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Abstract Background The Manhattan Lupus Surveillance Program (MLSP), a population-based retrospective registry of patients with systemic lupus erythematosus (SLE), was used to investigate the prevalence of cardiovascular disease events (CVE) and compare rates among sex, age and race/ethnicity to population-based controls. Methods Patients with prevalent SLE in 2007 aged ≥ 20 years in the MLSP were included. CVE required documentation of a myocardial infarction or cerebrovascular accident. We calculated crude risk ratios and adjusted risk ratios (ARR) controlling for sex, age group, race and ethnicity, and years since diagnosis. Data from the 2009–2010 National Health and Nutrition Examination Survey (NHANES) and the 2013–2014 NYC Health and Nutrition Examination Survey (NYC HANES) were used to calculate expected CVE prevalence by multiplying NHANES and NYC HANES estimates by strata-specific counts of patients with SLE. Crude prevalence ratios (PRs) using national and NYC estimates and age standardized prevalence ratios (ASPRs) using national estimates were calculated. Results CVE occurred in 13.9% of 1,285 MLSP patients with SLE, and risk was increased among men (ARR:1.7, 95%CI:1.2–2.5) and older adults (age > 60 ARR:2.5, 95%CI:1.7–3.8). Compared with non-Hispanic Asian patients, CVE risk was elevated among Hispanic/Latino (ARR:3.1, 95%CI:1.4-7.0) and non-Hispanic Black (ARR:3.5, 95%CI1.6-7.9) patients as well as those identified as non-Hispanic and in another or multiple racial groups (ARR:4.2, 95%CI:1.1–15.8). Overall, CVE prevalence was higher among patients with SLE than nationally (ASPR:3.1, 95%CI:3.0-3.1) but did not differ by sex. Compared with national race and ethnicity-stratified estimates, CVE among patients with SLE was highest among Hispanics/Latinos (ASPR:4.3, 95%CI:4.2–4.4). CVE was also elevated among SLE registry patients compared with all NYC residents. Comparisons with age-stratified national estimates revealed PRs of 6.4 (95%CI:6.2–6.5) among patients aged 20–49 years and 2.2 (95%CI:2.1–2.2) among those ≥ 50 years. Male (11.3, 95%CI:10.5–12.1), Hispanic/Latino (10.9, 95%CI:10.5–11.4) and non-Hispanic Black (6.2, 95%CI:6.0-6.4) SLE patients aged 20–49 had the highest CVE prevalence ratios. Conclusions These population-based estimates of CVE in a diverse registry of patients with SLE revealed increased rates among younger male, Hispanic/Latino and non-Hispanic Black patients. These findings reinforce the need to appropriately screen for CVD among all SLE patients but particularly among these high-risk patients.

Rosai-Dorfman disease (RDD) is a nonmalignant disease of histiocyte proliferation. RDD usually presents with painless cervical lymphadenopathy, although extranodal involvement can occur. Cardiac involvement was reported in

Abstract Background Chronic obstructive pulmonary disease (COPD) is commonly associated with anxiety/depression which can affect self-management and quality of life. The TANDEM trial evaluated a cognitive behavioural approach intervention targeting COPD-related symptoms of anxiety and/or depression, comprising up to eight one-to-one sessions delivered by respiratory healthcare professionals prior to pulmonary rehabilitation (PR). The intervention showed no improvement in anxiety/depression or uptake/completion of PR. We present patient perspectives of the intervention to help understand these results. Method Semi-structured individual interviews, using a semi-structured topic guide informed by Sekhon’s Theoretical Framework of Acceptability, were conducted with 19 patients between September 2019 and April 2020. The interviews were audio-recorded, transcribed verbatim and analysed thematically. Results The following could have limited the impact of the intervention: (1) The lives of patients were complex and commonly affected by competing comorbidities or other external stressors which they managed through previously adopted long-standing coping strategies. (2) Some patients were reluctant to talk about their mood despite the Facilitators' training and person centred-skills which aimed to enable patients to talk freely about mood. (3) The intervention handouts and ‘home-practice’ were perceived as helpful for some, but not suitable for all. (4) Many patients perceived improvements in their physical and mental health, but this was not sustained due to a mix of personal and external factors, and some did not perceive any benefits. (5) PR non-attendance/non-completion was a result of personal and PR service-related reasons. (6) Discussing COPD and mental health with the Facilitator was a novel experience. Many patients felt that TANDEM could be of benefit if it was offered earlier on/at different time points in the COPD illness journey. Conclusion We found the delivery of TANDEM prior to PR was not helpful for patients with advanced COPD often experiencing other comorbidities, and/or difficult personal/external events. These patients already utilised long-standing coping strategies to manage their COPD. Holistic interventions, that address the impact of COPD in relation to wider aspects of a patients’ life, may be more beneficial. Trial registration ISRCTN Registry 59,537,391. Registration date 20 March 2017.

Abstract The FRESHAIR4Life study aims to reduce the non-communicable disease (NCD) burden by implementing preventive interventions targeting adolescents’ exposure to tobacco use and air pollution (AP) worldwide. This paper presents the FRESHAIR4Life methodology and initial rapid review results. The rapid review, using various databases and PubMed, aimed to guide decision-making on risk factor focus, target areas, and populations. It showed variable NCD mortality rates related to tobacco use and AP across the participating countries, with tobacco as the main risk factor in the Kyrgyz Republic, Greece, and Romania, and AP prevailing in Pakistan and Uganda. Adolescent exposure levels, sources, and correlates varied. The study will continue with an in-depth situational analysis to guide the selection, adaptation, and integration of evidence-based interventions into the FRESHAIR4Life prevention package. This package will be implemented, evaluated, assessed for cost-effectiveness, and iteratively refined. The research places a strong emphasis on co-creation, capacity building, and comprehensive communication and dissemination.

Abstract Background In Malaysia, asthma is a common chronic respiratory illness. Poor asthma control may increase out-of-pocket payment for asthma care, leading to financial hardships Malaysia provides Universal Health Coverage for the population with low user fees in the public health system to reduce financial hardship. We aimed to determine out-of-pocket expenditure on outpatient care for adult patients with asthma visiting government-funded public health clinics. We examined the catastrophic impact and medical impoverishment of these expenses on patients and households in Klang District, Malaysia. Methods This is a cross-sectional face-to-face questionnaire survey carried out in six government-funded public health clinics in Klang District, Malaysia. We collected demographic, socio-economic profile, and outpatient asthma-related out-of-pocket payments from 1003 adult patients between July 2019 and January 2020. Incidence of catastrophic health expenditure was estimated as the proportion of patients whose monthly out-of-pocket payments exceeded 10% of their monthly household income. Incidence of poverty was calculated as the proportion of patients whose monthly household income fell below the poverty line stratified for the population of the Klang District. The incidence of medical impoverishment was estimated by the change in the incidence of poverty after out-of-pocket payments were deducted from household income. Predictors of catastrophic health expenditure were determined using multivariate regression analysis. Results We found the majority (80%) of the public health clinic attendees were from low-income groups, with 41.6% of households living below the poverty line. About two-thirds of the attendees reported personal savings as the main source of health payment. The cost of transportation and complementary-alternative medicine for asthma were the main costs incurred. The incidences of catastrophic expenditure and impoverishment were 1.69% and 0.34% respectively. The only significant predictor of catastrophic health expenditure was household income. Patients in the higher income quintiles (Q2, Q3, Q4) had lower odds of catastrophic risk than the lowest quintile (Q1). Age, gender, ethnicity, and poor asthma control were not significant predictors. Conclusion The public health system in Malaysia provides financial risk protection for adult patients with asthma. Although patients benefited from the heavily subsidised public health services, this study highlighted those in the lowest income quintile still experienced financial catastrophe and impoverishment, and the risk of financial catastrophe was significantly greater in this group. It is crucial to ensure health equity and protect patients of low socio-economic groups from financial hardship.

Introduction Asthma attacks are a leading cause of morbidity and mortality but are preventable in most if detected and treated promptly. However, the changes that occur physiologically and behaviourally in the days and weeks preceding an attack are not always recognised, highlighting a potential role for technology. The aim of this study ‘DIGIPREDICT’ is to identify early digital markers of asthma attacks using sensors embedded in smart devices including watches and inhalers, and leverage health and environmental datasets and artificial intelligence, to develop a risk prediction model to provide an early, personalised warning of asthma attacks.Methods and analysis A prospective sample of 300 people, 12 years or older, with a history of a moderate or severe asthma attack in the last 12 months will be recruited in New Zealand. Each participant will be given a smart watch (to assess physiological measures such as heart and respiratory rate), peak flow meter, smart inhaler (to assess adherence and inhalation) and a cough monitoring application to use regularly over 6 months with fortnightly questionnaires on asthma control and well-being. Data on sociodemographics, asthma control, lung function, dietary intake, medical history and technology acceptance will be collected at baseline and at 6 months. Asthma attacks will be measured by self-report and confirmed with clinical records. The collected data, along with environmental data on weather and air quality, will be analysed using machine learning to develop a risk prediction model for asthma attacks.Ethics and dissemination Ethical approval has been obtained from the New Zealand Health and Disability Ethics Committee (2023 FULL 13541). Enrolment began in August 2023. Results will be presented at local, national and international meetings, including dissemination via community groups, and submission for publication to peer-reviewed journals.Trial registration number Australian New Zealand Clinical Trials Registry ACTRN12623000764639; Australian New Zealand Clinical Trials Registry.

Digital interventions with artificial intelligence (AI) can potentially support people with asthma to reduce the risk of exacerbation. Engaging patients throughout the development process is essential to ensure usability of the intervention for the end-users. Using our Connected for Asthma (C4A) intervention as an exemplar, we explore how patient involvement can shape a digital intervention. Seven Patient and Public Involvement (PPI) colleagues from the Asthma UK Centre for Applied Research participated in four advisory workshops to discuss how they would prefer to use/interact with AI to support living with their asthma, the benefit and caveats to use the AI that incorporated asthma monitoring and indoor/outdoor environmental data. Discussion focussed on the three most wanted use cases identified in our previous studies. PPI colleagues wanted AI to support data collection, remind them about self-management tasks, teach them about asthma environmental triggers, identify risk, and empower them to confidently look after their asthma whilst emphasising that AI does not replace clinicians. The discussion informed the key components in the next C4A interventions, including the approach to interacting with AI, the technology features and the research topics. Attendees highlighted the importance of considering health inequities, the presentation of data, and concerns about data accuracy, data privacy, security and ownership. We have demonstrated how patient roles can shift from that of 'user' (the traditional 'tester' of a digital intervention), to a co-design partner who shapes the next iteration of the intervention. Technology innovators should seek practical and feasible strategies to involve PPI colleagues throughout the development cycle of a digital intervention; supporting researchers to explore the barriers, concerns, enablers and advantages of implementing digital healthcare.

Abstract Suicide attempt (SA) risk is elevated in individuals with bipolar disorder (BD), and DNA methylation patterns may serve as possible biomarkers of SA. We conducted epigenome-wide association studies (EWAS) of blood DNA methylation associated with BD and SA. DNA methylation was measured at >700,000 positions in a discovery cohort of n = 84 adults with BD with a history of SA (BD/SA), n = 79 adults with BD without history of SA (BD/non-SA), and n = 76 non-psychiatric controls (CON). EWAS revealed six differentially methylated positions (DMPs) and seven differentially methylated regions (DMRs) between BD/SA and BD/non-SA, with multiple immune-related genes implicated. There were no epigenome-wide significant differences when BD/SA and BD/non-SA were each compared to CON, and patterns suggested that epigenetics differentiating BD/SA from BD/non-SA do not differentiate BD/non-SA from CON. Weighted gene co-methylation network analysis and trait enrichment analysis of the BD/SA vs. BD/non-SA contrast further corroborated immune system involvement, while gene ontology analysis implicated calcium signalling. In an independent replication cohort of n = 48 BD/SA and n = 47 BD/non-SA, fold changes at the discovery cohort’s significant sites showed moderate correlation across cohorts and agreement on direction. In both cohorts, classification accuracy for SA history among individuals with BD was highest when methylation at the significant CpG sites as well as information from clinical interviews were combined, with an AUC of 88.8% (CI = 83.8–93.8%) and 82.1% (CI = 73.6–90.5%) for the combined epigenetic-clinical classifier in the discovery and replication cohorts, respectively. Our results provide novel insight to the role of immune system functioning in SA and BD and also suggest that integrating information from multiple levels of analysis holds promise to improve risk assessment for SA in adults with BD.

Abstract Background Supported asthma self-management, incorporating an asthma action plan and annual clinical review, has been recommended by UK/global guidelines for over three decades. However, implementation remains poor, as only around a third of individuals receive basic asthma care, according to the UKs leading respiratory charity Asthma and Lung UK. A systematic review of implementation studies recommended that a whole systems approach targeting patients, healthcare professional education, and organisations is needed to improve implementation of supported asthma self-management in primary care. The IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) is a national Hybrid-II implementation cluster randomised controlled trial that aims to evaluate such an approach. This paper describes the development of the implementation strategy for IMP2ART with particular focus on the integration of multiple level theories. Methods The Medical Research Council design and evaluation of complex interventions framework and the Person-Based Approach to intervention development were used as guidance for stages of strategy development. Specifically, we (i) set up a multidisciplinary team (including practicing and academic clinicians, health psychologists, public health and patient colleagues), (ii) reviewed and integrated evidence and theory, (iii) developed guiding principles, (iv) developed prototype materials, and (v) conducted a pre-pilot study before final refinement. Results The implementation strategy included resources for patients, team-based and individual healthcare professional education, practice audit and feedback, and an asthma review template, as well as a facilitator role accessible to primary care practices for 12 months. The synthesis of the integrated Promoting Action on Research Implementation in Health Services (iPARIHS) and Capability, Opportunity, Motivation and Behaviour (COM-B) frameworks led to an evolved framework bringing together important implementation and behaviour change elements which will be used as a basis for the study process evaluation. Conclusions A description of rigorous implementation strategy development for the IMP2ART study is provided along with newly theorised integration of implementation and behaviour change science which may be of benefit to others targeting implementation in primary care. Trial registration ISRCTN15448074. Registered on 2nd December 2019.

Abstract Introduction This systematic review sought predictors of unfavourable bleeding profiles in women using the etonogestrel contraceptive implant. Unfavourable bleeding is common and a leading cause of requests for removal. Methods We included randomised controlled trials (RCTs), and prospective and retrospective cohort studies from 1998 to October 2022. Inclusion criteria were healthy women using etonogestrel for contraception. Papers not in English were excluded as were ongoing or incomplete studies. We searched Pubmed, Pubmed Central, MEDLINE (Web of Science & Ovid), Cochrane library, CINAHL Plus, WHO (HINARI), Open Grey and Greynet.org. Risk of Bias was assessed using ROB2 IRPGv9 for RCTs and ROBINS‐I for non‐RCTs. We conducted a narrative analysis. Results We included 13 studies. Lower body mass index (BMI), younger age, parity and smoking status were statistically, significantly associated with unfavourable bleeding patterns in one or more studies. No studies reported post‐partum status having a significant association with unfavourable bleeding. The available data was too limited and too heterogeneous to perform a robust meta‐analysis. Discussion Heterogeneity in reported outcomes and timescales limited the accuracy of synthesis. Risk of bias was moderate to serious in non‐RCTs due to baseline differences and missing or imputed data. The protective effect of higher BMI for unfavourable bleeding is in keeping with previous reviews and studies and is a clinically important finding.

ObjectiveLeveraging the Manhattan Lupus Surveillance Program (MLSP), a population-based registry of cases of systemic lupus erythematosus (SLE) and related diseases, we investigated the proportion of SLE with concomitant rheumatic diseases, including Sjögren’s disease (SjD), antiphospholipid syndrome (APLS), and fibromyalgia (FM), as well as the prevalence of autoantibodies in SLE by sex and race/ethnicity.MethodsPrevalent SLE cases fulfilled one of three sets of classification criteria. Additional rheumatic diseases were defined using modified criteria based on data available in the MLSP: SjD (anti-SSA/Ro positive and evidence of keratoconjunctivitis sicca and/or xerostomia), APLS (antiphospholipid antibody positive and evidence of a blood clot), and FM (diagnosis in the chart).Results1,342 patients fulfilled SLE classification criteria. Of these, SjD was identified in 147 (11.0%, 95% CI 9.2–12.7%) patients with women and non-Latino Asian patients being the most highly represented. APLS was diagnosed in 119 (8.9%, 95% CI 7.3–10.5%) patients with the highest frequency in Latino patients. FM was present in 120 (8.9%, 95% CI 7.3–10.5) patients with non-Latino White and Latino patients having the highest frequency. Anti-dsDNA antibodies were most prevalent in non-Latino Asian, Black, and Latino patients while anti-Sm antibodies showed the highest proportion in non-Latino Black and Asian patients. Anti-SSA/Ro and anti-SSB/La antibodies were most prevalent in non-Latino Asian patients and least prevalent in non-Latino White patients. Men were more likely to be anti-Sm positive.ConclusionData from the MLSP revealed differences among patients classified as SLE in the prevalence of concomitant rheumatic diseases and autoantibody profiles by sex and race/ethnicity underscoring comorbidities associated with SLE.

Abstract Background Routine data are increasingly used in randomised controlled trials evaluating healthcare interventions. They can aid participant identification, outcome assessment, and intervention delivery. Randomised implementation trials evaluate the effect of implementation strategies on implementation outcomes. Implementation strategies, such as reminders, are used to increase the uptake of evidence-based interventions into practice, while implementation outcomes, such as adoption, are key measures of the implementation process. The use of routine data in effectiveness trials has been explored; however, there are no reviews on implementation trials. We therefore aimed to describe how routine data have been used in randomised implementation trials and the design characteristics of these trials. Methods We searched MEDLINE (Ovid) and Cochrane Central Register of Controlled Trials from Jan 2000 to Dec 2021 and manually searched protocols from trial registers. We included implementation trials and type II and type III hybrid effectiveness-implementation trials conducted using routine data. We extracted quantitative and qualitative data and narratively synthesised findings. Results From 4206 titles, we included 80 trials, of which 22.5% targeted implementation of evidence-based clinical guidelines. Multicomponent implementation strategies were more commonly evaluated (70.0%) than single strategies. Most trials assessed adoption as the primary outcome (65.0%). The majority of trials extracted data from electronic health records (EHRs) (62.5%), and 91.3% used routine data for outcome ascertainment. Reported reasons for using routine data were increasing efficiency, assessing outcomes, reducing research burden, improving quality of care, identifying study samples, confirming findings, and assessing representativeness. Data quality, the EHR system, research governance, and external factors such as government policy could act either as facilitators or barriers. Conclusions Adherence to guidance on designing and reporting implementation studies, and specifically to harmonise the language used in describing implementation strategies and implementation outcomes, would aid identification of studies and data extraction. Routine healthcare data are widely used for participant identification, outcome assessment and intervention delivery. Researchers should familiarise themselves with the barriers and facilitators to using routine data, and efforts could be made to improve data quality to overcome some of the barriers. Registration PROSPERO CRD42022292321.

Abstract Background Digital technology tailored for those with limited health literacy has the potential to reduce health inequalities. Although mobile apps can support self-management in chronic diseases, there is little evidence that this approach applies to people with limited health literacy. We aimed to determine the acceptability of a self-management app in adults living with asthma and have limited health literacy and the feasibility of delivering the intervention and assessing outcomes. Methods We recruited eligible adults from the Klang Asthma Cohort registry in primary care for a 3-month mixed-method study plus a 2-month extended observation. We collected baseline data on socio-demography, health literacy and asthma control level. The outcomes of the intervention were assessed at 1- and 3-month: i) adoption (app download and usage), ii) adherence (app usage), iii) retention (app usage in the observation period), iv) health outcomes (e.g., severe asthma attacks) and v) process outcomes (e.g., ownership and use of action plans). At 1-month, participants were purposively sampled for in-depth interviews, which were audio-recorded, transcribed verbatim, and analysed deductively. Results We recruited 48 participants; 35 participants (23 Female; median age = 43 years; median HLS score = 28) completed the 3 months study. Of these, 14 participants (10 Female; median age = 48 years; median HLS score = 28) provided interviews. Thirty-seven (77%) participants adopted the app (downloaded and used it in the first month of the study). The main factor reported as influencing adoption was the ease of using the app. A total of 950 app usage were captured during the 3-month feasibility study. App usage increased gradually, peaking at month 2 (355 total log-ins) accounting for 78% of users. In month 5, 51.4% of the participants used the app at least once. The main factors influencing continued use included adherence features (e.g., prompts and reminders), familiarity with app function and support from family members. Conclusions An asthma self-management app intervention was acceptable for adults with limited health literacy and it was feasible to collect the desired outcomes at different time points during the study. A future trial is warranted to estimate the clinical and cost-effectiveness of the intervention and to explore implementation strategies.

Abstract Introduction Extrapolating long-term overall survival (OS) from shorter-term clinical trial data is key to health technology assessment in oncology. However, extrapolation using conventional methods is often subject to uncertainty. Using ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell therapy for multiple myeloma, we used a flexible Bayesian approach to demonstrate use of external longer-term data to reduce the uncertainty in long-term extrapolation. Methods The pivotal CARTITUDE-1 trial (NCT03548207) provided the primary efficacy data for cilta-cel, including a 12-month median follow-up snapshot of OS. Longer-term (48-month median follow-up) survival data from the phase I LEGEND-2 study (NCT03090659) were also available. Twelve-month CARTITUDE-1 OS data were extrapolated in two ways: (1) conventional survival models with standard parametric distributions (uninformed), and (2) Bayesian survival models whose shape prior was informed from 48-month LEGEND-2 data. For validation, extrapolations from 12-month CARTITUDE-1 data were compared with observed 28-month CARTITUDE-1 data. Results Extrapolations of the 12-month CARTITUDE-1 data using conventional uninformed parametric models were highly variable. Using informative priors from the 48-month LEGEND-2 dataset, the ranges of projected OS at different timepoints were consistently narrower. Area differences between the extrapolation curves and the 28-month CARTITUDE-1 data were generally lower in informed Bayesian models, except for the uninformed log-normal model, which had the lowest difference. Conclusions Informed Bayesian survival models reduced variation of long-term projections and provided similar projections as the uninformed log-normal model. Bayesian models generated a narrower and more plausible range of OS projections from 12-month data that aligned with observed 28-month data. Trial Registration CARTITUDE-1 ClinicalTrials.gov identifier, NCT03548207. LEGEND-2 ClinicalTrials.gov identifier, NCT03090659, registered retrospectively on 27 March 2017, and ChiCTR-ONH-17012285.

Abstract Monitoring asthma is essential for self-management. However, traditional monitoring methods require high levels of active engagement, and some patients may find this tedious. Passive monitoring with mobile-health devices, especially when combined with machine-learning, provides an avenue to reduce management burden. Data for developing machine-learning algorithms are scarce, and gathering new data is expensive. A few datasets, such as the Asthma Mobile Health Study, are publicly available, but they only consist of self-reported diaries and lack any objective and passively collected data. To fill this gap, we carried out a 2-phase, 7-month AAMOS-00 observational study to monitor asthma using three smart-monitoring devices (smart-peak-flow-meter/smart-inhaler/smartwatch), and daily symptom questionnaires. Combined with localised weather, pollen, and air-quality reports, we collected a rich longitudinal dataset to explore the feasibility of passive monitoring and asthma attack prediction. This valuable anonymised dataset for phase-2 of the study (device monitoring) has been made publicly available. Between June-2021 and June-2022, in the midst of UK’s COVID-19 lockdowns, 22 participants across the UK provided 2,054 unique patient-days of data.

BackgroundGlobally, there is a growing focus on efficient trials, yet numerous interpretations have emerged, suggesting a significant heterogeneity in understanding "efficiency" within the trial context. Therefore in this study, we aimed to dissect the multifaceted nature of trial efficiency by establishing a comprehensive conceptual framework for its definition.ObjectivesTo collate diverse perspectives regarding trial efficiency and to achieve consensus on a conceptual framework for defining trial efficiency.MethodsFrom July 2022 to July 2023, we undertook a literature review to identify various terms that have been used to define trial efficiency. We then conducted a modified e-Delphi study, comprising an exploratory open round and a subsequent scoring round to refine and validate the identified items. We recruited a wide range of experts in the global trial community including trialists, funders, sponsors, journal editors and members of the public. Consensus was defined as items rated "without disagreement", measured by the inter-percentile range adjusted for symmetry through the UCLA/RAND approach.ResultsSeventy-eight studies were identified from a literature review, from which we extracted nine terms related to trial efficiency. We then used review findings as exemplars in the Delphi open round. Forty-nine international experts were recruited to the e-Delphi panel. Open round responses resulted in the refinement of the initial nine terms, which were consequently included in the scoring round. We obtained consensus on all nine items: 1) four constructs that collectively define trial efficiency containing scientific efficiency, operational efficiency, statistical efficiency and economic efficiency; and 2) five essential building blocks for efficient trial comprising trial design, trial process, infrastructure, superstructure, and stakeholders.ConclusionsThis is the first attempt to dissect the concept of trial efficiency into theoretical constructs. Having an agreed definition will allow better trial implementation and facilitate effective communication and decision-making across stakeholders. We also identified essential building blocks that are the cornerstones of an efficient trial. In this pursuit of understanding, we are not only unravelling the complexities of trial efficiency but also laying the groundwork for evaluating the efficiency of an individual trial or a trial system in the future.

ObjectiveIn this study, we aim to evaluate dietary supplement and complementary and alternative medicine (CAM) use in individuals with depressive symptoms. Furthermore, we conducted a comparative analysis of the usage of these agents among individuals with depressive symptoms, differentiating between those who were using antidepressants and those who were not. Additionally, we compared individuals with depressive symptoms who were not using antidepressants with participants who did not have depressive symptoms as well as individuals with depressive symptoms who were using antidepressants with individuals without depressive symptoms.MethodThe National Health and Nutrition Examination Survey 2007-2018 data was collected. Depressive symptoms were assessed using patient health questionnaire-9. Dietary supplement and antidepressants use was evaluated using Dietary Supplement Use and Prescription Medications Questionnaires.Results31,445 participants, with 2870 (8.05%) having depressive symptoms were included. Participants with depressive symptoms had significantly lower odds of dietary supplement use compared with those without depressive symptoms (aOR = 0.827, 95% CI: 0.700,0.977, p = 0.026). Participants with depressive symptoms who were using antidepressants had significantly higher odds of dietary supplement (aOR = 1.290, 95% CI: 1.038,1.604, p = 0.022) compared with participants with depressive symptoms who were not using antidepressants. Furthermore, Participants with depressive symptoms who weren't using antidepressants had significantly lower odds of dietary supplement use (aOR = 0.762, 95% CI: 0.632,0.918, p = 0.005) compared with participants without depressive symptoms. In individuals with treated depressive symptoms compared to those without depressive symptoms, CAM use was significantly lower (aOR = 0.763, 95% CI = 0.598,0.973, p = 0.030).ConclusionIndividuals with depressive symptoms have lower odds of dietary supplement use. Further studies are needed to replicate these findings and examine the underlying mechanisms for this association.

Background Understanding distinct neurobiological mechanisms underlying bipolar disorder (BD) and major depressive disorder (MDD) is crucial for accurate diagnosis and the discovery of novel and more effective targeted treatments. Previous diffusion-weighted MRI studies have suggested some common frontotemporal corticolimbic system white matter (WM) abnormalities across the disorders. However, critical to the development of more precise diagnosis and treatment is identifying distinguishing abnormalities. Promising candidates include more prominent frontotemporal WM abnormalities observed in BD in the uncinate fasciculus (UF) that have been associated with frontal-amygdala functional dysconnectivity, and with suicide that is especially high in BD. Prior work also showed differentiation in metabotropic glutamate receptor 5 (mGlu5) abnormalities in BD versus MDD, which could be a mechanism affected in the frontotemporal system. However, associations between WM and mGlu5 have not been examined previously as a differentiator of BD. Using a multimodal neuroimaging approach, we examined WM integrity alterations in the disorders and their associations with mGluR5 levels. Methods Individuals with BD ( N = 21), MDD ( N = 10), and HC ( N = 25) participated in structural and diffusion-weighted MRI scanning, and imaging with [ 18 F]FPEB PET for quantification of mGlu5 availability. Whole-brain analyses were used to assess corticolimbic WM matter fractional anisotropy (FA) across BD and MDD relative to HC; abnormalities were tested for associations with mGlu5 availability. Results FA corticolimbic reductions were observed in both disorders and altered UF WM integrity was observed only in BD. In BD, lower UF FA was associated with lower amygdala mGlu5 availability ( p

Background People with chronic obstructive pulmonary disease have high levels of anxiety and depression, which is associated with increased morbidity and poor uptake of effective treatments, such as pulmonary rehabilitation. Cognitive–behavioural therapy improves mental health of people with long-term conditions and could potentially increase uptake of pulmonary rehabilitation, enabling synergies that could enhance the mental health of people with chronic obstructive pulmonary disease. Aim Our aim was to develop and evaluate the clinical effectiveness and cost effectiveness of a tailored cognitive–behavioural approach intervention, which links into, and optimises the benefits of, routine pulmonary rehabilitation. Design We carried out a pragmatic multicentre randomised controlled trial using a 1.25 : 1 ratio (intervention : control) with a parallel process evaluation, including assessment of fidelity. Setting Twelve NHS trusts and five Clinical Commissioning Groups in England were recruited into the study. The intervention was delivered in participant’s own home or at a local NHS facility, and by telephone. Participants Between July 2017 and March 2020 we recruited adults with moderate/very severe chronic obstructive pulmonary disease and mild/moderate anxiety and/or depression, meeting eligibility criteria for assessment for pulmonary rehabilitation. Carers of participants were invited to participate. Intervention The cognitive–behavioural approach intervention (i.e. six to eight 40- to 60-minute sessions plus telephone support throughout pulmonary rehabilitation) was delivered by 31 trained respiratory healthcare professionals to participants prior to commencing pulmonary rehabilitation. Usual care included routine pulmonary rehabilitation referral. Main outcome measures Co-primary outcomes were Hospital Anxiety and Depression Scale – anxiety and Hospital Anxiety and Depression Scale – depression at 6 months post randomisation. Secondary outcomes at 6 and 12 months included health-related quality of life, smoking status, uptake of pulmonary rehabilitation and healthcare use. Results We analysed results from 423 randomised participants (intervention, n = 242; control, n = 181). Forty-three carers participated. Follow-up at 6 and 12 months was 93% and 82%, respectively. Despite good fidelity for intervention delivery, mean between-group differences in Hospital Anxiety and Depression Scale at 6 months ruled out clinically important effects (Hospital Anxiety and Depression Scale – anxiety mean difference –0.60, 95% confidence interval –1.40 to 0.21; Hospital Anxiety and Depression Scale – depression mean difference –0.66, 95% confidence interval –1.39 to 0.07), with similar results at 12 months. There were no between-group differences in any of the secondary outcomes. Sensitivity analyses did not alter these conclusions. More adverse events were reported for intervention participants than for control participants, but none related to the trial. The intervention did not generate quality-of-life improvements to justify the additional cost (adjusted mean difference £770.24, 95% confidence interval –£27.91 to £1568.39) to the NHS. The intervention was well received and many participants described positive affects on their quality of life. Facilitators highlighted the complexity of participants’ lives and considered the intervention to be of potential valuable; however, the intervention would be difficult to integrate within routine clinical services. Our well-powered trial delivered a theoretically designed intervention with good fidelity. The respiratory-experienced facilitators were trained to deliver a low-intensity cognitive–behavioural approach intervention, but high-intensity cognitive–behavioural therapy might have been more effective. Our broad inclusion criteria specified objectively assessed anxiety and/or depression, but participants were likely to favour talking therapies. Randomisation was concealed and blinding of outcome assessment was breached in only 15 participants. Conclusions The tailored cognitive–behavioural approach intervention delivered with fidelity by trained respiratory healthcare professionals to people with chronic obstructive pulmonary disease was neither clinically effective nor cost-effective. Alternative approaches that are integrated with routine long-term condition care are needed to address the unmet, complex clinical and psychosocial needs of this group of patients. Trial registration This trial is registered as ISRCTN59537391. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 13/146/02) and is published in full in Health Technology Assessment; Vol. 28, No. 1. See the NIHR Funding and Awards website for further award information. Plain language summary People with long-standing lung problems, such as chronic obstructive pulmonary disease, often also have anxiety and depression, which further reduces their quality of life. Two existing treatments could help. Pulmonary rehabilitation (a programme of exercise and education) improves both the physical and mental health of people with chronic obstructive pulmonary disease. Cognitive–behavioural therapy (a talking therapy) may reduce anxiety and depression. The TANDEM [Tailored intervention for Anxiety and Depression Management in chronic obstructive pulmonary disease (COPD)] intervention linked these two treatments by providing talking therapy based on cognitive–behavioural therapy during the waiting time following referral for pulmonary rehabilitation. The TANDEM treatment was delivered by respiratory healthcare professionals (e.g. nurses or physiotherapists) trained to deliver the talking therapy in six to eight weekly sessions. The sessions were conducted in the participant’s home (or another convenient location), with brief telephone support during the pulmonary rehabilitation. Of 423 participants recruited to the study, 242 participants received TANDEM talking therapy and 181 participants received usual care (including a referral to pulmonary rehabilitation). We measured mental health, quality of life, social life, attendance at pulmonary rehabilitation and healthcare use in both groups at 6 and 12 months. Forty-three carers joined the study and we assessed their mental well-being. We interviewed patients, carers and health professionals to find out their views and experience of the TANDEM treatment. We also examined whether or not the TANDEM treatment was good value for money. The TANDEM treatment did not improve the mental or the physical health of people with chronic obstructive pulmonary disease. In addition, the TANDEM treatment cost the NHS an extra £770 per patient, which was not good value for money. The TANDEM treatment was well received, and many participants told us how it had helped them. Heath-care professionals noted how participants did not just have chronic obstructive pulmonary disease, but were coping with many physical, mental and social problems. The TANDEM intervention was not effective and, therefore, other strategies will be needed to help people with chronic obstructive pulmonary disease and mental health problems live with their condition. Scientific summary Background Chronic obstructive pulmonary disease (COPD) is a major public health problem globally, and is associated with socioeconomic deprivation and with high morbidity and mortality. In the UK, about 1.2 million people have diagnosed COPD, incurring more than 140,000 hospital admissions, over a million bed-days and about 30,000 deaths each year. The condition costs the NHS around £1.9B annually. Symptoms of anxiety and depression are common comorbidities in people with COPD, with a prevalence of 30–40% or higher. These mood disorders may reduce people’s ability to manage their COPD effectively, reduce physical activity capacity and make patients susceptible to exacerbations (i.e. acute worsening of the condition), hospital admissions and re-admissions. There is robust evidence that pulmonary rehabilitation (PR), which is a multidisciplinary exercise and education intervention, improves health-related outcomes, including functional exercise capacity, quality of life and emotional well-being, and reduces breathlessness in COPD. National and international COPD guidelines recommend offering PR to patients. Unfortunately, more than one-third of people referred to PR do not attend and only two-thirds of attendees complete the course. A recent Cochrane review concluded that psychological interventions, including cognitive–behavioural therapy (CBT), may improve depression in people with COPD, but the reviewers called for larger, more methodologically robust studies. The current study was proposed in response to a National Institute for Health and Care Research (NIHR) Health Technology Assessment brief based on a systematic review that concluded that psychological interventions combined with exercise training resulted in clinically significant improvements in symptoms of anxiety and depression in COPD, compared with CBT alone. A more recent Cochrane review has concluded that a psychological therapy combined with a PR programme reduced depressive symptoms more than a PR programme alone. Aims and objectives The primary aim of the study was to evaluate a tailored psychological cognitive–behavioural approach (CBA) intervention [i.e. the TANDEM (Tailored intervention for Anxiety and Depression Management in COPD) intervention], which precedes, links into and optimises the benefits of attending an existing PR course, with the aim of reducing mild/moderate anxiety and/or depression symptoms in people with COPD and moderate to very severe airflow limitation. Specific objectives To develop and refine the TANDEM intervention to develop a training programme for healthcare professionals who will deliver the programme, and to document the training programme in a manual. To undertake a randomised controlled trial of the TANDEM intervention to examine the effectiveness of the TANDEM intervention on clinical outcomes compared with usual care (i.e. guideline-defined care, including the offer of PR). To examine the affect of the TANDEM intervention (which is directed at patients) on carers (where appropriate). To determine the cost effectiveness of the TANDEM intervention from an NHS and Personal Social Services perspective. To conduct a process evaluation to assist interpretation of findings and inform the implementation of the TANDEM intervention if the trial results are positive. Methods Design We carried out a pragmatic multicentre parallel-arm individual patient randomised controlled trial with an internal pilot, evaluating clinical effectiveness and health economics. A parallel process evaluation included assessing fidelity of intervention delivery. Co-primary outcomes were symptoms of anxiety and depression determined by the Hospital Anxiety and Depression Scale – anxiety (HADS-A) and Hospital Anxiety and Depression Scale – depression (HADS-D) at 6 months post randomisation. Participants were followed up for 12 months. There was full allocation concealment and baseline measures were collected before randomisation. Participants were inevitably aware of their allocation status, but all healthcare professionals were blind to allocation, as were the researchers who collected or analysed outcome measures. Study participants were recruited from primary and secondary care and from referral to PR in 12 geographic areas in England. Participants with chronic obstructive pulmonary disease Inclusion criteria Patients who were willing to provide informed consent. Patients with a confirmed diagnosis of COPD and spirometry with moderate to severe airflow limitation (note that, following the internal pilot, this was extended to include very severe airflow limitation). Patients who were eligible for referral to PR. Patients with a Hospital Anxiety and Depression Scale (HADS) score at the baseline screening suggestive of mild to moderate anxiety or depression, or both (i.e. a subscale score from 8 to 15). Exclusion criteria HADS scores suggestive of severe anxiety or depression. Patients who had received a psychological intervention in the last 6 months (note that patients on antidepressants/anxiolytics were not excluded). Patients who were to commence PR within 4 weeks. Patients with a comorbidity so severe that it would prevent engagement with the intervention/trial. Patients with insufficient fluency in English to complete the intervention or questionnaires (note that patients with literacy difficulties were not excluded). Recruitment of carers Participants were requested to identify a ‘particular family caregiver or friend who helps them’ for invitation to join a substudy examining the effect of the patient-directed TANDEM intervention on carers. Randomisation Computerised randomisation was conducted remotely by an independent statistician using a 1.25 : 1 ratio of intervention: control to account for clustering by facilitator. The TANDEM intervention The intervention was developed following the Medical Research Council’s framework for developing complex interventions and Yardley’s ‘person-based approach’. The intervention consisted of a tailored, manualised intervention based on CBAs and self-management support. Therapy consisted of six to eight sessions that were delivered weekly, face-to-face, in participants’ homes or in primary or secondary care settings, by experienced respiratory healthcare professionals (i.e. ‘facilitators’). Between completing the face-to-face intervention and up to 2 weeks after completing PR, facilitators offered brief telephone support. Facilitators were trained over 3 days (across 6 weeks) and were assessed on completion of training. Throughout intervention delivery, facilitators received regular supervision from an experienced CBT therapist. Control arm participants Control arm participants received usual care following local arrangements, including PR. All participants also received informational resources from the British Lung Foundation (London, UK). Outcome measures In addition to our co-primary outcomes, we collected patient-reported outcomes at baseline and at 6 and 12 months using the following supervised self-complete questionnaires: Beck Depression Inventory II, Beck Anxiety Inventory, the St George’s Respiratory Questionnaire, social integration and support, an adapted UK Time Use Survey, the Brief Illness Perception Questionnaire, smoking status and EuroQoL-5 Dimensions, five-level version (EQ-5D-5L). We collected information on medications and health and social care resource use via a modified Client Services Receipt Inventory. In addition, we collected information on medications and healthcare resource use from participants’ general practitioners. PR attendance data were collected from local services at 12 months. Data from carers At baseline and at 6 and 12 months, we collected carer-reported outcomes using the Warwick–Edinburgh Mental WellBeing Scale and the Zarit Burden Interview (22 items). Statistical analysis Statistical analysis followed our published analysis plan. The primary analysis was by intention to treat, assuming that outcomes were missing at random. In sensitivity analyses, we tested this assumption by modelling the affect of differences between missing and non-missing outcomes on the estimated treatment effect for both co-primary outcomes. All outcomes other than smoking were analysed using a mixed linear regression model, with adjustment for baseline HADS-A and HADS-D scores, breathlessness, smoking status, NHS trust and (except for HADS scores) the measurement of that outcome at baseline. Analyses allowed for clustering by facilitator in the intervention arm by adjusting for a random effect of facilitator. Economic evaluation Intervention costs were calculated using a combination of data from patients’ general practice records and a Client Service Receipt Inventory. General practice data acted as the primary source of information on health service contacts, and self-reported data were used as supplementary data. Health and social care utilisation were costed using NHS reference costs and unit costs of health and social care. We adopted a ‘cost–utility’ framework, with the incremental resource impact of TANDEM over usual care quantified from an NHS/Personal Social Services (PSS) perspective, and patient outcomes quantified as incremental quality-adjusted life-years (QALYs) gained. The QALYs gained over the 12-month follow-up were estimated, based on self-report, at baseline and at 6- and 12-month follow-up using the EQ-5D-5L. Health state utility scores applicable to the EQ-5D-5L were ‘cross-walked’ back to their equivalent three-level version values using a recommended algorithm. QALYs for each participant were quantified with respect to the entire 12 months’ follow-up using the area under the curve method. Intervention cost effectiveness was evaluated with reference to the incremental net health benefit of TANDEM combined with usual care compared with usual care alone (expressed in QALY units) and estimated assuming a cost-effectiveness threshold of £20,000 per QALY gained. Uncertainty was addressed using cost-effectiveness planes and acceptability curves. Adverse events Adverse events (AEs) and serious adverse events were recorded and reported in accordance with the Data Monitoring Ethics Committee’s and sponsors’ requirements, and following the standard operating procedures of the Joint Research Management Office for Barts Health NHS Trust (London, UK) and Queen Mary University of London (London, UK). Process evaluation The process evaluation adopted a mixed-methods design, incorporating qualitative and quantitative methods. We conducted 49 one-to-one qualitative interviews with the following four groups: (1) participants and carers, (2) TANDEM facilitators, (3) TANDEM facilitators’ clinical supervisors and (4) stakeholders. Data were analysed thematically using an inductive approach and constant comparison. Analysis was a reflexive, iterative process involving review and multidisciplinary discussion. NVivo 12 software (QSR International, Warrington, UK) was used to assist the organisation and analysis of the data. A thematic narrative was constructed for each group. Fidelity With participant permission, all TANDEM intervention sessions were recorded digitally. A bespoke fidelity treatment delivery framework, which included the Cognitive First Aid Rating Scale, and an intervention-specific adherence measure, which included assessment of whether or not core components and topic-specific sessions were delivered, were used to assess therapeutic competency. One or two entire TANDEM intervention courses were assessed per facilitator. Coding was conducted by a psychologist, and seven cases (19.4%) were duplicate coded by our co-applicant health psychologist for quality assurance. Results Forty-nine per cent (2191/4491) of potentially eligible participants approached agreed to be contacted by the research team, with 48% (n = 1062) of participants formally assessed for eligibility. Of these participants, 441 (41.5%) were eligible, 426 were recruited to the study and 423 were randomised and analysed (intervention, n = 242; control, n = 181). HADS-A and HADS-D primary outcome data were available for 205 (85%) and 204 (84%) of participants randomised to the intervention, respectively, and for 164 (90%) of control participants. At 12 months. HADS-A and HADS-D secondary outcome data were available for 191 (79%) and 190 (79%) of participants randomised to the intervention and for 150 (83%) and 152 (84%) control participants. More participants withdrew from the intervention arm (n = 16, 6.6%) than from the control arm (n = 5, 2.8%) and there were more deaths in the intervention arm than in the control arm [13 (5.4%) vs. 3 (1.7%), respectively]. No deaths or other AEs were associated with the study. Of the participants recruited, the median age was 69 (interquartile range 62–75) years, 50% (n = 213) were male and 42% (n = 176) lived alone. Only 40 (9.5%) participants were working and most (329/416, 79%) had completed full-time education by age 16 years. Overall, participants’ COPD was disabling. Participants has significant breathlessness and low health-related quality-of-life scores, and 78 (18%) participants were too breathless to leave the house. Comorbidities were common and 30% (n = 128) of participants were still smoking. Forty-three carers were recruited to the substudy. Twenty-four carers cared for intervention participants and 19 carers cared for control participants. A total of 196 (81%) intervention participants received at least two sessions of the TANDEM intervention (i.e. the predefined minimum dose) and 136 (56%) intervention participants received six or more sessions. Clinical effectiveness results At 6 months, the mean difference between the two study arms for anxiety [HADS-A –0.60, 95% confidence interval (CI) –1.40 to 0.21] and depression (HADS-D –0.66, 95% CI –1.39 to 0.07) was less than the minimal clinically important differences for these scales, and the 95% CIs ruled out clinically important effects on these outcomes. As in the primary outcome analysis, CIs for HADS-A and HADS-D at 12 months, and for all other questionnaire scores at 6 and 12 months, ruled out clinically important effects of the intervention. Overall, smoking prevalence fell across the 12 months of the study, but there was no discernible difference between participants in the two study arms (odds ratio at 12 months for intervention vs. control 0.90, 95% CI 0.54 to 1.50) and around one-quarter of participants were still smoking at 12 months. In the intervention arm, 122 (50%) participants were referred to PR, 121 participants attended at least one PR session and 73 (30%) participants completed the course. In the control arm, 88 (49%) participants were referred, 77 (43%) participants attended at least one PR session and 54 (30%) participants completed the course. No differences were seen in outcome measures at 6 or 12 months for carers of participants in the study arms. Health economics results The economic evaluation of the TANDEM intervention suggested that the intervention is highly unlikely to be a cost-effective means of improving mental health outcomes in patients with COPD. After jointly considering incremental effects on costs and QALYs, and allowing for sampling uncertainty in the trial data, there was a high degree of certainty that the TANDEM intervention would not offer sufficient value for money based on cost-effectiveness criteria routinely applied to assess whether or not new healthcare technologies should be funded by the NHS. Process evaluation results Respiratory health professionals recruited to train as TANDEM facilitators recognised the need for holistic care for patients with COPD and were keen to develop knowledge and skills in addressing psychological health needs. The health professionals valued developing skills in providing psychological care for patients using a collaborative decision-making approach, but the health professionals did not feel able to do this without training and found it challenging initially. The TANDEM intervention was generally well received by patients. Developing a therapeutic alliance was considered necessary by all interviewees; however, it took time to build rapport and the complexity of the therapeutic task was highlighted in patient, carer and facilitator interviews. The fidelity study found that the TANDEM intervention was delivered with therapeutic competency and that key tasks were delivered with fidelity. Most interviewees felt that it would not be possible to deliver the TANDEM intervention as part of usual care because of staff and financial resource constraints. Conclusions The study demonstrated that it is possible to train healthcare professionals to deliver a CBA competently and with fidelity, and that, overall, the TANDEM CBA intervention appeared to be popular with both those receiving it and those delivering it. However, the intervention did not improve mood or health status, nor did it improve any of our important secondary outcomes, such as uptake and completion of PR, healthcare resource use and smoking cessation. Recommendations for further research Given the considerable unmet need, alternative interventions to support people with advanced COPD and symptoms of anxiety and depression are required. It is worth exploring whether or not an intervention like the TANDEM intervention might be effective for people with COPD much earlier in their disease trajectories. We suggest evaluating the incorporation of development of cognitive–behavioural skills as part of undergraduate and postgraduate training for a variety of different healthcare professionals, with the aim of integrating this approach into routine healthcare delivery for long-term conditions. Trial registration This trial is registered as ISRCTN59537391. Funding This award was funded by the NIHR Health Technology Assessment programme (NIHR award ref: 13/146/02) and is published in full in Health Technology Assessment; Vol. 28, No. 1. See the NIHR Funding and Awards website for further award information.

Background Pulmonary rehabilitation (PR) is an effective strategy to improve breathlessness, health status and exercise tolerance and to reduce readmissions and mortality. In India, there is no government health programme for chronic obstructive pulmonary disease (COPD) management while in the private sector availability of PR is limited. Most PR centres are in urban areas, with few services accessible to rural populations. We aimed to assess the need for PR from the perspective of patients with COPD and healthcare professionals (HCPs: registered medical practitioners and medical officers) in rural Maharashtra.Methodology Between June and October 2020, we conducted semi-structured interviews with 14 patients with COPD and 9 HCPs to explore their perceptions of, and need for, PR in rural Maharashtra. Interviews were transcribed and analysed thematically.Results We approached 14 patients with COPD and 9 HCPs practising in rural areas. Five HCPs stated that they did not advise PR for patients with COPD citing poor compliance to PR referral and follow-up of the patients. Patients with COPD had symptoms and needs that could be helped by PR but commented how transportation would be a problem for them to visit a PR centre. In contrast, they could understand the benefits of PR and expressed their willingness to join such programmes. A PR service was established that addressed these needs.Conclusion Patients with COPD have unmet needs that could benefit from attending a PR programme, but there are barriers at both healthcare and patient levels that we addressed in a new PR service for people with chronic respiratory disease in rural Maharashtra.

ABSTRACTThe multi-attribute method (MAM), a liquid chromatography-mass spectrometry (LC-MS)-based peptide mapping method, has gained increased interest and applications in the biopharmaceutical industry. MAM can, in one method, provide targeted quantitation of multiple site-specific product quality attributes, as well as new peak detection. In this review, we focus on the scientific and regulatory considerations of using MAM in product quality attribute monitoring and quality control (QC) of therapeutic proteins. We highlight MAM implementation challenges and solutions with several case studies, and provide our perspective on the opportunities to use MS in QC for applications other than standard peptide mapping-based MAM.

Abstract Introduction Ciltacabtagene autoleucel (cilta-cel), is a B-cell maturation antigen-directed, genetically modified autologous chimeric antigen receptor T-cell (CAR-T) immunotherapy. It is indicated for treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The objective of this study was to estimate the per-patient US commercial healthcare costs related to cilta-cel (CARVYKTI®) CAR-T therapy (i.e., costs separate from cilta-cel therapy acquisition) for patients with RRMM. Methods US prescribing information for cilta-cel, publicly available data, and published literature were used with clinician input to identify the cost components and unit costs associated with administration of cilta-cel. Cost components included apheresis, bridging therapy, conditioning therapy, administration, and postinfusion monitoring for 1 year of follow-up. Adverse event (AE) management costs for all grades of cytokine release syndrome and neurologic toxicities, and additional AEs grade ≥ 3 occurring in > 5% of patients were included in the analysis. Results The estimated per-patient average costs of cilta-cel CAR-T therapy administered exclusively in an inpatient setting, excluding cilta-cel therapy acquisition costs, totaled US$160,933 over a 12 month period. Costs assuming different proportions of inpatient/outpatient administration (85%/15% and 70%/30%) were US$158,095 and US$155,257, respectively. Conclusion Cost estimates from this analysis, which disaggregates CAR-T therapy costs, provide a comprehensive view of the cost components of CAR-T therapy that can help healthcare decision-makers make informed choices regarding the use of cilta-cel. Real-world costs may differ with improved AE prevention and mitigation strategies.

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 Asthma, a common chronic respiratory illness is mostly managed in primary care. We aimed to determine healthcare resources, organisational support, and doctors’ practice in managing asthma in a Malaysian primary care setting. A total of six public health clinics participated. We found four clinics had dedicated asthma services. There was only one clinic which had a tracing defaulter system. Long-term controller medications were available in all clinics, but not adequately provided. Resources, educational materials, and equipment for asthma management were present, though restricted in number and not placed in main locations of the clinic. To diagnose asthma, most doctors used clinical judgement and peak flow metre measurements with reversibility test. Although spirometry is recommended to diagnose asthma, it was less practiced, being inaccessible and unskilled in using as the main reasons. Most doctors reported providing asthma self-management; asthma action plan, but for only half of the patients that they encountered. In conclusion, there is still room for improvement in the provision of clinic resources and support for asthma care. Utilising peak flow metre measurement and reversibility test suggest practical alternative in low resource for spirometry. Reinforcing education on asthma action plan is vital to ensure optimal asthma care.

Abstract Introduction Making a diagnosis of asthma can be challenging for clinicians and patients. A clinical decision support system (CDSS) for use in primary care including a patient‐facing mode, could change how information is shared between patients and healthcare professionals and improve the diagnostic process. Methods Participants diagnosed with asthma within the last 5 years were recruited from general practices across four UK regions. In‐depth interviews were used to explore patient experiences relating to their asthma diagnosis and to understand how a CDSS could be used to improve the diagnostic process for patients. Interviews were audio recorded, transcribed verbatim and analysed using a thematic approach. Results Seventeen participants (12 female) undertook interviews, including 14 individuals and 3 parents of children with asthma. Being diagnosed with asthma was generally considered an uncertain process. Participants felt a lack of consultation time and poor communication affected their understanding of asthma and what to expect. Had the nature of asthma and the steps required to make a diagnosis been explained more clearly, patients felt their understanding and engagement in asthma self‐management could have been improved. Participants considered that a CDSS could provide resources to support the diagnostic process, prompt dialogue, aid understanding and support shared decision‐making. Conclusion Undergoing an asthma diagnosis was uncertain for patients if their ideas and concerns were not addressed by clinicians and were influenced by a lack of consultation time and limitations in communication. An asthma diagnosis CDSS could provide structure and an interface to prompt dialogue, provide visuals about asthma to aid understanding and encourage patient involvement. Patient and Public Contribution Prespecified semistructured interview topic guides (young person and adult versions) were developed by the research team and piloted with members of the Asthma UK Centre for Applied Research Patient and Public Involvement (PPI) group. Findings were regularly discussed within the research group and with PPI colleagues to aid the interpretation of data.

Progressive pulmonary fibrosis (PF) is a complex interstitial lung disease that impacts substantially on patients' daily lives, requiring personalised and integrated care. We summarise the main needs of patients with PF and their caregivers, and suggest a supportive care approach. Individualised care, education, emotional and psychological support, specialised treatments, and better access to information and resources are necessary. Management should start at diagnosis, be tailored to the patient's needs, and consider end-of-life care. Pharmacological and non-pharmacological interventions should be individualised, including oxygen therapy and pulmonary rehabilitation, with digital healthcare utilised as appropriate. Further research is needed to address technical issues related to oxygen delivery and digital healthcare. Educational aims To identify the main needs of patients with PF and their caregivers. To describe the components of a comprehensive approach to a supportive care programme for patients with PF. To identify further areas of research to address technical issues related to the management of patients with PF.

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

It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of the laboratory-based science, clinical trials and qualitative research that were presented during the 2022 European Respiratory Society International Congress within the sessions from the five groups of Assembly 1 (Respiratory Clinical Care and Physiology). Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, mobile/electronic health (m-health/e-health), clinical respiratory physiology, exercise and functional imaging.

Abstract Background Process evaluations aim to understand how complex interventions bring about outcomes by examining intervention mechanisms, implementation, and context. While much attention has been paid to the methodology of process evaluations in health research, the value of process evaluations has received less critical attention. We aimed to unpack how value is conceptualised in process evaluations by identifying and critically analysing 1) how process evaluations may create value and 2) what kind of value they may create. Methods We systematically searched for and identified published literature on process evaluation, including guidance, opinion pieces, primary research, reviews, and discussion of methodological and practical issues. We conducted a critical interpretive synthesis and developed a practical planning framework. Results We identified and included 147 literature items. From these we determined three ways in which process evaluations may create value or negative consequences: 1) through the socio-technical processes of ‘doing’ the process evaluation, 2) through the features/qualities of process evaluation knowledge, and 3) through using process evaluation knowledge. We identified 15 value themes. We also found that value varies according to the characteristics of individual process evaluations, and is subjective and context dependent. Conclusion The concept of value in process evaluations is complex and multi-faceted. Stakeholders in different contexts may have very different expectations of process evaluations and the value that can and should be obtained from them. We propose a planning framework to support an open and transparent process to plan and create value from process evaluations and negotiate trade-offs. This will support the development of joint solutions and, ultimately, generate more value from process evaluations to all.

Abstract Background Primary healthcare workers (PHCWs) are at the frontline of dealing with viral pandemics. They may experience significant psychological stresses, which have hitherto not been examined in depth. We aimed to explore the impact of the COVID-19 pandemic on the psychological health and wellbeing of frontline PHCWs in Malaysia. Method We purposively recruited PHCWs with diverse backgrounds in Klang Valley, Malaysia. Using longitudinal qualitative methods, we conducted two sequential semi-structured telephone interviews, 3 to 4 weeks apart, to capture different stages of the pandemic. Interviews were audio-recorded, transcribed verbatim, and analysed thematically. Result Twenty-one PHCWs participated yielding a total of forty-two interviews. Themes clustered around stressors associated with work, home, and leisure activities, emotional changes, and modifying factors. In the first interviews, COVID-19 had just started in Malaysia. Participants expressed fear about the actual and perceived personal risk of COVID-19 infection. Most were worried about transmitting COVID-19 to their family members. Some felt stigmatized because of this perceived risk of infection. By the second interviews, participants felt safer, but instead focused on the need to keep other people safe. Participants’ emotions were influenced by their perceived risk of contracting COVID-19 infection. Internal factors such as religion enabled them to manage their concerns and develop personal coping strategies. Support from family members, colleagues, and employers promoted wellbeing during the pandemic. Training sessions, daily roll calls, and psychological support services were important in maintaining their psychological health and wellbeing. Many participants were hopeful and believed normalcy would return by the end of 2020. Conclusion PHCW’s psychological health and wellbeing evolved throughout the early stages of the pandemic and were influenced by their perceived risk of contracting the disease and personal belief structures. Clear updates on the disease and strategies for keeping safe at work and socially are essential to maintaining PHCWs’ psychological health and wellbeing.

Abstract Background Self‐management strategies improve asthma outcomes, although interventions for South Asian populations have been less effective than in White populations. Both self‐management and culture are dynamic, and factors such as acculturation and generation have not always been adequately reflected in existing cultural interventions. We aimed to explore the perspectives of Bangladeshi and Pakistani people in the United Kingdom, across multiple generations (first, second and third/fourth), on how they self‐manage their asthma, with a view to suggesting recommendations for cultural interventions. Methods We purposively recruited Bangladeshi and Pakistani participants, with an active diagnosis of asthma from healthcare settings. Semi‐structured interviews in the participants' choice of language (English, Sylheti, Standard Bengali or Urdu) were conducted, and data were analysed thematically. Results Twenty‐seven participants (13 Bangladeshi and 14 Pakistani) were interviewed. There were generational differences in self‐management, influenced by complex cultural processes experienced by South Asians as part of being an ethnic minority group. Individuals from the first generation used self‐management strategies congruent to traditional beliefs such as ‘sweating’ and often chose to travel to South Asian countries. Generations born and raised in the United Kingdom learnt and experimented with self‐management based on their fused identities and modified their approach depending on whether they were in familial or peer settings. Acculturative stress, which was typically higher in first generations who had migration‐related stressors, influenced the priority given to asthma self‐management throughout generations. The amount and type of available asthma information as well as social discussions within the community and with healthcare professionals also shaped asthma self‐management. Conclusions Recognizing cultural diversity and its influence of asthma self‐management can help develop effective interventions tailored to the lives of South Asian people. Patient or Public Contribution Patient and Public Involvement colleagues were consulted throughout to ensure that the study and its materials were fit for purpose.

Abstract Supported self-management reduces asthma-related morbidity and mortality. This paper is on a feasibility study, and observing the change in clinical and cost outcomes of pictorial action plan use is part of assessing feasibility as it will help us decide on outcome measures for a fully powered RCT. We conducted a pre–post feasibility study among adults with physician-diagnosed asthma on inhaled corticosteroids at a public primary-care clinic in Malaysia. We adapted an existing pictorial asthma action plan. The primary outcome was asthma control, assessed at 1, 3 and 6 months. Secondary outcomes included reliever use, controller medication adherence, asthma exacerbations, emergency visits, hospitalisations, days lost from work/daily activities and action plan use. We estimated potential cost savings on asthma-related care following plan use. About 84% (n = 59/70) completed the 6-months follow-up. The proportion achieving good asthma control increased from 18 (30.4%) at baseline to 38 (64.4%) at 6-month follow-up. The proportion of at least one acute exacerbation (3 months: % difference −19.7; 95% CI −34.7 to −3.1; 6 months: % difference −20.3; 95% CI −5.8 to −3.2), one or more emergency visit (1 month: % difference −28.6; 95% CI −41.2 to −15.5; 3 months: % difference −18.0; 95% CI −32.2 to −3.0; 6 months: % difference −20.3; 95% CI −34.9 to −4.6), and one or more asthma admission (1 month: % difference −14.3; 95% CI −25.2 to −5.3; 6 months: % difference −11.9; 95% CI −23.2 to −1.8) improved over time. Estimated savings for the 59 patients at 6-months follow-up and for each patient over the 6 months were RM 15,866.22 (USD3755.36) and RM268.92 (USD63.65), respectively. Supported self-management with a pictorial asthma action plan was associated with an improvement in asthma control and potential cost savings in Malaysian primary-care patients. Trial registration number: ISRCTN87128530; prospectively registered: September 5, 2019, http://www.isrctn.com/ISRCTN87128530 .

Abstract Background The COVID‐19 pandemic forced health care systems globally to adapt quickly to remote modes of health care delivery, including for routine asthma reviews. A core component of asthma care is supporting self‐management, a guideline‐recommended intervention that reduces the risk of acute attacks, and improves asthma control and quality of life. Objective We aimed to explore context and mechanisms for the outcomes of clinical effectiveness, acceptability and safety of supported self‐management delivery within remote asthma consultations. Design The review followed standard methodology for rapid realist reviews. An External Reference Group (ERG) provided expert advice and guidance throughout the study. We systematically searched four electronic databases and, with ERG advice, selected 18 papers that explored self‐management delivery during routine asthma reviews. Setting, Participants and Intervention Health care professional delivery of supported self‐management for asthma patients during remote (specifically including telephone and video) consultations. Main Outcome Measures Data were extracted using Context‐Mechanism‐Outcome (C‐M‐O) configurations and synthesised into overarching themes using the PRISMS taxonomy of supported self‐management as a framework to structure the findings. Results The review findings identified how support for self‐management delivered remotely was acceptable (often more acceptable than in‐person consultations), and was a safe and effective alternative to face‐to‐face reviews. In addition, remote delivery of supported self‐management was associated with; increased patient convenience, improved access to and attendance at remote reviews, and offered continuity of care. Discussion Remote delivery of supported self‐management for asthma was generally found to be clinically effective, acceptable, and safe with the added advantage of increasing accessibility. Remote reviews could provide the core content of an asthma review, including remote completion of asthma action plans. Conclusion Our findings support the option of remote delivery of routine asthma care for those who have this preference, and offer healthcare professionals guidance on embedding supported self‐management into remote asthma reviews. Patient and Public Contribution Patient and public contribution was provided by a representative of the Asthma UK Centre for Applied Research (AUKCAR) patient and public involvement (PPI) group. The PPI representative reviewed the findings, and feedback and comments were considered. This lead to further interpretations of the data which were included in the final manuscript.

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.

Abstract Background and Aims Asthma is common in Malaysia but neglected. Achieving optimal asthma control and care is a challenge in the primary care setting. In this study, we aimed to identify the risk factors for poor asthma control and pattern of care among adults and children (5–17 years old) with asthma attending six public health clinics in Klang District, Malaysia. Methods We conducted a cross‐sectional study collecting patients’ sociodemographic characteristics, asthma control, trigger factors, healthcare use, asthma treatment, and monitoring and use of asthma action plan. Descriptive statistics and stepwise logistic regression were used in data analysis. Results A total of 1280 patients were recruited; 85.3% adults and 14.7% children aged 5–17 years old. Only 34.1% of adults had well‐controlled asthma, 36.5% had partly controlled asthma, and 29.4% had uncontrolled asthma. In children, 54.3% had well‐controlled asthma, 31.9% had partly controlled, and 13.8% had uncontrolled asthma. More than half had experienced one or more exacerbations in the last 1 year, with a mean of six exacerbations in adults and three in children. Main triggers for poor control in adults were haze (odds ratio [OR] 1.51; 95% confidence interval [CI] 1.13–2.01); cold food (OR 1.54; 95% CI 1.15–2.07), extreme emotion (OR 1.90; 95% CI 1.26–2.89); air‐conditioning (OR 1.63; 95% CI 1.20–2.22); and physical activity (OR 2.85; 95% CI 2.13–3.82). In children, hot weather (OR 3.14; 95% CI 1.22–8.11), and allergic rhinitis (OR 2.57; 95% CI 1.13–5.82) contributed to poor control. The majority (81.7% of adults and 64.4% of children) were prescribed controller medications, but only 42.4% and 29.8% of the respective groups were compliant with the treatment. The importance of an asthma action plan was reported less emphasized in asthma education. Conclusion Asthma control remains suboptimal. Several triggers, compliance to controller medications, and asthma action plan use require attention during asthma reviews for better asthma outcomes.

Abstract Background Excess gestational weight gain (GWG) is associated with short-term perinatal complications and longer term cardiometabolic risks for mothers and their babies. Dietitian counselling and weight gain monitoring for women at risk of high pregnancy weight gain is recommended by clinical practice guidelines. However, face-to-face appointments, during a time with high appointment burden, can introduce barriers to engaging with care. Telephone counselling may offer a solution. The Living Well during Pregnancy (LWdP) program is a dietitian-delivered telephone coaching program implemented within routine antenatal care for women at risk of excess GWG. This program evaluation used a hybrid implementation-effectiveness design guided by the RE-AIM framework to report on the primary outcomes (reach, adoption, implementation, maintenance) and secondary outcomes (effectiveness) of the LWdP intervention. Methods The LWdP program evaluation compared data from women participating in the LWdP program with a historical comparison group (pregnant women receiving dietetic counselling for GWG in the 12 months prior to the study). The primary outcomes were described for the LWdP program. Between group comparisons were used to determine effectiveness of achieving appropriate GWG and pre and post intervention comparisons of LWdP participants was used to determine changes to dietary intake and physical activity. Results The LWdP intervention group (n = 142) were compared with women in the historical comparison group (n = 49). Women in the LWdP intervention group attended 3.4 (95% CI 2.9–3.8) appointments compared with 1.9 (95% CI, 1.6–2.2) in the historical comparison group. GWG was similar between the two groups, including the proportion of women gaining weight above the Institute of Medicine recommendations (70% vs 73%, p = 0.69). Within group comparison showed that total diet quality, intake of fruit and vegetables and weekly physical activity were all significantly improved from baseline to follow-up for the women in LWdP, while consumption of discretionary food and time spent being sedentary decreased (all p

Abstract Background IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) is a programme of work developing and evaluating a strategy for implementing supported asthma self-management in UK primary care. The strategy encompasses patient-facing resources, professional education, and organisational approaches to embed supported self-management. This paper reports the development of a theoretically informed interprofessional education programme which aims to raise awareness of and enable healthcare professionals to deliver effective supported self-management. Methods Aligned with the Medical Research Council (MRC) Complex Intervention Framework, the multidisciplinary team developed educational content in three phases: (1) developmental phase, identifying educational and behaviour change theory to guide development, in consultation with a professional advisory group; (2) feasibility pilot phase, testing the education using a ‘think-aloud’ method; and (3) pre-pilot phase, delivering the education within the IMP2ART strategy. Results The developmental phase identified educational and behaviour change theory and the need to provide two education modules: (1) a team module to raise awareness of supported asthma self-management for the whole team and (2) an individual study module for those who conduct asthma reviews with patients. The feasibility pilot highlighted content and design features in need of refinement and the pre-pilot identified substantial changes to the delivery strategy for the education modules. Conclusions A multi-stage development process, aligned with the MRC Framework, contributed to the module design and delivery. Prior explorative work, multi-disciplinary team discussions, and professional advisory group consultation, informed the initial development, and in-practice testing and pre-pilot stages enabled refinement. In our experience, there were important benefits of working together as an educationalist/researcher team. The education programme, a core component of the implementation strategy, is now being tested in the IMP2ART UK-wide cluster randomised controlled trial.

Here, Forster et al. compare 1354 cultured commensal strains (540 species) to 45,403 pathogen strains (12 species), identifying 64,188 MGE-mediated antibiotic resistance gene transfer events between the two groups, and show that 15 broad host range MGEs are able to transfer between phyla.

This article engages the situated knowledge of actors in radical(ising) milieus to enhance our understanding of radicalisation and how to counter it. The article draws on interviews and observations from two ethnographic case studies in the UK – one with young people from an ‘Islamist’ and one from young people in an ‘extreme-right’ milieu – as well as three mediated dialogue events organised with participants from these milieus. The article explores how actors in these two milieus themselves understand what ‘drives’ and what might ‘prevent’ radicalisation and the degree to which such emic understandings concur with, or deviate from, etic (academic, policy, practice) conceptualisations – in particular on actors’ understandings of the role of the state, and its counter-terrorism policies and agencies, in driving radicalisation. We outline the views and experiences of Preventing or Countering Violent Extremism (P/CVE) interventions among milieu actors, which they encounter through the ‘Prevent’ arm of the UK’s counter-terrorism strategy but also in the form of curtailment of their activity (prevention from attending events and bans on social media). Finally, we consider how these emic understandings and personal experiences are expressed in milieu actors’ own practices of preventing or constraining trajectories into extremism and the openness of research participants themselves to engaging with agencies involved in P/CVE employing dialogic approaches. The article brings new insight to the field by considering the understandings and experiences of counter-extremism policies and practices among those targeted by them and argues for the importance of engaging with individuals as subjects not objects of counter-extremism policy and practice.

Abstract Background Adjusting to life with a chronic condition is challenging, especially for people with limited health literacy, which is associated with low compliance with self‐management activities and poor clinical outcomes. Objective We explored how people with limited health literacy understand asthma and undertake self‐management practices. Design We adapted the arts‐based qualitative methodology Photovoice. Setting and Participants We sampled ethnically diverse adults with asthma and limited health literacy from four primary healthcare clinics in Malaysia. After a semistructured in‐depth interview, a subset of participants took part in the Photovoice component in which participants undertook a 2‐week photo‐taking activity and subsequent photo‐interview. Interviews, conducted in participants' preferred language, were audio‐recorded, transcribed verbatim, translated and analysed thematically. We used the Sorensen's framework (Domains: access, understand, appraise, apply) to describe participants' experience of living with asthma, what they understood about asthma and how they decided on self‐management practices. Results Twenty‐six participants provided interviews; eight completed the Photovoice activities. Participants with limited health literacy used various sources to access information about asthma and self‐management. Doctor–patient communication had a pivotal role in helping patients understand asthma. The lack of appraisal skills was significant and experiential knowledge influenced how they applied information. Self‐management decisions were influenced by sociocultural norms/practices, stigmatizing experiences, and available social support. Conclusion Locally tailored multilevel interventions (interpersonal, health system, community and policy) will be needed to support people with limited health literacy to live optimally with their asthma in an ethnically diverse population. Patient/Public Contribution Patients were involved in the study design, recruitment, analysis and dissemination.

Purpose/Objectives: Medical documentation has become increasingly challenging for providers, particularly with changes to telemedicine visit formats during the ongoing COVID-19 pandemic. Medical scribes may help mitigate this burden. Our objective was to determine how scribes affect provider efficiency during the COVID-19 pandemic. Materials/Methods: Providers completed a survey in February 2020 (S1, prepandemic) and 1 year into the COVID-19 pandemic in February 2021 (S2, during pandemic). S1 evaluated perceived impact of scribes on clerical work, medical documentation, and efficiency during office visits using the Likert scale. S2 also addressed scribe use during telemedicine visits. Provider time spent on documentation with or without a scribe was evaluated using a five-level ordinal scale. Provider response was assessed using descriptive frequency statistics. Fisher's exact test was used to compare categorical variables. Analysis was performed using SAS version 9.4 (SAS Institute, Inc., Cary, NC). All tests were two sided with an alpha level of 0.05. Results: Fifty-eight providers responded to the surveys: 36 (62%) for S1 and 22 (38%) for S2. Scribe use decreased perceived clerical work and facilitated chart review, and recording of physical examination findings, note documentation, and improved efficiency, both before and during the pandemic (p?=?0.5, p?=?0.7, p?=?0.8, p?=?0.8, p?=?0.9, respectively). Scribe use significantly decreased time to complete documentation prepandemic (p?=?0.002) and during the pandemic for both in-person (p???0.0001) and telemedicine visits (p?=?0.0004). More providers took >60?min to complete medical documentation without the use of a scribe prepandemic (72% vs. 30% with a scribe, p?=?0.006) and during the pandemic, after both in-person (40% vs. 0% with a scribe, p?=?0.002) and telemedicine visits (35% vs. 0% with a scribe, p?=?0.002). Conclusions: Scribe use decreases provider time spent on medical documentation and improves overall efficiency before and during the COVID-19 pandemic for both in-person and telemedicine visits. Integration of scribes into radiation oncology in-person and telemedicine clinics may improve provider satisfaction by reducing burden of documentation.

Background: Chronic respiratory diseases (CRD), especially asthma and chronic obstructive pulmonary disease (COPD), are common public health problems resulting in a substantial burden of disease for individuals. There is a need to understand the perceptions and practices of primary care physicians (“general practitioners [GPs]”) who provide most of the health care in rural India. We surveyed all private and public practitioners listed as practising in a rural area of Western India with the aim of identifying GPs (GPs: graduates, registered and allowed to practice in India) to understand their training, working arrangements, and asthma/COPD workload. Methodology: We administered a short questionnaire at educational meetings or via e-mail to all private and public practitioners listed as providing community-based services in the Junnar block, Pune district, Maharashtra. The survey asked about qualifications, experience, and working arrangements, and about current asthma and COPD workload. A descriptive analysis was performed. Results: We approached 474 practitioners (434 from private sector and 40 from public sector). Eighty-eight were no longer practising in the study area. The response rate was 330/354 (93.2%) of private and 28/32 (87.5%) of public sector practitioners. We excluded 135 nonrespiratory hospital specialists and 23 private practitioners whose highest qualification was a diploma. Our final sample of 200 GPs (70% males) was 177 from private sector and 23 from public sector. The private GPs had more experience in clinical practice in comparison to public GPs (18.6 vs. 12.8 years). Eighty-four percent of GPs from the private sector only had Ayurveda, Yoga, Naturopathy, Unani, Siddha, and Homoeopathy (AYUSH) qualifications, though >90% provided “modern medicine” services. In the public sector, 43.5% GPs only had AYUSH qualifications, though all provided “modern medicine” services. A minority (9% of private GPs and 16% of public GPs) provided both services. Nearly two-thirds (62%) of private GPs had inpatient facilities compared to only 9% of public sector GPs. In both sectors, more GPs stated that they managed people with asthma than treated COPD (Private: 97% vs. 75%; Public 87% vs. 57%). Conclusion: Many GPs practising “modern medicine” only had qualifications in Ayurveda/Homeopathy and fewer GPs are involved in the management of COPD as compared to asthma. These are important factors that form the context for initiatives seeking to improve the quality of community-based care for people with CRD in Maharashtra state in India.

Abstract Brain targets to lower the high risk of suicide in Bipolar Disorder (BD) are needed. Neuroimaging studies employing analyses dependent on regional assumptions could miss hubs of dysfunction critical to the pathophysiology of suicide behaviors and their prevention. This study applied intrinsic connectivity distribution (ICD), a whole brain graph‐theoretical approach, to identify hubs of functional connectivity (FC) disturbances associated with suicide attempts in BD. ICD, from functional magnetic resonance imaging data acquired while performing a task involving implicit emotion regulation processes important in BD and suicide behaviors, was compared across 40 adults with BD with prior suicide attempts (SAs), 49 with BD with no prior attempts (NSAs) and 51 healthy volunteers (HVs). Areas of significant group differences were used as seeds to identify regional FC differences and explore associations with suicide risk-related measures. ICD was significantly lower in SAs than in NSAs and HVs in bilateral ventromedial prefrontal cortex (vmPFC) and right anterior insula (RaIns). Seed connectivity revealed altered FC from vmPFC to bilateral anteromedial orbitofrontal cortex, left ventrolateral PFC (vlPFC) and cerebellum, and from RaIns to right vlPFC and temporopolar cortices. VmPFC and RaIns ICD were negatively associated with suicidal ideation severity, and vmPFC ICD with hopelessness and attempt lethality severity. The findings suggest that SAs with BD have vmPFC and RaIns hubs of dysfunction associated with altered FC to other ventral frontal, temporopolar and cerebellar cortices, and with suicidal ideation, hopelessness, and attempt lethality. These hubs may be targets for novel therapeutics to reduce suicide risk in BD.

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.

IntroductionPeople living with asthma require regular reviews to address their concerns and questions, assess control, review medication, and support self-management. However, practical barriers to attending face-to-face consultations might limit routine reviews. Reviewing asthma using asynchronous digital health interventions could be convenient for patients and an efficient way of maintaining communication between patients and healthcare professionals and improving health outcomes. We, therefore, aim to conduct a mixed-methods systematic review to assess the effectiveness of reviewing asthma by asynchronous digital health interventions and explore the views of patients and healthcare professionals about the role of such interventions in delivering asthma care.MethodsWe will search MEDLINE, Embase, Scopus, PsycInfo, CINAHL, and Cochrane Library from 2001 to present without imposing any language restrictions. We are interested in studies of asynchronous digital health interventions used either as a single intervention or contributing to mixed modes of review. Two review authors will independently screen titles and abstracts, and retrieve potentially relevant studies for full assessment against the eligibility criteria and extract data. Disagreements will be resolved by discussion with the review team. We will use 'Downs and Black' checklist, 'Critical Appraisal Skills Programme', and 'Mixed Methods Appraisal Tool' to assess methodological quality of quantitative, qualitative, and mixed-methods studies respectively. After synthesising quantitative (narrative synthesis) and qualitative (thematic synthesis) data separately, we will integrate them following methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions.ConclusionThe findings of this review will provide insights into the role of asynchronous digital health interventions in the routine care of people living with asthma.Trial registrationSystematic review registration: PROSPERO registration number: CRD42022344224.

Radiation therapy (RT) plays a key role in curative-intent treatments for head and neck cancer (HNC). Despite the advancements in RT, high doses of radiation can disrupt the oral cavity homeostasis and result in undesired reactions. Thus, intraoral stents (IOSs) are utilized for patients during RT to prevent unnecessary irradiation to surrounding tissues. However, no studies have compared commonly used IOS materials and their potential toxicity. Therefore, the objective of this study is to perform a detailed assessment of ten IOS materials in order to select the top-ranked material for HNC patients undergoing RT. Thus, beam attenuation measurements, and Raman spectroscopy and mechanical testing were conducted pre- and post-artificial saliva, RT, and artificial saliva and RT exposure. Finally, through a multi-criteria decision making (MCDM) analysis using Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS), our study demonstrated that Ethylene Vinyl Acetate (EVA) was the top-ranked material. The saliva samples were also tested via nuclear magnetic resonance (NMR) spectroscopy, which showed no leaching of irradiated materials. Taken together, these data suggest that EVA is an appropriate IOS material that can be utilized during RT to reduce significant morbidity for HNC patients and improve their quality of life.

Abstract Background Supported self‐management improves asthma outcomes, but implementation requires adaptation to the local context. Barriers reported in Western cultures may not resonate in other cultural contexts. We explored the views, experiences and beliefs that influenced self‐management among adults with asthma in multicultural Malaysia. Methods Adults with asthma were purposively recruited from an urban primary healthcare clinic for in‐depth interviews. Audio‐recordings were transcribed verbatim and analysed thematically. Results We interviewed 24 adults. Four themes emerged: (1) Participants believed in the ‘hot and cold’ concept of illness either as an inherent hot/cold body constitution or the ambient temperature. Hence, participants tried to ‘neutralize’ body constitution or to ‘warm up’ the cold temperature that was believed to trigger acute attacks. (2) Participants managed asthma based on past experiences and personal health beliefs as they lacked formal information about asthma and its treatment. (3) Poor communication and variable advice from healthcare practitioners on how to manage their asthma contributed to poor self‐management skills. (4) Embarrassment about using inhalers in public and advice from family and friends resulted in a focus on nonpharmacological approaches to asthma self‐management practice. Conclusions Asthma self‐management practices were learnt experientially and were strongly influenced by sociocultural beliefs and advice from family and friends. Effective self‐management needs to be tailored to cultural norms, personalized to the individuals' preferences and clinical needs, adapted to their level of health literacy and underpinned by patient–practitioner partnerships. Patient and Public Contributions Patients contributed to data. Members of the public were involved in the discussion of the results.

Abstract Background A shared decision-making model is preferred for engaging prostate cancer patients in treatment decisions. However, the process of assessing an individual’s preferences and values is challenging and not formalized. The purpose of this study is to develop an automated decision aid for patient-centric treatment decision-making using decision analysis, preference thresholds and value elicitations to maximize the compatibility between a patient’s treatment expectations and outcome. Methods A template for patient-centric medical decision-making was constructed. The inputs included prostate cancer risk group, pre-treatment health state, treatment alternatives (primarily focused on radiation in this model), side effects (erectile dysfunction, urinary incontinence, nocturia and bowel incontinence), and treatment success (5-year freedom from biochemical failure). A linear additive value function was used to combine the values for each attribute (side effects, success and the alternatives) into a value for all prospects. The patient-reported toxicity probabilities were derived from phase II and III trials. The probabilities are conditioned on the starting state for each of the side effects. Toxicity matrices for erectile dysfunction, urinary incontinence, nocturia and bowel incontinence were created for the treatment alternatives. Toxicity probability thresholds were obtained by identifying the patient’s maximum acceptable threshold for each of the side effects. Results are represented as a visual. R and Rstudio were used to perform analyses, and R Shiny for application creation. Results We developed a web-based decision aid. Based on preliminary use of the application, every treatment alternative could be the best choice for a decision maker with a particular set of preferences. This result implies that no treatment has determinist dominance over the remaining treatments and that a preference-based approach can help patients through their decision-making process, potentially affecting compliance with treatment, tolerance of side effects and satisfaction with the decision. Conclusions We present a unique patient-centric prostate cancer treatment decision aid that systematically assesses and incorporates a patient’s preferences and values to rank treatment options by likelihood of achieving the preferred outcome. This application enables the practice and study of personalized medicine. This model can be expanded to include additional inputs, such as genomics, as well as competing, concurrent or sequential therapies.