Hazard Ratio Values Research Articles

A Computational Recognition Analysis of Promising Prognostic Biomarkers in Breast, Colon and Lung Cancer Patients

Breast, colon, and lung carcinomas are classified as aggressive tumors with poor relapse-free survival (RFS), progression-free survival (PF), and poor hazard ratios (HRs) despite extensive therapy. Therefore, it is essential to identify a gene expression signature that correlates with RFS/PF and HR status in order to predict treatment efficiency. RNA-binding proteins (RBPs) play critical roles in RNA metabolism, including RNA transcription, maturation, and post-translational regulation. However, their involvement in cancer is not yet fully understood. In this study, we used computational bioinformatics to classify the functions and correlations of RBPs in solid cancers. We aimed to identify molecular biomarkers that could help predict disease prognosis and improve the therapeutic efficiency in treated patients. Intersection analysis summarized more than 1659 RBPs across three recently updated RNA databases. Bioinformatics analysis showed that 58 RBPs were common in breast, colon, and lung cancers, with HR values < 1 and >1 and a significant Q-value < 0.0001. RBP gene clusters were identified based on RFS/PF, HR, p-value, and fold induction. To define union RBPs, common genes were subjected to hierarchical clustering and were classified into two groups. Poor survival was associated with high genes expression, including CDKN2A, MEX3A, RPL39L, VARS, GSPT1, SNRPE, SSR1, and TIA1 in breast and colon cancer but not with lung cancer; and poor survival was associated with low genes expression, including PPARGC1B, EIF4E3, and SMAD9 in breast, colon, and lung cancer. This study highlights the significant contribution of PPARGC1B, EIF4E3, and SMAD9 out of 11 RBP genes as prognostic predictors in patients with breast, colon, and lung cancers and their potential application in personalized therapy.

Integrated multicenter deep learning system for prognostic prediction in bladder cancer

Precise survival risk stratification is crucial for personalized therapy in bladder cancer (BCa). This study developed and validated an end-to-end deep learning system using histological slides to predict overall survival (OS) risk in BCa patients. We employed the BlaPaSeg tile classifier to generate tissue probability heatmaps and segmentation maps, trained two prognostic networks, MacroVisionNet and UniVisionNet, and explored six potential BCa prognostic biomarkers. Across all cohorts, the AUC for BlaPaSeg ranged from 0.9906 to 0.9945, while the C-index varied from 0.655 to 0.834 for MacroVisionNet and 0.661 to 0.853 for UniVisionNet. After covariate adjustment, the hazard ratio (HR) values for high-risk groups were 1.97 to 5.06 in MacroVisionNet and 2.13 to 4.01 in UniVisionNet. The high-risk Coloc (Tumor Co-localization score) and IMTS (Integrated Muscle Tumor Score) groups illustrated a higher death risk with HR values from 1.41 to 10.16. The system improves BCa survival prediction and supports refined patient management.

Weight-adjusted waist index and disability: a cohort study from CHARLS

BackgroundThe association between weight-adjusted waist index (WWI) and disability is unclear. This study aimed to assess the relationship between WWI and disability in middle-aged and elderly Chinese individuals and provide more predictive indicators for disability prevention.MethodsIn this study, 13,015 middle-aged and older adults aged 45 years and above who were surveyed in 2011 by the China Health and Aging Tracking Survey (CHARLS) database were selected, and 8344 respondents with complete data were included for cohort analysis after seven years of follow-up. Information on clinical demographic characteristics, anthropometric indices, assessment of disability, and related covariates were collected, and the presence or absence of disability was assessed by the disability scale. WWI was calculated by dividing the waist circumference (cm) by the square root of the body weight (kg). Cox proportional hazards model was used to analyze the association between WWI and disability after follow-up.ResultsOur study found that 2912 of 8344 participants had disability after seven years of follow-up, and disability incidence was approximately 34.9%. Age, sex, place of residence, chronic disease, depression, waist circumference, and WWI were significantly associated with disability in univariate analysis. Among them, there was a positive association between WWI as a continuous variable and incidence of disability (hazard ratio (HR) = 1.26, 95% CI: 1.22–1.31, p < 0.001). WWI was transformed into categorical variables using quartiles as cutoffs for disability regression analysis. After adjusting covariates, HR values in the 2nd, 3rd and 4th quantile showed an increasing trend compared with the 1st quantile, and the risk of disability among WWI subjects in the 4th quantile increased by 43% (95% CI: 1.24–1.64). P values for the trend test in the model were all < 0.001. In subgroup analyses, the positive association between WWI and risk of disability remained robust for sex, age, alcohol consumption, smoking status, education level, marital status, and place of residence after adjusting for all covariates considered in this study.ConclusionsWWI is a new and reliable obesity-related indicator that can be used for disability prevention. WWI can be detected and controlled for reducing the risk of disability.

The liver fibrosis-8 index is a predictor for all-cause mortality in cardiovascular disease patients: A cohort study.

Participants with cardiovascular diseases (CVD) often exhibit liver function abnormalities, hepatic fibrosis and cirrhosis. The extent of liver fibrosis is closely related to the prognosis of CVD. However, the association between the liver fibrosis-8 (FIB-8) index, a marker of liver fibrosis, and all-cause mortality in CVD participants remains unclear. This study aims to investigate the relationship between the FIB-8 index and all-cause mortality among individuals with CVD. A total of 1727 CVD American participants were enrolled from the National Health and Nutrition Examination Survey (NHANES) spanning from 1999 to 2018. Initially, we constructed weighted COX regression models and performed sensitivity analyses to examine the correlation between the FIB-8 index and all-cause mortality in CVD participants. Subsequently, we employed restricted cubic spline (RCS) to visualize their linear relationship. Finally, the stratified analyses and interaction tests of covariates were performed and presented in the forest plot. A total of 1727 participants were included in our study, with a mean age of 61.68 ± 0.47 years, with men accounting for 59.19%. After adjustment for relevant covariables, weighted COX regression models indicated that the hazard ratio (HR) and 95% confidence interval (95% CI) for the association between the FIB-8 index and all-cause mortality in CVD participants was 1.21 (1.12, 1.30). Sensitivity analysis was then conducted, revealing that the results remained stable. In fully adjusted model, individuals in quartiles 3 and 4 demonstrated significant statistical differences compared to the lowest FIB-8 index quartile, with HR (95% CI) values of 1.88 (1.23, 2.87) and 2.17 (1.33, 3.53), respectively. Subsequently, RCS showed a linear relationship between the FIB-8 index and all-cause mortality among CVD participants. Finally, the interaction test revealed that no other covariables had significant interactions with the FIB-8 index in this study. A positive and linear correlation was observed between the FIB-8 index and all-cause mortality among CVD adult participants in NHANES from 1999 to 2018. Our findings indicated that the FIB-8 index could serve as an excellent indicator for assessing all-cause mortality within the CVD population. The lower the FIB-8 index, the lower the all-cause mortality among CVD participants.

The effect of different levels of systolic blood pressure control on new-onset chronic kidney disease in hypertension multimorbidity

To explore the effect of different levels of systolic blood pressure (SBP) control on new-onset chronic kidney disease in hypertension multimorbidity. The hypertensive patients with multimorbidity information were enrolled from the Kailuan Study. The isolated hypertension patients undergoing physical examination during the same period were selected in a 1:1 ratio as control. Finally, 12,897 participants were divided into six groups: Group SBP < 110 mmHg, Group 110 ≤ SBP < 120 mmHg, Group 120 ≤ SBP < 130 mmHg, Group 130 ≤ SBP < 140 mmHg, Group 140 ≤ SBP < 160 mmHg and Group SBP ≥ 160 mmHg. The outcomes were new-onset CKD, new onset proteinuria, decline in eGFR and high or very high risk of CKD. Cox proportional hazards regression was used to examine the hazard ratios (HRs) of the outcomes among SBP levels. When 110 ≤ SBP < 120 mmHg, the incidence density of new-onset CKD, new onset proteinuria and decline in eGFR were 59.54, 20.23 and 29.96 per 1000 person-years, respectively. Compared to this group, the HR (95% CI) values for the risk of new-onset CKD from Group SBP < 110 mmHg to Group SBP ≥ 160 mmHg were 1.03 (0.81–1.32), 1.04 (0.91–1.19), 1.09 (0.95–1.16), 1.16 (1.02–1.21) and 1.18 (1.04–1.24), respectively. For patients over 65 years old, the risks of outcomes were increased when SBP < 120 mmHg. The lowest HR of high or very high risk of CKD for participants with or without multimorbidity occurred when 120 ≤ SBP < 130 mmHg. The HR of new-onset CKD in hypertension multimorbidity was lowest at 110–120 mmHg. The optimal SBP level was between 120 and 130 mmHg for individuals with high or very high risk of CKD. For patients over 65 years old, the low limit of target BP is advised to be not lower than 120 mmHg.

Sex differences in all-cause mortality and life span between women with premature menopause and men: propensity score matching analysis.

This study investigated sex differences in all-cause mortality and life span between women undergoing premature menopause and men using propensity score matching analysis. Data were from the National Health and Nutrition Examination Survey (1999-2018) and the National Health and Nutrition Examination Survey III (1988-1994). We included 3,214 women experiencing premature menopause and 23,067 men. The participants were all older than 40 years. Propensity score matching analysis created matched cohorts of women and men using a 1:1 ratio. We employed Cox proportional hazard models to estimate unadjusted and adjusted hazard ratios (HR) (95% confidence interval [CI]) for the association between sex and both all-cause mortality and survival up to the 75th percentile of life span. A subgroup analysis examined the effects of hormone therapy on mortality and life span. Compared with men in the matched cohorts, the adjusted HR values (95% CI) for all-cause mortality in women with age at menopause at <35, 35 to 39, and <40 years were 0.65 (0.54-0.78), 0.72 (0.59-0.87), and 0.67 (0.60-0.76), respectively. However, the adjusted HR values (95% CI) for women and men to survive to the 75th percentile of life span were not statistically significant. Besides, there was no significant difference in the mean life span between deceased women and men in the matched cohorts. In the subgroup analysis, the mean life span did not differ significantly between deceased women taking hormone therapy and men. However, the average life span of women never using hormone therapy was significantly longer than that of men (78.3 ± 11.6 vs 76.6 ± 11.9 years, P = 0.0154). Women experiencing premature menopause had lower risks of all-cause mortality than men, but the advantage that women had in terms of life span was insignificant.

Neutrophil-Lymphocyte Ratio, prognostic nutritional index and CRP - Albumin Ratio significantly predict mortality in ICU patients with low nutrition risk.

Introduction and Methods: This observational retrospective cohort study was conducted in the ICU of Wahidin Sudirohusodo Hospital, Indonesia, from April 2022 to March 2023. All patients admitted to the ICU during the study period were considered. Data collected from medical records included patient demographics, clinical characteristics, prognostic indicators, and outcomes. Bivariate and multivariate regression analysis was used to evaluate the associations between prognostic indicators and mortality both in low-risk and high-risk subgroup. The results were presented as hazard ratios (HRs) with 95% confidence intervals (CIs). To predict accuracy of prognostic biomarker, Receiver Operating Characteristic (ROC) curve analysis was conducted. The area under the ROC curve (AUC) was calculated to evaluate the discriminative ability of each biomarker Result: In a study of 1,106 ICU patients. The length of stay in the ICU and hospital for survivors is shorter than for non-survivors. Hazard ratio analysis showed that higher PNI significantly reduced the risk of death (unadjusted HR 0.914, adjusted HR 0.910), whereas higher CAR and NLR were associated with increased risk of death (CAR unadjusted HR 1.020, adjusted HR 1.017; unadjusted NLR HR 1.018, adjusted HR 1.014 ). This effect was less pronounced in patients at high nutritional risk, with nonsignificant HR values. ROC curve analysis showed that CRP/Albumin (AUC: 0.696), NLR (AUC: 0.575), and PNI (AUC: 0.325). Conclusion: NLR, PNI, and CAR are valuable prognostic indicators in ICU settings, providing crucial information on mortality risk especially in patients with low nutritional risk. The data supports their use in clinical assessments to tailor interventions that address inflammation and nutritional deficits

Radiofrequency Ablation, Cryotherapy Ablation, or Pulsed-Field Ablation to Treat Paroxysmal Atrial Fibrillation Unresponsive to Pharmacological Treatments: Interpreting Efficacy Through Reconstruction of Individual Patient Data From Randomized Trials.

Three techniques of catheter ablation (CA; radiofrequency, cryoballoon, and pulsed-field ablation) are available to treat patients with paroxysmal atrial fibrillation (PAF) who do not adequately respond to pharmacological treatments. Our study was aimed at comparing these techniques based on the data of randomized studies because these are considered the best sources of efficacy data. After selecting pertinent trials, our analysis studied the time-to-event data published for these three techniques. An artificial intelligence method was used that reconstructs individual patient data from the Kaplan-Meier curves. The endpoint was an arrhythmia recurrence. A preliminary heterogeneity analysis was performed. Then, our main analysis was based on individual patient data reconstructed from Kaplan-Meier graphs. The hazard ratio (HR) was its main parameter. Three randomized trials were included. Our heterogeneity analysis confirmed an acceptable level of between-trial heterogeneity that allowed us to pool the curves from the different trials; however, cryoballoon ablation with a two-minute duration fared worse than the other techniques. Then, our main analysis estimated the following values of HR: pulsed-field ablation versus radiofrequency ablation, 0.549 (95%CI, 0.413-0.730; p<0.001); pulsed-field ablation versus cryoballoon ablation, 0.478 (95%CI, 0.364-0.633); radiofrequency ablation versus cryoballoon ablation, HR=0.871 (95%CI, 0.585-1.295; p=0.506). In conclusion, radiofrequency ablation and cryoballoon ablation showed similar effectiveness (except for the two-minute cryoballoon ablation, which fared worse). Our results showing the superiority of pulsed-field ablation versus thermal ablation must be interpreted with caution because the patients given pulsed-field ablation were limited, and their follow-up was shorter than that of patients receiving thermal ablation.

Automated Nuclear Morphometry: A Deep Learning Approach for Prognostication in Canine Pulmonary Carcinoma to Enhance Reproducibility.

The integration of deep learning-based tools into diagnostic workflows is increasingly prevalent due to their efficiency and reproducibility in various settings. We investigated the utility of automated nuclear morphometry for assessing nuclear pleomorphism (NP), a criterion of malignancy in the current grading system in canine pulmonary carcinoma (cPC), and its prognostic implications. We developed a deep learning-based algorithm for evaluating NP (variation in size, i.e., anisokaryosis and/or shape) using a segmentation model. Its performance was evaluated on 46 cPC cases with comprehensive follow-up data regarding its accuracy in nuclear segmentation and its prognostic ability. Its assessment of NP was compared to manual morphometry and established prognostic tests (pathologists' NP estimates (n = 11), mitotic count, histological grading, and TNM-stage). The standard deviation (SD) of the nuclear area, indicative of anisokaryosis, exhibited good discriminatory ability for tumor-specific survival, with an area under the curve (AUC) of 0.80 and a hazard ratio (HR) of 3.38. The algorithm achieved values comparable to manual morphometry. In contrast, the pathologists' estimates of anisokaryosis resulted in HR values ranging from 0.86 to 34.8, with slight inter-observer reproducibility (k = 0.204). Other conventional tests had no significant prognostic value in our study cohort. Fully automated morphometry promises a time-efficient and reproducible assessment of NP with a high prognostic value. Further refinement of the algorithm, particularly to address undersegmentation, and application to a larger study population are required.

Occurrence and health risk estimate of organochlorine pesticides in fruits and vegetables matrices.

Occurrence of 20 organochlorine pesticides (OCPs) in 60 organic and non-organic fruits and vegetables matrices was undertaken using QuEChERS Method EN 15662 for sample preparation analyzed by gas chromatography-mass spectrometry (GC-MS/MS). The procedural method was validated by spiking the OCP standard solutions at three fortified levels at 10, 50, and 100 µg/kg wet weight (ww) to the real matrix of fruit and vegetable with good recovery ranging from 75 to 108% with relative standard deviation (RSD) ≤ 11%, and the limits of detection and quantification (LODs and LOQs) were 0.002-0.02μg/kg and 0.004-0.1μg/kg ww, respectively. The assessment of health risks associated with pesticide residues through consumption of vegetables and fruits and the effect of washing and peeling on concentration of various pesticides were also studied. The results showed that the concentration levels of 60% of samples were lower than the LOQs, while the rest was contaminated by OCP residues. Organic fruits and vegetables showed the absence of OCPs, while several of the studied compounds were detected from conventional agriculture. Skin removal (peeling) was the most effective strategy to eliminate or decrease pesticide residues, and should be one of the solutions to reduce the health impact of pesticides in fruits and vegetables. The analysis of health risk assessment was based on the use of the estimated average daily intake (EDI), hazard index (HI), and hazard ratio (HR) for individuals in two weight categories: children (weighing 16.7kg) and adults (weighing 60kg). The HI values were less than 1 suggesting that there was no probable non-carcinogenic health effect, except for heptachlor for children (HI of 1.285). However, the values of HR revealed that children were more susceptible to the carcinogenic health effect associated with consuming contaminated vegetables.

The relationship between cardiometabolic abnormalities and mortality among women with and without cancer in the Women’s Health Initiative (WHI).

e24007 Background: Prior studies of women with obesity-associated cancers in the Women’s Health Initiative (WHI) showed higher overall and mortality due to cardiovascular disease (CVD) for women with a higher number of cardiometabolic risk factors at baseline. It is unclear if this risk differs from women without cancer. In order to determine if this relationship differs among both groups, we compared the association between cardiometabolic risk factors and mortality among women in the WHI with and without cancer. Methods: Women with one of five early-stage obesity-associated cancers (breast, colorectal, endometrial, ovarian, non-Hodgkin lymphoma), and matched controls without history of cancer, were selected from the WHI-Life and Longevity After Cancer (LILAC) study. Cardiometabolic risk factors included high waist circumference (WC) (≥88 cm), systemic hypertension ( &gt; 130/85 mm Hg) measured at study visits, and self-reported history of diabetes and elevated cholesterol. Multivariable Cox proportional hazards models (all-cause mortality) and Fine-Gray models (CVD and non-CVD mortality) were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) to evaluate the association between baseline cardiometabolic risk factors and survival outcomes for the cancer and non-cancer cohorts in separate models. Sensitivity analyses included women in the cancer-cohort who received cardiotoxic chemotherapy. Results: A total of 7,491 and 35,508 women were analyzed in the cancer and non-cancer cohorts respectively. CVD was the most common cause of death (excluding cancer) in both non-cancer (41.4%) and cancer (41.5%) cohorts. Adjusted Cox models showed that the proportion of deaths due to any cause, by number of cardiometabolic risk factors, was significantly higher in the non-cancer compared to the cancer cohort (p-value = 0.02), with the HR values being higher for those with 3-4 risk factors compared to 1-2. Similar results were seen for each individual risk factor except for WC. Regarding CVD and non-CVD mortality, in competing risks models, there were no significant differences in the risk of death by number of risk factors, between the cancer and non-cancer cohorts (p = 0.21 and 0.22) respectively. Sensitivity analyses for women who received a cardiotoxic regimen, (81.5% anthracyclines alone, 13.4% anti-HER2 alone, and 5.1% both) showed no differences in the results for all-cause mortality, and CVD mortality. However, for non-CVD mortality, the proportion of deaths was significantly higher for women in the non-cancer cohort (p = 0.03). Conclusions: Cardiometabolic risk factors had a greater impact on mortality among women without cancer compared to those with cancer, except for death due to CVD which was similar between groups, suggesting that CVD risk reducing interventions are of equal importance for women with and without cancer.

Ten-year incidence of keratoconus in relation to sex, age, and thyroid gland dysfunction: a nationwide population-based cohort study (2009-2018).

Keratoconus is a corneal ectatic disorder that often leads to visual impairment and may require corneal transplantation. However, its age and gender-based incidence and potential association with thyroid gland dysfunction (TGD) remain poorly understood. This study aims to clarify these aspects and investigate the possible connection between keratoconus and TGD. We conducted a nationwide population-based cohort study using data from the Korean National Health Insurance Service database. A retrospective chart review was conducted on 4,059,021 patients aged over 20 without underlying corneal diseases in 2009. The end of the review period was at ten years, or until the onset of keratoconus. To evaluate the association with TGD, multivariate Cox regression analysis was used with adjustment of confounding variables such as sex and age. During the review period, 2,334 patients developed keratoconus before the 10-year mark. Females exhibited a higher keratoconus incidence (7.101 per 100,000 person-years) compared to males (5.559) (P<0.001). After adjusting for age, the hazard ratio (HR) for keratoconus was 1.295 times higher [95% confidence interval (CI): 1.193-1.406] in females compared to males. Age groups were stratified in 10-year intervals. The highest incidence of keratoconus was observed in the 20 to 29-year age group (10.695 per 100,000 person-years). All other age groups had significantly lower HR values, with the lowest at 50-59 years (0.508, 95% CI: 0.447-0.577). Keratoconus incidence per 100,000 person-years was 6.227 in subjects without TGD, 6.019 in the hypothyroidism group and 8.287 in the hyperthyroidism group, respectively. Although not statistically significant, individuals with hyperthyroidism showed a higher HR (1.290, 95% CI: 0.939-1.771) for keratoconus when compared to those without TGD, after adjusting for age and sex. This study emphasizes a female predominance in keratoconus incidence and suggests a possible connection between hyperthyroidism and keratoconus. Furthermore, it affirms a higher incidence of keratoconus among young individuals.

Cost-effectiveness of treating relapsed or refractory 3L+ follicular lymphoma with axicabtagene ciloleucel vs mosunetuzumab in the United States

IntroductionNovel therapies for 3L+ relapsed/refractory (r/r) follicular lymphoma (FL) have been approved recently by the US Food and Drug Administration including anti-CD19 CAR-T therapies such as axicabtagene ciloleucel (axi-cel) and CD20 × CD3 T-cell-engaging bispecific monoclonal antibodies such as mosunetuzumab (mosun). The objective of this study was to assess the cost-effectiveness of axi-cel compared to mosun in 3L+ r/r FL patients from a US third-party payer perspective.MethodsA three-state (progression-free, progressed disease, and death) partitioned-survival model was used to compare two treatments over a lifetime horizon in a hypothetical cohort of US adults (age ≥18) receiving 3L+ treatment for r/r FL. ZUMA-5 and GO29781 trial data were used to inform progression-free survival (PFS) and overall survival (OS). Mosun survival was modeled via hazard ratios (HRs) applied to axi-cel survival curves. The PFS HR value was estimated via a matching-adjusted indirect comparison (MAIC) based on mosun pseudo-individual patient data and adjusted axi-cel data to account for trial populations differences. One-way sensitivity analysis (OWSA) and probabilistic sensitivity analyses (PSA) were conducted. Scenario analyses included: 1) the mosun HRs were applied to the weighted (adjusted) ZUMA-5 24-month data to most exactly reflect the MAIC, 2) mosun HR values were applied to axi-cel 48-month follow-up data, and 3) recent axi-cel health state utility values in diffuse large B-cell lymphoma patients.ResultsThe analysis estimated increases of 1.82 LY and 1.89 QALY for axi-cel compared to mosun. PFS for axi-cel patients was 6.42 LY vs. 1.60 LY for mosun. Increase of $257,113 in the progression-free state was driven by one-time axi-cel treatment costs. Total incremental costs for axi-cel were $204,377, resulting in an ICER of $108,307/QALY gained. The OWSA led to ICERs ranging from $240,255 to $75,624, with all but two parameters falling below $150,000/QALY. In the PSA, axi-cel had an 64% probability of being cost-effective across 5,000 iterations using a $150,000 willingness-to-pay threshold. Scenarios one and two resulted in ICERs of $105,353 and $102,695, respectively.DiscussionThis study finds that axi-cel is cost-effective compared to mosun at the commonly cited $150,000/QALY US willingness-to-pay threshold, with robust results across a range of sensitivity analyses accounting for parameter uncertainty.

Association, differences, and applications of three commonly used statistical indicators: risk ratio, hazard ratio, and odds ratio

Relative Risk (RR), Hazard Ratio (HR), and Odds Ratio (OR) are commonly used statistical measures in the field of public health to assess the magnitude of the effect of exposure factors on outcomes. These indicators have different calculation principles and implications in public health. However, a few researchers misused or misinterpreted RR, HR, and OR values when interpreting study results. Therefore, this article explores the relationships and differences among these measures, as well as the correct selection and application of RR, HR, and OR in both cohort study and case-control study.

Trophodynamics and health risk assessment of heavy metals in seafood from a tropical estuary in the gulf of Guinea

Seafood is an essential protein source for coastal communities. However, they can accumulate heavy metals from human activities which could pose a potential health risk to consumers. In this study, we investigated the distribution, bioaccumulation, trophic transfer and potential human health risk of heavy metals in sediments, shell and fin fish collected from the Escravos Estuary in southern Nigeria. Heavy metals (Ni, Cd, V, Pb and Cu) in sediments, periwinkles and tongue soles from the two study sites were lower than the permissible limits for fishery products. The metal distribution in fish tissues was in the decreasing order of liver > gills > muscles > gonads > rest of the fish. Moderate to high BSAF (>1) was reported for Cd, Pb and Cu. All the studied metals, except Pb, showed evidence of biomagnification from periwinkle to tongue sole. The estimated daily intake (EDI) and hazard ratio (HR) for metals in periwinkles from both study sites were lower or within the USEPA reference doses (RfD) for the respective daily intake and HR value < 1, except for Cd, V and Pb for children. In contrast, EDI values in the muscle of tongue soles were higher than the RfD values for heavy metals except for Ni and Pb, whereas HR values > 1 except for Ni, Cd and V. In the whole fish, EDI and HR values were disproportionately high in both study sites with higher values reported for children. This study provides the first insights on the trophic transfer and risk assessment of heavy metals from petroleum and gas operations impacting the Escravos Estuary and the implications to public health.

Neutrophil-to-Lymphocyte Ratio: A Promising Predictor of Mortality in Patients With Acute Respiratory Distress Syndrome. A Retrospective Analysis of a Single Hospital Center

ObjectivesTo examine how the neutrophil-to-lymphocyte ratio (NLR) affects both short-term and long-term mortality in individuals with acute respiratory distress syndrome (ARDS). DesignA retrospective study SettingCritical care unit ParticipantsA total of 785 patients with ARDS were included. InterventionsThere were three groups in the NLR study. To calculate the hazard ratio (HR) between the NLR and mortality (30-day, 90-day and 1-year mortality), a Cox proportional hazards regression model was utilised. Measurements and Main ResultsOf the 785 patients, 329 were women (41.9%) and 456 were men (58.1%), with a mean age of 63.4 ± 16.7 years and mean NLR of 14.2 ± 9.8. In the unadjusted model, the second (6.0–11.3) and third (>11.3) NLR groups had HR (95% CI) values of 1.12 (0.83, 1.52) and 2.39 (1.87, 3.04), respectively, for 30-day all-cause mortality compared with the first (<6.0) NLR group. This association remained significant after adjusting for potential confounding variables (HR = 1.54, 95% CI: 1.18–2.02), with a statistically significant trend (P = 0.0004) in the third (>11.3) NLR group. There was a similar effect on both 90-day and 1-year all-cause mortality. The R (95% CI) in a two-piecewise linear regression was 1.25 (1.06–1.48; P < 0.0001) on the left side of the inflection point (NLR 17.1). ConclusionsIn this retrospective single-centre study, the NLR was a potential predictor of both short-term and long-term mortality in patients with ARDS and may help with risk stratification.

Long-term ozone exposure and mortality in patients with chronic kidney disease: a large cohort study

BackgroundEpidemiologic studies on the effects of long-term exposure to ozone (O3) have shown inconclusive results. It is unclear whether to O3 has an effect on chronic kidney disease (CKD). We investigated the effects of O3 on mortality and renal outcome in CKD.MethodsWe included 61,073 participants and applied Cox proportional hazards models to examine the effects of ozone on the risk of end-stage renal disease (ESRD) and mortality in a two-pollutants model adjusted for socioeconomic status. We calculated the concentration of ozone exposure one year before enrollment and used inverse distance weighting (IDW) for interpolation, where the exposure was evenly distributed.ResultsIn the single pollutant model, O3 was significantly associated with an increased risk of ESRD and all-cause mortality. Based on the O3 concentration from IDW interpolation, this moving O3 average was significantly associated with an increased risk of ESRD and all-cause mortality. In a two-pollutants model, even after we adjusted for other measured pollutants, nitrogen dioxide did not attenuate the result for O3. The hazard ratio (HR) value for the district-level assessment is 1.025 with a 95% confidence interval (CI) of 1.014–1.035, while for the point-level assessment, the HR value is 1.04 with a 95% CI of 1.035–1.045. The impact of ozone on ESRD, hazard ratio (HR) values are, 1.049(95%CI: 1.044–1.054) at the district unit and 1.04 (95%CI: 1.031–1.05) at the individual address of the exposure assessment. The ozone hazard ratio for all-cause mortality was 1.012 (95% confidence interval: 1.008–1.017) for administrative districts and 1.04 (95% confidence interval: 1.031–1.05) for individual addresses.ConclusionsThis study suggests that long-term ambient O3 increases the risk of ESRD and mortality in CKD. The strategy to decrease O3 emissions will substantially benefit health and the environment.

The difference between 2-hour post-challenge and fasting plasma glucose associates with the risk of cardiovascular disease in a normoglycemic population: the Tehran lipid and glucose study

BackgroundElevated fasting plasma glucose (FPG) and 2-hour post-challenge glucose (2hPG) levels are known to be independent risk factors for cardiovascular disease (CVD). However, there is limited data on the association of the difference between these measures and the risk of CVD. This study aims to investigate this association in normoglycemic Iranian adults, particularly in those with low-normal FPG levels.MethodsThis prospective cohort study included 4,594 30-65-year-old participants from the Tehran Lipid and Glucose Study. Using multivariable Cox proportional hazards regression models adjusting for age, sex, body mass index, hypertension, hypercholesterolemia, smoking, education level and FPG, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the association between 2hPG-FPG, both as continuous and categorical variables, and the CVD risk. Analyses of receiver operating characteristic curves were undertaken to determine the optimal 2hPG-FPG cut-off value.ResultsDuring a median of 17.9 years of follow-up, 459 CVD events occurred. A one-unit increase in 2hPG-FPG was significantly associated with an elevated risk of cardiovascular disease in both normoglycemic (HR 1.10, 95% CI (1.01–1.19)) and low-normal FPG individuals (HR 1.16, 95% CI (1.04–1.30)); this association resisted adjustment for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) among normoglycemic individuals. However, those with 2hPG levels greater than FPG levels had a non-significant increased risk of incident CVD compared to those with 2hPG levels of less than or equal to FPG, with corresponding HR values of 1.18 (95% CI: 0.95–1.46) in normoglycemic and 1.32 (95% CI: 0.98–1.79) in low-normal FPG, respectively. For incident CVD, the optimal cut-off value for the 2hPG-FPG was found to be 1.06 mmol/L, which was applicable for both normoglycemic and low FPG populations; using this criterion, the corresponding risks for incident CVD were 1.36 (95% CI: 1.12–1.64) and 1.57 (95% CI: 1.22–2.03), respectively.ConclusionsThe difference between 2hPG and FPG levels within the normoglycemic range is related to an increased risk of CVD, an issue that was independent of HOMA-IR. A cut-off point for 2hPG-FPG > 1.06 mmol/L may stratify persons at higher risk. These findings were particularly notable in those with low-normal FPG.

Relationship between systemic immune inflammation index and mortality among US adults with different diabetic status: Evidence from NHANES 1999-2018

ObjectiveTo investigate the association between systemic immune inflammation index (SII) and all-cause or cardiovascular diseases (CVDs) mortality in US adults with different diabetic status based on the National Health and Nutrition Examination Survey (NHANES) database. Study design and settingAdults with follow-up data in the NHANES 1999–2018 cycles were included in this study. The SII was calculated based on blood cells counts (including neutrophils, lymphocytes, and platelets) measured in the laboratory data. According to the quartiles of SII, population were divided into four groups (Q1-Q4). Mortality data was determined by linking NHANES survey participants to the National Death Index records, which collect mortality data and determine their vital status. Cox regression models were also performed to explore the hazard ratio (HR) and the corresponding 95 % confidence interval (95 % CI) of SII related with all-cause and CVDs mortality. In addition, restricted cubic spline was used to explore the nonlinear relationship between SII and mortality. Subgroup analysis and sensitivity analysis were performed to confirm the robustness of our results. ResultsIn this study, there were 45,454 participants were enrolled (50.43 % females), with a mean age of 47.35 ± 0.19 years. Among of which, 7971 were diabetes patients and 3281 were pre-diabetes. With the mean 9.89 ± 0.08 follow-up years, there were 6935 (15.26 %) deaths occurred. Of which, 1795 deaths were caused by CVDs. The age-adjusted death rates were higher in participants with high SII levels compared to those with low SII levels. Cox regression analysis, after adjusting for covariates, revealed that SII levels were associated with an increased risk of all-cause mortality (HR, 1.02; 95 % CI, 1.02–1.03, P < 0.0001) and CVDs mortality (HR, 1.05; 95 % CI, 1.02–1.08, P = 0.002) in the fully adjusted Model. Moreover, there was a slight increase in HR values with the progression of diabetes status. Restricted cubic spline analysis demonstrated a “U-shaped” relationship between SII and all-cause mortality in diabetic, pre-diabetic and non-diabetic populations (all the P for nonlinear < 0.001). In addition, the relationship between SII and CVDs mortality was also nonlinear in both the pre-diabetic and non-diabetic populations (both P < 0.001). However, there was a linear relationship between SII and cardiovascular mortality in individuals with diabetes (P = 0.528). ConclusionThe SII is closely associated with the risk of all-cause and cardiovascular mortality. These associations vary among individuals with different diabetic states. Therefore, monitoring systemic inflammation and SII values is crucial in mitigating the risk of mortality.

Association of time-varying sleep duration and cognitive function with mortality in the elderly: a 12-year community-based cohort study

BackgroundSleeping problems and cognitive impairment are common in elders. Baseline sleep duration and cognitive status are predictors of mortality. But few studies have explored whether longitudinal changes in sleep duration and cognitive function are related to mortality in older adults. The present study investigated the time-varying relationships of sleep duration and cognitive function with subsequent mortality among community-dwelling elders by using 12 years of repeated-measure data.MethodsTaichung Community Health Study for Elders (TCHS-E) is a retrospective, population-based cohort that started in 2009 (wave 1) with a total of 912 elders aged 65 years or above. Follow up was conducted in 2010 (wave 2), 2018 (wave 3), and 2020 (wave 4). Sleep duration and Mini-Mental State Examination (MMSE) forms were executed at baseline and three visits during follow-up. Time-varying Cox proportional hazards regression estimated adjusted hazard ratios (HRs) of mortality with 95% confidence intervals (CIs).ResultsDuring about 12 years (9,396 person-years) follow-up, 329 deaths from all causes were documented, including 102 deaths due to expanded cardiovascular disease (CVD). In the multivariable-adjusted, time-varying Cox proportional hazard model, the adjusted HR values of all-cause mortality were 1.47 (1.02–2.12) for sleep duration > 9 h/day (vs. 7 h/day) and 1.81 (1.26–2.59) for MMSE < 27 (vs. 30). The adjusted HR values of the expanded CVD mortality were 2.91 (1.24–6.83) for MMSE of 29; 2.69 (1.20–6.05) for MMSE of 27–28; and 4.32 (95% CI: 1.92–9.74) for MMSE < 27. The dose-dependent relationship was significant (p < 0.001). The combinations of sleep duration longer than 9 h/day and MMSE < 27 were linked with the highest risks for expanded CVD and all-cause mortality.ConclusionsLong sleep duration and low cognitive function were jointly and independently linked with higher risk of mortality in elders residing in community.