Real-world prescription of anti-COVID-19 drugs in hospitalized patients with COVID-19 in Japan

by Haruka Shida, Maki Komamine, Kazuhiro Kajiyama, Takashi Waki, Hotaka Maruyama, Yoshiaki Uyama

Objective

Prescription trends and patterns of anti-COVID-19 drugs in hospitalized patients were examined based on real world data to understand the use of anti-COVID-19 drugs in clinical practice in Japan.

Design

The longitudinal and cross-sectional study was conducted utilizing data from January 1, 2019 to December 31, 2021 of the MID-NET^® medical information database, which stored the electronic medical records, administrative claim data, and diagnosis procedure combination data of patients in Japan.

Participants

Hospitalized patients with a COVID-19-related diagnosis who received at least one anti-COVID-19 drug between April 1, 2020 and December 31, 2021.

Exposures

The following 14 drugs were included in this study: remdesivir, baricitinib, combination product of casirivimab and imdevimab, favipiravir, dexamethasone, ivermectin, azithromycin, nafamostat mesylate, camostat mesylate, ciclesonide, tocilizumab, sarilumab, combination product of lopinavir and ritonavir, and hydroxychloroquine.

Results

We identified 5,717 patients hospitalized with COVID-19 and prescribed at least one anti-COVID-19 drug. The entire cohort generally included patients over 41–50 years and more males. The most common prescription pattern was dexamethasone monotherapy (22.9%), followed by the concomitant use of remdesivir and dexamethasone (15.0%), azithromycin monotherapy (15.0%), remdesivir monotherapy (10.2%), and nafamostat mesylate monotherapy (8.5%). However, an often prescribed anti-COVID-19 drug differed depending on the period.

Conclusions and relevance

This study revealed the real-world situation of anti-COVID-19 drug prescriptions in hospitalized COVID-19 patients in Japan. A prescribed drug would depend on the latest scientific evidence, such as efficacy, safety, and approval status, at the time of prescription. Understanding the prescription of anti-COVID-19 drugs will be important for providing the most up-to-date treatments to patients and evaluating the benefit and/or risk of anti-COVID-19 drugs based on the utilization of an electronic medical record database.

The relationship between sleep, gut microbiota, and metabolome in patients with depression and anxiety: A secondary analysis of the observational study

by Arisa Tanaka, Kenji Sanada, Katsuma Miyaho, Tomoyuki Tachibana, Shunya Kurokawa, Chiharu Ishii, Yoshihiro Noda, Shinichiro Nakajima, Shinji Fukuda, Masaru Mimura, Taishiro Kishimoto, Akira Iwanami

Background

Growing attention is paid to the association between alterations in the gut microbiota and their metabolites in patients with psychiatric disorders. Our study aimed to determine how gut microbiota and metabolomes are related to the sleep quality among patients with depression and anxiety disorders by analyzing the datasets of our previous study.

Methods

Samples were collected from 40 patients (depression: 32 patients [80.0%]); anxiety disorders: 8 patients [20.0%]) in this study. Gut microbiomes were analyzed using 16S rRNA gene sequencing and gut metabolomes were analyzed by a mass spectrometry approach. Based on the Pittsburgh Sleep Quality Index (PSQI), patients were categorized into two groups: the insomnia group (PSQI score ≥ 9, n = 20) and the non-insomnia group (PSQI score Results

The insomnia group showed a lower alpha diversity in the Chao1 and Shannon indices than the non-insomnia group after the false discovery rate (FDR) correction. The relative abundance of genus Bacteroides showed a positive correlation with PSQI scores in the non-insomnia group. The concentrations of glucosamine and N-methylglutamate were significantly higher in the insomnia group than in the non-insomnia group.

Conclusions

Our findings suggest that specific taxa could affect the sleep quality among patients with depression and anxiety disorders. Further studies are needed to elucidate the impact of sleep on specific gut microbiota and metabolomes in depression and anxiety disorders.

High frequency of germline recombination in Nestin-Cre transgenic mice crossed with Glucagon-like peptide 1 receptor floxed mice

by Yusuke Kajitani, Takashi Miyazawa, Tomoaki Inoue, Nao Kajitani, Masamichi Fujita, Yukina Takeichi, Yasutaka Miyachi, Ryuichi Sakamoto, Yoshihiro Ogawa

The Cre-loxP strategy for tissue-specific gene inactivation has become a widely employed tool in several research studies. Conversely, inadequate breeding and genotyping without considering the potential for non-specific Cre-recombinase expression may lead to misinterpretations of results. Nestin-Cre transgenic mice, widely used for the selective deletion of genes in neurons, have been observed to have an incidence of Cre-line germline recombination. In this study, we attempted to generate neuron-specific Glucagon-like peptide 1 receptor (Glp1r) knock-out mice by crossing mice harboring the Nestin-Cre transgene with mice harboring the Glp1r gene modified with loxP insertion, in order to elucidate the role of Glp1r signaling in the nervous system. Surprisingly, during this breeding process, we discovered that the null allele emerged in the offspring irrespective of the presence or absence of the Nestin-Cre transgene, with a high probability of occurrence (93.6%). To elucidate the cause of this null allele, we conducted breeding experiments between mice carrying the heterozygous Glp1r null allele but lacking the Nestin-Cre transgene. We confirmed that the null allele was inherited by the offspring independently of the Nestin-Cre transgene. Furthermore, we assessed the gene expression, protein expression, and phenotype of mice carrying the homozygous Glp1r null allele generated from the aforementioned breeding, thereby confirming that the null allele indeed caused a global knock-out of Glp1r. These findings suggest that the null allele in the NestinCre-Glp1r floxed breeding arose due to germline recombination. Moreover, we demonstrated the possibility that germline recombination may occur not only during the spermatogenesis at testis but also during epididymal sperm maturation. The striking frequency of germline recombination in the Nestin-Cre driver underscores the necessity for caution when implementing precise breeding strategies and employing suitable genotyping methods.

Hydrogen attenuates endothelial glycocalyx damage associated with partial cardiopulmonary bypass in rats

by Hiroki Iwata, Takasumi Katoh, Sang Kien Truong, Tsunehisa Sato, Shingo Kawashima, Soichiro Mimuro, Yoshiki Nakajima

Cardiopulmonary bypass (CPB) causes systemic inflammation and endothelial glycocalyx damage. Hydrogen has anti-oxidant and anti-inflammatory properties; therefore, we hypothesized that hydrogen would alleviate endothelial glycocalyx damage caused by CPB. Twenty-eight male Sprague–Dawley rats were randomly divided into four groups (n = 7 per group), as follows: sham, control, 2% hydrogen, and 4% hydrogen. The rats were subjected to 90 minutes of partial CPB followed by 120 minutes of observation. In the hydrogen groups, hydrogen was administered via the ventilator and artificial lung during CPB, and via the ventilator for 60 minutes after CPB. After observation, blood collection, lung extraction, and perfusion fixation were performed, and the heart, lung, and brain endothelial glycocalyx thickness was measured by electron microscopy. The serum syndecan-1 concentration, a glycocalyx component, in the 4% hydrogen group (5.7 ± 4.4 pg/mL) was lower than in the control (19.5 ± 6.6 pg/mL) and 2% hydrogen (19.8 ± 5.0 pg/mL) groups (P P = 0.999). The endothelial glycocalyces of the heart and lung in the 4% hydrogen group were thicker than in the control group. The 4% hydrogen group had lower inflammatory cytokine concentrations (interleukin-1β and tumor necrosis factor-α) in serum and lung tissue, as well as a lower serum malondialdehyde concentration, than the control group. The 2% hydrogen group showed no significant difference in the serum syndecan-1 concentration compared with the control group. However, non-significant decreases in serum and lung tissue inflammatory cytokine concentrations, as well as in serum malondialdehyde concentration, were observed. Administration of 4% hydrogen via artificial and autologous lungs attenuated endothelial glycocalyx damage caused by partial CPB in rats, which might be mediated by the anti-inflammatory and anti-oxidant properties of hydrogen.

Analysis of uterine evacuation methods in postabortion care after implementation of a surveillance network (CLAP MUSA-Network) at a university hospital

by Nelio N. Veiga-Junior, Caroline Eugeni, Beatriz D. Kajiura, Priscilla B. F. Dantas, Caroline B. Trabach, Aline A. Junqueira, Carina C. Nunes, Luiz F. Baccaro

Background

Management of uterine evacuation is essential for increasing safe abortion care. Monitoring through surveillance systems tracks changes in clinical practice and provides information to improve equity in abortion care quality.

Objective

This study aimed to evaluate the frequency of manual vacuum aspiration (MVA) and medical abortion (MA), and identify the factors associated with each uterine evacuation method after surveillance network installation at a Brazilian hospital.

Methods

This cross-sectional study included women admitted for abortion or miscarriage to the University of Campinas Women’s Hospital, Brazil, between July 2017 and November 2020. The dependent variables were the use of MVA and MA with misoprostol. The independent variables were the patients’ clinical and sociodemographic data. The Cochran–Armitage, chi-square, and Mann–Whitney U tests, as well as multiple logistic regression analysis, were used to compare uterine evacuation methods.

Results

We enrolled 474 women in the study, 91.35% of whom underwent uterine evacuation via uterine curettage (78.75%), MVA (9.46%), or MA (11.54%). MVA use increased during the study period (Z = 9.85, p Conclusion

MVA use increased following the installation of a surveillance network for good clinical practice. Being part of a network that encourages the use of evidence-based methods provides an opportunity for healthcare facilities to increase access to safe abortions.