特许医疗政策下的药械真实世界数据研究常见设计及其关键考虑

博鳌乐城国际医疗旅游先行区是全国唯一的真实世界数据应用试点地区,基于博鳌乐城特许医疗政策,开展真实世界数据研究,形成支持创新药械临床评价和审评审批的真实世界证据,已成为我国药品审评审批制度改革的重要领域,真实世界证据的产生不仅依靠高质量的真实世界数据,还需要合理可靠的研究设计。本文在国内外相关学术研究和监管部门所发布的真实世界数据研究指导原则或规范的基础上,结合博鳌乐城特殊政策环境和前期实践经验,总结了博鳌乐城真实世界数据研究的设计类型,并探讨了各设计类型在博鳌乐城特殊医疗政策环境中的关键考虑,旨在为进一步实施和开展真实世界数据研究提供借鉴。     

Research priorities to increase vaccination coverage in Europe (EU joint action on vaccination)

BackgroundDeciding how best to invest in healthcare is never an easy task and prioritization is therefore an area of great interest for policymakers. Too low public vaccine confidence, which results in insufficient vaccine uptake, remains an area of concern for EU policy-makers. Within the European Joint action on vaccination, a work-package dedicated to research aims to define tools and methods for priority‐setting in the field of vaccination research. We therefore propose a prioritization framework to identify research priorities towards generating and synthesizing evidence to support policies and strategies aiming at increasing vaccine coverage.Materials/methodsWe used a multi-criteria decision analysis (MCDA) method inspired by the Child Health and Nutrition Research Initiative developed by Rudan et al. This quantitative methodology follows a series of steps involving different groups of experts and relevant stakeholders. The first step consists in identifying key research questions through a broad consultation. In parallel, a first group of experts is tasked to select criteria for prioritization of research questions, taking into consideration the ultimate goal of the exercise. Another group of experts is then requested to assess a weight to each of the criteria, using pair-wise comparisons. The final step consists in gathering experts who will assess each research question against the weighted criteria. This evaluation leads to assigning a score to each individual research question, which can then be ranked in order of priority.ResultsWe focused our work on four pre-selected pilot vaccines (pertussis, measles containing combination vaccines, influenza and HPV). The consultation generated 124 questions, which were secondarily sorted and re-worded to obtain 27 questions to be ranked. Criteria for setting priorities were the following: accessibility, answerability, deliverability, disease prevalence/incidence, effectiveness, equity, generalization, and territory. During a final face-to-face meeting international experts ranked the 27 questions and agreed on a consensual list of six top-priorities.ConclusionsWe have developed a transparent, evidence-based rigorous framework to defined key research questions to generate evidence towards the design of policies and strategies to increase vaccine coverage. Results were disseminated broadly and submitted to the EC for potential funding in the context of The Horizon Europe Program. The same process will be conducted in 2021 to identify vaccination research priorities regarding all vaccines used in the EU as well as COVID-19 vaccines.     

The association between decision-making skills and subjective decision outcomes among administrative officers in the Swedish Social Insurance Agency

Social insurance administrative officers’ decision-making skills influence their efficiency at work and their general well-being. At work their tasks are characterised by complexity and a need for order and accountability. Moreover, cases should usually be handled and finalised within the imposed time frames. We investigated skills related to decision-making success among social insurance officers. In total, 118 administrative officers at the Swedish Social Insurance Agency (66% response rate) responded to questions on scales and measures relating to cognitive-rational, socio-emotional and time approach features of decision-making skill. In addition, they responded to questions on three scales pertaining to outcomes of everyday decisions in terms of subjective everyday difficulties, tendencies to burnout and depressive symptoms. The results showed that cognitive-rational competence was associated with lower reports of subjective everyday difficulties and depressive symptoms and thereby contributed to the explained variance in decision outcomes. Furthermore, socio-emotional and time approach features of decision-making skills contributed to the explanation for subjective everyday difficulties, tendencies to burnout and depressive symptoms. The results corroborate the basic assumption and usefulness of a broad approach in the definition and assessment of decision-making skills in human service professions in general, and of administrative officers in social insurance agencies in particular. Recommendations for future research and the implications of the results are discussed.     

基于数据挖掘的低增生性骨髓增生异常综合征与再生障碍性贫血分类模型研究

目的 构建低增生性骨髓增生异常综合征（hypo-MDS）与再生障碍性贫血（AA）鉴别诊断的决策树、贝叶斯、卷积神经网络、改进的支持向量机四种模型并选择出最优模型。方法 收集2010—2019年华北理工大学附属医院的AA与hypo-MDS患者的病例资料,使用统计学方法筛选指标,将处理后的样本以4[DK]∶1随机分为训练集和测试集,构建决策树、贝叶斯、卷积神经网络、改进的支持向量机四种模型,采用五折交叉验证法多次重复验证,通过灵敏度、AUC等指标评价鉴别诊断效果。结果 hypo-MDS患者红细胞、血红蛋白含量等指标低于AA患者,成熟单核细胞比例等指标高于AA患者,年龄和职业分布也存在差异(P＜0.05）;最终选出21个特异性指标。四种模型的分类效果比较:灵敏度分别为82.56%、65.12%、87.21%、79.07%;AUC分别为0.81、0.68、0.82、0.83;准确率分别为75.32%、69.48%、77.27%、74.03%。对卷积神经网络的误判病例分析得出年龄、血成熟淋巴细胞等7个指标均存在差异（P＜0.05）。结论 在决策树、贝叶斯、卷积神经网络、改进的支持向量机四种诊断模型中,卷积神经网络具有最佳分类效果。     

2018年济南市14株柯萨奇病毒A组6型VP1基因特征分析

目的 分析济南市导致手足口病(hand, foot and mouth disease, HFMD)的柯萨奇病毒A组6型(Coxsackievirus A6, CVA6)分离株VP1基因特征及氨基酸变异。方法 2018年济南市HFMD常规监测病例样本经实时荧光RT-PCR检测,随机选择部分CVA6核酸阳性样本进行细胞分离鉴定,扩增阳性分离株VP1基因序列并进行同源性比较、氨基酸变异及系统进化分析。结果 2018年共检测652份样本,其中CVA6核酸阳性率为47.85%（312/652）,远高于人肠道病毒A组71型（human enterovirus A 71, EV71）（7.06%, 46/652）和柯萨奇病毒A组16型(Coxsackievirus A16, CVA16)（8.44%,55/652 ）,为济南市HFMD最主要病原体。通过细胞分离成功获得14株CVA6病毒,经VP1基因系统进化分析显示,济南市CVA6分离株均为基因D5亚型,VP1基因核苷酸及氨基酸序列同源性分别为94.2%~100%和98.0%~100%,与2017年广东株（GenBank 登录号MG385796、MG385815）、广西株（GenBank 登录号MH018512）、云南株（GenBank 登录号LC413143）及2014年江西株（GenBank 登录号KY913482）等亲缘关系较近。VP1蛋白主要存在V174I等位点变异,与国内流行的D5亚型基本一致。结论 2018年CVA6病毒为导致济南HFMD的主要病原,与广东、广西、云南和江西等省分离株亲缘关系较近,属于我国目前流行的基因D5亚型。     

右肺支气管树的三维分形模拟

肺是天然的非对称不规则体。肺内的气管树呈复杂的自相似的结构。基于最小能耗思想 ,作者根据肺的解剖学数据 ,建立右肺的细分网格坐标 ,通过计算各级分块的质心 ,寻找分叉方向与确定分叉长度 ,以 Open GL 为工具 ,实现了右肺支气管树的三维分形模拟 ,并且得到各级的长度、分叉角度和管径的具体参数。所生成的图形在形态与几何参数上与现有统计数据很吻合。计算得到该模型的分形覆盖维数为 2 .19,与其他学者计算的人体肺的理想维数 2 .17[1 ] 比较接近。该模型为今后用分形思想研究肺的气体扩散传递功能奠定基础。从节省计算机存储、加快图形传输上方面来说也有一定意义     

A Model for Transport and Dispersion in the Circulatory System Based on the Vascular Fractal Tree

Materials are distributed throughout the body of mammals by fractal networks of branching tubes. Based on the scaling laws of the fractal structure, the vascular tree is reduced to an equivalent one-dimensional, tube model. A dispersion–convection partial differential equation with constant coefficients describes the heterogeneous concentration profile of an intravascular tracer in the vascular tree. A simple model for the mammalian circulatory system is built in entirely physiological terms consisting of a ring shaped, one-dimensional tube which corresponds to the arterial, venular, and pulmonary trees, successively. The model incorporates the blood flow heterogeneity of the mammalian circulatory system. Model predictions are fitted to published concentration-time data of indocyanine green injected in humans and dogs. Close agreement was found with parameter values within the expected physiological range. © 2003 Biomedical Engineering Society. PAC2003: 8710+e, 8719Hh, 8719Uv     

混合遗传算法在随机规划问题中的应用

以含有机会约束的生产管理动态规划问题为例,基于随机模拟技术的混合遗传算法实现最优化决策,构造了数学模型。采用ＶＢ编辑,计算机模拟结果显示该模型能很好解决生产过程中的最优化决策问题,它是简单的基于二进制编码的遗传算法所不能解决的。该算法具有很高的鲁棒性,避免了在局部最优解附近徘徊,且因为随机规划问题要求许多数学知识,而算法本身并不要求对优化问题的性质作一些深入的数学分析,从而对那些不太熟悉数学理论和     

Definition and pathology of primary sclerosing cholangitis

Although primary sclerosing cholangitis (PSC) is not a common disease, it is important in the differential diagnosis of hepatobiliary tract diseases in clinical practice. A diagnosis of PSC should be made only after the exclusion of similar diseases with well known etiologies or pathogeneses. In this review, the pathology of classical PSC and its variants or related diseases is highlighted. PSC is histologically characterized by progressive periductal fibrosis with luminal stenosis or obliteration, along with the formation of a fibrous core, as well as dilatation (cholangiectasis). Its etiology is unknown. Bacterial ascending cholangitis is superimposed on its long clinical course. Such a heterogeneous distribution of biliary lesions with biliary obliteration and cholangiectasis is responsible for the radiological demonstration of biliary abnormalities, particularly the beaded appearance. Sampling variability is common in needle or wedge biopsied specimens. As a result of biliary damage, the liver shows progressive cholestatic change followed by biliary fibrosis and cirrhosis, and this hepatic progression is divisible into four stages. There are several variants of PSC or related diseases, such as localized biliary sclerosis and stenosis, sclerosing cholangitis associated with inflammatory pseudotumor, and PSC-autoimmune hepatitis overlapping syndrome. Cholelithiasis, including secondary hepatolithiasis and, to a lesser degree, biliary carcinoma and dysplasia, are also known to develop at the perihilar bile ducts as a late complication of PSC. Received for publication on March 8, 1999; accepted on April 30, 1999