Postoperative infection and mortality following elective surgery in the International Surgical Outcomes Study (ISOS).

BACKGROUND: Postoperative infection is one of the most frequent and important complications after surgery. The epidemiology of infection following elective surgery remains poorly described. METHODS: This was a prospective analysis of the International Surgical Outcomes Study (ISOS) describing infection by 30 days after elective surgery. Associations between postoperative infection (primary outcome) and baseline demographic, surgical, and anaesthetic risk factors were assessed. Analyses were carried out using logistic and linear regression models. Secondary outcomes were 30-day mortality and duration of hospital stay. Treatments received by patients after different types of infection were evaluated. RESULTS: Some 44 814 patients were included in the analysis, with a total of 4032 infections occurring in 2927 patients (6.5 per cent). Overall, 206 patients died, of whom 99 of 2927 (3.4 per cent) had infection. Some 737 of 4032 infections (18.3 per cent) were severe; the most frequent types were superficial surgical-site infection (1320, 32.7 per cent), pneumonia (708, 17.6 per cent), and urinary tract infection (681, 16.9 per cent). Excluding missing data, antimicrobials were used in 2126 of 2749 infections (77.3 per cent), and 522 of 2164 patients (24.1 per cent) required admission to critical care. Factors associated with an increased incidence of infection in adjusted analyses were: age, male sex, ASA grade, co-morbid disease, preoperative anaemia, anaesthetic technique, surgical category, surgical severity, and cancer surgery. Infection significantly increased the risk of death (odds ratio 4.68, 95 per cent c.i. 3.39 to 6.47; P < 0.001), and duration of hospital stay by on average 6.45 (6.23 to 6.66) days (P < 0.001). CONCLUSION: Infection is a common complication after elective surgery. Recognition of modifiable risk factors will help inform appropriate prevention strategies.

Resource requirements for reintroducing elective surgery during the COVID-19 pandemic: modelling study.

BACKGROUND: The COVID-19 response required the cancellation of all but the most urgent surgical procedures. The number of cancelled surgical procedures owing to Covid-19, and the reintroduction of surgical acivirt, was modelled. METHODS: This was a modelling study using Hospital Episode Statistics data (2014-2019). Surgical procedures were grouped into four urgency classes. Expected numbers of surgical procedures performed between 1 March 2020 and 28 February 2021 were modelled. Procedure deficit was estimated using conservative assumptions and the gradual reintroduction of elective surgery from the 1 June 2020. Costs were calculated using NHS reference costs and are reported as millions or billions of euros. Estimates are reported with 95 per cent confidence intervals. RESULTS: A total of 4 547 534 (95 per cent c.i. 3 318 195 to 6 250 771) patients with a pooled mean age of 53.5 years were expected to undergo surgery between 1 March 2020 and 28 February 2021. By 31 May 2020, 749 247 (513 564 to 1 077 448) surgical procedures had been cancelled. Assuming that elective surgery is reintroduced gradually, 2 328 193 (1 483 834 - 3 450 043) patients will be awaiting surgery by 28 February 2021. The cost of delayed procedures is €5.3 (3.1 to 8.0) billion. Safe delivery of surgery during the pandemic will require substantial extra resources costing €526.8 (449.3 to 633.9) million. CONCLUSION: As a consequence of the Covid-19 pandemic, provision of elective surgery will be delayed and associated with increased healthcare costs.

Dental Surgical Activity in Hospitals during COVID-19: A Nationwide Observational Cohort Study.

INTRODUCTION: The number of surgical extractions performed in hospitals in England remains unclear. This study reports the volume of surgical extractions conducted in hospitals and change in activity during the COVID-19 pandemic. METHODS: We conducted a nationwide observational cohort study using Hospital Episode Statistics (HES) in England for patients undergoing surgical removal of a tooth (defined using OPSC-4 code F09) between April 1, 2015, and December 31, 2020. Procedures were stratified by age, gender, and urgency (elective or nonelective), reported using descriptive statistics, number, and percentage. We conducted post hoc modeling to predict surgical activity to December 2023. In addition, we contrasted this with aggregate national data on simple dental extraction procedures and drainage of dental abscesses in hospital as well as dental activity in general practice. RESULTS: We identified a total of 569,938 episodes for the surgical removal of a tooth (females 57%). Of these, 493,056/569,938 (87%) were for adults and 76,882/569,938 (13%) children ≤18 years. Surgical extractions were most frequent in adult females. Elective cases accounted for 96% (n = 548,805/569,938) of procedures. The median number of procedures carried out per quarter was 27,256, dropping to 12,003 during the COVID-19 pandemic, representing a 56% reduction in activity. This amounted to around 61,058 cancelled procedures. Modeling predicts that this activity has not returned to prepandemic levels. CONCLUSIONS: The number of surgical extractions taking place in hospitals during the pandemic fell by 56%. The true impact of this reduction is unknown, but delayed treatment increases the risk of complications, including life-threatening infections. KNOWLEDGE TRANSFER STATEMENT: The result of this study provides an evidence-based overview of the trends relating to surgical extractions of teeth in England taking place in hospitals. This information can be used to inform service and workforce planning to meet the needs of patients requiring surgical extractions. The data also provide an insight into the oral health needs of the population in England.

Health Resource Utilisation and Disparities: an Ecological Study of Admission Patterns Across Ethnicity in England Between 2017 and 2020.

BACKGROUND AND AIM: The COVID-19 pandemic highlighted adverse outcomes in Asian, Black, and ethnic minority groups. More research is required to explore underlying ethnic health inequalities. In this study, we aim to examine pre-COVID ethnic inequalities more generally through healthcare utilisation to contextualise underlying inequalities that were present before the pandemic. DESIGN: This was an ecological study exploring all admissions to NHS hospitals in England from 2017 to 2020. METHODS: The primary outcomes were admission rates within ethnic groups. Secondary outcomes included age-specific and age-standardised admission rates. Sub-analysis of admission rates across an index of multiple deprivation (IMD) deciles was also performed to contextualise the impact of socioeconomic differences amongst ethnic categories. Results were presented as a relative ratio (RR) with 95% confidence intervals. RESULTS: Age-standardised admission rates were higher in Asian (RR 1.40 [1.38-1.41] in 2019) and Black (RR 1.37 [1.37-1.38]) and lower in Mixed groups (RR 0.91 [0.90-0.91]) relative to White. There was significant missingness or misassignment of ethnicity in NHS admissions: with 11.7% of admissions having an unknown/not-stated ethnicity assignment and 'other' ethnicity being significantly over-represented. Admission rates did not mirror the degree of deprivation across all ethnic categories. CONCLUSIONS: This study shows Black and Asian ethnic groups have higher admission rates compared to White across all age groups and when standardised for age. There is evidence of incomplete and misidentification of ethnicity assignment in NHS admission records, which may introduce bias to work on these datasets. Differences in admission rates across individual ethnic categories cannot solely be explained by socioeconomic status. Further work is needed to identify ethnicity-specific factors of these inequalities to allow targeted interventions at the local level.

Genome-wide association study to identify genetic determinants of severe asthma.

BACKGROUND: The genetic basis for developing asthma has been extensively studied. However, association studies to date have mostly focused on mild to moderate disease and genetic risk factors for severe asthma remain unclear. OBJECTIVE: To identify common genetic variants affecting susceptibility to severe asthma. METHODS: A genome-wide association study was undertaken in 933 European ancestry individuals with severe asthma based on Global Initiative for Asthma (GINA) criteria 3 or above and 3346 clean controls. After standard quality control measures, the association of 480 889 genotyped single nucleotide polymorphisms (SNPs) was tested. To improve the resolution of the association signals identified, non-genotyped SNPs were imputed in these regions using a dense reference panel of SNP genotypes from the 1000 Genomes Project. Then replication of SNPs of interest was undertaken in a further 231 cases and 1345 controls and a meta-analysis was performed to combine the results across studies. RESULTS: An association was confirmed in subjects with severe asthma of loci previously identified for association with mild to moderate asthma. The strongest evidence was seen for the ORMDL3/GSDMB locus on chromosome 17q12-21 (rs4794820, p=1.03×10((-8)) following meta-analysis) meeting genome-wide significance. Strong evidence was also found for the IL1RL1/IL18R1 locus on 2q12 (rs9807989, p=5.59×10((-8)) following meta-analysis) just below this threshold. No novel loci for susceptibility to severe asthma met strict criteria for genome-wide significance. CONCLUSIONS: The largest genome-wide association study of severe asthma to date was carried out and strong evidence found for the association of two previously identified asthma susceptibility loci in patients with severe disease. A number of novel regions with suggestive evidence were also identified warranting further study.

Ethnic disparities in hospitalisation and hospital-outcomes during the second wave of COVID-19 infection in east London.

It is unclear if changes in public behaviours, developments in COVID-19 treatments, improved patient care, and directed policy initiatives have altered outcomes for minority ethnic groups in the second pandemic wave. This was a prospective analysis of patients aged ≥ 16 years having an emergency admission with SARS-CoV-2 infection between 01/09/2020 and 17/02/2021 to acute NHS hospitals in east London. Multivariable survival analysis was used to assess associations between ethnicity and mortality accounting for predefined risk factors. Age-standardised rates of hospital admission relative to the local population were compared between ethnic groups. Of 5533 patients, the ethnic distribution was White (n = 1805, 32.6%), Asian/Asian British (n = 1983, 35.8%), Black/Black British (n = 634, 11.4%), Mixed/Other (n = 433, 7.8%), and unknown (n = 678, 12.2%). Excluding 678 patients with missing data, 4855 were included in multivariable analysis. Relative to the White population, Asian and Black populations experienced 4.1 times (3.77-4.39) and 2.1 times (1.88-2.33) higher rates of age-standardised hospital admission. After adjustment for various patient risk factors including age, sex, and socioeconomic deprivation, Asian patients were at significantly higher risk of death within 30 days (HR 1.47 [1.24-1.73]). No association with increased risk of death in hospitalised patients was observed for Black or Mixed/Other ethnicity. Asian and Black ethnic groups continue to experience poor outcomes following COVID-19. Despite higher-than-expected rates of hospital admission, Black and Asian patients also experienced similar or greater risk of death in hospital since the start of the pandemic, implying a higher overall risk of COVID-19 associated death in these communities.

Endoglin expression in blood and endothelium is differentially regulated by modular assembly of the Ets/Gata hemangioblast code.

Endoglin is an accessory receptor for TGF-beta signaling and is required for normal hemangioblast, early hematopoietic, and vascular development. We have previously shown that an upstream enhancer, Eng -8, together with the promoter region, mediates robust endothelial expression yet is inactive in blood. To identify hematopoietic regulatory elements, we used array-based methods to determine chromatin accessibility across the entire locus. Subsequent transgenic analysis of candidate elements showed that an endothelial enhancer at Eng +9 when combined with an element at Eng +7 functions as a strong hemato-endothelial enhancer. Chromatin immunoprecipitation (ChIP)-chip analysis demonstrated specific binding of Ets factors to the promoter as well as to the -8, +7+9 enhancers in both blood and endothelial cells. By contrast Pu.1, an Ets factor specific to the blood lineage, and Gata2 binding was only detected in blood. Gata2 was bound only at +7 and GATA motifs were required for hematopoietic activity. This modular assembly of regulators gives blood and endothelial cells the regulatory freedom to independently fine-tune gene expression and emphasizes the role of regulatory divergence in driving functional divergence.

Achievement of equity and universal access in China's health service: a commentary on the historical reform perspective from the UK National Health Service.

This paper aims to examine the UK National Health Service (NHS) in the historical context of its background reforms and to investigate future developmental strategies for China's health system. We focus on the central issues facing China's future healthcare development: equity and access. China and the UK have approached healthcare reform from opposite perspectives, the NHS has maintained the core principle of providing universal health coverage throughout the decades. However, due to increasing demand, reforms to improve and sustain efficiency have meant increasing government funding while introducing elements of a market system. Conversely, China has moved from a centrally planned system to a fee-for-service system, but serious problems of inequity and access call for new methods of organisation and financing. With the future of both systems under constant debate, international experience will play a vital role in formulating health system reform strategies.

The paralogous hematopoietic regulators Lyl1 and Scl are coregulated by Ets and GATA factors, but Lyl1 cannot rescue the early Scl-/- phenotype.

Transcription factors are key regulators of hematopoietic stem cells (HSCs), yet the molecular mechanisms that control their expression are largely unknown. Previously, we demonstrated that expression of Scl/Tal1, a transcription factor required for the specification of HSCs, is controlled by Ets and GATA factors. Here we characterize the molecular mechanisms controlling expression of Lyl1, a paralog of Scl also required for HSC function. Two closely spaced promoters directed expression to hematopoietic progenitor, megakaryocytic, and endothelial cells in transgenic mice. Conserved binding sites required for promoter activity were bound in vivo by GATA-2 and the Ets factors Fli1, Elf1, Erg, and PU.1. However, despite coregulation of Scl and Lyl1 by the same Ets and GATA factors, Scl expression was initiated prior to Lyl1 in embryonic stem (ES) cell differentiation assays. Moreover, ectopic expression of Scl but not Lyl1 rescued hematopoietic differentiation in Scl-/- ES cells, thus providing a molecular explanation for the vastly different phenotypes of Scl-/- and Lyl1-/- mouse embryos. Furthermore, coregulation of Scl and Lyl1 later during development may explain the mild phenotype of Scl-/- adult HSCs.

Gata2, Fli1, and Scl form a recursively wired gene-regulatory circuit during early hematopoietic development.

Conservation of the vertebrate body plan has been attributed to the evolutionary stability of gene-regulatory networks (GRNs). We describe a regulatory circuit made up of Gata2, Fli1, and Scl/Tal1 and their enhancers, Gata2-3, Fli1+12, and Scl+19, that operates during specification of hematopoiesis in the mouse embryo. We show that the Fli1+12 enhancer, like the Gata2-3 and Scl+19 enhancers, targets hematopoietic stem cells (HSCs) and relies on a combination of Ets, Gata, and E-Box motifs. We show that the Gata2-3 enhancer also uses a similar cluster of motifs and that Gata2, Fli1, and Scl are expressed in embryonic day-11.5 dorsal aorta where HSCs originate and in fetal liver where they multiply. The three HSC enhancers in these tissues and in ES cell-derived hemangioblast equivalents are bound by each of these transcription factors (TFs) and form a fully connected triad that constitutes a previously undescribed example of both this network motif in mammalian development and a GRN kernel operating during the specification of a mammalian stem cell.