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1.
Yonsei Medical Journal ; : 217-226, 2024.
Artigo em Inglês | WPRIM | ID: wpr-1045607

RESUMO

Purpose@#Research on the relationship between diet and dementia among Koreans are lacking. This study investigated the association between dietary habits and dementia progression over 3 years in patients with Alzheimer’s disease dementia (ADD). @*Materials and Methods@#This study included 705 patients with mild-to-moderate ADD. Dietary habits were assessed using the Mini Dietary Assessment Index, comprising 10 questions. Outcome measures included the Clinical Dementia Rating scale-Sum of Boxes (CDR-SB), Seoul-Instrumental Activities of Daily Living, Caregiver-Administered Neuropsychiatric Inventory (CGA-NPI), and neuropsychological test battery (NTB) z-scores, which were evaluated annually over 3 years. @*Results@#In Q10 (eat all food evenly without being picky), the 3-year mean differences in CDR-SB (increases in scores represent worsening) compared to the “rarely” group were -1.86 [95% confidence interval (CI)=-3.64 – -0.09, p=0.039] for the “usually” group and -2.23 (95% CI=-4.40 – -0.06, p=0.044) for the “always” group. In Q7 (add salt or soy sauce to food when eating), the 3-year mean differences in CDR-SB compared to the “always” group were -2.47 (95% CI=-4.70 – -0.24, p=0.030) for the “usually” group and -3.16 (95% CI=-5.36 – -0.96, p=0.005) for the “rarely” group. The “rarely” and “usually” groups in Q7 showed significantly less decline in NTB z-score and CGA-NPI compared to the “always” group. @*Conclusion@#Eating a balanced diet and reducing salt intake were associated with a slower decline in dementia severity, cognition, and behavioral alterations in patients with ADD.

2.
Artigo em Inglês | WPRIM | ID: wpr-1042797

RESUMO

The Korean Dementia Association (KDA) has been organizing biennial international academic conferences since 2019, with the International Conference of the KDA (IC-KDA) 2023 held in Busan under the theme ‘Beyond Boundaries: Advancing Global Dementia Solutions.’ The conference comprised 6 scientific sessions, 3 plenary lectures, and 4luncheon symposiums, drawing 804 participants from 35 countries. Notably, a Korea– Taiwan Joint Symposium addressed insights into Alzheimer’s disease (AD). Plenary lectures by renowned scholars explored topics such as microbiome-related AD pathogenesis, social cognition in neurodegenerative diseases, and genetic frontotemporal dementia (FTD). On the first day, specific presentations covered subjects like the gut–brain axis and neuroinflammation in dementia, blood-based biomarkers in AD, and updates in AD therapeutics. The second day’s presentations addressed recent issues in clinical neuropsychology, FTD cohort studies, and the pathogenesis of non-AD dementia. The Academic Committee of the KDA compiles lecture summaries to provide comprehensive understanding of the advanced dementia knowledge presented at IC-KDA 2023.

3.
Artigo em Inglês | WPRIM | ID: wpr-1042799

RESUMO

Background@#and Purpose: This study aimed to evaluate the brain magnetic resonance imaging (MRI) of patients with acute transient global amnesia (TGA) using volumetric analysis to verify whether the brains of TGA patients have pre-existing structural abnormalities. @*Methods@#We evaluated the brain MRI data from 87 TGA patients and 20 age- and sexmatched control subjects. We included brain MRIs obtained from TGA patients within 72 hours of symptom onset to verify the pre-existence of structural change. For voxel-based morphometric analyses, statistical parametric mapping was employed to analyze the structural differences between patients with TGA and control subjects. @*Results@#TGA patients exhibited significant volume reductions in the bilateral ventral anterior cingulate cortices (corrected p<0.05). @*Conclusions@#TGA patients might have pre-existing structural changes in bilateral ventral anterior cingulate cortices prior to TGA attacks.

4.
Artigo em Inglês | WPRIM | ID: wpr-1042802

RESUMO

Background@#and Purpose: Dementia subtypes, including Alzheimer’s dementia (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), pose diagnostic challenges. This review examines the effectiveness of 18 F-Fluorodeoxyglucose Positron Emission Tomography ( 18 F-FDG PET) in differentiating these subtypes for precise treatment and management. @*Methods@#A systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted using databases like PubMed and Embase to identify studies on the diagnostic utility of 18 F-FDG PET in dementia. The search included studies up to November 16, 2022, focusing on peer-reviewed journals and applying the goldstandard clinical diagnosis for dementia subtypes. @*Results@#From 12,815 articles, 14 were selected for final analysis. For AD versus FTD, the sensitivity was 0.96 (95% confidence interval [CI], 0.88–0.98) and specificity was 0.84 (95% CI, 0.70–0.92). In the case of AD versus DLB, 18F-FDG PET showed a sensitivity of 0.93 (95% CI 0.88-0.98) and specificity of 0.92 (95% CI, 0.70–0.92). Lastly, when differentiating AD from non-AD dementias, the sensitivity was 0.86 (95% CI, 0.80–0.91) and the specificity was 0.88 (95% CI, 0.80–0.91). The studies mostly used case-control designs with visual and quantitative assessments. @*Conclusions@#18 F-FDG PET exhibits high sensitivity and specificity in differentiating dementia subtypes, particularly AD, FTD, and DLB. This method, while not a standalone diagnostic tool, significantly enhances diagnostic accuracy in uncertain cases, complementing clinical assessments and structural imaging.

5.
Artigo em Inglês | WPRIM | ID: wpr-1042970

RESUMO

Objectives@#In the Fourth Industrial Revolution, there is a focus on managing diverse medical data to improve healthcare and prevent disease. The challenges include tracking detailed medical records across multiple institutions and the necessity of linking domestic public medical entities for efficient data sharing. This study explores MyHealthWay, a Korean healthcare platform designed to facilitate the integration and transfer of medical data from various sources, examining its development, importance, and legal implications. @*Methods@#To evaluate the management status and utilization of MyHealthWay, we analyzed data types, security, legal issues, domestic versus international issues, and infrastructure. Additionally, we discussed challenges such as resource and infrastructure constraints, regulatory hurdles, and future considerations for data management. @*Results@#The secure sharing of medical information via MyHealthWay can reduce the distance between patients and healthcare facilities, fostering personalized care and self-management of health. However, this approach faces legal challenges, particularly relating to data standardization and access to personal health information. Legal challenges in data standardization and access, particularly for secondary uses such as research, necessitate improved regulations. There is a crucial need for detailed governmental guidelines and clear data ownership standards at institutional levels. @*Conclusions@#This report highlights the role of Korea's MyHealthWay, which was launched in 2023, in transforming healthcare through systematic data integration. Challenges include data privacy and legal complexities, and there is a need for data standardization and individual empowerment in health data management within a systematic medical big data framework.

6.
Artigo em Inglês | WPRIM | ID: wpr-1043278

RESUMO

Background@#and Purpose The association between physical activity and dementia has been shown in various observational studies. We aimed to determine the risk of dementia in the elderly with lower-body fractures. @*Methods@#We reconstructed a population-based matched cohort from the National Health Insurance Service—Senior Cohort data set that covers 511,953 recipients of medical insurance in South Korea. @*Results@#Overall 53,776 subjects with lower-body fractures were identified during 2006–2012, and triplicate control groups were matched randomly by sex, age, and years from the index date for each subject with a fracture. There were 3,573 subjects (6.6%) with and 7,987 subjects (4.9%) without lower-body fractures who developed dementia from 2008 up to 2015. Lowerbody fractures were independently associated with a subsequent dementia diagnosis with a higher adjusted hazard ratio (aHR) (1.55, 95% confidence interval [CI]=1.49–1.62) compared with upper-body fractures (aHR=1.19, 95% CI=1.14–1.23). @*Conclusions@#These results support the protective role of physical activity against dementia and highlight the importance of promoting fracture prevention in the elderly.

7.
Psychiatry Investigation ; : 1007-1017, 2023.
Artigo em Inglês | WPRIM | ID: wpr-1002741

RESUMO

Objective@#We aimed to examine the effectiveness of personalized light intervention using a blue-enriched light-emitting-diodes device on rest–activity rhythm (RAR) and light exposure rhythm (LER) in patients with mild and moderate Alzheimer’s disease (AD). @*Methods@#AD patients with poor sleep quality and/or insomnia symptoms were assigned into either an experimental group (EG) or control group (CG) in a single-blind design. Personalized light intervention was given at 9–10 h after individual dim light melatonin onset, lasting for 1 h every day for two weeks in the EG (77.36±5.79 years, n=14) and CG (78.10±7.98 years, n=10). Each patient of CG wore blue-attenuating sunglasses during the intervention. Actigraphy recording at home for 5 days was done at baseline (T0), immediate postintervention (T1), and at four weeks after intervention (T2). The variables of RAR and LER were derived using nonparametric analysis. @*Results@#We found a significant time effect on the intradaily variability (IV) of RAR at T2 with respect to T0 (p=0.039), indicating reduced IV of RAR at four weeks after personalized light intervention regardless of blue-enriched light intervention. There was a time effect on the IV of LER at T1 with respect to T0 (p=0.052), indicating a reduced tendency in the IV of LER immediately after intervention. @*Conclusion@#Our personalized light intervention, regardless of blue-enriched light source, could be useful in alleviating fragmentation of RAR and LER in AD patients.

8.
Artigo em Inglês | WPRIM | ID: wpr-1040624

RESUMO

Objective@#To investigate the relationship between reduced glutathione (GSH), a key molecule of the antioxidant defense system in the blood, and glutathione reductase (GR), which reduces oxidized glutathione (glutathione disulfide [GSSG]) to GSH and maintains the redox balance, with the prevalence of Alzheimer’s dementia and cognitive decline. @*Methods@#In all, 20 participants with Alzheimer’s dementia who completed the third follow-up clinical evaluation over 6 years were selected, and 20 participants with normal cognition were selected after age and sex matching. The GSH and GR concentrations were the independent variables. Clinical diagnosis and neurocognitive test scores were the dependent variables indicating cognitive status. @*Results@#The higher the level of GR, the greater the possibility of having normal cognition than of developing Alzheimer’s dementia. Additionally, the higher the level of GR, the higher the neurocognitive test scores. However, this association was not significant for GSH. After 6 years, the conversion rate from normal cognition to cognitive impairment was significantly higher in the lower 50th percentile of the GR group than in the upper 50th percentile. @*Conclusion@#The higher the GR, the lower the prevalence of Alzheimer’s dementia and incidence of cognitive impairment and the higher the cognitive test scores. Therefore, GR is a potential protective biomarker against Alzheimer’s dementia and cognitive decline.

9.
Artigo em Inglês | WPRIM | ID: wpr-1040644

RESUMO

Background@#and Purpose: The National Responsibility Policy for Dementia Care was implemented in September 2017 in Korea. This study aimed to compare dementia incidence in Seoul and Gangwon-do before and after the implementation of this policy. @*Methods@#We extracted insurance claim data from the Korean Health Insurance Review and Assessment Service for people diagnosed with diabetes, hypertension, or dyslipidemia for the first time in Seoul and Gangwon-do, Korea. We defined two enrollment groups based on the policy implementation date: 1) January 1, 2015 to December 31, 2016 (Index 1, pre-implementation), and 2) January 1, 2017 to December 31, 2018 (Index 2, postimplementation). Each group was followed up for 1 year from the time of enrollment. Then, we calculated hazard ratios to compare the incidence of dementia between the two groups, and between Seoul and Gangwon-do. @*Results@#In Seoul, the incidence of dementia was significantly lower in Index 2 than in Index 1 (hazard ratio [HR], 0.926; 95% confidence interval [CI], 0.875–0.979). However, the incidence rate did not differ between the 2 groups (HR, 1.113; 95% CI, 0.966–1.281) in Gangwon-do. In Index 1, the incidence of dementia did not differ between Seoul and Gangwon-do (HR, 1.043; 95% CI, 0.941–1.156), but in Index 2, was significantly higher in Gangwon-do than in Seoul (HR, 1.240; 95% CI, 1.109–1.386). @*Conclusions@#After implementing the National Responsibility Policy for Dementia Care, the dementia incidence rate decreased significantly in Seoul, consistent with other studies, but not in Gangwon-do.

10.
Artigo em Inglês | WPRIM | ID: wpr-1040651

RESUMO

Alzheimer’s disease (AD), one of the most representative neurodegenerative diseases, has diverse neurobiological and pathophysiological mechanisms. Treatment strategies targeting a single mechanism have repeated faced failures because the mechanism of neuronal cell death is very complex that is not fully understood yet. Since complex mechanisms exist to explain AD, a variety of diagnostic biomarkers for diagnosing AD are required.Moreover, standardized evaluations for comprehensive diagnosis using neuropsychological, imaging, and laboratory tools are needed. In this review, we summarize the latest clinical, neuropsychological, imaging, and laboratory evaluations to diagnose patients with AD based on our own experience in conducting a prospective study.

11.
Artigo em Inglês | WPRIM | ID: wpr-1040660

RESUMO

Background@#and Purpose: As it becomes an aging society, interest in senile diseases is increasing. Alzheimer’s dementia (AD) and osteoporosis are representative senile diseases.Various studies have reported that AD and osteoporosis share many risk factors that affect each other’s incidence. This aimed to determine if active medication treatment of AD could affect the development of osteoporosis. @*Methods@#The Health Insurance Review and Assessment Service provided data consisting of diagnosis, demographics, prescription drug, procedures, medical materials, and healthcare resources. In this study, data of all AD patients in South Korea who were registered under the national health insurance system were obtained. The cohort underwent conversion to an Observational Medical Outcomes Partnership–Common Data Model version 5 format. @*Results@#This study included 11,355 individuals in the good persistent group and an equal number of 11,355 individuals in the poor persistent group from the National Health Claims database for AD drug treatment. In primary analysis, the risk of osteoporosis was significantly higher in the poor persistence group than in the good persistence group (hazard ratio, 1.20 [95% confidence interval, 1.09–1.32]; p<0.001). @*Conclusions@#We found that the good persistence group treated with anti-dementia drugs for AD was associated with a significant lower risk of osteoporosis in this nationwide study. Further studies are needed to clarify the pathophysiological link in patients with two chronic diseases.

12.
Psychiatry Investigation ; : 567-574, 2023.
Artigo em Inglês | WPRIM | ID: wpr-977334

RESUMO

Objective@#Previous studies have shown the influence of visual and auditory sensory impairment on dementia incidence. In this study, we tested the hypothesis that the incidence of dementia will increase with visual and auditory impairments than with visual or auditory impairment. @*Methods@#Data from the Korea National Health Insurance Service database were used, including disease and medication codes from 2009 to 2018, and the 2011 national health check-up results. Participants were grouped based on their sensory abilities: normal, visual impairment, auditory impairment, and both visual and auditory impairments (dual sensory impairment). To compare the incidence of dementia, hazard ratios were calculated for each group, with reference to the normal sensory (NS) group. Sensitivity analyses were performed comparing dementia incidence from 2014 to 2018, excluding the onset of the disease in 2012 and 2013. @*Results@#We identified 8,289 cases of dementia during the seven-year follow-up. In the multiple Cox regression analysis, adjusted for sex, social economic status, age, comorbidities, smoking, alcohol consumption, and activity level, the auditory impairment (hazard ratio= 1.1908) and visual impairment (hazard ratio=1.3553) groups showed a significantly higher dementia incidence than the NS group. Dual sensory impairment (hazard ratio=1.5267) showed the highest incidence. The sensitivity analysis yielded similar results. @*Conclusion@#Visual and auditory impairments are associated with an increased risk of dementia, particularly in individuals with dual sensory impairment. Hence, visual and auditory impairments might have increased the risk of dementia through independent pathological processes. Therefore, preventing and correcting sensory impairment is necessary to reduce the risk of dementia.

14.
Artigo em Inglês | WPRIM | ID: wpr-914175

RESUMO

Background@#and Purpose: In this study we aimed to find the association between neuropsychological performance and body mass index (BMI) in patients with mild cognitive impairment (MCI). In addition, we investigated the effects of the apolipoprotein E (APOE) genotype in the relationship between the BMI and cognition in MCI. @*Methods@#We enrolled a cohort of 3,038 subjects with MCI aged 65–90 from the Clinical Research Center for Dementia of South Korea and a dementia cohort of the Ewha Womans University Mokdong Hospital. MCI patients were classified into three subgroups according to the Asian standard of BMI. We compared cognitive performances between groups by one-way analysis of variance. To investigate the effects of the APOE genotype, we used multivariate linear regression models after adjusting for possible confounders. @*Results@#Even though normal BMI groups were younger, had more females, and had less comorbidities, the higher BMI groups had better cognitive functions. Among subjects with APOE ε4 carriers, there was a positive relationship between the BMI and the memory task alone. @*Conclusions@#Our findings suggested that higher BMI in patients with MCI were associated with better cognitive performance. The effects of the APOE ε4 genotype in the associations between BMI and cognition were distinguishing. Therefore, according to physical status, APOE ε4 genotype-specific strategies in the assessments and treatments may be necessary in elderly patients with MCI.

15.
Artigo em Inglês | WPRIM | ID: wpr-924899

RESUMO

Recently, aducanumab, a beta amyloid targeted immunotherapy, has been approved by the US Food and Drug Administration for the treatment of Alzheimer’s dementia (AD). Although many questions need to be answered, this approval provides a promising hope for the development of AD drugs that could be supported by new biomarkers such as blood-based ones and composite neuropsychological tests that can confirm pathologic changes in early stages of AD. It is important to elucidate the complexity of AD which is known to be associated with other factors such as vascular etiologies and neuro-inflammation. Through the second international conference of the Korean Dementia Association (KDA), researchers from all over the world have participated in the exchange of opinions with KDA members on the most up-to-date topics. The Academic Committee of the KDA summarizes lectures to provide the depth of the conference as well as discussions. This will be an important milestone to widen the latest knowledge in the research of AD’s diagnosis, therapeutics, pathogenesis that can lead to the establishment of future directions.

16.
Artigo em Inglês | WPRIM | ID: wpr-925365

RESUMO

We report the case of a 54-year-old female who was diagnosed with clinical dementia and recovered to normal cognition in only 11 days through appropriate intervention. The patient was on a complicated regimen of psychiatric medications for underlying depression and panic disorder. The patient noted increased deterioration in executive function gradual memory impairment starting in early 2020.As a result of the neuroimaging, prominent neurodegeneration and in vivo brain pathology were not observed. During outpatient clinic follow-up, severe obstructive sleep apnea (OSA) was confirmed. Based on the diagnostic results, a clinical impression was made for reversible dementia due to psychiatric drugs and OSA. During hospitalization for 10 days, the patient’s regimen of psychiatric medications with anticholinergic effects was changed, and long-acting benzodiazepines were reduced. The patient also underwent continuous positive airway pressure titration to ameliorate OSA. The patient reported subjective cognitive improvement and a comprehensive neuropsychiatric test performed at discharge later showed a normal range in all cognitive domains, and the patient's activity of daily living evaluated at the outpatient clinic after discharge had recovered.

17.
Artigo em Inglês | WPRIM | ID: wpr-899101

RESUMO

Background@#and Purpose Dementia is rapidly becoming more common in the elderly population of South Korea, and there are regional difference in its demographics. This study investigated the trajectories in the prevalence and incidence of dementia based on the Seoul metropolitan area and other areas in South Korea using big data from the National Health Insurance Service (NHIS). @*Methods@#We examined a population-based elderly cohort obtained from the NHIS Senior Cohort (NHIS-SC) data set that comprises approximately half a million recipients of medical insurance in South Korea during 2003–2015. The age-standardized prevalence and incidence of dementia as well as their trajectories from 2003 were estimated. Regional differences in these rates between Seoul metropolitan area and other areas were also analyzed. @*Results@#The standardized prevalence of dementia per 100,000 increased significantly from 178.11 in 2003 to 5,319.01 in 2015 (p<0.001). The standardized prevalence of dementia was higher in other areas than in Seoul metropolitan area. The standardized incidence of dementia per 100,000 person-years also increased significantly, from 126.41 in 2003 to 2,218.25 in 2015 (p<0.001). The standardized incidence of dementia was similarly higher in other areas than in Seoul metropolitan area (p<0.001). @*Conclusions@#This study has shown that the standardized prevalence and incidence of dementia increased steadily from 2003 to 2015 in South Korea based on the NHIS-SC data set, and differed between Seoul metropolitan area and other areas.

18.
Artigo em Inglês | WPRIM | ID: wpr-899144

RESUMO

Background@#and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. @*Methods@#This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). @*Results@#Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. @*Conclusions@#In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

19.
Artigo em Inglês | WPRIM | ID: wpr-899145

RESUMO

Background@#and Purpose: Reportedly 30–50% of patients being treated for chronic illnesses do not adhere to their medication regimen. We assessed the impact of a nurse-led education program for caregivers of Korean de novo Alzheimer’s disease patients who had newly been prescribed donepezil. @*Methods@#This multicenter study analyzed 93 participants in a caregiver education group and 92 participants in a caregiver no-education group. At every visit up to the end of the study (1 year), caregivers in the education group were given educational brochures regarding Alzheimer’s disease and the efficacy and adverse events of donepezil treatment. The primary endpoint was the discontinuation rate of donepezil treatment during the 1-year observation period. The secondary endpoints included the effect of education on compliance with donepezil treatment assessed at each visit using a clinician rating scale (CRS) and visual analog scale (VAS), and changes from baseline in cognitive assessment tests. @*Results@#The donepezil discontinuation rates at 1 year were 5.38% (5/93) and 6.52% (6/92) in the caregiver education and no-education groups, respectively (p=0.742). No significant between-group differences in donepezil compliance rates on the CRS and VAS were observed, but significant changes were observed in some cognitive tests from baseline to the end of the study. @*Conclusions@#Caregiver education had no significant effect on treatment discontinuation, but this may have been due to the low severity of cognitive impairment among the included population at baseline. In addition, the low discontinuation rates meant that no significant difference in treatment compliance was observed.

20.
Artigo em Inglês | WPRIM | ID: wpr-891397

RESUMO

Background@#and Purpose Dementia is rapidly becoming more common in the elderly population of South Korea, and there are regional difference in its demographics. This study investigated the trajectories in the prevalence and incidence of dementia based on the Seoul metropolitan area and other areas in South Korea using big data from the National Health Insurance Service (NHIS). @*Methods@#We examined a population-based elderly cohort obtained from the NHIS Senior Cohort (NHIS-SC) data set that comprises approximately half a million recipients of medical insurance in South Korea during 2003–2015. The age-standardized prevalence and incidence of dementia as well as their trajectories from 2003 were estimated. Regional differences in these rates between Seoul metropolitan area and other areas were also analyzed. @*Results@#The standardized prevalence of dementia per 100,000 increased significantly from 178.11 in 2003 to 5,319.01 in 2015 (p<0.001). The standardized prevalence of dementia was higher in other areas than in Seoul metropolitan area. The standardized incidence of dementia per 100,000 person-years also increased significantly, from 126.41 in 2003 to 2,218.25 in 2015 (p<0.001). The standardized incidence of dementia was similarly higher in other areas than in Seoul metropolitan area (p<0.001). @*Conclusions@#This study has shown that the standardized prevalence and incidence of dementia increased steadily from 2003 to 2015 in South Korea based on the NHIS-SC data set, and differed between Seoul metropolitan area and other areas.

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