Significant Dose-response Association Research Articles

Association of magnesium deficiency scores with risk of rheumatoid arthritis and osteoarthritis in adults: a cross-sectional population-based study.

The magnesium depletion score (MDS) is a scoring system developed to predict magnesium deficiency based on pathophysiological factors that affect renal reabsorption. The relationship between systemic magnesium status and arthritis is unclear. The purpose of this study was to determine the association between the MDS and rheumatoid arthritis (RA) as well as osteoarthritis (OA). This study was conducted through a cross-sectional survey of 20,513 adults aged ≥ 20years who participated in NHANES from 2007 to 2018. The four dimensions of the MDS included diuretics, proton pump inhibitors, glomerular filtration rate, and excessive alcohol consumption. Univariate and multivariable-weighted logistic regression were used to assess the associations between MDS and RA/OA, and a test for trend was performed to analyze the presence of a dose-response relationship. Subgroup analyses and interaction tests were performed according to confounders. After adjustment for all covariates, we found a graded dose-response relationship between MDS and RA or OA. When MDS was considered as a continuous variable, each onefold increase in MDS was associated with a 1.21-fold increase in the odds of having RA (OR = 1.21, 1.10, 1.33) and a 1.12-fold increase in the odds of having OA (OR = 1.12, 1.04, 1.21). There was an interaction of sex in the effect of MDS on RA (Pinteraction = 0.004) and age in the effect of MDS on OA (Pinteraction = 0.006). In addition, these associations were further confirmed in sensitivity and subgroup analyses. Our study identified significant dose-response associations between MDS and both RA and OA. More biological mechanisms are needed in the future to validate and clarify the results of this study.

Association of maternal blood mercury concentration during the first trimester of pregnancy with birth outcomes.

Exposure to mercury has been associated with adverse effects on pregnancy outcomes. However, there is limited literature on mercury exposure and pregnancy outcomes in Chinese pregnant women. Our study was to investigate the possible association between maternal mercury exposure and spontaneous preterm birth and birth weight. This study was a nested case-control study. The association between blood mercury concentration and both spontaneous preterm birth and birth weight was analyzed using conditional logistic regression and linear regression adjusted for the potential confounding factors, respectively. The dose-response relationship between mercury concentration and birth outcomes was estimated using restricted cubic spline regression. The mean concentration of mercury was 2.8 ± 2.2µg/L. A positive relationship was observed between maternal blood mercury concentration and SPB when analyzed as a continuous variable. However, it was not found to be statistically significant (adjusted OR = 1.10, 95% CI = 0.95-1.26, P = 0.202). Moderate mercury exposure was associated with a higher risk of SPB (Q3 vs. Q1: crude OR = 2.50, 95% CI = 1.16-5.41, P = 0.02; adjusted OR = 3.49, 95% CI = 1.33-9.11, P = 0.011). After considering the combined effects of chemicals other than mercury exposure (including lead, selenium, and cadmium), the results remained consistent. There was no statistically significant association between blood mercury levels and birth weight (adjusted coefficient = 18.64, P-value = 0.075). There were no statistically significant dose-response associations between mercury concentration and birth outcomes (SPB: P = 0.076; birth weight: P = 0.885). Public health policies should focus on reducing environmental releases of mercury, improving food safety standards, and providing education to pregnant women about the risks of mercury exposure and preventive measures.

Gait speed, handgrip strength, and their combination, and risk of depression in later life: Evidence from a prospective study of community-dwelling older adults

ObjectiveThis study investigated the association between gait speed, handgrip strength, and their combination, and the risk for developing clinically relevant depressive symptoms in community-dwelling older adults. MethodsA secondary analysis was conducted using data from the ASPirin in Reducing Events in the Elderly study. Participants were community-dwelling older adults in Australia and the United States of America followed for a median (interquartile range) of 3.97 (2.26) years. Baseline handgrip strength and gait speed were used as exposure variables, and their combination categories were also explored. Depression was measured using the modified Center for Epidemiological Studies Depression 10-item scale (CES-D 10). Cox regression was used to estimate Adjusted Hazard Ratios (AHR) with 95 % Confidence Intervals (CI) after adjusting for a range of potential confounders. ResultA total of 17,231 participants (55.3 % women) were included in the analysis. Slow gait and weak grip at baseline were associated with the risk of depression (AHR: 1.20; CI: 1.11–1.29 and 1.14; 1.06–1.23, respectively). The combination of the two physical performance measures was associated with a 31 % increase in the risk of depression (1.31; 1.16–1.47) and a significant dose-response association was observed for quintiles of gait and grip with depression. LimitationsAlthough the CES-D 10 is a validated scale, it is a self-reported tool rather than a clinical diagnosis of depression. ConclusionLow physical function may be a risk factor for depression in older adults. This highlights the inextricable link between the physical and mental health of older adults, which can inform potential clinical and public health prevention strategies for depression in later life.

Exposure to per- and polyfluoroalkyl substances and age-related macular degeneration in U.S. middle-aged and older adults

Despite various health effects of per- and polyfluoroalkyl substances (PFAS) exposure, the association between PFAS exposure and age-related macular degeneration (AMD) has not been investigated. We aimed to assess associations of PFAS exposure with AMD, using data from 1722 U.S. adults aged 40 years or more participating in the National Health and Nutrition Examination Survey 2005–2008 with complete data on PFAS measurement, AMD diagnosis, and covariates. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS), were measured. An overall PFAS burden score was calculated using item response theory scoring. Individual PFAS concentration and overall PFAS burden score were categorized into low (reference), medium, and high groups. Diagnosis of AMD was based on retinal image examination. Any AMD was defined as the presence of early or late AMD. Survey-weighted logistic regression adjusted for potential confounders was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for presence of AMD according to PFAS exposure. Overall, 132 (6.5%) individuals were diagnosed as any AMD, including 115 (5.7%) individuals with early AMD. A significant dose-response association was observed between serum PFOS concentration and any AMD (p-trend = 0.03), with a significant OR of 1.99 (95% CI: 1.05, 3.79) for the high group compared to the reference. Overall PFAS burden showed a non-monotonic association with any AMD, with a significant OR of 2.18 (95% CI: 1.18, 4.04) for the medium. Inverted U-shaped associations were observed by restricted cubic spline analyses. Also, early AMD showed similar patterns in PFOS and overall PFAS burden and additionally an inverted U-shape association in PFNA. Our findings suggest that exposure to PFAS estimated by serum PFOS and PFNA as well as overall PFAS burden might be a risk factor for AMD in middle-aged and older population.

Association of caffeine intake with all-cause and cardiovascular mortality in diabetes and prediabetes

BackgroudThe association between caffeine intake and mortality in prediabetes and diabetes is not well defined. This study was designed to investigate the association between caffeine intake and all-cause mortality and cardiovascular disease (CVD) mortality in adults with prediabetes and diabetes in the United States.MethodsThis analysis included 18,914 adult patients with diabetes and prediabetes from the National Health and Nutrition Examination Survey (NHANES) 2003–2018. Follow-up extended to December 31, 2019. Weighted Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for all-cause mortality and CVD mortality.ResultsDuring 142,460 person-years of follow-up, there were 3,166 cases of all-cause mortality and 1,031 cases of CVD mortality recorded. In the fully adjusted models, caffeine intake showed a significant dose-response association with the risk of all-cause mortality and CVD mortality in individuals with diabetes and prediabetes. When comparing extreme quartiles of caffeine intake, the multivariable-adjusted hazard ratio for all-cause mortality was 0.78 (0.67–0.91) (P for trend = 0.007); however, there was no significant association with the risk of CVD mortality. Results remained consistent in stratified analyses by sex, age, race/ethnicity, education level, family income-poverty ratio, BMI, hypertension, smoking status, alcohol intake, and HEI-2015.ConclusionsThis study suggests that caffeine intake is significantly inversely associated with the risk of all-cause mortality in individuals with diabetes and prediabetes. In individuals with prediabetes, there is also a significant inverse association between caffeine intake and CVD events, but this association is not present in those with diabetes.Graphical

Association of body mass index with rapid eye movement sleep behavior disorder in Parkinson’s disease

BackgroundThe association between body mass index (BMI) and rapid eye-movement (REM) sleep-related behavioral disorder (RBD) in Parkinson’s disease (PD) remains unknown. Our study was to investigate the association of BMI with RBD in PD patients.MethodsIn this cross-sectional study, a total of 1,115 PD participants were enrolled from Parkinson’s Progression Markers Initiative (PPMI) database. BMI was calculated as weight divided by height squared. RBD was defined as the RBD questionnaire (RBDSQ) score with the cutoff of 5 or more assessed. Univariable and multivariable logistic regression models were performed to examine the associations between BMI and the prevalence of RBD. Non-linear correlations were explored with use of restricted cubic spline (RCS) analysis. And the inflection point was determined by the two-line piecewise linear models.ResultsWe identified 426 (38.2%) RBD. The proportion of underweight, normal, overweight and obese was 2.61, 36.59, 40.36, and 20.44%, respectively. In the multivariate logistic regression model with full adjustment for confounding variables, obese individuals had an odds ratio of 1.77 (95% confidence interval: 1.21 to 2.59) with RBD compared with those of normal weight. In the RCS models with three knots, BMI showed a non-linear association with RBD. The turning points of BMI estimated from piecewise linear models were of 28.16 kg/m2, 28.10 kg/m2, and 28.23 kg/m2 derived from univariable and multivariable adjusted logistic regression models. The effect modification by depression on the association between BMI and RBD in PD was also found in this study. Furthermore, the sensitivity analyses linked with cognition, education, and ethnic groups indicated the robustness of our results.ConclusionThe current study found a significant dose–response association between BMI and RBD with a depression-based difference in the impact of BMI on RBD in PD patients.

Early-life exposure to tobacco, genetic susceptibility, and accelerated biological aging in adulthood.

Early-life tobacco exposure serves as a non-negligible risk factor for aging-related diseases. To understand the underlying mechanisms, we explored the associations of early-life tobacco exposure with accelerated biological aging and further assessed the joint effects of tobacco exposure and genetic susceptibility. Compared with those without in utero exposure, participants with in utero tobacco exposure had an increase in Klemera-Doubal biological age (KDM-BA) and PhenoAge acceleration of 0.26 and 0.49 years, respectively, but a decrease in telomere length of 5.34% among 276,259 participants. We also found significant dose-response associations between the age of smoking initiation and accelerated biological aging. Furthermore, the joint effects revealed that high-polygenic risk score participants with in utero exposure and smoking initiation in childhood had the highest accelerated biological aging. There were interactions between early-life tobacco exposure and age, sex, deprivation, and diet on KDM-BA and PhenoAge acceleration. These findings highlight the importance of reducing early-life tobacco exposure to improve healthy aging.

Association between processed and unprocessed red meat consumption and risk of nonalcoholic fatty liver disease: A systematic review and dose-response meta-analysis.

The nature of the relationship between red meat consumption and nonalcoholic fatty liver disease (NAFLD) remains unclear. Through this meta-analysis, we aimed to determine the association and dose-response relationship between red meat consumption (both processed and unprocessed) and the risk of NAFLD. We systematically searched CENTRAL, PubMed, Embase, Web of Science and Scopus from inception to February 2022 for observational studies in which the exposure of interest was red meat consumption; the outcome of interest was the risk of NAFLD; and where odds ratios (ORs) or risk ratios were provided or could be calculated. We used random-effects meta-analyses to pool the effect sizes and performed analyses to estimate the linearity of the dose-response relationships between red meat intake and NAFLD risk. We included 10 studies in this review. The meta-analysis showed a significant association between the intake of red meat (OR = 1.27; 95% confidence interval (CI) = 1.07-1.50, P = 0.000, I2 = 81%), processed red meat (OR = 1.20; 95% CI = 1.04-1.3, P = 0.162, I2 = 34.9%) or unprocessed red meat (OR = 1.28; 95% CI = 1.05-1.55, P = 0.001, I2 = 76.2%) and the risk of NAFLD. We also found a significant linear dose-response association between processed red meat intake and NAFLD, with each 25-g increment of processed red meat intake per day was associated with an 11.1% higher risk of NAFLD (OR = 1.11; 95% CI = 1.01-1.22, P = 0.029), and a nonlinear association between unprocessed meat intake and NAFLD (P = 0.003 for nonlinearity). Our findings indicate a potential positive association between red meat consumption (both processed and unprocessed) and NAFLD risk, especially in relation to increased intake of processed red meat compared to unprocessed red meat. However, caution is advised in interpreting these results; further research could establish a clearer understanding of the relationship between red meat consumption and NAFLD risk. PROSPERO: CRD42022332839.

Dose-response associations between physical activity and sedentary time with functional disability in older adults with or without frailty: a prospective cohort study.

Evidence regarding the dose-response curve shapes of physical activity (PA) and sedentary time (ST) in older adults with functional disability (FD) is extremely limited. Moreover, these associations may differ depending on with/without frailty. We examined the dose-response associations between moderate-to-vigorous PA (MVPA) and ST with FD among older adults with/without frailty. We included 7,480 initially nondisabled adults (3,795 men and 3,685 women) aged 65-84 years in Ota City, Tokyo, Japan. MVPA and ST were evaluated using the International Physical Activity Questionnaire-Short Form. FD was prospectively identified using a nationally unified database of the long-term care insurance system. Frailty was determined using Check-List 15, validated against Fried's frailty criteria. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of MVPA and ST for FD were calculated, and dose-response curves were examined using restricted cubic splines. During 3.6 years of follow-up, 1,001 (13.4%) participants had FD. Among all participants, compared with no MVPA, the HRs for FD reduced linearly up to approximately 2000 metabolic equivalents (METs)■min/week of MVPA, and the lowest HR (HR: 0.61, 95% CI: 0.51-0.74) was reached at around 3,000-4,000 METs■min/week. Although the shape of this association was consistent regardless of with/without frailty, the magnitude of the association tended to be stronger in frail older adults than in non-frail older adults. Compared with those for the median (300 min/day) of ST, the HRs for FD increased linearly as ST reached approximately 600 min/day or more, independent of MVPA, with a maximum HR of 1.31 (95% CI: 1.01-1.71) for 1,080 min/day among all participants. This association was more pronounced among non-frail older adults but not statistically significant among frail older adults. Higher MVPA levels consistently reduced the incidence of FD regardless of frailty in a significant inverse nonlinear dose-response manner. A significant positive nonlinear dose-response association between ST and FD risk was identified among non-frail older adults but not among frail older adults. Increasing MVPA and reducing prolonged ST are important for preventing FD among non-frail older adults. However, reducing ST alone may be insufficient; increasing MVPA, even if by only small increments, is highly recommended for frail older adults.

Dose-response Associations of Physical Activity and Sitting Time With All-cause Mortality in Older Japanese Adults.

Although examining the dose-response curves of physical activity (PA) and sitting time with health-related outcomes is an important research agenda, the results for older Japanese adults are extremely limited. We examined the dose-response associations of PA and sitting time with all-cause mortality among older Japanese. Initially, 8,069 non-disabled residents (4,073 men; 3,996 women) aged 65-84 years of Ota City, Japan, were analyzed. Moderate-to-vigorous PA (MVPA) and sitting time were evaluated using the International Physical Activity Questionnaire-Short Form. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of MVPA and sitting time for all-cause mortality were calculated, and the dose-response curves were examined using restricted cubic splines (RCS). During 4.1 years of follow-up, 458 participants (5.7%; 331 men and 127 women) died. Compared with the low MVPA (<600 metabolic equivalents [METs]·minutes/week) group, HR for mortality gradually reduced in moderate (600-3,000 METs·minutes/week) and high (>3,000 METs·minutes/week) MVPA groups (moderate: HR 0.66; 95% CI, 0.54-0.82; high: HR 0.58; 95% CI, 0.45-0.75; P < 0.001 for trend). RCS showed that the HR for mortality reduced linearly up to approximately 2,000 METs·minutes/week of MVPA, and maximal risk reduction was seen at approximately 3,000-4,500 METs·minutes/week of MVPA. No significant dose-response association of sitting time with mortality was observed. Higher MVPA levels reduced all-cause mortality risk, in a significant inverse non-linear dose-response manner. Sitting time was not significantly associated with all-cause mortality. It is important to disseminate the significance of even a slight increase in the MVPA for reducing mortality risk.

Associations of Healthy Eating Behavior with Mental Health and Health-Related Quality of Life: Results from the Korean National Representative Survey.

Healthy eating behaviors may be related to mental health and health-related quality of life. This study investigates the associations between diet quality, mental health, and health-related quality of life among men and women in Korea. A total of 6823 participants, aged 19, from the 7th Korea National Health and Nutrition Examination Survey from 2016 to 2018 were included. Their overall diet quality was estimated using the Korean Healthy Eating Index (KHEI). Multivariate logistic regression was used to identify the associations between diet quality, mental health, and quality of life. The prevalence of stress perception and depression was highest in the lowest tertile of the KHEI score and higher for women than men. Among men, a significant association was observed only for stress perception and depressive symptoms in the second tertile, with odds ratios of 0.745 (95% CI, 0.585-0.949) and 0.519 (95% CI, 0.275-0.980). In contrast, the multivariate-adjusted odds ratios for stress perception, depressive symptoms, and low EQ-5D index among women in the highest tertile were 0.668 (95% CI, 0.541-0.823), 0.464 (95% CI, 0.288-0.746), and 0.722 (95% CI, 0.566-0.920), and significant dose-response associations were observed. A higher-quality diet was associated with a lower risk of stress and depression and a better quality of life. Thus, healthy eating behaviors may improve mental health and quality of life.

Moderate and vigorous leisure time physical activity in older adults and Alzheimer's disease-related mortality in the USA: a dose–response, population-based study

Data for the dose-response associations of moderate physical activity (MPA) and vigorous physical activity (VPA) with Alzheimer's disease-related mortality are scarce. We aimed to examine the prospective associations of such activity with Alzheimer's disease-related mortality. In this dose-response, population-based study, we pooled data from 22 consecutive waves of the US National Health Interview Survey (from 1997 to 2018). Participants aged 68 years or older were included in the study if they had full data for physical or muscle-strengthening activity, chronic conditions, functional limitations, marital status, education level, alcohol consumption, smoking status, and BMI, and follow-up time after study entry. Participants were linked to the National Death Index until Dec 31, 2019. We defined Alzheimer's disease-related mortality as a leading cause by using the G-30 code of the International Statistical Classification of Diseases and Related Health Problems tenth revision. Information on MPA and VPA was self-reported, with participants asked to answer four questions on the frequency and duration of both types of physical activity. We calculated hazard ratios (HRs) and used restricted cubic splines models to assess dose-response associations, and we estimated the annual number of Alzheimer's disease-related deaths that could be prevented through physical activity using adjusted population attributable fractions. After excluding 21 377 participants, 91 298 adults were included in the analysis. The weighted mean participant age was 75·8 years (SE 0·0); 55 658 (56·7%) were female and 76 796 (87·6%) were White (weighted percentages). The median follow-up was 6·5 years (IQR 3·6-10·7), corresponding to 703 393 person-years. 2176 (2·4%) participants died due to Alzheimer's disease as the leading cause. For MPA, we did not find a significant dose-response association with Alzheimer's disease-related mortality, whereas for VPA, we observed a significant L-shaped association between 20 weekly min and 190 weekly min. For VPA, we identified a minimal amount (ie, 50% of the optimal amount) at 40 min/week (HR 0·91, 95% CI 0·84-0·95) and an optimal amount (ie, the nadir of the curve) at 140 min/week (0·79, 0·66-0·95) for reducing Alzheimer's disease-related mortality. For the USA, we estimated that 40 weekly min of VPA would prevent 12 238 deaths per year (95% CI 89-23 172) and 140 weekly min of VPA would prevent 37 710 deaths per year (311-63 567), compared with a scenario in which US adults did not do any VPA. These findings might inform future guidelines for preventing Alzheimer's disease-related mortality by emphasising the importance of VPA over MPA and providing specific VPA targets. None.

Association of glyphosate exposure with multiple adverse outcomes and potential mediators

Glyphosate (GLY) is a widely used herbicide with potential adverse effects on public health. However, the current epidemiological evidence is limited. This study aimed to investigate the potential associations between exposure to GLY and multiple health outcomes. The data on urine GLY concentration and nine health outcomes, including type 2 diabetes mellitus (T2DM), hypertension, cardiovascular disease (CVD), obesity, chronic kidney disease (CKD), hepatic steatosis, cancers, chronic obstructive pulmonary disease (COPD), and neurodegenerative diseases (NGDs), were extracted from NHANES (2013–2016). The associations between GLY exposure and each health outcome were estimated using reverse-scale Cox regression and logistic regression. Furthermore, mediation analysis was conducted to identify potential mediators in the significant associations. The dose-response relationships between GLY exposure with health outcomes and potential mediators were analyzed using restricted cubic spline (RCS) regression. The findings of the study revealed that individuals with higher urinary concentrations of GLY had a higher likelihood of having T2DM, hypertension, CVD and obesity (p < 0.001, p = 0.005, p < 0.001 and p = 0.005, respectively). In the reverse-scale Cox regression, a notable association was solely discerned between exposure to GLY and the risk of T2DM (adjusted HR = 1.22, 95% CI: 1.10, 1.36). Consistent outcomes were also obtained via logistic regression analysis, wherein the adjusted OR and 95% CI for T2DM were determined to be 1.30 (1.12, 1.52). Moreover, the present investigation identified serum high-density lipoprotein cholesterol (HDL) as a mediator in this association, with a mediating effect of 7.14% (p = 0.040). This mediating effect was further substantiated by RCS regression, wherein significant dose-response associations were observed between GLY exposure and an increased risk of T2DM (p = 0.002) and reduced levels of HDL (p = 0.001). Collectively, these findings imply an association between GLY exposure and an increased risk of T2DM in the general adult population.

Life's Essential 8 and risk of non-communicable chronic diseases: Outcome-wide analyses.

Life's Simple 7, the former construct of cardiovascular health (CVH) has been used to evaluate adverse non-communicable chronic diseases (NCDs). However, some flaws have been recognized in recent years and Life's Essential 8 has been established. In this study, we aimed to analyze the association between CVH defined by Life's Essential 8 and risk of 44 common NCDs and further estimate the population attributable fractions (PAFs) of low-moderate CVH scores in the 44 NCDs. In the UK Biobank, 170,726 participants free of 44 common NCDs at baseline were included. The Life's Essential 8 composite measure consists of four health behaviours (diet, physical activity, nicotine exposure, and sleep) and four health factors (body mass index, non-high density lipoprotein cholesterol, blood glucose, and blood pressure), and the maximum CVH score was 100 points. CVH score was categorized into low, moderate, and high groups. Participants were followed up for 44 NCDs diagnosis across 10 human system disorders according to the International Classification of Diseases 10th edition (ICD-10) code using linkage to national health records until 2022. Cox proportional hazard models were used in this study. The hazard ratios (HRs) and PAFs of 44 NCDs associated with CVH score were examined. During the median follow-up of 10.85 years, 58,889 incident NCD cases were documented. Significant linear dose-response associations were found between higher CVH score and lower risk of 25 (56.8%) of 44 NCDs. Low-moderate CVH (<80 points) score accounted for the largest proportion of incident cases in diabetes (PAF: 80.3%), followed by gout (59.6%), sleep disorder (55.6%), chronic liver disease (45.9%), chronic kidney disease (40.9%), ischemic heart disease (40.8%), chronic obstructive pulmonary disease (40.0%), endometrium cancer (35.8%), lung cancer (34.0%), and heart failure (34.0%) as the top 10. Among the eight modifiable factors, overweight/obesity explained the largest number of cases of incident NCDs in endocrine, nutritional, and metabolic diseases (35.4%), digestive system disorders (21.4%), mental and behavioral disorders (12.6%), and cancer (10.3%); however, the PAF of ideal sleep duration ranked first in nervous system (27.5%) and neuropsychiatric disorders (9.9%). Improving CVH score based on Life's Essential 8 may lower risk of 25 common NCDs. Among CVH metrics, avoiding overweight/obesity may be especially important to prevent new cases of metabolic diseases, NCDs in digestive system, mental and behavioral disorders, and cancer.

Association between Low Blood Pressure and Subsequent Risk of Parkinson’s Disease in Older Adults Aged ≥75 Years

Introduction: The association between blood pressure (BP) and incidence of Parkinson’s disease (PD) in older adults remains uncertain. Therefore, this study aimed to investigate the association between BP (high or low) and PD incidence in adults aged ≥75 years. Methods: In this nationwide population-based cohort study, we enrolled participants aged ≥75 years without a prior PD diagnosis who had undergone health examination provided by the Korean National Health Insurance Service at least once from January 1, 2009, to December 31, 2012. The participants were followed up until December 31, 2019, or the date of their death. The Cox proportional hazards model was used to assess the risk of PD depending on systolic BP (SBP), diastolic BP (DBP), and pulse pressure. Results: Overall, 963,525 participants were enrolled in the analysis and followed up until December 31, 2019, or the date of death (40.7% male, mean age 78.5 ± 3.6 years). The mean SBP and DBP were 131.4 ± 16.7 and 77.9 ± 10.3 mm Hg, respectively. During the 10-year follow-up period, 16,414 (1.7%) newly diagnosed cases of PD were reported. A significant inverse dose-response association was found between SBP and PD incidence. In the subgroup analysis, this association was maintained for most variables, including sex, use of antihypertensive medication, comorbidities, alcohol consumption, physical activity, and body mass index, except for smoking status. Conclusion: Lower SBP and DBP were associated with a higher PD incidence in older adults. These results may have substantial implications for determining the optimal BP control target in adults aged ≥75 years.

Automated Digital Counseling Program (ODYSSEE-Kidney Health): A Pilot Study on Health-Related Quality of Life.

In-person counselling programs promote self-care behaviour and health-related quality of life (HRQoL). ODYSSEE Kidney Health (ODYSSEE-KH) is an automated, scalable, digital counselling program for patients with CKD. This open-label, single-arm pilot study tested the efficacy potential of ODYSSEE-KH to improve HRQoL in patients with CKD. Adults with categories G3b to 5D CKD were recruited from nephrology clinics in Toronto, Canada. Patients (n=29) received access to ODYSSEE-KH in conjunction with usual care. Generalized linear models and pairwise comparisons of mean change scores were conducted to assess the primary outcome: Mental Component Score (MCS) of the Kidney Disease Quality of Life - Short Form (KDQoL-SF) instrument. Secondary outcomes included: MCS mental health scale, 36-item KDQoL-SF, Generalized Anxiety Disorder scale (GAD-7), Patient Health Questionnaire for depression (PHQ-9), Enhancing Recovery in Coronary Heart Disease Social Support Instrument (ESSI), and 3-item Revised UCLA Loneliness (RULS-3) scale. Mean age was 53.5 years (SD=18.3); 35% women; 56% White; 93% completed ≥ post-secondary education; patients came from the Multi-Care Kidney Clinic (n=9), the Home Peritoneal Dialysis Unit (n=12), and the Home Hemodialysis Unit (n=8); and 24 participants completed the 4-month end of study questionnaires. Outcomes were assessed according to tertiles of program logon minutes: median (range) = 67 (62-108), 212 (119-355), and 500 (359-1573) minutes. Patients in the highest tertile of engagement showed significant improvements on the MCS vs. the moderate tertile group (p = 0.01). Significant dose-response associations were observed for MCS Mental Health (p<0.05), KDQoL Burden on Kidney Disease (p<0.01), KDQoL Effect of Kidney Disease on Everyday Life (p<0.01), aggregated KDQoL summary (p<0.05), GAD-7 (p<0.01), PHQ-9 (p<0.05), ENRICHD-SSI (p<0.01), and RULS-3 (p<0.01). ODYSSEE-KH demonstrated feasibility as an automated, scalable, digital self-care program for patients with CKD. There is evidence of efficacy potential to improve HRQoL. Further evaluation with a larger sample is warranted.

Association Between Incident Type 2 Diabetes and Opium Use: Mediation by Body Mass and Adiposity.

Opiates can affect glucose metabolism and obesity, but no large prospective study (to our knowledge) has investigated the association between long-term opium use, body mass index (BMI; weight (kg)/height (m)2), and incident type 2 diabetes mellitus (T2DM). We analyzed prospective data from 50,045 Golestan Cohort Study participants in Iran (enrollment: 2004-2008). After excluding participants with preexisting diseases, including diabetes, we used adjusted Poisson regression models to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for T2DM in opium users compared with nonusers, using mediation analysis to assess the BMI-mediated association of opium use with incident T2DM. Of 40,083 included participants (mean age = 51.4 (standard deviation, 8.8) years; 56% female), 16% were opium users (median duration of use, 10 (interquartile range), 4-20) years). During follow-up (until January 2020), 5,342 incident T2DM cases were recorded, including 8.5% of opium users and 14.2% of nonusers. Opium use was associated with an overall decrease in incident T2DM (IRR=0.83, 95% CI: 0.75, 0.92), with a significant dose-response association. Most (84.3%) of this association was mediated by low BMI or waist circumference, and opium use did not have a direct association with incident T2DM (IRR=0.97, 95% CI: 0.87, 1.08). Long-term opium use was associated with lower incidence of T2DM, which was mediated by low body mass and adiposity.

Social determinants of health and hypertension in women compared with men in the United States: An analysis of the NHANES study.

Social determinants of health (SDH) reflecting social deprivation have been developed for population health management. There is a paucity of data on the prevalence of SDH and its associations with prevalent hypertension in women compared with men. A total of 49 791 participants aged over 20 years from the 1999-2018 National Health and Nutrition Examination Surveys, were included. Information on the SDH, including race/ethnicity, education level, family income, housing, marriage status, employment, were collected. We calculated the prevalence ratio (PR) for each adverse SDH with prevalent hypertension and uncontrolled hypertension by using Cox regression with equal times of follow-up assigned to all individuals with adjustment for age, diabetes, taking lipid-lowering medication, and health behaviors. The population-attributable fractions (PAF) of the SDH were also assessed. A lower proportion of low education attainment was observed in women than men (women: 16.8% vs. men: 17.9%, p = .003), but women had higher proportions of low family income (15.3% vs. 12.5%, p < .001), unmarried state (47.3% vs. 40.9%, p < .001), and unemployment (22.7% vs. 10.7%, p < .001). All the SDH was significantly associated with hypertension in women. There were significant dose-response associations between the numbers of adverse SDH with hypertension. The total PAF of SDH for prevalent hypertension was greater in women (22.2%) than in men (13.9%). The widely influential SDH is associated with prevalent hypertension and uncontrolled hypertension. To improve hypertension management, health resources should prioritize socioeconomically disadvantaged groups considering gender differences.

Sex distinctive patterns in the association between serum bicarbonate and uric acid levels among healthy adults. Qatar biobank data.

Uric acid is the final product of purine metabolism and is a potent plasma antioxidant but with pro-inflammatory effects. At high levels, it may increase the risk of developing multiple chronic diseases, such as gout, atherosclerosis, hypertension, and renal diseases. The aim of this study was to assess the sex-specific association between serum bicarbonate and uric acid levels among healthy adults. This retrospective cross-sectional study included 2,989 healthy Qatari adults (36.4 ± 11.1 years) from the Qatar Biobank database. Serum uric acid and bicarbonate levels were estimated alongside other serological markers. Participants free from chronic diseases were divided into four quartiles based on serum bicarbonate levels. The sex-specific relationship between serum bicarbonate and uric acid levels was assessed through univariate and multivariate analyses. In men, low serum uric acid levels were significantly associated with higher quartiles of serum bicarbonate levels after adjusting for age. The association remained significant after further adjustment for BMI, smoking, and renal function. The subgroup analysis using the restricted cubic spline method confirmed a significant dose-response association between the variation coefficients of uric acid by serum bicarbonate level in men with adjustments for age, BMI, smoking, and renal function. In women, no significant association was found between quartiles of serum bicarbonate and uric acid levels following the same adjustments. However, using the restricted cubic spline method, a significant bidirectional relation was demonstrated between serum bicarbonate and the variation coefficients of uric acid that were positive for serum bicarbonate levels below 25 mEq/L and negative at higher levels. Serum bicarbonate levels are linearly associated with reduced serum uric acid levels among healthy adult men, which may be a potential protective factor against hyperuricemia-related complications. Further research is needed to determine the underlying mechanisms.

Phytochemical consumption and the risk of teratozoospermia: findings from a hospital-based case-control study in China.

Are dietary phytochemicals associated with the risk of teratozoospermia? Dietary intake of carotene, including total carotene, α-carotene, β-carotene as well as retinol equivalent, and lutein + zeaxanthin, were inversely correlated with the risk of teratozoospermia. Phytochemicals are natural plant derived bioactive compounds, which have been reported to be potentially associated with male reproductive health. To date, no study has investigated the association between phytochemical intake and the risk of teratozoospermia. This hospital-based case-control study, which included 146 newly diagnosed teratozoospermia cases and 581 controls with normozoospermia from infertile couples, was conducted in a hospital-based infertility clinic in China, from June 2020 to December 2020. Dietary information was collected using a validated semi-quantitative 110-item food frequency questionnaire. Unconditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between phytochemical (i.e. phytosterol, carotene, flavonoid, isoflavone, anthocyanidin, lutein + zeaxanthin, and resveratrol) intake and the risk of teratozoospermia. We observed a decreased risk of teratozoospermia for the highest compared with the lowest tertile consumption of total carotene (OR = 0.40, 95% CI = 0.21-0.77), α-carotene (OR = 0.53, 95% CI = 0.30-0.93), β-carotene (OR = 0.47, 95% CI = 0.25-0.88), retinol equivalent (OR = 0.47, 95% CI = 0.24-0.90), and lutein + zeaxanthin (OR = 0.35, 95% CI = 0.19-0.66), with all of the associations showing evident linear trends (all P trend <0.05). In addition, significant dose-response associations were observed between campestanol and α-carotene consumption and the risk of teratozoospermia. Moreover, there was a significant multiplicative interaction between BMI and lutein + zeaxanthin intake (P interaction <0.05). The cases and controls were not a random sample of the entire target population, which could lead to admission rate bias. Nevertheless, the controls were enrolled from the same infertility clinic, which could reduce the bias caused by selection and increase the comparability. Furthermore, our study only included a Chinese population, therefore caution is required regarding generalization of our findings to other populations. Dietary phytochemicals, namely carotene, lutein, and zeaxanthin, might exert a positive effect on teratozoospermia. These phytochemicals are common in the daily diet and dietary supplements, and thus may provide a preventive intervention for teratozoospermia. This study was funded by Natural Science Foundation of Liaoning Province (No. 2022-MS-219 to X.B.W.), Outstanding Scientific Fund of Shengjing Hospital (No. M1150 to Q.J.W.), Clinical Research Cultivation Project of Shengjing Hospital (No. M0071 to B.C.P.), and JieBangGuaShuai Project of Liaoning Province (No. 2021JH1/1040050 to Y.H.Z.). All authors declared that there was no conflict of interest. N/A.