination, there is a reduction in medical costs due to fewer inpatient stays and ED visits. This finding highlights the clinical and economic value of vaccination programs for reducing healthcare system burden and improving population health outcomes.

PMID:41159254 | DOI:10.1080/03007995.2025.2580031

Public Health Nurs. 2025 Oct 29. doi: 10.1111/phn.70032. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to examine the relationship between parents’ e-health literacy and attitudes toward childhood vaccination.

DESIGN: A descriptive-correlational study.

SAMPLE: The study included 396 parents of children aged 0 to 72 months, recruited between May and December 2022.

MEASUREMENTS: Data were collected using the Demographic Information Form, the E-Health Literacy Scale (E-HLS), and the Caregiver Vaccination Attitudes Scale (CVAS). Analyses were performed using SPSS (version 24).

RESULTS: The mean age of the parents was 30.13 ± 5.22 years. E-HLS scores differed significantly by education level (F = 6.914, p < 0.001, η² = 0.034), with higher scores among university-educated parents (29.72 ± 5.99) compared to those with secondary (26.86 ± 6.64) or primary education (27.48 ± 5.98). Economic status also showed significant differences in E-HLS (KW = 6.982, p = 0.03, ε² = 0.012); parents with good economic status (29.54 ± 5.89) scored higher than those with poor status (26.35 ± 4.32). A statistically significant but weak positive correlation was found between CVAS and E-HLS (r = 0.172, p < 0.001), indicating a small effect size.

CONCLUSIONS: This study showed that parents with higher e-health literacy tend to have more positive attitudes toward childhood vaccination. However, the relationship between these two variables was weak, suggesting only a limited association between e-health literacy and vaccination attitudes. In addition, parents with higher education and better economic status had higher e-health literacy scores. Due to the weak correlation observed, it is important for nurses to understand that increasing e-health literacy alone is unlikely to produce significant improvements in parental vaccination attitudes. Despite the weak correlation, these results may help guide future research exploring the broader context of vaccine attitudes among parents.

PMID:41159252 | DOI:10.1111/phn.70032

Laryngoscope. 2025 Oct 29. doi: 10.1002/lary.70064. Online ahead of print.

NO ABSTRACT

PMID:41159249 | DOI:10.1002/lary.70064

J Res Health Sci. 2025 Sep 15;25(4):e00662. doi: 10.34172/jrhs.9131. Epub 2025 Sep 15.

ABSTRACT

BACKGROUND: The urban poor represent a vulnerable population within society, particularly in terms of maternal health. Economic and access-related limitations often prevent this group from accessing healthcare services, especially in the institutional delivery process. This study aimed to analyze the barriers to institutional delivery among Indonesia’s poor urban society. Study Design: This study employed a cross-sectional design.

METHODS: Data were obtained from the 2023 Indonesian Health Survey, including 7,548 participants. Eight independent variables were analyzed, including age, education, marital status, employment, wealth, insurance, and parity, with institutional delivery used as the dependent variable. Binary logistic regression was employed for analysis.

RESULTS: Approximately 38.1% of Indonesian pregnant women had non-institutional deliveries. All age groups showed a higher likelihood of non-institutional delivery compared to those aged≥45. Lower education levels were associated with a heightened probability of choosing non-institutional delivery. Married women were 0.704 times less likely than divorced or widowed women to give birth in non-institutional settings (AOR: 0.704; 95% CI: 0.693-0.716). Unemployed women had 1.218 times higher likelihood of engaging in non-institutional delivery compared to employed women (AOR: 1.218; 95% CI: 1.1210-1.226). The poorest women were 0.973 times less likely than the poorer group to have non-institutional delivery (AOR: 0.973; 95% CI: 0.967-0.980). Uninsured women were 2.364 times more likely than insured women to give birth outside of healthcare institutions(AOR: 2.364; 95% CI: 2.345-2.379). Women with all other parity levels were less likely than grand multiparous women to have non-institutional deliveries.

CONCLUSION: Seven barrier factors to institutional delivery were younger age, low education, divorced/widowed marital status, unemployment, lower wealth status, lack of insurance, and grand multiparity.

PMID:41159206 | DOI:10.34172/jrhs.9131