Real-World Safety and Effectiveness of Fluticasone Furoate/Vilanterol in Patients with Asthma and/or Chronic Obstructive Pulmonary Disease: A Post-Marketing Study in Korea.

BACKGROUND AND OBJECTIVE: Fluticasone furoate/vilanterol (FF/VI; RELVAR ELLIPTA) is approved in Korea for patients with asthma or chronic obstructive pulmonary disease (COPD). This study evaluated the effectiveness and safety of FF/VI in Korean patients with asthma and/or COPD over a 6-year period. METHODS: This was an open-label, multicentre, observational, post-marketing surveillance study in patients newly treated with FF/VI (100 or 200 µg/25 µg once daily). Safety endpoints were the incidence of adverse events (AEs), including unexpected AEs/adverse drug reactions (ADRs) and serious AEs/ADRs. Effectiveness was assessed after 24 weeks by Global Physician Assessment (logistic regression) and forced expiratory volume in 1 s (FEV1; paired t-tests). RESULTS: Of the 3426 patients enrolled across 45 hospitals between July 2014 and June 2020, 3216 were included in the safety analysis (50.5% female; mean age ± standard deviation [SD]: 58.6 ± 16.3 years). Overall incidence of AEs was 30.9% (n = 992); 4.1% (n = 132) were ADRs. Serious AEs were reported in 4.1% (n = 132) of patients; 0.1% (n = 4) were ADRs. Of 1543 patients analysed for symptomatic improvement, 89.2% (n = 1377) improved, 9.4% (n = 145) were unchanged, and 1.4% (n = 21) worsened. Mean FEV1 (difference ± SD) increased significantly in patients with asthma (0.09 ± 0.29 L; p < 0.0001), COPD (0.11 ± 0.24 L; p = 0.0011), or both (0.05 ± 0.18 L; p = 0.0399), indicating improved lung function. CONCLUSION: In this real-world study, FF/VI administered to Korean patients was well tolerated and effective for the treatment of asthma and COPD. These results were consistent with other studies in Asian and global populations.

Microcurvature Controllable Metal-Organic Framework Nanoagents Capable of Ice-Lattice Matching for Cellular Cryopreservation.

Ice-binding proteins (IBPs) produced by psychrophilic organisms to adapt for the survival of psychrophiles in subzero conditions have received illustrious interest as a cryopreservation agent required for cells and tissues to completely recover after freezing/thawing. Depressing water-freezing point and avoiding ice-crystal growth affect their activities which are closely related to the presence of ice crystal well-matched binding moiety. The interaction of IBPs with ice and water is critical in enhancing their freeze avoidance against cell or tissue damage. Metal-organic frameworks (MOFs) with a controllable lattice at the molecular level and a size at the nanometer scale can offer periodically ordered ice-binding sites by modifying organic linkers and controlling microcurvature at the ice surface. Herein, zirconium (Zr)-based MOF-801 nanoparticles (NPs) with good biocompatibility were used as a cryoprotectant that is well dispersed and colloidal-stable in an aqueous solution. The MOF NP size was precisely controlled, and 10, 35, 100, and 250 nm NPs were prepared. The specific IBPs-mimicking pendants (valine and threonine) were simply introduced into the MOF NP-surface through the acrylate-based functionalization to endow with hydrophilic and hydrophobic dualities. When small-sized MOF-801 NPs were attached to ice, they confined ice growth in high curvature between the adsorption sites because of the decreased radius of the convex area of the growth region, leading to highly enhanced ice recrystallization inhibition (IRI). Surface-functionalized MOF NPs could increase the number of anchored clathrate water molecules with hydrophilic/hydrophobic balance of the ice-binding moiety, effectively inhibiting ice growth. The MOF-801 NPs were biocompatible with various cell lines regardless of concentration or NP surface-functionalization, whereas the smaller-sized surface-functionalized NPs showed a good cell recovery rate after freezing/thawing by induction of IRI. This study provides a strategy for the fabrication of low-cost, high-volume antifreeze nanoagents that can extend useful applications to organ transplantation, cord blood storage, and vaccines/drugs.

An Open-Label, Multicentre, Observational, Post-Marketing Study to Monitor the Safety and Effectiveness of Umeclidinium/Vilanterol in Korean Patients.

BACKGROUND: Umeclidinium/vilanterol (UMEC/VI; ANORO ELLIPTA, GSK) is a commonly used dual bronchodilator. This study evaluated the safety and effectiveness of UMEC/VI in Korean patients with chronic obstructive pulmonary disease (COPD) over a 6-year period. METHODS: This was an open-label, multicentre, observational, post-marketing surveillance study. A total of 3,375 patients were enrolled consecutively in 52 hospitals, by 53 physicians, between July 2014 and July 2020. Patients who were administered UMEC/VI (fixed-dose 62.5 µg/25 µg) at least once and were monitored for safety and effectiveness were included in the analysis. Incidence and severity of adverse events (AEs) reported after administrating at least one dose of UMEC/VI were monitored, including unexpected adverse events (UAEs) and adverse drug reactions (ADRs). Effectiveness of UMEC/VI after 24 weeks of administration was also assessed using physician's evaluation (effective, ineffective/no change, worsening, indeterminable) and lung function improvement. RESULTS: Of 3,375 patients, 3,086 were included in the safety assessment group (mean age±standard deviation: 69.76±8.80 years; 85.9% male [n=2,652]; 73.1% aged ≥65 years [n=2,255]). The overall incidence of AEs was 28.8% (n=890), of which 2.2% (n=67) were ADRs. Serious AEs and UAEs were reported in 181 (5.9%) and 665 (21.6%) patients, respectively, and two patients (<0.1%) reported unexpected severe ADR. Of the 903/3,086 patients analysed for effectiveness, most (82.8%, n=748) showed overall disease improvement after UMEC/VI treatment. CONCLUSION: This study confirmed UMEC/VI administered to Korean patients according to the prescribing information was well-tolerated and can be considered an effective option for COPD treatment.

Treatment patterns and cost of exacerbations in patients with chronic obstructive pulmonary disease using multiple inhaler triple therapy in South Korea.

BACKGROUND: Multiple inhaler triple therapy (MITT), comprising inhaled corticosteroids (ICS), long-acting beta-agonists (LABA), and long-acting muscarinic antagonists (LAMA), has been used as an escalation treatment for patients with chronic obstructive pulmonary disease (COPD). However, real-world use of MITT has not been investigated in Asia, including South Korea. This study reports baseline characteristics of patients with COPD initiated on MITT in South Korea, and their treatment patterns. Healthcare resource utilization (HRU) and costs associated with COPD exacerbations following MITT initiation were also assessed. METHODS: This was a retrospective cohort study using the South Korea National Health Insurance database (2014-2018). Included patients were ≥ 40 years, had a COPD diagnosis, were newly initiated on MITT and had ≥ 12 months' data both before (baseline) and after index date (the first day with overlapping supply of all MITT components). Treatment immediately before initiation and immediately following discontinuation of MITT were identified, and proportion of days covered (PDC) by MITT was calculated. HRU and costs (per person per year [PPPY]) associated with exacerbations were identified following MITT initiation; costs were calculated using the average 2020 exchange rate (0.0008 USD/KRW). RESULTS: Among 37,400 patients, the mean age was 69 (SD 10) years and 73% were males; 56% had ≥ 1 COPD exacerbation during the baseline period, with a mean of 2 (SD 5) events/year. ICS/LABA was the most frequent regimen prescribed immediately before initiation (37%) and immediately following discontinuation (41% of 34,264 patients) of MITT. At 3, 6, and 12 months from treatment initiation, mean PDC was 81%, 63% and 49%, respectively; median treatment duration was 102 days. The mean (95% confidence interval [CI]) number of total visits for severe COPD exacerbations was 0.77 PPPY (0.75-0.78); mean PPPY total healthcare costs were 2093 USD. CONCLUSIONS: Patients with COPD in South Korea experienced frequent exacerbations prior to MITT, and PDC by MITT was low. Patients may benefit from early optimization of COPD therapy, and greater emphasis on adherence to inhaled COPD therapy. Severe exacerbations were found to incur substantial costs; treatment alternatives that can reduce the rate of severe exacerbations are likely to minimize healthcare costs.

Synthesis of Yttria-Stabilized Zirconia Nanospheres from Zirconium-Based Metal-Organic Frameworks and the Dielectric Properties.

Yttria-stabilized zirconia (YSZ) nanospheres were synthesized by calcination at 900 °C after the adsorption of Y3+ ions into the pores of a zirconium-based metal-organic framework (MOF). The synthesized 3YSZ (zirconia doped with 3 mol% Y2O3), 8YSZ (8 mol% Y2O3), and 30YSZ (30 mol% Y2O3) nanospheres were found to exhibit uniform sizes and shapes. Complex permittivity and complex permeability were carried out in K-band (i.e., 18-26.5 GHz) to determine their suitability for use as low-k materials in 5G communications. The real and imaginary parts of the permittivity of the sintered 3YSZ were determined to be 21.24 and 0.12, respectively, while those of 8YSZ were 22.80 and 0.16, and those of 30YSZ were 7.16 and 0.38. Control of the real part of the permittivity in the sintered YSZ was facilitated by modifying the Y2O3 content, thereby rendering this material an electronic ceramic with potential for use in high-frequency 5G communications due to its excellent mechanical properties, high chemical resistance, and good thermal stability. In particular, it could be employed as an exterior material for electronic communication products requiring the minimization of information loss.