Search Results (5,025)

This study examines the extent to which Chile’s 18 state universities contribute to sustainability and the 2030 Agenda, with a specific focus on the 17 Sustainable Development Goals (SDGs). To this end, scientific publications, technological developments, innovation initiatives, and funded research projects carried out between 2022 and 2023 were analyzed using a combination of bibliometric analysis and document review. Data were collected from Scopus, Web of Science, and national databases, and classified using a structured keyword strategy aligned with each SDG. A PRISMA-inspired screening and selection workflow was employed to ensure consistency and transparency in the selection of the results. The analysis reveals a clear institutional focus on SDG 3 (Good Health and Well-being), SDG 4 (Quality Education), and SDG 11 (Sustainable Cities and Communities), which together account for the majority of outputs analyzed. In contrast, SDG 14 (Life Below Water) and SDG 15 (Life on Land) exhibit comparatively lower levels of representation. Differences were also observed among universities and across geographical macro-zones. The integrated analysis revealed important thematic asymmetries, territorial specialization patterns, and differentiated institutional sustainability profiles across the Chilean public university system. These findings highlight both the strengths and the current gaps in institutional alignment with the SDGs. The paper concludes by proposing concrete measures to improve coordination and information systems with the aim of reinforcing the strategic role of public universities in advancing sustainable development at both the national and regional levels. Full article

Energy security and efficiency governance are among the most critical policy challenges facing emerging economies in the post-Paris Agreement era. While international frameworks such as the IFCMA Climate Policy Database provide unprecedented comparative data on national mitigation instruments, the role of artificial intelligence (AI) in optimizing policy design across the efficiency–security nexus remains underexplored. This study develops an AI-driven analytical framework—integrating K-Means clustering, Principal Component Analysis (PCA), and Random Forest classification—and applies it to the April 2026 edition of the IFCMA Climate Policy Database, encompassing 4627 active policy instruments across 42 countries. We systematically compare the policy instrument portfolios of nine emerging economies with those of thirty-two developed counterparts, with a particular focus on energy efficiency standards, fiscal instruments, and strategic security objectives. The results reveal that emerging economies exhibit structural under-utilization of performance standards and trading schemes, disproportionately high energy security objective ratios relative to their efficiency instrument sophistication, and an over-reliance on tax instruments compared to their counterparts in developed economies. The Random Forest classifier achieves 83.1% cross-validated accuracy in predicting emerging economy status from policy features, with performance standards and efficiency objectives as the strongest discriminators. Three distinct policy regime archetypes are identified: Standard-Dominant Mixed (Cluster A), Tax-and-Label-Dominant (Cluster B), and Trading-Intensive Transition (Cluster C). These findings provide AI-supported, evidence-based policy intelligence for governments seeking to move beyond minimum regulatory compliance and align energy efficiency governance with strategic energy security objectives. Full article

This paper examines how artificial intelligence can support sustainability assessment in cultural industries, using national film industries as a test case. The Film Industry Sustainability Index (FISI) is introduced as a composite indicator covering cultural diversity, economic resilience, and Sustainable Development Goal (SDG) alignment for 42 national economies from 2005 to 2023. Knowledge-Enhanced Mamba (KE-Mamba), a selective state-space forecasting model, is then proposed to combine annual panel indicators with country-level film-industry knowledge graph (KG) embeddings and large language model (LLM)-derived screenplay-oriented narrative proxies from film synopses. To reduce factual errors in title-level narrative scoring, the LLM is anchored to verified United Nations Educational, Scientific and Cultural Organization (UNESCO) records and the European Audiovisual Observatory’s LUMIERE film-admissions database using rank-one model editing (ROME). On the 2020–2023 held-out test period, KE-Mamba achieves a composite FISI mean absolute error (MAE) of 0.0389, a mean absolute percentage error (MAPE) of 5.61%, and an $R^2$ of 0.934, outperforming autoregressive integrated moving average (ARIMA), tree-based, long short-term memory (LSTM), and base Mamba baselines. Additional robustness checks using a pre-pandemic split, two-way fixed-effects panel regression, alternative FISI weighting schemes, KG embedding ablations, and human validation of LLM narrative scores support the reliability of the proposed framework. Policy simulations are interpreted as model-based projected associations rather than causal estimates. The results show that knowledge-enhanced sequence models can provide transparent forecasting support for sustainable cultural-industry policy. Full article

Introduction: Pregnancy in women with end-stage kidney disease (ESKD) remains rare and high-risk, despite advancements in dialysis and supportive care. Using a nationwide database in South Korea, this study examined the maternal and neonatal outcomes among women undergoing maintenance hemodialysis, with a particular focus on dialysis modality and treatment patterns. Methods: This population-based retrospective cohort study utilized data from the Korean National Health Insurance Service database. The study included all live births between 1 January 2014 and 31 December 2022, linked to mothers who underwent hemodialysis at least twice per week during pregnancy. Results: Between 2014 and 2022, in the Republic of Korea, 31 live births were recorded among 29 women undergoing hemodialysis. The mean maternal age at delivery was 36.1 ± 4.94 years, and most patients had significant comorbidities, including hypertension (79.3%), and diabetes mellitus (48.3%). Cesarean section was the predominant mode of delivery (75.9%). Pregnancy-related complications included preterm delivery (48.4%), preeclampsia (16.1%), and gestational diabetes (16.1%). A total of 16.1% of the neonates had atrial septal defects. During the peripartum period, 93.1% of deliveries occurred at tertiary care centers, and trimester-wise escalation in dialysis frequency was observed. Conclusions: This study provided real-world data on pregnancy-related outcomes among women with ESKD undergoing maintenance dialysis in Korea. Given the rarity of this clinical condition, our findings may serve as a valuable reference for the management of pregnant women with ESKD. Full article

Background/Objectives: Spinal ependymoma is the most common intramedullary spinal cord tumor in adults, and maximal safe resection is the cornerstone of treatment. Patients aged 75 years and older are underrepresented in surgical neuro-oncology cohorts. We sought to characterize treatment patterns and identify predictors of overall survival in very elderly patients with spinal ependymoma. Methods: We performed a retrospective cohort study of patients aged 65 years or older with spinal ependymoma using the National Cancer Database. The primary cohort was patients aged 75 years or older (very elderly); patients aged 65–74 years served as a comparison cohort. Multivariable Cox proportional-hazards models were fit within each cohort, and a surgery-by-age-cohort interaction was tested. Results: Of 1497 eligible patients aged 65 years or older with spinal ependymoma, 422 patients (28.2%) met criteria for the final analytic cohort. Intramedullary versus extramedullary tumor status was not available in the NCDB PUF and therefore could not be characterized. Very elderly patients were less likely to undergo surgery than the comparison cohort (70% vs. 85%; p < 0.001) despite similar tumor characteristics. Among very elderly patients, median overall survival was 59.7 months without surgery and 106.0 months with surgery, an approximately 46-month difference favoring surgery. Surgery was independently associated with lower mortality (HR 0.46; 95% CI, 0.24–0.89; p = 0.021). Increasing age (HR 1.15 per year; 95% CI, 1.07–1.22; p < 0.001), Charlson–Deyo score ≥ 2 (HR 4.41; 95% CI, 1.65–11.79; p = 0.003), and increasing tumor size (HR 1.02 per mm; 95% CI, 1.01–1.04; p < 0.001) were also independently associated with worse survival. In the 65–74 cohort, no significant association between surgery and overall survival was detected (HR 1.23; 95% CI, 0.54–2.81; p = 0.623), though statistical power was limited by only 7 deaths in the no-surgery arm. The surgery-by-age-cohort interaction was significant (HR 0.37; p = 0.043). Conclusions: Surgical resection was independently associated with improved overall survival in very elderly patients with spinal ependymoma despite lower utilization. Chronological age alone may be an imperfect basis for excluding older adults from surgical consideration. Full article

Background: Liver diseases are an increasing public health concern in Morocco; reliable national population-based estimates of liver fibrosis and cirrhosis in Morocco are currently unavailable. Existing evidence is largely limited to selected high-risk groups and hospital-based cohorts. Generating reliable prevalence data is crucial for designing evidence-based screening pathways, targeting high-risk groups and informing prevention and treatment policies. Objectives: Our aim was to comprehensively review studies on the prevalence of liver fibrosis and cirrhosis in Morocco, focusing on characterizing study populations, specifically high-risk populations and hospital-based cohorts, diagnostic methods and thresholds used. The review also summarizes hospital-based cirrhosis cohorts without merging them with prevalence estimates, and identifies gaps in the literature, particularly the absence of population-based prevalence studies and national epidemiological data in Morocco. Methods: The study systematically reviewed literature up to 26 October 2025, including studies conducted in Morocco among high-risk populations or hospital-based cirrhosis cohorts, using multiple databases. Two reviewers independently screened and extracted data, assessing bias with the Joanna Briggs Institute (JBI) checklist. Due to heterogeneity in study populations and diagnostic approaches, a narrative synthesis was performed. Hospital-based cohorts were analyzed separately to provide contextual information and were not included in prevalence estimates. Results: From 1198 records, four Moroccan studies providing prevalence data on liver fibrosis and cirrhosis were included, primarily involving patients with hepatitis C, HIV, or rheumatoid arthritis. Additionally, three hospital-based cirrhosis cohorts were incorporated for a contextual analysis of disease severity and complications. In total, seven studies were included, with prevalence and hospital-based data analyzed separately to ensure clarity. Conclusions: Current evidence on liver disease in Morocco is limited but suggests a significant burden among high-risk groups. The findings highlight major gaps in national epidemiological data and underscore the urgent need for comprehensive nationwide data and improved diagnostic tools to guide effective screening, prevention, and resource allocation. Full article

The genus Tulipa L. is a common group of ornamental plants, characterized by high morphological variability and a complex taxonomy. Despite considerable interest in this group, assessments of its species composition remain inconclusive, as evidenced by discrepancies between contemporary taxonomic sources. The number of recognized taxa varies across major taxonomic databases, including Plants of the World Online, World Flora Online, and Euro+Med PlantBase, reflecting ongoing taxonomic revisions and differences in species concepts. In terms of distribution patterns, 7.6% are widely distributed taxa across transcontinental regions, 28.0% occur across multiple countries within a continent, and 66.9% are range-restricted taxa. The latter group includes 4.2% transnational endemics, 44.1% single-country endemics, 8.5% single-region endemics, and 10.2% single-site endemics. Recent taxonomic and evolutionary studies of Tulipa increasingly rely on molecular approaches, particularly DNA barcoding and chloroplast genome analyses, which have improved phylogenetic resolution and species delimitation in several cases. However, truly comprehensive studies combining morphological, cytogenetic, and molecular datasets remain limited and are typically restricted to individual taxa or species complexes rather than the genus as a whole. Modern molecular genetic studies demonstrate the high informativeness of both nuclear and plastid markers for studying the phylogeny, systematics, and genetic diversity of Tulipa species. Natural populations of Tulipa are under pressure from anthropogenic factors and climate change, resulting in reduced range and habitat degradation. According to the International Union for Conservation of Nature Red List of Threatened Species, among 118 taxa of the genus Tulipa, T. sprengeri Baker is classified as Extinct in the Wild, 5.9% as Critically Endangered, 5.9% as Endangered, 8.5% as Vulnerable, 11.9% as Near Threatened, and 11.0% as Least Concern. The use of exclusively national assessments to determine species extinction risk may be insufficiently objective, whereas global assessments provide a more informative and reliable approach for evaluating conservation status. In this review, we combine investigations of the morphology, taxonomy, and geographic diversity; population genetic structure and molecular diversity; and molecular phylogenetics and plastome-based genomics of the genus Tulipa. Furthermore, the review examines current challenges and future research prospects, emphasizing that studies of the genus Tulipa should integrate morphological, genomic, and ecological approaches to refine taxonomy and conserve genetic resources. Full article

Snake envenomation causes acute cerebrovascular complications, but its long-term effect on stroke risk remains unclear. This study suggests that snake envenomation may be associated with long-term stroke risk. Using the Korean National Health Insurance Service database, we conducted a nationwide population-based cohort study to evaluate the long-term risk of stroke following snake envenomation. A total of 764 adult patients diagnosed with snake envenomation and treated with antivenom were identified and matched with 3056 control patients (1:4) by age, sex, and socioeconomic status, excluding those with prior cerebrovascular disease. Stroke outcomes were defined using ICD-10 diagnostic codes and healthcare utilization criteria. After a 1-year lag period was applied to minimize reverse causation, multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios for total, ischemic, and hemorrhagic strokes. During 10 years of follow-up, snake envenomation was associated with a significantly increased risk of total stroke (aHR 1.42 (95% CI 1.01–1.99)), particularly hemorrhagic stroke (aHR 2.55 (95% CI 1.12–5.80)), whereas no significant association was observed with ischemic stroke. Interaction analyses showed a stronger association among men with diabetes mellitus, particularly for hemorrhagic stroke. In addition, severe envenomation with disseminated intravascular coagulation or requiring transfusion was associated with a higher long-term risk of hemorrhagic stroke. These findings highlight the need for further investigations of long-term cerebrovascular complications of snake envenomation, particularly hemorrhagic stroke in vulnerable populations. Full article

In the context of dynamic environmental changes, accurate geospatial information is fundamental for evidence-based decision-making in land-use planning. As urban areas undergo rapid structural transformations, characterizing their spatial morphology becomes essential for assessing ecosystem conditions and identifying pressure points within the urban–rural gradient. Drawing on the indicators for ecosystem condition and pressure recommended by the Mapping and Assessment of Ecosystem Services (MAES) framework, reflecting their trends, this study presents a methodology for comprehensive geospatial mapping of urban and peri-urban morphology, using the Functional Urban Area (FUA) of Burgas, Bulgaria, as a case study. The approach enables multi-scale spatial analysis (regional and local), integrates the structure and functions of urban ecosystems, and reveals the spatial heterogeneity of complex socio-economic systems. At the regional level, ecosystems within the FUA were identified using the national land-use/land-cover database. At the local level, within the city of Burgas, urban morphology was classified by combining building and land-cover types into 14 distinct urban morphological zones (local climate zones—LCZs) using high-resolution unmanned aerial vehicle (UAV)-based orthophotos. This precise spatial data allowed for a detailed assessment of the balance between pervious and impervious surfaces within each LCZ. By integrating Google Earth Engine (GEE) data, the appropriate conditions and pressure indicators in the case study are assessed. Regional ecosystem pressure is effectively captured through the spatial distribution of the Final Pressure Index (IPr). Concurrently, the Urban Ecosystem Performance Index (UEPI) highlights sharp spatial polarization, with critical stress concentrated in the industrial and port zones of the urban core. The results provide policy-makers and stakeholders with critical insights into current pressures and environmental changes in urban and peri-urban ecosystems, offering a robust foundation for evidence-based management and climate change adaptation strategies. Full article

Informed consent is a core ethical and legal requirement in clinical practice. For individuals with aphasia, language impairments can hinder communication during consent processes. However, aphasia is primarily a language disorder and does not inherently imply cognitive impairment, a distinction frequently overlooked in clinical and legal settings. This scoping review examines how decision-making capacity (DMC) is assessed and supported in adults with aphasia, and outlines the clinical, ethical, and medico-legal implications for consent procedures. The review followed PRISMA-ScR guidelines. A systematic search of biomedical and legal databases was conducted without time restrictions. Studies addressing informed consent or DMC in adults with aphasia were included and analyzed using a qualitative thematic approach. Out of 519 records, 9 studies (2010–2024) from Australia, Canada, the United Kingdom, and Ireland met inclusion criteria. These studies often referenced national legislation and rights-based frameworks to define clinical responsibilities. Three main themes emerged: (1) DMC assessments rely heavily on language, with limited involvement of speech–language pathologists (SLPs), despite their role in reducing bias; (2) supported communication strategies—such as simplified language, visual aids, alternative response formats, and structured tools—can uncover “hidden competence”; and (3) structural barriers, including time constraints, insufficient training, and limited access to aphasia services, restrict implementation. Current evidence remains limited, largely qualitative, and insufficient to support definitive clinical recommendations. Incorporating supported communication, multidisciplinary assessment, and thorough documentation may enhance fairness and legal robustness. Future research should focus on validating aphasia-sensitive tools and evaluating their impact on outcomes and medico-legal risk. Full article

Background: Parkinson’s disease and dementia are major neurodegenerative disorders that substantially contribute to disability, dependency, and mortality worldwide. Although prior CDC WONDER studies have separately evaluated Parkinson’s disease and dementia mortality trends, fewer analyses have examined national mortality patterns in which both conditions are recorded on death certificates simultaneously over extended time periods. Methods: We analyzed U.S. death certificates from 1999 through 2025 using the CDC WONDER Multiple Cause of Death database, identifying deaths among adults aged ≥45 years in which both Parkinson’s disease (ICD-10 G20) and dementia-related codes (F01, F03, G30, G31) were recorded anywhere on the certificate. This operational definition captures co-recorded diagnoses and does not identify clinically confirmed Parkinson’s disease dementia. Age-adjusted mortality rates (AAMRs) per 100,000 were standardized to the 2000 U.S. standard population, a method that controls for shifts in population age structure over time and allows valid temporal comparisons independent of absolute population growth. Joinpoint regression was used to quantify trends. Sensitivity analyses excluded 2025 provisional data and the COVID-19 period (1999–2019). Results: A total of 337,721 deaths were identified. Overall AAMR increased from 5.75 (95% CI: 5.60–5.90) in 1999 to 11.15 (95% CI: 10.98–11.32) in 2025 (AAPC: 2.07; p = 0.002). A sharp transient increase occurred in 2020, attributable to pandemic-related factors including disproportionate COVID-19 mortality among older adults with neurodegenerative conditions, care disruptions, and changes in death-certificate coding practices. Following this pandemic-era peak, AAMRs declined significantly through 2025 and should be interpreted cautiously given provisional data. Males (AAPC: 2.14), non-Hispanic White individuals (AAPC: 2.29), the Midwest region (AAPC: 2.65), and non-metropolitan areas carried the highest mortality burden. Mortality was greatest among adults aged ≥85 years. Conclusion: Population-level death rates involving co-recorded Parkinson’s disease and dementia demonstrated significant temporal changes over the study period, with marked demographic and geographic disparities. These findings reflect death-certificate surveillance data and cannot establish clinical co-occurrence, causal relationships, or individual disease risk. Full article

Compact urban form can reduce road transportation GHG emissions and mitigate resource supply bottlenecks associated with mass EV adoption. Global databases from Climate TRACE and the Global Human Settlement Layer are utilized to develop the Compact Urban Form Estimation Tool or CUFET for calculating the reduction in VKT and road transportation GHGs from shifting toward CUF. The CUFET does not explicitly account for mechanistic changes in driving (e.g., modal shift) but rather uses settlement density as a coarse proxy for walking and transit urban fabrics. VKT was modeled using weighted least squares regression from the independent variables settlement population, settlement population density, and country fixed effects. Population size banding was introduced to the model to improve explanatory power. The model was developed using 10,495 settlements in the 2021 Climate TRACE dataset. The CUFET VKT model was able to explain 78% (p < 0.001) of the variation in the VKT of test settlements and improved with the addition of a country fixed effect. The CUFET on average gave estimates of VKT within 24% of Climate TRACE-calculated VKT for countries with a GDP per capita between $20,000 and $45,000 and average estimates within 20% for countries with a GDP per capita above $45,000. Increased settlement density was associated with more substantial reductions in VKT in small (50,000 to 88,335) and medium (88,335 to 329,480) sized settlements relative to large (>329,480) settlements. Higher variability was observed in VKT estimates of small settlements. The CUFET VKT was validated by backcasting historical VKT data from 1960 to 2000. The backcasting exercise used historical administrative boundaries and only included high economic output nations (GDP per capita above $20,000 in 2021 USD). Despite these limitations, backcasting achieved a % difference of ~20% for settlements after 1990, suggesting the model can make useful estimates within 30 years of the model calibration year for high economic output nations. The VKT model was used to calculate emissions using a settlement-specific emissions factor. Settlements with annual road transportation emissions per capita greater than 2 t CO₂eq have the lowest population densities relative to their populations and are mostly located in the United States, Japan, Canada, and Australia. The nations with the highest transportation emissions are also nations where the CUFET provides the most accurate VKT estimates. The CUFET aims to bridge the gap between academic consensus and local decision-making practice by reducing the barriers to estimate VKT and transportation GHG reduction from shifting to compact urban form. Full article

Background: Virological suppression is a key outcome of antiretroviral therapy. Despite progress in HIV treatment in Kazakhstan, virological non-suppression remains a relevant clinical and public health issue requiring further analysis. This study aimed to assess the prevalence of virological suppression (VS) and to identify factors associated with the absence of VS among people living with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy (ART) in Kazakhstan. Methods: A retrospective cross-sectional analytical study was conducted using secondary analysis of a de-identified national registry database of people living with HIV (PLHIV) receiving ART in the Republic of Kazakhstan as of 30 September 2025. The primary outcome was virological non-suppression (VNS), defined as the last viral load (VL) value of at least 200 copies per milliliter. The analysis included sex, age, presumed route of HIV transmission, the first available cluster of differentiation 4 (CD4) cell count recorded in the registry, the last recorded percentage category of adherence to ART, and the aggregated category of ART regimen. The main descriptive, bivariate, and multivariable analyses were performed using a complete-case approach. Independent associations were assessed using multivariable logistic regression, and the results were presented as adjusted odds ratios (aORs) with 95 percent confidence intervals (CIs). Results: The initial registry extraction included 33,614 records, of which 32,130 patients were included in the final analytical sample. VS was achieved in 29,454 (91.7%) patients, whereas VNS was observed in 2676 (8.3%) patients. In the multivariable model, higher adjusted odds of VNS were observed among men compared with women (aOR 1.14; 95% CI 1.02–1.26), as well as among patients with a first CD4 count < 200 cells/μL compared with those with a first CD4 count of ≥500 cells/μL (aOR 1.25; 95% CI 1.09–1.44). The strongest association was found for reduced adherence to therapy. Compared with adherence of at least 95%, the adjusted odds of VNS were markedly higher among patients with adherence of 85–94% (aOR 28.66; 95% CI 25.85–31.77) and among those with adherence below 85% (aOR 61.05; 95% CI 50.50–73.81). In all age groups older than 25 years, the adjusted odds of VNS were lower than among patients younger than 25 years. Lower adjusted odds of VNS were also observed among patients with homosexual transmission, vertical transmission, and other or unspecified transmission routes compared with heterosexual transmission. Among ART regimens, regimens containing non-nucleoside reverse transcriptase inhibitors (NNRTIs) were associated with lower adjusted odds of VNS than dolutegravir-containing regimens (DTG-containing regimens) (aOR 0.68; 95% CI 0.52–0.88), whereas no statistically significant differences were identified for regimens containing protease inhibitors (PIs). Conclusions: Despite the high overall level of VS among PLHIV receiving ART in Kazakhstan, VNS remains concentrated in clinically and programmatically important subgroups. It was most strongly associated with reduced adherence and was also associated with younger age, marked baseline immunosuppression, and male sex in the primary model. These findings support the need for targeted interventions focused on adherence support, early diagnosis, and differentiated long-term follow-up of patients. Full article

Background: Pediatric influenza-like illness (ILI) represents a major global health burden. However, international treatment guidelines lack robust evidence specific to children. Umifenovir (Arbidol) is a broad-spectrum antiviral approved for pediatric use in several countries, but clinical data are fragmented and regionally limited. Methods: A comprehensive search of PubMed, Russian (RSCI, national archives, regulatory documents), and Chinese (CNKI) databases was conducted for pediatric randomized controlled trials (RCTs) and non-randomized trials comparing umifenovir to symptomatic therapy (ST) or oseltamivir. Risk of bias was assessed using the RoB 2 tool for RCTs, and ROBINS-I for non-RCTs. Outcomes included the duration of fever and other symptoms, prophylactic efficacy, and adverse events. Random-effects models were used (Hartung–Knapp–Sidik–Jonkman approach). The review was not registered. Results: We included 16 therapeutic and eight prophylactic trials enrolling approximately 4700 and 2000 children, respectively. Compared with ST, umifenovir reduced the duration of fever (MD −1.41 days, 95% CI: −1.78 to −1.05), cough (−1.15 days, 95% CI: −1.50 to −0.79), and hospitalization. The complication risk decreased (RR 0.34, 95% CI: 0.23–0.51). For prophylaxis, umifenovir reduced the risk of ILI (RR 0.68, 95% CI: 0.54–0.87) and laboratory-confirmed influenza (RR 0.41, 95% CI: 0.29–0.59). Adverse events were generally mild and did not differ significantly from ST or oseltamivir (RR 0.78, 95% CI: 0.51–1.20). Conclusions: Umifenovir may reduce symptom duration, complications, and infection risk in pediatric ILI, with a favorable safety profile. However, the overall certainty of evidence is limited by the age of the studies, geographic restriction, and methodological quality. Full article

Background: Sepsis remains one of the leading causes of hospital morbidity and mortality worldwide. While its epidemiology has been extensively investigated, the chronobiology of sepsis—the temporal patterns underlying its occurrence and outcomes—has received comparatively little attention, despite its potential relevance for anticipating clinical demand and optimizing healthcare resource allocation. Objective: To analyze trends in the epidemiology and chronobiology of hospital admissions for sepsis across a large healthcare region in Spain over a 21-year period. Design: Retrospective observational study based on clinical–administrative records. We included all patients ≥ 18 years who had a principal diagnosis of sepsis or septic shock admitted between 2001 and 2021, identified through ICD-9-CM and ICD-10-CM coding in the Spanish National Hospital Discharge Records Database. Annual incidence, in-hospital mortality, and temporal distribution of admissions and deaths were assessed. Joinpoint regression was used to evaluate trends, Fourier spectral analysis to identify dominant rhythms, and multi-harmonic cosinor models to test for circannual rhythmicity. Results: We identified 39,622 sepsis admissions. Hospital incidence increased significantly over time (annual percent change [APC]: +9.6%; p < 0.001), with two inflection points (2008 and 2014). In-hospital mortality decreased linearly from 42.1% in 2001 to 31.9% in 2021 (p < 0.001), despite a progressive increase in patient age. Chronobiological analyses revealed no significant circannual rhythm in incidence or mortality (cosinor p = 0.14), although mortality was disproportionately clustered in winter months (p < 0.001). In multivariable analyses, clinical and epidemiological variables were independent predictors of in-hospital mortality. Conclusions: Over the last two decades, sepsis incidence has risen steadily, whereas hospital mortality has declined. Although no regular biological rhythm was demonstrated, excess winter mortality suggests extrinsic seasonal influences. This study provides novel evidence by jointly examining the epidemiology and chronobiology of sepsis, and supports their integration into healthcare planning strategies. Full article