Exploration of the optimal GS-441524 trough concentration for treating COVID-19.

OBJECTIVES: Remdesivir (RDV) is the cornerstone for treating coronavirus disease 2019 (COVID-19). The active metabolite of RDV, GS-441524 (a nucleoside analogue), has high interindividual variability in plasma concentrations; however, its concentration-response relationship is still unclear. This study investigated the target GS-441524 trough concentration for symptom improvement in COVID-19 pneumonia. METHODS: This single-center, retrospective, observational study included Japanese patients (age ≥15 years) with COVID-19 pneumonia who were administered RDV for ≥3 days from May 2020 to August 2021. To determine the cut-off value of GS-441524 trough concentration on Day 3, achievement of the National Institute of Allergy and Infectious Disease Ordinal Scale (NIAID-OS) ≤3 after RDV administration was evaluated using the cumulative incidence function (CIF) with the Gray test and time-dependent receiver operating characteristic (ROC) analysis. Multivariate logistic regression analysis was performed to determine factors influencing GS-441524 target trough concentrations. RESULTS: The analysis comprised 59 patients. The CIF revealed that GS-441524 trough concentration ≥70 ng/mL was associated with the achievement of NIAID-OS ≤3 (P = 0.047), which was significant based on the time-dependent ROC analysis. Factors influencing GS-441524 trough concentration ≥70 ng/mL included a decrease in estimated glomerular filtration rate (eGFR) [adjusted odds ratio (aOR) = 0.96, 95% confidence interval (CI) 0.92-0.99; P = 0.027] and BMI ≥25 kg/m2 (aOR = 0.26, 95% CI 0.07-0.86; P = 0.031). CONCLUSION: GS-441524 trough concentration ≥70 ng/mL is a predictor of efficacy in COVID-19 pneumonia. The presence of lower eGFR or BMI ≥25 kg/m2 was associated with achieving GS-441524 trough concentration ≥70 ng/mL.

Overweight improves long-term survival in Japanese patients with asthma.

BACKGROUND: Obesity is a risk factor for severe and difficult-to-treat asthma. However, the impact of different physiques on long-term outcomes is poorly understood. We aimed to investigate the correlation between obesity and asthma-associated long-term mortality in Japanese adults. METHODS: From the data on 3146 individuals with air pollution-related respiratory diseases in the Omuta City Air Pollution-Related Health Damage Cohort Program, 697 adult patients with asthma were analyzed. Hazard ratios for long-term all-cause and respiratory disease -related mortality were compared in patients with different physiques using the Cox proportional hazard models. The classification of physiques was based on the WHO obesity criteria. RESULTS: Of the 697 patients, 439 died during the median observation period of 26.3 years. The number (% of total) of underweight, normal-weight, pre-obese, and obese class I-III individuals were 75 (10.8%), 459 (65.9%), 140 (20.1%), and 23 (3.3%), respectively. The Cox proportional hazard model (adjusted hazard ratio [95% confidence interval], P value) showed that pre-obese group had a significantly reduced risk for all-cause (0.65 [0.51 to 0.83], P < 0.05) and respiratory disease (0.55 [0.37 to 0.81], P < 0.05)-related mortality related to normal-weight group. CONCLUSIONS: Our cohort program demonstrated that being slightly overweight may reduce the risk of long-term mortality in patients with asthma. However, the influence of obesity on long-term outcomes remains unclear in asthma, because of the small number of obese patients included in our study. Our findings suggest that interventions, including nutrition and exercises, should be provided to Japanese patients with asthma.

Fulminant Tracheobronchial Aspergillosis in an Apparently Healthy Adult.

A 56-year-old healthy man who was a current smoker died from fulminant tracheobronchial aspergillosis despite a month of treatment with a combination of intravenous anti-fungal agents that had been started immediately after the diagnosis. This case report is important for understanding and managing fulminant Aspergillus infections in healthy subjects, although the pathogenesis and underlying pathways are still unknown.

[Nursing-home-acquired pneumococcal pneumonia--comparison of sputum cultures with Binax NOW Streptococcus pneumoniae urinary antigen assay].

To clarify the clinical significance of Pneumococcal pneumonia in nursing-home-acquired pneumonia, we examined the positive disease rate of using sputum cultures and the Binax NOW Streptococcus pneumoniae urinary antigen assay in 154 nursing-home patients with pneumonia. These included 54 males and 100 females with a mean age of 86.2 years. Bacteriological findings for sputum culture in 130 patients showed Streptococcus pneumoniae to be cultured in 11 cases (8%). In 72 in whom the Streptococcus pneumoniae-urinary antigen test (Binax NOW) was done, the urinary-antigen-positive rate (26/72 ; 36%) was higher than the culture positive rate for S. pneumoniae. Both examinations were done in 64 patients, among whom 5 in whom S. pneumoniae was cultured also had positive results for the urinary antigen test. Almost half of those undergoing percutaneous endoscopic gastroscopy (PEG) tube nutrition had positive results for the urinary antigen test, but not all such patients had positive cultures for S. pneumoniae. Although the culture-positive rate for S. pneumoniae in sputum was low, we concluded that S. pneumoniae was frequently linked to nursing-home-acquired pneumonia, especially in "total-care" patients.

Clinical efficacy of the transdermal tulobuterol patch in patients with chronic obstructive pulmonary disease: a comparison with slow-release theophylline.

BACKGROUND: There is insufficient evidence for the efficacy of a transdermal tulobuterol patch (TP), although combination therapy with bronchodilators is recommended for chronic obstructive pulmonary disease (COPD). OBJECTIVE: A randomized, controlled crossover study was conducted to evaluate the clinical efficacy and safety of the TP in 16 patients with COPD. Slow-release theophylline was used as a control drug. METHODS: Following a 2-week run-in period, patients were randomly allocated to two groups by the envelope method; they then received the TP and theophylline for 4 weeks each by the crossover method. Pulmonary function tests, peripheral blood examination, and electrocardiography were performed before and after each treatment period. Patients recorded in diaries their symptom scores, numbers of administrations of inhaled beta(2) agonists, and presence/absence of adverse reactions. RESULTS: Patients receiving TP exhibited significant improvement in the number and ease of sputum expectoration and in cough frequency score and wheezing severity score compared with baseline (p<0.05); the corresponding improvement in patients receiving theophylline was non-significant. Assessment of quality of life by the St. George's Hospital Respiratory Questionnaire revealed that treatment with TP was associated with significant improvement in symptoms, impact, and total scores compared with baseline (p<0.05); theophylline gave only a non-significant improvement in total score. Neither drug caused significant changes in the results of physiological examinations or in pulse or blood pressure. There was no difference in safety between the treatments. CONCLUSION: Treatment of COPD patients with TP is more effective than with theophylline.

[Antifungal susceptibility of Candida species causing candidemia in Kurume University Hospital and Shaiseikai Hutukaichi Hospital].

Prevention of candidemia has been difficult and empirical therapy may eventually reduce morbidity and mortality. Successful empirical therapies depend on understanding of fungal features and antifungal agents. Susceptibility to amphotericin B (AMPH-B), flucytosine (5-FC), fluconazole (FLCZ), itraconazole (ITCZ), miconazole (MCZ), and micafungin (MCFG) of 41 Candida species isolated from blood were determined. Candida albicans was the most common species (23 species), followed by C. parapsilosis (5 species), C. tropicalis (4 species), C. glabrata (3 species), C. guilliermondii (2 species), C. krusei (1 specie), and Candida spp (3 species). The isolation rates of the drug-resistant (DR) fungi were 5% for 5-FC. The rates of DR and susceptible dose dependent (S-DD) fungi were 0% and 2% for FLCZ, respectively. The rates of DR and S-DD fungi were 0% and 17% for ITCZ, respectively. No shift to resistant species in C. albicans occurred in our hospitals. All C. albicans were susceptible for the antifungal agents examined.