COVID-19 vaccine effectiveness against hospitalisation and death of people in clinical risk groups during the Delta variant period: English primary care network cohort study.

BACKGROUND: COVID-19 vaccines have been shown to be highly effective against hospitalisation and death following COVID-19 infection. COVID-19 vaccine effectiveness estimates against severe endpoints among individuals with clinical conditions that place them at increased risk of critical disease are limited. METHODS: We used English primary care medical record data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre sentinel network (N > 18 million). Data were linked to the National Immunisation Management Service database, Second Generation Surveillance System for virology test data, Hospital Episode Statistics, and death registry data. We estimated adjusted vaccine effectiveness (aVE) against COVID-19 infection followed by hospitalisation and death among individuals in specific clinical risk groups using a cohort design during the delta-dominant period. We also report mortality statistics and results from our antibody surveillance in this population. FINDINGS: aVE against severe endpoints was high, 14-69d following a third dose aVE was 96.4% (95.1%-97.4%) and 97.9% (97.2%-98.4%) for clinically vulnerable people given a Vaxzevria and Comirnaty primary course respectively. Lower aVE was observed in the immunosuppressed group: 88.6% (79.1%-93.8%) and 91.9% (85.9%-95.4%) for Vaxzevria and Comirnaty respectively. Antibody levels were significantly lower among the immunosuppressed group than those not in this risk group across all vaccination types and doses. The standardised case fatality rate within 28 days of a positive test was 3.9/1000 in people not in risk groups, compared to 12.8/1000 in clinical risk groups. Waning aVE with time since 2nd dose was also demonstrated, for example, Comirnaty aVE against hospitalisation reduced from 96.0% (95.1-96.7%) 14-69days post-dose 2-82.9% (81.4-84.2%) 182days+ post-dose 2. INTERPRETATION: In all clinical risk groups high levels of vaccine effectiveness against severe endpoints were seen. Reduced vaccine effectiveness was noted among the immunosuppressed group

Healthcare and social services resource use and costs of self-harm patients

Background: patients who have self-harmed have increased morbidity across a wide range of health outcomes, but there is no evidence on their pattern of health and social service use, and its relationship with repetition of self-harm. Previous studies have shown that resource use and costs in the short-term hospital management of self-harm is associated with certain patient and service characteristics but their impact in the longer term has not been demonstrated. The aim of this study is to test the association between changing levels of costs of health and social care with further episodes of self-harm and to identify the clinical and social factors associated with this. Method: this was a cost-analysis incidence study of a sample of patients from a cohort of self-harm patients who remained within one region over the course of their follow-up. Resource use was retrospectively observed from their first episode of self-harm (dating back on some occasions to the 1970’s), and costs applied. Panel data analyses were used to identify factors associated with observed costs over time. Results: patients with five or more episodes of self-harm had the highest levels of resource costs. Health and social care costs reduced with time from last episode of self-harm. In the year following the first episode of self-harm, psychiatric care accounted for 69% and psychotropic drug prescriptions 1% of the mean resource costs. Conclusions: the management of self-harm occurs within a complex system of health and social care. Major self-harm repeaters place the greatest cost burden on the system. Better understanding of the impact of risk assessment models and consequent service provision on clinical outcome may help in the design of effective services for this patient group

Post-pandemic development of sentinel surveillance of respiratory disease, in the context of the WHO mosaic framework: protocol for the English primary care network 2023-2024 (Preprint)

Pre-pandemic sentinel surveillance was orientated towards improved management of winter pressures, with influenza-like illness (ILI) the key clinical indicator. Recently the World Health Organisation (WHO) has published global standards for influenza surveillance, which include monitoring acute respiratory infection (ARI) as well as ILI. The WHO’s mosaic framework recommends countries’ surveillance strategies include the virological monitoring of influenza, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV) and other viruses with pandemic potential. The Oxford-Royal College of General Practitioner (RCGP) Research and Surveillance Centre (RSC) in collaboration with the UK Health Security Agency (UKHSA), has provided sentinel surveillance since 1967 including virology since 1993

Dissecting intratumour heterogeneity of nodal B-cell lymphomas at the transcriptional, genetic and drug-response levels

Tumour heterogeneity encompasses both the malignant cells and their microenvironment. While heterogeneity between individual patients is known to affect the efficacy of cancer therapy, most personalized treatment approaches do not account for intratumour heterogeneity. We addressed this issue by studying the heterogeneity of nodal B-cell lymphomas by single-cell RNA-sequencing and transcriptome-informed flow cytometry. We identified transcriptionally distinct malignant subpopulations and compared their drug-response and genomic profiles. Malignant subpopulations from the same patient responded strikingly differently to anti-cancer drugs ex vivo, which recapitulated subpopulation-specific drug sensitivity during in vivo treatment. Infiltrating T cells represented the majority of non-malignant cells, whose gene-expression signatures were similar across all donors, whereas the frequencies of T-cell subsets varied significantly between the donors. Our data provide insights into the heterogeneity of nodal B-cell lymphomas and highlight the relevance of intratumour heterogeneity for personalized cancer therapy. Roider et al. combine scRNA-seq and transcriptome-informed flow cytometry, and uncover transcriptionally different malignant subclones with distinct drug responses and T-cell profiles in B-cell non-Hodgkin lymphoma