Impact of prolonged carbapenem use-focused antimicrobial stewardship on antimicrobial consumption and factors affecting acceptance of recommendations: a quasi-experimental study.

This study aimed to assess the impact of a prolonged carbapenem use-focused antimicrobial stewardship program (ASP) on antimicrobial consumption and clinical outcomes and to analyze factors affecting adherence to interventions. Patients prescribed carbapenems for ≥ 2 weeks received intervention. Interrupted time-series analysis was performed to compare antimicrobial consumption before and after intervention. Factors associated with non-adherence to intervention were investigated. Of 273 patients who were eligible for intervention, discontinuation or de-escalation was recommended in 256 (94.1%) and intervention was accepted in 136 (53.1%) patients. Before intervention, carbapenem consumption significantly increased to 1.14 days of therapy (DOT)/1000 patient days (PD)/month (P = 0.018). However, it significantly declined by - 2.01 DOT/1000 PD/month without an increase in other antibiotic consumption (P < 0.001). Factors affecting non-adherence to intervention were younger age (odds ratio [OR] = 0.98; 95% confidence interval [CI] 0.96-1.00), solid organ malignancy (OR = 2.53, 95% CI 1.16-5.50), and pneumonia (OR = 2.59, 95% CI 1.08-6.17). However, ASP intervention was not associated with clinical outcomes such as length of hospital stay or mortality. Prolonged carbapenem prescription-focused ASP significantly reduced carbapenem consumption without adverse outcomes. Non-adherence to interventions was attributed more to prescriber-related factors, such as attitude, than patient-related factors including clinical severity.

Temporal Association of Total Serum Cholesterol and Pancreatic Cancer Incidence.

Previous studies have suggested a "cholesterol-lowering effect" of preclinical pancreatic cancer, suggesting lower total cholesterol as a potential diagnostic marker. Leveraging repeated measurements of total cholesterol, this study aims to examine the temporal association of total cholesterol and pancreatic cancer incidence. We conducted a nested case-control study based on a Korean National Health Insurance Service−Health Screening Cohort, including 215 pancreatic cancer cases and 645 controls matched on age and sex. Conditional logistic regression was applied to estimate the odds ratio (OR) and 95% confidence interval (CI) for the associations of pancreatic cancer incidence with total cholesterol levels across different time windows over 11 years before pancreatic cancer diagnosis (recent, mid, distant). We found that, compared to participants with total cholesterol < 200 mg/dL in the recent 3 years prior to diagnosis, those having total cholesterol ≥ 240 mg/dL showed a significantly lower pancreatic cancer incidence (OR = 0.50 (0.27−0.93)). No significant association was found in relation to total cholesterol measured in the mid and distant past. When changes in total cholesterol over the three time periods were analyzed, compared with those with total cholesterol levels consistently below 240 mg/dL over the entire period, the OR of pancreatic cancer was 0.45 (0.20−1.03) for participants with recent-onset hypercholesterolemia, 1.89 (0.95−3.75) for recent-resolved hypercholesterolemia, and 0.71 (0.30−1.66) for consistent hypercholesterolemia. In conclusion, while high total cholesterol in the recent past may indicate a lower pancreatic cancer incidence, a recent decrease in total cholesterol may suggest an elevated incidence of pancreatic cancer.

Trends in all-cause mortality among people with diagnosed diabetes in high-income settings: a multicountry analysis of aggregate data.

BACKGROUND: Population-level trends in mortality among people with diabetes are inadequately described. We aimed to examine the magnitude and trends in excess all-cause mortality in people with diabetes. METHODS: In this retrospective, multicountry analysis, we collected aggregate data from 19 data sources in 16 high-income countries or jurisdictions (in six data sources in Asia, eight in Europe, one from Australia, and four from North America) for the period from Jan 1, 1995, to Dec 31, 2016, (or a subset of this period) on all-cause mortality in people with diagnosed total or type 2 diabetes. We collected data from administrative sources, health insurance records, registries, and a health survey. We estimated excess mortality using the standardised mortality ratio (SMR). FINDINGS: In our dataset, there were approximately 21 million deaths during 0·5 billion person-years of follow-up among people with diagnosed diabetes. 17 of 19 data sources showed decreases in the age-standardised and sex-standardised mortality in people with diabetes, among which the annual percentage change in mortality ranged from -0·5% (95% CI -0·7 to -0·3) in Hungary to -4·2% (-4·3 to -4·1) in Hong Kong. The largest decreases in mortality were observed in east and southeast Asia, with a change of -4·2% (95% CI -4·3 to -4·1) in Hong Kong, -4·0% (-4·8 to -3·2) in South Korea, -3·5% (-4·0 to -3·0) in Taiwan, and -3·6% (-4·2 to -2·9) in Singapore. The annual estimated change in SMR between people with and without diabetes ranged from -3·0% (95% CI -3·0 to -2·9; US Medicare) to 1·6% (1·4 to 1·7; Lombardy, Italy). Among the 17 data sources with decreasing mortality among people with diabetes, we found a significant SMR increase in five data sources, no significant SMR change in four data sources, and a significant SMR decrease in eight data sources. INTERPRETATION: All-cause mortality in diabetes has decreased in most of the high-income countries we assessed. In eight of 19 data sources analysed, mortality decreased more rapidly in people with diabetes than in those without diabetes. Further longevity gains will require continued improvement in prevention and management of diabetes. FUNDING: US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Trends in Cardiovascular Complications and Mortality among Patients with Diabetes in South Korea.

We investigated the cardiovascular complications and mortality rates of patients with diabetes in South Korea. The rates of hospitalization due to cardiovascular complications and mortality were analyzed using the Korean National Health Insurance Service-National Sample Cohort. From 2006 to 2015, the rates of hospitalization due to major cardiovascular complications decreased, while those due to heart failure (from 72 to 146 and 124 to 161 per 10,000 men and women, respectively) and peripheral artery disease (from 39 to 55 and 19 to 35 per 10,000 men and women, respectively) increased. In the period 2007 to 2015, the mortality rates for cancer, cerebrovascular disease, diabetes, heart disease, and hypertensive disease all decreased. However, the mortality rate for pneumonia increased. We observed a continuous reduction in cardiovascular complications and mortality in adults with diabetes. However, with the increase in some diabetes complications, more efforts are needed to prevent diabetes complications.

Diabetic Retinopathy and Related Clinical Practice for People with Diabetes in Korea: A 10-Year Trend Analysis.

We performed a retrospective cohort study including people diagnosed with diabetes from 2006 to 2015 according to the Korean National Health Insurance Service-National Sample Cohort database, to analyze the changes in the prevalence, screening rate, and treatment patterns for diabetic retinopathy (DR) over 10 years. The proportion of people who underwent fundus screening for DR steadily increased over the past decade. The prevalence of DR increased from 13.4% in 2006 to 15.9% in 2015, while that of proliferative DR steadily decreased from 1.29% in 2006 to 1.16% in 2015. The proportion of patients undergoing retinal photocoagulation constantly decreased. The prevalence of DR increased over the past decade, while its severity seemed to have improved, with a decreased rate of proliferative DR and retinal photocoagulation. A higher proportion of patients underwent ophthalmic screening using fundus examination, but still less than 30% of patients with diabetes underwent comprehensive examination in 2015.

Increasing Incidence of B-Cell Non-Hodgkin Lymphoma and Occurrence of Second Primary Malignancies in South Korea: 10-Year Follow-up Using the Korean National Health Information Database.

PURPOSE: The epidemiology of B-cell non-Hodgkin lymphoma (BNHL) in Asia is not well described, and rates of second primary malignancies (SPM) in these patients are not known. We aimed to describe temporal changes in BNHL epidemiology and SPM incidence in Korea. MATERIALS AND METHODS: A retrospective cohort study used claims data from the National Health Insurance Service that provides universal healthcare coverage in Korea. Newly diagnosed patients aged at least 19 years with a confirmed diagnosis of one of six BNHL subtypes (diffuse large cell B-cell lymphoma [DLBCL], small lymphocytic and chronic lymphocytic [CLL/SLL], follicular lymphoma [FL], mantle cell lymphoma [MCL], marginal zone lymphoma [MZL], and lymphoplasmacytic lymphoma/Waldenström's macroglobulinemia [WM]) during the period 2006-2015 were enrolled and followed up until death, dis-enrolment, or study end, whichever occurred first. Patients with pre-existing primary cancers prior to the diagnosis of BNHL were excluded. RESULTS: A total of 19,500 patients with newly diagnosed BNHL were identified out of 27,866 with non-Hodgkin lymphoma (NHL). DLBCL was the most frequently diagnosed subtype (41.9%-48.4% of NHL patients annually, 2011-2015). Standardized incidence of the six subtypes studied per 100,000 population increased from 5.74 in 2011 to 6.96 in 2015, with most increases in DLBCL, FL, and MZL. The incidence (95% confidence interval) of SPM per 100 person-years was 2.74 (2.26-3.29) for CLL/SLL, 2.43 (1.57-3.58) for MCL, 2.41 (2.10-2.76) for MZL, 2.23 (2.07-2.40) for DLBCL, 1.97 (1.61-2.38) for FL, and 1.41 (0.69-2.59) for WM. CONCLUSION: BNHL has been increasingly diagnosed in Korea. High rates of SPM highlight the need for continued close monitoring to ensure early diagnosis and treatment.

Development and Validation of the Korean Diabetes Risk Score: A 10-Year National Cohort Study.

BACKGROUND: A diabetes risk score in Korean adults was developed and validated. METHODS: This study used the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) of 359,349 people without diabetes at baseline to derive an equation for predicting the risk of developing diabetes, using Cox proportional hazards regression models. External validation was conducted using data from the Korean Genome and Epidemiology Study. Calibration and discrimination analyses were performed separately for men and women in the development and validation datasets. RESULTS: During a median follow-up of 10.8 years, 37,678 cases (event rate=10.4 per 1,000 person-years) of diabetes were identified in the development cohort. The risk score included age, family history of diabetes, alcohol intake (only in men), smoking status, physical activity, use of antihypertensive therapy, use of statin therapy, body mass index, systolic blood pressure, total cholesterol, fasting glucose, and γ glutamyl transferase (only in women). The C-statistics for the models for risk at 10 years were 0.71 (95% confidence interval [CI], 0.70 to 0.73) for the men and 0.76 (95% CI, 0.75 to 0.78) for the women in the development dataset. In the validation dataset, the C-statistics were 0.63 (95% CI, 0.53 to 0.73) for men and 0.66 (95% CI, 0.55 to 0.76) for women. CONCLUSION: The Korean Diabetes Risk Score may identify people at high risk of developing diabetes and may be an effective tool for delaying or preventing the onset of condition as risk management strategies involving modifiable risk factors can be recommended to those identified as at high risk.

Long-term patterns of fasting blood glucose levels and pancreatic cancer incidence.

BACKGROUND: Whether type 2 diabetes is cause or consequence, or both, of pancreatic cancer (PaC) remains unresolved. Leveraging repeated measurements of fasting blood glucose (FBG), we examined the temporal relationship between hyperglycemia and PaC incidence. METHODS: We conducted a nested case-control study of 278 cases and 826 matched-controls from the Korean National Health Insurance Service-Health Screening Cohort. Over 11 years before index date (date of PaC diagnosis for cases), all participants had at least one FBG measurement in each of the three time windows: - 11 to - 8, - 7 to - 4, and - 3 to 0 years. Using conditional logistic regression, we estimated odds ratios(ORs) of PaC and 95% confidence intervals (CIs) for hyperglycemia in the overall period and at each interval; for major long-term patterns of FBG across the three intervals (recent-onset, medium-term, and long-standing hyperglycemia). RESULTS: Higher FBG over the past 11 years was associated with an increased odds of PaC (p trend < .0001), with recent FBG more predictive of PaC than distant FBG. By FBG assessed in the - 3 to 0 interval, OR was 1.97 (95% CI 1.32-2.93) for 110-125 mg/dL and 3.17 (95% CI 2.09-4.80) for ≥ 126 mg/dL. By long-term patterns of FBG, compared to consistent normoglycemia, OR was 2.02 (95% CI 1.24-3.31) for long-standing hyperglycemia and 3.38 (95% CI 1.87-6.13) for recent-onset hyperglycemia. These associations were more pronounced among never-smokers than ever-smokers (p interaction = .06). CONCLUSION: Recent-onset hyperglycemia may be an early manifestation of undetected PaC, while long-lasting hyperglycemia may serve as a moderate etiologic factor for PaC.

Association between Blood Mercury Level and Visceral Adiposity in Adults.

BACKGROUND: Few studies have examined the association between mercury exposure and obesity. The aim of this study is to investigate the association between blood mercury concentrations and indices of obesity in adults. METHODS: A total of 200 healthy subjects, aged 30 to 64 years, who had no history of cardiovascular or malignant disease, were examined. Anthropometric and various biochemical profiles were measured. Visceral adipose tissue (VAT) was measured using dual-energy X-ray absorptiometry (DXA). RESULTS: All subjects were divided into three groups according to blood mercury concentrations. Compared with the subjects in the lowest tertile of mercury, those in the highest tertile were more likely to be male; were current alcohol drinkers and smokers; had a higher body mass index (BMI), waist circumference (WC), and VAT; had higher levels of blood pressure, fasting glucose, and insulin resistance; and consumed more fish. The blood mercury concentration was significantly associated with anthropometric parameters, showing relationships with BMI, WC, and VAT. After adjusting for multiple risk factors, the odds ratios (ORs) for high mercury concentration was significantly higher in the highest VAT tertile than in the lowest VAT tertile (OR, 2.66; 95% confidence interval, 1.05 to 6.62; P<0.05). CONCLUSION: The blood mercury concentration was significantly associated with VAT in healthy adults. Further studies are warranted to confirm our findings.

Epidemiology of Childhood Obesity in Korea.

Over the past several decades, the prevalence of obesity has increased dramatically worldwide and is increasing not only in developed countries, but also in developing countries. This increase may lead to an increase in the incidence of chronic diseases throughout the lifespan. In Korean children and adolescents, the prevalence of obesity increased from 6.8% in 1998 to 10.0% in 2013. Obesity is a state that more commonly influences children and adolescents of lower socioeconomic status (SES) than those with a higher SES. However, the prevalence of metabolic syndrome in a nationally representative sample of Korean adolescents decreased from 1998 to 2012. According to the Diabetes Fact Sheet of the Korean Diabetes Association, the prevalence of type 2 diabetes among children aged 18 years or younger was 153.5 per 100,000 in 2006 and 205.0 per 100,000 in 2013. Obesity is a complex disease influenced by many interacting factors, such as adipocytokines, lipopolysaccharide-binding protein, adenovirus 36 infection, birth weight, lifestyle, and endocrine-disrupting chemicals. Obesity in youth can adversely impact practically every organ system and lead to serious consequences, such as metabolic, gastrointestinal, pulmonary, cardiovascular, and psychosocial complications. Therefore, coordinated efforts by governments, organizations, communities, and individuals are needed to prevent and treat childhood obesity. In particular, a long-term policy to improve the social environment will also be necessary.

Serum 25-Hydroxyvitamin D Concentration Is Independently Inversely Associated with Insulin Resistance in the Healthy, Non-Obese Korean Population.

BACKGROUND: We evaluated the associations between 25-hydroxyvitamin D (25(OH)D) concentrations in serum and insulin resistance in the healthy Korean population. METHODS: We conducted this cross-sectional analysis in 1,807 healthy Korean people (628 men and 1,179 women) aged 30 to 64 years in the Cardiovascular and Metabolic Disease Etiologic Research Center study. All participants were assessed for 25(OH)D, fasting glucose, and insulin levels, and completed a health examination and lifestyle questionnaire according to standard procedures. Insulin resistance was defined as the homeostasis model assessment insulin resistance higher than the 75 percentile. RESULTS: Compared to those in the highest tertile (≥14.3 ng/mL), the odds ratio (OR) for insulin resistance was 1.37 (95% confidence interval [CI], 1.01 to 1.86) for the 1st tertile (<9.7 ng/mL) and 1.19 (95% CI, 0.08 to 1.62) for the 2nd tertile (9.7 to 14.3 ng/mL) after adjusting for age, gender, waist circumference, alcohol consumption, smoking status, physical exercise, season, and cohort. After stratification of the subjects by adiposity, these associations remained only in non-obese subjects (lowest tertile vs. highest tertile, multivariable OR, 1.64; 95% CI, 1.05 to 2.56). CONCLUSION: Serum 25(OH)D has an independent inverse association with insulin resistance in the healthy, non-obese Korean population, even among people with vitamin D insufficiency.

Impact of Cadmium Exposure on the Association between Lipopolysaccharide and Metabolic Syndrome.

Cadmium (Cd) is an environmental contaminant that has a direct impact on the gut microbiome. Perturbations in the gut microbiome have been linked to metabolic disorders associated with inflammation generated by lipopolysaccharide (LPS). We investigated the impact of Cd on the association between LPS and metabolic syndrome. The study population consisted of 200 apparently healthy subjects (30-64 years of age; 96 men, 104 women). Serum LPS and blood Cd concentrations were measured by ELISA and graphite furnace-atomic absorption spectrophotometry (GF-AAS), respectively. The highest LPS quartile was associated with a greater prevalence of metabolic syndrome in men. There was a significant association between LPS activity and metabolic syndrome in men with blood Cd concentrations higher than the 50th percentile (OR = 3.05, 95% CI = 1.39-6.70); however, this relationship was not significant in men with blood Cd concentrations lower than the 50th percentile. The results of this study provide evidence for a strong association between high LPS activity and the prevalence of metabolic syndrome in men with relatively high blood Cd concentrations. Therefore, exposure to Cd may potentiate the association between LPS and metabolic syndrome in men.

Changes in the Practice of Coronary Revascularization between 2006 and 2010 in the Republic of Korea.

PURPOSE: Evidence suggests that technological innovations and reimbursement schemes of the National Health Insurance Service may have impacted the management of coronary artery disease. Thus, we investigated changes in the practice patterns of coronary revascularization. MATERIALS AND METHODS: Revascularization and in-hospital mortality among Koreans ≥20 years old were identified from medical claims filed between 2006 and 2010. The age- and sex-standardized procedure rate per 100,000 person-years was calculated directly from the distribution of the 2008 Korean population. RESULTS: The coronary revascularization rate increased from 116.1 (95% confidence interval, 114.9-117.2) in 2006 to 131.0 (129.9-132.1) in 2010. Compared to the rate ratios in 2006, the rate ratios for percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery in 2010 were 1.16 (1.15-1.17) and 0.80 (0.76-0.84), respectively. Among patients who received PCI, the percentage with drug-eluting stents increased from 89.1% in 2006 to 93.0% in 2010. In-hospital mortality rates from PCI significantly increased during the study period (p=0.03), whereas those from CABG significantly decreased (p=0.01). The in-hospital mortality rates for PCI and CABG were higher in elderly and female patients and at the lowest-volume hospitals. CONCLUSION: The annual volume of coronary revascularization continuously increased between 2006 and 2010 in Korea, although this trend differed according to procedure type. A high percentage of drug-eluting stent procedures and a high rate of in-hospital mortality at low-volume hospitals were noted.

Gender differences in the association between serum γ-glutamyltransferase and blood pressure change: a prospective community-based cohort study.

We evaluated the gender differences in the relation of baseline serum γ-glutamyltransferase (GGT) levels to blood pressure (BP) change during 4 yr. 4,025 normotensive subjects (1,945 men and 2,080 women) who aged 40-69 yr at baseline participated in the Ansung-Ansan cohort of the Korean Genome Epidemiology Study were included. The associations of GGT with baseline BP or 4-yr change of BP were evaluated. GGT levels were associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) at baseline after adjusting for age, body mass index (BMI), HDL-cholesterol, triglyceride, C-reactive protein (CRP), current smoking status and alcohol intake (SBP, ß=1.28, P<0.001; DBP, ß=1.41, P<0.001). GGT levels were also associated with 4-yr change in BP after adjusting for age, BMI, HDL-cholesterol, triglyceride, CRP, current smoking status, alcohol intake and SBP (SBP, ß=1.08, P=0.001; DBP, ß=0.64, P=0.003). This association was statistically significant in men (SBP, ß=1.82, P<0.001; DBP, ß=1.05, P=0.001), but not in women (SBP, ß=0.38, P=0.466; DBP, ß=-0.37, P=0.304). Remarkably, this association between GGT and BP was significant in men at 40-49 yr of age. In summary, we found positive associations between GGT levels at baseline and the change of BP. The relation of GGT level and the change of BP was only significant in men, not in women, which warrants further studies to elucidate the biologic mechanisms.

Association between body mass index and asthma symptoms among Korean children: a nation-wide study.

The purpose of this study was to investigate the association between body mass index (BMI) and the prevalence of wheeze using nation-wide cross-sectional study in Korean children. Total 50,200 children from 427 elementary schools were randomly selected according to residential areas (metropolitan, provincial, rural, and industrial areas) by the cluster sampling method. The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires were used to measure the prevalence of wheeze. Among 31,026 respondents, 25,322 were analyzed. BMI was classified into quartiles based on BMI-for-age percentile. In all residential areas, pets at home and visible mold or moisture were associated with an increased prevalence of wheeze in both genders. However, other living environment factors were not consistently associated among residential areas and gender. Among girls, lowest BMI was negatively associated with prevalence of wheeze and highest BMI was positively associated in all residential areas. In multilevel logistic regression analysis, environmental tobacco smoking exposure, pets at home, visible mold or moisture, and being in the lowest and highest BMI quartile were significantly associated with the prevalence of wheeze in both genders. BMI has become an important risk factor for asthma symptoms among Korean children.