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Kirsty Andresen,1,2 Marina Hinojosa-Campos,3 Bélène Podmore,1– 3 Myriam Drysdale,4 Nawab Qizilbash,1– 3 Marianne Cunnington4,5 1OXON Epidemiology, London, UK; 2London School of Hygiene and Tropical Medicine, London, UK; 3OXON Epidemiology, Madrid, Spain; 4GlaxoSmithKline, Middlesex, UK; 5Analysis Group, London, UKCorrespondence: Kirsty Andresen, Email Kirsty.andresen@oxonepi.comIntroduction: Regulatory guidance encourages transparent reporting of information on the quality and validity of electronic health record data being used to generate real-world benefit-risk evidence for vaccines and therapeutics. We aimed to provide an overview of the availability of validated diagnostic algorithms for selected safety endpoints for Coronavirus disease 2019 (COVID-19) vaccines and therapeutics in the context of the emerging pandemic prior to December 2020.Methods: We reviewed the literature up to December 2020 to identify validation studies for various safety events of interest, including myocardial infarction, arrhythmia, myocarditis, acute cardiac injury, vasculitis/vasculopathy, venous thromboembolism, stroke, respiratory distress syndrome (RDS), pneumonitis, cytokine release syndrome (CRS), multiple organ dysfunction syndrome, and renal failure. We included studies published between 2015 and 2020 that were considered high quality assessed with QUADAS and that reported positive predictive values (PPVs).Results: Out of 43 identified studies, we found that diagnostic algorithms for cardiovascular outcomes were supported by the highest number of validation studies (n=17). Accurate algorithms are available for myocardial infarction (median PPV 80%; IQR 22%), arrhythmia (PPV range > 70%), venous thromboembolism (median PPV: 73%) and ischaemic stroke (PPV range ≥ 85%). We found a lack of validation studies for less common respiratory and cardiac safety outcomes of interest (eg, pneumonitis and myocarditis), as well as for COVID-specific complications (CRS, RDS).Conclusion: There is a need for better understanding of barriers to conducting validation studies, including data governance restrictions. Regulatory guidance should promote embedding validation within real-world EHR research used for decision-making.Keywords: validation, routine health data, Covid-19, safety, vaccines, outcomes

Seroprevalence data among ethnic minority groups within England and Wales are rare. An opportunistic approach was taken to test residual oral fluid, collected from pre-adolescent school children from an ethnically diverse region of northwest England, for anti-hepatitis A virus (HAV) IgG. Individual data on ethnicity and country of birth were also available. Of the 257 children who consented to participate, 62% were of South Asian ethnic origin. The overall seroprevalence was 18.8%, higher than 13.1% reported from a recent population-based survey in England and Wales among a mainly Caucasian population of the same age. The only factor significantly associated with HAV seropositivity in a multivariable logistic regression model was birth of the child abroad. Association with the place of birth of the child, but not that of the parent indicates that infection within this group occurs mainly abroad. Larger studies among ethnic minority groups are needed to investigate this claim further. [ABSTRACT FROM AUTHOR]

Abstract Background Blood pressure (BP) has significant heritability, but the genes responsible remain largely unknown. Single nucleotide polymorphisms (SNPs) at the STK39 locus were recently associated with hypertension by genome-wide association in an Amish population; in vitro data from transient transfection experiments using reporter constructs suggested that altered STK39 expression might mediate the effect. However, other large studies have not implicated STK39 in hypertension. We determined whether reported SNPs influenced STK39 expression in vivo, or were associated with BP in a large British Caucasian cohort. Methods 1372 members of 247 Caucasian families ascertained through a hypertensive proband were genotyped for reported risk variants in STK39 (rs6749447, rs3754777, rs35929607) using Sequenom technology. MERLIN software was used for family-based association testing. Cis-acting influences on expression were assessed in vivo using allelic expression ratios in cDNA from peripheral blood cells in 35 South African individuals heterozygous for a transcribed SNP in STK39 (rs1061471) and quantified by mass spectrometry (Sequenom). Results No significant association was seen between the SNPs tested and systolic or diastolic BP in clinic or ambulatory measurements (all p > 0.05). The tested SNPs were all associated with allelic expression differences in peripheral blood cells (p < 0.05), with the most significant association for the intronic SNP rs6749447 (P = 9.9 × 10-4). In individuals who were heterozygous for this SNP, on average the G allele showed 13% overexpression compared to the T allele. Conclusions STK39 expression is modified by polymorphisms acting in cis and the typed SNPs are associated with allelic expression of this gene, but there is no evidence for an association with BP in a British Caucasian cohort.