Logistic Regression Likelihood Ratio Test Analysis for Detecting Signals of Adverse Events in Post-market Safety Surveillance

The Vaccine Adverse Event Reporting System (VAERS) and other product surveillance systems compile reports of product-associated adverse events (AEs), and these reports may include a wide range of information including age, gender, and concomitant vaccines. Controlling for possible confounding variables such as these is an important task when utilizing surveillance systems to monitor post-market product safety. A common method for handling possible confounders is to compare observed product–AE combinations with adjusted baseline frequencies where the adjustments are made by stratifying on observable characteristics. Though approaches such as these have proven to be useful, in this article we propose a more flexible logistic regression approach which allows for covariates of all types rather than relying solely on stratification. Indeed, a main advantage of our approach is that the general regression framework provides flexibility to incorporate additional information such as demographic factors and concomitant vaccines. As part of our covariate-adjusted method, we outline a procedure for signal detection that accounts for multiple comparisons and controls the overall Type 1 error rate. To demonstrate the effectiveness of our approach, we illustrate our method with an example involving febrile convulsion, and we further evaluate its performance in a series of simulation studies.     

Brain-derived neurotrophic factor immunoreactivity in the limbic system of rats after acute seizures and during spontaneous convulsions: temporal evolution of changes as compared to neuropeptide Y

Seizures increase the synthesis of brain-derived neurotrophic factor in forebrain areas, suggesting this neurotrophin has biological actions in epileptic tissue. The understanding of these actions requires information on the sites and extent of brain-derived neurotrophic factor production in areas involved in seizures onset and their spread. In this study, we investigated by immunocytochemistry the changes in brain-derived neurotrophic factor in the hippocampus, entorhinal and perirhinal cortices of rats at increasing times after acute seizures eventually leading to spontaneous convulsions. We also tested the hypothesis that seizure-induced changes in brain-derived neurotrophic factor induce later modifications in neuropeptide Y expression by comparing, in each instance, their immunoreactive patterns. As early as 100 min after seizure induction, brain-derived neurotrophic factor immunoreactivity increased in CA1 pyramidal and granule neurons and in cells of layers II–III of the entorhinal cortex. At later times, immunoreactivity progressively decreased in somata while increasing in fibres in the hippocampus, the subicular complex and in specific layers of the entorhinal and perirhinal cortices. Changes in neuropeptide Y immunoreactivity were superimposed upon and closely followed those of brain-derived neurotrophic factor. One week after seizure induction, brain-derived neurotrophic factor and neuropeptide Y immunoreactivities were similar to controls in 50% of rats. In rats experiencing spontaneous convulsions, brain-derived neurotrophic factor and neuropeptide Y immunoreactivity was strongly enhanced in fibres in the hippocampus/parahippocampal gyrus and in the temporal cortex. In the dentate gyrus, changes in immunoreactivity depended on sprouting of mossy fibres as assessed by growth-associated protein-43-immunoreactivity. These modifications were inhibited by repeated anticonvulsant treatment with phenobarbital.

The dynamic and temporally-linked alterations in brain-derived neurotrophic factor and neuropeptide Y in brain regions critically involved in epileptogenesis suggest a functional link between these two substances in the regulation of network excitability.     

基于网络药理学探讨白芷抗惊厥作用的潜在有效成分及作用机制

目的探讨白芷抗惊厥作用的潜在有效成分及作用机制。方法利用TCMSP数据库筛选白芷有效成分,并收集其对应作用靶点。通过疾病基因综合数据库(GeneCards、OMIM、TTD)检索与convulsion相关靶点;使用R×643.7.2软件绘制韦恩图,筛选白芷有效成分与convulsion交集靶点。采用Cytoscape 3.7.2软件构建“药物-成分-疾病-靶点”网络;使用STRING数据库进行蛋白质相互作用(PPI)网络构建与分析,通过Bioconductor数据库进行KEGG功能富集分析。结果筛选出白芷有效成分19个,有效成分与疾病convulsion交集靶点24个。“药物-成分-疾病-靶点”网络中,β-谷甾醇、豆甾醇、别欧前胡素、珊瑚菜素、欧前胡素和异珊瑚菜素等为该网络主要有效成分。PPI网络中ADRA1B、CASP3、CHRM1、ADRB2、AR和CHRM2等为该网络中核心靶点。KEGG富集分析表明白芷可能通过Neuroactive ligand-receptor interaction、Cocaine addiction和Cholinergic synapse等信号通路发挥抗惊厥作用。结论白芷抗惊厥潜在有效成分主要包括β-谷甾醇、豆甾醇、别欧前胡素、珊瑚菜素、欧前胡素、异珊瑚菜素等,其作用机制可能与参与调控Neuroactive ligand-receptor interaction、Cocaine addiction和Cholinergic synaps等信号通路相关,具有多成分、多靶点、多系统的特点。     

贫血与热性惊厥的相关性研究

目的:分析贫血与热性惊厥的相关性。方法:采用前瞻性研究,连续纳入2018年10月至2019年4月就诊于武汉大学人民医院东院儿科的发热患儿,伴有惊厥的纳入惊厥组,不伴有惊厥的纳入对照组。收集对照组和惊厥组患儿的临床资料如姓名、性别、年龄、发热的病因、热性惊厥的家族史、惊厥发作的类型、红细胞(RBC)、血红蛋白(Hb)、红细胞压积(HCT)、平均红细胞体积(MCV)、平均红细胞血红蛋白量(MCH)、平均血红蛋白浓度(MCHC)等;比较2组发热原因、阳性家族史及贫血情况。根据惊厥发作的类型、持续时间和惊厥发作的次数,进一步将惊厥组分为单纯性热性惊厥组和复杂性热性惊厥组,比较2组的阳性家族史。结果:本研究共纳入294例发热患儿,其中惊厥组154例(52.4%),对照组140例(47.6%)。2组性别、年龄、发热病因差异无统计学意义(P>0.05)。导致发热最常见的疾病为急性上呼吸道感染(63.3%)。惊厥组中家族史阳性者33例(21.4%),对照组5例(3.6%),差异具有统计学意义(P=0.000)。惊厥组中单纯性热性惊厥组121例(78.6%),家族史阳性7例(5.8%);复杂性热性...     

优质护理干预对高热惊厥患儿预后的影响

目的分析优质护理干预对高热惊厥患儿预后的影响。方法选取我院收治的84例高热惊厥患儿作为研究对象,采用随机数字表法将其分为对照组(42例,常规护理)与观察组(42例,优质护理)。比较两组的临床相关指标、并发症发生情况及护理满意度。结果观察组患儿护理30 min后的体温低于对照组,惊厥消失时间及住院时间均短于对照组(P<0.05)。观察组患儿的并发症总发生率低于对照组(P<0.05)。观察组患儿家属的护理满意度高于对照组(P<0.05)。结论优质护理干预用于高热惊厥患儿,护理可有效缩短其惊厥消失时间,降低并发症发生率,改善预后,提升护理满意度。     

“三位一体”模式在小儿高热惊厥急救护理中的应用

目的:探讨“三位一体”模式在小儿高热惊厥急救护理中的应用效果。方法:按随机数字表法将2017年3月—2019年3月收治的86例高热惊厥患儿分为对照组和观察组各43例,对照组行常规护理干预,观察组行“三位一体”模式护理干预。比较两组患儿临床症状改善情况、疾病复发率及患儿家属护理满意度情况。结果:观察组患儿退热时间、惊厥消失时间、住院时间均短于对照组,差异有统计学意义(P<0.05);观察组患儿疾病复发率低于对照组,差异有统计学意义(P<0.05);观察组患儿家属护理满意度优于对照组,差异有统计学意义(P<0.05)。结论:在小儿高热惊厥急救护理中应用“三位一体”模式可有效缓解临床症状,降低疾病复发率,缩短住院时间,提高护理满意度。     

参蒲汤抗大鼠癫痫的实验研究

目的探讨参蒲汤抗癫痫的作用及机理。方法采用匹罗卡品制备边缘系统癫痫大鼠模型，50只大鼠随机分为中药对照组8只、空白对照组8只、预防中药组（中药＋匹罗卡品）8只、匹罗卡品模型组26只（再进一步分为中药治疗组和模型对照组），观察模型大鼠的惊厥发生率及各组大鼠的脑组织游离氨基酸含量。结果预防中药组的惊厥发生率为0，匹罗卡品模型组为88.5%，两组间差异有显著性意义（P〈0.05）；匹罗卡品组和预防中药组大鼠脑组织的谷氨酸含量高于空白对照组（P〈0.05～0.01）；中药治疗组和预防中药组的γ-氨基丁酸含量高于模型对照组（P〈0.05）。结论参蒲汤能有效预防和终止匹多罗品诱导的边缘性癫痫模型大鼠的惊厥发作，具有良好抗惊厥、抗癫痫作用。     

小儿热性惊厥75例随访分析

目的 探讨小儿热性惊厥的相关因素.方法 对2002年12月～2005年12月本科收治的75例首次发作热性惊厥患儿的首发年龄、发作次数、发作时体温、持续时间、发病季节、伴随疾病、脑电图改变、治疗及转归等进行随访观察及研究.结果 热性惊厥患儿首次发病多见于6月龄～3岁,以7～9月发病率最高,62.7%的患儿发作一次,复发率为37.3%,FC的复发与首次发作时的年龄、体温、持续时间和FC分型、脑电图表现以及热性惊厥或癫痫家族史有一定的相关性.结论 热性惊厥的发生与年龄密切相关,有遗传倾向性,伴有危险因素者易复发且易转为癫痫,对首次发作患儿应进行危险因素评估,采取相应措施进行预防.     

石菖蒲醇提取物的抗惊厥作用

目的：研究石菖蒲醇提取物的抗惊厥作用。方法：采用最大电休克发作（ＭＥＳ）法,士的宁惊厥法和戊四氮最小阈发作（ＭＥＴ）法,观察石菖蒲醇提取物对动物惊厥的影响。结果;石菖蒲醇提取物能明显对抗大鼠,小鼠的最大电休克发作和小鼠的戊四氮最小阈发作及士的宁的惊厥的反应。结论;石菖蒲醇提取物具有明显的抗惊厥作用。