Nevin Manimala

Mil Med. 2025 Jun 6:usaf262. doi: 10.1093/milmed/usaf262. Online ahead of print.

ABSTRACT

INTRODUCTION: Most mortality studies among Norwegian military veterans from international peacekeeping missions were conducted among men, as the number of women participants in each mission has been too small to give statistically robust results. However, women have served in every peacekeeping operation since 1978. As the number of military women increases, knowledge about the causes of death among female military peacekeepers is increasingly important to ensure the Armed Forces’ military operability and preventive initiatives. Hence, we aimed to study mortality in a cohort comprising all military women who participated in such service back to 1978.

MATERIALS AND METHODS: The cohort was established by the Norwegian Armed Forces Health Registry and included 2,365 women eligible for follow-up from their first day of peacekeeping service through 2023. We calculated standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) by comparing the observed numbers of deaths with the expected numbers calculated from national population rates in Norway.

RESULTS: A total of 65 deaths observed during follow-up gave a lower-than-expected all-cause SMR of 0.79 bordering on statistical significance (95% CI, 0.61-1.01). This was because of to low mortality from diseases. Mortality from (nonmalignant) respiratory diseases was lower than expected (SMR = 0.18, 95% CI, 0.00-0.99), on the other hand, the risk of dying from cerebrovascular diseases (stroke) was elevated (SMR = 2.64, 95% CI, 1.21-5.01). Mortality from all external causes combined, as well as from accidents and suicide, did not differ from that of the national rates, the same was true for breast cancer and lung cancer mortality.

CONCLUSION: Generally, military women peacekeepers did not have an increased risk of mortality overall, but the risk of death from stroke was increased. Most of the stroke deaths were haemorrhagic, for which parity and old age at menopause are known risk factors.

PMID:40478536 | DOI:10.1093/milmed/usaf262

Mil Med. 2025 Jun 6:usaf254. doi: 10.1093/milmed/usaf254. Online ahead of print.

ABSTRACT

PURPOSE: Regulatory T cells (Tregs) are well-known to play an essential role in neuroinflammatory conditions. However, their role in visual deficits after military-relevant neurotrauma is not known. This study aims to decipher the role of CD4 + Foxp3 + Tregs in the development of visual deficits in a mild traumatic brain injury (mTBI) mouse model.

MATERIALS AND METHODS: Seventeen-week-old genetically modified mice [C57BL/6-Tg(Foxp3-HBEGF/EGFP)23.2 Spar/Mmjax] in which Foxp3 + Tregs are fluorescently labeled were used in the study. Mice were subjected to a 50-psi air pulse on the left side of the head overlying the forebrain, resulting in an mTBI. A low-dose diphtheria toxin (DTx, ip, 0.05 mg/g body weight) allowed for specific ablation of Foxp3 + Treg cells. DTx treatment began 3 days before causing a blast injury and continued every 3 days to keep Tregs depleted for 30 days after the injury. Mice receiving no DTx served as Treg control, with sham-blast mice serving as additional controls for blast injury. One month following the injury, vision function was assessed by opto kinetic nystagmus and electroretinography (ERG), followed by molecular and immunohistological analysis for neuroinflammatory markers.

RESULTS: Intraperitoneal administration of DTx effectively depleted Foxp3 + Treg cells in the spleen, both in sham and blast-injured mice. The blast injury resulted in a significant reduction in visual acuity and increased contrast sensitivity requirements, with these effects being exacerbated by DTx treatment. Electroretinography revealed a decrease in “b” wave amplitude post-blast injury, which was further reduced with DTx, though not significantly. Neuroinflammatory gene expression, including IL1β, CD86, TNFα, and CXCL10, was elevated in blast-injured mice, with DTx alone also inducing similar increases. Immunohistological analysis showed increased macroglia positive for GFAP and microglia/macrophages positive for IBA1 expression in the retina of blast-injured mice, with further increases observed in the DTx-treated group, although these changes did not reach statistical significance.

CONCLUSIONS: Our studies suggest that depletion of Treg cells followed by blast injury leads to increased retinal degeneration and neuroinflammation. This highlights the continuous requirement of Foxp3 + Treg cell activity to prevent neurodegeneration in mTBI. Future studies should fully explore the relationship of immunomodulatory Treg cells with neurodegeneration in blast-associated visual deficits. Therapeutics aiming to modulate Treg cells could be tested in DEREG transgenic mice after blast injury.

PMID:40478534 | DOI:10.1093/milmed/usaf254

Eur J Public Health. 2025 Jun 6:ckaf066. doi: 10.1093/eurpub/ckaf066. Online ahead of print.

ABSTRACT

Prostate cancer (PCa) poses a significant global health threat, with high incidence and mortality rates. In 2022, the Council of the European Union (EU) updated its screening recommendations, prioritizing PCa screening. This signals a crucial step towards establishing new early detection programmes in EU member states. This study investigates the role of policy makers and governance in cancer screening to inform the development of PCa screening. We had a mixed-method study design. First, a rapid review was conducted on policy making and governance in EU-funded cancer screening initiatives. Second, a focus group discussion reviewed study concepts and methods. Third, a systematic literature review was performed and, fourth, a series of in-depth interviews with actors involved in PCa screening pilots was conducted. Data were analysed thematically and the findings are used to propose 10 recommendations for policy makers. The results of the rapid review and focus group discussion framed the study in the context of existing cancer screening programmes across the EU, and highlighted what already exists in terms of governance tools and methodology. The literature review and in-depth interviews presented key learnings from the literature and real-life settings. These findings are reported using a pre-existing conceptional framework for effective health system governance. The study underscores the critical importance of governance in effective cancer screening programmes. Ten recommendations are proposed, including: defining cancer screening governance, allocating budgets and defining common approaches and key performance indicators for evaluation, establishing methods to enhance citizen participation, and reinforcing network governance.

PMID:40478531 | DOI:10.1093/eurpub/ckaf066

Mil Med. 2025 Jun 6:usaf274. doi: 10.1093/milmed/usaf274. Online ahead of print.

ABSTRACT

INTRODUCTION: Force readiness and disease prevention are critical responsibilities for military physicians. The prevalence of chronic noncommunicable diseases such as obesity and type II diabetes has been increasing among active duty service members. The Department of Defense spends over 3 billion dollars annually managing these conditions. Despite known links between lifestyle factors and disease, lifestyle and performance medicine (LPM) is not commonly integrated into medical education. This research aims to assess military medical students’ knowledge, perceptions, and preparedness regarding LPM.

MATERIALS AND METHODS: An Institutional Review Board (IRB)-approved survey among a select group of medical students participating in the Health Professions Scholarship Program (HPSP) or attending the Uniformed Services University of the Health Sciences (USUHS) was performed. The survey was distributed via the Student Association of Military Osteopathic Physicians and Surgeons email list and military social media pages. The survey intended to gather student perspectives and preparedness to incorporate LPM into future practice. Demographics data were also collected and statistical analysis was performed using SPSS and R-studio.

RESULTS: Of 107 students across 24 medical institutions, 95% felt LPM was relevant to their careers as military physicians. However, only 45% felt adequately prepared by their institutions, and only 30% felt they gained in-depth experience regarding LPM skills like nutrition and exercise prescriptions in medical school. Notably, 78% thought their medical institutions should dedicate more time to LPM in the medical school curriculum.

DISCUSSION: Most students in this study do not feel adequately prepared to incorporate LPM interventions and think they would benefit from more LPM training in their medical school curriculum. These results are consistent with previous studies performed among civilian medical students. This study was conducted exclusively among military medical students, many indicated that they feel the principles of LPM are important to force readiness and missions preparedness. However, they also feel that they lack the skills necessary to adequately integrate LPM into their future practice. This study has several limitations. Responses were collected voluntarily in a non-randomized fashion leaving the possibility for selection bias. Additionally, the survey was available for 4 weeks in the summer of 2024. The methods in which the survey was collected makes so an exact response rate cannot be calculated. However, this study offers valuable insight into the demand for LPM education among current military medical students and the implications LPM can have on future force health and deployment readiness.

CONCLUSIONS: Our findings underscore an expectation among military medical students to integrate more comprehensive LPM education within military medical training programs. By enhancing LPM education, military medical students may be better prepared to address noncommunicable diseases such as diabetes and obesity. This in turn may have broader implications as it pertains to improved force readiness and health outcomes.

PMID:40478528 | DOI:10.1093/milmed/usaf274

Qual Life Res. 2025 Jun 6. doi: 10.1007/s11136-025-03962-7. Online ahead of print.

ABSTRACT

BACKGROUND/OBJECTIVES: Long COVID is a long-term legacy of the global pandemic. This study aimed to illuminate how Long COVID impacts individuals, and how response-shift effects influence Long COVID’s impact. Methodologically, it expands the application of longitudinal statistical methods to test a more dynamic investigation of psychosocial factors in health over time.

METHODS: This quasi-experimental longitudinal cohort study collected data up to four times over 3 years of the COVID pandemic (May 2020 to April 2023). This study focused on 1151 participants divided into four Long-COVID Symptom Burden groups (Never Had COVID; Low, Medium, and High Long-COVID Symptom Burden). It examined COVID-specific outcomes: General Hardship, Healthcare Hardship, Worry, and Social Support. The Quality of Life Appraisal Profile_v2-Short Form assessed cognitive-appraisal processes. Direct and moderated response-shift effects were tested using longitudinal mixed models that examined main effects and interactions of individuals’ changes in cognitive-appraisal processes from their usual, over time, and by group over time, after adjusting for sociodemographic covariates and individual’s usual appraisal processes, and considering the impact of multiple comparisons.

RESULTS: Notable response-shift effects were revealed on all four COVID-specific outcomes, reflecting both direct and moderated response-shift effects. The experience of COVID-specific adversity was related to various appraisal processes but the nature of the relationship often varied by Long-COVID symptom burden. The appraisal processes that were most salient included patterns of emphasis related to getting used to and handling demands or recent changes, problem-solving goals, and comparing oneself to similar others. Individuals in the high Long-COVID Symptom-Burden Group were particularly highlighted in response-shift effects. The broad conclusions of both raw and multiplicity-adjusted results were similar. That is, there were notable reprioritization and reconceptualization response-shift effects for all outcomes, and notable but fewer recalibration response-shift effects.

CONCLUSIONS: Response-shift effects, measured via the direct assessment of cognitive-appraisal processes, were prominent in dealing with the COVID pandemic. The present study documented that COVID-specific adversity can be attenuated or exacerbated depending on individuals’ patterns of emphasis, goals, and standards of comparison. The study’s utilization of data collected at four time points over 3 years of the global pandemic provided a more comprehensive and far-reaching evaluation of response shift than earlier work. The theory-driven analytic methodology developed in the present work facilitated a more nuanced description of direct and moderated response-shift effects.

PMID:40478517 | DOI:10.1007/s11136-025-03962-7

Jpn J Ophthalmol. 2025 Jun 6. doi: 10.1007/s10384-025-01209-z. Online ahead of print.

ABSTRACT

PURPOSE: To examine the reoperation rate of amniotic membrane transplantation (AMT) and clarify the risk factors for AMT reoperation in severe ocular surface (OS) disorders (OSD).

STUDY DESIGN: Retrospective cohort study.

PARTICIPANTS: We reviewed the medical records of all AMT cases between April 1998 and June 2019 at the Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

METHODS: Primary diseases and AMT reoperation rates were examined. In severe OSD cases (Stevens-Johnson syndrome, ocular cicatricial pemphigoid, and chemical/thermal burns), preoperative OS Grading Score (OSGS), surgical procedures combined with AMT, and risk factors for reoperation were investigated and assessed.

RESULTS: Over a period of 21 years and 3 months, 750 AMTs were performed on 664 eyes of 594 cases. AMT was repeated on 51 of those 664 eyes (7.7%), and most frequently performed on 25 out of 196 eyes (12.8%) afflicted with severe OSDs. In severe OSDs, OSGS was significantly higher in the reoperation group compared to no-reoperation group (P<0.05), suggesting corneal epithelial defects, conjunctival hyperemia, trichiasis, mucocutaneous junction involvement, and corneal opacity as being risk factors for re-AMT (univariate analysis). In logistic regression analysis, only conjunctival hyperemia was a risk factor, with odds ratios (OR) of 2.65 (95%CI: 1.34-5.22, P=0.005). AMT combined with cultivated or donor corneal epithelial transplantation reduced reoperation risk with an OR of 0.92 and 0.63, respectively.

CONCLUSIONS: In severe OSD cases, the effect of AMT is limited. Higher OSGSs, especially in conjunctival hyperemia, are associated with a high risk of repeat AMT.

PMID:40478507 | DOI:10.1007/s10384-025-01209-z

J Neurooncol. 2025 Jun 6. doi: 10.1007/s11060-025-05025-w. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with meningiomas often suffer from brain tumor-related epilepsy for which they are prescribed antiseizure medication (ASM). ASMs have been associated with neuropsychiatric side effects such as depression, anxiety, and cognitive impairments. However, the association between ASM use and mood and cognition in meningioma patients remains unclear. In this study, we aimed to investigate the association of ASM use, and specifically the use of levetiracetam, with depression, anxiety, and neurocognitive functioning.

METHODS: In this multicentre retrospective study, data from 187 meningioma patients were collected from neurocognitive tests, the HADS questionnaire, and medical records. Multivariable logistic regression analyses were used to evaluate the association between ASM use, and depression, anxiety and neurocognitive impairment. Potential confounders were included based on the existing literature. Due to sample size limitations, the association of levetiracetam use with depression, anxiety and neurocognitive impairment could not be statistically analyzed.

RESULTS: The prevalence of depression, anxiety and cognitive impairment did not differ significantly for patients using ASM (n = 41) as compared to patients not using ASM (n = 146) (aOR = 0.81; 95% CI 0.26-2.54; aOR = 0.63; 95% CI 0.22-1.82; aOR = 1.42; 95% CI 0.51-3.98).

CONCLUSION: Our findings show no significant association between ASM use and mood and neurocognitive dysfunction in meningioma patients.

PMID:40478500 | DOI:10.1007/s11060-025-05025-w

Virchows Arch. 2025 Jun 6. doi: 10.1007/s00428-025-04117-2. Online ahead of print.

ABSTRACT

Current guidelines recommend pathologists to report percentage Gleason pattern 4 (GP4%) in Gleason score (GS) 7 prostate cancer (PCa) biopsies. However, it is unspecified whether the highest or overall GP4% should be reported. This study aims to clarify which quantification method correlates best with radical prostatectomy (RP) pathology. This study included 308 men with the highest GS 3 + 4 = 7, 4 + 3 = 7, or 4 + 4 = 8 on centrally revised systematic and/or targeted biopsies who underwent RP between 2018 and 2022. The highest and overall biopsy GP4% were compared with RP GP4% using Spearman’s rank correlation coefficient and adverse pathology (AP) (pT-stage ≥ T3, GS ≥ 4 + 3 = 7 and/or pN1) using multivariable logistic regression models adjusted for clinical tumor stage, prostate specific antigen (PSA), percentage of tumor positive biopsies, biopsy modality (systematic/targeted/both), and cribriform pattern. Both quantification methods correlated with RP GP4% (both rho = 0.59), and no significant difference was found between them (p = 0.78). On multivariable analyses, both GP4% quantification methods were significantly associated with AP (per 10% increase, highest GP4% odds ratio [OR] 1.26 [95% CI 1.14-1.39], overall GP4% OR 1.38 [95% CI 1.22-1.58], both p < 0.001). The area under the curve (AUC) was slightly better for overall (0.78 [95% CI 0.73-0.83]) than the highest GP4% (0.76 [95% CI 0.71-0.81], p = 0.041). This study found that the highest and overall biopsy GP4% both correlated with RP GP4%. Although the discriminative performance of the highest and overall GP4% was comparable with respect to AP at RP, the overall GP4% statistically slightly outperformed the highest GP4%. Including the overall GP4% may have added value in risk stratification and clinical decision-making in a subset of PCa patients.

PMID:40478475 | DOI:10.1007/s00428-025-04117-2

Arch Osteoporos. 2025 Jun 6;20(1):72. doi: 10.1007/s11657-025-01555-y.

ABSTRACT

This study evaluates the cost-effectiveness of a Fracture Liaison Service (FLS) compared to current practice for individuals aged 50 and older with fragility fractures in Iran. The FLS was associated with an additional cost of $50 and a gain of 0.03 QALYs, resulting in an incremental cost-effectiveness ratio of $1663 per QALY, demonstrating its cost-effectiveness.

PURPOSE: This study aimed to assess the cost-effectiveness of a FLS program compared to current practice in Iran, from a societal perspective.

METHODS: The target population was patients aged 50 years or older with recent sentinel fragility fractures. Data were collected using various resources, including previously published literature, treatment guidelines, and hospitals. A state-based microsimulation model with a lifetime horizon was designed to simulate costs and quality-adjusted life years (QALYs). Treatment pathways for patients under current practice and FLS were compared using incremental cost-effectiveness ratios (ICERs).

RESULTS: For patients aged 50 years and older with a sentinel fragility fracture, FLS was associated with an incremental cost of $50 and a gain of 0.03 QALYs compared to current practice. Consequently, the ICER was estimated at $1663 per QALY gained, which is below the willingness-to-pay (WTP) threshold of one GDP per capita ($4466 per QALY). Simulations showed that comparing the current practice, FLS could prevent 59 new fractures and 10 related deaths per 1000 patients. The one-way sensitivity analysis indicated that treatment efficacy and medication costs exert the greatest influence on the ICER.

CONCLUSION: The findings of this study demonstrate that FLS is cost-effective compared to current practice in Iran. Given the significant prevalence of osteoporosis and the increasing aging population in Iran, these results underscore the potential of FLS to enhance patient outcomes.

PMID:40478456 | DOI:10.1007/s11657-025-01555-y

J Magn Reson Imaging. 2025 Jun 6. doi: 10.1002/jmri.29835. Online ahead of print.

ABSTRACT

BACKGROUND: Hypertension-induced alterations in brain network topology remain poorly understood, and diffusion tensor imaging (DTI) offers a promising approach for detecting early structural changes.

HYPOTHESIS: Rich-club organization undergoes progressive disruption from prehypertension to hypertension, and these alterations may serve as potential imaging biomarkers for hypertension.

STUDY TYPE: Cross-sectional.

SUBJECTS: Five hundred thirteen participants (150 healthy controls, 175 prehypertensive individuals, and 188 hypertensive patients).

SEQUENCE: DTI with an echo planar imaging sequence at 3.0 T.

ASSESSMENT: Whole-brain structural networks were constructed using deterministic fiber tracking. Modularity, rich-club organization (rich-club, feeder and local connections), small-world property, global efficiency, local efficiency, clustering coefficient, and nodal efficiency were quantified using graph-theoretical analysis. Network-based statistics (NBS) were applied to identify significant group differences in white matter connectivity.

STATISTICAL TESTS: Analysis of variance for group comparisons, with post hoc least significant difference t-testing. Logistic regression assessed the predictive power of network features, while Pearson correlation evaluated relationships between blood pressure and network disruptions. Area under the receiver operating characteristic (ROC) curve (AUC) was used to assess diagnostic performance. A significance threshold of p < 0.05 was applied.

RESULTS: Prehypertensive individuals exhibited significant early reductions in feeder connections, whereas hypertensive patients demonstrated widespread significant deterioration in rich-club connections. A statistically significant compensatory increase in local connection strength was observed in prehypertension but declined in hypertension. Logistic regression confirmed that rich-club connection strength and density effectively differentiated hypertensive individuals, with ROC analysis showing good discriminatory power (AUC: 0.803 and 0.816, respectively).

DATA CONCLUSION: This study showed progressive disruption of rich-club organization in prehypertension and hypertension. This disruption has the potential to be an early neuroimaging biomarker for identifying individuals at risk of hypertension-related brain dysfunction.

EVIDENCE LEVEL: 2.

TECHNICAL EFFICACY: Stage 2.

PMID:40476333 | DOI:10.1002/jmri.29835