Real-World Safety and Effectiveness of Benralizumab in Japanese Patients with Severe Asthma: A Multicenter Prospective Observational Study.

Introduction: This study aimed to demonstrate whether benralizumab maintained the safety and effectiveness profiles established in randomized controlled trials among all patients with severe uncontrolled asthma initially prescribed benralizumab in the real-world setting in Japan. Methods: This was a prospective, observational, multicenter post-marketing study (ClinicalTrial.gov, NCT03588546). The safety and tolerability of benralizumab over 1 year were assessed by the incidence of adverse events (AEs), serious AEs, adverse drug reactions (ADRs), and serious ADRs. Patient background characteristics indicating a more frequent onset of ADRs with benralizumab were explored. The main effectiveness assessment was the change in Asthma Control Questionnaire-5 (ACQ-5) score from baseline. Patients with baseline ACQ-5 scores ≥1.5 were defined as having severe uncontrolled asthma. Results: In total, 632 patients were evaluated for safety and 274 for effectiveness; 139 patients were included in the severe uncontrolled asthma subgroup. ADRs were reported in 12.7% and serious AEs in 13.0% of patients. Serious infections occurred in 3.8%, serious hypersensitivity in 0.3%, and malignancy in 0.3% of patients. No helminthic infections occurred. In the effectiveness population, benralizumab improved the mean (standard deviation [95% confidence interval]) ACQ-5 score by -1.16 (1.40 [-1.36, -0.96]) from baseline; forced expiratory volume in 1 second by 0.151 (0.440 [0.09, 0.21]) L; and Mini-Asthma Quality of Life questionnaire score by 1.16 (1.29 [0.94, 1.38]) at the last observation. The annual asthma exacerbation rate was 0.42. A greater ACQ-5 score improvement was observed among patients with eosinophilic asthma characteristics. Conclusion: No new safety concerns were raised, and patients experienced benefits consistent with previous studies of benralizumab, thus supporting the use of benralizumab for the add-on maintenance treatment of patients with eosinophilic severe uncontrolled asthma.

Bacterial and fungal bioburden reduction on material surfaces using various sterilization techniques suitable for spacecraft decontamination.

Planetary protection is a guiding principle aiming to prevent microbial contamination of the solar system by spacecraft (forward contamination) and extraterrestrial contamination of the Earth (backward contamination). Bioburden reduction on spacecraft, including cruise and landing systems, is required to prevent microbial contamination from Earth during space exploration missions. Several sterilization methods are available; however, selecting appropriate methods is essential to eliminate a broad spectrum of microorganisms without damaging spacecraft components during manufacturing and assembly. Here, we compared the effects of different bioburden reduction techniques, including dry heat, UV light, isopropyl alcohol (IPA), hydrogen peroxide (H2O2), vaporized hydrogen peroxide (VHP), and oxygen and argon plasma on microorganisms with different resistance capacities. These microorganisms included Bacillus atrophaeus spores and Aspergillus niger spores, Deinococcus radiodurans, and Brevundimonas diminuta, all important microorganisms for considering planetary protection. Bacillus atrophaeus spores showed the highest resistance to dry heat but could be reliably sterilized (i.e., under detection limit) through extended time or increased temperature. Aspergillus niger spores and D. radiodurans were highly resistant to UV light. Seventy percent of IPA and 7.5% of H2O2 treatments effectively sterilized D. radiodurans and B. diminuta but showed no immediate bactericidal effect against B. atrophaeus spores. IPA immediately sterilized A. niger spores, but H2O2 did not. During VHP treatment under reduced pressure, viable B. atrophaeus spores and A. niger spores were quickly reduced by approximately two log orders. Oxygen plasma sterilized D. radiodurans but did not eliminate B. atrophaeus spores. In contrast, argon plasma sterilized B. atrophaeus but not D. radiodurans. Therefore, dry heat could be used for heat-resistant component bioburden reduction, and VHP or plasma for non-heat-resistant components in bulk bioburden reduction. Furthermore, IPA, H2O2, or UV could be used for additional surface bioburden reduction during assembly and testing. The systemic comparison of sterilization efficiencies under identical experimental conditions in this study provides basic criteria for determining which sterilization techniques should be selected during bioburden reduction for forward planetary protection.

The long-term safety and tolerability of anifrolumab for patients with systemic lupus erythematosus in Japan: TULIP-LTE subgroup analysis.

OBJECTIVES: Evaluate the long-term safety and tolerability of anifrolumab 300 mg, alongside standard therapy, in patients from Japan with systemic lupus erythematosus (SLE) in the TULIP-LTE trial (NCT02794285). METHODS: TULIP-LTE was a 3-year, randomized, double-blind, placebo-controlled long-term extension (LTE) of the TULIP trials. The primary safety outcome included serious adverse events (SAEs) and AEs of special interest (AESIs) during the LTE period. Exploratory efficacy outcomes included SLE Disease Activity Index 2000 (SLEDAI-2K) scores and glucocorticoid use. We performed a post hoc subgroup analysis of patients who enrolled in Japan. RESULTS: Exposure-adjusted incidence rates of SAEs during the LTE and follow-up for patients receiving anifrolumab 300 mg (n=21) were 8.7 per 100 patient-years; AESIs included influenza (6.9) and herpes zoster (3.5). One of three patients receiving placebo had an SAE (13.9). One patient per group discontinued due to an AE. There were no deaths. During the TULIP+LTE period, patients receiving anifrolumab 300 mg (n=24) had sustained reduction from baseline in mean SLEDAI-2K scores and cumulative glucocorticoid dosage. CONCLUSIONS: Anifrolumab 300 mg showed a favourable benefit-risk profile for the long-term treatment of adult patients with moderate to severe SLE from Japan, with safety, tolerability, and efficacy profiles consistent with the overall population.

Tumor immune microenvironment and clinical outcomes in stage IV urothelial cancer: YODO study.

BACKGROUND: Bladder cancer is the 10th most common cancer globally, with a growing incidence in Japan. Evaluation of molecular, genetic, and cellular biomarkers that predict treatment response and prognosis in patients with metastatic urothelial carcinoma (mUC) may help optimize sequential treatment strategies with chemotherapy and immune checkpoint inhibitors (ICIs). METHODS: This multicenter, retrospective cohort study, evaluated programmed death-ligand 1 (PD-L1) expression, tumor mutational burden (TMB), and cancer-immune phenotype as predictive prognostic biomarkers following first-/second-line treatment in Japanese adult patients with mUC. The primary endpoint was prevalence of PD-L1 expression. Secondary endpoints were TMB, overall survival (OS), and progression-free survival (PFS) from initiation of first-line treatment, and exploratory endpoints were cancer-immune phenotype, OS, PFS, and treatment response according to potential biomarker status. RESULTS: Of the 143 patients included (mean age 71.7 years), PD-L1 expression was high in 29.4% of patients. Non-synonymous TMB was high in 33.6% and low in 66.4%. Cancer-immune phenotype was immune-desert in 62.9%, immune-excluded in 30.8%, and inflamed in 6.3%. Median OS and PFS following first-line treatment were 18.2 and 7.4 months, respectively. Overall response to second-line treatment was slightly better with high versus low/negative PD-L1 expression. PD-L1 expression and TMB were non-significant predictors of OS or PFS, whereas immune-excluded phenotype was associated with better OS in comparison with immune-desert phenotype. CONCLUSION: PD-L1 expression and TMB were non-significant predictors of prognosis after first-line treatment in Japanese patients with mUC, but cancer-immune phenotype may be an important prognostic factor in chemotherapy-ICI sequential treatment strategies. Clinical trial registration number UMIN000037727.

Characterization of Severe Uncontrolled Asthma in Japan: Analysis of Baseline Data from the PROSPECT Study.

Purpose: Treatment patterns and patient characteristics are not well elucidated among Japanese patients with severe uncontrolled asthma who currently have various treatment options, including biologics. We analyzed baseline characteristics of patients who did/did not initiate biologic treatment in PROSPECT, a 24-month observational study. Patients and Methods: Patients with severe uncontrolled asthma were prospectively enrolled at 34 sites in Japan from December 2019 to September 2021. The enrolled population was divided based on initiation/non-initiation of biologic treatment within 12 weeks after enrollment. Patient demographics, clinical characteristics, biomarker levels, and asthma-related treatment were assessed at enrollment. Results: Of 289 patients meeting the enrollment criteria, 127 patients initiated biologic treatment (BIO group: omalizumab, n = 16; mepolizumab, n = 10; benralizumab, n = 41; and dupilumab, n = 60) and 162 patients did not (non-BIO group). The proportion of patients with ≥2 asthma exacerbations was higher in the BIO group than the non-BIO group (65.0% vs 47.5%). Patients receiving omalizumab had the highest frequency of allergic rhinitis (87.5% vs other BIOs: 40.0%-53.3%). Patients receiving benralizumab and dupilumab had the highest incidence of nasal polyps (benralizumab: 19.5%, dupilumab: 23.3%, other BIOs: 0.0%). The proportion of patients with blood eosinophils ≥300 cells/µL was higher with benralizumab (75.6%) than other BIOs (26.7%-42.9%). Conclusion: This analysis of baseline data from the PROSPECT study is the first to clarify the characteristics of Japanese patients with severe uncontrolled asthma. BIOs were not necessarily prescribed to patients in whom they were indicated; however, for patients who received them, selection appeared to be made appropriately based on asthma phenotypes.

Sterilization characteristics of narrow tubing by nitrogen oxides generated in atmospheric pressure air plasma.

The sterilization characteristics of active species generated by an atmospheric dielectric barrier discharge plasma using air and oxygen at the inner surface of silicone tubing were investigated. A dielectric barrier discharge torch plasma device was installed at one end of the tube and generated long-lived active species that flowed into the tube. A strip-type biological indicator with a 105-cell bacterial spore was placed at the opposite end of the 60 cm tube. Sterilization was completed within 30 min by active particles generated from the air plasma. The main factors contributing to the sterilization by air plasma were HNO3 and N2O5. When organic materials (keratin, aspartic acid, and dipicolinic acid) reflecting components of the bacterial spore, were treated by the sterilization procedure there was little effect on dipicolinic acid. Keratin was oxidized by ozone and NOx generated from the oxygen and air plasmas, respectively. Aspartic acid underwent little change in composition from ozone generated from the oxygen plasma, whereas nitro (NO2), nitroso (NO), and aldehyde (CHO) groups were formed from ozone and NOx generated from the air plasma.

Real-World Evidence on the Diagnostic and Clinical Characteristics of Asthma in Japanese Patients with COPD: The ACO Japan Cohort Study.

Introduction: The ACO Japan Cohort Study, a multicenter observational study, investigated the proportion of patients with chronic obstructive pulmonary disease (COPD) who met the Japanese Respiratory Society (JRS) asthma-COPD overlap (ACO) diagnostic criteria, characteristics of ACO and non-ACO patients, and the patient transitions between ACO/non-ACO diagnosis over 2 years. Patients and Methods: Patients with COPD were consecutively enrolled between June and December 2018 and followed up continuously for 2 years. All participating study sites were medical institutions where respiratory specialists routinely conducted medical examinations/tests required for ACO diagnosis. Results: Among 708 patients with COPD, 101 (14.3%), 118 (16.7%), and 125 (17.7%) were diagnosed with ACO at registration, 1 year, and 2 years, respectively. In total, 22.6% of patients lacked the data necessary for ACO diagnosis throughout the 2 years. Among patients who had the necessary data for ACO diagnosis, 24.7% were diagnosed with ACO at 2 years. More ACO patients had moderate or severe exacerbations in the past year than non-ACO patients at registration (15.8% vs 6.3%, p = 0.049) and 1 year (19.4% vs 7.6%, p = 0.025). ACO patients had a greater decrease in mean forced expiratory volume in one second over 2 years than non-ACO patients (-92.0 vs 43.4 mL). Among patients diagnosed with ACO at registration, 21.4% transitioned to non-ACO after 1 year. Conversely, almost all non-ACO patients at registration remained non-ACO after 1 year. Conclusion: COPD patients with ACO determined by the JRS criteria had a high risk of exacerbations and a rapid decline in respiratory function, indicating that the JRS criteria for ACO are useful for identifying high-risk COPD patients. Testing necessary for ACO diagnosis is insufficiently performed even in real-world clinical practice of COPD specialists.

The efficacy and safety of anifrolumab in Japanese patients with systemic lupus erythematosus: TULIP-2 subanalysis.

OBJECTIVES: Evaluate the efficacy and safety of anifrolumab in the subpopulation of Japanese patients with systemic lupus erythematosus (SLE) in phase 3 TULIP-2 trial. METHODS: TULIP-2 was a 52-week randomized placebo-controlled trial (N = 362) that evaluated efficacy and safety of anifrolumab 300 mg IV every 4 weeks vs. placebo in patients with moderate to severe SLE who were receiving standard therapy. We performed a post hoc analysis of the primary and key secondary endpoints, and safety, of TULIP-2 in the Japanese subpopulation. RESULTS: In the Japanese subpopulation (anifrolumab, n = 24; placebo, n = 19), the proportion of patients who achieved a British Isles Lupus Assessment Group-based Composite Lupus Assessment response at Week 52 (primary endpoint) was greater in the anifrolumab group vs. placebo [50.0% (12/24) vs. 15.8% (3/19); treatment difference: 34.2%, 95% confidence interval 6.9, 61.5; nominal p = .014]. Improvement in skin activity and flare rates (key secondary endpoints) were favourable for anifrolumab vs. placebo. Consistent with the overall population, anifrolumab had an acceptable safety and tolerability profile. CONCLUSIONS: The efficacy and safety of anifrolumab 300 mg in Japanese patients with SLE was consistent with the demonstrated clinical profile of anifrolumab for the overall TULIP-2 population.

One-year safety and tolerability of tezepelumab in Japanese patients with severe uncontrolled asthma: results of the NOZOMI study.

OBJECTIVE: To assess the long-term safety of tezepelumab in Japanese patients with severe uncontrolled asthma. METHODS: This phase III, 52-week, open-label, single-arm study (NOZOMI, NCT04048343) evaluated the safety/tolerability of subcutaneous (SC) tezepelumab 210 mg every 4 weeks (Q4W) in Japanese patients aged 12-80 years with severe uncontrolled asthma using medium- to high-dose inhaled corticosteroids and at least one additional asthma controller medication, with/without oral corticosteroids. Exploratory outcomes included efficacy (asthma exacerbations, lung function, and asthma control), pharmacokinetic parameters, and immunogenicity. RESULTS: Among 65 patients (median age 52 years), 39 (60%) experienced 94 adverse events (AEs; predominantly nasopharyngitis [13/65]) of mild (49.2%), moderate (7.7%), or severe (3.1%) intensity. Two patients had transient injection site erythema related to tezepelumab. Four patients reported serious AEs unrelated to tezepelumab and one AE led to treatment discontinuation. AEs of special interest were infrequent and generally mild/moderate. Apart from a decrease in blood eosinophils (an expected pharmacodynamic effect), no notable trends/clinically relevant changes in hematology, clinical chemistry, or urinalysis parameters were observed. Among exploratory outcomes, tezepelumab was associated with a low annualized asthma exacerbation rate over the study period (0.11/patient-year), improved lung function (mean [standard deviation] change from baseline of 0.075 [0.226] L in pre-dose/pre-bronchodilator forced expiratory volume in 1 s), and better asthma control versus baseline (responder rate: 71.4% at Week 52). CONCLUSION: Tezepelumab 210 mg SC Q4W in Japanese patients with severe uncontrolled asthma showed safety/tolerability profiles similar to international data, with low exacerbation rates and improvements in lung function and asthma control.

Efficacy and safety of tezepelumab in patients recruited in Japan who participated in the phase 3 NAVIGATOR study.

BACKGROUND: Tezepelumab, a human monoclonal antibody, blocks the activity of thymic stromal lymphopoietin. In the phase 3 NAVIGATOR study (NCT03347279), tezepelumab reduced exacerbations by 56% compared with placebo in adults and adolescents with severe, uncontrolled asthma. This analysis evaluated the efficacy and safety of tezepelumab in NAVIGATOR patients recruited in Japan. METHODS: NAVIGATOR was a phase 3, multicenter, randomized, double-blind, placebo-controlled study. Patients (12-80 years old) were randomized 1:1 to receive tezepelumab 210 mg or placebo subcutaneously every 4 weeks for 52 weeks. Endpoints assessed included: the annualized asthma exacerbation rate (AAER) over 52 weeks (primary endpoint) and the change from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 s (FEV1) and Asthma Control Questionnaire (ACQ)-6 score. The safety of tezepelumab was also assessed. RESULTS: Overall, 97 patients recruited in Japan were randomized (tezepelumab, n = 58; placebo, n = 39). The AAER over 52 weeks was 1.54 (95% confidence interval [CI]: 0.90, 2.64) with tezepelumab compared with 3.12 (95% CI: 1.82, 5.35) with placebo (rate ratio: 0.49 [95% CI: 0.25, 0.99]; 51% reduction). For tezepelumab and placebo, the least-squares mean (standard error) change from baseline to week 52 for pre-bronchodilator FEV1 was 0.23 (0.06) L and 0.19 (0.07) L and the ACQ-6 score was -1.12 (0.15) and -0.97 (0.19), respectively. The frequency of adverse events was similar between treatment groups (tezepelumab, 86.2%; placebo, 87.2%). CONCLUSIONS: Tezepelumab reduced exacerbations compared with placebo, and was well tolerated, in NAVIGATOR patients with severe, uncontrolled asthma recruited in Japan.

Effect of timing of bronchodilator therapy initiation on exacerbations in patients with chronic obstructive pulmonary disease: a retrospective cohort study.

BACKGROUND: The benefit of prompt vs delayed treatment initiation with inhaled long-acting bronchodilators in reducing exacerbations in chronic obstructive pulmonary disease (COPD) is unclear. This study aimed to investigate if long-acting bronchodilator therapy initiation within 30 days of COPD diagnosis reduces exacerbation risk in patients with COPD. METHODS: This was a retrospective cohort study of patients with COPD based on claims and electronic medical records data extracted from the Real World Data database. The index date (day 0) was the date of the first confirmed inpatient or outpatient COPD diagnosis between January 1, 2005, and December 31, 2018. Patients with COPD without an asthma diagnosis and aged ≥ 40 years at the index date were included. Patients who initiated inhaled long-acting bronchodilator therapy within the first 30 days (day 0 to day 29) were categorized into the "prompt therapy" group and the rest into the "delayed therapy" group. Time from day 30 post-diagnosis to the first exacerbation and annual exacerbation rate (AER) were evaluated for the overall population and those stratified by COPD phenotype, including chronic bronchitis (CB) and emphysema. RESULTS: Compared with the delayed therapy group (n = 1516), time to first exacerbation was prolonged (hazard ratio 0.78; 95% confidence interval [CI] [0.70, 0.87]) and annual rates of moderate or severe exacerbations were lower (rate ratio 0.74; 95% CI [0.65, 0.84]) in the prompt therapy group (n = 1466). Similarly, time to first exacerbation was prolonged and AERs were lower in the prompt therapy group in the subgroups of patients with CB or emphysema. CONCLUSIONS: This is the first study to demonstrate a prolonged time to first exacerbation upon initiation of long-acting bronchodilators within 30 days of COPD diagnosis. A beneficial effect was also observed in patients with CB and emphysema. Our data support advising patients to initiate long-acting bronchodilators soon after COPD diagnosis.

Real-world treatment patterns and clinical outcomes of Japanese patients with non-muscle invasive bladder cancer receiving intravesical bacillus Calmette-Guérin treatment.

OBJECTIVES: To investigate current patterns and outcomes of intravesical bacillus Calmette-Guérin treatment in Japanese patients with bladder cancer, including the proportion of patients completing induction therapy, and time to subsequent treatments. METHODS: This retrospective cohort study utilized administrative claims data from the Medical Data Vision Co., Ltd. database to identify patients with a diagnosis of bladder cancer who had received ≥1 prescription of intravesical bacillus Calmette-Guérin between April 2008 and September 2015, and had ≥1 database record dated ≥12 weeks after the initial bacillus Calmette-Guérin dose. Patients were followed until September 2018, the last date of available data, or in-hospital death. Patients receiving six doses of bacillus Calmette-Guérin at intervals of <21 days were considered to have completed induction according to guidelines. Time from initial bacillus Calmette-Guérin dose to subsequent bladder cancer treatment after the end of treatment was defined as the recurrence-free duration. RESULTS: Of 6140 patients identified (median age 73.0 years; 83.4% males), 4588 (74.7%) completed induction and 1552 (25.3%) did not. Median recurrence-free duration was 64.4, 77.7, and 31.6 months in the overall, complete-induction and incomplete-induction cohorts, respectively. Corresponding 3-year recurrence-free rate was 56.3%, 59.0%, and 48.2% in these groups. The rate of cystectomy was approximately 6% at 5 years in all cohorts. CONCLUSIONS: Approximately 75% of Japanese patients who undergo intravesical bacillus Calmette-Guérin treatment receive a guideline-compliant induction regimen, but outcomes were not satisfactory, highlighting the need for more effective treatments for non-muscle invasive bladder cancer.

Oxygen plasma modulates glucosinolate levels without affecting lipid contents and composition in Brassica napus seeds.

Rapeseed contains high levels of glucosinolates (GSLs), playing pivotal roles in defense against herbivores and pests. As their presence in rapeseed reduces the value of the meal for animal feeding, intensive efforts to reduce them produced low-seed GSL cultivars. However, there is no such variety suitable for the south part of Japan. Here, we tested the effects of cold oxygen plasma (oxygen CP) on seed germination and GSL and lipid content, in 3 rapeseed cultivars. According to the cultivars, oxygen CP slightly stimulated seed germination and modified the GSL levels, and decreased GSL levels in Kizakinonatane but increased those in Nanashikibu. In contrast, it negligibly affected the lipid content and composition in the 3 cultivars. Thus, oxygen CP modulated seed GSL levels without affecting seed viability and lipid content. Future optimization of this technique may help optimize rapeseed GSL content without plant breeding.

Removal of metal ions from water using oxygen plasma.

Zinc ion dissolved in water is attempted to be removed by generating the oxides of zinc using the oxygen gas in dielectric barrier discharge (DBD) plasma system. The removal rate of zinc oxides' production (ZnO and Zn(OH)2) are measured at different treatment periods by the oxygen plasma penetration in water. The removal rate of the deposit increases initially and then decreases with the treatment period. The maximum removal rate (29%) of zinc ion from water is achieved at the treatment period of 10 min, where pH is lower (7.4). From FTIR the generation properties of zinc oxide can be recognized. Initially the amount of the deposit increases with the ozone treatment period due to production of both ZnO and Zn(OH)2. After that, the production of Zn(OH)42- increases even when the total removal rate of the deposit decreases. Therefore, to remove zinc ion from water forming metal oxide deposit, the penetration amount of the active oxygens to the water must be controlled to keep the pH lower than around 7.5. Because with increasing pH amount of removal rate of zinc oxides' deposit decreases. The pH of the zinc dissolved water treated by ozone depends on both zinc ion and ozone concentration in water.

Safety and antitumor activity of acalabrutinib for relapsed/refractory B-cell malignancies: A Japanese phase I study.

This multicenter, open-label, phase I study assessed the safety and antitumor activity of acalabrutinib in Japanese patients with relapsed/refractory (r/r) B-cell malignancies. Parts 1 (dose confirmation) and 2 (dose expansion) of this three-part study are reported. Treatment was a single dose of 100 mg acalabrutinib (day 1), followed by a washout period and then twice daily 100 mg acalabrutinib in part 1, or twice daily 100 mg acalabrutinib in part 2. Patients from parts 1 and 2 with r/r chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), and r/r mantle cell lymphoma (MCL) were assessed as r/r CLL/SLL and r/r MCL cohorts, respectively. Twenty-five patients received treatment (part 1, n = 6). Median age was 71.0 years. Nine (one patient from part 1) and 13 (two patients from part 1) patients were included in the r/r CLL/SLL and r/r MCL cohorts, respectively. Treatment-related adverse events (AEs) occurred in 88% of patients (grade ≥3, 36%); the most common were headache (28%) and purpura (24%), both grade 1/2. No AEs resulted in treatment discontinuation or death. Median duration of treatment was 31, 20, and 7 months for part 1, r/r CLL/SLL cohort, and r/r MCL cohort, respectively. Overall response rate (ORR) was 89% and 62% for the r/r CLL/SLL and r/r MCL cohorts, respectively. The median progression-free survival (PFS) was not reached for the r/r CLL/SLL cohort and was 7 months for the r/r MCL cohort. Acalabrutinib (100 mg twice daily) was generally safe and well-tolerated in adult Japanese patients with B-cell malignancies.

Efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler delivered using co-suspension delivery technology in Japanese patients with moderate-to-very severe chronic obstructive pulmonary disease.

BACKGROUND: PINNACLE-4 evaluated the efficacy and safety of the long-acting muscarinic antagonist/long-acting ß2-agonist fixed-dose combination glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) in patients from Asia, Europe, and the USA with moderate-to-very severe chronic obstructive pulmonary disease (COPD). This pre-specified analysis included Japanese patients in PINNACLE-4. METHODS: In this double-blind randomized study (NCT02343458), patients received GFF MDI (18/9.6 µg), glycopyrrolate (GP) MDI (18 µg), formoterol fumarate (FF) MDI (9.6 µg), or placebo MDI twice daily for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over Weeks 12-24. Secondary lung function endpoints, patient-reported outcomes, and safety were assessed. The Japanese subpopulation (n = 150) analyses were exploratory. RESULTS: GFF MDI improved change from baseline in morning pre-dose trough FEV1 over Weeks 12-24 versus GP MDI, FF MDI, and placebo MDI (least squares mean [LSM] differences [95% confidence interval]: 69 [8-131], 60 [-1 to 121], and 275 [180-370] mL, respectively). GFF MDI numerically improved Transition Dyspnea Index focal score and change from baseline in St George's Respiratory Questionnaire total score versus placebo MDI (LSM differences 0.19 and -3.78, respectively). Treatment-related adverse events occurred in ≤4.5% of patients in any treatment group. CONCLUSIONS: GFF MDI improved lung function versus monocomponents and placebo MDI in the Japan subpopulation of PINNACLE-4. The efficacy and safety results were generally consistent with those of the global study population, supporting the use of GFF MDI in Japanese patients with moderate-to-very severe COPD.

A Non-Interventional, Cross-Sectional Study to Evaluate Factors Relating to Daily Step Counts and Physical Activity in Japanese Patients with Chronic Obstructive Pulmonary Disease: STEP COPD.

Purpose: Patients with chronic obstructive pulmonary disease (COPD) have decreased physical activity (PA) compared with healthy adults. As lower PA is associated with increased mortality, improving PA is an important objective for COPD management. This large-scale, multicenter, non-interventional, cross-sectional study examined the activity status of COPD patients in Japan and explored factors related to PA. Patients and Methods: Outpatients aged ≥40 years with confirmed COPD diagnosis and pulmonary function test data were enrolled. Primary study outcomes were measurement of daily steps (over 14 consecutive days, using an activity monitor), assessment of activity time by activity intensity (using metabolic equivalents [METs]), and evaluation of correlation between PA and patient characteristics. Secondary outcomes included further investigation of the influence of patient characteristics on PA. Results: Data from 417 patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages I (29.5%), II (43.9%), III (23.5%), and IV (3.1%) were evaluated. Median (Q1, Q3) daily step count was 3440.8 (1831.3, 5709.3). Median (Q1, Q3) durations of PA at ≥3 (moderate-to-vigorous) and ≥2 METs (light-to-vigorous) were 18.7 (6.5, 41.3) and 186.9 (126.9, 259.2) minutes, respectively. For >30% of patients, time spent in ≥3 METs activity was ≤10 minutes. Unemployment was significantly correlated with reduced activity time (≥3 and ≥2 METs) and step count. Severe GOLD stage was significantly correlated with reduced activity time (≥3 and ≥2 METs). High modified Medical Research Council (mMRC) dyspnea score was significantly correlated with reduced activity time (≥3 METs) and step count. Patients tended to overestimate the time spent in activities requiring ≥2 METs in their subjective reports compared with activity monitor measurements. Conclusion: Reduced PA was observed in the Japanese COPD patients with the majority of them being GOLD stage I/II. Employment status, GOLD stage, and mMRC dyspnea score could help identify patients at risk of reduced PA. Clinical Trial Registration: NCT03642613 (ClinicalTrials.gov); UMIN000032962 (UMIN-CTR, umin.ac.jp).

Evaluation of Low-Temperature Sterilization using Hydrogen Peroxide Gas Containing Peracetic Acid.

In low-temperature sterilization for the medical field, hydrogen peroxide sterilization is widely used for its safety. However, its low penetrability and residual amount of sterilant are major concerns. Recently, the combination of hydrogen peroxide and peracetic acid has been found to enforce sporicidal effect, with low concentration in hydrogen peroxide. The application of this finding in medical sterilization is still very limited. To elucidate the combination effect, we compare peracetic acid containing hydrogen peroxide gas sterilizer and conventional hydrogen peroxide gas (plasma) sterilizers. The sterilant penetrability was examined in hollow load process challenge devices with inner diameters of 1 and 2 mm and lengths of 1, 2, and 3 m. As a result, peracetic acid containing hydrogen peroxide gas sterilizer demonstrated total inactivation with all diameters and lengths and achieved the highest sterilant penetrability in this study. The amount of residual sterilant on the surface of the sterilized object was 4.2 µg/cm2, which corresponds to half amount of those of conventional hydrogen peroxide gas sterilizers. These results suggest that the addition of peracetic acid to hydrogen peroxide gas sterilizer can enhance sterilization efficiency and safety.

Association of low-dosage systemic corticosteroid use with disease burden in asthma.

There is an ongoing debate about the benefit-risk balance of systemic corticosteroids (SCS) in asthma treatment. We investigated the associations between SCS use and disease burden in a database cohort of asthmatics, categorized into SCS and non-SCS prescription at baseline and quartiles (Q) by cumulative SCS dosage. Of the 10,579 patients, the SCS cohort comprised 3103 patients (29.3%). Mean SCS dosages at baseline were 0.08, 0.29, 0.79, and 4.58 mg/day in Q1, Q2, Q3, and Q4, respectively. Similar SCS dosages were used within each quartile throughout the study period. No remarkable changes in asthma severity or control status were observed. All SCS cohorts had a higher risk of intermittent SCS exposure during the observation period. SCS use was associated with osteoporosis, diabetes, anxiety/neurosis, and depression. SCS-dependent treatment does not necessarily lead to the future improvement of asthma control; rather, it may negatively impact systemic health, even at mean dosages <5 mg/day.