Language：English   Publisher：Journal of Heart and Lung Transplantation  

Background: The management of chronic thromboembolic pulmonary hypertension (CTEPH) has advanced significantly in recent years, thereby improving patient prognosis. However, the impact of cancer on the outcomes of patients with CTEPH under current treatment remains unclear. This study aimed to investigate the prevalence of cancer in patients with CTEPH and determine how comorbid cancer affects their prognosis and clinical course. Methods: Data from an ongoing Japanese prospective cohort study were analyzed. Prevalence and primary cancer sites were evaluated. The association of a history of cancer with a composite endpoint, including all-cause death, lung transplantation, and worsening of CTEPH, as well as venous thromboembolism and bleeding events, was assessed. Results: Of the 1,270 patients in the cohort, 134 (10.6%) had a history of cancer, with the most common primary sites being the breast in women and the prostate in men. The incidence of composite outcome and all-cause death was higher in those with a history of cancer (p < 0.001, log-rank test). In the Cox proportional hazard model, age- and sex-adjusted hazard ratios for the composite outcome and all-cause death were 2.69 (95% confidence interval, 1.48–4.89, p = 0.001) and 4.25 (95% confidence interval, 1.98–9.10, p < 0.001), respectively, for patients with a history of cancer. No significant differences in venous thromboembolism and bleeding events were observed between patients with and those without a history of cancer. Conclusions: A history of cancer, with a prevalence of 10.6%, is an independent risk factor for mortality in patients with CTEPH undergoing the currently recommended treatment.

DOI： 10.1016/j.healun.2024.10.022

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BMC Complementary Medicine and Therapies  

BACKGROUND: Anxiety disorder is the most prevalent psychiatric disorder. Benzodiazepines, which are often used for anxiety in patients with anxiety disorder, have various side effects. Lavender, one of the most commonly used essential oils in aromatherapy, has the potential to reduce benzodiazepine use for anxiety disorders. METHODS: This study is a multicenter, double-masked, randomized, placebo-controlled clinical trial. The study will recruit patients aged 20-59 years old with generalized anxiety disorder and panic disorder among anxiety disorders. The bottle containing the test solution (lavender aroma essential oil or distilled water) will be given to the patients. Patients will carry the bottles with them in their daily life and use the drops on tissue paper when anxious. The primary endpoint is the number of times anxiolytics used in 28 days. DISCUSSION: If the use of benzodiazepines could be reduced by sniffing lavender aroma, which is inexpensive and safe, it would contribute not only to the risks associated with benzodiazepine use but also to the health care economy and could even be added as a standard treatment. TRIAL REGISTRATION: University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), ID: UMIN000034422 Registered 17 January 2019.

DOI： 10.1186/s12906-023-04231-1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JA Clinical Reports  

PURPOSE: Remimazolam, a newly developed ultra-short-acting benzodiazepine, provides early recovery of consciousness but its effects on memory recovery are unclear. This study examined memory recovery after emergence from general anesthesia using remimazolam. METHODS: Seventy-four patients undergoing breast surgery between October 2021 and March 2022 were enrolled and randomly assigned to receive propofol (control group) or remimazolam as general anesthetic during surgery. The primary endpoint was the number of posters patients remembered 24 h after surgery (among four posters shown after recovering from anesthesia) as an assessment of memory retention. The secondary endpoints were the recall of a numeric character patients had been shown just before anesthetic induction, as an assessment of retrograde amnesia 24 h after surgery. RESULTS: Sixty-six patients (propofol, 32; remimazolam, 34) were assessed. Patients in the remimazolam group remembered significantly fewer posters shown to them after surgery than those in the propofol group (0 [0 - 2] vs. 2 [1 - 3], p < 0.001). In the remimazolam group, the patients who received flumazenil remembered a higher number of posters than those who did not receive flumazenil (3 [1 - 4] vs. 0 [0 - 0], p < 0.001). All patients remembered all events that occurred during the preoperative period as well as the numeric character. CONCLUSION: Patients recovering from remimazolam anesthesia without receiving flumazenil do not remember events after regaining consciousness. IRB: Kyushu University School of Medicine Hospital Institutional Review Board (IRB) (approval number: 20212006). TRIAL REGISTRATION: This clinical trial was registered with the University Hospital Medical Information Network (UMIN) Center on September 28, 2021 (UMIN-CTR: UMIN000045593). IMPLICATION STATEMENT: Memory recovery is slower following emergence from remimazolam than from propofol anesthesia.

DOI： 10.1186/s40981-023-00635-7

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Language：English   Publisher：Springer Berlin Heidelberg  

全身麻酔に用いるレミマゾラムが麻酔からの覚醒後の記憶回復に及ぼす影響を検討した。2021年10月～2022年3月に乳房手術を予定した20～65歳の患者を登録し、全身麻酔薬にプロポフォール(対照群)またはレミマゾラムを用いる群に無作為化した。主要評価項目は記憶保持とし、麻酔回復後に提示した4枚のポスターのうち、術後24時間時点で患者が覚えているポスター数で評価した。副次評価項目は逆行性健忘とし、麻酔導入直前に提示した数字および導入前の5つの出来事(歩行入室、ベッド移動等)を術後24時間時点で患者が想起できるかにより評価した。無作為化した70例(各群35例)のうち66例(プロポフォール群:32例、平均50.4±7.6歳、レミマゾラム群:34例、平均51.1±10.0歳)を解析した。主要評価項目のポスター数はレミマゾラム群の方がプロポフォール群より有意に少なかった[中央値0(四分位範囲0～2]対2(1～3)、p<0.001]。レミマゾラム群のうち、フルマゼニル投与患者は非投与患者より覚えていたポスター数が多かった[3(1～4)対0(0～0)、p<0.001]。全患者が術前の出来事と数字を想起できた。以上より、レミマゾラムによる麻酔で逆行性健忘は生じないが、意識回復後の記憶が保持されないことが示された。

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers in Pharmacology  

Background: Alzheimer's disease (AD), the most prevalent form of dementia, is a debilitating, progressive neurodegeneration. Amino acids play a wide variety of physiological and pathophysiological roles in the nervous system, and their levels and disorders related to their synthesis have been related to cognitive impairment, the core feature of AD. Our previous multicenter trial showed that hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), has an adjuvant effect for Acetylcholine estelase inhibitors (AChEIs) and that it delays the deterioration of the cognitive dysfunction of female patients with mild AD. However, there are aspects of the molecular mechanism(s) by which HJG improves cognitive dysfunction that remain unclear. Objectives: To elucidate through metabolomic analysis the mechanism(s) of HJG for mild AD based on changes in plasma metabolites. Methods: Sixty-seven patients with mild AD were randomly assigned to either an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI (HJG:33, Control:34). Blood samples were collected before, 3 months, and 6 months after the first drug administration. Comprehensive metabolomic analyses of plasma samples were done by optimized LC-MS/MS and GC-MS/MS methods. The web-based software MetaboAnalyst 5.0 was used for partial least square-discriminant analysis (PLS-DA) to visualize and compare the dynamics of changes in the concentrations of the identified metabolites. Results: The VIP (Variable Importance in Projection) score of the PLS-DA analysis of female participants revealed a significantly higher increase in plasma metabolite levels after HJG administration for 6 months than was seen in the control group. In univariate analysis, the aspartic acid level of female participants showed a significantly higher increase from baseline after HJG administration for 6 months when compared with the control group. Conclusion: Aspartic acid was a major contributor to the difference between the female HJG and control group participants of this study. Several metabolites were shown to be related to the mechanism of HJG effectiveness for mild AD.

DOI： 10.3389/fphar.2023.1203349

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Hypertension Research  

A higher resting heart rate (RHR) is associated with an increased risk of cardiovascular events in patients with type 2 diabetes mellitus (T2DM) and cardiovascular diseases. The aim of this study was to investigate the association between RHR and cardiovascular events in T2DM patients with diabetic retinopathy and without known cardiovascular disease. We analyzed the association between RHR and cardiovascular events, including coronary, cerebral, renal and vascular events or cardiovascular death in T2DM patients with retinopathy and hyperlipidemia without prior cardiovascular events who were enrolled in the EMPATHY study. Data from 4746 patients were analyzed. The median RHR was 76 bpm. Patients were divided into four groups based on their baseline RHR ( < 60, 60-69, 70-79, and ≥80 bpm). Patients with a higher RHR were more likely to be younger and had a higher body mass index, blood pressure value, HbA1c value, and estimated glomerular filtration rate and a lower B-type natriuretic peptide value; they also had a higher proportion of current smoking status, neuropathy, and nephropathy. After adjusting for confounders, including the aforementioned risk factors, a RHR of 70-79 bpm and a RHR ≥ 80 bpm were significantly associated with cardiovascular events (hazard ratio 1.50, 95% CI 1.03-2.20; and hazard ratio 1.62, 95% CI 1.11-2.36; respectively) compared to a RHR of 60-69 bpm. The analysis using restricted cubic splines indicated that the cardiovascular risk seemed to be similarly high when the RHR range was ≥70 bpm. In conclusion, in T2DM patients with diabetic retinopathy and without known cardiovascular disease, a high RHR, particularly ≥70 bpm, was associated with the risk of cardiovascular events compared to a RHR of 60-69 bpm. High resting heart rate (RHR), particularly ≥70 bpm, was associated with the risk of cardiovascular events compared to RHR 60-69 bpm in patients with type 2 diabetes mellitus (T2DM), diabetic retinopathy, and hyperlipidemia, but without known cardiovascular disease.

DOI： 10.1038/s41440-023-01178-1

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Language：English   Publisher：Nature Publishing Group  

安静時心拍数(RHR)と心血管イベント(心、脳、腎血管疾患または関連死)の関連について検討した。EMPATHY(The standard versus intEnsive statin therapy for hypercholesteroleMic Patients with diAbetic retinopaTHY)試験に参加した網膜症合併2型糖尿病患者4746名を、ベースライン時のRHR(中央値76、四分位範囲69～85bpm)で4群に分け、心血管イベントの発生率を比較した。RHR高値群ほど低年齢であり、BMI、血圧、HbA1c、eGFR、喫煙率、糖尿病合併症の有病率が高かった。Cox比例ハザードモデルによる解析の結果、RHR高値は心血管イベントと有意に関連し、RHR 60～69bpm群に対する70～79bpm群および≧80bpm群の多変量調整ハザード比は、それぞれ1.50(95%CI 1.03～2.20)および1.62(1.11～2.36)であった(P<0.05)。心血管イベントリスクはRHRが70bpm以上であれば同様に高い傾向にあり、両者間に線形関係はみられなかった。

Language：English   Publishing type：Research paper (scientific journal)   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Clinical and Experimental Nephrology  

BACKGROUND: Hypertriglyceridemia is increasingly considered a residual risk of cardiovascular disease in patients with chronic kidney disease (CKD). Pemafibrate-a novel selective peroxisome proliferator-activated receptor alpha modulator and a new treatment for hypertriglyceridemia in CKD patients-is reported to have fewer side effects in CKD patients than other fibrates. Appropriate control of hypertriglyceridemia can be expected to improve renal prognosis. However, data on the renal protective effect of pemafibrate are limited. This study aims to evaluate the effectiveness of pemafibrate on urinary protein excretion in CKD patients. METHODS: The Pemafibrate, open-label, Randomized cOntrolled study to evaluate the renal protective eFfect In hyperTriglyceridemia patients with Chronic Kidney Disease (PROFIT-CKD) study is an investigator-initiated, multi-center, open-label, parallel-group, randomized controlled trial. Participants are outpatients with hypertriglyceridemia aged 20 years and over, who have received the care of a nephrologist or a diabetologist for more than 3 months. Inclusion criteria include the following: proteinuria (urine protein/creatinine ratio of ≥ 0.15 g/gCr) within three months before allocation, and hypertriglyceridemia (triglycerides ≥ 150 mg/dL and < 1,000 mg/dL) at allocation. In the treatment group, pemafibrate is added to conventional treatment, while conventional treatment is continued with no additional treatment in the control group. Target patient enrollment is 140 patients. The primary endpoint is the change from baseline in the logarithmic urine protein/creatinine ratio at 12 months after study start. CONCLUSION: This study will provide new findings on the renal protective effect of pemafibrate in CKD patients. CLINICAL TRIAL REGISTRATION: This clinical trial was registered at the University Hospital Medical Information Network (UMIN) Center (UMIN-CTR: UMIN000042284).

DOI： 10.1007/s10157-023-02322-4

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Language：English   Publisher：(一社)日本腎臓学会  

Language：English   Publisher：Circulation: Arrhythmia and Electrophysiology  

DOI： 10.1161/CIRCEP.122.011579

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Cytotherapy  

BACKGROUND AIMS: This prospective clinical study aimed to determine the efficacy and prognostic factors of adoptive activated αβT lymphocyte immunotherapy for various refractory cancers. The primary endpoint was overall survival (OS), and the secondary endpoint was radiological response. METHODS: The authors treated 96 patients. Activated αβT lymphocytes were infused every 2 weeks for a total of six times. Prognostic factors were identified by analyzing clinical and laboratory data obtained before therapy. RESULTS: Median survival time (MST) was 150 days (95% confidence interval, 105-191), and approximately 20% of patients achieved disease control (complete response + partial response + stable disease). According to the multivariate Cox proportional hazards model with Akaike information criterion-best subset selection, sex, concurrent therapy, neutrophil/lymphocyte ratio, albumin, lactate dehydrogenase, CD4:CD8 ratio and T helper (Th)1:Th2 ratio were strong prognostic factors. Using parameter estimates of the Cox analysis, the authors developed a response scoring system. The authors then determined the threshold of the response score between responders and non-responders. This threshold was able to significantly differentiate OS of responders from that of non-responders. MST of responders was longer than that of non-responders (317.5 days versus 74 days). The validity of this response scoring system was then confirmed by internal validation. CONCLUSIONS: Adoptive activated αβT lymphocyte immunotherapy has clinical efficacy in certain patients. The authors' scoring system is the first prognostic model reported for this therapy, and it is useful for selecting patients who might obtain a better prognosis through this modality.

DOI： 10.1016/j.jcyt.2022.09.007

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Language：Japanese   Publisher：The Japanese Society of Clinical Pharmacology and Therapeutics  

<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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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers in Pharmacology  

Background: Alzheimer's disease (AD) is a progressive neurodegeneration and is the most prevalent form of dementia. Intervention at an early stage is imperative. Although three acetylcholinesterase inhibitors (AChEIs) are currently approved for the treatment of mild AD, they are not sufficiently effective. Novel treatments for mild AD are of utmost importance. Objective: To assess the effectiveness of hachimijiogan (HJG), a traditional Japanese herbal medicine (Kampo), in the treatment of mild AD. Methods: This exploratory, open-label, randomized, multicenter trial enrolled patients with mild AD whose score on the Mini Mental State Examination (MMSE) was over 21points. All participants had been taking the same dosage of AChEI for more than 3 months. The participants were randomly assigned to an HJG group taking HJG extract 7.5 g/day in addition to AChEI or to a control group treated only with AChEI. The primary outcome was the change from baseline to 6 months post treatment initiation on the Alzheimer's Disease Assessment Scale-cognitive component- Japanese version(ADAS-Jcog). The secondary outcomes were change from baseline of the Instrumental Activity of Daily Life (IADL), Apathy scale, and Neuropsychiatric Inventory (NPI) -Q score. Results: Among the 77 enrollees, the data of 69(34 HJG and 35 control)were available for analysis. The difference in the change of ADAS-Jcog from baseline to 6 months of the HJG and control groups was 1.29 (90% Confidence interval (CI), -0.74 to 3.32 p = 0.293). In the subgroup analysis, the differences in the change from baseline to 3 and 6 months for women were 3.70 (90% CI ,0.50 to 6.91, p = 0.059) and 2.90 (90% CI,0.09 to 5.71, p = 0.090), respectively. For patients over 65 years, the difference at 3 months was 2.35 (90%CI, 0.01 to 4.68 p = 0.099). No significant differences were found between the HJG and control groups in IADL score, Apathy scale, or NPI-Q score. Conclusion: Although not conclusive, our data indicate that HJG has an adjuvant effect for acetylcholinesterase inhibitors and that it delays the deterioration of the cognitive dysfunction of mild Altzheimer's disease patients. Clinical Trial Registration: http://clinicaltrials.gov Japan Registry of clinical trials, identifier jRCTs 071190018.

DOI： 10.3389/fphar.2022.991982

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Therapeutic Hypothermia and Temperature Management  

Avoiding redistributional hypothermia that decreases core temperature by 0.5-1.5°C within the 1st hour of surgery is difficult. The efficacy of prewarming using a forced-air warming (FAW) device with a lower-body blanket on redistribution hypothermia during epidural procedures have not been investigated. After ethics approval, 113 patients undergoing laparoscopic surgery under general anesthesia combined with epidural anesthesia were enrolled. Intervention (prewarming) group patients who were warmed from operating room entry, including during epidural anesthesia, was compared with the control group that was warmed from just before surgery started. In total, 104 patients (52, control; 52, prewarming) were analyzed. In the prewarming group, compared to the control group, the core temperature 20 minutes after anesthesia induction (36.9 ± 0.4 vs. 37.1 ± 0.4°C, p < 0.02) was significantly higher. The core temperature was higher in the prewarming group than in the control group until 3 hours after the surgery. In the prewarming group, compared to the control group, the core temperature-time integral below baseline till 180 minutes after surgery start (65.1 ± 64.0 vs. 8.1 ± 18.6°C/min, p < 0.0001) or 30 minutes after anesthesia induction (5.3 ± 6.2 vs. 2.0 ± 4.7°C/min, p < 0.0001) were significantly smaller. Postoperative shivering was comparable between the groups. Prewarming during epidural catheter insertion with a FAW device could safely prevent a core temperature decrease induced by redistribution or heat loss without additional preparation, effort, space, or time requirements.

DOI： 10.1089/ther.2022.0009

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Frontiers in Public Health  

BACKGROUND: School refusal occurs in about 1-2% of young people. Anxiety and depression are considered to be the most common emotional difficulties for children who do not attend school. However, at present, no definitive treatment has been established for school refusal, although interventions such as cognitive behavioral therapy have been used. This paper reports a protocol for a cluster-randomized controlled trial of a mindfulness yoga intervention for children with school refusal. METHODS: This study is a multicenter, exploratory, open cluster-randomized controlled trial. This study will recruit children aged 10-15 years with school refusal. After a 2-week baseline, participants for each cluster will be randomly assigned to one of two groups: with or without mindfulness yoga for 4 weeks. Mindfulness yoga will be created for schoolchildren for this protocol and distributed to the participants on DVD. The primary outcome is anxiety among children with school refusal using the Spence Children's Anxiety Scale-Children. DISCUSSION: For this study, we developed a mindfulness yoga program and protocol, and examine whether mindfulness yoga can improve anxiety in children with school refusal. Our mindfulness yoga program was developed based on the opinions of children of the same age, and is a program that children can continue to do every day without getting bored. In this way, we believe that we can contribute to the smooth implementation of support to reduce the anxiety of children with school refusal, and to the reduction of the number of children who refuse to go to school.

DOI： 10.3389/fpubh.2022.881303

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：International Journal of Cardiology  

BACKGROUND: In patients with type 2 diabetes mellitus (T2DM) without known cardiovascular disease, the association between B-type natriuretic peptide (BNP) and cardiovascular events except for heart failure has not been elucidated. We aimed to investigate this association in high-risk T2DM patients. METHODS: We analyzed the association between BNP and cardiovascular events, including coronary, cerebral, renal, and vascular events or cardiovascular death based on the single and serial measurement of BNP in T2DM patients with retinopathy and hyperlipidemia without known cardiovascular disease enrolled in the EMPATHY study. RESULTS: Data from 4966 patients were analyzed for baseline BNP analysis. The median BNP value was 15.0 pg/mL. When analyzed in quartiles of baseline BNP (interquartile range 7.5-29.2 pg/mL), Q2, Q3, and Q4 were associated with cardiovascular events compared with Q1 (hazard ratio [HR]: Q2, 1.91 [P = 0.003]; Q3, 1.63 [P = 0.031]; Q4, 3.20 [P < 0.001]). The analysis of 12-month BNP showed similar associations. In serial BNP measurement, compared with low-low BNP group (baseline ≤35 pg/mL and 12-month ≤35 pg/mL), low-high BNP group as well as high-high BNP group was associated with cardiovascular events (HR: low-high, 2.05 [P = 0.004]; high-high, 2.07 [P = 0.001]) and non-renal cardiovascular events. High-low BNP group tended to be associated with non-renal cardiovascular events (HR vs low-low: 2.05 [P = 0.056]). CONCLUSIONS: BNP levels were associated with first cardiovascular events except for heart failure in T2DM patients with retinopathy and hyperlipidemia. Serial BNP measurement may be useful in further stratifying high-risk patients among this T2DM population.

DOI： 10.1016/j.ijcard.2022.03.049

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：European Heart Journal: Acute Cardiovascular Care  

AIMS: The delayed administration of epinephrine has been proven to worsen the neurological outcomes of patients with out-of-hospital cardiac arrest (OHCA) and shockable rhythm or asystole. We aimed to investigate whether the delayed administration of epinephrine might also worsen the neurological outcomes of patients with witnessed OHCA and initial pulseless electrical activity (PEA). METHODS AND RESULTS: The JAAM-OHCA Registry is a multicentre registry including OHCA patients between 2014 and 2017. Patients with emergency medical services (EMS)-treated OHCA and initial PEA rhythm were included. The primary exposure was the time from the EMS call to the administration of epinephrine. The secondary exposure was the time to epinephrine dichotomized as early (≤15 min) or delayed (>15 min). The primary outcome was the achievement of a favourable neurological outcome, defined as Cerebral Performance Categories Scale 1-2 at 30 days after OHCA. Out of 34 754 patients with OHCA, 3050 patients were included in the present study. After adjusting for potential confounders, the delayed administration of the epinephrine was associated with a lower likelihood of achieving a favourable neurological outcome [adjusted odds ratio (OR) 0.96; 95% confidence interval (CI) 0.93-0.99; P = 0.016]. The percentage of patients who achieved a favourable neurological outcome in the delayed epinephrine group was lower than that in the early epinephrine group (1.3% vs. 4.7%; adjusted OR 0.33; 95% CI 0.15-0.72; P = 0.005). A restricted cubic spline analysis demonstrated that delayed epinephrine administration could decrease the likelihood of achieving a favourable neurological outcome; this was significant within the first 10 min. CONCLUSIONS: The delayed administration of epinephrine was associated with worse neurological outcomes in patients with witnessed OHCA patients with initial PEA.

DOI： 10.1093/ehjacc/zuac026

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ESC Heart Failure  

AIMS: Angiotensin-converting enzyme inhibitors (ACEis) or angiotensin II receptor blockers (ARBs) have been shown to be associated with recovery of cardiac function in patients with dilated cardiomyopathy (DCM). The aim of this study was to assess comparative effectiveness of ACEis vs. ARBs on recovery of left ventricular ejection fraction (LVEF) among patients with DCM. METHODS AND RESULTS: We analysed the clinical personal records of DCM, a national database of the Japanese Ministry of Health, Labour and Welfare, from 2003 to 2014. Patients with LVEF < 40% and on either ACEis or ARBs were included. Eligible patients were divided into two groups according to the use of ACEis or ARBs. A one-to-one propensity case-matched analysis was used. The primary outcome was defined as LVEF ≥ 40% at 3 years of follow-up. Out of 4618 eligible patients, 2238 patients received ACEis and 2380 patients received ARBs. Propensity score matching yielded 1341 pairs. Mean age was 56.0 years, 2041 (76.1%) were male, median duration of heart failure was 1 year, and mean LVEF was 27.6%. The primary outcome was observed more frequently in ARB group than in ACEi group (59.8% vs. 54.1%; odds ratio 1.26; 95% confidence interval 1.08-1.47; P = 0.003). The per-protocol analysis showed similar results (62.0% vs. 54.0%; odds ratio 1.39; 95% confidence interval 1.17-1.66; P < 0.001). The change in LVEF from baseline to 3 years of follow-up was greater in ARB group than in ACEi group (15.8 ± 0.4% vs. 14.0 ± 0.4%, P = 0.003). The subgroup analysis showed that this effect was observed independently of systolic blood pressure, heart rate, LVEF, chronic kidney disease, and concomitant use of beta-blockers and mineralocorticoid receptor antagonists. CONCLUSIONS: The use of ARBs was associated with LVEF recovery more frequently than ACEis among patients with DCM and reduced LVEF.

DOI： 10.1002/ehf2.13790

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1097/MD.0000000000027808

Language：English   Publishing type：Research paper (scientific journal)  

Intensive lipid-lowering therapy is recommended in individuals exhibiting type 2 diabetes mellitus (T2DM) with microvascular complications (as high-risk patients), even without known cardiovascular disease (CVD). However, evidence is insufficient to stratify the patients who would benefit from intensive therapy among them. Hypertension is a major risk factor, and uncontrolled blood pressure (BP) is associated with increased CVD risk. We evaluated the efficacy of intensive vs. standard statin therapy for primary CVD prevention among T2DM patients with retinopathy stratified by BP levels. We used the dataset from the EMPATHY study, which compared intensive statin therapy targeting low-density lipoprotein cholesterol (LDL-C) levels of <70 mg/dL and standard therapy targeting LDL-C levels ranging from ≥100 to <120 mg/dL in T2DM patients with retinopathy without known CVD. A total of 4980 patients were divided into BP ≥ 130/80 mmHg (systolic BP ≥ 130 mmHg and/or diastolic BP ≥ 80 mmHg, n = 3335) and BP < 130/80 mmHg (n = 1645) subgroups by baseline BP levels. During the median follow-up of 36.8 months, 281 CVD events were observed. Consistent with previous studies, CVD events occurred more frequently in the BP ≥ 130/80 mmHg subgroup than in the BP < 130/80 mmHg subgroup (P < 0.001). In the BP ≥ 130/80 mmHg subgroup, intensive statin therapy was associated with lower CVD risk (HR 0.70, P = 0.015) than standard therapy after adjustment. No such association was observed in the BP < 130/80 mmHg subgroup. The interaction between BP subgroup and statin therapy was significant. In conclusion, intensive statin therapy targeting LDL-C < 70 mg/dL provided benefits in primary CVD prevention when compared with standard therapy among T2DM patients with retinopathy and BP ≥ 130/80 mmHg.

DOI： 10.1038/s41440-021-00734-x

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Remimazolam, a benzodiazepine ultra-short-acting sedative, has been used in general anesthesia since August 2020. It is used in awake surgeries that require awakening the patient in the middle of the surgery because of its rapid awakening effect as well as antagonistic interactions. If remimazolam has associated anterograde amnesia similar to benzodiazepines, it will have a positive effect on preventing psychological trauma. However, to our knowledge, the effect of remimazolam on anterograde amnesia has not been previously examined. METHODS/DESIGN: The aim of this exploratory, open, propofol-controlled, single-center, randomized clinical trial is to examine the effect of remimazolam on postoperative memory retention and delayed regeneration. Seventy patients undergoing breast surgery will be included in the study. The patients will be randomly assigned to receive propofol or remimazolam as sedatives during surgery. The primary endpoint is the number of posters patients remember 24 hours after surgery (among 4 posters shown after awakening from anesthesia) as an assessment of anterograde amnesia. Secondary endpoints are retrograde amnesia, dose of analgesic given from the time the patient returns to the ward until 24 hours after surgery, immediate postoperative pain numerical rating scale scores, and pain numerical rating scale scores 24 hours after leaving the operating room. Recruitment will take place between October 2021 and March 2022 to achieve the target sample size. DISCUSSION: To our knowledge, this is the first trial designed to examine the effects of remimazolam on postoperative memory retention and delayed regeneration in patients undergoing breast surgery. TRIAL REGISTRATION: This clinical trial was registered at the University Hospital Medical Information Network (UMIN) Center on September 28, 2021 (UMIN-CTR: UMIN000045593).

DOI： 10.1097/MD.0000000000027808

Language：Others   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ahjo.2021.100053

Language：English  

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Language：English   Publishing type：Research paper (scientific journal)  

Background: Female sex is reported to be associated with poor prognosis in hypertrophic cardiomyopathy (HCM). The plasma B-type natriuretic peptide (BNP) concentration is a prognostic predictor in HCM. However, the effect of sex on BNP concentrations remains unclear among HCM patients. Methods and Results: Patient records in the Clinical Personal Records of HCM national database of the Japanese Ministry of Health, Labour and Welfare from 2009 to 2014 were analyzed. Of 3,570 HCM patients, 611 in whom BNP concentrations were assessed at both baseline and the 2-year follow-up were included in this analysis. The mean age was 60.4 years and 254 (41.6&#37;) patients were female. Median (interquartile range) BNP concentrations were higher in females than males at both baseline (320.3 [159.0-583.1] vs. 182.8 [86.1-363.9] pg/mL; P<0.001) and the 2-year follow-up (299.2 [147.0-535.3] vs. 161.0 [76.2-310.0] pg/mL; P<0.001). Female sex was associated with higher natural log-transformed BNP at the 2-year follow-up regardless of clinical characteristics, including echocardiographic findings and BNP concentrations at baseline (coefficient 0.31; 95&#37; confidence interval 0.13-0.48; P<0.001). Cubic spline analysis showed that, among patients with high BNP concentrations at baseline, females had higher BNP concentrations at the 2-year follow-up than males. Conclusions: In HCM, female sex was associated with higher BNP concentrations than male sex, independent of clinical characteristics, including BNP concentrations at baseline.

DOI： 10.1253/circrep.CR-21-0110

Language：English   Publishing type：Research paper (bulletin of university, research institution)  

DOI： 10.1002/ehf2.13556

Language：English   Publishing type：Research paper (scientific journal)  

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&#37; 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&#37; confidence interval (CI) 0.751-0.803], SMART-HF: 0.765 [95&#37; CI 0.739-0.791], SHFM: 0.713 [95&#37; CI 0.684-0.742], MAGGIC: 0.726 [95&#37; 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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： https://doi.org/10.1253/circrep.CR-21-0110

Language：English  

DOI： 10.1253/circj.CJ-20-0947

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: With aging population, the prevalence and incidence of heart failure (HF) have been increasing worldwide. However, the characteristics and outcomes of patients with HF in an era of aging are not well established in Japan.Methods and Results:The Japanese Registry Of Acute Decompensated Heart Failure (JROADHF), a retrospective, multicenter, nationwide registry, was designed to study the clinical characteristics and outcomes of patients hospitalized with HF throughout Japan in 2013. One hundred and twenty-eight hospitals were selected by cluster random sampling and 13,238 hospitalized patients with HF were identified by medical record review. Demographics, medical history, severity, treatment, and in-hospital and long-term outcome data were collected from the Diagnostic Procedure Combination and medical charts. Data were analyzed using univariate and multivariate logistic regression or Cox regression analysis. The mean age of registered patients was 78.0±12.5 years and 52.8&#37; were male. Elderly patients (age >75 years) accounted for 68.9&#37;, and HF with preserved ejection fraction (HFpEF) accounted for 45.1&#37;. Median length of hospital stay was 18 days and in-hospital mortality was 7.7&#37;. The median follow-up period was 4.3 years, and the incidence rates for cardiovascular death and rehospitalization for HF were 7.1 and 21.1 per 100 person-years, respectively. CONCLUSIONS: A contemporary nationwide registry demonstrated that hospitalized HF patients were very elderly, HFpEF was common, and their prognosis was still poor in Japan.

DOI： 10.1253/circj.CJ-20-0947

Language：English   Publishing type：Research paper (scientific journal)  

Lung to finger circulation time (LFCT) has been used to estimate cardiac function. We developed a new LFCT measurement device using a laser sensor at fingertip. We measured LFCT by measuring time from re-breathing after 20 s of breath hold to the nadir of the difference of transmitted red light and infrared light, which corresponds to percutaneous oxygen saturation. Fifty patients with heart failure were enrolled. The intrasubject stability of the measurement was assessed by the intraclass correlation coefficient (ICC). The ICC calculated from 44 cases was 0.85 (95&#37; confidence interval: 0.77-0.91), which means to have "Excellent reliability." By measuring twice, at least one clear LFCT value was obtained in 89.1&#37; of patients and the overall measurability was 95.7&#37;. We conducted all LFCT measurements safely. High ICCs were obtained even after dividing patients according to age, cardiac index (CI); 0.85 and 0.84 (≥ 75 or < 75 years group, respectively), 0.81 and 0.84 (N = 26, ≥ or < 2.2 L/min/M2). These results show that our new method to measure LFCT is highly stable and feasible for any type of heart failure patients.

DOI： 10.1038/s41598-021-95192-3

Language：English   Publishing type：Research paper (scientific journal)  

Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) have been shown to prevent left ventricular remodeling and improve outcomes of patients with heart failure (HF). This study aimed to investigate whether the use of ACEi/ARB could be associated with HF with recovered ejection fraction (HFrecEF) in patients with dilated cardiomyopathy (DCM).We collected individual patient data regarding demographics, echocardiogram, and treatment in DCM between 2003 and 2014 from the clinical personal record, a national database of the Japanese Ministry of Health, Labour and Welfare. Patients with left ventricular ejection fraction (LVEF) < 40&#37; were included. Eligible patients were divided into two groups according to the use of ACEi/ARB. A propensity score matching analysis was employed. The primary outcome was defined as LVEF ≥ 40&#37; at 3 years of follow-up.Out of 5,955 patients with DCM and LVEF < 40&#37;, propensity score matching yielded 830 pairs. The mean age was 58.8 years, and 1,184 (71.3&#37;) of the patients were male. The primary outcome was observed more frequently in the ACEi/ARB group than in the no ACEi/ARB group (57.0&#37; versus 49.3&#37;; odds ratio 1.36; 95&#37; confidence interval (CI) 1.12-1.65; P = 0.002). Subgroup analysis revealed that the use of ACEi and ARB was associated with recovery of LVEF regardless of atrial fibrillation. The change in LVEF from baseline to 3 years of follow-up was greater in the ACEi-ARB group (14.9&#37; ± 0.6&#37; versus 12.3&#37; ± 0.5&#37;; P = 0.001).The use of ACEi/ARB is associated with HFrecEF in patients with DCM and reduced LVEF.

DOI： 10.1536/ihj.20-671

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Intensive lipid-lowering therapy is recommended in type 2 diabetes mellitus (T2DM) patients with target organ damage. However, the evidence is insufficient to stratify the patients who will benefit from the intensive therapy among them. High visit-to-visit variability in systolic blood pressure (SBP) is associated with increased risk of cardiovascular events. We investigated the effectiveness of intensive versus standard statin therapy in the primary prevention of cardiovascular events among T2DM patients with retinopathy stratified by visit-to-visit SBP variability. METHODS: The standard versus intensive statin therapy for hypercholesterolemic patients with diabetic retinopathy study was the first trial comparing statin intensive therapy targeting low-density lipoprotein cholesterol (LDL-C) <70 mg/dl and standard therapy targeting LDL-C ≥100 to <120 mg/dl in T2DM patients with retinopathy without known cardiovascular disease. Using this dataset, we divided the patients into two subpopulations based on standard deviation (SD) and average real variability (ARV) of clinic SBP within the initial 6 months. RESULTS: In a total of 4899 patients, 240 composite cardiovascular events were observed during a median follow-up of 37.3 months. In multivariable-adjusted model comparing intensive versus standard therapy, the hazard ratios for composite cardiovascular events were 0.64 (95&#37; CI 0.45-0.90) and 1.21 (95&#37; CI 0.82-1.80) in patients with high and low SBP variability as defined by SD, respectively. Interaction between SBP variability and statin therapy was significant (P = 0.018). The analysis using ARV of SBP showed similar results. CONCLUSION: Statin intensive therapy targeting LDL-C <70 mg/dl had benefits in primary prevention of cardiovascular events compared with standard therapy among T2DM patients with retinopathy having high, but not low, visit-to-visit SBP variability.

DOI： 10.1097/HJH.0000000000002823

Language：English   Publishing type：Research paper (scientific journal)  

Background Withdrawal of optimal medical therapy has been reported to relapse cardiac dysfunction in patients with dilated cardiomyopathy (DCM) whose cardiac function had improved. However, it is unknown whether beta-blockers can prevent deterioration of cardiac function in those patients. We examined the effect of beta-blockers on left ventricular ejection fraction (LVEF) in recovered DCM. Methods and Results We analyzed the clinical personal record of DCM, a national database of the Japanese Ministry of Health, Labor and Welfare, between 2003 and 2014. Recovered DCM was defined as a previously documented LVEF <40&#37; and a current LVEF ≥40&#37;. Patients with recovered DCM were divided into 2 groups according to the use of beta-blockers. A one-to-one propensity case-matched analysis was used. The primary outcome was defined as a decrease in LVEF >10&#37; at 2 years of follow-up. Of 5370 eligible patients, 4104 received beta-blockers. Propensity score matching yielded 1087 pairs. Mean age was 61.9 years, and 1619 (74.5&#37;) were men. Mean LVEF was 49.3±8.2&#37;, and median B-type natriuretic peptide was 46.6 (interquartile range, 18.0-118.1) pg/mL. The primary outcome was observed less frequently in the beta-blocker group than in the no-beta-blocker group (19.6&#37; versus 24.0&#37;; odds ratio [OR], 0.77; 95&#37; CI, 0.63-0.95; P=0.013). Subgroup analysis demonstrated that female patients (women: OR, 0.54; 95&#37; CI, 0.36-0.81; men: OR, 0.88; 95&#37; CI, 0.69-1.12; P for interaction=0.040) were benefited by beta-blockers. Conclusions Beta-blocker use could prevent deterioration of left ventricular systolic function in patients with recovered DCM.

DOI： 10.1161/JAHA.120.019240

Language：English   Publishing type：Research paper (scientific journal)  

Background: The clinical features of patients with cardiomyopathy, including dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), or restrictive cardiomyopathy (RCM), have not been recently elucidated in Japan. Methods and Results: We collected individual patient data regarding demographics, echocardiogram, and treatment in DCM from 2003 to 2014 and in HCM and RCM from 2009 to 2014 from the national registry of clinical personal records organized by the Japanese Ministry of Health, Labour and Welfare. In all, 44,136 patients were included in this registry: 40,537 with DCM, 3,553 with HCM, and 46 with RCM. The median age at diagnosis was older for DCM and HCM than RCM (54 and 55 vs. 42 years, respectively). Male patients accounted for 74.6&#37;, 58.7&#37;, and 60.9&#37; of the DCM, HCM, and RCM groups, respectively. NYHA functional Class III-IV was found in 26.9&#37;, 11.3&#37;, and 58.1&#37; of patients in the DCM, HCM, and RCM groups, respectively. In the DCM group, the rates of β-blocker and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker prescription were 69&#37; and 76&#37;, respectively. In regional subgroup analysis, the median age at diagnosis of DCM and HCM was younger in the Kanto region. A family history of HCM was less frequent in the Hokkaido/Tohoku region. Conclusions: The national registry of clinical personal records of cardiomyopathy could provide important information regarding the demographics, clinical characteristics, and management of cardiomyopathy throughout Japan.

DOI： 10.1253/circrep.CR-21-0001

Language：Japanese  

Language：English   Publishing type：Research paper (scientific journal)  

As timely measurement of the cardiac index (CI) is one of the key elements in heart failure management, a noninvasive, simple, and inexpensive method of estimating CI is keenly needed. We attempted to develop a new device that can estimate CI from the data of lung-to-finger circulation time (LFCT) obtained after a brief breath hold in the awake state. First, we attempted to estimate CI from the LFCT value by utilizing the correlation between 1/LFCT and CI estimated with MRI. Although we could obtain LFCT from 45 of 53 patients with cardiovascular diseases, we could not find the anticipated relation between 1/LFCT and CI. However, we realized that when we adopted only LFCT from patients with a finger temperature of ≥31°C, we could obtain a consistent and clear correlation with CI (correlation coefficient, r = .81). Thus, we next measured LFCT before and after warming the forearm. We found that LFCT decreased after the local temperature increased (from 27.5 ± 13.6 to 18.4 ± 5.3 s, p < 0.01). The correlation between the inverse of LFCT and CI improved after warming (1/LFCT vs. CI, from r = .69 to r = .82). The final Bland-Altman analysis between the measured and estimated CI values revealed that the bias and precision were -0.05 and 0.37 L min-1  m-2 , respectively, and the percentage error was 34.3&#37;. This study clarified that estimating CI using a simple measurement of LFCT is feasible in most patients and a low fingertip temperature strongly affects the CI-1/LFCT relationship, causing an error that can be corrected by proper local warming.

DOI： 10.14814/phy2.14632

Language：English  

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DOI： 10.1161/circ.142.suppl_3.14550

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Dementia among the Japanese aged 65 years or over population is estimated to approach about 700 million cases by 2025, and a corresponding rapid increase in Alzheimer disease (AD) can also be expected. The ballooning number of dementia patients, including AD, is creating major medical and social challenges. At present, only 3 drugs are recognized for the treatment of mild AD, and these are only used to alleviate symptoms. Although new therapies are needed to treat mild AD, insufficient development of disease-modifying drugs is being done. METHODS/DESIGN: The aim of this exploratory, open standard, treatment-controlled, randomized allocation, multicenter trial is to determine the efficacy of the traditional Japanese Kampo medicine hachimijiogan (HJG) on the cognitive dysfunction of mild AD.Eighty-six patients with AD diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 and as mild AD according to the Mini Mental State Examination (MMSE ≥21) will be included. All will already have been taking the same dose of Donepezil, Galantamine, or Rivastigmine for more than 3 months. The patients will be randomly assigned to receive additional treatment with HJG or to continue mild AD treatment without additional HJG. The primary endpoint is the change from baseline of the Alzheimer's Disease Assessment Scale-cognitive component- Japanese version (ADAS-Jcog). ADAS-Jcog is a useful index for detecting change over time that investigates memory and visuospatial cognition injury from the early stage. The secondary endpoints are the changes from baseline of the Instrumental Activity of Daily Life, Apathy scale, and Nueropsychiatric Inventory scores. In this protocol, we will examine the Geriatric depression scale and do Metabolome analysis as exploratory endpoints. The recruitment period will be from August 2019 to July 2021. DISCUSSION: This is the first trial of Kampo medicine designed to examine the efficacy of HJG for the cognitive dysfunction of patients with mild AD. TRIAL REGISTRATION: This trial was registered on the Japan Registry of Clinical trials on 2 August 2, 2019 (jRCTs 071190018).

DOI： 10.1097/MD.0000000000022370

Language：English   Publishing type：Research paper (scientific journal)  

Small studies in Western populations report a high prevalence of obstructive sleep apnea (OSA) in adults with Down syndrome. To date, ethnic differences have not been explored. A questionnaire sent to 2,752 adults with Down syndrome aged ≥16 years in Scotland and Japan (789 valid responses) estimated OSA prevalence based on reported symptoms. Symptoms were common in both countries, with snoring (p = 0.001) and arousals (p = 0.04) more prevalent in Japan. Estimated OSA prevalence in adults with Down syndrome was similar in the two countries, and raised in comparison with the general adult population (19.6&#37; in Scotland and 14.3&#37; in Japan; p = 0.08), though BMI was a confounder. Identification and treatment of OSA is recommended in adults with Down syndrome, regardless of ethnicity.

DOI： 10.1352/1944-7558-125.4.260

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: An inverse relationship exists between hospital case volume and mortality in patients with heart failure (HF). However, hospital performance factors associated with mortality in HF patients have not been examined. We aimed to identify these using exploratory factor analysis and assess the relationship between these factors and 7-day, 30-day, and in-hospital mortality among HF patients in Japan.Methods and Results:We analyzed the records of 198,861 patients admitted to 683 certified hospitals of the Japanese Circulation Society between 2012 and 2014. Records were obtained from the nationwide database of the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC). Using exploratory factor analysis, 90 hospital survey items were grouped into 5 factors, according to their collinearity: "Interventional cardiology", "Cardiovascular surgery", "Pediatric cardiology", "Electrophysiology" and "Cardiac rehabilitation". Multivariable logistic regression analysis was performed to determine the association between these factors and mortality. The 30-day mortality was 8.0&#37;. Multivariable logistic regression analysis showed the "Pediatric cardiology" (odds ratio (OR) 0.677, 95&#37; confidence interval [CI]: 0.628-0.729, P<0.0001), "Electrophysiology" (OR 0.876, 95&#37; CI: 0.832-0.923, P<0.0001), and "Cardiac rehabilitation" (OR 0.832, 95&#37; CI: 0.792-0.873, P<0.0001) factors were associated with lower mortality. In contrast, "Interventional cardiology" (OR 1.167, 95&#37; CI: 1.070-1.272, P<0.0001) was associated with higher mortality. CONCLUSIONS: Hospital factors, including various cardiovascular therapeutic practices, may be associated with the early death of HF patients.

DOI： 10.1253/circj.CJ-19-0759

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Left ventricular (LV) dysfunction due to anthracycline-induced cardiotoxicity (AIC) has been believed to be irreversible. However, this has not been confirmed and standard medical treatment for heart failure (HF) including renin-angiotensin inhibitors and β-blockers may lead to its recovery. METHODS AND RESULTS: We thus retrospectively studied 350 cancer patients receiving anthracycline-based chemotherapy from 2001 to 2015 in our institution. Fifty-two patients (14.9&#37;) developed AIC with a decrease in LV ejection fraction (LVEF) of 24.1&#37; at a median time of 6 months [interquartile range (IQR) 4-22 months] after anthracycline therapy. By multivariate analysis, AIC was independently associated with cardiac comorbidities including ischemic heart disease, valvular heart disease, arrhythmia, and cardiomyopathy [odds ratio (OR) 6.00; 95&#37; confidence interval (CI) 2.27-15.84, P = 0.00044), lower baseline LVEF (OR per 1&#37; 1.09; 95&#37; CI 1.04-1.14, P = 0.00034). During the median follow-up of 3.2 years, LV systolic dysfunction recovered among 33 patients (67.3&#37;) with a median time of 4 months (IQR 2-6 months), which was independently associated with the introduction of standard medical treatment for HF (OR 9.39; 95&#37; CI 2.27-52.9, P = 0.0014) by multivariate analysis. CONCLUSION: Early initiation of standard medical treatment for HF may lead to LV functional recovery in AIC.

DOI： 10.1007/s00392-018-1386-0

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: To compare the efficacy of twin-block (i.e., allows mouth opening) and fixed (i.e., maintains mouth closure) mandibular advancement splints (MASs) for the treatment of obstructive sleep apnea-hypopnea syndrome (OSA). MATERIALS AND METHODS: From 2011 to 2013, 23 patients with OSA in the twin-block group, and from 2013 to 2015, 29 patients in the fixed MAS group were included. All patients underwent polysomnography before and after 3 months of treatment. The two sets of polysomnographic and cephalometric variables were compared. RESULTS: A significant difference (p < 0.001) was observed in the apnea-hypopnea index before and after MAS treatment in both groups (twin-block group: 20.6 ± 11.5 vs. 14.7 ± 9.4; fixed group: 21.4 ± 15.2 vs. 11.2 ± 9.7). In the twin-block group, 5 patients (21.7&#37;) were complete responders, 9 (39.1&#37;) were fair responders, and 9 (39.1&#37;) were nonresponders; the corresponding figures for the fixed group were 14 (48.3&#37;), 9 (31.0&#37;), and 6 (20.7&#37;) patients. A significant between-group difference was observed in the distribution of responders (p = 0.046). The fixed group showed a significant improvement in the snoring index (p = 0.003), arousal index (p = 0.036), and desaturation rate (p = 0.012). Finally, the change in incisal overjet was larger in the fixed group than in the twin-block group (p < 0.001). CONCLUSIONS: These results suggest that fixed oral appliances are superior in treating OSA, based on their ability to prevent mouth opening and reduce incisal overjet.

DOI： 10.1111/jopr.12619

Language：English  

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Language：English  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Patients with heart failure and preserved ejection fraction (HFpEF) are supersensitive to volume overload, and a striking increase in left atrial pressure (LAP) often occurs transiently and is rapidly resolved by intravascular volume reduction. The arterial baroreflex is a powerful regulator of intravascular stressed blood volume. We examined whether arterial baroreflex failure (FAIL) mimicked by constant carotid sinus pressure (CSP) causes a striking increase in LAP and systemic arterial pressure (AP) by volume loading in rats with normal left ventricular (LV) function. METHODS AND RESULTS: In anesthetized Sprague-Dawley rats, we isolated bilateral carotid sinuses and controlled CSP by a servo-controlled piston pump. We mimicked the normal arterial baroreflex by matching CSP to instantaneous AP and FAIL by maintaining CSP at a constant value regardless of AP. We infused dextran stepwise (infused volume [Vi]) until LAP reached 15 mm Hg and obtained the LAP-Vi relationship. We estimated the critical Vi as the Vi at which LAP reached 20 mm Hg. In FAIL, critical Vi decreased markedly from 19.4 ± 1.6 mL/kg to 15.6 ± 1.6 mL/kg (P < .01), whereas AP at the critical Vi increased (194 ± 6 mm Hg vs 163 ± 6 mm Hg; P < .01). We demonstrated that an artificial arterial baroreflex system we recently developed could fully restore the physiologic volume intolerance in the absence of native arterial baroreflex. CONCLUSIONS: Arterial baroreflex failure induces striking volume intolerance in the absence of LV dysfunction and may play an important role in the pathogenesis of acute heart failure, especially in states of HFpEF.

DOI： 10.1016/j.cardfail.2013.11.007

Language：English   Publishing type：Research paper (scientific journal)  

INTRODUCTION: Effectiveness and safety of warfarin therapy for non-valvular atrial fibrillation (NVAF) patients are strongly associated with its stability presented such as time in therapeutic range (TTR) of PT-INR. However, the factors that affect TTR have not been fully elucidated in Japan where majority of patients are controlled within the range of 1.6-2.6 of PT-INR irrespective of the age. METHODS: We retrospectively analyzed 163 NVAF patients taking warfarin to determine the factors that affect TTR including metabolic enzymes polymorphisms after TTR calculation with both the standard PT-INR range and the actual control range of 1.6-2.6. RESULTS: Overall TTR calculated using Japanese Guideline was 69.7 ± 25.1&#37; (<70 and ≥ 70 years; 49.6 ± 24.8&#37; and 77.8 ± 20.3&#37;, respectively). After confirming that PT-INR values in patients < 70 years distributed in the same range as in those ≥ 70 years, as in a Japanese large cohort, we recalculated TTR of those < 70 years with 1.6-2.6 of PT-INR and found that it was 79.5 ± 20.1&#37;. Poor control of this new TTR were significantly associated with the lower height, the higher serum creatinine, the lower creatinine clearance, female gender, and presence of congestive heart failure, (p<0.05 respectively). Multivariate analysis revealed female gender and presence of congestive heart failure as independent predictor of the lower TTR (p<0.05, p<0.01, respectively). Polymorphism of CYP2C9 and VKORC1 were related to the dosage of warfarin but not determinant of TTR. CONCLUSIONS: When evaluated using a range of PT-INR actually used in Japan, TTR is generally well controlled and female gender and presence of congestive heart failure significantly affected the poorer TTR control.

DOI： 10.1016/j.thromres.2013.09.003

Language：English  

Language：English  

Language：Others   Publishing type：Research paper (scientific journal)  

DOI： 10.5551/jat.8730

Language：English  

Language：English  

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: The objective of this study was to formulate a nanoparticle (NP)-eluting drug delivery stent system by a cationic electrodeposition coating technology. BACKGROUND: Nanoparticle-mediated drug delivery systems (DDS) are poised to transform the development of innovative therapeutic devices. Therefore, we hypothesized that a bioabsorbable polymeric NP-eluting stent provides an efficient DDS that shows better and more prolonged delivery compared with dip-coating stent. METHODS: We prepared cationic NP encapsulated with a fluorescence marker (FITC) by emulsion solvent diffusion method, succeeded to formulate an NP-eluting stent with a novel cation electrodeposition coating technology, and compared the in vitro and in vivo characteristics of the FITC-loaded NP-eluting stent with dip-coated FITC-eluting stent and bare metal stent. RESULTS: The NP was taken up stably and efficiently by cultured vascular smooth muscle cells in vitro. In a porcine coronary artery model in vivo, substantial FITC fluorescence was observed in neointimal and medial layers of the stented segments that had received the FITC-NP-eluting stent until 4 weeks. In contrast, no substantial FITC fluorescence was observed in the segments from the polymer-based FITC-eluting stent or from bare metal stent. The magnitudes of stent-induced injury, inflammation, endothelial recovery, and neointima formation were comparable between bare metal stent and NP-eluting stent groups. CONCLUSIONS: Therefore, this NP-eluting stent is an efficient NP-mediated DDS that holds as an innovative platform for the delivery of less invasive nano-devices targeting cardiovascular disease.

DOI： 10.1016/j.jcin.2008.08.023

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: We have previously shown that the intramuscular transfer of the anti-monocyte chemoattractant protein-1 (MCP-1) gene (called 7ND) is able to prevent experimental restenosis. The aim of this study was to determine the in vivo efficacy and safety of local delivery of 7ND gene via the gene-eluting stent in reducing in-stent neointima formation in rabbits and in cynomolgus monkeys. METHODS AND RESULTS: We here found that in vitro, 7ND effectively inhibited the chemotaxis of mononuclear leukocytes and also inhibited the proliferation/migration of vascular smooth muscle cells. We then coated stents with a biocompatible polymer containing a plasmid bearing the 7ND gene, and deployed these stents in the iliac arteries of rabbits and monkeys. 7ND gene-eluting stents attenuated stent-associated monocyte infiltration and neointima formation after one month in rabbits, and showed long-term inhibitory effects on neointima formation when assessments were carried out at 1, 3, and 6 months in monkeys. CONCLUSIONS: Strategy of inhibiting the action of MCP-1 with a 7ND gene-eluting stent reduced in-stent neointima formation with no evidence of adverse effects in rabbits and monkeys. The 7ND gene-eluting stent could be a promising therapy for treatment of restenosis in humans.

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) plays a critical role in the vascular response to injury. However, the role of NF-kappaB in the mechanism of in-stent restenosis remains unclear. We therefore tested the hypothesis that blockade of NF-kappaB by stent-based delivery of a cis-element "decoy" of NF-kappaB reduces in-stent neointimal formation. METHODS AND RESULTS: Stents were coated with a polymer containing or not containing NF-kappaB decoy, which represented a fast-release formulation (<7 days). Bare, polymer-coated, and NF-kappaB decoy-eluting stents were implanted in iliac arteries of hypercholesterolemic rabbits. Increased NF-kappaB activity was noted at early stages after stenting, which was suppressed by stent-based delivery of NF-kappaB decoy. NF-kappaB decoy-eluting stents also reduced monocyte infiltration and monocyte chemoattractant protein-1 expression and suppressed CD14 activation on circulating leukocytes. Importantly, NF-kappaB decoy-eluting stents attenuated neointimal formation on day 28. There was no evidence of an incomplete healing process (persistent inflammation, hemorrhage, fibrin deposition, impaired endothelial regeneration) at the site of NF-kappaB decoy-eluting stents. Transfection of NF-kappaB decoy suppressed proliferation of human coronary artery smooth muscle cells in vitro. No systemic adverse effects of NF-kappaB decoy were detected. CONCLUSIONS: Stent-based local delivery of NF-kappaB decoy reduced in-stent neointimal formation with no evidence of incomplete healing. These data suggest that this strategy may be a practical and promising means for prevention of in-stent restenosis in humans.

Language：English   Publishing type：Research paper (scientific journal)  

The precise mechanism by which angiotensin II type 1 receptor blocker reduces in-stent restenosis in clinical trials is unclear. We, therefore, investigated the mechanism of in-stent neointima formation. Male cynomolgus monkeys and rabbits were fed a high-cholesterol diet and were allocated to untreated control and type 1 receptor blocker groups. Five days after grouping, multilink stents were implanted in the iliac artery. The type 1 receptor blocker reduced the development of in-stent neointima formation by approximately 30&#37; in rabbits and monkeys. To investigate potential mechanisms, we examined the expression of renin-angiotensin system markers, all of which increased in monocytes and smooth muscle-like cells in the neointima and media within 7 days. The type 1 receptor blocker attenuated increased oxidative stress, the enhanced expression of markers of the rennin-angiotensin system and monocyte chemoattractant protein-1, and macrophage infiltration. The effects of type 1 receptor blocker on the differentiation of peripheral blood mononuclear cells into vascular progenitor cells were also examined. Treatment with type 1 receptor blocker suppressed the enhanced differentiation to smooth muscle progenitor cells induced by stenting. The type 1 receptor blocker attenuated in-stent neointima formation by inhibiting redox-sensitive inflammatory changes and by reducing recruitment of the progenitor cells. These potential actions of type 1 receptor blocker on inflammation and progenitor cells constitute a novel mechanism of suppression of in-stent restenosis by type 1 receptor blocker.

Event date： 2022.2

Language：Others   Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

Event date： 2022.2

Language：Others   Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

Event date： 2022.2

Language：Others   Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

Event date： 2022.2

Venue：東京   Country：Japan  

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Event date： 2022.2

Venue：東京   Country：Japan  

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Event date： 2022.2

Venue：東京   Country：Japan  

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Event date： 2022.2

Venue：東京   Country：Japan  

【背景・目的】
臨床試験の地理的・時間的な制約を低減させる分散型臨床試験が注目されているが、eConsent（電子的同意）は、その構成要素として必須となる。また、人を対象とする生命科学・医学系研究に関する倫理指針でもeConsentが導入され、当院でも研究者からeConsent利用のためのインフラが要望された。

【方法】
ユースケースとして当院精神科で実施する「社会的ひきこもりを対象としたオンライン支援システムの開発および効果検証（代表 九州大学 加藤隆弘）」を用いた。
被験者は社会的引きこもり本人及び支援者。構築にはWEBベースのEDCであるREDCapを用い、同意書の署名にはREDCapの署名機能を用いた。REDCapのサーベイ機能でフォーム構成を工夫して有効な同意が形成されたと見なされる手順の実装を行った。

【結果】
以下の手順を実装した。
１） 被験者候補にQRコード等で臨床研究のHPへのアドレスを伝える。
２）被験者候補が入力したメールアドレスとパスコードで以降の連絡と個人認証を行う。
３）同意説明フォームでは研究者本人が説明する説明動画を流したうえで、同意書フォームへ進む。
４）同意書フォームで被験者候補が同意内容へのチェックとタブレットを用いた電子署名を行ってボタン操作で同意を行う。
５）同意内容はPDFでダウンロード可能とする。

【考察】
REDCapの標準機能のみでeConsentが実装できた。フォーム間の連携にメールを用いることにセキュリティ上の問題の指摘があったが、パスコードの利用や現状のグローバルなメールインフラのセキュリティ向上で対応可能だと考えるが、今後も引き続き検討を行う。

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Event date： 2022.1

Language：Others   Presentation type：Oral presentation (general)  

Venue：福岡   Country：Japan  

Event date： 2022.1

Venue：福岡   Country：Japan  

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Event date： 2021.9

Language：Others   Presentation type：Oral presentation (general)  

Venue：岡山   Country：Japan  

Event date： 2020.6

Language：Others   Presentation type：Oral presentation (general)  

Venue：web   Country：Japan  

Event date： 2020.6

Language：Others   Presentation type：Oral presentation (general)  

Venue：web   Country：Japan  

Event date： 2020.6

Language：Others   Presentation type：Oral presentation (general)  

Venue：web   Country：Japan  

Event date： 2020.6

Language：Others   Presentation type：Oral presentation (general)  

Venue：web   Country：Japan  

Event date： 2010.9

Language：Others  

Venue：Fukuoka   Country：Japan  

Event date： 2024.3 - 2024.5

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪市   Country：Japan  

【背景・目的】
治験ではデータ収集のためにワークシート(WS)を用いることが多いが、カルテからWSを経てElectronic Data Capture (EDC)への転記作業が発生し、情報収集のための時間や転記ミスなどの様々な負担を伴う。近年WSの電子化や電子カルテ(HIS)との連携の試み等が行われているが、日常診療との連続性の担保や効率的なデータ収集、新規システム導入にかかるコスト等に課題が残る。我々は日本医療研究開発機構(AMED)の医療技術実用化総合促進事業において、臨床研究中核病院が相互に使用可能な電子WS (eWS)の開発に取り組んだ。

【方法】
AMEDの平成30年度「標準的医療情報収集システム開発・利活用研究事業」で開発された標準化電子クリニカルパス(ePath)を基盤として、HIS内で使用できるeWSのシステムを開発した。

【結果】
臨床研究中核病院で使用されているIBM, NEC, 富士通のHIS 3ベンダーのシステムそれぞれにおいてHIS内にeWSを作成し、検査結果や処方などの診療の記載の引用と治験特有のデータの記載を、治験の各ビジットと紐づける形で構造化することができた。結果、eWSのデータをCSVとして出力し、それをEDCにインポートできるシステムのプロトタイプが11施設に導入された。

【考察】
ePathを基盤として用いることで、HISに記録した情報を効率的にeWSに収集し、その内容をベンダーの違いを越えて、EDCにインポートできることを示した。一方で、実用化にはまだ多くの課題がある。ベンダー各社の協力を得て引き続きの改修を進める他、特に治験とクリニカルパスの違いを含めた、運用上の留意事項も意識する必要があり、病院側の体制整備も並行して進める必要がある。治験主幹施設での立ち上げ（構築）までの運用や各施設でのeWSデータの出力の運用整備を進めている。

Event date： 2024.3 - 2024.5

Language：Japanese  

Venue：大阪市   Country：Japan  

【背景・目的】
治験ではデータ収集のためにワークシート(WS)を用いることが多いが、カルテからWSを経てElectronic Data Capture (EDC)への転記作業が発生し、情報収集のための時間や転記ミスなどの様々な負担を伴う。近年WSの電子化や電子カルテ(HIS)との連携の試み等が行われているが、日常診療との連続性の担保や効率的なデータ収集、新規システム導入にかかるコスト等に課題が残る。我々は日本医療研究開発機構(AMED)の医療技術実用化総合促進事業において、臨床研究中核病院が相互に使用可能な電子WS (eWS)の開発に取り組んだ。

【方法】
AMEDの平成30年度「標準的医療情報収集システム開発・利活用研究事業」で開発された標準化電子クリニカルパス(ePath)を基盤として、HIS内で使用できるeWSのシステムを開発した。

【結果】
臨床研究中核病院で使用されているIBM, NEC, 富士通のHIS 3ベンダーのシステムそれぞれにおいてHIS内にeWSを作成し、検査結果や処方などの診療の記載の引用と治験特有のデータの記載を、治験の各ビジットと紐づける形で構造化することができた。結果、eWSのデータをCSVとして出力し、それをEDCにインポートできるシステムのプロトタイプが11施設に導入された。

【考察】
ePathを基盤として用いることで、HISに記録した情報を効率的にeWSに収集し、その内容をベンダーの違いを越えて、EDCにインポートできることを示した。一方で、実用化にはまだ多くの課題がある。ベンダー各社の協力を得て引き続きの改修を進める他、特に治験とクリニカルパスの違いを含めた、運用上の留意事項も意識する必要があり、病院側の体制整備も並行して進める必要がある。治験主幹施設での立ち上げ（構築）までの運用や各施設でのeWSデータの出力の運用整備を進めている。

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Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪市   Country：Japan  

【背景・目的】
統一書式とは治験を実施するに当たり治験依頼者と医療機関の間でやり取りされる厚労省が定めた書式で、書式４はIRBに対する治験審査依頼、書式５はIRBでの審議結果を記した治験審査結果通知書である。
当院では、HOPE-GX内のHOPE-NMGCP（Fujitsu、以後治験管理システム）に登録した治験管理基本データを依頼者コミュニケーションシステム（Fujitsu）が臨床試験・治験支援システムCT-Portal（ファーマメディカルソリューションズ株式会社）に転送し、CT-Portalが統一書式４、５を生成していた。
依頼者コミュニケーションシステムのサーバの耐用年数が過ぎてリプレースが必要となったタイミングで、治験管理システムから直接、書式４，５を統一書式作成システムを内製化した。

【方法・結果】
IRB準備時やIRB中の関係者のタスクを洗い出して、フロー図に起こし、要求される機能を明確にした。治験管理基本データは複数のCSVファイルがZIPファイルとなってメールで1日1回出力されるため、これをデータベースに登録した。出力ファイルは、将来の電磁化を考慮しPDFファイルで作成することとした。
電子カルテの治験管理基本データと連携し書式４、５を円滑に作成するシステムが内製で構築できた。
依頼者コミュニケーションのリプレース費用・維持のためのライセンス費用や臨床試験・治験支援システムの保守費用を削減することができた。

【考察】
今回、書式４，５をPDF形式で作成・保存する構成としたことにより、従来の紙保存が不要となり、紙文書の保管スペースの削減も含めて治験の電磁化に大きく貢献した。

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪市   Country：Japan  

(背景)
我々はアカデミア向けEDC「REDCap」を利用し臨床研究の支援を行っている。医療技術実⽤化総合促進事業DCTの取組みで、体制整備のための模擬治験を行う際、治験実施施設外の医療者が診療範囲内の医療行為の結果を電子的医療者評価アウトカム(eClinRO)として報告するため、REDCap Mobile App(以下、Mobile App)をeClinROシステムとして使用した。Mobile Appの設定及び運用について検討結果を報告する。

(方法)
治験実施施設と治験実施施設外の医療提供施設は1対nの関係があるためデータへの複雑なアクセス管理を考慮した上で、模擬治験のデータフローに沿い仕様を確定した。

(結果)
当センターでREDCapの模擬治験プロジェクト(以下、PJ)に医療提供施設責任者を紐付けた。医療提供施設責任者はPJで発行されたQRコードを介してMobile Appインストール済みデバイスにデータ登録する準備を行った。医療提供者はMobile Appにデータ登録し(オフライン可)、オンライン環境でデータ送信操作をしてPJに反映できた。また医療提供者は同じ医療提供施設の所属者から登録されたデータのみをPJで確認できた。

(考察)
Mobile Appを使用することで通信環境があれば治験実施施設と医療提供施設間のデータがリアルタイムでEDCに反映される。ただしMobile App特有の課題も明らかになったためバージョンアップにより改善を期待する。なお当日はePROシステムとして利用した「MyCap」の設定及び運用についても報告する。

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪市   Country：Japan  

【背景】
我々はアカデミア向けEDC「REDCap」の国内展開を推進している。医療技術実用化総合促進事業DCTの取組みでは、体制整備のための模擬治験を行うが、我々はREDCapファミリーのePROソフトである「MyCap（以下旧MyCap）」を利用した。旧MyCapは国内での使用報告はほとんどなかったが、模擬治験を通して９件の課題が抽出できた。大規模DCT（複数実施施設）特有の課題も抽出できた。新バージョンのMyCap（以下新MyCap）では機能も進化／改善されており、新MyCapの改善内容の確認に加えて、大規模DCT（複数実施施設）の際に対応に関しても検証した。

【方法】
1)模擬治験時の旧MyCapの課題を抽出。2)開発中の新MyCap用最新REDCapサーバを新たに構築。3)模擬治験と同じ要件で新MyCapを構築し新旧を比較。4)改善点・残存課題を抽出きた。

【結果】
Visitに対応して柔軟な入力日指定が可能になった。スマートフォンOSの違いによる動きの違いが改善した。しかし、旧MyCapの課題9件のうち4件が残存していた。また、旧MyMacではなかった不具合も発生した。大規模DCTで必要な複雑なアクセス制限管理は改善されていなかった。

【考察】
開発中の新MyCapでも機能を考慮してデザインすれば運用に耐えるePROであることが確認できた。大規模DCTで必要な複雑なアクセス制限管理は、新MyCap単独では出来なかったが、我々が新たな手法を開発し対応できた。アプリ初期メニューの日本語化や機能改善の為、今後も積極的なVanderbilt大学への働きかけが必要と考えられた。

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪市   Country：Japan  

【背景・目的】
医療技術実用化総合促進事業では2022-23年度と模擬治験を通してDCTの運用整備を進めてきた。2022年度は、リモートeConsentシステムをREDCapと連携し実現した（第14回学術集会にて報告）。しかし、(1) 汎用性を考慮すると署名の対象者を被験者、代諾者だけでなく、代筆者、立会人にも応する必要があり、(2)説明文書のバージョン管理が必要、(3)被験者による同意書の受領確認が必要、(4) 施設間のシステム展開が煩雑、(5)今年度の模擬治験は対象疾患を筋萎縮性側索硬化症（ALS）としたためデバイス操作に細かい作業を被験者候補にさせることができないといった課題があった。
上記の課題を踏まえて、今年度新たにシステム構築を行った。

【方法・結果】
代筆者、立会人の署名に対応した。説明文書のバージョン管理を行った。同意書の被験者受領確認を行うために同意書のダウンロード日時を記録した。docker（コンテナ型仮想化システム）を利用し機能を集約することでシステム導入時の煩雑さを軽減した。同意システムへのアクセス方法にQRコードを用いることでメールアドレスのキー入力困難を排除できた。

【考察】
解決すべき課題を全て解決し、目的とするe-Consentシステムが構築できた。また、2023年3月に e-Consentガイドラインが発出されたが、我々のシステムは準拠できていることを確認した。
REDCap導入施設であれば、本システムを容易に実装可能であり、当院で開発したシステムを横展開することで、多くの施設でリモートeConsentを実装できる。

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪市   Country：Japan  

【背景・目的】
医療技術実用化総合促進事業では令和4-５年度と模擬治験を通して臨床研究中核病院医おけるDCTの運用整備を進めてきた。この間、オンライン診療の適切な実施に関する指針（厚労省）の改訂、FDAのDCTに関するドラフトガイダンス発表、オンライン診療におけるコロナ特例措置の終了などがあったが、このような行政・規制当局の動向への対応も重要である。また、DCTにおいても医師主導治験ではオンライン診療に対する保険請求が発生するため、決済手段の検討も必要となる。本事業では各臨床研究中核病院がそれぞれの実情に合わせて整備を行うが、全体の状況を把握するために調査を実施した。

【方法】
各病院の医療情報部門・あるいはAROのメンバーから構成されるワーキンググループを立ち上げ、アンケート調査を実施した。

【結果】
令和5年11月時点において、すべての臨床研究中核病院がDCT模擬治験を実施するためのオンライン診療システムを整備した。オンライン診療に特化したシステム（治験特化型・保険診療用）を利用する施設が約半数、残りは汎用web会議システムを利用する。また、診療費用の決済手段としてオンライン決済を検討する施設は２つのみであった。

【考察】
FDAのドラフトガイダンスでは、「ビデオインタラクションを、治験関係者と治験参加者の間のライブの情報交換とみなすため、電子記録とはみなされず、したがって21 CFR part 11の対象とはならない」と記載された。そのため、DCTではオンライン診療専用システムを必要としない可能性もあるが、専用システムには簡便さなどのメリットもあることから、今後も調査を継続したい。

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪市   Country：Japan  

【背景・目的】
医療技術実用化総合促進事業では令和4-５年度と模擬治験を通して臨床研究中核病院医おける分散型臨床試験（DCT）の運用整備を進めてきた。治験薬配送はDCTの重要な要素となるが、令和4年度では新型コロナ感染症に対する治療薬を念頭に整備を検討した時、治験実施施設から被験者宅に配送を行うとなると配送による服薬開始の遅れが感染症急性期には重症化リスクを高めかねず、DCTの要素として採用しなかった。令和5年度は、緩徐に進行する希少疾患（筋萎縮性側索硬化症、以後ALS）を念頭に治験薬配送を検討することとした。医師主導治験では競争的資金が潤沢とは言えず、金銭的コストが課題となるため、治験薬配送コストのシミュレーションを行った。
【方法】
目標症例数は150名。株式会社ウェルネスが公開する二次医療圏サマリーデータを利用した。人口統計は令和2年国勢調査人口等基本集計が出典となる。発症率を1.8/10万人・年とした。

【結果】
ALSの新規発症者は年間で約2300名。過疎地域の患者の医療機関へのアクセス不良を再現するために、各二次医療圏の人口を10で除して小数点以下を切り捨てたものをサイトベースの被験者局在マップ、各二次医療圏の人口を５で除して切り捨てたものをDCTベースの局在マップ、と想定した。組入スピードは、1.5年から0.5年に短縮することができた。治験薬配送費用は5000万円以上となった。
【考察】
DCTはエンロールメント期間の短縮が期待される一方で治験薬配送、訪問看護師のコストが発生する。今回はシミュレーションであったが、実際のDCTでのエビデンスの蓄積が待たれる。

Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：大阪市   Country：Japan  

分散型臨床試験（DCT）実施に係るIRBの審査において、IRBごとに要求する文書等が異なることが懸念される。特に、GCP第32条（治験審査委員会の責務）ガイダンスで示される文書のうち、「その他必要な文書」あるいは「その他治験審査委員会が必要と認める資料」とされる審査資料等の範囲が問題となることがある。
そこで、演者らは、日本医療研究開発機構（AMED）医療技術実用化総合促進事業DCTの取組みの一環で、各拠点のIRB関係者を対象に、上記の審査資料等について調査を行った。
本調査にあたっては、DCTの要素として考えられる事項を踏まえ、審査資料等の選択肢として以下を提示することにした。
すなわち、１）eConsent及び遠隔同意取得の実施に関する手順書、２）eConsentシステム操作説明資料、３）治験の費用負担に係る説明資料/被験者への支払いに関する資料、４）DCT体制に関する資料、５）被験者の募集手順に関する資料、６）オンライン診療システム操作説明資料、７）治験におけるオンライン診療実施に係る手順書、８）ePRO入力操作説明資料、９）サテライト医療機関における協力者リスト、10）訪問看護師への委託に係る業務手順書、11）訪問看護における協力者リスト、12）eClinRO（電子的医療者評価アウトカム）に関する資料、である。
本調査では、併せて上記の審査資料等に関する意見も収集した。
その結果、各拠点のDCTに関する審査資料等の考え方の概要について推察することができた。本発表ではこれらの結果からDCTに係るIRB審査の課題について考察を行うとともに、今後のIRB審査のあり方について展望してみたい。

Event date： 2024.3

Language：Japanese  

Venue：大阪市   Country：Japan  

【背景・目的】
医療技術実用化総合促進事業では2022-23年度と模擬治験を通してDCTの運用整備を進めてきた。2022年度は、リモートeConsentシステムをREDCapと連携し実現した（第14回学術集会にて報告）。しかし、(1) 汎用性を考慮すると署名の対象者を被験者、代諾者だけでなく、代筆者、立会人にも応する必要があり、(2)説明文書のバージョン管理が必要、(3)被験者による同意書の受領確認が必要、(4) 施設間のシステム展開が煩雑、(5)今年度の模擬治験は対象疾患を筋萎縮性側索硬化症（ALS）としたためデバイス操作に細かい作業を被験者候補にさせることができないといった課題があった。
上記の課題を踏まえて、今年度新たにシステム構築を行った。

【方法・結果】
代筆者、立会人の署名に対応した。説明文書のバージョン管理を行った。同意書の被験者受領確認を行うために同意書のダウンロード日時を記録した。docker（コンテナ型仮想化システム）を利用し機能を集約することでシステム導入時の煩雑さを軽減した。同意システムへのアクセス方法にQRコードを用いることでメールアドレスのキー入力困難を排除できた。

【考察】
解決すべき課題を全て解決し、目的とするe-Consentシステムが構築できた。また、2023年3月に e-Consentガイドラインが発出されたが、我々のシステムは準拠できていることを確認した。
REDCap導入施設であれば、本システムを容易に実装可能であり、当院で開発したシステムを横展開することで、多くの施設でリモートeConsentを実装できる。

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Event date： 2024.3

Language：Japanese  

Venue：大阪市   Country：Japan  

【背景・目的】
医療技術実用化総合促進事業では令和4-５年度と模擬治験を通して臨床研究中核病院医おける分散型臨床試験（DCT）の運用整備を進めてきた。治験薬配送はDCTの重要な要素となるが、令和4年度では新型コロナ感染症に対する治療薬を念頭に整備を検討した時、治験実施施設から被験者宅に配送を行うとなると配送による服薬開始の遅れが感染症急性期には重症化リスクを高めかねず、DCTの要素として採用しなかった。令和5年度は、緩徐に進行する希少疾患（筋萎縮性側索硬化症、以後ALS）を念頭に治験薬配送を検討することとした。医師主導治験では競争的資金が潤沢とは言えず、金銭的コストが課題となるため、治験薬配送コストのシミュレーションを行った。
【方法】
目標症例数は150名。株式会社ウェルネスが公開する二次医療圏サマリーデータを利用した。人口統計は令和2年国勢調査人口等基本集計が出典となる。発症率を1.8/10万人・年とした。

【結果】
ALSの新規発症者は年間で約2300名。過疎地域の患者の医療機関へのアクセス不良を再現するために、各二次医療圏の人口を10で除して小数点以下を切り捨てたものをサイトベースの被験者局在マップ、各二次医療圏の人口を５で除して切り捨てたものをDCTベースの局在マップ、と想定した。組入スピードは、1.5年から0.5年に短縮することができた。治験薬配送費用は5000万円以上となった。
【考察】
DCTはエンロールメント期間の短縮が期待される一方で治験薬配送、訪問看護師のコストが発生する。今回はシミュレーションであったが、実際のDCTでのエビデンスの蓄積が待たれる。

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Event date： 2024.3

Language：Japanese  

Venue：大阪市   Country：Japan  

【背景・目的】
統一書式とは治験を実施するに当たり治験依頼者と医療機関の間でやり取りされる厚労省が定めた書式で、書式４はIRBに対する治験審査依頼、書式５はIRBでの審議結果を記した治験審査結果通知書である。
当院では、HOPE-GX内のHOPE-NMGCP（Fujitsu、以後治験管理システム）に登録した治験管理基本データを依頼者コミュニケーションシステム（Fujitsu）が臨床試験・治験支援システムCT-Portal（ファーマメディカルソリューションズ株式会社）に転送し、CT-Portalが統一書式４、５を生成していた。
依頼者コミュニケーションシステムのサーバの耐用年数が過ぎてリプレースが必要となったタイミングで、治験管理システムから直接、書式４，５を統一書式作成システムを内製化した。

【方法・結果】
IRB準備時やIRB中の関係者のタスクを洗い出して、フロー図に起こし、要求される機能を明確にした。治験管理基本データは複数のCSVファイルがZIPファイルとなってメールで1日1回出力されるため、これをデータベースに登録した。出力ファイルは、将来の電磁化を考慮しPDFファイルで作成することとした。
電子カルテの治験管理基本データと連携し書式４、５を円滑に作成するシステムが内製で構築できた。
依頼者コミュニケーションのリプレース費用・維持のためのライセンス費用や臨床試験・治験支援システムの保守費用を削減することができた。

【考察】
今回、書式４，５をPDF形式で作成・保存する構成としたことにより、従来の紙保存が不要となり、紙文書の保管スペースの削減も含めて治験の電磁化に大きく貢献した。

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Event date： 2024.3

Language：Japanese  

Venue：大阪市   Country：Japan  

【背景・目的】
医療技術実用化総合促進事業では令和4-５年度と模擬治験を通して臨床研究中核病院医おけるDCTの運用整備を進めてきた。この間、オンライン診療の適切な実施に関する指針（厚労省）の改訂、FDAのDCTに関するドラフトガイダンス発表、オンライン診療におけるコロナ特例措置の終了などがあったが、このような行政・規制当局の動向への対応も重要である。また、DCTにおいても医師主導治験ではオンライン診療に対する保険請求が発生するため、決済手段の検討も必要となる。本事業では各臨床研究中核病院がそれぞれの実情に合わせて整備を行うが、全体の状況を把握するために調査を実施した。

【方法】
各病院の医療情報部門・あるいはAROのメンバーから構成されるワーキンググループを立ち上げ、アンケート調査を実施した。

【結果】
令和5年11月時点において、すべての臨床研究中核病院がDCT模擬治験を実施するためのオンライン診療システムを整備した。オンライン診療に特化したシステム（治験特化型・保険診療用）を利用する施設が約半数、残りは汎用web会議システムを利用する。また、診療費用の決済手段としてオンライン決済を検討する施設は２つのみであった。

【考察】
FDAのドラフトガイダンスでは、「ビデオインタラクションを、治験関係者と治験参加者の間のライブの情報交換とみなすため、電子記録とはみなされず、したがって21 CFR part 11の対象とはならない」と記載された。そのため、DCTではオンライン診療専用システムを必要としない可能性もあるが、専用システムには簡便さなどのメリットもあることから、今後も調査を継続したい。

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Event date： 2024.3

Language：Japanese  

Venue：大阪市   Country：Japan  

(背景)
我々はアカデミア向けEDC「REDCap」を利用し臨床研究の支援を行っている。医療技術実⽤化総合促進事業DCTの取組みで、体制整備のための模擬治験を行う際、治験実施施設外の医療者が診療範囲内の医療行為の結果を電子的医療者評価アウトカム(eClinRO)として報告するため、REDCap Mobile App(以下、Mobile App)をeClinROシステムとして使用した。Mobile Appの設定及び運用について検討結果を報告する。

(方法)
治験実施施設と治験実施施設外の医療提供施設は1対nの関係があるためデータへの複雑なアクセス管理を考慮した上で、模擬治験のデータフローに沿い仕様を確定した。

(結果)
当センターでREDCapの模擬治験プロジェクト(以下、PJ)に医療提供施設責任者を紐付けた。医療提供施設責任者はPJで発行されたQRコードを介してMobile Appインストール済みデバイスにデータ登録する準備を行った。医療提供者はMobile Appにデータ登録し(オフライン可)、オンライン環境でデータ送信操作をしてPJに反映できた。また医療提供者は同じ医療提供施設の所属者から登録されたデータのみをPJで確認できた。

(考察)
Mobile Appを使用することで通信環境があれば治験実施施設と医療提供施設間のデータがリアルタイムでEDCに反映される。ただしMobile App特有の課題も明らかになったためバージョンアップにより改善を期待する。なお当日はePROシステムとして利用した「MyCap」の設定及び運用についても報告する。

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Event date： 2024.3

Language：Japanese  

Venue：大阪市   Country：Japan  

【背景】
我々はアカデミア向けEDC「REDCap」の国内展開を推進している。医療技術実用化総合促進事業DCTの取組みでは、体制整備のための模擬治験を行うが、我々はREDCapファミリーのePROソフトである「MyCap（以下旧MyCap）」を利用した。旧MyCapは国内での使用報告はほとんどなかったが、模擬治験を通して９件の課題が抽出できた。大規模DCT（複数実施施設）特有の課題も抽出できた。新バージョンのMyCap（以下新MyCap）では機能も進化／改善されており、新MyCapの改善内容の確認に加えて、大規模DCT（複数実施施設）の際に対応に関しても検証した。

【方法】
1)模擬治験時の旧MyCapの課題を抽出。2)開発中の新MyCap用最新REDCapサーバを新たに構築。3)模擬治験と同じ要件で新MyCapを構築し新旧を比較。4)改善点・残存課題を抽出きた。

【結果】
Visitに対応して柔軟な入力日指定が可能になった。スマートフォンOSの違いによる動きの違いが改善した。しかし、旧MyCapの課題9件のうち4件が残存していた。また、旧MyMacではなかった不具合も発生した。大規模DCTで必要な複雑なアクセス制限管理は改善されていなかった。

【考察】
開発中の新MyCapでも機能を考慮してデザインすれば運用に耐えるePROであることが確認できた。大規模DCTで必要な複雑なアクセス制限管理は、新MyCap単独では出来なかったが、我々が新たな手法を開発し対応できた。アプリ初期メニューの日本語化や機能改善の為、今後も積極的なVanderbilt大学への働きかけが必要と考えられた。

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Event date： 2024.3

Language：Japanese  

Venue：大阪市   Country：Japan  

分散型臨床試験（DCT）実施に係るIRBの審査において、IRBごとに要求する文書等が異なることが懸念される。特に、GCP第32条（治験審査委員会の責務）ガイダンスで示される文書のうち、「その他必要な文書」あるいは「その他治験審査委員会が必要と認める資料」とされる審査資料等の範囲が問題となることがある。
そこで、演者らは、日本医療研究開発機構（AMED）医療技術実用化総合促進事業DCTの取組みの一環で、各拠点のIRB関係者を対象に、上記の審査資料等について調査を行った。
本調査にあたっては、DCTの要素として考えられる事項を踏まえ、審査資料等の選択肢として以下を提示することにした。
すなわち、１）eConsent及び遠隔同意取得の実施に関する手順書、２）eConsentシステム操作説明資料、３）治験の費用負担に係る説明資料/被験者への支払いに関する資料、４）DCT体制に関する資料、５）被験者の募集手順に関する資料、６）オンライン診療システム操作説明資料、７）治験におけるオンライン診療実施に係る手順書、８）ePRO入力操作説明資料、９）サテライト医療機関における協力者リスト、10）訪問看護師への委託に係る業務手順書、11）訪問看護における協力者リスト、12）eClinRO（電子的医療者評価アウトカム）に関する資料、である。
本調査では、併せて上記の審査資料等に関する意見も収集した。
その結果、各拠点のDCTに関する審査資料等の考え方の概要について推察することができた。本発表ではこれらの結果からDCTに係るIRB審査の課題について考察を行うとともに、今後のIRB審査のあり方について展望してみたい。

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Event date： 2024.3

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：横浜市   Country：Japan  

Event date： 2023.2

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Venue：石川県金沢市   Country：Japan  

Event date： 2023.2

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Venue：石川県金沢市   Country：Japan  

Event date： 2023.2

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Venue：石川県金沢市   Country：Japan  

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Event date： 2023.2

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Venue：石川県金沢市   Country：Japan  

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Event date： 2022.9

Language：Japanese   Presentation type：Oral presentation (general)  

Venue：千葉県柏市   Country：Japan  

Event date： 2022.9

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Venue：千葉県柏市   Country：Japan  

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Event date： 2022.3

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Venue：大阪   Country：Japan  

Event date： 2022.3

Venue：大阪   Country：Japan  

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Event date： 2022.3

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Venue：横浜   Country：Japan  

Event date： 2022.3

Venue：横浜   Country：Japan  

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Event date： 2021.2

Language：Others   Presentation type：Oral presentation (general)  

Venue：web   Country：Japan  

Event date： 2021.2

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Venue：web   Country：Japan  

Event date： 2021.2

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Venue：web   Country：Japan  

Event date： 2021.2

Language：Others   Presentation type：Oral presentation (general)  

Venue：web   Country：Japan  

Event date： 2021.2

Language：Others   Presentation type：Oral presentation (general)  

Venue：web   Country：Japan  

Event date： 2021.2

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Venue：web   Country：Japan  

Event date： 2021.2

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Venue：web   Country：Japan  

Event date： 2021.2

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Venue：web   Country：Japan  

Event date： 2021.2

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Venue：web   Country：Japan  

Event date： 2021.2

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Venue：web   Country：Japan  

Event date： 2021.1

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Venue：秋田   Country：Japan  

Event date： 2021.1

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Venue：秋田   Country：Japan  

Event date： 2020.11

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Venue：浜松   Country：Japan  

Event date： 2020.11

Language：Others   Presentation type：Symposium, workshop panel (public)  

Venue：浜松   Country：Japan  

Event date： 2020.11

Language：Others   Presentation type：Symposium, workshop panel (public)  

Venue：浜松   Country：Japan  

Event date： 2020.11

Language：Others   Presentation type：Oral presentation (general)  

Venue：浜松   Country：Japan  

Event date： 2020.11

Language：Others   Presentation type：Oral presentation (general)  

Venue：浜松   Country：Japan  

Event date： 2020.11

Language：Others   Presentation type：Symposium, workshop panel (public)  

Venue：浜松   Country：Japan  

Event date： 2020.11

Language：Others   Presentation type：Symposium, workshop panel (public)  

Venue：浜松   Country：Japan  

Event date： 2020.11

Language：Others   Presentation type：Oral presentation (general)  

Venue：浜松   Country：Japan  

Event date： 2020.10

Language：Others   Presentation type：Oral presentation (general)  

Venue：web   Country：Japan  

Event date： 2020.10

Language：Others   Presentation type：Oral presentation (general)  

Venue：web   Country：Japan  

Event date： 2020.8 - 2020.9

Language：Others   Presentation type：Oral presentation (general)  

Venue：web   Country：Netherlands  

Event date： 2020.8 - 2020.9

Language：Others   Presentation type：Oral presentation (general)  

Venue：web   Country：Netherlands  

Event date： 2010.12

Language：Others   Presentation type：Oral presentation (general)  

Venue：東京   Country：Japan  

Language：Japanese  

Language：Japanese  

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慢性腎臓病(CKD)の進展抑制に降圧薬は重要である。臨床研究中核病院の診療データを用いたリアルワールドデータ研究として、降圧薬の種類による電解質異常の実態を記述した。各機関に2018年4月から2年間通院または入院したCKD患者26,306名を対象とした。全患者の平均eGFRは48.5ml/min/1.73m2であり、そのうち7,448名(28%)で降圧薬を処方されていた。高カリウム(K)血症(≧130mEq/L)の発症率(95%信頼区間)は11.4(11.2-11.7)、4.23(4.06-4.41)/100人年であった。ミネラルコルチコイド受容体拮抗薬(MRA)は高K血症、低Na血症のリスクが有意に上昇した。MRAを処方された患者の高K血症はeGFRが45-60ml/min/1.73m2で特に顕著であった。MRAと高K血症の関連が腎機能に応じて異なること、そして低Na血症と関連することが、今回の我々のリアルワールドデータ解析によって新たに明らかとなった。(著者抄録)

Language：Japanese  

Language：Japanese  

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Language：English  

Language：Japanese   Publisher：(一社)日本医療情報学会  

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Language：Japanese   Publisher：(一社)日本医療情報学会  

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Language：Japanese  

Language：Japanese   Publisher：(一社)日本医療情報学会  

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Language：Japanese  

Language：Japanese   Publisher：(一社)日本糖尿病学会  

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：Japanese  

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DOI： 10.11272/jssabst.41.0_s123_2

Language：Japanese  

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A Novel Bioabsorbable Polymeric Nanoparticle Drug or Gene Eluting Stent developed using Electro-Deposit Nanoparticle-Coating Technology

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：Japanese