End of 2022/23 Season Influenza Vaccine Effectiveness in Primary Care in Great Britain.

Background: The 2022/23 influenza season in the United Kingdom saw the return of influenza to prepandemic levels following two seasons with low influenza activity. The early season was dominated by A(H3N2), with cocirculation of A(H1N1), reaching a peak late December 2022, while influenza B circulated at low levels during the latter part of the season. From September to March 2022/23, influenza vaccines were offered, free of charge, to all aged 2-13 (and 14-15 in Scotland and Wales), adults up to 49 years of age with clinical risk conditions and adults aged 50 and above across the mainland United Kingdom.

Influenza vaccination during the 2021/22 season: A data-linkage test-negative case-control study of effectiveness against influenza requiring emergency care in England and serological analysis of primary care patients.

We present England 2021/22 end-of-season adjusted vaccine effectiveness (aVE) against laboratory confirmed influenza related emergency care use in children aged 1-17 and in adults aged 50+, and serological findings in vaccinated vs unvaccinated adults by hemagglutination inhibition assay. Influenza vaccination has been routinely offered to all children aged 2-10 years and adults aged 65 years + in England. In 2021/22, the offer was extended to children to age 15 years, and adults aged 50-64 years.

Risk of cardiac arrhythmia and cardiac arrest after primary and booster COVID-19 vaccination in England: A self-controlled case series analysis.

Background: Various cardiac arrhythmias have been reported after COVID-19 infection and vaccination. We assessed the risk after primary immunisation with the ChAdOx1 adenovirus vectored vaccine, and primary and booster immunisation with an mRNA vaccine in 40 million vaccinated adults with 121 million doses (33.9% ChAdOx1 and 66.

COVID-19 vaccine effectiveness against hospitalisation and death of people in clinical risk groups during the Delta variant period: English primary care network cohort study.

Background: COVID-19 vaccines have been shown to be highly effective against hospitalisation and death following COVID-19 infection. COVID-19 vaccine effectiveness estimates against severe endpoints among individuals with clinical conditions that place them at increased risk of critical disease are limited.

Methods: We used English primary care medical record data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre sentinel network (N > 18 million).

Risk of myocarditis and pericarditis after a COVID-19 mRNA vaccine booster and after COVID-19 in those with and without prior SARS-CoV-2 infection: A self-controlled case series analysis in England.

Background: An increased risk of myocarditis or pericarditis after priming with mRNA Coronavirus Disease 2019 (COVID-19) vaccines has been shown but information on the risk post-booster is limited. With the now high prevalence of prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we assessed the effect of prior infection on the vaccine risk and the risk from COVID-19 reinfection.

Methods And Findings: We conducted a self-controlled case series analysis of hospital admissions for myocarditis or pericarditis in England between 22 February 2021 and 6 February 2022 in the 50 million individuals eligible to receive the adenovirus-vectored vaccine (ChAdOx1-S) for priming or an mRNA vaccine (BNT162b2 or mRNA-1273) for priming or boosting.

Real-world data on immune responses following heterologous prime-boost COVID-19 vaccination schedule with Pfizer and AstraZeneca vaccines in England.

Background: There are limited data on immune responses to heterologous COVID-19 immunisation schedules, especially following an extended ≥12-week interval between doses.

Methods: SARS-CoV-2 infection-naïve and previously-infected adults receiving ChAd-BNT (ChAdOx1 nCoV-19, AstraZeneca followed by BNT162b2, Pfizer-BioNTech) or BNT-ChAd as part of the UK national immunisation programme provided blood samples at 30 days and 12 weeks after their second dose. Geometric mean concentrations (GMC) of anti-SARS-CoV-2 spike (S-antibody) and nucleoprotein (N-antibody) IgG antibodies and geometric mean ratios (GMR) were compared with a contemporaneous cohort receiving homologous ChAd-ChAd or BNT-BNT.

Pfizer-BioNTech and Oxford AstraZeneca COVID-19 vaccine effectiveness and immune response amongst individuals in clinical risk groups.

Background COVID-19 vaccines approved in the UK are highly effective in general population cohorts, however, data on effectiveness amongst individuals with clinical conditions that place them at increased risk of severe disease are limited. Methods We used GP electronic health record data, sentinel virology swabbing and antibody testing within a cohort of 712 general practices across England to estimate vaccine antibody response and vaccine effectiveness against medically attended COVID-19 amongst individuals in clinical risk groups using cohort and test-negative case control designs. Findings There was no reduction in S-antibody positivity in most clinical risk groups, however reduced S-antibody positivity and response was significant in the immunosuppressed group.

Impact of COVID-19 vaccination program on seroprevalence in blood donors in England, 2021.

The COVID-19 vaccination programme commenced in England on 8th December 2020 primarily based on age; by 7th March 2021 approximately 93% of the English population aged 70+ years had received at least 1 dose of either the Pfizer BioNTech or AstraZeneca vaccines. Using a nucleoprotein assay that detects antibodies following natural infection only and a spike assay that detects infection and vaccine-induced responses, we aim to describe the impact of vaccination on SARS-CoV-2 antibody prevalence in English blood donors.

Serological surveillance of SARS-CoV-2: Six-month trends and antibody response in a cohort of public health workers.

Background: Antibody waning after SARS-CoV-2 infection may result in reduction in long-term immunity following natural infection and vaccination, and is therefore a major public health issue. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England.

Methods: Clinical and non-clinical healthcare workers were recruited across three English regions and tested monthly from March to November 2020 for SARS-CoV-2 spike (S) protein and nucleoprotein (N) antibodies using five different immunoassays.

Control yourself: ISPE-endorsed guidance in the application of self-controlled study designs in pharmacoepidemiology.

Purpose: Consensus is needed on conceptual foundations, terminology and relationships among the various self-controlled "trigger" study designs that control for time-invariant confounding factors and target the association between transient exposures (potential triggers) and abrupt outcomes. The International Society for Pharmacoepidemiology (ISPE) funded a working group of ISPE members to develop guidance material for the application and reporting of self-controlled study designs, similar to Standards of Reporting Observational Epidemiology (STROBE). This first paper focuses on navigation between the types of self-controlled designs to permit a foundational understanding with guiding principles.

Assessing the impact of preventive mass vaccination campaigns on yellow fever outbreaks in Africa: A population-level self-controlled case series study.

Background: The Eliminate Yellow fever Epidemics (EYE) strategy was launched in 2017 in response to the resurgence of yellow fever in Africa and the Americas. The strategy relies on several vaccination activities, including preventive mass vaccination campaigns (PMVCs). However, to what extent PMVCs are associated with a decreased risk of outbreak has not yet been quantified.

Self-controlled case series studies: Just how rare does a rare non-recurrent outcome need to be?

The self-controlled case series method assumes that adverse outcomes arise according to a non-homogeneous Poisson process. This implies that it is applicable to independent recurrent outcomes. However, the self-controlled case series method may also be applied to unique, non-recurrent outcomes or first outcomes only, in the limit where these become rare.

Thromboembolic and neurologic sequelae of discontinuation of an antihyperlipidemic drug during ongoing warfarin therapy.

Warfarin and antihyperlipidemics are commonly co-prescribed. Some antihyperlipidemics may inhibit warfarin deactivation via the hepatic cytochrome P450 system. Therefore, antihyperlipidemic discontinuation has been hypothesized to result in underanticoagulation, as warfarin metabolism is no longer inhibited.

Investigating the assumptions of the self-controlled case series method.

We describe some simple techniques for investigating 2 key assumptions of the self-controlled case series (SCCS) method, namely, that events do not influence subsequent exposures and that events do not influence the length of observation periods. For each assumption, we propose some simple tests based on the standard SCCS model, along with associated graphical displays. The methods also enable the user to investigate the robustness of the results obtained using the standard SCCS model to failure of assumptions.

Relative risk of hemorrhage during pregnancy in patients with brain arteriovenous malformations.

Background It is unclear whether the risk of bleeding from brain arteriovenous malformations is higher during pregnancy, delivery, or puerperium. We compared occurrence of brain arteriovenous malformation hemorrhage in women during this period with occurrence of hemorrhage outside this period during their fertile years. Methods We included all women with ruptured brain arteriovenous malformations (16-41 years) from a retrospective database of patients with brain arteriovenous malformations in four Dutch university hospitals (n = 95) and from the population-based Scottish Audit of Intracranial Vascular Malformations (n = 44).

Spline-based self-controlled case series method.

The self-controlled case series (SCCS) method is an alternative to study designs such as cohort and case control methods and is used to investigate potential associations between the timing of vaccine or other drug exposures and adverse events. It requires information only on cases, individuals who have experienced the adverse event at least once, and automatically controls all fixed confounding variables that could modify the true association between exposure and adverse event. Time-varying confounders such as age, on the other hand, are not automatically controlled and must be allowed for explicitly.

Flexible modelling of vaccine effect in self-controlled case series models.

The self-controlled case series (SCCS) method, commonly used to investigate the safety of vaccines, requires information on cases only and automatically controls all age-independent multiplicative confounders, while allowing for an age-dependent baseline incidence. Currently, the SCCS method represents the time-varying exposures using step functions with pre-determined cut points. A less prescriptive approach may be beneficial when the shape of the relative risk function associated with exposure is not known a priori, especially when exposure effects can be long-lasting.

Self-controlled case series method with smooth age effect.

The self-controlled case series method, commonly used to investigate potential associations between vaccines and adverse events, requires information on cases only and automatically controls all age-independent multiplicative confounders while allowing for an age-dependent baseline incidence. In the parametric version of the method, we modelled the age-specific relative incidence by using a piecewise constant function, whereas in the semiparametric version, we left it unspecified. However, mis-specification of age groups in the parametric version can lead to biassed estimates of exposure effect, and the semiparametric approach runs into computational problems when the number of cases in the study is moderately large.

Severe neuropsychiatric outcomes following discontinuation of long-term glucocorticoid therapy: a cohort study.

Background: It has been estimated that, at any point in time, about 1% of the general adult population of the United Kingdom is receiving long-term (ie, ≥ 3 months) oral glucocorticoid therapy. These patients may develop neuropsychiatric disorders when the drug is discontinued.

Method: Data were obtained for all adult patients registered from January 1, 1990, through December 31, 2008, at UK general practices that were contributors to The Health Improvement Network database.

A simulation study to compare three self-controlled case series approaches: correction for violation of assumption and evaluation of bias.

Purpose: The assumption that the occurrence of outcome event must not alter subsequent exposure probability is critical for preserving the validity of the self-controlled case series (SCCS) method. This assumption is violated in scenarios in which the event constitutes a contraindication for exposure. In this simulation study, we compared the performance of the standard SCCS approach and two alternative approaches when the event-independent exposure assumption was violated.

Correlated infections: quantifying individual heterogeneity in the spread of infectious diseases.

In this paper, we propose new methods for investigating the extent of heterogeneity in effective contact rates relevant to the transmission of infections. These methods exploit the correlations between ages at infection for different infections within individuals. The methods are developed for serological surveys, which provide accessible individual data on several infections, and are applied to a wide range of infections.

A modified self-controlled case series method to examine association between multidose vaccinations and death.

The self-controlled case series method (SCCS) was developed to analyze the association between a time-varying exposure and an outcome event. We consider penta- or hexavalent vaccination as the exposure and unexplained sudden unexpected death (uSUD) as the event. The special situation of multiple exposures and a terminal event requires adaptation of the standard SCCS method.