1.Brexpiprazole for the Treatment of Agitation Associated with Dementia due to Alzheimer’s Disease: Clinical Perspectives
Hayeon KIM ; Kyung Ho LEE ; Changsu HAN ; Ashwin A. PATKAR ; Prakash S. MASAND ; Won-Myong BAHK ; Chi-Un PAE
Clinical Psychopharmacology and Neuroscience 2026;24(1):15-29
Dementia is a neuropsychiatric disorder that primarily affects the elderly, leading to a widespread decline in cognitive function and significant impairment of occupational, social, and personal functioning. In addition to cognitive deficits, dementia is frequently comorbid with behavioral and psychological symptoms of dementia (BPSD), such as agitation.When present, these secondary symptoms can exacerbate the clinical course of the disease, reduced treatment responsiveness, increased rates of admission to long-term care facilities, extended hospitalization, higher risk of personal injury and a substantial socioeconomic burden. Given these consequences, early management of BPSD—particularly agitation—is critical to mitigating these risks. Although antipsychotics are commonly prescribed to manage agitation, risperidone remains the only agent approved by regulatory authorities for this indication. Recently, however, brexpiprazole, a medication with a pharmacological profile distinct from that of risperidone, received U.S. FDA approval (on May 11, 2023) for the treatment of agitation associated with Alzheimer’s disease. Agitation is among the most prevalent BPSD manifestations, with symptoms ranging from verbal to physical aggression. Given its recent approval and unique pharmacodynamic properties, brexpiprazole may have strong potential as a therapeutic option for this population. This paper aims to review the pharmacological mechanisms, clinical evidence, and future perspectives of brexpiprazole as a novel therapeutic option for managing agitation in patients with Alzheimer’s disease.
2.Non-Linear Association Between Physical Activities and Type 2Diabetes in 2.4 Million Korean Population, 2009–2022: A Nationwide Representative Study
Wonwoo JANG ; Seokjun KIM ; Yejun SON ; Soeun KIM ; Hayeon LEE ; Jaeyu PARK ; Kyeongmin LEE ; Jiseung KANG ; Damiano PIZZOL ; Jiyoung HWANG ; Sang Youl RHEE ; Dong Keon YON
Journal of Korean Medical Science 2025;40(12):e42-
Background:
Although excessive physical activity (PA) does not always confer additional health benefits, there is a paucity of studies that have quantitatively examined the doseresponse relationship between PA and type 2 diabetes. Therefore, this study investigated the relationship between the type 2 diabetes prevalence and intensity, frequency, and metabolic equivalent of task (MET) score of PA in a large population sample.
Methods:
We conducted a nationwide cross-sectional analysis examining sociodemographic variables, PA habits, and type 2 diabetes prevalence in 2,428,448 participants included in the Korea Community Health Survey. The non-linear association between MET score and odds ratios (ORs) for type 2 diabetes prevalence was plotted using a weighted generalized additive model. Categorical analysis was used to examine the joint association of moderate-intensity PA (MPA) and vigorous-intensity PA (VPA), and the influence of PA frequency.
Results:
MET score and diabetes prevalence revealed a non-linear association with the nadir at 1,028 MET-min/week, beyond which ORs increased with additional PA. Joint analysis of MPA and VPA showed the lowest OR of 0.79 (95% confidence interval, 0.75–0.84) for those engaging in 300–600 MET-min/week of MPA and > 600 MET-min/week of VPA concurrently, corresponding with World Health Organization recommendations. Additionally, both “weekend warriors” and “regularly active” individuals showed lower ORs compared to the inactive, although no significant difference was noted between the active groups.
Conclusion
In a large South Korean sample, higher PA is not always associated with a lower prevalence of type 2 diabetes, as the association follows a non-linear pattern; differences existed across sociodemographic variables. Considering the joint association, an adequate combination of MPA and VPA is recommended. The frequency of PA does not significantly influence the type 2 diabetes prevalence.
3.Non-Linear Association Between Physical Activities and Type 2Diabetes in 2.4 Million Korean Population, 2009–2022: A Nationwide Representative Study
Wonwoo JANG ; Seokjun KIM ; Yejun SON ; Soeun KIM ; Hayeon LEE ; Jaeyu PARK ; Kyeongmin LEE ; Jiseung KANG ; Damiano PIZZOL ; Jiyoung HWANG ; Sang Youl RHEE ; Dong Keon YON
Journal of Korean Medical Science 2025;40(12):e42-
Background:
Although excessive physical activity (PA) does not always confer additional health benefits, there is a paucity of studies that have quantitatively examined the doseresponse relationship between PA and type 2 diabetes. Therefore, this study investigated the relationship between the type 2 diabetes prevalence and intensity, frequency, and metabolic equivalent of task (MET) score of PA in a large population sample.
Methods:
We conducted a nationwide cross-sectional analysis examining sociodemographic variables, PA habits, and type 2 diabetes prevalence in 2,428,448 participants included in the Korea Community Health Survey. The non-linear association between MET score and odds ratios (ORs) for type 2 diabetes prevalence was plotted using a weighted generalized additive model. Categorical analysis was used to examine the joint association of moderate-intensity PA (MPA) and vigorous-intensity PA (VPA), and the influence of PA frequency.
Results:
MET score and diabetes prevalence revealed a non-linear association with the nadir at 1,028 MET-min/week, beyond which ORs increased with additional PA. Joint analysis of MPA and VPA showed the lowest OR of 0.79 (95% confidence interval, 0.75–0.84) for those engaging in 300–600 MET-min/week of MPA and > 600 MET-min/week of VPA concurrently, corresponding with World Health Organization recommendations. Additionally, both “weekend warriors” and “regularly active” individuals showed lower ORs compared to the inactive, although no significant difference was noted between the active groups.
Conclusion
In a large South Korean sample, higher PA is not always associated with a lower prevalence of type 2 diabetes, as the association follows a non-linear pattern; differences existed across sociodemographic variables. Considering the joint association, an adequate combination of MPA and VPA is recommended. The frequency of PA does not significantly influence the type 2 diabetes prevalence.
4.National Trends in Influenza Vaccination Rates in South Korea Before and During the COVID-19 Pandemic, 2011-2022.
Kyeongeun KIM ; Kyeongmin LEE ; Yejun SON ; Seoyoung PARK ; Raphael UDEH ; Jiseung KANG ; Hayeon LEE ; Soeun KIM ; Jaeyu PARK ; Hyeon Jin KIM ; Damiano PIZZOL ; Lee SMITH ; Jiyoung HWANG ; Dong Keon YON
Biomedical and Environmental Sciences 2025;38(9):1044-1057
OBJECTIVE:
Despite the global decrease in influenza infections during the coronavirus disease 2019 (COVID-19) pandemic, seasonal influenza remains a significant health issue. South Korea, known for its robust pandemic response and high influenza vaccination rates, offers a unique context for examining changes in vaccination trends during the pandemic. Using nationally representative data, we aimed to understand the impact of the pandemic on influenza vaccination behavior over a 12-year period and to identify vulnerable groups.
METHODS:
We analyzed influenza vaccination rates in South Korea between 2011-2022, focusing on pandemic-related impacts. The data of 2,426,139 adults (≥ 19 years) from the Korea Community Health Survey were used to assess demographic and sociological factors influencing vaccination behaviors.
RESULTS:
We observed an increase in influenza vaccination rates during the pre-COVID-19 period from 2011-2013 (weighted prevalence: 46.68% [95% confidence interval ( CI): 46.55-46.82]) to 2017-2019 (weighted prevalence: 52.50% [95% CI: 52.38-52.63]). However, a significant decline was observed in 2022, the late-COVID-19 pandemic period (weighted prevalence: 55.78% [95% CI: 55.56-56.01]), compared with the mid-pandemic period in 2021 (weighted prevalence: 59.12% [95% CI: 58.91-59.32]), particularly among populations traditionally prioritized for influenza vaccination, including older adults (≥ 65 years) and patients with chronic diseases and low educational and income levels.
CONCLUSION
The influenza vaccination rate in South Korea was significantly affected by the COVID-19 pandemic, showing a notable decrease among vulnerable demographic groups. This suggests the need for targeted public health strategies to address vaccine hesitancy and improve vaccination rates, particularly among high-risk populations.
Humans
;
Republic of Korea/epidemiology*
;
COVID-19/epidemiology*
;
Adult
;
Middle Aged
;
Influenza Vaccines/administration & dosage*
;
Male
;
Female
;
Influenza, Human/epidemiology*
;
Aged
;
Vaccination/statistics & numerical data*
;
Young Adult
;
Pandemics
;
SARS-CoV-2
5.Non-Linear Association Between Physical Activities and Type 2Diabetes in 2.4 Million Korean Population, 2009–2022: A Nationwide Representative Study
Wonwoo JANG ; Seokjun KIM ; Yejun SON ; Soeun KIM ; Hayeon LEE ; Jaeyu PARK ; Kyeongmin LEE ; Jiseung KANG ; Damiano PIZZOL ; Jiyoung HWANG ; Sang Youl RHEE ; Dong Keon YON
Journal of Korean Medical Science 2025;40(12):e42-
Background:
Although excessive physical activity (PA) does not always confer additional health benefits, there is a paucity of studies that have quantitatively examined the doseresponse relationship between PA and type 2 diabetes. Therefore, this study investigated the relationship between the type 2 diabetes prevalence and intensity, frequency, and metabolic equivalent of task (MET) score of PA in a large population sample.
Methods:
We conducted a nationwide cross-sectional analysis examining sociodemographic variables, PA habits, and type 2 diabetes prevalence in 2,428,448 participants included in the Korea Community Health Survey. The non-linear association between MET score and odds ratios (ORs) for type 2 diabetes prevalence was plotted using a weighted generalized additive model. Categorical analysis was used to examine the joint association of moderate-intensity PA (MPA) and vigorous-intensity PA (VPA), and the influence of PA frequency.
Results:
MET score and diabetes prevalence revealed a non-linear association with the nadir at 1,028 MET-min/week, beyond which ORs increased with additional PA. Joint analysis of MPA and VPA showed the lowest OR of 0.79 (95% confidence interval, 0.75–0.84) for those engaging in 300–600 MET-min/week of MPA and > 600 MET-min/week of VPA concurrently, corresponding with World Health Organization recommendations. Additionally, both “weekend warriors” and “regularly active” individuals showed lower ORs compared to the inactive, although no significant difference was noted between the active groups.
Conclusion
In a large South Korean sample, higher PA is not always associated with a lower prevalence of type 2 diabetes, as the association follows a non-linear pattern; differences existed across sociodemographic variables. Considering the joint association, an adequate combination of MPA and VPA is recommended. The frequency of PA does not significantly influence the type 2 diabetes prevalence.
6.Impact of low tacrolimus level on graft rejection, survival, and hepatocellular carcinoma recurrence
Hayeon DO ; Namkee OH ; Jiyoung BAIK ; Suk Min GWON ; Youngju RYU ; Eunjin LEE ; Sunghyo AN ; Jinsoo RHU ; Gyu-Seong CHOI ; Jae-Won JOH ; Jongman KIM
Annals of Liver Transplantation 2025;5(2):124-133
Background:
Tacrolimus is a key immunosuppressant after liver transplantation.Although guideline-recommended trough levels are 4–10 ng/mL, concerns about nephrotoxicity, metabolic complications, and malignancies have led to interest in minimizing tacrolimus use. However, the effects of lower tacrolimus levels on graft rejection and hepatocellular carcinoma (HCC) recurrence remain unclear.
Methods:
We conducted a single-center, retrospective study of adult patients (≥19 years) who underwent living donor liver transplantation between January 2000 and December 2021. Patients were divided into low tacrolimus (FK) (<6 ng/mL) and high FK (≥6 ng/mL) groups based on tacrolimus levels measured 1–2 years post-transplantation. We analyzed overall survival, biopsy-proven rejection-free survival, and HCC recurrence-free survival in relevant subgroups. Cox proportional hazards regression identified predictors of mortality, rejection, and HCC recurrence.
Results:
Among 1,117 recipients, 941 were in the low FK group and 176 in the high FK group. Landmark analysis showed significantly better 10-year overall survival in the low FK group (82.8% vs. 68.8%, p=0.016), while rejection-free survival did not differ significantly beyond 2 years (p=0.098), despite early separation favoring the low FK group (p<0.001). Higher tacrolimus levels independently predicted increased mortality (hazard ratio [HR]=1.98, 95% confidence interval [CI] 1.35–2.89; p<0.001) and rejection (HR=2.20, 95% CI 1.48–3.27; p<0.001). Among 614 HCC patients, landmark analysis revealed no significant difference in recurrence-free survival (77.7% vs. 81.2%, p=0.288) or overall survival (77.3% vs. 65.8%, p=0.215), and FK levels were not independently associated with either outcome.
Conclusion
Maintaining tacrolimus levels below 6 ng/mL was associated with better survival and rejection outcomes without increasing HCC recurrence, suggesting dose minimization may be feasible in selected patients.
7.Non-Linear Association Between Physical Activities and Type 2Diabetes in 2.4 Million Korean Population, 2009–2022: A Nationwide Representative Study
Wonwoo JANG ; Seokjun KIM ; Yejun SON ; Soeun KIM ; Hayeon LEE ; Jaeyu PARK ; Kyeongmin LEE ; Jiseung KANG ; Damiano PIZZOL ; Jiyoung HWANG ; Sang Youl RHEE ; Dong Keon YON
Journal of Korean Medical Science 2025;40(12):e42-
Background:
Although excessive physical activity (PA) does not always confer additional health benefits, there is a paucity of studies that have quantitatively examined the doseresponse relationship between PA and type 2 diabetes. Therefore, this study investigated the relationship between the type 2 diabetes prevalence and intensity, frequency, and metabolic equivalent of task (MET) score of PA in a large population sample.
Methods:
We conducted a nationwide cross-sectional analysis examining sociodemographic variables, PA habits, and type 2 diabetes prevalence in 2,428,448 participants included in the Korea Community Health Survey. The non-linear association between MET score and odds ratios (ORs) for type 2 diabetes prevalence was plotted using a weighted generalized additive model. Categorical analysis was used to examine the joint association of moderate-intensity PA (MPA) and vigorous-intensity PA (VPA), and the influence of PA frequency.
Results:
MET score and diabetes prevalence revealed a non-linear association with the nadir at 1,028 MET-min/week, beyond which ORs increased with additional PA. Joint analysis of MPA and VPA showed the lowest OR of 0.79 (95% confidence interval, 0.75–0.84) for those engaging in 300–600 MET-min/week of MPA and > 600 MET-min/week of VPA concurrently, corresponding with World Health Organization recommendations. Additionally, both “weekend warriors” and “regularly active” individuals showed lower ORs compared to the inactive, although no significant difference was noted between the active groups.
Conclusion
In a large South Korean sample, higher PA is not always associated with a lower prevalence of type 2 diabetes, as the association follows a non-linear pattern; differences existed across sociodemographic variables. Considering the joint association, an adequate combination of MPA and VPA is recommended. The frequency of PA does not significantly influence the type 2 diabetes prevalence.
8.Global, Regional, and National Trends in Liver Disease-Related Mortality Across 112 Countries From 1990 to 2021, With Projections to 2050:Comprehensive Analysis of the WHO Mortality Database
Jong Woo HAHN ; Selin WOO ; Jaeyu PARK ; Hyeri LEE ; Hyeon Jin KIM ; Jae Sung KO ; Jin Soo MOON ; Masoud RAHMATI ; Lee SMITH ; Jiseung KANG ; Damiano PIZZOL ; Mark A TULLY ; Elena DRAGIOTI ; Guillermo F. LÓPEZ SÁNCHEZ ; Kwanjoo LEE ; Yeonjung HA ; Jinseok LEE ; Hayeon LEE ; Sang Youl RHEE ; Yejun SON ; Soeun KIM ; Dong Keon YON
Journal of Korean Medical Science 2024;39(46):e292-
Background:
Liver disease causes over two million deaths annually worldwide, comprising approximately 4% of all global fatalities. We aimed to analyze liver disease-related mortality trends from 1990 to 2021 using the World Health Organization (WHO) Mortality Database and forecast global liver disease-related mortality rates up to 2050.
Methods:
This study examined age-standardized liver disease-related death rates from 1990 to 2021, employing data from the WHO Mortality Database across 112 countries across five continents. The rates over time were calculated using a locally weighted scatter plot smoother curve, with weights assigned based on the population of each country. Furthermore, this study projected liver disease-related mortality rates up to 2050 using a Bayesian age-periodcohort (BAPC) model. Additionally, a decomposition analysis was conducted to discern influencing factors such as population growth, aging, and epidemiological changes.
Results:
The estimated global age-standardized liver disease-related mortality rates surged significantly from 1990 to 2021 across 112 countries, rising from 103.4 deaths per 1,000,000 people (95% confidence interval [CI], 88.16, 118.74) in 1990 to 173.0 deaths per 1,000,000 people (95% CI, 155.15, 190.95) in 2021. This upward trend was particularly pronounced in low- and middle-income countries, in Africa, and in populations aged 65 years and older.Moreover, age-standardized liver disease-related mortality rates were correlated with a lower Human Development Index (P < 0.001) and sociodemographic index (P = 0.001). According to the BAPC model, the projected trend indicated a sustained and substantial decline in liver disease-related mortality rates, with an estimated decrease from 185.08 deaths per 1,000,000 people (95% CI, 179.79, 190.63) in 2021 to 156.29 (112.32, 214.77) in 2050. From 1990 to 2021, age-standardized liver disease-related deaths surged primarily due to epidemiological changes, whereas from 1990 to 2050, the impact of population aging and growth became the primary contributing factors to the overall increase.
Conclusion
Global age-standardized liver disease-related mortality has increased significantly and continues to emerge as a crucial global public health issue. Further investigation into liver disease-related mortality rates in Africa is needed, and updating policies is necessary to effectively manage the global burden of liver disease.
9.Vitamin K: Calcium Metabolism Modulator for Menopausal Women
Tae-Hee KIM ; Hayeon KIM ; Hae Hyeog LEE ; Jae Hong SANG
Journal of Menopausal Medicine 2024;30(3):152-163
Vitamin K (VitK) exists in multiple forms, with Vitamin K1 (VitK1) and Vitamin K2 (VitK2) being the most prominent. VitK1 primarily regulates clotting factors in the liver, whereas VitK2 plays a crucial role in activating extrahepatic proteins involved in various physiological processes. VitK plays a pivotal role in various physiological functions, including vascular health, bone metabolism, neuroprotection, hepatoprotection, immune response modulation, dental health, and glucose control. Particularly, activation of the matrix Gla protein and osteocalcin through VitK2 inhibits vascular calcification (VC) and promotes bone mineralization. This review provides an overview of the physiological functions of VitK2, underscoring its role in calcium metabolism modulation and its diverse effects on health. Additionally, this article provides a comprehensive overview of the beneficial functions of VitK, and discusses the significance of adequate dietary intake and oral supplementation of VitK. Particularly, emphasizing on the need for VitK2 supplementation owing to its relatively limited availability in Western diets. VitK2 supplementation effectively counters VC, enhances bone density, and offers neuroprotective, hepatoprotective, and anti-inflammatory benefits. Thus, the supplementation of VitK2, alongside dietary intake, is essential for preventive healthcare, particularly in the prevention of osteoporosis and vascular diseases. Incorporating adequate VitK2 intake highlights its significance in promoting overall well-being. Illustrated summary of the role of VitK in menopausal women.
10.Associations between weight-control methods and depression among Korean adolescents: a study based on a national dataset
Jaehyun KONG ; Kyeongmin LEE ; Sooji LEE ; Soeun KIM ; Jinyoung JEONG ; Yejun SON ; Hayeon LEE ; Louis JACOB ; Masoud RAHMATI ; Guillaume FOND ; Laurent BOYER ; Lee SMITH ; Elena DRAGIOTI ; Selin WOO ; Jiyoung HWANG ; Dong Keon YON
Nutrition Research and Practice 2024;18(6):818-828
BACKGROUND/OBJECTIVES:
The increasing prevalence of overweight and obesity has become a significant global burden, with more than 40% of the global adult population attempting to lose weight. Previous studies on the impact of weight-control methods on mental health, especially among adolescents, are limited. Thus, this study aimed to investigate the association between various weight-control methods and depression among adolescents, with the goal of informing healthier weight management decisions and promoting effective methods.
SUBJECTS/METHODS:
This nationwide study utilized data from the Korea Youth Risk Behavior Web-based Survey, including a sample of 418,254 adolescents collected over 12yrs (2007–2019). We conducted a weighted complex sample analysis to compare depression rates associated with specific weight-control methods, including exercise, fasting (≥ 24 h), eating less, taking prescriptionon-prescription weight-loss medication, taking laxatives or diuretics, vomiting, one-food diet, taking oriental medicine, and diet foods.
RESULTS:
Of the 418,254 participants, 45.96% (192,246) were male. Among male participants, fasting (≥ 24 h; weighted odds ratio [wOR], 1.43; 95% confidence interval [CI], 1.36–1.51) and vomiting (wOR, 1.49; 95% CI, 1.35–1.66) were associated with an increased risk of depression. Among female participants, prescribed (wOR, 0.82; 95% CI, 0.74–0.90) and non-prescribed (wOR, 0.89; 95% CI, 0.82–0.97) weight-loss medication reduced the risk of depression. However, fasting (≥ 24 h; wOR, 1.47; 95% CI, 1.41–1.52) vomiting (wOR, 1.45;95% CI, 1.36–1.55) significantly increased the risk of depression.
CONCLUSION
The risk of depression varies depending on the weight-control method, with a consistent trend observed across both sexes. Methods such as vomiting, fasting, taking oriental medicine for weight loss, and consuming diet foods increased the risk of depression, while weight-loss medications were associated with reduced depression symptoms in females. These findings highlight the need for further research on weightcontrol medications and policies that support effective weight management while reducing depressive effects.

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