Association of Uncontrolled Hypertension or Diabetes Mellitus With Major Adverse Cardiovascular Events and Mortality in South Korea: Population-Based Cohort Study.

BACKGROUND: Managing hypertension (HT) and diabetes mellitus (DM) is crucial to preventing cardiovascular diseases. Few studies have investigated the incidence and risk of cardiovascular diseases or mortality in uncontrolled HT or DM in the Asian population. Epidemiological studies of cardiovascular disease should be conducted with continuous consideration of the changing disease risk profiles, lifestyles, and socioeconomic status over time. OBJECTIVE: We aimed to examine the association of uncontrolled HT or DM with the incidence of cardiovascular events or deaths from any cause. METHODS: This population-based retrospective study was conducted using data from the Korean National Health Insurance Service-National Health Screening Cohort, including patients aged 40-79 years who participated in national screening from 2002 to 2003 and were followed up until 2015. The health screening period from 2002 to 2013 was stratified into 6 index periods in 2-year cycles, and the follow-up period from 2004 to 2015 was stratified accordingly into 6 subsequent 2-year periods. The incidence rates and hazard ratio (HR) for major adverse cardiovascular events (MACE) and death from any cause were estimated according to HT or DM control status. Extended Cox models with time-dependent variables updated every 2 years, including sociodemographic characteristics, blood pressure (BP), fasting blood glucose (FBG), medication prescription, and adherence, were used. RESULTS: Among the total cohort of 440,249 patients, 155,765 (35.38%) were in the uncontrolled HT or DM group. More than 60% of the patients with HT or DM who were prescribed medications did not achieve the target BP or FBG. The incidence of MACE was 10.8-15.5 and 9.6-13.3 per 1000 person-years in the uncontrolled DM and uncontrolled HT groups, respectively, and increased with age. In the uncontrolled HT and DM group, the incidence of MACE was high (15.2-17.5 per 1000 person-years) at a relatively young age and showed no age-related trend. Adjusted HR for MACE were 1.28 (95% CI 1.23-1.32) for the uncontrolled DM group, 1.32 (95% CI 1.29-1.35) for the uncontrolled HT group, and 1.54 (95% CI 1.47-1.60) for the uncontrolled HT and DM group. Adjusted HR for death from any cause were 1.05 (95% CI 1.01-1.10) for the uncontrolled DM group, 1.13 (95% CI 1.10-1.16) for the uncontrolled HT group, and 1.17 (95% CI 1.12-1.23) for the uncontrolled HT and DM group. CONCLUSIONS: This up-to-date evidence of cardiovascular epidemiology in South Korea serves as the basis for planning public health policies to prevent cardiovascular diseases. The high uncontrolled rates of HT or DM, regardless of medication prescription, have led us to suggest the need for a novel system for effective BP or glycemic control, such as a community-wide management program using mobile health technology.

Relationship between childhood trauma and resilience in patients with mood disorders.

BACKGROUND: Childhood trauma has lasting negative impacts on individuals' psychological functioning. However, there is limited empirical evidence on the association between childhood trauma and resilience and none examining such relationship among diverse clinical populations. This study aimed to investigate the relationship in patients with major depressive disorder, bipolar I disorder, bipolar II disorder, and a comparison group. METHODS: In total, 787 psychiatric patients and 734 people from the general population participated in the study. The Childhood Trauma Questionnaire-Short Form and Connor-Davidson Resilience Scale were used to assess childhood trauma and resilience, respectively. RESULTS: Individuals with childhood trauma showed lower levels of resilience in all subjects; among them, those who experienced emotional abuse and emotional neglect exhibited even stronger associations than other types of childhood trauma. There was a significant difference in the negative relationship between childhood trauma and resilience by group, where the association was more prominent in the comparison group than in MDD and BD II patient groups. LIMITATIONS: The generalizability of our results may be limited due to unproportionate patient sample size. Also, we could not examine the causal relationship between childhood trauma and resilience. CONCLUSION: Childhood trauma and resilience had a significantly negative association. Our results suggest that people who have experienced emotional abuse and emotional neglect should be closely assisted to develop resilience. Interventions that promote resilience should be provided to individuals predisposed to psychological risks as a result of childhood trauma.

Borderline Personality Pathology in Major Depressive Disorder, Bipolar I and II Disorder, and Its Relationship With Childhood Trauma.

OBJECTIVE: Mood disorder and borderline personality pathology (BPP) are frequently comorbid and relate to childhood trauma. We investigated the relationship between childhood trauma and BPP features in mood disorder patients versus controls. METHODS: A total of 488 mood disorder patients, particularly major depressive disorder (MDD), bipolar I disorder (BD I), and bipolar II disorder (BD II), and 734 controls were included. We examined between-group BPP-related differences and correlated between BPP and childhood trauma using the Childhood Trauma Questionnaire-Short Form (CTQ) and the Personality Assessment Inventory-Borderline Features Scale. RESULTS: BD II patients showed significantly higher BPP. Emotional abuse and neglect were prominently associated with BPP, while affective instability and negative relationships exhibited a stronger association with childhood trauma. We also found a positive relationship between childhood trauma and BPP in MDD, BD I, and BD II patients. CONCLUSION: The findings of the present study imply that BPP features are more likely to be found in patients with BD II than BD I or MDD. Mood disorder patients with severe childhood trauma may have higher BPP features. Thus, further study of the relationship between childhood trauma and BPP features could improve the therapeutic approaches and help understand patients with mood disorders.

Efficacy and safety of daily home-based transcranial direct current stimulation as adjunct treatment for bipolar depressive episodes: Double-blind sham-controlled randomized clinical trial.

Background: Although transcranial direct current stimulation (tDCS) is known to be a promising therapeutic modality for unipolar depression, the efficacy and safety of tDCS for bipolar depressive episodes (BD) are still unknown and clinical trials of home-based tDCS treatment are scarce. As a result, we set out to investigate the efficacy and safety of home-based tDCS for the treatment BD. Methods: Participants (n = 64), diagnosed as bipolar disorder as per the diagnostic and statistical manual of mental disorders (DSM-5), were randomly assigned to receive tDCS. Hamilton Depression Rating Scale (HDRS-17) scores were measured at the baseline, week 2, 4, and 6, and home-based tDCS (for 30 min with 2 mA) was self-administered daily. Results: Of the 64 patients (15.6% bipolar disorder I, 84.4% bipolar disorder II), 41 patients completed the entire assessment. In the intention-to-treat analysis, time-group interaction for the HDRS-17 [F (3, 146.36) = 2.060; p = 0.108] and adverse effect differences between two groups were not statistically significant, except the pain score, which was higher in the active group than the sham group (week 0-2: p < 0.01, week 2-4: p < 0.05, and week 4-6: p < 0.01). Conclusion: Even though we found no evidence for the efficacy of home-based tDCS for patients with BD, this tool was found to be a safe and tolerable treatment modality for BD. Clinical trial registration: [https://clinicaltrials.gov/show/NCT03974815], identifier [NCT03974815].

Korean Validation of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire.

OBJECTIVE: The Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A) has been validated in more than 30 languages and is noted for its broad application in research and clinical settings. This study presents the first attempt to examine the reliability and validity of the TEMPS-A in Korea. METHODS: A total of 540 non-clinical participants completed the Korean TEMPS-A, which was adapted from the original English version via a comprehensive translation procedure. Reliability was assessed using Cronbach's α, and associations between temperaments were examined using Spearman's correlation coefficient. Exploratory factor analysis (EFA) was performed, and differences in TEMPS-A scores between the gender- and age-based groups were examined using Kruskal-Wallis analysis. RESULTS: The Korean TEMPS-A exhibited excellent internal consistency (0.70-0.91) and significant correlations between subscales. EFA resulted in a two-factor structure: Factor I (depressive, cyclothymic, irritable, and anxious) and Factor II (hyperthymic). Gender and age group differences were observed. CONCLUSION: Overall, our results suggest that TEMPS-A is a reliable and valid measure of affective temperaments for the Korean population. This study opens new possibilities for further research on affective temperaments and their related traits.

The Primary Process and Key Concepts of Economic Evaluation in Healthcare.

Economic evaluations in the healthcare are used to assess economic efficiency of pharmaceuticals and medical interventions such as diagnoses and medical procedures. This study introduces the main concepts of economic evaluation across its key steps: planning, outcome and cost calculation, modeling, cost-effectiveness results, uncertainty analysis, and decision-making. When planning an economic evaluation, we determine the study population, intervention, comparators, perspectives, time horizon, discount rates, and type of economic evaluation. In healthcare economic evaluations, outcomes include changes in mortality, the survival rate, life years, and quality-adjusted life years, while costs include medical, non-medical, and productivity costs. Model-based economic evaluations, including decision tree and Markov models, are mainly used to calculate the total costs and total effects. In cost-effectiveness or costutility analyses, cost-effectiveness is evaluated using the incremental cost-effectiveness ratio, which is the additional cost per one additional unit of effectiveness gained by an intervention compared with a comparator. All outcomes have uncertainties owing to limited evidence, diverse methodologies, and unexplained variation. Thus, researchers should review these uncertainties and confirm their robustness. We hope to contribute to the establishment and dissemination of economic evaluation methodologies that reflect Korean clinical and research environment and ultimately improve the rationality of healthcare policies.

Development and Validation of the Mood Instability Questionnaire-Trait (MIQ-T).

Background and objectives: Mood instability (MI) is a stable trait associated with psychiatric disorders, yet there is a lack of tools to measure MI. The purpose of this study was to develop and validate the Mood Instability Questionnaire-Trait (MIQ-T) to evaluate MI in mood disorder patients. Material and methods: Items were taken from various established questionnaires to create an initial list of MIQ-T questions. Data from 309 psychiatric patients (n = 309; 62 major depressive disorder, 58 bipolar I disorder, and 189 bipolar II disorder) were gathered from their medical records and were utilized in an exploratory factor analysis to clarify the underlying components of MI. Then, anonymous survey data from 288 individuals from the general population were included in the analysis as a comparison group. Associations between MIQ-T and other previously validated clinical instruments for mood disorders were examined to test external validity. Results: The exploratory factor analysis demonstrated that the five-factor structure (Lability, Upward Tendency, Downward Tendency, Childhood Instability, and Seasonality) of 59 items was the most appropriate with clear, cohesive features. MIQ-T exhibited high internal consistency (α = 0.96) and moderate to strong correlations with other previously validated clinical instruments, which were consistent with theoretical predictions, providing evidence of criterion validity. Short forms were also created to address the high internal consistency value, which can indicate redundancy, and to increase the approachability of the measure. We found that the patients with bipolar II disorder had higher MIQ-T scores than the patients with bipolar I disorder or major depressive disorder and the comparison group. Conclusion: Together, these findings validate the newly developed MIQ-T as an instrument of mood instability. MIQ-T can be a potential research tool for mood disorder.

Prevalence and socioeconomic burden of diabetes mellitus in South Korean adults: a population-based study using administrative data.

BACKGROUND: Diabetes leads to severe complications and imposes health and financial burdens on the society. However, currently existing domestic public health studies of diabetes in South Korea mainly focus on prevalence, and data on the nationwide burden of diabetes in South Korea are lacking. The study aimed to estimate the prevalence and economic burden of diabetes imposed on the South Korean society. METHODS: A prevalence-based cost-of-illness study was conducted using the Korean national claims database. Adult diabetic patients were defined as those aged ≥20 years with claim records containing diagnostic codes for diabetes (E10-E14) during at least two outpatient visits or one hospitalization. Direct costs included medical costs for the diagnosis and treatment of diabetes and transportation costs. Indirect costs included productivity loss costs due to morbidity and premature death and caregivers' costs. Subgroup analyses were conducted according to the type of diabetes, age (< 65 vs. ≥65), diabetes medication, experience of hospitalization, and presence of diabetic complications or related comorbidities. RESULTS: A total of 4,472,133 patients were diagnosed with diabetes in Korea in 2017. The average annual prevalence of diabetes was estimated at 10.7%. The diabetes-related economic burden was USD 18,293 million, with an average per capita cost of USD 4090 in 2019. Medical costs accounted for the biggest portion of the total cost (69.5%), followed by productivity loss costs (17.9%), caregivers' costs (10.2%), and transportation costs (2.4%). According to subgroup analyses, type 2 diabetes, presence of diabetic complications or related comorbidities, diabetes medication, and hospitalization represented the biggest portion of the economic burden for diabetes. As the number of complications increased from one to three or more, the per capita cost increased from USD 3991 to USD 11,965. In inpatient settings, the per capita cost was ~ 10.8 times higher than that of outpatient settings. CONCLUSIONS: South Korea has a slightly high prevalence and economic burden of diabetes. These findings highlight the need for effective strategies to manage diabetic patients and suggest that policy makers allocate more health care resources to diabetes. This is the first study on this topic, conducted using a nationally representative claims database in South Korea.

Measurement of autophagy flux in benign prostatic hyperplasia in vitro.

BACKGROUND: Recent studies have suggested a novel therapeutic strategy for treatment of benign prostatic hyperplasia (BPH) via modulation of autophagy. However, it is not clear whether autophagy induction or inhibition can render better therapeutic efficacy for BPH treatment because autophagy activation in BPH tissue is not precisely known and still contradictory. The purpose of this study was to examine the levels of autophagy in BPH tissue cells. METHODS: We have analyzed and compared autophagic flux which is defined as a measure of autophagic degradation activity in two human prostate epithelial cell lines, RWPE-1 (normal prostate) and BPH-1 (BPH) using LC3-II turnover assay, to clarify the levels of autophagy in BPH. RESULTS: The in vitro autophagy flux assays showed that autophagy flux was significantly decreased in BPH-1 cell lines compared with RWPE-1 cells under all three conditions of using the original (~62%), the exchanged (~46%), and the same media (Hank's balanced salt solution (HBSS), ~40%), and these results were similar to those seen in the prostate of testosterone-induced BPH rats (~50%) (P < 0.05). CONCLUSION: It is suggested that defective autophagy, which is decreased autophagy flux in the prostate gland, may be implicated in BPH, and activating autophagy flux of the prostate with BPH may be used as a potential therapeutic target for treating and alleviating BPH disease.

Psychological Characteristics in Patients with Chronic Complex Regional Pain Syndrome: Comparisons with Patients with Major Depressive Disorder and Other Types of Chronic Pain.

OBJECTIVE: This study investigated psychological characteristics of patients with chronic complex regional pain syndrome (CRPS) and examined relationships between psychosocial factors and pain severity. METHODS: In total, 76 patients with CRPS, 95 patients with other types of chronic pain, 171 healthy controls, and 66 patients with major depressive disorder (MDD) were included. Minnesota Multiphasic Personality Inventory (MMPI-2) profiles and scores on the Beck Depression Inventory and State-Trait Anxiety Inventory were calculated. Pain intensity was measured using a visual analog scale (VAS). RESULTS: Patients with CRPS scored higher on the Hypochondriasis (Hs), Depression (D), Hysteria (Hy), Paranoia (Pa), and Psychasthenia (Pt) scales of the MMPI-2 compared to healthy controls. The CRPS group scored lower on the D, Psychopathic deviate (Pd), Pa, Pt, Schizophrenia (Sc), and Social introversion (Si) scales compared to the MDD group. Although CRPS patients reported higher levels of pain than patients with other types of pain, the MMPI profiles of the two pain groups did not differ significantly. Linear regression analyses revealed that pain severity was significantly associated with depression and scores on the Masculinity-Femininity (Mf) scale. CONCLUSION: This is the first comparative study of the psychological characteristics of chronic CRPS patients, healthy controls, and patients with MDD. The neurotic profiles of CRPS patients were more psychologically adaptable than were those of patients with MDD; however, this profile was shared by both pain groups. The present findings further showed that, although pain severity was not a major contributor to depression, patients with CRPS should be evaluated for depressive symptoms.

Cost-effectiveness of Bariatric Surgery for People with Morbid Obesity in South Korea.

OBJECTIVE: This study aimed to evaluate the cost-effectiveness of bariatric surgery (BS) compared to non-surgical treatment (NST) in Korean people with morbid obesity according to comorbidities and body mass index (BMI) severity. METHODS: The target cohort was people with morbid obesity, defined as BMI of ≥ 35 kg/m2, or obese people with BMI of 30-34.9 kg/m2 having obesity-related comorbidities. A decision-tree model for 1-year obesity treatment and Markov model for the rest of life were used. In the decision-tree model, the comorbidity remission rate and BMI change after 1-year treatment were decided based on a prospective clinical trial. In the Markov model, the transition probabilities were calculated considering the BMI level and age. The starting age of 20 years, a cycle length of 1 year, a time horizon of 80 years, and a 5% discount rate were applied for the base case from the healthcare system perspective. RESULTS: In the base case, BS improved quality-adjusted life years (QALYs) and was the cost-effective option in total cohort (incremental cost-effectiveness ratio of BS vs. NST was 674 USD/QALY). It was shown to be cost-effective in all subgroup analyses based on BMI level. In particular, BS was a dominant alternative for the subgroup with basal BMI of 35.0-37.4 kg/m2. Various sensitivity analyses showed the robustness of results indicating the cost-effectiveness of BS. CONCLUSION: BS at BMI of > 30 kg/m2 was more effective than NST for a reduction in BMI and remission of obesity-related comorbidities and was cost-effective in Korea.

Clinical Correlates of Alcohol Use Disorder in Depressed Patients with Unipolar and Bipolar Disorder.

OBJECTIVE: Alcohol use disorder (AUD) is one of the most frequent comorbid conditions in mood disorders. We aimed to examine the relationships between clinical phenotypes of acutely depressed subjects and co-occurring AUD. METHODS: Clinical assessment including diagnosis of mood disorder and co-occurring AUD, the severity of depressive or manic symptoms, and affective temperaments were conducted in 137 subjects suffering from a major depressive episode. According to the presence of AUD, clinical variables were compared between the two groups. Using binary logistic regression models, the effects of mood symptoms and affective temperaments on the risk of AUD were determined. RESULTS: Severity of manic symptoms, suicidal ideation, and childhood trauma were higher in the AUD group than in the non-AUD group. Scores for irritable and hyperthymic temperament were higher and the score for anxious temperament was lower in the AUD group. In regression models adjusting confounders, anxious temperament was an independent protector against AUD. On the other hand, the diagnosis of bipolar disorder and the irritable manic symptom dimension increased the risk of AUD. CONCLUSION: Anxious temperament decreased the AUD risk, whereas irritable manic symptoms increased the risk during depression. AUD in mood disorders may be an expression of manic psychopathology.

Temporal dynamics in meta longitudinal RNA-Seq data.

Identification of differentially expressed genes has been a high priority task of downstream analyses to further advances in biomedical research. Investigators have been faced with an array of issues in dealing with more complicated experiments and metadata, including batch effects, normalization, temporal dynamics (temporally differential expression), and isoform diversity (isoform-level quantification and differential splicing events). To date, there are currently no standard approaches to precisely and efficiently analyze these moderate or large-scale experimental designs, especially with combined metadata. In this report, we propose comprehensive analytical pipelines to precisely characterize temporal dynamics in differential expression of genes and other genomic features, i.e., the variability of transcripts, isoforms and exons, by controlling batch effects and other nuisance factors that could have significant confounding effects on the main effects of interest in comparative models and may result in misleading interpretations.

Outcomes of Stenting versus Endarterectomy for Symptomatic Extracranial Carotid Stenosis: A Retrospective Multicenter Study in Korea.

BACKGROUND: The present multicenter retrospective study aimed to compare the outcome of carotid artery stenting (CAS) versus carotid endarterectomy (CEA) among Korean patients with symptomatic extracranial carotid stenosis. METHODS: Between January 2008 and December 2011, 677 patients underwent either CAS (346, 51.1%) or CEA (331, 48.9%). The primary end point included the occurrence of major adverse cardiovascular events (MACEs), defined as fatal or nonfatal stroke and myocardial infarction, and all-cause mortality during the periprocedural period and within 4 years after CAS or CEA. RESULTS: Although patients undergoing CAS and CEA did not differ significantly in MACE incidence within 4 years (15.3% vs. 11.5%, P = 0.14), CEA showed lower periprocedural MACE incidence than CAS with clinical significance (6.1% vs. 3.0%, P = 0.06). During the periprocedural period, the incidence of any stroke was significantly higher in patients undergoing CAS (5.5% vs. 2.4%, P = 0.04) but not the incidence of myocardial infarction (0.6% vs. 0.3%, P > 0.99). Kaplan-Meier survival analysis showed similar MACE-free (P = 0.16), stroke-free (P = 0.24), and overall survival (P = 0.25) rates in both groups. On subgroup analysis, patients older than 70 years undergoing CAS had a significantly higher incidence of MACE at 4 years (22.7% vs. 13.7%, P = 0.03). CONCLUSIONS: Although the risk of MACE did not differ significantly within 4 years in this Korean population undergoing CAS and CEA, there was a higher risk of stroke with CAS during the periprocedural period.

The incremental economic burden of heart failure: A population-based investigation from South Korea.

BACKGROUND: The prevalence of heart failure (HF) and its economic burden are increasing with age of the South Korean population. This study aimed to assess the economic impact of HF from the societal perspective. METHODS: A prevalence-based, incremental cost-of-patient study was performed to estimate the cost ratio between patients with HF and those without HF based on the claims database of the national health insurance in South Korea. We defined adult HF patients as those aged ≥19 years who had at least one insurance claim record with a primary or secondary diagnosis of HF. Age- and gender-matched controls were defined using a 1:4 greedy matching method. Costs were estimated by including medical costs for insurance-covered and non-covered services, transportation costs, caregiver's cost, and time costs of patients. The ratio of costs between patients with HF and those without HF was adjusted for age, gender, and type of universal health security program in the multivariate regression model. RESULTS: The average annual per-capita cost was estimated to be $6,601 for patients with HF (n = 14,252), which is about 3.38 (95% confidence interval [CI]: 3.31-3.46) times higher than that for patients without HF (n = 1,116,882) and 1.64 (95% CI: 1.59-1.70) times higher than that for the age- and gender-matched patients without HF (n = 57,008). In the multivariate regression model, the annual per-capita total costs were 1.98-fold (95% CI: 1.94-2.02) statistically higher for patients with HF than for patients without HF after adjustment for age, gender, and type of universal health security program. CONCLUSIONS: This study demonstrates a significant incremental burden of HF. Given that the prevalence of HF is expected to increase with an increase in the aging population, the national economic burden is expected to be substantial in the future. Thus, greater emphasis on the prevention and treatment of HF is warranted.

Comparison of screening strategies for prevalent vertebral fractures in South Korea: vertebral fracture assessment vs. spine radiography.

BACKGROUND: Vertebral Fracture Assessment (VFA) is a useful tool to detect the vertebral fracture (VF) with low cost and radiation exposure. We aimed to compare screening strategies including VFA and spine radiography (X-ray) for detecting VF in terms of clinical effectiveness, cost and radiation exposure. METHODS: Three screening strategies: 1) X-ray following VFA, 2) VFA only, and 3) X-ray only were compared using a Markov model based on administrative data from South Korea in a population aged ≥50 years. We compared the incidence of new VFs, cost-effectiveness of reducing new VFs and radiation exposure in each strategy. RESULTS: The incidence of new VFs was reduced in all screening strategies compared to no screening: 29.4% for women and 12.5% for men in both X-ray following the VFA and VFA only strategies and 35% for women and 17.5% for men in the X-ray only strategy. The X-ray following VFA strategy had the lowest cost, followed by the X-ray only, and VFA only strategies. The radiation doses for X-ray only were 2,647-2,989 µSv and 3,253-3,398 µSv higher than in the X-ray following VFA and VFA only strategies. The new VF prevention effect was greater in women, and more prominent in older people (women ≥ 70, men ≥ 80) than people ≥ 50 years. CONCLUSIONS: The X-ray following VFA strategy is a cost-effective option for screening prevalent VF to prevent new VF in people aged ≥50 years due to its high effectiveness, lowest cost, and least radiation exposure.

Identification of target risk groups for population-based Clostridium difficile infection prevention strategies using a population attributable risk approach.

OBJECTIVES: We aimed to determine risk factors associated with Clostridium difficile infection (CDI) and assess the contributions of these factors on CDI burden. METHODS: We conducted a 1:4 matched case-control study using a national claims dataset. Cases were incident CDI without a history of CDI in the previous 84 days, and were age- and sex-matched with control patients. We ascertained exposure, defined as a history of morbidities and drug use within 90 days. The population attributable risk (PAR) percent for risk factors was estimated using odds ratios (ORs) obtained from the case-control study. RESULTS: Overall, the strongest CDI-associated risk factors, which have significant contributions to the CDI burden as well, were the experience of gastroenteritis (OR=5.08, PAR%=17.09%) and use of antibiotics (OR=1.69, PAR%=19.00%), followed by the experiences of female pelvic infection, irritable bowel syndrome, inflammatory bowel disease, and pneumonia, and use of proton-pump inhibitors (OR=1.52-2.37, PAR%=1.95-2.90). CONCLUSIONS: The control of risk factors that had strong association with CDI and affected large proportions of total CDI cases would be beneficial for CDI prevention. We suggest performing CDI testing for symptomatic patients with gastroenteritis and implementing antibiotics stewardship.

Comparisons of ELISA and Western blot assays for detection of autophagy flux.

We analyzed autophagy/mitophagy flux in vitro (C2C12 myotubes) and in vivo (mouse skeletal muscle) following the treatments of autophagy inducers (starvation, rapamycin) and a mitophagy inducer (carbonyl cyanide m-chlorophenylhydrazone, CCCP) using two immunodetection methods, ELISA and Western blotting, and compared their working range, accuracy, and reliability. The ELISAs showed a broader working range than that of the LC3 Western blots (Table 1). Table 2 showed that data value distribution was tighter and the average standard error from the ELISA was much smaller than those of the Western blot, directly relating to the accuracy of the assay. Test-retest reliability analysis showed good reliability for three individual ELISAs (interclass correlation, ≥ 0.7), but poor reliability for three individual Western blots (interclass correlation, ≤ 0.4) (Table 3).

Quantification of autophagy flux using LC3 ELISA.

Macroautophagy (hereafter referred to as autophagy) is a degradation system that delivers cytoplasmic materials to lysosomes via autophagosomes. Autophagic flux is defined as a measure of autophagic degradation activity. Despite several methods for monitoring autophagic flux being currently utilized, interest in finding a highly accurate, sensitive and well-quantifiable assay is still growing. Therefore, we introduce a new approach analyzing autophagic flux in vitro and in vivo using enzyme-linked immunosorbent assay (ELISA) technique. In order to adapt this assay from LC3-II turnover measured by Western blot in the presence and absence of lysosomal inhibitors, we induced autophagy by starvation or rapamycin and mitophagy (mitochondrial degradation by autophagy) by CCCP in C2C12 myotubes for 8 h and in mice for 48 h with and without Bafilomycin A1 or colchicine treatment, respectively. Following subcellular fractionation of mouse skeletal muscle cells and tissue, cytosolic, membrane, and mitochondrial fractions were analyzed through a sandwich ELISA using two LC3 antibodies, LC3 capture and HRP-conjugated LC3 detection antibodies. Using this ELISA, changes in the membrane-bound or mitochondrion-associated LC3-II levels, and the ratio of the LC3-II from each fraction to LC3-I levels (cytosolic fraction) were evaluated for measuring autophagy and mitophagy flux. This study demonstrates that this ELISA was more sensitive and reliable to measure autophagic/mitophagic flux in both in vitro and in vivo, compared with the most commonly used LC3 turnover assay via Western blot.