1.Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
Nam Hoon KIM ; Juneyoung LEE ; Suk CHON ; Jae Myung YU ; In-Kyung JEONG ; Soo LIM ; Won Jun KIM ; Keeho SONG ; Ho Chan CHO ; Hea Min YU ; Kyoung-Ah KIM ; Sang Soo KIM ; Soon Hee LEE ; Chong Hwa KIM ; Soo Heon KWAK ; Yong‐ho LEE ; Choon Hee CHUNG ; Sihoon LEE ; Heung Yong JIN ; Jae Hyuk LEE ; Gwanpyo KOH ; Sang-Yong KIM ; Jaetaek KIM ; Ju Hee LEE ; Tae Nyun KIM ; Hyun Jeong JEON ; Ji Hyun LEE ; Jae-Han JEON ; Hye Jin YOO ; Hee Kyung KIM ; Hyeong-Kyu PARK ; Il Seong NAM-GOONG ; Seongbin HONG ; Chul Woo AHN ; Ji Hee YU ; Jong Heon PARK ; Keun-Gyu PARK ; Chan Ho PARK ; Kyong Hye JOUNG ; Ohk-Hyun RYU ; Keun Yong PARK ; Eun-Gyoung HONG ; Bong-Soo CHA ; Kyu Chang WON ; Yoon-Sok CHUNG ; Sin Gon KIM
Endocrinology and Metabolism 2024;39(5):722-731
Background:
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods:
This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion
This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
2.Immune Responses After Vaccination With Primary 2-Dose ChAdOx1 Plus a Booster of BNT162b2 or Vaccination With Primary 2-Dose BNT162b2 Plus a Booster of BNT162b2 and the Occurrence of Omicron Breakthrough Infection
Seong-Ho CHOI ; Ji Young PARK ; Oh Joo KWEON ; Joung Ha PARK ; Min-Chul KIM ; Yaeji LIM ; Jin-Won CHUNG
Journal of Korean Medical Science 2023;38(20):e155-
Background:
Before the omicron era, health care workers were usually vaccinated with either the primary 2-dose ChAdOx1 nCoV-19 (Oxford-AstraZeneca) series plus a booster dose of BNT162b2 (Pfizer-BioNTech) (CCB group) or the primary 2-dose BNT162b2 series plus a booster dose of BNT162b2 (BBB group) in Korea.
Methods:
The two groups were compared using quantification of the surrogate virus neutralization test for wild type severe acute respiratory syndrome coronavirus 2 (SVNT-WT), the omicron variant (SVNT-O), spike-specific IgG, and interferon-gamma (IFN-γ), as well as the omicron breakthrough infection cases.
Results:
There were 113 participants enrolled in the CCB group and 51 enrolled in the BBB group. Before and after booster vaccination, the median SVNT-WT and SVNT-O values were lower in the CCB (SVNT-WT [before-after]: 72.02–97.61%, SVNT-O: 15.18–42.29%) group than in the BBB group (SVNT-WT: 89.19–98.11%, SVNT-O: 23.58–68.56%; all P < 0.001). Although the median IgG concentrations were different between the CCB and BBB groups after the primary series (2.677 vs. 4.700 AU/mL, respectively, P < 0.001), they were not different between the two groups after the booster vaccination (7.246 vs. 7.979 AU/mL, respectively, P = 0.108). In addition, the median IFN-γ concentration was higher in the BBB group than in the CCB group (550.5 and 387.5 mIU/mL, respectively, P = 0.014). There was also a difference in the cumulative incidence curves over time (CCB group 50.0% vs. BBB group 41.8%; P = 0.045), indicating that breakthrough infection occurred faster in the CCB group.
Conclusion
The cellular and humoral immune responses were low in the CCB group so that the breakthrough infection occurred faster in the CCB group than in the BBB group.
3.Quality of Acute Stroke Care within Emergency Medical Service System in Korea: Proposal for Severe Emergency Medical Center
Kyung Bok LEE ; Ji Sung LEE ; Jeong-Yoon LEE ; Jun Yup KIM ; Han-Yeong JEONG ; Seong-Eun KIM ; Jonguk KIM ; Do Yeon KIM ; Keon-Joo LEE ; Jihoon KANG ; Beom Joon KIM ; Tae Jung KIM ; Sang Joon AN ; Jang-Hyun BAEK ; Seongheon KIM ; Hyun-Wook NAH ; Jong Yun LEE, ; Jee-Hyun KWON ; Seong Hwan AHN ; Keun-Hwa JUNG ; Hee-Kwon PARK ; Tai Hwan PARK ; Jong-Moo PARK ; Yong-Jin CHO ; Im Seok KOH ; Soo Joo LEE ; Jae-Kwan CHA ; Joung-Ho RHA ; Juneyoung LEE ; Boung Chul LEE ; In Ok BAE ; Gui Ok KIM ; Hee-Joon BAE
Journal of the Korean Neurological Association 2023;41(1):18-30
Background:
Korea recently established 70 emergency medical service areas. However, there are many concerns that medical resources for stroke could not be evenly distributed through the country. We aimed to compare the treatment quality and outcomes of acute stroke among the emergency medical service areas.
Methods:
This study analyzed the data of 28,800 patients admitted in 248 hospitals which participated in the 8th acute stroke quality assessment by Health Insurance Review and Assessment Service. Individual hospitals were regrouped into emergency service areas according to the address of the location. Assessment indicators and fatality were compared by the service areas. We defined the appropriate hospital by the performance of intravenous thrombolysis.
Results:
In seven service areas, there were no hospitals which received more than 10 stroke patients for 6 months. In nine service areas, there were no patients who underwent intravenous thrombolysis (IVT). Among 167 designated emergency medical centers, 50 hospitals (29.9%) responded that IVT was impossible 24 hours a day. There are 97 (39.1%) hospitals that meet the definitions of appropriate hospital. In 23 service areas (32.9%) had no appropriate or feasible hospitals. The fatality of service areas with stroke centers were 6.9% within 30 days and 15.6% within 1 year from stroke onset than those without stroke centers (7.7%, 16.9%, respectively).
Conclusions
There was a wide regional gap in the medical resource and the quality of treatments for acute stroke among emergency medical service areas in Korea. The poststroke fatality rate of the service areas which have stroke centers or appropriate hospitals were significantly low.
4.Rhinovirus Incidence Rates Indicate We Are Tired of Non-pharmacological Interventions Against Coronavirus Disease 2019
Min-Chul KIM ; Joung Ha PARK ; Seong-Ho CHOI ; Jin-Won CHUNG
Journal of Korean Medical Science 2022;37(2):e15-
Background:
During the coronavirus disease 2019 (COVID-19) pandemic, the incidence of rhinovirus (RV) is inversely related to the intensity of non-pharmacological interventions (NPIs), such as universal mask wearing and physical distancing.
Methods:
Using RV surveillance data, changes in the effect of NPIs were investigated in South Korea during the pandemic. The time to the first visible effect of NPIs after the onset of NPIs (T1), time to the maximum effect (T2), and duration of the maximum effect (T3) were measured for each surge. For each week, the RVdiff [(RV incidence during the pandemic) − (RV incidence within 5 years before the pandemic)] was calculated, and number of weeks for RVdiff to be below zero after NPIs (time to RVdiff ≤ 0) and number of weeks RVdiff remains below zero after NPIs (duration of RVdiff ≤ 0) were measured for each surge.
Results:
During the study period, four surges of COVID-19 were reported. As the pandemic progressed, T1 and T2 increased, but T3 decreased. Additionally, the “time to RVdiff of ≤ 0” increased and “duration of RVdiff of ≤ 0” decreased. These changes became more pronounced during the third surge (mid-November 2020), before the introduction of the COVID-19 vaccine, and from the emergence of the delta variant.
Conclusion
The effect of NPIs appears slower, the duration of the effect becomes shorter, and the intensity also decreases less than a year after the onset of the pandemic owing to people’s exhaustion in implementing NPIs. These findings suggest that the COVID-19 response strategy must be completely overhauled
5.2022 Update of the Korean Clinical Practice Guidelines for Stroke: Antithrombotic Therapy for Patients with Acute Ischemic Stroke or Transient Ischemic Attack
Hong-Kyun PARK ; Sang-Bae KO ; Keun-Hwa JUNG ; Min Uk JANG ; Dae-Hyun KIM ; Joon-Tae KIM ; Jay Chol CHOI ; Hye Seon JEONG ; Chulho KIM ; Ji Hoe HEO ; Joung-Ho RHA ; Sun U. KWON ; Jong S. KIM ; Byung-Chul LEE ; Hee-Joon BAE ; Byung-Woo YOON ; Keun-Sik HONG
Journal of Stroke 2022;24(1):166-175
Antithrombotic therapy is a cornerstone of acute ischemic stroke (AIS) management and secondary stroke prevention. Since the first version of the Korean Clinical Practice Guideline (CPG) for stroke was issued in 2009, significant progress has been made in antithrombotic therapy for patients with AIS, including dual antiplatelet therapy in acute minor ischemic stroke or high-risk transient ischemic stroke and early oral anticoagulation in AIS with atrial fibrillation. The evidence is widely accepted by stroke experts and has changed clinical practice. Accordingly, the CPG Committee of the Korean Stroke Society (KSS) decided to update the Korean Stroke CPG for antithrombotic therapy for AIS. The writing members of the CPG committee of the KSS reviewed recent evidence, including clinical trials and relevant literature, and revised recommendations. A total of 35 experts were invited from the KSS to reach a consensus on the revised recommendations. The current guideline update aims to assist healthcare providers in making well-informed decisions and improving the quality of acute stroke care. However, the ultimate treatment decision should be made using a holistic approach, considering the specific medical conditions of individual patients.
6.Cilostazol and Probucol for Cognitive Decline after Stroke: A Cognitive Outcome Substudy of the PICASSO Trial
Jae-Sung LIM ; Sun U. KWON ; Kyung-Ho YU ; Sungwook YU ; Jong-Ho PARK ; Byung-Chul LEE ; Mi Sun OH ; Yong-Jae KIM ; Joung-Ho RHA ; Yang-Ha HWANG ; Ji Sung LEE ; Sung Hyuk HEO ; Seong Hwan AHN ; Woo-Keun SEO ; Jong-Moo PARK ; Ju-Hun LEE ; Jee-Hyun KWON ; Sung-Il SOHN ; Jin-Man JUNG ; Hahn Young KIM ; Eung-Gyu KIM ; Jae-Kwan CHA ; Man-Seok PARK ; Hyo Suk NAM ; Hee-Joon BAE ; Dong-Eog KIM ; Jaeseol PARK ; Yeonwook KANG ; Jimi CHOI ; Juneyoung LEE
Journal of Stroke 2021;23(1):128-131
7.Machine-Learning-Based Approach to Differential Diagnosis in Tuberculous and Viral Meningitis
Young-Seob JEONG ; Minjun JEON ; Joung Ha PARK ; Min-Chul KIM ; Eunyoung LEE ; Se Yoon PARK ; Yu-Mi LEE ; Sungim CHOI ; Seong Yeon PARK ; Ki-Ho PARK ; Sung-Han KIM ; Min Huok JEON ; Eun Ju CHOO ; Tae Hyong KIM ; Mi Suk LEE ; Tark KIM
Infection and Chemotherapy 2021;53(1):53-62
Background:
Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM.Material and Methods: For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machinelearning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information.
Results:
The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machinelearning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03).
Conclusion
The machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.
8.Machine-Learning-Based Approach to Differential Diagnosis in Tuberculous and Viral Meningitis
Young-Seob JEONG ; Minjun JEON ; Joung Ha PARK ; Min-Chul KIM ; Eunyoung LEE ; Se Yoon PARK ; Yu-Mi LEE ; Sungim CHOI ; Seong Yeon PARK ; Ki-Ho PARK ; Sung-Han KIM ; Min Huok JEON ; Eun Ju CHOO ; Tae Hyong KIM ; Mi Suk LEE ; Tark KIM
Infection and Chemotherapy 2021;53(1):53-62
Background:
Tuberculous meningitis (TBM) is the most severe form of tuberculosis, but differentiating between the diagnosis of TBM and viral meningitis (VM) is difficult. Thus, we have developed machine-learning modules for differentiating TBM from VM.Material and Methods: For the training data, confirmed or probable TBM and confirmed VM cases were retrospectively collected from five teaching hospitals in Korea between January 2000 - July 2018. Various machine-learning algorithms were used for training. The machinelearning algorithms were tested by the leave-one-out cross-validation. Four residents and two infectious disease specialists were tested using the summarized medical information.
Results:
The training study comprised data from 60 patients with confirmed or probable TBM and 143 patients with confirmed VM. Older age, longer symptom duration before the visit, lower serum sodium, lower cerebrospinal fluid (CSF) glucose, higher CSF protein, and CSF adenosine deaminase were found in the TBM patients. Among the various machinelearning algorithms, the area under the curve (AUC) of the receiver operating characteristics of artificial neural network (ANN) with ImperativeImputer for matrix completion (0.85; 95% confidence interval 0.79 - 0.89) was found to be the highest. The AUC of the ANN model was statistically higher than those of all the residents (range 0.67 - 0.72, P <0.001) and an infectious disease specialist (AUC 0.76; P = 0.03).
Conclusion
The machine-learning techniques may play a role in differentiating between TBM and VM. Specifically, the ANN model seems to have better diagnostic performance than the non-expert clinician.
9.Management of Acute Stroke Patients Amid the Coronavirus Disease 2019 Pandemic: Scientific Statement of the Korean Stroke Society
Beom Joon KIM ; Eu Suk KIM ; Myoung Jin SHIN ; Hong Bin KIM ; Hee Young LEE ; Keun-Sik HONG ; Hong-Kyun PARK ; Jun LEE ; Sung-Il SOHN ; Yang-Ha HWANG ; Sang-Bae KO ; Jong-Moo PARK ; Joung-Ho RHA ; Sun U. KWON ; Jong S. KIM ; Ji Hoe HEO ; Byung Chul LEE ; Byung-Woo YOON ; Hee-Joon BAE
Journal of Stroke 2020;22(2):203-205
10.2019 Update of the Korean Clinical Practice Guidelines of Stroke for Endovascular Recanalization Therapy in Patients with Acute Ischemic Stroke
Sang-Bae KO ; Hong-Kyun PARK ; Byung Moon KIM ; Ji Hoe HEO ; Joung-Ho RHA ; Sun U. KWON ; Jong S. KIM ; Byung-Chul LEE ; Sang Hyun SUH ; Cheolkyu JUNG ; Hae Woong JEONG ; Dong-Hun KANG ; Hee-Joon BAE ; Byung-Woo YOON ; Keun-Sik HONG
Journal of the Korean Neurological Association 2020;38(2):77-87
Endovascular recanalization therapy (ERT) has been a standard of care for patients with acute ischemic stroke due to large artery occlusion (LAO) within 6 hours after onset since the five landmark ERT trials up to 2015 demonstrated its clinical benefit. Recently, two randomized clinical trials demonstrated that ERT, even in the late time window up to 16 hours or 24 hours after last known normal time, improved the outcome of patients who had a target mismatch defined as either clinical-core mismatch or perfusion-core mismatch, which prompted the update of national guidelines in several countries. Accordingly, to provide evidence-based and up-to-date recommendations for ERT in patients with acute LAO in Korea, the Clinical Practice Guidelines Committee of the Korean Stroke Society decided to revise the previous Korean Clinical Practice Guidelines of Stroke for ERT. For this update, the members of the writing group were appointed by the Korean Stroke Society and the Korean Society of Interventional Neuroradiology. After thorough reviewing the updated evidence from two recent trials and relevant literature, the writing members revised recommendations, for which formal consensus was achieved by convening an expert panel composed of 45 experts from the participating academic societies. The current guidelines are intended to help healthcare providers, patients, and their caregivers make their well-informed decisions and to improve the quality of care regarding ERT. The ultimate decision for ERT in a particular patient must be made in light of circumstances specific to that patient.

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