Published papers

Background: Thyroid storm is a life-threatening disease with a mortality rate of over 10%. Although glucocorticoids have been recommended as a treatment option for thyroid storm, supportive evidence based on a large-scale clinical research is lacking. The objective of the current study was to evaluate the beneficial effects of glucocorticoids in the treatment of patients with severe thyroid storm. Methods: A retrospective nationwide cohort study was conducted using a Japanese national administrative claims database. Patients admitted to intensive care units due to severe thyroid storm between the financial years 2013 and 2017 were included in the study. The primary outcome was in-hospital mortality; secondary outcomes were mortality within 30 days and insulin administration during hospitalization. Generalized linear mixed model (GLMM) with maximum likelihood estimation (MLE) and Bayesian estimation using Markov chain Monte Carlo methods (MCMC), in addition to propensity score matching (PSM), were used for statistical analysis. Results: A total of 811 patients were included in the study, of which 600 patients were treated with glucocorticoids, and 211 patients were treated without glucocorticoids. The early administration of glucocorticoids was not associated with a significant improvement in the in-hospital mortality of patients with thyroid storm [adjusted odds ratio (95% confidence interval) = 1.77 (0.95-3.34), 1.44 (1.14-1.93), and 1.46 (0.72-3.00) in the GLMM (MLE), GLMM (MCMC), and PSM, respectively]. The results of mortality within 30 days were almost identical to the results of in-hospital mortality. However, insulin use was significantly higher in the glucocorticoid group. Conclusions: This analysis of a nationwide administrative database indicates that the administration of glucocorticoids does not improve the survival of patients with thyroid storm.

Objectives: An insomnia characterized by nighttime symptoms and daytime impairment is common. GABA-A receptor agonist (GABAA-RA) treatment is often used, but long-term use is controversial due to the poor risk-benefit ratio resulting from drug dependence and potential cognitive impairment. This study evaluated the effectiveness of add-on cognitive behavioral therapy for insomnia (CBT-I) and GABAA-RA dose-tapering in patients with primary insomnia resistant to pharmacotherapy. Methods: This randomized, multicenter, two-arm, parallel-group study compared CBT-I and treatment as usual (TAU) in patients with persistent primary insomnia despite GABAA-RA treatment. Screening was based on sleep diary entries, with ≥31-min sleep latency or wake after sleep onset, occurring ≥3 times in a week and total score of ≥8 on the Insomnia Severity Index (ISI). Primary outcome measures were severity of insomnia and GABAA-RA tapering rate. Results: A total of 51 patients were randomized and 49 patients were analyzed (CBT-I; n = 23, TAU; n = 26). A mixed-effects repeated-measures model revealed significant improvement in insomnia symptoms (ISI score) during the post-intervention (PI) and follow-up (FU) periods in the CBT-I versus the TAU group (PI; 10.91 vs. 14.33, p < 0.05, FU; 10.17 vs. 14.34, p < 0.01). GABAA-RA tapering rate approached 30% during follow-up in the CBT-I group; no significant intergroup difference was observed. Conclusion: Add-on CBT-I improved insomnia symptoms that were unresponsive to GABAA-RA therapy. No effect on tapering rate was observed in this study. CBT-I may promote dose reduction by optimizing the protocol and duration of treatment. Trial registration: UMIN Clinical Trials Registry identifier: UMIN000014297.

Introduction Development of a support system for families caring for people with schizophrenia in routine psychiatric care settings is an important issue worldwide. Regional mental health systems are inadequate for delivering effective services to such family members. Despite evidence that family psychoeducation (FPE) alleviates the burden of schizophrenia on families, its dissemination in routine clinical practice remains insufficient, suggesting the need for developing an effective and implementable intervention for family caregivers in the existing mental health system setting. In Japan, the visiting nurse service system would be a practical way of providing family services. Visiting nurses in local communities are involved in the everyday lives of people with schizophrenia and their families. Accordingly, visiting nurses understand their needs and are able to provide family support as a service covered by national health insurance. The purpose of this study is to discover whether a brief FPE programme provided by visiting nurses caring for people with schizophrenia will alleviate family burden through a cluster randomised controlled trial (cRCT). Methods and analysis The study will be a two-arm, parallel-group (visiting nurse agency) cRCT. Forty-seven visiting nurse agencies will be randomly allocated to the brief FPE group (intervention group) or treatment as usual group (control group). Caregivers of people with schizophrenia will be recruited by visiting nurses using a randomly ordered list. The primary outcome will be caregiver burden, measured using the Japanese version of Zarit Burden Interview. Outcome assessments will be conducted at baseline, 1-month follow-up and 6-month follow-up. Multiple levels of three-way interactions in mixed models will be used to examine whether the brief FPE programme will alleviate the burden on caregivers relative to treatment as usual. Ethics and dissemination The Research Ethics Committee of the Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Japan (No 2019065NI) approved this study. The results will be published in a scientific peer-reviewed journal. Trial registration number UMIN000038044.

Duchenne muscular dystrophy (DMD) is a recessive X-linked genetic disease caused by a mutation in the dystrophin gene. The new drug NS-065/NCNP-01 utilizing exon-skipping therapy targeting specific deletions has been used in a first-in-human trial for the treatment of DMD. We surveyed 10 pairs of DMD participants and their parents within this clinical trial via an iPad survey form and through interviews regarding their understanding of the trial, expectations, anxieties, and reasons for participating in the trial. Approximately half of the participants actively decided to participate of their own volition, and none considered quitting the trial. This indicates that participants participated more positively in this clinical trial than previously expected. However, some potential concerns were also revealed, with one being that the desire to please those around them might be more important to the DMD participants than the effects of the drug. Another issue is the possibility of biased information originating from the study subjects’ parents; while seven out of 10 of the parents told their children that the study drug might work, only four of these parents also explained that it might not work. Only two study participants received an explanation concerning the drug's side effects from their parents. This result implies that caution should be taken when family expectations are high, and there is a possibility that subjects will be given biased information from their parents.