We examined the efficacy and safety of nintedanib in Japanese patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD) in the global Safety and Efficacy of Nintedanib in ...Systemic Sclerosis (SENSCIS) trial.
Randomised patients received oral nintedanib 150 mg (N = 34) twice daily or placebo (N = 36) until the last patient reached 52 weeks of treatment (up to 100 weeks). Data were analysed using a subgroup analysis model with Japanese and non-Japanese patients as subgroup variables.
In Japanese patients, the adjusted annual rate of forced vital capacity (FVC) decline over 52 weeks was -86.2 mL/year (nintedanib) and -90.9 mL/year (placebo); treatment difference, 4.67 mL/year (95% confidence interval, −103.28, 112.63). Treatment effect heterogeneity between Japanese and non-Japanese patients was not detected (treatment-by-visit-by-subgroup interaction; p = .49). FVC decline was smaller for nintedanib versus placebo through 100 weeks in Japanese patients. The most commonly reported adverse events with nintedanib were gastrointestinal and liver disorder events; most were mild-to-moderate in severity.
In both Japanese and non-Japanese patients with SSc-ILD, nintedanib slowed the progression of ILD, with no heterogeneity detected between the subgroups. The safety profile for nintedanib in Japanese patients was similar to that observed in patients with idiopathic pulmonary fibrosis (ClinicalTrials.gov: NCT02597933).
Vasorelaxant effects of a series of bis(bibenzyls) from liverworts such as
Marchantia polymorpha and
Marchantia paleacea on rat aorta demonstrated that they relaxed phenylephrine (PE)-induced ...contractions, which may be mediated through the increased release of NO from endothelial cells as well as opening of K
+ channels, and inhibition of Ca
2+ influx through voltage-dependent Ca
2+ channels (VDCs) and/or receptor-operated Ca
2+ channels (ROCs). Structure–activity relationship based on their structures was discussed. The presence of two aromatic rings which can be connected through two atoms bridge spacer may play an important role for vasorelaxant effect.
Introduction
Systemic sclerosis (SSc) is a complex autoimmune disease with increased mortality, and interstitial lung disease (ILD) is a major cause of death. There are no recent epidemiological data ...on SSc and SSc-associated ILD (SSc-ILD) in Japan and little is known about how patients with these diseases are treated.
Methods
The incidence rate and prevalence of SSc and SSc-ILD in Japan were estimated using the Japanese Medical Data Centre (JMDC) database. The demographic and clinical characteristics of patients and the immunomodulatory medications they received were also assessed using JMDC and the Medical Data Vision (MDV) databases. All analyses were descriptive.
Results
The overall incidence rates of SSc and SSc-ILD per 100,000 person-years were 6.6 (95% confidence interval CI 6.2–7.1) and 1.9 (95% CI 1.6–2.1), respectively, and the overall prevalence per 100,000 persons was 37.0 (95% CI 35.6–38.5) and 13.9 (95% CI 13.0–14.8), respectively. ILD was the most common comorbidity in patients with SSc present in approximately 30% of patients (JMDC, 29.3%; MDV, 30.1%). The immunomodulatory medications prescribed were similar in patients with SSc and SSc-ILD, and each of the medications in this analysis was prescribed in less than 15% of patients.
Conclusion
We have demonstrated that estimates of prevalence and incidence rates of SSc and SSc-ILD in Japan are comparable to similar database studies conducted in the USA, using a medical claims database. Only a small proportion of patients were receiving immunomodulatory treatments, suggesting undertreatment in Japan.
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Incidence Rate and Prevalence of Systemic Sclerosis and Systemic Sclerosis-associated Interstitial Lung Disease in Japan: Analysis Using Japanese Claims Databases—A Video Abstract. (MP4 68892 KB)
Five bisbenzyl isoquinolines (1–5), three benzyl isoquinolines (6–8), four isoquinoline alkaloids (9–12), and two unclassified compounds (13 and 14) from Popowia perakensis and Phaeanthus ...crassipetalus were evaluated for their vasorelaxant effect on rat aortic arteries. In aortic rings pre-contracted with phenylephrine (PE, 0.3 μM), some of the bisbenzyl isoquinoline alkaloids, benzyl isoquinoline alkaloids, and isoquinoline alkaloids showed clearly vasorelaxant effects at 30 μM. The action of (−)-limacine (4) was deduced to be mediated through the increased release of NO from endothelial cells, and that of pecrassipine A (7) and backebergine (12) partly mediated by NO release. Further, the action of pecrassipine A (7) and backebergine (12) may be attributed to their inhibition of the voltage-dependent Ca²⁺ channel and receptor-operated Ca²⁺ channel.
This article surveys the history of English studies and education in Japan, paying special attention to the role of literary texts and stylistics. Firstly, the role of literature and stylistics in ...Japan is discussed from a pedagogical point of view, including both English as a foreign language and Japanese as a native language. Secondly, the way in which stylistics has contributed to literary criticism in the country is examined, with reference to the history of literary stylistics since 1980. Finally, this article considers further applications of stylistics to language study in Japan, offering two examples: analysis of thought presentation in Yukio Mishima’s Megami (20061955), and the teaching of an English poem and a Japanese haiku to Japanese EFL students. The overall aim of this article is to demonstrate that literature as language teaching material and stylistics as a critical and teaching method are significant not only in understanding English, but also in appreciating our own native language if it is not English.
We collaborated to team-teach an English presentation skills class via Zoom plurilingually, introducing concepts from cognitive linguistics (e.g. frame semantics, prototype, and category membership) ...to move students to “re-conceptualize” their tools, words, and master their presentation skills. Students were overall confident in casual English conversation, yet tended to either write grammatically correct sentences in limited patterns, or try to raise readability scores by merely switching everyday vocabularies with archaic ones. Focusing on the “weight” of the verbs used in their writings, students were asked to explore the frame semantics afforded by verbs through translation options and bilingual discussions. Each participant prepared and presented creative new stories, challenging the next speaker to try out other possibilities to entertain the audience. Showing marked improvement launched by this broadminded approach, students displayed clear understandings of scenes implied by the verb in focus (‘escape’) and created and filled in imaginative new frames to entertain their audience. They used powerful verbs and equally strong tropes to present multiple thematic roles, extending elementary frames and harnessing the encyclopedic nature of semantics.
S-1 is an oral fluoropyrimidine whose antitumor effects have been demonstrated in treating various gastrointestinal cancers, including metastatic colon cancer, when administered as monotherapy or in ...combination chemotherapy. We conducted a randomized phase III study investigating the efficacy of S-1 as adjuvant chemotherapy for colon cancer by evaluating its noninferiority to tegafur–uracil plus leucovorin (UFT/LV).
Patients aged 20–80 years with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80–120mg/day on days 1–28 every 42 days; four courses) or UFT/LV (UFT: 300–600mg/day and LV: 75mg/day on days 1–28 every 35 days; five courses). The primary end point was disease-free survival (DFS) at 3 years.
A total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively) were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5% in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval: 0.70–1.03), demonstrating the noninferiority of S-1 (noninferiority stratified log-rank test, P < 0.001). In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the treatment groups.
Adjuvant chemotherapy using S-1 for stage III colon cancer was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer.
NCT00660894.
Seven new ajmaline type alkaloids, alstiphyllanines I–O (1–7) were isolated from the leaves of Alstonia macrophylla together with six related alkaloids (8–13). Structures and stereochemistry of 1–7 ...were fully elucidated and characterized by 2D NMR analysis. A series of alstiphyllanines I–O (1–7) as well as the known ajmaline type alkaloids (8–13) showed that they relaxed phenylephrine (PE)-induced contractions against rat aortic ring. Among them, vincamedine (10) showed potent vasorelaxant activity, which may be mediated through inhibition of Ca2+ influx through voltage-dependent Ca2+ channels (VDCs) and/or receptor-operated Ca2+ channels (ROCs) as well as partially mediated the NO release from endothelial cells. The presence of substituents at both N-1 and C-17 may be important to show vasorelaxation activity.
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