Recent trends in opioid prescriptions in Korea from 2002 to 2015 based on the Korean NHIS-NSC cohort / 한국역학회지

OBJECTIVES@#Opioids are prescribed to treat moderate to severe pain. We investigated recent trends in opioid (morphine, oxycodone, fentanyl, and hydromorphone) prescriptions using data from the Korean National Health Insurance Service-National Sample Cohort between 2002 and 2015. @*METHODS@#The morphine milligram equivalent (MME) was calculated to standardize the relative potency of opioids. The number (cases) or amount (MME) of annual opioid prescriptions per 10,000 registrants was computed to analyze trends in opioid prescriptions after age standardization. Joinpoint regression analysis was conducted to calculate the annual percentage change and average annual percentage change (AAPC). @*RESULTS@#The number (cases) of prescriptions per 10,000 registrants increased from 0.07 in 2002 to 41.23 in 2015 (AAPC, 76.0%; 95% confidence interval [CI], 61.6 to 91.7). The MME per 10,000 registrants increased from 15.06 in 2002 to 40,727.80 in 2015 (AAPC, 103.0%; 95% CI, 78.2 to 131.3). The highest AAPC of prescriptions and MME per 10,000 registrants were observed in the elderly (60-69 years) and in patients treated at general hospitals. Fentanyl prescriptions increased most rapidly among the 4 opioids. @*CONCLUSIONS@#Consumption of opioids greatly increased in Korea over the 14-year study period.

Exposure to Secondhand Smoke and a Tobacco-Specific Carcinogen in Non-Smokers / 가정의학회지

Background@#The International Agency for Research on Cancer classifies 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) as a known carcinogen. This study aimed to investigate the association between exposure to secondhand smoke (SHS) and NNAL concentrations in non-smokers. @*Methods@#This was a cross-sectional study based on data from the 2016 to 2018 Korea National Health and Nutrition Examination Survey. Urine NNAL concentrations were categorized into tertiles of 3,615 study participants who were non-smokers. All sampling and weight variables were stratified, and analyses to account for the complex sampling design were conducted. @*Results@#The overall, male, and female percentages of SHS exposure among non-smokers were 22.4%, 29.2%, and 20.4%, respectively. The geometric means of urine NNAL concentrations were 1.896±0.098 pg/mL and 1.094±0.028 pg/mL in the SHS exposure and non-exposure groups, respectively. After adjusting for confounding variables, in the total group, the geometric mean of urine NNAL concentrations was significantly higher in the SHS exposure group than in the SHS non-exposure group (adjusted P-value <0.001). Compared with the non-exposure group, the adjusted odds ratios (95% confidence intervals) for the highest NNAL tertile group of overall SHS exposure in the total, men, and women groups were 2.44 (1.95–3.05), 1.65 (1.08–2.53), and 2.73 (2.11–3.52), respectively, after full adjustment. @*Conclusion@#The urine NNAL concentration in the SHS exposure group was significantly higher than that in the non-exposure group. Exposure to SHS was associated with a higher risk of elevated urine NNAL concentrations in non-smokers.

Clinical Practice Guidelines for Managing Frailty in Community-Dwelling Korean Elderly Adults in Primary Care Settings / 가정의학회지

Aging has become a global problem, and the interest in healthy aging is growing. Healthy aging involves a focus on the maintenance of the function and well-being of elderly adults, rather than a specific disease. Thus, the management of frailty, which is an accumulated decline in function, is important for healthy aging. The adaptation method was used to develop clinical practice guidelines on frailty management that are applicable in primary care settings. The guidelines were developed in three phases: preparation (organization of committees and establishment of the scope of development), literature screening and evaluation (selection of the clinical practice guidelines to be adapted and evaluation of the guidelines using the Korean Appraisal of Guidelines for Research and Evaluation II tool), and confirmation of recommendations (three rounds of Delphi consensus and internal and external reviews). A total of 16 recommendations (five recommendations for diagnosis and assessment, 11 recommendations for intervention of frailty) were made through the guideline development process. These clinical practice guidelines provide overall guidance on the identification, evaluation, intervention, and monitoring of frailty, making them applicable in primary care settings. As aging and “healthy aging” become more and more important, these guidelines are also expected to increase in clinical usefulness.

Defining Essential Topics and Procedures for Korean Family Medicine Residency Training / 가정의학회지

Background@#This study aims to create a comprehensive list of essential topics and procedural skills for family medicine residency training in Korea. @*Methods@#Three e-mailed surveys were conducted. The first and second surveys were sent to all board-certified family physicians in the Korean Academy of Family Medicine (KAFM) database via e-mail. Participants were asked to rate each of the topics (117 in survey 1, 36 in survey 2) and procedures (65 in survey 1, 19 in survey 2) based on how necessary it was to teach it and personal experience of utilizing it in clinical practice. Agreement rates of the responses were calculated and then sent to the 32 KAFM board members in survey 3. Opinions on potential cut-off points to divide the items into three categories and the minimum achievement requirements needed to graduate for each category were solicited. @*Results@#Of 6,588 physicians, 256 responded to the first survey (3.89% response rate), 209 out of 6,669 to the second survey (3.13%), and 100% responded to the third survey. The final list included 153 topics and 81 procedures, which were organized into three categories: mandatory, recommended, and optional (112/38/3, 27/33/21). For each category of topics and procedures, the minimum requirement for 3-year residency training was set at 90%/60%/30% and 80%/60%/30%, respectively. @*Conclusion@#This national survey was the first investigation to define essential topics and procedures for residency training in Korean family medicine. The lists obtained represent the opinions of Korean family physicians and are expected to aid in the improvement of family medicine training programs in the new competency-based curriculum.

Association between Second-hand Smoke Exposure and Urinary NNAL Level in Korean Adolescents

Background@#The 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a metabolite of tobacco-specific lung carcinogen that can be found in both smokers and non-smokers.Particularly, NNAL levels of children with a history of exposure to second-hand smoke (SHS) are higher than those of adults. Thus, we aimed to investigate the association between SHS exposure and urine NNAL levels in Korean adolescents. @*Methods@#This cross-sectional study used data from the Korea National Health and Nutrition Examination Survey VII. Overall, 648 never-smoking adolescents (425 boys and 223 girls) aged 12 to 18 were included in this study. Logistic regression analyses identified the relationship between SHS exposure and elevated urine NNAL levels. @*Results@#The mean urine NNAL levels of the no exposure and exposure group in boys were 1.39 and 2.26 ng/mL, respectively, whereas they were 1.01 and 2.45 ng/mL in girls, respectively (P < 0.001). Among the adolescents exposed to SHS, the confounder-adjusted odds ratio (95% confidence intervals) for elevated urine NNAL levels according to exposure area as overall, home, and public area were 2.68 (1.58–4.53), 31.02 (9.46–101.74), and 1.89 (1.12–3.17) in boys;and 6.50 (3.22–13.11), 20.09 (7.08–57.04), and 3.94 (1.98–7.77) in girls, respectively. @*Conclusion@#SHS exposure was significantly associated with elevated urine NNAL levels in Korean adolescents, particularly in female adolescents and in those with home exposure.These findings remind us of the need to protect adolescents from SHS.

Association between Second-hand Smoke Exposure and Urinary NNAL Level in Korean Adolescents

Background@#The 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a metabolite of tobacco-specific lung carcinogen that can be found in both smokers and non-smokers.Particularly, NNAL levels of children with a history of exposure to second-hand smoke (SHS) are higher than those of adults. Thus, we aimed to investigate the association between SHS exposure and urine NNAL levels in Korean adolescents. @*Methods@#This cross-sectional study used data from the Korea National Health and Nutrition Examination Survey VII. Overall, 648 never-smoking adolescents (425 boys and 223 girls) aged 12 to 18 were included in this study. Logistic regression analyses identified the relationship between SHS exposure and elevated urine NNAL levels. @*Results@#The mean urine NNAL levels of the no exposure and exposure group in boys were 1.39 and 2.26 ng/mL, respectively, whereas they were 1.01 and 2.45 ng/mL in girls, respectively (P < 0.001). Among the adolescents exposed to SHS, the confounder-adjusted odds ratio (95% confidence intervals) for elevated urine NNAL levels according to exposure area as overall, home, and public area were 2.68 (1.58–4.53), 31.02 (9.46–101.74), and 1.89 (1.12–3.17) in boys;and 6.50 (3.22–13.11), 20.09 (7.08–57.04), and 3.94 (1.98–7.77) in girls, respectively. @*Conclusion@#SHS exposure was significantly associated with elevated urine NNAL levels in Korean adolescents, particularly in female adolescents and in those with home exposure.These findings remind us of the need to protect adolescents from SHS.

Cigarette Smoking in Men and Women and Electronic Cigarette Smoking in Men are Associated with Higher Risk of Elevated Cadmium Level in the Blood

Clinical Practice Guideline for Care in the Last Days of Life / 한국호스피스완화의료학회지

A clinical practice guideline for patients in the dying process in general wards and their families, developed through an evidence-based process, is presented herein. The purpose of this guideline is to enable a peaceful death based on an understanding of suitable management of patients’ physical and mental symptoms, psychological support, appropriate deci-sion-making, family care, and clearly-defined team roles. Although there are limits to the available evidence regarding medical issues in patients facing death, the final recommendations were determined from expert advice and feedback, considering values and preferences related to medical treatment, benefits and harms, and applicability in the real world. This guideline should be applied in a way that takes into account specific health care environments, including the resources of medical staff and differences in the available resources of each institution. This guideline can be used by all medical institutions in South Korea.

Trends in Influenza Vaccination Coverage Rates among Korean Cancer Survivors: Analysis of the Korea National Health and Nutrition Examination Survey III–VI / 가정의학회지

Background@#Few studies have reported on the trends in influenza vaccination rates among cancer survivors in Korea. We investigated these trends over a recent 11-year period (2005–2015). @*Methods@#Data were obtained from the Korea National Health and Nutrition Examination Survey (KNHANES) III– VI (2005–2015). After excluding individuals younger than 40 years of age, the participants included 2,210 cancer survivors (861 men and 1,349 women). We categorized these study participants into four groups according to age and sex. @*Results@#The influenza vaccination rate decreased significantly among male cancer survivors, with rates of 74.8, 64.7, 56.2, and 55.2% (β coefficient=-0.257, P for trend <0.001) in KNHANES III, VI, V, and VI, respectively. While influenza vaccination rates decreased significantly among older male cancer survivors (≥65 years) (β coefficient=-0.359, P for trend=0.017), they increased among older female cancer survivors (β coefficient=0.375, P for trend=0.011) from 2005 to 2015. @*Conclusion@#Influenza vaccination rates in older cancer survivors significantly decreased in men but increased in women in successive KNHANES phases. Efforts are needed to improve immunization education and awareness, especially in older male cancer survivors.

Performance of the PSS, APACHE II, and SOFA score as in-hospital prognostic tool in glufosinate-poisoned patients in the intensive care unit

Objective@#Glufosinate-containing herbicide is being used increasingly in agriculture. Its poisoning is a worldwide concern. This study assessed the ability of the Poison Severity Score (PSS), Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring systems, and Sequential Organ Failure Assessment (SOFA) score to predict mortality in intensive care unit patients poisoned with glufosinate. @*Methods@#This was a retrospective cohort study conducted from January 2001 to January 2019. The demographic factors, hemodynamic variables, and laboratory variables were compared in survivors and non-survivors. Using multivariate logistic analysis, the data for the total population were analyzed retrospectively to determine the factors associated with mortality. Significant predictive variables, PSS, APACHE II scoring system, and SOFA score were compared by analyzing the receiver operating characteristic curves. @*Results@#Two hundred seventy-six patients (mean age, 56 years) were enrolled in this study. Of the 276 patients, 240 (87.0%) survived, and 36 (13.0%) died. The factors associated with mortality were a decreased mean arterial blood pressure, Glasgow Coma Scale, partial pressure of arterial oxygen/fraction of inspired oxygen, HCO3-, pH, and HCO3-, and an increased lactate, ammonia, C-reactive protein, PSS, SOFA score, and APACHE II score. Dyspnea, use of vasopressors, and application of mechanical ventilation were associated with mortality. In multivariate analysis, Glasgow Coma Scale5.2 mmol/L, use of vasopressors, and application of mechanical ventilation were predictive of mortality. The areas under the curve and 95% confidence intervals for these indicators were 0.920 (0.834-0.981), 0.865 (0.792-0.923), and 0.824 (0.752-0.897) for the PSS, APACHE II, and SOFA, respectively. @*Conclusion@#The PSS can be used to predict in-hospital mortality and stratify the risk among glufosinate-poisoned patients.

Cigarette Smoking in Men and Women and Electronic Cigarette Smoking in Men are Associated with Higher Risk of Elevated Cadmium Level in the Blood

BACKGROUND@#We investigated the association between blood concentration of cadmium and smoking status including use of electronic cigarettes (E-cigars).@*METHODS@#We used data from the Korea National Health and Nutritional Survey 2013 and 2016. A total of 4,744 participants (2,162 men and 2,582 women) were included and were categorized into five groups (Non-smokers, E-cigar non-users in past-smokers, E-cigar users in past-smokers, E-cigar non-users in cigarette-smokers and E-cigar users in cigarette-smokers). Cadmium blood concentration was categorized into tertiles. All sampling and weight variables were stratified, and analysis to account for the complex sampling design was conducted.@*RESULTS@#In both genders, the geometric cadmium concentration was significantly different according to smoking status (both genders, analysis of variance P value < 0.001). In men, E-cigar users were significantly higher than the non-smokers (P value = past-smokers, 0.017; cigarette-smokers, < 0.001) when fully adjusted. Compared with non-smokers, fully-adjusted odds ratios (95% confidence intervals) for the highest cadmium tertiles of E-cigar non-users in cigarette-smokers and E-cigar users in cigarette-smokers were 6.56 (3.55–12.11) and 5.68 (1.96–16.50) in men and 2.74 (1.42–5.29) and 1.29 (0.10–17.44) in women.@*CONCLUSION@#Conventional cigarette smoking in men and women and E-cigar use in men are associated with higher risk of elevated blood cadmium level. Preventive management of cadmium exposure monitoring in conventional cigarette-smokers and E-cigar users may be needed.

Performance of the PSS, APACHE II, and SOFA score as in-hospital prognostic tool in glufosinate-poisoned patients in the intensive care unit

Objective@#Glufosinate-containing herbicide is being used increasingly in agriculture. Its poisoning is a worldwide concern. This study assessed the ability of the Poison Severity Score (PSS), Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring systems, and Sequential Organ Failure Assessment (SOFA) score to predict mortality in intensive care unit patients poisoned with glufosinate. @*Methods@#This was a retrospective cohort study conducted from January 2001 to January 2019. The demographic factors, hemodynamic variables, and laboratory variables were compared in survivors and non-survivors. Using multivariate logistic analysis, the data for the total population were analyzed retrospectively to determine the factors associated with mortality. Significant predictive variables, PSS, APACHE II scoring system, and SOFA score were compared by analyzing the receiver operating characteristic curves. @*Results@#Two hundred seventy-six patients (mean age, 56 years) were enrolled in this study. Of the 276 patients, 240 (87.0%) survived, and 36 (13.0%) died. The factors associated with mortality were a decreased mean arterial blood pressure, Glasgow Coma Scale, partial pressure of arterial oxygen/fraction of inspired oxygen, HCO3-, pH, and HCO3-, and an increased lactate, ammonia, C-reactive protein, PSS, SOFA score, and APACHE II score. Dyspnea, use of vasopressors, and application of mechanical ventilation were associated with mortality. In multivariate analysis, Glasgow Coma Scale5.2 mmol/L, use of vasopressors, and application of mechanical ventilation were predictive of mortality. The areas under the curve and 95% confidence intervals for these indicators were 0.920 (0.834-0.981), 0.865 (0.792-0.923), and 0.824 (0.752-0.897) for the PSS, APACHE II, and SOFA, respectively. @*Conclusion@#The PSS can be used to predict in-hospital mortality and stratify the risk among glufosinate-poisoned patients.

Cigarette Smoking in Men and Women and Electronic Cigarette Smoking in Men are Associated with Higher Risk of Elevated Cadmium Level in the Blood

BACKGROUND@#We investigated the association between blood concentration of cadmium and smoking status including use of electronic cigarettes (E-cigars).@*METHODS@#We used data from the Korea National Health and Nutritional Survey 2013 and 2016. A total of 4,744 participants (2,162 men and 2,582 women) were included and were categorized into five groups (Non-smokers, E-cigar non-users in past-smokers, E-cigar users in past-smokers, E-cigar non-users in cigarette-smokers and E-cigar users in cigarette-smokers). Cadmium blood concentration was categorized into tertiles. All sampling and weight variables were stratified, and analysis to account for the complex sampling design was conducted.@*RESULTS@#In both genders, the geometric cadmium concentration was significantly different according to smoking status (both genders, analysis of variance P value < 0.001). In men, E-cigar users were significantly higher than the non-smokers (P value = past-smokers, 0.017; cigarette-smokers, < 0.001) when fully adjusted. Compared with non-smokers, fully-adjusted odds ratios (95% confidence intervals) for the highest cadmium tertiles of E-cigar non-users in cigarette-smokers and E-cigar users in cigarette-smokers were 6.56 (3.55–12.11) and 5.68 (1.96–16.50) in men and 2.74 (1.42–5.29) and 1.29 (0.10–17.44) in women.@*CONCLUSION@#Conventional cigarette smoking in men and women and E-cigar use in men are associated with higher risk of elevated blood cadmium level. Preventive management of cadmium exposure monitoring in conventional cigarette-smokers and E-cigar users may be needed.

Monitoring Glutathione Dynamics and Heterogeneity in Living Stem Cells

Glutathione (GSH) is a major antioxidant in cells, and plays vital roles in the cellular defense against oxidants and in the regulation of redox signals. In a previous report, we demonstrated that stem cell function is critically affected by heterogeneity and dynamic changes in cellular GSH concentration. Here, we present a detailed protocol for the monitoring of GSH concentration in living stem cells using FreSHtracer, a real-time GSH probe. We describe the steps involved in monitoring GSH concentration in single living stem cells using confocal microscopy and flow cytometry. These methods are simple, rapid, and quantitative, and able to demonstrate intracellular GSH concentration changes in real time. We also describe the application of FreSHtracer to the sorting of stem cells according to their GSH content using flow cytometry. Typically, microscopic or flow cytometric analyses of FreSHtracer and MitoFreSHtracer signals in living stem cells take ~2~3 h, and the fractionation of stem cells into subpopulations on the basis of cellular GSH levels takes 3~4.5 h. This method could be applied to almost every kind of mammalian cell with minor modifications to the protocol described here.

Nafamostat Mesilate Inhibits TNF-alpha-Induced Vascular Endothelial Cell Dysfunction by Inhibiting Reactive Oxygen Species Production

Nafamostat mesilate (NM) is a serine protease inhibitor with anticoagulant and anti-inflammatory effects. NM has been used in Asia for anticoagulation during extracorporeal circulation in patients undergoing continuous renal replacement therapy and extra corporeal membrane oxygenation. Oxidative stress is an independent risk factor for atherosclerotic vascular disease and is associated with vascular endothelial function. We investigated whether NM could inhibit endothelial dysfunction induced by tumor necrosis factor-alpha (TNF-alpha). Human umbilical vein endothelial cells (HUVECs) were treated with TNF-alpha for 24 h. The effects of NM on monocyte adhesion, vascular cell adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) protein expression, p38 mitogen-activated protein kinase (MAPK) activation, and intracellular superoxide production were then examined. NM (0.01~100 microg/mL) did not affect HUVEC viability; however, it inhibited the increases in reactive oxygen species (ROS) production and p66shc expression elicited by TNF-alpha (3 ng/mL), and it dose dependently prevented the TNF-alpha-induced upregulation of endothelial VCAM-1 and ICAM-1. In addition, it mitigated TNF-alpha-induced p38 MAPK phosphorylation and the adhesion of U937 monocytes. These data suggest that NM mitigates TNF-alpha-induced monocyte adhesion and the expression of endothelial cell adhesion molecules, and that the anti-adhesive effect of NM is mediated through the inhibition of p66shc, ROS production, and p38 MAPK activation.

The Molecular Nature of Very Small Embryonic-Like Stem Cells in Adult Tissues

Pluripotent stem cells (PSCs) have been considered as the most important cells in regenerative medicine as they are able to differentiate into all types of cells in the human body. PSCs have been established from several sources of embryo tissue or by reprogramming of terminally differentiated adult tissue by transduction of so-called Yamanaka factors (Oct4, Sox2, Klf4, and cMyc). Interestingly, accumulating evidence has demonstrated the residence of PSCs in adult tissue and with the ability to differentiate into multiple types of tissue-committed stem cells (TCSCs). We also recently demonstrated that a population of pluripotent Oct4(+) SSEA-1(+)Sca-1(+)Lin-CD45(-) very small embryonic-like stem cells (VSELs) resides in the adult murine bone marrow (BM) and in other murine tissue. These very small (~3-6 microm) cells express pluripotent markers such as Oct4, Nanog, and SSEA-1. VSELs could be specified into several tissue-residing TCSCs in response to tissue/organ injury, and thus suggesting that these cells have a physiological role in the rejuvenation of a pool of TCSCs under steady-state conditions. In this review article, we discuss the molecular nature of the rare population of VSELs which have a crucial role in regulating the pluripotency, proliferation, differentiation, and aging of these cells.

Nafamostat Mesilate: Can It Be Used as a Conduit Preserving Agent in Coronary Artery Bypass Surgery?

BACKGROUND: Graft vessel preservation solution in coronary artery bypass surgery is used to maintain the graft conduit in optimal condition during the perioperative period. Nafamostat mesilate (NM) has anticoagulation and anti-inflammatory properties. Therefore, we investigated NM as a conduit preservative agent and compared it to papaverine. METHODS: Sprague-Dawley (SD) rat thoracic aortas were examined for their contraction-relaxation ability using phenylephrine (PE) and acetylcholine (ACh) following preincubation with papaverine and NM in standard classical organ baths. Human umbilical vein endothelial cells (HUVECs) were cultured to check for the endothelial cell viability. Histopathological examination and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were performed on the thoracic aortas of SD rats. RESULTS: The anti-contraction effects of papaverine were superior to those of NM at PE (p90% in various concentrations of both NM and papaverine. A histopathological study showed a protective effect against necrosis and apoptosis (p<0.05) in the NM group. CONCLUSION: NM exhibited good vascular relaxation and a reasonable anti-vasocontraction effect with a better cell protecting effect than papaverine; therefore, we concluded that NM is a good potential conduit preserving agent.