People's experiences of cancer within the first year following diagnosis. Final Report

The aim of the study was to explore the experiences of people affected by cancer in the first year following diagnosis with breast, lung, colorectal, prostate or gynaecological cancer. This was a descriptive qualitative study conducted over a period of 18 months during which three serial, longitudinal semi-structured interviews with 66 people, their nominated partner/carer1 (n=43) and healthcare professional (n=20) were conducted. The study included 18 people with colorectal cancer, 12 women with breast cancer, 9 women with gynaecological cancer, 17 people with lung cancer and 10 men with prostate cancer. The sampling strategy was not designed to derive a representative sample but to enable the researchers to understand experience of cancer and cancer care from men and women with a different cancer diagnosis and who had different socio-economic backgrounds and lived either in a rural or urban area. A conscious effort was made to include people from different ethnic minority groups but this was unsuccessful because no or very small numbers of people from these groups were diagnosed with cancer during the period of recruitment in the cancer centres where healthcare professionals were recruiting for the study

A decade and a half of learning from Madagascar’s first locally managed marine area

While the participatory management of small scale fisheries has been widely promoted, we have limited understanding of the factors influencing its effectiveness. Here, we highlight lessons learnt from the implementation of Madagascar’s first locally managed marine area (LMMA), drawing on our insights and experiences as staff of a co-managing non-governmental organisation (NGO). We describe the LMMA’s context and history, and highlight aspects of our approach that we feel underpin its outcomes, including: i) co-management rather than community-management, ii) the permanent field presence of a supporting NGO, iii) a management focus on locally-important natural resources, iv) the implementation of poverty-alleviation initiatives aimed at reducing barriers to management, v) decision-making by resource users rather than scientists, vi) a diversified, entrepreneurial funding model, and vii) an emphasis on monitoring and adaptive management. We also highlight several challenges, including: i) the inability to influence fishery supply chains, ii) promoting participation and good governance, iii) promoting rule application, iv) standing up to outsiders, v) promoting environmental management in the long term, and vi) maintaining funding. Our experiences suggest that small scale fishers can be effective natural resource managers in low income contexts, but may need extended support from outsiders; however the role of supporting NGO is nuanced and complex

Supporting Parents Living in Disadvantaged Areas of Edinburgh to Create a Smoke-Free Home Using Nicotine Replacement Therapy (NRT): A Two-Phase Qualitative Study

Exposure to second-hand smoke (SHS) in the home is largely associated with socio-economic disadvantage. Disadvantaged parents face specific challenges creating a smoke-free home, often caring for children in accommodation without access to outdoor garden space. Existing smoke-free home interventions largely fail to accommodate these constraints. Innovative approaches are required to address this inequality. In this two-phase study, we engaged with parents living in disadvantaged areas of Edinburgh, Scotland, to explore tailored approaches to creating a smoke-free home and develop and pilot-test an intervention based on their views and preferences. In Phase 1, qualitative interviews with 17 parents recruited from Early Years Centres explored alternative approaches to smoke-free home interventions. In Phase 2, an intervention based on parents’ views and preferences was pilot-tested with parents recruited through Early Years and Family Nurse Partnership centres. Seventeen parents took part in an interview to share their views/experiences of the intervention. Data from both study phases were thematically analysed. Phase 1 findings suggested that parents associated nicotine replacement therapy (NRT) with quit attempts but supported the idea of NRT use for temporary abstinence to create a smoke-free home, viewing this as a safer option than using e-cigarettes indoors. In Phase 2, 54 parents expressed an interest in accessing NRT to create a smoke-free home, 32 discussed NRT product choice during a home visit from a smoking adviser, and 20 collected their free NRT prescription from the pharmacy. NRT was used for up to 12 weeks in the home, with ongoing advice available from pharmacy staff. During qualitative interviews (n = 17), parents self-reported successfully creating a smoke-free home, quitting smoking, and reduced cigarette consumption, often exceeding their expectations regarding changes made. The intervention was acceptable to parents, but the multi-step process used to access NRT was cumbersome. Some participants were lost to this process. Parents living in disadvantaged circumstances may benefit from access to NRT for temporary abstinence in the home to assist them to protect their children from SHS exposure. Further research using a more streamlined approach to NRT access is required to determine the feasibility and cost-effectiveness of this approach

Ongoing developments in sporadic inclusion body myositis

Sporadic inclusion body myositis (IBM) is an acquired muscle disorder associated with ageing, for which there is no effective treatment. Ongoing developments include: genetic studies that may provide insights regarding the pathogenesis of IBM, improved histopathological markers, the description of a new IBM autoantibody, scrutiny of the diagnostic utility of clinical features and biomarkers, the refinement of diagnostic criteria, the emerging use of MRI as a diagnostic and monitoring tool, and new pathogenic insights that have led to novel therapeutic approaches being trialled for IBM, including treatments with the objective of restoring protein homeostasis and myostatin blockers. The effect of exercise in IBM continues to be investigated. However, despite these ongoing developments, the aetiopathogenesis of IBM remains uncertain. A translational and multidisciplinary collaborative approach is critical to improve the diagnosis, treatment, and care of patients with IBM

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant

SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Background: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. Methods: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. Findings: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. Interpretation: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. Funding: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant