Published papers

Maintaining a social environment that enables going out freely is important for older people and aids the prevention of frailty syndrome. However, losing a driver's license can increase the long-term care needs of older people. Therefore, outing support systems are important. However, the utilization rate of these systems is currently relatively low. We conducted a demonstration experiment among older people aged 70 years and over, living in Iruma City, Saitama Japan, by implementing the Choisoko outing support system developed by Aisin Co., Ltd., in conjunction with an approach for improving motivation. Using this system, elderly people were able to go shopping freely whenever they chose, without a driver's license. Participants in the demonstration experiment exhibited higher Functional Independence Measure scores after the intervention, irrespective of whether or not they used the Choisoko system. The number of uses per person increased over time, and the subjective well-being of Choisoko users improved. However, few male participants engaged with the system. Although improving motivation is important for inducing positive behaviors and enabling the elderly to go out, motivation-improving factors differ between men and women.

Although results of clinical trials are thoroughly analyzed to define benefits of the treatment, but are not fully analyzed to extract interindividual differences to achieve precise medicine. We are analyzing individual patient data from previous clinical studies for this purpose utilizing clinical trial disclosure systems. Exercise therapy is generally recommended as an adjunctive treatment in chronic heart failure. However, interindividual differences in benefit of exercise mostly have not been analyzed. In this study, we obtained patient data on the HF-ACTION study (2331 subjects) from the National Heart, Lung, and Blood Institute. With regard to clinical endpoints such as all-caused mortality (AD), significant interactions with the exercise effect were analyzed including patient backgrounds and medications (renin-angiotensin system inhibitors [RASIs] and beta-blockers [BBs]) with multivariate Cox regression models, and the selected covariates were validated by bootstrapping. Based on the results, SEEM score was constructed to judge exercise suitability. It was revealed that exercise reduced AD in patients taking both BB and RASI with a hazard ratio (HR) of 0.86, but increased in patients not taking BB with a HR of 4.58. The exercise effect on AD was also influenced by pulse pressure, hemoglobin, ECG status, BMI, and history of stroke, thus SEEM score was constructed including these factors. AD was expected to be reduced with HR 0.54 when exercise therapy was selected according SEEM, compared to the opposite selection (95% CI, 0.44-0.68). Although this study is a post-hoc and should be interpreted with caution, exercise therapy in heart failure patients should be carefully selected, taking into account the patient background. The analysis of data from clinical trial disclosure system was of great significance to improve precise medicine.

BACKGROUND: Treatment options for patients with chronic thromboembolic pulmonary hypertension ineligible for pulmonary endarterectomy (inoperable CTEPH) include balloon pulmonary angioplasty (BPA) and riociguat. However, these two treatment options have not been compared prospectively. We aimed to compare the safety and efficacy of BPA and riociguat in patients with inoperable CTEPH. METHODS: This open-label, randomised controlled trial was conducted at four high-volume CTEPH centres in Japan. Patients aged 20-80 years with inoperable CTEPH (mean pulmonary arterial pressure ≥25 to <60 mm Hg and pulmonary artery wedge pressure ≤15 mm Hg) and WHO functional class II or III were randomly assigned (1:1) to BPA or riociguat via a computer program located at the registration centre using a minimisation method with biased-coin assignment. In the BPA group, the aim was for BPA to be completed within 4 months of the initial date of the first procedure. BPA was repeated until mean pulmonary arterial pressure decreased to less than 25 mm Hg. The frequency of BPA procedures depended on the difficulty and number of the lesions. In the riociguat group, 1·0 mg riociguat was administered orally thrice daily. When the systolic blood pressure was maintained at 95 mm Hg or higher, the dose was increased by 0·5 mg every 2 weeks up to a maximum of 2·5 mg thrice daily; dose adjustment was completed within 4 months of the date of the first dose. The primary endpoint was change in mean pulmonary arterial pressure from baseline to 12 months, measured in the full analysis set (patients who were enrolled and randomly assigned to one of the study treatments, and had at least one assessment after randomisation). BPA-related complications and indices related to clinical worsening were recorded throughout the study period. Adverse events were recorded throughout the study period and evaluated in the safety analysis set (patients who were enrolled and randomely assigned to one of the study treatments, and had received part of or all the study treatments). This trial is registered in the Japan Registry of Clinical Trials (jRCT; jRCTs031180239) and is completed. FINDINGS: Between Jan 8, 2016, and Oct 31, 2019, 61 patients with inoperable CTEPH were enrolled and randomly assigned to BPA (n=32) or riociguat (n=29). Patients in the BPA group underwent an average of 4·7 (SD 1·6) BPA procedures. In the riociguat group, the mean maintenance dose was 7·0 (SD 1·0) mg/day at 12 months. At 12 months, mean pulmonary arterial pressure had improved by -16·3 (SE 1·6) mm Hg in the BPA group and -7·0 (1·5) mm Hg in the riociguat group (group difference -9·3 mm Hg [95% CI -12·7 to -5·9]; p<0·0001). A case of clinical worsening of pulmonary hypertension occurred in the riociguat group, whereas none occurred in the BPA group. The most common adverse event was haemosputum, haemoptysis, or pulmonary haemorrhage, affecting 14 patients (44%) in the BPA group and one (4%) in the riociguat group. In 147 BPA procedures done in 31 patients, BPA-related complications were observed in 17 procedures (12%) in eight patients (26%). INTERPRETATION: Compared with riociguat, BPA was associated with a greater improvement in mean pulmonary arterial pressure in patients with inoperable CTEPH at 12 months, although procedure-related complications were reported. These findings support BPA as a reasonable option for inoperable CTEPH in centres with experienced BPA operators, with attention to procedure-related complications. FUNDING: Bayer Yakuhin. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.