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1.
J Infect Dis ; 229(4): 1026-1034, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38097377

ABSTRACT

BACKGROUND: Solid organ transplant recipients (SOTRs) are at higher risk for severe infection. However, the risk for severe COVID-19 and vaccine effectiveness among SOTRs remain unclear. METHODS: This retrospective study used a nationwide health care claims database and COVID-19 registry from the Republic of Korea (2020 to 2022). Adult SOTRs diagnosed with COVID-19 were matched with up to 4 non-SOTR COVID-19 patients by propensity score. Severe COVID-19 was defined as treatment with high-flow nasal cannulae, mechanical ventilation, or extracorporeal membrane oxygenation. RESULTS: Among 6783 SOTRs with COVID-19, severe COVID-19 was reported with the highest rate in lung transplant recipients (13.16%), followed by the heart (6.30%), kidney (3.90%), and liver (2.40%). SOTRs had a higher risk of severe COVID-19 compared to non-SOTRs, and lung transplant recipients showed the highest risk (adjusted odds ratio, 18.14; 95% confidence interval [CI], 8.53-38.58). Vaccine effectiveness against severe disease among SOTRs was 47% (95% CI, 18%-65%), 64% (95% CI, 49%-75%), and 64% (95% CI, 29%-81%) for 2, 3, and 4 doses, respectively. CONCLUSIONS: SOTRs are at significantly higher risk for severe COVID-19 compared to non-SOTRs. Vaccination is effective in preventing the progression to severe COVID-19. Efforts should be made to improve vaccine uptake among SOTRs, while additional protective measures should be developed.


Subject(s)
COVID-19 , Organ Transplantation , Adult , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Retrospective Studies , Transplant Recipients , Vaccination , Organ Transplantation/adverse effects
2.
J Neuroinflammation ; 21(1): 47, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38347588

ABSTRACT

BACKGROUND: Progranulin (PGRN) haploinsufficiency due to progranulin gene (GRN) variants can cause frontotemporal dementia (FTD) with aberrant TAR DNA-binding protein 43 (TDP-43) accumulation. Despite microglial burden with TDP-43-related pathophysiology, direct microglial TDP-43 pathology has not been clarified yet, only emphasized in neuronal pathology. Thus, the objective of this study was to investigate TDP-43 pathology in microglia of patients with PGRN haploinsufficiency. METHODS: To design a human microglial cell model with PGRN haploinsufficiency, monocyte-derived microglia (iMGs) were generated from FTD-GRN patients carrying pathogenic or likely pathogenic variants (p.M1? and p.W147*) and three healthy controls. RESULTS: iMGs from FTD-GRN patients with PGRN deficiency exhibited severe neuroinflammation phenotype and failure to maintain their homeostatic molecular signatures, along with impaired phagocytosis. In FTD-GRN patients-derived iMGs, significant cytoplasmic TDP-43 aggregation and accumulation of lipid droplets with profound lysosomal abnormalities were observed. These pathomechanisms were mediated by complement C1q activation and upregulation of pro-inflammatory cytokines. CONCLUSIONS: Our study provides considerable cellular and molecular evidence that loss-of-function variants of GRN in human microglia can cause microglial dysfunction with abnormal TDP-43 aggregation induced by inflammatory milieu as well as the impaired lysosome. Elucidating the role of microglial TDP-43 pathology in intensifying neuroinflammation in individuals with FTD due to PGRN deficiency and examining consequential effects on microglial dysfunction might yield novel insights into the mechanisms underlying FTD and neurodegenerative disorders.


Subject(s)
Frontotemporal Dementia , Pick Disease of the Brain , Humans , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Frontotemporal Dementia/genetics , Haploinsufficiency , Lysosomes/metabolism , Microglia/pathology , Neuroinflammatory Diseases , Pick Disease of the Brain/metabolism , Progranulins/genetics , Progranulins/metabolism
3.
Biomed Microdevices ; 26(1): 15, 2024 Jan 30.
Article in English | MEDLINE | ID: mdl-38289481

ABSTRACT

There is a clinical need for differential diagnosis of the latent versus active stages of tuberculosis (TB) disease by a simple-to-administer test. Alpha-crystallin (Acr) and early secretory antigenic target-6 (ESAT-6) are protein biomarkers associated with the latent and active stages of TB, respectively, and could be used for differential diagnosis. We therefore developed a microneedle patch (MNP) designed for application to the skin to quantify Acr and ESAT-6 in dermal interstitial fluid by enzyme-linked immunosorbent assay (ELISA). We fabricated mechanically strong microneedles made of polystyrene and coated them with capture antibodies against Acr and ESAT-6. We then optimized assay sensitivity to achieve a limit of detection of 750 pg/ml and 3,020 pg/ml for Acr and ESAT-6, respectively. This study demonstrates the feasibility of an MNP-based ELISA for differential diagnosis of latent TB disease.


Subject(s)
Tuberculosis , Humans , Enzyme-Linked Immunosorbent Assay , Tuberculosis/diagnosis , Antibodies , Biological Transport , Biomarkers
4.
J Korean Med Sci ; 39(7): e67, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38412612

ABSTRACT

BACKGROUND: The measurement of health levels and monitoring of characteristics and trends among populations and subgroups are essential for informing evidence-based policy decisions. This study aimed to examine the burden of disease in Korea for both the total population and subgroups in 2020, as well as analyze changes in disease burden from 2008 to 2020. METHODS: We employed the methodology developed in the Korean National Burden of Disease and Injuries Study to calculate disability-adjusted life years (DALYs) by sex, causes, region, and income level from 2008 to 2020. DALYs were derived by combining years of life lost and years lived with disability. RESULTS: In 2020, the burden of disease for the Korean population was estimated to be 25,439 DALYs per 100,000 population, reflecting a 13.8% increase since 2008. The leading causes of DALYs were diabetes mellitus, followed by low back pain and ischemic stroke. A sex-specific gap reversal was observed, with the disease burden for men surpassing that of women starting in 2017. Furthermore, variations in disease burden were identified across 250 regions and income quintiles. CONCLUSION: It is imperative to establish appropriate health policies that prioritize the diseases with significantly increasing burdens and subgroups experiencing high disease burdens. The findings of this study are expected to serve as a foundation for developing healthcare policies aimed at improving the health levels of Koreans and achieving health equity.


Subject(s)
Disability-Adjusted Life Years , Life Expectancy , Male , Humans , Female , Quality-Adjusted Life Years , Cost of Illness , Health Policy , Republic of Korea/epidemiology , Global Burden of Disease , Global Health
5.
J Korean Med Sci ; 39(6): e46, 2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38374624

ABSTRACT

BACKGROUND: Healthy life expectancy is a well-recognized indicator for establishing health policy goals used in Korea's Health Plan. This study aimed to explore Koreans' healthy life expectancy and its gender, income, and regional disparities from 2008 to 2020. METHODS: This study was conducted on the entire population covered by health insurance and medical aid program in Korea. The incidence-based "years lived with disability" for 260 disease groups by gender, income level, and region was calculated employing the methodology developed in the Korean National Burden of Disease Study, and it was used as the number of healthy years lost to calculate health-adjusted life expectancy (HALE). RESULTS: Koreans' HALE increased from 68.89 years in 2008 to 71.82 years in 2020. Although the gender disparity in HALE had been decreasing, it increased to 4.55 years in 2020. As of 2020, 5.90 years out of 8.67 years of the income disparity (Q5-Q1) in HALE were due to the disparity between Q1 and Q2, the low-income groups. Income and regional disparities in HALE exhibited an increasing trend, and these disparities were higher in men than in women. CONCLUSION: A subgroup with a low health level was identified through the HALE results, and it was confirmed that improving the health level of this population can reduce health inequalities and improve health at the national level. Further exploration of the HALE calculation methodology may help in the development of effective policies such as prioritizing interventions for health risk factors.


Subject(s)
Disabled Persons , Life Expectancy , Male , Humans , Female , Healthy Life Expectancy , Health Status , Republic of Korea/epidemiology
6.
J Korean Med Sci ; 39(17): e145, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38711316

ABSTRACT

BACKGROUND: Health-adjusted life expectancy (HALE) is an indicator of the average lifespan in good health. Through this study, we aimed to identify regional disparities in the gap between HALE and life expectancy, considering the trends that have changed over time in Korea. METHODS: We employed a group-based multi-trajectory modeling approach to capture trends in the gap between HALE and life expectancy at the regional level from 2008 to 2019. HALE was calculated using incidence-based "years lived with disability." This methodology was also employed in the Korean National Burden of Disease Study. RESULTS: Based on five different information criteria, the most fitted number of trajectory groups was seven, with at least 11 regions in each group. Among the seven groups, one had an exceptionally large gap between HALE and life expectancy compared to that of the others. This group was assigned to 17 regions, of which six were metropolitan cities. CONCLUSION: Based on the results of this study, we identified regions in which health levels have deteriorated over time, particularly within specific areas of metropolitan cities. These findings can be used to design comprehensive policy interventions for community health promotion and urban regeneration projects in the future.


Subject(s)
Life Expectancy , Humans , Life Expectancy/trends , Republic of Korea/epidemiology , Male , Female , Quality-Adjusted Life Years
7.
J Infect Dis ; 228(10): 1326-1335, 2023 11 11.
Article in English | MEDLINE | ID: mdl-37549237

ABSTRACT

BACKGROUND: Our study aimed to determine the risk of herpes zoster reactivation and coronavirus disease 2019 (COVID-19) vaccination (mRNA vaccine [BNT162b2] and adenovirus-vectored vaccine [ChAdOx1 nCoV-19]). METHODS: This retrospective study analyzed herpes zoster cases diagnosed between 26 February 2021 and 30 June 2021 and registered in the National Health Insurance Service database. A matched case-control study with a 1:3 matching ratio and a propensity score matching (PSM) study with a 1:1 ratio of vaccinated and unvaccinated individuals were performed. RESULTS: In the matched case control analysis, BNT162b2 was associated with an increased risk of herpes zoster reactivation (first dose adjusted odds ratio [aOR], 1.11; 95% confidence interval [CI], 1.06-1.15; second dose aOR, 1.17; 95% CI, 1.12-1.23). PSM analysis revealed a statistically significant increase in risk within 18 days following any vaccination (adjusted hazard ratio [aHR], 1.09; 95% CI, 1.02-1.16). BNT162b2 was associated with an increased risk at 18 days postvaccination (aHR, 1.65; 95% CI, 1.35-2.02) and second dose (aHR, 1.10; 95% CI, 1.02-1.19). However, the risk did not increase in both analyses of ChAdOx1 vaccination. CONCLUSIONS: mRNA COVID-19 vaccination possibly increases the risk of herpes zoster reactivation, and thus close follow-up for herpes zoster reactivation is required.


Subject(s)
Adenoviridae Infections , COVID-19 Vaccines , COVID-19 , Herpes Zoster Vaccine , Herpes Zoster , Humans , Adenoviridae/genetics , BNT162 Vaccine , Case-Control Studies , ChAdOx1 nCoV-19 , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Herpes Zoster/epidemiology , Herpes Zoster/prevention & control , Herpes Zoster Vaccine/adverse effects , Herpesvirus 3, Human/genetics , Retrospective Studies , Vaccination/adverse effects , Vaccines, Attenuated/adverse effects
8.
Article in English | MEDLINE | ID: mdl-37498607

ABSTRACT

OBJECTIVE: We investigated the incidence rate and risk factors of myelodysplastic syndromes (MDS) in patients with rheumatologic disease. METHODS: We conducted a retrospective cohort study of patients who were diagnosed with rheumatologic diseases at a tertiary-care hospital between May 2009 and July 2022 and identified the patients who were subsequently diagnosed with MDS. Each patient with MDS was matched with five age- and sex-matched controls chosen from the cohort of patients with each specific rheumatologic disease. RESULTS: During a total follow-up of 55 841 person-years (PY), MDS occurred in 64 patients, yielding an incidence rate of 1.15/1000 PY (median age, 57.0 [IQR, 41.0-69.0]; median duration to MDS diagnosis, 6.5 years [IQR, 3.0-9.0]). In an age-matched analysis, systemic lupus erythematosus (SLE) was a significant risk factor for MDS (adjusted hazard ratio, 2.61 [CI, 1.19-36.06], P= 0.01). Refractory cytopenia with multilineage dysplasia was the most common phenotype of MDS (35.9%), and more than half of the patients had karyotypes with favorable prognoses (54.7%). Compared with matched controls, rheumatoid arthritis, SLE, and ankylosing spondylitis patients with MDS had lower levels of haemoglobin at the time of diagnosis of rheumatologic disease. Furthermore, the MDS patients with SLE and Behcet's disease had higher levels of glucocorticoid use in terms of frequency of use or mean dose than the control patients. CONCLUSION: SLE is a significant risk factor for MDS among patients with rheumatologic diseases. A lower haemoglobin level at the time of diagnosis of rheumatologic disease was associated with the future development of MDS.

9.
Proc Natl Acad Sci U S A ; 117(24): 13529-13540, 2020 06 16.
Article in English | MEDLINE | ID: mdl-32482852

ABSTRACT

The Hippo pathway plays a pivotal role in tissue homeostasis and tumor suppression. YAP and TAZ are downstream effectors of the Hippo pathway, and their activities are tightly suppressed by phosphorylation-dependent cytoplasmic retention. However, the molecular mechanisms governing YAP/TAZ nuclear localization have not been fully elucidated. Here, we report that Mastermind-like 1 and 2 (MAML1/2) are indispensable for YAP/TAZ nuclear localization and transcriptional activities. Ectopic expression or depletion of MAML1/2 induces nuclear translocation or cytoplasmic retention of YAP/TAZ, respectively. Additionally, mutation of the MAML nuclear localization signal, as well as its YAP/TAZ interacting region, both abolish nuclear localization and transcriptional activity of YAP/TAZ. Importantly, we demonstrate that the level of MAML1 messenger RNA (mRNA) is regulated by microRNA-30c (miR-30c) in a cell-density-dependent manner. In vivo and clinical results suggest that MAML potentiates YAP/TAZ oncogenic function and positively correlates with YAP/TAZ activation in human cancer patients, suggesting pathological relevance in the context of cancer development. Overall, our study not only provides mechanistic insight into the regulation of YAP/TAZ subcellular localization, but it also strongly suggests that the miR30c-MAML-YAP/TAZ axis is a potential therapeutic target for developing novel cancer treatments.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Cell Nucleus/metabolism , DNA-Binding Proteins/metabolism , Neoplasms/metabolism , Trans-Activators/metabolism , Transcription Factors/metabolism , Adaptor Proteins, Signal Transducing/genetics , Carcinogenesis/genetics , Carcinogenesis/metabolism , Cell Nucleus/genetics , DNA-Binding Proteins/genetics , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Neoplasms/genetics , Protein Transport , Signal Transduction , Trans-Activators/genetics , Transcription Factors/genetics , Transcriptional Coactivator with PDZ-Binding Motif Proteins , YAP-Signaling Proteins
10.
J Korean Med Sci ; 38(32): e248, 2023 Aug 14.
Article in English | MEDLINE | ID: mdl-37582498

ABSTRACT

The pediatric population with comorbidities is a high-risk group for severe coronavirus disease 2019 (COVID-19). As of January 2023, the COVID-19 vaccination rate for at least two doses among Korean children 5-11 years is low at 1.1%. We summarized the COVID-19 vaccination status for the pediatric population (5-17 years) with comorbidities through July 2022 using the National Health Insurance Service database. Pediatric patients with comorbidities had higher vaccination rates than the general pediatric population (2.4% vs. 1.1% in 5-11-year-olds [P < 0.001], 76.5% vs. 66.1% in 12-17-year-olds [P < 0.001]). However, there were substantial differences according to comorbidity category, and the 2-dose vaccination rate was lowest among children with immunodeficiency in all age groups (1.1% in 5-11-year-olds, 51.2% in 12-17-year-olds). The COVID-19 vaccination rate among Korean children has remained stagnant at a low proportion despite ongoing outreach. Thus, more proactive strategies are needed alongside continuous surveillance.


Subject(s)
COVID-19 , Humans , Child , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Comorbidity , Vaccination , Republic of Korea/epidemiology
11.
J Korean Med Sci ; 38(16): e130, 2023 Apr 24.
Article in English | MEDLINE | ID: mdl-37096313

ABSTRACT

BACKGROUND: To precisely build a healthcare delivery system at regional levels, local patients' healthcare service utilization patterns must be examined. Hence, this study utilized trend analysis of the relevance index of each disease of each essential medical service field at the municipal and provincial levels. METHODS: This study analyzed customized databases released by the National Health Insurance Service from 2016-2020. Diseases defined in the Korean National Burden of Disease (KNBD) study were categorized into the following essential medical service fields: trauma care, cardiocerebrovascular, maternal and neonatal, mental health, infection, cancer, older adults' care and rehabilitation, and others. Relevance index, the percentage of medical service utilization in a region by the residents of that region relative to their total medical service utilization, was examined by region (17 municipal and provincial regions) and disease area. The relevance index was determined based on the number of patients and the total out-of-pocket expenses. RESULT: Eight of the 17 regions showed over a 90.0% relevance index in the infection area. In the cancer area, 14 regions (not including Seoul, Daegu, and Busan) had a relevance index lower than 75.0%. Throughout the analysis period (2016-2020), there were no significant variations in the relevance index. Diseases such as bone and connective tissue cancer (39.0%), neural tube defects (16.7%), and autism (57.1%) had low relevance index in the essential medical service fields. In all 17 regions, the relevance index of inpatients was lower than that of outpatients, and that for out-of-pocket expenses was lower than that based on the number of patients. CONCLUSION: The relevance index of major diseases of each essential medical service field calculated in this study can provide good indicators for monitoring the level of an independent regional healthcare delivery system.


Subject(s)
Delivery of Health Care , Neoplasms , Infant, Newborn , Humans , Aged , Retrospective Studies , Health Expenditures , Republic of Korea
12.
J Korean Med Sci ; 38(47): e408, 2023 Dec 04.
Article in English | MEDLINE | ID: mdl-38050917

ABSTRACT

The coronavirus disease 2019 pandemic has brought significant changes to infectious disease management globally. This study explored changes in clinical microbiological testing trends and their implications for infectious disease incidence and medical utilization during the pandemic. We collected nationwide claims for monthly clinical microbiology tests from January 2018 to March 2022 using the National Health Insurance Service database. Seasonal autoregressive integrated moving average models were employed to make predictions for each disease based on the baseline period (January 2018 to January 2020). The results showed a significant decrease in general bacterial and fungal cultures, respiratory infectious disease-related, and inflammatory markers, while the representatives of tests for vector-borne diseases, healthcare-associated infections, and chronic viral infections remained stable. The study highlights the potential of clinical microbiological testing trends as an additional surveillance tool and offers implications for future infectious disease management and surveillance strategies in pandemic settings.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Pandemics , SARS-CoV-2 , COVID-19 Testing , Republic of Korea/epidemiology
14.
J Korean Med Sci ; 38(7): e26, 2023 Feb 20.
Article in English | MEDLINE | ID: mdl-36808542

ABSTRACT

BACKGROUND: To examine the incidence of traumatic spinal cord injury (TSCI) from all etiologies, we measured and compared the incidence of TSCI from three national or quasi-national databases in South Korea, namely, the National Health Insurance Service (NHIS), automobile insurance (AUI), and Industrial Accident Compensation Insurance (IACI). METHODS: We reviewed patients with TSCI reported in the NHIS database between 2009 and 2018, and in the AUI and IACI databases between 2014 and 2018. TSCI patients were defined as those first admitted to the hospital with a diagnosis of TSCI according to the International Classification of Diseases (10th revision) criteria. Age-adjusted incidence was calculated using direct standardization using the 2005 South Korean population or the 2000 US population as the standard population. The annual percentage changes (APC) of TSCI incidence were calculated. The Cochrane-Armitage trend test was performed according to the injured body region. RESULTS: In the NHIS database, age-adjusted TSCI incidence using the Korean standard population increased significantly from 2009 to 2018 (from 33.73 per million in 2009 to 38.14 per million in 2018, APC = 1.2%, P = 0.014). Contrarily, age-adjusted incidence in the AUI database significantly decreased from 13.88 per million in 2014 to 11.57 per million in 2018 (APC = - 5.1%, P = 0.009). In the IACI database, the age-adjusted incidence showed no significant difference, while crude incidence showed a significant increase (from 22.02 per million in 2014 to 28.92 per million in 2018, APC = 6.1%, P = 0.038). According to the age group, all the three databases showed high incidences of TSCI in those in their 60s and 70s or older. Among those in their 70s or older, the incidence of TSCI increased dramatically in the NHIS and IACI databases, while no significant trend was found in AUI database. In 2018, the number of TSCI patients was the highest among those over 70 years of age in the NHIS, whereas among those in their 50s were the highest in both AUI and IACI. The proportion of patients with cervical spinal cord injury was the most common in all these databases. CONCLUSIONS: The differences in trends in the incidence of TSCI may be due to the different etiologies and different characteristics of subjects depending on insurance type. These results imply the need for tailored medical strategies for the different injury mechanisms represented by three national insurance services in South Korea.


Subject(s)
Insurance , Spinal Cord Injuries , Aged , Aged, 80 and over , Humans , Accidents, Occupational , Automobiles , Incidence , Republic of Korea
15.
BMC Med ; 20(1): 93, 2022 03 21.
Article in English | MEDLINE | ID: mdl-35307033

ABSTRACT

BACKGROUND: The effect of ezetimibe, Niemann-Pick C1-like 1 inhibitor, on liver fat is not clearly elucidated. Our primary objective was to evaluate the efficacy of ezetimibe plus rosuvastatin versus rosuvastatin monotherapy to reduce liver fat using magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) in patients with non-alcoholic fatty liver disease (NAFLD). METHODS: A randomized controlled, open-label trial of 70 participants with NAFLD confirmed by ultrasound who were assigned to receive either ezetimibe 10 mg plus rosuvastatin 5 mg daily or rosuvastatin 5 mg for up to 24 weeks. The liver fat change was measured as average values in each of nine liver segments by MRI-PDFF. Magnetic resonance elastography (MRE) was used to measure liver fibrosis change. RESULTS: Combination therapy significantly reduced liver fat compared with monotherapy by MRI-PDFF (mean difference: 3.2%; p = 0.020). There were significant reductions from baseline to study completion by MRI-PDFF for both the combination and monotherapy groups, respectively (18.1 to 12.3%; p < 0.001 and 15.0 to 12.4%; p = 0.003). Individuals with higher body mass index, type 2 diabetes, insulin resistance, and severe liver fibrosis were likely to be good responders to treatment with ezetimibe. MRE-derived change in liver fibrosis was not significantly different (both groups, p > 0.05). Controlled attenuation parameter (CAP) by transient elastography was significantly reduced in the combination group (321 to 287 dB/m; p = 0.018), but not in the monotherapy group (323 to 311 dB/m; p = 0.104). CONCLUSIONS: Ezetimibe and rosuvastatin were found to be safe to treat participants with NAFLD. Furthermore, ezetimibe combined with rosuvastatin significantly reduced liver fat in this population. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (registration number: NCT03434613 ).


Subject(s)
Diabetes Mellitus, Type 2 , Elasticity Imaging Techniques , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Non-alcoholic Fatty Liver Disease , Ezetimibe/therapeutic use , Humans , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/pathology
16.
J Neurol Neurosurg Psychiatry ; 93(2): 201-206, 2022 02.
Article in English | MEDLINE | ID: mdl-34518333

ABSTRACT

OBJECTIVE: The only identified cause of amyotrophic lateral sclerosis (ALS) are mutations in a number of genes found in familial cases but also in sporadic cases. De novo mutations occurring in a parental gonadal cell, in the zygote or postzygotic during embryonal development can result in an apparently sporadic/isolated case of ALS later in life. We searched for de novo mutations in SOD1 as a cause of ALS. METHODS: We analysed peripheral-blood exome, genome and Sanger sequencing to identify deleterious mutations in SOD1 in 4000 ALS patients from Germany, South Korea and Sweden. Parental kinship was confirmed using highly polymorphic microsatellite markers across the genome. Medical genealogical and clinical data were reviewed and compared with the literature. RESULTS: We identified four sporadic ALS cases with de novo mutations in SOD1. They aggregate in hot-spot codons earlier found mutated in familial cases. Their phenotypes match closely what has earlier been reported in familial cases with pathogenic mutations in SOD1. We also encountered familial cases where de novo mutational events in recent generations may have been involved. CONCLUSIONS: De novo mutations are a cause of sporadic ALS and may also be underpinning smaller families with few affected ALS cases. It was not possible to ascertain if the origin of the de novo mutations was parental germline, zygotic or postzygotic during embryonal development. All ALS patients should be offered genetic counselling and genetic screening, the challenges of variant interpretation do not outweigh the potential benefits including earlier confirmed diagnosis and possible bespoken therapy.


Subject(s)
Amyotrophic Lateral Sclerosis/genetics , Superoxide Dismutase-1/genetics , Adult , Amyotrophic Lateral Sclerosis/etiology , Female , Genetic Association Studies , Genetic Testing , Germany , Humans , Longitudinal Studies , Male , Mutation , Phenotype , RNA-Binding Protein FUS/genetics , Republic of Korea , Sweden , Young Adult
17.
Lupus ; 31(6): 716-722, 2022 May.
Article in English | MEDLINE | ID: mdl-35369787

ABSTRACT

OBJECTIVES: To examine the long-term renal outcomes of systemic lupus erythematosus (SLE) patients with transient proteinuria. METHODS: The medical records of SLE patients who showed improvement in proteinuria (urine protein/creatinine ratio < 500 mg/g) after receiving corticosteroid therapy without immunosuppressants were reviewed. RESULTS: A total of 38 patients (mean creatinine: 0.74 ± 0.33 mg/dl) showed an improvement of proteinuria (1361 ± 1053 mg/g to 289 ± 125 mg/g) after receiving corticosteroid therapy alone for a median of 25 days (IQR, 10-55). After follow-up (median, 23 months [IQR, 15-121]), 25 (65%) patients maintained the resolution of proteinuria without renal dysfunction. The remaining 13 (34%) patients experienced a relapse of proteinuria during a median follow-up of 13.9 months from baseline (IQR, 1.6-25). There was no significant difference in the baseline laboratory data according to the occurrence of proteinuria relapse, but longer SLE disease duration at baseline was associated with the risk of proteinuria relapse (HR, 1.007; p = 0.033). Of the patients who underwent renal biopsy with proteinuria relapse, class II (53%) lupus nephritis was the most common pathology. None progressed to end-stage renal disease during an additional long-term further follow-up of median 33 months (IQR, 22-49) after proteinuria relapse. CONCLUSION: Two-thirds of SLE patients who showed improvement in proteinuria after corticosteroid alone maintained the non-proteinuric state without renal dysfunction. Thus, performing a kidney biopsy at the first onset of proteinuria could be delayed in patients who show an improvement in proteinuria after treatment with corticosteroids.


Subject(s)
Lupus Erythematosus, Systemic , Lupus Nephritis , Creatinine , Female , Humans , Kidney/pathology , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/pathology , Lupus Nephritis/complications , Lupus Nephritis/drug therapy , Lupus Nephritis/pathology , Male , Proteinuria/complications , Proteinuria/etiology , Recurrence , Retrospective Studies
18.
J Korean Med Sci ; 37(45): e325, 2022 Nov 21.
Article in English | MEDLINE | ID: mdl-36413798

ABSTRACT

As most individuals acquire immunity to severe acute respiratory syndrome coronavirus 2, South Korea declared a return to normalcy a few months ago. However, epidemic waves continue because of endlessly emerging variants and waning immunity. Health authorities are focusing on those at high risk of severe coronavirus disease 2019 to minimize damage to public health and the economy. In this regard, we investigated the vaccination rates in patients with various chronic medical conditions by examining the national health insurance claims data and the national immunization registry. We found that patients with chronic medical conditions, especially those of higher severity, such as malignancy, had vaccination rates approximately 10-20% lower than those of the general population. Public health authorities and healthcare providers should try to vaccinate these patients to avoid preventable morbidity and mortality.


Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , Cross-Sectional Studies , COVID-19/prevention & control , Vaccination , Immunization , Chronic Disease
19.
J Ment Health ; 31(4): 471-478, 2022 Aug.
Article in English | MEDLINE | ID: mdl-32438841

ABSTRACT

BACKGROUND: The lifetime prevalence of mental disorders in South Korea was 25.4% in 2016. The Act on Mental Health enabled the expansion of psychiatric facilities; however, resources were allocated without considering the population structure or the characteristics of mental health problems. AIMS: This paper investigates the status and trends of disease burden and the government budget for Korean mental health. METHODS: The burden of mental and behavioral disorders (MBDs) was measured using the incidence-based disability-adjusted life years (DALYs), and the mental health budget data was from the Ministry of Health and Welfare of South Korea. RESULTS: We estimated that the disease burden of MBDs accounted for 6.4% of the total disease burden, ranking as the seventh leading cause of Korean DALYs. The mental health budget in South Korea was USD 253.4 million in 2019 (USD 90.3 million from the general account, USD 65.8 million from the National Health Promotion Fund, and USD 97.3 million from the special account for the national mental hospitals). CONCLUSIONS: Challenges are created by the MBD burden on the Korean healthcare system, and the budget is insufficient to address this disease burden, suggesting that resource allocation systems should be improved.


Subject(s)
Mental Disorders , Mental Health , Cost of Illness , Government , Humans , Mental Disorders/epidemiology , Prevalence , Quality-Adjusted Life Years
20.
Thorax ; 76(9): 939-941, 2021 09.
Article in English | MEDLINE | ID: mdl-33782081

ABSTRACT

Non-pharmaceutical interventions (NPIs) have been widely implemented to mitigate the spread of COVID-19. We assessed the effect of NPIs on hospitalisations for pneumonia, influenza, COPD and asthma. This retrospective, ecological study compared the weekly incidence of hospitalisation for four respiratory conditions before (January 2016-January 2020) and during (February-July 2020) the implementation of NPI against COVID-19. Hospitalisations for all four respiratory conditions decreased substantially during the intervention period. The cumulative incidence of admissions for COPD and asthma was 58% and 48% of the mean incidence during the 4 preceding years, respectively.


Subject(s)
Asthma/epidemiology , COVID-19/prevention & control , Influenza, Human/epidemiology , Patient Admission/statistics & numerical data , Pulmonary Disease, Chronic Obstructive/epidemiology , Administrative Claims, Healthcare/statistics & numerical data , Humans , Republic of Korea/epidemiology , Retrospective Studies , SARS-CoV-2
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