Reference set for performance testing of pediatric vaccine safety signal detection methods and systems

BackgroundSafety signal detection in spontaneous reporting system databases and electronic healthcare records is key to detection of previously unknown adverse events following immunization. Various statistical methods for signal detection in these different datasources have been developed, however none are geared to the pediatric population and none specifically to vaccines. A reference set comprising pediatric vaccine-adverse event pairs is required for reliable performance testing of statistical methods within and across data sources.MethodsThe study was conducted within the context of the Global Research in Paediatrics (GRiP) project, as part of the seventh framework programme (FP7) of the European Commission. Criteria for the selection of vaccines considered in the reference set were routine and global use in the pediatric population. Adverse events were primarily selected based on importance. Outcome based systematic literature searches were performed for all identified vaccine-adverse event pairs and complemented by expert committee reports, evidence based decision support systems (e.g. Micromedex), and summaries of product characteristics. Classification into positive (PC) and negative control (NC) pairs was performed by two independent reviewers according to a pre-defined algorithm and discussed for consensus in case of disagreement.ResultsWe selected 13 vaccines and 14 adverse events to be included in the reference set. From a total of 182 vaccine-adverse event pairs, we classified 18 as PC, 113 as NC and 51 as unclassifiable. Most classifications (91) were based on literature review, 45 were based on expert committee reports, and for 46 vaccine-adverse event pairs, an underlying pathomechanism was not plausible classifying the association as NC.ConclusionA reference set of vaccine-adverse event pairs was developed. We propose its use for comparing signal detection methods and systems in the pediatric population.     

Comparison between a new platelet count drop method PL-11, light transmission aggregometry,VerifyNow aspirin system and thromboelastography for monitoring short-term aspirin effects in healthy individuals

Platelet function has been described by many laboratory assays, and PL-11 is a new point-of-care platelet function analyzer based on platelet count drop method, which counts platelet before and after the addition of agonists in the citrated whole blood samples. The present study sought to compare PL-11 with other three major more established assays, light transmission aggregometry (LTA), VerifyNow? aspirin system and thromboelastography (TEG), for monitoring the short-term aspirin responses in healthy individuals. Ten healthy young men took 100?mg/d aspirin for 3-day treatment. Platelet function was measured via PL-11, LTA, VerifyNow and TEG, respectively. The blood samples were collected at baseline, 2 hour, 1 day during the aspirin treatment and 1 day, 5?±?1 days, 8?±?1 days after the aspirin withdrawal. Moreover, 90 additional healthy subjects were recruited to establish a reference range for PL-11. Platelet function of healthy subjects decreased significantly 2 hours after 100?mg/d aspirin intake and began to recover during 4–6 days after the aspirin withdrawal. Correlations between methods were PL-11 vs. LTA (r?=?0.614, p?<?0.01); PL-11 vs. VerifyNow (r?=?0.829, p?<?0.01); PL-11 vs. TEG (r?=?0.697, p?<?0.001). There was no significant bias between PL-11 and LTA at baseline (bias?=?1.94%, p?=?0.804) using Bland-Altman analysis, while the data of PL-11 were significantly higher than LTA (bias?=?24.02%, p?<?0.001) during the aspirin therapy. The reference range for PL-11 in healthy young individuals was from 66.8 to 90.5% (95%CI). When aspirin low-responsiveness was defined as LTA?>?20%, the cut-off values for each method were, respectively: PL-11?>?50%, VerifyNow?>?533 ARU, TEG?>?60.2%. The results of different platelet function assays were uninterchangeable for monitoring aspirin response and correlations among them were also varied. Correlations among PL-11 and other three major assays suggested the ability of PL-11 to assess the treatment effects of aspirin. But a large cohort study is needed to confirm the cut-off value of aspirin response detected by PL-11.     

Determinants of Regional Variation in Health Expenditures in Germany

Health care expenditure in Germany shows clear regional differences. Such geographic variations are often seen as an indicator for inefficiency. With its homogeneous health care system, low co‐payments and uniform prices, Germany is a particularly suited example to analyse regional variations. We use data for the year 2011 on expenditure, utilization of health services and state of health in Germany's statutory health insurance system. This data, which originate from a variety of administrative sources and cover about 90% of the population, are enriched with a wealth of socio‐economic variables, data on pollutants, prices and individual preferences. State of health and demography explains 55% of the differences as measured by the standard deviation while all control variables account for a total of 72% of the differences at county level. With other measures of variation, we can account for an even greater proportion. A higher proportion of variation than usually supposed can thus be explained. Whilst this study cannot quantify inefficiencies, our results contradict the thesis that regional variations reflect inefficiency. Copyright © 2015 John Wiley & Sons, Ltd.     

基于子宫内膜异位症与恶性肿瘤的相关性探析补肾化瘀法作用机制及中医理论依据

子宫内膜异位症其异位内膜组织虽然在形态学上呈良性表现，却具有类似恶性肿瘤的生物学特性。中医学一般认为，“正虚伏邪”为恶性肿瘤的病机特点；那么，肾虚血瘀既属于“正虚伏邪”的范畴，又体现了EMs发病学和疾病发生、发展过程中的主要特点。在“病证相应”的中医治则之下，补肾化瘀法的临床疗效主要表现为：缓解痛经症状、提高受孕率，以及调整月经周期。本文基于EMs与恶性肿瘤的相关性，通过分析补肾化瘀法治疗EMs的理论依据及其抑制异位内膜侵袭的调控机制，主要包括解除免疫抑制、阻断局部微血管新生等，旨在阐明其疗效显著的原因，为临床推广提供可靠的基础研究证据。     

经穹隆结膜入路埋线法重睑成形术应用探讨

目的:通过分析重睑形成原理,综合比较多种重睑成形的方法,讨论埋线法重睑成形术的优点和可行性。方法:对387例患者行经穹隆结膜入路间断缝合埋线法重睑术。其中88例为其他方法埋线后重睑线消失的患者。结果:手术方法可靠,术后所形成的重睑外形良好,重睑维持时间长。最长随访时间38个月。结论:此方法因符合重睑形成原理,可以充分的将较多的上睑提肌腱膜与上睑皮肤结扎固定、故术后所形成的重睑牢固。且在直视下经穹隆结膜入路,降低了对眼球组织损伤的危险性。是埋线法重睑成形术一种可靠的手术方法。     

启发式教学在生理学教学中的应用研究

针对生理学课程理论抽象、实验操作复杂等特点,阐述了启发式教学方法取代传统填鸭式教学方法的必然性。因生理学教学难度大、实验操作条件高,故着重介绍了问答式、讨论式、演绎式、归纳式、直观式等五种启发式教学方法在生理学教学中的应用。     

外剥、内扎硬化注射术治疗混和痔800例

目的观察和评价外剥、内扎硬化注射术治疗混合痔的近期疗效.方法作者采用外剥、内扎硬化注射术治疗混和痔800例.结果近期治愈788例,治愈率98.5%,好转12例,好转率1.5%.治愈天数10～21天.结论外剥、内扎硬化注射术治疗混合痔简单实用,手术时间短,术后痛苦小,伤面愈合快,并发症少,无后遗症,复发率低,是治疗混合痔的较好方法.     

肾损伤的治疗进展

轻度、中度的肾损伤可行保守治疗。严重的肾损伤出血应首选超选择性肾动脉栓塞术,因该技术定位准确,止血迅速,创伤小,恢复快,并发症少,能最大限度地保护肾脏功能,是一种安全可靠治疗肾损伤出血的有效方法。