Nevin Manimala

Appl Health Econ Health Policy. 2025 Aug 18. doi: 10.1007/s40258-025-00992-7. Online ahead of print.

ABSTRACT

OBJECTIVES: Despite an increasing number of mapping studies being conducted in China, there is an absence of a systematic reviews, which makes it difficult to inform the applications and further assess the methodological consistency, accuracy, and applicability of existing mapping studies. The objective of this review is to consolidate existing evidence, identify methodological gaps, and provide recommendations for improving mapping studies conducted among the Chinese population.

METHODS: A systematic literature search was conducted in 14 databases from inception to May 31, 2025 to identify studies that developed mapping algorithms to estimate health utility values, specifically among Chinese populations. A data template was applied to extract dataset information, source and target measures, mapping types (direct vs indirect), models used, goodness-of-fit indicators, validation methods, and the optimal mapping algorithms selected. Potential challenges for future related studies were further discussed.

RESULTS: A total of 33 studies was included. Most studies (87.9%) focused on mapping disease-specific non-preference-based measures (PBMs) to generic PBMs. The studies covered a broad range of disease areas, including oncology (36.4%), musculoskeletal disorders (15.2%), metabolic diseases (15.2%), cardiovascular diseases (9.1%), and neurological conditions (6.1%). All studies used direct mapping, with the ordinary least squares model (n = 37) being used most frequently, followed by Tobit model (n = 32) and Beta model (n = 22). Eleven studies explored indirect mapping, with the Ordered Logit and Ordered Probit models being the most employed techniques. Thirty-two studies conducted internal validation, with the N-fold cross-validation being the most used method-no study conducted external validation. The sample size ranged from 133 to 3320, with a median sample size of 553. Conducted conceptual analysis was performed in 81.8% of the studies to assess the degree of overlap between the source measure and target measure; 72.7% of the studies reported the utility/score distributions, and 15.2% of studies further reported the response distributions.

CONCLUSION: This systematic review provides insights into methodologies employed in mapping studies in China and identifies key areas for improvement. Addressing issues related to sample size, conceptual overlap, model selection, and validation methods will enhance the quality and applicability of mapping algorithms, ultimately supporting more robust cost-utility analyses in the Chinese healthcare system.

PMID:40824559 | DOI:10.1007/s40258-025-00992-7

Pharmacoeconomics. 2025 Aug 18. doi: 10.1007/s40273-025-01533-9. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Heart failure (HF) is a complex clinical syndrome associated with high mortality and extensive healthcare use. Using longitudinal data, we aimed to estimate the lifetime healthcare and long-term care (LTC) use and costs of Dutch patients with HF.

METHODS: We used linked administrative data on mortality, LTC, and healthcare use covering the entire Dutch population for the period 2013-2024. Newly diagnosed patients with HF were defined as patients who were not hospitalized for HF 2 years before their index hospitalization for HF in 2015. Using regression modeling, we estimated hospitalized patients’ life expectancy and lifetime healthcare costs as a function of age, sex, comorbidity, and income (all costs were adjusted to 2021 values).

RESULTS: We identified 21,011 unique hospitalized patients with HF (mean age 80 years), of whom 86% died during follow-up. Estimated lifetime total healthcare and LTC costs varied between €35,000 and €170,000, depending on patient characteristics. Lifetime LTC costs varied between €9000 and €50,000. While comorbidity affects life expectancy substantially, it did not have a strong impact on lifetime costs. Income level affects costs more than comorbidities, and lower-income groups incur higher lifetime LTC costs.

CONCLUSIONS: Despite people with lower incomes having shorter lifespans than those with higher incomes, their lifetime LTC costs are higher. However, people with higher incomes have higher hospital costs, partly owing to their longer life expectancy.

PMID:40824555 | DOI:10.1007/s40273-025-01533-9

Discov Oncol. 2025 Aug 18;16(1):1579. doi: 10.1007/s12672-025-03215-6.

ABSTRACT

BACKGROUND: Mitochondrial dynamics, particularly the balance between fission and fusion, play a crucial role in cancer progression, including prostate cancer, by influencing cellular metabolism and survival. MTFP1 and MTFP2 are key regulators of mitochondrial fission, and their roles in prostate cancer warrant further investigation.

METHODS: We conducted a comprehensive bioinformatics analysis using RNA-seq data from The Cancer Genome Atlas (TCGA) and SNP data from the UK Biobank (ukb-b-13348) GWAS dataset. Differential gene expression analysis was performed using the limma package, and pathway enrichment analysis was conducted using clusterProfiler. Hub genes were ranked using the CytoHubba algorithms. MCC was prioritized due to its robustness in identifying fully connected subgraphs. Mendelian Randomization (MR) analysis was performed using the TwoSampleMR package to assess the causal relationships between identified hub genes and prostate cancer.

RESULTS: The analysis revealed significant differential expression of MTFP1 and MTFP2 between tumor and adjacent normal tissues, with MTFP2 showing a highly significant upregulation (p-value = 7.06e-06) and an AUC of 0.698, suggesting its potential as a biomarker. In the MR analysis, several hub genes, including ANLN, CDC45, CDCA2, and KIF15, were identified as having a significant causal relationship with prostate cancer, with effect estimates ranging from – 0.03 to 0.15 and statistically significant p-values. These findings suggest that mitochondrial dynamics and related pathways play a critical role in prostate cancer pathogenesis.

CONCLUSION: The study highlights the potential diagnostic and prognostic value of mitochondrial fission-related genes, particularly MTFP2, in prostate cancer and underscores the importance of further investigating these pathways as therapeutic targets.

PMID:40824549 | DOI:10.1007/s12672-025-03215-6

Eur Heart J. 2025 Aug 18:ehaf465. doi: 10.1093/eurheartj/ehaf465. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Dementia is a leading cause of death and disability that shares risk factors with atherosclerotic cardiovascular disease (ASCVD). High lipoprotein(a) is a causal risk factor for ASCVD while results for dementia are conflicting. With lipoprotein(a) lowering drugs in clinical trials, it was tested whether lipoprotein(a) levels are associated with the risk of Alzheimer’s disease and/or vascular-related dementia.

METHODS: Lipoprotein(a) measurements were available in 539 478 individuals from the Copenhagen General Population Study, the Copenhagen City Heart Study, and the UK Biobank. Individuals were followed for up to 30.2 years, during which 6404 developed Alzheimer’s disease and 7866 vascular-related dementia. LPA kringle IV type 2 (KIV-2) number of repeats, which determines lipoprotein(a) isoform size and correlates inversely with lipoprotein(a) levels, were available in 117 029 individuals from the Copenhagen studies. Statistical analyses accounted for competing risk of death, important for studies of dementia occurring late in life.

RESULTS: On continuous scales, lipoprotein(a) levels were not associated with the risk of Alzheimer’s disease or vascular-related dementia. When accounting for competing risk of death, absolute risks of vascular-related dementia increased with higher lipoprotein(a) levels in the UK Biobank (n = 452 989; events = 5132; P = .01), but not in the Copenhagen studies (n = 80 313; events = 2734; P = .42). In the Copenhagen studies, LPA KIV-2 number of repeats ≤5th vs > 50th percentiles associated with a subdistribution hazard ratio for Alzheimer’s disease of 1.25 (95% confidence interval, 1.06-1.46).

CONCLUSIONS: Low lipoprotein(a) levels were not associated with the risk of Alzheimer’s disease or vascular-related dementia. It cannot be excluded that very high lipoprotein(a) or small isoform size increases the risk of dementia.

PMID:40824531 | DOI:10.1093/eurheartj/ehaf465

Int J Comput Assist Radiol Surg. 2025 Aug 18. doi: 10.1007/s11548-025-03500-3. Online ahead of print.

ABSTRACT

PURPOSE: Computed tomography perfusion (CTP) imaging for acute ischemic stroke relies on accurately identifying hypoperfused brain tissue to guide treatment decisions. However, deconvolution-based methods often suffer from variability in perfusion parameters and lesion volumes across different software. This study evaluated the feasibility of temporal fractal analysis, specifically, time series-derived fractal dimension (FD) using the Higuchi method, as a biomarker for detecting hypoperfused brain tissue.

METHODS: Fractal analysis was applied to voxel-wise time-series data from both simulated phantom datasets and 149 CTP images from the publicly available Ischemic Stroke Lesion Segmentation (ISLES) 2024 dataset. FD was calculated using optimized parameters determined through the phantom study. In the patient study, the ischemic core was defined by follow-up MRI, and the penumbra was defined as tissue with Tmax > 6 s. FD values were statistically compared between core, penumbra, and normal tissue. Diagnostic performance was assessed using receiver operating characteristic (ROC) analysis.

RESULTS: In the phantom study, FD showed a strong correlation (ρ > 0.9) with true cerebral blood flow (CBF) across all cerebral blood volume (CBV) values when the tuning parameter k_max was optimized based on the number of CTP frames. In the patient study, FD differed significantly across tissue types (p < 0.001). For penumbra versus normal classification, FD achieved an AUC of 0.732, outperforming CBF and CBV (p < 0.001). In core versus penumbra classification, FD showed the highest AUC of 0.641 among all metrics.

CONCLUSION: Time series-derived FD offers a promising approach to characterizing perfusion abnormalities in stroke, with potential as a complementary metric to conventional CTP parameters.

PMID:40824507 | DOI:10.1007/s11548-025-03500-3

J Cancer Educ. 2025 Aug 18. doi: 10.1007/s13187-025-02709-9. Online ahead of print.

ABSTRACT

Patient-reported outcomes (PROs) and caregiver-reported outcomes (CROs) are tools for evaluating behavioral medicine interventions and for bringing the patient voice into observational research. This study aimed to identify barriers to using PROs/CROs in behavioral cancer research and to equitably address those barriers. Forty-nine members of a cancer special interest group from a research society completed surveys in early 2023 about needs related to the use of PROs and CROs. Descriptive statistics were used to summarize results. Most participants used PROs (n = 34, 69%) but few frequently used CROs (n = 12, 24%). More than 80% of the sample were familiar with common PRO/CRO properties such as reliability and validity. Participants reported considering a wide variety of population characteristics when using PROs and CROs, including language (n = 31, 70%) and education level (n = 31, 70%). The most common barriers to using PROs/CROs in research were time, funding, and technology with many reflecting potential reasons for inequitable representation of certain groups in research. Webinars were the most preferred educational format (n = 38, 78%) for resources related to PROs/CROs. Many participants encountered barriers to using PROs in research. Creation and dissemination of educational resources to promote equitable use of PROs/CROs across underrepresented groups and overcome common barriers to use of these measurement tools are warranted.

PMID:40824476 | DOI:10.1007/s13187-025-02709-9

Blood Res. 2025 Aug 18;60(1):46. doi: 10.1007/s44313-025-00094-2.

ABSTRACT

BACKGROUND: Inflammation indices are emerging predictors of diseases. Monoclonal gammopathy of undetermined significance (MGUS) is a precancerous state and chronic inflammation may drive MGUS progression. This study aimed to evaluate the association between inflammatory markers and MGUS.

METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) III and 1999-2004 were collected from 6,383 participants. MGUS subtypes were identified using immunofixation electrophoresis. Seven inflammatory indices [lymphocyte count (LC), neutrophil count (NC), platelet-neutrophil product (PPN), systemic immune inflammation index (SII), platelet-lymphocyte ratio (PLR), and C-reactive protein (CRP)] were calculated. Weighted multivariate regression and subgroup analyses assessed the relationships, reported as odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS: Of the 6383 patients included in the study, 157 (2.45%) underwent MGUS. There was a significant correlation trend between ln PPN level and the development of MGUS, especially at low levels (OR: 2.62, 95% CI: 1.54-4.75, p-trend = 0.001), while the correlation between PLR level and MGUS was not obvious. In the subgroup analysis, a significant association between PPN level and MGUS was mainly found in the overall population, female sex, non-Hispanic black, non-hypercholesterolemia, non-type 2 diabetes (T2D), high school education or above, and divorced or widowed; however, there was no significant interaction between PPN level and MGUS in each subgroup.

CONCLUSION: PPN levels were significantly associated with MGUS development. Our study identified PPN as a novel and convenient inflammatory marker with potential clinical relevance. Although preliminary, the observed associations highlight the need for validation through longitudinal studies before considering their clinical applications.

PMID:40824475 | DOI:10.1007/s44313-025-00094-2

J Robot Surg. 2025 Aug 18;19(1):492. doi: 10.1007/s11701-025-02679-6.

ABSTRACT

The relative benefits of single-port (SP) versus multi-port (MP) robot-assisted radical prostatectomy (RARP) for prostate cancer remain uncertain, with conflicting evidence reported in the literature. This systematic review aimed to compare perioperative outcome metrics, oncologic efficacy, and functional recovery outcomes between SP-RARP and MP-RARP. A thorough literature search was conducted using PubMed, Embase, Web of Science, and the Cochrane Library to locate English-language research published until June 2025. All statistical analyses, encompassing meta-analyses, were performed utilizing R software (version 4.3.1). Weighted mean differences (WMDs) and 95% CIs were used to summarize continuous outcomes, while odds ratios (ORs) with 95% CIs were computed for dichotomous variables. Statistical significance was established at P < 0.05. The review protocol was registered prospectively in PROSPERO (CRD420251114408). A total of 15 studies involving 3,116 patients (SP-RARP: 1,525; MP-RARP: 1,591) were included. Patients undergoing SP-RARP experienced significantly lower estimated blood loss (WMD -41.36 (-68.79, -13.94); P = 0.003), shorter hospital stays (SMD -0.95 (-1.77, -0.13); P = 0.02), and earlier urinary catheter removal (WMD -1.77 (-2.88, -0.66); P = 0.002) compared with those receiving MP-RARP. SP-RARP was also associated with lower pain scores on the day of surgery (WMD -0.88 (-1.29, -0.48); P < 0.001) and reduced opioid use during hospitalization (OR 0.35 (0.22, 0.54); P < 0.001) and at discharge (OR 0.03 (0.01, 0.10); P < 0.001). Nonetheless, for functional outcomes related to potency and continence, along with perioperative complications, positive surgical margins, biochemical recurrence, and duration of surgery, no statistically significant differences were seen between the groups. SP-RARP offers advantages in reducing intraoperative blood loss, accelerating recovery, and improving postoperative pain control compared to MP-RARP. Although operative time is longer, both approaches provide comparable oncological and functional outcomes.

PMID:40824469 | DOI:10.1007/s11701-025-02679-6

Cancer Chemother Pharmacol. 2025 Aug 18;95(1):81. doi: 10.1007/s00280-025-04804-6.

ABSTRACT

PURPOSE: Inherited dihydropyrimidine dehydrogenase (DPD) deficiency is a risk factor for severe 5-fluorouracil toxicity. We report a phenotyping approach (thymine challenge test) to prospectively determine DPD activity and the association with severe adverse events.

METHODS: The primary aim of this prospective study was to determine whether a thymine challenge test could prospectively identify patients at risk of severe toxicity from treatment with 5-fluorouracil/capecitabine in combination chemotherapy schedules or monotherapy. The focus was prediction of those at risk of ≥ grade 3 gastrointestinal toxicity. DPD activity was determined from the thymine/dihydrothymine (THY/DHT) ratio measured in a urine sample after a thymine test dose (250 mg, oral).

RESULTS: Of the 166 patients, 11.7% had severe diarrhoea/mucositis. The THY/DHT ratio was not significantly different in these individuals compared to those with minimal toxicity. However, post hoc analysis found decreased DPD activity in those who had non-gastrointestinal toxicity, most notably grade ≥ 2 Hand-Foot syndrome (p = 0.001).

CONCLUSION: The data do not support our primary hypothesis that this phenotyping approach would discriminate those at risk of severe/life-threatening gastrointestinal toxicity. The clinical factors which influence gastrointestinal toxicity, particularly in patients receiving CAPOX require further investigation.

CLINICAL TRIAL REGISTRATION: ACTRN 12,617,001,109,392 registered 28/07/2017.

PMID:40824448 | DOI:10.1007/s00280-025-04804-6

AMB Express. 2025 Aug 18;15(1):119. doi: 10.1186/s13568-025-01930-5.

ABSTRACT

Evidence from observational studies and clinical trials has reported that gut microbiota (GM) was associated with chronic lung diseases (CLDs). However, the causal relationships between GM and CLDs have yet to be fully ascertained. The Mendelian randomization (MR) based causal analysis was performed using the genome-wide association study (GWAS) summary statistics from the MiBioGen and FinnGen consortium. GM served as exposure, and CLDs were taken for outcomes. Inverse variance weighted, MR-Egger, and weighted median methods were utilized to examine the causal association between GM and CLDs. The sensitivity analyses were then conducted to validate the robustness of the results. Further, the reverse MR analysis was performed to evaluate the possibility of reverse causation. Finally, the in-silico in-situ microbiota resequencing (ISSMR) of high-throughput sequencing data was utilized as a supplement to dissect the role of microbiota spatial distribution disturbance on the onset of idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD). This study revealed that GM had causal associations with CLDs. Conversely, reverse MR analysis suggested that the presence of COPD and IPF may causally influence the abundance of specific GM. And ISSMR further provided clues to the interaction of intra-tissue as well as gut microbe disturbance in IPF and COPD from synergistic or independent perspectives. In short, the MR analysis revealed a causal relationship between GM and CLDs from a host genetic perspective, and ISSMR extended the host-microbe regulatory modality from a microbe genetic perspective, thus together providing novel insights into the gut microbiota-mediated development mechanism of CLDs.

PMID:40824435 | DOI:10.1186/s13568-025-01930-5