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.

Association of changes in predicted body composition with subsequent risk of dementia.

OBJECTIVE: The effect of body composition change on the risk of dementia is not clear. This study analyzed the associations of changes in predicted lean body mass index (pLBMI), predicted appendicular skeletal muscle mass index (pASMI), and predicted body fat mass index (pBFMI) with the risk of dementia. METHODS: In this nationwide cohort study, data were obtained from the Korean National Health Insurance Service database. The exposure was defined as changes in pLBMI, pASMI, and pBFMI derived from validated prediction equations. The outcome was dementia, defined based on the dementia diagnosis with prescription of anti-dementia medication. Cox proportional hazards regression analyses were performed to obtain the hazard ratio with a 95% confidence interval for risk of dementia according to changes in predicted body composition. RESULTS: A total of 13,215,208 individuals with no prior record of dementia who underwent health screenings twice between 2009-2010 and 2011-2012 were included. A 1-kg/m2 increase in pLBMI and pASMI had an association with reduced risk of dementia (aHR: 0.85, 95% CI 0.84-0.87; aHR: 0.70, 95% CI 0.69-0.72, respectively for men, and aHR: 0.69, 95% CI 0.67-0.71; aHR: 0.59, 95% CI 0.57-0.61, respectively for women). A 1-kg/m2 increase in pBFMI had an association with a raised risk of dementia (aHR: 1.19, 95% CI 1.17-1.21 for men and aHR: 1.53, 95% CI 1.48-1.57 for women). These results remained consistent regardless of sex or weight change. INTERPRETATION: Increase in pLBMI or pASMI, or reduction in pBFMI was linked to lower risk of dementia.

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.

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.

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.

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 Thyroid Hormone Medication Adherence With Risk of Dementia.

CONTEXT: Recent studies suggest that hypothyroidism is a risk factor for dementia. Based on existing literature, it is unclear if treatment or compliance to treatment is associated with decreased dementia risk in hypothyroidism patients. OBJECTIVE: To determine the association between thyroid hormone medication adherence and risk of dementia. METHODS: A population-based cohort study following patients with newly diagnosed hypothyroidism until incidence of dementia, death, or December 31, 2020, whichever came earliest. The study comprised 41 554 older adults age 50 and above with newly diagnosed hypothyroidism between 2004 and 2008 who underwent health screening. Risk of dementia was evaluated using multivariable-adjusted Cox proportional hazards regression. RESULTS: Among 5188 men (12.5%) and 36 366 (87.5%) women, 2120 cases of incident dementia were identified. After stratification of the participants according to the interquartile range of the medication possession ratio (MPR), the fourth quartile (highest adherence) showed a 14% lower risk of overall dementia compared with the first quartile (lowest adherence) (adjusted hazard ratio 0.86; 95% CI 0.76-0.97). No consistent association was observed between thyroid hormone medication adherence and vascular dementia. After a dichotomous stratification of the MPR, higher MPR (≥0.8) showed a lower risk of Alzheimer disease (adjusted hazard ratio 0.91; 95% CI 0.84-0.99) than lower MPR (<0.8). CONCLUSION: Better adherence to thyroid hormone medication may be beneficial in preventing incident dementia, especially Alzheimer disease, in older adults with newly diagnosed hypothyroidism. Along with the resolution of hypothyroid symptoms and the reduction of cardiovascular risk factors, the reduction of dementia risk may be another potential benefit of thyroid hormone medication.

Association of post-smoking cessation changes in fasting serum glucose with changes in predicted fatty liver score.

Major post-cessation metabolic changes include weight gain and hyperglycemia. However, the association of post-cessation change in fasting serum glucose (FSG) with risk of fatty liver remains unclear. A total of 111,106 participants aged 40 and above who underwent health screening at least once in two examination periods were extracted from the Korean National Health Insurance Service-National Sample Cohort. Fatty liver status was evaluated using the Korean National Health and Nutrition Examination Survey nonalcoholic fatty liver disease (K-NAFLD) score. Linear and logistic regression were used to calculate the adjusted mean (aMean) and adjusted odds ratio (aOR) with 95% confidence intervals. Compared to stable (aMean 0.10; 95% CI 0.03-0.18) and decline (aMean - 0.60; 95% CI - 0.71 to 0.49) groups, FSG elevation (aMean 1.28; 95% CI 1.16-1.39) was associated with higher K-NAFLD score even within different body mass index change groups. Risk of fatty liver was significantly reduced among participants with stable (aOR 0.38; 95% CI 0.31-0.45) and declined (aOR 0.17; 95% CI 0.13-0.22) FSG levels after smoking cessation compared to FSG elevation group. This study suggests that quitters with elevated FSG are associated with higher NAFLD risk and may benefit from careful monitoring of FSG levels and management of other cardiovascular risk factors.

Changes in total cholesterol level and cardiovascular disease risk among type 2 diabetes patients.

Despite many diabetic patients having hypercholesterolemia, the association of total cholesterol (TC) levels with CVD risk in type 2 diabetes (T2D) patients is unclear. Diagnosis of type 2 diabetes often leads to changes in total cholesterol (TC) levels. Thus, we examined whether changes in TC levels from pre- to post-diagnosis of T2D were associated with CVD risk. From the National Health Insurance Service Cohort, 23,821 individuals diagnosed with T2D from 2003 to 2012 were followed-up for non-fatal CVD incidence through 2015. Two measurements of TC, 2 years before and after T2D diagnosis, were classified into 3 levels (low, middle, high) to define changes in cholesterol levels. Cox proportional hazards regression was performed to estimate adjusted hazards ratios (aHRs) and 95% confidence intervals (CIs) for the associations between changes in cholesterol levels and CVD risk. Subgroup analyses were performed by use of lipid-lowering drugs. Compared with low-low, aHR of CVD was 1.31 [1.10-1.56] for low-middle and 1.80 [1.15-2.83] for low-high. Compared with middle-middle, aHR of CVD was 1.10 [0.92-1.31] for middle-high but 0.83 [0.73-0.94] for middle-low. Compared with high-high, aHR of CVD was 0.68 [0.56-0.83] for high-middle and 0.65 [0.49-0.86] for high-low. The associations were observed regardless of use of lipid-lowering drugs. For diabetic patients, management of TC levels may be important to lower CVD risk.

Association of antibiotic use with risk of lung cancer: A nationwide cohort study.

BACKGROUND: Although recent studies indicated that antibiotics may be a risk factor for lung cancer, further understanding is needed. We investigated the association of long-term antibiotic exposure with lung cancer risk. METHODS: This population-based retrospective cohort study investigated 6,214,926 participants aged ≥ 40 years who underwent health screening examinations (2005-2006) from the Korean National Health Insurance Service database. The date of the final follow-up was December 31, 2019. Exposures were the cumulative days of antibiotics prescription and the number of antibiotics classes. The adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for lung cancer risk according to antibiotic use were assessed using multivariable Cox proportional hazards regression. RESULTS: Compared with the antibiotic non-user group, participants with ≥ 365 days of antibiotics prescribed had a significantly increased risk of lung cancer (aHR, 1.21; 95% CI, 1.16-1.26). Participants with ≥ 365 days of antibiotics prescribed also had a significantly increased risk of lung cancer (aHR, 1.21; 95% CI, 1.17-1.24) than 1-14 days of the antibiotic user group. The results were also consistent in competing risk analyses and adjusted Cox regression models that fitted restricted cubic spline. Compared with the antibiotic non-user group, ≥ 5 antibiotic classes prescribed group had a higher lung cancer risk (aHR, 1.15; 95% CI, 1.10-1.21). CONCLUSION: The long-term cumulative days of antibiotic use and the increasing number of antibiotics classes were associated with an increased risk of lung cancer in a clear duration-dependent manner after adjusting for various risk factors.

Association of hemoglobin variability with the risk of cardiovascular disease: a nationally representative retrospective cohort study from South Korea.

Hemoglobin variability is known to increase cardiovascular mortality in chronic kidney disease, but the association of hemoglobin variability with the risk of cardiovascular disease (CVD) in the general population is yet unclear. This retrospective cohort study based on 'the South Korean National Health Insurance Service database' consisted of 198,347 adults who went through all three health examinations. Hemoglobin variability is defined as the average successive variability of three separate hemoglobin values from each health screening period. Participants were followed up for 6 years to determine the risk of coronary heart disease and stroke. We used multivariate Cox proportional hazards regression to examine the adjusted hazard ratios for CVD according to hemoglobin variability. Per 1 unit increase of hemoglobin variability, the risk for CVD (aHR 1.06, 95% CI 1.02-1.09) and stroke (aHR 1.08, 95% CI 1.03-1.13) increased significantly. The risk-increasing trend was preserved in the low-to-moderate risk group of CVDs (aHR 1.07, 95% CI 1.02-1.11). This result suggests that subjects with high hemoglobin variability who would otherwise be categorized as having low-to-moderate CVD risk may have higher risk of CVD than those with low hemoglobin variability.

Association of Change in Smoking Status and Subsequent Weight Change with Risk of Nonalcoholic Fatty Liver Disease.

Background/Aims: Smoking is considered a risk factor for the development of nonalcoholic fatty liver disease (NAFLD). However, the association of a weight change after a change in smoking status and the risk of NAFLD remains undetermined. Methods: This study used the Korean National Health Insurance Service-National Sample Cohort. Based on the first (2009 to 2010) and second (2011 to 2012) health examination periods, 139,180 adults aged at least 40 years were divided into nonsmoking, smoking cessation, smoking relapse, and sustained smoking groups. NAFLD was operationally defined using the fatty liver index. The adjusted odds ratio (aOR) and 95% confidence interval (CI) were calculated using multivariable-adjusted logistic regression. Results: Compared to nonsmoking with no body mass index (BMI) change, the risk of NAFLD was significantly increased among subjects with BMI gain and nonsmoking (aOR, 4.07; 95% CI, 3.77 to 4.39), smoking cessation (aOR, 5.52; 95% CI, 4.12 to 7.40), smoking relapse (aOR, 7.51; 95% CI, 4.81 to 11.72), and sustained smoking (aOR, 6.65; 95% CI, 5.33 to 8.29), whereas the risk of NAFLD was reduced among participants with BMI loss in all smoking status groups. In addition, smoking cessation (aOR, 1.76; 95% CI, 1.35 to 2.29) and sustained smoking (aOR, 1.64; 95% CI, 1.39 to 1.94) were associated with higher risk of NAFLD among participants with no BMI change. The liver enzyme levels were higher among participants with smoking cessation and BMI gain. Conclusions: Monitoring and management of weight change after a change in smoking status may be a promising approach to reducing NAFLD.

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.

Association between community-level social trust and the risk of dementia: A retrospective cohort study in the Republic of Korea.

Introduction: It is known that biological risk factors and lifestyle behaviors are important determinants of dementia. However, there has been yet to be sufficient evidence to prove that community-level social capital is one of the determinants of dementia. This retrospective cohort study is a large, long-term, population-based study that investigated the association between community-level social trust and the risk of dementia in the Republic of Korea. Methods: Data came from the Korean National Health Insurance Service database. The community-level social trust values were determined by the Korean Community Health Survey. The study population consisted of 1,974,944 participants over 50 years of age and was followed up from 1 January 2012 to 31 December 2019 with a latent period of 5 years from 1 January 2012 to 31 December 2016. Cox proportional hazards regression was utilized to obtain the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the risk of dementia according to social trust quintiles. Results: Participants within the highest quintile of community-level social trust had a lower risk for overall dementia (aHR, 0.90; 95% CI, 0.86-0.94) and Alzheimer's disease (aHR, 0.90; 95% CI, 0.85-0.94) compared to those within the lowest quintile of community-level social trust. The alleviating trend association of high community-level social trust on dementia risk was maintained regardless of whether the participants had health examinations. Conclusions: Our findings suggest that higher community-level social trust is associated with a reduced risk of dementia. Community-level social trust is a crucial indicator of dementia and improving community-level social trust may lead to a lower risk of dementia.

Association between antibiotics and dementia risk: A retrospective cohort study.

Background: The possible relation between antibiotic exposure and the alteration of gut microbiota, which may affect dementia risk, has been revealed. However, the association between antibiotics and dementia incidence has rarely been studied. We aimed to determine the association between antibiotic exposure and the risk of dementia. Methods: This population-based retrospective cohort study used data from the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) in South Korea. Exposure was the cumulative days of antibiotic prescription from 2002 to 2005. Newly diagnosed overall dementia, Alzheimer's disease (AD), and vascular dementia (VD) were identified based on diagnostic codes and prescriptions for dementia-related drugs. The follow-up investigation was carried out from 1 January 2006 to 31 December 2013. The Cox proportional hazards regression was used to assess the association between cumulative antibiotic prescription days and dementia incidence. Results: A total of 313,161 participants were analyzed in this study. Compared to antibiotic non-users, the participants who used antibiotics for 91 or more days had an increased risk of overall dementia [adjusted hazard ratio (aHR), 1.44; 95% confidence interval (CI), 1.19-1.74], AD (aHR, 1.46; 95% CI, 1.17-1.81), and VD (aHR, 1.38; 95% CI, 0.83-2.30). Those who used five or more antibiotic classes had higher risks of overall dementia (aHR, 1.28; 95% CI, 1.00-1.66) and AD (aHR, 1.34; 95% CI, 1.00-1.78) than antibiotic non-users. Conclusion: Antibiotic exposure may increase the risk of dementia in a cumulative duration-dependent manner among adult participants. Future studies are needed to assess the causality between the long-term prescription of antibiotics and dementia risk.

Association of the presence of allergic disease with subsequent risk of liver cancer in a nationwide retrospective cohort among Koreans.

A number of studies have proposed an inverse association between allergic diseases and risk of cancer, but only a few studies have specifically investigated the risk of primary liver cancer, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The aim of this study was to evaluate the association of allergic diseases with risk of primary liver cancer. We conducted a retrospective cohort study of the Korean National Health Insurance Service database consisted of 405,512 Korean adults ages 40 and above who underwent health screening before January 1st, 2005. All participants were followed up until the date of liver cancer, death, or December 31st, 2013, whichever happened earliest. Those who died before the index date or had pre-diagnosed cancer were excluded from the analyses. Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for risk of primary liver cancer according to the presence of allergic diseases, including atopic dermatitis, asthma, and allergic rhinitis. The aHR (95% CI) for overall liver cancer among allergic patients was 0.77 (0.68-0.87) compared to those without allergic disease. Allergic patients had significantly reduced risk of HCC (aHR, 0.72; 95% CI 0.62-0.85) but not ICC (aHR, 0.95; 95% CI 0.73-1.22). The presence of allergies was associated with significantly lower risk of liver cancer among patients whose systolic blood pressure is lower than 140 mmHg (aHR, 0.64; 95% CI 0.62-0.78 for overall liver cancer; aHR, 0.64; 95% CI 0.52-0.78 for HCC) but this effect was not observed among patients whose systolic blood pressure is higher than 140 mmHg (aHR, 0.91; 95% CI 0.71-1.18 for overall liver cancer; aHR, 0.91; 95% CI 0.71-1.18 for HCC) The aHR (95% CI) for overall liver cancer of allergic patients with and without chronic hepatitis virus infection were 0.60 (95% CI 0.44-0.81) and 0.77 (95% CI 0.64-0.93), respectively. In addition, allergic patients without cirrhosis showed significantly lower risk of overall liver cancer (aHR, 0.73; 95% CI 0.63-0.83). Patients with allergic diseases have significantly lower risk of primary liver cancer compared to those without allergic diseases, which supports the rationale for immunotherapy as an effective treatment for liver cancer.

Association between Proton Pump Inhibitor Use and Risk of Hepatocellular Carcinoma: A Korean Nationally Representative Cohort Study.

(1) Background: The association between proton pump inhibitor (PPI) use and hepatocellular carcinoma (HCC) has been controversial, especially in the general population. We aimed to determine the impact of PPI on HCC risk in participants without liver cirrhosis or chronic hepatitis virus infection. (2) Methods: We assessed 406,057 participants from the Korean National Health Insurance Service database who underwent health screening from 2003 to 2006. We evaluated exposure to PPI before the index date using a standardized daily defined dose (DDD) system. The association of proton pump inhibitor use with the risk of HCC was evaluated using multivariable-adjusted Cox proportional hazards regression. (3) Results: Compared with non-users, PPI use was not associated with the HCC risk in low (<30 DDDs; aHR, 1.07; 95% CI, 0.91−1.27), intermediate (30 ≤ PPI < 60 DDDs; aHR, 0.96; 95% CI, 0.73−1.26), and high (≥60 DDDs; aHR, 0.86; 95% CI, 0.63−1.17) PPI groups in the final adjustment model. In addition, risks of cirrhosis-associated HCC and non-cirrhosis-associated HCC were not significantly associated with PPI use. The results remained consistent after excluding events that occurred within 1, 2, and 3 years to exclude pre-existing conditions that may be associated with the development of HCC. We also found no PPI-associated increase in HCC risk among the selected population, such as those with obesity, older age, and chronic liver diseases. (4) Conclusions: PPI use may not be associated with HCC risk regardless of the amount. We call for future studies conducted in other regions to generalize our findings.

Association of short-term particulate matter exposure with suicide death among major depressive disorder patients: a time-stratified case-crossover analysis.

There is growing evidence that suggests a potential association between particulate matter (PM) and suicide. However, it is unclear that PM exposure and suicide death among major depressive disorder (MDD) patients, a high-risk group for suicide. We aimed to assess the effect of short-term exposure to PM on the risk of suicide in MDD patients who are at high risk for suicide. We investigated the risk of suicide among 922,062 newly-diagnosed MDD patients from 2004 to 2017 within the Korean National Health Insurance Service (NHIS) database. We identified 3,051 suicide cases from January 1, 2015, to December 31, 2017, within the death statistics database of the Korean National Statistical Office. PMs with aerodynamic diameter less than 2.5 µm (PM2.5), less than 10 µm (PM10), and 2.5-10 µm (PM2.5-10) were considered, which were provided from the National Ambient Air Monitoring System in South Korea. Time-stratified case-crossover analysis was performed to investigate the association of particulate matter exposure to suicide events. The risk of suicide was significantly high upon the high level of exposure to PM2.5, PM2.5-10 (coarse particle) and PM10 on lag 1 (p for trend < 0.05). Short-term exposure to a high level of PM was associated with an elevated risk for suicide among MDD patients. There is a clear dose-response relationship between short-term PM exposures with suicide death among MDD patients. This result will be used as an essential basis for consideration when establishing an air pollution alarm system for reducing adverse health outcomes by PM.