Nevin Manimala

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

J Health Organ Manag. 2025 Aug 5:1-17. doi: 10.1108/JHOM-01-2025-0036. Online ahead of print.

ABSTRACT

PURPOSE: Understanding what drives turnover among nurses and how to address that is an important issue facing hospitals, society and organizational researchers. While turnover has many causes, the perception that organizations have failed to meet expected norms (a perceived psychological contract breach – PCB) is a salient cause. Due to dynamic changes in the workplace, PCBs increase in the workplace, and when PCBs are perceived, turnover intention (TI) increases. We investigate whether individual differences among nurses in the need to belong (NTB) determine exit or voice behavior when PCB is perceived.

DESIGN/METHODOLOGY/APPROACH: Using survey methodology and a sample of nurses currently employed, we tested the moderating effects of individual differences in NTB on the PCB-TI link.

FINDINGS: The strength of PCB leading to TI was significantly moderated by the level of NTB. After accounting for perceived job alternatives and the need for affiliation, the interaction between NTB and PCB was statistically significant ((Δ R2 = 0.02) in explaining TI.

ORIGINALITY/VALUE: There is limited research on the boundary conditions surrounding the PCB-TI relationship, and this study brings in a unique perspective by incorporating an individual difference on the PCB-TI relationship. The study has implications for the social exchange theory, refinement of the NTB construct and models of turnover, and its results highlight the importance of supervisors and managers honoring obligations and promises made to nurses.

PMID:40763245 | DOI:10.1108/JHOM-01-2025-0036

Hum Vaccin Immunother. 2025 Dec;21(1):2535755. doi: 10.1080/21645515.2025.2535755. Epub 2025 Aug 5.

ABSTRACT

Older adults and adults with certain chronic conditions are at increased risk for severe respiratory syncytial virus (RSV) disease. In 2023, RSV vaccines first became available in the United States (US) for adults aged ≥60 years. This retrospective database analysis evaluated RSV vaccination uptake from August 2023-February 2025 using IQVIA’s open-source pharmacy (LRx) and medical (Dx) claims data. The study included US adults aged ≥60 years with ≥1 claim in 2023. For those without RSV vaccination in 2023, ≥1 claim was also required between January 2024-February 2025. Uptake was assessed as the number and percentage of eligible adults who received an RSV vaccine during the study period. Multivariable logistic regression modeling explored factors associated with RSV vaccination. Nearly 12.8 million adults aged ≥60 years (16.4%) received RSV vaccination between August 2023-February 2025. Uptake generally increased with age and was higher among those with ≥1 potential risk factor for severe RSV disease. Disparities in uptake were observed by race, ethnicity, and other social determinants of health. In multivariable analyses, odds of RSV vaccination were nearly 24 times higher for those who received ≥1 non-RSV vaccine from August 2023-February 2025 versus those who had not. Despite the increased risk of severe RSV disease among older adults and those with certain risk factors, relatively limited RSV vaccination uptake was observed during the 2023-2025 seasons, with disparities observed. Additional efforts are needed to support RSV prevention among those at highest risk and to ensure equitable access to vaccination.

PMID:40763207 | DOI:10.1080/21645515.2025.2535755

Comput Inform Nurs. 2025 Aug 1. doi: 10.1097/CIN.0000000000001351. Online ahead of print.

ABSTRACT

Artificial intelligence, including chatbots that produce outputs in response to user prompts, is poised to revolutionize nursing education and program evaluation. This article summarizes a pilot evaluation of three core features in a chatbot system: (1) defining a persona or system prompt, (2) creating specific task prompts, and (3) developing an improvement mechanism. First, an “act as” system prompt was written to generate “Future-FLO” based on professional values. Second, a task prompt was written to generate outputs specific to program evaluation. Third, a separate ImproverBot was created to provide structured assessments of chatbot outputs. Human raters, knowledgeable about grant goals, provided feedback on AI-generated outputs from FLO and non-FLO system prompts. The ImproverBot rated the same outputs as the human raters on accuracy, completeness, and usefulness. Statistical tests were used to compare ratings across AI versions and rater types. The custom prompt provided no added benefits compared with using the standard model, as rated by human raters and the ImproverBot. The ImproverBot gave significantly higher ratings than human raters. Comments indicated that outputs were error-filled and unreliable. Engaging with artificial intelligence to support the work of grant evaluation will require ongoing efforts to develop chatbots and evaluate their outputs.

PMID:40763202 | DOI:10.1097/CIN.0000000000001351

PLOS Glob Public Health. 2025 Aug 5;5(8):e0004966. doi: 10.1371/journal.pgph.0004966. eCollection 2025.

ABSTRACT

Interventions are needed to reduce the global disparity in prostate cancer outcomes. Our research aimed to evaluate the acceptability, feasibility and appropriateness of a stakeholder-developed intervention for the early detection of prostate cancer in Nigeria. This was a mixed methods study conducted at three cities in Nigeria. The intervention mapping framework was utilized as the primary framework for the study. During intervention development, a six-member team developed an implementation research logic model and then conducted stakeholder engagement to prioritize the preliminary intervention strategies among 12 purposively selected stakeholders. This was followed by brainstorming sessions by the same intervention development team for the selection of multi-faceted intervention strategies. Key informant interviews were then conducted among 10 purposively selected Nigerian clinicians, institutional leaders, and policymakers for contextual inquiry on the developed intervention. Descriptive statistics and qualitative analysis were performed. At the end of the intervention development process, the primary intervention strategies included supported risk assessment and patient navigation. The secondary strategies were education and training, and cancer information communication. The main actors of the intervention were trained community-based healthcare providers while the targeted population were adult men 40 years and above. The informants strongly noted that the intervention actions were feasible. Regarding acceptability, informants strongly believed that the intervention had numerous relative advantages but noted its complexity and the potential risk for overdiagnosis. Informants also consistently acknowledged that the intervention was appropriate but had mixed disposition on implementation preparedness. Further adaptations were made to address the stakeholder-identified gaps. In conclusion, this study developed a prostate cancer early detection intervention with preliminary feasibility, the first rigorously developed systems-strengthening intervention to optimize the detection of early-stage prostate cancer in Nigeria. A pilot implementation trial will be helpful in further testing the intervention in the field setting.

PMID:40763189 | DOI:10.1371/journal.pgph.0004966