Tag: pubmed

JCO Clin Cancer Inform. 2025 Aug;9:e2500055. doi: 10.1200/CCI-25-00055. Epub 2025 Aug 5.

ABSTRACT

PURPOSE: The COVID-19 pandemic disrupted cancer screenings in the United States, with disproportionate impact on health disparity populations. The objective of this study was to examine the impact of the pandemic on routine screening for breast, cervical, and colorectal cancer among Medicaid enrollees.

MATERIALS AND METHODS: This study is a retrospective, descriptive analysis to estimate the rate of breast, colorectal, and cervical cancer screenings among Medicaid enrollees age 50-75 years in New Jersey. Secondary enrollment and claims from the 2017-2022 Medicaid Management Information System were used. The results were stratified by screening type and socioeconomic factors. Bivariate analysis assessed between-group differences.

RESULTS: Although April 2020 had the lowest screening rates in the 6-year period, rates for all three cancer types rebounded to prepandemic levels by late summer 2020. In 2022, breast cancer screening rates exceeded previous peaks. However, cervical and colorectal screening rates did not resume their prepandemic trajectories. Key findings comparing 2022 with 2019 were (1) across all three cancer screening groups, the younger group (50-64 years) had a higher screening rate than the older group (65-75 years); (2) Hispanic enrollees consistently had the highest screening rates; (3) the screening rate among dually eligible enrollees increased throughout the pandemic; and (4) there was wide screening variation by geographic region.

CONCLUSION: Multilevel, multisectoral approaches, including policy and health system strategies, are critical to addressing gaps in care for Medicaid enrollees. Future efforts should focus on bolstering cervical and colorectal cancer screening rates and ensuring equitable access to cancer screening and treatment.

PMID:40763321 | DOI:10.1200/CCI-25-00055

J Clin Oncol. 2025 Aug 5:JCO2500812. doi: 10.1200/JCO-25-00812. Online ahead of print.

ABSTRACT

PURPOSE: The US Food and Drug Administration (FDA) approved trastuzumab deruxtecan (T-DXd, DS-8201a) for patients with unresectable or metastatic breast cancer (MBC) who have tumor progression on previous endocrine therapy (ET) and have hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-low (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization [ISH]-) or HER2-ultralow (IHC 0 with membrane staining) tumors.

PATIENTS AND METHODS: Approval was based on DESTINY-Breast06, a randomized, open-label, multicenter trial of 866 patients with HR-positive breast cancer, including 713 patients with HER2-low and 153 with HER2-ultralow tumors. Patients were required to have progressed on previous ET and must not have received chemotherapy in the metastatic setting. Random assignment was 1:1 to T-DXd or investigator’s choice of chemotherapy (paclitaxel, nab-paclitaxel, or capecitabine). Previous CDK4/6 inhibitor treatment, previous taxane use in the (neo)adjuvant setting, and HER2 status (IHC2+/ISH- v 1+ v IHC 0 with membrane staining) were stratification factors.

RESULTS: There was a statistically significant improvement in progression-free survival (PFS) by blinded independent central review (BICR) in the HER2-low population of 13.2 months (95% CI, 11.4 to 15.2) in the T-DXd arm and 8.1 months (95% CI, 7.0 to 9.0) in the chemotherapy arm (hazard ratio [HR], 0.62 [95% CI, 0.52 to 0.75], P < .0001). The trial also met its key secondary end point, PFS by BICR in the overall population, with a HR of 0.64 (95% CI, 0.54 to 0.76, P < .0001).

CONCLUSION: T-DXd is a new treatment option for patients with hormone receptor-positive, unresectable or MBC with HER2-low or HER2-ultralow tumors who have experienced progression on ET. This is the first indication specifying the category of HER2-ultralow expression in breast cancer, and an assay to select patients for this category was approved contemporaneously.

PMID:40763319 | DOI:10.1200/JCO-25-00812

PLoS Comput Biol. 2025 Aug 5;21(8):e1013361. doi: 10.1371/journal.pcbi.1013361. Online ahead of print.

ABSTRACT

The nosocomial transmission of respiratory pathogens is an ongoing healthcare challenge, with consequences for the health of vulnerable individuals. Outbreaks in hospitals can require the closure of bays or entire wards, reducing hospital capacity and having a financial impact upon healthcare providers. Here we evaluate a novel strategy of pre-exposure prophylaxis as a means to reduce the nosocomial transmission of SARS-CoV-2. We model the effect of ursodeoxycholic acid (UDCA) upon levels of angiotensin-converting enzyme 2 (ACE2) expression, SARS-CoV-2 viral entry, and ultimately the probability of an infection. We then implement this model within simulations describing the spread of SARS-CoV-2 infections within a hospital context, simulating an intervention in which UDCA is given to patients on a ward for 10 days following the detection of a case of SARS-CoV-2 on that ward. Under default model parameters we infer a potential 17% reduction in the nosocomial transmission of SARS-CoV-2 to patients, with increased importation of cases into the hospital increasing the effectiveness of the intervention, and of the order 1000-2000 patient treatment days per nosocomial patient infection prevented. Our study provides preliminary evidence of the value of pre-exposure prophylaxis with UDCA as a strategy to reduce nosocomial SARS-CoV-2 transmission.

PMID:40763307 | DOI:10.1371/journal.pcbi.1013361

Pediatr Infect Dis J. 2025 Jun 1;44(6):e225-e228. doi: 10.1097/INF.0000000000004734. Epub 2025 Jan 10.

ABSTRACT

In this brief report, we describe Mycoplasma pneumoniae infections admitted to our pediatric intensive care unit during 2023-2024. We compare with the previous 6 years and analyze their treatments and outcomes. We observe an increase of cases, half of them with underlying conditions. Hypoxemia was their main severity sign. Viral coinfections were common. Bacterial coinfections appeared to worsen outcomes.

PMID:40763306 | DOI:10.1097/INF.0000000000004734

CPT Pharmacometrics Syst Pharmacol. 2025 Aug 5. doi: 10.1002/psp4.70082. Online ahead of print.

ABSTRACT

The development of new treatments for rare neurological diseases (RNDs) may be very challenging due to limited natural history data, lack of relevant biomarkers and clinical endpoints, small and heterogeneous patient populations, and other complexities. A systematic approach is needed for comparing various design and analysis strategies to identify “optimal” approaches for a clinical trial in a chosen RND with the given resource constraints. For this purpose, we propose a pharmacometrics-informed clinical scenario evaluation framework (CSE-PMx), which includes some important research hallmarks relevant to RND clinical trials: a disease progression model for simulating individual longitudinal outcomes, the choice of a suitable randomization method for trial design, and an option to perform subsequent statistical analysis with randomization tests. We illustrate the utility of CSE-PMx for an exemplary randomized trial to compare the disease-modifying effect of an experimental treatment versus control in patients with Autosomal-Recessive Spastic Ataxia Charlevoix Saguenay (ARSACS). In the considered example, our simulation evidence suggests that a nonlinear mixed-effects model (NLMEM) with a population-based likelihood ratio test analysis is valid, robust, and more powerful than some conventional methods such as two-sample t-test, analysis of covariance (ANCOVA), or a mixed model with repeated measurements (MMRM). Our proposed framework is very flexible and generalizable to clinical research in other rare disease indications.

PMID:40763305 | DOI:10.1002/psp4.70082

PLoS Negl Trop Dis. 2025 Aug 5;19(8):e0013313. doi: 10.1371/journal.pntd.0013313. Online ahead of print.

ABSTRACT

BACKGROUND: Taenia solium (T. solium), a neglected zoonotic tapeworm transmitted between humans and pigs, is a leading cause of acquired epilepsy in endemic areas where it is propagated by poor sanitation and pig husbandry practices. The World Health Organisation (WHO) NTD roadmap 2021-2030, recommended that targeted control interventions need to be initiated, and intensified in T. solium hyperendemic areas. Geospatial risk maps have identified Northern Uganda as a potential hyperendemic area. This study aimed to validate these findings and provide contextual evidence to support design and implementation of targeted interventions to control the parasite.

METHODS: A cross-sectional study was conducted in 2023 in four districts of northern Uganda. Blood samples were collected for serological analysis from 1049 pigs drawn from 714 households. Self-reported and observational data, and environmental variables from secondary sources were also collected. A subset of the seropositive pigs was dissected to confirm the presence of the parasite. The crude prevalence was adjusted for the test’s sensitivity (Se = 0.867) and specificity (Sp = 0.947). Risk factors for seropositivity were evaluated using generalized mixed-effects models run in both R and Stata statistical software.

RESULTS: The prevalence of porcine cysticercosis in this area was 17.4% (15.1- 19.7; 95% CI). Pig level predictors of infection were pigs that were eight months or older (odds ratio (OR)=1.88; p = 0.001), and non-local breeds of the pig (OR=1.7; p = 0.01). Household-level risk factors included the use of borehole water, (OR=6.39; P = 0.001), free-roaming pigs (OR=1.92; p = 0.023), whilst the presence of a toilet in the compound was protective (OR=0.64, p = 0.05).

CONCLUSION: Our findings confirm that the study area is hyperendemic for T. solium infections, as the geospatial risk maps predicted. To achieve the targets laid out in the 2021-2030 WHO roadmap for control of NTDs, this region requires intensified targeted control interventions, preferably targeting both human and porcine hosts using the One Health approach.

PMID:40763303 | DOI:10.1371/journal.pntd.0013313

PLoS One. 2025 Aug 5;20(8):e0330029. doi: 10.1371/journal.pone.0330029. eCollection 2025.

ABSTRACT

BACKGROUND: Progress testing is a longitudinal assessment method used to monitor the acquisition and retention of knowledge throughout medical training. While progress tests (PTs) have been widely adopted internationally through collaborative networks of medical schools, in Peru, their implementation has been primarily institutional. This study aimed to evaluate longitudinal trends in PT scores at a Peruvian medical school.

METHODS: We conducted a longitudinal analysis using data from PTs administered annually between 2017 and 2024. The PT assessed students’ knowledge based on the subjects completed at the time of testing. Scores ranged from 0 to 250 and were converted to a 20-point scale. Independent variables included number of PTs taken (1-7), year of entry into medical school (entry cohort; 2017-2024), year of test administration (2017-2024), and sex. Generalized estimating equations (GEE) were used to assess score trends over time, applying an identity link function with a Gaussian distribution and robust standard errors clustered by student ID.

RESULTS: We included 1,899 test scores from 669 medical students. The mean score across all tests was 9.19 (standard deviation = 2.34). No consistent upward trend in PT scores was observed over the study period; scores decreased by 0.088 points per additional year (CI95% CI: -0.147 to -0.029, p = 0.003). Students who completed five PTs scored significantly higher than those who took four (β = 1.40; 95% CI: 0.79 to 2.01). When stratified by entry cohort, no sustained improvement in scores was observed within cohorts over time.

CONCLUSION: Over an eight-year period of administering a progress test at a Peruvian medical school, student performance remained stable, with an average of approximately 50% of questions answered correctly per test. Longitudinal analysis did not reveal a sustained increase in scores as students advanced through the curriculum. This pattern may be explained by the PT design, which assesses only the content covered by students at the time of each administration, in contrast to other PTs that measure end-of-curriculum knowledge across all cohorts. Nevertheless, an increase in median scores was observed during the transition from basic science to clinical subjects.

PMID:40763293 | DOI:10.1371/journal.pone.0330029

PLoS One. 2025 Aug 5;20(8):e0329893. doi: 10.1371/journal.pone.0329893. eCollection 2025.

ABSTRACT

Longitudinal studies that analyze the changes in the axial diffusivity (AxD) and radial diffusivity (RD) values over time can elucidate the progression of white matter damage and its causal relationship with cognitive decline. This study aimed to investigate the longitudinal changes in white matter integrity based on AxD and RD and their association with cognitive decline in patients with mild cognitive impairment (MCI) that progressed to Alzheimer’s disease (AD). Eighteen participants diagnosed with MCI at baseline and AD at the follow-up examination were selected from the AD Neuroimaging Initiative and included in this 2-year study Tract-based spatial statistics (TBSS) was used to assess longitudinal changes in WM. Voxel-wise and region-of-interest (ROI) analyses were conducted, and statistical models controlled for age, sex, education, and APOE ε4 status. Correlation and multiple regression analyses were performed to examine the association between AxD/RD changes and changes in clinical dementia rating (CDR) scores. Significant increases in AxD and RD were observed over 2 years in widespread WM tracts, including the corpus callosum, internal capsule, corona radiata, cingulum, superior longitudinal fasciculus, and fornix. AxD changes, particularly in the left retrolenticular internal capsule, left posterior corona radiata, left fornix, and right superior longitudinal fasciculus, showed significant correlations with cognitive decline. In contrast, RD changes were not significantly associated with CDR changes in any region. Multivariate regression analysis identified AxD in the left retrolenticular internal capsule as a significant independent predictor of CDR changes. AxD was sensitive to microstructural alterations in WM associated with cognitive decline during the transition from MCI to AD and may serve as a valuable biomarker for early detection and monitoring of AD progression. Longitudinal DTI analyses provide critical insights into the temporal dynamics of WM degeneration and its role in clinical deterioration.

PMID:40763286 | DOI:10.1371/journal.pone.0329893

PLoS One. 2025 Aug 5;20(8):e0329350. doi: 10.1371/journal.pone.0329350. eCollection 2025.

ABSTRACT

The essence of the influence maximization (IM) problem is how to identify the set of seed nodes so that the node numbers ultimately affected in the network reach the maximum under a certain spreading model. In the field of influence maximization research, the investigation of seed nodes identifying algorithms is a hot yet challenging work. Although conventional greedy algorithms and heuristic algorithms have high performance, their efficiency remains a challenge when applied to large-scale social networks. In recent years, swarm intelligence-based optimization algorithms have seen increasing application in addressing this problem, with notable improvements in performance. However, the efficiency of these swarm intelligence-based algorithms still needs to be improved in large-scale social networks. Based on this issue, a parallel discrete crow search algorithm (PDCSA) designed for parallel computing is proposed. Based on the evolution characteristics, PDCSA makes full use of the efficiency advantage of parallel computing to improve the time efficiency of solving IM problems.The results of experiments conducted on six datasets show that PDCSA achieves performance comparable to state-of-the-art algorithms, with the added advantages of high efficiency and robustness.

PMID:40763283 | DOI:10.1371/journal.pone.0329350

Blood Adv. 2025 Aug 5:bloodadvances.2025016117. doi: 10.1182/bloodadvances.2025016117. Online ahead of print.

ABSTRACT

High-grade B-cell lymphomas [HGBL, including double-hit/triple-hit (HGBL-DH/TH) and HGBL not otherwise specified (HGBL-NOS)] have a poor prognosis upon failure of first-line therapy. Anti-CD19 chimeric antigen receptor (CAR) T-cells for third-line aggressive large B-cell lymphomas resulted in long-term remission in up to 40% of patients. This study evaluated factors that can predict outcomes in HGBL compared to Diffuse Large B-cell lymphomas (DLBCL). We assessed the predictive value of the subtype (HGBL versus DLBCL) using weighted log-rank tests and weighted Cox models, and overall survival (OS) following CAR T-cells failure. The prospective study cohort comprised 432 patients [HGBL (n=78); DLBCL (n=354)] with a median follow-up of 22.8 months for HGBL and 18 months for DLBCL. Interestingly, there was no statistically significant difference in progression-free survival (PFS) and OS between patients with HGBL-DH/TH lymphomas versus other high-grade histotypes. CAR T-cells expansion in HGBL did not correlate with response. Before weighting, a significant difference in OS was observed between HGBL versus DLBCL (24-month OS: 37% vs. 49%, p=0.0036). After weighting, the difference in 2-year OS remained significant (37% versus 44%, p=0.0343), and it was related to an inferior survival following CAR T-cells failure. The 2-year NRM and incidence of secondary malignancies were similar in HGBL and DLBCL patients (11% versus 11%, p=0.830; 6.4% versus 11.4%, p=0.844). Among patients failing CAR T-cells, the 1-year OS post failure was significantly higher in transformed than de novo DLBCL and HGBL (59% versus 32% versus 11%, <0.0004). Earlier use of CAR T-cells may improve the outcome of HGBL. NCT06339255.

PMID:40763273 | DOI:10.1182/bloodadvances.2025016117