1.Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial
Jie-Eun LEE ; Seung Hee YU ; Sung Rae KIM ; Kyu Jeung AHN ; Kee-Ho SONG ; In-Kyu LEE ; Ho-Sang SHON ; In Joo KIM ; Soo LIM ; Doo-Man KIM ; Choon Hee CHUNG ; Won-Young LEE ; Soon Hee LEE ; Dong Joon KIM ; Sung-Rae CHO ; Chang Hee JUNG ; Hyun Jeong JEON ; Seung-Hwan LEE ; Keun-Young PARK ; Sang Youl RHEE ; Sin Gon KIM ; Seok O PARK ; Dae Jung KIM ; Byung Joon KIM ; Sang Ah LEE ; Yong-Hyun KIM ; Kyung-Soo KIM ; Ji A SEO ; Il Seong NAM-GOONG ; Chang Won LEE ; Duk Kyu KIM ; Sang Wook KIM ; Chung Gu CHO ; Jung Han KIM ; Yeo-Joo KIM ; Jae-Myung YOO ; Kyung Wan MIN ; Moon-Kyu LEE
Diabetes & Metabolism Journal 2024;48(4):730-739
Background:
It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
Methods:
This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
Results:
After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events.
Conclusion
The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
2.Efficacy and Safety of Alogliptin-Pioglitazone Combination for Type 2 Diabetes Mellitus Poorly Controlled with Metformin: A Multicenter, Double-Blind Randomized Trial
Ji-Yeon PARK ; Joonyub LEE ; Yoon-Hee CHOI ; Kyung Wan MIN ; Kyung Ah HAN ; Kyu Jeung AHN ; Soo LIM ; Young-Hyun KIM ; Chul Woo AHN ; Kyung Mook CHOI ; Kun-Ho YOON ;
Diabetes & Metabolism Journal 2024;48(5):915-928
Background:
Guidelines for switching to triple combination therapy directly after monotherapy failure are limited. This study investigated the efficacy, long-term sustainability, and safety of either mono or dual add-on therapy using alogliptin and pioglitazone for patients with type 2 diabetes mellitus (T2DM) who did not achieve their target glycemic range with metformin monotherapy.
Methods:
The Practical Evidence of Antidiabetic Combination Therapy in Korea (PEAK) was a multicenter, placebo-controlled, double-blind, randomized trial. A total of 214 participants were randomized to receive alogliptin+pioglitazone (Alo+Pio group, n=70), alogliptin (Alo group, n=75), or pioglitazone (Pio group, n=69). The primary outcome was the difference in glycosylated hemoglobin (HbA1c) levels between the three groups at baseline to 24 weeks. For durability, the achievement of HbA1c levels <7% and <6.5% was compared in each group. The number of adverse events was investigated for safety.
Results:
After 24 weeks of treatment, the change of HbA1c in the Alo+Pio, Alo, and Pio groups were –1.38%±0.08%, –1.03%±0.08%, and –0.84%±0.08%, respectively. The Alo+Pio group had significantly lower HbA1c levels than the other groups (P=0.0063, P<0.0001) and had a higher proportion of patients with target HbA1c achievement. In addition, insulin sensitivity and β-cell function, lipid profiles, and other metabolic indicators were also improved. There were no significant safety issues in patients treated with triple combination therapy.
Conclusion
Early combination triple therapy showed better efficacy and durability than the single add-on (dual) therapy. Therefore, combination therapy with metformin, alogliptin, and pioglitazone is a valuable early treatment option for T2DM poorly controlled with metformin monotherapy.
3.Korea Seroprevalence Study of Monitoring of SARS-COV-2 Antibody Retention and Transmission (K-SEROSMART): findings from national representative sample
Jina HAN ; Hye Jin BAEK ; Eunbi NOH ; Kyuhyun YOON ; Jung Ae KIM ; Sukhyun RYU ; Kay O LEE ; No Yai PARK ; Eunok JUNG ; Sangil KIM ; Hyukmin LEE ; Yoo-Sung HWANG ; Jaehun JUNG ; Hun Jae LEE ; Sung-il CHO ; Sangcheol OH ; Migyeong KIM ; Chang-Mo OH ; Byengchul YU ; Young-Seoub HONG ; Keonyeop KIM ; Sunjae JUNG ; Mi Ah HAN ; Moo-Sik LEE ; Jung-Jeung LEE ; Young HWANGBO ; Hyeon Woo YIM ; Yu-Mi KIM ; Joongyub LEE ; Weon-Young LEE ; Jae-Hyun PARK ; Sungsoo OH ; Heui Sug JO ; Hyeongsu KIM ; Gilwon KANG ; Hae-Sung NAM ; Ju-Hyung LEE ; Gyung-Jae OH ; Min-Ho SHIN ; Soyeon RYU ; Tae-Yoon HWANG ; Soon-Woo PARK ; Sang Kyu KIM ; Roma SEOL ; Ki-Soo PARK ; Su Young KIM ; Jun-wook KWON ; Sung Soon KIM ; Byoungguk KIM ; June-Woo LEE ; Eun Young JANG ; Ah-Ra KIM ; Jeonghyun NAM ; ; Soon Young LEE ; Dong-Hyun KIM
Epidemiology and Health 2023;45(1):e2023075-
OBJECTIVES:
We estimated the population prevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including unreported infections, through a Korea Seroprevalence Study of Monitoring of SARS-CoV-2 Antibody Retention and Transmission (K-SEROSMART) in 258 communities throughout Korea.
METHODS:
In August 2022, a survey was conducted among 10,000 household members aged 5 years and older, in households selected through two stage probability random sampling. During face-to-face household interviews, participants self-reported their health status, COVID-19 diagnosis and vaccination history, and general characteristics. Subsequently, participants visited a community health center or medical clinic for blood sampling. Blood samples were analyzed for the presence of antibodies to spike proteins (anti-S) and antibodies to nucleocapsid proteins (anti-N) SARS-CoV-2 proteins using an electrochemiluminescence immunoassay. To estimate the population prevalence, the PROC SURVEYMEANS statistical procedure was employed, with weighting to reflect demographic data from July 2022.
RESULTS:
In total, 9,945 individuals from 5,041 households were surveyed across 258 communities, representing all basic local governments in Korea. The overall population-adjusted prevalence rates of anti-S and anti-N were 97.6% and 57.1%, respectively. Since the Korea Disease Control and Prevention Agency has reported a cumulative incidence of confirmed cases of 37.8% through July 31, 2022, the proportion of unreported infections among all COVID-19 infection was suggested to be 33.9%.
CONCLUSIONS
The K-SEROSMART represents the first nationwide, community-based seroepidemiologic survey of COVID-19, confirming that most individuals possess antibodies to SARS-CoV-2 and that a significant number of unreported cases existed. Furthermore, this study lays the foundation for a surveillance system to continuously monitor transmission at the community level and the response to COVID-19.
4.Clinical nurses’ experiences of workplace verbal violence: a phenomenological study
Min Soo WOO ; Hyoung Suk KIM ; Jeung-Im KIM
Korean Journal of Women Health Nursing 2022;28(2):154-164
Purpose:
This study aimed to describe clinical nurses’ lived experiences of workplace verbal violence through qualitative research using descriptive phenomenology.
Methods:
Six female Korean nurses who had less than 5 years of clinical experience and had experienced verbal violence in the workplace within the past year participated in the study. Data were collected through one-on-one in-depth interviews with the participants and analyzed using Colaizzi’s phenomenological method.
Results:
A total of 27 codes, eight themes, and four theme clusters were derived from the participants’ statements. The four theme clusters of the clinical nurses’ experiences of verbal violence in the workplace were as follows: “tip of the iceberg,” “beyond me and my control,” “fear and resignation,” and “personal burden.” The participants recognized that nurses experienced verbal violence daily, and that the causes of and responses to verbal violence were determined by external situational factors rather than nurses’ individual problems. This suggests that nurses felt that they had no choice but to personally cope with verbal violence and bear the consequences due to systematic indifference and silence about verbal violence experienced by clinical nurses.
Conclusion
The findings show that verbal violence was pervasive and unmerited, yet often endured at the cost of a personal burden to nurses. A clear definition of verbal violence and education for employees are needed, and a reporting system should be established to report all forms of violence regardless of the severity of the incident.
5.Benefit of Extracorporeal Membrane Oxygenation before Revascularization in Patients with Acute Myocardial Infarction Complicated by Profound Cardiogenic Shock after Resuscitated Cardiac Arrest
Min Chul KIM ; Youngkeun AHN ; Kyung Hoo CHO ; Doo Sun SIM ; Young Joon HONG ; Ju Han KIM ; Myung Ho JEONG ; Jeong Gwan CHO ; Dowan KIM ; Kyoseon LEE ; Inseok JEONG ; Yong Soo CHO ; Yong Hun JUNG ; Kyung Woon JEUNG
Korean Circulation Journal 2021;51(6):533-544
Background and Objectives:
The study sought to investigate the impact of early extracorporeal membrane oxygenation (ECMO) support before revascularization in patients with acute myocardial infarction (AMI) complicated by profound cardiogenic shock after resuscitated cardiac arrest. It is difficult to determine optimal timing of ECMO in patients with AMI complicated by profound cardiogenic shock after resuscitated cardiac arrest.
Methods:
Among 116,374 patients experiencing out-of-hospital cardiac arrest in South Korea, a total of 184 resuscitated patients with AMI complicated by profound cardiogenic shock, and who were treated successfully with percutaneous coronary intervention (PCI) and ECMO, were enrolled. Patients were divided into 2 groups according to the timing of ECMO: pre-PCI ECMO (n=117) and post-PCI ECMO (n=67). We compared 30-day mortality between the 2 groups.
Results:
In-hospital mortality was 78.8% in the entire study population and significantly lower in the pre-PCI ECMO group (73.5% vs. 88.1%, p=0.020). Thirty-day mortality was also lower in the pre-PCI ECMO group compared to the post-PCI ECMO group (74.4% vs.91.0%; adjusted hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.47–0.93; p=0.017). Shockable rhythm at the emergency room (HR, 0.57; 95% CI, 0.36–0.91; p=0.019) and successful therapeutic hypothermia (HR, 0.40; 95% CI, 0.23–0.69; p=0.001) were also associated with improved 30-day survival.
Conclusions
ECMO support before revascularization was associated with an improved short-term survival rate compared to ECMO after revascularization in patients with AMI complicated by profound cardiogenic shock after resuscitated cardiac arrest.
6.Benefit of Extracorporeal Membrane Oxygenation before Revascularization in Patients with Acute Myocardial Infarction Complicated by Profound Cardiogenic Shock after Resuscitated Cardiac Arrest
Min Chul KIM ; Youngkeun AHN ; Kyung Hoo CHO ; Doo Sun SIM ; Young Joon HONG ; Ju Han KIM ; Myung Ho JEONG ; Jeong Gwan CHO ; Dowan KIM ; Kyoseon LEE ; Inseok JEONG ; Yong Soo CHO ; Yong Hun JUNG ; Kyung Woon JEUNG
Korean Circulation Journal 2021;51(6):533-544
Background and Objectives:
The study sought to investigate the impact of early extracorporeal membrane oxygenation (ECMO) support before revascularization in patients with acute myocardial infarction (AMI) complicated by profound cardiogenic shock after resuscitated cardiac arrest. It is difficult to determine optimal timing of ECMO in patients with AMI complicated by profound cardiogenic shock after resuscitated cardiac arrest.
Methods:
Among 116,374 patients experiencing out-of-hospital cardiac arrest in South Korea, a total of 184 resuscitated patients with AMI complicated by profound cardiogenic shock, and who were treated successfully with percutaneous coronary intervention (PCI) and ECMO, were enrolled. Patients were divided into 2 groups according to the timing of ECMO: pre-PCI ECMO (n=117) and post-PCI ECMO (n=67). We compared 30-day mortality between the 2 groups.
Results:
In-hospital mortality was 78.8% in the entire study population and significantly lower in the pre-PCI ECMO group (73.5% vs. 88.1%, p=0.020). Thirty-day mortality was also lower in the pre-PCI ECMO group compared to the post-PCI ECMO group (74.4% vs.91.0%; adjusted hazard ratio [HR], 0.66; 95% confidence interval [CI], 0.47–0.93; p=0.017). Shockable rhythm at the emergency room (HR, 0.57; 95% CI, 0.36–0.91; p=0.019) and successful therapeutic hypothermia (HR, 0.40; 95% CI, 0.23–0.69; p=0.001) were also associated with improved 30-day survival.
Conclusions
ECMO support before revascularization was associated with an improved short-term survival rate compared to ECMO after revascularization in patients with AMI complicated by profound cardiogenic shock after resuscitated cardiac arrest.
7.All-Trans Retinoic Acid Synergizes with Enasidenib to Induce Differentiation of IDH2-Mutant Acute Myeloid Leukemia Cells
Yundeok KIM ; Hoi-Kyung JEUNG ; June-Won CHEONG ; Jaewoo SONG ; Soo Han BAE ; Jong In LEE ; Yoo Hong MIN
Yonsei Medical Journal 2020;61(9):762-773
Purpose:
Pharmacological inhibition of mutant isocitrate dehydrogenase (IDH) reduces R-2-hydroxyglutarate (2-HG) levels and restores cellular differentiation in vivo and in vitro. The IDH2 inhibitor enasidenib (AG-221) has been approved by the FDA as a first-in-class inhibitor for the treatment of relapsed or refractory (R/R) IDH2-mutant acute myeloid leukemia (AML). In this study,the effects of a combination of all-trans retinoic acid (ATRA) and AG-221 on AML cell differentiation was explored, along with the mechanisms employed by IDH2-mutant cells in AML. Materials and Methods: We treated the human AML cell line, IDH2-mutant-TF-1, and primary human AML cells carrying IDH2 mutation with 30 μM AG-221 and 100 nM ATRA, alone or in combination.
Results:
Combined treatment with AG-221 and ATRA inhibited 2-HG production and resulted in synergistic effects on differentiation among IDH2-mutant AML cells and primary AML cells expressing IDH2 mutation. Combined treatment with AG-221 and ATRA altered autophagic activity. AG-221 and ATRA treatment-induced differentiation of IDH2-mutant AML cells was associated with autophagy induction, without suppressing autophagy flux at maturation and degradation stages. A RAF-1/MEK/ERK pathway was founded to be associated with AG-221 and ATRA-induced differentiation in IDH2-mutant AML cells. IDH-associated changes in histone methylation markers decreased after AG-221 and ATRA combination treatment.
Conclusion
Our preliminary evidence indicates that the addition of ATRA to treatments with IDH2 inhibitor may lead to further improvements or increases in response rates in IDH2-mutant AML patients who do not appear to benefit from treatments with IDH2 inhibitor alone.
8.Performance of four different tools for predicting mortality in elderly patients with severe trauma
Ji Ho LEE ; Yong Il MIN ; Dong Hun LEE ; Yong Hun JUNG ; Kyung Woon JEUNG ; Byung Kook LEE ; Hyoung Youn LEE ; Yong Soo CHO ; Tag HEO
Journal of the Korean Society of Emergency Medicine 2020;31(1):111-119
Objective:
The present study aimed to analyze and compare the prognostic performances of Revised Trauma Score (RTS), Injury Severity Score (ISS), shock index (SI), and modified Early Warning Score (MEWS) for in-hospital mortality in severe trauma.
Methods:
This retrospective observational study included elderly (≥65 years) patients admitted for severe trauma between January 2018 and December 2018. Receiver operating characteristics analysis was performed to examine the prognostic performance of the four different tools. The primary outcome was in-hospital mortality following an injury.
Results:
Of the 279 patients included in the study, in-hospital mortality was 20.1% (n=56). In multivariate analysis, age (odds ratio [OR], 1.055; 95% confidence interval [CI], 1.004-1.109), ISS (OR, 1.080; 95% CI, 1.008-1.157), Glasgow Coma Scale (OR, 0.842; 95% CI, 0.785-0.904), and respiratory rate (OR, 1.261; 95% CI, 1.071-1.486) were independently associated with in-hospital mortality. The area under the curves (AUCs) of MEWS, RTS, ISS, and SI were 0.851 (95% CI, 0.763-0.857), 0.733 (0.677-0.784), 0.664 (0.606-0.720), and 0.567 (0.506-0.626), respectively. The AUC of MEWS was significantly different from those of RTS (P=0.034), ISS (P=0.001), and SI (P<0.001).
Conclusion
MEWS has the highest prognostic performance for in-hospital mortality among four different tools in elderly patients with severe trauma.
9.Clinical Course and Outcomes of 3,060 Patients with Coronavirus Disease 2019 in Korea, January–May 2020
Ho Kyung SUNG ; Jin Yong KIM ; Jeonghun HEO ; Haesook SEO ; Young soo JANG ; Hyewon KIM ; Bo Ram KOH ; Neungsun JO ; Hong Sang OH ; Young Mi BAEK ; Kyung-Hwa PARK ; Jeung A SHON ; Min-Chul KIM ; Joon Ho KIM ; Hyun-Ha CHANG ; Yukyung PARK ; Yu Min KANG ; Dong Hyun LEE ; Dong Hyun OH ; Hyun Jung PARK ; Kyoung-Ho SONG ; Eun Kyoung LEE ; Hyeongseok JEONG ; Ji Yeon LEE ; Ja-Young KO ; Jihee CHOI ; Eun Hwa RYU ; Ki-hyun CHUNG ; Myoung-don OH ;
Journal of Korean Medical Science 2020;35(30):e280-
Background:
The fatality rate of patients with coronavirus disease 2019 (COVID-19) varies among countries owing to demographics, patient comorbidities, surge capacity of healthcare systems, and the quality of medical care. We assessed the clinical outcomes of patients with COVID-19 during the first wave of the epidemic in Korea.
Methods:
Using a modified World Health Organization clinical record form, we obtained clinical data for 3,060 patients with COVID-19 treated at 55 hospitals in Korea. Disease severity scores were defined as: 1) no limitation of daily activities; 2) limitation of daily activities but no need for supplemental oxygen; 3) supplemental oxygen via nasal cannula; 4) supplemental oxygen via facial mask; 5) non-invasive mechanical ventilation; 6) invasive mechanical ventilation; 7) multi-organ failure or extracorporeal membrane oxygenation therapy; and 8) death. Recovery was defined as a severity score of 1 or 2, or discharge and release from isolation.
Results:
The median age of the patients was 43 years of age; 43.6% were male. The median time from illness onset to admission was 5 days. Of the patients with a disease severity score of 3–4 on admission, 65 (71.5%) of the 91 patients recovered, and 7 (7.7%) died due to illness by day 28. Of the patients with disease severity scores of 5–7, 7 (19.5%) of the 36 patients recovered, and 8 (22.2%) died due to illness by day 28. None of the 1,324 patients who were < 50 years of age died; in contrast, the fatality rate due to illness by day 28 was 0.5% (2/375), 0.9% (2/215), 5.8% (6/104), and 14.0% (7/50) for the patients aged 50–59, 60–69, 70–79, and ≥ 80 years of age, respectively.
Conclusion
In Korea, almost all patients of < 50 years of age with COVID-19 recovered without supplemental oxygen. In patients of ≥ 50 years of age, the fatality rate increased with age, reaching 14% in patients of ≥ 80 years of age.
10.Lack of Association between Helicobacter pylori Infection and Various Markers of Systemic Inflammation in Asymptomatic Adults.
Tae Jun KIM ; Jeung Hui PYO ; Hyuk LEE ; Sun Young BAEK ; Soo Hyun AHN ; Yang Won MIN ; Byung Hoon MIN ; Jun Haeng LEE ; Hee Jung SON ; Poong Lyul RHEE ; Jae J KIM
The Korean Journal of Gastroenterology 2018;72(1):21-27
BACKGROUND/AIMS: Helicobacter pylori (H. pylori) infection has been known to cause various extra-gastric diseases, which may be mediated by an increase in systemic inflammation. Thus, we examined the association between H. pylori infection and various markers of systemic inflammation in a large sample of asymptomatic adults. METHODS: Cross-sectional data were obtained from 17,028 adults who completed routine health check-ups. H. pylori infection status was determined using a serum immunoglobulin G test, and systemic inflammation was assessed using the C-reactive protein (CRP) levels, neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR). RESULTS: Multiple linear regression model-adjusted for potential confounders-revealed that H. pylori infection was not associated with CRP levels (coefficient: −0.012, 95% confidence interval [CI]: −0.037, 0.012, p=0.319), NLR (coefficient: 0.055, 95% CI: −0.027, 0.138, p=0.192), or PLR (coefficient: 1.798, 95% CI: −1.979, 5.574, p=0.351). In a multivariable logistic regression model, H. pylori infection was not associated with the risk of CRP levels being elevated to ≥0.1 mg/dL (odds ratio: 0.96, 95% CI: 0.81, 1.08) or ≥0.3 mg/dL (odds ratio: 1.02, 95% CI: 0.84, 1.19). In the multivariable model, CRP levels elevated to ≥0.1 mg/dL were significantly associated with body mass index, current smoking status, hypertension, and diabetes mellitus. Regular exercise and high-density lipoprotein cholesterol were factors that minimized the elevation of CRP levels. CONCLUSIONS: Chronic infection with H. pylori was not associated with various inflammatory markers. Further investigation is needed to clarify the interaction between H. pylori infection, systemic inflammation, and extra-gastric disease.
Adult*
;
Body Mass Index
;
C-Reactive Protein
;
Cholesterol
;
Diabetes Mellitus
;
Helicobacter pylori*
;
Helicobacter*
;
Humans
;
Hypertension
;
Immunoglobulin G
;
Inflammation*
;
Linear Models
;
Lipoproteins
;
Logistic Models
;
Smoke
;
Smoking

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