Lower Mortality Risk Research Articles

Changes in the overall survival of patients with metastatic renal cell carcinoma in the era of immune-checkpoint inhibitors

BackgroundThe advent of immune checkpoint inhibitors (ICI) has brought about a significant transformation in the treatment of immunogenic tumors. On November 23, 2015, the United States Food and Drug Administration approved Nivolumab to treat metastatic renal cell carcinoma (RCC). We aimed to assess potential changes in the survival rates of patients with metastatic RCC at a population level after the approval of Nivolumab. MethodsWe used data from the latest version of the Surveillance, Epidemiology, and End Results (SEER) database which encompasses data up to the year 2020. We included patients with age ≥ 20 years who were diagnosed with ‘distant’ RCC from 2011 through 2020. Based on the approval of Nivolumab, the period from 2011 to 2020 was further grouped into 2011–2015 (pre-ICI era) and 2016–2020 (ICI era). ResultsThe median overall survival (OS) was 8 months in the pre-ICI era compared to 11 months in the ICI era (log-rank test, χ2 = 102.53, p < 0.001). Patients diagnosed with metastatic RCC in the ICI era had a significantly lower risk of dying [Cox proportional Hazard Ratio of 0.77, 95 % CI (0.74–0.80)] compared to patients diagnosed in the pre-ICI era. Additionally, patients under the age of 75 had a lower risk of death compared to those aged 75 years or older. Patients who received chemotherapy (systemic therapy), radiotherapy, or surgery faced a significantly lower risk of mortality. Individuals with metastasis to the brain, bone, liver, or lung had a significantly higher risk of death than those without metastasis to these locations. Marital status also played a role, as married individuals had a significantly lower risk of death compared to those who were divorced, separated, or widowed at the time of diagnosis. Furthermore, income level influenced survival, with patients earning a median annual household income of more than USD 75,000 exhibiting a significantly lower risk of mortality compared to those earning between USD 50,000 and USD 74,000. There was no significant difference in survival observed between non-Hispanic blacks and non-Hispanic whites. ConclusionThe advent of immune checkpoint inhibitors has led to a substantial improvement in the median overall survival of individuals diagnosed with metastatic renal cell carcinoma.

Prognostic Nutritional Index (PNI) as an Independent Predictor of 3-Year Postoperative Mortality in Elderly Patients with Hip Fracture: A Post hoc Analysis of a Prospective Cohort Study.

The prognostic nutritional index (PNI) has been reported as a significant predictor in various diseases. However, the prognostic value of the PNI in geriatric hip fracture patients has not been thoroughly evaluated. This study aimed to investigate the association between admission PNI and 3-year mortality in those patients. In this post hoc analysis, we included patients aged ≥65 years who underwent surgery for hip fracture between 2018 and 2019. The admission PNI was calculated as serum albumin (g/L) +5 × total lymphocyte count (×109/L). Patients were categorized into four groups based on PNI quartiles (≤ 43.55, 43.55-46.55, 46.55-49.20, and >49.20, respectively). The median follow-up duration was 3.1 years. Cox proportional hazards models were used to calculate the hazard ratio (HR). Receiver operating characteristic curve (ROC) was conducted for using PNI to predict mortality. Of the 942 eligible patients, 190 (20.2%) patients died during the follow-up. Compared to patients in the first quartile (Q1), those in the second (Q2), third (Q3), and fourth (Q4) quartiles had significantly lower mortality risks (HRs 0.50, 95% CI 0.35-0.74; 0.41, 95% CI 0.26-0.64; and 0.26, 95% CI 0.15-0.45, respectively). The optimal cutoff of PNI for predicting mortality was set as 45.275 (sensitivity, 0.674; specificity, 0.692; area under the curve (AUC), 0.727). Patients with higher PNI (>45.275) had a significant lower mortality risk (HR 0.39, 95% CI 0.28-0.55) compared to those with lower PNI (≤ 45.275). PNI is a reliable and independent predictor of 3-year mortality after hip fracture surgery in the elderly.

Combined association of aerobic and muscle strengthening activity with mortality in individuals with hypertension.

Evidence on the association between meeting both aerobic physical activity (PA) and muscle-strengthening activity (MSA) guidelines with mortality in individuals with hypertension is scarce. We included 34,990 adults from the 2007 to 2013 Korea National Health and Nutrition Examination Survey, linking mortality follow-up data until 2019. Adherence to PA guidelines was assessed based on the current PA guidelines using a self-reported questionnaire and categorized as follows: meeting MSA only, aerobic PA only, both MSA and aerobic PA, or neither. Associations of hypertension and adherence to PA guidelines with all-cause and cardiovascular disease (CVD) mortality were examined using Cox proportional hazard models. Over 9.2 years, 1948 participants died from any cause and 419 from CVD. Meeting both PA guidelines was associated with the lowest risk of all-cause and CVD mortalities in the total sample regardless of hypertension status. In individuals with hypertension, meeting aerobic PA guidelines only had a 24% lower risk of both all-cause and CVD mortality, and meeting both PA guidelines further reduced risks by 40% and 43%, respectively; however, meeting MSA guidelines only was not associated with either all-cause or CVD mortality. In individuals without hypertension, only meeting both MSA and aerobic PA guidelines, but not meeting either MSA or aerobic PA guidelines, showed reduced risk of CVD mortality. In Korean population, non-hypertensive individuals who met both guidelines had a lower risk of CVD mortality. However, hypertensive individuals showed a reduced risk of both all-cause and CVD mortality when meeting aerobic PA or both guidelines, but not MSA alone.

Comparison of Complete Versus Incomplete Percutaneous Revascularization in Patients With Chronic Total Occlusion: A Systematic Review and Meta-Analysis.

The optimal extent of revascularization in patients with chronic total occlusion (CTO) undergoing percutaneous coronary intervention (PCI) remains debated. This meta-analysis aimed to compare the clinical outcomes of complete versus incomplete revascularization in CTO patients. A systematic search of EMBASE, PubMed, and Web of Science was conducted up to July 6, 2024. Studies reporting outcomes in CTO patients undergoing PCI with complete or incomplete revascularization were included. The primary outcomes were major adverse cardiovascular events (MACE), all-cause mortality, and cardiovascular mortality. Eight studies with a total of 7,067 patients (4,854 complete and 2,213 incomplete revascularization) were included. Complete revascularization was associated with a significantly lower risk of MACE (RR: 0.57, 95% CI: 0.43-0.77), all-cause mortality (RR: 0.54, 95% CI: 0.37-0.78), and cardiovascular mortality (RR: 0.46, 95% CI: 0.29-0.75) compared to incomplete revascularization. There was no significant difference in the risk of recurrent myocardial infarction between the two groups (RR: 0.60, 95% CI: 0.20-1.80). In patients with CTO undergoing PCI, complete revascularization is associated with significantly better clinical outcomes, including lower risks of MACE, all-cause mortality, and cardiovascular mortality, compared to incomplete revascularization. These findings suggest that achieving complete revascularization should be prioritized when feasible in CTO patients.

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.

Plant and Animal Fat Intake and Overall and Cardiovascular Disease Mortality

The impact of dietary fat intake on long-term human health has attracted substantial research interest, and the health effects of diverse dietary fats depend on available food sources. Yet there is a paucity of data elucidating the links between dietary fats from specific food sources and health. To study associations of dietary plant and animal fat intake with overall mortality and cardiovascular disease (CVD) mortality. This large prospective cohort study took place in the US from 1995 to 2019. The analysis of men and women was conducted in the National Institutes of Health-AARP Diet and Health Study. Data were analyzed from February 2021 to May 2024. Specific food sources of dietary fats and other dietary information were collected at baseline, using a validated food frequency questionnaire. Hazard ratios (HRs) and 24-year adjusted absolute risk differences (ARDs) were estimated using multivariable-adjusted Cox proportional hazards regression. The analysis included 407 531 men and women (231 881 [56.9%] male; the mean [SD] age of the cohort was 61.2 [5.4] years). During 8 107 711 person-years of follow-up, 185 111 deaths were ascertained, including 58 526 CVD deaths. After multivariable adjustment (including adjustment for the relevant food sources), a greater intake of plant fat (HRs, 0.91 and 0.86; adjusted ARDs, -1.10% and -0.73%; P for trend < .001), particularly fat from grains (HRs, 0.92 and 0.86; adjusted ARDs, -0.98% and -0.71%; P for trend < .001) and vegetable oils (HRs, 0.88 and 0.85; adjusted ARDs, -1.40% and -0.71%; P for trend < .001), was associated with a lower risk for overall and CVD mortality, respectively, comparing the highest to the lowest quintile. In contrast, a higher intake of total animal fat (HRs, 1.16 and 1.14; adjusted ARDs, 0.78% and 0.32%; P for trend < .001), dairy fat (HRs, 1.09 and 1.07; adjusted ARDs, 0.86% and 0.24%; P for trend < .001), or egg fat (HRs, 1.13 and 1.16; adjusted ARDs, 1.40% and 0.82%; P for trend < .001) was associated with an increased risk for mortality for overall and CVD mortality, respectively, comparing the highest to the lowest quintile. Replacement of 5% energy from animal fat with 5% energy from plant fat, particularly fat from grains or vegetable oils, was associated with a lower risk for mortality: 4% to 24% reduction in overall mortality, and 5% to 30% reduction in CVD mortality. The findings from this prospective cohort study demonstrated consistent but small inverse associations between a higher intake of plant fat, particularly fat from grains and vegetable oils, and a lower risk for both overall and CVD mortality. A diet with a high intake of animal-based fat, including fat from dairy foods and eggs, was also shown to be associated with an elevated risk for both overall and CVD mortality.

Comparing clinical outcomes in patients with type 2 diabetes mellitus after ischaemic stroke: Sodium-glucose cotransporter 2 inhibitors users versus non-users. A propensity score matching National Cohort Study.

This nationwide cohort study evaluated the impact of sodium-glucose co-transporter-2 inhibitors (SGLT2i) on patients with type 2 diabetes mellitus (T2DM) after ischaemic stroke (IS), aiming to compare clinical outcomes between SGLT2i-treated patients and those not receiving SGLT2i. Utilizing Taiwan's National Health Insurance Research Database, we identified 707 patients with T2DM treated with SGLT2i and 27 514 patients not treated with SGLT2i after an IS, respectively, from 1 May 2016 to 31 December 2019. Propensity score matching was applied to balance baseline characteristics. The follow-up period extended from the index date (3 months after the index acute IS) until the independent occurrence of the study outcomes, 6 months after discontinuation of the index drug, or the end of the study period (31 December 2020), whichever came first. After propensity score matching, compared with the non-SGLT2i group (n = 2813), the SGLT2i group (n = 707) exhibited significantly lower recurrent IS rates (3.605% per year vs. 5.897% per year; hazard ratio: 0.55; 95% confidence interval: 0.34-0.88; p = 0.0131) and a significant reduction in all-cause mortality (5.396% per year vs. 7.489% per year; hazard ratio: 0.58; 95% confidence interval: 0.39-0.85; p = 0.0058). No significant differences were observed in the rates of acute myocardial infarction, cardiovascular death, heart failure hospitalization, or lower limb amputation. Our findings indicate significantly lower risks of recurrent IS and all-cause mortality among patients with T2DM receiving SGLT2i treatment. Further studies are required to validate these results and investigate the underlying mechanisms behind the observed effects.

History-restricted marginal structural model and latent class growth analysis of treatment trajectories for a time-dependent outcome.

In previous work, we introduced a framework that combines latent class growth analysis (LCGA) with marginal structural models (LCGA-MSM). LCGA-MSM first summarizes the numerous time-varying treatment patterns into a few trajectory groups and then allows for a population-level causal interpretation of the group differences. However, the LCGA-MSM framework is not suitable when the outcome is time-dependent. In this study, we propose combining a nonparametric history-restricted marginal structural model (HRMSM) with LCGA. HRMSMs can be seen as an application of standard MSMs on multiple time intervals. To the best of our knowledge, we also present the first application of HRMSMs with a time-to-event outcome. It was previously noted that HRMSMs could pose interpretation problems in survival analysis when either targeting a hazard ratio or a survival curve. We propose a causal parameter that bypasses these interpretation challenges. We consider three different estimators of the parameters: inverse probability of treatment weighting (IPTW), g-computation, and a pooled longitudinal targeted maximum likelihood estimator (pooled LTMLE). We conduct simulation studies to measure the performance of the proposed LCGA-HRMSM. For all scenarios, we obtain unbiased estimates when using either g-computation or pooled LTMLE. IPTW produced estimates with slightly larger bias in some scenarios. Overall, all approaches have good coverage of the 95 % confidence interval. We applied our approach to a population of older Quebecers composed of 57,211 statin initiators and found that a greater adherence to statins was associated with a lower combined risk of cardiovascular disease or all-cause mortality.

Renin-angiotensin system inhibitors and risk of hepatocellular carcinoma among patients with hepatitis B virus infection.

Hepatitis B virus (HBV) infection is a common cause of liver-related morbidity and mortality. Evidence suggests that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) decrease liver fibrosis, an intermediate step between liver injury and hepatocellular carcinoma (HCC). Our aim was to investigate the association between the use of ACEIs and ARBs on incident HCC and liver-related mortality among patients with HBV infection. We conducted a population-based study on a new-user cohort of patients seen at 24 hospitals across China. We included adult patients with HBV infection who started ACEIs or ARBs (ACEIs/ARBs), or calcium channel blockers or thiazide diuretics (CCBs/THZs) from January 2012 to December 2022. The primary outcome was incident HCC; secondary outcomes were liver-related mortality and new-onset cirrhosis. We used propensity score matching and Cox proportional hazards regression to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of study outcomes. Among 32 692 eligible patients (median age 58 [interquartile range (IQR) 48-68] yr, and 18 804 male [57.5%]), we matched 9946 pairs of patients starting ACEIs/ARBs or CCBs/THZs. During a mean follow-up of 2.3 years, the incidence rate of HCC per 1000 person-years was 4.11 and 5.94 among patients who started ACEIs/ARBs and CCBs/THZs, respectively, in the matched cohort. Use of ACEIs/ARBs was associated with lower risks of incident HCC (HR 0.66, 95% CI 0.50-0.86), liver-related mortality (HR 0.77, 95% CI 0.64-0.93), and new-onset cirrhosis (HR 0.81, 95% CI 0.70-0.94). In this cohort of patients with HBV infection, new users of ACEIs/ARBs had a lower risk of incident HCC, liver-related mortality, and new-onset cirrhosis than new users of CCBs/THZs.

Physical activity modification following a Transient Ischemic Attack in individuals with diabetes

BackgroundIndividuals with diabetes exhibit a higher risk of cardiovascular disease and mortality compared to healthy individuals. Following a transient ischemic attack (TIA) the risk of stroke and death increase further. Physical activity engagement after a TIA is an effective way of secondary prevention. However, there's a lack of research on how individuals with diabetes modify physical activity levels and how these adjustments impact survival post-TIA. This study aimed to determine the extent to which individuals with diabetes alter their physical activity levels following a TIA and to assess the impact of these changes on mortality.MethodsThis was a nationwide longitudinal study, employing data from national registers in Sweden spanning from 01/01/2003 to 31/12/2019. Data were collected 2 years retro- and prospectively of TIA occurrence, in individuals with diabetes. Individuals were grouped based on decreasing, remaining, or increasing physical activity levels after the TIA. Cox proportional hazards models were fitted to evaluate the adjusted relationship between change in physical activity and all-cause, cardiovascular, and non-cardiovascular mortality.ResultsThe final study sample consisted of 4.219 individuals (mean age 72.9 years, 59.4% males). Among them, 35.8% decreased, 37.5% kept steady, and 26.8% increased their physical activity after the TIA. A subsequent stroke occurred in 6.7%, 6.4%, and 6.1% of individuals, while death occurred in 6.3%, 7.3%, and 3.7% of individuals, respectively. In adjusted analyses, participants who increased their physical activity had a 45% lower risk for all-cause mortality and a 68% lower risk for cardiovascular mortality, compared to those who decreased their physical activity.ConclusionsPositive change in physical activity following a ΤΙΑ was associated with a reduced risk of mortality. Increased engagement in physical activity should be promoted after TIA, thereby actively supporting individuals with diabetes in achieving improved health outcomes.

Comparing the effectiveness of molnupiravir and nirmatrelvir-ritonavir in non-hospitalized and hospitalized COVID-19 patients with type 2 diabetes: A target trial emulation study.

To compare the effectiveness of molnupiravir and nirmatrelvir-ritonavir for non-hospitalized and hospitalized COVID-19 patients with type 2 diabetes (T2DM). Territory-wide electronic health records in Hong Kong were used to perform target trial emulation using a sequential trial approach. Patients (1) aged ≥18 years, (2) with T2DM, (3) with COVID-19 infection, and (4) who received molnupiravir or nirmatrelvir-ritonavir within 5 days of infection between 16 March 2022 and 31 December 2022 in non-hospital and hospital settings were included. Molnupiravir and nirmatrelvir-ritonavir initiators were matched using one-to-one propensity-score matching and followed for 28 days. Risk of outcomes was compared between groups by Cox regression adjusted for baseline characteristics. Subgroup analyses were performed on age (<70 years, ≥70 years), sex, Charlson comorbidity index (<4, ≥4), and number of COVID-19 vaccine doses (<2 doses, ≥2 doses). Totals of 17 974 non-hospitalized (8987 in each group) and 3678 hospitalized (1839 in each group) patients were identified. Non-hospitalized nirmatrelvir-ritonavir initiators had lower risk of all-cause mortality (absolute risk reduction [ARR] at 28 days 0.80%, 95% confidence interval [CI] 0.56-1.04; hazard ratio [HR] 0.47, 95% CI 0.30-0.73) and hospitalization (ARR at 28 days 4.01%, 95% CI 3.19-4.83; HR 0.73, 95% CI 0.66-0.82) as compared with molnupiravir initiators. Hospitalized nirmatrelvir-ritonavir initiators had reduced risk of all-cause mortality (ARR at 28 days 2.94%, 95% CI 1.65-4.23; HR 0.56, 95% CI 0.40-0.80) as compared with molnupiravir initiators. Consistent findings were found across all subgroups. The use of nirmatrelvir-ritonavir may be preferred to molnupiravir for COVID-19 patients with T2DM and without contraindication to either treatment.

Associations of multiple carotenoid co-exposure with all-cause and cause-specific mortality in US adults: a prospective cohort study.

Epidemiological evidence regarding circulating carotenoids and mortality risk remains conflicting, and most studies focus on the impact of individual carotenoids. This study aimed to elucidate the effects of co-exposure to multiple serum carotenoids on mortality risk. We enrolled 22,472 participants aged ≥20 from the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES 2003-2006. Baseline serum levels of five major carotenoids (α-carotene, β-carotene, lycopene, β-cryptoxanthin, and lutein/zeaxanthin) were measured, and individuals were followed up until December 31, 2019. Carotenoid co-exposure patterns were identified using the K-means method. Cox proportional hazard models were used to investigate the associations between carotenoid exposure and mortality risk. During a median follow-up of 16.7 years, 7,901 deaths occurred. K-means clustered participants into low-level, low-lycopene, high-lycopene, and high-level exposure groups. In the fully adjusted model, low-lycopene, high-lycopene, and high-level exposure groups had significantly lower all-cause mortality risks compared to the low-level exposure group, with hazard ratios (HRs) and 95% confidence intervals (CIs) of 0.79 (0.72, 0.87), 0.75 (0.67, 0.84), and 0.67 (0.61, 0.74), respectively. For cardiovascular disease mortality, the high-lycopene exposure group had a 27% reduced risk (HR: 0.73, 95% CI: 0.61-0.86), and the high-level exposure group had a 21% reduced risk (HR: 0.79, 95% CI: 0.67-0.93). For cancer mortality, the high-lycopene and high-level exposure groups had 30% and 35% lower risks, with HRs (95% CIs) of 0.70 (0.57, 0.86) and 0.65 (0.54, 0.79), respectively. This study revealed that co-exposure to multiple serum carotenoids was associated with reduced mortality risk, highlighting the potential health benefits of increased carotenoid intake. Further investigation is warranted to elucidate the underlying mechanisms of interactions among different carotenoids.

Plant-based diets for kidney disease prevention and treatment.

Plant-based diets are associated with a lower risk of hypertension, diabetes, cardiovascular disease, and mortality. Using the most recent evidence, we critically appraised the role of plant-based diets in primary and secondary prevention of chronic kidney disease (CKD) with a focus on key nutritional factors (dietary acid load, phosphorus, potassium, sodium, and fiber). In healthy individuals, observational studies found that greater intake of plant protein and higher adherence to plant-based diets (overall, healthful, and provegetarian) was associated with a lower risk of CKD. In those with CKD, plant-based diets were associated with a lower risk of mortality, improved kidney function, and favorable metabolic profiles (fibroblast growth factor-23, uremic toxins, insulin sensitivity, inflammatory biomarkers). Only few studies reported nutrient content of plant-based diets. These studies found that plant-based diets had lower dietary acid load, lower or no significant difference in phosphorus and sodium, and higher potassium and fiber. One study reported that vegetarian diets were associated with severe vitamin D deficiency compared to nonvegetarian diets. Plant-based diets provide several benefits for prevention and management of CKD, with little risk for individuals with CKD. Incorporation of vitamin D rich foods in plant-based diets may be helpful.

Impact of body mass index on mortality outcomes in intensive care patients with Staphylococcus aureus sepsis: A retrospective analysis.

Evidence associating body mass index (BMI) with the prognosis of Staphylococcus aureus sepsis remains scarce. To explore the association between BMI and clinical outcomes in intensive care units patients with Staphylococcus aureus sepsis. A retrospective analysis of patients with Staphylococcus aureus sepsis was conducted using the MIMIC-IV database from the Critical Care Medicine Information. Data were collected within the first 24 hours of intensive care units admission. The primary endpoint was 28-day mortality. The association between BMI and 28-day all-cause mortality was assessed using multivariable logistic regression, subgroup analyses, restricted cubic spline curves and Kaplan-Meier survival analysis. The study included 2,295 patients with an average age of 63.5 (16.1) years, 60.2% of whom were male. Multivariate analysis revealed that each 1 kg/m2 increase in BMI was linked to a 2.8% decrease in the risk of 28-day mortality (adjusted OR = 0.972, 95% CI: 0.955-0.990, P = 0.002). Patients in the medium and high BMI categories had significantly lower risks of 28-day mortality compared to those in the low BMI group (OR [95% CI] 0.650 [0.474-0.891]; OR [95% CI] 0.516 [0.378-0.705]; P trend < 0.0001). The RCS model showed a non-linear association between BMI and 28-day mortality (P = 0.014). Kaplan-Meier analysis showed that patients with elevated BMI had lower 28-day mortality (P < 0.0001). Notably, significant interactions between AKI and SOFA with BMI were observed (P<0.05). Increased BMI is associated with a reduced risk of 28-day all-cause mortality in patients with Staphylococcus aureus sepsis.

Serum 25-hydroxyvitamin D levels and risk of all-cause and cause-specific mortality: A 14-year prospective cohort study

Background & AimsThe circulating vitamin D level that is optimal for health is unknown. This study aimed to examine the association between circulating vitamin D level and risk of all-cause and cause-specific mortality. MethodsThis prospective cohort study included 18,797 Korean adults aged 40 years or older, living in rural areas, with no history of cancer or cardiovascular disease (CVD) at baseline. Serum 25-hydroxyvitamin D (25(OH)D) levels were measured at baseline. Participants were followed-up from the survey date (2005–2012) until December 31, 2021. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality by baseline vitamin D level. Restricted cubic splines were used to explore the nonlinearity. ResultsThe median (interquartile range) of 25(OH)D level was 55.8 (40.8–71.8) nmol/L. During a median follow-up of 14.3 years, 2,250 deaths were recorded. Compared with participants with a 25(OH)D level < 30 nmol/L, higher vitamin D levels (30 to < 50, 50 to < 75, and ≥ 75 nmol/L) were associated with a lower risk of all-cause mortality: HR (95% CI) of 0.82 (0.69–0.98), 0.74 (0.62–0.88), and 0.69 (0.57–0.84), respectively. A nonlinear relationship between vitamin D level and all-cause mortality was observed, with the risk plateauing between 50 and 60 nmol/L (p for nonlinearity = 0.009). The association was more pronounced for cancer-related mortality. HR 0.55 (95% CI: 0.39–0.77) for a 25(OH)D level ≥ 75 nmol/L compared with < 30.0 nmol/L. Low vitamin D levels were associated with increased CVD mortality in men. ConclusionsVitamin D level was inversely associated with all-cause and cause-specific mortality in middle-aged and older adults. Maintaining a serum 25(OH)D level of approximately 50–60 nmol/L may contribute to longevity and warrants further investigation.

Impact of prior oral anticoagulation therapies on post-discharge outcomes after COVID-19: Results from aglobal federated health network analysis.

The impact of chronic oral anticoagulant (OACs) use on long-term post-discharge outcomes after coronavirus disease 2019 (COVID-19) hospitalisation remains unclear. Herein, we compared clinical outcomes up to 2-years after COVID-19 hospitalisation between patients on vitamin K antagonists (VKAs), direct-acting OACs (DOACs) and no OAC therapy. Data from TriNetX, a global federated health research network, were used. Adult patients on VKAs, DOACs or no OAC therapy at diagnosis of COVID-19 between 20 January 2020 and 31 December 2021, who were hospitalised for COVID-19, were included. The primary outcomes were all-cause mortality, ischaemic stroke/transient ischaemic attack (TIA)/systemic embolism (SE) and the composite of intracranial haemorrhage (ICH)/gastrointestinal bleeding, at 2 years after COVID-19 hospitalisation. We included 110,834 patients with COVID-19. Following propensity score matching (PSM), we identified a decreased mortality risk in DOAC-treated patients compared to the no OAC cohort (RR .808, 95% CI .751-.870). A higher risk of ischaemic stroke/TIA/SE was observed in VKA users compared to DOAC users (RR 1.100, 95% CI 1.020-1.220) and in VKA users compared to patients not taking OAC (RR 1.400, 95% CI 1.140-1.720). VKA use was associated with a greater risk of ICH/gastrointestinal bleeding than DOAC users (RR 1.198, 95% CI 1.066-1.347), while DOAC users had a lower risk compared to no OAC-treated patients (RR .840, 95% CI .754-.936). COVID-19 patients taking prior DOACs were associated with lower long-term mortality risk and ICH/gastrointestinal bleeding than patients not taking OAC. Compared to patients on DOACs, VKA users were associated with higher risks of mortality, ischaemic stroke/TIA/SE and ICH/gastrointestinal bleeding.

Trajectory Patterns of Macronutrient Intake and Their Associations with Obesity, Diabetes, and All-Cause Mortality: A Longitudinal Analysis over 25 Years.

Over the past decades, China has been undergoing rapid economic growth, which may have significantly influenced the dietary patterns and health status of the Chinese population. Our study aimed to assess the associations of potential macronutrient trajectory patterns with chronic diseases and all-cause mortality using the latent class trajectory model (LCTM) and the longitudinal data of the China Health and Nutrition Survey obtained between 1991 and 2015. A 24-hour diet recall was used to assess the dietary intake. The Poisson regression model was employed to investigate the correlations between trajectory patterns and chronic diseases and all-cause mortality. A total of 8115 participants were included in the final analysis. We explored four and three trajectory patterns for male and female populations, respectively. We found that a decreasing very high-carbohydrate trajectory together with a U-shape protein trajectory was associated with a higher risk of diabetes in the male population (odds ratio (OR): 2.23; 95% confidence interval (CI): 1.31-3.77). A similar pattern for moderate protein intake was also associated with the risk of diabetes in the female population (OR: 1.82; 95% CI: 1.18-2.79). In addition, we show that a decreasing low-carbohydrate trajectory and an increasing high-fat trajectory were associated with a lower risk of all-cause mortality (OR: 0.76; 95% CI: 0.60-0.96) and a higher risk of obesity (OR: 1.24; 95% CI: 1.05-1.47) in males. Our results shed light on some salient nutritional problems in China, particularly the dual challenges of undernutrition and overnutrition.

Dietary magnesium intake and rheumatoid arthritis patients’ all-cause mortality: evidence from the NHANES database

BackgroundRheumatoid arthritis (RA) is a chronic inflammatory joint disease with all-cause mortality increasing globally. Dietary magnesium (Mg), an anti-inflammatory nutrient, has been proven to be associated with the all-cause mortality. The association of dietary Mg intake and all-cause mortality in RA patients remains unknown. The aim of this study was to assess the association between dietary Mg intake and all-cause mortality in RA patients.MethodsRA patients were extracted from the NHANES 1999–2018, and followed for survival through December 31, 2019. Dietary Mg intake data were obtained from 24-h dietary recall interview. The association between dietary Mg intake and RA patients’ all-cause mortality was explored based on weighted univariate and multivariate Cox proportional hazard models and described as absolute risk difference (ARD), hazard ratios (HRs) and 95% confidence intervals (CIs). This association was further explored in subgroup analyses based on different age, gender and body mass index (BMI).ResultsTotally 2,952 patients were included. Until 31 December 2019, a total of 825 deaths were documented. RA patients with higher dietary Mg intake had a 11.12% reduction of all-cause mortality (ARD=-11.12%; HR = 0.74, 95%CI: 0.56–0.99) in the fully adjusted model, especially in female (HR = 0.68, 95%CI: 0.47–0.98), aged < 65 years (HR = 0.59, 95%CI: 0.37–0.94) and BMI ≤ 30 kg/m2 (HR = 0.62, 95%CI: 0.42–0.91).ConclusionRA patients who consumed adequate dietary Mg from diet as well as supplements may had a lower risk of all-cause mortality.

Prognosis of Patients With Ischemic Stroke With Prior Anticoagulant Therapy: Direct Oral Anticoagulants Versus Warfarin.

Direct oral anticoagulants (DOACs) have been the drug of choice for preventing ischemic stroke in patients with atrial fibrillation since 2014. In previous studies, the stroke risk while taking warfarin was 2 per 100 patient-years and 1.5% per year while taking DOACs. We hypothesized that even if ischemic stroke occurred during anticoagulation therapy with DOACs, the prognosis was likely to be better than that with warfarin. Data from 2002 to 2019, sourced from a nationwide claims database, were used to identify atrial fibrillation patients using International Classification of Diseases codes. Patients who experienced an ischemic stroke during anticoagulation were categorized by the drugs used (warfarin, dabigatran, apixaban, rivaroxaban, and edoxaban). The primary outcome was mortality within 3 months and 1 year after the ischemic stroke. Among the 9578 patients with ischemic stroke during anticoagulation, 3343 received warfarin, and 6235 received DOACs (965 dabigatran, 2320 apixaban, 1702 rivaroxaban, 1248 edoxaban). The DOACs group demonstrated lower risks of 3-month (adjusted hazard ratio [HR], 0.550, [95% CI, 0.473-0.639]; P<0.0001) and 1-year mortality (adjusted HR, 0.596 [95% CI, 0.536-0.663]; P<0.0001) than the warfarin group. Apixaban and edoxaban within the DOAC group exhibited particularly reduced 1-year mortality risk compared with other DOACs (P<0.0001). Our study confirmed that DOACs have a better prognosis than warfarin after ischemic stroke. The apixaban and edoxaban groups had a lower risk of death after ischemic stroke than the other DOAC groups.

Risk Factors for Perioperative Complications, Treatment Outcomes and Aggressive Behavior of the Tumor in Patients with Pheochromocytoma

Introduction. Pheochromocytomas are catecholamine-secreting tumors arising from chromaffin cells of the adrenal gland. Surgery is the only curative treatment with a high biochemical cure rate, low mortality and high risk of perioperative complications. Objectives. To study the demographic characteristics of patients with pheochromocytoma and to identify the risk factors for perioperative complications, treatment outcomes, and aggressive behavior of the tumor. Methodology. We retrospectively studied the data of pheochromocytoma patients registered from 2012 to 2022. Results. In our study, a total of 30 patients with pheochromocytoma were included. The mean age of presentation was 35 ± 12.8 years. Fifty-six percent were females, and the sex ratio was 1.3:1. Pheochromocytoma spells (60%) was the most common complaint, followed by abdominal pain (53%), orthostatic complaints (10%) and incidentalomas (6%). The baseline mean 24-hour urinary total metanephrines was 2963.7 ± 2658 mcg/24 hours, and the mean tumor size was 7.3±0.53 cm. Forty-three percent of patients underwent laparoscopic adrenalectomy, while the rest underwent open surgery. The mean Pheochromocytoma of Adrenal gland Scaled Score (PASS) was 3.41 ± 0.28, and 23% had a high risk for malignancy. Among perioperative complications, hypertension crisis (17%) was the most common, followed by posoperative hypotension (13%), hypoglycemia (3%) and right-sided pneumothorax (3%). These patients with complications had higher metanephrine levels (5490 vs. 1880mcg/24 hours, p=0.001). Blood pressure normalized in 50%, and this was associated with male sex, younger age (29.5 vs. 40 years, p=0.03), higher metanephrines (4619 vs. 1855mcg/24 hours, p=0.001) and smaller tumors (5.91 vs. 8.61cm, p=0.046). PASS score greater than or equal to 4 was associated with higher metanephrine levels (5104 vs. 2312mcg/24 hours, p=0.021) and larger tumors (9.28 vs. 6.68 cm, p=0.024). Biochemical cure rate was achieved in 76% of patients after surgery and was associated with older age (37.7 years vs. 27.7 years, p=0.047) and absence of pheochromocytoma spells (100% vs. 61%, p=0.014). Conclusion. Young age, smaller tumor size and higher metanephrine concentrations were associated with normalization of blood pressure post-surgery. On the other hand, older patients and those without pheochromocytoma spells had better biochemical cure rates. Patients with higher baseline metanephrine levels had increased perioperative complications. More aggressive tumor behavior was associated with higher metanephrine levels and larger tumors. Sex, baseline blood pressure and mode of surgery did not have any influence on treatment outcomes.