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.

Suicide loss, changes in medical care utilization, and hospitalization for cardiovascular disease and diabetes mellitus.

AIMS: The impact of suicide loss on family members' cardiometabolic health has little been evaluated in middle-aged and elderly people. We investigated the effect of suicide loss on risks for cardiovascular disease (CVD) and diabetes mellitus (DM) in suicide completers' family members using a national representative comparison group. METHODS AND RESULTS: The study subjects were 4253 family members of suicide completers and 9467 non-bereaved family members of individuals who were age and gender matched with the suicide completers in the Republic of Korea. National health insurance data were used to identify medical care utilization during the year before and after a suicide loss. A recurrent-events survival analysis was performed to estimate the hazard ratios (HRs) of hospitalizations for CVD, DM, or psychiatric disorders, after adjusting for age, residence, and socioeconomic status. Among subjects without a past history of CVD, DM, or psychiatric disorders, the increased risks of recurrent hospitalizations were observed for CVD [HR 1.343, 95% confidence interval (CI) 1.001-1.800 in men; HR 1.240, 95% CI 1.025-1.500 in women] and DM (HR 2.238, 95% CI 1.379-3.362 in men; HR 1.786, 95% CI 1.263-2.527 in women). In subjects with a past history of CVD, DM, or psychiatric disorders, the number of medical care visits decreased after a suicide loss, and suicide completers' family members showed lower rates of hospitalization for CVD and DM than the comparison group. CONCLUSION: Compared with non-bereaved family members, suicide completers' family members without a past history of CVD, DM, or psychiatric disorder showed a high risk of hospitalization for those conditions.

Association between body mass index and cortical thickness: among elderly cognitively normal men and women.

BACKGROUND: There is increasing evidence of a relationship between underweight or obesity and dementia risk. Several studies have investigated the relationship between body weight and brain atrophy, a pathological change preceding dementia, but their results are inconsistent. Therefore, we aimed to evaluate the relationship between body mass index (BMI) and cortical atrophy among cognitively normal participants. METHODS: We recruited cognitively normal participants (n = 1,111) who underwent medical checkups and detailed neurologic screening, including magnetic resonance imaging (MRI) in the health screening visits between September 2008 and December 2011. The main outcome was cortical thickness measured using MRI. The number of subjects with five BMI groups in men/women was 9/9, 148/258, 185/128, 149/111, and 64/50 in underweight, normal, overweight, mild obesity, and moderate to severe obesity, respectively. Linear and non-linear relationships between BMI and cortical thickness were examined using multiple linear regression analysis and generalized additive models after adjustment for potential confounders. RESULTS: Among men, underweight participants showed significant cortical thinning in the frontal and temporal regions compared to normal weight participants, while overweight and mildly obese participants had greater cortical thicknesses in the frontal region and the frontal, temporal, and occipital regions, respectively. However, cortical thickness in each brain region was not significantly different in normal weight and moderate to severe obesity groups. Among women, the association between BMI and cortical thickness was not statistically significant. CONCLUSIONS: Our findings suggested that underweight might be an important risk factor for pathological changes in the brain, while overweight or mild obesity may be inversely associated with cortical atrophy in cognitively normal elderly males.

Association between exposure to polycyclic aromatic hydrocarbons and brain cortical thinning: The Environmental Pollution-Induced Neurological EFfects (EPINEF) study.

BACKGROUND: Although some studies have suggested that exposure to polycyclic aromatic hydrocarbons (PAHs) induces neurodevelopmental disturbances in children and neurodegeneration in animals, the neurotoxic effect of PAH exposure is unclear in adults. The aim was to examine the associations of PAH exposure with brain structure and neuropsychological function in adults without known neurological diseases. METHODS: This study included 421 men and 528 women dwelling in four cities in the Republic of Korea. Urinary concentrations of four PAH metabolites (1-hydroxypyrene, 2-naphthol, 1-hydroxyphenanthrene, and 2-hydroxyfluorene) were obtained. Participants underwent brain 3 T magnetic resonance imaging and neuropsychological tests. Cortical thickness and volume were estimated using the region-of-interest method. Separate generalized linear models were constructed for each sex, adjusting for age, years of education, cohabitation status, income, tobacco use, alcohol consumption, and vascular risk factors. RESULTS: The mean (standard deviation) age was 68.3 (6.6) years in men and 66.4 (6.1) years in women. In men, those in quartile 4 (versus quartile 1, the lowest) of urinary 2-naphthol concentration had cortical thinning in the global (ß = -0.03, P = .02), parietal (ß = -0.04, P = .01), temporal (ß = -0.06, P < .001), and insular lobes (ß = -0.05, P = .02). Higher quartiles of urinary 2-naphthol concentration were associated with cortical thinning in the global (P = .01), parietal (P = .004), temporal (P < .001), and insular lobes (P = .01). In women, those in quartile 4 (versus quartile 1) of urinary 1-hydroxypyrene concentration had cortical thinning in the frontal (ß = -0.03, P = .006) and parietal lobes (ß = -0.03, P = .003). Higher quartiles of urinary 1-hydroxypyrene concentration were associated with cortical thinning in the frontal (P = .006) and parietal lobes (P = .001). In both sexes, verbal learning and memory scores significantly declined with an increase in quartile of urinary 1-hydroxypyrene concentration. CONCLUSIONS: PAH exposure was associated with cortical thinning and decline in verbal learning and memory function in cognitively healthy adults. This suggests PAHs as an environmental risk factor for neurodegeneration.

Long-Term Ambient Air Pollution Exposures and Brain Imaging Markers in Korean Adults: The Environmental Pollution-Induced Neurological EFfects (EPINEF) Study.

BACKGROUND: Only a limited number of neuroimaging studies have explored the effects of ambient air pollution in adults. The prior studies have investigated only cortical volume, and they have reported mixed findings, particularly for gray matter. Furthermore, the association between nitrogen dioxide (NO2) and neuroimaging markers has been little studied in adults. OBJECTIVES: We investigated the association between long-term exposure to air pollutants (NO2, particulate matter (PM) with aerodynamic diameters of ≤10µm (PM10) and ≤2.5µm (PM2.5), and neuroimaging markers. METHODS: The study included 427 men and 530 women dwelling in four cities in the Republic of Korea. Long-term concentrations of PM10, NO2, and PM2.5 at residential addresses were estimated. Neuroimaging markers (cortical thickness and subcortical volume) were obtained from brain magnetic resonance images. A generalized linear model was used, adjusting for potential confounders. RESULTS: A 10-µg/m3 increase in PM10 was associated with reduced thicknesses in the frontal [-0.02mm (95% CI: -0.03, -0.01)] and temporal lobes [-0.06mm (95% CI: -0.07, -0.04)]. A 10-µg/m3 increase in PM2.5 was associated with a thinner temporal cortex [-0.18mm (95% CI: -0.27, -0.08)]. A 10-ppb increase in NO2 was associated with reduced thicknesses in the global [-0.01mm (95% CI: -0.01, 0.00)], frontal [-0.02mm (95% CI: -0.03, -0.01)], parietal [-0.02mm (95% CI: -0.03, -0.01)], temporal [-0.04mm (95% CI: -0.05, -0.03)], and insular lobes [-0.01mm (95% CI: -0.02, 0.00)]. The air pollutants were also associated with increased thicknesses in the occipital and cingulate lobes. Subcortical structures associated with the air pollutants included the thalamus, caudate, pallidum, hippocampus, amygdala, and nucleus accumbens. DISCUSSION: The findings suggest that long-term exposure to high ambient air pollution may lead to cortical thinning and reduced subcortical volume in adults. https://doi.org/10.1289/EHP7133.

Correction: Big data and analysis of risk factors for gallbladder disease in the young generation of Korea.

[This corrects the article DOI: 10.1371/journal.pone.0211480.].

Cost-Effectiveness of Rivaroxaban Compared to Warfarin for Stroke Prevention in Atrial Fibrillation.

BACKGROUND AND OBJECTIVES: Rivaroxaban is noninferior to warfarin for preventing stroke or systemic embolism in patients with high-risk atrial fibrillation (AF) and is associated with a lower rate of intracranial hemorrhage (ICH). We assessed the cost-effectiveness of rivaroxaban compared to adjusted-dose warfarin for the prevention of stroke in patients with nonvalvular AF. METHODS: We built a Markov model using the Korean Health Insurance Review & Assessment Service database. The base-case analysis assumed a cohort of patients with prevalent AF who were aged 18 years or older without contraindications to anticoagulation. RESULTS: Number of patients with CHA2DS2-VASc scores 0, 1 and ≥2 were 56 (0.2%), 1,944 (6.3%) and 28,650 (93.5%), respectively. In patients with CHA2DS2-VASc scores ≥2, the incidence rate of ischemic stroke was 3.11% and 3.76% in warfarin and rivaroxaban groups, respectively. The incidence rates of ICH were 0.42% and 0.15%, and those of gastrointestinal bleeding were 0.32% and 0.15% in warfarin and rivaroxaban, respectively. Patients with AF treated with rivaroxaban lived an average of 11.8 quality-adjusted life years (QALYs) at a lifetime treatment cost of $20,886. Those receiving warfarin lived an average of 11.4 QALYs and incurred costs of $17,151. Patients with rivaroxaban gained an additional 0.4 QALYs over a lifetime with an additional cost of $3,735, resulting in an incremental cost-effectiveness ratio of $9,707 per QALY. CONCLUSIONS: Patients who had been treated with rivaroxaban may be a cost-effective alternative to warfarin for stroke prevention in Korean patients with AF.

Big data and analysis of risk factors for gallbladder disease in the young generation of Korea.

BACKGROUND/PURPOSE: Few studies have examined the risk factors for gallbladder (GB) disease in young adults. This study aimed to evaluate risk factors for GB disease in young adults based on big data in Korea. METHODS: All participants underwent routine checkup at the Korea Medical Institute from June 2014 to May 2015. After excluding 677 individuals with missing information in records, 724,114 individuals (435,635 men, 288,479 women) were finally included. The definition of abnormal GB finding included stones, sludge, polyps, and adenomyomatosis detected using ultrasonography. All statistical analyses were performed using SAS software version 9.2. RESULTS: Overall, 27,130 (17.5%) individuals were diagnosed as having abnormal GB finding in the young age group (N = 154,463, aged 20-39 years). In men, significant differences in low-density lipoprotein (LDL) and cholesterol levels were observed between the abnormal GB finding group and normal GB group (p < 0.05). In women, a significant difference in smoking history was noted between the abnormal GB finding group and normal GB group (p < 0.05). The prevalence rate of GB stones was 1.9% (27,979/154,463) in the young age group. High body mass index (BMI), large thigh circumference, and low high-density lipoprotein (HDL) level in women and low HDL level in men were independent risk factors for the presence of GB stones (p < 0.05). CONCLUSION: In this study, obesity-related factors (BMI, waist size, thigh circumference, and cholesterol, LDL, and HDL levels) correlated with GB disease in the young generation of Korea.

Prediction Models of Cognitive Trajectories in Patients with Nonamnestic Mild Cognitive Impairment.

To evaluate prediction models of cognitive trajectories in patients with nonamnestic mild cognitive impairment (naMCI) using group-based trajectory analysis, we evaluated 121 patients with naMCI who underwent at least their first three yearly assessments. Group-based trajectory models were used to classify cognitive trajectories based on Clinical Dementia Rating Sum of Boxes scores over four years in patients with naMCI. A total of 22 patients (18.2%) were classified into the "fast-decliners" group, while 99 patients (81.8%) were classified into the "slow-decliners" group. The mean age was higher in the fast-decliners than in the slow-decliners (p = 0.037). Compared to the slow-decliners, the fast-decliners were more frequently impaired in the domains of language (p = 0.038) and frontal/executive functions (p = 0.042), and had more frequent multiple-domain cognitive impairment (p = 0.006) on baseline neuropsychological tests. The rate of conversion to dementia was significantly higher in the fast-decliners than in the slow-decliners (86.4% vs. 10.1%, p < 0.001). Our findings showed that there are indeed distinct patterns of cognitive trajectories in patients with naMCI. Close observation of naMCI patients' baseline demographic and clinical profiles in clinical settings may help identify individuals at greatest risk for dementia.

Effect of Socioeconomic Status and Underlying Disease on the Association between Ambient Temperature and Ischemic Stroke.

PURPOSE: Inconsistent findings have been reported regarding the effect of ambient temperature on ischemic stroke. Furthermore, little is known about how underlying disease and low socioeconomic status influence the association. We, therefore, investigated the relationship between ambient temperature and emergency department (ED) visits for ischemic stroke, and aimed to identify susceptible populations. MATERIALS AND METHODS: Using medical claims data, we identified ED visits for ischemic stroke during 2005-2009 in Seoul, Korea. We conducted piecewise linear regression analyses to find optimum ambient temperature thresholds in summer and winter, and estimated the relative risks (RR) and 95% confidence intervals (CI) per a 1°C increase in temperature above/below the thresholds, adjusting for relative humidity, holidays, day of the week, and air pollutant levels. RESULTS: There were 63564 ED visits for ischemic stroke. In summer, the risk of ED visits for ischemic stroke was not significant, with the threshold at 26.8°C. However, the RRs were 1.055 (95% CI, 1.006-1.106) above 25.0°C in medical aid beneficiaries and 1.044 (1.007-1.082) above 25.8°C in patients with diabetes. In winter, the risk of ED visits for ischemic stroke significantly increased as the temperature decreased above the threshold at 7.2°C. This inverse association was significant also in patients with hypertension and diabetes mellitus above threshold temperatures. CONCLUSION: Ambient temperature increases above a threshold were positively associated with ED visits for ischemic stroke in patients with diabetes and medical aid beneficiaries in summer. In winter, temperature, to a point, and ischemic stroke visits were inversely associated.

Short-term Effects of Ambient Air Pollution on Emergency Department Visits for Asthma: An Assessment of Effect Modification by Prior Allergic Disease History.

OBJECTIVES: The goal of this study was to investigate the short-term effect of ambient air pollution on emergency department (ED) visits in Seoul for asthma according to patients' prior history of allergic diseases. METHODS: Data on ED visits from 2005 to 2009 were obtained from the Health Insurance Review and Assessment Service. To evaluate the risk of ED visits for asthma related to ambient air pollutants (carbon monoxide [CO], nitrogen dioxide [NO2], ozone [O3], sulfur dioxide [SO2], and particulate matter with an aerodynamic diameter <10 µm [PM10]), a generalized additive model with a Poisson distribution was used; a single-lag model and a cumulative-effect model (average concentration over the previous 1-7 days) were also explored. The percent increase and 95% confidence interval (CI) were calculated for each interquartile range (IQR) increment in the concentration of each air pollutant. Subgroup analyses were done by age, gender, the presence of allergic disease, and season. RESULTS: A total of 33 751 asthma attack cases were observed during the study period. The strongest association was a 9.6% increase (95% CI, 6.9% to 12.3%) in the risk of ED visits for asthma per IQR increase in O3 concentration. IQR changes in NO2 and PM10 concentrations were also significantly associated with ED visits in the cumulative lag 7 model. Among patients with a prior history of allergic rhinitis or atopic dermatitis, the risk of ED visits for asthma per IQR increase in PM10 concentration was higher (3.9%; 95% CI, 1.2% to 6.7%) than in patients with no such history. CONCLUSIONS: Ambient air pollutants were positively associated with ED visits for asthma, especially among subjects with a prior history of allergic rhinitis or atopic dermatitis.

Air pollution and unintentional injury deaths in South Korea.

This study aimed to assess the association between exposure to air pollution and unintentional injury deaths in South Korea. Data regarding all unintentional injury deaths (17,566) in seven metropolitan cities from 2002 to 2008 were collected. Using a time-stratified case-crossover study, conditional logistic regression and subgroup analyses were performed after stratification by age, gender, and season. To evaluate immediate and delayed effects of air pollutants, we used both single lag and distributed lag models. The risk was expressed as an odds ratio (OR) per one interquartile range (IQR) of each air pollutant. During the study period, the median (IQR) levels of air pollutants were 0.005 (0.004-0.007) ppm for sulfur dioxide (SO2), 0.02 (0.02-0.03) ppm for nitrogen dioxide (NO2), 0.03 (0.02-0.04) ppm for ozone (O3), 48.3 (34.9-67.0) µg/m(3) for particulate matter ≤10 µm in aerodynamic diameter (PM10), and 0.36 (0.1-0.6) ppm for carbon monoxide (CO). All air pollutants, with the exception of PM10 and O3, were significantly associated with an increased risk of unintentional injury deaths; the maximum risk was observed in the distributed lag 1 model for SO2 (OR, 1.119; 95% confidence interval, 1.022-1.226), NO2 (1.208; 1.043-1.400), and CO (1.012; 1.000-1.024). After stratification of the subjects by age, SO2, NO2, and CO were significantly associated with increased risk of unintentional injury deaths among subjects aged 60 years or older in the distributed lag 1 model, while O3 and PM10 were associated with increased risk among subjects aged 40 to 59 years. However, in subjects younger than 40 years of age, we found no significant associations for any of the air pollutants. Our study suggested evidence for a short-term association between air pollutants and unintentional injury deaths, even at low pollutants levels.

Admission route and use of invasive procedures during hospitalization for acute myocardial infarction: analysis of 2007-2011 National Health Insurance database.

OBJECTIVES: The goal of this study was to investigate trends in admission to the emergency department and the use of invasive or surgical procedures during hospitalization for acute myocardial infarction (AMI) in Korea. METHODS: The National Health Insurance (NHI) claims database between 2007 and 2011 was used. We identified all admission claims that included codes from the tenth revision of the International Classification of Diseases beginning with I21 as the primary or secondary diagnosis. Information about the admission route, admission date, discharge date, and whether coronary artery angiography, angioplasty, or bypass surgery was performed was also obtained from the NHI database. RESULTS: Of the 513,886 relevant admission claims over the five years encompassed by this study, 295,001 discrete episodes of admission for AMI were identified by analyzing the date and length of each admission and the interval between admissions. The number of AMI admissions gradually decreased from 66,883 in 2007 to 47,656 in 2011. The number and proportion of admissions through the emergency department also decreased from 38,118 (57.0%) in 2007 to 24,001 (50.4%) in 2011. However, during the same period, admissions in which invasive or surgical procedures were performed increased from 15,342 (22.9%) to 17,505 (36.7%). CONCLUSIONS: The reported numbers of emergency department visits and admissions for AMI decreased from 2007 to 2011. However, only a small portion of the patients underwent invasive or surgical procedures during hospitalization, although the number of admissions involving invasive or surgical procedures has increased. These findings suggest that simply counting the number of admission claims cannot provide valid information on trends in AMI occurrence.

Ambient ozone concentration and emergency department visits for panic attacks.

The effect of ambient air pollution on panic disorder in the general population has not yet been thoroughly elucidated, although the occurrence of panic disorder in workers exposed to organic solvents has been reported previously. We investigated the association of ambient air pollution with the risk of panic attack-related emergency department visits. Using health insurance claims, we collected data from emergency department visits for panic attacks in Seoul, Republic of Korea (2005-2009). Daily air pollutant concentrations were obtained using automatic monitoring system data. We conducted a time-series study using a generalized additive model with Poisson distribution, which included spline variables (date of visit, daily mean temperature, and relative humidity) and parametric variables (daily mean air pollutant concentration, national holiday, and day of the week). In addition to single lag models (lag1 to lag3), cumulative lag models (lag0-1 to lag0-3) were constructed using moving-average concentrations on the days leading up to the visit. The risk was expressed as relative risk (RR) per one standard deviation of each air pollutant and its 95% confidence interval (95% CI). A total of 2320 emergency department visits for panic attacks were observed during the study period. The adjusted RR of panic attack-related emergency department visits was 1.051 (95% CI, 1.014-1.090) for same-day exposure to ozone. In cumulative models, adjusted RRs were 1.068 (1.029-1.107) in lag0-2 and 1.074 (1.035-1.114) in lag0-3. The ambient ozone concentration was significantly associated with emergency department visits for panic attacks.

Changes in the Practice of Coronary Revascularization between 2006 and 2010 in the Republic of Korea.

PURPOSE: Evidence suggests that technological innovations and reimbursement schemes of the National Health Insurance Service may have impacted the management of coronary artery disease. Thus, we investigated changes in the practice patterns of coronary revascularization. MATERIALS AND METHODS: Revascularization and in-hospital mortality among Koreans ≥20 years old were identified from medical claims filed between 2006 and 2010. The age- and sex-standardized procedure rate per 100,000 person-years was calculated directly from the distribution of the 2008 Korean population. RESULTS: The coronary revascularization rate increased from 116.1 (95% confidence interval, 114.9-117.2) in 2006 to 131.0 (129.9-132.1) in 2010. Compared to the rate ratios in 2006, the rate ratios for percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery in 2010 were 1.16 (1.15-1.17) and 0.80 (0.76-0.84), respectively. Among patients who received PCI, the percentage with drug-eluting stents increased from 89.1% in 2006 to 93.0% in 2010. In-hospital mortality rates from PCI significantly increased during the study period (p=0.03), whereas those from CABG significantly decreased (p=0.01). The in-hospital mortality rates for PCI and CABG were higher in elderly and female patients and at the lowest-volume hospitals. CONCLUSION: The annual volume of coronary revascularization continuously increased between 2006 and 2010 in Korea, although this trend differed according to procedure type. A high percentage of drug-eluting stent procedures and a high rate of in-hospital mortality at low-volume hospitals were noted.

Air pollution as a risk factor for depressive episode in patients with cardiovascular disease, diabetes mellitus, or asthma.

BACKGROUND: There is currently insufficient evidence to confirm the effect of ambient air pollution on mental disorders, especially among susceptible populations. This study investigated the short-term effect of ambient air pollution on the risk of depressive episode and the effect modification across disease subpopulations. METHODS: Subjects who visited the emergency department (ED) for depressive episode from 2005 to 2009 (n=4985) in Seoul, Republic of Korea were identified from medical claims data. We conducted a time-stratified case-crossover study using conditional logistic regression. Subgroup analyses were conducted after the subjects were stratified by underlying disease (cardiovascular disease, diabetes mellitus, chronic obstructive pulmonary disease, asthma, and depressive disorder). The risk was expressed as an odds ratio (OR) per 1 standard deviation of each air pollutant. RESULTS: SO2, PM10, NO2, and CO were positively associated with ED visits for depressive episode. The maximum risk was observed in the distributed lag 0-3 model for PM10 (OR, 1.120; 95% confidence interval, 1.067-1.176). PM10, NO2, and CO significantly increased the risks of ED visits for depressive episode in subjects with either underlying cardiovascular disease, diabetes mellitus, asthma, or depressive disorder. LIMITATIONS: Our data may include a misclassification bias due to the validity of a diagnosis determined from medical services utilization data. CONCLUSIONS: SO2, PM10, NO2, and CO significantly increased the risk of ED visits for depressive episode, especially among individuals with pre-existing cardiovascular disease, diabetes mellitus, or asthma.