Association between antibiotics use and the risk of rheumatoid arthritis: a retrospective cohort study in South Korea.

OBJECTIVES: Certain studies propose that antibiotic use may influence rheumatoid arthritis (RA) incidence, but the clear association between antibiotics and RA remains unclear. Therefore, this study aimed to examine the relationship between antibiotics and RA risk to provide additional epidemiological evidence. METHODS: This population-based retrospective cohort study was conducted with adults aged 40 years or older using the Korean National Health Insurance Service (NHIS) database. Antibiotic exposure was measured from 2003 to 2007. Study participants were followed up from January 1, 2008, to December 31, 2019. Multivariable Cox hazard regression was utilized to evaluate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the risk of RA according to accumulative days of antibiotic use and the number of antibiotic classes used, respectively. RESULTS: During 3,395 590 person-years of follow-up, 29 274 cases of RA were identified. Participants who used antibiotics for 91 or more days had a higher risk of RA (aHR, 1.79; 95% CI, 1.67-1.92) than antibiotic non-users. Additionally, individuals who used four or more kinds of antibiotic classes had a higher risk of RA (aHR, 1.61; 95% CI, 1.51-1.71) than those who did not prescribe antibiotics. The risk of RA was positively associated with both higher cumulative days of antibiotic exposure and a larger number of drug classes. These trends were maintained in sensitivity analyses, including variations in antibiotic exposure periods. CONCLUSION: Our findings suggest a possible association between the long-term use of antibiotics and RA incidence. Further studies are necessary for a clearer understanding of this association.

Association between antibiotic use and cardiovascular diseases in metabolic dysfunction-associated steatotic liver disease: A nationally representative retrospective cohort study.

AIM: Various subcategories for steatotic liver disease (SLD) were proposed globally. Previous studies suggested a heightened risk of cardiovascular diseases (CVD) with prolonged antibiotic exposure and metabolic dysfunction-associated SLD (MASLD), respectively. This study investigates the impact of antibiotic usage on CVD in MASLD patients. METHODS: From the Korean National Health Insurance Service database, 276 520 adults aged 40 and older were included. Antibiotic exposure was defined by the cumulative prescription days and the number of classes. Participants were categorized into no SLD and MASLD groups. Hepatic steatosis was defined by using the fatty liver index ≥60. From 2013 to 2019, 16 197 CVD cases were recorded. A multivariate Cox model, adjusting for covariates, assessed adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CVD risk associated with MASLD and antibiotic prescriptions. RESULTS: The group with ≥91 days of antibiotics prescribed and MASLD showed a significantly increased risk of CVD (aHR, 1.56; 95% CI, 1.39-1.74) compared with antibiotic non-users without SLD. Furthermore, the group with ≥4 classes of antibiotics prescribed and MASLD had an elevated risk of CVD (aHR, 1.49; 95% CI, 1.34-1.66) compared with antibiotic non-users without SLD. Consistent results were observed in several sensitivity analyses. CONCLUSIONS: Our study identified prolonged antibiotic exposure may be a factor that increases the risk of CVD in MASLD patients. These findings suggest an epidemiological basis for the therapeutic application of antibiotics in MASLD patients, and emphasize the need for further studies to deepen the understanding of these intricate relationships.

Changes in high-density lipoprotein cholesterol with risk of Cardiovascular Disease among initially high-density lipoprotein-high participants.

BACKGROUND: High-density lipoprotein cholesterol's (HDL-C) long-held status as a cardiovascular disease (CVD) preventative has been called into question. Most of the evidence, however, focused on either the risk of death from CVD, or on single time point level of HDL-C. This study aimed to determine the association between changes in HDL-C levels and incident CVD in individuals with high baseline HDL-C levels (≥ 60 mg/dL). METHODS: 77,134 people from the Korea National Health Insurance Service-Health Screening Cohort were followed for 517,515 person-years. Cox proportional hazards regression was used to evaluate the association between change in HDL-C levels and the risk of incident CVD. All participants were followed up until 31 December 2019, CVD, or death. RESULTS: Participants with the greatest increase in their HDL-C levels had higher risks of CVD (adjusted hazard ratio [aHR], 1.15; 95% confidence interval [CI], 1.05-1.25) and CHD (aHR 1.27, CI 1.11-1.46) after adjusting for age, sex, household income, body mass index, hypertension, diabetes mellitus, dyslipidemia, smoking, alcohol consumption, moderate-to-vigorous physical activity, Charlson comorbidity index, and total cholesterol than those with the lowest increase in HDL-C levels. Such association remained significant even among participants with decreased low-density lipoprotein cholesterol (LDL-C) levels for CHD (aHR 1.26, CI 1.03-1.53). CONCLUSIONS: In people with already high HDL-C levels, additional increases in HDL-C levels may be associated with an increased risk of CVD. This finding held true irrespective of the change in their LDL-C levels. Increasing HDL-C levels may lead to unintentionally elevated risk of CVD.

Exercise Frequency Reduction Is Associated With Higher Risk of Infection in Newly Diagnosed Diabetes: A Nationally Representative Cohort Study.

BACKGROUND: Exercise is an important method to control the progression of diabetes. Since diabetes compromises immune function and increases the risk of infectious diseases, we hypothesized that exercise may affect the risk of infection by its immunoprotective effects. However, population-based cohort studies regarding the association between exercise and the risk of infection are limited, especially regarding changes in exercise frequency. The aim of this study was to determine the association between the change in exercise frequency and the risk of infection among patients with newly diagnosed diabetes. METHODS: Data of 10,023 patients with newly diagnosed diabetes were extracted from the Korean National Health Insurance Service-Health Screening Cohort. Self-reported questionnaires for moderate-to-vigorous physical activity (MVPA) were used to classify changes in exercise frequency between two consecutive two-year periods of health screenings (2009-2010 and 2011-2012). The association between changes in exercise frequency and the risk of infection was evaluated using multivariable Cox proportional-hazards regression. RESULTS: Compared with engaging in ≥ 5 times of MVPA/week during both periods, a radical decrease in MVPA (from ≥ 5 times of MVPA/week to physical inactivity) was associated with a higher risk of pneumonia (adjusted hazard ratio [aHR], 1.60; 95% confidence interval [CI], 1.03-2.48) and upper respiratory tract infection (aHR, 1.15; 95% CI, 1.01-1.31). In addition, a reduction of MVPA from ≥ 5 to < 5 times of MVPA/week was associated with a higher risk of pneumonia (aHR, 1.52; 95% CI, 1.02-2.27), whereas the risk of upper respiratory tract infection was not higher. CONCLUSION: Among patients with newly diagnosed diabetes, a reduction in exercise frequency was related to an increase in the risk of pneumonia. For patients with diabetes, a modest level of physical activity may need to be maintained to reduce the risk of pneumonia.

Effects of meteorological factors and air pollutants on the incidence of COVID-19 in South Korea.

Air pollution and meteorological factors can exacerbate susceptibility to respiratory viral infections. To establish appropriate prevention and intervention strategies, it is important to determine whether these factors affect the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Therefore, this study examined the effects of sunshine, temperature, wind, and air pollutants including sulfur dioxide (SO2), carbon monoxide (CO), ozone (O3), nitrogen dioxide (NO2), particulate matter ≤2.5 µm (PM2.5), and particulate matter ≤10 µm (PM10) on the age-standardized incidence ratio of coronavirus disease (COVID-19) in South Korea between January 2020 and April 2020. Propensity score weighting was used to randomly select observations into groups according to whether the case was cluster-related, to reduce selection bias. Multivariable logistic regression analyses were used to identify factors associated with COVID-19 incidence. Age 60 years or over (odds ratio [OR], 1.29; 95% CI, 1.24-1.35), exposure to ambient air pollutants, especially SO2 (OR, 5.19; 95% CI, 1.13-23.9) and CO (OR, 1.17; 95% CI, 1.07-1.27), and non-cluster infection (OR, 1.28; 95% CI, 1.24-1.32) were associated with SARS-CoV-2 infection. To manage and control COVID-19 effectively, further studies are warranted to confirm these findings and to develop appropriate guidelines to minimize SARS-CoV-2 transmission.

Incidence of hearing loss following COVID-19 among young adults in South Korea: a nationwide cohort study.

Background: The association of COVID-19 with hearing loss (HL) is unclear among young adults and needs to be investigated. This study was conducted to determine the association of COVID-19 with HL and sudden sensorineural hearing loss (SSNHL) in young adults. Methods: This nationwide population-based cohort study used data from the Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service. The study population consisted of young adult citizens aged 20-39 years without a history of HL. All participants were followed up from July 1, 2022 until HL, death, or December 31, 2022. A positive diagnosis of SARS-CoV-2 infection was determined through laboratory testing employing real-time reverse transcription polymerase chain reaction assays using nasopharyngeal or oropharyngeal swabs. The primary and secondary outcomes were HL and SSNHL, respectively. Age, sex, household income, Charlson comorbidity index, COVID-19 vaccination, hypertension, diabetes, and dyslipidemia-adjusted subdistribution hazard ratios (aSHRs) and 95% confidence intervals (CIs) were evaluated using the Fine-Gray subdistribution hazard regression model, considering overall death as a competing event to compare the aSHRs between COVID-19 positive and negative groups. Findings: A total of 6,716,879 young adults were eligible for the analyses. During 40,260,757 person-months (PMs) of follow-up, 38,269 cases of HL and 5908 cases of SSNHL were identified. The risk of HL (incidence: 11.9 versus 3.4/10,000 PMs; SHR, 3.51; 95% CI, 3.39-3.63; aSHR, 3.44; 95% CI, 3.33-3.56; P < 0.0001) and SSNHL (incidence: 1.8 versus 0.5/10,000 PMs; SHR, 3.58; 95% CI, 3.29-3.90; aSHR, 3.52; 95% CI, 3.23-3.83; P < 0.0001) was higher in COVID-19 group as compared to no COVID-19 group. In the sensitivity analyses that evaluated HL and SSNHL risks after adopting multiple imputations, utilizing inverse probability of treatment weighting, limiting study population to the cohort with a health screening examination, the results were consistent to the primary analysis. Interpretation: Our findings suggest a heightened risk of HL and SSNHL following COVID-19 in young adults. Due to study limitations, including the lack of objective audiological data, issues with generalizability to other populations, and the retrospective design, careful interpretation is necessary. Further studies with objective audiological data and a longer follow-up period are warranted. Funding: IITP (Institute for Information & Communications Technology Planning & Evaluation; IITP-2024- RS-00156439) and Jeju National University Hospital Research Fund (2023).

Risk of pulmonary embolism and deep vein thrombosis following COVID-19: a nationwide cohort study.

Recent studies elucidate that coronavirus disease 2019 (COVID-19) patients may face a higher risk of cardiovascular complications. This study aimed to evaluate association of COVID-19 with the risk of pulmonary embolism (PE) or deep vein thrombosis (DVT). This nationwide population-based retrospective cohort study included Korean adult citizens between January 2021 and March 2022 from the Korea Disease Control and Prevention Agency COVID-19 National Health Insurance Service cohort. The Fine and Gray's regression with all-cause death as a competing event was adopted to evaluate PE and DVT risks after COVID-19. This study included a total of 1,601,835 COVID-19 patients and 14,011,285 matched individuals without COVID-19. The risk of PE (adjusted hazard ratio [aHR], 6.25; 95% confidence interval [CI], 3.67-10.66; p < 0.001) and DVT (aHR, 3.05; 95% CI, 1.75-5.29; p < 0.001) was higher in COVID-19 group in individuals without complete COVID-19 vaccination. In addition, individuals with complete COVID-19 vaccination still had a higher risk of COVID-19-related PE (aHR, 1.48; 95% CI, 1.15-1.88; p < 0.001). However, COVID-19 was not a significant risk factor for DVT among those with complete COVID-19 vaccination. COVID-19 was identified as an independent factor that elevated PE and DVT risks, especially for individuals without complete COVID-19 vaccination.

Tramadol use and incident dementia in older adults with musculoskeletal pain: a population-based retrospective cohort study.

We aimed to assess the association of tramadol use with the risk of dementia. This population-based retrospective cohort study using the Korean National Health Insurance Service database included a total of 1,865,827 older adult patients aged 60 years or older with common musculoskeletal pain between January 1, 2003, and December 31, 2007. Individuals who were newly dispensed tramadol (N = 41,963) were identified and propensity score-matched with those who were not (N = 41,963). Over a maximum of 14-year follow-up, the incidence rates (events per 1000 person-years) of all-cause dementia were 6.1 for nonusers, 6.2 for those with cumulative tramadol use of 1-14 days, 7.7 for those with 15-90 days of use, and 8.0 for those with > 90 days of use. Longer cumulative duration of tramadol use was associated with an increased risk of all-cause dementia compared with nonuse (1 to 14 days: aHR 1.06, 95% CI 0.96-1.17; 15 to 90 days: aHR 1.14, 95% CI 1.10-1.35; and more than 90 days: aHR 1.18, 95% CI 1.00-1.39; test for trend: P < 0.001). The results showed a similar pattern for Alzheimer's disease and were robust across subgroup and sensitivity analyses, but not for vascular dementia. This study found that exposure to tramadol was associated with an increased risk of dementia. Taking this potential risk into consideration, clinicians should carefully weigh potential benefits and risks when prescribing tramadol to older adults with musculoskeletal pain.

Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study.

BACKGROUND/AIMS: To determine the association between evolutionary changes in metabolic dysfunction-associated steatotic liver disease (MASLD) status and the risk of hepatocellular carcinoma (HCC) in a nationwide population-based cohort. METHODS: Information on study participants was derived from the Korea National Health Insurance Service database. The study population consisted of 5,080,410 participants who underwent two consecutive biennial health screenings between 2009 and 2012. All participants were followed up until HCC, death, or 31 December 2020. The association of evolutionary changes in MASLD status, as assessed by the fatty liver index and cardiometabolic risk factors, including persistent non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD, with HCC risk was evaluated using multivariable-adjusted Cox proportional hazards regression. RESULTS: Among the 5,080,410 participants with 39,910,331 person-years of follow-up, 4,801 participants developed HCC. The incidence of HCC in participants with resolved, incident, and persistent MASLD was approximately 2.2-, 2.3-, and 4.7-fold higher, respectively, than that in those with persistent non-MASLD among the Korean adult population. When stratifying the participants according to the evolutionary change in MASLD status, persistent (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 2.68-3.21; P<0.001), incident (aHR, 1.85; 95% CI, 1.63-2.10; P<0.001), and resolved MASLD (aHR, 1.33; 95% CI, 1.18-1.50; P<0.001) had an increased risk of HCC compared to persistent non-MASLD. CONCLUSION: The evolutionary changes in MASLD were associated with the differential risk of HCC independent of metabolic risk factors and concomitant medications, providing additional information on the risk of HCC stratification in patients with MASLD.

Association between antibiotics use and osteoporotic fracture risk: a nationally representative retrospective cohort study.

This population-based retrospective cohort study aimed to estimate the association between antibiotic exposure and osteoporotic fracture risk. Long-term antibiotic use was associated with the risk of osteoporotic fracture. An increase in the number of antibiotic classes prescribed may also be associated with an increased osteoporotic fracture risk. PURPOSE: This study aims to examine the association between antibiotic usage and osteoporotic fractures in a large cohort of Korean adults, with a specific focus on the duration of antibiotic exposure and the number of antibiotic classes used. METHODS: This retrospective cohort study from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) database from January 1, 2002, to December 31, 2019, included 167,370 Korean adults aged 50 years or older (mean [SD] age, 59.3 [7.82] years; 65,425 [39.09%] women). The cumulative antibiotic prescription days and the classes of antibiotics prescribed between 2004 and 2008 were exposure variables, respectively. The main outcome was a newly diagnosed osteoporotic fracture during follow-up. Cox proportional hazard regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the incident osteoporotic fractures associated with antibiotic exposure. RESULTS: The antibiotic user group with 91 days had a higher risk of osteoporotic fracture in comparison to the antibiotic non-user group (aHR, 1.12; 95% CI, 1.03-1.21). Additionally, those who used more than four different antibiotic classes had an elevated risk of osteoporotic fracture compared to the non-user group (aHR, 1.10; 95% CI, 1.02-1.18). CONCLUSION: This extensive population-based cohort study conducted on a large population has identified an association between the utilization of antibiotics and an elevated risk of osteoporotic fractures. The cumulative days exposed to antibiotics and osteoporotic fractures may be positively associated.

Association of balance impairment with risk of incident cardiovascular diseases among older adults.

BACKGROUND: Rapid decline in balance is a hallmark of aging, elevating the risk of falls and other age-related geriatric illnesses among older adults. OBJECTIVE: Our aim was to assess whether impairment in balance function is associated with the risk of incident CVD in older adults. DESIGN: Retrospective cohort analysis. PARTICIPANTS: A total of 129,024 participants who had undergone health screening between 2002 and 2009 were derived from the National Health Insurance Service-Senior cohort. MAIN MEASURES: Balance impairment was evaluated using the open-eyes one-leg standing (OLS) test. The association between balance impairment and incident CVD was analyzed using the Cox proportional hazards regression model. All participants were followed up with until either the date of the first incident of CVD, death, or 31 December 2019. KEY RESULTS: Those with abnormal balance function (< 10 s in OLS test) had a higher risk of CVD (adjusted hazard ratio [aHR] 1.23, CI 1.16-1.31). The association was significant in both the obese and the non-obese, but it seemed to be more pronounced in the latter. Results were supported by sensitivity analyses that did not include cases of CVD development in the first 1, 2, or 3 years and that used a different criterion to define balance dysfunction (< 9 s in OLS test). CONCLUSIONS: Older adults with balance impairment were found to have an increased risk of incident CVD. Patients with impaired balance function may be a high-risk population who require preventive managements against CVD.

Association Between Hearing Impairment and Incident Depression: A Nationwide Follow-up Study.

BACKGROUND: Accumulating evidence suggests that hearing impairment is associated with the onset of depression. However, large-scale epidemiological studies are required to define this association more clearly. We aimed to investigate the risk of new-onset depression in Korean older adults with and without hearing impairment. METHODS: From the National Health Insurance Service-Senior Cohort, which is a retrospective-prospective hybrid database, we analyzed data for 254,466 older adults enrolled in the Korea National Health Insurance Service-Senior Cohort who underwent at least one health screening between 2003 and 2019. A Cox proportional hazards regression model was used to evaluate the association between hearing impairment and the risk of incident depression, which was presented as adjusted hazard ratios (aHR) with 95% confidence intervals (CIs). All participants were followed up until the date of incident depression, death, or December 31, 2019. RESULTS: During 3,417,682 person-years of follow-up investigation, hearing impairment was associated with a higher risk of incident depression (vs. no hearing impairment) in the final adjusted model (aHR, 1.11; 95% CI, 1.01-1.21; p = 0.033). Stratified analyses revealed a significant interaction among age, hearing impairment, and the risk of depression. Participants aged <65 years had a higher risk of depression (aHR, 1.29; 95% CI, 1.12-1.50; p < 0.001) than those aged 65 or above (aHR, 1.15; 95% CI, 1.01-1.30; p = 0.032). CONCLUSIONS: Hearing impairment is independently associated with a higher risk of depression among older adults. The prevention and treatment of hearing impairment may aid in mitigating the risk of incident depression. LEVEL OF EVIDENCE: Level 3 Laryngoscope, 133:3144-3151, 2023.

Risk of Bell's palsy following SARS-CoV-2 infection: a nationwide cohort study.

OBJECTIVES: Despite some evidence of an increased risk of neurologic symptoms following viral vector COVID-19 vaccine administration, it is unclear whether SARS-CoV-2 infection is associated with Bell's palsy (BP), especially over a long enough follow-up period. METHODS: The study population of this nationwide population-based study was derived from the South Korean population, including 11 593 365 and 36 565 099 participants with and without COVID-19, respectively. The Fine and Gray's regression model was utilized to calculate the adjusted subdistribution hazard ratio (aSHR), considering death as a competing risk, to assess the association between SARS-CoV-2 infection and the risk of BP. All participants were followed up from 1 December 2021, until the incident BP, SARS-CoV-2 infection, death, or 31 March 2022. Subgroup analyses were conducted based on participants' vaccination status (completion of the primary series vs. unvaccinated). RESULTS: COVID-19 was associated with an increased risk of BP in all participants (aSHR, 1.24; CI, 1.19-1.29). However, the size of the COVID-19-related BP risk was significantly lower among those who completed the primary series of the COVID-19 vaccine (aSHR, 1.20; 95% CI, 1.15-1.25) compared to those who were unvaccinated (aSHR, 1.84; 95% CI, 1.59-2.12; p for interaction: <0.001). The severity of COVID-19 exhibited a gradual escalation in BP risk for both vaccinated and unvaccinated individuals. DISCUSSION: While both unvaccinated individuals and those who completed the primary series of the COVID-19 vaccine may be at an increased risk of developing BP due to COVID-19, the risk appears to be lower among those who completed the vaccination.

Safety of COVID-19 Vaccines among Patients with Type 2 Diabetes Mellitus: Real-World Data Analysis.

BACKGROUND: Little is known about the adverse events (AEs) associated with coronavirus disease 2019 (COVID-19) vaccination in patients with type 2 diabetes mellitus (T2DM). METHODS: This study used vaccine AE reporting system data to investigate severe AEs among vaccinated patients with T2DM. A natural language processing algorithm was applied to identify people with and without diabetes. After 1:3 matching, we collected data for 6,829 patients with T2DM and 20,487 healthy controls. Multiple logistic regression analysis was used to calculate the odds ratio for severe AEs. RESULTS: After COVID-19 vaccination, patients with T2DM were more likely to experience eight severe AEs than controls: cerebral venous sinus thrombosis, encephalitis myelitis encephalomyelitis, Bell's palsy, lymphadenopathy, ischemic stroke, deep vein thrombosis (DVT), thrombocytopenia (TP), and pulmonary embolism (PE). Moreover, patients with T2DM vaccinated with BNT162b2 and mRNA-1273 were more vulnerable to DVT and TP than those vaccinated with JNJ-78436735. Among patients with T2DM administered mRNA vaccines, mRNA-1273 was safer than BNT162b2 in terms of the risk of DVT and PE. CONCLUSION: Careful monitoring of severe AEs in patients with T2DM may be necessary, especially for those related to thrombotic events and neurological dysfunctions after COVID-19 vaccination.

Inverse association between changes in systolic and diastolic blood pressure and risk of depression: A nationally representative cohort study.

BACKGROUND: Depression is one of complex mental disorders with diverse etiological factors but the association between blood pressure (BP) and depression is unknown. We aimed to investigate the association between changes in BP (systolic and diastolic) and incident depression. METHODS: From the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS), 224,192 participants who underwent biennial health screenings from period I (2004-05) and II (2006-07) were included in the study. Systolic BP (SBP) and diastolic BP (DBP) categories were defined as follows: SBP into 5 categories (<90 mmHg, 90 mmHg -119 mmHg, 120 mmHg -129 mmHg, 130 mmHg -139 mmHg, ≥140 mmHg) and DBP into 4 categories (<60 mmHg, 60 mmHg -79 mmHg, 80 mmHg -89 mmHg, ≥90 mmHg). Also, BP levels were classified into 5 groups: normal, elevated BP, stage 1 BP, stage 2 BP, hypotension. Using the Cox proportional hazards regression, changes in SBP and DBP between two screening periods and the risk of depression were calculated by adjusted hazard ratio (aHR) and 95 % confidence interval (CI). RESULTS: There were 17,780 depression events during 1.5 million person-year of follow-up. Compared to the participants with SBP ≥ 140 mmHg or DBP ≥ 90 mmHg from both periods, those who decreased SBP from ≥140 mmHg to 120 mmHg-129 mmHg (aHR 1.13; 95 % CI 1.04-1.24; P = 0.001) and those who decreased DBP from ≥90 mmHg to 60 mmHg-79 mmHg (aHR 1.10; 95 % CI 1.02-1.20; P = 0.020) showed a higher risk of depression, respectively. CONCLUSIONS: Changes in SBP and DBP showed an inverse relationship with depression risk.

Association between visit-to-visit fasting glycemic variability and depression: a retrospective cohort study in a representative Korean population without diabetes.

Glycemic variability (GV) is a risk factor for depression in patients with diabetes. However, whether it is also a predictor of incident depression in people without diabetes remains unclear. We aimed to investigate the association between visit-to-visit variability in fasting serum glucose (FSG) levels and the incidence of depression among Koreans without diabetes. This retrospective cohort study included data of people without diabetes who did not have depression at baseline and had at least three FSG measurements (n = 264,480) extracted from the 2002-2007 Korean National Health Insurance Service-National Health Screening Cohort. GV was calculated as the average successive variability of FSG. Among 264,480 participants, 198,267 were observed during 2008-2013 and their hazard ratios (HR) of incident depression were calculated. Participants with the highest GV showed a higher risk of depression in fully adjusted models than those with the lowest GV (HR, 1.09; 95% CI, 1.02-1.16). The risk of incident depression heightened with increasing GV (p for trend < 0.001). Greater visit-to-visit GV may be associated with the risk of developing depression in people without diabetes. Conversely, maintaining steady FSG levels may reduce the risk of incident depression in people without diabetes.

Development and validation of a nonalcoholic fatty liver disease-based self-diagnosis tool for diabetes.

Background: Prediction of type 2 diabetes mellitus (DM) has been studied widely. However, a hospital visit was necessary to apply previous prediction models for the evaluation of DM. This study was conducted to develop and validate a hospital visit-free self-diagnosis tool for DM. Methods: Participants who underwent health screening between 2017-2018 (n=7,519; training cohort) and 2019-2020 (n=7,564; validation cohort) were extracted from the Korea National Health and Nutrition Examination Survey (KNHANES). DM was defined as doctor-diagnosed DM in a questionnaire. Logistic regression was used to determine independent predictors for DM, and a multivariable logistic regression-based nomogram was developed for the prediction of DM, which was validated in a cohort consisting of an independent population. The presence of nonalcoholic fatty liver disease (NAFLD) was operationally defined using the KNHANES-NAFLD score. Results: Age, sex, waist circumference, systolic blood pressure, total cholesterol, triglyceride, aspartate aminotransferase, blood urea nitrogen, urinary protein, urinary glucose, and NAFLD were identified as independent predictors for DM. After excluding laboratory variables that require laboratory tests, a simplified multivariable model was conducted based on hospital visit-free variables, including age, sex, waist circumference, systolic blood pressure, and NAFLD. The full and simplified prediction models for DM were presented as nomograms. In the independent validation cohort, the full and simplified DM prediction models were validated with an area under the curve values of 0.903 and 0.824 from the receiver operating characteristic curves, respectively. Conclusions: Involvement of NAFLD has allowed satisfactory prediction of DM without laboratory tests that require a hospital visit. The developed model may be promising in terms of early diagnosis of DM among individuals without hospital visits and may reduce the socioeconomic burden of DM in the real-world, which awaits future prospective trials to confirm.

Health-Screening-Based Chronic Obstructive Pulmonary Disease and Its Effect on Cardiovascular Disease Risk.

Chronic obstructive pulmonary disease (COPD) is considered a major cause of death worldwide, and various studies have been conducted for its early diagnosis. Our work developed a scoring system by predicting and validating COPD and performed predictive model implementations. Participants who underwent a health screening between 2017 and 2020 were extracted from the Korea National Health and Nutrition Examination Survey (KNHANES) database. COPD individuals were defined as aged 40 years or older with prebronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC < 0.7). The logistic regression model was performed, and the C-index was used for variable selection. Receiver operating characteristic (ROC) curves with area under the curve (AUC) values were generated for evaluation. Age, sex, waist circumference and diastolic blood pressure were used to predict COPD and to develop a COPD score based on a multivariable model. A simplified model for COPD was validated with an AUC value of 0.780 from the ROC curves. In addition, we evaluated the association of the derived score with cardiovascular disease (CVD). COPD scores showed significant performance in COPD prediction. The developed score also showed a good effect on the diagnostic ability for CVD risk. In the future, studies comparing the diagnostic accuracy of the derived scores with standard diagnostic tests are needed.

The Partner Switching System of the SigF Sigma Factor in Mycobacterium smegmatis and Induction of the SigF Regulon Under Respiration-Inhibitory Conditions.

The partner switching system (PSS) of the SigF regulatory pathway in Mycobacterium smegmatis has been previously demonstrated to include the anti-sigma factor RsbW (MSMEG_1803) and two anti-sigma factor antagonists RsfA and RsfB. In this study, we further characterized two additional RsbW homologs and revealed the distinct roles of three RsbW homologs [RsbW1 (MSMEG_1803), RsbW2 (MSMEG_6129), and RsbW3 (MSMEG_1787)] in the SigF PSS. RsbW1 and RsbW2 serve as the anti-sigma factor of SigF and the protein kinase phosphorylating RsfB, respectively, while RsbW3 functions as an anti-SigF antagonist through its protein interaction with RsbW1. Using relevant mutant strains, RsfB was demonstrated to be the major anti-SigF antagonist in M. smegmatis. The phosphorylation state of Ser-63 was shown to determine the functionality of RsfB as an anti-SigF antagonist. RsbW2 was demonstrated to be the only protein kinase that phosphorylates RsfB in M. smegmatis. Phosphorylation of Ser-63 inactivates RsfB to render it unable to interact with RsbW1. Our comparative RNA sequencing analysis of the wild-type strain of M. smegmatis and its isogenic Δaa 3 mutant strain lacking the aa 3 cytochrome c oxidase of the respiratory electron transport chain revealed that expression of the SigF regulon is strongly induced under respiration-inhibitory conditions in an RsfB-dependent way.