30 research outputs found

    A mathematical model for dynamics of soluble form of DNAM-1 as a biomarker for graft-versus-host disease.

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    DNAM-1 (CD226) is an activating immunoreceptor expressed on T cells and NK cells and involved in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We previously reported that a soluble form of DNAM-1 (sDNAM-1) is generated by shedding from activated T cells. Moreover, higher serum levels of sDNAM-1 in patients before allo-HSCT is a predictive biomarker for the development of aGVHD based on the retrospective univariate and multivariate analyses in allo-HSCT patients. However, it remains unclear how the serum levels of sDNAM-1 are regulated after allo-HSCT and whether they are associated with the development of aGVHD. Here, we constructed a mathematical model to assess the dynamics of sDNAM-1 after allo-HSCT by assuming that there are three types of sDNAM-1 (the first and the second were from alloreactive and non-alloreactive donor lymphocytes, respectively, and the third from recipient lymphocytes). Our mathematical model fitted well to the data set of sDNAM-1 in patients (n = 67) who had undergone allo-HSCT and suggest that the high proportion of the first type of sDNAM-1 to the total of the first and second types is associated with high risk of the development of severe aGVHD. Thus, sDNAM-1 after allo-HSCT can be a biomarker for the development of aGVHD

    Phase 3, multicentre, randomised, double-blind, placebo-controlled, parallel-group study of ustekinumab in Japanese patients with active polymyositis and dermatomyositis who have not adequately responded to one or more standard-of-care treatments

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    Objectives To evaluate the efficacy and safety of ustekinumab (UST) in a multicentre, randomised, double-blind, placebo-controlled trial in adult Japanese patients with active polymyositis (PM) and dermatomyositis (DM).Methods Fifty-one Japanese adults diagnosed with active PM/DM who did not respond adequately to one or more standard-of-care treatments were randomised 1:1 to receive UST (n=25) or placebo (n=26). Participants received body weight-range based intravenous administration of UST (6 mg/kg) or placebo at week 0 followed by 90 mg subcutaneous (SC) administration of UST or placebo every 8 weeks from week 8 to week 24. At week 24, placebo group crossed over to receive body weight-range based intravenous administration of UST, and thereafter, all participants received/were to receive SC administration of UST 90 mg every 8 weeks (week 32 through to week 72). The primary efficacy endpoint was the proportion of participants who achieved minimal improvement (≥20) in the International Myositis Assessment and Clinical Studies Total Improvement Score (IMACS TIS) at week 24.Results No statistically significant difference was seen in the proportion of participants who achieved minimal improvement (≥20) in IMACS TIS at week 24 between the treatment groups (UST 64.0% vs placebo 61.5%, p=0.94) based on the primary estimand of the primary endpoint analysis.Conclusions UST was safe and well tolerated but did not meet the primary efficacy endpoint in adult Japanese participants with active PM/DM based on the primary analysis at week 24 in the study.Trial registration number NCT03981744

    The development of a scale to measure stress recognition during the treatment of diabetes patients

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     The purpose of this study was to establish a measurement scale for "stress recognition in receiving treatment" in patients with diabetes. A self-completed questionnaire was distributed to 149 type-2 diabetes outpatients in March-May 2015 after authorization from Okayama Prefectural University and the ethics committee of the hospital.  The "stress recognition in receiving treatment" scale was designed as a second-order factor model consisting of 14 items and the following four factors : the respondent's sense of (1) the burden of being sick, (2) the burden on interpersonal relationships, (3) the burden of treatment, and (4) the burden of medical expenses.  Stress recognition in treatment means recognition of being stressed in the burdens related to the illness, interpersonal relationships, treatment and medical expenses.  The suitability of the questionnaire data was then evaluated with a structural equation model. The suitability of the factor model to the data satisfied the statistically acceptable standards as Comparative Fit Index (CFI) =0.931, Root Mean Square Error of Approximation (RMSEA) =0.096, Tucker-Lewis Index (TLI) =0.946.  As the construct validity was not examined by the scale created in this study or by existing scale, it was verified by using the degrees of mental healthiness and HbA1c that were proved to be associated with the sense of burden.  In addition, the construct validity of the questionnaire was supported by a significant correlation between the Japanese version of the WHO-Five Well-being Index (S-WHO-5-J) and the patients' HbA1c levels. The use of this measure is expected to contribute to the early detection of a decline in a diabetic patient's activities of daily living and to the early confirmation of patients' support status
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