Safety signal identification for COVID-19 bivalent booster vaccination using tree-based scan statistics in the Vaccine Safety Datalink

BackgroundTraditional active vaccine safety monitoring involves pre-specifying health outcomes and biologically plausible outcome-specific time windows of concern, limiting the adverse events that can be evaluated. In this study, we used tree-based scan statistics to look broadly for >60,000 possible adverse events after bivalent COVID-19 vaccination.MethodsVaccine Safety Datalink enrollees aged ≥5 years receiving Moderna or Pfizer-BioNTech bivalent COVID-19 vaccine through November 2022 were followed for 56 days post-vaccination. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within the hierarchical ICD-10-CM diagnosis code “tree” and temporally within post-vaccination follow-up. The conditional self-controlled tree-temporal scan statistic was used, conditioning on total number of cases of each diagnosis and total number of cases of any diagnosis occurring during the scanning risk window across the entire tree. P = 0.01 was the pre-specified cut-off for statistical significance.ResultsAnalysis included 352,509 doses of Moderna and 979,189 doses of Pfizer-BioNTech bivalent vaccines. After Moderna vaccination, no statistically significant clusters were found. After Pfizer-BioNTech, there were clusters of unspecified adverse events (Days 1–3, p = 0.0001–0.0007), influenza (Days 35–56, p = 0.0001), cough (Days 44–55, p = 0.0002), and COVID-19 (Days 52–56, p = 0.0004).ConclusionsFor Pfizer-BioNTech only, we detected clusters of: (1) unspecified adverse effects, as have been observed in other vaccine studies using this method, and (2) respiratory disease toward the end of follow-up. The respiratory clusters were likely due to overlap of follow-up with the spread of respiratory syncytial virus, influenza, and COVID-19, i.e., confounding by seasonality. The untargeted nature of the method and its inherent adjustment for the many diagnoses and risk intervals evaluated are unique advantages. Limitations include susceptibility to time-varying confounding, lower statistical power for assessing risks of specific outcomes than in traditional studies targeting fewer outcomes, and the possibility of missing adverse events not strongly clustered in time or within the “tree.”     

Effectiveness of COVID-19 vaccines against infection in Japan: A test-negative study from the VENUS study

BackgroundAlthough the effectiveness of coronavirus disease 2019 (COVID-19) vaccines is a crucial public health concern, evidence from Western Pacific countries is limited, including Japan. This study aimed to estimate the COVID-19 vaccines effectiveness (VE) against infection during the Delta variant predominance (July–September 2021) in Japan.MethodsWe performed a test-negative study using COVID-19 test data of ≥20-year-old residents in four municipalities who were tested in medical institutions between July 1 and September 30, 2021. We extracted COVID-19 test data from healthcare claims data, and the vaccination status at the testing date was ascertained using the Vaccination Record System data. Confirmed positive cases were identified using data from the national system for COVID-19, Health Center Real-time Information-sharing System on COVID-19. Logistic regression analyses were conducted to estimate the odds of testing positive according to vaccination status. VE was calculated as (1 − odds ratio) × 100%.ResultsThis study included 530 positive and 15,650 negative results. Adjusted manufacturer-unspecified VE was 4.1% (95% confidence interval [CI], −36.5–32.6) at 0–13 days after the first dose, 45.2% (95% CI, 13.4–65.3) at ≥14 days after the first dose, 85.2% (95% CI, 69.9–92.7) at 0–13 days after the second dose, and 79.6% (95% CI, 72.6–84.8) at ≥14 days after the second dose. In addition, the VE after the second dose was highest at 14–34 days after the dose (VE, 89.1%; 95% CI, 80.5–93.9).ConclusionsHigh real-world effectiveness of COVID-19 vaccines, especially two doses, against infection during the Delta variant predominance in Japan was confirmed.     

PCR鉴别诊断间日疟及恶性疟的研究

目的 :在同一反应体系中建立能鉴别诊断间日疟与恶性疟的 PCR检测方法。方法 :根据红内期疟原虫 SSUr RNA编码基因序列 ,设计合成 3个引物 ,采用聚合酶链反应技术 ,在同一反应体系中 ,间日疟原虫和恶性疟原虫分别预期被扩增出 34 1bp和 4 31bp的 DNA条带。结果 :间日疟原虫和恶性疟原虫模板在同一反应体系中分别被扩增出预期大小的 DNA片段 ,并经限制性酶切证实 ;杜氏利什曼原虫、弓形虫、健康人血及空白对照均无特异性扩增条带 ;以该检测体系至少可检出原虫血症为 2 .56× 10 ^-7间日疟原虫感染和 1.0 8× 10 ^-5恶性疟原虫感染 ;69份镜检阳性的间日疟和 2份恶性疟患者血样 PCR检测均为阳性 ,1例发热待查患者PCR诊断为间日疟 ,与镜检复查结果一致 ,所有疟疾阳性标本中未检出混合感染 ,2 0份健康人血 PCR均为阴性。结论 :该检测体系灵敏、特异 ,对于诊断间日疟和恶性疟以及鉴别间日疟原虫和恶性疟原虫混合感染具有一定的应用价值。     

不同地域株华支睾吸虫基因差异的研究

目的探讨湖北、广东、辽宁和韩国4地华支睾吸虫的基因差异,为华支睾吸虫种下分型提供依据。方法取湖北、广东两地的华支睾吸虫,提取基因组DNA,PCR特异性扩增18S rDNA V4区并测序;登陆GenBank,检索中国辽宁(AF217100)和韩国(AF408144)的华支睾吸虫18S rDNA的登录序列,应用系统发生学分析法对所有序列进行排列比较,分析4地华支睾吸虫的基因差异,并构建系统发生树,分析其亲缘关系。结果获得的湖北和广东两地华支睾吸虫18S rDNA V4区的碱基数分别为392 bp和440 bp。通过对18S rDNA V4区基因序列的比较与进化树的构建,证实4个地域株华支睾吸虫的18S rDNA V4区具有较高的同源性(98%~100%),彼此间遗传距离较小(0~0.013);在系统发生树中,湖北株和广东株华支睾吸虫形成一个支系,韩国株和辽宁株华支睾吸虫形成另外一个支系。结论以18S rDNA V4区为分子标记的DNA序列分析表明,湖北、广东、辽宁和韩国4地华支睾吸虫存在基因差异,但亲缘关系较近,即起源于共同的祖先。     

银杏叶提取物对星形胶质细胞增殖周期的影响

目的:探讨银杏叶提取物(EGb)对体外培养的大鼠大脑皮质星形胶质细胞(Ast)增殖周期的影响。方法:体外培养、纯化及鉴定大鼠大脑皮质Ast;MTT比色法选择EGb作用浓度;1×10-7μL·L-1EGb50μL分别加入对照组和实验组培养液;利用流式细胞仪分析技术检测细胞周期。结果:随着Ast培养时间的延长,12h内EGb诱导Ast进入S期+G2/M期的细胞百分率有上升趋势,但24h后稍有下降。结论:EGb可通过影响Ast的细胞周期促进Ast的增殖。