Background: We aimed to investigate the comparative risk of fracture among patients with atrial fibrillation (AF) treated with warfarin or non-vitamin K antagonist oral anticoagulants (NOACs). Methods: Using the Korean National Health Insurance Service database, patients with AF who received a prescrip‑ tion for apixaban, dabigatran, rivaroxaban, or warfarin between 2013 and 2016 were included. Risk of major fractures (osteoporotic hip, vertebral, or pelvic fractures) were compared using inverse probability of treatment weighting. Results: There were 70,481 patients identified (41.3% women; mean [SD] age 70.5 [11.3] years); 16,992 apixaban, 22,514 dabigatran, 27,998 rivaroxaban, and 29,390 warfarin users. During a median follow-up of 390 days, 2412 major fractures occurred with weighted incidences per 100 patient-years of 2.56 for apixaban, 2.39 for dabigatran, 2.78 for rivaroxaban, and 3.43 for warfarin. NOAC use was associated with a lower risk for fracture than warfarin use: HR 0.70 (95% confidence interval [CI] 0.57–0.86) for apixaban, HR 0.69 (95% CI 0.60–0.78) for dabigatran, and HR 0.79 (95% CI 0.70–0.90) for rivaroxaban. In head-to-head comparisons between NOACs, there was no significant difference between apixaban and dabigatran. Rivaroxaban was associated with a higher risk for fracture than dabigatran (HR 1.15, 95% CI 1.02–1.31). Conclusion In patients with AF, NOAC use may result in a lower risk for osteoporotic fracture compared with warfa‑ rin use. Fracture risk does not seem to be altered by the choice of NOAC type, except for rivaroxaban. These associa‑ tions may help inform benefit–risk assessments when choosing between the different anticoagulant types.

Background: We aimed to investigate the comparative risk of fracture among patients with atrial fibrillation (AF) treated with warfarin or non-vitamin K antagonist oral anticoagulants (NOACs). Methods: Using the Korean National Health Insurance Service database, patients with AF who received a prescrip‑ tion for apixaban, dabigatran, rivaroxaban, or warfarin between 2013 and 2016 were included. Risk of major fractures (osteoporotic hip, vertebral, or pelvic fractures) were compared using inverse probability of treatment weighting. Results: There were 70,481 patients identified (41.3% women; mean [SD] age 70.5 [11.3] years); 16,992 apixaban, 22,514 dabigatran, 27,998 rivaroxaban, and 29,390 warfarin users. During a median follow-up of 390 days, 2412 major fractures occurred with weighted incidences per 100 patient-years of 2.56 for apixaban, 2.39 for dabigatran, 2.78 for rivaroxaban, and 3.43 for warfarin. NOAC use was associated with a lower risk for fracture than warfarin use: HR 0.70 (95% confidence interval [CI] 0.57–0.86) for apixaban, HR 0.69 (95% CI 0.60–0.78) for dabigatran, and HR 0.79 (95% CI 0.70–0.90) for rivaroxaban. In head-to-head comparisons between NOACs, there was no significant difference between apixaban and dabigatran. Rivaroxaban was associated with a higher risk for fracture than dabigatran (HR 1.15, 95% CI 1.02–1.31). Conclusion In patients with AF, NOAC use may result in a lower risk for osteoporotic fracture compared with warfa‑ rin use. Fracture risk does not seem to be altered by the choice of NOAC type, except for rivaroxaban. These associa‑ tions may help inform benefit–risk assessments when choosing between the different anticoagulant types.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

Chronic spontaneous urticaria (CSU) is defined as the occurrence of spontaneous wheals, angioedema, or both for >6 weeks in the absence of specific causes. It is a common condition associated with substantial disease burden both for affected individuals and societies in many countries, including Korea. CSU frequently persists for several years and requires high-intensity treatment; therefore, patients experience deteriorations in quality of life and medication-associated complications. During the last decade, there have been major advances in the pharmacological treatment of CSU and there is an outstanding need for evidence-based guidelines that reflect clinical practice in Korea. The guidelines reported here represent a joint initiative of the Korean Academy of Asthma, Allergy and Clinical Immunology and the Korean Dermatological Association, and aim to provide evidence-based guidance for the management of CSU in Korean adults and children. In Part 1, disease definition, guideline scope and development methodology as well as evidence-based recommendations on the use of antihistamines and corticosteroids are summarized.

BACKGROUND AND OBJECTIVES: Nationwide social inequalities of oral anticoagulation (OAC) usage after the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) have not been well identified in patients with atrial fibrillation (AF). This study assessed overall rate and social inequalities of OAC usage after the introduction of NOAC in Korea.METHODS: Between January 2002 and December 2016, we identified 888,540 patients with AF in the Korea National Health Insurance system database. The change of OAC rate in different medical systems after the introduction of NOAC were evaluated.RESULTS: In all population, overall OAC use increased from 13.2% to 23.4% (p for trend <0.001), and NOAC use increased from 0% to 14.6% (p for trend <0.001). Compared with pre-reimbursement (0.48%), the annual increase of OAC use was significantly higher after partial (1.16%, p<0.001), and full reimbursement of OAC (3.72%, p<0.001). Full reimbursement of NOAC (adjusted odds ratio, 2.10; 95% confidence interval, 2.04–2.15) was independently associated with higher OAC use. However, the difference of overall OAC usage between tertiary referral hospitals and nursing or public health centers increased from 17.9% in 2010 to 36.8% in 2016. Moreover, usage rate of NOAC was significantly different among different medical systems from 37.2% at the tertiary referral hospital and 5.5% at nursing or public health centers.CONCLUSIONS: Introduction of NOACs in routine practice for stroke prevention in AF was associated with improved rates of overall OAC use. However, significant practice-level variations in OAC and NOAC use remain producing social inequalities of OAC despite full reimbursement.
Anticoagulants ; Atrial Fibrillation ; Humans ; Insurance ; Korea ; National Health Programs ; Nursing ; Odds Ratio ; Public Health ; Socioeconomic Factors ; Stroke ; Tertiary Care Centers

BACKGROUND AND OBJECTIVES: The objective of this study was to evaluate the long-term clinical outcomes and the incidence of permanent pacemaker implantation after catheter ablation in patients with of atrial fibrillation (AF) and sinus node dysfunction (SND).METHODS: Among 3,068 total consecutive patients who underwent AF catheter ablation (AFCA), this study included 222 (9.5%; men 53.2%, 63.7±9.2 years of age, 81.5% paroxysmal AF) with underlying SND and a regular rhythm follow-up. We analyzed the rhythm outcomes, changes in the mean heart rate or heart rate variability, and permanent pacemaker implantation rate.RESULTS: During 47.5±28.8 months of follow-up, 25 (11.3%) patients received pacemaker implantations due to symptomatic SND. More than half (56.0%, 14/25) underwent a pacemaker implantation within 3 months of the AFCA, and the annual pacemaker implantation rate was 2.0% afterwards. Both the early (68.0% vs. 31.0%, p<0.001) and clinical AF recurrence (68.0% vs. 32.5%, p=0.001) rates and continuous antiarrhythmic drug use after 3 months (44.0% vs. 24.4%, p=0.036) were significantly higher in patients requiring pacemaker implantations than those that did not. An anterior linear ablation (odds ratio [OR], 9.37 [3.03–28.9]; p<0.001) and the E/Em (OR, 1.15 [1.02–1.28]; p=0.018) were independently associated with permanent pacemaker implantations after AFCA in patients with AF and SND.CONCLUSIONS: After AFCA in patients with AF and SND, 1 of 9 patients needed a pacemaker implantation and half needed implantations within 3 months. The AF recurrence rate was significantly higher in those who required pacemaker implantations after the AFCA.
Atrial Fibrillation ; Catheter Ablation ; Catheters ; Follow-Up Studies ; Heart Rate ; Humans ; Incidence ; Male ; Pacemaker, Artificial ; Recurrence ; Sick Sinus Syndrome ; Sinoatrial Node

BACKGROUND AND OBJECTIVES: The objective of this study was to evaluate the long-term clinical outcomes and the incidence of permanent pacemaker implantation after catheter ablation in patients with of atrial fibrillation (AF) and sinus node dysfunction (SND). METHODS: Among 3,068 total consecutive patients who underwent AF catheter ablation (AFCA), this study included 222 (9.5%; men 53.2%, 63.7±9.2 years of age, 81.5% paroxysmal AF) with underlying SND and a regular rhythm follow-up. We analyzed the rhythm outcomes, changes in the mean heart rate or heart rate variability, and permanent pacemaker implantation rate. RESULTS: During 47.5±28.8 months of follow-up, 25 (11.3%) patients received pacemaker implantations due to symptomatic SND. More than half (56.0%, 14/25) underwent a pacemaker implantation within 3 months of the AFCA, and the annual pacemaker implantation rate was 2.0% afterwards. Both the early (68.0% vs. 31.0%, p<0.001) and clinical AF recurrence (68.0% vs. 32.5%, p=0.001) rates and continuous antiarrhythmic drug use after 3 months (44.0% vs. 24.4%, p=0.036) were significantly higher in patients requiring pacemaker implantations than those that did not. An anterior linear ablation (odds ratio [OR], 9.37 [3.03–28.9]; p<0.001) and the E/Em (OR, 1.15 [1.02–1.28]; p=0.018) were independently associated with permanent pacemaker implantations after AFCA in patients with AF and SND. CONCLUSIONS After AFCA in patients with AF and SND, 1 of 9 patients needed a pacemaker implantation and half needed implantations within 3 months. The AF recurrence rate was significantly higher in those who required pacemaker implantations after the AFCA.

BACKGROUND AND OBJECTIVES: Nationwide social inequalities of oral anticoagulation (OAC) usage after the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) have not been well identified in patients with atrial fibrillation (AF). This study assessed overall rate and social inequalities of OAC usage after the introduction of NOAC in Korea. METHODS: Between January 2002 and December 2016, we identified 888,540 patients with AF in the Korea National Health Insurance system database. The change of OAC rate in different medical systems after the introduction of NOAC were evaluated. RESULTS: In all population, overall OAC use increased from 13.2% to 23.4% (p for trend <0.001), and NOAC use increased from 0% to 14.6% (p for trend <0.001). Compared with pre-reimbursement (0.48%), the annual increase of OAC use was significantly higher after partial (1.16%, p<0.001), and full reimbursement of OAC (3.72%, p<0.001). Full reimbursement of NOAC (adjusted odds ratio, 2.10; 95% confidence interval, 2.04–2.15) was independently associated with higher OAC use. However, the difference of overall OAC usage between tertiary referral hospitals and nursing or public health centers increased from 17.9% in 2010 to 36.8% in 2016. Moreover, usage rate of NOAC was significantly different among different medical systems from 37.2% at the tertiary referral hospital and 5.5% at nursing or public health centers. CONCLUSIONS Introduction of NOACs in routine practice for stroke prevention in AF was associated with improved rates of overall OAC use. However, significant practice-level variations in OAC and NOAC use remain producing social inequalities of OAC despite full reimbursement.

Purpose: Implantable cardioverter defibrillators (ICD) are the standard of care for primary prevention (PP) in patients with ischemic cardiomyopathy (ICM). However, PP ICD implantation is underused in Asian countries. This study investigated ICD implantation rates and factors associated with appropriate PP ICD implants for ICM. Materials and Methods: In this prospective multicenter observational registry (ADVANCE-ICM registry), ICM patients who were eligible for PP ICD were screened and enrolled. Factors associated with appropriate ICD implantation, including hospital and clinical factors, were investigated. Results: Of the 1453 ICM patients eligible for PP ICD [1111 male; median age, 71.0 (61.0–78.0) years], only 76 (5.2%) patients underwent ICD implantation. Among hospital factors, a non-monetary incentive for referral (72.4% vs. 52.9%, p=0.001) and total hospital system score (6.0 vs. 5.0, p=0.013) were higher in the ICD than in the no-ICD group. In multivariate analysis, total hospital system score [odds ratio (OR), 1.28; 95% confidence interval (CI), 1.10–1.50] was an independent factor for predicting ICD implantation, along with clinical factors, including high New York Heart Association class (≥III: OR, 7.29; 95% CI, 2.97–17.87) and younger age (<70 years: OR, 2.14; 95% CI, 1.30–3.53). Conclusion PP ICD implantation for ICM patients is underused in Korea. Hospital factors were important for improving PP ICD implantation rate, suggesting that new screening and referral systems for ICM patients would improve the PP ICD implantation rate (Clinical trial registration No. NCT03590925).

This study focused on investigation of the immunosuppressive inhibitory effect through determination of IL-2 production of nine compounds (1 − 9) isolated from Chlamydomonas sp. KSF108. Among them, compounds 1, 5, and 6 displayed moderately inhibitory effects on IL-2 production at a concentration of 100 μM. In addition, the related ones including cytotoxic, anti-inflammatory, and anti-oxidant activities were also elucidated. 6 further displayed cytotoxic activity against the MCF-7 cell line, with an IC50 value of 17.2 μM and 4, 6 − 7, and 9 possessed significant DPPH radical scavenging activity, with IC50 values ranging from 3.1 to 4.4 μM. To the best of our knowledge, this is the first report on the bioactivity of isolated chemical constituents from the genus Chlamydomonas. Compounds 1 and 5 investigated for the first time in the activity of immunosuppressivity and 6 may come to serve as the most important marker in broad-spectrum activities of the secondary metabolites identified from C. sp. KSF108.