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Respiratory dysfunction in old mice could be related to inflammation and lung fibrosis induced by hyperphosphatemia. 老龄小鼠的呼吸功能障碍可能与高磷血症诱发的炎症和肺纤维化有关。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-08-18 DOI: 10.1111/eci.14302
Ana Asenjo-Bueno, Elena Alcalde-Estévez, Gemma Olmos, Patricia Martínez-Miguel, María Piedad Ruiz-Torres, Susana López-Ongil

Background: With age, lungs undergo typical changes that lead to a deterioration of respiratory function. Our aim was to assess the role of age-associated hyperphosphatemia in these changes.

Methods: We used C57BL6 mice to study an ageing model in vivo and human lung fibroblasts were treated with a phosphate donor, beta-glycerophosphate (BGP), to explore mechanisms involved. Respiratory function was registered with a double chamber plethysmograph. Lung structure was analysed by different staining, phosphate and cytokines levels by colorimeric kits, expression of fibrosis, inflammation and ET-1 system by western blot or RT-PCR.

Results: Old mice showed hyperphosphatemia, along with lung fibrosis, loss of elastin, increased expression of pro-inflammatory cytokines and impaired respiratory function. BGP induced inflammation and fibrosis in fibroblasts through the activation and binding of NFkB to the MCP-1 or FN promoters. BGP increased ECE-1 expression by inducing NFkB binding to the ECE-1 promoter. QNZ, an NFkB inhibitor, blocked these effects. When ECE-1 was inhibited with phosphoramidon, BGP-induced inflammation and fibrosis were significantly reduced, suggesting a role for ET-1 in BGP-mediated effects.ET-1 produced effects similar to those of BGP, which were also dependent on NFkB. To study the pathophysiological relevance of hyperphosphatemia in vivo, a low-P diet was administered to a group of old animals, showing an improvement in fibrosis, inflammation and respiratory function compared to old mice on a standard diet.

Conclusion: These results suggest that age-related hyperphosphatemia induces inflammation, fibrosis, and impaired respiratory function in old mice; these effects appear to be mediated by ET-1 and NFkB activation.

背景:随着年龄的增长,肺部会发生典型的变化,导致呼吸功能衰退。我们的目的是评估与年龄相关的高磷血症在这些变化中的作用:方法:我们使用 C57BL6 小鼠研究体内老化模型,并用磷酸盐供体--β-甘油磷酸酯(BGP)处理人肺成纤维细胞,以探索相关机制。呼吸功能由双腔式胸透仪记录。用不同的染色法分析肺部结构,用比色试剂盒分析磷酸盐和细胞因子水平,用 Western 印迹或 RT-PCR 分析纤维化、炎症和 ET-1 系统的表达:结果:老龄小鼠表现为高磷血症、肺纤维化、弹性蛋白丧失、促炎细胞因子表达增加和呼吸功能受损。BGP 通过激活 NFkB 并使其与 MCP-1 或 FN 启动子结合,诱导成纤维细胞发生炎症和纤维化。BGP 通过诱导 NFkB 与 ECE-1 启动子结合,增加了 ECE-1 的表达。NFkB抑制剂QNZ阻断了这些作用。当用磷酰氨抑制 ECE-1 时,BGP 诱导的炎症和纤维化明显减轻,这表明 ET-1 在 BGP 介导的效应中发挥作用。ET-1 产生的效应与 BGP 相似,也依赖于 NFkB。为了研究高磷血症在体内的病理生理相关性,给一组老年动物喂食低磷饮食,结果显示,与食用标准饮食的老年小鼠相比,纤维化、炎症和呼吸功能均有所改善:这些结果表明,与年龄相关的高磷血症会诱发老年小鼠的炎症、纤维化和呼吸功能受损;这些影响似乎是由 ET-1 和 NFkB 激活介导的。
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引用次数: 0
Triglyceride-glycaemic index: Insights into predicting fetal macrosomia and its interaction with gestational diabetes mellitus: A cohort study of Chinese pregnant women. 甘油三酯-血糖指数:预测胎儿巨大儿及其与妊娠糖尿病相互作用的见解:一项针对中国孕妇的队列研究。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-08-13 DOI: 10.1111/eci.14300
Dan Zhao, Sanbao Chai, Ning Yuan, Jianbin Sun, Xin Zhao, Xiaomei Zhang

Objective: This study investigates the association between a new insulin resistance indicator, the triglyceride-glucose (TyG) index, and the risk of macrosomia.

Design: This is a prospective cohort study.

Methods: This study included 1332 women who delivered at Peking University International Hospital between October 2017 and August 2019. Participants were divided equally into three groups based on the TyG index. Logistic regression and restricted cubic spline (RCS) analyses were used to evaluate the relationship between the TyG index and macrosomia and conducted subgroup analyses. The TyG index's ability to predict macrosomia was assessed using the receiver operating characteristic (ROC) curve.

Results: Multivariable logistic regression analysis revealed that the TyG index is an independent risk factor for macrosomia (Odds ratio [OR] 1.84, 95% confidence interval [CI] 1.02-3.30, p < .05). RCS analysis indicates that the risk of macrosomia increases with the rise of the TyG index (p for nonlinearity <.001) when the TyG index is >6.53. Subgroup analysis showed a synergistic additive interaction between the TyG index and gestational diabetes mellitus (GDM) of macrosomia. The area under the ROC curve for the predictive model was 0.733 (95% CI 0.684, 0.781), with a sensitivity of 76.4% and specificity of 66.9%. Incorporating the TyG index alongside traditional risk factors notably enhances macrosomia prediction (p < .05).

Conclusions: The TyG index independently predicts macrosomia, and exhibits an additive interaction with GDM in its occurrence. Integrating the TyG index with traditional risk factors improves the prediction of macrosomia.

Trial registry: Clinical trials. gov [NCT02966405].

研究目的本研究探讨了一种新的胰岛素抵抗指标--甘油三酯-葡萄糖(TyG)指数与巨型畸形风险之间的关联:设计:这是一项前瞻性队列研究:本研究纳入了2017年10月至2019年8月期间在北京大学国际医院分娩的1332名产妇。根据 TyG 指数将参与者平均分为三组。采用逻辑回归和限制性立方样条(RCS)分析评估TyG指数与巨畸症之间的关系,并进行亚组分析。使用接收者操作特征曲线(ROC)评估了TyG指数预测巨畸形的能力:多变量逻辑回归分析显示,TyG指数是巨型畸形的独立风险因素(Odds ratio [OR] 1.84,95%置信区间[CI] 1.02-3.30,P 6.53)。亚组分析表明,TyG 指数与妊娠糖尿病(GDM)之间存在协同相加作用。预测模型的 ROC 曲线下面积为 0.733(95% CI 0.684,0.781),灵敏度为 76.4%,特异度为 66.9%。将TyG指数与传统的风险因素结合在一起可显著提高巨型畸形的预测能力(P 结论:TyG指数可独立预测巨型畸形:TyG指数可独立预测巨型畸形,并在巨型畸形的发生中与GDM表现出相加的相互作用。将 TyG 指数与传统的风险因素相结合可提高对巨型畸形的预测能力:临床试验.gov [NCT02966405]。
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引用次数: 0
COVID-19 vaccine adverse events: Evaluating the pathophysiology with an emphasis on sulfur metabolism and endotheliopathy COVID-19 疫苗不良事件:评估病理生理学,重点是硫代谢和内皮病变。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-08-08 DOI: 10.1111/eci.14296
Heidi N. du Preez, Johnson Lin, Glenn E. M. Maguire, Colleen Aldous, Hendrik G. Kruger

In this narrative review, we assess the pathophysiology of severe adverse events that presented after vaccination with DNA and mRNA vaccines against COVID-19. The focus is on the perspective of an undersulfated and degraded glycocalyx, considering its impact on immunomodulation, inflammatory responses, coagulation and oxidative stress. The paper explores various factors that lead to glutathione and inorganic sulfate depletion and their subsequent effect on glycocalyx sulfation and other metabolites, including hormones. Components of COVID-19 vaccines, such as DNA and mRNA material, spike protein antigen and lipid nanoparticles, are involved in possible cytotoxic effects. The common thread connecting these adverse events is endotheliopathy or glycocalyx degradation, caused by depleted glutathione and inorganic sulfate levels, shear stress from circulating nanoparticles, aggregation and formation of protein coronas; leading to imbalanced immune responses and chronic release of pro-inflammatory cytokines, ultimately resulting in oxidative stress and systemic inflammatory response syndrome. By understanding the underlying pathophysiology of severe adverse events, better treatment options can be explored.

在这篇叙述性综述中,我们评估了接种 COVID-19 DNA 和 mRNA 疫苗后出现的严重不良反应的病理生理学。重点是从糖萼硫化不足和降解的角度,考虑其对免疫调节、炎症反应、凝血和氧化应激的影响。论文探讨了导致谷胱甘肽和无机硫酸盐耗竭的各种因素及其对糖萼硫化和其他代谢物(包括激素)的后续影响。COVID-19 疫苗的成分,如 DNA 和 mRNA 材料、尖峰蛋白抗原和脂质纳米颗粒,都参与了可能的细胞毒性效应。连接这些不良事件的共同点是内皮病变或糖萼降解,其原因是谷胱甘肽和无机硫酸盐水平降低、循环纳米粒子产生剪切应力、聚集和形成蛋白质冠状体;导致免疫反应失衡和促炎细胞因子的慢性释放,最终导致氧化应激和全身炎症反应综合征。通过了解严重不良事件的潜在病理生理学,可以探索出更好的治疗方案。
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引用次数: 0
Correction to ‘Prognostic implication of lipidomics in patients with coronary total occlusion undergoing PCI’ 对 "接受 PCI 治疗的冠状动脉全闭塞患者血脂组学的预后意义 "的更正。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-08-08 DOI: 10.1111/eci.14301

Zhou Y, Chen J, Li S, et al. Prognostic implication of lipidomics in patients with coronary total occlusion undergoing PCI. Eur J Clin Invest. 2022;52(11):e13826.

We apologize for this error.

Zhou Y, Chen J, Li S, et al. 脂质组学对接受 PCI 治疗的冠状动脉全闭塞患者的预后影响。Eur J Clin Invest.2022;52(11):e13826.We apologize for this error.
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引用次数: 0
Synovial expression of glucocorticoid receptor parallels fibroblast activation in patients with rheumatoid arthritis. 类风湿性关节炎患者滑膜中糖皮质激素受体的表达与成纤维细胞的活化平行。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-08-06 DOI: 10.1111/eci.14298
Nikolaos I Vlachogiannis, Kleio-Maria Verrou, Maria P Yavropoulou, Maria Tektonidou, George P Chrousos, Petros P Sfikakis

Background: Hypocortisolemia is associated with increased expression of NR3C1 (glucocorticoid receptor, GR) in blood cells. As endogenous cortisol production is decreased in some RA patients, we tested the hypothesis that GR may be aberrantly expressed in rheumatoid synovium.

Methods: We defined the cellular pattern of NR3C1 synovial expression using human and mouse single-cell RNA-sequencing data. Bulk synovial RNA-sequencing data from early (n = 57) or established (n = 94) RA were compared to osteoarthritis (n = 22) and healthy synovium (n = 28).

Results: GR was expressed in all synovial cell types in both human and experimental arthritis. GR synovial expression, as well as 11β-HSD1/11β-HSD2 enzyme ratio, were higher in RA than healthy and osteoarthritic tissue, regardless of disease duration or treatment. Given that GR expression varied across samples, we searched for differences between RA patients with higher versus lower GR expression. Indeed, the synovial transcriptome of RA patients with high versus low GR expression (1st quartile, 30,517 ± 4876 vs. 4th quartile, 19,382 ± 2523 normalized counts) was enriched for proinflammatory gene-sets, including 'inflammatory response', 'IFN-γ response' and 'IL6/JAK/STAT3 signalling'. High synovial GR expression was also associated with increased JAK2 and PTPRK expression, denoting activation of the proinflammatory sublining fibroblasts. In contrast, low GR expression was associated with increased COMP and COL6A2 expression, denoting a resting synovial state.

Conclusions: GR is overexpressed in the synovium of some RA patients in association with proinflammatory gene expression and activated sublining fibroblast status. Further studies should examine whether GR overexpression may act as a compensatory mechanism sensitizing synovial tissue to glucocorticoid action in RA.

背景:低皮质醇血症与NR3C1(糖皮质激素受体,GR)在血细胞中的表达增加有关。由于部分类风湿关节炎患者的内源性皮质醇分泌减少,我们测试了类风湿滑膜中 GR 可能异常表达的假设:方法:我们利用人类和小鼠单细胞 RNA 序列数据确定了 NR3C1 滑膜表达的细胞模式。将早期(n = 57)或已确诊(n = 94)RA 的大量滑膜 RNA 序列数据与骨关节炎(n = 22)和健康滑膜(n = 28)进行比较:结果:GR在人类和实验性关节炎的所有滑膜细胞类型中均有表达。无论病程长短或治疗方法如何,GR滑膜表达以及11β-HSD1/11β-HSD2酶比率在RA中均高于健康组织和骨关节炎组织。鉴于不同样本的 GR 表达不同,我们寻找 GR 表达较高和较低的 RA 患者之间的差异。事实上,GR表达量高与低的RA患者的滑膜转录组(第1四分位数,30517 ± 4876 vs. 第4四分位数,19382 ± 2523归一化计数)富含促炎基因组,包括 "炎症反应"、"IFN-γ反应 "和 "IL6/JAK/STAT3信号"。滑膜 GR 的高表达还与 JAK2 和 PTPRK 表达的增加有关,这表明促炎性下层成纤维细胞被激活。相反,GR的低表达与COMP和COL6A2的表达增加有关,表示滑膜处于静止状态:结论:GR在一些RA患者的滑膜中过度表达,这与促炎基因表达和激活的下层成纤维细胞状态有关。进一步的研究应探讨 GR 的过度表达是否可作为一种代偿机制,使 RA 患者的滑膜组织对糖皮质激素的作用敏感。
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引用次数: 0
Impact of prior oral anticoagulation therapies on post-discharge outcomes after COVID-19: Results from a global federated health network analysis. 先前口服抗凝疗法对 COVID-19 出院后疗效的影响:全球联合医疗网络分析结果。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-08-06 DOI: 10.1111/eci.14299
José Miguel Rivera-Caravaca, Freddy Frost, Francisco Marín, Gregory Y H Lip

Background: The impact of chronic oral anticoagulant (OACs) use on long-term post-discharge outcomes after coronavirus disease 2019 (COVID-19) hospitalisation remains unclear. Herein, we compared clinical outcomes up to 2-years after COVID-19 hospitalisation between patients on vitamin K antagonists (VKAs), direct-acting OACs (DOACs) and no OAC therapy.

Methods: Data from TriNetX, a global federated health research network, were used. Adult patients on VKAs, DOACs or no OAC therapy at diagnosis of COVID-19 between 20 January 2020 and 31 December 2021, who were hospitalised for COVID-19, were included. The primary outcomes were all-cause mortality, ischaemic stroke/transient ischaemic attack (TIA)/systemic embolism (SE) and the composite of intracranial haemorrhage (ICH)/gastrointestinal bleeding, at 2 years after COVID-19 hospitalisation.

Results: We included 110,834 patients with COVID-19. Following propensity score matching (PSM), we identified a decreased mortality risk in DOAC-treated patients compared to the no OAC cohort (RR .808, 95% CI .751-.870). A higher risk of ischaemic stroke/TIA/SE was observed in VKA users compared to DOAC users (RR 1.100, 95% CI 1.020-1.220) and in VKA users compared to patients not taking OAC (RR 1.400, 95% CI 1.140-1.720). VKA use was associated with a greater risk of ICH/gastrointestinal bleeding than DOAC users (RR 1.198, 95% CI 1.066-1.347), while DOAC users had a lower risk compared to no OAC-treated patients (RR .840, 95% CI .754-.936).

Conclusion: COVID-19 patients taking prior DOACs were associated with lower long-term mortality risk and ICH/gastrointestinal bleeding than patients not taking OAC. Compared to patients on DOACs, VKA users were associated with higher risks of mortality, ischaemic stroke/TIA/SE and ICH/gastrointestinal bleeding.

背景:慢性口服抗凝剂(OACs)的使用对2019年冠状病毒病(COVID-19)住院后出院后长期预后的影响仍不清楚。在此,我们比较了接受维生素K拮抗剂(VKA)、直接作用口服抗凝剂(DOAC)治疗和未接受OAC治疗的患者在COVID-19住院后长达2年的临床预后:方法:使用全球联合健康研究网络 TriNetX 的数据。纳入了 2020 年 1 月 20 日至 2021 年 12 月 31 日期间确诊 COVID-19 时正在使用 VKA、DOAC 或无 OAC 治疗的成人患者,这些患者因 COVID-19 住院。主要结果为COVID-19住院2年后的全因死亡率、缺血性卒中/短暂性脑缺血发作(TIA)/系统性栓塞(SE)以及颅内出血(ICH)/消化道出血的综合结果:我们纳入了 110,834 名 COVID-19 患者。经过倾向评分匹配 (PSM),我们发现与不使用 OAC 的队列相比,使用 DOAC 治疗的患者的死亡风险降低(RR .808, 95% CI .751-.870)。与使用 DOAC 的患者相比,使用 VKA 的患者发生缺血性卒中/TIA/SE 的风险更高(RR 1.100,95% CI 1.020-1.220),与未使用 OAC 的患者相比,使用 VKA 的患者发生缺血性卒中/TIA/SE 的风险更高(RR 1.400,95% CI 1.140-1.720)。与使用 DOAC 的患者相比,使用 VKA 的患者发生 ICH/消化道出血的风险更高(RR 1.198,95% CI 1.066-1.347),而与未接受 OAC 治疗的患者相比,使用 DOAC 的患者发生 ICH/消化道出血的风险更低(RR 0.840,95% CI 0.754-0.936):结论:与未服用 OAC 的患者相比,曾服用 DOAC 的 COVID-19 患者的长期死亡风险和 ICH/消化道出血风险较低。与服用 DOACs 的患者相比,VKA 使用者的死亡率、缺血性中风/TIA/SE 和 ICH/消化道出血风险更高。
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引用次数: 0
When less is more: The association between the expression of polymorphic CYPs and AFB1-induced HCC. 少即是多多态 CYPs 的表达与 AFB1 诱导的 HCC 之间的关联。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-08-05 DOI: 10.1111/eci.14297
Asmaa Ashraf Mohamed, Monica Armanious, Rana W Bedair, Nada Sherif Amin, Hend M El Tayebi

Background: An individual's genetic fingerprint is emerging as a pivotal predictor of numerous disease- and treatment-related factors. Single nucleotide polymorphisms (SNPs) in drug-metabolizing enzymes play key roles in an individual's exposure to a malignancy-associated risk, such as Aflatoxin B1 (AFB1)-induced hepatocellular carcinoma (HCC).

Aim: This study aimed at reviewing literature on the polymorphisms that exist in CYP enzymes and their possible link with susceptibility to AFB1-induced HCC.

Materials & methods: A set of keywords associated with the study subject of interest was used to search the Google Scholar and the PubMed database. The last ten years' worth of research projects were included in the results filter. The research involved HCC patients and any connection between polymorphic forms of CYP enzymes and their susceptibility to AFB1-induced HCC, including older but significant data.

Results: Variations in CYP1A2 and CYP3A4 were reported to impact the rate and magnitude of AFB1 bio-activation, thus influencing an individual's vulnerability to develop HCC. In HCC patients, the activity of CYP isoforms varies, where increased activity has been reported with CYP2C9, CYP2D6, and CYP2E1, while CYP1A2, CYP2C8, and CYP2C19 exhibit decreased activity. CYP2D6*10 frequency has been discovered to differ considerably in HCC patients. Rs2740574 (an upstream polymorphism in CYP3A4 as detected in CYP3A4*1B) and rs776746 (which affects CYP3A5 RNA splicing), both of which influence CYP3A expression, thus impacting the variability of AFB1-epoxide adducts in HCC patients.

Discussion: CYP1A2 is the primary enzyme accountable for the formation of harmful AFBO globally. CYP3A4, CYP3A5, CYP3A7, CYP2B7, and CYP3A3 are also implicated in the bio-activation of AFB1 to mutagenic metabolites. It is thought that CYP3A4 is the protein that interacts with AFB1 metabolism the most.

Conclusion: Polymorphic variants of CYP enzymes have a functional impact on the susceptibility to AFB1-induced HCC. Outlining such variation and their implications may provide deeper insights into approaching HCC in a more personalized manner for guiding future risk-assessment, diagnosis, and treatment.

背景:个人的遗传指纹正在成为众多疾病和治疗相关因素的关键预测因子。药物代谢酶中的单核苷酸多态性(SNPs)在个体暴露于恶性肿瘤相关风险(如黄曲霉毒素 B1(AFB1)诱导的肝细胞癌(HCC))中发挥着关键作用:使用一组与研究主题相关的关键词在谷歌学术和 PubMed 数据库中进行搜索。结果筛选包括过去十年的研究项目。研究涉及 HCC 患者及其 CYP 酶多态形式与 AFB1 诱导的 HCC 易感性之间的任何联系,包括较早但重要的数据:结果:据报道,CYP1A2 和 CYP3A4 的变异会影响 AFB1 生物活化的速度和程度,从而影响个人患 HCC 的易感性。在 HCC 患者中,CYP 同工酶的活性各不相同,有报告称 CYP2C9、CYP2D6 和 CYP2E1 的活性增加,而 CYP1A2、CYP2C8 和 CYP2C19 的活性降低。已发现 CYP2D6*10 频率在 HCC 患者中差异很大。Rs2740574(CYP3A4*1B中检测到的CYP3A4上游多态性)和rs776746(影响CYP3A5 RNA剪接)都会影响CYP3A的表达,从而影响HCC患者中AFB1-环氧化物加合物的变化:讨论:CYP1A2 是在全球范围内形成有害 AFBO 的主要酶。CYP3A4、CYP3A5、CYP3A7、CYP2B7 和 CYP3A3 也参与了 AFB1 转化为诱变代谢物的生物活化过程。据认为,CYP3A4 是与 AFB1 代谢相互作用最大的蛋白质:结论:CYP 酶的多态变异对 AFB1 诱导的 HCC 易感性具有功能性影响。概述这种变异及其影响可为以更个性化的方式处理 HCC 提供更深入的见解,从而指导未来的风险评估、诊断和治疗。
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引用次数: 0
Patient autonomy and shared decision-making in the context of clinical trial participation 参与临床试验时的患者自主权和共同决策。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-07-31 DOI: 10.1111/eci.14291
Fabio Dennstädt, Paul Martin Putora, Thomas Iseli, Theresa Treffers, Cédric Panje, Galina Farina Fischer
<div> <section> <h3> Aims</h3> <p>This study aimed to explore how incorporating shared decision-making (SDM) can address recruitment challenges in clinical trials. Specifically, it examines how SDM can align the trial process with patient preferences, enhance patient autonomy and increase active patient participation. Additionally, it identifies potential conflicts between SDM and certain clinical trial aspects, such as randomization or blinding, and proposes solutions to mitigate these issues.</p> </section> <section> <h3> Materials and Methods</h3> <p>We conducted a comprehensive review of existing literature on patient recruitment challenges in clinical trials and the role of SDM in addressing these challenges. We analysed case studies and trial reports to identify common obstacles and assess the effectiveness of SDM in improving patient accrual. Additionally, we evaluated three proposed solutions: adequate trial design, communication skill training and patient decision aids.</p> </section> <section> <h3> Results</h3> <p>Our review indicates that incorporating SDM can significantly enhance patient recruitment by promoting patient autonomy and engagement. SDM encourages physicians to adopt a more open and informative approach, which aligns the trial process with patient preferences and reduces psychological barriers such as fear and mental stress. However, implementing SDM can conflict with elements such as randomization and blinding, potentially complicating trial design and execution.</p> </section> <section> <h3> Discussion</h3> <p>The desire for patient autonomy and active engagement through SDM may clash with traditional clinical trial methodologies. To address these conflicts, we propose three solutions: redesigning trials to better accommodate SDM principles, providing communication skill training for physicians and developing patient decision aids. By focussing on patient wishes and emotions, these solutions can integrate SDM into clinical trials effectively.</p> </section> <section> <h3> Conclusion</h3> <p>Shared decision-making provides a framework that can promote patient recruitment and trial participation by enhancing patient autonomy and engagement. With proper implementation of trial design modifications, communication skill training and patient decision aids, SDM can support rather than hinder clinical trial execution, ultimately contributing to the advancement of evidence-based medicine.</p> </section>
目的:本研究旨在探讨共同决策(SDM)如何解决临床试验中的招募难题。具体来说,它探讨了 SDM 如何使试验过程符合患者的偏好、增强患者的自主性并提高患者的参与积极性。此外,它还指出了 SDM 与随机化或盲法等某些临床试验方面的潜在冲突,并提出了缓解这些问题的解决方案:我们对有关临床试验中患者招募挑战以及 SDM 在应对这些挑战中的作用的现有文献进行了全面回顾。我们分析了案例研究和试验报告,以确定常见的障碍,并评估 SDM 在改善患者招募方面的效果。此外,我们还评估了三种建议的解决方案:充分的试验设计、沟通技巧培训和患者决策辅助工具:我们的研究表明,通过促进患者的自主性和参与度,SDM 可以显著提高患者招募率。SDM 鼓励医生采用更开放、信息更丰富的方法,使试验过程符合患者的偏好,减少恐惧和精神压力等心理障碍。然而,实施 SDM 可能会与随机化和盲法等要素发生冲突,从而可能使试验设计和执行复杂化:讨论:通过 SDM 实现患者自主和积极参与的愿望可能与传统的临床试验方法相冲突。为了解决这些冲突,我们提出了三种解决方案:重新设计试验以更好地适应 SDM 原则、为医生提供沟通技巧培训以及开发患者决策辅助工具。通过关注患者的意愿和情感,这些解决方案可以有效地将 SDM 纳入临床试验:结论:共同决策提供了一个框架,可通过提高患者的自主性和参与度来促进患者招募和试验参与。通过适当实施试验设计修改、沟通技巧培训和患者决策辅助工具,SDM 可以支持而不是阻碍临床试验的执行,最终促进循证医学的发展。
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引用次数: 0
How strong is the evidence supporting the WHO guidelines on physical activity, sedentary behaviour and sleep in early childhood? 支持世界卫生组织关于幼儿期体育活动、久坐行为和睡眠的指导方针的证据有多强?
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-07-31 DOI: 10.1111/eci.14294
Alessandro Bianconi, Matteo Fiore, Enrico Zauli, Cecilia Acuti Martellucci, Annalisa Rosso, Laura Dallolio, Maria Elena Flacco, Lamberto Manzoli

Background: The WHO issued recommendations about the ideal amount of physical activity, sedentary behaviour and sleep in infants, toddlers and preschool children. To facilitate their interpretation and translation into public health policies, we analysed the quantity and quality of the evidence that supported the development of each WHO recommendation.

Methods: All data for each exposure-outcome pair analysed in the studies informing WHO guidelines were extracted, and predefined criteria, based upon GRADE methodology, were used to classify each outcome and study result.

Results: Among the 237 studies that could be included, 37 were experimental and 200 were observational, yielding 920 analyses of exposure-outcome associations. Sixty-two analyses used a relevant outcome, with or without significant results. Five of the 10 WHO recommendations were based upon zero analyses with significant results on relevant health outcomes. The remaining recommendations were mostly based upon analyses evaluating obesity-related outcomes. Eight of the 10 GLs thresholds were not supported by any significant analysis on clinically relevant outcomes.

Conclusion: While these findings should not be interpreted as an attempt to disprove the benefits of healthy lifestyle habits in early childhood, neither to minimize the work of the experts in this complex research field, very limited evidence currently supports the adoption of recommended thresholds as behavioural surveillance and public health interventions targets. Therefore, until further data are available, public health interventions should be developed balancing whether to focus on the achievement of specific targets that are still not supported by high-quality evidence or on the general promotion of healthy behaviours.

背景:世卫组织就婴幼儿和学龄前儿童理想的运动量、久坐行为和睡眠时间提出了建议。为了便于解释这些建议并将其转化为公共卫生政策,我们分析了支持世卫组织制定每项建议的证据的数量和质量:方法:我们提取了为世卫组织指南提供信息的研究中分析的每对暴露-结果的所有数据,并根据 GRADE 方法使用预定义的标准对每种结果和研究结果进行分类:在可纳入的 237 项研究中,37 项为实验性研究,200 项为观察性研究,共对 920 项暴露-结果关联进行了分析。62项分析使用了相关结果,无论结果是否显著。世卫组织的 10 项建议中有 5 项是基于对相关健康结果进行的零项有显著结果的分析。其余建议大多基于对肥胖相关结果的评估分析。在 10 项 GLs 临界值中,有 8 项没有得到任何临床相关结果的重要分析支持:虽然这些研究结果不应被解释为试图否定幼儿期健康生活习惯的益处,也不应贬低这一复杂研究领域专家的工作,但目前支持采用推荐阈值作为行为监测和公共卫生干预目标的证据非常有限。因此,在获得更多数据之前,应平衡制定公共卫生干预措施,是侧重于实现仍未得到高质量证据支持的具体目标,还是侧重于普遍推广健康行为。
{"title":"How strong is the evidence supporting the WHO guidelines on physical activity, sedentary behaviour and sleep in early childhood?","authors":"Alessandro Bianconi, Matteo Fiore, Enrico Zauli, Cecilia Acuti Martellucci, Annalisa Rosso, Laura Dallolio, Maria Elena Flacco, Lamberto Manzoli","doi":"10.1111/eci.14294","DOIUrl":"https://doi.org/10.1111/eci.14294","url":null,"abstract":"<p><strong>Background: </strong>The WHO issued recommendations about the ideal amount of physical activity, sedentary behaviour and sleep in infants, toddlers and preschool children. To facilitate their interpretation and translation into public health policies, we analysed the quantity and quality of the evidence that supported the development of each WHO recommendation.</p><p><strong>Methods: </strong>All data for each exposure-outcome pair analysed in the studies informing WHO guidelines were extracted, and predefined criteria, based upon GRADE methodology, were used to classify each outcome and study result.</p><p><strong>Results: </strong>Among the 237 studies that could be included, 37 were experimental and 200 were observational, yielding 920 analyses of exposure-outcome associations. Sixty-two analyses used a relevant outcome, with or without significant results. Five of the 10 WHO recommendations were based upon zero analyses with significant results on relevant health outcomes. The remaining recommendations were mostly based upon analyses evaluating obesity-related outcomes. Eight of the 10 GLs thresholds were not supported by any significant analysis on clinically relevant outcomes.</p><p><strong>Conclusion: </strong>While these findings should not be interpreted as an attempt to disprove the benefits of healthy lifestyle habits in early childhood, neither to minimize the work of the experts in this complex research field, very limited evidence currently supports the adoption of recommended thresholds as behavioural surveillance and public health interventions targets. Therefore, until further data are available, public health interventions should be developed balancing whether to focus on the achievement of specific targets that are still not supported by high-quality evidence or on the general promotion of healthy behaviours.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The prognostic value of mean platelet volume in patients with coronary artery disease: An updated systematic review with meta-analyses. 冠心病患者平均血小板体积的预后价值:最新系统综述与荟萃分析。
IF 4.4 3区 医学 Q1 MEDICINE, GENERAL & INTERNAL Pub Date : 2024-07-31 DOI: 10.1111/eci.14295
Akhmetzhan Galimzhanov, Han Naung Tun, Yersyn Sabitov, Francesco Perone, Tigen Mustafa Kursat, Erhan Tenekecioglu, Mamas A Mamas

Background: Mean platelet volume (MPV) is a widely available laboratory index, however its prognostic significance in patients with coronary artery disease (CAD) is still unclear. We intended to investigate and pool the evidence on the prognostic utility of admission MPV in predicting clinical outcomes in patients with CAD.

Methods: PubMed, Web of Science, and Scopus were the major databases used for literature search. The risk of bias was assessed using the quality in prognostic factor studies. We used random-effects pairwise analysis with the Knapp and Hartung approach supported further with permutation tests and prediction intervals (PIs).

Results: We identified 52 studies with 47,066 patients. A meta-analysis of nine studies with 14,864 patients demonstrated that one femtoliter increase in MPV values was associated with a rise of 29% in the risk of long-term mortality (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.22-1.37) in CAD as a whole. The results were further supported with PIs, permutation tests and leave-one-out sensitivity analyses. MPV also demonstrated its stable and significant prognostic utility in predicting long-term mortality as a linear variable in patients treated with percutaneous coronary intervention (PCI) and presented with acute coronary syndrome (ACS) (HR 1.29, 95% CI 1.20-1.39, and 1.29, 95% CI 1.19-1.39, respectively).

Conclusion: The meta-analysis found robust evidence on the link between admission MPV and the increased risk of long-term mortality in patients with CAD patients, as well as in patients who underwent PCI and patients presented with ACS.

背景:平均血小板体积(MPV)是一种广泛使用的实验室指标,但其在冠状动脉疾病(CAD)患者中的预后意义仍不明确。我们打算调查并汇集有关入院时平均血小板容积在预测冠状动脉疾病患者临床结局方面的预后作用的证据:方法:PubMed、Web of Science 和 Scopus 是用于文献检索的主要数据库。采用预后因素研究质量评估偏倚风险。我们使用 Knapp 和 Hartung 方法进行随机效应配对分析,并辅以置换检验和预测区间(PIs):我们确定了 52 项研究,涉及 47066 名患者。对9项研究、14,864名患者进行的荟萃分析表明,MPV值每增加1毫升,整个CAD患者的长期死亡风险就会增加29%(危险比[HR]1.29,95%置信区间[CI]1.22-1.37)。PI、置换检验和撇除敏感性分析进一步证实了这一结果。对于接受经皮冠状动脉介入治疗(PCI)和急性冠状动脉综合征(ACS)的患者,MPV 作为线性变量在预测长期死亡率方面也显示出稳定而显著的预后作用(HR 分别为 1.29,95% CI 1.20-1.39 和 1.29,95% CI 1.19-1.39):该荟萃分析发现了强有力的证据,证明入院时的 MPV 与 CAD 患者、接受 PCI 的患者和出现 ACS 的患者长期死亡风险增加之间存在联系。
{"title":"The prognostic value of mean platelet volume in patients with coronary artery disease: An updated systematic review with meta-analyses.","authors":"Akhmetzhan Galimzhanov, Han Naung Tun, Yersyn Sabitov, Francesco Perone, Tigen Mustafa Kursat, Erhan Tenekecioglu, Mamas A Mamas","doi":"10.1111/eci.14295","DOIUrl":"https://doi.org/10.1111/eci.14295","url":null,"abstract":"<p><strong>Background: </strong>Mean platelet volume (MPV) is a widely available laboratory index, however its prognostic significance in patients with coronary artery disease (CAD) is still unclear. We intended to investigate and pool the evidence on the prognostic utility of admission MPV in predicting clinical outcomes in patients with CAD.</p><p><strong>Methods: </strong>PubMed, Web of Science, and Scopus were the major databases used for literature search. The risk of bias was assessed using the quality in prognostic factor studies. We used random-effects pairwise analysis with the Knapp and Hartung approach supported further with permutation tests and prediction intervals (PIs).</p><p><strong>Results: </strong>We identified 52 studies with 47,066 patients. A meta-analysis of nine studies with 14,864 patients demonstrated that one femtoliter increase in MPV values was associated with a rise of 29% in the risk of long-term mortality (hazard ratio [HR] 1.29, 95% confidence interval [CI] 1.22-1.37) in CAD as a whole. The results were further supported with PIs, permutation tests and leave-one-out sensitivity analyses. MPV also demonstrated its stable and significant prognostic utility in predicting long-term mortality as a linear variable in patients treated with percutaneous coronary intervention (PCI) and presented with acute coronary syndrome (ACS) (HR 1.29, 95% CI 1.20-1.39, and 1.29, 95% CI 1.19-1.39, respectively).</p><p><strong>Conclusion: </strong>The meta-analysis found robust evidence on the link between admission MPV and the increased risk of long-term mortality in patients with CAD patients, as well as in patients who underwent PCI and patients presented with ACS.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141855251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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European Journal of Clinical Investigation
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