論文

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.

一般に臨床試験の解析では、治療のベネフィットは精密に判定されるが、医療個別化のための情報の抽出は決して十分にはなされない。我々は臨床試験情報の公開制度を利用し、医療個別化の観点から独自の精密な分析を進めている。慢性心不全において運動療法は、補助的治療法として多くの患者に推奨されている。しかし、患者背景による運動療法の効果の違いはほとんど解析されていない。本研究では、HF-ACTION 試験(被験者2331人)の患者情報をNational Heart, Lung, and Blood Instituteより入手し、使用薬剤（レニン-アンジオテンシン系阻害薬(RASI)、β遮断薬(BB)）などの患者背景から、運動療法の効果との交互作用に着目して多変量Cox回帰モデルで共変量候補を系統的に選択し、ブートストラップ法で検証した。また、その解析結果から患者の運動療法への適性を示すSEEMスコアを構築した。BBとRASIの両方を服用していた患者では、運動療法は全死亡(AD)のリスクをハザード比(HR) 0.86で減少させたが、BBを服用しない患者ではHR 4.58と逆に増大させていたことが見いだされた。また、ADに対する運動の効果は、脈圧、ヘモグロビン値、心電図の状態、肥満度、脳卒中の既往にも影響されていた。そこで、これらの因子からSEEMスコアを構築した。スコアに基づいて運動療法を選択した場合には、それとは逆の選択をした場合に比べて運動はADをHR 0.54で有意に減少させると期待された(95% CI、0.44–0.68)。本研究は事後解析であることから、その解釈は慎重に行う必要があるが、心不全患者における運動療法は、患者背景を考慮し、慎重に選択する必要があると考えられた。臨床試験情報の事後解析は、医療個別化に大きな意義を持つと考えられた。

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.