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30-day mortality might be a useful indicator of avoidable harm to patients from systemic anticancer treatments, but data for this indicator are limited. The Systemic Anti-Cancer Therapy (SACT) dataset collated by Public Health England allows the assessment of factors affecting 30-day mortality in a national patient population. The aim of this first study based on the SACT dataset was to establish national 30-day mortality benchmarks for breast and lung cancer patients receiving SACT in England, and to start to identify where patient care could be improved. In this population-based study, we included all women with breast cancer and all men and women with lung cancer residing in England, who were 24 years or older and who started a cycle of SACT in 2014 irrespective of the number of previous treatment cycles or programmes, and irrespective of their position within the disease trajectory. We calculated 30-day mortality after the most recent cycle of SACT for those patients. We did logistic regression analyses, adjusting for relevant factors, to examine whether patient, tumour, or treatment-related factors were associated with the risk of 30-day mortality. For each cancer type and intent, we calculated 30-day mortality rates and patient volume at the hospital trust level, and contrasted these in a funnel plot. Between Jan 1, and Dec, 31, 2014, we included 23 228 patients with breast cancer and 9634 patients with non-small cell lung cancer (NSCLC) in our regression and trust-level analyses. 30-day mortality increased with age for both patients with breast cancer and patients with NSCLC treated with curative intent, and decreased with age for patients receiving palliative SACT (breast curative: odds ratio [OR] 1·085, 99% CI 1·040–1·132; p<0·0001; NSCLC curative: 1·045, 1·013–1·079; p=0·00033; breast palliative: 0·987, 0·977–0·996; p=0·00034; NSCLC palliative: 0·987, 0·976–0·998; p=0·0015). 30-day mortality was also significantly higher for patients receiving their first reported curative or palliative SACT versus those who received SACT previously (breast palliative: OR 2·326 99% CI 1·634–3·312; p<0·0001; NSCLC curative: 3·371, 1·554–7·316; p<0·0001; NSCLC palliative: 2·667, 2·109–3·373; p<0·0001), and for patients with worse general wellbeing (performance status 2–4) versus those who were generally well (breast curative: 6·057, 1·333–27·513; p=0·0021; breast palliative: 6·241, 4·180–9·319; p<0·0001; NSCLC palliative: 3·384, 2·276–5·032; p<0·0001). We identified trusts with mortality rates in excess of the 95% control limits; this included seven for curative breast cancer, four for palliative breast cancer, five for curative NSCLC, and seven for palliative NSCLC. Our findings show that several factors affect the risk of early mortality of breast and lung cancer patients in England and that some groups are at a substantially increased risk of 30-day mortality. The identification of hospitals with significantly higher 30-day mortality rates should promote review of clinical decision making in these hospitals. Furthermore, our results highlight the importance of collecting routine data beyond clinical trials to better understand the factors placing patients at higher risk of 30-day mortality, and ultimately improve clinical decision making. Our insights into the factors affecting risk of 30-day mortality will help treating clinicians and their patients predict the balance of harms and benefits associated with SACT. Public Health England.

Objectives To quantify the use of sunbeds in young people across England, identify geographical variation, and explore patterns of use, including supervision.Design Two random location sampling surveys.Setting National Prevalence Study in England; Six Cities Study in Liverpool, Stoke/Stafford, Sunderland, Bath/Gloucester, Oxford/Cambridge, and Southampton.Participants 3101 children aged 11-17 in the National Prevalence study and 6209 in the Six Cities study.Results In the National Prevalence Study 6.0% (95% confidence interval 5.1% to 6.8%) of those aged 11-17 had used a sunbed. Use was higher in girls than in boys (8.6% (7.2% to 10.0%) v 3.5% (2.6% to 4.4%), respectively), in those aged 15-17 compared with those aged 11-14 (11.2% (9.5% to 12.9%) v 1.8% (1.2% to 2.4%), respectively), and in those from lower rather than higher social grades (7.6% (5.7% to 9.5%) v 5.4% (4.5% to 6.3%), respectively). Sunbed use was higher in the “north” (11.0%, 8.9% to 13.0%) than in the “midlands” (4.2%, 2.5% to 5.8%) and the “south” (4.2%, 3.3% to 5.2%). In the Six Cities Study, sunbed use was highest in Liverpool and Sunderland (20.0% (17.5% to 22.4%) and 18.0% (15.6% to 20.3%), respectively), with rates especially high in girls, those aged 15-17, or from lower social grades. Mean age of first use was 14, and 38.4% (34.7% to 42.1%) of children used a sunbed at least once a week. Nearly a quarter (23.0%, 19.8% to 26.1%) of children had used a sunbed at home (including home of friends/relatives), and 24.7% (21.0% to 28.4%) said they had used sunbeds unsupervised in a tanning/beauty salon or gym/leisure centre.Conclusions Sunbed use by children is widespread in England, is often inadequately supervised, and is a health risk. National legislation is needed to control sunbed outlets.

Background Abnormally sustained immune reactions drive B-cell proliferation in some cases of marginal zone lymphoma but the CD4 + T-cell subsets, which are likely to contribute to the B-cell responses in the tumour microenvironment, are not well characterised and neither has the spatial distribution of the different subsets in involved lymph nodes been investigated. Methods Employing a workflow of multiplex semi-automated immunohistochemistry combined with image processing we investigated association between infiltrating T-cells and proliferating lymphoma B-cells. Results Both total numbers of activating follicular helper (Tfh) cells (defined by high expression of PD1) and suppressive regulatory (Treg) T-cells (defined by FOXP3 + expression) and the Tfh:Treg ratio, assessed over relatively large areas of tissue, varied among cases of marginal zone lymphoma. We determined spatial distribution and demonstrated that PD1 hi cells showed significantly more clustering than did FOXP3 + . To investigate the association of infiltrating T-cells with lymphoma B-cells we employed Pearson correlation and Morisita-Horn index, statistical measures of interaction. We demonstrated that PD1 hi cells were associated with proliferating B-cells and confirmed this by nearest neighbour analysis. Conclusions The unexpected architectural complexity of T-cell infiltration in marginal zone lymphoma, revealed in this study, further supports a key role for Tfh cells in driving proliferation of lymphoma B-cells. We demonstrate the feasibility of digital analysis of spatial architecture of T-cells within marginal zone lymphoma and future studies will be needed to determine the clinical importance of these observations.

Abnormally sustained immune reactions drive B-cell proliferation in some cases of marginal zone lymphoma but the CD4 T-cell subsets, which are likely to contribute to the B-cell responses in the tumour microenvironment, are not well characterised and neither has the spatial distribution of the different subsets in involved lymph nodes been investigated. Employing a workflow of multiplex semi-automated immunohistochemistry combined with image processing we investigated association between infiltrating T-cells and proliferating lymphoma B-cells. Both total numbers of activating follicular helper (Tfh) cells (defined by high expression of PD1) and suppressive regulatory (Treg) T-cells (defined by FOXP3 expression) and the Tfh:Treg ratio, assessed over relatively large areas of tissue, varied among cases of marginal zone lymphoma. We determined spatial distribution and demonstrated that PD1 cells showed significantly more clustering than did FOXP3 . To investigate the association of infiltrating T-cells with lymphoma B-cells we employed Pearson correlation and Morisita-Horn index, statistical measures of interaction. We demonstrated that PD1 cells were associated with proliferating B-cells and confirmed this by nearest neighbour analysis. The unexpected architectural complexity of T-cell infiltration in marginal zone lymphoma, revealed in this study, further supports a key role for Tfh cells in driving proliferation of lymphoma B-cells. We demonstrate the feasibility of digital analysis of spatial architecture of T-cells within marginal zone lymphoma and future studies will be needed to determine the clinical importance of these observations.

Campylobacter is the most common cause of bacterial gastroenteritis worldwide and diarrheal disease is a major cause of child morbidity, growth faltering and mortality in low- and middle-income countries (LMICs). Despite evidence of high incidence and differences in disease epidemiology, there is limited genomic data from studies in developing countries. In this study, we characterised the genetic diversity and accessory genome content of a collection of Campylobacter isolates from Cairo, Egypt. In total, 112 Campylobacter isolates were collected from broiler carcasses (n=31), milk and dairy products (n=24) and patients (n=57) suffering from gastroenteritis. Among the most common sequence types (STs) we identified were the globally disseminated, host generalist ST-21 clonal complex (CC21) and the poultry specialist CC206, CC464 and CC48. Notably, CC45 and the cattle-specialist CC42 were under-represented with a total absence of CC61. Comparative genomics were used to quantify core and accessory genome sharing among isolates from the same country compared to sharing between countries. Lineage-specific accessory genome sharing was significantly higher among isolates from the same country, particularly CC21 which demonstrated greater local geographical clustering. In contrast, no geographic clustering was noted in either the core or accessory genomes of the CC828, suggesting a highly admixed population. A greater proportion of C. coli isolates were multidrug resistant (MDR) compared to C. jejuni. This is a significant public health concern as MDR food chain pathogens are difficult to treat and often pose increased mortality risk demanding enhanced prevention strategies in the Egyptian market to combat such a threat. Campylobacter is the leading bacterial cause of gastroenteritis worldwide and despite high incidence in low- and middle-income countries, where infection can be fatal, culture-based isolation is rare and the genotypes responsible for disease are seldom identified. Here, we sequenced the genomes of a collection of isolates from clinical cases and potential infection reservoirs from Cairo in Egypt and characterised their genetic diversity. Among the most common genotypes we identified were globally disseminated lineages implicated in human disease worldwide, including the host generalist ST-21 clonal complex (CC21) and the poultry specialist genotypes CC206, CC464 and CC48. Notably however, some other globally common genotypes were under-represented or entirely absent from our collection, including those from cattle-specialist lineages, CC42 and CC61. By focussing on specific lineages, we demonstrate that there is increased accessory genome sharing in specific clonal complexes. This increased local sharing of genes may have contributed to a greater proportion of C. coli isolates possessing antimicrobial resistance determinants that suggest they could be multidrug resistant (MDR). This is a significant public health concern as MDR food chain pathogens are difficult to treat and often pose increased mortality risk demanding enhanced prevention strategies. Short read data are available on the NCBI Sequence Read Archive, associated with BioProject PRJNA576513 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA576513). Assembled genomes, supplementary material and additional analysis files are available from FigShare: https://doi.org/10.6084/m9.figshare.9956597. Phylogenetic trees can be visualised and manipulated on Microreact for C. jejuni (https://next.microreact.org/project/Cjejuni_Egypt) and C. coli (https://next.microreact.org/project/Ccoli_Egypt) separately, or combined Cairo and Oxford data with additional PopPunk network clustering (https://microreact.org/project/Campy-Egypt).