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Abstract Background Antimicrobial resistance is a global patient safety priority and inappropriate antimicrobial use is a key contributing factor. Evidence have shown that delayed (back-up) antibiotic prescriptions (DP) are an effective and safe strategy for reducing unnecessary antibiotic consumption but its use is controversial. Methods We conducted a realist review to ask why, how, and in what contexts general practitioners (GPs) use DP. We searched five electronic databases for relevant articles and included DP-related data from interviews with healthcare professionals in a related study. Data were analysed using a realist theory-driven approach – theorising which context(s) influenced (mechanisms) resultant outcome(s) (context-mechanism-outcome-configurations: CMOCs). Results Data were included from 76 articles and 41 interviews to develop a program theory comprising nine key and 56 related CMOCs. These explain the reasons for GPs’ tolerance of risk to different uncertainties and how these may interact with GPs’ work environment, self-efficacy and perceived patient concordance to make using DP as a safety-net or social tool more or less likely, at a given time-point. For example, when a GP uses clinical scores or diagnostic tests: a clearly high or low score/test result may mitigate scientific uncertainty and lead to an immediate or no antibiotic decision; an intermediary result may provoke hermeneutic (interpretation-related) uncertainty and lead to DP becoming preferred and used as a safety net. Our program theory explains how DP can be used to mitigate some uncertainties but also provoke or exacerbate others. Conclusion This review explains how, why and in what contexts GPs are more or less likely to use DP, as well as various uncertainties GPs face which DP may mitigate or provoke. We recommend that efforts to plan and implement interventions to optimise antibiotic prescribing in primary care consider these uncertainties and the contexts when DP may be (dis)preferred over other interventions to reduce antibiotic prescribing. We also recommend the following and have included example activities for: (i) reducing demand for immediate antibiotics; (ii) framing DP as an ‘active’ prescribing option; (iii) documenting the decision-making process around DP; and (iv) facilitating social and system support.

Abstract Background Use of electronic health records (EHR) to provide real-world data for research is established, but using EHR to deliver randomised controlled trials (RCTs) more efficiently is less developed. The Allergy AntiBiotics And Microbial resistAnce (ALABAMA) RCT evaluated a penicillin allergy assessment pathway versus usual clinical care in a UK primary care setting. The aim of this paper is to describe how EHRs were used to facilitate efficient delivery of a large-scale randomised trial of a complex intervention embracing efficient participant identification, supporting minimising GP workload, providing accurate post-intervention EHR updates of allergy status, and facilitating participant follow up and outcome data collection. The generalisability of the EHR approach and health economic implications of EHR in clinical trials will be reported in the main ALABAMA trial cost-effectiveness analysis. Methods A descriptive account of the adaptation of functionality within SystmOne used to deliver/facilitate multiple trial processes from participant identification to outcome data collection. Results An ALABAMA organisation group within SystmOne was established which allowed sharing of trial functions/materials developed centrally by the research team. The ‘ALABAMA unit’ within SystmOne was also created and provided a secure efficient environment to access participants’ EHR data. Processes of referring consented participants, allocating them to a trial arm, and assigning specific functions to the intervention arm were developed by adapting tools such as templates, reports, and protocols which were already available in SystmOne as well as pathways to facilitate allergy de-labelling processes and data retrieval for trial outcome analysis. Conclusions ALABAMA is one of the first RCTs to utilise SystmOne EHR functionality and data across the RCT delivery, demonstrating feasibility and applicability to other primary care RCTs. Trial registration ClinicalTrials.gov: NCT04108637, registered 05/03/2019. ISRCTN: ISRCTN20579216.

Abstract Background Tuberculosis (TB) is a stigmatised disease with intersectional associations with poverty, HIV, transmission risk and mortality. The use of visible TB infection prevention and control (IPC) measures, such as masks or isolation, can contribute to stigma. Methods To explore stigma in this condition, we conducted in-depth individual interviews with 18 health workers and 15 patients in the rural Eastern Cape of South Africa using a semi-structured interview guide and narrative approach. We used reflexive thematic analysis guided by line-by-line coding. We then interpreted these key findings using Link and Phelan’s theoretical model of stigma, related this to stigma mitigation recommendations from participants and identified levels of intervention with the Health Stigma and Discrimination Framework. Results Participants shared narratives of how TB IPC measures can contribute to stigma, with some describing feeling ‘less than human’. We found TB IPC measures sometimes exacerbated stigma, for example through introducing physical isolation that became prolonged or through a mask marking the person out as being ill with TB. In this context, stigma emerged from the narrow definition of what mask-wearing symbolises, in contrast with broader uses of masks as a preventative measure. Patient and health workers had contrasting perspectives on the implications of TB IPC-related stigma, with patients focussing on communal benefit, while health workers focussed on the negative impact on the health worker-patient relationship. Participant recommendations to mitigate TB IPC-related stigma included comprehensive information on TB IPC measures, respectful communication between health workers and patients, shifting the focus of TB IPC messages to communal safety (which could draw on ubuntu, a humanist framework) and using universal IPC precautions instead of measures targeted at someone with infectious TB. Conclusions Health facilities may unwittingly perpetuate stigma through TB IPC implementation, but they also have the potential to reduce it. Evoking ‘ubuntu’ as an African humanist conceptual framework could provide a novel perspective to guide future TB IPC stigma mitigation interventions, including policy changes to universal IPC precautions.

Abstract One of the main challenges in coral reef conservation and restoration is the identification of coral populations resilient under global warming. Seascape genomics is a powerful tool to uncover genetic markers potentially involved in heat tolerance among large populations without prior information on phenotypes. Here, we aimed to provide first insights on the role of candidate heat associated loci identified using seascape genomics in driving the phenotypic response of Acropora millepora from New Caledonia to thermal stress. We subjected 7 colonies to a long-term ex-situ heat stress assay (4 °C above the maximum monthly mean) and investigated their physiological response along with their Symbiodiniaceae communities and genotypes. Despite sharing similar thermal histories and associated symbionts, these conspecific individuals differed greatly in their tolerance to heat stress. More importantly, the clustering of individuals based on their genotype at heat-associated loci matched the phenotypic variation in heat tolerance. Colonies that sustained on average lower mortality, higher Symbiodiniaceae/chlorophyll concentrations and photosynthetic efficiency under prolonged heat stress were also the closest based on their genotypes, although the low sample size prevented testing loci predictive accuracy. Together these preliminary results support the relevance of coupling seascape genomics and long-term heat stress experiments in the future, to evaluate the effect size of candidate heat associated loci and pave the way for genomic predictive models of corals heat tolerance.

Abstract Background Ethnicity is known to be an important correlate of health outcomes, particularly during the COVID-19 pandemic, where some ethnic groups were shown to be at higher risk of infection and adverse outcomes. The recording of patients’ ethnic groups in primary care can support research and efforts to achieve equity in service provision and outcomes; however, the coding of ethnicity is known to present complex challenges. We therefore set out to describe ethnicity coding in detail with a view to supporting the use of this data in a wide range of settings, as part of wider efforts to robustly describe and define methods of using administrative data. Methods We describe the completeness and consistency of primary care ethnicity recording in the OpenSAFELY-TPP database, containing linked primary care and hospital records in > 25 million patients in England. We also compared the ethnic breakdown in OpenSAFELY-TPP with that of the 2021 UK census. Results 78.2% of patients registered in OpenSAFELY-TPP on 1 January 2022 had their ethnicity recorded in primary care records, rising to 92.5% when supplemented with hospital data. The completeness of ethnicity recording was higher for women than for men. The rate of primary care ethnicity recording ranged from 77% in the South East of England to 82.2% in the West Midlands. Ethnicity recording rates were higher in patients with chronic or other serious health conditions. For each of the five broad ethnicity groups, primary care recorded ethnicity was within 2.9 percentage points of the population rate as recorded in the 2021 Census for England as a whole. For patients with multiple ethnicity records, 98.7% of the latest recorded ethnicities matched the most frequently coded ethnicity. Patients whose latest recorded ethnicity was categorised as Other were most likely to have a discordant ethnicity recording (32.2%). Conclusions Primary care ethnicity data in OpenSAFELY is present for over three quarters of all patients, and combined with data from other sources can achieve a high level of completeness. The overall distribution of ethnicities across all English OpenSAFELY-TPP practices was similar to the 2021 Census, with some regional variation. This report identifies the best available codelist for use in OpenSAFELY and similar electronic health record data.

Abstract Background Long COVID potentially increases healthcare utilisation and costs. However, its impact on the NHS remains to be determined. Methods This study aims to assess the healthcare utilisation of individuals with long COVID. With the approval of NHS England, we conducted a matched cohort study using primary and secondary care data via OpenSAFELY, a platform for analysing anonymous electronic health records. The long COVID exposure group, defined by diagnostic codes, was matched with five comparators without long COVID between Nov 2020 and Jan 2023. We compared their total healthcare utilisation from GP consultations, prescriptions, hospital admissions, A&E visits, and outpatient appointments. Healthcare utilisation and costs were evaluated using a two-part model adjusting for covariates. Using a difference-in-difference model, we also compared healthcare utilisation after long COVID with pre-pandemic records. Results We identified 52,988 individuals with a long COVID diagnosis, matched to 264,867 comparators without a diagnosis. In the 12 months post-diagnosis, there was strong evidence that those with long COVID were more likely to use healthcare resources (OR: 8.29, 95% CI: 7.74–8.87), and have 49% more healthcare utilisation (RR: 1.49, 95% CI: 1.48–1.51). Our model estimated that the long COVID group had 30 healthcare visits per year (predicted mean: 29.23, 95% CI: 28.58–29.92), compared to 16 in the comparator group (predicted mean visits: 16.04, 95% CI: 15.73–16.36). Individuals with long COVID were more likely to have non-zero healthcare expenditures (OR = 7.66, 95% CI = 7.20–8.15), with costs being 44% higher than the comparator group (cost ratio = 1.44, 95% CI: 1.39–1.50). The long COVID group costs approximately £2500 per person per year (predicted mean cost: £2562.50, 95% CI: £2335.60–£2819.22), and the comparator group costs £1500 (predicted mean cost: £1527.43, 95% CI: £1404.33–1664.45). Historically, individuals with long COVID utilised healthcare resources more frequently, but their average healthcare utilisation increased more after being diagnosed with long COVID, compared to the comparator group. Conclusions Long COVID increases healthcare utilisation and costs. Public health policies should allocate more resources towards preventing, treating, and supporting individuals with long COVID.

Abstract Macrophages provide a crucial environment for Salmonella enterica serovar Typhi (S. Typhi) to multiply during typhoid fever, yet our understanding of how human macrophages and S. Typhi interact remains limited. In this study, we delve into the dynamics of S. Typhi replication within human macrophages and the resulting heterogeneous transcriptomic responses of macrophages during infection. Our study reveals key factors that influence macrophage diversity, uncovering distinct immune and metabolic pathways associated with different stages of S. Typhi intracellular replication in macrophages. Of note, we found that macrophages harboring replicating S. Typhi are skewed towards an M1 pro-inflammatory state, whereas macrophages containing non-replicating S. Typhi exhibit neither a distinct M1 pro-inflammatory nor M2 anti-inflammatory state. Additionally, macrophages with replicating S. Typhi were characterized by the increased expression of genes associated with STAT3 phosphorylation and the activation of the STAT3 transcription factor. Our results shed light on transcriptomic pathways involved in the susceptibility of human macrophages to intracellular S. Typhi replication, thereby providing crucial insight into host phenotypes that restrict and support S. Typhi infection.

IntroductionRespiratory syncytial virus (RSV) causes acute respiratory tract infection (ARTI) and reinfects adults throughout life, posing a risk for hospitalization in older adults (>60 years) with frailty and comorbidities.MethodsTo investigate serum and mucosal antibodies for protection against RSV infections, baseline serum samples were compared for RSV-pre- and -post-fusion (F) binding, and RSV-A2 neutralizing IgG antibodies between symptomatic RSV-ARTI (N = 30), non-RSV (RSV negative) ARTI (N = 386), and no ARTI (N = 338). Mucosal RSV-pre-F IgA and IgG levels, as well as serum RSV-G IgG antibodies, were analyzed to determine their association with protection from symptomatic RSV-ARTI in a subset study.ResultsUsing a receiver operating characteristic (ROC) analysis, we established thresholds of 1.4- to 1.6-fold change (FC) for RSV-pre-F and -post-F, and RSV-A2 neutralizing IgG antibodies, respectively, enabling the identification of asymptomatic RSV cases with high sensitivity and specificity (>80% and >90%, respectively). As a result, serum RSV-pre-F, RSV-G IgG, and mucosal pre-F binding IgA antibodies showed correlations with protection against symptomatic RSV infection. RSV-pre-F IgG antibodies were correlated with protection from RSV infections irrespective of the symptoms.DiscussionThis study provides insights into antibody-mediated protection for symptomatic RSV infection in a community-dwelling older-adult population and establishes a threshold to identify asymptomatic RSV infection using a data-driven approach.

Given the various motivational challenges that students experience when engaging in academic tasks, there is an emerging interest in investigating students' cost perceptions and how to reduce them. However, most of the research has investigated general cost perceptions with a one-time assessment, often divorced from context in which cost is experienced. Centreing the situatedness of students' motivational processes, we conducted an experience sampling study (57 undergraduates; 1,504 responses) to examine the link between general and "in-situ" momentary cost perceptions in students' daily lives, as well as the potential moderating role of motivational regulation. Results showed that certain dimensions of momentary cost perceptions (outside effort cost and emotional cost) were positively associated with their corresponding general cost perceptions. Other dimensions of momentary cost (task effort cost and loss of valued alternatives cost) showed nonsignificant associations, suggesting higher sensitivity to context than others. Moreover, motivational regulation moderated the relationship between general and momentary cost for the majority of the dimensions, suggesting that interventions designed to improve students' motivational regulation may reduce their momentary cost perceptions and increase the positivity of learning experiences.

IntroductionInfants with congenital heart disease (CHD) are at high risk for developmental differences which can be explained by the cumulative effect of medical complications along with sequelae related to the hospital and environmental challenges. The intervention of individualized developmental care (IDC) minimizes the mismatch between the fragile newborn brain's expectations and the experiences of stress and pain inherent in the intensive care unit (ICU) environment.MethodsA multidisciplinary group of experts was assembled to implement quality improvement (QI) to increase the amount of IDC provided, using the Newborn Individualized Developmental Care and Assessment Program (NIDCAP), to newborn infants in the cardiac ICU. A Key Driver Diagram was created, PDSA cycles were implemented, baseline and ongoing measurements of IDC were collected, and interventions were provided.ResultsWe collected 357 NIDCAP audits of bedside IDC. Improvement over time was noted in the amount of IDC including use of appropriate lighting, sound management, and developmentally supportive infant bedding and clothing, as well as in promoting self-regulation, therapeutic positioning, and caregiving facilitation. The area of family participation and holding of infants in the CICU was the hardest to support change over time, especially with the most ill infants. Infants with increased medical complexity were less likely to receive IDC.DiscussionThis multidisciplinary, evidence-based QI intervention demonstrated that the implementation of IDC in the NIDCAP model improved over time using bedside auditing of IDC.

Abstract Background High participant retention enhances the validity of clinical trials. A monetary incentive can increase retention, but it is not known if when it is provided and if it is conditional matters. We aimed to determine whether there was a difference in the number of follow-up trial questionnaires returned when a monetary (gift voucher) incentive was given to participants at recruitment (non-conditional), compared to informing participants at recruitment that the incentive would be given only once their 14-day daily diary (questionnaire) had been returned (conditional). Method A cluster randomised study within a trial embedded within the Antivirals for influenza-Like Illness, An rCt of Clinical and Cost effectiveness in primary CarE (ALIC4E) Trial. Matched site pairs (GP practices) were randomised using computer-generated random numbers, to either a non-conditional or conditional monetary voucher incentive (only once their 14-day daily diary (questionnaire) had been returned. Sites were matched on previous recruitment levels and practice list size. Analyses were conducted according to randomised groups irrespective of compliance with a two-sided 5% level statistical significance level. The main analysis of the primary outcome (site proportion of diaries returned) was linear regression accounting for site pair (using cluster-robust variance). Additional weighted, paired and non-parametric sensitivity analyses were conducted. Secondary outcomes were the site average number of completed pages, time to return diary, and cost related to the incentive (administration and postage). Results Of the 42 randomised sites (21 for each intervention), only 28 recruited at least one participant with only 10 practice pairs recruiting participants at both constituent sites. Raw diaries return proportions were 0.58 (127/220) and 0.73 (91/125) for non-conditional and conditional incentive groups. Regression analysis adjusted for site pair showed no significant difference in returns, − 0.09, (95% CI, − 0.29, 0.10, p = 0.34); when weighted, there was still no clear difference: 0.15 (95% CI, − 0.02, 0.31, p = 0.07). There was no clear statistical evidence of a difference in time taken to return questionnaires, nor the proportion of pages completed, by the intervention group in the main analyses (all p > 0.05). The conditional incentive was approximately £23 cheaper per diary returned based upon observed data. Conclusion There was no clear evidence of a statistically significant difference in the proportion of participant-completed diaries returned between conditional or non-conditional incentive groups. The time to questionnaire return and completeness of the returned questionnaires were similar in both groups. There was substantial statistical uncertainty in the findings. Some of the sensitivity analyses suggested that a meaningful benefit of a conditional incentive of a magnitude that would be meaningful was plausible. The conditional approach costs less in cash terms.

Abstract Real-time 3D tracking and high-speed videography was used to examine the behaviour of a worldwide greenhouse pest, the western flower thrips (WFT), in response to different colours in the context of improving trap design. Measurements were taken of the number of landings on, and flight activity near, a lamp containing two LEDs of either the same colour or a combination of two colours presented side by side. Main findings show that landing patterns of WFT are different between colours, with landings on UV(+ red) as highly attractive stimulus being mostly distributed at the bottom half of the lamp, while for yellow also as very attractive and green as a ‘neutral’ stimulus, landings were clearly on the upper rim of the lamp. Additionally, a positive interaction with the UV-A(+ red) and yellow combination elicited the highest number of landings and flight time in front of the LED lamp. Conversely, a negative interaction was observed with decreased landings and flight time found for yellow when blue was present as the adjacent colour. Overall, differences between treatments were less obvious for flight times compared to number of landings, with tracking data suggesting that WFT might use different colours to orientate at different distances as they approach a visual stimulus.

Objective Timely access to primary care and supporting specialist care relative to need is essential for health equity. However, use of services can vary according to an individual’s socioeconomic circumstances or where they live. This study aimed to quantify individual socioeconomic variation in general practitioner (GP) and specialist use in New South Wales (NSW), accounting for area-level variation in use.Design Outcomes were GP use and quality-of-care and specialist use. Multilevel logistic regression was used to estimate: (1) median ORs (MORs) to quantify small area variation in outcomes, which gives the median increased risk of moving to an area of higher risk of an outcome, and (2) ORs to quantify associations between outcomes and individual education level, our main exposure variable. Analyses were adjusted for individual sociodemographic and health characteristics and performed separately by remoteness categories.Setting Baseline data (2006–2009) from the 45 and Up Study, NSW, Australia, linked to Medicare Benefits Schedule and death data (to December 2012).Participants 267 153 adults aged 45 years and older.Results GP (MOR=1.32–1.35) and specialist use (1.16–1.18) varied between areas, accounting for individual characteristics. For a given level of need and accounting for area variation, low education-level individuals were more likely to be frequent users of GP services (no school certificate vs university, OR=1.63–1.91, depending on remoteness category) and have continuity of care (OR=1.14–1.24), but were less likely to see a specialist (OR=0.85–0.95).Conclusion GP and specialist use varied across small areas in NSW, independent of individual characteristics. Use of GP care was equitable, but specialist care was not. Failure to address inequitable specialist use may undermine equity gains within the primary care system. Policies should also focus on local variation.

AbstractBackground Early in the COVID-19 pandemic, GPs had to distinguish SARS-CoV-2 from other aetiologies in patients presenting with respiratory tract infection (RTI) symptoms on clinical grounds and adapt management accordingly.Objectives To test the diagnostic accuracy of GPs’ clinical diagnosis of a SARS-CoV-2 infection in a period when COVID-19 was a new disease. To describe GPs’ management of patients presenting with RTI for whom no confirmed diagnosis was available. To investigate associations between patient and clinical features with a SARS-CoV-2 infection.Methods In April 2020–March 2021, 876 patients (9 countries) were recruited when they contacted their GP with symptoms of an RTI of unknown aetiology. A swab was taken at baseline for later analysis. Aetiology (PCR), diagnostic accuracy of GPs’ clinical SARS-CoV-2 diagnosis, and patient management were explored. Factors related to SARS-CoV-2 infection were determined by logistic regression modelling.Results GPs suspected SARS-CoV-2 in 53% of patients whereas 27% of patients tested positive for SARS-CoV-2. True-positive patients (23%) were more intensively managed for follow-up, antiviral prescribing and advice than true-negatives (42%). False negatives (5%) were under-advised, particularly for social distancing and isolation. Older age (OR: 1.02 (1.01–1.03)), male sex (OR: 1.68 (1.16–2.41)), loss of taste/smell (OR: 5.8 (3.7–9)), fever (OR: 1.9 (1.3–2.8)), muscle aches (OR: 2.1 (1.5–3)), and a known risk factor for COVID-19 (travel, health care worker, contact with proven case; OR: 2.7 (1.8–4)) were predictive of SARS-CoV-2 infection. Absence of loss of taste/smell, fever, muscle aches and a known risk factor for COVID-19 correctly excluded SARS-CoV-2 in 92.3% of patients, whereas presence of 3, or 4 of these variables correctly classified SARS-CoV-2 in 57.7% and 87.1%.Conclusion Correct clinical diagnosis of SARS-CoV-2 infection, without POC-testing available, appeared to be complicated.

AbstractBackground Access to testing during the first wave of the COVID-19 pandemic was limited, impacting patients with COVID-19-like symptoms. Current qualitative studies have been limited to one country or were conducted outside Europe.Objectives To explore - in eight European countries - the experiences of patients consulting in primary care with COVID-19-like symptoms during the first wave of the pandemic.Methods Sixty-six semi-structured interviews, informed by a topic guide, were conducted by telephone or in person between April and July 2020. Patients with COVID-19-like symptoms were purposively recruited in primary care sites in eight countries and sampled based on age, gender, and symptom presentation. Deductive and inductive thematic analysis techniques were used to develop a framework representing data across settings. Data adequacy was attained by collecting rich data.Results Seven themes were identified, which described the experiences of patients consulting. Two themes are reported in this manuscript describing the role of COVID-19 testing in this experience. Patients described significant distress due to their symptoms, especially those at higher risk of complications from COVID-19, and those with severe symptoms. Patients wanted access to testing to identify the cause of their illness and minimise the burden of managing uncertainty. Some patients testing positive for COVID-19 assumed they would be immune from future infection.Conclusion Patients experiencing novel and severe symptoms, particularly those with comorbidities, experienced a significant emotional and psychological burden due to concerns about COVID-19. Testing provided reassurance over health status and helped patients identify which guidance to follow. Testing positive for SARS-CoV-2 led to some patients thinking they were immune from future infection, thus influencing subsequent behaviour.

IntroductionThe immune mechanisms supporting partial protection from reinfection and disease by the respiratory syncytial virus (RSV) have not been fully characterized. In older adults, symptoms are typically mild but can be serious in patients with comorbidities when the infection extends to the lower respiratory tract.MethodsThis study formed part of the RESCEU older-adults prospective-cohort study in Northern Europe (2017–2019; NCT03621930) in which a thousand participants were followed over an RSV season. Peripheral-blood samples (taken pre-season, post-season, during illness and convalescence) were analyzed from participants who (i) had a symptomatic acute respiratory tract infection by RSV (RSV-ARTI; N=35) or (ii) asymptomatic RSV infection (RSV-Asymptomatic; N=16). These analyses included evaluations of antibody (Fc-mediated–) functional features and cell-mediated immunity, in which univariate and machine-learning (ML) models were used to explore differences between groups.ResultsPre–RSV-season peripheral-blood biomarkers were predictive of symptomatic RSV infection. T-cell data were more predictive than functional antibody data (area under receiver operating characteristic curve [AUROC] for the models were 99% and 76%, respectively). The pre-RSV season T-cell phenotypes which were selected by the ML modelling and which were more frequent in RSV-Asymptomatic group than in the RSV-ARTI group, coincided with prominent phenotypes identified during convalescence from RSV-ARTI (e.g., IFN-γ+, TNF-α+ and CD40L+ for CD4+, and IFN-γ+ and 4-1BB+ for CD8+).ConclusionThe evaluation and statistical modelling of numerous immunological parameters over the RSV season suggests a primary role of cellular immunity in preventing symptomatic RSV infections in older adults.

Abstract Introduction Novel point‐of‐care assays which measure urine tenofovir (TFV) concentrations may have a role in improving adherence monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART). However, further studies of their diagnostic accuracy, and whether results are associated with viraemia and drug resistance, are needed to guide their use, particularly in the context of the global dolutegravir rollout. Methods We conducted a cross‐sectional evaluation among PLHIV receiving first‐line ART containing tenofovir disoproxil fumarate at enrolment into a randomized trial in two South African public sector clinics. We calculated the diagnostic accuracy of the Abbott point‐of‐care immunoassay to detect urine TFV compared to liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). We evaluated the association between point‐of‐care urine TFV results and self‐reported adherence, viraemia ≥1000 copies/ml and HIV drug resistance, among people receiving either efavirenz or dolutegravir‐based ART. Results Between August 2020 and March 2022, we enrolled 124 participants. The median age was 39 (IQR 34–45) years, 55% were women, 74 (59.7%) were receiving efavirenz and 50 (40.3%) dolutegravir. The sensitivity and specificity of the immunoassay to detect urine TFV ≥1500 ng/ml compared to LC‐MS/MS were 96.1% (95% CI 90.0−98.8) and 95.2% (75.3−100.0), respectively. Urine TFV results were associated with short (p

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.

Introduction There is an urgent need to determine the safety, effectiveness and cost-effectiveness of novel antiviral treatments for COVID-19 in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19.Methods and analysis PANORAMIC is a UK-wide, open-label, prospective, adaptive, multiarm platform, randomised clinical trial that evaluates antiviral treatments for COVID-19 in the community. A master protocol governs the addition of new antiviral treatments as they become available, and the introduction and cessation of existing interventions via interim analyses. The first two interventions to be evaluated are molnupiravir (Lagevrio) and nirmatrelvir/ritonavir (Paxlovid). Eligibility criteria: community-dwelling within 5 days of onset of symptomatic COVID-19 (confirmed by PCR or lateral flow test), and either (1) aged 50 years and over, or (2) aged 18–49 years with qualifying comorbidities. Registration occurs via the trial website and by telephone. Recruitment occurs remotely through the central trial team, or in person through clinical sites. Participants are randomised to receive either usual care or a trial drug plus usual care. Outcomes are collected via a participant-completed daily electronic symptom diary for 28 days post randomisation. Participants and/or their Trial Partner are contacted by the research team after days 7, 14 and 28 if the diary is not completed, or if the participant is unable to access the diary. The primary efficacy endpoint is all-cause, non-elective hospitalisation and/or death within 28 days of randomisation. Multiple prespecified interim analyses allow interventions to be stopped for futility or superiority based on prespecified decision criteria. A prospective economic evaluation is embedded within the trial.Ethics and dissemination Ethical approval granted by South Central–Berkshire REC number: 21/SC/0393; IRAS project ID: 1004274. Results will be presented to policymakers and at conferences, and published in peer-reviewed journals.Trial registration number ISRCTN30448031; EudraCT number: 2021-005748-31.

C-reactive protein (CRP) point-of-care testing can reduce antibiotic prescribing in primary care patients with febrile and respiratory illness, yet little is known about its effects on treatment-seeking behavior. If patients go on to source antibiotics elsewhere, the impact of CRP testing will be limited. A randomized controlled trial assessed the impact of CRP testing on antibiotic prescriptions in Myanmar and Thai primary care patients with a febrile illness. Here we report patients’ treatmentseeking behavior before and during the twoweek study period. Self-reported antibiotic use is compared against urine antibacterial activity. Patients’ opinions towards CRP testing were evaluated. Antibiotic use before study enrolment was reported by 5.4% while antimicrobial activity was detected in 20.8% of samples tested. During the study period, 14.8% of the patients sought additional healthcare, and 4.3% sourced their own antibiotics. Neither were affected by CRP testing. Overall, patients’ satisfaction with their care and CRP testing was high. CRP testing did not affect patients’ treatment-seeking behavior during the study period whilst modestly reducing antibiotic prescriptions. CRP testing appears to be acceptable to patients and their caregivers.

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.

Introduction Chronic disease remains the leading cause of morbidity and mortality among Aboriginal and Torres Strait Islander peoples in Australia. Regular structured, comprehensive health assessments are available to Aboriginal and Torres Strait Islander people as annual health checks funded through the Medicare Benefits Schedule. This realist review aims to identify context-specific enablers and tensions and contribute to developing an evidence framework to guide the implementation of health checks in the prevention and early detection of chronic diseases for Aboriginal and Torres Strait Islander people.Methods and analysis The review will involve the following steps: (1) Aboriginal and Torres Strait Islander engagement and research governance; (2) defining the scope of the review; (3) search strategy; (4) screening, study selection and appraisal; (5) data extraction and organisation of evidence; (6) data synthesis and drawing conclusions. This realist review will follow the Realist and MEta-narrative Evidence Syntheses: Evolving Standards guidance and will be reported as set up by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols statement. The realist programme theory will be developed through a literature review using multiple database searches from 1 November 1999 to 31 June 2022, limited to the English language, and stakeholder consultation, which will be refined throughout the review process. The study findings will be reported by applying the context–mechanism–outcome configuration to gain a deeper understanding of context and underlying mechanisms that influence the implementation of health checks in the prevention and early detection of chronic diseases among Aboriginal and Torres Strait Islander people in Australia.Ethics and dissemination Ethical approval is not required as this review will be using secondary data. Findings will be published in a peer-reviewed journal and presented at scientific conferences.Systematic review registration The review protocol has been registered on the international prospective register of systematic reviews: CRD42022326697.

Chromospheric condensations (CCs) are a prominent feature of flare footpoint heating in the solar flare standard model, yet their timescales and velocities are not well understood. Fisher derived several important analytical relationships, which have rarely been examined with modern spectral observations. The Interface Region Imaging Spectrograph (IRIS) provides a wealth of flare data with a high enough cadence to sufficiently capture CC evolution. We analyzed Doppler shifts in Mg ii 2791 and Fe ii 2814 from a sample of flare footpoint pixels observed by IRIS to compare with Fisher's analytics and recent flare models. We found a detection lifetime of 1 minute occurs in 50% of the sample, with Mg ii showing several pixels with longer values and Fe ii almost categorically shorter, and both growing with the maximum velocity, v _max . The shifts’ half-life is commonly

Innate immunity is essential for the anti-microbial defense, but excessive immune activation may cause severe disease. In this study, immunotherapy was shown to prevent excessive innate immune activation and restore the anti-bacterial defense. E. coli-infected Asc−/− mice develop severe acute cystitis, defined by IL-1 hyper-activation, high bacterial counts, and extensive tissue pathology. Here, the interleukin-1 receptor antagonist (IL-1RA), which inhibits IL-1 hyper-activation in acute cystitis, was identified as a more potent inhibitor of inflammation and NK1R- and substance P-dependent pain than cefotaxime. Furthermore, IL-1RA treatment inhibited the excessive innate immune activation in the kidneys of infected Irf3−/− mice and restored tissue integrity. Unexpectedly, IL-1RA also accelerated bacterial clearance from infected bladders and kidneys, including antibiotic-resistant E. coli, where cefotaxime treatment was inefficient. The results suggest that by targeting the IL-1 response, control of the innate immune response to infection may be regained, with highly favorable treatment outcomes, including infections caused by antibiotic-resistant strains.

Abstract Objective: To inform national evidence gaps on cardiovascular disease (CVD) preventive medication use and factors relating to under‐treatment ‐ including primary healthcare engagement ‐ among CVD survivors in Australia. Methods: Data from 884 participants with self‐reported CVD from the 2014–15 National Health Survey were linked to primary care and pharmaceutical dispensing data for 2016 through the Multi‐Agency Data Integration Project. Logistic regression quantified the relation of combined blood pressure‐ and lipid‐lowering medication use to participant characteristics. Results: Overall, 94.8% had visited a general practitioner (GP) and 40.0% were on both blood pressure‐ and lipid‐lowering medications. Medication use was least likely in: women versus men (OR=0.49[95%CI:0.37‐0.65]), younger participants (e.g. 45–64y versus 65–85y: OR=0.58[0.42–0.79])and current versus never‐smokers (OR=0.73[0.44–1.20]). Treatment was more likely in those with ≥9 versus ≤4 conditions (OR=2.15[1.39–3.31]), with ≥11 versus 0–2 GP visits/year (OR=2.62[1.53–4.48]) and with individual CVD risk factors (e.g. high blood pressure OR=3.13 [2.34–4.19]) versus without); the latter even accounting for GP service‐use frequency. Conclusions: Younger people, smokers, those with infrequent GP visits or without CVD risk factors were the least likely to be on medication. Implications for public health: Substantial under‐treatment, even among those using GP services, indicates opportunities to prevent further CVD events in primary care.

Abstract Background Opportunistic recruitment in primary care is challenging due to the inherent unpredictability of incident conditions, and workload and time pressures. Many clinical trials do not recruit to target, leading to equivocal answers to research questions. Learning from the experiences of patients and recruiters to trials of incident conditions has the potential to improve recruitment and retention to future trials, thereby enhancing the quality and impact of research findings. The aim of this research was to learn from the trial experiences of UTI patients and recruiters to the Cranberry for UTI (CUTI) trial, to help plan an adequately powered trial of similar design. Methods One-to-one semi-structured interviews were embedded within the CUTI feasibility trial, an open-label, randomised feasibility trial of cranberry extract for symptoms of acute, uncomplicated Urinary Tract Infection (UTI) in primary care. Interviews were conducted with a sample of: CUTI trial participants; non-CUTI trial UTI patients; and, recruiters to the CUTI trial. Verbatim transcripts were analysed thematically. Results Twenty-six patients with UTI and eight recruiters (nurses and GPs) to the CUTI trial were interviewed. Three themes were developed around: reasons for participating in research; barriers to opportunistic recruitment; and, UTI patients’ experiences of trial procedures. Recruiters found that targeted electronic prompts directed at healthcare practitioners based in clinics where patients with incident conditions were likely to present (e.g. minor illness clinic) were more effective than generic prompts (e.g. desk prompts) at filtering patients from their usual clinical pathway to research clinics. Using a script to explain the delayed antibiotic trial group to patients was found to be helpful, and may have served to boost recruitment. For UTI patients, using an electronic diary to rate their symptoms was considered an acceptable medium, and often preferable to using a paper diary or mobile phone application. Conclusions The use of targeted prompts directed at clinicians, a script to explain trial groups that may be deemed less desirable, and an appropriate diary format for patient-reported outcomes, may help to improve trial recruitment and retention.

Nitrate contamination of ground water is a serious problem due to the intensive agricultural activities needed to feed the world’s growing population. While effective, drinking water treatment using commercial ion exchange polymers is often too expensive to be employed. At the same time, lignocellulosic waste from crop production—an abundant source of the renewable polymer cellulose—is often burned to clear fields. This results in not only adverse health outcomes, but also wastes a valuable resource. In this study, wheat straw was pretreated to extract cellulose, then selectively oxidized with periodate, crosslinked with an alkyl diamine (1,7-diaminoheptane or 1,10-diaminodecane), and functionalized with a quaternary ammonium compound ((2-aminoethyl)trimethyl ammonium chloride) to generate a cellulose-based anion exchange polymer. This polymer lowered aqueous nitrate concentrations to health-based drinking water standards. Unlike commercial ion exchange polymers, its synthesis did not require the use of toxic epichlorohydrin or flammable solvents. The pretreatment conditions did not significantly affect nitrate uptake, but the crosslinker chain length did, with polymers crosslinked with 1,10-diaminodecane showing no nitrate uptake. Agricultural-waste-based anion exchange polymers could accelerate progress toward the sustainable development goals by providing low-cost materials for nitrate removal from water.

Developmental disorders, disabilities, and delays are a common outcome for individuals with complex congenital heart disease, yet targeting early factors influencing these conditions after birth and during the neonatal hospitalization for cardiac surgery remains a critical need. The purpose of this science advisory is to (1) describe the burden of developmental disorders, disabilities, and delays for infants with complex congenital heart disease, (2) define the potential health and neurodevelopmental benefits of developmental care for infants with complex congenital heart disease, and (3) identify critical gaps in research aimed at evaluating developmental care interventions to improve neurodevelopmental outcomes in complex congenital heart disease. This call to action targets research scientists, clinicians, policymakers, government agencies, advocacy groups, and health care organization leadership to support funding and hospital‐based infrastructure for developmental care in the complex congenital heart disease population. Prioritization of research on and implementation of developmental care interventions in this population should be a major focus in the next decade.

Insulin resistance is the major risk factor for Type 2 diabetes (T2D). In vulnerable individuals, insulin resistance induces a progressive loss of insulin secretion with islet pathology revealing a partial deficit of beta cells and islet amyloid derived from islet amyloid polypeptide (IAPP). IAPP is co-expressed and secreted with insulin by beta cells, expression of both proteins being upregulated in response to insulin resistance. If IAPP expression exceeds the threshold for clearance of misfolded proteins, beta cell failure occurs exacerbated by the action of IAPP toxicity to compromise the autophagy lysosomal pathway. We postulated that suppression of IAPP expression by an IAPP antisense oligonucleotide delivered to beta cells by the GLP-1 agonist exenatide (eGLP1-IAPP-ASO) is a potential disease modifying therapy for T2D. While eGLP1-IAPP-ASO suppressed mouse IAPP and transgenic human IAPP expression in mouse islets, it had no discernable effects on IAPP expression in human islets under the conditions studied. Suppression of transgenic human IAPP expression in mouse islets attenuated disruption of the autophagy lysosomal pathway in beta cells, supporting the potential of this strategy.

Dermatology is often tasked with balancing the clinical appearance of aging skin with the reality of what healthy aging means. In this article, we review some of the core principles of healthy aging and explore common misconceptions, both from patients and physicians, regarding aging. Recognition of the basics of healthy aging and awareness of these aging myths can empower providers to advise patients accurately and productively regarding their aging goals.

Objective Recovery time and treatment effect of oseltamivir in influenza-like illness (ILI) differs between patient groups. A point-of-care test to better predict ILI duration and identify patients who are most likely to benefit from oseltamivir treatment would aid prescribing decisions in primary care. This study aimed to investigate whether a C-reactive protein (CRP) concentration of ≥30 mg/L can predict (1) ILI disease duration, and (2) which patients are most likely to benefit from oseltamivir treatment. Design Secondary analysis of randomized controlled trial data. Setting Primary care in Lithuania, Sweden and Norway during three consecutive influenza seasons 2016–2018. Subjects A total of 277 ILI patients aged one year or older and symptom duration of ≤72 h. Main outcome measures Capillary blood CRP concentration at baseline, and ILI recovery time defined as having ‘returned to usual daily activity’ with residual symptoms minimally interfering. Results At baseline, 20% (55/277) had CRP concentrations ≥30mg/L (range 0–210). CRP concentration ≥30 mg/L was not associated with recovery time (adjusted hazards ratio (HR) 0.80: 95% CI 0.50–1.3; p = 0.33). Interaction analysis of CRP concentration ≥30 mg/L and oseltamivir treatment did not identify which patients benefit more from oseltamivir treatment (adjusted HR 0.69: 95% CI 0.37–1.3; p = 0.23). Conclusion There was no association between CRP concentration of ≥30 mg/L and recovery time from ILI. Furthermore, CRP could not predict which ILI patients benefit more from oseltamivir treatment. Hence, we do not recommend CRP testing for predicting ILI recovery time or identifying patients who will receive particular benefit from oseltamivir treatment.Key Points Predicting disease course of influenza-like illness (ILI), and identifying which patients benefit from oseltamivir treatment is a challenge for physicians. • There was no association between CRP concentration at baseline and recovery time in patients consulting with ILI in primary care. • There was no association between CRP concentration at baseline and benefit from oseltamivir treatment. • We, therefore, do not recommend CRP testing for predicting recovery time or in decision-making concerning oseltamivir prescribing in ILI patients.

Abstract Background Trials show that antimicrobial stewardship (AMS) strategies, including communication skills training, point-of-care C-reactive protein testing (POC-CRPT) and delayed prescriptions, help optimise antibiotic prescribing and use in primary care. However, the use of these strategies in general practice is limited and inconsistent. We aimed to develop an intervention to enhance uptake and implementation of these strategies in primary care. Methods We drew on the Person-Based Approach to develop an implementation intervention in two stages. (1) Planning and design: We defined the problem in behavioural terms drawing on existing literature and conducting primary qualitative research (nine focus groups) in high-prescribing general practices. We identified ‘guiding principles’ with intervention objectives and key features and developed logic models representing intended mechanisms of action. (2) Developing the intervention: We created prototype intervention materials and discussed and refined these with input from 13 health professionals and 14 citizens in two sets of design workshops. We further refined the intervention materials following think-aloud interviews with 22 health professionals. Results Focus groups highlighted uncertainties about how strategies could be used. Health professionals in the workshops suggested having practice champions, brief summaries of each AMS strategy and evidence supporting the AMS strategies, and they and citizens gave examples of helpful communication strategies/phrases. Think-aloud interviews helped clarify and shorten the text and user journey of the intervention materials. The intervention comprised components to support practice-level implementation: antibiotic champions, practice meetings with slides provided, and an ‘implementation support’ website section, and components to support individual-level uptake: website sections on each AMS strategy (with evidence, instructions, links to electronic resources) and material resources (patient leaflets, POC-CRPT equipment, clinician handouts). Conclusions We used a systematic, user-focussed process of developing a behavioural intervention, illustrating how it can be used in an implementation context. This resulted in a multicomponent intervention to facilitate practice-wide implementation of evidence-based strategies which now requires implementing and evaluating. Focusing on supporting the uptake and implementation of evidence-based strategies to optimise antibiotic use in general practice is critical to further support appropriate antibiotic use and mitigate antimicrobial resistance.

Background Children with acute respiratory tract infections (ARTIs) receive ≈11.4 million unnecessary antibiotic prescriptions annually. A noted contributor is inadequate parent–clinician communication, however, efforts to reduce overprescribing have only indirectly targeted communication or been impractical.Objectives Compare two feasible (higher vs lower intensity) interventions for enhancing parent–clinician communication on the rate of inappropriate antibiotic prescribing.Design Multisite, parallel group, cluster randomised comparative effectiveness trial. Data collected between March 2017 and March 2019.Setting Academic and private practice outpatient clinics.Participants Clinicians (n=41, 85% of eligible approached) and 1599 parent–child dyads (ages 1–5 years with ARTI symptoms, 71% of eligible approached).Interventions All clinicians received 20 min ARTI diagnosis and treatment education. Higher intensity clinicians received an additional 50 min communication skills training. All parents viewed a 90 second antibiotic education video.Main outcome(s) and measure(s) Inappropriate antibiotic treatment was assessed via blinded medical record review by study clinicians and a priori defined as prescriptions for the wrong diagnosis or use of the wrong agent. Secondary outcomes were revisits, adverse drug reactions (both assessed 2 weeks after the visit) and parent ratings of provider communication, shared decision-making and visit satisfaction (assessed at end of the visit on Likert-type scales).Results Most clinicians completed the study (n=38, 93%), were doctors (n=25, 66%), female (n=30, 78%) and averaged 8 years in practice. All parent–child dyad provided data for the main outcome (n=855 (54%) male, n=1043 (53%)

Abstract Background Six percent of patients are allergic to penicillin according to their medical records. While this designation protects a small number of truly allergic patients from serious reactions, those who are incorrectly labelled may be denied access to recommended first line treatment for many infections. Removal of incorrect penicillin allergy may have positive health consequences for the individual and the general population. We aimed to explore primary care physicians’ (PCPs) and patients’ views and understanding of penicillin allergy with a focus on clinical management of infections in the face of a penicillin allergy record. Methods We conducted an interview study with 31 patients with a penicillin allergy record, and 19 PCPs in the North of England. Data were analysed thematically. Results Patients made sense of their allergy status by considering the timing and severity of symptoms. Diagnosis of penicillin allergy was reported to be ‘imperfect’ with PCPs relying on patient reports and incomplete medical records. PCPs and patients often suspected that an allergy record was incorrect, but PCPs were reluctant to change records. PCPs had limited knowledge of allergy services. PCPs often prescribed alternative antibiotics which were easy to identify. Both patients and PCPs differed in the extent to which they were aware of the negative consequences of incorrect penicillin allergy records, their relevance and importance to their lives, and management of penicillin allergy. Conclusions PCPs and patients appear insufficiently aware of potential harms associated with incorrect penicillin allergy records. Some of the problems experienced by PCPs could be reduced by ensuring the details of newly diagnosed reactions to antibiotics are clearly documented. In order for PCPs to overturn more incorrect penicillin records through appropriate use of allergy services, more information and training about these services will be needed.

Partially unfolded alpha-lactalbumin forms an oleic acid complex with antitumorigenic properties. Here, the authors define a structurally flexible, peptide-based oleate complex and report a phase I/II clinical trial where this complex is used to treat patients with bladder cancer.

Background: Between-country differences have been described in antibiotic prescribing for respiratory tract infection (RTI) in primary care, but not yet for diagnostic testing procedures and prescribing confidence. Aim: To describe between-country differences in RTI management, particularly diagnostic testing and antibiotic prescribing, and investigate which factors relate to antibiotic prescribing and GPs’ prescribing confidence. Design & setting: Prospective audit in 18 European countries. Method: An audit of GP-registered patient, clinical, and management characteristics for patients presenting with sore throat and/or lower RTI (n = 4982), and GPs' confidence in their antibiotic prescribing decision. Factors related to antibiotic prescribing and confidence were analysed using multi-level logistic regression. Results: Antibiotic prescribing proportions varied considerably: 40% in six countries. There was also considerable variation in point-of-care (POC) testing (0% in Croatia, Moldova, and Romania, and >65% in Denmark and Norway, mainly for C-reactive protein [CRP] and group A streptococcal [strep A] infection), and in laboratory or hospital-based testing (30% in Croatia, Georgia, Greece, and Moldova, mainly chest X-ray and white blood cell counting). Antibiotic prescribing was related to illness severity, comorbidity, age, fever, and country, but not to having performed a POC test. In nearly 90% of consultations, GPs were confident in their antibiotic prescribing decision. Conclusion: Despite high confidence in decisions about antibiotic prescribing, there is considerable variation in the primary care of RTI in European countries, with GPs prescribing antibiotics overall more often than is considered appropriate. POC testing may enhance the quality of antibiotic prescribing decisions if it can safely reverse decisions confidently made on clinical grounds alone to prescribe antibiotics.

Background: The impact of the COVID-19 pandemic on patients’ and clinicians’ perceptions of healthcare-seeking behaviour and delivery of care is unclear. The pandemic accelerated the use of remote care, and understanding its benefits and drawbacks may inform its implementation during current and future healthcare emergencies. Aim: To explore patients’ and primary care professionals’ (PCPs) experiences of primary care delivery in the first wave of the pandemic. Design & setting: Qualitative study using semi-structured interviews in primary care in eight European countries (England, Ireland, Belgium, the Netherlands, Greece, Poland, Sweden, and Germany). Method: A total of 146 interviews were conducted with 80 PCPs and 66 patients consulting for respiratory tract infection (RTI) symptoms, in eight European countries. Data were collected between April and July 2020, and analysed using thematic analysis. Results: It was found that patients accepted telemedicine when PCPs spent time to understand and address their concerns, but a minority preferred in-person consultations. PCPs felt that remote consultations created emotional distance between themselves and patients, and they reported having to manage diverse COVID-19-related medical and social concerns. Conclusion: Remote consultations for RTI symptoms may be acceptable long term if both groups are happy to use this format, but it is important that PCPs take time to address patients’ concerns and provide safety-netting advice.

Using phasor-FLIM (Fluorescence Lifetime Imaging Microscopy), Wang et al. reveal differential usages of oxidative phosphorylation and glycolysis in living islet cells following glucose stimulation. This study suggests the applicability of FLIM as a drug discovery tool as it reports perturbations in glucose metabolism in living islet cells.

Anthropogenic loss of phosphorus to surface waters not only causes environmental problems but depletes valuable phosphorus reserves. In this study, magnesium amended biochars and magnesium silicate, synthesized from corn cobs and rice straw, respectively, were evaluated for phosphorus uptake including the effects of pH and alkalinity. The overall goal was to close the phosphorus loop by recovering phosphorus from animal waste and reusing it as fertilizer. After phosphorus uptake, spent materials were tested for phosphorus release using modified soil tests representing different soil pH and alkalinity conditions. In experiments using model animal wastewaters containing both ammonia and bicarbonate alkalinity, dissolved phosphorus was removed by struvite (MgNH4PO4·6H2O) formation, whereas in deionized water, dissolved phosphorus was removed by adsorption. Alkalinity in the model animal wastewaters competed with phosphate for dissolved or solid-associated magnesium, thereby reducing phosphorus uptake. Spent materials released significant phosphorus in waters with bicarbonate alkalinity. This work shows that abundant agricultural wastes can be used to synthesize solids for phosphorus uptake, with the spent materials having potential application as fertilizers. HIGHLIGHTS Magnesium modified biochar and magnesium silicate were prepared from corn cobs and rice straw, respectively.; These materials removed phosphorus from model wastewaters by struvite precipitation.; Phosphorus uptake was limited by wastewater alkalinity.; Spent materials released phosphorus under conditions mimicking calcareous soils.; These materials show promise for phosphorus recovery and reuse.;

Up to 80% of antibiotics are prescribed in the community. An assessment of prescribing by indication will help to identify areas where improvement can be made. A point prevalence audit study (PPAS) of consecutive respiratory tract infection (RTI) consultations in general practices in 13 European countries was conducted in January–February 2020 (PPAS-1) and again in 2022 (PPAS-4). The European Surveillance of Antibiotic Consumption quality indicators (ESAC-QI) were calculated to identify where improvements can be made. A total of 3618 consultations were recorded for PPAS-1 and 2655 in PPAS-4. Bacterial aetiology was suspected in 26% (PPAS-1) and 12% (PPAS-4), and an antibiotic was prescribed in 30% (PPAS-1) and 16% (PPAS-4) of consultations. The percentage of adult patients with bronchitis who receive an antibiotic should, according to the ESAC-QI, not exceed 30%, which was not met by participating practices in any country except Denmark and Spain. For patients (≥1) with acute upper RTI, less than 20% should be prescribed an antibiotic, which was achieved by general practices in most countries, except Ireland (both PPAS), Croatia (PPAS-1), and Greece (PPAS-4) where prescribing for acute or chronic sinusitis (0–20%) was also exceeded. For pneumonia in adults, prescribing is acceptable for 90–100%, and this is lower in most countries. Prescribing for tonsillitis (≥1) exceeded the ESAC-QI (0–20%) in all countries and was 69% (PPAS-1) and 75% (PPAS-4). In conclusion, ESAC-QI applied to PPAS outcomes allows us to evaluate appropriate antibiotic prescribing by indication and benchmark general practices and countries.

Abstract Background Trials have shown that delayed antibiotic prescriptions (DPs) and point-of-care C-Reactive Protein testing (POC-CRPT) are effective in reducing antibiotic use in general practice, but these were not typically implemented in high-prescribing practices. We aimed to explore views of professionals from high-prescribing practices about uptake and implementation of DPs and POC-CRPT to reduce antibiotic use. Methods This was a qualitative focus group study in English general practices. The highest antibiotic prescribing practices in the West Midlands were invited to participate. Clinical and non-clinical professionals attended focus groups co-facilitated by two researchers. Focus groups were audio-recorded, transcribed verbatim and analysed thematically. Results Nine practices (50 professionals) participated. Four main themes were identified. Compatibility of strategies with clinical roles and experience – participants viewed the strategies as having limited value as ‘clinical tools’, perceiving them as useful only in ‘rare’ instances of clinical uncertainty and/or for those less experienced. Strategies as ‘social tools’ – participants perceived the strategies as helpful for negotiating treatment decisions and educating patients, particularly those expecting antibiotics. Ambiguities – participants perceived ambiguities around when they should be used, and about their impact on antibiotic use. Influence of context – various other situational and practical issues were raised with implementing the strategies. Conclusions High-prescribing practices do not view DPs and POC-CRPT as sufficiently useful ‘clinical tools’ in a way which corresponds to the current policy approach advocating their use to reduce clinical uncertainty and improve antimicrobial stewardship. Instead, policy attention should focus on how these strategies may instead be used as ‘social tools’ to reduce unnecessary antibiotic use. Attention should also focus on the many ambiguities (concerns and questions) about, and contextual barriers to, using these strategies that need addressing to support wider and more consistent implementation.

Input from diverse stakeholders is critical to the process of designing healthcare interventions. This study applied a novel mixed-methods, stakeholder-engaged approach to co-design a psychosocial intervention for mothers expecting a baby with congenital heart disease (CHD) and their partners to promote family wellbeing. The research team included parents and clinicians from 8 health systems. Participants were 41 diverse parents of children with prenatally diagnosed CHD across the 8 health systems. Qualitative data were collected through online crowdsourcing and quantitative data were collected through electronic surveys to inform intervention co-design. Phases of intervention co-design were: (I) Engage stakeholders in selection of intervention goals/outcomes; (II) Engage stakeholders in selection of intervention elements; (III) Obtain stakeholder input to increase intervention uptake/utility; (IV) Obtain stakeholder input on aspects of intervention design; and (V) Obtain stakeholder input on selection of outcome measures. Parent participants anticipated the resulting intervention, HEARTPrep , would be acceptable, useful, and feasible for parents expecting a baby with CHD. This model of intervention co-design could be used for the development of healthcare interventions across chronic diseases.

Objective: To quantify Aboriginal and Torres Strait Islander health check claims in Australian adults in relation to sociodemographic and health characteristics, including prior cardiovascular disease (CVD) and CVD risk factors. Methods: The study involved analysis of baseline data (2006–2009) from the Sax Institute’s 45 and Up Study, involving 1753 Aboriginal and Torres Strait Islander adults in New South Wales, Australia, linked to Medicare Benefits Schedule (MBS) hospital and death data (to December 2015). The outcome was a claim for receiving a Medicare-funded Health Assessment for Aboriginal and Torres Strait Islander People (MBS item 715) in the 2 years before December 2015. Logistic regression was used to estimate odds ratios (ORs) for receiving a health check in relation to sociodemographic and health characteristics. Results: One-third (32%) of participants received at least one Medicare-funded health check in the 2-year period. The probability of receiving a health check was higher for women than men (adjusted OR 1.47; 95% CI 1.18, 1.84), for those with lowest education than for those with highest education (OR 1.58; CI 1.11, 2.24), for those in a regional area (OR 1.56; CI 1.22, 2.01) or remote area (OR 2.38; CI 1.8, 3.16) than for those in major cities, for those with prior CVD than for those without (OR 1.80; CI 1.42, 2.27), for those with CVD risk factors than for those without (adjusted OR between 1.28 and 2.28, depending on risk factor), for those with poor self-rated health than for those with excellent self-rated health (OR 3.15; CI 1.76, 6.65) and for those with more than 10 visits to a general practitioner (GP) per year than for those with 0–2 visits (OR 33.62; CI 13.45, 84.02). Additional adjustment for number of GP visits or self-rated health substantially attenuated ORs for prior CVD and most CVD risk factors. When mutually adjusted, use of GP services and poorer self-rated health remained strongly associated with receiving a health check. Conclusions: Aboriginal and Torres Strait Islander people with the greatest healthcare need and at highest risk of CVD were more likely to receive a health check; however, a significant proportion of those who were eligible had not received this preventive care intervention. Findings indicate that there is greater potential for the use of health checks (MBS item 715) in improving identification and management of Aboriginal and Torres Strait Islander people at high risk of CVD, potentially preventing future CVD events.

Objective Identifying influenza A or B as cause of influenza-like illness (ILI) is a challenge due to non-specific symptoms. An accurate, cheap and easy to use biomarker might enhance targeting influenza-specific management in primary care. The aim of this study was to investigate if C-reactive protein (CRP) is associated with influenza A or B, confirmed with PCR testing, in patients presenting with ILI. Design Cross-sectional study. Setting Primary care in Lithuania, Norway and Sweden. Subjects A total of 277 patients at least 1 year of age consulting primary care with ILI during seasonal influenza epidemics. Main outcome measures Capillary blood CRP analysed as a point-of-care test and detection of influenza A or B on nasopharyngeal swabs in adults, and nasal and pharyngeal swabs in children using PCR. Results The prevalence of positive tests for influenza A among patients was 44% (121/277) and the prevalence of influenza B was 21% (58/277). Patients with influenza A infection could not be identified based on CRP concentration. However, increasing CRP concentration in steps of 10 mg/L was associated with a significantly lower risk for influenza B with an adjusted odds ratio of 0.42 (0.25–0.70; p

Abstract Background To reduce inappropriate antibiotic use, public health campaigns often provide fear-based information about antimicrobial resistance (AMR). Meta-analyses have found that fear-based campaigns in other contexts are likely to be ineffective unless respondents feel confident they can carry out the recommended behaviour (‘self-efficacy’). This study aimed to test the likely impact of fear-based messages, with and without empowering self-efficacy elements, on patient consultations/antibiotic requests for influenza-like illnesses, using a randomised design. Methods We hypothesised that fear-based messages containing empowering information about self-management without antibiotics would be more effective than fear alone, particularly in a pre-specified subgroup with low AMR awareness. Four thousand respondents from an online panel, representative of UK adults, were randomised to receive three different messages about antibiotic use and AMR, designed to induce fear about AMR to varying degrees. Two messages (one ‘strong-fear’, one ‘mild-fear’) also contained empowering information regarding influenza-like symptoms being easily self-managed without antibiotics. The main outcome measures were self-reported effect of information on likelihood of visiting a doctor and requesting antibiotics, for influenza-like illness, analysed separately according to whether or not the AMR information was ‘very/somewhat new’ to respondents, pre-specified based on a previous (non-randomised) survey. Results The ‘fear-only’ message was ‘very/somewhat new’ to 285/1000 (28.5%) respondents, ‘mild-fear-plus-empowerment’ to 336/1500 (22.4%), and ‘strong-fear-plus-empowerment’ to 388/1500 (25.9%) (p = 0.002). Of those for whom the respective information was ‘very/somewhat new’, only those given the ‘strong-fear-plus-empowerment’ message said they would be less likely to request antibiotics if they visited a doctor for an influenza-like illness (p