Genetic variations in HMGCR and PCSK9 and kidney function: a Mendelian randomization study

Background@#The genetically predicted lipid-lowering effect of HMGCR or PCSK9 variant can be used to assess drug proxy effects on kidney function. @*Methods@#Mendelian randomization (MR) analysis-identified HMGCR and PCSK9 genetic variants were used to predict the low-density lipoprotein (LDL) cholesterol-lowering effects of medications targeting related molecules. Primary summary-level outcome data for log-estimated glomerular filtration rate (eGFR; creatinine) were provided by the CKDGen Consortium (n = 1,004,040 European) from a meta-analysis of CKDGen and UK Biobank data. We also conducted a separate investigation of summary-level data from CKDGen (n = 567,460, log-eGFR [creatinine]) and UK Biobank (n = 436,581, log-eGFR [cystatin C]) samples. Summary-level MRs using an inverse variance weighted method and pleiotropy-robust methods were performed. @*Results@#Summary-level MR analysis indicated that the LDL-lowering effect predicted genetically by HMGCR variants (50-mg/dL decrease) was significantly associated with a decrease in eGFR (–1.67%; 95% confidence interval [CI], –2.20% to –1.13%). Similar significance was found in results from the pleiotropy-robust MR methods when the CKDGen and UK Biobank data were analyzed separately. However, the LDL-lowering effect predicted genetically by PCSK9 variants was significantly associated with an increase in eGFR (+1.17%; 95% CI, 0.10%–2.25%). The results were similarly supported by the weighted median method and in each CKDGen and UK Biobank dataset, but the significance obtained by MR-Egger regression was attenuated. @*Conclusion@#Genetically predicted HMG-CoA reductase inhibition was associated with low eGFR, while genetically predicted PCSK9 inhibition was associated with high eGFR. Clinicians should consider that the direct effect of different types of lipid-lowering medication on kidney function can vary.

Comparison of Overall Immunity Levels among Workers at Grape Orchard, Rose Greenhouse, and Open-Field Onion Farm

Background@#Occupational hazards in crop farms vary diversely based on different field operations as soil management, harvesting processes, pesticide, or fertilizer application. We aimed at evaluating the immunological status of crop farmers, as limited systematic investigations on immune alteration involved with crop farming have been reported yet. @*Methods@#Immunological parameters including plasma immunoglobulin level, major peripheral immune cells distribution, and level of cytokine production from activated T cell were conducted. Nineteen grape orchard, 48 onion open-field, and 21 rose greenhouse farmers were participated. @*Results@#Significantly low proportion of natural killer (NK) cell, a core cell for innate immunity, was revealed in the grape farmers (19.8 ± 3.3%) in comparison to the onion farmers (26.4 ± 3.1%) and the rose farmers (26.9 ± 2.5%), whereas cytotoxic T lymphocyte proportion was lower in the grape and the onion farmers than the rose farmers. The proportion of NKT cell, an immune cell implicated with allergic response, was significantly higher in the grape (2.3 ± 0.3%) and the onion (1.6 ± 0.8%) farmers compared with the rose farmers (1.0 ± 0.4%). A significantly decreased interferon-gamma:interleukin-13 ratio was observed from ex vivo stimulated peripheral blood mononuclear cells of grape farmers compared with the other two groups. The grape farmers revealed the lowest levels of plasma IgG1 and IgG4, and their plasma IgE level was not significantly different from that of the onion or the rose farmers. @*Conclusion@#Our finding suggests the high vulnerability of workplace-mediated allergic immunity in grape orchard farmers followed by open-field onion farmers and then the rose greenhouse farmers.

Causal effect of alcohol use on the risk of end-stage kidney disease and related comorbidities: a Mendelian randomization study

Background@#An inverse observational association between alcohol use and the risk of chronic kidney disease (CKD) or end-stage kidney disease (ESKD) has been reported. The causal effect of alcohol use on the risk of ESKD warrants additional investigation. @*Methods@#The study was an observational cohort study investigating the UK Biobank and performed Mendelian randomization (MR) analysis. Amounts of alcohol use were collected using a touchscreen questionnaire. In the observational analysis, 212,133 participants without prevalent ESKD were studied, and the association between alcohol use and the risk of prevalent CKD or incident ESKD was investigated. The genetic analysis included 337,138 participants of white British ancestry. For one-sample MR, an analysis based on a polygenic risk score (PRS) was conducted with genetically predicted alcohol intake. The MR analysis investigated ESKD outcome and related comorbidities. @*Results@#Lower alcohol use was observationally associated with a higher risk of prevalent CKD or incident ESKD. However, the genetic risk of CKD was significantly associated with lower alcohol use, suggesting reverse causation. A higher PRS for alcohol use was significantly associated with a higher risk of ESKD (per units of one phenotypical alcohol drink; adjusted odds ratio of 1.16 [95% confidence interval, 1.02–1.31]) and related comorbidities, including hypertension, diabetes mellitus, obesity, and central obesity. @*Conclusion@#The inverse observational association between alcohol use and the risk of CKD or ESKD may have been affected by reverse causation. Our study supports a causal effect of alcohol use on a higher risk of ESKD and related predisposing comorbidities.

Causal effect of alcohol use on the risk of end-stage kidney disease and related comorbidities: a Mendelian randomization study

Background@#An inverse observational association between alcohol use and the risk of chronic kidney disease (CKD) or end-stage kidney disease (ESKD) has been reported. The causal effect of alcohol use on the risk of ESKD warrants additional investigation. @*Methods@#The study was an observational cohort study investigating the UK Biobank and performed Mendelian randomization (MR) analysis. Amounts of alcohol use were collected using a touchscreen questionnaire. In the observational analysis, 212,133 participants without prevalent ESKD were studied, and the association between alcohol use and the risk of prevalent CKD or incident ESKD was investigated. The genetic analysis included 337,138 participants of white British ancestry. For one-sample MR, an analysis based on a polygenic risk score (PRS) was conducted with genetically predicted alcohol intake. The MR analysis investigated ESKD outcome and related comorbidities. @*Results@#Lower alcohol use was observationally associated with a higher risk of prevalent CKD or incident ESKD. However, the genetic risk of CKD was significantly associated with lower alcohol use, suggesting reverse causation. A higher PRS for alcohol use was significantly associated with a higher risk of ESKD (per units of one phenotypical alcohol drink; adjusted odds ratio of 1.16 [95% confidence interval, 1.02–1.31]) and related comorbidities, including hypertension, diabetes mellitus, obesity, and central obesity. @*Conclusion@#The inverse observational association between alcohol use and the risk of CKD or ESKD may have been affected by reverse causation. Our study supports a causal effect of alcohol use on a higher risk of ESKD and related predisposing comorbidities.

Reduced risk for chronic kidney disease after recovery from metabolic syndrome: A nationwide populationbased study

Background@#Metabolic syndrome (MetS) is linked to various chronic comorbidities, including chronic kidney disease (CKD). However, few large studies have addressed whether recovery from MetS is associated with reduction in the risks of such comorbidities. @*Methods@#This nationwide population-based study in Korea screened 10,664,268 people who received national health screening ≥ 3 times between 2012 and 2016. Those with a history of major cardiovascular events or preexisting CKD were excluded. We classified study groups into four, according to the course of MetS state, as defined by the harmonizing criteria. The main study outcome was incidental CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2 which was persistent until the last health exams). The study outcomes were investigated using multivariable logistic regression analysis, which was adjusted for clinical variables and the previous severity of MetS. @*Results@#Four study groups included 6,315,301 subjects: 4,537,869 people without MetS, 1,034,605 with chronic MetS, 438,287 who developed MetS, and 304,540 who recovered from preexisting MetS. Those who developed MetS demonstrated higher risk of CKD (adjusted odds ratio [OR], 1.26 [1.23-1.29]) than did those who did not develop MetS. In contrast, MetSrecovery was associated with decreased risk of CKD (adjusted OR, 0.84 [0.82-0.86]) than that in people with chronic MetS. Among the MetS components, change in hypertension was associated with the largest difference in CKD risk. @*Conclusion@#Reducing or preventing MetS may reduce the burden of CKD on a population-scale. Clinicians should consider the clinical importance of altering MetS status for risk of CKD.

Risk of cancer in pre-dialysis chronic kidney disease: A nationwide population-based study with a matched control group

BACKGROUND: Cancer risk and epidemiology in pre-dialysis chronic kidney disease (CKD) warrant further investigation in a large-scale cohort. METHODS: We performed a nationwide population-based study using the national health insurance database of Korea. We screened records from 18,936,885 individuals who received a national health examination ≥ 2 times from 2009 to 2016. Pre-dialysis CKD was identified based on serum creatinine and dipstick albuminuria results. Individuals with preexisting cancer history, renal replacement therapy, or transient CKD were excluded. A control group without evidence of kidney function impairment and matched for age, sex, low-income status, and smoking history was included. Risk of cancers, as identified in the claims database, was investigated using a multivariable Cox regression model including matched variables and other unmatched clinical characteristics as covariates. RESULTS: A total of 471,758 people with pre-dialysis CKD and the same number of matched controls were included. Urinary (adjusted hazard ratio [HR], 1.97; 95% confidence interval [95% CI], 1.82–2.13) and hematopoietic (adjusted HR, 1.53; 95% CI, 1.38–1.68) malignancy risk was increased in pre-dialysis CKD and all CKD stages. However, the risk of digestive cancer was lower in the pre-dialysis CKD group (adjusted HR, 0.89; 95% CI, 0.87–0.92). The risk of digestive, respiratory, thyroid, and prostate malignancy demonstrated a non-linear association with CKD stage, with stage 1 or stage 4/5 CKD without dialysis demonstrating relatively lower risk. CONCLUSION: Cancer risk varied in pre-dialysis CKD compared to controls, and the association between cancer risk and CKD stage varied depending on the cancer type.

Epidemiology of continuous renal replacement therapy in Korea: Results from the National Health Insurance Service claims database from 2005 to 2016

BACKGROUND: Continuous renal replacement therapy (CRRT) is an important treatment modality for severe acute kidney injury. As such, the epidemiology of CRRT in Korea needs further investigation. METHODS: We conducted a nationwide, population-based study analyzing the claims data from National Health Insurance Service of Korea. All index intensive care unit admission cases of CRRT in government-designated tertiary referral hospitals in Korea from 2005 to 2016 were included. Patients with a history of renal replacement therapy or who were under 20 years old were not considered. In addition to baseline and treatment characteristics, patient outcomes, including all-cause mortality and renal survival rates, were investigated. We stratified the study patients according to 3-year time periods and major regions of the nation. RESULTS: We included 37,337 patients who received CRRT in Korea. The overall use of CRRT increased over time, and more than 80% of cases of acute renal replacement therapy were CRRT after 2014. Seoul was the region in which the majority of CRRT (45.0%) was performed. The clinical characteristics of CRRT patients were significantly different among time-intervals and regions. Both all-cause mortality and renal survival rates after CRRT were prominently improved in the recent time periods (P < 0.001). CONCLUSION: CRRT is a widely used treatment strategy for severe acute kidney injury in Korea. The prognosis of CRRT patients has improved compared to the past. This epidemiological study of CRRT in Korea revealed notable trends with regard to time period and geographic region.

Predictors of Institutionalization in Patients with Alzheimer's Disease in South Korea

BACKGROUND AND PURPOSE: We investigated predictors of institutionalization in patients with Alzheimer's disease (AD) in South Korea. METHODS: In total, 2,470 patients with AD aged 74.5±7.8 years (mean±standard deviation, 68.1% females) were enrolled from November 2005 to December 2013. The dates of institutionalization were identified from the public Long-Term-Care Insurance program in January 2014. We used a Cox proportional-hazards model to identify predictors for future institutionalization among characteristics at the time of diagnosis in 2,470 AD patients. A similar Cox proportional-hazards model was also used to investigate predictors among variables that reflected longitudinal changes in clinical variables before institutionalization in 816 patients who underwent follow-up testing. RESULTS: A lower Mini Mental State Examination score [hazard ratio (HR)=0.95, 95% confidence interval (CI)=0.92–0.97] and higher scores for the Clinical Dementia Rating and Neuro-Psychiatric Inventory (HR=1.01, 95% CI=1.00–1.01) at baseline were independent predictors of institutionalization. The relationship of patients with their main caregivers, presence of the apolipoprotein E e4 allele, and medication at baseline were not significantly associated with the rate of institutionalization. In models with variables that exhibited longitudinal changes, larger annual change in Clinical Dementia Rating Sum of Boxes score (HR=1.15, 95% CI=1.06–1.23) and higher medication possession ratio of antipsychotics (HR=1.89, 95% CI=1.20–2.97) predicted earlier institutionalization. CONCLUSIONS: This study shows that among Korean patients with AD, lower cognitive ability, higher dementia severity, more-severe behavioral symptoms at baseline, more-rapid decline in dementia severity, and more-frequent use of antipsychotics are independent predictors of earlier institutionalization.

Heart rate is associated with mortality in patients undergoing continuous renal replacement therapy

BACKGROUND: Heart rate (HR) is an essential vital sign based on the finding that HR beyond its normal range is associated with several conditions or diseases, including high mortality in several clinical settings. Nevertheless, the clinical implications of HR remain unresolved in patients undergoing continuous renal replacement therapy (CRRT). METHODS: This retrospective cohort study included 828 patients who underwent CRRT due to acute kidney injury between 2010 and 2014. HR and other baseline parameters at the time of CRRT initiation were retrieved. The odds ratio (OR) of 30-day mortality was calculated using a multivariate logistic model. RESULTS: CRRT significantly lowered the HR of patients such that the pre- and post-CRRT HRs (average 6 hours) were 107 beats/min and 103 beats/min, respectively (P < 0.001). When we explored the relationship with 30-day mortality, only HR at the time of CRRT initiation, but not pre- or post-CRRT HR, had a significant relationship with mortality outcome. Based on this result, we divided patients into quartiles of HR at the time of CRRT initiation. Mortality OR in the 4th quartile HR group was 2.6 (1.78–3.92) compared with the 1st quartile HR group. This relationship remained consistent despite adjusting for 28 baseline covariates: OR, 1.7 (1.09–2.76); P = 0.020. However, HR was not associated with the weaning rate from CRRT. CONCLUSION: High HR at the time of CRRT initiation is subsequently related with high mortality. These results can be a basis for a future predictive model of CRRT-related mortality.

Influence of Fatigue, Depression and Anxiety on Quality of Life in Pregnant Women with Preterm Labor

PURPOSE: The purpose of this study was to identify effects of fatigue, depression and anxiety on quality of life in pregnant women with preterm labor. METHODS: With a survey design, data were collected from 138 mothers who were admitted at a hospital in Seoul, between June 2014 and September 2015. Instruments used to collect the data for the study were: Fatigue Continuum Form, Depression anxiety stress scale (DASS-21) and maternal postpartum quality of life (MAPP-QOL). RESULTS: The mean fatigue score was 68.30 with 50.7% of women being depressed and 79.7% of the 138 women being anxious. The mean quality of life was 18.92 with quality of life being associated with fatigue, depression and anxiety. Depression and fatigue explained 26% of the variance in quality of life. CONCLUSION: Depression and fatigue adversely affected women's quality of life. It is important to address appropriate management of depression and fatigue in order to improve quality of life in pregnant women with preterm labor.

Factors Contributing to Increases in Prescription Drug Expenditures Borne by National Health Insurance in South Korea

PURPOSE: Rapid growth of prescription drug expenditures is a problem in South Korea. The objective of this study was to assess the contributions of four variables (therapeutic choice, drug-mix, original use, and price changes) to increases in drug expenditures paid by the National Health Insurance (NHI) in Korea. MATERIALS AND METHODS: A retrospective cohort study was conducted between January 1, 2008 and June 30, 2012 utilizing data from the NHI Claims Database of the Health Insurance Review and Assessment Service. The number of target drug types for final analysis was 13959. To analyze the growth rates of drug expenditures, this study used Fisher ideal index and the Laspeyres and Paasche indexes. RESULTS: With the exception of 2012, therapeutic choice contributed to about 40-60% of the increase in drug expenditures every year, while drug-mix contributed to another 30-40%. CONCLUSION: The rapid growth in prescription drug expenditure was found to be largely due to drug-mix and therapeutic choice over time. Original use had little impact on drug spending.

A factor of periodontal disease and dietary patterns in Korean adults using data from Korea National Health and Nutrition Examination Survey V / 대한구강보건학회지

OBJECTIVES: This study was aimed to identify the socioeconomic factors, health behavior factors and dietary patterns that have an influence on the periodontal disease in adults. METHODS: This study used data collected from the fifth Korea National Health and Nutrition Examination Survey (NHANES V-1). The final sample included 2,386 subjects who were 30-59 years old and who had completed the necessary health examinations, the health behaviors survey and nutrition survey. RESULTS: Eleven dietary patterns emerged from the factor analysis with different factor loading. After controlling for potential confounders, multiple logistic regression analysis of the dietary patterns showed that 'legumes/mixed grains' and 'instant foods' affected the periodontal disease. Lower consumption of 'legumes/mixed grains' and higher consumption of 'instant foods' were significantly associated only with an increased risk of periodontal disease. CONCLUSIONS: In the light of the results of this study, it appears pretty likely that the risk of developing periodontal disease can be reduced by changing a person's dietary patterns.

Cost-Effectiveness of Drug-Eluting vs. Bare-Metal Stents in Patients with Coronary Artery Disease from the Korean National Health Insurance Database

PURPOSE: The aim of this study was to evaluate the cost-effectiveness of the use of drug-eluting stents (DESs), as compared with bare-metal stents (BMSs) in Korea. MATERIALS AND METHODS: A retrospective cohort study was conducted between January 2000 and December 2007. Subjects were stent-treated for the first time between 2004 and 2005, with four years of follow-up (2004-2007) (n=43674). The incremental cost-effectiveness ratio (ICER) was used to calculate the costs of DESs compared with BMSs among patients with coronary artery disease (CAD). Cost-effectiveness was assessed with effectiveness defined as a reduction in major adverse cardiac events after six months and after one, two, three, and four years. RESULTS: The total costs of a DESs were 674108 Korean won (KRW) higher than that of a BMSs at the end of the follow-up; 13635 thousand KRW per patient treated with DESs and 12960 thousand KRW per patient treated with BMSs. The ICER was 256315 per KRW/death avoided and 293090 per KRW/re-stenting avoided among the CAD patients at the end of the follow-up. CONCLUSION: The ICER for the high-risk patients was lower than that for the low-risk patients. The use of DESs is clinically more useful than the use of BMSs for CAD and myocardial infarction patients, especially for those considered to be high-risk patients in Korea.

Correlation between vitamin C intake and periodontal disease: The Fifth Korea National Health and Nutrition Examination Survey, 2010 / 대한구강보건학회지

OBJECTIVES: Vitamin C is important for maintaining periodontal health. The purpose of this study was to examine the correlation between vitamin C intake and periodontal disease in adults. METHODS: The data collected from the 2010 Fifth Korea National Health and Nutrition Examination Survey was retrospectively reviewed. The final sample included 2,878 subjects, aged between 30 and 59 years. These patients had also undergone the required oral examinations and had taken health and nutrition surveys. RESULTS: The incidence of periodontal disease was 24.4%. The patients' gender, age, spouse, education level, smoking habits, brushing frequency, and vitamin C intake were considered to be significant risk factors for periodontal disease based on complex sampling analysis. The multivariate-adjusted odds ratio for occurrence of periodontal disease was 0.69 (95% confidence interval, 0.477-0.987) when the vitamin C intake of subjects in quartile 4 (Q4) and Q1 were compared (P=0.0421). CONCLUSIONS: The findings of this study suggest that vitamin C intake is significantly associated with periodontal disease, and also provide information that will aid in the prevention of periodontal disease.

Association between parental history of allergic diseases and atopic dermatitis in school aged children

PURPOSE: This study aimed to examine the relationship between parent's history of allergic disease and children's atopic dermatitis. METHODS: Data from the 2011 Research on the Current Status of Atopic Disease with Elementary Schools and Kindergartens in Suwon were used for analysis. Among 20,052 persons consenting to the survey, 18,943 who had answered parent's history were included in the study. RESULTS: The prevalence of father, mother, and parent's allergic disease history were 8.5%, 9.5%, and 2.3%, respective. The children with atopic dermatitis comprised 15.1% of the study population. In multivariate analysis, gender, weight at birth, the practice of breast-feeding, father's educational level, the presence of chemical products in the inside, and the presence of mold were significant risk factors for children's atopic dermatitis. The multivariate-adjusted odds ratio for the occurrence of children's atopic dermatitis was 3.19 (95% confidence interval, 2.57-3.95) when subjects with and without parent's history were compared. CONCLUSION: When fathers have a history of allergic disease, children tend to have atopic dermatitis.

Contamination status of groundwater used as livestock drinking in beef and dairy cattle farms, Korea / 대한수의학회지

In Korea, groundwater is main water source in livestock farms. Most dairy and cattle farms have constructed their own wells for human drinking and livestock farming. However, these private residential wells have not been controlled by government and also there was scant study about livestock drinking water quality. Therefore this study was to monitor of the livestock farms' groundwater quality in Korea. Water samples were collected at 123 dairy and cattle farms and were analysed forty six substances with quality standard for drinking water approved by the Minister of Environment. Seventy eight (63.4%) of 123 samples failed to drinking water stand a test. The most frequent contaminants were nitrate-nitrogen and microbial. 22.8% (n = 28) of samples showed nitrate-N concentration of higher than 10 mg/L meant that can't be used drinking water for human and the Nitrate-N concentration analysed in the range of 0.2 to 61.2 mg/L. All of 78 failed to drinking samples had microbial problems, especially 5.7% (n = 7) of samples indicated water could be contaminated by feces. Other contaminants detected were zinc and evaporation residue. Especially detected zinc concentration (32 mg/L) was about ten times higher than standard of zinc (3 mg/L). Regression analysis indicated that groundwater pH did not influence to nitrate-N concentration but the hardness and chloride could affect to nitrate-N concentration in the groundwater. Most livestock farms were adjacent to crop farmland in Korea. This could cause contamination of groundwater with nitrate-N and pesticide that could accumulate livestock product. Moreover Heavy metal such as zinc and copper could be released from a corrosive plated water pipe in livestock farm. Put together, Korea livestock system is indoor, not pasture-based, hence livestock could be exposed to potential contaminated water consistently. Therefore on the basis of these data, appropriate livestock drinking water quality standards should be prepared to keep livestock healthy and their product safe. Further, livestock drinking water quality should be monitored continuously in suitable livestock drinking water standards.

Does Abdominal Obesity Accelerate the Effect of Hypertriglyceridemia on Impaired Fasting Glucose?

PURPOSE: This study sought to determine whether abdominal obesity is a risk factor for impaired fasting glucose (IFG) and hypertriglyceridemia and to verify whether moderate effect of abdominal obesity on the relationship between IFG and hypertriglyceridemia in Korea. MATERIALS AND METHODS: Data from the Korean National Health and Nutrition Examination Survey was used for the analysis. The study population included 5,938 subjects aged 20 year old drawn from non-diabetic participants in a health examination survey. The subjects were classified according to the presence of abdominal obesity based on waist circumference, IFG based on their fasting blood glucose level, and hypertriglyceridemia on their fasting triglyceride. RESULTS: The multivariate-adjusted odds ratios for the occurrence of hypertriglyceridemia were 2.91 in the abdominal obesity group as compared with the nonobesity group and 1.31 in subjects with IFG compared with the normoglycemia controls. Abdominal obesity was found to be positively moderated in the interaction between waist circumference and fasting blood sugar. CONCLUSION: The moderate effect between abdominal obesity and IFG contributes to the development of hypertriglyceridemia in Korea.

Association between Emotional Labor and Symptoms of Depression among Bankers / 대한산업의학회지

OBJECTIVES: We focused on the relationship between symptoms of depression and emotional labor to investigate the mental health status of workers. METHODS: In this cross-sectional study, a total of 2,346 workers among bankers were our study subjects. A self-administered questionnaire was used to assess the socio-demographics, job characteristics, emotional labor and, the Center for Epidemiologic Studies-Depression scale (CES-D). We used multiple logistic regression analysis to estimate the relationship between emotional labor and the symptoms of depression. RESULTS: The prevalence of symptoms of depression among the survey subjects was 20.6%. After adjusting for confounding factors, emotional effort (OR: 1.7, 95% CI=1.28~2.31) and, emotional disharmony (OR: 4.5, 95% CI=3.13~6.44) in men and emotional effort (OR: 1.9, 95% CI=1.33~2.75), emotional disharmony (OR: 6.1, 95% CI=4.12~9.09) in women showed a statistically significant association with symptoms of depression. CONCLUSIONS: These results suggest that emotional disharmony and emotional effort are related to symptoms of depression. Managing emotional disharmony is important in managing symptoms of depression.