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

A conceptual framework for characterising lifecourse determinants of multiple long-term condition multimorbidity

Objective: Social, biological and environmental factors in early-life, defined as the period from preconception until age 18, play a role in shaping the risk of multiple long-term condition multimorbidity. However, there is a need to conceptualise these early-life factors, how they relate to each other, and provide conceptual framing for future research on aetiology and modelling prevention scenarios of multimorbidity. We develop a conceptual framework to characterise the population-level domains of early-life determinants of future multimorbidity. Method: This work was conducted as part of the Multidisciplinary Ecosystem to study Lifecourse Determinants and Prevention of Early-onset Burdensome Multimorbidity (MELD-B) study. The conceptualisation of multimorbidity lifecourse determinant domains was shaped by a review of existing research evidence and policy, and co-produced with public involvement via two workshops. Results: Early-life risk factors incorporate personal, social, economic, behavioural and environmental factors, and the key domains discussed in research evidence, policy, and with public contributors included adverse childhood experiences, socioeconomics, the social and physical environment, and education. Policy recommendations more often focused on individual-level factors as opposed to the wider determinants of health discussed within the research evidence. Some domains highlighted through our co-production process with public contributors, such as religion and spirituality, health screening and check-ups, and diet, were not adequately considered within the research evidence or policy. Conclusions: This co-produced conceptualisation can inform research directions using primary and secondary data to investigate the early-life characteristics of population groups at risk of future multimorbidity, as well as policy directions to target public health prevention scenarios of early-onset multimorbidity

139 - Leveraging Third Generation DNA Sequencing Technology to Explore Role of Epigenetics in Round Scad Fish under Global Climate Stress

Global climate change has been a recent pressing issue that has been seen to have environmental impacts on various ecosystems. Such environmental changes induce stress-related heritable traits without changes to the genome’s coding, a concept known as epigenetics. DNA methylation plays a key role in these cellular responses to environmental stress. The Round Scad fish is an affordable source of protein for common citizens in the Philippines, but is currently facing rapid decline both in population and average body size. The purpose of our study is to explore the patterns of DNA methylation in wild Round Scad to determine whether these changes are associated with epigenetic response to stress due to global climate change. Samples of fish DNA from the Philippines were collected and isolated. Using nanopore MinION, a portable third generation DNA sequencing technology, we are able to obtain initial DNA sequences. This technology has the advantage of directly identifying methylated nucleotides using built in softwares. Here, we shall report on the initial data comparing it with DNA methylation patterns in stress response genes of the model organism, Zebrafish. We anticipate that long term findings from this project will provide information critical to managing Round Scad and other marine fish facing similar environmental stressors

Multidisciplinary ecosystem to study lifecourse determinants and prevention of early-onset burdensome multimorbidity (MELD-B) – protocol for a research collaboration

Background: Most people living with multiple long-term condition multimorbidity (MLTC-M) are under 65 (defined as ‘early onset’). Earlier and greater accrual of long-term conditions (LTCs) may be influenced by the timing and nature of exposure to key risk factors, wider determinants or other LTCs at different life stages. We have established a research collaboration titled ‘MELD-B’ to understand how wider determinants, sentinel conditions (the first LTC in the lifecourse) and LTC accrual sequence affect risk of early-onset, burdensome MLTC-M, and to inform prevention interventions. Aim: Our aim is to identify critical periods in the lifecourse for prevention of early-onset, burdensome MLTC-M, identified through the analysis of birth cohorts and electronic health records, including artificial intelligence (AI)-enhanced analyses. Design: We will develop deeper understanding of ‘burdensomeness’ and ‘complexity’ through a qualitative evidence synthesis and a consensus study. Using safe data environments for analyses across large, representative routine healthcare datasets and birth cohorts, we will apply AI methods to identify early-onset, burdensome MLTC-M clusters and sentinel conditions, develop semi-supervised learning to match individuals across datasets, identify determinants of burdensome clusters, and model trajectories of LTC and burden accrual. We will characterise early-life (under 18 years) risk factors for early-onset, burdensome MLTC-M and sentinel conditions. Finally, using AI and causal inference modelling, we will model potential ‘preventable moments’, defined as time periods in the life course where there is an opportunity for intervention on risk factors and early determinants to prevent the development of MLTC-M. Patient and public involvement is integrated throughout

Gendered landscapes: expectations and limitations of marginalized women in Brazilian cinema

Over the years, Brazilian cinema has added many internationally critically acclaimed films to the world of cinema. While some critics would argue that Brazilian cinema itself has established itself as a key player in comparison to other national cinemas, Brazilian cinema, over time has established a definitive set of characteristics as well as genres that have made it stand out in its own right. The trajectory of Brazilian cinema over time has always been tightly linked with the unstable governmental and social issues. This is especially true of the Cinema Novo movement of the 1960s. Therefore, “what is generally true of film—the impossibility of separating filmic text from social context- is perhaps more obvious true in the case of Brazilian cinema” (Johnson and Stam 56). This characteristic has endured the development of Brazilian national cinema and still holds true today with many productions covering a wide variety of social commentary. Contemporary Brazilian films are projecting similar themes that center themselves around particular Brazilian landscapes which encapsulate within them certain socio-historical characteristics. Such landscapes (in this case: the favela, the sertão, and the urban periphery) depicted within these films create unique sets of limitations and expectations for the people living within them. Particularly, this thesis will take a gendered lens to analyze these differences and similarities within three Brazilian films, of which the protagonist is female, looking at how gender is depicted within these marginalized landscapes

Educational change and self-governing agreements: a Yukon first nation case study

More recent developments in Canada's Yukon Territory draw attention to how political changes have potential for accelerating practices in education that are responsive to Indigenous People's cultural knowledge systems and practices. In contrast to other provincial jurisdictions across Canada, treaties were historically never negotiated in the Yukon. Over the past three decades the Governments of both Canada and the Yukon have moved towards actualizing policy developments with YFNs (Yukon First Nations), called Self-Government Agreements (SGAs). The SGAs have come to finalization within the last decade and set out the powers of the First Nation government to govern itself, its citizens and its land. Self-government agreements provide self-governing First Nations (SGFNs) with law-making authority in specific areas of First Nation jurisdiction, including education. With the establishment of SGFNs, each FN, with the required co-operation of Yukon Education (YE), faces the challenge of reversing assimilation and regaining a sense of identity especially within the processes that influence the education of their children, especially at the school and, more specifically, classroom level. Although this reversal draws into question the need for changes in the content or what of classrooms, it moves beyond this to reconsider the how and why of classrooms. This paper draws from a variety of data including the accounts of key stakeholders (First Nation Chief, Elders, parents, students and Education Manager; Local Teachers and Principal; Government Leader and Curriculum Director) in describing the processes contributing to this change and the tensions that remain, ultimately at the classroom level

Our stories about teaching and learning: a pedagogy of consequences for Yukon First Nation settings

In this study, First Nation community members in Canada’s Yukon Territory share their stories about teaching and learning, both in informal and formal settings, in an effort to identify practices that might serve teachers to be more responsive to their First Nation students. In all, 52 community members between the ages of 15 and 82 shared their stories and assisted in identifying eight categories of practice and thought associated with effective teaching practices for this First Nation. Based upon these categories of thought and practice, we present a pedagogical framework for teachers and, finally, illustrate how this profile and the stories about teaching and learning are being used for adjusting and improving teaching practice in this First Nation

Severe COVID-19 outcomes after full vaccination of primary schedule and initial boosters: pooled analysis of national prospective cohort studies of 30 million individuals in England, Northern Ireland, Scotland, and Wales

BackgroundCurrent UK vaccination policy is to offer future COVID-19 booster doses to individuals at high risk of serious illness from COVID-19, but it is still uncertain which groups of the population could benefit most. In response to an urgent request from the UK Joint Committee on Vaccination and Immunisation, we aimed to identify risk factors for severe COVID-19 outcomes (ie, COVID-19-related hospitalisation or death) in individuals who had completed their primary COVID-19 vaccination schedule and had received the first booster vaccine.MethodsWe constructed prospective cohorts across all four UK nations through linkages of primary care, RT-PCR testing, vaccination, hospitalisation, and mortality data on 30 million people. We included individuals who received primary vaccine doses of BNT162b2 (tozinameran; Pfizer–BioNTech) or ChAdOx1 nCoV-19 (Oxford–AstraZeneca) vaccines in our initial analyses. We then restricted analyses to those given a BNT162b2 or mRNA-1273 (elasomeran; Moderna) booster and had a severe COVID-19 outcome between Dec 20, 2021, and Feb 28, 2022 (when the omicron (B.1.1.529) variant was dominant). We fitted time-dependent Poisson regression models and calculated adjusted rate ratios (aRRs) and 95% CIs for the associations between risk factors and COVID-19-related hospitalisation or death. We adjusted for a range of potential covariates, including age, sex, comorbidities, and previous SARS-CoV-2 infection. Stratified analyses were conducted by vaccine type. We then did pooled analyses across UK nations using fixed-effect meta-analyses.FindingsBetween Dec 8, 2020, and Feb 28, 2022, 16 208 600 individuals completed their primary vaccine schedule and 13 836 390 individuals received a booster dose. Between Dec 20, 2021, and Feb 28, 2022, 59 510 (0·4%) of the primary vaccine group and 26 100 (0·2%) of those who received their booster had severe COVID-19 outcomes. The risk of severe COVID-19 outcomes reduced after receiving the booster (rate change: 8·8 events per 1000 person-years to 7·6 events per 1000 person-years). Older adults (≥80 years vs 18–49 years; aRR 3·60 [95% CI 3·45–3·75]), those with comorbidities (≥5 comorbidities vs none; 9·51 [9·07–9·97]), being male (male vs female; 1·23 [1·20–1·26]), and those with certain underlying health conditions—in particular, individuals receiving immunosuppressants (yes vs no; 5·80 [5·53–6·09])—and those with chronic kidney disease (stage 5 vs no; 3·71 [2·90–4·74]) remained at high risk despite the initial booster. Individuals with a history of COVID-19 infection were at reduced risk (infected ≥9 months before booster dose vs no previous infection; aRR 0·41 [95% CI 0·29–0·58]).InterpretationOlder people, those with multimorbidity, and those with specific underlying health conditions remain at increased risk of COVID-19 hospitalisation and death after the initial vaccine booster and should, therefore, be prioritised for additional boosters, including novel optimised versions, and the increasing array of COVID-19 therapeutics