Penicillin allergy status and its effect on antibiotic prescribing, patient outcomes and antimicrobial resistance (ALABAMA): protocol for a multicentre, parallel-arm, open-label, randomised pragmatic trial.

INTRODUCTION: Incorrect penicillin allergy records are recognised as an important barrier to the safe treatment of infection and affect an estimated 2.7 million people in England. Penicillin allergy records are associated with worse health outcome and antimicrobial resistance. The ALlergy AntiBiotics And Microbial resistAnce (ALABAMA) trial aims to determine if an intervention package, centred around a penicillin allergy assessment pathway (PAAP) initiated in primary care, is safe and effective in improving patient health outcomes and antibiotic prescribing. METHODS AND ANALYSIS: The ALABAMA trial is a multicentre, parallel-arm, open-label, randomised pragmatic trial with a nested pilot study. Adults (≥18 years) with a penicillin allergy record and who have received antibiotics in the previous 24 months will be eligible for participation. Between 1592 and 2090 participants will be recruited from participating National Health Service general practices in England. Participants will be randomised to either usual care or intervention to undergo a pre-emptive PAAP using a 1:1 allocation ratio. The primary outcome measure is the percentage of treatment response failures within 28 days of an index prescription. 2090 and 1592 participants are estimated to provide 90% and 80% power, respectively, to detect a clinically important absolute difference of 7.9% in primary outcome at 1 year between groups. The trial includes a mixed-methods process evaluation and cost-effectiveness evaluation. ETHICS AND DISSEMINATION: This trial has been approved by London Bridge Research Ethics Committee (ref: 19/LO/0176). It will be conducted in compliance with Good Clinical Practice guidelines according to the Declaration of Helsinki. Informed consent will be obtained from all subjects involved in the study. The primary trial results will be submitted for publication to an international, peer-reviewed journal. TRIAL REGISTRATION: ISRCTN20579216.

Management of asthma in primary care in the changing context of the COVID-19 pandemic: a qualitative longitudinal study with patients.

BACKGROUND: The COVID-19 pandemic dramatically affected asthma monitoring in primary care, but exploration of patients' views and their experiences of managing their asthma and seeking help from primary care during the pandemic has been limited. AIM: To investigate patients' experiences of asthma management in the community during the COVID-19 pandemic. DESIGN AND SETTING: A qualitative longitudinal study using semi-structured interviews with patients from four GP practices across diverse regions including Thames Valley, Greater Manchester, Yorkshire, and North West Coast. METHOD: Interviews were undertaken with patients with asthma, who were usually managed in primary care. The interviews were audiorecorded, transcribed, and analysed using inductive temporal thematic analysis and a trajectory approach. RESULTS: Forty-six interviews were conducted with 18 patients over an 8-month period that covered contrasting stages of the COVID-19 pandemic. Patients felt less vulnerable as the pandemic subsided, but the process of making sense of risk was dynamic and influenced by multiple factors. Patients relied on self-management strategies, but felt that routine asthma reviews should still have been conducted during the pandemic and highlighted that they had limited opportunities to discuss their asthma with health professionals. Patients with well-controlled symptoms felt that remote reviews were largely satisfactory, but still thought face-to-face reviews were necessary for certain aspects, such as physical examination and patient-led discussions of sensitive or broader issues associated with asthma, including mental health. CONCLUSION: The dynamic nature of patients' perception of risk throughout the pandemic highlighted the need for greater clarity regarding personal risk. Having an opportunity to discuss their asthma is important to patients, even when access to face-to-face consultations in primary care is more restricted than usual.

Re-examining advice to complete antibiotic courses: a qualitative study with clinicians and patients.

BACKGROUND: Antibiotic treatment duration may be longer than sometimes needed. Stopping antibiotics early, rather than completing pre-set antibiotic courses, may help reduce unnecessary exposure to antibiotics and antimicrobial resistance (AMR). AIM: To identify clinicians' and patients' views on stopping antibiotics when better (SAWB) for urinary tract infections (UTIs), and to explore comparisons with other acute infections. DESIGN & SETTING: An exploratory qualitative study with general practice clinicians and patients in England. METHOD: Primary care clinicians and patients who had recent UTI experience were recruited in England. Remote one-to-one interviews with clinicians and patients, and one focus group with patients, were conducted. Data were audiorecorded, transcribed, and analysed thematically. RESULTS: Eleven clinicians (seven GPs) and 19 patients (14 with experience of recurrent and/or chronic UTIs) were included. All participants considered SAWB unfamiliar and contradictory to well-known advice to complete antibiotic courses, but were interested in the evidence for risks and benefits of SAWB. Clinicians were amenable if evidence and guidelines supported it, whereas patients were more averse because of concerns about the risk of UTI recurrence and/or complications and AMR. Participants viewed SAWB as potentially more appropriate for longer antibiotic courses and other infections (with longer courses and lower risk of recurrence and/or complications). Participants stressed the need for unambiguous advice and SAWB as part of shared decision making and personalised advice. CONCLUSION: Patients were less accepting of SAWB, whereas clinicians were more amenable to it. Patients and clinicians require good evidence that this novel approach to self-determining antibiotic duration is safe and beneficial. If evidence based, SAWB should be offered with an explanation of why the advice differs from the 'complete the course' instruction, and a clear indication of when exactly to stop antibiotics should be given.

Antibiotic review kit for hospitals (ARK-Hospital): a stepped-wedge cluster-randomised controlled trial.

BACKGROUND: Strategies to reduce antibiotic overuse in hospitals depend on prescribers taking decisions to stop unnecessary antibiotic use. There is scarce evidence for how to support these decisions. We evaluated a multifaceted behaviour change intervention (ie, the antibiotic review kit) designed to reduce antibiotic use among adult acute general medical inpatients by increasing appropriate decisions to stop antibiotics at clinical review. METHODS: We performed a stepped-wedge, cluster (hospital)-randomised controlled trial using computer-generated sequence randomisation of eligible hospitals in seven calendar-time blocks in the UK. Hospitals were eligible for inclusion if they admitted adult non-elective general or medical inpatients, had a local representative to champion the intervention, and could provide the required study data. Hospital clusters were randomised to an implementation date occurring at 1-2 week intervals, and the date was concealed until 12 weeks before implementation, when local preparations were designed to start. The intervention effect was assessed using data from pseudonymised routine electronic health records, ward-level antibiotic dispensing, Clostridioides difficile tests, prescription audits, and an implementation process evaluation. Co-primary outcomes were monthly antibiotic defined daily doses per adult acute general medical admission (hospital-level, superiority) and all-cause mortality within 30 days of admission (patient level, non-inferiority margin of 5%). Outcomes were assessed in the modified intention-to-treat population (ie, excluding sites that withdrew before implementation). Intervention effects were assessed by use of interrupted time series analyses within each site, estimating overall effects through random-effects meta-analysis, with heterogeneity across prespecified potential modifiers assessed by use of meta-regression. This trial is completed and is registered with ISRCTN, ISRCTN12674243. FINDINGS: 58 hospital organisations expressed an interest in participating. Three pilot sites implemented the intervention between Sept 25 and Nov 20, 2017. 43 further sites were randomised to implement the intervention between Feb 12, 2018, and July 1, 2019, and seven sites withdrew before implementation. 39 sites were followed up for at least 14 months. Adjusted estimates showed reductions in total antibiotic defined daily doses per acute general medical admission (-4·8% per year, 95% CI -9·1 to -0·2) following the intervention. Among 7 160 421 acute general medical admissions, the ARK intervention was associated with an immediate change of -2·7% (95% CI -5·7 to 0·3) and sustained change of 3·0% (-0·1 to 6·2) in adjusted 30-day mortality. INTERPRETATION: The antibiotic review kit intervention resulted in sustained reductions in antibiotic use among adult acute general medical inpatients. The weak, inconsistent intervention effects on mortality are probably explained by the onset of the COVID-19 pandemic. Hospitals should use the antibiotic review kit to reduce antibiotic overuse. FUNDING: UK National Institute for Health and Care Research.

Qualitative study on perceptions of use of Fractional Exhaled Nitric Oxide (FeNO) in asthma reviews.

Current methods to assess asthma and guide inhaled corticosteroid (ICS) dose titration mainly centre on patient-reported symptoms and lung function assessments. However, these methods correlate only weakly with airway inflammation making them unreliable predictors of future exacerbations and ICS requirement. Fractional Exhaled Nitric Oxide (FeNO) is a simple non-invasive objective measure of airways inflammation used predominantly in specialist clinics. Previous qualitative studies have mainly focused on the acceptability of FeNO in secondary care and there is limited insight to support clinicians and patients using FeNO in primary care asthma reviews. This study aimed to explore adult patient with asthma and primary care health care professional (HCP) views on introducing FeNO as part of routine asthma reviews. Twenty-three health care professionals and 22 patients were interviewed over the phone or online. Both groups reported that current asthma reviews are often seen as tick-box exercises and that introducing the FeNO test would make reviews more tailored to the individual patient, rather than relying on subjective patient reports of asthma control. Adults with asthma also highlighted support more open communication and their understanding of asthma, as they desired to feel more engaged in decisions and conversations about their asthma. HCPs reported valuing patient education and empowerment over a paternalistic approach, when time and resources allow. They also recognised FeNO to provide an objective measure of inflammation that could support them in the education and empowerment of patients. FeNO was seen by both groups as a potentially valuable addition to current asthma reviews mainly led by nurses, both for increasing their understanding of current risk of exacerbation and also to provide more tailored and personalised asthma management to patients. Our findings highlighted the need for open and clear communication about how to interpret FeNO results.

The value, challenges and practical considerations of conducting qualitative research on antimicrobial stewardship in primary care.

In order to design appropriate antimicrobial stewardship (AMS) programmes, it is crucial to understand challenges to tackling antibiotic resistance (AMR) specific to each healthcare setting. Antibiotic prescribing in primary care accounts for most prescriptions with a significant proportion considered clinically inappropriate. Qualitative research has a long history in social sciences, but its value and contribution are still contested in medical journals including in the AMR/AMS field. However, through its focus on understanding, meaning making and explaining, qualitative research can offer insights in how to improve AMS efforts in primary care. This paper provides an overview of unique considerations, contributions and challenges related to using qualitative research in AMS to help the AMS community new to qualitative research to utilize its potential most fully. First, we discuss specific considerations for AMS in relation to the stages of conducting a qualitative study, including identifying a research question and choosing a suitable methodology; sampling appropriate participants; planning a recruitment strategy; choosing a method of data collection; and conducting data analysis. These are illustrated with examples of qualitative AMS studies in primary care. Second, we highlight the importance of patient and public involvement throughout all stages of the project and ensuring quality in qualitative AMS research. Finally, drawing on these considerations, we make a further case for the value and contribution of qualitative methodologies in AMS/AMR research while outlining future directions for both AMS and qualitative research, including the need for studies with diverse actors; interdisciplinary collaborations; and complex decisions on methodologies and timelines.

How can behavioural science contribute to qualitative research on antimicrobial stewardship in primary care?

Antibiotic use (and misuse) accelerates antimicrobial resistance (AMR), and addressing this complex problem necessitates behaviour change related to infection prevention and management and to antibiotic prescribing and use. As most antibiotic courses are prescribed in primary care, a key focus of antimicrobial stewardship (AMS) is on changing behaviours outside of hospital. Behavioural science draws on behaviour change theories, techniques and methods developed in health psychology, and can be used to help understand and change behaviours related to AMR/AMS. Qualitative methodologies can be used together with a behavioural science approach to explore influences on behaviour and develop and evaluate behavioural interventions. This paper provides an overview of how the behavioural science approach, together with qualitative methods, can contribute and add value to AMS projects. First, it introduces and explains the relevance of the behavioural science approach to AMR/AMS. Second, it provides an overview of behaviour change 'tools': behaviour change theories/models, behavioural determinants and behaviour change techniques. Third, it explains how behavioural methods can be used to: (i) define a clinical problem in behavioural terms and identify behavioural influences; (ii) develop and implement behavioural AMS interventions; and (iii) evaluate them. These are illustrated with examples of using qualitative methods in AMS studies in primary care. Finally, the paper concludes by summarizing the main contributions of taking the behavioural science approach to qualitative AMS research in primary care and discussing the key implications and future directions for research and practice.

Mixed-methods evaluation of a behavioural intervention package to identify and amend incorrect penicillin allergy records in UK general practice.

OBJECTIVES: About 6% of the UK general practice population has a record of a penicillin allergy but fewer than 10% of these are likely to be truly allergic. In the ALABAMA (Allergy Antibiotics and Microbial resistance) feasibility trial, primary care patients with penicillin allergy were randomised to penicillin allergy assessment pathway or usual care to assess the effect on health outcomes. A behavioural intervention package was developed to aid delabelling. This study aimed to investigate patients' and clinicians' views of penicillin allergy testing (PAT). DESIGN: We conducted a mixed-methods process evaluation embedded within the ALABAMA trial, which included a clinician survey, a patient survey (at baseline and follow-up) and semistructured interviews with patients and clinicians. SETTINGS: The study was conducted in primary care, as part of the feasibility stage of the ALABAMA trial. PARTICIPANTS: Patients and primary care clinicians. RESULTS: Clinicians (N=53; 52.2%) were positive about PAT and its potential value but did not have previous experience of referring patients for a PAT and were unsure whether patients would take penicillin after a negative allergy test. Patients (N=36; 46%) were unsure whether they were severely allergic to penicillin and did not fear a severe allergic reaction to penicillin. Clinician interviews showed that they were already aware of the benefit of PAT. Interviews with patients suggested the importance of safety as patients valued having numerous opportunities to address their concerns about safety of the test. CONCLUSIONS: This study highlights the positive effects of the ALABAMA behavioural intervention for both patients and clinicians. TRIAL REGISTRATION NUMBER: NCT04108637; ISRCTN20579216; Pre-results.

Developing a behavioural intervention package to identify and amend incorrect penicillin allergy records in UK general practice and subsequently change antibiotic use.

OBJECTIVES: To develop a behavioural intervention package to support clinicians and patients to amend incorrect penicillin allergy records in general practice. The intervention aimed to: (1) support clinicians to refer patients for penicillin allergy testing (PAT), (2) support patients to attend for PAT and (3) support clinicians and patients to prescribe or consume penicillin, when indicated, following a negative PAT result. METHODS: Theory-based, evidence-based and person-based approaches were used in the intervention development. We used evidence from a rapid review, two qualitative studies, and expert consultations with the clinical research team to identify the intervention 'guiding principles' and develop an intervention plan. Barriers and facilitators to the target behaviours were mapped to behaviour change theory in order to describe the proposed mechanisms of change. In the final stage, think-aloud interviews were conducted to optimise intervention materials. RESULTS: The collated evidence showed that the key barriers to referral of patients by clinicians were limited experience of referral and limited knowledge of referral criteria and PAT. Barriers for patients attending PAT were lack of knowledge of the benefits of testing and lack of motivation to get tested. The key barriers to the prescription and consumption of first-line penicillin following a negative test result were patient and clinician beliefs about the accuracy of PAT and whether taking penicillin was safe. Intervention materials were designed and developed to address these barriers. CONCLUSIONS: We present a novel behavioural intervention package designed to address the multiple barriers to uptake of PAT in general practice by clinicians and patients. The intervention development details how behaviour change techniques have been incorporated to hypothesise how the intervention is likely to work to help amend incorrect penicillin allergy records. The intervention will go on to be tested in a feasibility trial and randomised controlled trial in England.

Patient engagement with antibiotic messaging in secondary care: a qualitative feasibility study of the 'review and revise' experience.

BACKGROUND: We aimed to investigate and optimise the acceptability and usefulness of a patient leaflet about antibiotic prescribing decisions made during hospitalisation, and to explore individual patient experiences and preferences regarding the process of antibiotic prescription 'review and revise' which is a key strategy to minimise antibiotic overuse in hospitals. METHODS: In this qualitative study, run within the feasibility study of a large, cluster-randomised stepped wedge trial of 36 hospital organisations, a series of semi-structured, think-aloud telephone interviews were conducted and data were analysed using thematic analysis. Fifteen adult patients who had experienced a recent acute medical hospital admission during which they had been prescribed antimicrobials and offered a patient leaflet about antibiotic prescribing were recruited to the study. RESULTS: Participants reacted positively to the leaflet, reporting that it was both an accessible and important source of information which struck the appropriate balance between informing and reassuring. Participants all valued open communication with clinicians, and were keen to be involved in antibiotic prescribing decisions, with individuals reporting positive experiences regarding antibiotic prescription changes or stopping. Many participants had prior experience or knowledge of antibiotics and resistance, and generally welcomed efforts to reduce antibiotic usage. Overall, there was a feeling that healthcare professionals (HCPs) are trusted experts providing the most appropriate treatment for individual patient conditions. CONCLUSIONS: This study offers novel insights into how patients within secondary care are likely to respond to messages advocating a reduction in the use of antibiotics through the 'review and revise' approach. Due to the level of trust that patients place in their care provider, encouraging HCPs within secondary care to engage patients with greater communication and information provision could provide great advantages in the drive to reduce antibiotic use. It may also be beneficial for HCPs to view patient experiences as cumulative events that have the potential to impact future behaviour around antibiotic use. Finally, pre-testing messages about antibiotic prescribing and resistance is vital to dispelling any misconceptions either around effectiveness of treatment for patients, or perceptions of how messages may be received. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12674243 (10 April 2017).

Antibiotic Review Kit for Hospitals (ARK-Hospital): study protocol for a stepped-wedge cluster-randomised controlled trial.

BACKGROUND: To ensure patients continue to get early access to antibiotics at admission, while also safely reducing antibiotic use in hospitals, one needs to target the continued need for antibiotics as more diagnostic information becomes available. UK Department of Health guidance promotes an initiative called 'Start Smart then Focus': early effective antibiotics followed by active 'review and revision' 24-72 h later. However in 2017, < 10% of antibiotic prescriptions were discontinued at review, despite studies suggesting that 20-30% of prescriptions could be stopped safely. METHODS/DESIGN: Antibiotic Review Kit for Hospitals (ARK-Hospital) is a complex 'review and revise' behavioural intervention targeting healthcare professionals involved in antibiotic prescribing or administration in inpatients admitted to acute/general medicine (the largest consumers of non-prophylactic antibiotics in hospitals). The primary study objective is to evaluate whether ARK-Hospital can safely reduce the total antibiotic burden in acute/general medical inpatients by at least 15%. The primary hypotheses are therefore that the introduction of the behavioural intervention will be non-inferior in terms of 30-day mortality post-admission (relative margin 5%) for an acute/general medical inpatient, and superior in terms of defined daily doses of antibiotics per acute/general medical admission (co-primary outcomes). The unit of observation is a hospital organisation, a single hospital or group of hospitals organised with one executive board and governance framework (National Health Service trusts in England; health boards in Northern Ireland, Wales and Scotland). The study comprises a feasibility study in one organisation (phase I), an internal pilot trial in three organisations (phase II) and a cluster (organisation)-randomised stepped-wedge trial (phase III) targeting a minimum of 36 organisations in total. Randomisation will occur over 18 months from November 2017 with a further 12 months follow-up to assess sustainability. The behavioural intervention will be delivered to healthcare professionals involved in antibiotic prescribing or administration in adult inpatients admitted to acute/general medicine. Outcomes will be assessed in adult inpatients admitted to acute/general medicine, collected through routine electronic health records in all patients. DISCUSSION: ARK-Hospital aims to provide a feasible, sustainable and generalisable mechanism for increasing antibiotic stopping in patients who no longer need to receive them at 'review and revise'. TRIAL REGISTRATION: ISRCTN Current Controlled Trials, ISRCTN12674243 . Registered on 10 April 2017.

Mentorship for newly appointed consultants: what makes it work?

BACKGROUND: Mentorship has been identified as a beneficial practice for doctors and may be particularly valuable for newly appointed consultants. It is associated with a number of potential clinical and non-clinical gains, such as enhanced job satisfaction and well-being. Despite strong support, many formalised schemes fail to launch or gain momentum. Research to date has largely focused on the gains associated with mentorship but has lacked study of the factors that facilitate uptake and maintenance of mentoring relationships by physicians. OBJECTIVES: To explore perceptions of mentorship, the extent to which UK doctors appear to value mentorship and factors that may contribute to its successful use. DESIGN: Qualitative, descriptive, multi-centre study. SAMPLE: 30 doctors including registrars, those newly appointed to consultant grade, senior doctors and medical leaders from nine hospitals in the north of England. METHOD: Semistructured individual interviews were undertaken between August and December 2013. RESULTS: Findings revealed a demand for mentorship for new consultants, with widely recognised benefits associated with its use. Several factors were identified as critical to successful mentorship relationships, including consistent understanding and expectations of mentorship between mentee and mentor, positive prior experiences, a suitable match between mentee and mentor, making time for people to act as mentors and the ensuring that mentors can meet a diverse and changing set of needs. CONCLUSIONS: Mentorship for newly appointed consultants is valued, but current models of mentorship may suffer from rigid structures, mismatched expectations of participants and the absence of a culture of mentorship from training into practice. A social network approach, in which doctors have the opportunity to engage with a range of mentors through informal and naturally occurring relationships, may be one way to encourage successful and sustained mentoring relationships among doctors. An organisational culture in which mentorship is permitted and is the norm may enable such approaches to be widely adopted.