Incidence, healthcare-seeking behaviours, antibiotic use and natural history of common infection syndromes in England: results from the Bug Watch community cohort study.

BACKGROUND: Better information on the typical course and management of acute common infections in the community could inform antibiotic stewardship campaigns. We aimed to investigate the incidence, management, and natural history of a range of infection syndromes (respiratory, gastrointestinal, mouth/dental, skin/soft tissue, urinary tract, and eye). METHODS: Bug Watch was an online prospective community cohort study of the general population in England (2018-2019) with weekly symptom reporting for 6 months. We combined symptom reports into infection syndromes, calculated incidence rates, described the proportion leading to healthcare-seeking behaviours and antibiotic use, and estimated duration and severity. RESULTS: The cohort comprised 873 individuals with 23,111 person-weeks follow-up. The mean age was 54 years and 528 (60%) were female. We identified 1422 infection syndromes, comprising 40,590 symptom reports. The incidence of respiratory tract infection syndromes was two per person year; for all other categories it was less than one. 194/1422 (14%) syndromes led to GP (or dentist) consultation and 136/1422 (10%) to antibiotic use. Symptoms usually resolved within a week and the third day was the most severe. CONCLUSIONS: Most people reported managing their symptoms without medical consultation. Interventions encouraging safe self-management across a range of acute infection syndromes could decrease pressure on primary healthcare services and support targets for reducing antibiotic prescribing.

COVID-19 infection and attributable mortality in UK care homes: cohort study using active surveillance and electronic records (March-June 2020).

BACKGROUND: epidemiological data on COVID-19 infection in care homes are scarce. We analysed data from a large provider of long-term care for older people to investigate infection and mortality during the first wave of the pandemic. METHODS: cohort study of 179 UK care homes with 9,339 residents and 11,604 staff. We used manager-reported daily tallies to estimate the incidence of suspected and confirmed infection and mortality in staff and residents. Individual-level electronic health records from 8,713 residents were used to model risk factors for confirmed infection, mortality and estimate attributable mortality. RESULTS: 2,075/9,339 residents developed COVID-19 symptoms (22.2% [95% confidence interval: 21.4%; 23.1%]), while 951 residents (10.2% [9.6%; 10.8%]) and 585 staff (5.0% [4.7%; 5.5%]) had laboratory-confirmed infections. The incidence of confirmed infection was 152.6 [143.1; 162.6] and 62.3 [57.3; 67.5] per 100,000 person-days in residents and staff, respectively. Sixty-eight percent (121/179) of care homes had at least one COVID-19 infection or COVID-19-related death. Lower staffing ratios and higher occupancy rates were independent risk factors for infection.Out of 607 residents with confirmed infection, 217 died (case fatality rate: 35.7% [31.9%; 39.7%]). Mortality in residents with no direct evidence of infection was twofold higher in care homes with outbreaks versus those without (adjusted hazard ratio: 2.2 [1.8; 2.6]). CONCLUSIONS: findings suggest many deaths occurred in people who were infected with COVID-19, but not tested. Higher occupancy and lower staffing levels were independently associated with risks of infection. Protecting staff and residents from infection requires regular testing for COVID-19 and fundamental changes to staffing and care home occupancy.

Complementing chronic frailty assessment at hospital admission with an electronic frailty index (FI-Laboratory) comprising routine blood test results.

BACKGROUND: Acutely ill and frail older adults have complex social and health care needs. It is important to understand how this complexity affects acute outcomes for admission to hospital. We validated a frailty index using routine admission laboratory tests with outcomes after patients were admitted to hospital. METHODS: In a prospective cohort of older adults admitted to a large tertiary hospital in the United Kingdom, we created a frailty index from routine admission laboratory investigations (FI-Laboratory) linked to data comprising hospital outcomes. We evaluated the association between the FI-Laboratory and total days spent in hospital, discharge to a higher level of care, readmission and mortality. RESULTS: Of 2552 admissions among 1750 older adults, we were able to generate FI-Laboratory values for 2254 admissions (88.3% of the cohort). More than half of admitted patients were women (55.3%) and the mean age was 84.6 (SD 14.0) years. We found that the FI-Laboratory correlated weakly with the Clinical Frailty Scale (CFS; r 2 = 0.09). An increase in the CFS and the equivalent of 3 additional abnormal laboratory test results in the FI-Laboratory, respectively, were associated with an increased proportion of inpatient days (rate ratios [RRs] 1.43, 95% confidence interval [CI] 1.35-1.52; and 1.47, 95% CI 1.41-1.54), discharge to a higher level of care (odd ratios [ORs] 1.39, 95% CI 1.27-1.52; and 1.30, 95% CI 1.16-1.47) and increased readmission rate (hazard ratios [HRs] 1.26, 95% CI 1.17-1.37; and 1.18, 95% CI 1.11-1.26). Increases in the CFS and FI-Laboratory were associated with increased mortality HRs of 1.39 (95% CI 1.28-1.51) and 1.45 (95% CI 1.37-1.54), respectively. INTERPRETATION: We determined that FI-Laboratory, distinct from baseline frailty, could be used to predict risk of many adverse outcomes. The score is therefore a useful way to quantify the degree of acute illness in frail older adults.

Alcohol use and breast cancer risk: A qualitative study of women's perspectives to inform the development of a preventative intervention in breast clinics.

OBJECTIVE: This study aimed to explore women's views about breast cancer risk and alcohol use, to inform the design of a prototype for an intervention in breast clinics about alcohol as a modifiable risk factor for breast cancer. METHODS: Women recruited in NHS breast screening and symptomatic clinics in Southampton, UK, were invited to take part in semi-structured telephone interviews or a focus group to discuss their perspectives of breast cancer risk, alcohol consumption and their information needs about these topics. Data were analysed thematically. Twenty-eight women took part in telephone interviews, and 16 attended one of three focus groups. RESULTS: While most women reported a personal responsibility for their health and were interested in advice about modifiable risk factors, few without (or prior to) experience of breast symptoms independently sought information. Many considered alcohol advice irrelevant as the association with breast cancer was largely unknown, and participants did not consider their drinking to be problematic. Women reported trusting information from health organisations like the NHS, but advice needs to be sensitive and non-blaming. CONCLUSION: NHS breast screening and symptomatic clinics offer a "teachable moment" to engage women with context-specific advice about alcohol and cancer risk that, if targeted correctly, may assist them in making informed lifestyle choices.

The spatial structure of chronic morbidity: evidence from UK census returns.

BACKGROUND: Disease prevalence models have been widely used to estimate health, lifestyle and disability characteristics for small geographical units when other data are not available. Yet, knowledge is often lacking about how to make informed decisions around the specification of such models, especially regarding spatial assumptions placed on their covariance structure. This paper is concerned with understanding processes of spatial dependency in unexplained variation in chronic morbidity. METHODS: 2011 UK census data on limiting long-term illness (LLTI) is used to look at the spatial structure in chronic morbidity across England and Wales. The variance and spatial clustering of the odds of LLTI across local authority districts (LADs) and middle layer super output areas are measured across 40 demographic cross-classifications. A series of adjacency matrices based on distance, contiguity and migration flows are tested to examine the spatial structure in LLTI. Odds are then modelled using a logistic mixed model to examine the association with district-level covariates and their predictive power. RESULTS: The odds of chronic illness are more dispersed than local age characteristics, mortality, hospitalisation rates and chance alone would suggest. Of all adjacency matrices, the three-nearest neighbour method is identified as the best fitting. Migration flows can also be used to construct spatial weights matrices which uncover non-negligible autocorrelation. Once the most important characteristics observable at the LAD-level are taken into account, substantial spatial autocorrelation remains which can be modelled explicitly to improve disease prevalence predictions. CONCLUSIONS: Systematic investigation of spatial structures and dependency is important to develop model-based estimation tools in chronic disease mapping. Spatial structures reflecting migration interactions are easy to develop and capture autocorrelation in LLTI. Patterns of spatial dependency in the geographical distribution of LLTI are not comparable across ethnic groups. Ethnic stratification of local health information is needed and there is potential to further address complexity in prevalence models by improving access to disaggregated data.

Patterns and Drivers of Antifungal Prescribing in Acute Leukemia: A Retrospective Cohort Study.

Background: Patients with hematological malignancy are at high risk of invasive fungal infections (IFIs). Diagnosis is challenging, which can lead to overtreatment. Reducing exposure to inappropriate antifungal prescribing is likely to improve patient safety, but modifying prescribing behavior is difficult. We aimed to describe patterns and drivers of therapeutic antifungal prescribing in a large tertiary hemato-oncology center in the United Kingdom. Methods: We studied adults receiving treatment for acute leukemia at our center between 1 April 2019 and 14 October 2022. We developed a reproducible method to analyze routinely collected data on antifungal therapy episodes in a widely used electronic health record system. We report antifungal use in days of therapy stratified by level of diagnostic confidence, as defined by consensus diagnostic guidelines (European Organisation for Research and Treatment of Cancer/Mycoses Study Group). Results: Two hundred ninety-eight patients were included in the analysis; 21.7% of inpatient antifungal use occurred in cases of proven/probable IFI. Substantial antifungal use occurred in the absence of strong evidence of infection in patients receiving high-intensity first-line chemotherapy or approaching death (81.0% and 77.9%, respectively). Approximately 33% of high-resolution computed tomography (HRCT) reports were indeterminate for IFI. Indeterminate reports were around 8 times more likely to be followed by a new antifungal therapy episode than a negative report. Conclusions: Antifungal stewardship remains challenging in the absence of reliable diagnostics, particularly in more unwell patients. The proportion of antifungal therapy given for proven/probable infection is a new metric that will likely be useful to target antifungal stewardship programs. The thoracic HRCT report is an important contributor to diagnostic uncertainty.

Clinical testing of transcriptome-wide expression profiles in high-risk localized and metastatic prostate cancer starting androgen deprivation therapy: an ancillary study of the STAMPEDE abiraterone Phase 3 trial.

Metastatic and high-risk localized prostate cancer respond to hormone therapy but outcomes vary. Following a pre-specified statistical plan, we used Cox models adjusted for clinical variables to test associations with survival of multi-gene expression-based classifiers from 781 patients randomized to androgen deprivation with or without abiraterone in the STAMPEDE trial. Decipher score was strongly prognostic (p<2×10-5) and identified clinically-relevant differences in absolute benefit, especially for localized cancers. In metastatic disease, classifiers of proliferation, PTEN or TP53 loss and treatment-persistent cells were prognostic. In localized disease, androgen receptor activity was protective whilst interferon signaling (that strongly associated with tumor lymphocyte infiltration) was detrimental. Post-Operative Radiation-Therapy Outcomes Score was prognostic in localized but not metastatic disease (interaction p=0.0001) suggesting the impact of tumor biology on clinical outcome is context-dependent on metastatic state. Transcriptome-wide testing has clinical utility for advanced prostate cancer and identified worse outcomes for localized cancers with tumor-promoting inflammation.

Concurrent validity of an estimator of weekly alcohol consumption (EWAC) based on the extended AUDIT.

BACKGROUND AND AIMS: The three-question Alcohol Use Disorders Identification Test (AUDIT-C) is frequently used in healthcare for screening and brief advice about levels of alcohol consumption. AUDIT-C scores (0-12) provide feedback as categories of risk rather than estimates of actual alcohol intake, an important metric for behaviour change. The study aimed to (i) develop a continuous metric from the Extended AUDIT-C expressed in United Kingdom (UK) units (8 g pure ethanol), offering equivalent accuracy, and providing a direct estimator of weekly alcohol consumption (EWAC) and (ii) evaluate the EWAC's bias and error using the graduated-frequency (GF) questionnaire as a reference standard of alcohol consumption. DESIGN: Cross-sectional diagnostic study based on a nationally-representative survey. SETTINGS: Community dwelling households in England. PARTICIPANTS: A total of 22 404 household residents aged ≥16 years reporting drinking alcohol at least occasionally. MEASUREMENTS: Computer-assisted personal interviews consisting of (i) AUDIT questionnaire with extended response items (the 'Extended AUDIT') and (ii) GF. Primary outcomes were: mean deviation <1 UK unit (metric of bias); root-mean-square deviation <2 UK units (metric of total error) between EWAC and GF. The secondary outcome was the receiver operating characteristic area under the curve for predicting alcohol consumption in excess of 14 and 35 UK units. FINDINGS: EWAC had a positive bias of 0.2 UK units (95% CI = 0.08, 0.4) compared with GF. Deviations were skewed: whereas the mean error was ±11 UK units/week [9.5, 11.9], in half of participants the deviation between EWAC and GF was between 0 and ±2.1 UK units/week. EWAC predicted consumption in excess of 14 UK units/week with a significantly greater area under the curve (0.918 [0.914, 0.923]) than AUDIT-C (0.870 [0.864, 0.876]) or the full AUDIT (0.854 [0.847, 0.860]). CONCLUSIONS: A new estimator of weekly alcohol consumption, which uses answers to the Extended AUDIT-C, meets the targeted bias tolerance. It is superior in accuracy to AUDIT-C and the full 10-item AUDIT when predicting consumption thresholds, making it a reliable complement to the Extended AUDIT-C for health promotion interventions.

An interdisciplinary mixed-methods approach to developing antimicrobial stewardship interventions: Protocol for the Preserving Antibiotics through Safe Stewardship (PASS) Research Programme.

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.

A Context-Specific Digital Alcohol Brief Intervention in Symptomatic Breast Clinics (Abreast of Health): Development and Usability Study.

BACKGROUND: Potentially modifiable risk factors account for approximately 23% of breast cancer cases. In the United Kingdom, alcohol consumption alone is held responsible for 8% to 10% of cases diagnosed every year. Symptomatic breast clinics focus on early detection and treatment, but they also offer scope for delivery of low-cost lifestyle interventions to encourage a cancer prevention culture within the cancer care system. Careful development work is required to effectively translate such interventions to novel settings. OBJECTIVE: The aim of this study was to develop a theory of change and delivery mechanism for a context-specific alcohol and lifestyle brief intervention aimed at women attending screening and symptomatic breast clinics. METHODS: A formative study combined evidence reviews, analysis of mixed method data, and user experience research to develop an intervention model, following the 6 Steps in Quality Intervention Development (6SQuID) framework. RESULTS: A Web app focused on improving awareness, encouraging self-monitoring, and reframing alcohol reduction as a positive choice to improve health was found to be acceptable to women. Accessing this in the clinic waiting area on a tablet computer was shown to be feasible. An important facilitator for change may be the heightened readiness to learn associated with a salient health visit (a teachable moment). Women may have increased motivation to change if they can develop a belief in their capability to monitor and, if necessary, reduce their alcohol consumption. CONCLUSIONS: Using the 6SQuID framework supported the prototyping and maximized acceptability and feasibility of an alcohol brief intervention for women attending symptomatic breast clinics, regardless of their level of alcohol consumption.

Health Data Linkage for UK Public Interest Research: Key Obstacles and Solutions.

INTRODUCTION: Analysis of linked health data can generate important, even life-saving, insights into population health. Yet obstacles both legal and organisational in nature can impede this work. APPROACH: We focus on three UK infrastructures set up to link and share data for research: the Administrative Data Research Network, NHS Digital, and the Secure Anonymised Information Linkage Databank. Bringing an interdisciplinary perspective, we identify key issues underpinning their challenges and successes in linking health data for research. RESULTS: We identify examples of uncertainty surrounding legal powers to share and link data, and around data protection obligations, as well as systemic delays and historic public backlash. These issues require updated official guidance on the relevant law, approaches to linkage which are planned for impact and ongoing utility, greater transparency between data providers and researchers, and engagement with the patient population which is both high-profile and carefully considered. CONCLUSIONS: Health data linkage for research presents varied challenges, to which there can be no single solution. Our recommendations would require action from a number of data providers and regulators to be meaningfully advanced. This illustrates the scale and complexity of the challenge of health data linkage, in the UK and beyond: a challenge which our case studies suggest no single organisation can combat alone. Planned programmes of linkage are critical because they allow time for organisations to address these challenges without adversely affecting the feasibility of individual research projects.

Outcomes of domestic violence screening at an acute London trust: are there missed opportunities for intervention?

OBJECTIVES: Domestic violence screening is advocated in some healthcare settings. Evidence that it increases referral to support agencies or improves health outcomes is limited. This study aimed to (1) investigate the proportion of hospital patients reporting domestic violence, (2) describe characteristics and previous hospital attendances of affected patients and (3) assess referrals to an in-house domestic violence advisor from Camden Safety Net. DESIGN: A series of observational studies. SETTING: Three outpatient clinics at the Royal Free London NHS Foundation Trust. PARTICIPANTS: 10,158 patients screened for domestic violence in community gynaecology, genitourinary medicine (GUM) and HIV medicine clinics between 1 October 2013 and 30 June 2014. Also 2253 Camden Safety Net referrals over the same period. MAIN OUTCOME MEASURES: (1) Percentage reporting domestic violence by age group gender, ethnicity and clinic. (2) Rates of hospital attendances in the past 3 years for those screening positive and negative. (3) Characteristics, uptake and risk assessment results for hospital in-house domestic violence referrals compared with Camden Safety Net referrals from other sources. RESULTS: Of the 10,158 patients screened, 57.4% were female with a median age of 30 years. Overall, 7.1% reported ever-experiencing domestic violence, ranging from 5.7% in GUM to 29.4% in HIV services. People screening positive for domestic violence had higher rates of previous emergency department attendances (rate ratio (RR) 1.63, 95% CI 1.09 to 2.48), emergency inpatient admissions (RR 2.27, 95% CI 1.37 to 3.84) and day-case admissions (RR 2.03, 95% CI 1.23 to 3.43) than those screening negative. The 77 hospital referrals to the hospital-based domestic violence advisor during the study period were more likely to be taken up and to be classified as high risk than referrals from elsewhere. CONCLUSIONS: Selective screening for domestic violence in high-risk hospital clinic populations has the potential to identify affected patients and promote good uptake of referrals for in-house domestic violence support.