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We lead multidisciplinary applied research and training to rethink the way health care is delivered in general practice and across the community.
The impact of the COVID-19 pandemic on antimicrobial usage: An international patient-level cohort study
Background: This study aimed to evaluate the trends in antimicrobial prescription during the first 1.5 years of COVID-19 pandemic. Methods: This was an observational, retrospective cohort study using patient-level data from Bangladesh, Brazil, India, Italy, Malawi, Nigeria, South Korea, Switzerland and Turkey from patients with pneumonia and/or acute respiratory distress syndrome and/or sepsis, regardless of COVID-19 positivity, who were admitted to critical care units or COVID-19 specialized wards. The changes of antimicrobial prescription between pre-pandemic and pandemic were estimated using logistic or linear regression. Pandemic effects on month-wise antimicrobial usage were evaluated using interrupted time series analyses (ITSAs). Results: Antimicrobials for which prescriptions significantly increased during the pandemic were as follows: meropenem in Bangladesh (95% CI: 1.94-4.07) with increased prescribed daily dose (PDD) (95% CI: 1.17-1.58) and Turkey (95% CI: 1.09-1.58), moxifloxacin in Bangladesh (95% CI: 4.11-11.87) with increased days of therapy (DOT) (95% CI: 1.14-2.56), piperacillin/tazobactam in Italy (95% CI: 1.07-1.48) with increased DOT (95% CI: 1.01-1.25) and PDD (95% CI: 1.05-1.21) and azithromycin in Bangladesh (95% CI: 3.36-21.77) and Brazil (95% CI: 2.33-8.42). ITSA showed a significant drop in azithromycin usage in India (95% CI: -8.38 to -3.49â€...g/100 patients) and South Korea (95% CI: -2.83 to -1.89 g/100 patients) after WHO guidelines v1 release and increased meropenem usage (95% CI: 93.40-126.48 g/100 patients) and moxifloxacin (95% CI: 5.40-13.98 g/100 patients) in Bangladesh and sulfamethoxazole/trimethoprim in India (95% CI: 0.92-9.32 g/100 patients) following the Delta variant emergence. Conclusions: This study reinforces the importance of developing antimicrobial stewardship in the clinical settings during inter-pandemic periods.
Burden of RSV infections among young children in primary care: a prospective cohort study in five European countries (2021–23)
Background: The majority of respiratory syncytial virus (RSV) infections in young children are managed in primary care, however, the disease burden in this setting remains poorly defined. Methods: We did a prospective cohort study in primary care settings in Belgium, Italy, Spain, the Netherlands, and the UK during the RSV seasons of 2020–21 (UK only; from Jan 1, 2021), 2021–22, and 2022–23. Children aged younger than 5 years presenting to their general practitioner or primary care paediatrician with symptoms of an acute respiratory tract infection were eligible for RSV testing. Children who tested positive for RSV were consented and followed up for 30 days via a physician clinical report (initial primary care visit on day 1) and two parent-report questionnaires (days 14 and 30). We assessed the burden of RSV in terms of clinical course (symptoms, illness duration, and complications), health-care resource utilisation (primary care visits, emergency department visits, hospitalisation rate, and medication use), and societal impact (daycare or school absence and parental work absence) for the 30-day follow-up period. Findings: Among 3414 tested children, 1124 (32·9%; 95% CI 31·3–34·5) tested positive for RSV. Among children with data on age, RSV positivity rate was 38·9% (36·1–41·7; n=466 of 1198) in children younger than 1 year and 25·9% (24·0–27·9; n=513 of 1979) in those aged 1 to <5 years. Of the 1124 RSV-positive children, 878 (78·1%) were enrolled and had day 1 data collected (median age 11·1 months [IQR 6·0–22·0]; 446 [50·9%] boys and 431 [49·1%] girls [N=877]). RSV illness lasted a mean of 11·7 days (95% CI 11·2–12·2; n=794). At day 14 and day 30, any remaining symptoms were reported in 451 of 804 (56·1% [95% CI 52·6–59·6]) and 261 of 724 (36·0% [32·6–39·7]) children. The mean number of primary care visits per child ranged from 1·4 (95% CI 1·2–1·6; the Netherlands) to 3·0 (2·8–3·3; Spain), and was higher in children younger than 1 year (2·7 visits [2·4–2·9]) than in those aged 1 to <5 years (2·1 [1·9–2·2]). Prescribed medication use varied, from 25 of 96 children (26·0% [95% CI 17·6–36·0]; the UK) to 228 of 297 children (76·8% [71·5–81·5]; Italy), with bronchodilators and antibiotics being the most commonly prescribed medicines across all countries. Prescribed medication use was reported in 258 of 418 children aged 1 to <5 years (61·7% [56·9–66·4]) and 196 of 394 children younger than 1 year (49·7% [44·7–54·8]). Missed working days by parents due to their child's RSV illness were reported in 340 of 744 cases (45·7% [42·1–49·4]); the mean number of missed workdays ranged from 1·3 days (95% CI 0·5–2·2) in Spain to 4·1 days (3·3–5·0) in Belgium. Interpretation: RSV infections in children younger than 5 years in primary care are associated with substantial symptomatology, health-care utilisation, and parental work absence. Notable differences in RSV burden existed across countries, likely due to differences in primary health-care systems, clinical practice, and health-care-seeking behaviour. This study emphasises the importance of considering country-specific primary care burden estimates when considering the implementation of RSV immunisations programmes. Funding: Sanofi and AstraZeneca.
Fundamental causation and candidacy: Harnessing explanatory frames to better understand how structural determinants of health inequalities shape disengagement from primary healthcare.
This paper aims to better understand how structural determinants of health inequalities shape disengagement from healthcare for vulnerable groups across a range of social conditions. Using a sub-sample (N = 20) from a qualitative interview UK study of those missing from primary-care, it illuminates how structural drivers of health inequalities operate at organisational and practice levels to weaken engagement with primary-care. Finding ways of better analysing and demonstrating the causal chains between structural determinants and patterns of disengagement is important because previous research has shown that practitioner and policy understanding of structural determination, an important precursor for mitigatory action, is not always sufficient, and research on healthcare utilisation can itself be weak in investigating structures of inequality. We address this deductively by testing a novel combination of Link and Phelan's Fundamental Cause Theory and Dixon-Woods and colleagues' Candidacy framework. Combining elements of these frameworks compensates for identified gaps in each. We demonstrate how Candidacy can be strengthened through incorporating more systematic theorisation of structural processes and that the more abstract arguments of fundamental (structural) causes can be made concrete via Candidacy's focus on inequalities in patients' access to, and utilisation of, healthcare. We also argue that both theories are enhanced by including Metzl and Hansen's concept of 'structural competency' as a potential mitigatory mechanism operating between fundamental causes and patient engagement.
Shift workers' experiences and views of sleep disturbance, fatigue and healthy behaviors: a systematic review and qualitative evidence synthesis.
OBJECTIVE: Shift work is common across most societies but poses significant risks to the health of shift workers. In part, this risk is due to the disruption of healthy sleep-wake schedules. This systematic review identified qualitative research on shift workers' experiences of sleep disturbance, fatigue and healthy behaviors. METHODS: We conducted a systematic search of four databases (CINAHL, EMBASE, MEDLINE, PsycINFO) and identified 28 eligible studies involving 1519 participants. We appraised the studies using an adapted Critical Appraisal Skills Programme (CASP) checklist, and confidence in the review findings was formally assessed using the Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) approach. Data were thematically synthesized. RESULTS: Three analytical themes were generated. 'Inevitability of fatigue and tiredness' outlines how shift workers experience a culture where they feel "peer pressure to soldier through" their shifts regardless of fatigue. 'Balancing sleep needs with competing responsibilities' highlights how shift workers struggle to balance the need for daytime sleep with family, leisure, and work responsibilities, often prioritizing family needs over their own sleep. 'Obstacles to engaging in healthy behaviors' describes how shift workers often know which actions would benefit their health and reduce fatigue but find it challenging to translate this knowledge into behavior due to fatiguing and stressful work environments. For the purposes of the GRADE-CERQual assessment, short summary statements were developed to describe 22 review findings: there was moderate or high confidence in all but one of these findings. CONCLUSION: This review suggests that sleep education alone is unlikely to be effective. Interventions should focus on helping shift workers self-regulate their behaviors, thoughts, and emotions to better manage sleep and fatigue.
Is “nature” a policy solution to mental health in schools?
The UK faces a growing youth mental health crisis (NHS, 2023; RCPsych 2025). Schools may play a key role in preventing these difficulties from worsening. The integration of nature-based programs (NbPs) into school settings has been proposed as a policy solution to address such mental health challenges but robust evidence is lacking (Lomax et al., 2024), particularly at the secondary school level. This Sprint utilised an implementation science framework to co-produce evidence on NbPs in secondary schools with stakeholders including policymakers from the Government’s Department for Education (DfE), young people, and educators. Using a range of methodologies we are evaluating effectiveness, amplifying stakeholder voices, and creating actionable, evidence-based education policy insights.
Is it time to revisit the scoring of Slow Wave (N3) Sleep?
The use of a fixed electroencephalogram (EEG) amplitude threshold of 75 µV for labelling slow waves is a subject of ongoing discussion given EEG amplitude is known to vary with age and sex. This paper investigates the impact of this amplitude threshold on age- and sex-related trends in visually-annotated SWS. Automated methods for labelling SWS using data-driven thresholds and amplitude- or frequency-based inputs are developed. Age- and sex-related trends in SWS derived from visual annotation and automated labelling are then compared across a cohort of 2,913 participants from the Sleep Heart Health Study. In the selected cohort, males exhibit an age-related decrease in visually-annotated SWS, which is preserved when using automated labelling. In contrast, females exhibit a mild age-related increase in visually-annotated and amplitude-labelled SWS, but an age-related decrease in frequency-labelled SWS. Further, using frequency-labelled SWS results in a reduction in SWS in females to a level comparable to that of males. Overall, the consistency of age-related trends in SWS in males between visual annotation and automated labelling, as well as the lack of consistency in these trends in females, is striking. Given that the 75 µV amplitude threshold was established using data acquired primarily from young males, these results suggest that observed sex-based differences in visually-annotated SWS may be artefactual rather than physiological, and a result of the 75 µV amplitude criterion. This sex-related disparity highlights the need for the AASM guidelines for scoring SWS to be reviewed and updated to provide equivalent performance for males and females.
Favipiravir for COVID-19 in adults in the community in PRINCIPLE, an open-label, randomised, controlled, adaptive platform trial of short- and longer-term outcomes
Background: Evidence for the effect of favipiravir treatment of acute COVID-19 on recovery, hospital admissions and longer-term outcomes in community settings is limited. Methods: In this multicentre. open-label, multi-arm, adaptive platform randomised controlled trial participants aged ≥18 years in the community with a positive test for SARS-CoV-2 and symptoms lasting ≤14 days were randomised to: usual care; usual care plus favipiravir tablets (loading dose of 3600 mg in divided doses on day one, then 800 mg twice a day for four days); or, usual care plus other interventions. Co-primary endpoints were time to first self-reported recovery and hospitalisation/death related to COVID-19, within 28 days, analysed using Bayesian models. Recovery at six months was the primary longer-term outcome. Trial registration: ISRCTN86534580. Findings: The primary analysis model included 8811 SARS-CoV-2 positive mostly COVID vaccinated participants, randomised to favipiravir (n = 1829), usual care (n = 3256), and other treatments (n = 3726). Time to self-reported recovery was shorter in the favipiravir group than usual care (estimated hazard ratio 1·23 [95% credible interval 1·14 to 1·33]), a reduction of 2·98 days [1·99 to 3·94] from 16 days in median time to self-reported recovery for favipiravir versus usual care alone. COVID-19 related hospitalisations/deaths were similar (estimated odds ratio 0·99 [0·61 to 1·61]; estimated difference 0% [−0·9% to 0·6%]). 14 serious adverse events occurred in the favipiravir group and 4 in usual care. By six months, the proportion feeling fully recovered was 74·9% for favipiravir versus 71·3% for usual care (RR = 1·05, [1·02 to 1·08]). Interpretation: In this open-label trial in a largely vaccinated population with COVID-19 in the community, favipiravir did not reduce hospital admissions, but shortened time to recovery and had a marginal positive impact on long term outcomes.
Democratising clinical trials research to strengthen primary health care
The World Health Assembly has called for clinical trials to be strengthened, with broader demographic and geographical inclusion of populations. The objective of this paper is to highlight the importance of rigorous evidence to maximise the health gains of primary health care, and to identify strategies for strengthening clinical trials in primary care. Clinical trials should evaluate interventions of all kinds, including preventive manoeuvres, diagnostics, health service research questions, behavioural and educational interventions, vaccines, therapeutics, and policies. Single question trials can be inefficient and seldom strengthen health systems. New approaches that develop or strengthen health research infrastructure and embed research in primary care will identify effective interventions faster, how to deliver them better, and more accurately determine to whom they should be applied. When patients and community members, together with researchers, contribute to conception, design, and delivery, research will result in more useful, relevant evidence. Traditional site-based recruitment (where the participant comes to the trial) can be complemented by approaches that give people the opportunity to contribute regardless of where they live and receive their health care (taking the trials to the people). However, this cannot be done until regulation is modernised to make it easier for health-care professionals, researchers, and research participants to co-design, deliver, and implement such trials, and to develop processes to coordinate and monitor progress against goals for budget shifts, delivery, engagement, trials activity, and impact. Strengthening primary care trials is especially important in those regions where primary care is most under-resourced and is key to pandemic preparedness. Not doing so risks widening inequities further.
Cost-effectiveness of routine COVID-19 adult vaccination programmes in England
In England, and many other countries, immunity to SARS-CoV-2 infection and COVID-19 disease is highly heterogeneous. Immunity has been acquired through natural infection, primary and booster vaccination, while protection has been lost through waning immunity and viral mutation. During the height of the pandemic in England, the main aim was to rapidly protect the population and large supplies of vaccine were pre-purchased, eliminating the need for cost-effective calculations. As we move to an era where for the majority of the population SARS-CoV-2 infections cause relatively mild disease, and vaccine stocks need to be re-purchased, it is important we consider the cost-effectiveness and economic value of COVID-19 vaccination programmes. Here using data from 2023 and 2024 in England on COVID-19 hospital admissions, ICU admissions and deaths, coupled with bespoke health economic costs, we consider the willingness to pay threshold for COVID-19 vaccines in different age and risk groups. Willingness to pay thresholds vary from less than £1 for younger age-groups without any risk factors, to over £100 for older age-groups with comorbidities that place them at risk. This extreme non-linear dependence on age, means that despite the different method of estimating vaccine effectiveness, there is considerable qualitative agreement on the willingness to pay threshold, and therefore which ages it is cost-effective to vaccinate. The historic offer of COVID-19 vaccination to those 65 and over for the autumn 2023 programme and those over 75 for the spring 2023 programme, aligns with our cost- effective threshold for pre-purchased vaccine when the only cost was administration. However, for future programmes, when vaccine costs are included, the age-thresholds slowly increase thereby demonstrating the continued importance of protecting the eldest and most vulnerable in the population.
The Creation of Intensional Medication Lists Using the NHS Dictionary of Medicines and Devices
The identification of medications prescribed to patients in routinely collected health records is an important part of the identification of cohorts for surveillance and research. Preparations available for prescription can change frequently and this presents challenges to the maintenance of extensional or 'flat lists' of medications, particularly in ongoing studies such as disease surveillance. The NHS publishes a Dictionary of Medicines and Devices weekly, listing almost all the medications available in the UK as an extension to the UK edition of SNOMED CT. We developed a method of creating intensional specifications of medications using specified active ingredients and the form of the medication. The specifications can be expressed using the SNOMED CT Expression Constraint Language, and can be used to form a library which may be used across multiple projects. We have developed intensional definitions of medication groups for all drugs likely to be used in primary care. We have shown that these can be shared as FHIR valuesets using the NHS Terminology Server. Here we show examples of expressions about medications used for neuropathic pain. We have created expressions which improve the specificity of the extraction by filtering on the form and number of ingredients.
Evaluation of metrics for benchmarking antimicrobial use in the UK dairy industry.
The issue of antimicrobial resistance is of global concern across human and animal health. In 2016, the UK government committed to new targets for reducing antimicrobial use (AMU) in livestock. Although a number of metrics for quantifying AMU are defined in the literature, all give slightly different interpretations. This paper evaluates a selection of metrics for AMU in the dairy industry: total mg, total mg/kg, daily dose and daily course metrics. Although the focus is on their application to the dairy industry, the metrics and issues discussed are relevant across livestock sectors. In order to be used widely, a metric should be understandable and relevant to the veterinarians and farmers who are prescribing and using antimicrobials. This means that clear methods, assumptions (and possible biases), standardised values and exceptions should be published for all metrics. Particularly relevant are assumptions around the number and weight of cattle at risk of treatment and definitions of dose rates and course lengths; incorrect assumptions can mean metrics over-represent or under-represent AMU. The authors recommend that the UK dairy industry work towards the UK-specific metrics using the UK-specific medicine dose and course regimens as well as cattle weights in order to monitor trends nationally.
Evaluation of the diagnostic accuracy of two point-of-care tests for COVID-19 when used in symptomatic patients in community settings in the UK primary care COVID diagnostic accuracy platform trial (RAPTOR-C19)
Background and objective Point-of-care lateral flow device antigen testing has been used extensively to identify individuals with active SARS-CoV-2 infection in the community. This study aimed to evaluate the diagnostic accuracy of two point-of-care tests (POCTs) for SARS-CoV-2 in routine community care. Methods Adults and children with symptoms consistent with suspected current COVID-19 infection were prospectively recruited from 19 UK general practices and two COVID-19 testing centres between October 2020 and October 2021. Participants were tested by trained healthcare workers using at least one of two index POCTs (Roche-branded SD Biosensor Standard™ Q SARS-CoV-2 Rapid Antigen Test and/or BD Veritor™ System for Rapid Detection of SARS-CoV-2). The reference standard was laboratory triplex reverse transcription quantitative PCR (RT-PCR) using a combined nasal/oropharyngeal swab. Diagnostic accuracy parameters were estimated, with 95% confidence intervals (CIs), overall, in relation to RT-PCR cycle threshold and in pre-specified subgroups.
The Impact of Point-of-Care Testing for Influenza on Antimicrobial Stewardship (PIAMS) in UK Primary Care: Protocol for a Mixed Methods Study
Background: Molecular point-of-care testing (POCT) used in primary care can inform whether a patient presenting with an acute respiratory infection has influenza. A confirmed clinical diagnosis, particularly early in the disease, could inform better antimicrobial stewardship. Social distancing and lockdowns during the COVID-19 pandemic have disturbed previous patterns of influenza infections in 2021. However, data from samples taken in the last quarter of 2022 suggest that influenza represents 36% of sentinel network positive virology, compared with 24% for respiratory syncytial virus. Problems with integration into the clinical workflow is a known barrier to incorporating technology into routine care. Objective: This study aims to report the impact of POCT for influenza on antimicrobial prescribing in primary care. We will additionally describe severe outcomes of infection (hospitalization and mortality) and how POCT is integrated into primary care workflows. Methods: The impact of POCT for influenza on antimicrobial stewardship (PIAMS) in UK primary care is an observational study being conducted between December 2022 and May 2023 and involving 10 practices that contribute data to the English sentinel network. Up to 1000 people who present to participating practices with respiratory symptoms will be swabbed and tested with a rapid molecular POCT analyzer in the practice. Antimicrobial prescribing and other study outcomes will be collected by linking information from the POCT analyzer with data from the patient’s computerized medical record. We will collect data on how POCT is incorporated into practice using data flow diagrams, unified modeling language use case diagrams, and Business Process Modeling Notation. Results: We will present the crude and adjusted odds of antimicrobial prescribing (all antibiotics and antivirals) given a POCT diagnosis of influenza, stratifying by whether individuals have a respiratory or other relevant diagnosis (eg, bronchiectasis). We will also present the rates of hospital referrals and deaths related to influenza infection in PIAMS study practices compared with a set of matched practices in the sentinel network and the rest of the network. We will describe any difference in implementation models in terms of staff involved and workflow. Conclusions: This study will generate data on the impact of POCT testing for influenza in primary care as well as help to inform about the feasibility of incorporating POCT into primary care workflows. It will inform the design of future larger studies about the effectiveness and cost-effectiveness of POCT to improve antimicrobial stewardship and any impact on severe outcomes.