Search Results (1,174)

Background: Past workplace exposure to asbestos in combination with tobacco smoking has increased the risk of lung cancer for some residents in an area within the Friuli Venezia Giulia region, Northeast Italy. In light of studies showing that lung cancer screening (LCS) with low-dose computed tomography (LDCT) can reduce mortality, local stakeholders and decision-makers decided to assess the potential benefits, harms and cost-effectiveness of a single round of LCS with LDCT versus standard care among people aged 55 to 80 who were formerly exposed to asbestos and with at least 10 pack-years of smoking. Methods: An economic model was developed using a decision tree connected to a Markov cohort model. The primary outcome was the incremental cost per additional quality-adjusted life year (QALY). Other outcomes included the number of life years saved, the number of deaths averted and overdiagnosis. Results: Per 10,000 people screened, the intervention led to 395 additional QALYs (95% credible interval: 129 to 831) and incremental total costs of EUR 1,086,345 (95% credible interval: −852,607 to 2,155,826). The incremental cost per QALY gained was EUR 2750. There was a probability of cost-effectiveness of 99.5% relative to a threshold of EUR 25,000. Conclusions: The model estimated that the intervention was cost-effective. The model’s simplifications and limitations should be considered when interpreting the findings in relation to policy-making decisions. Further research could include the costs and benefits of incidental findings and could assess the cost-effectiveness of repeated rounds of screening for the same population. Full article

Background and Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce cardiovascular (CV) death and heart failure hospitalizations (HFH) in patients with heart failure with reduced ejection fraction (HFrEF). However, data regarding their use in combination with different doses of guideline-directed medical therapy (GDMT) remain limited. This study aimed to evaluate whether SGLT2i combined with low-dose conventional triple therapy is non-inferior to high-dose conventional triple therapy in preventing adverse cardiovascular outcomes. Materials and Methods: This retrospective observational study included 334 patients with HFrEF treated between 31 March 2018 and 31 March 2024. Of these, 110 received SGLT2i plus low-dose conventional triple therapy, and 224 received high-dose conventional triple therapy. A non-inferiority framework was applied to compare outcomes between groups. The primary endpoint was a composite of CV death and HFH, while secondary endpoints included the individual components. Results: The composite endpoint occurred more frequently in the SGLT2i plus low-dose group. After inverse probability of treatment weighting and multivariable Cox analysis, this group demonstrated a significantly higher risk of the composite outcome (adjusted HR 4.10, 95% CI 2.07–8.13; p < 0.001). CV death was similar between groups; however, HFH was significantly more frequent in the SGLT2i plus low-dose group. Conclusions: In patients with HFrEF, SGLT2i combined with low-dose conventional triple therapy did not demonstrate comparable clinical outcomes to high-dose conventional triple therapy in reducing CV death and HFH, particularly in patients with a higher baseline burden of disease severity. These findings underscore the importance of optimizing background GDMT dosing alongside the incorporation of SGLT2i into clinical practice. Full article

Cardiac arrest is a way of demise of patients who are affected by heart failure (HF), being more frequent in those with HF with a reduced left ventricular ejection fraction (HFrEF), and is, as such, responsible for 30–50% of cardiac death. Specific data on the risk of sudden cardiac death (SCD) related to HF with a preserved ejection fraction (HFpEF) and HF with a mildly reduced ejection fraction (HFmrEF) are lacking, as well as data regarding ventricular arrhythmias in this population. Considering the 0.3% person/year incidence rate of investigator-reported ventricular tachycardia (VT) and ventricular fibrillation (VF), the rate of SCD in the analyzed population seems to be 1.3% per year. Age, gender, history of diabetes and myocardial infarction, left bundle branch block (LBBB) on electrocardiogram (ECG), and a natural logarithm of N-terminal pro B-type natriuretic peptide (NT-proBNP), identified a subgroup of HFpEF patients with a higher risk (5-year cumulative incidence of 11%) of sudden death (SD). In HFpEF patients, both glifozins and finerenone did not demonstrate a beneficial effect on SCD incidence in comparison to placebo. A significantly lower rate of SCD emerged in patients who were treated with dapaglifozin (10 vs. 26 pts) among patients with HF with an improved ejection fraction (HFimpEF), who were defined as patients with a previous left ventricular ejection fraction (LVEF) < 40%. Promising methods discussed include cardiac magnetic resonance, myocardial scintigraphy, genetic assessment, and electrophysiologic studies for predicting SCD in those patients. In conclusion, arrhythmic SCD in HFpEF patients should not be considered merely as an effect of VT/VF; bradyarrhythmia is probably more frequent and dangerous. The effects of drugs in preventing SCD in HFpEF have not been demonstrated yet. Full article

Background and Objective: After SARS-CoV-2 infection, Long COVID (LC) syndrome has occurred in a high proportion of patients, affecting their health. The aim of this study was to estimate the incidence of LC, as well as its risk and protective factors. Materials and Methods: We conducted a prospective population-based cohort study of the Borriana COVID-19 cohort (Castellon Province, Valencia Community, Spain) from May 2020 to August 2023, with a follow-up of 40 months, using the LC definition given by the World Health Organization. Inverse probability-weighted regression adjustment was applied in the statistical analysis. Results: With a participation rate of 63.8% and a total of 722 participants, the mean age was 37.7 ± 17.4 years, and 460 (62.3%) were female. Among them, 644 had experienced a SARS-CoV-2 infection, and 184 developed LC, corresponding to a cumulative incidence of 28.6%. At the time of follow-up, 135 patients remained affected by LC, and one LC-related death was recorded. Significant risk factors for LC included older age, female sex, being part of a small family, having a chronic disease, SARS-CoV-2 exposure, and disease severity. Asymptomatic COVID-19 infection and SARS-CoV-2 vaccination were significantly protective factors. Conclusions: A substantial incidence of LC was observed, along with a low recovery rate. Several risk and protective factors were identified. Continued follow-up of this cohort, improved medical care for patients with non-recovered LC, ongoing surveillance of SARS-CoV-2 infections, and vaccination of the at-risk populations against SARS-CoV-2 are recommended. Full article

Ferroptosis, a type of iron overload-induced cell death, is involved in diabetes-induced testicular dysfunction. Hence, this study was designed to investigate, for the first time, the impact of lipoxin A4 (LXA4) administration on testicular tissue in diabetic rats and explore its probable role in regulating ferroptosis in comparison with the standard ferroptosis inhibitor (ferrostatin-1, Fer-1). Albino rats of Wistar strain were divided into a control group, a type II diabetes mellitus (DM) group, a DM + Fer-1group, and a DM + LXA4 group. Serum levels of iron, insulin, glucose, total cholesterol, triglycerides, and testosterone were assayed. Testicular tissue markers of oxidative stress, ferroptosis, and inflammation were also assessed by different methods. Our results confirmed diabetes-induced testicular injury and disruption of its function via inducement of ferroptosis, but this was ameliorated with LXA4 and Fer-1 administration. However, Fer-1 showed a greater protective effect compared to LXA4 under the conditions of this study. We concluded that LXA4 partially secured the testicular tissue of diabetic rats against ferroptosis via augmenting the antioxidant Nrf2/SLC7A11/GPX4 pathway. Therefore, LXA4 may have a possible protective effect on the testicular tissue of diabetic patients. Full article

Saprophagic flies can have a vital role in forensic investigations of suspicious death by providing an estimate of the minimum post-mortem interval (minPMI). An exemplar blow fly species, Calliphora vicina (Diptera: Calliphoridae), is frequently reported as being of greatest importance in this role, but without significant corroborating evidence. Therefore, the present study examined 122 anonymised, historic cases of suspicious death investigated in Great Britain (GB) to determine the role of Diptera and of C. vicina in particular. Thirty-seven fly species in eighteen families were recorded, with greater diversity outdoors (17 families) than indoors (11 families). Family diversity and the age of the oldest developmental stage increased as estimated minPMI increased. Indoor minPMIs tended to be lower than outdoor minPMIs, probably due to the higher likelihood of finding a body indoors. The most commonly collected family and species were Calliphoridae and C. vicina, respectively, the latter recorded in 69.7% (85/122) of all cases. The four main reasons for the importance of C. vicina are: (1) widespread distribution; (2) broad seasonality; (3) low thermal tolerance; and (4) ability to colonise bodies soon after death. It was used to determine minPMI in 85.9% of cases in which it was collected (73/85). Where a most likely PMI could be compared by regression analysis with a minPMI from C. vicina evidence, the relationship was robust (R² > 0.98), accurate to within 2.5–2.7 days at a most likely PMI of 20 days. With greater research effort, Calliphora vicina and more neglected fly species can have an increasing role in future forensic investigations of suspicious death. Full article

Background: Drug-resistant tuberculosis (DR-TB) continues to pose a major challenge in Limpopo Province, a predominantly rural region of South Africa with high prevalence of HIV and mobility of the cross-border population. Despite the scale-up of short all-oral bedaquiline-based regimens, there is limited recent provincial evidence describing DR-TB epidemiological characteristics and treatment outcomes in the post-COVID-19 period. This study aimed to assess resistance patterns, treatment outcomes, and factors associated with unfavorable outcomes among patients with DR-TB in Limpopo Province from 2020 to 2024. Methods: A retrospective cohort study was conducted using routinely collected data from the Electronic Drug Resistant Tuberculosis Register (EDRWeb). All laboratory-confirmed DR-TB cases diagnosed between January 2020 and December 2024 were included. Descriptive statistics were used to summarize demographic and clinical characteristics. Multivariable logistic regression was performed to identify predictors of unfavorable outcomes (treatment failure, death, and loss to follow-up). Kaplan–Meier survival analysis was used to estimate survival probability following treatment initiation. Results: A total of 1240 DR-TB cases were recorded, of which 1165 (94%) had documented treatment outcomes. Rifampicin-resistant TB (RR-TB) predominated throughout the study period, accounting for 76% (951/1240) of cases and remaining stable over time. Treatment success improved from 173/260 (67%) in 2020 to 130/166 (78%) in 2024, while loss to follow-up declined from 34/260 (13%) to 4/166 (2%). Kaplan–Meier survival analysis showed that mortality occurred predominantly during the early phase of treatment. Patients receiving bedaquiline-containing regimens demonstrated significantly higher survival probability compared with those not receiving bedaquiline (log-rank p = 0.024; HR 0.58, 95% CI: 0.35–0.94). In multivariable analysis, HIV infection was independently associated with unfavorable outcomes (aOR 1.36; 95% CI: 1.04–1.77; p = 0.025), while increasing age showed a modest association with poorer outcomes. Conclusions: Treatment outcomes for DR-TB improved over the study period, accompanied by declining loss to follow-up and improved survival. The survival advantage observed among patients receiving bedaquiline-containing regimens supports continued prioritization of bedaquiline-based treatment strategies in DR-TB management. Strengthening access to these regimens, alongside integrated HIV care, may further improve treatment outcomes in Limpopo Province and similar high-burden settings in South Africa. Full article

Background: In end-stage liver disease (ESLD), cardiovascular changes are frequent and relate to the presence of hyperdynamic circulation. In 2019, diagnostic criteria for cirrhotic cardiomyopathy (CCM) were updated to include tissue Doppler and speckle tracking imaging in defining left ventricle (LV) systolic and diastolic dysfunction. Evaluation of diastolic function remains challenging, with frequent indeterminate cases and emerging evidence of worse prognosis. The aim of the present study was to evaluate the prevalence of LV systolic and diastolic dysfunction in cirrhosis, in correlation with liver disease severity and potential prognostic implications. Methods: We performed an observational, retrospective, non-randomized, single-center study that included 99 cirrhotic patients evaluated for liver transplant (LT) in a tertiary center. Liver disease severity and complications were analyzed with survival and echocardiography data to determine potential correlations with prognosis. For statistical analysis, IBM^® SPSS^® Statistics version 20 (Chicago, IL, USA) was utilized. A two-sided p-value < 0.05 was considered statistically significant. Results: Left atrial (LA) volume index (r = 0.230, p = 0.022), LA reservoir strain (r = 0.291, p = 0.003), and LA contraction strain absolute value (r = 0.223, p = 0.027) positively correlated with the severity of liver disease expressed by MELD Na score. LA dilation (≥34 mL/m²) was the most common echocardiographic finding. It was present in 69.7% of patients, with one third having severe LA dilation (>45 mL/m²), which was associated with worse survival (log rank p = 0.019). LA contraction strain with an absolute value higher than 16% was also associated with worse survival (log rank p = 0.024). In multivariable Cox analysis, only MELD-Na and LA volume index remained independently associated with mortality. Diastolic dysfunction appeared more prevalent among the non-surviving patients irrespective of the diagnostic criteria used (p = 0.023 for American Society of Echocardiography 2016 criteria; p = 0.032 for CCM 2019 criteria). On binomial logistic regression, the presence of significant diastolic dysfunction (>grade 1) was associated with an increased probability of composite end-point of death or LT in the presence of liver disease severity confounders. The use of the LA stiffness index in discerning diastolic function in patients with standard inconclusive evaluation may warrant further investigation. Conclusions: Echocardiographic alterations, particularly LA enlargement, are associated with liver disease severity and clinical outcomes in ESLD. These findings are hypothesis-generating and suggest a potential role for echocardiography in risk stratification, warranting validation in larger prospective studies. Full article

Background: Cervical cancer remains a leading cause of cancer-related deaths among women in Nigeria. In 2023, the Government of Nigeria, with support from Gavi and partners, introduced the single-dose human papillomavirus (HPV) vaccine through a phased, school-based campaign. The first phase was launched in October 2023 across 16 states, followed by a second phase in May 2024 that expanded coverage to the remaining states and the Federal Capital Territory. This study evaluates the additional impact of a behavioral insights–informed digital intervention, comprising a social media campaign amplified by trained pharmacists serving as local influencers, implemented in 2025 to increase acceptance and uptake of HPV vaccination during routine immunization. Methods: A pre-test/post-test quasi-experimental design with a control group was implemented in three Nigerian states in 2025 to assess the additional impact of a behavioral insights–informed social media campaign designed to strengthen social approval for HPV vaccination, increase awareness of vaccination locations, and reinforce caregivers’ recognition of their adolescent daughters’ desire to be vaccinated. Messages were amplified by trained pharmacists who served as local influencers. Caregivers of adolescent girls aged 9–17 years were recruited online through targeted Facebook and Instagram advertisements during Nigeria’s transition from school-based HPV vaccination campaigns to routine immunization. Caregivers in treatment areas were exposed to geofenced social media advertisements on Facebook and Instagram and pharmacist counseling, while those in control areas were not. Logistic regression models using a difference-in-difference approach estimated the campaign’s effect on HPV vaccination, controlling for caregiver and adolescent characteristics. Additional statistical models assessed the campaign’s impact on caregivers’ motivation and ability—key drivers of behavior according to the Fogg Behavior Model. Results: HPV vaccination increased at a significantly higher rate in the treatment compared to the control area. The adjusted odds of an adolescent girl being vaccinated were 1.48 times higher in the treatment area at follow-up (95% CI: 1.14–1.92). Adjusted marginal effects indicated that exposure to the campaign increased the probability of vaccination by 8.9 percentage points relative to the control group. The rate at which caregivers’ motivation (aOR = 1.31, 95% CI: 1.00–1.70) and ability (knowing where to get vaccinated: aOR = 1.38, 95% CI: 1.07–1.79; ease of vaccination: aOR = 1.59, 95% CI: 1.22–2.06) increased was also higher in the treatment area. There was no relative increase in intervention versus control groups in factual knowledge regarding HPV vaccination. Conclusions: A behavioral insights–informed social media campaign in which pharmacists served as influencers was associated with higher HPV vaccine uptake during routine immunization. The higher rate of vaccination observed in intervention areas was associated with higher rates of caregiver motivation and ability but not with higher rates of caregiver knowledge. These findings are consistent with the potential of behavioral insights–informed digital campaigns to complement routine immunization efforts and improve vaccine uptake in low- and middle-income countries. Full article

This manuscript is a continuation of the research published in Fire 2025, 8(8), 302, i.e., it deals with the examination of the cause-and-effect relationships of fires in the Republic of Serbia from the aspect of human safety. Among others, variables related to gender, age, and severity of injuries caused by fires are introduced, on which various methods of statistical analysis and stochastic modeling are first applied. Continuous age variables are modelled using the flexible Generalized Additive Models for Location, Scale, and Shape (GAMLSS) framework, where the Generalized Normal Distribution (GND) is identified as the optimal generative model for injuries, while a Reflected Log-Normal Distribution with positive support (RefLOGND+) provides the best fit for fatalities. The quality of such modeling is formally verified, and the probabilities of injury and death of individuals in certain age categories are predicted, revealing a pronounced concentration of injuries in the working-age population and a markedly higher relative risk of fatal outcomes among elderly individuals. Thereafter, by applying certain Data Mining (DM) techniques, primarily the Apriori algorithm, the most frequently occurring association rules are found, which indicate typical patterns and demographic structure of injuries and deaths in fires in Serbia. Finally, using the CART (Classification and Regression Trees) algorithm, several decision trees are formed that describe the impact and relationship of different causes of fires on injury and death in fires. In this way, some important and frequent patterns are observed that indicate key fire risk factors that significantly affect the demographic structure of human casualties. The results thus obtained provide a basis for developing targeted strategies for fire prevention and improving emergency response planning. Full article

Background/Objectives: Chronic kidney disease (CKD) is associated with substantial clinical and economic burden, largely driven by progression to dialysis. Nutritional interventions have shown potential in delaying disease progression, yet evidence on their cost-effectiveness remains limited. This study evaluated the long-term cost–utility profile of a low-protein diet supplemented with ketoanalogues (s-LPD) versus a standard low-protein diet (LPD) in patients with stage 4+ CKD from both the Italian National Health System (NHS) and societal perspectives. Methods: A Markov model with monthly cycles simulated disease progression from pre-dialysis to dialysis or death. Clinical inputs were derived from the published literature, while costs reflected 2024 Italian tariffs. Three effectiveness scenarios (optimistic, conservative, and pessimistic) were explored to account for uncertainty in the treatment effect. Outcomes included costs, life-years, quality-adjusted life-years (QALYs), and incremental cost–utility ratios. Deterministic and probabilistic sensitivity analyses assessed model robustness. Results: Across all scenarios, s-LPD improved survival (up to +0.59 life-years), increased QALYs (up to +0.48), and delayed dialysis initiation (up to +2.88 years) compared with LPD. From the NHS perspective, s-LPD was dominant in the optimistic scenario and cost-effective in both conservative and pessimistic scenarios, with cost savings or only a marginal cost that increases under extreme assumptions. Probabilistic sensitivity analyses confirmed a high probability of cost-effectiveness across scenarios. Results remained robust in additional scenario analyses, including the societal perspective. Conclusions: This first Italian cost–utility analysis of s-LPD highlights that s-LPD is a cost-effective strategy for patients with advanced CKD, offering clinically meaningful benefits while reducing or containing healthcare costs. These findings support the adoption of s-LPD as part of conservative management strategies aimed at safely delaying dialysis initiation. Full article

Background/Objectives: Inequality in survival across socioeconomic strata has been growing in the US for decades. Traditional measures of this inequality increasingly fail to capture the heterogeneous biological realities of the US population. Using new measures, this study provides a fresh perspective on the dynamics of mortality inequality across ten socioeconomic deciles in the United States from 1982 to 2019. Methods: The data come from annual life tables from US counties, aggregated according to their socioeconomic characteristics. Measures of Inequality: Three measures of inequality are used, capturing survival inequality from different perspectives, inequality in ages of death over the lifecycle, inequality in survival at older ages, and inequality in survival in midlife. For the latter, the equal survivorship age (ESA)—a metric defined as the age at which a specific subgroup’s survival probability from age 20 matches the survival probability from age 20 to 65 of the total population—is used. Results: We find consistently growing inequality, largely unaffected by economic circumstances such as the Great Recession. By 2019, the ESA for the lowest socioeconomic decile was nearly 11 years lower than the ESA of the highest decile. Conclusions: This “survival gap” in the ESA suggests that low-socioeconomic status (SES) populations effectively exhaust their survival reserves a decade earlier than their high SES counterparts. These findings challenge the equity of the use of universal chronological ages in public policies and underscore the need for “Social-Determinant-Adjusted” geriatric policy models. The growing inequality in the ESA suggests the importance of cohort-based influences. Full article

In a network invaded by a mutant according to the birth–death updating rule and uniform initialization, in order to minimize the amplifying effect of any directed network, the adjacency matrix is modified at each time step up to a given time horizon, subject to resource constraints. The fixation probability of an invasive mutant is deduced from the first eigenvector of the resulting modified Markov transition matrix. Large-scale minimization is solved numerically for a representative sample of directed graphs of dimensions 6 to 8. The effects of the determinants of the optimal reduction of the fixation probability are estimated using a Heckman selection model. The number of neighbors, the heterogeneity of the incoming edge weights, and the homogeneity of the outgoing edge weights of the initial network increase the likelihood that the graphs are amendable. Among the amended networks, the reduction in the fixation probability is greater when the outgoing edge weights of the initial network are heterogeneous, those of its incoming edges are homogeneous, and the sequence of modifications increases the variance of the outgoing edge weights and decreases that of the incoming edge weights, thereby creating a trade-off, which is estimated numerically. Full article

Candida species are frequently detected in bile cultures during endoscopic retrograde cholangiopancreatography (ERCP), but their clinical significance and the value of antifungal treatment remain unclear. We performed a retrospective single-center cohort study of adults with growth of Candida species from bile cultures collected by ERCP performed between 2010 and 2023. We compared inpatients who received vs. those who did not receive antifungals within one week of ERCP and a subgroup with acute cholangitis. The primary outcome was a composite of death and invasive candidiasis within one year. Secondary outcomes included death, invasive candidiasis, and rehospitalization. Inverse probability of treatment weighting (IPTW) was performed using baseline characteristics. Adjusted hazard ratios and odds ratios were calculated. Among 197 inpatients, 51 (25.9%) received antifungals. At one year, the primary outcome occurred in 23 of 51 patients (45.1%) receiving antifungal therapy and in 67 of 146 patients (45.9%) who did not; the IPTW-adjusted hazard ratio was 0.93 (95% confidence interval 0.69–1.27; p = 0.66). No significant differences were seen in the acute cholangitis subgroup (n = 117). In this study, antifungal therapy was not associated with improved survival, lower rates of invasive candidiasis, or fewer readmissions. Findings support a conservative, stewardship-oriented approach to managing Candida-positive bile cultures in the absence of invasive disease. Full article

Background/Objectives: Several chemotherapeutic regimens and targeted therapies are currently established as standard second-line treatments for patients with advanced biliary tract cancer (BTC). However, evidence regarding the benefits of treatment after first-line therapy failure remains limited, particularly among Thai populations. This study aimed to explore the efficacy of second-line chemotherapy in patients with advanced BTC. Methods: We conducted a single-institution, retrospective study including patients with locally advanced or metastatic BTC who experienced disease progression following first-line treatment between January 2017 and December 2019. Overall survival (OS) was defined as the primary endpoint. The secondary endpoint was the restricted mean survival time (RMST). To minimize confounding, propensity scores were estimated and applied using inverse probability of treatment weighting (IPTW). Results: A total of 110 patients were included, of whom 69 (62%) received second-line chemotherapy in combination with best supportive care (2LCMT + BSC), while 41 (38%) received best supportive care (BSC) alone. The majority of cases were intrahepatic cholangiocarcinoma (73.9% and 70.7% in each group, respectively). The median OS was 5.3 months (95% CI 3.5–7.0) in the 2LCMT + BSC group and 1.0 months (95% CI 0.5–1.9) in the BSC-only group (unadjusted HR 0.40, 95% CI 0.26–0.59; p < 0.001). In IPTW-adjusted flexible parametric regression analysis, second-line chemotherapy was associated with a 53% reduction in the risk of death compared with BSC alone (p = 0.009). The restricted mean survival time (RMST) differences between groups at 3, 6, and 12 months were 1.3 months (95% CI 0.9–1.6; p < 0.001), 2.6 months (95% CI 1.9–3.3; p < 0.001), and 3.9 months (95% CI 2.7–5.1; p < 0.001), sequentially. Conclusions: These findings demonstrate that second-line chemotherapy provides a significant overall survival benefit compared with best supportive care alone in patients with advanced BTC. Full article