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for the GENCAT Study Group IMPORTANCE Carbamazepine, a commonly used antiepileptic drug, is one of the most common causes of cutaneous adverse drug reactions (cADRs) worldwide. The allele HLA-A*31:01 is reportedly associated with carbamazepine-induced cADRs in Japanese and European populations; however, the clinical utility of HLA-A*31:01 has not been evaluated.OBJECTIVE To assess the use of HLA-A*31:01 genetic screening to identify Japanese individuals at risk of carbamazepine-induced cADRs.DESIGN, SETTING, AND PARTICIPANTS This cohort study was conducted across 36 hospitals in Japan from January 2012 to November 2014 among 1202 patients who had been deemed suitable to start treatment with carbamazepine. Preemptive HLA-A*31:01 genetic screening was performed for 1187 participants. Patients who did not start treatment with carbamazepine or alternative drugs were excluded. Participants were interviewed once weekly for 8 weeks to monitor the development of cADRs. Data analysis was performed from June 8, 2015, to December 27, 2016.EXPOSURES Neuropsychiatrists were asked to prescribe carbamazepine for patients who tested negative for HLA-A*31:01 and alternative drugs for those who tested positive for HLA-A*31:01. MAIN OUTCOMES AND MEASURES Incidence of carbamazepine-induced cADRs.RESULTS Of the 1130 included patients who were prescribed carbamazepine or alternative drugs, the mean (range) age was 37.4 (0-95) years, 614 (54.3%) were men, and 198 (17.5%) were positive for HLA-A*31:01. Expert dermatologists identified 23 patients (2.0%) who had carbamazepine-induced cADRs, of which 4 patients required hospitalization. Drug-induced hypersensitivity syndrome was observed for 3 patients, maculopapular eruption for 9 patients, erythema multiforme for 5 patients, and an undetermined type of cADR for 6 patients. No patient developed Stevens-Johnson syndrome or toxic epidermal necrolysis. Compared with historical controls, the incidence of carbamazepine-induced cADRs was significantly decreased (for BioBank Japan data: incidence, 3.4%; odds ratio, 0.60; 95% CI, 0.36-1.00; P = .048; for the Japan Medical Data Centre claims database: incidence, 5.1%; odds ratio, 0.39; 95% CI, 0.26-0.59; P < .001).CONCLUSIONS AND RELEVANCE Preemptive HLA-A*31:01 genetic screening significantly decreased the incidence of carbamazepine-induced cADRs among Japanese patients, which suggests that it may be warranted in routine clinical practice.

ObjectivePrevious studies conducted in Japan targeted only mothers who cared for children with disabilities, and lacked reference subjects, such as mothers of children without disabilities. The aim of this study was to examine the association between raising one or two children with a disability and maternal psychological distress compared to mothers of children without a disability, and to assess differences among partnered mothers living with grandparent(s), partnered mothers without grandparent(s), and single mothers.MethodsThis study utilized data from the Comprehensive Survey of Living Conditions (CSLC) in 2010. We merged the data of the children (aged six and over), mothers, and fathers. This study obtained 33,739 study subjects as a triad of a child (33,110 children without disabilities and 629 children with disabilities), mother, and father. The Japanese version of Kessler 6 (K6) was used to assess the psychological distress of mothers. Multivariate logistic regression was performed to assess the independent association of a child with a disability on maternal psychological distress after controlling for the basic characteristics of the children, mothers, and households.ResultsThis study reported that raising one or two children with disabilities was significantly related to maternal psychological distress (odds ratio: 1.72 for one child, 2.85 for two children) compared to mothers of children without disability. After stratifying the analyses by family structure, significant associations remained among mothers in two-parent families but not for mothers in three-generation families and single mothers due to a small number of children with disabilities in these families.ConclusionsThis study reported the significant association between raising a child with a disability and maternal psychological distress in comparison to mothers of children without disabilities. Attention should be paid to not only single mothers, but also partnered mothers in two-parent families who have a child with a disability. It is important for health professionals to focus on the mental health of every mother of a child with a disability and to assess their needs for psychological support.

The idea of a space with smooth structure is a generalization of an idea of a manifold. K. T. Chen introduced such a space as a differentiable space in his study of a loop space to employ the idea of iterated path integrals [2,3,4,5]. Following the pattern established by Chen, J. M. Souriau [10] introduced his version of a space with smooth structure, which is called a diffeological space. These notions are strong enough to include all the topological spaces. However, if one tries to show de Rham theorem, he must encounter a difficulty to obtain a partition of unity and thus the Mayer-Vietoris exact sequence in general. In this paper, we introduce a new version of differential forms to obtain a partition of unity, the Mayer-Vietoris exact sequence and a version of de Rham theorem in general. In addition, if we restrict ourselves to consider only CW complexes, we obtain de Rham theorem for a genuine de Rham complex, and hence the genuine de Rham cohomology coincides with the ordinary cohomology for a CW complex.In this paper, we deal with both differentiable and diffeological spaces. A differentiable space is introduced by K. T. Chen [5] and a diffeological space is introduced by J. M. Souriau [10]. Both of them are developed with an idea of a plot -a map from a domain.Let n ≧ 0. A non-void open set in R n is called an open n-domain or simply an open domain and a convex set with non-void interior in R n is called a convex n-domain or simply a convex domain. We reserve the word 'smooth' for 'differentiable infinitely many times' in the ordinary sense. More precisely, a map from an open or convex domain A to an euclidean space is smooth on A, if it is smooth on Int A in the ordinary sense and all derivatives extend continuously and uniquely to A (see A. Kriegl and P. W. Michor [9]). 1. Differentiable/diffeological spaces Let us recall a concrete site given by Chen [5] (see J. C. Baes and A. E. Hoffnung [1]). Definition 1.1. Let Convex be the category of convex domains and smooth maps between them. Then Convex is a concrete site with Chen's coverage: a covering family on a convex domain is an open covering by convex domains.

Long-Term Care Insurance (LTCI), introduced in Japan in 2000, is rapidly turning into a system of rationed benefits due to financial difficulty. Based on our survey of 2,530 family care-givers and the Zarit Care-Giver Burden Index, we have examined how LTCI is affecting their subjective burden. We have found that, as Kishida and Tanigaki (2004) had shown, (i) insufficient provision of short-term stays, day services and home-helper services, as well as (ii) disruptive or antisocial behaviors of the elderly, increase the care-giver's burden. We then argue that (iii) these results establish the positive contribution of LTCI in the well-being of family care-givers, (iv) short-term stay is the most efficient service, followed by home-helper service, and day service is the least efficient, and we show that (v) J-ZBIC-8 works well enough for many practical purposes.