記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Global medical devices have become more popular, but investment money for medical device development is not easily available in the market. Worldwide health-care budget constraints mean that efficient medical device development has become essential. To achieve efficient development, globalization is a key to success. Spending large amounts of money in different regions for medical device development is no longer feasible. Methods and Results: In order to streamline processes of global medical device development, an academic, governmental, and industrial consortium, called the Harmonization by Doing program, has been set up. The program has been operating between Japan and the USA since 2003. The program has 4 working groups: (1) Global Cardiovascular Device Trials; (2) Study on Post-Market Registry; (3) Clinical Trials; and (4) Infrastructure and Methodology Regulatory Convergence and Communication. Each working group has as its goals the achievement of speedy and efficient medical device development in Japan and the USA. The program has held multiple international meetings to deal with obstacles against efficient medical device development. Conclusions: This kind of program is very important to deliver novel medical devices. Involvement of physicians in this type of activity is also very helpful to achieve these goals.

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Pediatric Blood and Cancer  

Programs allowing access to investigational drugs and off-label drug use for serious diseases have often been applied to pediatric cancers. A clinical study conducted under the Japanese “Patient-Proposed Healthcare Services” evaluated the efficacy and safety of dabrafenib plus trametinib in children with BRAF V600 mutant glioma (jRCTs071210071). This study successfully provided unapproved and off-label medications to four enrolled patients, two with low-grade glioma and two with high-grade glioma (median age: 10.5 years), until regulatory approval. The timeframe and data collection from such access programs need to be optimized for pediatric patients in accordance with the healthcare system of each nation.

DOI： 10.1002/pbc.31510

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Amyloid deposition in myocardial tissue is a definitive feature for diagnosing cardiac amyloidosis, though less invasive imaging modalities such as bone tracer cardiac scintigraphy and cardiac magnetic resonance imaging have been established as first steps for its diagnosis. This study aimed to develop a deep learning model to support the diagnosis of cardiac amyloidosis from haematoxylin/eosin (HE)-stained myocardial tissue. METHODS AND RESULTS: This single-centre retrospective observational study enrolled 166 patients who underwent myocardial biopsies between 2008 and 2022, including 76 patients diagnosed with cardiac amyloidosis and 90 with other diagnoses. A deep learning model was developed to output the probabilities of cardiac amyloidosis for all the small patches cutout from each myocardial specimen. The developed model highlighted the area in the stained images as highly suspicious, corresponding to where Dylon staining marked amyloid deposition, and discriminated the patches in the evaluation dataset with an area under the curve of 0.965. Provided that the diagnostic criterion for cardiac amyloidosis was defined as a median probability of cardiac amyloidosis >50% in all patches, the model achieved perfect performance in discriminating patients with cardiac amyloidosis from those without it, with an area under the curve of 1.0. CONCLUSION: A deep learning model was developed to diagnose cardiac amyloidosis from HE-stained myocardial tissue accurately. Although further prospective validation of this model using HE-stained myocardial tissues from multiple centres is needed, it may help minimize the risk of missing cardiac amyloidosis and maximize the utility of histological diagnosis in clinical practice.

DOI： 10.1093/ehjimp/qyae141

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記述言語：日本語   出版者・発行元：(一社)日本医療情報学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Journal of Ophthalmology  

Purpose: To assess the safety and efficacy of ripasudil for retinopathy of prematurity (ROP). Study design: Phase 1/2, multicenter, open-label, single-arm, 12-week clinical trial. Methods: Infants born with gestational age (GA) of ≤ 32 weeks or weight of ≤ 1500 g with zone I or II, ≥ stage 1, ROP in both eyes were enrolled. Ripasudil eye drops were administered to patients in both eyes. Phase 1 was a dose-escalation study (once daily for 1 week, then twice daily for 2 weeks); an additional dosing up to 9 weeks was allowed if no safety issues occurred. In phase 2, ripasudil was administered twice daily for up to 12 weeks. Adverse events were assessed. The proportion of patients with type 1 ROP progression, number of days for type 1 ROP progression, and progression to the most advanced ROP stage were estimated. Results: Twenty-four infants were enrolled (phase 1, n = 3; phase 2, n = 21). Nineteen and four patients experienced systemic and ocular adverse events, respectively. Efficacy endpoints were not different between the ripasudil and historical control groups. However, in the GA ≤ 27 weeks subgroup, fewer patients progressed to type 1 ROP in the ripasudil than in the historical control group (P = 0.09). In the GA ≤ 27 weeks subgroups, the 25th percentile for the number of days for type 1 ROP progression was 22 days in the historical control group and 44 days in the ripasudil group. Conclusion: Ripasudil was safe and inhibited/delayed type 1 ROP progression, especially in infants with short GA.

DOI： 10.1007/s10384-024-01100-3

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記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

未熟児網膜症(ROP)に対するリパスジル点眼剤の安全性と有効性を検討した。Zone I・IIにステージ1以上のROPを呈する在胎32週以下または体重1500g未満の早産児24例(男児14例、女児10例、平均在胎週数25.2±1.6)を対象に、第I/II相多施設オープン単群12週試験を行った。第I相試験ではリパスジル点眼剤の用量漸増試験を実施し、1週目は1日1回投与、2週目は1日投与とし、安全性に問題がみられなければ最長9週まで継続した。第II相試験では最長12週、1日2回投与とし、安全性を評価するとともに、1型ROPへの増悪率、無増悪期間、ROPの進行度を検討した。第I相試験の完遂例は15例、リパスジルの投与中止は9例[1型ROPへの増悪7例、投与不同意1例、侵襲性後部(AP)-ROPへの増悪1例]であった。全身性有害事象(AEs)の発現を19例(79.2%)に53件認め、このうち重篤例は5例(20.8%)7件であったが、AEsとリパスジルとの明確な因果関係はないと判定された。有効性に関して、1型ROPへの増悪率にリパスジル投与群と既存対照群84例(男児48例、女児36例、平均在胎週数26.9±2.3)との間に有意差はみられなったが、在胎27週以下の患児に限定すると増悪率はリパスジル群の方が有意に低値を示していた。特に在胎週数が短いROPに対してリパスジルは有効であることが示された。

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：European Journal of Preventive Cardiology  

Aims Exercise intolerance is a clinical feature of patients with heart failure (HF). Cardiopulmonary exercise testing (CPET) is the first-line examination for assessing exercise capacity in patients with HF. However, the need for extensive experience in assessing anaerobic threshold (AT) and the potential risk associated with the excessive exercise load when measuring peak oxygen uptake (peak VO2) limit the utility of CPET. This study aimed to use deep-learning approaches to identify AT in real time during testing (defined as real-time AT) and to predict peak VO2 at real-time AT. Methods and results This study included the time-series data of CPET recorded at the Department of Cardiovascular Medicine, Kyushu University Hospital. Two deep neural network models were developed to: (i) estimate the AT probability using breath-by-breath data and (ii) predict peak VO2 using the data at the real-time AT. The eligible CPET contained 1472 records of 1053 participants aged 18–90 years and 20% were used for model evaluation. The developed model identified real-time AT with 0.82 for correlation coefficient (Corr) and 1.20 mL/kg/min for mean absolute error (MAE), and the corresponding AT time with 0.86 for Corr and 0.66 min for MAE. The peak VO2 prediction model achieved 0.87 for Corr and 2.25 mL/kg/min for MAE. Conclusion Deep-learning models for real-time CPET analysis can accurately identify AT and predict peak VO2. The developed models can be a competent assistant system to assess a patient’s condition in real time, expanding CPET utility.

DOI： 10.1093/eurjpc/zwad375

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記述言語：英語   出版者・発行元：一般社団法人 日本温泉気候物理医学会  

DOI： 10.11390/onki.87_1.8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Circulation  

DOI： 10.1161/CIRCULATIONAHA.123.067528

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記述言語：日本語   出版者・発行元：(一社)日本臨床薬理学会  

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記述言語：日本語   出版者・発行元：(公財)福田記念医療技術振興財団  

カテーテルアブレーションの施行中に記録される電位波高図の画像処理にDeep learningを活用することで再発リスクを予測するモデルを開発した。本モデルは、半年後および1年以内の早期再発に対して高い予測性能を示し、再発リスクに対する新たな層別化アプローチとしての有用性が示唆された。

記述言語：日本語   出版者・発行元：(一社)日本医療情報学会  

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記述言語：日本語   出版者・発行元：(一社)日本医療情報学会  

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記述言語：日本語   出版者・発行元：日本難病医療ネットワーク学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Thrombosis and Haemostasis  

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) requires lifelong anticoagulation. Long-term outcomes of CTEPH under current anticoagulants are unclear. Objectives: The CTEPH AC registry is a prospective, nationwide cohort study comparing the safety and effectiveness of direct oral anticoagulants (DOACs) and warfarin for CTEPH. Patients/Methods: Patients with CTEPH, both tre atment-naïve and on treatment, were eligible for the registry. Inclusion criteria were patients aged ≥20 years and those who were diagnosed with CTEPH according to standard guidelines. Exclusion criteria were not specified. The primary efficacy outcome was a composite morbidity, and mortality outcome comprised all-cause death, rescue reperfusion therapy, initiation of parenteral pulmonary vasodilators, and worsened 6-minute walk distance and WHO functional class. The safety outcome was clinically relevant bleeding, including major bleeding. Results: Nine hundred twenty-seven patients on oral anticoagulants at baseline were analyzed: 481 (52%) used DOACs and 446 (48%) used warfarin. The 1-, 2-, and 3-year rates of composite morbidity and mortality outcome were comparable between the DOAC and warfarin groups (2.6%, 3.1%, and 4.2% vs 3.0%, 4.8%, and 5.9%, respectively; P = .52). The 1-, 2-, and 3-year rates of clinically relevant bleeding were significantly lower in DOACs than in the warfarin group (0.8%, 2.4%, and 2.4% vs 2.5%, 4.8%, and 6.4%, respectively; P = 0.036). Multivariable Cox proportional-hazards regression models revealed lower risk of clinically relevant bleeding in the DOAC group than the warfarin group (hazard ratio: 0.35; 95% CI: 0.13-0.91; P = .032). Conclusion: This registry demonstrated that under current standard of care, morbidity and mortality events were effectively prevented regardless of anticoagulants, while the clinically relevant bleeding rate was lower when using DOACs compared with warfarin.

DOI： 10.1016/j.jtha.2023.03.036

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記述言語：英語   出版者・発行元：(一社)日本動脈硬化学会  

冠動脈ステント留置術を受けた冠動脈疾患の患者をスタチン(S)またはSとエゼチミブの併用(S+E)で治療するCuVIC試験から、治療前と6～8ヵ月追跡調査後の非責任病変の血管内超音波(IVUS)画像が得られた79症例(S群39名、S+E群40名)を抽出し解析した。治療期間後のS+E群のLDL-コレステロール(LDL-C)値はS群と比べて有意に低かった。S+E群ではコレステロール吸収のマーカーであるcampesterol、オキシステロール(β-epoxycholesterol、4β-hydroxycholesterol、27-hydroxycholesterol)も低かった。IVUS解析でS+E群のプラーク退縮率はS群と比べて大きかった。campesterolおよび27-hydroxycholesterolの低下はプラーク退縮と正相関し、LDL-Cの低下は相関しなかった。

記述言語：英語   出版者・発行元：Nutrients  

Oxysterols have been implicated in the pathogenesis of cardiovascular diseases. Serum levels of oxysterols could be positively correlated with cholesterol absorption and synthesis. However, physiological regulation of various serum oxysterols is largely unknown. The aim of this study was to investigate the relationship between clinical factors and cholesterol metabolism markers, and identify oxysterols associated with cholesterol absorption and synthesis in patients with coronary artery disease. Subjects (n = 207) who underwent coronary stenting between 2011 and 2013 were studied cross-sectionally. We measured lipid profiles including serum oxysterols. As for the serum biomarkers of cholesterol synthesis and absorption, oxysterol levels were positively correlated with campesterol and lathosterol. Covariance structure analysis revealed that dyslipidemia and statin usage had a positive correlation with “cholesterol absorption”. Statin usage also had a positive correlation with “cholesterol synthesis”. Several oxysterols associated with cholesterol absorption and/or synthesis. In conclusion, we elucidated the potential clinical factors that may affect cholesterol metabolism, and the associations between various oxysterols with cholesterol absorption and/or synthesis in patients with coronary artery disease.

DOI： 10.3390/nu15132997

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/nu15132997.

記述言語：日本語   出版者・発行元：(一社)日本医療情報学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jtha.2023.03.036.

記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：JACC: Asia  

DOI： 10.1016/j.jacasi.2022.11.013

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Circulation: Arrhythmia and Electrophysiology  

DOI： 10.1161/CIRCEP.122.011579

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記述言語：日本語   出版者・発行元：一般社団法人 日本臨床薬理学会  

<p>臨床研究中核病院ではReal World Evidence創出基盤の構築に2018年度より取り組み、電子カルテから品質の高いデータ抽出が実施されている。しかしながら観察研究であるため、通常診療に用いない有効性指標を収集したり、定期的な評価スケジュール(ビジット)を設定するなど、介入試験に特有なものには対応が難しい。 これらの課題に対応すべく標準化電子ワークシートを開発した。2018~20年度、標準クリニカルパス(ePath日本医療情報学会標準)を開発、電子カルテに実装しており、ベンダー横断的に標準業務実施、標準化データ収集が可能である。 このePathを下敷にした標準化電子ワークシートを実装し、治験実施の上、電子カルテ/ワークシートとEDCの連結を可能とする。 </p><p>同時に、治験実施を促進する分散型臨床試験(DCT)の枠組みを臨床研究中核病院中心に整備している。DCTには大きく分けて、規制面、技術面、運用面の課題がある。規制面の課題は主に厚労省マターであり2022年度以降に発出されるガイダ ンス群を待たねばならないが、AMED先進的臨床研究環境基盤整備プログラムでは、技術面、運用面での整備を行った。 技術面に関しては、DCTを構成する複数の要素(eConsent、eCOA、遠隔診療等)を包括的に運用し記録を効率化するため に標準化電子ワークシートを用いる。 一方、運用面の整備としてDCTを実施するための要素群を統合して運用するために必要なSOP等の作成支援とトレーニングを行った。軽症COVID-19を対象とする経口治療薬を想定した模擬プロトコルを用いて全臨床研究中核病院で模擬治験を実施し、各施設での運用の課題を抽出し対応を行った。</p>

DOI： 10.50993/jsptsuppl.44.0_2-c-s30-3

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記述言語：日本語   出版者・発行元：一般社団法人 日本臨床薬理学会  

<p>【目的】原資料の直接閲覧(SDV:Source Data Verification)は、治験データの信頼性確保のためにGCP上定められている。近年、多施設共同試験の増加や実施医療機関ごとの被験者数減少により、SDVに多大な労力やコストを費やしていることが問題となっている。効率化のために「臨床研究・治験活性化5か年計画2012」でリモートSDVの推進が提言され、医療機関側で様々な取り組みが行われている。今回、九州大学病院においてセキュアな環境を用いた新たなリモートSDVシステムを開発し、導入したので紹介する。【方法】医師向けの病院敷地外からも電子カルテの画面を操作・閲覧することを可能とするシステムが別目的で存在していた。厚生労働省の「医療情報システムの安全管理に関するガイドライン」に準拠し、VPN（Virtual Private Network）の暗号化通信回線を用いて仮想デスクトップ（VDI:Virtual Desktop Infrastructure）上で電子カルテを閲覧することとした。閲覧者の本人確認は通常の電子カルテと同じで生体認証（手のひら静脈認証）とした。また、運用開始前に協力の得られた3試験において、リモートSDVを試行し、問題点の抽出と対応について検討した。【結果・考察】専用モバイルPCをSDV用に権限、周辺システムなどの閲覧可能な範囲をカスタマイズしたリモートSDV用端末として、治験依頼者に貸し出し、リモートSDV用端末～VDI端末にVPNを構築し、通信内容を秘匿した状態でセキュアに電子カルテを閲覧できるようにした。リモートSDV用端末にはCLOMOの位置情報監視機能を利用し、SDV用の隔離した個室等、事前に登録した場所以外では閲覧できない設定とした。また、リモートSDV用端末の貸与は治験依頼者と契約を締結し、閲覧できる患者は該当する試験の被験者のみとした。試行の結果、遠隔地からVPN機能を用いて安全にリモートSDVの実施が可能であることを確認したため、2023年4月より本格運用を開始している。【結論】VDI機能とVPN技術を組み合わせたセキュアな環境により、安全なリモートSDVの実施が可能となった。リモートSDVの導入により、モニタリングの効率化による品質向上やコスト削減等のメリットが見込まれる。</p>

DOI： 10.50993/jsptsuppl.44.0_2-c-p-e5

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記述言語：日本語   出版者・発行元：一般社団法人 日本臨床薬理学会  

<p>当AROでは臨床現場に新薬等を届けることを使命とし、薬事承認の出口として医師主導治験に注力している。「ハイリスク症候性人工弁周囲逆流に対する経カテーテル逆流閉鎖術の安全性及び有効性を検討する医師主導治験」及び「レジストリを活用した慢性血栓塞栓性肺高血圧症に対するエドキサバンの適応拡大のための第III相医師主導治験」等、成果の出た・出つつあるシーズ支援を通して、AROの役割について論じる。</p>

DOI： 10.50993/jsptsuppl.44.0_3-c-s42-2

CiNii Research

記述言語：日本語   出版者・発行元：一般社団法人 日本臨床薬理学会  

<p>【目的】九州大学病院では、2022年12月よりクラウドシステム（Agatha）を用いて治験関連文書の電磁的管理を開始している。モニタリング業務や申請資料の作成、提出を担っているCRAを対象にアンケート調査を行い、当院での電磁化システムの環境をどのように評価しているかを検討した。【方法】2023年５月時点で実施中の企業治験（196試験）において、Agathaを利用している当院担当のCRA 166人を対象にwebアンケート調査を行った。アンケートはREDCapを用いて作成し、各個人の自主的なweb入力により回答を得た。主な調査項目は、「IRB審議資料の提出のしやすさ」や「電磁化導入前と比較した業務量の変化」といった内容とした。【結果・考察】対象者166人のうち114人（68.6％）から回答が得られた。回答者の所属機関はCROが92人（80.7％）、製薬企業が22人であった。「IRB審議資料の提出のしやすさ」の質問に「とても提出しやすい」「提出しやすい」と112人が回答し、2人は「提出したことがない」と回答した。「業務量の変化」については、「かなり減った」「減った」と94人が回答し、「変わらない」7人、「導入前を知らない」13人であった。軽減した業務は、「IRB審議資料の提出」が最も多く91人、次いで「文書の授受」57人、「責任医師保管文書の提出」38人であった。また電磁化システムの環境については「アップロード時の作業工程が少ない」、「システム内での書式作成がないため使い易い」との好意的な意見が多かった。一方、「保管文書一覧の抽出機能がない」、「システム上で責任医師による確認ができない」といった追加機能に関する要望もあった。本アンケート調査の結果より、治験関連文書の電磁的保管によって資料の授受についてはモニタリング業務の効率化に寄与していると考えられたが、一方、保管文書一覧の抽出や責任医師の確認方法に関しては、治験業務の効率的な運用を目指す上で今後の課題と考える。</p>

DOI： 10.50993/jsptsuppl.44.0_2-c-p-e4

CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：一般社団法人 日本動脈硬化学会  

AIM: Several clinical trials using intravascular ultrasound (IVUS) evaluation have demonstrated that intensive lipid-lowering therapy by statin or a combination therapy with statin and ezetimibe results in significant regression of coronary plaque volume. However, it remains unclear whether adding ezetimibe to statin therapy affects coronary plaque composition and the molecular mechanisms of plaque regression. We conducted this prospective IVUS analysis in a subgroup from the CuVIC trial. METHODS: The CuVIC trial was a prospective randomized, open, blinded-endpoint trial conducted among 11 cardiovascular centers, where 260 patients with coronary artery disease who received coronary stenting were randomly allocated into either the statin group (S) or the combined statin and ezetimibe group (S＋E). We enrolled 79 patients (S group, 39 patients; S＋E group, 40 patients) in this substudy, for whom serial IVUS images of nonculprit lesion were available at both baseline and after 6-8 months of follow-up. RESULTS: After the treatment period, the S＋E group had significantly lower level of low-density lipoprotein cholesterol (LDL-C; 80.9±3.7 vs. 67.7±3.8 mg/dL, p=0.0143). Campesterol, a marker of cholesterol absorption, and oxysterols (β-epoxycholesterol, 4β-hydroxycholesterol, and 27-hydroxycholesterol) were also lower in the S ＋E group. IVUS analyses revealed greater plaque regression in the S＋E group than in the S group (-6.14% vs. -1.18% for each group, p=0.042). It was noteworthy that the lowering of campesterol and 27-hydroxycholesterol, but not LDL-C, had a significant positive correlation with plaque regression. CONCLUSIONS: Compared with statin monotherapy, ezetimibe in combination with statin achieved significantly lower LDL-C, campesterol, and 27-hydroxycholesterol, which resulted in greater coronary plaque regression.

DOI： 10.5551/jat.63507

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ Open  

Introduction Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of prior pulmonary thromboembolism (PE), caused by incomplete clot dissolution after PE. In patients with CTEPH, lifelong anticoagulation is mandatory to prevent recurrence of PE and secondary in situ thrombus formation. Warfarin, a vitamin K antagonist, is commonly used for anticoagulation in CTEPH based on historical experience and evidence. The anticoagulant activity of warfarin is affected by food and drug interactions, requiring regular monitoring of prothrombin time. The lability of anticoagulant effect often results in haemorrhagic and thromboembolic complications. Thus, lifelong warfarin is a handicap in terms of safety and convenience. Currently, the use of direct oral anticoagulants (DOACs) in CTEPH has increased with the advent of four DOACs. The safety of DOACs is superior to warfarin, with less intracranial bleeding in patients with non-valvular atrial fibrillation and venous thromboembolism. Edoxaban, the latest DOAC, also has proven efficacy and safety for those diseases in two large clinical trials; the ENGAGE-AF trial and HOKUSAI-VTE trial. The present trial seeks to evaluate whether edoxaban is non-inferior to warfarin in preventing worsening of CTEPH. Methods and analysis The KABUKI trial (is an investigator-initiated, multicentre, phase 3, randomised, single-blind, parallel-group, warfarin-controlled, non-inferiority trial to evaluate the efficacy and safety of edoxaban versus warfarin (vitamin K Antagonist) in subjects with chronic thromBoembolic pUlmonary hypertension taking warfarin (vitamin K antagonIst) at baseline) is designed to prove the non-inferiority of edoxaban to warfarin in terms of efficacy and safety in patients with CTEPH. Ethics and dissemination This study is approved by the Institutional Review Board of each participating institution. The findings will be published in a peer-reviewed journal, including positive, negative and inconclusive results. Trial registration number NCT04730037. Protocol version This paper was written per the study protocol V.4.0, dated 29 January 2021.

DOI： 10.1136/bmjopen-2022-061225

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記述言語：その他   掲載種別：研究論文（学術雑誌）   出版者・発行元：eBioMedicine  

Background: We conducted an exploratory study to assess the safety tolerability, and anti-fibrotic effects of PRI-724, a CBP/β-catenin inhibitor, in patients with hepatitis C virus (HCV)- and hepatitis B virus (HBV)-induced cirrhosis. Methods: This multicentre, open-label, non-randomised, non-placebo-controlled phase 1/2a trial was conducted at three hospitals in Japan. Between July 27, 2018, and July 13, 2021, we enrolled patients with HCV- and HBV-induced cirrhosis classified as Child–Pugh (CP) class A or B. In phase 1, 15 patients received intravenous infusions of PRI-724 at escalating doses of 140, 280, and 380 mg/m2/4 h twice weekly for 12 weeks. In phase 2a, 12 patients received the recommended PRI-724 dose. The primary endpoints of phases 1 and 2a were the frequency and severity of adverse events and efficacy in treating cirrhosis based on liver biopsy. This study was registered at ClinicalTrials.gov (no. NCT 03620474). Findings: Three patients from phase 1 who received the recommended PRI-724 dose were evaluated to obtain efficacy and safety data in phase 2a. Serious adverse events occurred in three patients, one of which was possibly related to PRI-724. The most common adverse events were diarrhoea and nausea. PRI-724 did not decrease hepatic fibrosis with any statistical significance, either by ordinal scoring or measurement of collagen proportionate area at 12 weeks; however, we observed statistically significant improvements in liver stiffness, Model for End-stage Liver Disease score, and serum albumin level. Interpretation: Intravenous administration of 280 mg/m2/4 h PRI-724 over 12 weeks was preliminarily assessed to be well tolerated; however, further evaluation of anti-fibrotic effects in patients with cirrhosis is warranted. Funding: AMED, Ohara Pharmaceutical

DOI： 10.1016/j.ebiom.2022.104069

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記述言語：日本語   出版者・発行元：一般社団法人 日本臨床薬理学会  

<p>2003年に薬事法が改正され「医師主導治験」という世界的に見ても特異な制度が始まった。製薬会社等が開発・治験を実施してくれない採算性の低い製品・適応に対して、医師が自ら薬事承認のための臨床試験を計画・設計・実施する。最終的にそのデータを製薬会社等が承認申請に用いるという本質的に捻れた仕組みを持ち、元々はドラッグラグ、デバイスラグ等を解消する手段の一つとして始められた。昨今は企業開発品の初期治験でさえアカデミアに任せ、ある程度医師主導治験で成績が出るまで様子見をするという企業が出て来ているのも事実である。７月時点のjRCTで実施中の未承認薬医師主導治験が43試験ある。うち15件（35%）は研究資金等の提供組織として製薬企業も記載されている。適応外薬も同じく43試験あり、21件（49%）は製薬企業も記載されている。AMED公募において「なぜ企業治験ではないのか？」としばしば問題となるが、市場性が低い製品の臨床開発をどこが負担して実施すべきかについて明確な基準が無く、未だコンセンサスは得られていない。　</p><p>リポジショニングでよく見受ける特許切れ成分の新作用機序が臨床ニーズを満たす場合、臨床現場で発したneeds pull開発として医療従事者の熱意で推進するものの、必ずしも市場が要求したmarket pullではないことから来る弊害もある。研究費を獲得して医師主導治験を実施し有効性を証明して、先発薬を適応拡大できたとしても、沢山ある後発薬と差別化が難しい。用途特許等で法的に保護する事は可能であるが、後発薬の適応外使用を止める実効性には乏しい。従って採算が取れる目処が無いなどの理由により企業が承認申請を請け負わない場合がある。国内であまねく使用できるようにするという医師主導治験の本来目的は出口で頓挫してしまう。米国では保険適用を伴った臨床使用が薬事承認範囲を超えてcompendiaという形で広く認められているため、適応拡大に限れば我が国の保険行政特有の問題と言える。　</p><p>制度開始から20年近くたち、ARO初めとして現場は医師主導治験に慣れてきたが上記のような弊害も目立つ。アカデミアも企業もこの特有な制度を今後どのように活用して行くのか、規制当局とともに再考する時期に来ている。</p>

DOI： 10.50993/jsptsuppl.43.0_4-c-s44-2

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記述言語：日本語   出版者・発行元：一般社団法人 日本臨床薬理学会  

<p>【目的】治験薬の作用機序や製剤特性の多様化・複雑化に伴い、非盲検薬剤師が必要となる場合や、製剤的な側面から調剤・調製方法が煩雑になる場合も多く、治験における薬剤師の重要性が高まっている。こうした複雑な治験に関与する薬剤師に対し、Risk based Approachに基づく適切なトレーニングを行うことは、治験の質向上という観点からも重要である。しかしながら、求められるトレーニング内容や形式は試験ごとに異なるため、Quality Management System（QMS）の観点からトレーニングの現状について調査を行った。【方法】2018～2021年度に九州大学病院が契約を行った企業治験のうち、当院で治験開始前に中止となった試験を除く174試験を対象に調査を実施した。その中で、2022年6月までに治験依頼者が提示を求めたトレーニングについて、トレーニング内容及び件数、対象者、契約年度、治験デザイン、非盲検薬剤師の有無に関する評価を行った。【結果・考察】薬剤師に対して治験開始時の初回トレーニングを求めた治験は127試験であり、そのうちの74.0%(94試験)が国際共同試験であった。また、契約年度毎にみると初回トレーニングを求めたものは、2018年度の60.9％から2021年度の77.8％へと経年的に増加した。一方、治験情報の改訂に伴うトレーニングを求めた試験は75試験（336件）であり、その内訳は、治験薬管理手順書関連が31.3%(105件)、プロトコール関連が28.6%(96件)、治験薬概要書関連が26.5%(89件)、IRT関連5.4%(18件)、盲検化手順関連が2.4%(8件)などであった。なお、このうち3割の試験において、軽微な変更のトレーニングを求めた事例や、試験途中でトレーニング対象者や内容を変更した事例、事実と異なる記録の作成や詳細に記載方法を指定した記録を求めた事例が見られた。また、非盲検薬剤師が必要な試験(23試験)のうち65.2％(15試験)が治験情報の改訂に伴うトレーニングを求めたが、非盲検薬剤師が不要な試験(151試験)では39.7％(60試験)と、リスクに応じた対策に違いが見られた。【結論】ICH-E6(R2)の改訂に伴い治験の品質管理にQMSの必要性が明記され、Risk based Approachに基づいたトレーニングが求められている。しかし、トレーニングの記録作成を重視するあまり、治験の質向上という本質が欠如した内容も散見された。QMSの概念に基づくトレーニングのあり方を規制当局、依頼者、実施施設が共に検討していく必要があると考える。</p>

DOI： 10.50993/jsptsuppl.43.0_2-c-p-047

CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Therapeutic Innovation and Regulatory Science  

<jats:title>Abstract</jats:title><jats:sec>
<jats:title>Background</jats:title>
<jats:p>The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is undertaking a major revision of ICH E6 Good Clinical Practice (GCP) decided to involve external stakeholders in ICH-GCP renovation. Activities such as surveys and public conferences have taken place in the United States, European Union, and Japan. For stakeholder engagement in Japan, a designated research group conducted a survey of academic stakeholders.</jats:p>
</jats:sec><jats:sec>
<jats:title>Methods</jats:title>
<jats:p>A total of 105 academic stakeholders from 18 institutions responded to the survey. The research group developed recommendations reflecting the survey results and the opinions from patients and the public.</jats:p>
</jats:sec><jats:sec>
<jats:title>Results</jats:title>
<jats:p>The survey showed the top four principles needing renovation were (i) informed consent (Chapter 2.9, 12.4% of respondents believed it needed renovation), (ii) systems for quality assurance (Chapter 2.13, 9.5%), (iii) information on an investigational product (Chapter 2.4, 5.7%), and (iv) procedures on clinical trial information (Chapter 2.10, 5.7%). The top three sections identified as needing renovation were: (i) informed consent (Chapter 4.8, 27.6%), (ii) monitoring (Chapter 5.18, 22.9%), and (iii) composition, functions, and operations of the ethics committee (Chapter 3.2, 14.3%). Recommendations included clarification of ICH-GCP’s scope, proportionality in various aspects of clinical trials, diversity and liquidity of ethics committee members, modernization of informed consent procedures, variations in monitoring, and regulatory grade when using real-world data.</jats:p>
</jats:sec><jats:sec>
<jats:title>Conclusion</jats:title>
<jats:p>The recommendations from Japanese investigators and patients have been submitted to the ICH E6 Expert Working Group, which will strengthen the robustness of the GCP renovation. </jats:p>
</jats:sec>

DOI： 10.1007/s43441-021-00350-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s43441-021-00350-4.

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Aims: Individual risk stratification is a fundamental strategy in managing patients with heart failure (HF). Artificial intelligence, particularly machine learning (ML), can develop superior models for predicting the prognosis of HF patients, and administrative claim data (ACD) are suitable for ML analysis because ACD is a structured database. The objective of this study was to analyse ACD using an ML algorithm, predict the 1 year mortality of patients with HF, and finally develop an easy-to-use prediction model with high accuracy using the top predictors identified by the ML algorithm. Methods and results: Machine learning-based prognostic prediction models were developed from the ACD on 10 175 HF patients from the Japanese Registry of Acute Decompensated Heart Failure with 17% mortality during 1 year follow-up. The top predictors for prognosis in HF were identified by the permutation feature importance technique, and an easy-to-use prediction model was developed based on these predictors. The c-statistics and Brier scores of the developed ML-based models were compared with those of conventional risk models: Seattle Heart Failure Model (SHFM) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC). A voting classifier algorithm (ACD-VC) achieved the highest c-statistics among the six ML algorithms. The permutation feature importance technique enabled identification of the top predictors such as Barthel index, age, body mass index, duration of hospitalization, last hospitalization, renal disease, and non-loop diuretics use (feature importance values were 0.054, 0.025, 0.010, 0.005, 0.005, 0.004, and 0.004, respectively). Upon combination of some of the predictors that can be assessed from a brief interview, the Simple Model by ARTificial intelligence for HF risk stratification (SMART-HF) was established as an easy-to-use prediction model. Compared with the conventional models, SMART-HF achieved a higher c-statistic {ACD-VC: 0.777 [95% confidence interval (CI) 0.751–0.803], SMART-HF: 0.765 [95% CI 0.739–0.791], SHFM: 0.713 [95% CI 0.684–0.742], MAGGIC: 0.726 [95% CI 0.698–0.753]} and better Brier scores (ACD-VC: 0.121, SMART-HF: 0.124, SHFM: 0.139, MAGGIC: 0.130). Conclusions: The ML model based on ACD predicted the 1 year mortality of HF patients with high accuracy, and SMART-HF along with the ML model achieved superior performance to that of the conventional risk models. The SMART-HF model has the clear merit of easy operability even by non-healthcare providers with a user-friendly online interface (https://hfriskcalculator.herokuapp.com/). Risk models developed using SMART-HF may provide a novel modality for risk stratification of patients with HF.

DOI： 10.1002/ehf2.13556

記述言語：英語   掲載種別：研究論文（学術雑誌）  

<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title>Context</jats:title>
<jats:p>11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitors demonstrate antimetabolic and antisarcopenic effects in Cushing’s syndrome (CS) and autonomous cortisol secretion (ACS) patients.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Objective</jats:title>
<jats:p>To confirm the efficacy and safety of S-707106 (11β-HSD1 inhibitor) administered to CS and ACS patients.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Design</jats:title>
<jats:p>A 24-week single-center, open-label, single-arm, dose-escalation, investigator-initiated clinical trial on a database.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Setting</jats:title>
<jats:p>Kyushu University Hospital, Kurume University Hospital, and related facilities.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Patients</jats:title>
<jats:p>Sixteen patients with inoperable or recurrent CS and ACS, with mildly impaired glucose tolerance.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Intervention</jats:title>
<jats:p>Oral administration of 200 mg S-707106 after dinner, daily, for 24 weeks. In patients with insufficient improvement in oral glucose tolerance test results at 12 weeks, an escalated dose of S-707106 (200 mg twice daily) was administered for the residual 12 weeks.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Main Outcome Measures</jats:title>
<jats:p>The rate of participants responding to glucose tolerance impairment, defined as those showing a 25% reduction in the area under the curve (AUC) of plasma glucose during the 75-g oral glucose tolerance test at 24 weeks.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results</jats:title>
<jats:p>S-707106 administration could not achieve the primary endpoint of this clinical trial (>20% of responsive participants). AUC glucose decreased by −7.1% [SD, 14.8 (90% CI −14.8 to −1.0), P = 0.033] and −2.7% [14.5 (−10.2 to 3.4), P = 0.18] at 12 and 24 weeks, respectively. S-707106 administration decreased AUC glucose significantly in participants with a high body mass index. Body fat percentage decreased by −2.5% [1.7 (−3.3 to −1.8), P < 0.001] and body muscle percentage increased by 2.4% [1.6 (1.7 to 3.1), P < 0.001].</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>S-707106 is an effective insulin sensitizer and antisarcopenic and antiobesity medication for these patients.</jats:p>
</jats:sec>

DOI： 10.1210/clinem/dgab450

記述言語：英語   掲載種別：研究論文（学術雑誌）  

<jats:sec><jats:title>Introduction</jats:title><jats:p>Retinopathy of prematurity (ROP) is a vascular proliferative disorder that occurs in preterm infants. Existing treatments are only indicated in severe ROP cases due to the high invasiveness and the potential risk of irreversible side effects. We previously elucidated that ripasudil, a selective inhibitor of the Rho-associated protein kinase, has the ability to inhibit abnormal retinal neovascularisation in animal models. In addition, ripasudil eye drops (Glanatec ophthalmic solution 0.4%) have been already used for the treatment of glaucoma. Since eye drop therapy is less invasive, early intervention for ROP is possible. The purpose of this phase I/II trial is to evaluate the safety and efficacy of ripasudil eye drops for preterm infants with ROP.</jats:p></jats:sec><jats:sec><jats:title>Methods and analysis</jats:title><jats:p>This is a multicentre, open-label, single-arm phase I/II trial. To evaluate the safety and efficacy of ripasudil as much as possible, ripasudil will be administered to all enrolled preterm infants with zone I/II, stage 1, or worse ROP. The safety and efficacy of ripasudil in treated patients will be assessed in comparison to a historical control group. Because this is the first trial of ripasudil in preterm infants, a dose-escalation study (once daily for 1 week, then two times per day for 2 weeks) will be conducted in phase I. After obtaining approval from the independent data and safety monitoring board to continue the trial after the completion of phase I, phase II will be conducted. In phase II, ripasudil eye drops will be administered two times per day for 12 weeks. The primary endpoint in phase II is also safety. Efficacy and pharmacokinetics will be evaluated as secondary endpoints.</jats:p></jats:sec><jats:sec><jats:title>Ethics and dissemination</jats:title><jats:p>This study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals.</jats:p></jats:sec><jats:sec><jats:title>Trial registration numbers</jats:title><jats:p><jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" specific-use="clinicaltrial pre-results" xlink:href="NCT04621136">NCT04621136</jats:ext-link> and jRCT2071200047.</jats:p></jats:sec>

DOI： 10.1136/bmjopen-2020-047003

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1136/bmjopen-2020-047003.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1210/clinem/dgab450.

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Timely reporting and appropriate response to safety information related to ongoing clinical trials is crucial for conducting trials appropriately and safely. However, it is difficult to understand exactly what, when, and to whom information should be reported because there are different types of clinical trials in Japan, governed by different laws and regulations. For example, principal investigators need to report serious, unrelated adverse events in ＂Chiken＂clinical trials, but not in clinical trials specified under the Clinical Trials Act 2017. This paper clarifies the principal investigator's responsibility for reporting under the three laws related to clinical trials: the Pharmaceuticals and Medical Devices Act, the Clinical Trials Act, and the Act on the Safety of Regenerative Medicine. Report items were explained and summarized in a table. The paper also separately covers trials under other frameworks, such as the Ethical Guidelines for Medical and Health Research Involving Human Subjects. The paper will therefore help principal investigators to better understand their responsibilities and manage safety information in clinical trials under various frameworks in Japan. The paper also discusses some current issues that still need resolving.

DOI： 10.3999/JSCPT.52.13

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Safety Information Management of Investigator-initiated Clinical Trials in Japan

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Purpose: To evaluate the safety and efficacy of BBG (Brilliant Blue G250) for lens capsular staining during cataract surgery with continuous curvilinear capsulorhexis. Study design: Prospective clinical study. Methods: This clinical trial enrolled 30 eyes of 30 patients who underwent cataract surgery with BBG (0.25 mg/mL Brilliant Blue G250) for capsular staining. Visualization of the lens capsule and the ease of capsulorhexis with BBG staining were evaluated in five grades (grade 0 to 4) by the Independent Data Monitoring Committee and the surgeons. The safety of BBG was also evaluated in terms of ocular and systemic tolerance for 7 days after surgery. Results: The use of BBG improved visualization of the lens capsule and complete capsulorhexis was performed in all patients. The major endpoint (Independent Data Monitoring Committee evaluation) showed that use of BBG improved visualization of the lens capsule and the ease of capsulorhexis (grades 2 to 4); the committee’s grading results were similar to those of the surgeons. Frequent complications observed in more than two eyes were conjunctival injection, corneal edema and intraocular pressure elevation. No severe complications were observed in ocular and systemic evaluations. Conclusion: BBG staining contributed to improved visualization of the lens capsule and aided in the completion of capsulorhexis during cataract surgery. The use of BBG for capsular staining also exhibited favorable safety results.

DOI： 10.1007/s10384-020-00763-y

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Although the obesity paradox may vary depending upon clinical background factors such as age, gender, aetiology of heart failure and comorbidities, the reasons underlying the heterogeneous impact of body mass index (BMI) on in-hospital cardiac mortality under various conditions in patients with acute heart failure syndromes (AHFSs) remain unclear. Methods: Among 4617 hospitalised patients with AHFSs enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, the patient characteristics and in-hospital cardiac mortality rates in those with low BMI (BMI <25 kg/m(2), n = 3263) were compared to those with high BMI (BMI > 25 kg/m(2), n = 1354). Results: Compared to the high-BMI group, the low-BMI group was significantly older, less likely to be male and to have hypertensive or idiopathic dilated aetiologies and more likely to have valvular aetiologies and a history of prior hospitalisation for AHFS. The low-BMI group also had lower prevalence rates of diabetes, dyslipidaemia, hypertension and atrial fibrillation and higher prevalence rates of anaemia and chronic obstructive pulmonary disease. In addition, cardiac mortality was significantly higher in the low-BMI group than in the high-BMI group (5.5 vs. 1.5%, p < 0.001). Logistic regression analysis demonstrated that low BMI was a predictor of cardiac mortality (odds ratio: 3.89, 95% confidence interval: 2.44-6.21). In subgroup analyses, the impact of BMI on cardiac mortality differed depending on the presence of hypertensive aetiology, hypertension, chronic obstructive pulmonary disease and hyponatremia (all p < 0.05), although there were no interactions between the impacts of BMI and age, gender, other aetiologies, prior hospitalisation, diabetes, anaemia, cardio-renal function and in-hospital management. Conclusion: It is necessary to appreciate the obesity paradox in AHFS patients, and a patient's heterogeneous background should also be considered.

DOI： 10.1177/2048872617703061

記述言語：英語  

DOI： 10.1093/annonc/mdz343.086

記述言語：英語  

記述言語：その他   掲載種別：研究論文（その他学術会議資料等）  

Although daily variations of blood pressure (BP) predict cardiovascular event risk, their assessment requires ambulatory BP monitoring which hinders the clinical application of this approach. Since the baroreflex is a major determinant of BP variations, especially in the frequency range of 0.01-0.1 Hz (baro-frequency), we hypothesized that the power spectral density (PSD) of short-term BP recordings in the baro-frequency range may predict daily variations of BP. In nine-week-old Wister-Kyoto male rats (N =5) with or without baroreflex dysfunction, we telemetrically recorded continuous BP for 24 hours and estimated PSD using Welch's periodogram for the recordings during the 12-hour light period. We compared the reference PSD of 12-hour recording with the PSDs obtained from shorter data lengths ranging from 5 to 240 minutes. The 30-minute BP recordings reproduced PSD of 12-hour recordingswell, and PSD in the baro-frequency range paralleled the standard deviation of 12-hour BP. Thus, the PSD of 30-minute BP reflects the daily BP variability in rats. In human subjects, we estimated PSD from 30-minute noninvasive continuous BP recordings. The rat and human PSDs shared remarkably similar characteristics. Furthermore, comparison of PSD between elderly and young subjects suggested that the baro-frequency range in humans overlapped with that in rats. In conclusion, PSD derived from 30-minute BP recordings is capable of predicting daily BP variations. Our proposed method may serve as a simple, noninvasive and practical tool for predicting cardiovascular events in the clinical setting.

DOI： 10.1109/EMBC.2018.8513040

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pulmonary hypertension (PH) is a disease with poor prognosis, caused by the obstruction/stenosis of small pulmonary arteries. Statin is known to have vasodilating and anti-inflammatory property and is considered to be a candidate of therapeutic agents for the treatment of PH, but its efficacy has not been verified in clinical trials. We have formulated pitavastatin incorporating nanoparticles composed of poly (lactic-co-glycolic acid) (NK-104-NP) to improve drug delivery to the pulmonary arteries and evaluated their safety and pharmacokinetics in healthy volunteers. To accomplish this purpose, phase I clinical trials were conducted. In the single intravenous administration regimen, 40 healthy subjects were enrolled and PK (pharmacokinetic) parameters in 4 groups (1, 2, 4, and 8 mg as pitavastatin calcium) were as follows: 1.00 hour after the administration, the plasma concentration of pitavastatin reached Cmax (the maximum drug concentration) in all groups. Cmax, AUC0-t (area under the curve from time 0 to the last measurable concentration) and AUC0-∞ (area under the curve from time 0 extrapolated to infinite time) were increased in a dose-dependent manner. Population pharmacokinetic analysis based on these results indicated no accumulation of pitavastatin after repeated administration of NK-104-NP for 7 days. In this 7-day administration trial, the mean Cmax and AUC0-∞ of pitavastatin were not significantly different between days 1 and 7, suggesting that pitavastatin is unlikely to accumulate after repeated administration. In these trials, three adverse events (AEs) were reported, but they were resolved without any complications and judged to have no causal relationships with NK-104-NP. These results indicate that the innovative nanotechnology-based medicine NK-104-NP exhibited dose-dependent pharmacokinetics and was well tolerated with no significant AEs in healthy volunteers.

DOI： 10.1536/ihj.17-555

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: New drug and medical device introduction in Japan usually lags behind that in the West. Many reports indicate that in Japan, the associated risks are considered greater than the benefits recognized in other countries. This study aimed to compare the relationship between risk-benefit perception and acceptance of medical technologies in 3 leading markets. METHODS: A tripartite cross-sectional survey of the general public was used. In total, 3345 adults in the United Kingdom, the United States, and Japan participated, and sexes and age groups were equally represented. Questions about the perception of risk, benefit, and acceptance of medical and other scientific technologies, and trust of medical product providers or regulatory authorities were included. RESULTS: Five-step Likert coding for risk/benefit/acceptance of 4 medical items (x-rays, antibiotics, vaccines, and cardiac pacemakers) and 6 general items (such as automobiles and airplanes) were collected. Relationships between benefit perception and acceptance were linear for 4 medical technologies. The relationship had a similar slope but was shifted downward in Japan compared with the UK and US ( P < .01), suggesting a lower acceptance in Japan for all benefit perceptions. The trend was the same between risk perception and acceptance, except for slopes that were negative. Correspondence analysis showed a strong correlation among acceptance of medical technologies, benefits of medical technologies, trust in doctors, and trust in the Department of Health. The UK and US attributes were clustered with positive responses such as "useful," "acceptable," and "trustworthy," whereas Japan was clustered with intermediate to negative responses such as "neither" and "untrustworthy." CONCLUSIONS: Acceptance of medical technologies was low in Japan because of significant differences in trust for doctors and authorities compared with that in the UK and US. This is a possible basis for delays of 24 to 60 months for medical product approval in Japan.

DOI： 10.1177/2168479017739267

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1536/ihj.17-555

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although daily variations of blood pressure (BP) predict cardiovascular event risk, their assessment requires ambulatory BP monitoring which hinders the clinical application of this approach. Since the baroreflex is a major determinant of BP variations, especially in the frequency range of 0.01-0.1 Hz (baro-frequency), we hypothesized that the power spectral density (PSD) of short-term BP recordings in the baro-frequency range may predict daily variations of BP. In nine-week-old Wister-Kyoto male rats (N = 5) with or without baroreflex dysfunction, we telemetrically recorded continuous BP for 24 hours and estimated PSD using Welch's periodogram for the recordings during the 12-hour light period. We compared the reference PSD of 12-hour recording with the PSDs obtained from shorter data lengths ranging from 5 to 240 minutes. The 30-minute BP recordings reproduced PSD of 12-hour recordings well, and PSD in the baro-frequency range paralleled the standard deviation of 12-hour BP. Thus, the PSD of 30-minute BP reflects the daily BP variability in rats. In human subjects, we estimated PSD from 30-minute noninvasive continuous BP recordings. The rat and human PSDs shared remarkably similar characteristics. Furthermore, comparison of PSD between elderly and young subjects suggested that the baro-frequency range in humans overlapped with that in rats. In conclusion, PSD derived from 30-minute BP recordings is capable of predicting daily BP variations. Our proposed method may serve as a simple, noninvasive and practical tool for predicting cardiovascular events in the clinical setting.

DOI： 10.1109/EMBC.2018.8513040

記述言語：その他   掲載種別：研究論文（学術雑誌）  

The aim of this study was to evaluate the association of functional mitral regurgitation (FMR), preserved or reduced ejection fraction (EF), and ischemic or nonischemic origin with outcomes in patients discharged alive after hospitalization for acute decompensated heart failure (HF). Of the 4,842 patients enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, 3,357 patients were evaluated to assess the association of FMR, preserved or reduced EF, and ischemic or nonischemic origin with the primary end point (all-cause death and readmission for HF after discharge). At the time of discharge, FMR was assessed semiquantitatively (classified as none, mild, or moderate to severe) by color Doppler analysis of the regurgitant jet area. According to multivariable analysis, in the ischemic group, either mild or moderate to severe FMR in patients with a preserved EF had a significantly higher risk of the primary end point than patients without FMR (hazard ratio [HR] 1.60; 95% confidence interval [CI] 1.12 to 2.29; p = 0.010 and HR 1.98; 95% CI 1.30 to 3.01; p = 0.001, respectively). In patients with reduced EF with an ischemic origin, only moderate to severe FMR was associated with a significantly higher risk of the primary end point (HR 1.67; 95% CI 1.11 to 2.50; p = 0.014). In the nonischemic group, there was no significant association between FMR and the primary end point in patients with either a preserved or reduced EF. In conclusion, among patients with acute decompensated HF with a preserved or reduced EF, the association of FMR with adverse outcomes may differ between patients who had an ischemic or nonischemic origin of HF.

DOI： 10.1016/j.amjcard.2017.05.051

記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

Numerous studies have shown in animal models that vagal nerve stimulation (VNS) strikingly reduces infarct size of acute myocardial infarction (AMI) and prevents heart failure. However, the lack of techniques to noninvasively stimulate the vagal nerve hinders VNS from clinical applications. Transcranial magnetic stimulation is noninvasive and capable of stimulating central neurons in patients. In this study, we examined whether the magnetic stimulation could noninvasively activate the cervical vagal nerve in healthy human. Sixteen healthy males and 4 females were enrolled in this study. We used Magstim Rapid2 with a 70-mm double coil in the right neck. We randomly assigned the subjects to 5 Hz or 20 Hz stimulation. We defined the maximum intensity of stimulation (MAX) which is the intensity just below the threshold of adverse effects. We defined HALF as a half of MAX. Protocols comprised 2 sets of MAX and 2 sets of HALF. Each stimulation continued for 3 minutes. We monitored heart rate (HR) and assessed the bradycardic response as an index of successful VNS. Nineteen subjects completed all protocols. They had no problematic adverse events during and/or after magnetic VNS. The magnetic VNS induced transient bradycardic responses in some subjects, whereas failed to induce sustained bradycardia in pooled data in any settings. Arterial pressure did not change either. Successful magnetic stimulation requires technical improvements including narrowing the magnetic focus and optimization of stimulation site. These improvements may enable us to apply magnetic VNS in the management of AMI.

DOI： 10.1109/EMBC.2017.8037812

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background There is currently no anti-fibrotic drug therapy available to treat hepatitis C virus (HCV) cirrhosis. The aim of this study was to assess the safety, tolerability, and anti-fibrotic effect of PRI-724, a small-molecule modulator of Wnt signaling, in patients with HCV cirrhosis. Methods In this single-center, open-label, phase 1 trial, we sequentially enrolled patients with HCV cirrhosis who were classified as Child-Pugh (CP) class A or B. PRI-724 was administered as a continuous intravenous infusion of 10, 40, or 160 mg/m2/day for six cycles of 1 week on and 1 week off. The primary endpoints were frequency and severity of adverse events. The secondary endpoint was efficacy of PRI-724 in treating cirrhosis based on CP score and liver biopsy. This study is registered with ClinicalTrials.gov (no. NCT02195440). Findings Between Sept 3, 2014 and May 2, 2016, 14 patients were enrolled: CP class A:B, 6:8; median age, 62 (range: 43 to 74) years; male:female, 10:4. Twelve of the 14 patients completed six cycles of treatment; one was withdrawn from the study due to possible study drug-related liver injury (grade 3) in the 160 mg/m2/day dose cohort and one withdrew for personal reasons. Serious adverse events occurred in three patients [21% (3/14)], one of which was possibly related to PRI-724. The most common adverse events were nausea [29% (4/14)] and fatigue [21% (3/14)]. After PRI-724 administration, the CP scores worsened by 1 point in two patients in the 10 mg/m2/day cohort, improved in three patients at 1, 1, and 2 points in the 40 mg/m2/day cohort, and improved in one patient by 3 points in the 160 mg/m2/day cohort. The histology activity index scores of the liver tissue improved in two patients and exacerbated in two patients in the 10 mg/m2/day cohort, and improved in one patient in the 40 mg/m2/day cohort. Interpretation This study showed that administration of 10 or 40 mg/m2/day intravenous PRI-724 over 12 weeks was well-tolerated by patients with HCV cirrhosis; however, liver injury as a possible related serious adverse event was observed in the 160 mg/m2/day cohort. Funding Source AMED.

DOI： 10.1016/j.ebiom.2017.08.016

記述言語：英語   掲載種別：研究論文（学術雑誌）  

<jats:sec>
<jats:title>Objectives—</jats:title>
<jats:p>We sought to investigate whether treatment with ezetimibe in combination with statins improves coronary endothelial function in target vessels in coronary artery disease patients after coronary stenting.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Approach and Results—</jats:title>
<jats:p>
We conducted a multicenter, prospective, randomized, open-label, blinded-end point trial among 11 cardiovascular treatment centers. From 2011 to 2013, 260 coronary artery disease patients who underwent coronary stenting were randomly allocated to 2 arms (statin monotherapy, S versus ezetimibe [10 mg/d]+statin combinational therapy, E+S). We defined target vessel dysfunction as the primary composite outcome, which comprised target vessel failure during treatment and at the 6- to 8-month follow-up coronary angiography and coronary endothelial dysfunction determined via intracoronary acetylcholine testing performed in cases without target vessel failure at the follow-up coronary angiography. Coadministration of ezetimibe with statins further lowered low-density lipoprotein cholesterol levels (83±23 mg/dL in S versus 67±23 mg/dL in E+S;
<jats:italic>P</jats:italic>
<0.0001), with significant decreases in oxidized low-density lipoprotein and oxysterol levels. Among patients without target vessel failure, 46 out of 89 patients (52%) in the S arm and 34 out of 96 patients (35%) in the E+S arm were found to have coronary endothelial dysfunction (
<jats:italic>P</jats:italic>
=0.0256), and the incidence of target vessel dysfunction at follow-up was significantly decreased in the E+S arm (69/112 (62%) in S versus 47/109 (43%) in E+S;
<jats:italic>P</jats:italic>
=0.0059). A post hoc analysis of post-treatment low-density lipoprotein cholesterol–matched subgroups revealed that the incidence of both target vessel dysfunction and coronary endothelial dysfunction significantly decreased in the E+S arm, with significant reductions in oxysterol levels.
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions—</jats:title>
<jats:p>The CuVIC trial (Effect of Cholesterol Absorption Inhibitor Usage on Target Vessel Dysfunction after Coronary Stenting) has shown that ezetimibe with statins, compared with statin monotherapy, improves functional prognoses, ameliorating endothelial dysfunction in stented coronary arteries, and was associated with larger decreases in oxysterol levels.</jats:p>
</jats:sec>

DOI： 10.1161/atvbaha.116.308388

記述言語：その他   掲載種別：研究論文（学術雑誌）  

PURPOSE: To investigate the efficacy and safety of A0001 (brilliant blue G250) for visualization of the internal limiting membrane (ILM) during and after vitrectomy.

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Global medical devices have become more popular, but investment money for medical device development is not easily available in the market. Worldwide health-care budget constraints mean that efficient medical device development has become essential. To achieve efficient development, globalization is a key to success. Spending large amounts of money in different regions for medical device development is no longer feasible. Methods and Results: In order to streamline processes of global medical device development, an academic, governmental, and industrial consortium, called the Harmonization by Doing program, has been set up. The program has been operating between Japan and the USA since 2003. The program has 4 working groups: (1) Global Cardiovascular Device Trials; (2) Study on Post-Market Registry; (3) Clinical Trials; and (4) Infrastructure and Methodology Regulatory Convergence and Communication. Each working group has as its goals the achievement of speedy and efficient medical device development in Japan and the USA. The program has held multiple international meetings to deal with obstacles against efficient medical device development. Conclusions: This kind of program is very important to deliver novel medical devices. Involvement of physicians in this type of activity is also very helpful to achieve these goals.

DOI： 10.1253/circj.CJ-12-1431

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

記述言語：英語  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

掲載種別：研究論文（学術雑誌）  

記述言語：日本語   掲載種別：研究論文（その他学術会議資料等）  

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Although a simple concept of load-independent behavior of the intact heart evolved from early studies of isolated, intact blood-perfused hearts, more recent studies showed that, as in isolated muscle, the mode of contraction (isovolumic vs. ejection) impacts on end-systolic elastance. The purpose of the present study was to test whether a four-state model of myofilament interactions with length-dependent rate constants could explain the complex contractile behavior of the intact, ejecting heart. Studies were performed in isolated, blood-perfused canine hearts with intracellular calcium transients measured by macroinjected aequorin. Measured calcium transients were used as the driving function for the model, and length-dependent rate constants yielding the highest concordance between measured and model-predicted midwall stress at different isovolumic volumes were determined. These length-dependent rate constants successfully predicted contractile behavior on ejecting contractions. This, along with additional model analysis, suggests that length-dependent changes in calcium binding affinity may not be an important factor contributing to load-dependent contractile performance in the intact heart under physiological conditions.

DOI： 10.1152/ajpheart.00498.2001

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Behçet's disease frequently involves the venous system, usually affecting small vessels, but sometimes large vessels such as the vena cava. Antiphospholipid antibody syndrome is associated with an increased incidence of arterial and venous thrombosis. A 29-year-old male with Behçet's disease developed bilateral leg edema secondary to thrombotic occlusion of the inferior vena cava. Laboratory tests revealed positive antiphospholipid antibodies and lupus anticoagulant. Treatment with steroid and warfarin subsequent to intravenous administration of uro-kinase resulted in improvement of symptoms. The association of antiphospholipid antibody syndrome and Behçet's disease may have caused the total thrombotic occlusion of the vena cava in this case.

DOI： 10.1253/jcj.65.837

記述言語：その他   掲載種別：研究論文（学術雑誌）  

BAY y 5959 is a dihydropyridine derivative with positive inotropic actions mediated by a direct increase in intracellular calcium. We characterized the direct myocardial actions of this new agent in hearts isolated from seven normal dogs and from five dogs with repeated coronary microembolization-induced heart failure. Inotropic actions of BAY y 5959 were accompanied by little effect on duration of contraction and by prolongation of the monophasic action potential (MAP); in contrast, isoproterenol decreased contraction and MAP durations. Whereas inotropic responsiveness to isoproterenol was blunted in embolized hearts, these actions of BAY y 5959 were relatively preserved in the heart failure state. Isoproterenol increased heart rate, whereas BAY y 5959 had little effect. Changes in coronary vascular resistance also decreased similarly for isoproterenol and BAY y 5959. Finally, for comparable inotropy, increases in myocardial oxygen consumption were similar for isoproterenol and for BAY y 5959. In summary, preserved inotropic responsiveness and lack of positive chronotropic actions are two clinically favorable features of this type of inotropic agents compared with a typical β-adrenergic agonist.

DOI： 10.1152/ajpheart.1998.274.5.h1560

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Isovolumic contractions were imposed by intraventricular balloon in 39 isolated, blood-perfused canine hearts to investigate the effects of myocardial stretch on contractile force. After stabilization at 37°C, left ventricular volume was increased so that end-diastolic pressure increased from 0 to 5 mmHg. After the immediate increase in developed pressure [DP; from 37 ± 14 to 82 ± 22 mmHg (means ± SD)], there was a slow secondary rise in DP (97 ± 27 mmHg) that peaked at 3 min. However, DP subsequently decreased over the next 7 min back to the initial value (84 ± 25 mmHg). Light emission from macroinjected aequorin (n = 10 hearts) showed that changes in intracellular calcium [3 min: 124 ± 15% (P < 0.01); 10 min: 99 ± 18% of baseline] paralleled DP changes. Increases in myocardial adenosine 3',5'-cyclic monophosphate (cAMP) content (n = 12) accompanied the secondary rise in DP. In contrast, the gradual elevation of DP after the stretch was not exerted during continuous [β-adrenergic stimulation by isoproterenol. Thus, in contrast to isolated muscle, stretch only transiently increases intracellular calcium and contractile strength in intact hearts. The findings of changes in cAMP and abolition of the phenomena by β-stimulation suggest that a primary stretch-mediated influence on cAMP metabolism may underlie these phenomena.

DOI： 10.1152/ajpheart.1998.274.3.h990

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Three-compartment elastance modeling predicts that the magnitude of gain is solely dependent on the ratio of free wall and septal elastances. However, when nonlinearities in pressure-volume relationships are considered, the same model predicts that gain is load dependent. We therefore studied left-to- right ventricular interactions in the isolated cross-perfused canine heart preparation to determine whether, in fact, right ventricular volume modulates left-to-right ventricular interaction. We found that left-to-right systolic gain increased from 0.035 ± 0.022 to 0.073 ± 0.017 (P = 0.003) and left- to-right diastolic gain increased from 0.067 ± 0.050 to 0.186 ± 0.097 (P = 0.03) in response to increased right ventricular volume. This degree of volume dependency of gain is predicted by the three-compartment model when measured nonlinearities in time-varying elastance are taken into account. Future studies will need to account for changes in loading conditions when interpreting changes in systolic and diastolic interactions.

DOI： 10.1152/ajpheart.1997.272.6.h2869

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Objectives: The impact of acute collagen disruption by the disulfide donor, 5,5'-dithio-2-nitrobenzoic acid (DTNB) on ventricular properties was tested in rat hearts. Methods: Collagen was degraded acutely in 13 isolated, isovolumically contracting rat hearts by perfusion with 1 mM DTNB added to Krebs Henseleit solution for 1 hour followed by 2-hour perfusion with normal solution. Another 13 hearts were perfused with normal solution for 3 hours (Control). Results: Collagen content was 3.5 ± 0.5% of ventricular dry weight in control group compared with 2.1 ± 0.4% in DTNB group (decrease by 40%, p < 0.01). Scanning electron micrographs revealed loss of the delicate collagen network surrounding muscle fibers in DTNB treated hearts. Developed pressure at a fixed volume decreased to 86 ± 17% of the baseline value after 3-hour perfusion in the control group, whereas in DTNB treated hearts developed pressure fell to 68 ± 13% (p < 0.01). End-diastolic pressure was set at 5 mmHg at the beginning of the experiment and rose to 15 ± 8 mmHg in control and 30 ± 13 mmHg (p < 0.01) in the treated hearts. Concomitantly, wet-to-dry weight ratio increased from 5.63 ± 0.26 in control to 6.07 ± 0.11 (p < 0.05) in the DTNB treated hearts. A separate set of experiments on isolated myocytes excluded the possibility of a direct effect of DTNB on myocyte contractile function. Conclusions: These data suggested that with 40% collagen disruption by DTNB there is a significant increase in tissue edema that results in a decrease in chamber capacitance; in addition, there is a significant decrease in systolic performance which reflects the combined effect of edema and loss of collagen.

DOI： 10.1007/BF00788632

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Exercise training improves functional class in patients with chronic heart failure (CHF) via effects on the periphery with no previously documented effect on intrinsic left ventricular (LV) properties. However, because methods used to evaluate in vivo LV function are limited, it is possible that some effects of exercise training on the failing heart have thus far eluded detection. Twelve dogs were instrumented for cardiac pacing and hemodynamic recordings. Hearts were paced rapidly for 4 wk. Six of the dogs received daily treadmill exercise (CHFEX, 4.4 km/h, 2 h/day) concurrent with rapid pacing, while the other dogs remained sedentary (CHFs). Hemodynamic measurements taken in vivo at the end of 4 wk revealed relative preservation of maximum rate of pressure rise (2, 540 ±440 vs. 1, 720 ±300 mmHg/s, P < 0.05) and LV end-diastolic pressure (9 ±5 vs. 19 ±4 mmHg, P < 0.05) in CHFEX compared with CHFs. The hearts were then isolated and cross perfused for in vitro measurement of isovolumic pressure-volume relations; these results were compared with those of six normal dogs (N). Systolic function was similarly depressed in both groups of pacing animals [end-systolic elastance (Ees) values of 1.66 ±0.47 in CHFS, 1.77 ±0.38 in CHFEX, and 3.05 ±0.81 mmHg/ml in N, with no changes in volume axis interceptors of the end-systolic pressure-volume relationship]. The diastolic myocardial stiffness constant, k, was elevated in CHFs and was normalized by exercise training (32 ±3 in CHFs, 21 ±3 in CHFEx, 20 ±4 in N). Thus daily exercise training preserved in vivo hemodynamics during 4 wk of rapid cardiac pacing and was accompanied by a significant change in diastolic myocardial stiffness in vitro. These findings suggest that changes in heart function may contribute to the overall beneficial hemodynamic effects of exercise training in CHF by a significant effect on diastolic properties. Copyright © 1997 the American Physiological Society.

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Myocardial mechanics and energetics were investigated in an animal model of moderate chronic heart failure (CHF) created by repeated coronary microembolizations in six dogs. The final fractional area change was 34 ± 4%. Hearts of these animals were isolated and cross-perfused, and balloons were placed in the left ventricle (LV). Chamber contractile state was markedly depressed in embolized hearts as assessed by the slope (E(es): 2.74 ± 0.49 vs. 4.00 ± 1.18 mmHg/ml, P < 0.01) and volume axis intercept (V0: 8.7 ± 5.9 vs. 1.0 ± 3.2 ml, P < 0.01) of end-systolic pressure-volume relation compared with a group of six normal dogs. The end-diastolic pressure-volume relation of embolized hearts was shifted to the right, indicating a dilation of the LV. However, systolic and diastolic stress- strain relationships were similar in the two groups, suggesting that the average myocardial properties of the embolized hearts are similar to those of normal hearts. The relationship between oxygen consumption and pressure- volume area in embolized hearts had smaller intercept (2.98 ± 0.44 vs. 3.92 ± 0.39 x 10-2 ml O2 · beat-1 · 100 g LV-1 P < 0.01) compared with the control group, with no change in the slope. These results contrast with previous findings in pacing CHF and serve as an important characterization of ventricular properties in this model of CHF from different etiology.

DOI： 10.1152/ajpheart.1997.272.1.h186

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Levosimendan is hypothesized to be primarily a calcium sensitizer in vitro. Therefore, its inotropic action may be similar in both the normal and the congestive heart failure (CHF) state, and it may be associated with a decreased energetic cost of inotropism in vivo. To test these hypotheses, we gave levosimendan to cross-circulated isolated hearts from normal (n = 11) and CHF (n = 7, 4-week rapid pacing) dogs. Peak isovolumic left ventricular pressure at an end-diastolic pressure of 5 mm Hg (P(max,5)) measured by an intraventricular balloon was 120 ± 15 mm Hg in normal dogs, and it was increased by ~40% in response to ~0.63 μM levosimendan. In CHF dogs, base- line P(max,5)) was only 60 ± 12 mm Hg (P < .01 compared to normals), and ~8.4 μM levosimendan (P < .05) was required to increase P(max,5)) by ~40%. The inotropic actions were associated with increases in unloaded myocardial oxygen consumption by comparable amounts in normal and failing hearts. The blunted inotropic response in CHF and the energetic cost of inotropism were also comparable to those obtained with isoproterenol. In other studies, there was no significant inotropic action of levosimendan in Langendorff-perfused rat hearts (n = 5), and intracellular calcium concentration, estimated by macroinjected aequorin, in ferret hearts (n = 2) increased dose-dependently. These findings suggest that inotropic actions of levosimendan in vivo may be mediated in part by factors other than calcium sensitization.

記述言語：その他   掲載種別：研究論文（その他学術会議資料等）  

In the human the heart contracts more than 2.0 billion times during the lifetime. The total amount of energy required in this period is equivalent to lift a huge tanker (more than 200 thousand tons) above your head. Thus there is no question that the heart requires a huge amount of energy. Since minimization of energy requirements would be one of the major design goals of the cardiovascular system, we investigated energy efficiency of ventriculo-arterial coupling under various conditions. In normal conscious dogs, the arterial system extracted maximal work from the left ventricle during exercise as well as at rest. At the same time,the energy consumption of the left ventricle to support the peripheral demand was minimum. This optimal coupling condition was well maintained despite changes in blood volume. The baroreflex system appeared to play a crucial role in this optimization. In the presence of left ventricular dysfunction, however, this optimality was no longer maintained. We conclude that the efficiency of cardiac contraction is fairly well maintained under various stresses as long as left ventricular function is normal.

記述言語：その他   掲載種別：研究論文（学術雑誌）  

We evaluated dynamic effects of the carotid sinus baroreflex on ventriculoarterial coupling. In seven anesthetized, vagotomized dogs, we bilaterally isolated carotid sinuses and randomly changed carotid sinus pressure while measuring aortic pressure, aortic flow, and left ventricular pressure. Estimating left ventricular end-systolic elastance (E(es)) and effective arterial elastance (E(a)) on a beat-to-beat basis, we determined transfer functions from the carotid sinus pressure to E(es) (H(Ees)) and from the carotid sinus pressure to E(a) (H(Ea)) over the frequency range spanning 0.002-0.25 Hz. Both H(Ees) and H(Ea) exhibited characteristics of a second- order low-pass filter. The gains of H(Ees) and H(Ea) were 0.085±0.065 (mean±SD) and 0.081±0.049 mm Hg/ml/mm Hg, respectively. There were no significant differences in natural frequencies (0.039±0.013 versus 0.039±0.007 Hz) or damping ratios (0.65±0.11 versus 0.64±0.24). The results indicated that the carotid sinus baroreflex dynamically altered E(es) and E(a) to the same extent in the process of stabilizing arterial pressure. Because the arterial system extracts maximal external work from a given heart when E(a) equals E(es), the carotid sinus baroreflex appeared to be designed to regulate the ventricular and arterial properties to optimize the energy transmission from the left ventricle to the arterial system in anesthetized, vagotomized dogs.

DOI： 10.1161/01.RES.70.5.1044

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Beneficial effects of cardiotonic phosphodiesterase inhibitors on congestive heart failure are possibly mediated in part by a reduction of afterload. 1,2-Dihydro-5-imidazo[1,2-a]pyridin-6-yl-6-methyl-2-oxo-3-pyridine-car bonitrile hydrochloride monohydrate (E-1020, CAS 119615-63-3), a new cardiotonic phosphodiesterase inhibitor was evaluated for its effect on aortic input impedance in eight anesthetized open-chest dogs. First instantaneous aortic pressure and flow under random ventricular pacing before and after E-1020 infusions (10, 30, and 100 μg/kg i.v.) were measured. Then aortic input impedance over the frequency range of 0.024 to 20 Hz was estimated using a multichannel autoregressive model. With the infusion of E-1020, aortic input impedance was decreased in the low frequency range (below 0.1 Hz) and shifted leftward in the transitional frequency range (from 0.1 to 2 Hz), while it remained unchanged in the high frequency range (above 2 Hz). Parameterization of the aortic input impedance using a three-element Windkessel model indicated that E-1020 (at a dose of 100 μg/kg i.v.) decreased arterial resistance by 35% (p < 0. 01) and increased arterial compliance by 12% (p < 0. 01). It is concluded that E-1020 improves cardiac performance by unloading static and dynamic afterload in addition to its cardiotonic effect.

記述言語：その他   掲載種別：研究論文（学術雑誌）  

We evaluated the advantages of the autoregressive (AR) model over the conventional Fourier transform in estimating aortic input impedance. In 10 anesthetized open-chest dogs, we digitized aortic pressure and flow at 200 Hz for 51.20 s under random ventricular pacing and subdivided them into five segments. We obtained aortic input impedance over the frequency range of 0.1-20 Hz both by AR model and by Fourier transform for various lengths of data, i.e., from one to four consecutive segments. For any given data length, the impedance spectrum estimated by the AR model was smoother than that obtained by the Fourier transform. To evaluate the accuracy of the estimated impedance, we predicted instantaneous aortic pressure of the fifth segment by convolving corresponding aortic flow with the impulse response of aortic input impedance. The prediction error was less with the AR model than that resulting from Fourier transform as long as the number of the segments was less than four. We conclude that the AR model provides a more accurate estimate of aortic input impedance than does the Fourier transform when data length is limited.

DOI： 10.1152/ajpheart.1991.260.3.h998

記述言語：その他   掲載種別：研究論文（学術雑誌）  

We identified, in 17 α-chloralose-anesthetized rabbits, the dynamic transduction characteristics of the aortic arch baroreceptors using a 'white-noise technique'. We recorded aortic pressure and aortic depressor nerve activity while perturbing pressure by rapid, intermittent ventricular pacing (400 beats/min). Dividing the cross-power spectrum between nerve activity and pressure by the power spectrum of pressure yielded the transfer function. The gain of the transfer function increased threefold as the frequency increased from 0.005 to 5 Hz, suggesting that the baroreceptors responded primarily to dynamic rather than to static changes in pressure. To quantify the nonlinear properties of baroreceptor transduction, we compared measured instantaneous nerve activity with that linearly predicted. We demonstrated that the major nonlinearity was attributable to 'threshold'. The overall baroreceptor transduction properties could be represented by a cascade connection of a linear subsystem followed by a nonlinear subsystem with threshold. The white-noise technique made it possible to identify the unbiased linear properties in a nonlinear system, and thus was very useful in identifying complex biological systems.

DOI： 10.1152/ajpheart.1990.258.3.h887

記述言語：その他   掲載種別：研究論文（学術雑誌）  

記述言語：その他   掲載種別：研究論文（学術雑誌）  

To improve the performance of exercise stress testing in the diagnosis of effort angina while minimizing risks of serious complications, we evaluated an impulse response of ST changes, which is a transient ST response resulting from a hypothetical, strenous-impulselike exercise, without actually imposing the strenuous load. To obtain the impulse response, subjects walked intermittently according to a computer-generated random binary sequence on a treadmill for 20 minutes (with a constant speed of 1.7 mph and a slope of 10&#37;). We used Fourier transform for beat-to-beat changes in ST level and the binary sequence of exercise. We then determined the transfer function by taking the ratio of Fourier transformed ST level to exercise over the frequency range of 0.5 through 5.0 cycles/min. Converting the transfer function to the time domain yielded the impulse response of ST change. The subjects consisted of 49 patients (60 ± 9 years) with effort angina, 13 patients with atypical chest pain (56 ± 9 years), and 30 healthy, male volunteers (23 ± 7 years). In 82 subjects (89&#37;), the ST impulse response showed an initial depression followed by a smooth, gradual restoration toward the preexercise ST level (type I response). The average duration of the initial depression was 8 ± 3 seconds in the healthy volunteers, whereas it was significantly prolonged to 23 ± 14 seconds in effort angina (p < 0.05). The depression in patients with atypical chest pain was not significantly different from that in the healthy volunteers. Although the level of exercise was milder in the proposed exercise test than in the conventional treadmill exercise test, the sensitivity and the specificity were significantly better in the proposed exercise test than in the conventional one in the same population. We conclude that this random exercise test is a sensitive, safe tool and is very accurate for the diagnosis of effort angina.

DOI： 10.1161/01.CIR.78.4.825

開催年月日： 2023年12月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：神戸国際会議場・神戸国際展示場   国名：日本国  

開催年月日： 2023年12月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：神戸国際会議場・神戸国際展示場   国名：日本国  

開催年月日： 2023年11月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：Jaipur, India   国名：インド  

In 2007, the Japanese government began establishing academic research organizations (AROs) at several universities in order to overcome the situation in Japan, where promising basic research results had not led to the practical application of new drugs. At the same time, an R&D method in which AROs incubate inventions from academia to some extent and then license them out to pharmaceutical companies is becoming a global trend. The majority of new drugs approved by the US FDA from 1998 to 2007 were discoveries made in academia. In Japan as well, results are beginning to emerge, with 23 cases being approved over the three-year period from 2020 to 2022 through a system of investigator- initiated clinical trials for approval purpose, which is rare in the world. From the beginning, Kyushu University received support from the Ministry of Education and the Ministry of Health through the Translational Research Hub Project and Clinical Research Core Hospital Project, respectively, and has been developing an ARO staffed by around 100 experts. We have a system in place to cover every step to mature basic research into new drugs (intellectual property, pharmaceutical affairs, toxicology, engineering, CMC [chemistry, manufacturing and control], project management, data management, biostatistics, trial quality control, IT, ethics, regulatory science) within the university. Although there are many development targets for incurable and rare diseases that are difficult for pharmaceutical and medical device companies to reach and also to make a profit, the morale of the staff is high in delivering new treatments to bedside, which leads to gathering talented people and efficient development. Examples of approved products include alveolar bone fillers and staining materials for eye surgery, which have become de facto standard products and are used around the world. We also have new drug development technologies that have a wide range of applications, including the production of protein preparations by introducing genes into special silkworms that have been cultivated in the Faculty of Agriculture for over 100 years, and technology that allows even larger molecules of 500 Da or more to penetrate into the body through normal skin. We are actively working on international contributions, and especially in Asia. We are conducting joint research and development with local academia to resolve unmet medical needs such as infectious diseases, which are caused by regionally specific circumstances. Your country's CDSCO have a reference country rule that simplifies domestic evaluations by referring to approvals in Japan, which can hopefully be utilized. We hope that the introduction of our university's activities in this lecture will lead to joint development and international clinical trials with academia in your country.

開催年月日： 2023年11月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：Jaipur, India   国名：インド  

開催年月日： 2023年8月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京都八王子市多摩メッセ   国名：日本国  

開催年月日： 2023年5月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京都新橋   国名：日本国  

開催年月日： 2023年5月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：別府国際コンベンションセンター   国名：日本国  

開催年月日： 2023年5月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：鹿児島市城山ホテル   国名：日本国  

開催年月日： 2022年3月

記述言語：日本語  

国名：日本国  

開催年月日： 2021年12月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

国名：日本国  

開催年月日： 2021年9月

記述言語：日本語  

国名：日本国  

開催年月日： 2021年3月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：大阪   国名：日本国  

開催年月日： 2021年2月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京   国名：日本国  

開催年月日： 2020年12月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：福岡   国名：日本国  

開催年月日： 2020年2月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京   国名：日本国  

開催年月日： 2020年2月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京   国名：日本国  

開催年月日： 2019年12月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京   国名：日本国  

開催年月日： 2019年2月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京   国名：日本国  

開催年月日： 2018年11月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：Glasgow   国名：グレートブリテン・北アイルランド連合王国(英国)  

開催年月日： 2018年8月 - 2018年9月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：福岡   国名：日本国  

開催年月日： 2018年7月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：Kobe   国名：日本国  

開催年月日： 2017年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：福岡   国名：日本国  

開催年月日： 2017年10月

記述言語：日本語   会議種別：口頭発表（招待・特別）  

開催地：福岡   国名：日本国  

開催年月日： 2017年9月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：名古屋   国名：日本国  

開催年月日： 2017年2月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：福岡   国名：日本国  

開催年月日： 2017年1月

記述言語：日本語   会議種別：口頭発表（招待・特別）  

開催地：熊本   国名：日本国  

開催年月日： 2017年1月

記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

開催地：福岡   国名：日本国  

開催年月日： 2016年10月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：京都   国名：日本国  

開催年月日： 2016年4月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：Seoul   国名：大韓民国  

開催年月日： 2015年11月

記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

開催地：福岡市   国名：日本国  

開催年月日： 2015年11月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：沖縄   国名：日本国  

開催年月日： 2015年9月

記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

開催地：福岡市   国名：日本国  

開催年月日： 2015年9月

記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

開催地：福岡市   国名：日本国  

開催年月日： 2015年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京   国名：日本国  

開催年月日： 2015年3月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：神戸市   国名：日本国  

開催年月日： 2015年2月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：秋田   国名：日本国  

開催年月日： 2014年11月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：千葉   国名：日本国  

開催年月日： 2014年3月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：熊本市   国名：日本国  

開催年月日： 2013年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京   国名：日本国  

特別シンポジウム『革新的医療機器の実用化促進にむけて』

開催年月日： 2013年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京   国名：日本国  

開催年月日： 2013年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京   国名：日本国  

開催年月日： 2013年7月

記述言語：英語   会議種別：口頭発表（一般）  

開催地：神戸市   国名：日本国  

Town Hall Meeting: “Global Harmonization for Medical Device Innovation”

開催年月日： 2013年7月

記述言語：英語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：tokyo   国名：日本国  

Japan-US HBD East 2013 (July 9 – 10, 2013, Tokyo) Kazuhiro Sase, Takeshi Nakatani, Koji Todaka, Masayuki Kawahara Update from Working Group 2

開催年月日： 2013年6月

記述言語：日本語   会議種別：公開講演，セミナー，チュートリアル，講習，講義等  

開催地：福岡市   国名：日本国  

開催年月日： 2012年11月 - 2012年12月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：沖縄県   国名：日本国  

【目的】薬や医療機器に対するリスク・ベネフィット認知が国内外で異なる可能性が指摘されている。ドラッグ／デバイスラグの一因とも考えられるがデータとしては皆無であるため国内外での直接比較を試みた。 【方法】一般市民を対象として言語以外は同一のアンケート票を用いて多肢選択方式のインターネット調査を日米英で同時に行った。医療を含む科学技術についての認識や医療機器承認、規制当局に係る質問・認識等についての回答を比較分析した。年代・性分布が均等になるように割り付け、約３千人から有効な回答を得た。１０の一般事象（喫煙、飲酒、車、飛行機、原子力発電、遺伝子組み換え作物、医療X線、抗生物質、ワクチン、ペースメーカ）それぞれの有用性／危険性／受容するかについて５点尺度（とても役立つ／危険／必ず受け容れる、やや役立つ、どちらとも言えず、余り役立たない、全く役立たない）の回答、厚生労働省や医師を信頼するか、何らかの治療歴があるか等についてコレスポンデンス分析を行った。 【結果・考察】医療技術関係（上記後半4項目）に対する有用性／危険性／受容度は同様のマッピング傾向を示し治療歴の有無の影響は小さかった。ペースメーカと飛行機の受容は同じ傾向を示した。米国人、英国人は近くに位置し有用性／危険性／受容度について、「とても有用で、危険が小さく、受容する」と言ったはっきりとした回答とクラスターし、日本人は「どちらでもない」といった中庸回答が多くなる傾向があり第一軸において大きく離れていた。厚生労働省や医師に対する信頼は回答の明瞭さと関連があり必ずしも好意的な判断とは関連しなかった。 【結論】リスク・ベネフィット認知には日本と米英で差異があり厚労省や医師に対する信頼がリスク・ベネフィットひいては受容するか否かの判断を明瞭にさせていることがコレスポンデンス分析から示唆された。

開催年月日： 2012年9月

会議種別：口頭発表（一般）  

開催地：東京   国名：日本国  

【目的】医療技術に対して本邦では有用性よりリスクを重要視する傾向が指摘されている。リスク・ベネフィット認知の違いはデバイスラグの遠因として興味深いが実際のデータは皆無であるため国内外での直接比較を試みた。 【方法】一般市民を対象として言語以外は同一のアンケート票を用いて多肢選択方式のインターネット調査を日米英で同時に行った。医療を含む科学技術についての認識や医療機器承認、規制当局に係る質問・認識等について回答を比較した。 【結果】年代・性分布が均等になるように割り付け、約３千人から有効な回答を得た。何らかの治療中である割合（＝患者）は日本２３％、米国４３％、英国３６％とやや日本が少ない傾向であった。 木下らの手法に倣って科学技術を含む１０の一般事象（喫煙、飲酒、車、飛行機、原子力発電、遺伝子組換作物、医療X線、抗生物質、ワクチン、ペースメーカ）について５点尺度（とても役立つ・危険、やや役立つ、どちらとも言えず、余り役立たない、全く役立たない）で有用性、危険性、受容するかについて尋ねた。５点尺度に＋２〜—２の点を与えてその加重平均を計算し国ごとに１０事象の散布図を描いた。有用性ｘと受容度ｙとの関係を直線回帰すると日本はy = 0.73x + 0.15、 R² 0.85、米国y = 0.77x + 0.40、R² 0.95、英国y = 0.79x + 0.38、R² 0.93といずれも相関が高く、傾きはほぼ同じで日本より英米の切片が大きい事から全体に英米の受容が良い事が示唆された。危険性と受容の関係は英米の切片が大きいのは共通であるがR² は日米英それぞれ0.68、0.79、0.76とやや低くどの地域でも有用性がより重視されていると思われた。 　医療技術関係の４項目（X線、抗生物質、ワクチン、ペースメーカ）は差が小さいものの英＞日＞米の順に有用・危険でないと感じる割合が多かった。しかし受け容れるかどうかは英＞米＞日の順となり全般的受容度の低さが日本について大きく影響した。受容度の順番は奇しくも新薬や新医療機器が導入される一般的順序と一致した。 【考察】本邦において医療技術の受容に危険性の認知が有用性より影響が大きいとの結果は簡易解析では得られなかった。何か副作用が起こった場合に元々英米より受容が良くない本邦においては更に受容度が低下してしまい、リスクを過大視しているように見えているのかもしれない。規制当局への信頼に関する質問では日本と英米で大差がついていることも背景として重要と考えられる。

会議種別：口頭発表（一般）  

開催地：栃木県前橋市   国名：日本国  

会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：福岡市   国名：日本国  

会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：福岡市   国名：日本国  

会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：北九州市   国名：日本国  

会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：横浜  

会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：北九州  

会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：大分県別府市  

会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：Tokyo   国名：日本国  

会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：東京  

会議種別：口頭発表（一般）  

開催地：福岡市  

会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：名古屋市   国名：日本国  

記述言語：英語  

記述言語：英語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語   掲載種別：機関テクニカルレポート，技術報告書，プレプリント等  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

記述言語：その他  

DOI： 10.1161/CIRCEP.122.011579

記述言語：日本語  

2003年に薬事法が改正され「医師主導治験」という世界的に見ても特異な制度が始まった。製薬会社等が開発・治験を実施してくれない採算性の低い製品・適応に対して、医師が自ら薬事承認のための臨床試験を計画・設計・実施する。最終的にそのデータを製薬会社等が承認申請に用いるという本質的に捻れた仕組みを持ち、元々はドラッグラグ、デバイスラグ等を解消する手段の一つとして始められた。昨今は企業開発品の初期治験でさえアカデミアに任せ、ある程度医師主導治験で成績が出るまで様子見をするという企業が出て来ているのも事実である。７月時点のjRCTで実施中の未承認薬医師主導治験が43試験ある。うち15件（35&#37;）は研究資金等の提供組織として製薬企業も記載されている。適応外薬も同じく43試験あり、21件（49&#37;）は製薬企業も記載されている。AMED公募において「なぜ企業治験ではないのか？」としばしば問題となるが、市場性が低い製品の臨床開発をどこが負担して実施すべきかについて明確な基準が無く、未だコンセンサスは得られていない。

リポジショニングでよく見受ける特許切れ成分の新作用機序が臨床ニーズを満たす場合、臨床現場で発したneeds pull開発として医療従事者の熱意で推進するものの、必ずしも市場が要求したmarket pullではないことから来る弊害もある。研究費を獲得して医師主導治験を実施し有効性を証明して、先発薬を適応拡大できたとしても、沢山ある後発薬と差別化が難しい。用途特許等で法的に保護する事は可能であるが、後発薬の適応外使用を止める実効性には乏しい。従って採算が取れる目処が無いなどの理由により企業が承認申請を請け負わない場合がある。国内であまねく使用できるようにするという医師主導治験の本来目的は出口で頓挫してしまう。米国では保険適用を伴った臨床使用が薬事承認範囲を超えてcompendiaという形で広く認められているため、適応拡大に限れば我が国の保険行政特有の問題と言える。

制度開始から20年近くたち、ARO初めとして現場は医師主導治験に慣れてきたが上記のような弊害も目立つ。アカデミアも企業もこの特有な制度を今後どのように活用して行くのか、規制当局とともに再考する時期に来ている。

DOI： 10.50993/jsptsuppl.43.0_4-c-s44-2

J-GLOBAL

researchmap

記述言語：日本語  

【目的】

革新的なアカデミア発創薬のため整備されてきたAROは来年度から橋渡し認定事業が開始され新たな局面を迎える。AMED ARO機能推進事業の昨年度結果を中心に我が国におけるAROの多様性とその活用についてご紹介する。

【方法】

ARO機能を有すると考えられる病院に対し、リソース指標(FTE人数、人件費等)、成果指標(医師主導治験数、実用化製品数等)それぞれについて調査票形式による調査を実施した。

【結果・考察】

129の機関から有効な回答を得た。得られた調査票項目を57に縮約し、リソース、成果を敢えて区別することなく主成分分析を行った。臨床試験関連中間成果(企業治験等)が臨床試験支援人材（CRC等）と共に多くは上寄りに布置されており、第3主成分(y軸)上方向はエビデンス創出に関連した方向性を示していると考えられる。逆に臨床試験以外の中間成果(特許等)やライセンスアウトといった最終成果は、臨床試験関連以外の支援人材(プロジェクトマネージャ等)と共に多くが下寄りに位置しており、下方向は実用化指向を表していると解釈される。一方、横方向について第2主成分(x軸)では再生医療・医療機器や倫理指針試験等、コスト負担や個別対応を求められるような「創意工夫」が必要なリソース要求度の高い項目や獲得研究費が右に位置しており、高リソース要求容認を表していると判断される。逆に左には患者申出療養や医師主導治験などの規制の強い試験群とそれに必要な臨床試験実施関連のリソース(phase I施設等)が並んでおり規制が強いが定型的な業務として収益を上げやすく、比較的リソース投入がし易い方向性（収益性が高い）を示していると判断される。施設スコアについては昨年度と同じく第1主成分（規模）の小さなその他の病院が原点付近に集まり、結果的に平均的な特性になったと判断される。拠点やARO規模の大きな特定機能病院は負荷図に沿った特徴に従って外側寄りに分布していると解釈される。

【結論】

我が国のAROはエビデンス/実用化指向性、コスト容認/効率重視の方向性の違いにより大まかに分類され、拠点AROが特に特徴ある分布を示した。結果を利用してAROの特徴を可視化したポータルを作成し、研究者とAROのマッチングが容易となるよう公開した（https://www.aro-portal.com/ja/home）。本邦全体としてARO機能が広く整備され、橋渡し研究を目指す研究者に必要な支援が行き渡ることが肝要と考えられる。

DOI： 10.50993/jsptsuppl.42.0_2-sps-4

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

CLINICAL STUDY AND MEDICAL PRODUCT DEVELOPMENT:ROLE OF THE ACADEMIC RESEARCH ORGANIZATION

DOI： 10.3919/jjsa.77.1292

記述言語：日本語  

記述言語：日本語  

DOI： 10.11312/ccm.35.177

記述言語：日本語  

記述言語：その他  

記述言語：日本語  

DOI： 10.3999/jscpt.37.4_69s

記述言語：日本語  

記述言語：日本語  

記述言語：その他  

記述言語：日本語  

記述言語：日本語  

Division of Circulatory Physiology, Department of Medicine, College of Physicians & Surgeons, Columbia University in the City of New York, USA

記述言語：その他  

記述言語：日本語  

記述言語：日本語   掲載種別：記事・総説・解説・論説等（学術雑誌）  

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種別：大会・シンポジウム等 

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種別：審査・学術的助言 

種別：審査・学術的助言 

種別：大会・シンポジウム等 

種別：大会・シンポジウム等 

種別：審査・学術的助言 

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Clinical questionに答える方法としての臨床研究　和白病院臨床研究講演会

第85回日本循環器学会学術集会　倫理に関する講演
公正な研究活動とは　〜臨床研究に重点を置いて〜

医薬品医療機器レギュラトリーサイエンス財団
医療機器エキスパート研修講座
臨床研究法とその課題　〜解決の方向性〜

PI（Principal Investigator）認定講習

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臨床研究認定講習

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臨床研究認定講習

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臨床研究を実施するために　和白病院臨床研究講演会

公正な研究活動とは　〜臨床研究に重点を置いて〜　福岡大学コンプライアンス教育講演会

厚生労働省　倫理審査委員会・治験審査委員会委員養成研修

厚生労働省　臨床研究・治験従事者研修

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PI（Principal Investigator）認定講習

ＡＭＥＤ倫理審査委員会・治験審査委員会委員養成研修

ＡＭＥＤ臨床研究・治験従事者研修

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臨床研究認定講習

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ＡＭＥＤ倫理審査委員会・治験審査委員会委員養成研修

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ＡＭＥＤ臨床研究・治験従事者研修

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臨床研究認定講習

臨床研究認定更新講習、司会
演 題：１）「患者申出療養及び関連する各種制度について」
　　　　　　　国立がん研究センター中央病院
　　　　　　　副病院長 ・企画戦略局長　藤原 康弘先生
　　　　　 ２）「国立がん研究センターにおける患者申出療養対応体制」
　　　　　　　国立がん研究センター研究支援センター　
　　　　　　　研究管理部研究管理課長　後澤 乃扶子先生

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ＡＭＥＤ臨床研究・治験従事者研修

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臨床研究認定講習

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臨床研究担当看護師育成研修

臨床試験に関するセミナー（リサーチアシスタントセミナー）

臨床研究認定講習

臨床試験に関するセミナー（リサーチアシスタントセミナー）

臨床研究認定講習

臨床研究担当看護師育成研修

臨床試験に関するセミナー（リサーチアシスタントセミナー）

臨床試験に関するセミナー（リサーチアシスタントセミナー）

臨床研究認定講習

臨床研究認定講習

臨床研究認定講習

対象：社会人・一般,　学術団体,　企業,　市民団体,　行政機関

種別：講演会

対象：社会人・一般,　学術団体,　企業,　市民団体,　行政機関

種別：講演会

対象：社会人・一般,　学術団体,　企業,　市民団体,　行政機関

種別：講演会

対象：社会人・一般,　学術団体,　企業,　市民団体,　行政機関

種別：講演会

対象：社会人・一般,　学術団体,　企業,　市民団体,　行政機関

種別：講演会

対象：社会人・一般,　学術団体,　企業,　市民団体,　行政機関

種別：講演会

対象：社会人・一般,　学術団体,　企業,　市民団体,　行政機関

種別：講演会

対象：社会人・一般,　学術団体,　企業,　市民団体,　行政機関

種別：セミナー・ワークショップ

対象：社会人・一般,　学術団体,　企業,　市民団体,　行政機関

種別：講演会

対象：社会人・一般,　学術団体,　企業,　市民団体,　行政機関

種別：講演会

◆心臓病 サイン見逃すな
　狭心症や心筋梗塞の症状は胸の痛みや圧迫感、絞められるような不快感が多いのですが、脳が痛みの情報を混信させ、下あごや歯、のど、首、腕、上腹部などでも痛みを感じることがあります。全く痛みのない場合もあります。心筋梗塞の女性のうち、４３％に胸痛がなかったという報告もあります。このため、女性は男性より精密検査を受ける機会が少なく、結果として心臓病による死亡率も高くなっています。
◆睡眠時無呼吸症候群 周囲も注意してあげて
　昼間の眠気は、睡眠時無呼吸症候群（ＳＡＳ）の症状の一つです。睡眠中に無呼吸が繰り返し起こるため、たびたび脳が目覚めて熟睡できずに起こります。無呼吸の時には血中の酸素が不足し、心筋梗塞や脳卒中など動脈硬化性疾患の危険性を高めるほか、メタボリック症候群の３要素（脂質異常、高血圧、高血糖）のすべてを悪化させます。
　本人は気づかないことが多く、周りの人の注意が必要です。脳波を用いた精密検査を受け、治療法は就寝時に▽マウスピース状の「スリープ・スプリント」を口に入れ、気道を確保する▽空気を加圧して鼻から送り込むＣＰＡＰ治療（持続陽圧呼吸）などがあります。これらの治療で、心臓発作や脳卒中を予防できることが証明されています。
　日本人の死因では、がんに次いで多いのが心臓病です。発作は歩き始めや寒い時、食後に多発します。異常を感じたら循環器内科を受診してください。

身体障害者福祉法指定医師（心臓機能障害）