Current state of biologic pharmacovigilance in the European Union: improvements are needed

Introduction: Pharmacovigilance is essential to monitoring the safety profiles of authorized medicines. Compared with small-molecule drugs, biological drugs are more complex, more susceptible to structural variability due to manufacturing processes, and have the potential to induce immune-related reactions, underscoring the importance of safety monitoring for these products. Although highly similar to reference products, biosimilars are not expected to be structurally identical. For these reasons, proper reporting of potential adverse drug reactions (ADRs) using distinguishable names and batch numbers is essential for accurate tracing of all biological drugs. To address the need for robust pharmacovigilance, the European Parliament and Council of the European Union provided legislation regarding pharmacovigilance of biologics in 2010.

Areas covered: This narrative review examines the current state of pharmacovigilance for biologics in the European Union (EU) and discusses relevant information on pharmacovigilance of biosimilars, the current EU pharmacovigilance system, and areas that could be improved.

Expert opinion: Although steps have been taken to improve pharmacovigilance of biologics in the EU, several enhancements can still be made, including additional training for healthcare professionals on ADR reporting, the use of 2D barcodes that enhance traceability, and an open discussion of potentially missed opportunities in the pharmacovigilance of biosimilars.     

颈椎终板弧形高度与椎间隙后缘骨赘的相关性研究

目的：通过对颈椎病患者上下终板弧形高度、椎间隙高度与椎间隙后骨赘的影像学测量，研究其相关性及其临床应用价值。方法：收集2017年9月至2018年9月颈椎病手术108例患者的临床资料，男48例，年龄30~72岁，平均52岁，女60例，年龄37~79岁，平均54岁。其中C_2，3 6例，C_3，4 15例，C_4，5 32例，C_5，6 42例，C_6，7 13例。术前及术后摄颈椎X线片，利用PACS（Picture Archiving and Communication Systems）调阅影像，测量椎间隙的下上终板弧形高度（L₁，L₂），椎间隙高度（L₃）及后方骨赘的宽度（L₄）。利用Spearman分析它们之间的相关性。结果：L₁与L₄对比（r=-0.34，P<0.05），L₃与L₄对比（r=-0.36，P<0.05），存在负相关。L₁与L₃对比（r=0.38，P<0.05），L₂与L₃对比（r=0.48，P<0.05），存在正相关。L₁与L₂对比（P>0.05），L₂与L₄对比（P>0.05），差异无统计学意义。结论：下终板弧形高度与椎间隙后缘骨赘宽度呈负相关，通过其测量可明确颈椎退变程度，对颈椎病的早期防治有指导意义。     

川陈皮素对糖尿病肾病大鼠AMPK和eNOS表达的影响研究

【摘要】目的 观察川陈皮素对糖尿病肾病大鼠的治疗作用，并从腺苷酸蛋白活化激酶（AMPK）和内皮型一氧化氮酶（eNOS）途径探讨其作用机理。方法 采用高脂高糖饲料喂养+链脲佐菌素（STZ）腹腔注射复制2型糖尿病肾脏损害大鼠模型，模型构建成功后，将其随机分为正常组、模型组、贝那普利干预组以及川陈皮素低、中和高剂量治疗组（n=20）。实验中密切监测大鼠一般情况，治疗期结束后收集尿液检测24h蛋白尿，收集血液检测肾功能指标、抗氧化指标，收集肾脏观察肾脏病理学，同时检测肾脏组织中AMPK及eNOS蛋白和mRNA的表达结果。结果 正常组肾小球正常，无明显病理特征；模型组出现肾小球增大，系膜和肾间质纤维组织增生；贝那普利组和川陈皮素三个剂量组相较于模型组明显减轻。与正常组相比，模型组24h尿蛋白定量、UREA、CREA和MDA明显升高(P＜005)；SOD和GSH明显降低(P＜005)，与模型组相比，贝那普利和川陈皮素三个剂量组24h尿蛋白定量、UREA、CREA和MDA明显降低(P＜005)，SOD和GSH明显升高(P＜005)。与正常组相比，模型组p AMPK、AMPK和eNOS蛋白和mRNA表达均明显降低(P＜005)；与模型组相比，贝那普利组和川陈皮素低、中和高剂量组AMPK和eNOS蛋白和mRNA表达明显升高(P＜005)。结论 川陈皮素可保护肾功能，提高血清和肾脏抗氧化指标，同时增加AMPK和eNOS蛋白和mRNA表达，最终保护糖尿病肾脏损害。     

Recall of emotional and neutral words and paragraphs in traumatic brain injury

Background: Traumatic brain injury (TBI) results in verbal recall deficits and impaired processing of emotion encoded in facial appearance, prosody and the linguistic content of messages. Emotion facilitates memory (emotional memory advantage) for non-brain injured (NBI) individuals but the impact of emotion on verbal recall for linguistically encoded stimuli in TBI has not been explored.

Aims: The purpose of this study was to determine the effects of stimulus emotional content on verbal recall of words and paragraphs in TBI compared to NBI individuals.

Methods and procedures: Six 10-item lists, each with five emotional and five neutral words, and six paragraphs (three emotional, three neutral) were counterbalanced and presented in random order to 20 individuals with TBI and 44 NBI. The number of words from lists and the number of content units from paragraphs were compared for the two groups.

Outcomes and results: The NBI participants recalled more words from the lists and content units from the paragraphs than the individuals with TBI. Both groups recalled significantly more emotional than neutral words. NBI but not TBI participants had significantly greater recall for information in paragraphs with emotional content.

Conclusions: Participants with TBI showed impaired recall of words and paragraph content. Emotion facilitated word and paragraph content recall for neurotypical individuals but emotional memory advantage was limited to words for the TBI participants.     

不同年龄阿尔茨海默病患者脑核团ADC值与年龄的相关性

目的 探讨不同年龄阿尔茨海默病（AD）患者ADC值与年龄的相关性。方法 选取30例AD患者（AD组）和年龄与之相匹配的30名志愿者（对照组），按年龄段各分为6个亚组[55~59岁（n=3）、60~64岁（n=4）、65~70岁（n=9）、71~74岁（n=5）、75~80岁（n=6）、>80岁（n=3）]，测量双侧海马、红核、尾状核、杏仁体、壳核ADC值，并进行配对t检验、独立样本t检验、单因素方差分析及Pearson相关分析。结果 AD组红核左、右侧ADC值有统计学差异（P=0.022）。AD组不同年龄亚组右侧海马、双侧尾状核、右侧壳核ADC值差异有统计学意义（P均<0.05）；2组不同年龄亚组双侧海马、壳核、尾状核ADC值差异有统计学意义（P均<0.05）。AD组右侧海马（r=0.615，P<0.001）、右侧壳核（r=0.653，P=0.001）及双侧尾状核（左侧：r=0.397，P=0.030；右侧：r=0.429，P=0.020）ADC值与年龄呈正相关。结论 AD患者右侧海马和壳核、双侧尾状核ADC值随年龄增加而增大。ADC值可为临床预测和早期诊断AD脑内右侧海马和壳核、双侧尾状核神经退行性病变提供参考。