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ABSTRACT Recent guidelines have recognized several factors, including blood pressure (BP), body mass index (BMI), low‐density lipoprotein cholesterol (LDL‐C), hemoglobin A1c (HbA1c), smoking, and physical activity, as key contributors to stroke risk. However, the impact of simultaneous management of these risk factors on stroke susceptibility in individuals with hypertension remains ambiguous. This study involved 238 388 participants from the UK Biobank, followed up from their recruitment date until April 1, 2023. Cox proportional hazard models with hazard ratios (HRs) and 95% confidence intervals (CIs) were used to illustrate the correlation between the joint modifiable risk factor control and the stroke risk. As the degree of risk factor control increased, a gradual reduction in stroke risk was observed. Hypertensive patients who had the optimal risk factor control (≥5 risk factor controls) had a 14.6% lower stroke risk than those who controlled 2 or fewer (HR: 0.854; 95% CI: 804–0.908; p < 0.001). The excess risk of stroke linked to hypertension slowly diminished as the number of controlled risk factors increased. However, the risk was still 25.1% higher for hypertensive patients with optimal risk factor control as compared to the non‐hypertensive population (HR: 1.251; 95% CI: 1.100–1.422; p < 0.001). The protective effect of joint risk factor control against the stroke risk due to hypertension was stronger in medicated hypertensive patients than in those not medicated. This finding leads to the conclusion that joint risk factor control combined with pharmacological treatment could potentially eliminate the excess risk of stroke associated with hypertension.

Background Acute kidney injury (AKI) is one of the most common complications for critically ill patients with cirrhosis, but it has remained unclear whether urine output fluctuations are associated with the risk of AKI in such patients. Thus, we explored the influence of 24-h urine-output trajectory on AKI in patients with cirrhosis through latent category trajectory modeling.Materials and Methods This retrospective cohort study examined patients with cirrhosis using the MIMIC-IV database. Changes in the trajectories of urine output within 24 h after admission to the intensive care unit (ICU) were categorized using latent category trajectory modeling. The outcome examined was the occurrence of AKI during ICU hospitalization. The risk of AKI in patients with different trajectory classes was explored using the cumulative incidence function (CIF) and the Fine-Gray model with the sub-distribution hazard ratio (SHR) and the 95% confidence interval (CI) as size effects.Results The study included 3,562 critically ill patients with cirrhosis, of which 2,467 (69.26%) developed AKI during ICU hospitalization. The 24-h urine-output trajectories were split into five classes (Classes 1–5). The CIF curves demonstrated that patients with continuously low urine output (Class 2), a rapid decline in urine output after initially high levels (Class 3), and urine output that decreased slowly and then stabilized at a lower level (Class 4) were at higher risk for AKI than those with consistently moderate urine output (Class 1). After fully adjusting for various confounders, Classes 2, 3, and 4 were associated with a higher risk of AKI compared with Class 1, and the respective SHRs (95% CIs) were 2.56 (1.87–3.51), 1.86 (1.34–2.59), and 1.83 1.29–2.59).Conclusions The 24-h urine-output trajectory is significantly associated with the risk of AKI in critically ill patients with cirrhosis. More attention should be paid to the dynamic nature of urine-output changes over time, which may help guide early intervention and improve patients’ prognoses.

Abstract Background Larynx cancer is one of the most common cancers in head and neck, and imposes heavy burden on individual and societies. A comprehensive understanding of the burden of larynx cancer is necessary to improve prevention and control strategies. However, the secular trend of larynx cancer incidence and mortality in China remains unclear. Methods The incidence and deaths rates of larynx cancer from 1990 to 2019 were collected from the Global Burden of Disease Study 2019 database. The temporal trend of larynx cancer was analyzed using a joinpoint regression model. The age–period–cohort model was used to explore the age, period, and cohort effects on larynx cancer and predict future trends up to 2044. Results From 1990 to 2019, the age‐standardized incidence rate of larynx cancer in China increased by 1.3% (95% CI 1.1 to 1.5) in males, but decreased by 0.5% (95% CI −0.1 to 0) in females. The age‐standardized mortality rate of larynx cancer in China decreased by 0.9% (95% CI −1.1 to −0.6) and 2.2% (95% CI −2.8 to −1.7) in males and females, respectively. Among the four risk factors, smoking and alcohol use contributed to a heavier burden compared to occupational exposure to asbestos and sulfuric acid with respect to mortality. Age effects showed that the incidence and deaths of larynx cancer were concentrated in people older than 50 years old. Period effects exerted the most significant effect on larynx cancer incidence for males. In terms of cohort effects, people born in the earlier cohorts presented a higher risk of larynx cancer compared with the later cohorts. From 2020 to 2044, the age‐standardized incidence rates of larynx cancer continued to increase in males, whereas the age‐standardized mortality rates continued to decrease in both males and females. Conclusion The burden of larynx cancer in China has a significant gender difference. The age‐standardized incidence rates will continue to increase in males up to 2044. The disease pattern and risk factors of larynx cancer should be comprehensively studied to promote the development of timely intervention measures and relieve the burden effectively.

ObjectiveTonsillar squamous cell carcinoma (TSCC) and second primary malignancies (SPMs) are the most common causes of mortality in patients with primary TSCC. However, the competing data on TSCC-specific death (TSD) or SPM-related death in patients with TSCC have not been evaluated. This study aimed to analyze the mortality patterns and formulate prediction models of mortality risk caused by TSCC and SPMs.MethodsData on patients with a first diagnosis of TSCC were extracted as the training cohort from the 18 registries comprising the Surveillance, Epidemiology, and End Results (SEER) database. A competing risk approach of cumulation incidence function was used to estimate cumulative incidence curves. Fine and gray proportional sub-distributed hazard model analyses were performed to investigate the risk factors of TSD and SPMs. A nomogram was developed to predict the 5- and 10-year risk probabilities of death caused by TSCC and SPMs. Moreover, data from the 22 registries of the SEER database were also extracted to validate the nomograms.ResultsIn the training cohort, we identified 14,530 patients with primary TSCC, with TSCC (46.84%) as the leading cause of death, followed by SPMs (26.86%) among all causes of death. In the proportion of SPMs, the lungs and bronchus (22.64%) were the most common sites for SPM-related deaths, followed by the larynx (9.99%), esophagus (8.46%), and Non-Melanoma skin (6.82%). Multivariate competing risk model showed that age, ethnicity, marital status, primary site, summary stage, radiotherapy, and surgery were independently associated with mortality caused by TSCC and SPMs. Such risk factors were selected to formulate prognostic nomograms. The nomograms showed preferable discrimination and calibration in both the training and validation cohorts.ConclusionPatients with primary TSCC have a high mortality risk of SPMs, and the competing risk nomogram has an ideal performance for predicting TSD and SPMs-related mortality. Routine follow-up care for TSCC survivors should be expanded to monitor SPMs.

BackgroundMyocardial infarction (MI) is a common cardiovascular disease (CVD) in critically ill patients, leading to 17% mortality in the intensive care unit (ICU) setting. Patients with CVD frequently suffer from thiamine insufficiency, thereby thiamine supplements may be helpful. Unfortunately, the relationship between thiamine treatment and survival outcomes in ICU patients with MI is still unknown. The purpose of the research is to demonstrate the survival advantage of thiamine application in these patients.MethodsThe Medical Information Mart of Intensive Care-IV database served as the foundation for this retrospective cohort analysis. Depending on whether patients were given thiamine therapy during the hospital stay, critically ill MI patients were split into the thiamine and non-thiamine groups. The Kaplan–Meier (KM) method and Cox proportional hazard models were used to evaluate the relationship between thiamine use and the risk of in-hospital, 30-day, and 90-day mortality. To validate the results, a 1:2 closest propensity-score matching (PSM) was also carried out.ResultsThis study included 1782 patients for analysis with 170 and 1,612 individuals in the thiamine and non-thiamine groups, respectively. The KM survival analyses revealed that the risk of in-hospital, 30-day, and 90-day mortality was significantly lower in the thiamine group than the none-thiamine group. After modifying for a variety of confounding factors, the Cox regression models demonstrated substantial positive impacts of thiamine use on in-hospital, 30-d, and 90-d mortality risk among critically ill patients with MI with hazard ratio being 0.605 [95% confidence interval (CI): 0.397–0.921, p = 0.019], 0.618 (95% CI: 0.398–0.960, p = 0.032), and 0.626 (95% CI: 0.411–0.953, p = 0.028), respectively, in the completely modified model. PSM analyses also obtained consistent results.ConclusionThiamine supplementation is related to a decreased risk of mortality risk in critically ill patients with MI who are admitted to the ICU. More multicenter, large-sample, and well-designed randomized controlled trials are needed to validate this finding.

Background: Thiamine deficiency is common in patients with heart failure, and thiamine supplement can benefit these patients. However, the association between thiamine administration and prognosis among critically ill patients with heart failure remains unclear. Thus, this study aims to prove the survival benefit of thiamine use in critically ill patients with heart failure.Methods: A retrospective cohort analysis was performed on the basis of the Medical Information Mart of Intensive Care-Ⅳ database. Critically ill patients with heart failure were divided into the thiamine and non-thiamine groups depending on whether they had received thiamine therapy or not during hospitalization. The association between thiamine supplement and in-hospital mortality was assessed by using the Kaplan−Meier (KM) method and Cox proportional hazard models. A 1:1 nearest propensity-score matching (PSM) and propensity score-based inverse probability of treatment weighting (IPW) were also performed to ensure the robustness of the findings.Results: A total of 7,021 patients were included in this study, with 685 and 6,336 in the thiamine and non-thiamine groups, respectively. The kaplan−meier survival curves indicated that the thiamine group had a lower in-hospital mortality than the none-thiamine group. After adjusting for various confounders, the Cox regression models showed significant beneficial effects of thiamine administration on in-hospital mortality among critically ill patients with heart failure with a hazard ratio of 0.78 (95% confidence interval: 0.67–0.89) in the fully adjusted model. propensity-score matching and probability of treatment weighting analyses also achieved consistent results.Conclusion: Thiamine supplement is associated with a decreased risk of in-hospital mortality in critically ill patients with heart failure who are admitted to the ICU. Further multicenter and well-designed randomized controlled trials with large sample sizes are necessary to validate this finding.

Abstract Background Acute kidney injury (AKI) is the most common and serious complication of sepsis, accompanied by high mortality and disease burden. The early prediction of AKI is critical for timely intervention and ultimately improves prognosis. This study aims to establish and validate predictive models based on novel machine learning (ML) algorithms for AKI in critically ill patients with sepsis. Methods Data of patients with sepsis were extracted from the Medical Information Mart for Intensive Care III (MIMIC- III) database. Feature selection was performed using a Boruta algorithm. ML algorithms such as logistic regression (LR), k-nearest neighbors (KNN), support vector machine (SVM), decision tree, random forest, Extreme Gradient Boosting (XGBoost), and artificial neural network (ANN) were applied for model construction by utilizing tenfold cross-validation. The performances of these models were assessed in terms of discrimination, calibration, and clinical application. Moreover, the discrimination of ML-based models was compared with those of Sequential Organ Failure Assessment (SOFA) and the customized Simplified Acute Physiology Score (SAPS) II model. Results A total of 3176 critically ill patients with sepsis were included for analysis, of which 2397 cases (75.5%) developed AKI during hospitalization. A total of 36 variables were selected for model construction. The models of LR, KNN, SVM, decision tree, random forest, ANN, XGBoost, SOFA and SAPS II score were established and obtained area under the receiver operating characteristic curves of 0.7365, 0.6637, 0.7353, 0.7492, 0.7787, 0.7547, 0.821, 0.6457 and 0.7015, respectively. The XGBoost model had the best predictive performance in terms of discrimination, calibration, and clinical application among all models. Conclusion The ML models can be reliable tools for predicting AKI in septic patients. The XGBoost model has the best predictive performance, which can be used to assist clinicians in identifying high-risk patients and implementing early interventions to reduce mortality.

PurposeThis study aimed to provide a comprehensive assessment of burden estimates and the secular trend of blindness and vision loss, as measured by years lived with disability (YLDs), at the global, regional, and national levels.MethodsThe age-standardized YLD rates (ASYRs) due to blindness and vision loss and its subtypes, including moderate vision loss, severe vision loss, blindness, and presbyopia, from 1990 to 2019 were extracted from the Global Burden of Disease Study 2019 database. The estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in the ASYRs due to blindness and vision loss.ResultsIn 2019, the global ASYRs per 100,000 population was 327.98 for blindness and vision loss, specifically, 85.81 for moderate vision loss, 74.86 for severe vision loss, 95.03 for blindness, and 62.27 for presbyopia. From 1990 to 2019, the ASYRs due to blindness and vision loss slightly decreased. Females showed higher ASYRs than males in 2019. The global highest ASYRs were observed in South Asia and sub-Saharan Africa. Negative associations were found between the burden estimates of blindness and vision loss and the sociodemographic index levels. The EAPCs of ASYRs in blindness and vision loss were significantly negatively correlated with the ASYRs in 1990 and positively correlated with human development indices in 2019.ConclusionsGlobally, blindness and vision loss continue to cause great losses of healthy life. Reasonable resource allocation and health-service planning are needed for the prevention and early intervention of disabilities caused by vision loss.

ObjectiveMultiple myeloma (MM) imposes a heavy burden in China. Understanding the secular trend of MM burden and projecting its future trend could facilitate appropriate public health planning and improve the management of MM.MethodsSex-specific incidence and mortality rates of MM in China from 1990 to 2019 were collected from the Global Burden of Disease 2019 study. The secular trend of MM burden was analyzed by joinpoint regression. Age–period–cohort model was used to analyze the effects of age, period, and birth cohort on MM burden and project future trends up to 2044.ResultsFrom 1990 to 2019, the age-standardized incidence and mortality rates of MM continued to increase in males. For females, the age-standardized rates were stable in MM incidence and decreased in MM mortality. Males had a higher disease burden of MM than females. Age effects were the most significant risk factor for MM incidence and mortality. Moreover, the risk of MM incidence and mortality increased with increasing time period but decreased with birth cohort in males and females. The age-standardized incidence and mortality rates of MM in China is predicted to be continuously increasing over the next 25 years.ConclusionThe burden of MM in China is expected to continue to increase in the future, with significant sex difference. A comprehensive understanding of the risk characteristics and disease pattern of MM could help develop timely intervention measures to effectively reduce its burden.

This study aimed to explore the relationship between tumor size (Ts) and prognosis in endometrial cancer (EC). A total of 52,208 patients with EC who underwent total hysterectomy were selected from the Surveillance, Epidemiology, and End Results Program database. Overall survival (OS) and endometrial cancer-specific survival (ESS) were chosen as survival outcomes. The Cox proportional hazards model was used to explore the effect of Ts on prognosis. The restricted cubic splines based on the Cox regression model were used to determine the nonlinear relationship between Ts and survival. When Ts was analyzed as a categorical variable, the risk of death increased with Ts, with the highest risk in patients with Ts > 9 cm with regard to all-cause death (ACD) (hazard ratio [HR] 1.317; 95% confidence interval [CI], 1.196-1.450; P < 0.001) and endometrial cancer-specific death (ESD) (HR, 1.378; 95% CI, 1.226-1.549; P < 0.001). As a continuous variable, Ts showed a nonlinear relationship with ACD (HR, 1.061; 95% CI, 1.053-1.069; P < 0.001) and ESD (HR, 1.062; 95% CI, 1.052-1.073; P < 0.001). The risk of mortality increased quickly with Ts when Ts was less than 7.5 cm and then leveled off when Ts was larger than 7.5 cm in all patients. Among patients with lymph node metastasis, the risk of poor prognosis decreased rapidly with Ts when Ts was less than 3.5 cm, and subsequently increased sharply with Ts when Ts ranged from 3.5 cm to 7.5 cm, and then increased slowly when Ts was larger than 7.5 cm (P < 0.001 for nonlinearity). There was a nonlinear relationship between Ts and prognosis in patients with EC. Clinicians should not ignore the impact of small tumors on prognosis in EC patients with lymph node metastasis.

ObjectivesTo provide a comprehensive assessment of the estimated burden and trend of urolithiasis at the global, regional, and national levels.MethodsThe age-standardized rates (ASRs) of the incidence and disability-adjusted life years (DALYs) of urolithiasis from 1990 to 2019 were obtained from the Global Burden of Disease Study 2019 database. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in urolithiasis burden.ResultsIn 2019, the ASRs of the incidence and DALYs were 1,394.03/100,000 and 7.35/100,000, respectively. The ASRs of the incidence and DALYs of urolithiasis decreased from 1990 to 2019 with EAPCs of −0.83 and −1.77, respectively. Males had a higher burden of urolithiasis than females. In 2019, the highest burden of urolithiasis was observed in regions with high–middle sociodemographic index (SDI), particularly in Eastern Europe, Central Asia, and Southeast Asia. The burden of urolithiasis increased in most countries or territories. The burden of urolithiasis and SDI had a non-linear relationship, and the estimated value of urolithiasis burden was the highest when the SDI value was ~0.7.ConclusionGlobally, the ASRs of the incidence and DALYs of urolithiasis decreased from 1990 to 2019, but an increasing trend was observed among many countries. More effective and appropriate medical and health policies are needed to prevent and early intervene in urolithiasis.

Background. As a novel inflammatory index, the ratio of red cell distribution width (RDW) to platelet count (RPR) may have prognostic value in some critical illnesses. However, studies on the prognostic influence of RPR in patients with sepsis are few. This study is aimed at investigating the association between RPR levels and 28-day mortality in patients with sepsis. Methods. Data of patients with sepsis were obtained from the Medical Information Mart for Intensive Care III database. The best cut-off value was calculated by establishing the receiver operating characteristic curve (ROC), and the predictive ability of different indicators was compared through the area under the curve (AUC). The association between RPR levels and 28-day mortality was assessed using the Cox proportional hazards model. Restrictive cubic spline analysis was applied to the multivariable Cox model to investigate the nonlinear relationship between RPR and 28-day mortality. Results. A total of 3367 patients with sepsis were included in the study. A nonlinear relationship was observed between RPR and 28-day mortality, showing a trend of a first rapid increase and a gradual increase. For the prediction of mortality, the best cut-off value for RPR was 0.109, with an AUC of 0.728 (95% confidence interval [CI]: 0.709–0.747). The predictive capability of RPR was superior to those of RDW, platelet, SOFA score, and SAPS II score. After adjusting for various confounding factors, high RPR was significantly associated with increased mortality with adjusted hazard ratios of 1.210 (95% CI: 1.045–1.400) for categorical variables and 2.826 (95% CI: 2.025–3.944) for continuous variables. Conclusion. Elevated RPR level is significantly correlated with a high risk of 28-day mortality in patients with sepsis and can be a new predictor of patient prognosis.