Novel Trial Design: CHIEF-HF.

新颖的试验设计: 首席-HF。

  • 影响因子:4.83
  • DOI:10.1161/CIRCHEARTFAILURE.120.007767
  • 作者列表:"Spertus JA","Birmingham MC","Butler J","Lingvay I","Lanfear DE","Abbate A","Kosiborod ML","Fawcett C","Burton P","Damaraju CV","Januzzi JL","Whang J
  • 发表时间:2021-03-01

BACKGROUND:The expense of clinical trials mandates new strategies to efficiently generate evidence and test novel therapies. In this context, we designed a decentralized, patient-centered randomized clinical trial leveraging mobile technologies, rather than in-person site visits, to test the efficacy of 12 weeks of canagliflozin for the treatment of heart failure, regardless of ejection fraction or diabetes status, on the reduction of heart failure symptoms. METHODS:One thousand nine hundred patients will be enrolled with a medical record-confirmed diagnosis of heart failure, stratified by reduced (≤40%) or preserved (>40%) ejection fraction and randomized 1:1 to 100 mg daily of canagliflozin or matching placebo. The primary outcome will be the 12-week change in the total symptom score of the Kansas City Cardiomyopathy Questionnaire. Secondary outcomes will be daily step count and other scales of the Kansas City Cardiomyopathy Questionnaire. RESULTS:The trial is currently enrolling, even in the era of the coronavirus disease 2019 (COVID-19) pandemic. CONCLUSIONS:CHIEF-HF (Canagliflozin: Impact on Health Status, Quality of Life and Functional Status in Heart Failure) is deploying a novel model of conducting a decentralized, patient-centered, randomized clinical trial for a new indication for canagliflozin to improve the symptoms of patients with heart failure. It can model a new method for more cost-effectively testing the efficacy of treatments using mobile technologies with patient-reported outcomes as the primary clinical end point of the trial. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04252287.


背景: 临床试验的费用要求新的策略有效地产生证据和测试新的疗法。在这种情况下,我们设计了一项分散的、以患者为中心的随机临床试验,利用移动技术,而不是面对面的现场访问,来测试12周卡格列净治疗心力衰竭 (无论射血分数或糖尿病状态如何) 对心力衰竭症状减轻的疗效. 方法: 纳入900例经病历证实诊断为心力衰竭的患者,按射血分数降低 (≤ 40%) 或保留 (>40%) 分层,随机1:1至100 mg卡格列净或匹配安慰剂。主要结局是堪萨斯城心肌病问卷总症状评分的12周变化。次要结局将是堪萨斯城心肌病问卷的每日步数和其他量表。 结果: 即使在冠状病毒疾病2019 (新型冠状病毒肺炎) 大流行的时代,该试验目前仍在注册。 结论: CHIEF-HF (Canagliflozin: 对心力衰竭患者的健康状况、生活质量和功能状态的影响) 正在采用一种新的模式,即进行一项分散的、以患者为中心的随机临床试验,寻找canagliflozin改善心力衰竭患者症状的新适应症。它可以模拟一种新的方法,以患者报告的结果作为试验的主要临床终点,使用移动技术更经济有效地测试治疗的疗效。注册: URL: https://www.clinicaltrials.gov; 唯一标识符: nct04252287。



作者列表:["Juan-Carlos PM","Perla-Lidia PP","Stephanie-Talia MM","Mónica-Griselda AM","Luz-María TE"]

METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.

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作者列表:["Sawada H","Oeda T","Kohsaka M","Tomita S","Umemura A","Park K","Yamamoto K","Kiyohara K"]

METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.

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作者列表:["Louvrier A","Terranova L","Meyer C","Meyer F","Euvrard E","Kroemer M","Rolin G"]

METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.

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