Clinical outcomes with high-intensity statins according to atherothrombotic risk stratification after acute myocardial infarction: The FAST-MI registries.
- 作者列表："Desjobert E","Tea V","Schiele F","Ferrières J","Simon T","Danchin N","Puymirat E","FAST-MI investigators.
BACKGROUND:Current guidelines strongly recommend high-intensity statin therapy after acute myocardial infarction. AIMS:To analyse the relationship between prescription of high-intensity statin therapy at discharge and long-term clinical outcomes according to risk level defined by the Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention (TRS-2P) after acute myocardial infarction. METHODS:We used data from the FAST-MI 2005 and 2010 registries - two nationwide French surveys including 7839 consecutive patients with acute myocardial infarction. Level of risk was stratified in three groups using the TRS-2P score: Group 1 (low risk; TRS-2P=0-1); Group 2 (intermediate risk; TRS-2P=2); and Group 3 (high risk; TRS-2P≥3). RESULTS:Among the 7348 patients discharged alive with a TRS-2P available, high-intensity statin therapy was used in 41.3% in Group 1, 31.3% in Group 2 and 18.5% in Group 3. After multivariable adjustment, high-intensity statin therapy was associated with a non-significant decrease in major adverse cardiovascular events (death, stroke or recurrent myocardial infarction) at 5 years in the overall population compared with that in patients receiving intermediate- or low-intensity statins or without a statin prescription (14.3% vs 29.6%; hazard ratio 0.94, 95% confidence interval 0.81-1.09; P=0.42). In absolute terms, the decrease in major adverse cardiovascular events was positively correlated with risk level (Group 1: 8.1% vs 10.7%; Group 2: 14.8% vs 21.6%; Group 3: 30.8% vs 51.6%). However, after adjustment, the benefits of high-intensity statin therapy were associated with lower mortality only in high-risk patients (hazard ratio 0.79, 95% confidence interval 0.64-0.97; P=0.02). CONCLUSIONS:High-intensity statin therapy at discharge after acute myocardial infarction was associated in absolute terms with fewer major adverse cardiovascular events at 5 years, regardless of atherothrombotic risk stratification, although the highest absolute reduction was found in the high-risk TRS-2P class.
背景: 目前的指南强烈推荐急性心肌梗死后高强度他汀治疗。 目的: 根据急性心肌梗死后二级预防溶栓风险评分 (TRS-2P) 定义的风险水平，分析出院时高强度他汀治疗处方与长期临床结局的关系。 方法: 我们使用了来自FAST-MI 2005和2010登记系统的数据 -- 两项法国全国范围的调查，包括7839名连续的急性心肌梗死患者。使用TRS-2P评分对三组的风险水平进行分层: 组1 (低风险; TRS-2P = 0-1); 组2 (中等风险; TRS-2P = 2); 组3 (高风险; TRS-2P ≥ 3). 结果: 在7348例存活出院的TRS-2P患者中，高强度他汀类药物治疗在组1为41.3%，组2为31.3%，组3为18.5%。经过多变量调整后，高强度他汀类药物治疗与主要不良心血管事件 (死亡，卒中或复发性心肌梗死) 的非显著降低相关与接受中等或低强度他汀类药物或未接受他汀类药物处方的患者相比，总体人群5年时 (14.3% vs 29.6%; 风险比0.94，95% 置信区间0.81-1.09; P = 0.42)。就绝对值而言，主要不良心血管事件的减少与风险水平呈正相关 (组1: 8.1% vs 10.7%; 组2: 14.8% vs 21.6%; 组3: 30.8% vs 51.6%)。然而，经过调整后，高强度他汀类药物治疗的益处仅与高危患者较低的死亡率相关 (风险比0.79，95% 置信区间0.64-0.97; P = 0.02)。 结论: 急性心肌梗死后出院时高强度他汀类药物治疗与5年主要不良心血管事件较少相关，无论动脉粥样硬化血栓形成风险分层如何，尽管在高风险TRS-2P级中发现绝对降幅最高。
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.
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.
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.