The role of dementia in the association between APOE4 and all-cause mortality: pooled analyses of two population-based cohort studies.

BACKGROUND: The ε4 allele of the apolipoprotein E gene (APOE4) plays a role in neurodegeneration and in cardiovascular disease, but findings on its association with mortality are inconsistent. We aimed to examine the association between APOE4 and mortality, and the role of dementia in this association. METHODS: In this pooled analysis, data on White participants aged 45-90 years who underwent APOE genotyping were drawn from two population-based cohorts: the Whitehall II study (UK), which began in 1985 and is ongoing, and the Three-City study (France), initiated in 1999 and ended in 2012. In the Three-City study, vital status was ascertained through linkage to the national registry of death Institut National de la Statistique des Études économiques, and dementia was ascertained via a neuropsychological evaluation and validation of diagnoses by an independent committee of neurologists and geriatricians. In the Whitehall II study, vital status was ascertained through linkage to the UK national mortality register, and dementia cases were ascertained by linkage to three national registers. Participants with prevalent dementia at baseline and participants missing an APOE genotype were excluded from analyses. Cox regression proportional hazard models were used to examine the association of APOE4 with all-cause, cardiovascular, and cancer mortality. The role of dementia in the association between APOE4 status and mortality was examined by excluding participants who developed dementia during follow-up from the analyses. An illness-death model was then used to examine the role of incident dementia in these associations. FINDINGS: 14 091 participants (8492 from the Three-City study and 5599 from the Whitehall II study; 6668 [47%] of participants were women and 7423 [53%] were men), with a median follow-up of 15·4 years (IQR 10·6-21·2), were included in the analyses. Of these participants, APOE4 carriers (3264 [23%] of the cohort carried at least one ε4 allele) had a higher risk of all-cause mortality compared with non-carriers, with hazard ratios (HR) of 1·16 (95% CI 1·07-1·26) for heterozygotes and 1·59 (1·24-2·06) for homozygotes. Compared with APOE3 homozygotes, higher cardiovascular mortality was observed in APOE4 carriers, with a HR of 1·23 (1·01-1·50) for heterozygotes, and no association was found between APOE4 and cancer mortality. Excluding cases of incident dementia over the follow-up resulted in attenuated associations with mortality in homozygotes but not in heterozygotes. The illness-death model indicated that the higher mortality risk in APOE4 carriers was not solely attributable to dementia. INTERPRETATION: We found a robust association between APOE4 and all-cause and cardiovascular mortality but not cancer mortality. Dementia explained a significant proportion of the association with all-cause mortality for APOE4 homozygotes, while non-dementia factors, such as cardiovascular disease mortality, are likely to play a role in shaping mortality outcomes in APOE4 heterozygotes. FUNDING: National Institutes of Health. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Cause of death coding in asthma.

BACKGROUND: While clinical coding is intended to be an objective and standardized practice, it is important to recognize that it is not entirely the case. The clinical and bureaucratic practices from event of death to a case being entered into a research dataset are important context for analysing and interpreting this data. Variation in practices can influence the accuracy of the final coded record in two different stages: the reporting of the death certificate, and the International Classification of Diseases (Version 10; ICD-10) coding of that certificate. METHODS: This study investigated 91,022 deaths recorded in the Scottish Asthma Learning Healthcare System dataset between 2000 and 2017. Asthma-related deaths were identified by the presence of any of ICD-10 codes J45 or J46, in any position. These codes were categorized either as relating to asthma attacks specifically (status asthmatic; J46) or generally to asthma diagnosis (J45). RESULTS: We found that one in every 200 deaths in this were coded as being asthma related. Less than 1% of asthma-related mortality records used both J45 and J46 ICD-10 codes as causes. Infection (predominantly pneumonia) was more commonly reported as a contributing cause of death when J45 was the primary coded cause, compared to J46, which specifically denotes asthma attacks. CONCLUSION: Further inspection of patient history can be essential to validate deaths recorded as caused by asthma, and to identify potentially mis-recorded non-asthma deaths, particularly in those with complex comorbidities.

Causes of Death in Patients Asking for Polyclinic Care for Coronary Heart Disease.

AIM: Retrospective analysis of the underlying causes for death of patients who did and did not seek outpatient medical care (OPMC) for ischemic heart disease (IHD), and discussion of a possibility for using administrative anonymized but individualized databases for analysis. MATERIAL AND METHODS: The electronic database of the Central Administration of the Civil Registry Office of the Moscow Region (Unified State Register of the Civil Registry Office of the Moscow Region), including medical death certificates (MDC) for 2021, was used to select all cases of fatal outcomes with the disease codes of the International Classification of Diseases, Tenth Revision (ICD-10) (codes of external causes, injuries, poisonings excluded) that were indicated as the primary cause of death (PCD). Personalized data of the deceased were combined with data from electronic medical records of patients who sought OPMC at institutions of the Moscow Region within up to 2 years before death. In addition to IHD, the following PCD codes were taken into account: malignant tumors, COVID-19, diabetes mellitus, cerebrovascular diseases, hypertension, chronic obstructive pulmonary disease, alcohol-associated diseases, and, as examples of unspecified PCD, old age and unspecified encephalopathy.Results In total, among those who died from diseases, the proportion of those who died from IHD was 18.9%; for another 8.4%, IHD was indicated as a comorbid disease in Part II of the MDC. Among those who sought OPMC for IHD, the IHD proportion indicated as PCD was 27.5%, and among those who did not seek OPMC 17.4% (p <0.0001). Those who died from IHD and who had sought OPMC were older (mean age, 75.59 ± 10.94 years) than those who died from IHD and had not sought OMPM (mean age, 73.96 ± 10.94 years; p < 0.0001). The frequency of myocardial infarction as PCD among those who had and had not sought OPMC was the same (12%), chronic forms of IHD were 83.9% and 79.7%, the frequencies of "unspecified" acute forms of IHD (codes I24.8-9) were 4.1% and 8.3%, respectively. The proportion of deaths from COVID-19 was the highest (21.7% and 24.3%, respectively), from malignant neoplasms 11.6% and 12.7%, respectively, and from unspecified encephalopathy 10.6% and 10.7%, respectively. CONCLUSION: Only 25% of patients who had sought OPMC for IHD died from IHD, otherwise the causes of death were the same as for patients who had not sought OPMC for IHD. Analysis of administrative databases allows identifying disparities in the PCD structure and to direct the efforts of specialists to reconciling the criteria for death from various forms of IHD.

Heavy Lifetime Cannabis Use and Mortality by Sex.

Importance: The association between mortality and cannabis use remains unclear. Objective: To examine sex-stratified associations of cumulative lifetime cannabis use with all-cause, cardiovascular disease (CVD), and cancer mortality in the UK Biobank population. Design, Setting, and Participants: This cohort study used data from volunteers in the UK Biobank population. Participant monitoring for mortality in the UK Biobank study commenced from the point of their inclusion between 2006 and 2010 and continued until December 19, 2020. Data regarding the causes of death were sourced from the National Health Service Information Centre. Data were analyzed from inception of study inclusion to December 2020. Exposure: Cannabis use status was assessed by questionnaire and categorized as heavy, moderate, low, and never. Main Outcomes and Measures: The main outcomes were all-cause, CVD, and cancer mortality. Sex-stratified associations of cumulative lifetime cannabis use with mortality were estimated using Cox proportional hazards regression with adjustment for demographic and clinical variables. Results: Among 121 895 participants (54.51% females with mean [SD] age of 55.15 [7.64] years; 45.49% males with mean [SD] age of 56.46 [7.79] years) during an overall median of 11.80 years (IQR, 10.53-13.22 years) of follow-up, 2375 total deaths occurred, including 1411 deaths from CVD and 440 from cancer. In males, after full adjustment, the hazard ratios (HRs) were 1.28 (95% CI, 0.90-1.81) for all-cause mortality, 0.98 (95% CI, 0.43-2.25) for CVD mortality, and 1.09 (95% CI, 0.71-1.67) for cancer mortality among heavy cannabis users compared with never users. In females, after full adjustment, the HRs were 1.49 (95% CI, 0.92-2.40) for all-cause mortality, 2.67 (95% CI, 1.19-4.32) for CVD mortality, and 1.61 (95% CI, 0.91-2.83) for cancer mortality among heavy cannabis users compared with never users. In female current tobacco users, after full adjustment, heavy cannabis use was associated with all-cause mortality (HR, 2.25; 95% CI, 1.12-4.53), CVD mortality (HR, 2.56; 95% CI, 1.43-15.36), and cancer mortality (HR, 3.52; 95% CI, 1.50-8.33) and among never tobacco users was associated with CVD mortality (HR, 2.98; 95% CI, 1.67-6.61). In male current tobacco users, heavy cannabis use was associated with cancer mortality (HR, 2.44; 95% CI, 1.14-5.23). Conclusions and Relevance: In this study, a positive association between CVD mortality and heavy lifetime cannabis use was observed among females. Longitudinal studies are needed in general populations to investigate the potential effects of cannabis on mortality.

Depressive symptoms and all-cause mortality among middle-aged and older people in China and associations with chronic diseases.

Introduction: It remains unclear whether depressive symptoms are associated with increased all-cause mortality and to what extent depressive symptoms are associated with chronic disease and all-cause mortality. The study aims to explore the relationship between depressive symptoms and all-cause mortality, and how depressive symptoms may, in turn, affect all-cause mortality among Chinese middle-aged and older people through chronic diseases. Methods: Data were collected from the China Health and Retirement Longitudinal Study (CHARLS). This cohort study involved 13,855 individuals from Wave 1 (2011) to Wave 6 (2020) of the CHARLS, which is a nationally representative survey that collects information from Chinese residents ages 45 and older to explore intrinsic mechanisms between depressive symptoms and all-cause mortality. The Center for Epidemiological Studies Depression Scale (CES-D-10) was validated through the CHARLS. Covariates included socioeconomic variables, living habits, and self-reported history of chronic diseases. Kaplan-Meier curves depicted mortality rates by depressive symptom levels, with Cox proportional hazards regression models estimating the hazard ratios (HRs) of all-cause mortality. Results: Out of the total 13,855 participants included, the median (Q1, Q3) age was 58.00 (51.00, 63.00) years. Adjusted for all covariates, middle-aged and older adults with depressive symptoms had a higher all-cause mortality rate (HR = 1.20 [95% CI, 1.09-1.33]). An increased rate was observed for 55-64 years old (HR = 1.23 [95% CI, 1.03-1.47]) and more than 65 years old (HR = 1.32 [95% CI, 1.18-1.49]), agricultural Hukou (HR = 1.44, [95% CI, 1.30-1.59]), and nonagricultural workload (HR = 1.81 [95% CI, 1.61-2.03]). Depressive symptoms increased the risks of all-cause mortality among patients with hypertension (HR = 1.19 [95% CI, 1.00-1.40]), diabetes (HR = 1.41[95% CI, 1.02-1.95]), and arthritis (HR = 1.29 [95% CI, 1.09-1.51]). Conclusion: Depressive symptoms raise all-cause mortality risk, particularly in those aged 55 and above, rural household registration (agricultural Hukou), nonagricultural workers, and middle-aged and older people with hypertension, diabetes, and arthritis. Our findings through the longitudinal data collected in this study offer valuable insights for interventions targeting depression, such as early detection, integrated chronic disease care management, and healthy lifestyles; and community support for depressive symptoms may help to reduce mortality in middle-aged and older people.

[Pollution attributable mortality]. / Mortalité attribuable à la pollution.

POLLUTION ATTRIBUTABLE MORTALITY. Pollution is estimated to be responsible for 9 million premature deaths per year in the world. For each cause of death with a risk increased by a pollutant, the number of deaths attributable to it is computed by comparison with the number of deaths expected under a reference pollution level, which is 10 µg/m3 for ambient particulate matter pollution. Only 8% of the deaths attributable to pollution occur in high income countries, because of the large effects of water and indoor air pollution (caused by traditional cooking methods) in low and middle-income countries. In France, by this method, one estimates that 13.200 deaths a year are attributable to ambient particulate matter pollution and 1.100 to ozone. Santé publique France, which has concluded that 48.000 deaths a year were attributable to air pollution in France, overvalues the risk by a factor of nearly 4 by overestimating the risks associated with air pollution and taking a utopian reference scenario.

MORTALITÉ ATTRIBUABLE À LA POLLUTION. On estime que la pollution est responsable de 9 millions de décès prématurés par an dans le monde. Pour chaque cause de décès dont le risque est augmenté par la pollution, un nombre de décès attribuable à la pollution est calculé par comparaison avec le nombre attendu pour un niveau de pollution de référence qui est de 10 µg/m3 pour la pollution particulaire de l'air extérieur. Seulement 8 % des décès attribuables à la pollution surviennent dans les pays à revenu élevé (effets importants des pollutions de l'eau et de l'air intérieur par des modes de cuisson traditionnels dans les pays à revenus bas ou moyens). En France, par cette méthode, on estime que 13 200 décès par an sont liés à la pollution particulaire de l'air extérieur et 1 100 à l'ozone. Santé publique France, qui conclut que 48 000 décès par an sont attribuables à la pollution de l'air en France, surévalue donc le risque d'un facteur proche de 4 en surestimant l'effet de la pollution et en prenant une pollution de référence utopique.

Body Roundness Index and All-Cause Mortality Among US Adults.

Importance: Obesity, especially visceral obesity, is an established risk factor associated with all-cause mortality. However, the inadequacy of conventional anthropometric measures in assessing fat distribution necessitates a more comprehensive indicator, body roundness index (BRI), to decipher its population-based characteristics and potential association with mortality risk. Objective: To evaluate the temporal trends of BRI among US noninstitutionalized civilian residents and explore its association with all-cause mortality. Design, Setting, and Participants: For this cohort study, information on a nationally representative cohort of 32 995 US adults (age ≥20 years) was extracted from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 and NHANES Linked Mortality File, with mortality ascertained through December 31, 2019. Data were analyzed between April 1 and September 30, 2023. Exposures: Biennial weighted percentage changes in BRI were calculated. Restricted cubic spline curve was used to determine optimal cutoff points for BRI. Main Outcome and Measures: The survival outcome was all-cause mortality. Mortality data were obtained from the Centers for Disease Control and Prevention website and linked to the NHANES database using the unique subject identifier. Weibull regression model was adopted to quantify the association between BRI and all-cause mortality. Results: Among 32 995 US adults, the mean (SD) age was 46.74 (16.92) years, and 16 529 (50.10%) were women. Mean BRI increased gradually from 4.80 (95% CI, 4.62-4.97) to 5.62 (95% CI, 5.37-5.86) from 1999 through 2018, with a biennial change of 0.95% (95% CI, 0.80%-1.09%; P < .001), and this increasing trend was more obvious among women, elderly individuals, and individuals who identified as Mexican American. After a median (IQR) follow-up of 9.98 (5.33-14.33) years, 3452 deaths (10.46% of participants) from all causes occurred. There was a U-shaped association between BRI and all-cause mortality, with the risk increased by 25% (hazard ratio, 1.25; 95% CI, 1.05-1.47) for adults with BRI less than 3.4 and by 49% (hazard ratio, 1.49; 95% CI, 1.31-1.70) for those with BRI of 6.9 or greater compared with the middle quintile of BRI of 4.5 to 5.5 after full adjustment. Conclusions and Relevance: This national cohort study found an increasing trend of BRI during nearly 20-year period among US adults, and importantly, a U-shaped association between BRI and all-cause mortality. These findings provide evidence for proposing BRI as a noninvasive screening tool for mortality risk estimation, an innovative concept that could be incorporated into public health practice pending consistent validation in other independent cohorts.

Gene therapy for people with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is the most common type of liver cancer, accounting for 70% to 85% of individuals with primary liver cancer. Gene therapy, which uses genes to treat or prevent diseases, holds potential for treatment, especially for tumours. Trials on the effects of gene therapy in people with hepatocellular carcinoma have been published or are ongoing. OBJECTIVES: To evaluate the benefits and harms of gene therapy in people with hepatocellular carcinoma, irrespective of sex, administered dose, and type of formulation. SEARCH METHODS: We identified randomised clinical trials through electronic searches in The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS, Science Citation Index Expanded, and Conference Proceedings Citation Index-Science. We searched five online clinical trial registries to identify unpublished or ongoing trials. We checked reference lists of the retrieved studies for further trials. The date of last search was 20 January 2023. SELECTION CRITERIA: We aimed to include randomised clinical trials assessing any type of gene therapy in people diagnosed with hepatocellular carcinoma, irrespective of year, language of publication, format, or outcomes reported. DATA COLLECTION AND ANALYSIS: We followed Cochrane methodology and used Review Manager to prepare the review. The primary outcomes were all-cause mortality/overall survival (whatever data were provided), serious adverse events during treatment, and health-related quality of life. The secondary outcomes were proportion of people with disease progression, adverse events considered non-serious, and proportion of people without improvement in liver function tests. We assessed risk of bias of the included trials using RoB 2 and the certainty of evidence using GRADE. We presented the results of time-to-event outcomes as hazard ratios (HR), dichotomous outcomes as risk ratios (RR), and continuous outcomes as mean difference (MD) with their 95% confidence intervals (CI). Our primary analyses were based on intention-to-treat and outcome data at the longest follow-up. MAIN RESULTS: We included six randomised clinical trials with 364 participants. The participants had unresectable (i.e. advanced inoperable) hepatocellular carcinoma. We found no trials assessing the effects of gene therapy in people with operable hepatocellular carcinoma. Four trials were conducted in China, one in several countries (from North America, Asia, and Europe), and one in Egypt. The number of participants in the six trials ranged from 10 to 129 (median 47), median age was 55.2 years, and the mean proportion of males was 72.7%. The follow-up duration ranged from six months to five years. As the trials compared different types of gene therapy and had different controls, we could not perform meta-analyses. Five of the six trials administered co-interventions equally to the experimental and control groups. All trials assessed one or more outcomes of interest in this review. The certainty of evidence was very low in five of the six comparisons and low in the double-dose gene therapy comparison. Below, we reported the results of the primary outcomes only. Pexastimogene devacirepvec (Pexa-Vec) plus best supportive care versus best supportive care alone There is uncertainty about whether there may be little to no difference between the effect of Pexa-Vec plus best supportive care compared with best supportive care alone on overall survival (HR 1.19, 95% CI 0.78 to 1.82; 1 trial (censored observation at 20-month follow-up), 129 participants; very low-certainty evidence) and on serious adverse events (RR 1.42, 95% CI 0.60 to 3.33; 1 trial at 20 months after treatment, 129 participants; very low-certainty evidence). The trial reported quality of life narratively as "assessment of quality of life and time to symptomatic progression was confounded by the high patient dropout rate." Adenovirus-thymidine kinase with ganciclovir (ADV-TK/GCV) plus liver transplantation versus liver transplantation alone There is uncertainty about whether ADV-TK/GCV plus liver transplantation may benefit all-cause mortality at the two-year follow-up (RR 0.39, 95% CI 0.20 to 0.76; 1 trial, 45 participants; very low-certainty evidence). The trial did not report serious adverse events other than mortality or quality of life. Double-dose ADV-TK/GCV plus liver transplantation versus liver transplantation alone There is uncertainty about whether double-dose ADV-TK/GCV plus liver transplantation versus liver transplantation may benefit all-cause mortality at five-year follow-up (RR 0.40, 95% CI 0.22 to 0.73; 1 trial, 86 participants; low-certainty evidence). The trial did not report serious adverse events other than mortality or quality of life. Recombinant human adenovirus-p53 with hydroxycamptothecin (rAd-p53/HCT) versus hydroxycamptothecin alone There is uncertainty about whether there may be little to no difference between the effect of rAd-p53/HCT versus hydroxycamptothecin alone on the overall survival at 12-month follow-up (RR 3.06, 95% CI 0.16 to 60.47; 1 trial, 48 participants; very low-certainty evidence). The trial did not report serious adverse events or quality of life. rAd-p53/5-Fu (5-fluorouracil) plus transarterial chemoembolisation versus transarterial chemoembolisation alone The trial included 46 participants. We had insufficient data to assess overall survival. The trial did not report serious adverse events or quality of life. E1B-deleted (dl1520) adenovirus versus percutaneous ethanol injection The trial included 10 participants. It did not report data on overall survival, serious adverse events, or health-related quality of life. One trial did not provide any information on sponsorship; one trial received a national research grant, one trial by the Pedersen foundation, and three were industry-funded trials. We found five ongoing randomised clinical trials. AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effects of gene therapy on the studied outcomes because of high risk of bias and imprecision of outcome results. The trials were underpowered and lacked trial data on clinically important outcomes. There was only one trial per comparison, and we could not perform meta-analyses. Therefore, we do not know if gene therapy may reduce, increase, or have little to no effect on all-cause mortality or overall survival, or serious adverse events in adults with unresectable hepatocellular carcinoma. The impact of gene therapy on adverse events needs to be investigated further. Evidence on the effect of gene therapy on health-related quality of life is lacking.

Prognostic effect of triglyceride glucose-related parameters on all-cause and cardiovascular mortality in the United States adults with metabolic dysfunction-associated steatotic liver disease.

BACKGROUNDS: Insulin resistance (IR) plays a vital role in the pathogenesis of the metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unclear whether triglyceride-glucose (TyG) related parameters, which serve as useful biomarkers to assess IR, have prognostic effects on mortality outcomes of MASLD. METHODS: Participants in the National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2018 years were included. TyG and its related parameters [TyG-waist circumference (TyG-WC) and TyG-waist to height ratio (TyG-WHtR)] were calculated. Kaplan-Meier curves, Cox regression analysis, and restricted cubic splines (RCS) were conducted to evaluate the association between TyG-related indices with the all-cause and cardiovascular mortality of adults with MASLD. The concordance index (C-index) was used to evaluate the prediction accuracy of TyG-related indices. RESULTS: A total of 8208 adults (4209 men and 3999 women, median age 49.00 years) with MASLD were included in this study. Multivariate-adjusted Cox regression analysis revealed that high quartile levels of TyG-related indices were significantly associated with the all-cause mortality of participants with MASLD [TyGadjusted hazard ratio (aHR) = 1.25, 95% confidence interval (CI) 1.05-1.50, P = 0.014; TyG-WCaHR for all-cause mortality = 1.28, 95% CI 1.07-1.52, P = 0.006; TyG-WHtRaHR for all-cause mortality = 1.50, 95% CI 1.25-1.80, P < 0.001; TyG-WCaHR for cardiovascular mortality = 1.81, 95% CI 1.28-2.55, P = 0.001; TyG-WHtRaHR for cardiovascular mortality = 2.22, 95% CI 1.55-3.17, P < 0.001]. The C-index of TyG-related indices for predicting all-cause mortality was 0.563 for the TyG index, 0.579 for the TyG-WC index, and 0.585 for the TyG-WHtR index, respectively. Regarding cardiovascular mortality, the C-index was 0.561 for the TyG index, 0.607 for the TyG-WC index, and 0.615 for the TyG-WHtR index, respectively. Nonlinear trends were observed between TyG and TyG-WC indices with all-cause mortality of MASLD (P < 0.001 and = 0.012, respectively). A non-linear relationship was observed between the TyG index and cardiovascular mortality of MASLD (P = 0.025). Subgroup analysis suggested that adults aged < 65 years old and those without comorbidities were more sensitive to the mortality prediction of TyG-related indices. CONCLUSION: Findings of this study highlight the predictive value of TyG-related indices, especially the TyG-WHtR index, in the mortality outcomes of adults with MASLD. TyG-related indices would be surrogate biomarkers for the clinical management of MASLD.

Weight training and risk of all-cause, cardiovascular disease and cancer mortality among older adults.

BACKGROUND: While previous studies indicate muscle-strengthening exercises may reduce mortality risk, further research is needed to increase certainty of the evidence. We investigated overall and dose-response associations between weight training and the risks of all-cause, cardiovascular disease (CVD) and cancer mortality in a large cohort of older adults with long follow-up time and a large number of deaths. We also investigated the joint associations of weight training and aerobic exercise with mortality risk. METHODS: Weight training was assessed via self-report in 2004-05 in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study (USA; n = 216 339), with follow-up to 2019. Cox regression estimated the hazard ratios (HR) and 95% confidence intervals (CI) for the associations between weight training and mortality, after adjusting for confounders including aerobic exercise. RESULTS: Around 25% of participants [mean age = 69.9 years (standard deviation = 5.4), 58% men] reported engaging in weight training over the past year, and there were 79 107 (37%) deaths. Engaging in any weight training (vs none) was associated with lower risks of all-cause (HR = 0.94; 95% CI = 0.93-0.96), CVD (HR = 0.92; 95% CI = 0.90-0.95) and cancer mortality (HR = 0.95; 95% CI = 0.92-0.98). More time spent in weight training was associated with only marginally greater risk reductions. Larger risk reductions were observed among women than men. Performing both aerobic exercise and weight training conferred the greatest mortality risk reduction; weight training was not associated with mortality risk among participants who did no aerobic exercise. CONCLUSION: Performing any amount of weight training lowered mortality risk.

Association between monocyte-lymphocyte ratio and all-cause and cardiovascular mortality in patients with chronic kidney diseases: A data analysis from national health and nutrition examination survey (NHANES) 2003-2010.

BACKGROUND: The relationship between monocyte-to-lymphocyte ratio (MLR) and prognosis in patients with chronic kidney disease (CKD) remains unclear. The aim of this study was to investigate the association between MLR and both all-cause mortality and cardiovascular disease (CVD) mortality in patients with CKD. METHODS: This study analyzed data from National Health and Nutrition Examination Survey 2003-2010. This study included 11262 eligible subjects, and 3015 of them were with CKD. We first compared the differences in clinical characteristics between individuals with and without CKD, and then grouped the CKD population based on quartiles of MLR. The partial correlation analysis was conducted to assess the relationships between MLR and some important clinical features. Cox proportional hazards models were used to investigate the associations between MLR and mortality from all-cause and cardiovascular disease. Restricted cubic spline (RCS) was used to investigate the dose-response relationship between MLR and mortality, the receiver operating characteristic (ROC) curves is used to compare the efficacy of MLR with different clinical biological indicators in assessing the risk of death. RESULTS: During a median follow-up of 10.3 years in CKD population, 1398 (43%) all-cause deaths and 526 (16%) CVD deaths occurred. It has been found that individuals with CKD have higher MLR level. The partial correlation analysis results showed that even after adjusting for age, sex, and race, MLR is still correlated with blood glucose, lipid levels, and kidney function indicators. The results of the cox proportional hazards regression model and Kaplan-Meier curve shown after adjusting for covariates, higher MLR was significantly associated with an increased risk of mortality. Consistent results were also observed when MLR was examined as categorical variable (quartiles). The RCS demonstrated a positive association between MLR and the risk of all-cause mortality and cardiovascular mortality. The ROC results indicate that the predictive efficacy of MLR for all-cause mortality risk is comparable to eGFR, higher than NLR and CRP. The predictive efficacy of MLR for cardiovascular mortality risk is higher than these three indicators. CONCLUSION: Compared to non-CKD population, the CKD population has higher levels of MLR. In the CKD population, MLR is positively correlated with the risk of death. Furthermore, the predictive efficacy of MLR for mortality risk is higher than other clinical indicators. This suggests that MLR can serve as a simple and effective clinical indicator for predicting mortality risk in CKD patients.

Cytoreductive nephrectomy in metastatic renal cell carcinoma.

BACKGROUND: Nephrectomy is the surgical removal of all or part of a kidney. When the aim of nephrectomy is to reduce tumor burden in people with established metastatic disease, the procedure is called cytoreductive nephrectomy (CN). CN is typically combined with systemic anticancer therapy (SACT). SACT can be initiated before or immediately after the operation or deferred until radiological signs of disease progression. The benefits and harms of CN are controversial. OBJECTIVES: To assess the effects of cytoreductive nephrectomy combined with systemic anticancer therapy versus systemic anticancer therapy alone or watchful waiting in newly diagnosed metastatic renal cell carcinoma. SEARCH METHODS: We performed a comprehensive search in the Cochrane Library, MEDLINE, Embase, Scopus, two trial registries, and other gray literature sources up to 1 March 2024. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated SACT and CN versus SACT alone or watchful waiting. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. Primary outcomes were time to death from any cause and quality of life. Secondary outcomes were time to disease progression, treatment response, treatment-related mortality, discontinuation due to adverse events, and serious adverse events. We performed statistical analyses using a random-effects model. We rated the certainty of evidence using the GRADE approach. MAIN RESULTS: Our search identified 10 records of four unique RCTs that informed two comparisons. In this abstract, we focus on the results for the two primary outcomes. Cytoreductive nephrectomy plus systemic anticancer therapy versus systemic anticancer therapy alone Three RCTs informed this comparison. Due to the considerable heterogeneity when pooling across these studies, we decided to present the results of the prespecified subgroup analysis by type of systemic agent. Cytoreductive nephrectomy plus interferon immunotherapy versus interferon immunotherapy alone CN plus interferon immunotherapy compared with interferon immunotherapy alone probably increases time to death from any cause (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.51 to 0.89; I²= 0%; 2 studies, 326 participants; moderate-certainty evidence). Assuming 820 all-cause deaths at two years' follow-up per 1000 people who receive interferon immunotherapy alone, the effect estimate corresponds to 132 fewer all-cause deaths (237 fewer to 37 fewer) per 1000 people who receive CN plus interferon immunotherapy. We found no evidence to assess quality of life. Cytoreductive nephrectomy plus tyrosine kinase inhibitor therapy versus tyrosine kinase inhibitor therapy alone We are very uncertain about the effect of CN plus tyrosine kinase inhibitor (TKI) therapy compared with TKI therapy alone on time to death from any cause (HR 1.11, 95% CI 0.90 to 1.37; 1 study, 450 participants; very low-certainty evidence). Assuming 574 all-cause deaths at two years' follow-up per 1000 people who receive TKI therapy alone, the effect estimate corresponds to 38 more all-cause deaths (38 fewer to 115 more) per 1000 people who receive CN plus TKI therapy. We found no evidence to assess quality of life. Immediate cytoreductive nephrectomy versus deferred cytoreductive nephrectomy One study evaluated CN followed by TKI therapy (immediate CN) versus three cycles of TKI therapy followed by CN (deferred CN). Immediate CN compared with deferred CN may decrease time to death from any cause (HR 1.63, 95% CI 1.05 to 2.53; 1 study, 99 participants; low-certainty evidence). Assuming 620 all-cause deaths at two years' follow-up per 1000 people who receive deferred CN, the effect estimate corresponds to 173 more all-cause deaths (18 more to 294 more) per 1000 people who receive immediate CN. We found no evidence to assess quality of life. AUTHORS' CONCLUSIONS: CN plus SACT in the form of interferon immunotherapy versus SACT in the form of interferon immunotherapy alone probably increases time to death from any cause. However, we are very uncertain about the effect of CN plus SACT in the form of TKI therapy versus SACT in the form of TKI therapy alone on time to death from any cause. Immediate CN versus deferred CN may decrease time to death from any cause. We found no quality of life data for any of these three comparisons. We also found no evidence to inform any other comparisons, in particular those involving newer immunotherapy agents (programmed death receptor 1 [PD-1]/programmed death ligand 1 [PD-L1] immune checkpoint inhibitors), which have become the backbone of SACT for metastatic renal cell carcinoma. There is an urgent need for RCTs that explore the role of CN in the context of contemporary forms of systemic immunotherapy.

U.S. Army mortality surveillance in active duty soldiers, 2014-2019.

Mortality surveillance is an important activity for capturing information on a population's health. This retrospective surveillance analysis utilizes administrative data sources to describe active duty U.S. Army soldiers who died from 2014 to 2019, and calculate mortality rates, assess trends by category of death, and identify leading causes of death within subpopulations. During the surveillance period, 2,530 soldier deaths were reported. The highest crude mortality rates observed during the 6-year surveillance period were for deaths by suicide, followed by accidental (i.e., unintentional injury) deaths. The crude mortality rates for natural deaths decreased significantly over the 6-year period, by an average of 6% annually. The leading causes of death were suicide by gunshot wound, motor vehicle accidents, suicide by hanging, neoplasms, and cardiovascular events. Significant differences were observed in the leading causes of death in relation to demographic characteristics, which has important implications for the development of focused educational campaigns to improve health behaviors and safe driving habits. Current public health programs to prevent suicide should be evaluated, with new approaches for firearm safety considered.

Alcohol-Related Deaths of US Health Care Workers.

This cohort study investigates the risk of alcohol-related death among US health care workers compared with non­health care workers.

Obstetric risk profiles and causes of death: Estimating their association with cesarean sections among maternal deaths in Mexico.

BACKGROUND: Maternal mortality is a critical indicator of healthcare quality, and in Mexico, this has become increasingly concerning due to the stagnation in its decline, alongside a concurrent increase in cesarean section (C-section) rates. This study characterizes maternal deaths in Mexico, focusing on estimating the association between obstetric risk profiles, cause of death, and mode of delivery. METHODS: Utilizing a retrospective observational design, 4,561 maternal deaths in Mexico from 2010-2014 were analyzed. Data were sourced from the Deliberate Search and Reclassification of Maternal Deaths database, alongside other national databases. An algorithm was developed to extract the Robson Ten Group Classification System from clinical summaries text, facilitating a nuanced analysis of C-section rates. Information on the reasons for the performance of a C-section was also obtained. Logistic regression and multinomial logistic regression models were used to estimate the relation between obstetric risk factors, mode of delivery and causes of maternal death, adjusting for covariates. RESULTS: Among maternal deaths in Mexico from 2010-2014, 47.1% underwent a C-section, with a significant history of previous C-sections observed in 31.4% of these cases, compared to 17.4% for vaginal deliveries (p<0.001). Early prenatal care in the first trimester was more common in C-section cases (46.8%) than in vaginal deliveries (38.3%, p<0.001). A stark contrast was noted in the place of death, with 82.4% of post-C-section deaths occurring in public institutions versus 69.1% following vaginal births. According to Robson's classification, the highest C-section rates were in Group 4 (67.2%, p<0.001) and Group 8 (66.9%, p<0.001). Logistic regression analysis revealed no significant difference in the odds of receiving a C-section in private versus other settings after adjusting for Robson criteria (OR: 1.21; 95% CI: 0.92, 1.60). A prior C-section significantly increased the likelihood of another (OR: 2.38; CI 95%: 2.01, 2.81). The analysis also indicated C-sections were significantly tied to deaths from hypertensive disorders (RRR = 1.25, 95% CI [1.12, 1.40]). In terms of indications, 6.3% of C-sections were performed under inadequate indications, while the indication was not identifiable in 33.1% of all C-sections. CONCLUSIONS: This study highlights a significant overuse of C-sections among maternal deaths in Mexico (2010-2014), revealed through the Robson classification and ana analysis of the reported indications for the procedure. It underscores the need for revising clinical decision-making to promote evidence-based guidelines and favor vaginal deliveries when possible. High C-section rates, especially noted disparities between private and public sectors, suggest economic and non-clinical factors may be at play. The importance of accurate data systems and further research with control groups to understand C-section practices' impact on maternal health is emphasized.

Association between triglyceride glucose-body mass index and long-term adverse outcomes of heart failure patients with coronary heart disease.

BACKGROUND: The triglyceride glucose-body mass index (TyG-BMI) is recognized as a reliable surrogate for evaluating insulin resistance and an effective predictor of cardiovascular disease. However, the link between TyG-BMI index and adverse outcomes in heart failure (HF) patients remains unclear. This study examines the correlation of the TyG-BMI index with long-term adverse outcomes in HF patients with coronary heart disease (CHD). METHODS: This single-center, prospective cohort study included 823 HF patients with CHD. The TyG-BMI index was calculated as follows: ln [fasting triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2] × BMI. To explore the association between the TyG-BMI index and the occurrences of all-cause mortality and HF rehospitalization, we utilized multivariate Cox regression models and restricted cubic splines with threshold analysis. RESULTS: Over a follow-up period of 9.4 years, 425 patients died, and 484 were rehospitalized due to HF. Threshold analysis revealed a significant reverse "J"-shaped relationship between the TyG-BMI index and all-cause mortality, indicating a decreased risk of all-cause mortality with higher TyG-BMI index values below 240.0 (adjusted model: HR 0.90, 95% CI 0.86-0.93; Log-likelihood ratio p = 0.003). A distinct "U"-shaped nonlinear relationship was observed with HF rehospitalization, with the inflection point at 228.56 (adjusted model: below: HR 0.95, 95% CI 0.91-0.98; above: HR 1.08, 95% CI 1.03-1.13; Log-likelihood ratio p < 0.001). CONCLUSIONS: This study reveals a nonlinear association between the TyG-BMI index and both all-cause mortality and HF rehospitalization in HF patients with CHD, positioning the TyG-BMI index as a significant prognostic marker in this population.

Association between the stress hyperglycemia ratio and 28-day all-cause mortality in critically ill patients with sepsis: a retrospective cohort study and predictive model establishment based on machine learning.

BACKGROUND: Sepsis is a severe form of systemic inflammatory response syndrome that is caused by infection. Sepsis is characterized by a marked state of stress, which manifests as nonspecific physiological and metabolic changes in response to the disease. Previous studies have indicated that the stress hyperglycemia ratio (SHR) can serve as a reliable predictor of adverse outcomes in various cardiovascular and cerebrovascular diseases. However, there is limited research on the relationship between the SHR and adverse outcomes in patients with infectious diseases, particularly in critically ill patients with sepsis. Therefore, this study aimed to explore the association between the SHR and adverse outcomes in critically ill patients with sepsis. METHODS: Clinical data from 2312 critically ill patients with sepsis were extracted from the MIMIC-IV (2.2) database. Based on the quartiles of the SHR, the study population was divided into four groups. The primary outcome was 28-day all-cause mortality, and the secondary outcome was in-hospital mortality. The relationship between the SHR and adverse outcomes was explored using restricted cubic splines, Cox proportional hazard regression, and Kaplan‒Meier curves. The predictive ability of the SHR was assessed using the Boruta algorithm, and a prediction model was established using machine learning algorithms. RESULTS: Data from 2312 patients who were diagnosed with sepsis were analyzed. Restricted cubic splines demonstrated a "U-shaped" association between the SHR and survival rate, indicating that an increase in the SHR is related to an increased risk of adverse events. A higher SHR was significantly associated with an increased risk of 28-day mortality and in-hospital mortality in patients with sepsis (HR > 1, P < 0.05) compared to a lower SHR. Boruta feature selection showed that SHR had a higher Z score, and the model built using the rsf algorithm showed the best performance (AUC = 0.8322). CONCLUSION: The SHR exhibited a U-shaped relationship with 28-day all-cause mortality and in-hospital mortality in critically ill patients with sepsis. A high SHR is significantly correlated with an increased risk of adverse events, thus indicating that is a potential predictor of adverse outcomes in patients with sepsis.

Association of diabetic retinopathy on all-cause and cause-specific mortality in older adults with diabetes: National Health and Nutrition Examination Survey, 2005-2008.

To evaluate the effect of diabetic retinopathy (DR) status or severity on all-cause and cause-specific mortality among diabetic older adults in the United States using the most recent National Health and Nutrition Examination Survey (NHANES) follow-up mortality data. The severity of DR was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) grading scale. Multiple covariate-adjusted Cox proportional hazards regression models, Fine and Gray competing risk regression models, and propensity score matching (PSM) methods were used to assess the risk of all-cause and cause-specific mortality in individuals with diabetes. All analyses adopted the weighted data and complex stratified design approach proposed by the NHANES guidelines. Time to death was calculated based on the time between baseline and date of death or December 31, 2019, whichever came first. Ultimately 1077 participants, representing 3,025,316 US non-hospitalized individuals with diabetes, were included in the final analysis. After a median follow-up of 12.24 years (IQR, 11.16-13.49), 379 participants were considered deceased from all-causes, with 43.90% suffering from DR, including mild DR (41.50%), moderate to severe DR (46.77%), and proliferative DR (PDR) (67.21%). DR was associated with increased all-cause, cardiovascular disease (CVD) and diabetes mellitus (DM)-specific mortality, which remained consistent after propensity score matching (PSM). Results of DR grading assessment suggested that the presence of mild, moderate to severe NPDR was significantly associated with increased risk of all-cause and CVD-specific mortality, while the presence and severity of any DR was associated with increased DM-specific mortality, with a positive trend. The presence of DR in elderly individuals with diabetes is significantly associated with the elevated all-cause and CVD mortality. The grading or severity of DR may reflect the severity of cardiovascular disease status and overall mortality risk in patients with diabetes.

Floods and cause-specific mortality in the UK: a nested case-control study.

BACKGROUND: Floods are the most frequent weather-related disaster, causing significant health impacts worldwide. Limited studies have examined the long-term consequences of flooding exposure. METHODS: Flood data were retrieved from the Dartmouth Flood Observatory and linked with health data from 499,487 UK Biobank participants. To calculate the annual cumulative flooding exposure, we multiplied the duration and severity of each flood event and then summed these values for each year. We conducted a nested case-control analysis to evaluate the long-term effect of flooding exposure on all-cause and cause-specific mortality. Each case was matched with eight controls. Flooding exposure was modelled using a distributed lag non-linear model to capture its nonlinear and lagged effects. RESULTS: The risk of all-cause mortality increased by 6.7% (odds ratio (OR): 1.067, 95% confidence interval (CI): 1.063-1.071) for every unit increase in flood index after confounders had been controlled for. The mortality risk from neurological and mental diseases was negligible in the current year, but strongest in the lag years 3 and 4. By contrast, the risk of mortality from suicide was the strongest in the current year (OR: 1.018, 95% CI: 1.008-1.028), and attenuated to lag year 5. Participants with higher levels of education and household income had a higher estimated risk of death from most causes whereas the risk of suicide-related mortality was higher among participants who were obese, had lower household income, engaged in less physical activity, were non-moderate alcohol consumers, and those living in more deprived areas. CONCLUSIONS: Long-term exposure to floods is associated with an increased risk of mortality. The health consequences of flooding exposure would vary across different periods after the event, with different profiles of vulnerable populations identified for different causes of death. These findings contribute to a better understanding of the long-term impacts of flooding exposure.