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.Contemporary Statistics of Acute Ischemic Stroke and Transient Ischemic Attack in 2021: Insights From the CRCS-K-NIH Registry
Do Yeon KIM ; Tai Hwan PARK ; Yong-Jin CHO ; Jong-Moo PARK ; Kyungbok LEE ; Minwoo LEE ; Juneyoung LEE ; Sang Yoon BAE ; Da Young HONG ; Hannah JUNG ; Eunvin KO ; Hyung Seok GUK ; Beom Joon KIM ; Jun Yup KIM ; Jihoon KANG ; Moon-Ku HAN ; Sang-Soon PARK ; Keun-Sik HONG ; Hong-Kyun PARK ; Jeong-Yoon LEE ; Byung-Chul LEE ; Kyung-Ho YU ; Mi Sun OH ; Dong-Eog KIM ; Dong-Seok GWAK ; Soo Joo LEE ; Jae Guk KIM ; Jun LEE ; Doo Hyuk KWON ; Jae-Kwan CHA ; Dae-Hyun KIM ; Joon-Tae KIM ; Kang-Ho CHOI ; Hyunsoo KIM ; Jay Chol CHOI ; Joong-Goo KIM ; Chul-Hoo KANG ; Sung-il SOHN ; Jeong-Ho HONG ; Hyungjong PARK ; Sang-Hwa LEE ; Chulho KIM ; Dong-Ick SHIN ; Kyu Sun YUM ; Kyusik KANG ; Kwang-Yeol PARK ; Hae-Bong JEONG ; Chan-Young PARK ; Keon-Joo LEE ; Jee Hyun KWON ; Wook-Joo KIM ; Ji Sung LEE ; Hee-Joon BAE ;
Journal of Korean Medical Science 2024;39(34):e278-
This report presents the latest statistics on the stroke population in South Korea, sourced from the Clinical Research Collaborations for Stroke in Korea-National Institute for Health (CRCS-K-NIH), a comprehensive, nationwide, multicenter stroke registry. The Korean cohort, unlike western populations, shows a male-to-female ratio of 1.5, attributed to lower risk factors in Korean women. The average ages for men and women are 67 and 73 years, respectively.Hypertension is the most common risk factor (67%), consistent with global trends, but there is a higher prevalence of diabetes (35%) and smoking (21%). The prevalence of atrial fibrillation (19%) is lower than in western populations, suggesting effective prevention strategies in the general population. A high incidence of large artery atherosclerosis (38%) is observed, likely due to prevalent intracranial arterial disease in East Asians and advanced imaging techniques.There has been a decrease in intravenous thrombolysis rates, from 12% in 2017–2019 to 10% in 2021, with no improvements in door-to-needle and door-to-puncture times, worsened by the coronavirus disease 2019 pandemic. While the use of aspirin plus clopidogrel for noncardioembolic stroke and direct oral anticoagulants for atrial fibrillation is well-established, the application of direct oral anticoagulants for non-atrial fibrillation cardioembolic strokes in the acute phase requires further research. The incidence of early neurological deterioration (13%) and the cumulative incidence of recurrent stroke at 3 months (3%) align with global figures. Favorable outcomes at 3 months (63%) are comparable internationally, yet the lack of improvement in dependency at 3 months highlights the need for advancements in acute stroke care.
3.Does a Lower Limb Balance Test after Anterior Cruciate Ligament Reconstruction Have a Significant Correlation with Postoperative Clinical Score, Stability, and Functional Performance Test?
Jin Seong KIM ; Moon Young CHOI ; Doo Hwan KONG ; Jeong Ku HA ; Kyu Sung CHUNG
Clinics in Orthopedic Surgery 2023;15(3):402-409
Background:
Lower limb balance ability is reduced after anterior cruciate ligament reconstruction (ACLR). However, the recovery of balance based on functional test scores after ACLR is not known because the correlation between balance and clinical scores remains unclear. We aimed to analyze the correlation between lower limb balance assessed by functional test and clinical knee test scores after ACLR.
Methods:
We evaluated lower limb balance using the anterior-posterior stability index (APSI) of the Biodex Balance System (BBS).Patients underwent clinical tests to evaluate the knee, including the Tegner activity score, International Knee Documentation Committee (IKDC) subjective score, Lysholm score, and KT-2000 arthrometer measurement, hamstring per quadriceps muscle strength ratio at 60°/sec (HQ ratio), and functional performance tests (single-leg hop and single-leg vertical jump tests) 1 year after ACLR.We used a paired t-test to compare continuous preoperative and postoperative variables and Pearson’s correlation coefficient to determine the relationship between BBS-APSI and clinical scores.
Results:
Forty-eight patients (35 men and 13 women; mean age, 28.9 ± 8.3 years) were included. The follow-up period and BBSAPSI were 12.4 ± 2.0 months and 0.9 ± 0.4, respectively. Tegner activity score, IKDC subjective score, Lysholm score, and KT-2000 arthrometer measurement improved significantly postoperatively (p < 0.001). BBS-APSI was correlated with the Tegner activity score (r = –0.335, p = 0.020), IKDC subjective score (r = –0.301, p = 0.037), Lysholm score (r = –0.323, p = 0.025), single-leg hop test results (r = –0.300, p = 0.038), and single-leg vertical jump test results (r = –0.336, p = 0.019). There was no correlation between KT-2000 arthrometer measurement and HQ ratio.
Conclusions
BBS-APSI was correlated with functional performance test scores after ACLR, rendering the BBS-APSI as a useful assessment tool to evaluate postoperative functional recovery. Continuously improving balance after ACLR could be useful for functional recovery after surgery.
4.Psychometric Properties of the Korean Version of Functioning Assessment Short Test in Bipolar Disorder
Hangoeunbi KANG ; Bo-Hyun YOON ; Won-Myong BAHK ; Young Sup WOO ; Won KIM ; Jonghun LEE ; InKi SOHN ; Sung-Yong PARK ; Duk-In JON ; Myung Hun JUNG ; Moon-Doo KIM ; Young-Eun JUNG ; Hyung-Mo SUNG ; Young-Min PARK ; Jung Goo LEE ; Sang-Yeol LEE ; Seung-Ho JANG ; Eun-Sung LIM ; In Hee SHIM ; Kwanghun LEE ; Sae-Heon JANG
Clinical Psychopharmacology and Neuroscience 2023;21(1):188-196
Objective:
The Functioning Assessment Short Test (FAST) is a relatively specific test for bipolar disorders designed to assess the main functioning problems experienced by patients. This brief instrument includes 24 items assessing impairment or disability in 6 domains of functioning: autonomy, occupational functioning, cognitive functioning, financial issues, interpersonal relationships, and leisure time. It has already been translated into standardized versions in several languages. The aim of this study is to measure the validity and reliability of the Korean version of FAST (K-FAST).
Methods:
A total of 209 bipolar disorder patients were recruited from 14 centers in Korea. K-FAST, Young Mania Rating Scale (YMRS), Bipolar Depression Rating Scale (BDRS), Global Assessment of Functioning (GAF) and the World Health Organization Quality of Life Assessment Instrument Brief Form (WHOQOL-BREF) were administered, and psychometric analysis of the K-FAST was conducted.
Results:
The internal consistency (Cronbach’s alpha) of the K-FAST was 0.95. Test-retest reliability analysis showed a strong correlation between the two measures assessed at a 1-week interval (ICC = 0.97; p < 0.001). The K-FAST exhibited significant correlations with GAF (r = −0.771), WHOQOL-BREF (r = −0.326), YMRS (r = 0.509) and BDRS (r = 0.598). A strong negative correlation with GAF pointed to a reasonable degree of concurrent validity. Although the exploratory factor analysis showed four factors, the confirmatory factor analysis of questionnaires had a good fit for a six factors model (CFI = 0.925; TLI = 0.912; RMSEA = 0.078).
Conclusion
The K-FAST has good psychometric properties, good internal consistency, and can be applicable and acceptable to the Korean context.
5.Korean Medication Algorithm Project for Bipolar Disorder 2022:Comparisons with Other Treatment Guidelines
Jong-Hyun JEONG ; Won-Myong BAHK ; Young Sup WOO ; Bo-Hyun YOON ; Jung Goo LEE ; Won KIM ; InKi SOHN ; Sung-Yong PARK ; Se-Hoon SHIM ; Jeong Seok SEO ; IL Han CHOO ; Chan-Mo YANG ; Myung Hun JUNG ; Duk-In JON ; Moon-Doo KIM
Clinical Psychopharmacology and Neuroscience 2023;21(1):32-48
The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2022 (KMAP-BP 2022) with other recently published guidelines for treating bipolar disorder. We reviewed a total of six recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2022 with those of other guidelines. For initial treatment of mania, there were no significant differences across treatment guidelines. All guidelines recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or a combination of an MS with an AAP as a first-line treatment strategy in a same degree for mania. However, the KMAP-BP 2022 recommended MS + AAP combination therapy for psychotic mania, mixed mania and psychotic depression as treatment of choice. Aripiprazole, quetiapine and olanzapine were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Some guideline suggested olanzapine is a second-line options during maintenance treatment, related to concern about long-term tolerability. Most guidelines advocated newer AAPs (asenapine, cariprazine, long-acting injectable risperidone, and aripiprazole once monthly) as first-line treatment options for all phases while lamotrigine was recommended for depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. KMAP-BP 2022 guidelines were similar to other guidelines, reflecting current changes in prescription patterns for bipolar disorder based on accumulated research data. Strong preference for combination therapy was characteristic of KMAP-BP 2022, predominantly in the treatment of psychotic mania, mixed mania and psychotic depression.
6.Rehabilitation after Repair of Medial Meniscus Posterior Root Tears: A Systematic Review of the Literature
Jin Seong KIM ; Min Ki LEE ; Moon Young CHOI ; Doo Hwan KONG ; Jeong Ku HA ; Jin Goo KIM ; Kyu Sung CHUNG
Clinics in Orthopedic Surgery 2023;15(5):740-751
Background:
There is no consensus established on postoperative rehabilitation after medial meniscus posterior root tear (MMPRT) repair, including when and how physicians can apply range of motion (ROM) exercise, weight-bearing (WB), brace use, and return to sports (RTS). The purpose of this study was to systematically review the literature on postoperative rehabilitation characteristics of MMPRT repair regarding ROM, WB, brace use, and RTS.
Methods:
A literature search was performed using the Medline/PubMed, Cochrane Central Register of Controlled Trials, and Embase databases. The inclusion criteria were English language, human clinical studies, and studies describing rehabilitation protocols after MMPRT repair such as ROM, WB, brace use, and RTS. Abstracts, case reports, cohort studies, controlled laboratory studies, human cadaveric or animal studies, systematic reviews, and meta-analyses were excluded.
Results:
Thirteen studies were included. Of the 12 ROM studies, ROM was started immediately within 1 or 2 days after operation in 6 studies and after 2 to 3 weeks of knee immobilization in the rest. Of the 13 WB studies, partial weight-bearing was initiated 1 to 4 weeks after operation in 8 studies and 6 weeks in the rest. Of the 9 brace studies, patients were immobilized by a splint for 2 weeks in 3 studies, and in the rest, a brace with full extension was applied for 3 to 6 weeks after several days of splint application.Of the 7 RTS studies, RTS was allowed at 6 months in 6 studies and 5 to 7 months in 1 study.
Conclusions
This systematic review revealed conservative rehabilitation protocols were more widely adapted as ROM and WB were restricted at certain degrees during postoperative periods in most protocols analyzed. However, it is impossible to identify a consensus on rehabilitation protocols as the protocols analyzed in this review were distinct each other and heterogeneous. In the future, a well-designed comparative study among different rehabilitation protocols is essential to establish a consensus.
7.The Multifaceted Clinical Characteristics of Congenital Cytomegalovirus Infection: From Pregnancy to Long-Term Outcomes
Yejin KIM ; Yoo-min KIM ; Doo Ri KIM ; Han Gyeol KIM ; Ji-Hee SUNG ; Suk-Joo CHOI ; Soo-young OH ; Yae-Jean KIM ; Yun Sil CHANG ; Dongsub KIM ; Jung-Sun KIM ; Il Joon MOON ; Cheong-Rae ROH
Journal of Korean Medical Science 2023;38(32):e249-
Background:
The aim of this study was to capture multifaceted clinical characteristics of congenital cytomegalovirus (CMV) infection from diagnosis to treatment using a multidisciplinary approach including obstetrics, pediatrics, pathology, and otorhinolaryngology-head and neck surgery.
Methods:
This is a retrospective study including 30 consecutive cases of congenital CMV infection that were diagnosed at a single tertiary hospital located in Seoul, Korea from January 2009 to December 2020. Congenital CMV infection was defined as a positive result by polymerase chain reaction from urine, saliva or cerebrospinal fluid or positive CMV IgM from neonatal blood sampled within 3 weeks after birth. All cases were analyzed with respect to whole clinical characteristics from diagnosis to treatment of congenital CMV by a multidisciplinary approach including prenatal sonographic findings, maternal immune status regarding CMV infection, detailed placental pathology, neonatal clinical manifestation, auditory brainstem response test, and antiviral treatment (ganciclovir or valganciclovir). Long-term outcomes including developmental delay and hearing loss were also investigated.
Results:
The total number of births during the study period in our institution was 19,385, with the prevalence of congenital infection estimated to be 0.15%. Among 30 cases of congenital CMV, the median gestational age at delivery was 32.2 weeks [range, 22.6–40.0] and 66.7% of these infants were delivered preterm at less than 37 weeks. Suspected fetal growth restriction was the most common prenatal ultrasound finding (50%) followed by ventriculomegaly (17.9%) and abnormal placenta (17.9%), defined as thick placenta with calcification. No abnormal findings on ultrasound examination were observed in one-third of births. Maternal CMV serology tests were conducted in only 8 cases, and one case each of positive and equivocal IgM were found. The most common placental pathologic findings were chronic villitis (66.7%) and calcification (63.0%), whereas viral inclusions were identified in only 22.2%. The most common neonatal manifestations were jaundice (58.6%) followed by elevation of aspartate aminotransferase (55.2%) and thrombocytopenia (51.7%). After excluding cases for which long-term outcomes were unavailable due to death (n = 4) or subsequent follow up loss (n = 3), developmental delay was confirmed in 43.5% of infants (10/23), and hearing loss was confirmed in 42.9% (9/21) during the follow-up period. In our cohort, 56.7% (17/30) of neonates were treated for congenital CMV with ganciclovir or valganciclovir.
Conclusion
Our data show that prenatal findings including maternal serologic tests and ultrasound have limited ability to detect congenital CMV in Korea. Given that CMV is associated with high rates of developmental delay and hearing loss in infants, there is an urgent need to develop specific strategies for the definite diagnosis of congenital CMV infection during the perinatal period by a multidisciplinary approach to decrease the risks of neurologic impairment and hearing loss through early antiviral treatment.
8.Korean Medication Algorithm Project for Bipolar Disorder 2022:Mixed Features
Won KIM ; Won-Myong BAHK ; Young Sup WOO ; Jong-Hyun JEONG ; Jeong Seok SEO ; IL Han CHOO ; Chan-Mo YANG ; Jung Goo LEE ; Se-Hoon SHIM ; Bo-Hyun YOON ; Sung-Yong PARK ; InKi SOHN ; Moon-Doo KIM ; Myung Hun JUNG ; Duk-In JON
Journal of Korean Neuropsychiatric Association 2022;61(2):133-142
Objectives:
Treatment guidelines or an algorithm can help clinicians implement better practices and clinical decisions. Therefore, the Korean Medication Algorithm Project for Bipolar Disorder 2022 (KMAP-BP 2022) was revised again through a consensus of expert opinion. The diagnosis and treatment of mixed features are not simple, and there are many things to discuss. We describe the preferences and recommendations from KMAP-BP 2022 for the treatment of mood episodes with mixed features.
Methods:
We revised the KMAP-BP 2018 questionnaire and conducted the survey with expert clinicians. Out of ninety-three members of the review committee, eighty-seven completed the survey. We analyzed the answers, discussed the data, and held a clinician hearing.
Results:
In first-step strategies for mixed features with more manic symptoms, a combination of a mood stabilizer and an atypical antipsychotic is the treatment of choice. Mood stabilizer monotherapy and atypical antipsychotic monotherapy are preferred strategies. For mixed features with more depressive symptoms, a combination of mood stabilizer and atypical antipsychotic, a combination of atypical antipsychotic and lamotrigine (LMT), atypical antipsychotic monotherapy, a combination of mood stabilizer and LMT, and mood stabilizer monotherapy are preferred. For mixed features with similar manic symptoms and depressive symptoms, a combination of mood stabilizer and atypical antipsychotic, atypical antipsychotic monotherapy, and mood stabilizer monotherapy are preferred.
Conclusion
For mixed features, a combination of mood stabilizer and atypical antipsychotic is generally preferred, and LMT is preferred for depressive symptoms. Compared with KMAP-BP 2018, more diverse strategies and drugs are being attempted for the treatment of mixed features.
9.Korean Medication Algorithm Project for Bipolar Disorder 2022:Depressive Episode
Jeong Seok SEO ; Young Sup WOO ; Won-Myong BAHK ; Jong-Hyun JEONG ; Bo-Hyun YOON ; IL Han CHOO ; Chan-Mo YANG ; Won KIM ; Jung Goo LEE ; Se-Hoon SHIM ; Myung Hun JUNG ; Duk-In JON ; Sung-Yong PARK ; InKi SOHN ; Moon-Doo KIM
Journal of Korean Neuropsychiatric Association 2022;61(2):123-132
Objectives:
After the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed in 2002, its fifth revision was completed in 2022 to reflect the recent rapid developments and research into bipolar disorder and its psychopharmacology.
Methods:
According to the methodology for previous versions, the depressive episode section of KMAP-BP 2022 was revised based on a survey consisting of 11 questions. Among ninetythree experts, eighty-seven members of the review committee (93.5%) completed the survey.The executive committee analyzed the results and discussed the final production of an algorithm by considering the scientific evidence.
Results:
Overall, the results from this study showed little change in comparison with previous versions of KMAP-BP. However, there have been significant changes in recommendations over the span of about 20 years. The preferences for lamotrigine and atypical antipsychotics, especially aripiprazole, quetiapine, and olanzapine, have shown a tendency to continuously increase, but the preferences for risperidone and ziprasidone have not increased, but have decreased. Moreover, the preference for typical antipsychotics has significantly decreased. Additionally, concerns over the use of antidepressants in bipolar depression have been raised, and their use is not recommended in KMAP-BP 2022 as a first-line treatment.
Conclusion
Pharmacotherapy for acute depressive episodes with various clinical progressions and various subtypes still shows diversity, compared to pharmacotherapy for mania. We look forward to the development of bipolar depressive, episode-specific therapeutic drugs in the future, and hope the fifth update of KMAP-BP will be a complementary option for clinicians and their patients with bipolar disorder.
10.Korean Medication Algorithm Project for Bipolar Disorder 2022:Manic Episode
Young Sup WOO ; Won-Myong BAHK ; Jong-Hyun JEONG ; Bo-Hyun YOON ; Jeong Seok SEO ; IL Han CHOO ; Chan-Mo YANG ; Won KIM ; Jung Goo LEE ; Se-Hoon SHIM ; Myung Hun JUNG ; Duk-In JON ; Sung-Yong PARK ; InKi SOHN ; Moon-Doo KIM
Journal of Korean Neuropsychiatric Association 2022;61(2):110-122
Objectives:
The Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) is a consensus-based medication guideline. To reflect advances in pharmacotherapy for bipolar disorders, we updated KMAP-BP to provide more timely information for clinicians.
Methods:
We conducted a survey using a questionnaire on treatments formanic/hypomanic episodes. Eighty-seven members among ninety-three members of the review committee (93.5%) completed the survey. Each treatment strategy or treatment option for manic/hypomanic episodes was evaluated with an overall score of 9, and the resulting 95% confidence interval treatment options were categorized into three recommendation levels (primary, secondary, and tertiary). The executive committee analyzed the results and discussed the final production of an algorithm by considering the scientific evidence.
Results:
The combination of a mood stabilizer and an atypical antipsychotic, monotherapy with a mood stabilizer, or monotherapy with an atypical antipsychotic were recommended as the firstline pharmacotherapeutic strategy for the initial treatment of mania without psychotic features. The mood stabilizer and atypical antipsychotic combination was the treatment of choice, and atypical antipsychotic monotherapy was the first-line treatment for mania with psychotic features. When initial treatment fails, a combination of mood stabilizer+atypical antipsychotic and switching to another first-line agent is recommended. For hypomania, monotherapy with either mood stabilizer or atypical antipsychotic is the recommended first-line treatment, but the mood stabilizer+atypical antipsychotic combination is recommended as well.
Conclusion
It is notable that there were changes in the preferences for the use of individual atypical antipsychotics, and the preference for the use of mood stabilizer increased for treatment-resistant mania.

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