Detecting possible vaccine adverse events in clinical notes of the electronic medical record

The Vaccine Safety Datalink (VSD) is a collaboration between the CDC and eight large HMOs to investigate adverse events following immunization through analyses of clinical data. We modified an existing system, called MediClass, that uses natural language processing to identify clinical events recorded in electronic medical records (EMRs). We customized MediClass so it could detect possible vaccine adverse events (VAEs) generally, and gastrointestinal-related VAEs in particular, in the text clinical notes of encounters recorded in the EMR of a large HMO. Compared to methods that use diagnosis and utilization codes assigned to encounters by clinicians and administrators, the MediClass system can both find more adverse events and improve the positive predictive value for detecting possible VAEs.     

高血压病患者血压参数与尿微量蛋白的关系

目的:通过分析高血压病(EH)患者的5种血压参数(收缩压、舒张压、平均动脉压、脉压、夜间血压下降百分比)与尿敏感肾功能试验的常用指标尿微量白蛋白(MA)、转铁蛋白(TRF)和α1-微球蛋白(α1-MG)的关系,来寻找保护EH患者肾功能的途径。方法:对年龄在58岁~84(71.00(5.00))岁的240名EH患者进行24h动态血压检测和尿敏感肾功能检测,运用多元线性回归分析方法,从血压参数中筛选影响EH患者MA、TRF、α1-MG的影响因素。结果:EH患者MA的独立影响变量为24平均收缩压(β=1.135,P<0.001);TRF的独立影响变量是夜间脉压(β=0.117,P<0.001);α1-MG独立影响变量是夜间收缩压下降百分比(β=-0.140,P<0.01)。结论:在EH患者中,不同的血压参数对肾功能的影响不尽相同。积极采取有效措施,控制高血压,维持良好的脉压和血压昼夜变化节律,是保护EH患者肾功能的重要途径。     

乙型肝炎治疗研究进展

乙性肝炎病毒感染所导致的慢性肝炎是我国的一个大问题,给患者及社会带来了很大负担。慢性乙型肝炎现行治疗主要依靠干扰素、核苷类似物等,其存在高耐药、低耐受以及不良反应等问题。新的、更为安全有效的治疗药物及方法亟待发展。最近,科学家们发现人体内的TRIM22分子对抑制乙肝病毒的复制起到重要作用,为乙肝的治疗及有效药物的研发开辟了新的道路。     

预防接种与自身免疫病的关系

感染与自身免疫性疾病之间的联系已引出一场争论 :疫苗是否也能激发自身免疫性疾病。有关这种风险有众多正反两方面的主张。在此复习感染诱导自身免疫病的相关机制 ,并对预防接种和自身免疫病之间的相对危险度进行评估。     

美国疫苗伤害救济制度对我国的启示

目的:探索建立我国疫苗伤害救济制度。方法:介绍美国疫苗伤害救济制度相关情况,分析我国现有的与疫苗伤害救济有关的规定的不足。结果与结论:我国应通过建立相关法律法规,协调多部门实施,设立救济基金,细化给付范围等方面的工作建立符合我国实际的疫苗伤害救济制度,以保障患者的权益。     

Search for poliovirus long-term excretors among patients affected by agammaglobulinemia

Patients with agammaglobulinemia may excrete enteroviruses, including vaccine-derived poliovirus, for prolonged periods of time. This poses a risk to the patients but it also may pose a risk to the population after eradication of poliovirus and the cessation of routine vaccination. To assess this risk, a pilot study was performed to identify potential poliovirus long-term excretors in a cohort of 38 patients with a definite/presumptive diagnosis of X-linked agammaglobulinemia (XLA). Stool samples were analyzed to detect any polio or other enteroviruses replicating in the gut and neutralizing antibodies against polioviruses were measured in the sera. No viruses were isolated from the stool samples and most sera had neutralizing antibody levels against all three poliovirus serotypes considered by the WHO to be protective in immunocompetent individuals. This suggests that long-term excretion of enteroviruses in patients with agammaglobulinemia is relatively uncommon.     

A trade-off in replication in mosquito versus mammalian systems conferred by a point mutation in the NS4B protein of dengue virus type 4

An acceptable live-attenuated dengue virus vaccine candidate should have low potential for transmission by mosquitoes. We have identified and characterized a mutation in dengue virus type 4 (DEN4) that decreases the ability of the virus to infect mosquitoes. A panel of 1248 mutagenized virus clones generated previously by chemical mutagenesis was screened for decreased replication in mosquito C6/36 cells but efficient replication in simian Vero cells. One virus met these criteria and contained a single coding mutation: a C-to-U mutation at nucleotide 7129 resulting in a Pro-to-Leu change in amino acid 101 of the nonstructural 4B gene (NS4B P101L). This mutation results in decreased replication in C6/36 cells relative to wild-type DEN4, decreased infectivity for mosquitoes, enhanced replication in Vero and human HuH-7 cells, and enhanced replication in SCID mice implanted with HuH-7 cells (SCID-HuH-7 mice). A recombinant DEN4 virus (rDEN4) bearing this mutation exhibited the same set of phenotypes. Addition of the NS4B P101L mutation to rDEN4 bearing a 30 nucleotide deletion (Delta30) decreased the ability of the double-mutant virus to infect mosquitoes but increased its ability to replicate in SCID-HuH-7 mice. Although the NS4B P101L mutation decreases infectivity of DEN4 for mosquitoes, its ability to enhance replication in SCID-HuH-7 mice suggests that it might not be advantageous to include this specific mutation in an rDEN4 vaccine. The opposing effects of the NS4B P101L mutation in mosquito and vertebrate systems suggest that the NS4B protein is involved in maintaining the balance between efficient replication in the mosquito vector and the human host.     

人乳头状瘤病毒16型不同基因疫苗联合免疫的实验研究

目的 探索联合免疫策略在预防和治疗人乳头状瘤病毒16型（HPV16）相关肿瘤中的作用。方法 在C57BL／6动物模型中，观察了表达HPV16基因的融合蛋白L2E7疫苗和重组痘苗病毒mE67疫苗的不同联合免疫方式在预防和治疗HPV16相关肿瘤中的作用。用酶联免疫斑点（ELISPOT）和细胞毒T淋巴细胞（CTL）反应评价它们在诱发机体产生细胞免疫应答中的作用。结果 我们发现以HPV16 L2E7融合蛋白＋佐剂（CpG）初免，用重组痘苗病毒rVVmE67加强免疫的联合免疫方式在C57BL／6小鼠实验中可以有效预防和治疗HPV16相关肿瘤的攻击。ELISPOT可以检测到高水平的E749-57肽特异性，分泌IFN-γ的效应T细胞。CTL检测同样反应出这种联合免疫方式所诱发的CTL细胞可以有效识别并杀伤含HPV16E6／E7的靶细胞。结论 以HPV16L2E7融合蛋白＋CpG初免，用重组痘苗病毒rVVmE67加强的联合免疫策略可以有效防治HPV16相关肿瘤，为进一步研究提供了科学基础。