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Aims: A meta‐analysis of short‐term studies revealed no significant differences between the doses of asenapine, 10 and 20 mg/day, in the acute treatment of schizophrenia. However, it should be noted that many patients from clinical practice were excluded, and the dose–response to asenapine in a real‐world setting is still unclear. Additionally, the dose–response in the maintenance phase is not clear. This study aimed to evaluate the differences in the efficacy of different asenapine doses in patients with maintenance phase of schizophrenia in a real‐world setting. Methods: This study conducted post‐marketing surveillance of asenapine in clinical settings in Japan. It followed patients diagnosed with schizophrenia who received asenapine for the first time for a maximum of 52 weeks. These patients were divided into two categories based on their average daily asenapine dosage: ≤10 mg/day and >10 mg/day. Asenapine efficacy was assessed by adjusting for patient demographics using multivariate logistic regression analysis, employing the Clinical Global Impression‐Global Improvement (CGI‐I) scale, which has seven categories. Results: A total of 2774 patients were included in the analysis. Of these, 1689 and 1085 patients were treated with asenapine ≤10 mg/day and >10 mg/day, respectively. The CGI‐I improvement rate was significantly higher in the asenapine >10 group (p = 0.012) after adjusting for patient background factors. Conclusion: These results suggest that asenapine doses >10 mg/day may be more effective than 10 mg/day in the treatment of schizophrenia; however, further studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Abstract: Lowering the carburization temperature of Ti-oxide into TiC down to 1173K could be achieved by the addition of Co. Co-promoted TiC/SiO2 catalysts were prepared by the temperature programmed reaction (TPR) method. Co–Ti/SiO2 precursors were prepared by use of the successive impregnation method (sc) and the co-impregnation method (co). Samples were characterized by X-ray absorption fine structure (XAFS) measurements and X-ray diffraction (XRD) results. The carburization degree of TiC was affected by the method of Co addition. The carburization degree of sc Co–TiC/SiO2 was better than that of co Co–TiC/SiO2. The activity of thiophene hydrodesulfurization reaction at 693K on sc Co–TiC/SiO2 was higher than that on co Co–TiC/SiO2. The HDS activity was related to the carburization degree of TiC. [Copyright &y& Elsevier]

Background: We previously showed that ARCT-154, a self-amplifying mRNA COVID-19 vaccine, had improved immunogenicity and antibody persistence compared with conventional mRNA or adenovirus vector vaccines. In this study, we compared ARCT-2301, a bivalent self-amplifying mRNA vaccine (Asp614Gly and omicron BA.4/5 variant), with the bivalent Comirnaty omicron BA.4-5 vaccine, to determine whether this improved response persisted in bivalent formulations against different SARS-CoV-2 variants., Methods: This randomised, multicentre, phase 3, observer-masked, active-controlled comparative study was done at nine hospitals in Japan. Eligible participants were healthy Japanese adults, aged at least 18 years, who had previously received a full immunisation series of three to five doses of mRNA COVID-19 vaccines (Comirnaty or Spikevax [Moderna]), with the last dose received at least 3 months before screening for this trial. Participants were randomly assigned (1:1) to either ARCT-2301 or Comirnaty BA.4-5 mRNA vaccine using interactive computer-generated randomisation with a block size of four. Randomisation was stratified by gender (men vs women), age group (<65 years vs ≥65 years), type of vaccine used for last vaccination (bivalent omicron BA.1 vs bivalent omicron BA.4/5), and time since last COVID-19 vaccination (<5 months vs ≥5 months). ARCT-2301 was supplied in vials containing 100 μg lyophilised mRNA, 50 μg mRNA each coding for the full-length spike proteins of the ancestral Asp614Gly SARS-CoV-2 strain and omicron BA.4/5 variant. Immediately before use, each vial was reconstituted with 10 mL saline. The comparator original omicron BA.4/5 mRNA vaccine (Comirnaty BA.4-5) was supplied in ready-to-use vials containing a single dose of 30 μg mRNA in 0·3 mL volume. Both vaccines were administered by intramuscular injection in the deltoid of the non-dominant arm. The primary outcome of the study was to show non-inferiority of immunogenicity of ARCT-2301 versus Comirnaty BA.4-5 at day 29 as neutralising antibody geometric mean titres (GMT) and seroresponse rates against omicron BA.4/5. Primary analyses were done in a per-protocol manner. The trial is registered with the Japan Registry for Clinical Trials, jRCT2031230340., Findings: Between Sept 29 and Nov 18, 2023, we enrolled 930 participants (451 men and 479 women) to receive a booster dose of ARCT-2301 (n=465) or Comirnaty BA.4-5 (n=465). The primary immunogenicity outcome to show that the antibody response at day 29 against omicron BA.4/5 elicited by ARCT-2301 was non-inferior to that elicited with Comirnaty BA.4-5 was achieved, both by GMT ratio (1·49, 95% CI 1·26-1·76) and difference in seroresponse rate (7·2%, 95% CI 0·6-13·7). Furthermore, the differences in antibody response between the groups showed superiority for ARCT-2301 against Wuhan-Hu-1 using both criteria, with a GMT ratio of 1·45 (95% CI 1·28-1·63) and a difference in seroresponse rate of 12·5% (95% CI 5·9-19·0), and omicron XBB.1.5, with a GMT ratio of 1·63 (95% CI 1·36-1·94) and a seroresponse rate difference of 16·7% (95% CI 10·1-23·2). Both vaccines were well-tolerated with mainly mild, transient solicited adverse events and no causally related severe or serious adverse events., Interpretation: Boosting mRNA-immunised adults with ARCT-2301 induced superior immunogenicity compared with Comirnaty BA.4-5 against both Wuhan-Hu-1 and omicron BA.4/5 variant COVID-19, and elicited a higher response against omicron XBB.1.5. Both vaccines had similar tolerability profiles. Self-amplifying mRNA vaccines could provide a substantial contribution to pandemic preparedness and response, inducing robust immune responses with a lower dose of mRNA to allow wider and more equitable distribution., Funding: Japanese Ministry of Health, Labour, and Welfare and Meiji Seika Pharma., Competing Interests: Declaration of interests YO, IO, MO, NI, YI, TM, and YY are full-time employees of and TK is a board member of the study sponsor (Meiji Seika Pharma). YK received fees from Meiji Seika Pharma for medical consultation during this study. IS and YZ are full-time employees of Arcturus Therapeutics, who developed the vaccine. JvB is a full-time employee of CSL Sequiris, which has a marketing agreement for the vaccine. JLW is an independent consultant working for Arcturus Therapeutics., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Rheumatic fever and acute glomerulonephritis are known to occur secondary to infection with Streptococcus pyogenes, and early elimination of the Streptococcus pyogenes by treatment with an appropriate antibiotic is required. Treatment with penicillins for 10 days has been recommended for Streptococcus pyogenes infections, but cephems are also now being used, and cefditoren pivoxil (CDTR-PI) is listed as one of the recommended drugs in the Guidelines for the Management of Respiratory Infectious Disease in Children in Japan 2007. We therefore conducted this study in order to collect appropriate use information in the clinical setting of CDTR-PI to treat Streptococcus pyogenes infections. In this study, 790 patients were enrolled in 147 institutions. Of them, 734 and 718 patients were chosen for safety and efficacy analysis, respectively. There were 11 adverse drug reactions in 11 patients, and the incidence of adverse drug reactions was 1.50% (11/734 patients). The most common adverse drug reactions were diarrhea and hematuria, and there were 3 events of each, but a positive urinalysis after administration were only obserbed without the clinical symptoms. With the exception of the 3 patients in which the patient did not return to the hospital and the outcome is unknown, the patients either recovered from all of the adverse drug reactions or they were relieved. No serious adverse drug reactions were reported in this study. The response rate was 98.5% for laryngopharyngitis (457/464 patients) and 98.4% (250/254 patients) for tonsillitis. Examination of the response rates according to patient background showed that they were high, 95% or more, in every group. The Streptococcus pyogenes eradication rate was 94.6% for laryngopharyngitis (194/205 patients) and 92.4% (110/119 patients) for tonsillitis. In summary, CDTR-PI exhibited excellent safety and efficacy in laryngopharyngitis and tonsillitis caused by Streptococcus pyogenes, and CDTR-PI was reconfirmed as a useful drug.

A Clinical Practice Guideline for the Diagnosis and Management of Acute Otitis Media in Children, in view of the causative organisms of the disease and their drug susceptibility, was issued in March 2006. In the guideline, cefditoren pivoxil (CDTR-PI, Meiact MS fine granules 10% for pediatric use) is recommended as an oral cephem antibiotic for the treatment of the disease. To collect information on the appropriate use of the drug in the clinical setting after issuance of the guideline, we conducted a specific postmarketing study of CDTR-PI in pediatric patients with acute otitis media. With this study, 2144 patients were enrolled in 305 medical institutions. Of them, 2006 and 1958 patients were chosen for safety and efficacy analysis, respectively. The incidence of adverse drug reactions was 1.79% (36/2006 patients). No unexpected or serious adverse drug reactions were reported by this study. The most common adverse drug reaction was diarrhea, which was reported in 26 cases (1.30%). The symptom resolved or subsided during CDTR-PI therapy or after discontinuation or completion of the therapy in all cases. The incidence of diarrhea in patients treated with CDTR-PI at 1.5- to 2-fold the usual dose was 2.70%, which was slightly higher than the usual dose, but that in patients more than 2-fold the usual dose was 1.92% which was not higher than 1.5- to 2-fold the usual dose. The incidence of diarrhea itself was not substantially high. Concerning the clinical efficacy of CDTR-PI, the response rate was 93.5% (1831/1958 patients). Among 1217 strains from whom 832 patients were detected as causative organisms at baseline bacteriological examination, the response rate by causative organism was 89.7% for Streptococcus pneumoniae, 90.3% for Haemophilus influenzae, and 92.2% for Moraxella catarrhalis. Among documented eradication of 577 strains with 427 patients, the bacterial eradication rate by causative organism was 83.3% for S. pneumoniae, 87.1% for H. influenzae, and 88.9% for M. catarrhalis. For each major resistant strain, the response rate was 88.0% for penicillin-intermediate S. pneumoniae (PISP), 90.1% for penicillin-resistant S. pneumoniae (PRSP), and 92.5% for beta-lactamase negative ampicillin-resistant H. influenzae (BLNAR), while the bacterial eradication rate was 85.7% for PISP, 77.5% for PRSP, and 81.8% for BLNAR. In addition, 457 patients "without myringotomy" and "tympanic swelling or otorrhea rated as a severity score of 8" (symptoms emphasized in the guideline) were selected as a subpopulation allowing us to define the dose-efficacy relationship more clearly. In this subpopulation, the relationship between the dose and the efficacy of CDTR-PI was assessed. The assessment revealed that the response rate was significantly higher in patients with a mean daily dose of at least 13.5 mg/kg than in those with a mean daily dose below 13.5 mg/kg. In summary, CDTR-PI raised no noteworthy concerns about its safety or efficacy in pediatric patients with acute otitis media. These findings reconfirm the usefulness of the drug.