Adverse events following first and second dose COVID-19 vaccination in England,October 2020 to September 2021: a national vaccine surveillance platform self-controlled case series study

BackgroundPost-authorisation vaccine safety surveillance is well established for reporting common adverse events of interest (AEIs) following influenza vaccines, but not for COVID-19 vaccines.AimTo estimate the incidence of AEIs presenting to primary care following COVID-19 vaccination in England, and report safety profile differences between vaccine brands.MethodsWe used a self-controlled case series design to estimate relative incidence (RI) of AEIs reported to the national sentinel network, the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub. We compared AEIs (overall and by clinical category) 7 days pre- and post-vaccination to background levels between 1 October 2020 and 12 September 2021.ResultsWithin 7,952,861 records, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs, 4.85% within 7 days post-vaccination. Overall, medically attended AEIs decreased post-vaccination against background levels. There was a 3–7% decrease in incidence within 7 days after both doses of Comirnaty (RI: 0.93; 95% CI: 0.91–0.94 and RI: 0.96; 95% CI: 0.94–0.98, respectively) and Vaxzevria (RI: 0.97; 95% CI: 0.95–0.98). A 20% increase was observed after one dose of Spikevax (RI: 1.20; 95% CI: 1.00–1.44). Fewer AEIs were reported as age increased. Types of AEIs, e.g. increased neurological and psychiatric conditions, varied between brands following two doses of Comirnaty (RI: 1.41; 95% CI: 1.28–1.56) and Vaxzevria (RI: 1.07; 95% CI: 0.97–1.78).ConclusionCOVID-19 vaccines are associated with a small decrease in medically attended AEI incidence. Sentinel networks could routinely report common AEI rates, contributing to reporting vaccine safety.     

Pre-clinical properties of the α4β2 nicotinic acetylcholine receptor partial agonists varenicline,cytisine and dianicline translate to clinical efficacy for nicotine dependence

Background and purpose:

Smoking cessation trials with three high-affinity partial agonists of α4β2 neuronal nicotinic acetylcholine receptors (nAChRs) have demonstrated differences in their clinical efficacy. This work examines the origin of the differences by taking into account brain exposure and pharmacological effects at human α4β2 nAChRs.

Experimental approach:

Rat plasma and brain pharmacokinetics were characterized and used to predict human steady-state plasma and brain concentrations following recommended doses of each of the three compounds. The pharmacological characterization included in vitro affinities at different nAChR subtypes, functional efficacies and potencies at the human α4β2 nAChR, as well as in vivo effects on rat mesolimbic dopamine turn-over.

Key results:

A comparison of predicted human brain concentrations following therapeutic doses demonstrated that varenicline and nicotine, but not dianicline and cytisine, can extensively desensitize and, to a lesser extent, activate α4β2 nAChRs. The limited clinical efficacy of dianicline may be accounted for by a combination of weak functional potency at α4β2 nAChRs and moderate brain penetration, while recommended doses of cytisine, despite its high in vitro potency, are predicted to result in brain concentrations that are insufficient to affect α4β2 nAChRs.

Conclusions and implications:

The data provide a plausible explanation for the higher abstinence rate in smoking cessation trials following treatment with varenicline than with the two other α4β2 nAChR partial agonists. In addition, this retrospective analysis demonstrates the usefulness of combining in vitro and in vivo parameters with estimated therapeutic human brain concentrations for translation to clinical efficacy.     

实践表现的自我评估:美国内科委员会实践改善教育活动

为了评估美国内科委员会(American Board of Internal Medicine,ABIM)开展的实践改善单元(Practice Improvement Module,PIM)教育活动的效果,以及参与心脏疾病预防PIM教育活动的专科医师临床实践改善的表现,美国内科委员会进行了一项以自我指导为基础的观察研究.     

蝙蝠葛碱对麻醉兔体内希氏束电图的影响及与几种药物的相互作用

蝙蝠葛碱(Dau)剂量依赖性延长麻醉家兔希氏束电图(HBE)的A-H,H-V间期,使V波增宽,并延长心房和房室结不应期。利多卡因(Lid)、对HBE各间期无明显影响,但有减弱Dau延长H-V间期的作用。异丙肾上腺素(Iso)可对抗Dau延长A-H,H-V间期及增宽V波的作用。阿托品(Atr)可缩短Dau已延长的A-H间期。提示Atr和Lid可分别改善Dau抑制的房室及希—浦系统的传导,而Iso对房室传导和室内传导均有改善作用。     

Comparison of chronic exposures received by radiation workers using different biological end‐points with the doses recorded by TLD

The frequency of different biological end‐points such as translocation, dicentrics (DC) and micronuclei (MN) was studied in 14 radiation workers and 21 non‐radiation workers. The average frequencies for different types of aberrations were significantly higher in radiation workers compared to those of respective aberrations in non‐radiation workers. Out of 14 radiation workers, eight subjects showed a dose above the detection limit as per translocation and seven subjects as per DC frequency and no patient showed a dose above the detection limit as per MN frequency. Regression analysis carried out between the recorded doses according to Thermo Luminescence Dosimeter (TLD) and the dose estimated as per translocation frequency gave a correlation coefficient of 0.32, whereas that obtained with TLD dose and the dose estimated as per DC was 0.81. When the correlation was made between the TLD dose, which was above 0.15 Gy (the detection limit for translocation), and the dose estimated as per translocation frequency in these subjects, a correlation coefficient of 0.98 was found. A similar analysis between the TLD dose above 0.5 Gy (the detection limit for DC) and the dose estimated as per DC frequency in these subjects, a correlation coefficient of 0.26 resulted. This paper discusses the reasons for the poor correlation obtained between TLD dose and dose estimated as per DC and MN frequency.     

1－（2，6－二甲基苯氧基）－2－（3，4－二甲氧基苯乙氨基）丙烷盐酸盐对兔血小板胞浆游离钙浓度的影响

１－（２，６－二甲基苯氧基）－２－（３，４－二甲氧基苯乙氨基）丙烷盐酸盐对兔血小板胞浆游离钙浓度的影响夏敬生，罗湘，曾繁典（同济医科大学临床药理研究室，武汉４３００３０）１－（２，６－二甲基苯氧基）－２－（３，４－二甲氧基苯乙氨基）丙烷盐酸盐［１－（...