Association between antibiotic use and subsequent risk of prostate cancer: A retrospective cohort study in South Korea.

OBJECTIVES: Several studies suggest that antibiotic use may affect overall cancer incidence, but the association between antibiotics and prostate cancer is still unclear. This retrospective cohort study aimed to assess the association between antibiotics and the risk of prostate cancer. METHODS: A population-based retrospective cohort study was conducted using the Korean National Health Insurance Service (NHIS) database. 1 032 397 individuals were followed up from January 1, 2007, to December 31, 2019. Multivariable Cox hazards regression was utilized to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the risk of prostate cancer according to accumulative days of antibiotic use and the number of antibiotic classes used from 2002 to 2006. RESULTS: Individuals who used antibiotics for 180 or more days had a higher risk of prostate cancer (aHR, 1.46; 95% CI, 1.11-1.91) than those who did not use antibiotics. Also, individuals who used four or more kinds of antibiotics had a higher risk of prostate cancer (aHR, 1.18; 95% CI, 1.07-1.30) than antibiotic non-users. An overall trend was observed among participants who underwent health examinations. CONCLUSIONS: Our findings suggest that long-term use of antibiotics may affect prostate cancer incidence. Further studies are needed to improve understanding of the association between antibiotic use and prostate cancer incidence.

Association of the combined effects of air pollution and changes in physical activity with cardiovascular disease in young adults.

AIMS: Little is known about the trade-off between the health benefits of physical activity (PA) and the potential harmful effects of increased exposure to air pollution during outdoor PA. We examined the association of the combined effects of air pollution and changes in PA with cardiovascular disease (CVD) in young adults. METHODS AND RESULTS: This nationwide cohort study included 1 469 972 young adults aged 20-39 years. Air pollution exposure was estimated by the annual average cumulative level of particulate matter (PM). PA was calculated as minutes of metabolic equivalent tasks per week (MET-min/week) based on two consecutive health examinations from 2009 to 2012. Compared with the participants exposed to low-to-moderate levels of PM2.5 or PM10 who continuously engaged in ≥1000 MET-min/week of PA, those who decreased their PA from ≥1000 MET-min/week to 1-499 MET-min/week [PM10 adjusted hazard ratio (aHR) 1.22; 95% confidence interval (CI) 1.00-1.48] and to 0 MET-min/week (physically inactive; PM10 aHR 1.38; 95% CI 1.07-1.78) had an increased risk of CVD (P for trend <0.01). Among participants exposed to high levels of PM2.5 or PM10, the risk of CVD was elevated with an increase in PA above 1000 MET-min/week. CONCLUSION: Reducing PA may lead to subsequent elevation of CVD risk in young adults exposed to low-to-moderate levels of PM2.5 or PM10, whereas a large increase in PA in a high-pollution environment may adversely affect cardiovascular health.

Association between physical activity and subsequent cardiovascular disease among 5-year breast cancer survivors.

PURPOSE: To examine the association of physical activity among long-term breast cancer survivors on the occurrence of subsequent cardiovascular disease (CVD). METHODS: We investigated the risk of CVD among 39,775 breast cancer patients who were newly diagnosed in 2006 and survived until 2011 within the Korean National Health Insurance Service database. Patients were followed up from 5 years after breast cancer diagnosis to the date of CVD event, death, or December 31, 2018, whichever came earliest. Every 500 MET-mins/week correspond to 152, 125, and 62.5 min per week of light-, moderate-, and vigorous-intensity physical activity, respectively. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CVD were calculated using Cox proportional hazards regression by physical activity levels. RESULTS: Compared with those with physical activity of 0 MET-min/week, those with 1-499 (aHR 0.82, 95% CI 0.69-0.98), 500-999 (aHR 0.75, 95% CI 0.63-0.90), and ≥ 1,000 (aHR 0.76, 95% CI 0.63-0.93) MET-min/week of PA had lower risk of CVD. Higher levels of PA were associated with lower risk of stroke (p for trend = 0.016). The benefits of PA on obese and overweight breast cancer survivors were smaller than those in normal weight survivors. The frequency of moderate-to-vigorous physical activity (MVPA) showed a reverse J-curve association with CVD, and the best benefit occurred in the 3-4 times MVPA per week group (aHR 0.59, 95% CI 0.46-0.74). CONCLUSIONS: The study showed that even small amounts of PA may be beneficial in potentially decreasing the risk of CVD, CHD, and stroke in breast cancer survivors. Our result will be useful to prescribe and delivery exercise among long-term breast cancer survivors.

Association of particulate matter with autoimmune rheumatic diseases among adults in South Korea.

OBJECTIVE: The primary objective of this study was to investigate adverse effects of ambient particulate matter of various sizes on the incidence of the prevalent autoimmune rheumatic diseases (AIRDs): RA, AS and SLE. METHODS: We investigated 230 034 participants in three metropolitan cities of South Korea from the National Health Insurance Service-National Sample Cohort (NHIS-NSC). Starting from January 2010, subjects were followed up until the first event of prevalent AIRDs, death, or December 2013. The 2008-2009 respective averages of particulate matter2.5 (<2.5 µm) and particulate mattercoarse (2.5 µm to 10 µm) were linked with participants' administrative district codes. Adjusted hazard ratios (aHRs) and 95% CIs were estimated using Cox regression analysis in one- and two-pollutant models. RESULTS: Adjusted for age, sex, region, and household income, in the two-pollutant model, RA incidence was positively associated with the 10 µg/m³ increment of particulate matter2.5 (aHR = 1.74, 95% CI: 1.06, 2.86), but not with particulate mattercoarse (aHR = 1.27, 95% CI: 0.87, 1.85). In the one-pollutant model, the elevated incidence rate of RA was slightly attenuated (particulate matter2.5 aHR = 1.61, 95% CI: 0.99, 2.61; particulate mattercoarse aHR = 1.13, 95% CI: 0.80, 1.61), with marginal statistical significance for particulate matter2.5. The RA incidence was also higher in the 4th quartile group of particulate matter2.5 compared with the first quartile group (aHR = 1.83, 95% CI: 1.07, 3.11). Adverse effects from particulate matter were not found for AS or SLE in either the one- or two-pollutant models. CONCLUSION: The important components of particulate matter10 associated with RA incidence were the fine fractions (particulate matter2.5); no positive association was found between particulate matter and AS or SLE.

Explaining the Rationale of Deep Learning Glaucoma Decisions with Adversarial Examples.

PURPOSE: To illustrate what is inside the so-called black box of deep learning models (DLMs) so that clinicians can have greater confidence in the conclusions of artificial intelligence by evaluating adversarial explanation on its ability to explain the rationale of DLM decisions for glaucoma and glaucoma-related findings. Adversarial explanation generates adversarial examples (AEs), or images that have been changed to gain or lose pathologic characteristic-specific traits, to explain the DLM's rationale. DESIGN: Evaluation of explanation methods for DLMs. PARTICIPANTS: Health screening participants (n = 1653) at the Seoul National University Hospital Health Promotion Center, Seoul, Republic of Korea. METHODS: We trained DLMs for referable glaucoma (RG), increased cup-to-disc ratio (ICDR), disc rim narrowing (DRN), and retinal nerve fiber layer defect (RNFLD) using 6430 retinal fundus images. Surveys consisting of explanations using AE and gradient-weighted class activation mapping (GradCAM), a conventional heatmap-based explanation method, were generated for 400 pathologic and healthy patient eyes. For each method, board-trained glaucoma specialists rated location explainability, the ability to pinpoint decision-relevant areas in the image, and rationale explainability, the ability to inform the user on the model's reasoning for the decision based on pathologic features. Scores were compared by paired Wilcoxon signed-rank test. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUC), sensitivities, and specificities of DLMs; visualization of clinical pathologic changes of AEs; and survey scores for locational and rationale explainability. RESULTS: The AUCs were 0.90, 0.99, 0.95, and 0.79 and sensitivities were 0.79, 1.00, 0.82, and 0.55 at 0.90 specificity for RG, ICDR, DRN, and RNFLD DLMs, respectively. Generated AEs showed valid clinical feature changes, and survey results for location explainability were 3.94 ± 1.33 and 2.55 ± 1.24 using AEs and GradCAMs, respectively, of a possible maximum score of 5 points. The scores for rationale explainability were 3.97 ± 1.31 and 2.10 ± 1.25 for AEs and GradCAM, respectively. Adversarial example provided significantly better explainability than GradCAM. CONCLUSIONS: Adversarial explanation increased the explainability over GradCAM, a conventional heatmap-based explanation method. Adversarial explanation may help medical professionals understand more clearly the rationale of DLMs when using them for clinical decisions.

Associations between alcohol consumption and cardiovascular disease among long-term survivors of colorectal cancer: a population-based, retrospective cohort study.

BACKGROUND: There is no evidence whether it is best to stop drinking alcohol at all or whether it is okay to drink a little in that light-to-moderate alcohol use was associated with low cardiovascular disease (CVD) compared to non-drinker among colorectal cancer (CRC) survivors, who are regarded as vulnerable to CVD. Therefore, we evaluated the association between alcohol consumption and incident CVD among long-term survivors of CRC. METHODS: This population-based, retrospective cohort study utilized data from the Korean National Insurance Service of 20,653 long-term survivors of CRC diagnosed between 2006 and 2012. Participants were followed up to the date of CVD, death, or December 31, 2018. All patients were categorized according to their daily alcohol consumption (g/day). The outcomes were incident CVD, including ischemic heart disease (IHD) and ischemic and hemorrhagic stroke, analyzed using the Cox proportional hazards regression after adjusting for cardiovascular risk factors and history of chemotherapy and radiotherapy. RESULTS: There was no association between alcohol consumption and incident CVD among long-term survivors of CRC. Additionally, hazardous alcohol consumption (≥ 40 g/day in male patients and ≥ 20 g/day in female patients) was associated with increased CVD, ischemic stroke, and hemorrhagic stroke (adjusted hazard ratio [95% confidence interval]: 1.51 [1.15-1.97], 1.60 [1.03-2.48], and 2.65 [1.25-5.62], respectively) compared with non-drinkers. CONCLUSION: No discernable protective association was found between alcohol consumption and incident CVD for even light-to-moderate drinking among long-term survivors of CRC. Alcohol consumption ≥40 g/day in male patients and ≥ 20 g/day in female patients was associated with an increased risk of stroke compared with non-drinkers. These novel results provide useful evidence when advising survivors of CRC regarding alcohol use.

Association of tibolone and dementia risk: a cohort study using Korean claims data.

OBJECTIVE: Few studies have examined whether tibolone (TIB), a type of hormone replacement therapy widely used in Asia and Europe, affects dementia risk in postmenopausal women. Our study aims to investigate the association of TIB and dementia risk in Korean women aged 50-80 years. METHODS: A population-based longitudinal study was conducted using the Korean National Health Insurance Service claims database merged with national health examination data from 2002 to 2015. Among 13,110 participants, exposure to TIB was determined using the standardized defined daily dose (DDD) system from 2003 to 2007. Starting from 2007, participants were followed up for overall dementia, Alzheimer's disease (AD) and vascular dementia (VD) until 2015. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of dementia according to TIB use. RESULTS: TIB use was not significantly associated with the risk of total dementia (aHR = 1.040; 95% CI = 0.734-1.472; p = .827), AD (aHR = 0.949; 95% CI = 0.652-1.381; p = .785) and VD (aHR = 1.245; 95% CI = 0.631-2.457; p = .528). CONCLUSIONS: Our results suggest that TIB use does not have a significant association with dementia risk. Further randomized controlled trials are necessary to elucidate the role of exogenous hormones in the development of dementia.

The Association of 5α-Reductase Inhibitor With Suicidality.

OBJECTIVE: Using a large nationwide cohort, this study aimed to determine the risk of suicide after the use of a 5α-reductase inhibitor, an antiandrogenic medication commonly used in the treatment of lower urinary tract symptoms. METHODS: A retrospective population-based cohort study was performed using the Korean National Health Insurance Service database. The study consisted of 51,466 men 60 years or older who underwent health examinations between 2005 and 2006. Individuals using a 5α-reductase inhibitor were compared with nonusers based on drug exposure between 2003 and 2006. Individuals using a 5α-reductase inhibitor were additionally divided into tertiles based on cumulative 5α-reductase inhibitor exposure. The incidence of completed suicide was documented during 7 years of follow-up, starting January 1, 2007. RESULTS: No significant risk of suicide was observed among 5α-reductase inhibitor users compared with 5α-reductase inhibitor nonusers (hazard ratio = 1.02, 95% confidence interval = 0.70-1.48). Cumulative 5α-reductase inhibitor exposure was also not associated with increased risk of suicide (p for trend = .543). CONCLUSIONS: 5α-Reductase inhibitor use was not associated with an elevated risk of suicide during a long-term follow-up period. A limitation of this study is that possible drug exposure after the index date was not accounted for. Although 5α-reductase inhibitor may increase the risk of depressive symptoms, the present data indicate that the drug is safe in terms of long-term suicide risk.

Association of air pollution with osteoporotic fracture risk among women over 50 years of age.

INTRODUCTION: Air particulate matter (PM) is an environmental exposure associated with oxidation and inflammation. Whether particulate matter is associated with risk of osteoporotic bone fracture is unclear. We investigated the association between exposure to PM and risk of bone fractures. MATERIALS AND METHODS: We collected data of 44,602 participants living in three metropolitan cities in Republic of Korea from National Health Insurance Service database. We examined the association of 2 year averaged concentrations of PM and osteoporotic fracture over 4 years. Exposure to 2-year averaged air pollution [PM2.5 (< 2.5 µm in aerodynamic diameter), PM10 [< 10 µm in aerodynamic diameter], PM coarse (PM ranging from 2.5 µm to 10 µm)] concentrations were estimated from 2008 to 2009 in Air Korea data. The adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for osteoporotic fractures were calculated using the multivariate Cox proportional hazards model. RESULTS: After adjusting for age, household income, and Charlson Comorbidity Index, PM 2.5 in one pollutant model increased the risk of osteoporotic fractures, compared to the first quartile group (4th quartile group aHR = 1.13, 95% CI 1.02-1.24). Also, PM 2.5 increased the risk of spine and non-spine fractures compared to the first quartile group (4th quartile group aHR = 1.17, 95% CI 1.00-1.38, aHR = 1.16, 95% CI 1.01-1.33). We found no association between PM10/PM coarse and osteoporotic fractures. CONCLUSION: We found that PM2.5 is a risk factor for osteoporotic bone fractures.

Association of smoking cessation after atrial fibrillation diagnosis on the risk of cardiovascular disease: a cohort study of South Korean men.

BACKGROUND: While smoking elevates the risk for cardiovascular disease (CVD) among atrial fibrillation (AF) patients, whether smoking cessation after AF diagnosis actually leads to reduced CVD risk is unclear. We aimed to determine the association of smoking cessation after AF diagnosis with subsequent CVD Risk among South Korean men. METHODS: This retrospective cohort study included 2372 newly diagnosed AF male patients during 2003-2012 from the Korean National Health Insurance Service database. Self-reported smoking status within 2 years before and after diagnosis date were determined, after which the participants were divided into continual smokers, quitters (smokers who quit after AF diagnosis), sustained-ex smokers (those who quit prior to AF diagnosis), and never smokers. Participants were followed up from 2 years after AF diagnosis until 31 December 2015 for CVD. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence interval (CIs) for CVD according to the change in smoking habits before and after AF diagnosis. RESULTS: The mean (standard deviation, minimum-maximum) age of the study subjects was 62.5 (8.6, 41-89) years. Among AF patients, quitters had 35% reduced risk (aHR 0.65, 95% CI 0.44-0.97) and never smokers had 32% reduced risk (aHR 0.68, 95% CI 0.52-0.90) for CVD compared to continual smokers (p for trend 0.020). Similarly, compared to continual smokers, quitters had 41% risk-reduction (aHR 0.59, 95% CI 0.35-0.99) and never smokers 34% risk-reduction (aHR 0.66, 95% CI 0.46-0.93) for total stroke (p for trend 0.047). Quitters had 50% reduction (aHR 0.50, 95% CI 0.27-0.94), sustained ex-smokers had 36% reduction (aHR 0.64, 95% CI 0.42-0.99), and never smokers had 39% reduction (aHR 0.61, 95% CI 0.41-0.91) in ischemic stroke risk (p for trend 0.047). The risk-reducing effect of quitting on CVD risk tended to be preserved regardless of aspirin or warfarin use. CONCLUSIONS: Smoking cessation after AF diagnosis was associated with reduced CVD, total stroke, and ischemic stroke risk.

One-Dimensional Anomalous Diffusion of Gold Nanoparticles in a Polymer Melt.

We investigated the dynamics of polymer-grafted gold nanoparticles loaded into polymer melts using x-ray photon correlation spectroscopy. For low molecular weight host matrix polymer chains, normal isotropic diffusion of the gold nanoparticles is observed. For larger molecular weights, anomalous diffusion of the nanoparticles is observed that can be described by ballistic motion and generalized Lévy walks, similar to those often used to discuss the dynamics of jammed systems. Under certain annealing conditions, the diffusion is one-dimensional and related to the direction of heat flow during annealing and is associated with an dynamic alignment of the host polymer chains. Molecular dynamics simulations of a single gold nanoparticle diffusing in a partially aligned polymer network semiquantitatively reproduce the experimental results to a remarkable degree. The results help to showcase how nanoparticles can under certain circumstances move rapidly in polymer networks.

Chronic periodontitis and community-acquired pneumonia: a population-based cohort study.

BACKGROUND: This study aimed to determine the association between chronic periodontitis (CP) and community-acquired pneumonia (CAP) according to CP severity in the Korean population based on the National Health Insurance Service database. METHODS: Data from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS), conducted from 2002 to 2013, were analyzed. A total of 363,541 participants were enrolled in this retrospective cohort study. Data on socio-demographic characteristics and CAP-related variables were collected. Participants were divided into 4 groups according to CP severity. Cox proportional hazards regression was performed after adjusting for sociodemographic and related covariates. RESULTS: A total of 363,541 participants were included in the analysis. The number of CAP cases in the index period was 14,838 (4.1%). Among the 4 groups, the mean age was significantly higher in the severe CP group. The incidence rates of severe and non-severe CP were 5.68 and 4.99, respectively (per 103 person-years). The hazard ratio for CAP was not significant in any of the models regardless of the presence or absence of CP. On stratification analysis by sex, smoking and Charlson comorbidity index, there were no significant differences between CAP and CP in any of the models. CONCLUSION: The results of this study show that CP may not be a potential risk factor for CAP.

Cumulative Dose Threshold for the Chemopreventive Effect of Aspirin Against Gastric Cancer.

OBJECTIVES: Many studies have found evidence that aspirin has protective effects against certain cancers, but quantitative dose-response data have been available only on a limited basis. This study aimed to confirm the dose-response relationship of aspirin usage and gastric cancer and to estimate the cumulative dose threshold of aspirin to achieve protective effects against gastric cancer in the general population. METHODS: A total of 461,489 individuals in a population-based longitudinal cohort provided by the National Health Insurance Services (NHIS) in the Republic of Korea were observed from 2007 to 2012 to identify gastric cancer incident cases. The pharmacy claims data of these individuals from 2002 to 2006 were reviewed to assess cumulative medication exposure using the defined daily dose (DDD) system. Hazard ratios (HRs) of aspirin use for gastric cancer were estimated using multivariate Cox Proportional Hazard regression. Sensitivity analyses, including propensity-score matching and a nested case-control design, were performed to evaluate the variability caused by study design. RESULTS: A total of 5674 incident gastric cancers were identified from 2,965,500 person-years of follow-up observation, giving an overall incidence rate of 191.00 gastric cancers per 100,000 person-years. Compared to non-users, those with aspirin use of ≥3 DDD-years showed a statistically significant protective effect of aspirin use against gastric cancer; the adjusted HR (95% confidence intervals) were 0.79 (0.63-0.98) and 0.63 (0.48-0.83) for those with aspirin use of 3-4 DDD-years and 4-5 DDD-years, respectively (P for trend < 0.001). Sensitivity analyses using propensity-score matching and a nested case-control design consistently showed a chemopreventive effect of aspirin. CONCLUSION: Long-term aspirin use was associated with reduced gastric cancer incidence in the general population of South Korea when the cumulative dose was >3 DDD-years.

A Nationwide Population-Based Cohort Study of Dementia Risk Among Acid Suppressant Users.

OBJECTIVE: Data regarding the potential link between acid suppressant use and dementia are inconsistent. This study assessed the association between cumulative exposure to proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) and dementia risk among Korean adults. DESIGN AND METHODS: A population-based longitudinal study was conducted using the Korean National Health Insurance Corporation claims database merged with national health examination data for 2002-2013. The study cohort included 70,529 subjects who were dementia-free in 2007. Incident dementia was assessed throughout follow-up until 2013. Exposure to acid suppressants prior to 2007 was assessed using a standardized defined daily dose system. Potential associations between acid suppressant use and dementia risk were analyzed using time-dependent Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: There were 1,297 cases of dementia during the study period. Multivariate analyses identified several factors associated with dementia risk: old age, female, current smoker, Type 2 diabetes, comorbidities, and use of nonaspirin nonsteroidal anti-inflammatory drugs. H2RA users had a significantly increased risk of dementia compared with non-H2RA users (HR 1.31, 95% CI 1.13-1.51), whereas PPI use was not associated with increased risk. CONCLUSION: Our results indicate that exposure to H2RAs (but not PPIs) is associated with increased dementia risk. Further randomized controlled trials and basic research examining the underlying mechanism are needed to confirm this association.

Cardiovascular Benefit of Statin Use Against Air Pollutant Exposure in Older Adults.

BACKGROUND AND AIMS: Little is known about the cardiovascular benefit of statin use against ambient air pollution among older adults who are at higher risk of cardiovascular disease (CVD) potentially owing to age-related declines in cardiovascular functions along with other risk factors. METHODS AND RESULTS: This retrospective, population-based cohort study consisted of adults aged 60 years and older free of CVD at baseline identified from the National Health Insurance Service (NHIS) database linked to the National Ambient Air Monitoring Information System (NAMIS) for average daily exposure to PM10 and PM2.5 in 2015 in the major metropolitan areas in the Republic of Korea. Follow-up period began on January 1, 2016 and lasted until December 31, 2021. Cox proportional hazards model was used to evaluate association of cardiovascular benefit with statin use against different levels of air pollutant exposure. Of 1,229,444 participants aged 60 years and older (mean age, 67.4; 37.7% male), 377,076 (30.7%) were identified as statin-users. During 11,963,322 person-years (PY) of follow-up, a total of 86,018 incident stroke events occurred (719.0 events per 100,000 PYs). Compared to statin non-user exposed to high level of PM10 (>50 µg/m3) and PM2.5 (>25 µg/m3), statin users had 20% (adjusted hazard ratio [HR], 0.80; 95% confidence intervals [CI], 0.75 to 0.85) and 17% (adjusted HR, 0.80; 95% CI, 0.80 to 0.86) lower adjusted risk of incident stroke for PM10 and PM2.5, respectively. Similar risk reduction for incident CVD was also found among statin-users exposed to low or moderate level of PM10 (≤50 µg/m3) and PM2.5 (≤25 µg/m3) exposure. CONCLUSION: Among adults aged 60 years and older with high and low or moderate levels of exposure to PM10 and PM2.5, statin use was associated with a significantly lower risk of stroke.

In a retrospective cohort study of older adults exposed to high and low or moderate levels of PM10 and PM2.5, statin use was associated with a significantly lower risk of incident stroke.

Association Between Antibiotic Exposure and Thyroid Cancer: A Nationwide Cohort Study in South Korea.

Background: Although recent studies have introduced antibiotics as a potential risk factor for thyroid cancer, further studies are necessary. We examined the association between long-term antibiotic usage and thyroid cancer risk. Methods: This nationwide cohort study investigated 9,804,481 individuals aged 20 years or older who participated in health screening (2005-2006) with follow-up ending on December 31, 2019, using the Korean National Health Insurance Service database. Multivariable Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for thyroid cancer risk according to the cumulative days of antibiotic prescription and the number of antibiotic classes, respectively. A 1:1 propensity score (PS) matching was also performed for analysis. Results: Compared with nonusers of antibiotics, participants prescribed ≥365 days of antibiotics showed an increased risk of thyroid cancer (aHR, 1.71; CI, 1.66-1.78) after adjusting for covariates including age, smoking status, comorbidities including thyroid-related diseases, and the number of head and neck computed tomography scans. Participants prescribed ≥365 days of antibiotics also had a significantly increased risk of thyroid cancer (aHR, 1.37; CI, 1.34-1.40) compared with participants prescribed 1-14 days of antibiotics. Association remained significant in the 1:1 PS-matched cohort. Moreover, compared with nonusers of antibiotics, the 5 or more antibiotic class user group had a higher thyroid cancer risk (aHR, 1.71; CI, 1.65-1.78). Conclusions: Long-term antibiotic prescriptions and an increasing number of antibiotic classes may be associated with a higher risk of thyroid cancer in a duration-dependent manner. The effects of long-term antibiotic exposure on thyroid cancer should be further investigated.

Antibiotic exposure and depression incidence: A cohort study of the Korean population.

Recent research highlights the crucial role of the gut-brain axis in understanding depression etiologies. While burgeoning studies suggest an association between disruptions in gut microbiota and the development of depression, limited longitudinal studies have investigated this link. To address this gap, we conducted a retrospective cohort study using National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data in South Korea, involving 199,144 individuals aged 40-79. We examined the impact of cumulative antibiotic exposure (2004-2008) on subsequent depression incidence (2009-2013) by conducting Cox proportional hazards regressions. Our findings show an increasing depression risk with extended antibiotic exposure after adjusting for comorbidities and behavioral covariates. A broader antibiotic spectrum was associated with a higher depression risk. These trends persisted after adjusting for the original antibiotic indications. In conclusion, our study highlights the duration-dependent association between antibiotic exposure and increased depression risk, offering insights into depression etiologies and relevant novel therapeutic tools, and advocating for heightened antibiotic stewardship considering their impact on mental health.

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.

Associations of cholecystectomy with metabolic health changes and incident cardiovascular disease: a retrospective cohort study.

Although some studies conducted about the risk of cholecystectomy and cardiovascular disease, there was a limit to explaining the relationship. We investigated the short-term and long-term relationship between cholecystectomy and cardiovascular disease, and evidence using the elements of the metabolic index as an intermediate step. It was a retrospective cohort study and we used the National Health Insurance Service database of South Korea between 2002 and 2015. Finally, 5,210 patients who underwent cholecystectomy and 49,457 at 1:10 age and gender-matched controls of subjects were collected. The main results was estimated by Multivariate Cox proportional hazard regression to calculate the hazard ratio (HR) with 95% confidence interval (CI) for risk of cardiovascular disease after cholecystectomy. Regarding short-term effects of cholecystectomy, increased risk of cardiovascular disease (aHR 1.35, 95% CI 1.15-1.58) and coronary heart disease (aHR 1.77, 95% CI 1.44-2.16) were similarly seen within 2 years of surgery. When analyzing the change in metabolic risk factors, cholecystectomy was associated with a change in systolic blood pressure (adjusted mean [aMean]: 1.51, 95% CI: [- 1.50 to - 4.51]), total cholesterol (aMean - 14.14, [- 20.33 to 7.95]) and body mass index (aMean - 0.13, [- 0.37 to 0.11]). Cholecystectomy patients had elevated risk of cardiovascular disease in the short-term, possibly due to the characteristics of the patient before surgery. The association of cholecystectomy and cardiovascular disease has decreased after 2 years in patients who underwent cholecystectomy, suggesting that because of improvement of metabolic health, cholecystectomy-associated elevation of cardiovascular disease risk may be ameliorated 2 years after cholecystectomy.