Effects of ambient air pollution on brain cortical thickness and subcortical volume: A longitudinal neuroimaging study.

INTRODUCTION: Long-term exposure to air pollutants is associated with an increased risk of Alzheimer's disease and mild cognitive impairment. Therefore, we investigated the association between long-term air pollution exposure and changes in neuroimaging markers. METHODS: In this longitudinal study, we studied a prospective cohort of 361 adults residing in four cities in the Republic of Korea. Long-term concentrations of particulate matter with aerodynamic diameters of ≤10 µm (PM10) and ≤2.5 µm (PM2.5) and nitrogen dioxide (NO2) at residential addresses were estimated. Neuroimaging markers (cortical thickness and subcortical volume) were obtained from brain magnetic resonance images at baseline (August 2014 to March 2017) and at the 3-year follow-up (until September 2020). Linear mixed-effects models were used, adjusting for covariates. RESULTS: A 10-µg/m3 increase in PM10 was associated with reduced whole-brain mean (ß= -0.45, standard error (SE)= 0.10, P< 0.001), frontal (ß= -0.53, SE= 0.11; P< 0.001) and temporal thicknesses (ß= -0.37, SE= 0.12; P= 0.002). A 10-ppb increase in NO2 was associated with a decline in the whole brain mean cortical thickness (ß= -0.23, SE= 0.05; P< 0.001), frontal (ß= -0.25, SE= 0.05; P< 0.001), parietal (ß= -0.12, SE= 0.05; P= 0.025), and temporal thicknesses (ß= -0.19, SE= 0.06; P= 0.001). Subcortical structures associated with air pollutants include the thalamus volume. CONCLUSIONS: Long-term exposure to PM10 and NO2 may lead to cortical thinning in adults.

Physical Activity-Induced Modification of the Association of Long-Term Air Pollution Exposure with the Risk of Depression in Older Adults.

PURPOSE: Evidence suggests that long-term air pollution exposures may induce depression; however, the influence of physical activity on this effect is unclear. We investigated modification of the associations between air pollution exposures and depression by the intensity of physical activity. MATERIALS AND METHODS: This cross-sectional study included 1454 Korean adults. Depression was defined as a Geriatric Depression Scale score ≥8. Concentrations of particulate matter (PM10 and PM2.5: diameter ≤10 µm and ≤2.5 µm, respectively) and nitrogen dioxide (NO2) level at each participant's residential address were estimated. Based on metabolic equivalents, physical activity intensity was categorized as inactive, minimally active, or health-enhancing physical activity (HEPA). RESULTS: Each 1-part per billion (ppb) NO2 concentration increase was significantly associated with a 6% [95% confidence interval (CI), 4%-8%] increase in depression risk. In older adults (≥65 years), a 1-ppb NO2 increase was associated (95% CI) with a 4% (1%-7%), 9% (5%-13%), and 21% (9%-33%) increase in depression risk in the inactive, minimally active, and HEPA groups, respectively. Compared with the inactive group, the minimally active (p=0.039) and HEPA groups (p=0.004) had higher NO2 exposure-associated depression risk. Associations of PM10 and PM2.5 with depression did not significantly differ by the intensity of physical activity. CONCLUSION: We suggest that older adults who vigorously exercise outdoors may be susceptible to air pollution-related depression.

Association between exposure to heavy metals in atmospheric particulate matter and sleep quality: A nationwide data linkage study.

BACKGROUND: Recent studies have demonstrated that long-term exposure to particulate matter (PM) is associated with poor sleep quality. However, no studies have linked PM constituents, particularly heavy metals, to sleep quality. OBJECTIVE: This study investigated the association between exposure to heavy metals in PM and sleep quality. METHODS: We obtained nationwide data from the Korean Community Health Survey conducted in 2018 among adults aged 19-80 years. Sleep quality was evaluated using Pittsburgh Sleep Quality Index (PSQI). Poor sleep quality was defined as PSQI ≥5. One-year and three-month average concentrations of heavy metals (lead, manganese, cadmium, and aluminum) in PM with diameter ≤10 µm were obtained from nationwide air quality monitoring data and linked to the survey data based on individual district-level residential addresses. Logistic regression analyses were performed after adjusting for age, gender, education level, marital status, smoking status, alcohol consumption, history of hypertension, and history of diabetes mellitus. RESULTS: Of 32,050 participants, 17,082 (53.3%) reported poor sleep quality. Increases in log-transformed one-year average lead (odds ratio, 1.14; 95% confidence interval, 1.08-1.20), manganese (1.31; 1.25-1.37), cadmium (1.03; 1.00-1.05), and aluminum concentrations (1.17; 1.10-1.25) were associated with poor sleep quality. Increases in log-transformed three-month average manganese (odds ratio, 1.13; 95% confidence interval, 1.09-1.17) and aluminum concentrations (1.28; 1.21-1.35) were associated with poor sleep quality. CONCLUSION: We showed for the first time that exposure to airborne lead, manganese, cadmium, and aluminum were associated with poor sleep quality. This study may be limited by self-reported sleep quality and district-level exposure data.

Heavy metal exposure linked to metabolic syndrome in Korean male firefighters: FRESH cohort cross-sectional analysis.

This study aimed to identify the relationship between blood lead and Cadmium (Cd) concentrations and metabolic syndromes (MetS), including its components (central obesity, hypertriglyceridemia, low high-density lioioritein, hypertension, and hyperglycemia) among Korean firefighters. A total of 965 firefighters of the Enhancement of Safety and Health cohort were analyzed in this study. MetS was defined according to the 2005 revised National Cholesterol Education Program-Adult Treatment Panel III criteria and the Korean Society for the Study of Obesity criteria for waist circumference. The collected data were analyzed using a logistic regression model. Of the 965 participants, 190 (19.7%) had MetS. After adjusting for age, body mass index, smoking, drinking, exercise, shift duty, and main duty position, the Cd level was significantly associated with an increased risk of MetS in the Korean firefighter population (odds ratio [OR] = 1.62, 95% confidence interval [CI] 1.07, 2.46). This association was significant among non-smokers and ex-smokers (OR = 1.58, 95% CI 1.03, 2.43), non-drinkers and ex-drinkers (OR = 1.77, 95% CI 1.06, 2.94), firefighters aged 40 year or older (OR = 1.77, 95% CI 1.10, 2.86), and office administrators (OR = 3.85, 95% CI 1.42, 10.39). This outcome suggests that exposure to Cd is likely to increase risk of MetS among firefighters.

Remnant cholesterol, but not low-density lipoprotein cholesterol, is associated with intra-pancreatic fat deposition.

AIM: To investigate the associations of components of the lipid panel (and its derivatives) with intra-pancreatic fat deposition (IPFD). METHODS: All participants underwent abdominal magnetic resonance imaging on the same 3.0-Tesla scanner and IPFD was quantified. Blood samples were collected in the fasted state for analysis of lipid panel components. A series of linear regression analyses was conducted, adjusting for age, sex, ethnicity, body mass index, fasting plasma glucose, homeostatic model assessment of insulin resistance, and liver fat deposition. RESULTS: A total of 348 participants were included. Remnant cholesterol (P = 0.010) and triglyceride levels (P = 0.008) were positively, and high-density lipoprotein cholesterol level (P = 0.001) was negatively, associated with total IPFD in the most adjusted model. Low-density lipoprotein cholesterol and total cholesterol were not significantly associated with total IPFD. Of the lipid panel components investigated, remnant cholesterol explained the greatest proportion (9.9%) of the variance in total IPFD. CONCLUSION: Components of the lipid panel have different associations with IPFD. This may open up new opportunities for improving outcomes in people at high risk for cardiovascular diseases (who have normal low-density lipoprotein cholesterol) by reducing IPFD.

Polycyclic aromatic hydrocarbons and changes in brain cortical thickness and an Alzheimer's disease-specific marker for cortical atrophy in adults: A longitudinal neuroimaging study of the EPINEF cohort.

Although several epidemiological studies have suggested that exposure to polycyclic aromatic hydrocarbons (PAHs) may induce brain atrophy, no longitudinal study has investigated the effect of PAH exposure on brain structural changes. This study examined the longitudinal associations between urinary PAH metabolites and brain cortical thickness. We obtained urinary concentrations of PAH metabolites and brain magnetic resonance images from 327 adults (≥50 years of age) without dementia at baseline and 3-year follow-up. We obtained whole-brain and regional cortical thicknesses, as well as an Alzheimer's disease (AD)-specific marker for cortical atrophy (a higher score indicated a greater similarity to patients with AD) at baseline and follow-up. We built a linear mixed-effect model including each of urinary PAH metabolites as the time-varying exposure variable of interest. We found that increases in urinary concentrations of 1-hydroxypyrene (ß = -0.004; 95% CI, -0.008 to -0.001) and 2-hydroxyfluorene (ß = -0.011; 95% CI, -0.015 to -0.006) were significantly associated with a reduced whole-brain cortical thickness. A urinary concentration of 2-hydroxyfluorene was significantly associated with an increased AD-specific cortical atrophy score (ß = 2.031; 95% CI, 0.512 to 3.550). The specific brain regions showing the association of urinary concentrations of 1-hydroxypyrene, 2-naphthol, 1-hydroxyphenanthrene, or 2-hydroxyfluorene with cortical thinning were the frontal, parietal, temporal, and cingulate lobes. These findings suggested that exposure to PAHs may reduce brain cortical thickness and increase the similarity to AD-specific cortical atrophy patterns in adults.

All-Cause and Cause-Specific Mortality Attributable to Seasonal Influenza: A Nationwide Matched Cohort Study.

BACKGROUND: Although influenza poses substantial mortality burden, most studies have estimated excess mortality using time-aggregated data. Here, we estimated mortality risk and population attributable fraction (PAF) attributed to seasonal influenza using individual-level data from a nationwide matched cohort. METHODS: Individuals with influenza during four consecutive influenza seasons (2013-2017) (n = 5,497,812) and 1:4 age- and sex-matched individuals without influenza (n = 20,990,683) were identified from a national health insurance database. The endpoint was mortality within 30 days after influenza diagnosis. All-cause and cause-specific mortality risk ratios (RRs) attributed to influenza were estimated. Excess mortality, mortality RR, and PAF of mortality were determined, including for underlying disease subgroups. RESULTS: Excess mortality rate, mortality RR, and PAF of all-cause mortality were 49.5 per 100,000, 4.03 (95% confidence interval [CI], 3.63-4.48), and 5.6% (95% CI, 4.5-6.7%). Cause-specific mortality RR (12.85; 95% CI, 9.40-17.55) and PAF (20.7%; 95% CI, 13.2-27.0%) were highest for respiratory diseases. In subgroup analysis according to underlying disorders, PAF of all-cause mortality was 5.9% (95% CI, 0.6-10.7%) for liver disease, 5.8% (95% CI, 2.9-8.5%) for respiratory disease, and 3.8% (95% CI, 1.4-6.1%) for cancer. CONCLUSION: Individuals with influenza had a 4-fold higher mortality risk than individuals without influenza. Preventing seasonal influenza may lead to 5.6% and 20.7% reductions in all-cause and respiratory mortality, respectively. Individuals with respiratory disease, liver disease, and cancer may benefit from prioritization when establishing influenza prevention strategies.

Associations of ambient manganese exposure with brain gray matter thickness and white matter hyperintensities.

Manganese (Mn) exposure is associated with increased risks of dementia and cerebrovascular disease. However, evidence regarding the impact of ambient Mn exposure on brain imaging markers is scarce. We aimed to investigate the association between ambient Mn exposure and brain imaging markers representing neurodegeneration and cerebrovascular lesions. We recruited a total of 936 adults (442 men and 494 women) without dementia, movement disorders, or stroke from the Republic of Korea. Ambient Mn concentrations were predicted at each participant's residential address using spatial modeling. Neurodegeneration-related brain imaging markers, such as the regional cortical thickness, were estimated using 3 T brain magnetic resonance images. White matter hyperintensity volume (an indicator of cerebrovascular lesions) was also obtained from a certain number of participants (n = 397). Linear regression analyses were conducted after adjusting for potential confounders. A log-transformed ambient Mn concentration was associated with thinner parietal (ß = -0.02 mm; 95% confidence interval [CI], -0.05 to -0.01) and occipital cortices (ß = -0.03 mm; 95% CI, -0.04 to -0.01) after correcting for multiple comparisons. These associations remained statistically significant in men. An increase in the ambient Mn concentration was also associated with a greater volume of deep white matter hyperintensity in men (ß = 772.4 mm3, 95% CI: 36.9 to 1508.0). None of the associations were significant in women. Our findings suggest that ambient Mn exposure may induce cortical atrophy in the general adult population.

Health Effects of Microplastic Exposures: Current Issues and Perspectives in South Korea.

Microplastics are environmental pollutants that prevail in the oceans, remote islands, and polar regions. Exposure to microplastics presents a major emerging threat to the ecosystems due to their potential adverse effects. Herein, we reviewed the literature to provide an up-to-date synopsis of the current understanding of the sources, compositions, and adverse effects of microplastics in humans and the environment. Most studies on microplastics have focused on developing standardized methods for monitoring the occurrence, distribution, and movement of microplastics in the environment, as well as developing microplastic substitutes; however, although humans are exposed to microplastics via various routes, research on the adverse effects of microplastics in humans remains limited. Little is known about the impact of microplastics on human health and the toxic effects that may vary depending on the type, size, shape, and concentration of microplastics. Therefore, more research is needed to understand the cellular and molecular mechanisms of microplastic toxicity and related pathologies.

Associations of Particulate Matter Exposures With Brain Gray Matter Thickness and White Matter Hyperintensities: Effect Modification by Low-Grade Chronic Inflammation.

BACKGROUND: Numerous studies have shown the effect of particulate matter exposure on brain imaging markers. However, little evidence exists about whether the effect differs by the level of low-grade chronic systemic inflammation. We investigated whether the level of c-reactive protein (CRP, a marker of systemic inflammation) modifies the associations of particulate matter exposures with brain cortical gray matter thickness and white matter hyperintensities (WMH). METHODS: We conducted a cross-sectional study of baseline data from a prospective cohort study including adults with no dementia or stroke. Long-term concentrations of particulate matter ≤ 10 µm in diameter (PM10) and ≤ 2.5 µm (PM2.5) at each participant's home address were estimated. Global cortical thickness (n = 874) and WMH volumes (n = 397) were estimated from brain magnetic resonance images. We built linear and logistic regression models for cortical thickness and WMH volumes (higher versus lower than median), respectively. Significance of difference in the association between the CRP group (higher versus lower than median) was expressed as P for interaction. RESULTS: Particulate matter exposures were significantly associated with a reduced global cortical thickness only in the higher CRP group among men (P for interaction = 0.015 for PM10 and 0.006 for PM2.5). A 10 µg/m3 increase in PM10 was associated with the higher volumes of total WMH (odds ratio, 1.78; 95% confidence interval, 1.07-2.97) and periventricular WMH (2.00; 1.20-3.33). A 1 µg/m3 increase in PM2.5 was associated with the higher volume of periventricular WMH (odds ratio, 1.66; 95% confidence interval, 1.08-2.56). These associations did not significantly differ by the level of high sensitivity CRP. CONCLUSION: Particulate matter exposures were associated with a reduced global cortical thickness in men with a high level of chronic inflammation. Men with a high level of chronic inflammation may be susceptible to cortical atrophy attributable to particulate matter exposures.

Alzheimer's disease-like cortical atrophy mediates the effect of air pollution on global cognitive function.

Little is known about the effect of air pollution on Alzheimer's disease (AD)-specific brain structural pathologies. There is also a lack of evidence on whether this effect leads to poorer cognitive function. We investigated whether, and the extent to which, AD-like cortical atrophy mediated the association between air pollution exposures and cognitive function in dementia-free adults. We used cross-sectional data from 640 participants who underwent brain magnetic resonance imaging and the Montreal Cognitive Assessment (MoCA). Mean cortical thickness (as the measure of global cortical atrophy) and machine learning-based AD-like cortical atrophy score were estimated from brain images. Concentrations of particulate matter with diameters ≤ 10 µm (PM10) and ≤ 2.5 µm (PM2.5) and nitrogen dioxide (NO2) were estimated based on each participant's residential address. Following the product method, a mediation effect was tested by conducting a series of three regression analyses (exposure to outcome; exposure to mediator; and exposure and mediator to outcome). A 10 µg/m3 increase in PM10 (ß = -1.13; 95 % CI, -1.73 to -0.53) and a 10 ppb increase in NO2 (ß = -1.09; 95 % CI, -1.40 to -0.78) were significantly associated with a lower MoCA score. PM10 (ß = 0.27; 95 % CI, 0.06 to 0.48) and NO2 (ß = 0.35; 95 % CI, 0.25 to 0.45) were significantly associated with an increased AD-like cortical atrophy score. Effects of PM10 and NO2 on MoCA scores were significantly mediated by mean cortical thickness (proportions mediated: 25 %-28 %) and AD-like cortical atrophy scores (13 %-16 %). The findings suggest that air pollution exposures may induce AD-like cortical atrophy, and that this effect may lead to poorer cognitive function in dementia-free adults.

Metabolic traits affecting the relationship between liver fat and intrapancreatic fat: a mediation analysis.

AIMS/HYPOTHESIS: The clinical importance of fat deposition in the liver and pancreas is increasingly recognised. However, to what extent deposition of fat in these two depots is affected by intermediate variables is unknown. The aim of this work was to conduct a mediation analysis with a view to uncovering the metabolic traits that underlie the relationship between liver fat and intrapancreatic fat deposition (IPFD) and quantifying their effect. METHODS: All participants underwent MRI/magnetic resonance spectroscopy on the same 3.0 T scanner to determine liver fat and IPFD. IPFD of all participants was quantified manually by two independent raters in duplicate. A total of 16 metabolic traits (representing markers of glucose metabolism, incretins, lipid panel, liver enzymes, pancreatic hormones and their derivatives) were measured in blood. Mediation analysis was conducted, taking into account age, sex, ethnicity and BMI. Significance of mediation was tested by computing bias-corrected bootstrap CIs with 5000 repetitions. RESULTS: A total of 353 individuals were studied. Plasma glucose, HDL-cholesterol and triacylglycerol mediated 6.8%, 17.9% and 24.3%, respectively, of the association between liver fat and IPFD. Total cholesterol, LDL-cholesterol, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, insulin, glucagon, amylin, C-peptide, HbA1c, glucagon-like peptide-1 and gastric inhibitory peptide did not mediate the association between liver fat and IPFD. CONCLUSIONS/INTERPRETATION: At least one-quarter of the association between liver fat and IPFD is mediated by specific blood biomarkers (triacylglycerol, HDL-cholesterol and glucose), after accounting for potential confounding by age, sex, ethnicity and BMI. This unveils the complexity of the association between the two fat depots and presents specific targets for intervention.

Factors Affecting the Circulating Levels of Oxyntomodulin in Health and After Acute Pancreatitis.

OBJECTIVES: To investigate the factors associated with the circulating levels of oxyntomodulin in healthy individuals and individuals after an episode of acute pancreatitis (AP). METHODS: Blood samples were collected from all participants after an overnight fast and analyzed for 28 biomarkers. Participants also underwent comprehensive body composition analysis on a 3-T magnetic resonance imaging scanner. Regression analyses were done to investigate the associations between oxyntomodulin and the studied factors. RESULTS: The study included 105 individuals who had a primary diagnosis of AP and 58 healthy individuals. Peptide YY (B coefficient, 0.094; 95% confidence interval [95% CI], 0.164-0.123), pancreatic polypeptide (0.048; 95% CI, 0.030-0.066), and leptin (0.394; 95% CI, 0.128-0.661) had significant associations with oxyntomodulin in healthy individuals. Peptide YY was the most prominent factor associated with oxyntomodulin, explaining 60% of its variance in health. Cholecystokinin (0.014; 95% CI, 0.010-0.018), amylin (-0.107; 95% CI, -0.192 to -0.021), and glycated hemoglobin (-0.761; 95% CI, -1.249 to -0.273) had significant associations with oxyntomodulin in individuals after AP. Cholecystokinin was the most prominent factor associated with oxyntomodulin, explaining 44% of its variance after AP. CONCLUSIONS: Factors affecting the circulating levels of oxyntomodulin are different in health and after AP. These insights will enable the determination of populations that benefit from oxyntomodulin therapeutics in the future.

Reduced brain subcortical volumes in patients with glaucoma: a pilot neuroimaging study using the region-of-interest-based approach.

BACKGROUND: While numerous neuroimaging studies have demonstrated that glaucoma is associated with smaller volumes of the visual cortices in the brain, only a few studies have linked glaucoma with brain structures beyond the visual cortices. Therefore, the objective of this study was to compare brain imaging markers and neuropsychological performance between individuals with and without glaucoma. METHODS: We identified 64 individuals with glaucoma and randomly selected 128 age-, sex-, and education level-matched individuals without glaucoma from a community-based cohort. The study participants underwent 3 T brain magnetic resonance imaging and neuropsychological assessment battery. Regional cortical thickness and subcortical volume were estimated from the brain images of the participants. We used a linear mixed model after adjusting for potential confounding variables. RESULTS: Cortical thickness in the occipital lobe was significantly smaller in individuals with glaucoma than in the matched individuals (ß = - 0.04 mm, P = 0.014). This did not remain significant after adjusting for cardiovascular risk factors (ß = - 0.02 mm, P = 0.67). Individuals with glaucoma had smaller volumes of the thalamus (ß = - 212.8 mm3, P = 0.028), caudate (ß = - 170.0 mm3, P = 0.029), putamen (ß = - 151.4 mm3, P = 0.051), pallidum (ß = - 103.6 mm3, P = 0.007), hippocampus (ß = - 141.4 mm3, P = 0.026), and amygdala (ß = - 87.9 mm3, P = 0.018) compared with those without glaucoma. Among neuropsychological battery tests, only the Stroop color reading test  score was significantly lower in individuals with glaucoma compared with those without glaucoma (ß = - 0.44, P = 0.038). CONCLUSIONS: We found that glaucoma was associated with smaller volumes of the thalamus, caudate, putamen, pallidum, amygdala, and hippocampus.

Risk of Cerebro-Cardiovascular Diseases among Police Officers and Firefighters: A Nationwide Retrospective Cohort Study.

PURPOSE: Police officers and firefighters are exposed to risk factors for cerebro-cardiovascular diseases, and the actual risk is expected to increase compared with other occupational groups. The present study aimed to estimate the risks of cerebro-cardiovascular diseases in police officers and firefighters compared to other occupational groups. MATERIALS AND METHODS: Using the National Health Insurance Service data, we constructed a retrospective cohort of public officers. Three-year consecutive health insurance registration data were used to identify police officers and firefighters. Cerebro-cardiovascular diseases consisted of acute myocardial infarction, other ischemic heart disease, cardiac arrhythmia, and stroke. We compared the incidences of cerebro-cardiovascular diseases between each of the two occupational groups (police officers and firefighters) and other public officers by calculating standardized incidence ratios (SIRs). RESULTS: SIRs and 95% confidence intervals of all cerebro-cardiovascular diseases for police officers and firefighters were 1.71 (1.66-1.76) and 1.22 (1.12-1.31), respectively, as compared with all public officers. The incidence ratios remained significantly higher compared to general and education officers. Subgroup analyses for myocardial infarction, stroke, and cardiac arrhythmia exhibited significant increases in incidence ratios among police officers and firefighters. CONCLUSION: This study suggests that both police officers and firefighters are at high risk of cerebro-cardiovascular diseases. Therefore, medical protection measures for these occupational groups should be improved.

Cost-effectiveness of Direct Oral Anticoagulant vs. Warfarin Among Atrial Fibrillation Patients With Intermediate Stroke Risk.

Background: Several studies have shown the cost-effectiveness of direct oral anticoagulants (DOACs), compared with warfarin, to prevent atrial fibrillation (AF) related complications. However, few have reported cost-effectiveness of DOACs in AF patients with intermediate stroke risk. Thus, we investigated the cost-effectiveness of DOACs vs. warfarin in non-valvular AF patients with intermediate stroke risk using national representative data. Methods: We identified 7,954 newly diagnosed non-valvular AF patients (≥18 years) with intermediate stroke risk (CHA2DS2-VASc score: 1 for men and 2 for women) using the national healthcare utilization data from August 1, 2016, to July 31, 2019. Annual incidence rate of AF-related composite outcomes (heat failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, and gastrointestinal bleeding) was estimated. Cost-effectiveness was estimated using a Markov chain model with the transition probability of 1 year. The willingness-to-pay (WTP) was set at $32,000 per quality-adjusted life-year (QALY) gained. Results: The total cost of warfarin, rivaroxaban, apixaban, dabigatran and edoxaban was $2,874, $5,761, $5,151, $5,761 and $5,851, respectively. The QALYs gained were 10.83, 10.95, 11.10, 10.49 and 10.99 years, respectively. The incremental cost-effectiveness ratio of rivaroxaban, apixaban, dabigatran and edoxaban was $29,743.99, $8,426.71, -$8,483.04 and $18,483.55, respectively. The WTP was set at $32,000. DOACs (except dabigatran) were more cost-effective compared with warfarin because they did not exceed the WTP in the base-case analysis. Conclusion: Our findings showed that DOACs were more cost-effective than warfarin in non-valvular AF patients with intermediate stroke risk.

Fat Distribution Within the Pancreas According to Diabetes Status and Insulin Traits.

A growing body of evidence suggests that intrapancreatic fat is associated with diabetes, but whether distribution of intrapancreatic fat across the regions of the pancreas has a pathophysiologic role is unknown. The aim of this study was to investigate the differences in intrapancreatic fat deposition between the head, body, and tail of the pancreas, as well as the relationship between regional intrapancreatic fat deposition and diabetes status and insulin traits. A total of 368 adults from the general population underwent MRI on a 3 Tesla scanner, and intrapancreatic fat was manually quantified in duplicate. Statistical models included adjustment for age, sex, ethnicity, BMI, and liver fat. Intrapancreatic fat deposition in the head, body, and tail of the pancreas did not differ significantly in adjusted models in either the overall cohort or the three subgroups based on diabetes status. HOMA of insulin resistance and fasting insulin were significantly positively associated with fat in the tail and body of the pancreas. There was no significant association between regional intrapancreatic fat and HOMA of ß-cell function. The association of increased intrapancreatic fat deposition in the tail and body regions with increased insulin resistance may have an important role in the early identification of patients at risk for developing insulin resistance and diseases that stem from it.

Glucose variability during the early course of acute pancreatitis predicts two-year probability of new-onset diabetes: A prospective longitudinal cohort study.

BACKGROUND: Acute pancreatitis (AP) is the largest contributor to diabetes of the exocrine pancreas. However, there is no accurate predictor at the time of hospitalisation for AP to identify individuals at high risk for new-onset diabetes. OBJECTIVE: To investigate the accuracy of indices of glucose variability (GV) during the early course of AP in predicting the glycated haemoglobin (HbA1c) trajectories during follow-up. METHODS: This was a prospective longitudinal cohort study of patients without diabetes at the time of hospitalisation for AP. Fasting blood glucose was regularly measured over the first 72 h of hospital admission. The study endpoint was the HbA1c trajectories - high-increasing, moderate-stable, normal-stable - over two years of follow-up. Multinomial logistic regression analyses were conducted to investigate the associations between several common GV indices and the HbA1c trajectories, adjusting for covariates (age, sex, and body mass index). A sensitivity analysis constrained to patients with non-necrotising AP was conducted. RESULTS: A total of 120 consecutive patients were studied. All patients in the high-increasing HbA1c trajectory group had new-onset diabetes at 18 and 24 months of follow-up. Glycaemic lability index had the strongest significant direct association (adjusted odds ratio = 13.69; p = 0.040) with the high-increasing HbA1c trajectory. High admission blood glucose, standard deviation of blood glucose, and average real variability significantly increased the patients' odds of taking the high-increasing HbA1c trajectory by at least two-times. Admission blood glucose, but not the other GV indices, had a significant direct association (adjusted odds ratio = 1.46; p = 0.034) with the moderate-stable HbA1c trajectory. The above findings did not change materially in patients with non-necrotising AP alone. CONCLUSIONS: High GV during the early course of AP gives a prescient warning of worsening HbA1c pattern and new-onset diabetes after hospital discharge. Determining GV during hospitalisation could be a relatively straightforward approach to early identification of individuals at high risk for new-onset diabetes after AP.

Relationship between Energy Balance and Circulating Levels of Hepcidin and Ferritin in the Fasted and Postprandial States.

Markers of iron metabolism are altered in new-onset diabetes, but their relationship with metabolic signals involved in the maintenance of energy balance is poorly understood. The primary aim was to explore the associations between markers of iron metabolism (hepcidin and ferritin) and markers of energy balance (leptin, ghrelin, and the leptin/ghrelin ratio) in both the fasted and postprandial states. These associations were also studied in the sub-groups stratified by diabetes status. This was a cross-sectional study of individuals without disorders of iron metabolism who were investigated after an overnight fast and, in addition, some of these individuals underwent a mixed meal test to determine postprandial responses of metabolic signals. The associations between hepcidin, ferritin, and leptin, ghrelin, leptin/ghrelin ratio were studied using several multiple linear regression models. A total of 76 individuals in the fasted state and 34 individuals in the postprandial state were included. In the overall cohort, hepcidin was significantly inversely associated with leptin (in the most adjusted model, the ß coefficient ± SE was -883.45 ± 400.94; p = 0.031) and the leptin/ghrelin ratio (in the most adjusted model, the ß coefficient ± SE was -148.26 ± 61.20; p = 0.018) in the fasted state. The same associations were not statistically significant in the postprandial state. In individuals with new-onset prediabetes or diabetes (but not in those with normoglycaemia or longstanding prediabetes or diabetes), hepcidin was significantly inversely associated with leptin (in the most adjusted model, the ß coefficient ± SE was -806.09 ± 395.44; p = 0.050) and the leptin/ghrelin ratio (in the most adjusted model, the ß coefficient ± SE was -129.40 ± 59.14; p = 0.037). Leptin appears to be a mediator in the link between iron metabolism and new-onset diabetes mellitus. These findings add to the growing understanding of mechanisms underlying the derangements of glucose metabolism.

Developing a Dementia Platform Databank Using Multiple Existing Cohorts.

This study was conducted as a pilot project to evaluate the feasibility of building an integrate dementia platform converging preexisting dementia cohorts from several variable levels. The following four cohorts were used to develop this pilot platform: 1) Clinical Research Center for Dementia of South Korea (CREDOS), 2) Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's disease (K-BASE), 3) Environmental Pollution-induced Neurological Effects (EPINEF) study, and 4) a prospective registry in Dementia Platform Korea project (DPKR). A total of 29916 patients were included in the platform with 348 integrated variables. Among participants, 13.9%, 31.5%, and 44.2% of patients had normal cognition, mild cognitive impairment, and dementia, respectively. The mean age was 72.4 years. Females accounted for 65.7% of all patients. Those with college or higher education and those without problems in reading or writing accounted for 12.3% and 46.8%, respectively. Marital status, cohabitation, family history of Parkinson's disease, smoking and drinking status, physical activity, sleep status, and nutrition status had rates of missing information of 50% or more. Although individual cohorts were of the same domain and of high quality, we found there were several barriers to integrating individual cohorts, including variability in study variables and measurements. Although many researchers are trying to combine pre-existing cohorts, the process of integrating past data has not been easy. Therefore, it is necessary to establish a protocol with considerations for data integration at the cohort establishment stage.