Cardiovascular-Kidney-Metabolic (CKM) syndrome became the leading cause of death among U.S. adults in 2021. However, the relationship between different stages of CKM and the risk of all-cause mortality in the U.S. population remains unclear. Data from NHANES 2005–2018 and the Public-use Linked Mortality Files (LMF) were utilized in this study. Kaplan–Meier survival curves were generated to estimate survival probabilities across five CKM stages (stages 0 to 4) and compared using the log-rank test. Hazard ratio (HR) and 95

Risk factors at different stages of COVID-19 may interact with each other, forming a risk network. Identifying the key risk factors within this network and their interrelationships is crucial for reducing the overall risk of COVID-19. We constructed three Bayesian Belief Network (BBN) models by combining data-driven approaches with expert validation. Using the Tree-Augmented Naive Bayes (TAN) algorithm, we developed the INFORM COVID-19 Risk BBN model and the COVID-19 Regional Safety Assessment BBN model. The joint BBN model was established using the Greedy Thick Thinning (GTT) algorithm. Parameter learning was performed through maximum likelihood estimation. Expert validation, 10-fold cross-validation, and model performance metrics were employed to comprehensively assess the overall performance of the models. Additionally, mutual information analysis and sensitivity analysis were used to explore the importance of risk factors at each stage and their interdependencies. "INFORM Vulnerability" and "INFORM Lack of Coping Capacity" were identified as the two key risk factors influencing the risk of early outbreak. In the mid-to-late stages of the pandemic, "Emergency Preparedness" and "Monitoring and Detection" had the greatest impact on regional safety and control measures. Furthermore, the joint BBN model indicated that the most important risk factors affecting the overall COVID-19 risk were "Lack of Coping Capacity," "Government Risk Management Efficiency," and "Regional Resiliency," while the influence of other variables was relatively minor. The main contribution of this study lies in identifying the key risk factors at different stages of the pandemic and their interdependencies, providing policymakers with valuable insights for the rational allocation of limited health resources and the formulation of appropriate and effective prevention and control policies.

The consumption of ultra-processed food (UPF) has been linked to bone metabolism in adults, but its impact on bone mineral density (BMD) in children and adolescents remains unclear. This study analysed data from 4809 children and adolescents aged 8–19 years, drawn from the National Health and Nutrition Examination Survey (NHANES) 2011–2018. UPF intake was categorised according to the NOVA classification system, with the percentage of energy derived from UPF divided into quartiles (Q1–Q4). A weighted multiple linear regression model was used to examine the relationship between UPF intake and lumbar spine BMD (LSBMD) and subtotal BMD (SBMD). Stratified analyses were conducted to explore associations across various subgroups. The results indicated that UPF intake was positively associated with LSBMD. This association was significant in girls for both LSBMD and SBMD. Positive correlations with LSBMD also emerged in 12–15 years old and specific subgroups. Moreover, mediation analysis showed total cholesterol mediated 4·8 % of the UPF–LSBMD link, and HDL-cholesterol mediated 0·9 % of the UPF–SBMD one. These findings indicate that UPF intake is associated with increased BMD in children and adolescents. Future research should further investigate the complex effects of UPF on the health of this population.

BACKGROUND AND OBJECTIVES:Chronic pain is a significant risk factor for limitations in activities of daily living (ADL). However, previous studies have mostly assessed pain severity at a single time point, overlooking its temporal variability. This study aims to explore the longitudinal associations between trajectories of chronic generalized pain severity, the number of pain sites, and trajectories of chronic site-specific pain severity with the risk of developing ADL limitations. METHODS:This study utilized longitudinal data from individuals aged 50 and above in two cohorts: the English Longitudinal Study of Ageing (ELSA) and the Korean Longitudinal Study of Aging (KLoSA). By analyzing dynamic changes in pain severity states, trajectories of chronic generalized pain severity, the number of pain sites, and chronic site-specific pain severity were identified. Cox proportional hazards models were applied to assess the associations between various pain severity trajectories and the incidence of ADL limitations. Mediation analysis was conducted to investigate the mediating effect of depression. RESULTS:The Cox proportional hazards models showed that, among trajectories of chronic generalized pain severity and pain severity at the back, feet, and knees, the persistent high-level pain and worsening pain trajectory groups exhibited the highest increased risk of ADL limitations. Additionally, all trajectories of the number of pain sites were positively associated with ADL limitation risk, with the increasing number of pain sites trajectory showing the strongest association (HR = 2.738, 95% CI: 2.147-3.492). Depression mediated the associations between various pain severity trajectories and ADL limitations. CONCLUSION:The research findings underscore the significant role of long-term, persistently high levels and progressively worsening severity of chronic systemic and localized pain in the limitations of ADL functions in older adults. Incorporating longitudinal monitoring of chronic pain severity trajectories into ADL function limitation management programs is crucial for enhancing preventive and therapeutic interventions.

Cardiovascular and cerebrovascular diseases represent leading global health challenges, accounting for approximately one-third of worldwide mortality, yet current therapeutic approaches remain inadequate due to complex etiology and limited drug delivery efficiency. This review examines engineered exosome technologies through analysis of preparation methodologies, biological characteristics, therapeutic applications, and clinical translation challenges. The review evaluates engineering approaches including viral/plasmid transfection, CRISPR/Cas9 genome editing, and post-isolation modifications such as electroporation, ultrasonication, and surface functionalization. Engineered exosomes demonstrate superior advantages over conventional synthetic systems through natural biocompatibility, enhanced circulation stability, blood-brain barrier penetration, reduced immunogenicity, and precise cellular targeting via receptor-mediated interactions. Key findings reveal successful therapeutic applications across atherosclerosis, myocardial infarction, heart failure, pulmonary arterial hypertension, stroke, intracerebral hemorrhage, and neurodegenerative conditions, effectively delivering diverse payloads including small molecules, proteins, nucleic acids, and diagnostic probes. Critical challenges requiring resolution include standardization of preparation protocols, scalable production methodologies, comprehensive pharmacokinetic characterization, preservation technologies, and rigorous safety evaluation frameworks. Through continued technological advancement, engineered exosomes present transformative opportunities for precision medicine approaches to cardiovascular and cerebrovascular disorders, establishing revolutionary nanoscale delivery platforms that address synthetic nanomaterial limitations.

Effective identification and correction of diabetes mellitus (DM)-related garbage codes (GCs) in mortality surveillance data is crucial for accurately estimating regional DM mortality rates. This study applied a structured, three-step approach-using standard WHO ICD-10 mortality coding rules, coarsened exact matching (CEMM), and fixed proportion reassignment (FPRM)-to redistribute diabetes-related GCs in Weifang's mortality data (2010-2022). Using ICD-10 coding rules, we reclassified 29 deaths originally assigned to DM as the underlying cause of death (UCD) to other causes, and reassigned 1,945 records previously not attributed to DM to DM as the UCD. CEMM then reclassified 283 DM-related GC records to DM, followed by FPRM, which reassigned 160 "unknown cause" records to DM. Together, these steps increased the number of DM deaths by 22.82%. Based on the reallocated data, crude DM mortality rates rose from 7.64 to 17.75 per 100,000 between 2010 and 2022, with males experiencing a greater overall increase than females. While no new algorithms were developed, this study demonstrates how internationally recommended coding standards-often neglected in routine subnational settings-can be systematically and rigorously applied to improve DM mortality surveillance. This work highlights operational gaps in local death certification and presents a replicable protocol for enhancing mortality data reliability using existing tools.

Abstract Background and purpose Ischemic stroke is a significant public health concern, particularly in Eastern Europe, where the burden remains high. This study aims to evaluate the trends and burden of ischemic stroke in Eastern Europe from 1990 to 2021, providing insights into epidemiological changes and informing public health strategies. Methods We used data from the Global Burden of Disease 2021 database to comprehensively assess regional and national ischemic stroke indicators in Eastern Europe. These indicators included the number of cases, incidence, number of deaths, mortality, disability-adjusted life years (DALYs), DALY rates, and estimated annual percentage change (EAPC). Joinpoint analysis was employed to examine sex-specific time trends in the burden of ischemic stroke across Eastern European countries. These estimates incorporated the Socio-Demographic Index (SDI). Results In 2021, Eastern Europe reported 490,197 cases of ischemic stroke, with an age-standardized incidence rate (ASIR) of 142.57 (95% UI: 122.12 to 164.67), exceeding the global level. The region recorded 329,291 deaths, with an age-standardized mortality rate (ASMR) of 90.99 (95% UI: 82.79 to 98.48), significantly higher than the global rate. Disability-adjusted life years (DALYs) totaled 5,713,718, with an age-standardized DALYs rate (ASDR) of 1601.20 (95% UI: 1483.51 to 1723.12). Our joinpoint regression analysis indicates that the disease burden remains notably high in Eastern Europe, despite an overall declining trend from 1990 to 2021 in ASIR and ASMR across most countries, with estimated annual percentage changes (EAPC) of -1.13 (95% CI: -1.24 to -1.02) and − 2.78 (95% CI: -3.24 to -2.32), respectively. Lithuania reported the highest incidence rate, while the Russian Federation had the highest mortality and DALY rate. Conversely, Estonia showed significant improvements in stroke indicators. Key risk factors included low temperature and smoking, contributing notably to environmental and behavioral risks. Conclusion Ischemic stroke continues to be a significant global health issue. Our temporal trends study results indicate that the disease burden remains notably high in Eastern Europe, particularly in Lithuania and the Russian Federation.

Background The potentially risky effects of metabolites of phthalates (mPAEs) on inflammation and immune function have attracted much attention in recent years. However, direct studies on the relationship between these metabolites and the systemic immune inflammatory index (SII) and systemic inflammatory response index (SIRI) are limited.Methods This cross-sectional study used generalized linear regression models (GLM), restricted cubic splines (RCS), weighted quantile sum (WQS), and Bayesian kernel-machine regression (BKMR) to analyze data from 2,763 U.S. adults aged between 20 and 80 years, obtained from the U.S. National Health and Nutrition Examination Survey (NHANES) conducted between 2013 and 2018. The study aimed to investigate the relationship between urine samples of nine mPAEs and levels of SII/SIRI in a single, nonlinear, and mixed relationship and explored the robustness of the findings under single and mixed effects using two sensitivity analyses for completeness. In addition, the effects of six variables (age, sex, BMI, the percentage of total daily energy intake from ultra-processed foods (UPFs), total vegetable intake, and dietary supplements) on the association results were explored through subgroup analyses to identify potentially important confounders.Results In single exposure analyses, mono-n-butyl phthalate (MnBP), mono-ethyl phthalate (MEP), and monobenzyl phthalate (MBzP) were positively associated with SII/SIRI. The findings from the two mixed exposure models demonstrated a positive association between the collective concentrations of mPAEs and levels of SII/SIRI, with MBzP being identified as a significant contributor to the urinary levels of mPAEs. The subgroup analysis results of the effects of single and mixed exposures show that the association between mPAEs and SII/SIRI is more significant in females, overweight/obese populations, young/middle-aged populations, and populations with high levels of intake of UPFs.Conclusion Positive associations were identified between mPAEs and SII/SIRI. MBzP was determined to have the most significant impact. The association between mPAEs and SII/SIRI is significantly influenced by female groups, young and middle-aged populations, overweight and obese individuals, as well as those with a higher intake of UPFs.

BackgroundThe prevalence of carbapenem-resistant Enterobacteriaceae (CRE) has emerged as a serious public health problem worldwide, and the data on the fecal carriage of CRE strains in hospitalized children remain limited. This study aimed to investigate the molecular characteristics of intestinal colonization of CRE in hospitalized children in Shandong, China.MethodsA retrospective study was conducted from August to November 2023. Antimicrobial susceptibility testing was performed by the broth microdilution method. Carbapenemase genes, drug resistance genes, and plasmid replicon types were detected using multiplex real-time PCR and whole-genome sequencing. Multilocus sequence typing (MLST) was used to determine the genetic relationships between strains.ResultsA total of 20 CRE isolates were identified from 432 fecal samples, with a fecal carriage rate of 4.6%. The CRE isolates predominantly consisted of Escherichia coli (E. coli, n = 13) and Klebsiella strains (n = 6). CRE isolates showed a high resistance rate of 90–100% to seven β-lactam antibiotics. Resistance rates for other antibiotics such as trimethoprim-sulfamethoxazole, tetracycline, azithromycin, ciprofloxacin, chloramphenicol, nalidixic acid, and streptomycin were 90, 85, 85, 80, 75, 75, and 75%, respectively. CRE isolates showed low resistance to amikacin (20%), and none of the isolates were resistant to tigecycline. Additionally, the multidrug resistance rate of CRE isolates was 95%. All CRE strains carried sulfonamide antibiotic and β-lactamase resistance genes, of which the most common β-lactamase resistance genes were blaNDM-1 (n = 9), blaNDM-5 (n = 7) and blaOXA-1 (n = 7). Resistance genes to tetracycline and macrolide antibiotics were also widespread among the strains. The study found that IncFIB and IncFII series plasmids were present in 84 and 42% of the CRE strains, respectively. Additionally, Col, IncFIA, IncC, IncHI2, and IncX series plasmids were also detected. MLST analysis revealed diverse sequence types (STs) among CRE isolates, with ST167 being a common ST among E. coli isolates.ConclusionThis study revealed blaNDME. coli were the dominant isolates in fecal samples of hospitalized children in Shandong Province, with a broad multidrug resistance to antibiotics, emphasizing that infection control measures need to be taken to limit the spread of these strains.

The study aimed to evaluate the relationship between immunonutritional indicators such as the systemic immune-inflammation index (SII), the Naples prognostic score (NPS), nutritional risk index (NRI), serum albumin (ALB), total cholesterol (TC) and all-cause mortality in adult stroke patients. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) databases for 2005-2018. To determine mortality outcomes, participants were matched with National Death Index records until December 31, 2019. Spearman's correlation analysis and the random survival forest (RSF) were employed to assess the relationships among NPS, NRI, SII, ALB, and TC, and to determine the most predictive indicator for all-cause mortality in stroke patients. For the selected prognostic indicator, Kaplan-Meier survival analysis and Cox proportional hazards regression models were subsequently utilized to evaluate their associations with all-cause mortality in stroke patients. The study included 1076 stroke patients, with a median (IQR) age of 67 (56, 77) years. During a median follow-up of 67 months, a total of 372 (weighted 31%) stroke participants died from all causes. Among the immunonutritional indicators evaluated, NPS had the strongest predictive power for all-cause mortality in stroke patients. The Kaplan-Meier curve and Log-rank test showed that all-cause mortality was higher in the higher NPS group (3-4) compared to the lower NPS group (0-2) (P < 0.001). After adjusting for multiple potential confounders, the Cox regression model indicated that the higher NPS (3-4) group remained an independent predictor for higher all-cause mortality risk (HR = 1.89, 95% CI 1.44-2.47, P < 0.001). As a comprehensive evaluation index of inflammation and nutrition, NPS is a powerful predictor of all-cause mortality in stroke patients.

>Cause of death surveillance data is most important for developing effective health policies,whose quality is crucially affected by the accuracy of the underlying cause of death（UCOD） provided in death certificates. The World Health Organization（WHO） has clearly defined a UCOD as “the disease or injury which initiated the train of morbid events leading directly to death, or the circumstance of the accident or violence which produced the fatal injuries” [1] .

ObjectivesLower respiratory infections are the most significant health threat to children under 5 years old, leading to the highest disease burden across all age groups. This study aims to provide an up-to-date assessment of the global burden of lower respiratory infections in children under 5 years of age.MethodsThis study utilizes data and methodologies from the Global Burden of Disease Study 2021 to analyze changes in the burden of lower respiratory infections from 1990 to 2021, focusing on incidence, mortality, and disability-adjusted life years. A jointpoint model is employed to calculate trends and the average annual percentage change in the disease burden among children under 5 years old over the period 1990–2021. Additionally, frontier analysis is used to visually depict the potential for burden reduction in each country or region based on their level of development.ResultsIn 2021, the global burden of lower respiratory infections in children under 5 years old included 37,828,159 incidence cases, 501,909.50 deaths, and 44,779,174.70 disability-adjusted life years. From 1990 to 2021, the global burden of LRIs in this age group showed a marked decline. Incidence, mortality, and disability-adjusted life years decreased by 54.02, 37.57, and 39.49%, respectively. The average annual percent change for age-standardized incidence rate, age-standardized mortality rate, and age-standardized disability-adjusted life years rate were −3.35, −4.53%, and −4.52%, respectively. The disease burden was notably higher in children under 1 year old compared to those aged 2–4 years and the overall under-5 age group, with significant gender differences observed. Additionally, there was a strong negative correlation between the burden of lower respiratory infections in children under 5 and the socio-demographic index. Frontier analysis indicated that countries or regions with higher socio-demographic index values showed greater potential for reducing the burden.ConclusionThe global burden of lower respiratory infections in children under 5 years old has declined significantly from 1990 to 2021. However, given the substantial disease burden, particularly in low-SDI countries, it is crucial to address risk factors and implement more effective interventions to further reduce the impact of lower respiratory infections on this vulnerable population.

Background: Pneumococcal Diseases (PDs) remains a serious public health problem around the world and in China. Pneumococcal vaccination is the most cost-effective measure to prevent PDs. In 2021, the government of Weifang City, Shandong Province, China introduced a free dose of domestic 13-valent Pneumococcal Conjugate Vaccine (PCV 13) to vaccinate registered children aged 6 months-2 years. This study aimed to evaluate the vaccination rate of PCV13 in children aged under 5 years before and after the vaccination program to provide evidences for further improving the prevention and control strategy for PDs. Methods: We collected data from the children's vaccination information management system in Weifang City and analyzed the PCV13 vaccination coverage and characteristics in all vaccination clinics of Weifang City for children aged under 5 years. We compared the differences in vaccination rates by gender, birth year, manufacturer, and county before and after innovative immunization strategy. Results: Among the included 593,784 children aged under 5 years, the PCV13 vaccination rate in Weifang was generally low before the innovative immunization strategy. Urban children had a higher PCV13 coverage than rural children (P < 0.001), and parents tended to vaccinate their children with imported PCV13.The full vaccination rate for domestic and imported PCV13 was 0.67 % and 1.70 %, respectively. After the vaccination program, the PCV13 coverage of children increased significantly in all counties within Weifang City (P < 0.001), especially for children above 12 months of age. Most parents preferred to vaccinate their children with domestic PCV13, and the full vaccination rate of domestic and imported PCV13 was 6.59 % and 0.16 %, respectively. Conclusions: The vaccination rate of PCV13 in children is still much lower than the global average, posting a severe health challenge that needs to be addressed thoroughly. To improve the prevention and control strategy for PDs, it is recommended to continue to explore other relevant incentives based on the innovative immunization strategy. Furthermore, it is also recommended that China should incorporate PCV13 into the National Immunization Programs (NIP) as soon as possible.

AbstractBackgroundThis study aimed to delineate the temporal patterns of esophageal cancer epidemic trends and spatial clustering patterns among male populations in China's mainland from 1990 to 2021. This analysis aimed to provide a scientific rationale and empirical data to facilitate the formulation of targeted prevention and control strategies.MethodsData on the number of cases and deaths, crude and age‐standardized incidence and mortality rates of esophageal cancer in men were collected from the Global Burden of Disease Study and the Chinese Cancer Registry Annual Report. Global and local Moran's I spatial autocorrelation index was employed to quantify spatial clustering, and a disease map was drawn.ResultsFrom 1990 to 2021, the cumulative incidence and mortality of esophageal cancer in men were 6 100 342 and 5 972 294, respectively. The crude incidence and death rates increased in 2021, yet the age‐standardized rates decreased significantly. Cixian County in Hebei Province had the highest age‐standardized rates. The disease displayed spatial clustering, with relatively high rates in Shandong, Jiangsu, and Hebei Provinces.ConclusionSince 1990, the incidence and mortality of esophageal cancer among men in mainland China have remained high, imposing a considerable burden. Although age‐adjusted rates have declined, they are still relatively high overall, especially in Shandong, Hebei, and Jiangsu Provinces.

AbstractBackgroundLeukemia is the tenth most common cause of cancer death worldwide and one of the most important causes of disability. To understand the current status and changing trends of the disease burden of leukemia at the global, regional, and national levels, and to provide a scientific basis for the development of leukemia prevention and treatment strategies.MethodsBased on open data from the Global Burden of Disease Study 2019 (GBD 2019), R software was used to calculate estimated annual percentage changes to estimate trends in the age‐standardized incidence (ASIR) and the age‐standardized disability‐adjusted life years (DALY) rate due to leukemia and its major subtypes from 1990 to 2019.ResultsIn 2019, globally, the number of incidences and DALYs of leukemia were 643.6 × 103 (587.0 × 103, 699.7 × 103) and 11,657.5 × 103 (10529.1 × 103, 12700.7 × 103), respectively. The ASIR (estimated annual percentage change (EAPC) = −0.37, 95%UI −0.46 to −0.28) and the age‐standardized DALY rate (EAPC = −1.72, 95%UI −1.80 to −1.65) of leukemia showed a decreasing trend from 1990 to 2019. The APC model analysis showed that the age effect of leukemia risk was a “U”‐shaped distribution of relative risk (RR) with increasing age from 1990 to 2019, globally. The time effect was an increase in incidence rate with increasing years but a decrease in DALY rate with increasing years. The cohort effects of both incidence and DALY rates tended to increase and then decrease with the development of the birth cohort. In 1990 and 2019, smoking, high body‐mass index, occupational exposure to benzene, and occupational exposure to formaldehyde were risk factors for DALY in leukemia, especially in areas with high SDI.ConclusionsFrom 1990 to 2019, the disease burden of leukemia showed a decreasing trend, but it is worth noting that its overall severity is still very high. The disease burden of leukemia varies greatly from region to region, and exclusive strategies for the prevention and treatment of leukemia should be developed according to the economic and cultural development of each region.

Muscle mass is vital for physical activity and fundamental physiological processes supporting long-term health. While aging is inevitable, certain modifiable factors positively influence muscle preservation and overall well-being. However, the relationship between the consumption of ultra-processed foods (UPF) and muscle mass is not yet clear. This study included 7,173 men and nonpregnant women aged 20–59 years with valid 24-hour dietary recalls and accessible whole-body dual-energy x-ray absorptiometry (DXA) scans from NHANES 2011–2018. UPFs were identified through the NOVA classification system, and the percentage of energy derived from UPF consumption was evaluated in quintiles. Muscle mass measures were derived from DXA scans and quantified by the total and regional muscle mass index (MMI, kg/m²) and appendicular muscle mass index (AMMI, kg/m²). Multivariable-adjusted generalized linear regression models were applied to investigate the association between consumption of UPFs and muscle mass measures overall and by sociodemographic subgroups. The multivariable-adjusted differences of total MMI from the lowest to highest quintile of UPF consumption were 0 (reference), -0.03 (95

BACKGROUND AND PURPOSE:Ischemic stroke, a major contributor to global disability and mortality, is underpinned by intricate pathophysiological mechanisms, notably neuroinflammation and immune cell dynamics. Prior research has identified a nuanced and often paradoxical link between immune cell phenotypes and ischemic stroke susceptibility. The aim of this study was to elucidate the potential causal links between the median fluorescence intensity (MFI) and morphological parameters (MP) of 731 immune cell types and ischemic stroke risk. METHODS:By analyzing extensive genetic datasets, we conducted comprehensive Mendelian randomization (MR) analyses to discern the genetic correlations between diverse immune cell attributes (MFI and MP) and ischemic stroke risk. RESULTS:Our study identified key immune cell signatures linked to ischemic stroke risk. Both B cells and T cells, among other immune cell types, have a bidirectional influence on stroke risk. Notably, the regulatory T-cell phenotype demonstrates significant neuroprotective properties, with all odds ratio (OR) values and confidence intervals (CIs) being less than 1. Furthermore, CD39 phenotype immune cells, particularly CD39+ CD8+ T cells (inverse variance weighting [IVW] OR 0.92, 95% CI 0.87-0.97; p = 0.002) and CD39+ activated CD4 regulatory T cells (IVW OR 0.93, 95% CI 0.90-0.97; p < 0.001), show notable neuroprotection against ischemic stroke. CONCLUSION:This investigation provides new genetic insights into the interplay between various immune cells and ischemic stroke, underscoring the complex role of immune processes in stroke pathogenesis. These findings lay a foundation for future research, which may confirm and expand upon these links, potentially leading to innovative immune-targeted therapies for stroke prevention and management.

BACKGROUND AND PURPOSE:This study aims to examine the global, regional, and national burden of ischemic stroke from 1990 to 2021. METHOD:We used data from the Global Burden of Disease (GBD) 2021 database to comprehensively assess ischemic stroke indicators globally, regionally, and in 204 countries, including incidence, deaths, disability-adjusted life years (DALYs), estimated annual percentage change (EAPC), and Joinpoint regression analysis. RESULTS:In 2021, there were a total of 7,804,449 cases of ischemic stroke globally (95% uncertainty interval = 6,719,760-8,943,692), with an age-standardized incidence rate (ASIR) of 92.39. This represents a declining trend compared to 1990, with an EAPC of -0.67 (95% confidence interval [CI] = -0.76 to -0.58). Mortality and DALY rates also showed a downward trend (EAPC in age-standardized mortality rate: -1.83, 95% CI = -1.92 to -1.74; EAPC in age-standardized DALY rate = -1.59, 95% CI = -1.68 to -1.50). The burden of ischemic stroke was inversely correlated with gross domestic product. Regionally, from 2014 to 2021, the Caribbean experienced the fastest increase in ASIR (annual percent change = 0.15, 95% CI = 0.13 to 0.18). Among 204 countries, North Macedonia had the highest incidence, mortality, and DALY rates. In addition to metabolic risks, particulate matter pollution and low temperatures were significant environmental and occupational risk factors for ischemic stroke. Smoking and a diet high in sodium were identified as key behavioral risk factors. CONCLUSIONS:Ischemic stroke remains a serious global health challenge, and our results from this cross-sectional study suggest that the burden of disease remains high in Eastern Europe, East Asia, Central Asia, and Sub-Saharan Africa.

Objectives: This study examines the recommendation behaviors and influencing factors for the 13-valent Pneumococcal Conjugate Vaccine (PCV13) among 3579 Chinese healthcare workers (HCWs), including 1775 pediatric care providers (Peds-PCPs) and 1804 primary care providers (PCPs). Data were collected from May to July 2023 through a national cross-sectional survey using a structured questionnaire, distributed across hospitals providing pediatric services in five provincial-level administrative divisions. Methods: The sociodemographic data, vaccine knowledge, and recommendation practices were analyzed using Pearson's chi-square test, Wilcoxson rank-sum test, and multivariate logistic regression. Results show that while PCPs are more likely to recommend PCV13, vaccine hesitancy persists among Peds-PCPs. Logistic regression revealed that higher influenza vaccination intention, salary, vaccine consultation frequency, familiarity with immunization, work ethic, and flexible schedules positively impacted HCWs' recommendation behavior. Results: Factors influencing Peds-PCPs' recommendations include vaccine training (OR: 1.470, CI: 1.049-2.509), safety recognition (OR: 1.986, CI: 1.163-3.391), concern over rejection (OR = 1.274, CI: 1.076-1.508) and vaccine cost (OR = 1.203, CI: 1.023-1.414). For PCPs, influencing factors were the perceived susceptibility of children to pneumonia (OR = 2.185, CI: 1.074-4.445), acceptance of herd immunity (OR: 1.717, CI: 1.101-2.677), and belief that parents with better family conditions are more likely to accept vaccine recommendations (OR = 1.229, CI: 1.024-1.477). Conclusion: This survey underscores the need for tailored interventions to address differing perceptions and enhance confidence in the safety and efficacy of vaccines among HCWs, particularly Peds-PCPs.