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VIVALDI (ISRCTN14447421) is a government-funded longitudinal open observational cohort study of staff and residents in care homes for older people in England. The study aimed to describe epidemiology (including seroprevalence) and immune responses to COVID-19 in a subset of care homes, in the context of extremely high mortality in this setting, in the first 12-18 months of the pandemic. Data linkage to routine health data was undertaken for all staff and residents and a subset of individuals who consented to sequential blood sampling to investigate SARS-CoV-2 immunity. This paper aims to describe the samples stored within the VIVALDI biobank and associated linked data, available for use by researchers. Over 70,000 individuals from 346 care homes were included in the data linkage cohort (1st March 2020–31st March 2023). 4971 samples from 2264 individuals (1415 staff, 827 residents) collected between 29th October 2020 and 10th March 2023 are stored. Amongst these samples, there was a maximum of seven per participant however, 217 (26.2%) residents and 551 (38.9%) staff participated in one round only. Key study findings include high COVID-19 seroprevalence among surviving residents, exceeding rates in community-dwelling peers. COVID-19 vaccinations generated robust immune responses in staff and residents which waned, supporting the need for booster vaccination, particularly in response to new variants. Prior infection significantly improved vaccine-induced immune responses, however protection from infection declined following Omicron variant emergence. This is a unique cohort of pre- and post-infection samples linked to data on COVID-19 infections, vaccinations, and outcomes. The cohort spans host immune response evolution to infection and vaccination in this rarely sampled population of frail older care home residents who are especially vulnerable to infection and severe outcomes. These samples can be used to investigate biological mechanisms behind disparate infection responses in older people and make a valuable contribution to research into ageing.

Introduction Older adults in care homes experienced some of the highest rates of mortality from SARS-CoV-2 globally and were subjected to strict and lengthy non-pharmaceutical interventions, which severely impacted their daily lives. The VIVALDI ASCOT and Ethnography Study aims to assess the impact of respiratory outbreaks on care home residents’ quality of life, psychological well-being, loneliness, functional ability and use of space. This study is linked to the VIVALDI-CT, a randomised controlled trial of staff’s asymptomatic testing and sickness payment support in care homes (ISRCTN13296529).Methods and analysis This is a mixed-methods, longitudinal study of care home residents (65+) in Southeast England. Group 1—exposed includes residents from care homes with a recent COVID-19 or other respiratory infection outbreak. Group 2—non-exposed includes residents from care homes without a recent outbreak. The study has two components: (a) a mixed-methods longitudinal face-to-face interviews with 100 residents (n=50 from group 1 and n=50 from group 2) to assess the impact of outbreaks on residents’ quality of life, psychological well-being, loneliness, functional ability and use of space at time 1 (study baseline) and time 2 (at 3–4 weeks after the first visit); (b) ethnographic observations in communal spaces of up to 10 care homes to understand how outbreaks and related restrictions to the use of space and social activities impact residents’ well-being. The study will interview only care home residents who have the mental capacity to consent. Data will be compared and integrated to gain a more comprehensive understanding of the impact of outbreaks on residents’ quality of life and well-being.Ethics and dissemination The VIVALDI ASCOT and Ethnography Study obtained ethical approval from the Health Research Authority (HRA) Social Care REC (24/IEC08/0001). Only residents with the capacity to consent will be included in the study. Findings will be published in scientific journals.

Abstract Aims Surgical Antibiotic Prophylaxis (SAP) in Nigeria is often not evidence based. The aim of this study is to test if the GADSA application can change prescription behaviour of surgeons in Nigeria. In addition, the study aims to identify AMS strategies and policies for the future. Methods The GADSA gamified decision support app uses WHO and Sanford prescribing guidelines to deliver real-time persuasive technology feedback to surgeons through an interactive mentor. The app can advise on whether clinician’s decisions align with SAP recommendations and provides the opportunity for clinicians to make adjustments. Twenty surgeons actively participated in a 6-month pilot study in three hospitals in Nigeria. The surgeons determined the risk of infection of a surgical procedure, and the need, type and duration of SAP. The study used a longitudinal approach to test whether the GADSA app significantly changed prescribing behaviour of participating surgeons by analysing the reported prescription decisions within the app. Results 321 SAP prescriptions were recorded. Concerning the surgical risk decision, 12% of surgeons changed their decision to be in line with guidelines after app feedback (p

Abstract Background The COVID-19 pandemic disproportionately affected people living and working in UK care homes causing high mortality rates. Vaccinating staff members and residents is considered the most effective intervention to reduce infection and its transmission rates. However, uptake of the first dose of the COVID-19 vaccine in care homes was variable. We sought to investigate factors influencing uptake of COVID-19 vaccination in care home staff to inform strategies to increase vaccination uptake and inform future preparedness. Methods Twenty care home staff including managerial and administrative staff, nurses, healthcare practitioners and support staff from nine care homes across England participated in semi-structured telephone interviews (March-June 2021) exploring attitudes towards the COVID-19 vaccine and factors influencing uptake. We used thematic analysis to generate themes which were subsequently deductively mapped to the Capability, Opportunity, Motivation-Behaviour (COM-B) model. The Behavioural Change Wheel (BCW) was used to identify potential intervention strategies to address identified influences. Results Enablers to vaccine uptake included the willingness to protect care home residents, staff and family/friends from infection and the belief that vaccination provided a way back to normality (reflective motivation); convenience of vaccination and access to accurate information (physical opportunity); and a supporting social environment around them favouring vaccination (social opportunity). Barriers included fears about side-effects (automatic motivation); a lack of trust due to the quick release of the vaccine (reflective motivation); and feeling pressurised to accept vaccination if mandatory (automatic motivation). Conclusions We identified influences on COVID-19 vaccine uptake by care home staff that can inform the implementation of future vaccination programmes. Strategies likely to support uptake include information campaigns and facilitating communication between staff and managers to openly discuss concerns regarding possible vaccination side effects. Freedom of choice played an important role in the decision to be vaccinated suggesting that the decision to mandate vaccination may have unintended behavioural consequences.

Abstract Background Antimicrobial resistance (AMR) is a major global health threat caused by the inappropriate use of antimicrobials in healthcare and other settings. Antimicrobial stewardship (AMS) is a broad multi-component health services intervention that promotes and monitors the judicious use of antimicrobials to preserve their future effectiveness. A main component of AMS is education and training (E&T). However, there are often discrepancies in how such interventions are implemented and delivered in hospital-based care. The aim of this study was to explore the factors influencing the implementation of AMS E&T in UK hospitals. Methods Semi-structured interviews were carried out with AMS E&T trainers in UK hospitals. The interview schedule was developed using the Capability, Opportunity, Motivation = Behaviour (COM-B) model. Participants were identified via professional networks and social media. Interviews were analysed using inductive thematic analysis, followed by deductive analysis using the COM-B model as a framework. Results A total of 34 participants (26 antimicrobial pharmacists, 3 nurses, 1 advanced clinical practitioner, 2 infectious disease consultants, 1 microbiologist and 1 clinical scientist). responsible for designing, implementing and evaluating AMS E&T in UK hospitals (five from Northern Ireland, four from Wales, two from Scotland and 23 from England) took part in virtual interviews. Key themes were: (1) The organisational context, including system-level barriers to AMS included competing organisational targets (Reflective motivation and physical opportunity) and the impact of the COVID-19 pandemic on activity (Physical opportunity); (2) Healthcare professionals’ roles and the wider multi-disciplinary team, such that AMS roles were defined and addressed poorly in E&T (Social opportunity); and (3) The individual perception of the need for AMS E&T in hospital-based care, manifest in a perceived lack of conviction of the wider threat of AMR and the resulting need for AMS E&T (Reflective motivation). Conclusion This study has identified factors influencing implementation of AMS E&T in UK hospitals and further identified where implemented, AMS E&T did not address real-world challenges. Current AMS E&T needs to be optimised to elicit practice change, with recommendations including training and engaging the wider work-force and drawing upon theoretically-informed intervention development frameworks to inform AMS E&T to better target AMS behaviour change.

Background We have previously demonstrated that older residents of long-term care facilities (LTCF) in the UK show levels of anti-spike antibodies that are comparable to the general population following primary series and booster vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, data on the humoral response to other SARS-CoV-2 proteins associated with natural infection are scarce in this vulnerable population. Methods We measured quantitative levels of anti-nucleocapsid antibodies in blood samples taken from LTCF residents and staff after initial and repeat SARS-CoV-2 infections, between December 2020 and March 2023. Data on SARS-CoV-2 infection and vaccination were obtained through linkage to national datasets. Linear mixed effects models were used to investigate anti-nucleocapsid antibody levels, using log10 scale, in relation to time from most recent infection. This included evaluation of associations between repeat infection, staff/resident status, age, sex, Omicron infection and vaccination history and peak antibody level and slope of decline with time. Results We analysed 405 antibody observations from 220 residents and 396 observations from 215 staff. Repeat infection was associated with 8.5-fold (95%CI 4.9-14.8-fold) higher initial (peak) median anti-nucleocapsid antibody level, with steeper subsequent slope of decline. There were no significant differences in antibody level associated with resident (vs. staff) status or age, but Omicron infection was associated with 3.6-fold (95%CI 2.4–5.4-fold) higher levels. There was stronger evidence of waning of antibody levels over time in a sensitivity analysis in which observations were censored in cases with suspected undetected repeat infection. Conclusions We found similar levels of anti-nucleocapsid antibody in residents and staff of LTCFs. Repeat infection and infection with an Omicron strain were associated with higher peak values. There was evidence of waning of anti-nucleocapsid antibody levels over time.

Care home residents are vulnerable to severe outcomes from infections such as COVID-19 and influenza. However, measures to control outbreaks, such as care home closures to visitors and new admissions, have a detrimental impact on their quality of life. Many infections and outbreaks could be prevented but the first step is to measure them reliably. This is challenging in care homes due to the lack of data and research infrastructure. During the pandemic, the VIVALDI study measured COVID-19 infections in residents and staff by partnering with care providers and using routinely collected data. This study aims to establish sentinel surveillance and a research database to enable observational and future interventional studies in care homes. The project has been co-produced with care providers, staff, residents, relatives, and researchers. The study (October 2023 to March 2025) will explore the feasibility of establishing a network of 500-1500 care homes for older adults in England that is underpinned by a linked data platform. No data will be collected from staff. The cohort will be created by regularly extracting resident identifiers from Digital Social Care Records (DSCR), followed by pseudonymisation and linkage to routinely collected datasets. Following extensive consultation, we decided not to seek informed consent from residents for data collection, but they can ‘opt out’ of the study. Our goal is to be inclusive, and it is challenging to give every resident the opportunity to ‘opt in’ due to cognitive impairment and the requirement for consultees. The project, and all requests to use the data will be overseen by relatives, residents, staff, and care providers. The study has been approved by the Health Research Authority Confidentiality Advisory Group (23/CAG/0134&0135) and the South-West Frenchay Research Ethics Committee (23/SW/0105). It is funded by the UK Health Security Agency.

Introduction Care home residents have experienced significant morbidity, mortality and disruption following outbreaks of SARS-CoV-2. Regular SARS-CoV-2 testing of care home staff was introduced to reduce transmission of infection, but it is unclear whether this remains beneficial. This trial aims to investigate whether use of regular asymptomatic staff testing, alongside funding to reimburse sick pay for those who test positive and meet costs of employing agency staff, is a feasible and effective strategy to reduce COVID-19 impact in care homes.Methods and analysis The VIVALDI-Clinical Trial is a multicentre, open-label, cluster randomised controlled, phase III/IV superiority trial in up to 280 residential and/or nursing homes in England providing care to adults aged >65 years. All regular and agency staff will be enrolled, excepting those who opt out. Homes will be randomised to the intervention arm (twice weekly asymptomatic staff testing for SARS-CoV-2) or the control arm (current national testing guidance). Staff who test positive for SARS-CoV-2 will self-isolate and receive sick pay. Care providers will be reimbursed for costs associated with employing temporary staff to backfill for absence arising directly from the trial.The trial will be delivered by a multidisciplinary research team through a series of five work packages.The primary outcome is the incidence of COVID-19-related hospital admissions in residents. Secondary outcomes include the number and duration of outbreaks and home closures. Health economic and modelling analyses will investigate the cost-effectiveness and cost consequences of the testing intervention. A process evaluation using qualitative interviews will be conducted to understand intervention roll out and identify areas for optimisation to inform future intervention scale-up, should the testing approach prove effective and cost-effective. Stakeholder engagement will be undertaken to enable the sector to plan for results and their implications and to coproduce recommendations on the use of testing for policy-makers.Ethics and dissemination The study has been approved by the London—Bromley Research Ethics Committee (reference number 22/LO/0846) and the Health Research Authority (22/CAG/0165). The results of the trial will be disseminated regardless of the direction of effect. The publication of the results will comply with a trial-specific publication policy and will include submission to open access journals. A lay summary of the results will also be produced to disseminate the results to participants.Trial registration number ISRCTN13296529.

Urinary tract infections (UTIs) are a major cause of emergency hospital admissions, but it remains challenging to diagnose them reliably. Application of machine learning (ML) to routine patient data could support clinical decision-making. We developed a ML model predicting bacteriuria in the ED and evaluated its performance in key patient groups to determine scope for its future use to improve UTI diagnosis and thus guide antibiotic prescribing decisions in clinical practice. We used retrospective electronic health records from a large UK hospital (2011-2019). Non-pregnant adults who attended the ED and had a urine sample cultured were eligible for inclusion. The primary outcome was predominant bacterial growth ≥104 cfu/mL in urine. Predictors included demography, medical history, ED diagnoses, blood tests, and urine flow cytometry. Linear and tree-based models were trained via repeated cross-validation, re-calibrated, and validated on data from 2018/19. Changes in performance were investigated by age, sex, ethnicity, and suspected ED diagnosis, and compared to clinical judgement. Among 12,680 included samples, 4,677 (36.9%) showed bacterial growth. Relying primarily on flow cytometry parameters, our best model achieved an area under the ROC curve (AUC) of 0.813 (95% CI 0.792-0.834) in the test data, and achieved both higher sensitivity and specificity compared to proxies of clinician's judgement. Performance remained stable for white and non-white patients but was lower during a period of laboratory procedure change in 2015, in patients ≥65 years (AUC 0.783, 95% CI 0.752-0.815), and in men (AUC 0.758, 95% CI 0.717-0.798). Performance was also slightly reduced in patients with recorded suspicion of UTI (AUC 0.797, 95% CI 0.765-0.828). Our results suggest scope for use of ML to inform antibiotic prescribing decisions by improving diagnosis of suspected UTI in the ED, but performance varied with patient characteristics. Clinical utility of predictive models for UTI is therefore likely to differ for important patient subgroups including women

BackgroundCOVID-19 data have been generated across the United Kingdom as a by-product of clinical care and public health provision, as well as numerous bespoke and repurposed research endeavors. Analysis of these data has underpinned the United Kingdom’s response to the pandemic, and informed public health policies and clinical guidelines. However, these data are held by different organizations, and this fragmented landscape has presented challenges for public health agencies and researchers as they struggle to find relevant data to access and interrogate the data they need to inform the pandemic response at pace. ObjectiveWe aimed to transform UK COVID-19 diagnostic data sets to be findable, accessible, interoperable, and reusable (FAIR). MethodsA federated infrastructure model (COVID - Curated and Open Analysis and Research Platform [CO-CONNECT]) was rapidly built to enable the automated and reproducible mapping of health data partners’ pseudonymized data to the Observational Medical Outcomes Partnership Common Data Model without the need for any data to leave the data controllers’ secure environments, and to support federated cohort discovery queries and meta-analysis. ResultsA total of 56 data sets from 19 organizations are being connected to the federated network. The data include research cohorts and COVID-19 data collected through routine health care provision linked to longitudinal health care records and demographics. The infrastructure is live, supporting aggregate-level querying of data across the United Kingdom. ConclusionsCO-CONNECT was developed by a multidisciplinary team. It enables rapid COVID-19 data discovery and instantaneous meta-analysis across data sources, and it is researching streamlined data extraction for use in a Trusted Research Environment for research and public health analysis. CO-CONNECT has the potential to make UK health data more interconnected and better able to answer national-level research questions while maintaining patient confidentiality and local governance procedures.

Abstract Background Urinary tract infection (UTI) is a leading cause of hospital admissions and is diagnosed based on urinary symptoms and microbiological cultures. Due to lags in the availability of culture results of up to 72 h, and the limitations of routine diagnostics, many patients with suspected UTI are started on antibiotic treatment unnecessarily. Predictive models based on routinely collected clinical information may help clinicians to rule out a diagnosis of bacterial UTI in low-risk patients shortly after hospital admission, providing additional evidence to guide antibiotic treatment decisions. Methods Using electronic hospital records from Queen Elizabeth Hospital Birmingham (QEHB) collected between 2011 and 2017, we aim to develop a series of models that estimate the probability of bacterial UTI at presentation in the emergency department (ED) among individuals with suspected UTI syndromes. Predictions will be made during ED attendance and at different time points after hospital admission to assess whether predictive performance may be improved over time as more information becomes available about patient status. All models will be externally validated for expected future performance using QEHB data from 2018/2019. Discussion Risk prediction models using electronic health records offer a new approach to improve antibiotic prescribing decisions, integrating clinical and demographic data with test results to stratify patients according to their probability of bacterial infection. Used in conjunction with expert opinion, they may help clinicians to identify patients that benefit the most from early antibiotic cessation.

Abstract Background Overuse of antibiotics has contributed to antimicrobial resistance; a growing public health threat. In long-term care facilities, levels of inappropriate prescribing are as high as 75%. Numerous interventions targeting long-term care facilities’ antimicrobial stewardship have been reported with varying, and largely unexplained, effects. Therefore, this review aimed to apply behavioural science frameworks to specify the component behaviour change techniques of stewardship interventions in long-term care facilities and identify those components associated with improved outcomes. Method A systematic review (CRD42018103803) was conducted through electronic database searches. Two behavioural science frameworks, the Behaviour Change Wheel and Behaviour Change Technique Taxonomy were used to classify intervention descriptions into intervention types and component behaviour change techniques used. Study design and outcome heterogeneity prevented meta-analysis and meta-regression. Interventions were categorised as ‘very promising’ (all outcomes statistically significant), ‘quite promising’ (some outcomes statistically significant), or ‘not promising’ (no outcomes statistically significant). ‘Promise ratios’ (PR) were calculated for identified intervention types and behaviour change techniques by dividing the number of (very or quite) promising interventions featuring the intervention type or behaviour change technique by the number of interventions featuring the intervention type or behaviour change technique that were not promising. Promising intervention types and behaviour change techniques were defined as those with a PR ≥ 2. Results Twenty studies (of19 interventions) were included. Seven interventions (37%) were ‘very promising’, eight ‘quite promising’ (42%) and four ‘not promising’ (21%). Most promising intervention types were ‘persuasion’ (n = 12; promise ratio (PR) = 5.0), ‘enablement’ (n = 16; PR = 4.33) and ‘education’ (n = 19; PR = 3.75). Most promising behaviour change techniques were ‘feedback on behaviour’ (n = 9; PR = 8.0) and ‘restructuring the social environment’ (e.g. staff role changes; n = 8; PR = 7.0). Conclusion Systematic identification of the active ingredients of antimicrobial stewardship in long-term care facilities was facilitated through the application of behavioural science frameworks. Incorporating environmental restructuring and performance feedback may be promising intervention strategies for antimicrobial stewardship interventions within long-term care facilities.

Abstract Background There is an urgent need to develop biomarkers that stratify risk of bacterial infection in order to support antimicrobial stewardship in emergency hospital admissions. Methods We used computational machine learning to derive a rule-out blood transcriptomic signature of bacterial infection (SeptiCyte™ TRIAGE) from eight published case-control studies. We then validated this signature by itself in independent case-control data from more than 1500 samples in total, and in combination with our previously published signature for viral infections (SeptiCyte™ VIRUS) using pooled data from a further 1088 samples. Finally, we tested the performance of these signatures in a prospective observational cohort of emergency department (ED) patients with fever, and we used the combined SeptiCyte™ signature in a mixture modelling approach to estimate the prevalence of bacterial and viral infections in febrile ED patients without microbiological diagnoses. Results The combination of SeptiCyte™ TRIAGE with our published signature for viral infections (SeptiCyte™ VIRUS) discriminated bacterial and viral infections in febrile ED patients, with a receiver operating characteristic area under the curve of 0.95 (95% confidence interval 0.90–1), compared to 0.79 (0.68–0.91) for WCC and 0.73 (0.61–0.86) for CRP. At pre-test probabilities 0.35 and 0.72, the combined SeptiCyte™ score achieved a negative predictive value for bacterial infection of 0.97 (0.90–0.99) and 0.86 (0.64–0.96), compared to 0.90 (0.80–0.94) and 0.66 (0.48–0.79) for WCC and 0.88 (0.69–0.95) and 0.60 (0.31–0.72) for CRP. In a mixture modelling approach, the combined SeptiCyte™ score estimated that 24% of febrile ED cases receiving antibacterials without a microbiological diagnosis were due to viral infections. Our analysis also suggested that a proportion of patients with bacterial infection recovered without antibacterials. Conclusions Blood transcriptional biomarkers offer exciting opportunities to support precision antibacterial prescribing in ED and improve diagnostic classification of patients without microbiologically confirmed infections.

Summary: We reviewed all genomic epidemiology studies on COVID-19 in long-term care facilities (LTCFs) that had been published to date. We found that staff and residents were usually infected with identical, or near identical, SARS-CoV-2 genomes. Outbreaks usually involved one predominant cluster, and the same lineages persisted in LTCFs despite infection control measures. Outbreaks were most commonly due to single or few introductions followed by a spread rather than a series of seeding events from the community into LTCFs. The sequencing of samples taken consecutively from the same individuals at the same facilities showed the persistence of the same genome sequence, indicating that the sequencing technique was robust over time. When combined with local epidemiology, genomics allowed probable transmission sources to be better characterised. The transmission between LTCFs was detected in multiple studies. The mortality rate among residents was high in all facilities, regardless of the lineage. Bioinformatics methods were inadequate in a third of the studies reviewed, and reproducing the analyses was difficult because sequencing data were not available in many facilities.

Summary: Background: Long-term care facilities (LTCFs) have reported high SARS-CoV-2 infection rates and related mortality, but the proportion of infected people among those who have survived, and duration of the antibody response to natural infection, is unknown. We determined the prevalence and stability of nucleocapsid antibodies (the standard assay for detection of previous infection) in staff and residents in LTCFs in England. Methods: This was a prospective cohort study of residents 65 years or older and of staff 65 years or younger in 201 LTCFs in England between March 1, 2020, and May 7, 2021. Participants were linked to a unique pseudo-identifier based on their UK National Health Service identification number. Serial blood samples were tested for IgG antibodies against SARS-CoV-2 nucleocapsid protein using the Abbott ARCHITECT i-system (Abbott, Maidenhead, UK) immunoassay. Primary endpoints were prevalence and cumulative incidence of antibody positivity, which were weighted to the LTCF population. Incidence rate of loss of antibodies (seroreversion) was estimated from Kaplan-Meier curves. Findings: 9488 samples were included, 8636 (91·0%) of which could be individually linked to 1434 residents and 3288 staff members. The cumulative incidence of nucleocapsid seropositivity was 34·6% (29·6–40·0) in residents and 26·1% (23·0–29·5) in staff over 11 months. 239 (38·6%) residents and 503 women (81·3%) were included in the antibody-waning analysis, and median follow-up was 149 days (IQR 107–169). The incidence rate of seroreversion was 2·1 per 1000 person-days at risk, and median time to reversion was 242·5 days. Interpretation: At least a quarter of staff and a third of surviving residents were infected with SAR-CoV-2 during the first two waves of the pandemic in England. Nucleocapsid-specific antibodies often become undetectable within the first year following infection, which is likely to lead to marked underestimation of the true proportion of people with previous infection. Given that natural infection might act to boost vaccine responses, better assays to identify natural infection should be developed. Funding: UK Government Department of Health and Social Care.

Objectives: Studies of storytelling (ST) used as a research tool to extract information and/or as an intervention to effect change in the public knowledge, attitudes, and behavior/practice (KAB/P) were sought and analyzed.Methods: Medline, EMBASE, PsycINFO, ERIC, Web of Science, Art and Humanities database, Scopus, and Google Scholar were searched, and a basic and broad quantitative analysis was performed, followed by an in-depth narrative synthesis of studies on carefully selected topics.Results: From this search, 3,077 studies were identified. 145 studies entered quantitative analysis [cancer and cancer screening (32/145), HIV (32/145), mental health (10/145), vaccination (8/145), and climate change (3/145)]. Ten studies entered final analysis [HIV/AIDs (5), climate change (1), sexual health (3), and croup (1)]. ST techniques included digital ST (DST), written ST, verbal ST, and use of professional writers. Of the ten studies, seven used ST to change KAB/P; the remainder used ST to extract insights. Follow-up and evaluation were very limited.Conclusion: ST reveals insights and serves as an intervention in public health. Benefits of ST largely outweigh the limitations, but more follow-up/evaluation is needed. ST should play a more significant role in tackling public health issues.PROSPERO registration number: CRD42019124704

Abstract Background Driven by alcohol consumption and obesity, the prevalence of non-viral liver disease in the UK is increasing. Due to its silent and slow nature, the progression of liver disease is currently unpredictable and challenging to monitor. The latest National Institute for Health Care Excellence cirrhosis guidelines call for a validated risk tool that would allow general practitioners to identify patients that are at high risk of developing cirrhosis. Methods Using linked electronic health records from the Clinical Practice Research Datalink (a database of > 10 million patients in England), we aim to develop and validate a prediction model to estimate 2-, 5- and 10-year risk of cirrhosis. The model will provide individualised cirrhosis risk predictions for adult primary care patients, free from underlying liver disease or viral hepatitis infection, whose liver blood test results come back abnormal. We will externally validate the model in patients from 30 further Clinical Practice Research Datalink general practices in England. Discussion The prediction model will provide estimates of cirrhosis risk in primary care patients with abnormal liver blood test results to guide referral to secondary care, to identify patients who are in serious need of preventative health interventions and to help reassure patients at low risk of cirrhosis in the long term.

Summary: Background: SARS-CoV-2 infection represents a major challenge for long-term care facilities (LTCFs) and many residents and staff are seropositive following persistent outbreaks. We aimed to investigate the association between the SARS-CoV-2 antibody status at baseline and subsequent infection in this population. Methods: We did a prospective cohort study of SARS-CoV-2 infection in staff (aged 65 years) at 100 LTCFs in England between Oct 1, 2020, and Feb 1, 2021. Blood samples were collected between June and November, 2020, at baseline, and 2 and 4 months thereafter and tested for IgG antibodies to SARS-CoV-2 nucleocapsid and spike proteins. PCR testing for SARS-CoV-2 was done weekly in staff and monthly in residents. Cox regression was used to estimate hazard ratios (HRs) of a PCR-positive test by baseline antibody status, adjusted for age and sex, and stratified by LTCF. Findings: 682 residents from 86 LCTFs and 1429 staff members from 97 LTCFs met study inclusion criteria. At baseline, IgG antibodies to nucleocapsid were detected in 226 (33%) of 682 residents and 408 (29%) of 1429 staff members. 93 (20%) of 456 residents who were antibody-negative at baseline had a PCR-positive test (infection rate 0·054 per month at risk) compared with four (2%) of 226 residents who were antibody-positive at baseline (0·007 per month at risk). 111 (11%) of 1021 staff members who were antibody-negative at baseline had PCR-positive tests (0·042 per month at risk) compared with ten (2%) of 408 staff members who were antibody-positive staff at baseline (0·009 per month at risk). The risk of PCR-positive infection was higher for residents who were antibody-negative at baseline than residents who were antibody-positive at baseline (adjusted HR [aHR] 0·15, 95% CI 0·05–0·44, p=0·0006), and the risk of a PCR-positive infection was also higher for staff who were antibody-negative at baseline compared with staff who were antibody-positive at baseline (aHR 0·39, 0·19–0·82; p=0·012). 12 of 14 reinfected participants had available data on symptoms, and 11 of these participants were symptomatic. Antibody titres to spike and nucleocapsid proteins were comparable in PCR-positive and PCR-negative cases. Interpretation: The presence of IgG antibodies to nucleocapsid protein was associated with substantially reduced risk of reinfection in staff and residents for up to 10 months after primary infection. Funding: UK Government Department of Health and Social Care.

Background: Antimicrobial resistance (AMR) is a global health priority. Acne vulgaris is a common skin condition for which antibiotic use ranges from a few months to years of daily exposure. Aim: To systemically search for and synthesise evidence on the risk of treatment-resistant infections, and other evidence of AMR, following long-term oral antibiotic use for acne. Design & setting: In this systematic review, a literature search was carried out using the databases Embase, MEDLINE, Cochrane, and Web of Science. They were searched using MeSH, Emtree, or other relevant terms, and followed a pre-registered protocol. Method: Search strategies were developed with a librarian and undertaken in July 2019. All searches date from database inception. The primary outcome was antibiotic treatment failure or infection caused by a resistant organism. Secondary outcomes included detection of resistant organisms without an infection, rate of infection, or changes to flora. Results: A total of 6996 records were identified. Seventy-three full-text articles were shortlisted for full review, of which five were included. Two investigated rates of infection, and three resistance or changes to microbial flora. Three studies had 35 or fewer participants (range 20–118 496). Three studies had a serious or high risk of bias, one moderate, and one a low risk of bias. Weak evidence was found for an association between antibiotic use for acne and subsequent increased rates of upper respiratory tract infections and pharyngitis. Conclusion: There is a lack of high quality evidence on the relationship between oral antibiotics for acne treatment and subsequent AMR sequelae. This needs to be urgently addressed with rigorously conducted studies.

Summary: Background: Outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have occurred in long-term care facilities (LTCFs) worldwide, but the reasons why some facilities are particularly vulnerable to outbreaks are poorly understood. We aimed to identify factors associated with SARS-CoV-2 infection and outbreaks among staff and residents in LTCFs. Methods: We did a national cross-sectional survey of all LTCFs providing dementia care or care to adults aged 65 years or older in England between May 26 and June 19, 2020. The survey collected data from managers of eligible LTCFs on LTCF characteristics, staffing factors, the use of disease control measures, and the number of confirmed cases of infection among staff and residents in each LTCF. Survey responses were linked to individual-level SARS-CoV-2 RT-PCR test results obtained through the national testing programme in England between April 30 and June 13, 2020. The primary outcome was the weighted period prevalence of confirmed SARS-CoV-2 infections in residents and staff reported via the survey. Multivariable logistic regression models were fitted to identify factors associated with infection in staff and residents, an outbreak (defined as at least one case of SARS-CoV-2 infection in a resident or staff member), and a large outbreak (defined as LTCFs with more than a third of the total number of residents and staff combined testing positive, or with >20 residents and staff combined testing positive) using data from the survey and from the linked survey–test dataset. Findings: 9081 eligible wLTCFs were identified, of which 5126 (56·4%) participated in the survey, providing data on 160 033 residents and 248 594 staff members. The weighted period prevalence of infection was 10·5% (95% CI 9·9–11·1) in residents and 3·8% (3·4–4·2) in staff members. 2724 (53·1%) LTCFs reported outbreaks, and 469 (9·1%) LTCFs reported large outbreaks. The odds of SARS-CoV-2 infection in residents (adjusted odds ratio [aOR] 0·80 [95% CI 0·75–0·86], p

Global infection and mortality rates from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are disproportionately high in certain populations, including amongst older people. Care home residents are frequently exposed to infection due to contact with staff and other residents, and are highly susceptible to infection due to their age and co-morbidity. In England, official statistics suggest that at least 25% of all deaths in care home residents since the start of pandemic are linked to coronavirus disease 2019 (COVID-19), but limited testing for SARS-CoV-2 early in the pandemic means estimates of the true burden of disease are lacking. Additionally, little is known about patterns of transmission between care homes, the community and hospitals, or the relationship between infection and immunity in care home staff and residents. The VIVALDI study plans to address these questions. VIVALDI is a prospective cohort study aiming to recruit 6,500 staff and 5000 residents from 105 care homes across England. Successive rounds of testing for infection will be performed over a period of 12 months. Nasopharyngeal swabs will detect evidence of viral RNA and therefore active infection (accompanied by collection of data on symptoms), whereas blood tests will detect antibodies and evidence of cellular immunity to SARS-CoV-2. Whole genome sequencing of viral isolates to investigate pathways of transmission of infection is planned in collaboration with the COVID-19 Genomics UK Consortium. Qualitative interviews with care home staff will investigate the impact of the pandemic on ways of working and how test results influence infection control practices and behaviours. Data from residents and staff will be linked to national datasets on hospital admissions, antibody and PCR test results, mortality and care home characteristics. Data generated will support national public health efforts to prevent transmission of COVID-19 and protect care home staff and residents from infection. Protocol registration: ISRCTN14447421 05/06/2020

Background: Diagnostic testing forms a major part of the UK’s response to the current coronavirus disease 2019 (COVID-19) pandemic with tests offered to anyone with a continuous cough, high temperature or anosmia. Testing capacity must be sufficient during the winter respiratory season when levels of cough and fever are high due to non-COVID-19 causes. This study aims to make predictions about the contribution of baseline cough or fever to future testing demand in the UK. Methods: In this analysis of the Bug Watch community cohort study, we estimated the incidence of cough or fever in England in 2018-2019. We then estimated the COVID-19 diagnostic testing rates required in the UK for baseline cough or fever cases for the period July 2020-June 2021. This was explored for different rates of the population requesting tests, four COVID-19 second wave scenarios and high and low baseline cough or fever incidence scenarios. Results: Under the high baseline cough or fever scenario, incidence in the UK is expected to rise rapidly from 250,708 (95%CI 181,095 - 347,080) cases per day in September to a peak of 444,660 (95%CI 353,084 - 559,988) in December. If 80% of these cases request tests, testing demand would exceed 1.4 million tests per week for five consecutive months. Demand was significantly lower in the low cough or fever incidence scenario, with 129,115 (95%CI 111,596 - 151,679) tests per day in January 2021, compared to 340,921 (95%CI 276,039 - 424,491) tests per day in the higher incidence scenario. Conclusions: Our results show that national COVID-19 testing demand is highly dependent on background cough or fever incidence. This study highlights that the UK’s response to the COVID-19 pandemic must ensure that a high proportion of people with symptoms request tests, and that testing capacity is sufficient to meet the high predicted demand.

BackgroundResearch has questioned the safety of delaying or withholding antibiotics for suspected urinary tract infection (UTI) in older patients. We evaluated the association between antibiotic treatment for lower UTI and risk of bloodstream infection (BSI) in adults aged ≥65 years in primary care.Methods and findingsWe analyzed primary care records from patients aged ≥65 years in England with community-onset UTI using the Clinical Practice Research Datalink (2007-2015) linked to Hospital Episode Statistics and census data. The primary outcome was BSI within 60 days, comparing patients treated immediately with antibiotics and those not treated immediately. Crude and adjusted associations between exposure and outcome were estimated using generalized estimating equations. A total of 147,334 patients were included representing 280,462 episodes of lower UTI. BSI occurred in 0.4% (1,025/244,963) of UTI episodes with immediate antibiotics versus 0.6% (228/35,499) of episodes without immediate antibiotics. After adjusting for patient demographics, year of consultation, comorbidities, smoking status, recent hospitalizations, recent accident and emergency (A&E) attendances, recent antibiotic prescribing, and home visits, the odds of BSI were equivalent in patients who were not treated with antibiotics immediately and those who were treated on the date of their UTI consultation (adjusted odds ratio [aOR] 1.13, 95% CI 0.97-1.32, p-value = 0.105). Delaying or withholding antibiotics was associated with increased odds of death in the subsequent 60 days (aOR 1.17, 95% CI 1.09-1.26, p-value < 0.001), but there was limited evidence that increased deaths were attributable to urinary-source BSI. Limitations include overlap between the categories of immediate and delayed antibiotic prescribing, residual confounding underlying differences between patients who were/were not treated with antibiotics, and lack of microbiological diagnosis for BSI.ConclusionsIn this study, we observed that delaying or withholding antibiotics in older adults with suspected UTI did not increase patients' risk of BSI, in contrast with a previous study that analyzed the same dataset, but mortality was increased. Our findings highlight uncertainty around the risks of delaying or withholding antibiotic treatment, which is exacerbated by systematic differences between patients who were and were not treated immediately with antibiotics. Overall, our findings emphasize the need for improved diagnostic/risk prediction strategies to guide antibiotic prescribing for suspected UTI in older adults.

Behaviour change is key to combating antimicrobial resistance. Antimicrobial stewardship (AMS) programmes promote and monitor judicious antibiotic use, but there is little consideration of behavioural and social influences when designing interventions. We outline a programme of research which aims to co-design AMS interventions across healthcare settings, by integrating data-science, evidence- synthesis, behavioural-science and user-centred design. The project includes three work-packages (WP): WP1 (Identifying patterns of prescribing): analysis of electronic health-records to identify prescribing patterns in care-homes, primary-care, and secondary-care. An online survey will investigate consulting/antibiotic-seeking behaviours in members of the public. WP2 (Barriers and enablers to prescribing in practice): Semi-structured interviews and observations of practice to identify barriers/enablers to prescribing, influences on antibiotic-seeking behaviour and the social/contextual factors underpinning prescribing. Systematic reviews of AMS interventions to identify the components of existing interventions associated with effectiveness. Design workshops to identify constraints influencing the form of the intervention. Interviews conducted with healthcare-professionals in community pharmacies, care-homes, primary-, and secondary-care and with members of the public. Topic guides and analysis based on the Theoretical Domains Framework. Observations conducted in care-homes, primary and secondary-care with analysis drawing on grounded theory. Systematic reviews of interventions in each setting will be conducted, and interventions described using the Behaviour Change Technique taxonomy v1. Design workshops in care-homes, primary-, and secondary care. WP3 (Co-production of interventions and dissemination). Findings will be integrated to identify opportunities for interventions, and assess whether existing interventions target influences on antibiotic use. Stakeholder panels will be assembled to co-design and refine interventions in each setting, applying the Affordability, Practicability, Effectiveness, Acceptability, Side-effects and Equity (APEASE) criteria to prioritise candidate interventions. Outputs will inform development of new AMS interventions and/or optimisation of existing interventions. We will also develop web-resources for stakeholders providing analyses of antibiotic prescribing patterns, prescribing behaviours, and evidence reviews.

Introduction There is a growing trend to use storytelling as a research tool to extract information and/or as an intervention to effect change in the public knowledge, attitudes and behaviour (KAB) in relation to public health issues, primarily those with a strong element of disease prevention. However, evidence of its use in either or both capacities is limited. This protocol proposes a systematic narrative review of peer-reviewed, published literature on the use of storytelling as a research tool within the public health arena.Methods and analysis Medline, EMBASE, PsycINFO, ERIC (Educational Resources Information Center), Web of Science, Art and Humanities database (ProQuest), Scopus and Google Scholar will be searched for studies that look at the use of storytelling in the research of pressing current public health issues, for example, vaccinations, antimicrobial resistance, climate change and cancer screening. The review will synthesise evidence of how storytelling is used as a research tool to (a) gain insights into KAB and (b) to effect change in KAB when used as an intervention. Included studies will be selected according to carefully defined criteria relevant to public health issues of interest, and data from qualitative, quantitative and mixed-methods studies will be extracted with a customised data extraction form. A narrative synthesis will be performed according to Economic and Social Research Council guidance from Popay, J, 2006.The study protocol follows the recommendations by the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P).Ethics and dissemination Formal ethical approval is not required for this study, as no primary data will be collected. Dissemination will involve publishing results of this study in relevant peer-reviewed journal(s). Where possible, the study results will also be presented as posters or talks at relevant medical conferences and meetings.PROSPERO registration number CRD42019124704

Objectives Patients with liver disease frequently require hospitalisation with infection often the trigger. Influenza vaccination is an effective infection prevention strategy in healthy and elderly but is often perceived less beneficial in patients with liver disease. We investigated whether influenza vaccination triggered serological response and prevented hospitalisation and death in liver disease.Design Systematic review and meta-analysis.Data sources MEDLINE, EMBASE, PubMed and CENTRAL up to January 2019.Eligibility criteria Randomised or observational studies of the effects of influenza vaccine in adults with liver disease.Data extraction and synthesis Two reviewers screened studies, extracted data and assessed risk of bias and quality of evidence. Primary outcomes were all-cause hospitalisation and mortality. Secondary outcomes were cause-specific hospitalisation and mortality, and serological vaccine response. Random-effects meta-analysis was used to estimate pooled effects of vaccination.Results We found 10 041 unique records, 286 were eligible for full-text review and 12 were included. Most patients had viral liver disease. All studies were of very low quality. Liver patients both with and without cirrhosis mounted an antibody response to influenza vaccination, and vaccination was associated with a reduction in risk of hospital admission from 205/1000 to 149/1000 (risk difference −0.06, 95% CI −0.07 to 0.04) in patients with viral liver disease. Vaccinated patients were 27% less likely to be admitted to hospital compared with unvaccinated patients (risk ratio 0.73, 95% CI 0.66 to 0.80). No effect against all-cause or cause-specific mortality or cause-specific hospitalisation was found.Conclusions The low quantity and quality of the evidence means that the protective vaccine effect may be uncertain. Considering the high risk of serious health outcomes from influenza infection in patients with liver disease and the safety and low cost of vaccination, overall, the potential benefits of seasonal vaccination both to patients and the healthcare systems are likely to outweigh the costs and risks associated with vaccination.PROSPERO registration number CRD42017067277.

An amendment to this paper has been published and can be accessed via the original article.

Introduction: Rates of community-acquired Escherichia coli bacteraemia (ECB) have been consistently rising. As rates of antimicrobial resistance (AMR), particularly in Gram-negative bacteria, are also increasing, this is of concern both for management of individual patients and healthcare systems. There is currently little data on the risk factors for development of community-acquired ECB: this review aims to identify these risk factors in order to inform community interventions to reduce ECB as well as antibiotic prescribing policy. Methods and analysis: We will search Medline (Ovid), Embase (Ovid), Web of Science/Scopus and the Cochrane Central Register of Controlled Trials for published reports on observational and experimental primary research studies involving patients admitted to hospital with community-acquired ECB. Two reviewers will independently screen the studies for eligibility, perform data collection and assess study quality and risk of bias. Random effects meta-analyses will be performed if appropriate. Ethics and dissemination: No primary data will be collected for this study and so formal ethical approval is not required. We will publish the results of our review in relevant peer-reviewed medical journals, and will also seek to present them at relevant medical conferences. PROSPERO registration number: CRD42018104402

Background: Most antibiotic prescribing occurs in primary care, largely in children under 5 years old, and often inappropriately. This study investigated knowledge, attitudes and behaviours (KABs) towards common childhood infections, antibiotic use and antimicrobial resistance (AMR), among parents of children under 5 years old. The concept of individual sacrifice (forgoing antibiotics—a selective pressure for AMR) to mitigate future societal risk of AMR and how the COVID-19 pandemic shaped views were explored. Methods: This qualitative study included three, one-hour, virtual focus groups with mothers from parenting networks across inner-city London and semi-rural England, held mid-pandemic (2020) . All had ≥1 child The Framework Method of analysis was used. Parents' KABs towards antibiotic use/AMR formed the primary outcome, with emphases on their sense of personal agency towards mitigating the threat of AMR for society, plus how the pandemic influenced views on infection prevention and care. Results: Fourteen mothers (groups of six, four, four) participated, with mixed ethnicities, education and employment status. Parent perceptions of their individual child's immediate need for antibiotics outweighed concerns for any possible future threat of AMR to society. Four key themes were identified: uncertainty around symptoms; impact of socio-cultural background on KAB; poor understanding of how antibiotics/AMR work; and opportunities within the doctor–patient dialogue to shape mindset around AMR. The pandemic influenced views across themes. Conclusion: Parents prioritising their child's perceived, immediate, individual 'need' for antibiotics over any future impact of AMR on society highlights a continuing need to engage parents in how to mitigate AMR through appropriate antibiotic use, reducing threat to both their child and others. Framing point-of-care dialogue around antibiotic use/AMR in the present (versus future), drawing on pandemic insights and tailoring according to nuanced socio-cultural influences, may encourage a greater sense of personal agency towards taking action to mitigate antibiotic resistance.