Pharmaceuticals and Medical Device Agency approval summary: Amenamevir for the treatment of herpes zoster.

In July 2017, Japan's Ministry of Health, Labor and Welfare issued a marketing authorization valid throughout Japan for N-(2,6-dimethylphenyl)-N-(2-{[4-(1,2,4-oxadiazol-3-yl)phenyl]amino}-2-oxoethyl)-1,1-dioxothiane-4-carboxamide (amenamevir) for the first time worldwide. The decision was based on the favorable opinion of the Pharmaceuticals and Medical Device Agency (PMDA) recommending a marketing authorization of amenamevir for treatment of herpes zoster (HZ). Amenamevir has a different action mechanism from previously approved synthetic nucleoside compounds for the treatment of HZ including acyclovir, valacyclovir and famciclovir. The usual adult dose is 400 mg amenamevir p.o. once daily for 7 days. The benefit is its ability to cure HZ as well as preventing postherpetic neuralgia. The most common side-effects are increase of urine N-acetyl-ß-D-glucosaminidase and α1-microglobulin levels. However, based on the detailed evaluation of the submitted clinical studies, there seems to be no serious safety concerns about amenamevir regarding the kidney of both renally normal and impaired patients. The objective of this article is to summarize the scientific review of the application. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the PMDA website (www.pmda.go.jp/PmdaSearch/iyakuSearch/).

A Dialogue-Based Approach to Subjective Well-Being: Co-Interpreting the Meaning of Daily Experiences.

Different from statistically analyzed self-reports of Subjective Well-Being (SWB), we explored how dialogue engenders the meaning of SWB as constituted through an individual's daily experiences. A revised Day Reconstruction Method (DRM; Kahneman et al. 2004) was used to describe the participants' previous day episodically, followed by a semi-structured life world interview (Kvale 1996) for the explication through dialogue of those episodes. The results of qualitative analyses on the structure and contents of the discourse of the DRM and interviews with three participants highlighted the following: 1) the participants construed the meaning of daily experiences by organizing and weighting them in individualized ways; 2) the meaning of daily episodes emerged and was clarified in the process of collaborative dialogue in the interview as well as in the analyses, and was vividly expressed in particular protocol sequences; and 3) Kelly's (1955) notion of Personal Construct is applicable to make sense of individualized narratives as a form of Well-Being. We concluded that the subjectivity of SWB does not merely imply the first-person authority in charge of the evaluation in the questionnaires, but rather is understood as a construct that reveals the personal meaning of one's daily experiences. The emergent quality of this process is crucial for understanding the nature of subjectivity in SWB.

Impact of demographic factors on the antidepressant effect: A patient-level data analysis from depression trials submitted to the Pharmaceuticals and Medical Devices Agency in Japan.

A substantial and variable placebo response can cause unreliable findings in clinical trials designed to demonstrate the efficacy of antidepressants, and the high rate of failed trials represents a major obstacle in the development of new drugs for major depressive disorder (MDD). However, the influence of demographic and symptom factors on the antidepressant effect remains to be established. The purpose of this study was to estimate the magnitude of this influence. A patient-level meta-analysis of data from double-blind, randomized, placebo-controlled trials involving the use of antidepressants for adults with MDD was performed. Data from five confirmatory trials evaluating the efficacy of four antidepressants that were submitted to the Pharmaceuticals and Medical Devices Agency (PMDA) to support new drug applications were pooled (n = 1898). The change in the total score of 17-item Hamilton Depression Rating Scale (HDRS17) was the primary outcome of interest in our analysis. The changes in the total HDRS17 score in both the antidepressant medication group (ADM) and the placebo group (PBO) increased in relation to baseline symptom severity. Among older patients and those with a history of prior treatment with antidepressants, the changes in the total HDRS17 score decreased in ADM and remained static in PBO. There were no notable clinical symptoms that influenced the change in the total HDRS17 score. Baseline symptom severity, participant age and a history of previous treatment with antidepressants were suggested as moderators of the antidepressant effect. The drug-placebo difference in the estimated changes as a function of baseline symptom severity varied depending on the regression models used, and further studies are required to investigate appropriate models.

High cell density cultivation of Pseudomonas putida strain HKT554 and its application for optically active sulfoxide production.

Culture conditions with Pseudomonas putida strain HKT554, expressing naphthalene dioxygenase, known as the biocatalyst showing wide substrate specificity, were optimized for high cell density cultivation (HCDC). Culture in a medium TK-B modified from that for HCDC of Escherichia coli with glucose fed-batch and dissolved oxygen stat resulted in a high cell density growth of 114 g dry cell/l at 40 h of cultivation. This system was further applied for S-(+)-methyl phenyl sulfoxide (MPSO) production from methyl phenyl sulfide. Addition of nonpolar organic solvent, such as n-hexadecane, greatly enhanced the MPSO production due to the prevention of substrate evaporation, resulting in a MPSO production up to 39 mM in 30 h with a conversion rate of 95.7 mol%.