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A new national research project to study the effects of emerging mutations in SARS-CoV-2 will be launched with £2.5 million funding from UK Research and Innovation (UKRI).
Age differences in immunity to human seasonal coronaviruses and the immunogenicity of ChAdOx1 nCoV-19 (AZD1222).
BackgroundChAdOx1 nCoV-19 (AZD1222) vaccine was widely deployed to protect against severe COVID-19 in adults, but the relationship between pre-existing immunity to human seasonal coronaviruses (HCoVs) and vaccine-induced SARS-CoV-2 (SCoV2) response across age groups remains unclear.MethodsWe analysed SCoV2 and HCoVs antibody profiles in UK volunteers (aged 6-≥70), assessing antibody levels, avidity, and FcγR binding after receiving one or two doses of ChAdOx1 nCoV-19. Adult cohorts from trials in Brazil and Kenya were also included to evaluate geographical impacts on baseline HCoVs and SCoV2 induced response.FindingsIn the UK cohort, younger individuals had higher SCoV2 IgG, avidity, FcγR binding and cross-reactivity, particularly towards OC43 and HKU1. The greatest differences were seen after the first dose of ChAdOx1 nCoV-19, but these effects diminished after the second dose. Although baseline HCoVs IgG varied geographically, similar trends were observed across adult cohorts with younger adults showing higher SCoV2 IgG compared to older adults (UK and Brazil).InterpretationThese findings contribute to a better understanding of the immunogenicity of ChAdOx1-based vaccines in various age groups. Determining whether this applies across other vaccines using same platform is essential for evaluating the viability of one-dose regimens in outbreak responses.FundingThe clinical trials COV002, COV003, COV004, and COV006 were made possible by funding from Astra Zeneca, the NIHR and the University of Oxford, UK Department of Health and Social Care, through the UK National Institute for Health and Care Research, the Wellcome Trust (220991), and Innovate UK (project 971614).
Emerging strategies in the transplantation of HCV-infected pancreases to uninfected recipients: A narrative review.
The scarcity of suitable candidates for solid organ transplantation (SOT) represents a major barrier to the reduction of waiting lists. The introduction of direct-acting antiviral (DAA) therapeutics eliminates many of the risks associated with the transplantation of Hepatitis C Virus (HCV)-infected donor organs (D+) to uninfected recipients (R-) and may facilitate access to a substantial organ pool, previously considered unacceptably high risk. The extent of clinical investigation into the safety and feasibility of HCV D+/R- SOT varies between allograft types. Here, we review the current state of pancreatic HCV D+/R-transplant research. Studies are limited to small cohorts who received pancreas allografts from HCV-viraemic donors alongside a regimen of DAA therapy. As of 2025, seven studies investigated a total of 22 patients, using prophylactic or reactive treatment regimens. Outcomes have been positive, with universal viral eradication, favourable allograft function, and minimal HCV-related complications. A favourable adverse event profile is reported, mirroring studies in other transplanted organs. With the aim to increase clinical use of pancreatic HCV D+/R- SOT, further investigation in the field is necessary to validate these preliminary data. Larger studies are essential to evaluate long-term sequelae and optimise treatment protocols to subsequently establish a standard of care.
Mpox stigma in the UK and implications for future outbreak control: a cross-sectional mixed methods study.
BACKGROUND: Stigma emerged as a prominent public health challenge in the global mpox outbreak that began in 2022, impeding outbreak control efforts and the well-being of affected individuals. Addressing stigma is important for improving infection prevention and control. Despite frequent mention in public and policy discourse, robust assessment of mpox stigma is lacking. This study investigated the causes, manifestations, and impacts of mpox-related stigma in the UK, focusing on anticipated stigma among directly and indirectly affected communities. METHODS: We conducted an online, mixed-methods cross-sectional survey to assess mpox stigma. We developed and content validated a new tool, the Stigma Survey and Community-based Assessment for New and Re-emerging outbreaks (Stigma-SCANR) for this purpose. Through quota sampling, the survey targeted populations most affected by mpox at the time of data collection (March-July 2024), including gay, bisexual, and other men who have sex with men (GBMSM), and healthcare workers. The survey primarily explored anticipated stigma. Respondents with previous mpox diagnoses were asked about personal experiences of stigma. RESULTS: Of 479 respondents who initiated the survey, 437 (91%) were included in analyses. In modules related to drivers of stigma, pre-existing prejudices towards associated groups such as GBMSM and migrants were emphasised, alongside fear and misinformation. On average, respondents anticipated higher levels of negative judgement and unwarranted avoidance compared to other forms of social stigma, particularly from casual partners and the public. Among the 13 respondents who reported a previous mpox diagnosis, 11 (85%) had experienced mpox-related stigma. Nearly a quarter of respondents (24%) said they would not, or were unlikely to, tell a recent sexual partner about an mpox diagnosis. Feelings of shame were considered the most common barrier to care-seeking (299 respondents, 68%). CONCLUSIONS: This analysis of mpox stigma in the UK offers insights for international outbreak response, particularly in countries with similarly affected communities. Lessons learnt may also be transferable to other disease outbreaks. We propose practical recommendations for reducing stigma in future outbreaks, including peer support initiatives, distributing accessible information about safe timelines for returning to socialising and work or school, and co-designing public communications and contact tracing programmes with affected community members.
Communication Between Anaesthesia Providers for Clinical and Professional Purposes: A Scoping Review
Background: Anaesthesia providers in all contexts need to be able to communicate with colleagues to meet a variety of clinical and professional needs, including physical help, advice and support as well as learning, supervision and mentorship. Such communication can be regarded as a ‘social resource’ which underpins anaesthesia providers’ practice, but which has not itself been extensively studied. The objective of this scoping review is to provide an overview of the literature related to communication among anaesthesia providers to meet clinical and professional goals, focusing on the modalities, contexts and purposes or outcomes of such communication, as well as which providers are involved.Methods: We conducted a scoping review using the JBI methodology to examine the current literature available, searching the Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials, Medline, Embase, CINAHL and Google Scholar. Papers were eligible for inclusion where they primarily addressed the subject of communication between trained anaesthesia providers for any clinical or professional purpose (excluding purely social interactions). Data were charted for the location and cadre of providers represented, means of communication and the situation, purposes and outcomes of communication.Results: 3872 records were identified for screening, and 225 papers were ultimately included. Communication was reported both as a variable influencing a wide range of clinical and nonclinical outcomes and as an outcome in itself which might be modified by other factors. It was also considered in a smaller group of studies as a resource with varying availability to anaesthesia providers. Physician providers were well represented in included documents, but nurse anaesthetists, clinical officers and other nonphysician, nonnurse anaesthetists were far less commonly included. The majority of identified studies on communication between anaesthesia providers originated from and related to high‐income countries.Conclusion: Communication between anaesthesia providers affects all aspects of their practice and has implications for both patient outcomes and workforce capacity. More research is necessary to understand how the availability of communication as a resource affects patient care and health worker well‐being, particularly in low‐ and middle‐income contexts and among nonphysician anaesthesia providers.
Core collections: Essential titles for health libraries.
Core collections have been produced by CILIP's Health Libraries Group, then called the Library Association's Medical Section, since 1952. Maintained by a Working Group of health librarians based in the UK NHS, higher education and specialist libraries, the collections provide an up-to-date curated list of reliable titles essential to health libraries. The core collections currently include nursing, midwifery, medicine and dentistry. The newest core collection is being developed in collaboration with the African Hospital Libraries to provide a list of key resources relevant to sub-Saharan Africa. Expressions of interest to help develop this latest collection are invited.
Characterisation of between-cluster heterogeneity in malaria cluster randomised trials to inform future sample size calculations.
Cluster randomised trials (CRTs) are important tools for evaluating the community-wide effect of malaria interventions. During the design stage, CRT sample sizes need to be inflated to account for the cluster heterogeneity in measured outcomes. The coefficient of variation (k), a measure of such heterogeneity, is typically used in malaria CRTs yet is often predicted without prior data. Underestimation of k decreases study power, thus increases the probability of generating null results. In this meta-analysis of cluster-summary data from 24 malaria CRTs, we calculate true prevalence and incidence k values using methods-of-moments and regression modelling approaches. Using random effects regression modelling, we investigate the impact of empirical k values on original trial power and explore factors associated with elevated k. Results show empirical estimates of k often exceed those used in sample size calculations, which reduces study power and effect size precision. Elevated k values are associated with incidence outcomes (compared to prevalence), lower endemicity settings, and uneven intervention coverage across clusters. Study findings can enhance the robustness of future malaria CRT sample size calculations by providing informed k estimates based on expected prevalence or incidence, in the absence of cluster-level data.
MetE: a promising protective antigen for tuberculosis vaccine development
IntroductionTuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a significant global health concern. The existing vaccine, Bacillus Calmette-Guérin (BCG), provides inconsistent protection, highlighting the pressing need for a more effective vaccine. We aimed to identify novel MTB antigens and assess their protective efficacy as TB vaccine candidates.MethodsUsing immunopeptidomics, we identified 64 and 80 unique mycobacterial antigens derived from BCG and MTB, respectively. We prioritised antigens based on HLA allele coverage through an immunoinformatics approach.ResultsThe candidates, hisD, metE, and mmpL12, delivered as DNA vaccines, were evaluated for efficacy in mice using the ex vivo Mycobacterial Growth Inhibition Assay (MGIA) and metE was identified as a promising candidate. In vivo murine MTB challenge experiments confirmed the protective efficacy conferred by metE when formulated as recombinant protein with AS01™ or AddaS03™ adjuvants, compared to the naïve group. The immunogenic profiles of metE formulated in the two different adjuvants differed, with metE-AS01™ inducing antigen-specific IFN-γ, TNF-α, IL-2, IL-17, IgG1 and IgG2a-c, while metE-AddaS03™ induced TNF-α, IL-2, IL-17, IL-4, IgM, IgG1, IgG2b.ConclusionOur findings highlight metE as a promising protective antigen for future TB vaccine development.
Factors Influencing Health Workers' Acceptance of Guideline-Based Clinical Decision Support Systems for Preventive Services in Thailand: Questionnaire-Based Study.
BACKGROUND: A guideline-based clinical decision support system (CDSS) is a knowledge-based system designed to collect crucial data from electronic medical records to generate decision-making based on system data requirements and inputs from standard guidelines. Despite the potential to enhance health care delivery, the adoption rate of CDSSs in clinical practice remains suboptimal. OBJECTIVE: This study aimed to evaluate the determinants influencing the intention to use a new CDSS in preventive care within clinical practice. METHODS: A single-center, questionnaire-based, cross-sectional study was conducted among physicians and medical students responsible for providing comprehensive preventive services at the Continuity of Care Clinic, Siriraj Hospital, Thailand. RESULTS: In total, 89 participants were enrolled. Relationships between factors impacting the adoption of CDSSs were analyzed using correlation and regression analysis. We found that physicians' intentions to adopt the CDSS for preventive care were high, with 79% (70/89) of participants expressing their intention to use the system. According to the study's conceptual framework, modified from the original unified theory of acceptance and use of technology model, physicians' positive attitudes toward CDSS use in preventive services and a high level of effort expectancy emerged as crucial factors influencing the intention to use the new CDSS. The odds ratios for these factors were 5.44 (95% CI 1.62-18.34, P=.006) and 7.60 (95% CI 1.55-31.37, P=.01), respectively. Similar results were observed for medical students and for physicians who had graduated. The most prevalent barriers to CDSS implementation were related to physicians' attitudes, followed by issues such as the accuracy and burden of data input, time constraints for clinicians, and the risk of workflow disruption. CONCLUSIONS: There was a high intention to adopt the CDSS in preventive care. Positive physician attitudes toward CDSS use in preventive services and effort expectancy were found to be critical factors influencing the intention to use the new CDSS.
Diagnosis of Plasmodium falciparum malaria at very low parasitaemias using a commercially available LAMP assay and RDT.
BackgroundMalaria is the most common tropical infection in the UK. Current guidelines suggest that testing on 3 consecutive days is required following an initial negative result. This study aimed to see whether newer diagnostics (loop-mediated amplification assay [LAMP]) had sufficient sensitivity to support a change in diagnostic practice.MethodsBlood samples from 11 participants who had undergone controlled human malaria infection (CHMI) with Plasmodium falciparum malaria were assessed from day 6 (C+6) for malaria positivity using the Carestart Malaria rapid diagnostic test (RDT) and from C+4 using the Alethia Malaria LAMP assay. Quantitative polymerase chain reaction had been performed twice daily during CHMI follow-up. A retrospective analysis of samples submitted to the Sheffield Teaching Hospitals for malaria testing over a 5-y period was conducted, evaluating the combination of the Carestart RDT alongside blood film analysis, as per UK guidelines.ResultsIn CHMI samples, LAMP was positive for all parasitaemias >1000 parasites/ml, whereas RDTs were less reliable (59% positive for parasitaemias >1000 parasites/ml). The combination of RDT and blood films for clinical samples diagnosed most infections, but only a minority of negative samples had subsequent tests.ConclusionsLAMP has higher sensitivity than current UK recommended methods, with a potential to review the requirement for additional days of testing in the majority of patients.
A new paradigm of islet adaptations in human pregnancy: insights from immunohistochemistry and proteomics
Abstract Physiological changes during pregnancy support foetal growth, including adaptations in pancreatic islets to maintain glucose homeostasis. We investigate these adaptations using rare, high-quality pancreatic tissue from pregnant human donors and matched controls. We profile islets from pregnant donors using proteomics and assess α- and β-cell characteristics, as well as prolactin receptor and serotonin 2B receptor expression. Proteomic profiling of microdissected human islets identifies 7546 proteins but shows minimal differences in protein expression. In pregnancy, we show that islet area increases 1.9-fold, α- and β-cell areas increase 4.3- and 1.9-fold, driven by an increase in cell number rather than hypertrophy. Prolactin receptor expression is higher in α but not β cells, and serotonin 2B receptor is undetectable in β cells. Glucagon-like peptide-1 abundance increases 2.9-fold in α cells. These findings indicate that the molecular mechanisms driving pregnancy-induced islet adaptations in humans differ from those in mice, highlighting the need for human-based studies.