Fluorescence lifetime imaging microscopy (FLIM) is sensitive to molecular environments and enables high-resolution mapping of cellular heterogeneity. Yet, the journey from raw photon decays to biological insight remains fragmented by multi-step data extraction and siloed analyses, creating burdens for experts and non-experts alike. This work presents FLIM Playground, the first interactive graphical platform that unifies single-cell FLIM workflows. Modularly designed to encompass data extraction (if desired) and data analysis, FLIM Playground can check field-of-view metadata, calibrate and extract fluorescence lifetime features per region of interest along with morphology and texture features across channels, merge multiple datasets, and provide real-time visual analytic modules. Lifetime extraction was validated against commercial software and published results, and both data extraction and analysis were demonstrated on a FLIM dataset of cancer cell lines. By adopting best practices and offering interactivity, FLIM Playground promotes reproducibility, allows for expansion to new imaging modalities, and accelerates hypothesis-driven discovery.
To our knowledge, no previous systematic review and meta-analysis of doping prevalence in sport from indirect estimation models (IEM) exists. To conduct a systematic review and meta-analysis of empirical IEM-based studies of admitted doping prevalence in sport. We conducted electronic database and ad hoc searches up to March 2025, and estimated lifetime and past year prevalence rates through a cross-classified model including prevalence (lifetime vs. past year), sample (competitive vs. recreational) and sports (multi-sport vs. single-sport) types. Forty-six records (K) were included in the review (k [subset records included in the meta-analysis] = 30, n [independent studies from the records] = 34). The World Anti-Doping Agency's definition of doping use was applied for data collection in most studies (k = 18), and doping prevalence was mostly assessed as past year/season (k = 20). Studies included in the meta-analysis were mostly conducted in Europe (k = 22) and applied the Unrelated Question (k = 8) and Forced Response with Cheater Detection (k = 6) models. Study participants were mostly multi-sport (k = 20) and competed at diverse levels, and most data (k = 28) was collected outside sport events. The corpus included articles that re-analysed existing data (k = 4). Lifetime prevalence was highest for multi-sport competitive athletes (22.6%) and lowest for single-sport competitive athletes (12.7%), whereas past year prevalence was highest for single-sport recreational sportspersons (15.5%) and lowest for multi-sport recreational sportspersons (8.7%). Under IEM, about one of five multi-sport competitive athletes admitted to ever doping whereas about one of six of single-sport recreational sportspersons admitted to doping in the past year. Furthermore, multi-sport (vs. single-sport) competitive athletes show relatively higher doping prevalences, whereas single-sport (vs. multi-sport) recreational sportspersons report relatively higher doping prevalences. Secondary (re-)analysis presents a novel methodological challenge for meta-analyses. Registration PROSPERO: CRD42022373691.
Indigenous Australians in rural and remote areas experience substantial health-related quality of life (HRQoL) impacts alongside persistent healthcare access barriers. Community-led virtual primary care services offer an innovative approach to improving access to health care services for Indigenous Australians in rural and remote areas. To examine age-stratified HRQoL patterns and estimate the lifetime quality-adjusted life year (QALY) loss among Indigenous Australians with chronic conditions enrolled in a rural virtual primary care service. We conducted a cross-sectional analysis of 75 Indigenous adults residing in rural Queensland. HRQoL was measured using the EQ-5D-5L instrument. Lifetime QALY loss was calculated using Queensland Indigenous life tables and population norms, with sensitivity analyses using Australian norms and varying discount rates. Overall mean utility was 0.775 (SD = 0.246). Age-stratified analysis revealed significant heterogeneity, with three age groups (18-54, 55-64, 65-74 years) demonstrating lower HRQoL than Queensland norms. The 55-64 age group experienced poorest HRQoL (utility = 0.701, SD = 0.287) and highest projected lifetime QALY loss (4.44 QALYs undiscounted; 2.63 with 5% discount). In contrast, participants aged 75 years and above exceeded population norms (utility = 0.872 vs. 0.863). Chronic disease burden was associated with HRQoL decline in adults aged 18-64 years, while physical activity was associated with higher HRQoL in those aged 65 years and over. Indigenous Australians aged 55-64 years represent a critical priority for virtual primary care interventions. Targeted support strategies for this 'at-risk' age group are essential to address substantial lifetime health burdens and improve long-term outcomes within remote delivery models.
Vaccination serves as the most efficacious intervention to prevent influenza-related illness. The aim of this study was to compare the lifetime cost-effectiveness of a fully-funded trivalent inactivated influenza vaccine (TIV) strategy for people aged 60 years and over. A static decision-tree Markov model was employed to conduct a lifetime economic evaluation from a societal perspective. Model parameters such as probabilities, costs and utility values, were derived from regional health information platform, published literature, and investigation. The number of cases and deaths averted, quality-adjusted life years (QALYs) gained, and the incremental cost-effectiveness ratio (ICER) were predicted. Sensitivity analyses were performed to evaluate the uncertainty of results. Compared with self-paid vaccination, the implementation of the free influenza vaccination program is projected to cumulatively reduce 261,374 non-medically attended influenza cases,370,155 outpatient influenza cases, 13,678 hospitalized influenza cases, and 1987 influenza-associated deaths. It is estimated that this programme will generate cumulative cost savings of $2,184,312 and an additional 14,324 QALYs, rendering it a dominant strategy. At a willingness-to-pay (WTP) threshold of one times of the per capita gross domestic product (GDP) of Ningbo, the probability of the programme being cost-effective is 99.88%. The threshold analysis revealed that the threshold price of TIV is $11.18 under the most conservative WTP threshold. It has been demonstrated that the free influenza vaccination policy are cost-effective for the elderly individuals. The government and health authorities are supposed to implement and promote a universal free influenza vaccination programme for the elderly, with particular emphasis on the oldest age groups.
Data on survivorship and epidemiology in patients aged <50 years undergoing primary knee arthroplasty (KA) are limited. This study used nationwide registry data to evaluate epidemiology, implant survivorship, and revision risk in patients aged 16-49 years. This retrospective analysis of prospectively collected data from the Scottish Arthroplasty Project evaluated patients aged 16-49 years undergoing primary KA between 2000 and 2019. A date-matched cohort aged ≥50 years served as comparison. Data were analysed using SPSS and R. Outcomes included revision rate, time to revision, and mortality. Competing risk analysis assessed cumulative incidence, and lifetime revision risk was estimated using parametric survival modelling. 3069 patients (58.6% female; mean age 44, range 16-49) were included, with median follow-up of 8 years (range 1-21). Nonosteoarthritis indications were more common in patients aged <35 years. KA incidence increased significantly over time in patients aged <50 (IRR 1.05/year, p < 0.001). Overall, 8.3% underwent revision, with 21-year cumulative incidence of 15.5%. Patients aged ≥50 years had lower revision risk (HR 0.4, p < 0.001). Estimated lifetime revision risk was 31.3% (95% CI 24.6-38.4), with wide confidence intervals in younger subgroups. Mortality at 21 years was 18.2%, higher in nonosteoarthritis indications (HR 0.5 for OA, p < 0.001). KA in patients under 50 years demonstrates acceptable long-term survivorship but a higher revision risk compared to older populations, with an estimated lifetime revision risk of approximately 30%. Subgroup findings should be interpreted cautiously due to small sample sizes and key confounders, particularly implant type and underlying diagnosis. These results support KA in selected younger patients while highlighting the importance of counselling regarding long-term revision risk and the need for more granular future research. Level III.
Digestive system cancers are a leading cause of death in China, with a growing projected burden. Yet, data on the lifetime risk (LTR) of these cancers remain limited. We aimed to estimate the LTR of digestive system cancers in China at national and regional levels for 2023. For this population-based systematic analysis, we obtained estimates of incidence and mortality of digestive system cancers from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, alongside population data from the World Population Prospects, China Statistical Yearbook. The LTR of digestive system cancers was estimated with a standard method that adjusts for multiple primaries, taking into account competing risks of death from causes other than cancer and life expectancy. The LTR (95% uncertainty interval [UI]) of developing and dying from digestive system cancers in China in 2023 was 11.36% (10.90-12.01%) and 8.28% (7.76-8.87%), respectively. Males exhibited higher risks for both incidence (10.82% vs. 6.85% in females) and mortality (7.58% vs. 4.95% in females). The remaining LTR of digestive system cancers decreased with advancing age. Colorectal cancer showed the highest lifetime incidence risk (3.98%), while stomach cancer had the highest lifetime mortality risk (2.69%). Gallbladder cancer consistently demonstrated the lowest risks, with a lifetime incidence of 0.32% and mortality of 0.25%. Geographic disparities were evident, with the highest LTR observed in Eastern and Northeastern regions. Northwestern region had the lowest LTR. In China, approximately one in 9 people will develop and one in 12 will die from digestive system cancers during their lifetime. Significant regional variations highlight the need for precision prevention and tailored health planning.
Stage III melanoma carries a substantial risk of recurrence despite complete surgical resection. Pembrolizumab improves recurrence-free survival, but its cost-effectiveness and potential budget impact in Australia remain important considerations. This study aims to evaluate the cost-effectiveness and potential budget impact of adjuvant pembrolizumab vs standard care (chemotherapy) for resected stage III melanoma from the Australian health care system perspective and to estimate the potential 5-year budget impact under alternative eligible population and uptake scenarios. A lifetime state-transition Markov model was developed for patients with completely resected stage III melanoma. Health states included recurrence-free, locoregional recurrence, distant metastasis, and death. Transition probabilities were derived from published trials and long-term follow-up data, with mortality informed by Australian life tables. Australian cost inputs were derived from the Pharmaceutical Benefits Scheme and Medicare Benefits Schedule, and health state utilities were obtained from published literature. Costs and QALYs were discounted at 5% annually. Outcomes included lifetime costs, QALYs, ICERs, INMBs, and cost-effectiveness probabilities. Cost-effectiveness was interpreted using AU$50,000 per QALY gained as the primary Australian willingness-to-pay (WTP) reference value; AU$100,000 per QALY was considered only as a scenario analysis and was not used for the main conclusion. Parameter uncertainty was assessed using deterministic and probabilistic sensitivity analyses. A scenario-based budget impact analysis was also conducted over a 5-year horizon using alternative eligible population assumptions and conservative, moderate, and high uptake scenarios. Pembrolizumab increased both lifetime costs and QALYs compared with standard care, with a base-case ICER of AU$43,132 per QALY gained. At the primary Australian reference value of AU$50,000 per QALY gained, pembrolizumab had a positive INMB of AU$15,247 and a 65.3% probability of being cost-effective. Results were most sensitive to the recurrence-free survival hazard ratio, pembrolizumab cost, and utility estimates for recurrence states. Using the modelled lifetime incremental cost, the 5-year budget impact ranged from AU$61.30 million under the conservative population and conservative uptake scenario to AU$581.70 million under the upper-bound population and high uptake scenario. Using the treatment-period incremental cost, the corresponding range was AU$88.87 million to AU$843.33 million. Adjuvant pembrolizumab was likely to be cost-effective for appropriately selected patients with resected stage III melanoma in Australia when interpreted against the primary Australian WTP reference value of AU$ 50,000 per QALY gained. However, affordability depends on treatment eligibility, uptake, treatment duration, and acquisition costs, highlighting the need to consider budget impact alongside cost-effectiveness evidence when informing reimbursement and implementation decisions.
This paper introduces a novel, computationally efficient nonparametric test for assessing the null hypothesis of exponentiality against alternatives belonging to the Decreasing Mean Residual Life (DMRL) class. The test statistic is developed using Laplace transform techniques in conjunction with the theory of U-statistics, ensuring asymptotic normality and scale invariance. In addition, we establish the preservation of the proposed methodology under the Homogeneous Poisson Shock Model, further extending its theoretical robustness in reliability contexts. Critical values are obtained through extensive Monte Carlo simulations under both complete and right-censored data, enhancing the method's practical applicability. A comprehensive simulation study demonstrates that the proposed test consistently outperforms classical procedures in terms of power across a wide range of alternative distributions commonly encountered in reliability and survival analysis. The usefulness of the method is further illustrated with real datasets, including COVID-19 mortality and clinical survival data, where the test successfully detects departures from exponentiality with DMRL characteristics. By combining advanced probabilistic transforms with nonparametric inference, this work provides a rigorous and scalable framework for lifetime data analysis, adaptable to the complex censoring mechanisms prevalent in medical and engineering applications.
In the phase III clinical trial named APOLLO (NCT04344158), anlotinib plus penpulimab significantly improved PFS and OS compared with sorafenib in the first-line treatment of unresectable hepatocellular carcinoma (uHCC). Although targeted agents combined with immunotherapy offer a new treatment option for uHCC and provide significant benefits, their cost-effectiveness in China remains unclear. This study aimed to evaluate the cost-effectiveness of anlotinib plus penpulimab for uHCC from the perspective of the Chinese healthcare system, in accordance with the latest China Guidelines for Pharmacoeconomic Evaluations 2025. A partitioned survival model was used to assess the cost-effectiveness of anlotinib plus penpulimab over sorafenib monotherapy as a first-line treatment therapy for uHCC from the perspective of the Chinese healthcare system. The time horizon was the patient's lifetime, with a cycle of 21 days. Clinical information was derived from the APOLLO trial, cost and health state utility data were derived from local databases and published literature. Quality-adjusted life years (QALY) were used as the model's main outcome indicator, sensitivity analyses were conducted. In the base-case analysis, anlotinib plus penpulimab provided an additional 0.58 QALYs at an incremental total cost of United States dollar ($)24,637.23, with an incremental cost-effectiveness ratio (ICER) of $ 42,319.31/QALY, which was higher than the willingness-to-pay (WTP) threshold of $ 27,766.48/QALY. One-way sensitivity analysis showed that the results of the model were most sensitive to the utility value of the PD state and the price of penpulimab. Sensitivity analyzes indicated that our results were robust to the variation ranges of key inputs. Scenario analysis confirmed that when the prices of penpulimab was reduced by 50%, the cost-effectiveness of the anlotinib plus penpulimab is significantly improved. In this economic evaluation comparing two first-line treatments for patients with uHCC, anlotinib plus penpulimab was not more cost-effective than sorafenib from the perspective of the Chinese healthcare system. However, this outcome could be altered if penpulimab undergoes a substantial price reduction.
Transthyretin amyloid cardiomyopathy (ATTR-CM) causes heart failure with substantial morbidity, mortality, and healthcare utilization. ATTRibute-CM showed that acoramidis improves clinical outcomes, but its cost-effectiveness and budget impact in the German statutory health insurance (SHI) system remain uncertain. We developed a cohort Markov model (lifetime horizon) discounting costs and outcomes at 3% annually. Overall survival was modeled with recalibrated Weibull functions fitted to randomized-phase ATTRibute-CM data and anchored to match month-30 survival. Health-related quality of life used Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) trajectories mapped to EQ-5D utilities, with a plateau after 30 months in the base case. Direct medical costs (2025€) included drug, background management and hospitalization costs. Uncertainty was assessed with sensitivity analyses, scenario analyses and a budget impact analysis. Discounted mean lifetime costs were €13,881.50 (placebo) and €828,127.07 (acoramidis), for an incremental €814,245.57. QALYs increased from 2.743 to 4.029 (incremental 1.286) and life-years from 4.023 to 6.045 (incremental 2.022), yielding an ICER of €633,081 per QALY. Survival scenario analyses produced lifetime ICERs from €458,953/QALY in an optimistic scenario to €2,139,712/QALY in a pessimistic waning-benefit scenario. At a WTP of €100,000/QALY, the probability of cost-effectiveness was very low and results were driven primarily by acoramidis acquisition cost. In the budget impact analysis, year-1 SHI expenditure was €80,813,995, €134,689,992, and €269,379,983 for 30%, 50%, and 100% uptake, respectively. Despite benefits, acoramidis is unlikely to be cost-effective at current prices in Germany and could increase SHI spending. Price reductions could better align value with affordability.
The field of HIV/STI prevention research has primarily focused on gay men, leaving bisexual men overshadowed in broader discussions on sexual minority men's health. Although also at increased risk of HIV acquisition, bisexual men are less likely to access biomedical HIV prevention. This systematic review and meta-analysis summarizes the prevalence of implementation of biomedical HIV prevention strategies among bisexual men as compared with gay men. We searched PsycINFO, CINAHL, Scopus, PubMed and Web of Science for studies published between 1 January 2012 and 1 February 2024, with prevalence data of specified HIV biomedical prevention strategies (awareness, intention, adherence and use of pre-exposure prophylaxis [PrEP], post-exposure prophylaxis [PEP] and U = U). Studies that did not provide bisexual-specific data were excluded. We conducted six random-effect meta-analysis models to analyse PrEP awareness, PrEP intention, PrEP use and U = U use among bisexual men and gay men. We conducted trend analyses to determine variations in the prevalence of PrEP awareness, intention and use, fitted by locally estimated scatterplot smoothing regression and linear regression. This study was registered with PROSPERO (CRD42024519650). Data were extracted from 114 articles, encompassing 514,543 participants, including 94,004 bisexual men (18.3%) and 420,539 gay men (81.7%). The overall pooled prevalence of PrEP awareness (g: 61.4% vs. b: 42.9%), any PrEP use (g: 22.5% vs. b: 15.2%), lifetime PrEP use (g: 21.5% vs. b: 11.9%), current PrEP use (g: 20.9% vs. b: 16.0%) and U = U use (g: 76.3% vs. b: 69.3%) among gay men was significantly higher than among bisexual men, with odds ratios ranging from 1.52 to 2.77. There was no difference for PrEP intention (g: 55.6% vs. b: 56.7%). For both gay and bisexual men, the trends for PrEP awareness and use generally increased, while the trend for PrEP intention decreased over time. Results demonstrate that bisexual men are engaging less than gay men with biomedical HIV prevention strategies, indicating the need for increased dissemination, awareness, and tailored policies and strategies for bisexual men.
The cost-effectiveness of low-dose atropine SYD-101 (0.01%) eye drops in combination with standard of care (SoC) was evaluated in comparison with SoC alone for pediatric myopia. The SoC included single-vision eyeglasses or soft, daily-wear, single-vision contact lenses. A cohort state-transition model with nine mutually exclusive states encompassing myopia severity, complications, and death was developed. Population characteristics and clinical data were obtained from the STudy of Atropine for the Reduction (STAR) of Myopia Progression in Children. The model included children with a myopia progression rate of ≥ 0.50 D per year and myopia between -0.5 D and -6.0 D, inclusive, in both eyes. The analysis used the English National Health Services and Personal Social Services perspective, applying a lifetime horizon and annual discounting of costs and health effects at 3.5%, and 2023 as a common year of costing. The main outcomes were total and disaggregated costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). SYD-101 (0.01%) increased QALYs by 0.139 at an added cost of £2239 compared to SoC, resulting in an ICER of £16,164/QALY, below the willingness-to-pay threshold. The improved health outcomes were primarily driven by a reduced proportion of individuals progressing to high myopia and fewer myopia-related complications. Scenario and sensitivity analyses together validated the robustness of base-case results. In the probabilistic sensitivity analysis, 85% of the simulations for SYD-101 (0.01%) compared to SoC were in the northeast quadrant of the cost-effectiveness plane. The probability of SYD-101 (0.01%) being more cost-effective compared to SoC was 58.2% or 64.2% at a willingness-to-pay threshold of £20,000/QALY or £25,000/QALY, respectively. Adding SYD-101 (0.01%) to SoC can be considered a cost-effective option for treating pediatric myopia in the United Kingdom over a lifetime horizon. These results support the integration of SYD-101 (0.01%) into routine clinical practice to enhance long-term visual outcomes and lower healthcare expenses.
Better understanding of the aetiology of suicidal ideation, including modifiable and protective factors, can enhance preventive strategies. Negative mood regulation expectancies ('NMRE'; beliefs in one's ability to alleviate negative mood) are associated with suicidal ideation and negative affect but little is known about the underlying mechanisms of these associations. We conducted secondary analyses of cross-sectional data from 1546 adults (69.8% female; Mean age = 34 years; 92% White) recruited from the community in Scotland, 32% of whom reported a lifetime history of suicidal ideation and 8% a lifetime suicide attempt. Analysis aimed to understand whether NMRE are associated with current suicidal ideation and would buffer the association of stress on current suicidal ideation and depressive symptoms. Relevant measures included in this study were self-reported demographics, stress, NMRE, depressive symptoms and current suicidal ideation. A cross-sectional moderated mediation model indicated that depressive symptoms mediated the relationship between stress and suicidal ideation and that NMRE significantly moderated this relationship. Specifically, the indirect relationship between stress and suicidal ideation via depressive symptoms was significant at all levels of NMRE tested, although the strength of association declined as NMRE increased (low NMRE: B = 0.28, 95% CI [0.22, 0.35], moderate NMRE: B = 0.21, 95% CI [0.16, 0.25], high NMRE: B = 0.14, 95% CI [0.10, 0.18]). Stronger beliefs in one's expectations to regulate negative mood may therefore buffer against the effects of perceived stress on suicidal ideation directly, and indirectly by mitigating the effect of stress on depressive symptoms.
Sports/exercise engagement across the lifetime has been proposed to contribute to cognitive reserve and promote healthy brain aging. Few studies have examined whether past sports experiences are associated with current cognitive and social functions and resting-state brain activity in lifespan. The present study aimed to address that gap. Ninety healthy participants aged 20-83 years were categorized into four groups based on their self-reported sports experience: single sports (N = 25), team sports (N = 11), combined single and team sports (N = 20), and no experience (N = 34). We assessed cognitive function, social adaptation, and quality of life. Resting-state functional magnetic resonance imaging data were analyzed using amplitude of low-frequency fluctuations and seed-based functional connectivity to investigate local spontaneous activity and network-level integration. Participants with sports experience demonstrated enhanced performance in several cognitive tasks and higher social adaptation scores than those without experience. Neuroimaging analyses revealed increased amplitude of low-frequency fluctuations in the right middle frontal gyrus in the team-sport group. Furthermore, exploratory functional connectivity analysis showed reduced coupling between the right middle frontal gyrus and posterior sensory-visual regions, including the postcentral gyrus, lateral occipital cortex, and occipital fusiform gyrus. These findings suggest that lifetime sports engagement may be associated with differences in cognitive and psychosocial functioning, together with a tentative pattern of resting-state brain variation. Although the observed connectivity pattern may be broadly consistent with accounts of functional specialization or neural efficiency, the principal ALFF finding did not survive correction for multiple comparisons. Accordingly, the neuroimaging results should be regarded as preliminary and hypothesis-generating rather than confirmatory, while still providing a concrete basis for future hypothesis-driven investigation.
Noninvasive quantification of immune markers such as programmed death ligand-1 (PD-L1) remains a major challenge because conventional molecular imaging methods cannot readily distinguish target-bound from nonspecifically retained probes within the tumor microenvironment. Here, we establish a framework for noninvasive quantification of PD-L1 expression in deep-seated hepatocellular carcinoma (HCC) using asymptotic time-domain (ATD) fluorescence lifetime tomography. In vivo time-domain fluorescence imaging was performed in mice bearing orthotopic HCC tumors following administration of a PD-L1-targeted near-infrared fluorescent probe (αPDL1-800). Multi-exponential analysis of time-domain fluorescence data was used to derive four amplitude-based metrics of PD-L1 expression. Quantitative in vivo measurements obtained from ATD tomography were validated against ex vivo PD-L1 expression measured by Western blotting. Among the evaluated metrics, a normalized parameter that accounts for inter-lifetime crosstalk demonstrated the strongest correlation with ex vivo PD-L1 expression (r 2  = 0.77). These findings establish a foundation for a noninvasive, nonionizing imaging approach to quantify and monitor receptor expression and support a future path for the longitudinal assessment of immune biomarkers in both preclinical studies and clinical settings.
Sexual violence (SV) against children and youth is a global problem. Minimal evidence exists on how contextual factors, such as those at the community or societal levels, influence the prevalence of SV in low- and middle-income countries (LMICs). Data from the Violence against Children and Youth Surveys in Cambodia, Colombia, Côte d'Ivoire, El Salvador, Kenya, Mozambique, and Nigeria (nmale = 9,245; nfemale = 10,022) were merged with the Out of the Shadows Index (OOSI), a global index of national child protection efforts developed by Economist Impact. Age- and sex-stratified sequential fixed effects random intercepts models assessed associations between cluster-level community-aggregated attitudes and OOSI indicators with forced sexual initiation (FSI), lifetime non-consensual sexual touching (NCST), and lifetime SV. We found that aggregated harmful attitudes about women and men at the community-level were associated with FSI among females (adjusted odds ratio (aOR) = 4.43, p =< .001), and NCST (aOR = 2.86, p < .001), and SV (aOR = 2.70, p < .001) among males. Aggregated community attitudes supportive of intimate partner violence were significantly associated with lifetime SV among females (aOR = 2.09, p < .001) and males (aOR = 3.16, p < .001), and NCST (aOR = 3.10, p < .001) among males. The OOSI legal indicator was associated with lower prevalence of NCST (aOR = 0.94, p =< .001) and SV (aOR = 0.94, p =< .001) among males, and NCST among females aged 13 to 17 years (aOR = 0.96, p = .009). Community attitudes are associated with youth experiences of SV, and protective national legislation is associated with a lower risk of youth experiencing SV in LMICs. National policies and programs that alter these factors have the potential to help prevent SV among children and youth.
The treatment of tricuspid valve (TV) disease has increased over the last decades. This study evaluates trends, patient characteristics, and outcomes of surgical and transcatheter TV interventions over 30 years. All consecutive adult patients undergoing TV surgery or transcatheter intervention at the Heart Center Leipzig were included in this unadjusted descriptive analysis. Patients with TV endocarditis were excluded. Surgical data covered 1996-2024, transcatheter edge-to-edge repair (T-TEER) 2016-2024, and transcatheter TV replacement (TTVR) 2021-2025. All information was obtained from the institutional database. A total of 982 patients were analyzed: 450 (46%) surgical, 498 (51%) T-TEER, and 34 (3%) TTVR patients. Surgical patients were younger (67 vs. 79 vs. 81 years, respectively, P<0.001) and had fewer comorbidities than those treated interventionally. Higher-grade TR was more common in T-TEER and TTVR cohorts. Device leads crossing the TV were present in 109 (24%) surgical, 147 (30%) T-TEER, and seven (21%) TTVR patients (P=0.13). Reoperations accounted for 165 (37%) surgical cases, while prior cardiac operations were documented in 148 (30%) T-TEER and 7 (21%) TTVR patients. Surgery after T-TEER was infrequent (n=4, 1%). One-year survival was 88% after surgery, 83% after T-TEER, and 94% after TTVR (log-rank P=0.036). Among surgical patients, 335 (74%) did not require any re-hospitalizations during the first year postoperatively. Surgical reoperations showed survival comparable to primary procedures (actuarial survival at 9 years, 55% vs. 59%, respectively; log-rank P=0.07). Surgical TV replacement was associated with worse survival than surgical TV repair (at 9 years. 55% vs. 65%, respectively; log-rank P=0.03). Surgical TV repair yields better outcomes than replacement. Long-term survival after reoperation parallels that of primary TV surgery. Surgical and transcatheter therapies address distinct patient populations. Multidisciplinary heart team evaluation remains essential for optimal management of TV disease.
Psoriasis is a chronic, inflammatory skin disease that significantly impairs patients' quality of life (QOL). Several biologics with varying mechanisms of action are approved for treating moderate-to-severe plaque psoriasis (PSO) in Japan; bimekizumab is the only one that selectively binds to and inhibits interleukin (IL)-17F in addition to IL-17A. However, there is currently no recommended biologics treatment sequence, and their high cost limits treatment accessibility. This study evaluated bimekizumab cost-effectiveness versus IL-23 inhibitors in patients with PSO in Japan from a public healthcare payer's perspective, and explored variables that affect cost-effectiveness. A cohort simulation, lifetime Markov model with 2-week cycles simulated the treatment pathway in adults with moderate-to-severe PSO who had an inadequate response to previous treatments. Bimekizumab was compared with the IL-23p19 inhibitors guselkumab, risankizumab, and tildrakizumab in the first line; brodalumab was the second-line treatment for all arms. Transition to second-line treatment was triggered by not achieving a ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75), or discontinuation due to adverse events. A network meta-analysis provided PASI response rates. QOL scores were derived from EuroQol 5-Dimension 3-Level health questionnaire responses from global bimekizumab phase 3 studies. Drug and management costs were estimated on the basis of Diagnosis Procedure Combination-based data in Japan; 2%/year discounting was applied to costs and quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios (ICERs) were calculated, and sensitivity and scenario analyses performed. Bimekizumab generated the highest number of QALYs and was cost-effective against all IL-23 inhibitor comparators at a willingness-to-pay threshold of ¥5,000,000/QALY (bimekizumab versus guselkumab: ¥3,202,863/QALY; risankizumab: ¥4,732,268/QALY; tildrakizumab: ¥4,950,972/QALY). ICERs were sensitive to QOL scores, with PASI 100 QOL score being a key cost-effectiveness driver. Findings of the cost-effectiveness of bimekizumab against IL-23 inhibitors support the potential consideration of bimekizumab as a first-line treatment for moderate-to-severe PSO in Japan.
Retinopathy of prematurity (ROP) is a leading cause of preventable childhood blindness, particularly in low- and middle-income countries. In Iran, where the prevalence of ROP among premature infants exceeds 20%, limited access to subspecialist ophthalmologists constrains timely screening. This study evaluated the cost-utility of three alternative ROP screening strategies to inform national policy on optimizing resource allocation. A lifetime, societal-perspective cost-utility analysis was conducted using a state-transition Markov model. Three strategies were compared: (1) universal referral of all at-risk infants to tertiary centers; (2) RetCam-based nurse-led imaging with remote ophthalmologist review (telemedicine); and (3) local screening by general ophthalmologists with selective referral. Model inputs were derived from national data, published literature, and expert opinion. Costs (2025 Iranian Tomans) and quality-adjusted life years (QALYs) were discounted at 5.8%. Deterministic and probabilistic sensitivity analyses were performed to assess parameter uncertainty. The Direct Examination scenario (general ophthalmologist screening) had the lowest mean cost (33.52 USD) and effectiveness (16.83 QALYs). RetCam imaging achieved higher effectiveness (17.14 QALYs) at a cost of 122.69 USD, yielding an incremental cost-effectiveness ratio (ICER) of 288.81 USD per QALY gained, well below Iran's willingness-to-pay (WTP) threshold of USD 7,047. The Universal Referral strategy was dominated, being both more costly and less effective. Probabilistic sensitivity analysis confirmed that RetCam imaging was cost-effective in 95.2% of 10,000 Monte Carlo simulations at a WTP of USD 6,000 per QALY. Diagnostic specificity and long-term vision care costs were the key ICER drivers. RetCam-based telemedicine screening for ROP in Iran is highly cost-effective compared to traditional direct examination or universal referral, offering substantial long-term health gains at an acceptable cost. Scaling up telemedicine screening, supported by quality assurance and training programs, could reduce preventable childhood blindness and improve efficiency of neonatal eye care delivery.
This study conducted a systematic review and meta-analysis of radionuclide concentrations of Cesium-137 (Cs-137), Cesium-134 (Cs-134), Iodine-131 (I-131), Lead-210 (Pb-210), and Potassium-40 (K-40) in milk worldwide, along with an assessment of human health risks, in accordance with the PRISMA guidelines. Pooled radionuclide concentrations were estimated using a random-effects model, while excess lifetime cancer risk (ELCR) was calculated to evaluate carcinogenic effects using the Monte Carlo Simulation (MCS) model. A comprehensive search of Scopus, PubMed, Embase, and Web of Science identified 66 papers (200 data reports, 2000-2025) that cover milk samples from 32 countries. The global pooled mean concentrations (Bq/L) followed the order: K-40: 57.494 > Cs-137: 0.904 > I-131: 0.301 > Pb-210: 0.136 > Cs-134: 0.032. Extreme concentrations were observed in the United Kingdom (Cs-137: 288.000), Syria (I-131: 76.000; K-40: 243.500), and India (Pb-210: 1.080), whereas Mali (Cs-137: 0.003) and Algeria (K-40: 2.349) showed the lowest levels. Probabilistic human health risk assessments revealed that the mean cancer risk (CR) for adults from Cs-137 ingestion exceeded the acceptable limit (1E-4) in the United Kingdom, Austria, South Korea, Serbia, the Czech Republic, Germany, Kazakhstan, and Iceland. For Cs-134, the CR in Finland and France remained below the limit. The CR from K-40 exceeded the limit in Spain, Syria, Bangladesh, Mali, Iraq, Singapore, Thailand, Japan, Italy, and Turkey. For I-131, the limit was exceeded in Syria, Romania, Greece, and Spain. The CR of Pb-210 exceeded the limit in Tunisia, Slovenia, India, the Czech Republic, Italy, and Syria. These disparities reflect variations in environmental contamination, nuclear legacy, and regulatory standards. The results highlight the necessity for strict monitoring, especially in high-risk areas, and promote enhanced agricultural practices and food safety policies to reduce radionuclide exposure through milk consumption.