Risk of skin cancer after neonatal phototherapy : retrospective cohort study

Peer reviewedPostprin

How do world and European standard populations impact burden of disease studies? A case study of disability-adjusted life years (DALYs) in Scotland

Background Disability-Adjusted Life Years (DALYs) are an established method for quantifying population health needs and guiding prioritisation decisions. Global Burden of Disease (GBD) estimates aim to ensure comparability between countries and over time by using age-standardised rates (ASR) to account for differences in the age structure of different populations. Different standard populations are used for this purpose but it is not widely appreciated that the choice of standard may affect not only the resulting rates but also the rankings of causes of DALYs. We aimed to evaluate the impact of the choice of standard, using the example of Scotland. Methods DALY estimates were derived from the 2016 Scottish Burden of Disease (SBoD) study for an abridged list of 68 causes of disease/injury, representing a three-year annual average across 2014–16. Crude DALY rates were calculated using Scottish national population estimates. DALY ASRs standardised using the GBD World Standard Population (GBD WSP) were compared to those using the 2013 European Standard Population (ESP2013). Differences in ASR and in rank order within the cause list were summarised for all-cause and for each individual cause. Results The ranking of causes by DALYs were similar using crude rates or ASR (ESP2013). All-cause DALY rates using ASR (GBD WSP) were around 26% lower. Overall 58 out of 68 causes had a lower ASR using GBD WSP compared with ESP2013, with the largest falls occurring for leading causes of mortality observed in older ages. Gains in ASR were much smaller in absolute scale and largely affected causes that operated early in life. These differences were associated with a substantial change to the ranking of causes when GBD WSP was used compared with ESP2013. Conclusion Disease rankings based on DALY ASRs are strongly influenced by the choice of standard population. While GBD WSP offers international comparability, within-country analyses based on DALY ASRs should reflect local age structures. For European countries, including Scotland, ESP2013 may better guide local priority setting by avoiding large disparities occurring between crude and age-standardised results sets, which could potentially confuse non-technical audiences

Inequalities in population health loss by multiple deprivation: COVID-19 and pre-pandemic all-cause disability-adjusted life years (DALYs) in Scotland

Background: COVID-19 has caused almost unprecedented change across health, education, the economy and social interaction. It is widely understood that the existing mechanisms which shape health inequalities have resulted in COVID-19 outcomes following this same, familiar, pattern. Our aim was to estimate inequalities in the population health impact of COVID-19 in Scotland, measured by disability-adjusted life years (DALYs) in 2020. Our secondary aim was to scale overall, and inequalities in, COVID-19 DALYs against the level of pre-pandemic inequalities in all-cause DALYs, derived from the Scottish Burden of Disease (SBoD) study. Methods: National deaths and daily case data were input into the European Burden of Disease Network consensus model to estimate DALYs. Total Years of Life Lost (YLL) were estimated for each area-based deprivation quintile of the Scottish population. Years Lived with Disability were proportionately distributed to deprivation quintiles, based on YLL estimates. Inequalities were measured by: the range, Relative Index of Inequality (RII), Slope Index of Inequality (SII), and attributable DALYs were estimated by using the least deprived quintile as a reference. Results: Marked inequalities were observed across several measures. The SII range was 2048 to 2289 COVID-19 DALYs per 100,000 population. The rate in the most deprived areas was around 58% higher than the mean population rate (RII = 1.16), with 40% of COVID-19 DALYs attributed to differences in area-based deprivation. Overall DALYs due to COVID-19 ranged from 7 to 20% of the annual pre-pandemic impact of inequalities in health loss combined across all causes. Conclusion: The substantial population health impact of COVID-19 in Scotland was not shared equally across areas experiencing different levels of deprivation. The extent of inequality due to COVID-19 was similar to averting all annual DALYs due to diabetes. In the wider context of population health loss, overall ill-health and mortality due to COVID-19 was, at most, a fifth of the annual population health loss due to inequalities in multiple deprivation. Implementing effective policy interventions to reduce health inequalities must be at the forefront of plans to recover and improve population health

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p