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BackgroundAntimicrobial resistance (AMR) represents a growing concern for public health. ObjectiveWe sought to explore the challenges associated with development and implementation of a complex intervention designed to improve AMS in hospitals. MethodsWe conducted a qualitative evaluation of a complex AMS intervention with educational, behavioral, and technological components in 5 wards of an English hospital. At 2 weeks and 7 weeks after initiating the intervention, we interviewed 25 users of the intervention, including senior and junior prescribers, a senior nurse, a pharmacist, and a microbiologist. Topics discussed included perceived impacts of different elements of the intervention and facilitators and barriers to effective use. Interviews were supplemented by 2 observations of ward rounds to gain insights into AMS practices. Data were audio-recorded, transcribed, and inductively and deductively analyzed thematically using NVivo12. ResultsTracing the adoption and impact of the various components of the intervention was difficult, as it had been introduced into a setting with competing pressures. These particularly affected behavioral and educational components (eg, training, awareness-building activities), which were often delivered ad hoc. We found that the participatory intervention design had addressed typical use cases but had not catered for edge cases that only became visible when the intervention was delivered in real-world settings (eg, variations in prescribing workflows across different specialties and conditions). ConclusionsEffective user-focused design of complex interventions to promote AMS can support acceptance and use. However, not all requirements and potential barriers to use can be fully anticipated or tested in advance of full implementation in real-world settings.

Background: The relationships between spirometric assessment of lung function and symptoms (including exacerbations) in patients with asthma and/or chronic obstructive pulmonary disease (COPD) in a real-life setting are uncertain. Objectives: To assess the relationships between baseline post-bronchodilator (post-BD) spirometry measures of lung function and symptoms and exacerbations in patients with a physician-assigned diagnosis of asthma and/or COPD. Design: The NOVEL observational longiTudinal studY (NOVELTY) is a global, prospective, 3-year observational study. Methods: Logistic regression analysis was used to evaluate relationships. Spirometry measures were assessed as percent predicted (%pred). Symptoms were assessed at baseline, and exacerbations were assessed at baseline and Year 1. Results: A total of 11,181 patients in NOVELTY had spirometry data (asthma, n = 5903; COPD, n = 3881; asthma + COPD, n = 1397). A 10% lower post-BD %pred forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) – adjusted for age and sex – were significantly associated with dyspnea (modified Medical Research Council ⩾ grade 2), frequent breathlessness [St George’s Respiratory Questionnaire (SGRQ)], frequent wheeze attacks (SGRQ), nocturnal awakening (Respiratory Symptoms Questionnaire; ⩾1 night/week), and frequent productive cough (SGRQ). Lower post-BD %pred FEV 1 and, to a lesser extent, lower post-BD %pred FVC were significantly associated with ⩾1 physician-reported exacerbation at baseline or Year 1. This association was stronger in patients with COPD than in those with asthma. Conclusion: In a real-life setting, reduced lung function is consistently associated with symptoms in patients with asthma, COPD, or asthma + COPD. The relationship with exacerbations is stronger in COPD only than in asthma. Trail registration: clinicaltrials.gov identifier: NCT02760329 ( www.clinicaltrials.gov ).

Background In healthcare research, leveraging data is vital for driving advancements in treatment, diagnosis, and healthcare delivery. However, transparency in data use is pivotal for credible, reproducible findings. Introduction Our initiative was designed to improve transparency in accessing the Optimum Patient Care Research Database (OPCRD: https://doi.org/10.2147/POR.S395632) and to highlight public benefits from utilising anonymised primary electronic medical record data. Our goal was to enhance user accessibility, transparency, and education about its use for research. Through new website content and case studies, we aimed to foster openness, accountability, and trust in research outcomes. Methods • Researcher engagement to outline the data access process, to improve accessible formats with clear guidance. HDRUK Transparency Standard 2 (application process). • Stakeholder engagement to tailor our website content effectively by involving researchers, information governance professionals, and the public. HDRUK Transparency Standard 4 (audience). • Patient and Public Involvement (PPI) workshops were held to find out what the public had to say about their health data being used for research and how it could directly benefit the public and improve healthcare outcomes. HDRUK Transparency Standard 6 (data use). Results Enhanced Online Portal: our new online platform provides comprehensive information and educational guides on the OPCRD data access and data transparency procedures. This portal serves as a crucial resource for healthcare researchers and the public, facilitating transparent and efficient data utilisation. (https://www.opcrd.optimumpatientcare.org/health-data-for-research) Content Creation: we created new content and animated videos for the online portal. The additions ensured the accuracy of content on the platform, improved transparency and facilitated easier navigation of the data access protocols. The animated guides on general data transparency and accessing OPCRD data for research purposes resources significantly enhance the accessibility and understanding of health data for research initiatives. Case Studies Repository: we curated a repository of case studies showcasing the tangible societal benefits and the real-world impact of utilising healthcare data, contributing to a deeper understanding of its broader implications. These were created following PPI engagement workshops where we explored the public benefits of data for healthcare research. This initiative provided invaluable insights into public perspectives to utilising health data transparently and effectively. The PPI engagement events were attended by a diverse participant demographic. Conclusions By applying HDRUK’s Transparency Standards and implementing user-friendly resources, stakeholder engagement, and public involvement, Optimum Patient Care UK has developed an accessible online portal and a repository of animated guides and case studies relating to accessing and utilising data from the Optimum Patient Care Research Database. These efforts improve user accessibility and education on healthcare data use and foster openness, accountability, and trust in research outcomes. Our project contributes to the broader goal of ensuring transparency in data utilisation, thereby advancing healthcare research and promoting public health initiatives. This project was funded by Health Data Research UK (HDRUK2023.0469), Optimum Patient Care UK Limited and Optimum Patient Care Global Limited.

For the past decades, photogrammetry has been increasingly used for monitoring spatial arrangement or temporal dynamics of submerged man-made structures and natural systems. As photogrammetry remains a nascent technique for data collection in the underwater environment, acquisition workflows have evolved constrained by specific methodological practicalities (e.g. euphotic environments vs. deep-sea waters). The annual GeoHab conference gathers a world-wide range of scientists interested in mapping and is, therefore, an adequate event to set up a state-of-the-art workshop on (underwater) photogrammetry. More specifically, a preliminary survey identified the overall lack of photogrammetry knowledge from the audience. A programme was conceptualised to explore within a day theoretical concepts, sampling design and practicalities and a wide range of case studies in various underwater environments. Furthermore, we provided manual training on data acquisition and processing. In overall, a post-survey demonstrated the audience’s satisfaction despite a remaining lack of confidence for implementing their own photogrammetry studies. As this workshop gathers a diversity of materials and a training relevant for a scientific audience, it sets the stage for a reproducible event and leaves room for future improvements. Finally, it provided relevant materials and discussions that enabled us to identify the aspects limiting photogrammetry methodology across scientific applications and institutes, in order to work towards standardisation.

BackgroundNeuroendocrine prostate cancer (NEPCa) is the most aggressive type of prostate cancer (PCa). However, energy metabolism, one of the hallmarks of cancer, in NEPCa has not been well studied. Pyruvate kinase M (PKM), which catalyzes the final step of glycolysis, has two main splicing isoforms, PKM1 and PKM2. The expression pattern of PKM1 and PKM2 in NEPCa remains unknown.MethodsIn this study, we used immunohistochemistry, immunofluorescence staining, and bioinformatics analysis to examine the expression of PKM1 and PKM2 in mouse and human prostatic tissues.ResultsWe found that PKM2 was the predominant isoform expressed throughout prostate development and PCa progression, with slightly reduced expression in murine NEPCa. PKM1 was mostly expressed in stromal cells but low-level PKM1 was also detected in prostate basal epithelial cells. Its expression was absent in the majority of prostate adenocarcinoma (AdPCa) specimens but present in a subset of NEPCa. Additionally, we evaluated the mRNA levels of ten PKM isoforms that express exon 9 (PKM1-like) or exon 10 (PKM2-like). Some of these isoforms showed notable expression levels in PCa cell lines and human PCa specimens.DiscussionOur study characterized the expression pattern of PKM1 and PKM2 in prostatic tissues including developing, benign, and cancerous prostate. These findings lay the groundwork for understanding the metabolic changes in different PCa subtypes.

The importance of Indonesia’s Corruption Eradication Commission (Komisi Pemberantasan Korupsi [KPK]), has once again been brought into focus during the 2024 presidential election campaign period when politics and corruption collide. This article suggests that legislative and political actions since 2019 to the KPK’s purpose and structure severely limit its capacity and independence making it susceptible to greater political interference and coercion. The KPK was established by Law 30/2002, as a response to and recognition of rampant corruption throughout the governmental, political and public sectors, business communities, and society in general, which became common practice during President Suharto’s New Order Regime. The KPK’s commission encompasses conducting investigations, indictments, and prosecutions. However, in late 2019, the People’s Representative Council enacted amending legislation to weaken its authority and ability to operate independently. Crucial legislative changes included creating a government-appointed supervisory body overseeing the KPK’s internal operations and changing KPK employee status from independent agents to public servants. These two provisions alone seriously weaken the KPK’s autonomy and create the risk of turning it into a politically controlled auxiliary state agency. In some respects, KPK has become a victim of its own successes, having achieved convictions of senior ministers, politicians, government officials, and business leaders, which in turn has produced enemies. Without political protection, the KPK faces the prospect of not only becoming, in essence, a nonentity but also facing further deterioration of its credibility and authority.

Background The diagnosis of COPD requires the demonstration of non-fully reversible airflow limitation by spirometry in the appropriate clinical context. Yet, there are patients with symptoms and relevant exposures suggestive of COPD with either normal spirometry (pre-COPD) or preserved ratio but impaired spirometry (PRISm). Their prevalence, clinical characteristics and associated outcomes in a real-life setting are unclear. Methods To investigate them, we studied 3183 patients diagnosed with COPD by their attending physician included in the NOVELTY study (clinicaltrials.gov identifier NCT02760329), a global, 3-year, observational, real-life cohort that included patients recruited from both primary and specialist care clinics in 18 countries. Results We found that 1) approximately a quarter of patients diagnosed with (and treated for) COPD in real life did not fulfil the spirometric diagnostic criteria recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), and could be instead categorised as pre-COPD (13%) or PRISm (14%); 2) disease burden (symptoms and exacerbations) was highest in GOLD 3–4 patients (exacerbations per person-year (PPY) 0.82) and lower but similar in those in GOLD 1–2, pre-COPD and PRISm (exacerbations range 0.27–0.43 PPY); 3) lung function decline was highest in pre-COPD and GOLD 1–2, and much less pronounced in PRISm and GOLD 3-4; 4) PRISm and pre-COPD were not stable diagnostic categories and change substantially over time; and 5) all-cause mortality was highest in GOLD 3–4, lowest in pre-COPD, and intermediate and similar in GOLD 1–2 and PRISm. Conclusions Patients diagnosed COPD in a real-life clinical setting present great diversity in symptom burden, progression and survival, warranting medical attention.

Abstract Background Correct inhaler use depends on a complex interplay of factors, including device preparation and generating sufficient inspiratory flow. It is currently unknown which inhalation technique errors can be considered critical in Chronic Obstructive Pulmonary Disease (COPD) patients on Dry Powder Inhaler (DPI) maintenance therapy. Objective To investigate the association between inhalation technique errors and health status or exacerbations in patients with COPD. Additionally, the association between the number of errors and COPD outcomes was determined. Methods The PIFotal study is a cross-sectional multi-country observational study in a primary care setting, including 1434 COPD patients aged ≥ 40 years (50.1% female; mean age 69.2 yrs) using a DPI for their maintenance therapy. Inhalation technique was video recorded and scored by two independent researchers using inhaler-specific checklists. Health status was assessed with two questionnaires; the Clinical COPD Questionnaire (CCQ) and the COPD Assessment Test (CAT). The number of moderate and severe exacerbations in the past 12 months was recorded. Critical errors were identified based on their association with health status or exacerbations through multi-level prediction models adjusted for identified confounding. Results Errors in inhalation technique steps ‘Breathe in’, ‘Hold breath’, and ‘Breathe out calmly after inhalation’ were significantly associated with poorer CCQ and CAT outcomes and thus deemed critical. None of the errors were significantly associated with moderate exacerbations. Patients with errors ‘Preparation’, ‘Hold inhaler in correct position during inhalation’, and ‘Breathe in’ had significantly more severe exacerbations, and therefore these errors were also deemed critical. 81.3% of patients with COPD made at least one critical error. Specific combinations of errors were associated with worse outcomes. The more inhalation technique errors identified, the poorer the health status and the higher the exacerbation rate. Conclusion In this study, we identified multiple critical inhalation technique errors in COPD patients using DPIs each associated with poorer outcomes. Explorative analysis revealed that specific combinations of errors may be of clinical relevance, especially those related to the inhalation manoeuvre. COPD outcomes worsened with increasing error count. These results warrant further prospective longitudinal studies to establish the effect of correcting these errors on COPD control. Trial registration https://clinicaltrials.gov/ct2/show/NCT04532853 (31/08/2020)

Abstract Background Community-academic partnerships (CAPs) can improve the relevance, sustainability, and uptake of new innovations within the community. However, little is known about what topics CAPs focus on and how their discussions and decisions impact implementation at ground level. The objectives of this study were to better understand the activities and learnings from implementation of a complex health intervention by a CAP at the planner/decision-maker level, and how that compared to experiences implementing the program at local sites. Methods The intervention, Health TAPESTRY, was implemented by a nine-partner CAP including academic, charitable organizations, and primary care practices. Meeting minutes were analyzed using qualitative description, latent content analysis, and a member check with key implementors. An open-answer survey about the best and worst elements of the program was completed by clients and health care providers and analyzed using thematic analysis. Results In total, 128 meeting minutes were analyzed, 278 providers and clients completed the survey, and six people participated in the member check. Prominent topics of discussion categories from the meeting minutes were: primary care sites, volunteer coordination, volunteer experience, internal and external connections, and sustainability and scalability. Clients liked that they learned new things and gained awareness of community programs, but did not like the volunteer visit length. Clinicians liked the regular interprofessional team meetings but found the program time-consuming. Conclusions An important learning was about who had “voice” at the planner/decision-maker level: many of the topics discussed in meeting minutes were not identified as issues or lasting impacts by clients or providers; this may be due to differing roles and needs, but may also identify a gap. Overall, we identified three phases that could serve as a guide for other CAPs: Phase (1) recruitment, financial support, and data ownership; Phase (2) considerations for modifications and adaptations; Phase (3) active input and reflection.

Abstract Despite national and international guidelines, asthma is frequently misdiagnosed, control is poor and unnecessary deaths are far too common. Large scale asthma management programme such as that undertaken in Finland, can improve asthma outcomes. A primary care asthma management quality improvement programme was developed with the support of the British Lung Foundation (now Asthma + Lung UK) and Optimum Patient Care (OPC) Limited. It was delivered and cascaded to all relevant staff at participating practices in three Clinical Commissioning Groups. The programme focussed on improving diagnostic accuracy, management of risk and control, patient self-management and overall asthma control. Patient data were extracted by OPC for the 12 months before (baseline) and after (outcome) the intervention. In the three CCGs, 68 GP practices participated in the programme. Uptake from practices was higher in the CCG that included asthma in its incentivised quality improvement programme. Asthma outcome data were successfully extracted from 64 practices caring for 673,593 patients. Primary outcome (Royal College of Physicians Three Questions [RCP3Q]) data were available in both the baseline and outcome periods for 10,328 patients in whom good asthma control (RCP3Q = 0) increased from 36.0% to 39.2% (p

Our study aimed to describe patient experience of information coordination between their primary care physician and specialists and to examine the associations between their experience and their personal and primary care characteristics. We conducted a cross-sectional study of Ontario residents rostered to a primary care physician and visited a specialist physician in the previous 12 months by linking population-based health administrative data to the Health Care Experience Survey collected between 2013 and 2020. We described respondents' sociodemographic and health care utilization characteristics and their experience of information coordination between their primary care physician and specialists. We measured the adjusted association between patient-reported measures of information coordination before and after respondents received care from a specialist physician and their type of primary care model. 1,460 out 20,422 (weighted 7.5%) of the respondents reported that their specialist physician did not have basic medical information about their visit from their primary care physician in the previous 12 months. 2,298 out of 16,442 (weighted 14.9%) of the respondents reported that their primary care physician seemed uninformed about the care they received from the specialist. Females, younger individuals, those with a college or undergraduate level of education, and users of walk-in clinics had a higher likelihood of reporting a lack of information coordination between the primary care and specialist physicians. Only respondents rostered to an enhanced fee-for-service model had a higher odds of reporting that the specialist physician did not have basic medical information about their visit compared to those rostered to a Family Health Team (OR 1.22, 95% Cl 1.12-1.40). We found no significant association between respondent's type of primary care model and that their primary care physician was uninformed about the care received from the specialist physician. In this population-based health study, respondents reported high information coordination between their primary care physician and specialists. Except for respondents rostered to an enhanced fee-for-service model of care, we did not find any difference in information coordination across other primary care models.

Abstract Successful restoration of human‐disturbed landscapes and ecosystems will be increasingly compromised by the impacts of climate warming. Assisted migration and climate‐informed restoration, in which populations and species adapted to future climates are selected for restoration planting, have emerged as management tools to mitigate climate change effects. However, it is unclear whether climate‐informed restoration could offset the negative effects of climate change and enable successful restoration. We used a forest landscape model to evaluate the potential for reclamation activities to restore western Canadian boreal forest landscapes severely degraded by oil sands mining. We parametrized tree populations adapted to growing in warmer climates and then simulated the planting of local or southern tree populations under different climate change, mining, and wildfire disturbance scenarios. We found that planting trees better adapted to a warmer climate mitigated climate‐change and wildfire‐caused decreases in biomass across the landscape, but only under moderate climate change scenarios. The compensatory effect of planting populations adapted to warmer southern climates disappeared under a more severe climate change scenario. The advantage of planting southern populations also disappeared under wildfire scenarios, generally doubling the biomass loss compared with scenarios without wildfire. With wildfire and strong climate change effects, forest cover disappeared from much of the landscape, regardless of the planting scenario, causing it to change markedly from present‐day continuous boreal forest cover. We argue that such conditions would have large ecological and economic consequences. Scenario modeling with forest landscape models could be used as a tool to identify the long‐term success of restoration actions and to understand possible consequences of climate‐informed restoration.

Background Dupilumab has been shown to improve clinical outcomes long term while reducing oral corticosteroid (OCS) dose in patients with severe OCS-dependent asthma. This post hoc analysis assesses the impact of OCS dose at baseline (≤10 or >10 mg·day−1) on long-term outcomes of dupilumab treatment. Methods Annualised severe asthma exacerbation rates, forced expiratory volume in 1 s (FEV1), measures of asthma control and quality of life, and OCS dose were evaluated in patients from the phase 3 VENTURE trial with severe OCS-dependent asthma, further categorised by OCS dose ≤10 or >10 mg·day−1 at parent study baseline (PSBL), who enrolled in TRAVERSE. Results Dupilumab reduced the annualised exacerbation rate in VENTURE, and it remained low throughout TRAVERSE (0.202–0.265 (OCS ≤10 mg·day−1 at PSBL) and 0.221–0.366 (OCS >10 mg·day−1 at PSBL)). Improvements in pre-bronchodilator FEV1, asthma control and quality of life observed in VENTURE dupilumab patients were sustained throughout TRAVERSE. Patients on placebo during VENTURE showed rapid improvements in FEV1 upon initiating dupilumab in TRAVERSE, which were sustained to the end of TRAVERSE. Reductions in OCS dose observed in VENTURE were maintained throughout TRAVERSE, with more than two-thirds of patients achieving reductions in OCS doses to ≤5 mg·day−1 by TRAVERSE week 48. Conclusions Improvements in clinical outcomes and reductions in OCS dose with dupilumab observed in VENTURE were maintained throughout TRAVERSE, regardless of baseline disease severity. Patients who switched from placebo in VENTURE to dupilumab in TRAVERSE had improved clinical outcomes and reductions in OCS dose comparable to those given dupilumab in VENTURE.

Abstract Background No short patient-reported outcome (PRO) instruments assess overall health status across different obstructive lung diseases. Thus, the wording of the introduction to the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) was modified to permit use in asthma and/or COPD. This tool is called the Chronic Airways Assessment Test (CAAT). Methods The psychometric properties of the CAAT were evaluated using baseline data from the NOVELTY study (NCT02760329) in patients with physician-assigned asthma, asthma + COPD or COPD. Analyses included exploratory/confirmatory factor analyses, differential item functioning and analysis of construct validity. Responses to the CAAT and CAT were compared in patients with asthma + COPD and those with COPD. Results CAAT items were internally consistent (Cronbach’s alpha: > 0.7) within each diagnostic group (n = 510). Models for structural and measurement invariance were strong. Tests of differential item functioning showed small differences between asthma and COPD in individual items, but these were not consistent in direction and had minimal overall impact on the total score. The CAAT and CAT were highly consistent when assessed in all NOVELTY patients who completed both (N = 277, Pearson’s correlation coefficient: 0.90). Like the CAT itself, CAAT scores correlated moderately (0.4–0.7) to strongly (> 0.7) with other PRO measures and weakly (

Abstract Background Asthma is a common long-term condition and major public health problem. Supported self-management for asthma that includes a written personalised asthma action plan, supported by regular professional review, reduces unscheduled consultations and improves asthma outcomes and quality of life. However, despite unequivocal inter/national guideline recommendations, supported self-management is poorly implemented in practice. The IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) implementation strategy has been developed to address this challenge. The aim of this implementation trial is to determine whether facilitated delivery of the IMP2ART strategy increases the provision of asthma action plans and reduces unscheduled care in the context of routine UK primary care. Methods IMP2ART is a parallel group, cluster randomised controlled hybrid II implementation trial. One hundred forty-four general practices will be randomly assigned to either the IMP2ART implementation strategy or control group. Following a facilitation workshop, implementation group practices will receive organisational resources to help them prioritise supported self-management (including audit and feedback; an IMP2ART asthma review template), training for professionals and resources to support patients to self-manage their asthma. The control group will continue with usual asthma care. The primary clinical outcome is the between-group difference in unscheduled care in the second year after randomisation (i.e. between 12 and 24 months post-randomisation) assessed from routine data. Additionally, a primary implementation outcome of asthma action plan ownership at 12 months will be assessed by questionnaire to a random sub-group of people with asthma. Secondary outcomes include the number of asthma reviews conducted, prescribing outcomes (reliever medication and oral steroids), asthma symptom control, patients’ confidence in self-management and professional support and resource use. A health economic analysis will assess cost-effectiveness, and a mixed methods process evaluation will explore implementation, fidelity and adaptation. Discussion The evidence for supported asthma self-management is overwhelming. This study will add to the literature regarding strategies that can effectively implement supported self-management in primary care to reduce unscheduled consultations and improve asthma outcomes and quality of life. Trial registration ISRCTN15448074. Registered on 2 December 2019.

Abstract An algorithm to describe patterns of intermittent oral corticosteroid use in the UK (n = 476,167) found that one-third of patients receiving intermittent oral corticosteroids for asthma only had short gaps (

Management of deep-sea fisheries in areas beyond national jurisdiction by Regional Fisheries Management Organizations/Arrangements (RFMO/As) requires identification of areas with Vulnerable Marine Ecosystems (VMEs). Currently, fisheries data, including trawl and longline bycatch data, are used by many RFMO/As to inform the identification of VMEs. However, the collection of such data creates impacts and there is a need to collect non-invasive data for VME identification and monitoring purposes. Imagery data from scientific surveys satisfies this requirement, but there currently is no established framework for identifying VMEs from images. Thus, the goal of this study was to bring together a large international team to determine current VME assessment protocols and establish preliminary global consensus guidelines for identifying VMEs from images. An initial assessment showed a lack of consistency among RFMO/A regions regarding what is considered a VME indicator taxon, and hence variability in how VMEs might be defined. In certain cases, experts agreed that a VME could be identified from a single image, most often in areas of scleractinian reefs, dense octocoral gardens, multiple VME species’ co-occurrence, and chemosynthetic ecosystems. A decision flow chart is presented that gives practical interpretation of the FAO criteria for single images. To further evaluate steps of the flow chart related to density, data were compiled to assess whether scientists perceived similar density thresholds across regions. The range of observed densities and the density values considered to be VMEs varied considerably by taxon, but in many cases, there was a statistical difference in what experts considered to be a VME compared to images not considered a VME. Further work is required to develop an areal extent index, to include a measure of confidence, and to increase our understanding of what levels of density and diversity correspond to key ecosystem functions for VME indicator taxa. Based on our results, the following recommendations are made: 1. There is a need to establish a global consensus on which taxa are VME indicators. 2. RFMO/As should consider adopting guidelines that use imagery surveys as an alternative (or complement) to using bycatch and trawl surveys for designating VMEs. 3. Imagery surveys should also be included in Impact Assessments. And 4. All industries that impact the seafloor, not just fisheries, should use imagery surveys to detect and identify VMEs.

Introduction: Accurately diagnosing asthma can be challenging. We aimed to derive and validate a prediction model to support primary care clinicians assess the probability of an asthma diagnosis in children and young people. Methods: The derivation dataset was created from the Avon Longitudinal Study of Parents and Children (ALSPAC) linked to electronic health records. Participants with at least three inhaled corticosteroid prescriptions in 12-months and a coded asthma diagnosis were designated as having asthma. Demographics, symptoms, past medical/family history, exposures, investigations, and prescriptions were considered as candidate predictors. Potential candidate predictors were included if data were available in ≥60% of participants. Multiple imputation was used to handle remaining missing data. The prediction model was derived using logistic regression. Internal validation was completed using bootstrap re-sampling. External validation was conducted using health records from the Optimum Patient Care Research Database (OPCRD). Results: Predictors included in the final model were wheeze, cough, breathlessness, hay-fever, eczema, food allergy, social class, maternal asthma, childhood exposure to cigarette smoke, prescription of a short acting beta agonist and the past recording of lung function/reversibility testing. In the derivation dataset, which comprised 11,972 participants aged

Summary: Background: In this study, we compare management of patients with high-risk chronic obstructive pulmonary disease (COPD) in the United States to national and international guidelines and quality standards, including the COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST). Methods: Patients were identified from the DARTNet Practice Performance Registry and categorized into three high-risk cohorts in each year from 2011 to 2019: newly diagnosed (≤12 months after diagnosis), already diagnosed, and patients with potential undiagnosed COPD. Patients were considered high-risk if they had a history of exacerbations or likely exacerbations (respiratory consult with prescribed medication). Descriptive statistics for 2019 are reported, along with annual trends. Findings: In 2019, 10% (n = 16,610/167,197) of patients met high-risk criteria. Evidence of spirometry for diagnosis was low; in 2019, 81% (n = 1228/1523) of patients newly diagnosed at high-risk had no record of spirometry/peak expiratory flow in the 12 months pre- or post-diagnosis and 43% (n = 651/1523) had no record of COPD symptom review. Among those newly and already diagnosed at high-risk, 52% (n = 4830/9350) had no evidence of COPD medication. Interpretation: Findings suggest inconsistent adherence to evidence-based guidelines, and opportunities to improve identification, documentation of services, assessment, therapeutic intervention, and follow-up of patients with COPD. Funding: This study was conducted by the Observational and Pragmatic Research Institute (OPRI) Pte Ltd and was partially funded by Optimum Patient Care Global and AstraZeneca Ltd. No funding was received by the Observational & Pragmatic Research Institute Pte Ltd (OPRI) for its contribution.

Abstract Over 1400 patients using dry powder inhalers (DPIs) to deliver COPD maintenance therapies were recruited across Europe and Australia. Their peak inspiratory flow (PIF) was measured, inhaler technique was observed, and adherence to treatment assessed. From relating the findings with patient health status, and thereby identifying critical errors, key clinical recommendations for primary care clinicians were determined, namely – measure PIF before prescribing a DPI to ensure inhalation manoeuvre ability is well-matched with the device. Some patients could benefit from inhalation training whereas others should have their DPI changed for one better suited to their inspiratory ability or alternatively be prescribed an active device (such as a soft mist inhaler or pressurized metered dose inhaler). Observing the inhalation technique was valuable however this misses suboptimal PIF (approaching one fourth of patients with a satisfactory observed manoeuvre had a suboptimal PIF for their DPI). Assess adherence as deliberate non-adherence can point to a mismatch between a patient and their inhaler (deliberate non-adherence was significantly associated with PIFs below the minimum for the DPI). In-person observation of inhalation technique was found to be inferior to video rating based on device-specific checklists. Where video assessments are not possible, observation training for healthcare professionals would therefore be valuable particularly to improve the ability to identify the critical errors associated with health status namely ‘teeth and lips sealed around mouthpiece’, ‘breathe in’ and ‘breathing out calmly after inhalation’. However, it is recommended that observation alone should not replace PIF measurement in the DPI selection process. Trial registration: https://clinicaltrials.gov/ct2/show/NCT04532853 .

Abstract Background SARS-CoV-2 infection is associated with a significant risk of hospitalisation, death, and prolonged impact on quality of life. Evaluation of new treatment options and optimising therapeutic management of people hospitalised with SARS-CoV-2 infection remains essential, but rapid changes in pandemic conditions and potential therapies have limited the utility of traditional approaches to randomised controlled trials. Methods ASCOT ADAPT is an international, investigator-initiated, adaptive platform, randomised controlled trial of therapeutics for non-critically ill patients hospitalised with COVID-19. The study design is open label and pragmatic. Potential participants are hospitalised adults with PCR confirmed, symptomatic, SARS-CoV-2 infection, within 14 days of symptom onset. Domains include antiviral, antibody and anticoagulant interventions, with a composite primary outcome of 28-day mortality or progression to intensive-care level respiratory or haemodynamic support. Initial interventions include intravenous nafamostat and variable dose anticoagulation. A range of secondary endpoints, and substudies for specific domains and interventions are outlined. Discussion This paper presents the trial protocol and management structure, including international governance, remote site monitoring and biobanking activities and provides commentary on ethical and pragmatic considerations in establishing the ASCOT ADAPT trial under pandemic conditions. Trial registration Australian and New Zealand Clinical Trials Registry (ACTRN12620000445976) and ClinicalTrials.gov (NCT04483960).

Abstract Short-acting β2-agonist (SABA) prescriptions and associated outcomes were assessed in 1440 patients with asthma from the SABA use IN Asthma (SABINA) III study treated in primary care. Data on asthma medications were collected, and multivariable regression models analysed the association of SABA prescriptions with clinical outcomes. Patients (mean age, 47.9 years) were mostly female (68.6%); 58.3% had uncontrolled/partly controlled asthma and 38.8% experienced ≥1 severe exacerbation (reported in 39% of patients with mild asthma). Overall, 44.9% of patients were prescribed ≥3 SABA canisters (over-prescription) and 21.5% purchased SABA over-the-counter. Higher SABA prescriptions (vs 1−2 canisters) were associated with significantly decreased odds of having at least partly controlled asthma (6–9 and 10–12 canisters) and an increased incidence rate of severe exacerbations (10–12 and ≥13 canisters). Findings revealed a high disease burden, even in patients with ‘mild’ asthma, emphasising the need for local primary care guidelines based on international recommendations.

Background: Coronavirus disease (COVID-19) manifests many clinical symptoms, including an exacerbated immune response and cytokine storm. Autoantibodies in COVID-19 may have severe prodromal effects that are poorly understood. The interaction between these autoantibodies and self-antigens can result in systemic inflammation and organ dysfunction. However, the role of autoantibodies in COVID-19 complications has yet to be fully understood.Methods: The current investigation screened two independent cohorts of 97 COVID-19 patients [discovery (Disc) cohort from Qatar (case = 49 vs. control = 48) and replication (Rep) cohort from New York (case = 48 vs. control = 28)] utilizing high-throughput KoRectly Expressed (KREX) Immunome protein-array technology. Total IgG autoantibody responses were evaluated against 1,318 correctly folded and full-length human proteins. Samples were randomly applied on the precoated microarray slides for 2 h. Cy3-labeled secondary antibodies were used to detect IgG autoantibody response. Slides were scanned at a fixed gain setting using the Agilent fluorescence microarray scanner, generating a 16-bit TIFF file. Group comparisons were performed using a linear model and Fisher’s exact test. Differentially expressed proteins were used for KEGG and WIKIpathway annotation to determine pathways in which the proteins of interest were significantly over-represented.Results and conclusion: Autoantibody responses to 57 proteins were significantly altered in the COVID-19 Disc cohort compared to healthy controls (p ≤ 0.05). The Rep cohort had altered autoantibody responses against 26 proteins compared to non-COVID-19 ICU patients who served as controls. Both cohorts showed substantial similarities (r2 = 0.73) and exhibited higher autoantibody responses to numerous transcription factors, immunomodulatory proteins, and human disease markers. Analysis of the combined cohorts revealed elevated autoantibody responses against SPANXN4, STK25, ATF4, PRKD2, and CHMP3 proteins in COVID-19 patients. The sequences for SPANXN4 and STK25 were cross-validated using sequence alignment tools. ELISA and Western blot further verified the autoantigen–autoantibody response of SPANXN4. SPANXN4 is essential for spermiogenesis and male fertility, which may predict a potential role for this protein in COVID-19-associated male reproductive tract complications, and warrants further research.

BackgroundAntimicrobial resistance, the ability of microorganisms to survive antimicrobial drugs, is a public health emergency. Although electronic prescribing (ePrescribing)–based interventions designed to reduce unnecessary antimicrobial usage exist, these often do not integrate effectively with existing workflows. As a result, ePrescribing-based interventions may have limited impact in addressing antimicrobial resistance. ObjectiveWe sought to understand the existing ePrescribing-based antimicrobial stewardship (AMS) practices in an English hospital preceding the implementation of functionality designed to improve AMS. MethodsWe conducted 18 semistructured interviews with medical prescribers and pharmacists with varying levels of seniority exploring current AMS practices and investigating potential areas for improvement. Participants were recruited with the help of local gatekeepers. Topic guides sought to explore both formal and informal practices surrounding AMS, and challenges and opportunities for ePrescribing-based intervention. We coded audio-recorded and transcribed data with the help of the Technology, People, Organizations, and Macroenvironmental factors framework, allowing emerging themes to be added inductively. We used NVivo 12 (QSR International) to facilitate coding. ResultsAntimicrobial prescribing and review processes were characterized by competing priorities and uncertainty of prescribers and reviewers around prescribing decisions. For example, medical prescribers often had to face trade-offs between individual patient benefit and more diffuse population health benefits, and the rationale for prescribing decisions was not always clear. Prescribing involved a complex set of activities carried out by various health care practitioners who each only had a partial and temporary view of the whole process, and whose relationships were characterized by deeply engrained hierarchies that shaped interactions and varied across specialties. For example, newly qualified doctors and pharmacists were hesitant to change a consultant’s prescribing decision when reviewing prescriptions. Multidisciplinary communication, collaboration, and coordination promoted good AMS practices by reducing uncertainty. ConclusionsDesign of ePrescribing-based interventions to improve AMS needs to take into account the multitude of actors and organizational complexities involved in the prescribing and review processes. Interventions that help reduce prescriber or reviewer uncertainty and improve multidisciplinary collaboration surrounding initial antimicrobial prescribing and subsequent prescription review are most likely to be effective. Without such attention, interventions are unlikely to fulfill their goal of improving patient outcomes and combatting antimicrobial resistance.

Background: Electronic templates are frequently used in long-term condition (LTC) reviews (for example, asthma) to act as reminders and improve documentation; however, they can restrict patient-centred care and opportunities for patients to discuss concerns and self-management. Aim: The IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) programme aimed to develop a patient-centred asthma review template that encourages supported self-management. Design & setting: This was a mixed-methods study, which integrated qualitative and systematic review data, primary care Professional Advisory Group feedback, and qualitative data from clinician interviews. Method: Aligned with the Medical Research Council complex intervention framework, a template was developed in the following three phases: (1) development phase, which consisted of a qualitative exploration with clinicians and patients, a systematic review, and prototype template development; (2) feasibility pilot phase, which involved feedback from clinicians (n = 7); and (3) pre-piloting phase, which consisted of delivering the template within the IMP2ART implementation strategy (incorporating the template with patient and professional resources) and eliciting clinician feedback (n = 6). Results: Template development was guided by the preliminary qualitative work and the systematic review. A prototype template was developed with an opening question to establish patient agendas, and a closing prompt to confirm agendas have been addressed and an asthma action plan provided. The feasibility pilot identified refinements needed, including focusing the opening question on asthma. Pre-piloting ensured integration with the IMP2ART strategy. Conclusion: Following the multi-stage development process, the implementation strategy, including the asthma review template, is now being tested in a cluster randomised controlled trial.

Summary: Background: This study compared management of high-risk COPD patients in the UK to national and international management recommendations and quality standards, including the COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST). The primary comparison was in 2019, but trends from 2000 to 2019 were also examined. Methods: Patients identified in the Optimum Patient Care Research Database were categorised as newly diagnosed (≤12 months after diagnosis), already diagnosed, and potential COPD (smokers having exacerbation-like events). High-risk patients had a history of ≥2 moderate or ≥1 severe exacerbations in the previous 12 months. Findings: For diagnosed patients, the median time between diagnosis and first meeting the high-risk criteria was 617 days (Q1-Q3: 3246). The use of spirometry for diagnosis increased dramatically after 2004 before plateauing and falling in recent years. In 2019, 41% (95% CI 39–44%; n = 550/1343) of newly diagnosed patients had no record of spirometry in the previous year, and 45% (95% CI 43–48%; n = 352/783) had no record of a COPD medication review within 6 months of treatment initiation or change. In 2019, 39% (n = 6893/17,858) of already diagnosed patients had no consideration of exacerbation rates, 46% (95% CI 45–47%; n = 4942/10,725) were not offered or referred for pulmonary rehabilitation, and 41% (95% CI 40–42%; n = 3026/7361) had not had a COPD review within 6 weeks of respiratory hospitalization. Interpretation: Opportunities for early diagnosis of COPD patients at high risk of exacerbations are being missed. Newly and already diagnosed patients at high-risk are not being assessed or treated promptly. There is substantial scope to improve the assessment and treatment optimisation of these patients. Funding: This study is conducted by the Observational & Pragmatic Research International Ltd and was co-funded by Optimum Patient Care and AstraZeneca. No funding was received by the Observational & Pragmatic Research Institute Pte Ltd (OPRI) for its contribution.

Abstract The study aimed to determine the associations of Peak Inspiratory Flow (PIF), inhalation technique and adherence with health status and exacerbations in participants with COPD using DPI maintenance therapy. This cross-sectional multi-country observational real-world study included COPD participants aged ≥40 years using a DPI for maintenance therapy. PIF was measured three times with the In-Check DIAL G16: (1) typical PIF at resistance of participant’s inhaler, (2) maximal PIF at resistance of participant’s inhaler, (3) maximal PIF at low resistance. Suboptimal PIF (sPIF) was defined as PIF lower than required for the device. Participants completed questionnaires on health status (Clinical COPD Questionnaire (CCQ)), adherence (Test of Adherence to Inhalers (TAI)) and exacerbations. Inhalation technique was assessed by standardised evaluation of video recordings. Complete data were available from 1434 participants (50.1% female, mean age 69.2 years). GOLD stage was available for 801 participants: GOLD stage I (23.6%), II (54.9%), III (17.4%) and IV (4.1%)). Of all participants, 29% had a sPIF, and 16% were shown able to generate an optimal PIF but failed to do so. sPIF was significantly associated with worse health status (0.226 (95% CI 0.107–0.346), worse units on CCQ; p = 0.001). The errors ‘teeth and lips sealed around mouthpiece’, ‘breathe in’, and ‘breathe out calmly after inhalation’ were related to health status. Adherence was not associated with health status. After correcting for multiple testing, no significant association was found with moderate or severe exacerbations in the last 12 months. To conclude, sPIF is associated with poorer health status. This study demonstrates the importance of PIF assessment in DPI inhalation therapy. Healthcare professionals should consider selecting appropriate inhalers in cases of sPIF.

Adaptive clinical trials have designs that evolve over time because of changes to treatments or changes to the chance that participants will receive these treatments. These changes might introduce confounding that biases crude comparisons of the treatment arms and makes the results from standard reporting methods difficult to interpret for adaptive trials. To deal with this shortcoming, a reporting framework for adaptive trials was developed based on concurrently randomised cohort reporting. A concurrently randomised cohort is a subgroup of participants who all had the same treatments available and the same chance of receiving these treatments. The reporting of pre-randomisation characteristics and post-randomisation outcomes for each concurrently randomised cohort in the study is recommended. This approach provides a transparent and unbiased display of the degree of baseline balance and the randomised treatment comparisons for adaptive trials. The key concepts, terminology, and recommendations underlying concurrently randomised cohort reporting are presented, and its routine use in adaptive trial reporting is advocated.

Abstract Background Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta blocker use in people with COPD is associated with a reduced risk of COPD exacerbations. The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease. Methods BICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post-bronchodilator FEV1

Abstract Background Contextual factors can act as barriers or facilitators to scaling-up health care interventions, but there is limited understanding of how context and local culture can lead to differences in implementation of complex interventions with multiple stakeholder groups. This study aimed to explore and describe the nature of and differences between communities implementing Health TAPESTRY, a complex primary care intervention aiming to keep older adults healthier in their homes for longer, as it was scaled beyond its initial effectiveness trial. Methods We conducted a comparative case study with six communities in Ontario, Canada implementing Health TAPESTRY. We focused on differences between three key elements: interprofessional primary care teams, volunteer program coordination, and the client experience. Sources of data included semi-structured focus groups and interviews. Data were analyzed through the steps of thematic analysis. We then created matrices in NVivo by splitting the qualitative data by community and comparing across the key elements of the Health TAPESTRY intervention. Results Overall 135 people participated (39 clients, 8 clinical managers, 59 health providers, 6 volunteer coordinators, and 23 volunteers). The six communities had differences in size and composition of both their primary care practices and communities, and how the volunteer program and Health TAPESTRY were implemented. Distinctions between communities relating to the work of the interprofessional teams included characteristics of the huddle lead, involvement of physicians and the volunteer coordinator, and clarity of providers’ role with Health TAPESTRY. Key differences between communities relating to volunteer program coordination included the relationship between the volunteers and primary care practices, volunteer coordinator characteristics, volunteer training, and connections with the community. Differences regarding the client experience between communities included differing approaches used in implementation, such as recruitment methods. Conclusions Although all six communities had the same key program elements, implementation differed community-by-community. Key aspects that seemed to lead to differences across categories included the size and spread of communities, size of primary care practices, and linkages between program elements. We suggest future programs engaging stakeholders from the beginning and provide clear roles; target the most appropriate clients; and consider the size of communities and practices in implementation. Trial registration ClinicalTrials.gov: NCT03397836 .

Abstract Respiratory diseases remain a significant cause of global morbidity and mortality and primary care plays a central role in their prevention, diagnosis and management. An e-Delphi process was employed to identify and prioritise the current respiratory research needs of primary care health professionals worldwide. One hundred and twelve community-based physicians, nurses and other healthcare professionals from 27 high-, middle- and low-income countries suggested 608 initial research questions, reduced after evidence review by 27 academic experts to 176 questions covering diagnosis, management, monitoring, self-management and prognosis of asthma, COPD and other respiratory conditions (including infections, lung cancer, tobacco control, sleep apnoea). Forty-nine questions reached 80% consensus for importance. Cross-cutting themes identified were: a need for more effective training of primary care clinicians; evidence and guidelines specifically relevant to primary care, adaption for local and low-resource settings; empowerment of patients to improve self-management; and the role of the multidisciplinary healthcare team.

Systemic corticosteroids (SCS) are a highly effective treatment for acute exacerbations and long-term symptom control in asthma. Long-term SCS use is highly prevalent across all asthma severities, occurring in over 20% of patients with severe or uncontrolled disease globally. It is now well known that exposure to both long-term and repeated acute courses of SCS is associated with a high risk of serious adverse effects (AEs), such as osteoporosis, and metabolic and cardiovascular complications, especially when prescribed onto a background of other corticosteroids. The aim of this call-to-action article, endorsed by the World Allergy Organization and the Respiratory Effectiveness Group, is to review the accumulating evidence on the burden of SCS on patients with asthma and provide an overview of potential strategies for implementing SCS Stewardship.Primary prevention of exacerbations and improvement of asthma control is a key first step in achieving SCS Stewardship, by optimizing maintenance asthma medications and addressing modifiable risk factors, such as adherence and inhaler technique. Other key elements of SCS Stewardship include increasing appropriate specialist referrals for multidisciplinary review, assessment of biomarkers, and consideration of oral corticosteroid-sparing add-on therapies (eg, biologics). In cases where SCS use is deemed clinically justified, it should be tapered to the lowest possible dose. In addition, patients receiving long-term SCS or frequent acute courses should be closely monitored for emergence of SCS-related AEs.Because of the extensive data available on the costly and burdensome AEs associated with SCS use, as well as the range of treatment options now available, there is a need for healthcare providers (HCPs) to carefully evaluate whether the benefits of SCS outweigh the potential harms, to adopt SCS-sparing and Stewardship strategies, and to consider alternative therapies where possible. Development of a structured and collaborative SCS Stewardship approach is urgently required to protect patients from the potential harm of SCS use.

Abstract Background Urticaria is a common condition presenting both as acute and chronic disease within primary care. To those without specialist training it is poorly understood from the points of view of diagnosis and management. It causes a considerable disease burden to sufferers with marked impact on quality of life. Purpose of this review The recent publication of the EAACI/GA²LEN/EuroGuiDerm/APAAACI Guideline for the Definition, Classification, Diagnosis and Management of Urticaria guideline prompted us to take this excellent resource and re‐configure its findings and recommendations to a non‐specialist audience with particular reference to the needs of the primary care team.

Background: The role of fractional exhaled nitric oxide in guiding asthma treatment in children is uncertain. Objective: To compare treatment guided by both fractional exhaled nitric oxide and symptoms (intervention) with treatment guided by symptoms alone (standard care) in children with asthma who are at risk of an asthma exacerbation, in terms of the number of asthma exacerbations over 12 months. Design: This was a pragmatic, multicentre, randomised controlled trial with embedded cost-effectiveness and qualitative process evaluations. Randomisation (1 : 1) was carried out using a remote web-based system and was minimised on recruitment centre, age, sex and British Thoracic Society treatment step. Clinical teams and participants were not blind to treatment allocation. Setting: The trial took place in 35 hospitals and seven primary care practices in the UK. Participants: Children aged 6–15 years with a diagnosis of asthma who were currently prescribed inhaled corticosteroids and who had one or more parent-/patient-reported asthma exacerbation treated with oral corticosteroids in the 12 months prior to recruitment. Interventions: Asthma treatment guided by symptoms alone (standard care) and asthma treatment guided by symptoms plus fractional exhaled nitric oxide (intervention). Treatment recommendations in both groups were protocolised within a web-based algorithm, incorporating inhaled corticosteroid adherence (objectively measured using an electronic logging device) and current treatment. Main outcome measures: The primary outcome measure was asthma exacerbations treated with oral corticosteroids in the year post randomisation. Secondary outcomes included time to first exacerbation, number of exacerbations, lung function, fractional exhaled nitric oxide, daily dose of inhaled corticosteroid, asthma control and quality of life. Results: In total, 509 eligible participants were recruited and the primary outcome was available for 506 participants. The primary outcome occurred in 123 out of 255 (48.2%) participants in the intervention group and 129 out of 251 (51.4%) participants in the standard-care group (adjusted odds ratio 0.88, 95% confidence interval 0.61 to 1.27). There was algorithm non-compliance on 21% of assessments. Per-protocol and complier-average causal effect analysis did not change the interpretation. This non-statistically significant estimate was consistent across predefined subgroups. There were no differences between the groups in secondary outcomes. There were no serious adverse events or deaths. No meaningful differences in health service costs, direct patient costs or indirect costs to society were identified between the groups. The economic evaluation does not provide evidence to support the cost-effectiveness of the intervention. In the qualitative process evaluation, 15 trial staff and six families were interviewed. Overall, their experiences were positive. The intervention was broadly acceptable, with caveats around clinicians using the algorithm recommendation as a guide and wariness around extreme step ups/downs in treatment in the light of contextual factors not being taken into account by the algorithm. Limitations: Potential limitations included the choice of cut-off point to define uncontrolled asthma and the change in fractional exhaled nitric oxide to trigger a change in treatment. Furthermore, the treatment decisions in the two groups may not have been sufficiently different to create a difference in outcomes. Conclusions: The RAACENO (Reducing Asthma Attacks in Children using Exhaled Nitric Oxide) trial findings do not support the routine use of fractional exhaled nitric oxide measurements as part of asthma management in a secondary care setting. The potential for other objective markers to guide asthma management in children needs to be evaluated. Trial registration: This trial was registered as ISRCTN67875351. Funding: This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health and Care Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 9, No. 4. See the NIHR Journals Library website for further project information.

Abstract COPD remains largely undiagnosed or is diagnosed late in the course of disease. We report findings of a specialist outreach programme to identify undiagnosed COPD in primary care. An electronic case-finding algorithm identified 1602 at-risk patients from 12 practices who were invited to attend the clinic. Three hundred and eighty-three (23.9%) responded and 288 were enrolled into the study. Forty-eight (16.6%) had undiagnosed mild and 28 (9.7%) had moderate airway obstruction, meeting spirometric diagnostic criteria for COPD. However, at 12 months only 8 suspected COPD patients (10.6%) had received a diagnostic label in their primary care record. This constituted 0.38% of the total patient population, as compared with 0.31% of control practices, p = 0.306. However, if all patients with airway obstruction received a coding of COPD, then the diagnosis rate in the intervention group would have risen by 0.84%. Despite the low take-up and diagnostic yield, this programme suggests that integrated case-finding strategies could improve COPD recognition.

Abstract Background Inhaled corticosteroids (ICS) are indicated for prevention of exacerbations in patients with COPD, but they are frequently overprescribed. ICS withdrawal has been recommended by international guidelines in order to prevent side effects in patients in whom ICS are not indicated. Method Observational comparative effectiveness study aimed to evaluate the effect of ICS withdrawal versus continuation of triple therapy (TT) in COPD patients in primary care. Data were obtained from the Optimum Patient Care Research Database (OPCRD) in the UK. Results A total of 1046 patients who withdrew ICS were matched 1:4 by time on TT to 4184 patients who continued with TT. Up to 76.1% of the total population had 0 or 1 exacerbation the previous year. After controlling for confounders, patients who discontinued ICS did not have an increased risk of moderate or severe exacerbations (adjusted HR: 1.04, 95% confidence interval (CI) 0.94–1.15; p = 0.441). However, rates of exacerbations managed in primary care (incidence rate ratio (IRR) 1.33, 95% CI 1.10–1.60; p = 0.003) or in hospital (IRR 1.72, 95% CI 1.03–2.86; p = 0.036) were higher in the cessation group. Unsuccessful ICS withdrawal was significantly and independently associated with more frequent courses of oral corticosteroids the previous year and with a blood eosinophil count ≥ 300 cells/μL. Conclusions In this primary care population of patients with COPD, composed mostly of infrequent exacerbators, discontinuation of ICS from TT was not associated with an increased risk of exacerbation; however, the subgroup of patients with more frequent courses of oral corticosteroids and high blood eosinophil counts should not be withdrawn from ICS. Trial registration European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (EUPAS30851).

BackgroundAs health care becomes more fragmented, it is even more important to focus on the provision of integrated, coordinated care between health and social care systems. With the aging population, this coordination is even more vital. Information and communication technology (ICT) can support integrated care if the form of technology follows and supports functional integration. Health TAPESTRY (Teams Advancing Patient Experience: Strengthening Quality) is a program centered on the health of older adults, supported by volunteers, primary care teams, community engagement and connections, and an ICT known as the Health TAPESTRY application (TAP-App), a web-based application that supports volunteers in completing client surveys, volunteer coordinators in managing the volunteer program, and primary care teams in requesting and receiving information. ObjectiveThis paper describes the development, evolution, and implementation of the TAP-App ICT to share the lessons learned. MethodsA case study was conducted with the TAP-App as the case and the perspectives of end users and stakeholders as the units of analysis. The data consisted of researchers’ perspectives on the TAP-App from their own experiences, as well as feedback from other stakeholders and end user groups. Data were collected through written retrospective reflection with the program manager, a specific interview with the technology lead, key emailed questions to the TAP-App developer, and viewpoints and feedback during paper drafting from other research team members. There were 2 iterations of Health TAPESTRY and the TAP-App and we focused on learnings from the second implementation (2018-2020) which was a pragmatic implementation scale-up trial using the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework at 6 primary care sites across Ontario, Canada. ResultsTAP-App (version 1.0), which was iteratively developed, was introduced as a tool to schedule volunteer and client visits and collect survey data using a tablet computer. TAP-App (version 2.0) was developed based on this initial experience and a desire for a program management tool that focused more on dual flow among users and provided better support for research. The themes of the lessons learned were as follows: iterative feedback is valuable; if ICT will be used for research, develop it with research in mind; prepare for challenges in the integration of ICT into the existing workflow; ask whether interoperability should be a goal; and know that technology cannot do it alone yet—the importance of human touch points. ConclusionsHealth TAPESTRY is human-centered. The TAP-App does not replace these elements but rather helps enable them. Despite this shift in supporting integrated care, barriers remained to the uptake of the TAP-App that would have allowed a full flow of information between health and social settings in supporting patient care. This indicates the need for an ongoing focus on the human use of ICT in similar programs.

Summary: Background: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. Methods: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. Findings: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. Interpretation: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. Funding: UK National Institute for Health Research and UK Medical Research Council.

Abstract Background Asthma affects up to nearly 40% of patients with allergic rhinitis (AR). Poor control of AR symptoms is associated with poor asthma control. The goal of this study was to evaluate the effect of AR treatment with MP-AzeFlu on symptoms of AR as well as symptoms of asthma. Methods This prospective study used a visual analog scale (VAS) to assess symptoms of AR and asthma before and after treatment with MP-AzeFlu (Dymista®; azelastine hydrochloride plus fluticasone propionate; 1 spray in each nostril twice daily for 2 weeks). Participants suffered from moderate-to-severe AR according to Allergic Rhinitis and its Impact on Asthma criteria, with acute AR symptoms (AR-VAS scores ≥ 50 mm) on inclusion day. In addition to symptom assessment, patients recorded the impact of AR symptoms on quality-of-life measures before, during, and at the conclusion of the treatment period (approximately 14 days). Patients self-reported change in frequency of their usage of asthma reliever medication on the last day of treatment. Results Of 1103 study participants, 267 (24.2%) had comorbid asthma. These participants reported using a mean of 5.1 puffs of asthma reliever medication in the week before treatment with MP-AzeFlu. A total of 81.8% of patients with comorbid asthma responded to AR therapy (AR-VAS

Abstract Background Health TAPESTRY (Health Teams Advancing Patient Experience: STRengthening qualitY) aims to help people stay healthier for longer where they live by providing person-focused care through the integration of four key program components: (1) trained volunteers who visit clients in their homes, (2) an interprofessional primary health care team, (3) use of technology to collect and share information, and (4) improved connections to community health and social services. The initial randomized controlled trial of Health TAPESTRY found promising results in terms of health care use and patient outcomes, indicating a shift from reactive to preventive care. The trial was based on one clinical academic center, thus limiting generalizability. The study objectives are (1) to test reproducibility of the established effectiveness of Health TAPESTRY on physical activity and hospitalizations, (2) to test the feasibility of, and understand the contributing factors to, the implementation of Health TAPESTRY in six diverse communities across Ontario, Canada, and (3) to determine the value for money of implementing Health TAPESTRY. Methods This planned study is a pragmatic parallel randomized controlled trial with a delayed intervention for control participants at 6 months. This trial will simultaneously assess effectiveness and implementation in a real-world setting (type II hybrid) in six diverse communities across Ontario. Participants 70 years of age and older will be randomized into the Health TAPESTRY intervention or the control group (usual care). Intervention clients will receive an individualized plan of care from an interprofessional care team. The plan will be based on a client’s goals and current health risks identified through volunteer visits. The study’s outcomes are mapped onto the RE-AIM framework, with levels of physical activity and number of hospitalizations as the co-primary outcomes. The main analysis will be a comparison at 6 months. Discussion It is important to evaluate the effectiveness and implementation of Health TAPESTRY in multiple communities prior to scaling or widespread adoption. Trial registration ClinicalTrials.gov NCT03397836 . Registered on 12 January 2018

Abstract Background Increasing the integration of community volunteers into primary health care delivery has the potential to improve person-focused, coordinated care, yet the use of volunteers in primary care is largely unexplored. Health Teams Advancing Patient Experience: Strengthening Quality (Health TAPESTRY) is a multi-component intervention involving trained community volunteers functioning as extensions of primary care teams, supporting care based on older adults’ health goals and needs. This study aimed to gain an understanding of volunteer experiences within the program and client and health care provider perspectives on the volunteer role. Methods This study used a qualitative descriptive approach embedded in a pragmatic randomized controlled trial. Participants included Health TAPESTRY volunteers, health care providers, volunteer coordinator, and program clients, all connected to two primary care practice sites in a large urban setting in Ontario, Canada. Data collection included semi-structured focus groups and interviews with all participants, and the completion of a measure of attitudes toward older adults and self-efficacy for volunteers. Qualitative data were inductively coded and analyzed using a constant comparative approach. Quantitative data were summarized using descriptive statistics. Results Overall, 30 volunteers and 64 other participants (clients, providers, volunteer coordinator) were included. Themes included: 1. Volunteer training: “An investment in volunteers”; 2. Intergenerational volunteer pairing: “The best of both worlds”; 3. Understanding the volunteer role and its scope: “Lay people involved in care”; 4. Volunteers as extensions of primary care teams: “Being the eyes where they live”; 5. The disconnect between volunteers and the clinical team: “Is something being done?”; 6. “Learning… all the time”: Impacts on volunteers; and 7. Clients’ acceptance of volunteers. Conclusions This study showed that it is possible to integrate community volunteers into the primary care setting, adding human connections to deepen the primary care team’s understanding of their patients. Program implementation suggestions that emerged included: using role play in training, making volunteer role boundaries and specifications clear, and making efforts to connect volunteers and the primary care team they are supporting. This exploration of stakeholder voices has the potential to help improve volunteer program uptake and acceptability, as well as volunteer recruitment, retention, and training. Trial registration For RCT: https://clinicaltrials.gov/ct2/show/NCT02283723 , November 5, 2014.

Summary: We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.