Highest Quartile Research Articles

The effect of geopolitical risk on carbon emissions: influence mechanisms and heterogeneity analyzed using evidence from China.

To meet the goals of reducing adverse effects, continuing economic transformation, and achieving sustainable development, it is necessary to understand the impact mechanism and heterogeneous effects of geopolitical risk on carbon emissions. Using panel data from 30 provinces in China gathered between 2003 and 2019, we show that (1) geopolitical risk significantly contributes to the growth of carbon emissions, as does non-renewable energy consumption, trade, and economic growth, but that technological progress, industrial structure upgrading, and marketization inhibit the growth of carbon emissions; (2) geopolitical risk inhibits carbon emissions by suppressing non-renewable energy consumption and trade, and promoting technological progress; and (3) geopolitical risk has heterogeneous effects on carbon emissions in different quartiles. In the lower quartiles (i.e., groups with lower emission levels), geopolitical risk suppresses carbon emissions, while in higher quartiles (i.e., groups with higher emission levels), geopolitical risk promotes carbon emissions. As growing geopolitical risk and carbon emissions are now common problems for all countries, this study serves as a valuable reference not only for China, but for every member of the global community seeking to mitigate geopolitical risk shocks and achieve carbon emission reduction targets.

Healthcare use and fear of recurrence in adult cancer survivors at 2.5years after a cancer diagnosis: a nationwide register study in Denmark.

To investigate the association between fear of cancer recurrence (FCR) and healthcare use in general practice among cancer survivors. We linked nationwide register data to survey data on FCR in cancer survivors at 2.5years after a cancer diagnosis. Multiple regression models were used to analyse the association between high FCR level and quartiles of healthcare use at 18-30months before the cancer diagnosis (habitual healthcare use) and between high FCR level and healthcare use at 18-30months after the cancer diagnosis (survivorship healthcare use). We included 1538 cancer survivors in the study. High habitual healthcare use was associated with a high level of FCR (odds ratio = 2.07 (95% confidence interval (CI): 1.36-3.15)) for the 4th quartile of healthcare use compared to the 1st quartile. A high FCR score was also associated with higher healthcare use during cancer survivorship (incidence rate ratio (IRR) = 1.26 (95% CI: 1.14-1.40)). This association remained statistically significant when adjusting for habitual healthcare use (IRR = 1.20 (95% CI: 1.09-1.33)). High healthcare use before the cancer diagnosis was associated with high FCR during survivorship. This indicates that FCR is partly explained by a general (pre-diagnostic) health concern. High FCR predicted high healthcare use during cancer survivorship, even when adjusting for habitual healthcare use. Our results suggest that FCR in cancer survivors is triggered by a general high level of health concern, and the cancer diagnosis may further exacerbate this concern.

Medicare Part B Spending on Macular Degeneration Treatments Associated With Manufacturer Payments to Ophthalmologists

Age-related macular degeneration (ARMD) therapies aflibercept and ranibizumab are among the highest-cost Medicare Part B drugs, even though off-label use of lower-cost bevacizumab is clinically noninferior. Payments from manufacturers of these ARMD therapies to ophthalmologists are hypothesized to be factors in ophthalmologists' therapeutic choice, controlling for ophthalmologist and patient characteristics. To assess the association between manufacturer payments to ophthalmologists and choice of ARMD treatment as well as to identify ophthalmologist-level characteristics associated with prescribing lower-cost ARMD therapies. This retrospective cross-sectional study of longitudinal (2013-2019) Medicare Part B data was conducted from December 2021 to December 2022. Ophthalmologists prescribing aflibercept (manufactured by Regeneron Pharmaceuticals Inc), rabinizumab, or bevacizumab (both manufactured by Genentech Inc) for ARMD treatment of Medicare Part B beneficiaries were included. Data on manufacturer payments to ophthalmologists were obtained from the Open Payments database. The primary outcome was the percentage of bevacizumab prescribed by ophthalmologists among all ARMD therapies. Regression analysis assessed variation in bevacizumab prescribing by acceptance of manufacturer payments as well as by ophthalmologist and patient characteristics. Ophthalmologist characteristics were duration of practice and Medicare Administrative Contractor region, and patient characteristics were aggregated at the ophthalmologist level and included mean beneficiary age, percentage of dual-eligible beneficiaries, mean beneficiary risk score, and percentage of White beneficiaries. Savings were estimated by projecting the change in bevacizumab use had ophthalmologists not accepted manufacturer payments, controlling for all ophthalmologist and patient characteristics and comparing with observed use and costs. A total of 21 584 ophthalmologists (18 489 males [85.7%]) were included. Ophthalmologists who accepted manufacturer payments were significantly less likely to prescribe bevacizumab (28.0% [95% CI, 24.6%-42.5%] of patients) compared with those who did not accept manufacturer payments (45.8% [95% CI, 44.5%-47.1%]). Ophthalmologists who saw dual-eligible beneficiaries had greater bevacizumab prescribing (50.0% [95% CI, 40.6%-68.3%] in the highest quartile vs 36.1% [95% CI, 33.5%-38.8%] in the lowest quartile; β coefficient, 0.139; P < .001), while those who saw patients with higher mean beneficiary risk scores had lower bevacizumab use (38.0% [95% CI, 23.7%-44.1%] in the highest quartile vs 48.2% [95% CI, 45.5%-50.8%] in the lowest quartile; β coefficient, -0.102, P < .001). Had ophthalmologists who accepted manufacturer payments prescribed ARMD drugs as those who did not accept payments, Medicare spending on these treatments would have been $642 779 703.08 lower from 2013 to 2019, a 2.0% savings. Results of this cross-sectional study suggest that drug manufacturer payments to ophthalmologists were associated with selection of higher-cost therapies for ARMD, which is a factor in increased Medicare and patient spending. Development of manufacturer payment models that encourage ophthalmologists to choose lower-cost therapies are needed.

Composite dietary antioxidant index was negatively associated with the prevalence of diabetes independent of cardiovascular diseases

AimThe association between composite dietary antioxidant index (CDAI) and diabetes remains unknown. Our study was to investigate the association of CDAI with diabetes.MethodsA total of 11,956 participants were enrolled from the National Health and Nutrition Examination Surveys (NHANES). The CDAI was calculated from the intake of six dietary antioxidants. Multivariable logistic regressions were performed to explore the associations between CDAI and the prevalence of diabetes and glycemic index. Non-linear associations were explored using restricted cubic splines.ResultsIn the multivariate logistic regression model, the odds ratio (95% confidence interval) of CDAI associating with obesity was 0.98 (0.97-1.00; p = 0.033). Compared with the lowest quartile, the highest quartile was related to 0.84-fold risk of diabetes (0.71–0.99; p = 0.035). However, CDAI was not independently associated with fasting glucose and hemoglobin A1c.ConclusionCDAI was negatively associated with diabetes and the relationship was independent of other traditional risk factors.

Emergency Department Pediatric Readiness and Disparities in Mortality Based on Race and Ethnicity

Presentation to emergency departments (EDs) with high levels of pediatric readiness is associated with improved pediatric survival. However, it is unclear whether children of all races and ethnicities benefit equitably from increased levels of such readiness. To evaluate the association of ED pediatric readiness with in-hospital mortality among children of different races and ethnicities with traumatic injuries or acute medical emergencies. This cohort study of children requiring emergency care in 586 EDs across 11 states was conducted from January 1, 2012, through December 31, 2017. Eligible participants included children younger than 18 years who were hospitalized for an acute medical emergency or traumatic injury. Data analysis was conducted between November 2022 and April 2023. Hospitalization for acute medical emergency or traumatic injury. The primary outcome was in-hospital mortality. ED pediatric readiness was measured through the weighted Pediatric Readiness Score (wPRS) from the 2013 National Pediatric Readiness Project assessment and categorized by quartile. Multivariable, hierarchical, mixed-effects logistic regression was used to evaluate the association of race and ethnicity with in-hospital mortality. The cohort included 633 536 children (median [IQR] age 4 [0-12] years]). There were 557 537 children (98 504 Black [17.7%], 167 838 Hispanic [30.1%], 311 157 White [55.8%], and 147 876 children of other races or ethnicities [26.5%]) who were hospitalized for acute medical emergencies, of whom 5158 (0.9%) died; 75 999 children (12 727 Black [16.7%], 21 604 Hispanic [28.4%], 44 203 White [58.2%]; and 21 609 of other races and ethnicities [27.7%]) were hospitalized for traumatic injuries, of whom 1339 (1.8%) died. Adjusted mortality of Black children with acute medical emergencies was significantly greater than that of Hispanic children, White children, and of children of other races and ethnicities (odds ratio [OR], 1.69; 95% CI, 1.59-1.79) across all quartile levels of ED pediatric readiness; but there were no racial or ethnic disparities in mortality when comparing Black children with traumatic injuries with Hispanic children, White children, and children of other races and ethnicities with traumatic injuries (OR 1.01; 95% CI, 0.89-1.15). When compared with hospitals in the lowest quartile of ED pediatric readiness, children who were treated at hospitals in the highest quartile had significantly lower mortality in both the acute medical emergency cohort (OR 0.24; 95% CI, 0.16-0.36) and traumatic injury cohort (OR, 0.39; 95% CI, 0.25-0.61). The greatest survival advantage associated with high pediatric readiness was experienced for Black children in the acute medical emergency cohort. In this study, racial and ethnic disparities in mortality existed among children treated for acute medical emergencies but not traumatic injuries. Increased ED pediatric readiness was associated with reduced disparities; it was estimated that increasing the ED pediatric readiness levels of hospitals in the 3 lowest quartiles would result in an estimated 3-fold reduction in disparity for pediatric mortality. However, increased pediatric readiness did not eliminate disparities, indicating that organizations and initiatives dedicated to increasing ED pediatric readiness should consider formal integration of health equity into efforts to improve pediatric emergency care.

Lipoprotein(a): A Residual Cardiovascular Risk Factor in Statin-Treated Stroke Survivors: Insights From the SPARCL Trial

BackgroundIn the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol levels) trial, atorvastatin (80 mg/d) was compared to placebo in patients with recent stroke or transient ischemic attack (TIA) and no known coronary artery disease. ObjectivesThis study aimed to assess the contribution of lipoprotein(a) [Lp(a)] to subsequent cerebrovascular and cardiovascular events in stroke/TIA survivors. MethodsLp(a) levels and apolipoprotein(a) [apo(a)] isoform size were determined by liquid-chromatography mass spectrometry in samples collected at baseline from 2,814 SPARCL participants (1,418 randomized to atorvastatin and 1,396 to placebo). Within each treatment arm, patients in the highest quartile (≥84.0 nmol/L) were compared with those in the lowest quartiles of Lp(a) concentrations. Patients in the lowest quartile (≤25.9 Kringle IV domains) of apo(a) isoform sizes were compared with those in the highest quartiles. Multivariable-adjusted HRs were calculated using Cox proportional regression models. ResultsThere was no significant association between Lp(a) concentrations or apo(a) isoform sizes and the risk of recurrent stroke, the primary outcome of SPARCL, or cerebrovascular events in patients randomized to atorvastatin or placebo. In contrast, in patients randomized to atorvastatin, elevated Lp(a) concentrations and short apo(a) isoforms were positively and independently associated with an increased risk of coronary events (HR: 1.607 [95% CI: 1.007-2.563] and HR: 2.052 [95% CI: 1.303-3.232]). No such association was found in patients randomized to placebo (HR: 1.025 [95% CI: 0.675-1.555] and HR: 1.097 [95% CI: 0.735-1.637]). ConclusionsLp(a) contributes to the residual coronary artery disease risk of statin-treated stroke/TIA survivors, paving the way for use of therapies targeting Lp(a) in this population with stroke. (Lipitor In The Prevention Of Stroke, For Patients Who Have Had A Previous Stroke [SPARCL]; NCT00147602)

Elevated Calcium after Acute Ischemic Stroke Predicts Severity and Prognosis.

The aim of this study is to investigate whether there is a correlation between serum calcium levels and clinical severity or functional outcome at discharge in Chinese patients with acute ischemic stroke. Data from 339 patients admitted to our hospital between July 2020 and July 2021 were analyzed. Baseline demographic and clinical information was collected within 24h of admission, including serum calcium levels, stroke severity (measured by the National Institutes of Health Stroke Scale [NIHSS] score), and lesion volumes. The modified Rankin Scale [mRS] assessed functional outcomes at discharge. Our analysis showed that the median age of patients included in the study was 65 years (interquartile range [IQR], 60-70), and 60.8% were men. We found a positive correlation between serum calcium levels and stroke severity (r[spearman] = 0.266, P < 0.001), with calcium levels increasing as stroke severity increased. In a subgroup of 188 patients with available MRI data, serum calcium concentrations positively correlated with infarct size. Furthermore, in multivariate analysis, a calcium serum level in the highest quartile was associated with a higher risk of unfavorable outcome (odds ratios [OR] = 3.27; 95% confidence intervals [CI] = 1.91-5.59; P < 0.001). In conclusion, our study indicates that higher calcium serum levels are associated with stroke severity and early neurologic outcome after acute ischemic stroke, indicating that calcium may serve as a prognostic biomarker for stroke in Chinese patients.

Associations between multiple metals during early pregnancy and gestational diabetes mellitus under four statistical models.

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy. Metal exposure is an emerging factor affecting the risk of GDM. However, the effects of metal mixture on GDM and key metals within the mixture remain unclear. This study was aimed at investigating the association between metal mixture during early pregnancy and the risk of GDM using four statistical methods and further at identifying the key metals within the mixture associated with GDM. A nested case-control study including 128 GDM cases and 318 controls was conducted in Beijing, China. Urine samples were collected before 13 gestational weeks and the concentrations of 13 metals were measured. Single-metal analysis (unconditional logistic regression) and mixture analyses (Bayesian kernel machine regression (BKMR), quantile g-computation, and elastic-net regression (ENET) models) were applied to estimate the associations between exposure to multiple metals and GDM. Single-metal analysis showed that Ni was associated with lower risk of GDM, while positive associations of Sr and Sb with GDM were observed. Compared with the lowest quartile of Ni, the ORs of GDM in the highest quartiles were 0.49 (95% CI 0.24, 0.98). In mixture analyses, Ni and Mg showed negative associations with GDM, while Co and Sb were positively associated with GDM in BKMR and quantile g-computation models. No significant joint effect of metal mixture on GDM was observed. However, interestingly, Ni was identified as a key metal within the mixture associated with decreased risk of GDM by all three mixture methods. Our study emphasized that metal exposure during early pregnancy was associated with GDM, and Ni might have important association with decreased GDM risk.

Thoracic skeletal muscle index is effective for CT-defined sarcopenia evaluation in patients with head and neck cancer

PurposeComputed tomography (CT)-defined sarcopenia, as a measurement of low skeletal muscle (SM), is a poor prognostic indicator in patients with head and neck cancer (HNC), independent of weight or nutritional status. We used SM measures at the second thoracic vertebra (T2) to determine T2-SM index (SMI) thresholds for sarcopenia, and investigate the impact of low T2-SMI on overall survival (OS), and weight loss during radiotherapy (RT).MethodsAdult patients with newly diagnosed HNC with a diagnostic PET–CT or RT planning CT scan were included. SM was analysed at T2 and a model applied to predict SM at L3. T2-SMI thresholds for sarcopenia were established with predicted measures, stratified by BMI and sex. Impact of sarcopenia and low T2-SMI on OS and weight loss during RT was investigated.ResultsA total of 361 scans were analysed (84% males, 54% oropharynx tumours). Sarcopenia was found in 49%, demonstrating worse OS (p = 0.037). T2-SMI cutoff values were: females—74 cm2/m2 [area under the curve (AUC): 0.89 (95%CI 0.80–0.98)], males (BMI < 25)—63 cm2/m2 [AUC 0.93 (95%CI 0.89–0.96)], males (BMI ≥ 25)—88cm2/m2 [AUC 0.86 (95%CI 0.78–0.93)]. No difference in OS with T2-SMI categories. Lowest T2-SMI quartile of < 63 cm2/m2 demonstrated worse OS (p = 0.017). Weight loss during RT was higher in patients; who were not sarcopenic (6.2% vs 4.9%, p = 0.023); with higher T2-SMI (6.3% vs 4.9%, p = 0.014) and; in the highest quartiles (3.6% vs 5.7% vs 7.2%, p < 0.001).ConclusionsThese T2-SMI thresholds are effective in assessing CT-defined sarcopenia in HNC. Further assessment of clinical application is warranted.

Moderate selenium alleviates the pulmonary function impairment induced by cadmium and lead in adults: A population-based study

Selenium (Se) has been reported to have an antagonistic effect on heavy metals in animals. However, there is no epidemiological study investigating whether Se could protect against the pulmonary toxicity of Cadmium (Cd) and Lead (Pb). Data was collected from the 2011–2012 National Health and Nutrition Examination Survey (NHANES) cycle. Pulmonary function was assessed by Forced Vital Capacity (FVC), Forced Expiratory Volume 1st Second (FEV1) and FEV1/FVC. Blood concentrations of Cd, Pb, and Se were measured using inductively coupled plasma mass spectrometry. Linear regression, restricted cubic splines, and quantile-based g-computation (qgcomp) were performed to evaluate the individual and joint associations of Cd and Pb with pulmonary function and whether Se modified these associations. In the adjusted multi-metal model, every 1-unit increase in Cd, FEV1, FVC, and FEV1/FVC decreased by 76.437 mL (95 % CI: −110.928 to −41.947), 42.719 mL (95 % CI: −84.553 to −0.885), and 0.012 (95 % CI: −0.016 to −0.007), respectively. Meanwhile, FEV1 decreased by 9.37 mL (95 % CI: −18.61 to −0.13) for every 1 unit increase in Pb. Furthermore, we found an inverted U-shape association between Se and lung function, and participants in the second quartile Se group had the highest increases in FEV1 and FVC compared with participants in the lowest quartile. Qgcomp model also revealed that the toxic metal mixture (Cd and Pb) exhibited a significant inverse association with FEV1 and FEV1/FVC. Furthermore, we found that the inverse association of Pb and Cd, either alone or in combination, with pulmonary function first diminished with increasing Se levels but was re-enforced when blood Se concentrations were in the highest quartile. Our results indicated that moderate Se attenuated the harmful effects of Cd and Pb on lung function.

Serum lipid levels are associated with orthostatic hypotension in multiple system atrophy patients

ObjectivesOrthostatic hypotension (OH) is one of the most important autonomic features of multiple system atrophy (MSA). This study was established to confirm the correlation between lipid levels and OH in MSA. MethodsA total of 580 patients with probable or possible MSA from neurological wards in six hospitals in Tianjin, Beijing, Hebei Province, and Henan Province, China, were included in this study. The tilt test or stand test was used to assess the severity of OH. Lipid contents, including total cholesterol, low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), and triglyceride were evaluated. ResultsSerum levels of total cholesterol, LDL-C, and triglyceride in MSA-OH patients were significantly lower than those in MSA without OH. The risks of OH were significantly higher in the lowest quartiles of triglyceride and LDL-C than in the highest quartiles, after adjusting for confounders (OR = 2.17, 95% CI: 1.23–3.82, P = 0.008 and OR = 2.02, 95% CI: 1.16–3.47, P = 0.012). The risk of severe OH was significantly higher in the lowest quartile and the second quartile of triglyceride than in the highest quartile after adjusting for confounders (OR = 2.16, 95% CI: 1.20–3.87, P = 0.010 and OR = 2.25, 95% CI: 1.24–4.07, P = 0.007). Moreover, the risk of OH was significantly higher in the lowest quartile, and the third quartile of TC than in the highest quartile after adjusting for confounders (OR = 2.04, 95% CI: 1.18–3.52, P = 0.010 and OR = 2.06, 95% CI: 1.19–3.56, P = 0.010). ConclusionLow levels of TC, LDL-C, and triglyceride increased the risk of OH in MSA. A low level of triglyceride predicted severe OH in MSA.

Association of preoperative CA-125 levels with early POAF after heart valve surgery: a single-center, retrospective study

ObjectiveCancer antigen-125 (CA-125), a tumor marker, has received increasing attention in recent years for its role in the cardiovascular field. However, no study has reported the association of CA-125 with early postoperative atrial fibrillation (POAF) after heart valve surgery. Therefore, the aim of this study was to assess whether there is a correlation between CA-125 and early postoperative POAF after heart valve surgery.MethodsPatients who underwent valve surgery at Fujian Heart Medical Center from January 2020 to August 2022 were retrospectively analyzed and divided into postoperative atrial fibrillation group (POAF group) and postoperative non-atrial fibrillation group (NO-POAF), and the differences in clinical data between the two groups were compared, and the variables with statistical significance in the univariate analysis were included in the COX regression analysis, and finally the receivers’ operating characteristics (ROC) curves were drawn.ResultsFrom January 2020 to August 2022, a total of 1653 patients underwent valve surgery. A total of 344 patients were finally included, including 52 patients (15.1%) in the POAF group and 292 patients (84.9%) in the NO-POAF group. Univariate analysis showed higher CA-125 levels in patients in the POAF group than in those in the NO-POAF group [27.89 (13.64, 61.54), 14.48 (9.87, 24.08), P = 0.000]. Analysis of the incidence of POAF based on CA-125 quartiles showed an incidence of up to 29.2% in the highest quartile (> 27.88). Multivariate COX regression analysis showed that CA-125 [OR = 1.006, 95% CI (1.002, 1.010), P = 0.001] was an independent predictor of POAF. The final ROC curve plot showed that the area under the curve for CA-125 was 0.669, with an optimal cut-off value of 27.08 U/ml, and the difference in the area under the curve between the two groups was statistically significant (P = 0.000).ConclusionElevated preoperative CA-125 levels can affect the incidence of POAF and have a predictive value for the occurrence of POAF in the early stage after valve surgery. However, due to the small sample size and single-center retrospective study, further validation of this result is needed.

Associations of circulating multiple metals with the risk of incident hyperuricemia and the average annual change in uric acid levels

BackgroundHyperuricemia has been linked to exposure to certain metals in cross-sectional studies. However, prospective studies evaluating the associations of multiple metal exposures with incident hyperuricemia are scarce. ObjectivesTo prospectively investigate the associations of multiple metal/metalloid concentrations with incident hyperuricemia as well as average annual change in uric acid levels in a longitudinal cohort. MethodsA longitudinal cohort study included 3957 subjects who were free of cardiovascular disease with certain risk factors for cardiovascular disease at baseline. Incident hyperuricemia was ascertained if serum uric acid level was ≥ 420 μmol/L for men and ≥ 360 μmol/L for women during the follow-up visit in 2013. The relationships between 17 single plasma metals/metalloids and incident hyperuricemia were assessed using unconditional logistic regression models. For metals/metalloids significantly related to incident hyperuricemia, we further utilized generalized linear regression models to evaluate their associations with the average annual change in uric acid levels. Finally, we applied the weighted quantile sum (WQS) regression to investigate the joint effects of metals/metalloids on hyperuricemia risk and uric acid changes, and to identify the most significant metals. ResultsAfter adjusting for potential confounders, plasma aluminum, arsenic, barium, lead, strontium, vanadium, and zinc concentrations were positively associated with incident hyperuricemia in both main analyses and sensitivity analyzes. Compared to the lowest quartiles, participants in the highest quartiles had 63 %−125 % higher risks of incident hyperuricemia (all FDR < 0.05). Furthermore, the positive associations of these seven metals with an average annual uric acid increase reinforced the findings. Finally, the WQS analyses showed that plasma metals mixtures were positively associated with the risk of incident hyperuricemia (OR: 1.47; 95 % CI: 1.23, 1.76) and the average annual change in uric acid levels (β: 3.17; 95 % CI: 2.42, 3.93), and strontium and vanadium were the most heavily weighted metals, respectively. ConclusionOur findings identify aluminum, arsenic, barium, lead, strontium, vanadium, and zinc exposures as independent risk factors for hyperuricemia and provide new insights into the prevention of hyperuricemia.

Vitamin K insufficiency predicts incidence of frailty in community-dwelling older adults: The Otassha Study.

Vitamin K is a fat-soluble vitamin discovered as an essential factor for blood coagulation. It is suggested that vitamin K can benefit several aging-related diseases, including osteoporosis, osteoarthritis, and dementia. We previously reported the cross-sectional association of vitamin K insufficiency with frailty in community-dwelling older adults. In October 2020, a health examination of community-dwelling older adults (The Otassha Study) was performed, including frailty evaluation and blood tests. We used a ucOC and OC ratio (ucOC/OC) to indicate vitamin K insufficiency. One year later, we conducted a follow-up evaluation of frailty on 518 people who were not frail at baseline. The serum ucOC/OC at the baseline examination was divided into quartiles (Q1, Q2, Q3, and Q4). Odds ratio (OR) and 95% confidence interval (CI) were calculated using multivariate binary logistic regression for each quartile of ucOC/OC to determine the risk of incident frailty in the follow-up study, with the lowest quartile (Q1) as the reference. Among the 518 older adults who were not frail at baseline, 66 people (12.7%) became frail in the follow-up study. In the multivariate binary logistic regression analysis, setting the lowest quartile of ucOC/OC (Q1) as a reference, the OR of the incident frailty in the highest quartile (Q4) was 2.53 (95% CI 1.07, 4.92) which was significantly different from Q1. The findings of this longitudinal study suggest that vitamin K insufficiency has nutritional importance in predicting the future incidence of frailty in the Japanese older adult population.

Consumption of Coffee, Tea, and Caffeine at Midlife, and the Risk of Physical Frailty in Late Life

ObjectivesOur study evaluated the prospective association between the consumption of caffeine-containing beverages at midlife and the risk of physical frailty at late life within a population-based cohort of Chinese adults living in Singapore over a follow-up period of 20 years. DesignProspective cohort study. Setting and ParticipantsWe used data from 12,583 participants from the baseline and third follow-up interviews of the Singapore Chinese Health Study (SCHS). Participants had a mean age of 53 years at baseline (1993–1998), and a mean age of 73 years during the third follow-up (2014–2017). MethodsAt baseline, habitual consumption of caffeine-containing beverages was evaluated using a validated semi-quantitative food-frequency questionnaire. During the third follow-up, physical frailty was assessed using the modified Cardiovascular Health Study phenotype. ResultsCompared with non-daily drinkers, those who drank 4 or more cups of coffee daily had reduced odds of physical frailty [odds ratio (OR), 0.54; 95% CI, 0.38–0.76]. Similarly, compared with those who hardly drank tea, participants who drank tea everyday also had reduced odds (OR, 0.82; 95% CI, 0.71–0.95). Total daily caffeine intake at midlife was associated with reduced likelihood of frailty at late life in a dose-response relationship (Ptrend < .001). Relative to their counterparts in the lowest quartile of daily caffeine intake (0–67.6 mg/d), participants in the highest quartile (223.0–910.4 mg/d) had an OR of 0.77 (95% CI, 0.66–0.91). Higher caffeine consumption was associated with lower likelihood of being in the slowest quintile for timed up-and-go (TUG) and weakest quintile for handgrip strength. Conclusions and ImplicationsIn this cohort of Chinese adults, higher consumption of caffeine at midlife, via coffee and tea, was associated with a reduced likelihood of physical frailty in late life.

A novel human papillomavirus and host DNA methylation score and detection of cervical adenocarcinoma.

The widespread introduction of Pap testing in the 1960s was followed by substantial reductions in the incidence of cervical squamous cell cancer (SCC). However, the incidence of cervical adenocarcinoma (ADC) did not decrease, likely because of low Pap test sensitivity for ADC and adenocarcinoma in situ (AIS). This study assessed a novel human papillomavirus (HPV) and host DNA Methylation Score for AIS and ADC screening. We measured methylation levels at CpG sites in the L2/L1 open reading frames of HPV16, HPV18, and HPV45-as well as 2 human loci, DCC and HS3ST2. Specifically, we tested exfoliated cervicovaginal cells from women in the HPV Persistence and Progression (PaP) cohort who were positive for 1 of HPV16, 18, or 45, including: 1) 176 withAIS/ADC, 2) 353 with cervical intraepithelial neoplasia-3 (CIN3) or SCC, and 3) controls who either cleared (HPV-Clearers; n = 579) or had persistent HPV16, 18, or 45 infection (HPV-Persisters; n = 292). CpG site-specific methylation percentages were measured using our reported next-generation methods. The Methylation Score was the average methylation percentage across all 35 CpG sites tested. Each individual CpG site had higher methylation percentages in exfoliated cervicovaginal cells collected from patients with AIS/ADC, and as well as those with CIN3/SCC, relative to either control group (weakest P = .004). The Methylation Score for AIS/ADC had a sensitivity of 74% and specificity of 89%. The multivariate odds ratio (OR) between the Methylation Score (4th vs 1st quartile) for AIS/ADC was ORq4-q1 = 49.01 (PBenjamini-Hochberg = 4.64E-12), using HPV-Clearers as controls. CIN3/SCC had similar, albeit weaker, associations with the Methylation Score. HPV16/18/45-infected women with Methylation Scores in the highest quartile had very high odds of AIS/ADC, suggesting they may warrant careful histologic evaluation of the cervical transition zone (eg, conization or loop electrosurgical excision procedure [LEEP]).

Association between brominated flame retardants exposure and markers of oxidative stress in US adults: An analysis based on the National Health and Nutrition Examination Survey 2007–2016

We aimed to investigate the relationship between oxidative stress indicators and brominated flame retardant (BFR) levels in US adults. Using data from the NHANES (National Health and Nutrition Examination Survey) from 2007 to 2016, 8028 participants aged 18 and over were enrolled in this study. PBDE28, PBDE47, PBDE85, PBDE99, PBDE100, PBDE153, PBDE154, PBDE209, and PBB153, with over 75 % detection rates, were extracted in this study. Survey-weighted linear regression model, weighted quantile sum (WQS) model, and quantile-based g calculation (QGC) model were used to assess the correlation between serum BFRs levels and oxidative stress indicators (serum bilirubin and gamma-glutamyl transferase [GGT]). Besides, the nonlinear association was explored using restricted cubic splines (RCS). Each of the BFRs was confirmed by the survey-weighted linear regression model to be positively associated with GGT after controlling for variables, and BFRs except for PBDE153 were positively associated with serum bilirubin. Except for PBDE153, serum bilirubin in the highest quartile of BFRs was significantly higher than in the lowest high quartile. Additionally, except for PBDE85, serum GGT in the highest quartile of BFRs was higher than in the lowest high quartile. A significant nonlinear association between all BFRs with bilirubin and the PBDE153, PBDE209, and PBB153 with GGT was identified by RCS analysis. By WQS analysis, combined BFR exposure was associated with serum GGT (β: 0.093; 95 % CI = 0.066–0.121; P < 0.0001) and bilirubin (β: 0.090; 95 % CI = 0.068–0.113; P < 0.0001). QGC analysis found a similar correlation between BFR mixtures with serum GGT (β: 0.098; 95 % CI = 0.075–0.120; P < 0.0001) and bilirubin (β: 0.073; 95 % CI = 0.048–0.097; P < 0.0001). Exposure to BFRs is positively associated with markers of oxidative stress (serum bilirubin and GGT) in US adults, which needs further exploration by a large-scale cohort study.

Fungal plasma biomarkers in patients admitted for inpatient treatment of alcohol use disorder.

Fungal plasma biomarkers have not been studied in patients with unhealthy alcohol use and no apparent end-stage liver disease. We examined the prevalence of fungal plasma biomarkers, assessed by the presence of anti-Saccharomyces cerevisiae antibodies (ASCA; IgA and IgM), and its disease correlates in patients with alcohol use disorder (AUD). We performed logistic regression analyses to detect the association between clinical and laboratory characteristics and the presence of fungal plasma biomarkers. We included 395 patients (75.9% male, median age of 49 years, and median body mass index of 25.6) who drank a median of 150 g of alcohol daily and had a median duration of AUD of 20 years. ASCA IgA and IgG were present in 34.4% and 14.9%, respectively, and 9.9% had both ASCA IgA and ASCA IgG. The presence of ASCA IgA was associated with male sex (p < 0.01); values of serum aspartate transferase (AST) (p = 0.02), gamma-glutamyl transferase (GGT) (p < 0.01), alkaline phosphatase (ALP) (p < 0.01), and bilirubin in the highest quartile (p < 0.01); Fibrosis-4 Index (FIB-4) values suggestive of advanced liver fibrosis (p < 0.01); and values of the macrophage activation factors sCD163 (p < 0.01) and sCD14 (p < 0.01), the cytokine IL-6 (p = 0.01), and lipopolysaccharide-binding protein in the highest quartile (p < 0.01). The presence of ASCA IgG was associated with omeprazole use (p = 0.04); values of AST (p = 0.04) and GGT (p = 0.04) in the highest quartile; FIB-4 values suggestive of advanced liver fibrosis (p < 0.01); and values of sCD163 (p < 0.01) in the highest quartile. The variables associated with the presence of both ASCA IgA and IgG were male sex (p = 0.04) and values of GGT (p = 0.04) and sCD163 in the highest quartile (p < 0.01). In AUD patients, the presence of fungal biomarkers in plasma was common and associated with FIB-4 values suggestive of advanced liver fibrosis and with markers of liver damage, monocyte activation, and microbial translocation, male gender, and omeprazole use. These findings suggest that the presence of plasma anti-Saccharomyces cerevisiae antibodies could be used as a biomarker for an elevated risk of progressive liver disease in patients with AUD.

Associations between Low-Carbohydrate Diets and Low-Fat Diets with Frailty in Community-Dwelling Aging Chinese Adults.

Frailty is a major health issue associated with aging. Diet affects frailty status; however, studies on the associations between the low-carbohydrate diet (LCD) score, low-fat diet (LFD) score and frailty in older Chinese adults are scarce. This study aimed to examine the associations between the LCD score, LFD score and risk of frailty in older Chinese adults. We analyzed data from 6414 participants aged ≥ 60 years from the China Northwest Natural Population Cohort: Ningxia Project. Frailty was measured using the frailty index (FI), calculated from 28 items comprising diseases, behavioral disorders and blood biochemistry and classified as robust, pre-frail and frail. LCD and LFD scores were calculated using a validated food frequency questionnaire (FFQ). Multiple logistic regression models were used to evaluate associations between LCD, LFD scores and frail or pre-frail status after adjusting for confounders. Participants' mean age was 66.60 ± 4.15 years, and 47.8% were male. After adjusting for age, sex, educational level, drinking, smoking, BMI, physical activity and total energy, compared to the lowest quartile (Q1: reference), the odds ratios (ORs) for pre-frail and frail status in the highest quartile (Q4) of LCD score were 0.73 (95% confidence intervals: 0.61-0.88; p for trend = 0.017) and 0.73 (95%CI: 0.55-0.95; p for trend = 0.035), respectively. No significant associations were observed between LFD score and either pre-frail or frail status. Our data support that lower-carbohydrate diets were associated with lower pre-frail or frail status, particularly in females, while diets lower in fat were not significantly associated with the risk of either pre-frail or frail status in older Chinese adults. Further intervention studies are needed to confirm these results.

Association of dietary total antioxidant capacity and its distribution across three meals with all-cause, cancer, and non-cancer mortality among cancer survivors: the US National Health and Nutrition Examination Survey, 1999-2018.

The effect of the antioxidant capacity of diet and its distribution across three meals on mortality risk among cancer patients remains unexplored. We aimed to prospectively investigate the association of dietary total antioxidant capacity (DAC) and its distribution across three meals with all-cause, cancer, and noncancer mortality among cancer survivors. We included 5,009 patients with cancer from the National Health and Nutrition Examination Survey conducted between 1999 and 2018. The adjusted hazard ratio (aHR) was estimated using the survey-weighted Cox proportional hazards model. During a median follow-up of 7.9 years, 1811 deaths, including 575 cancer-related deaths, were recorded. Among cancer survivors, compared with participants in the lowest quartile of total DAC from three meals, those in the highest quartile had a 24% decreased risk of noncancer mortality (aHR = 0.76, 95% confidence interval [CI]: 0.60-0.92), but not of all-cause and cancer mortality (each p trend >0.1). However, this association became insignificant for total DAC after excluding dinner DAC. In addition, higher dinner DAC rather than breakfast or lunch DAC was associated with a 21% lower risk of all-cause mortality (aHR = 0.79, 95% CI: 0.65-0.98) and 28% lower risk of noncancer mortality (aHR = 0.72, 95% CI: 0.57-0.90). Similar associations were found for ΔDAC (dinner DAC - breakfast DAC) with noncancer mortality (aHR = 0.56, 95% CI: 0.38-0.83), but DAC was not associated with cancer mortality (p trend >0.3). Among cancer survivors, total DAC from three meals was associated with reduced noncancer mortality, with the primary effect attributable to increased DAC intake from dinner. Our findings emphasize that DAC consumption from dinner should be advocated to reduce mortality risk in cancer survivors.