Developing a typology of interventions to support doctors' mental health and wellbeing.

BACKGROUND: The problem of mental ill-health in doctors is complex, accentuated by the COVID-19 pandemic, and impacts on healthcare provision and broader organisational performance. There are many interventions to address the problem but currently no systematic way to categorise them, which makes it hard to describe and compare interventions. As a result, implementation tends to be unfocussed and fall short of the standards developed for implementing complex healthcare interventions. This study aims to develop: 1) a conceptual typology of workplace mental health and wellbeing interventions and 2) a mapping tool to apply the typology within research and practice. METHODS: Typology development was based on iterative cycles of analysis of published and in-practice interventions, incorporation of relevant theories and frameworks, and team and stakeholder group discussions. RESULTS: The newly developed typology and mapping tool enable interventions to be conceptualised and/or mapped into different categories, for example whether they are designed to be largely preventative (by either improving the workplace or increasing personal resources) or to resolve problems after they have arisen. Interventions may be mapped across more than one category to reflect the nuance and complexity in many mental health and wellbeing interventions. Mapping of interventions indicated that most publications have not clarified their underlying assumptions about what causes outcomes or the theoretical basis for the intervention. CONCLUSION: The conceptual typology and mapping tool aims to raise the quality of future research and promote clear thinking about the nature and purpose of interventions, In doing so it aims to support future research and practice in planning interventions to improve the mental health and wellbeing of doctors.

Improving the Detection, Assessment, Management and Prevention of Delirium in Hospices (the DAMPen-D study): Feasibility study of a flexible and scalable implementation strategy to deliver guideline-adherent delirium care.

BACKGROUND: Delirium is a complex condition, stressful for all involved. Although highly prevalent in palliative care settings, it remains underdiagnosed and associated with poor outcomes. Guideline-adherent delirium care may improve its detection, assessment and management. AIM: To inform a future definitive study that tests whether an implementation strategy designed to improve guideline-adherent delirium care in palliative care settings improves patient outcomes (reduced proportion of in-patient days with delirium). DESIGN: With Patient Involvement members, we conducted a feasibility study to assess the acceptability of and engagement with the implementation strategy by hospice staff (intervention), and whether clinical record data collection of process (e.g. guideline-adherent delirium care) and clinical outcomes (evidence of delirium using a validated chart-based instrument;) pre- and 12-weeks post-implementation of the intervention would be possible. SETTING/PARTICIPANTS: In-patient admissions in three English hospices. RESULTS: Between June 2021 and December 2022, clinical record data were extracted from 300 consecutive admissions. Despite data collection during COVID-19, target clinical record data collection (n = 300) was achieved. Approximately two-thirds of patients had a delirium episode during in-patient stay at both timepoints. A 6% absolute reduction in proportion of delirium days in those with a delirium episode was observed. Post-implementation improvements in guideline-adherent metrics include: clinical delirium diagnosis 15%-28%; delirium risk assessment 0%-16%; screening on admission 7%-35%. CONCLUSIONS: Collection of data on delirium outcomes and guideline-adherence from clinical records is feasible. The signal of patient benefit supports formal evaluation in a large-scale study.

LymphActiv: A Digital Physical Activity Behavior Intervention for the Treatment of Lymphedema and Lipedema.

Background: Lymphedema and lipedema are debilitating conditions with no proven drug or surgical therapy. Effective treatment requires self-management through movement and compression to reduce limb volume and the incidence of cellulitis. The addition of personalized everyday physical activity (PA) could be transformative, increasing the therapy window to include all waking hours per week and enabling an increased dose of PA. Aim: This service evaluation aimed to determine the feasibility of LymphActiv as a treatment option for lymphedema and lipedema patients. Methods: This service evaluation followed an open observational cohort design, including 55 patients who participated in LymphActiv over 24 weeks. Patients wore an objective PA monitor and interacted with their data in an online dashboard, alongside remote mentor support. Primary outcomes were changes to PA, body weight, limb volume and quality of life. Clinical assessments occurred at baseline and after the 24-week program. Noncompleters were used as a quasi-control group for comparison. Results: Thirty-seven patients completed, of which 81% improved PA. On average, completers reduced their right and left lower limb volumes by -1.8% and -2.1%, respectively. Completers also experienced small average weight losses of -1.2 kg. Noncompleters experienced small average increases in each of these outcome measures. Discussion: These results establish the value of LymphActiv, providing benefit to patients who might otherwise have deteriorated. For services, this could lead to substantial cost-savings through reduced admissions, greater patient independence, and less need for community health care input. The next step is to undertake a randomized, controlled trial comparing the intervention with standard care.

Correction: Supported: Supporting, enabling, and sustaining homecare workers to deliver end-of-life care: A qualitative study protocol.

[This corrects the article DOI: 10.1371/journal.pone.0291525.].

Mucus clears from the trachea in a helix: a new twist to understanding airway diseases.

BACKGROUND: Mucociliary clearance (MCC) is critical to lung health and is impaired in many diseases. The path of MCC may have an important impact on clearance but has never been rigorously studied. The objective of this study is to assess the three-dimensional path of human tracheal MCC in disease and health. METHODS: Tracheal MCC was imaged in 12 ex-smokers, 3 non-smokers (1 opportunistically imaged during acute influenza and repeated after recovery) and 5 individuals with primary ciliary dyskinesia (PCD). Radiolabelled macroaggregated albumin droplets were injected into the trachea via the cricothyroid membrane. Droplet movement was tracked via scintigraphy, the path of movement mapped and helical and axial models of tracheal MCC were compared. MEASUREMENTS AND MAIN RESULTS: In 5/5 participants with PCD and 1 healthy participant with acute influenza, radiolabelled albumin coated the trachea and did not move. In all others (15/15), mucus coalesced into globules. Globule movement was negligible in 3 ex-smokers, but in all others (12/15) ascended the trachea in a helical path. Median cephalad tracheal MCC was 2.7 mm/min ex-smokers vs 8.4 mm/min non-smokers (p=0.02) and correlated strongly to helical angle (r=0.92 (p=0.00002); median 18o ex-smokers, 47o non-smokers (p=0.036)), but not to actual speed on helical path (r=0.26 (p=0.46); median 13.6 mm/min ex-smokers vs 13.9 mm/min non-smokers (p=1.0)). CONCLUSION: For the first time, we show that human tracheal MCC is helical, and impairment in ex-smokers is often caused by flattened helical transit, not slower movement. Our methodology provides a simple method to map tracheal MCC and speed in vivo.

Developing a strategy to scale up place-based arts initiatives that support mental health and wellbeing: A realist evaluation of 'Arts for the Blues'.

Place-based arts initiatives are regarded as rooted in local need and as having capacity to engage local assets. However, many place-based arts initiatives remain poorly funded and short-lived, receiving little attention on how to scale up and sustain their activities. In this study we make a unique contribution to knowledge about scaling up place-based arts initiatives that support mental health and wellbeing through focusing on the example of 'Arts for the Blues', an arts-based psychological group intervention designed to reduce depression and improve wellbeing amongst primary care mental health service users in deprived communities. Methodologically, we used realist evaluation to refine the study's theoretical assumptions about scaling up, drawing on the lived and professional experiences of 225 diverse stakeholders' and frontline staff through a series of focus groups and evaluation questions at two stakeholders' events and four training days. Based on our findings, we recommend that to scale up place-based arts initiatives which support mental health and wellbeing: (i) the initiative needs to be adaptable, clear, collaborative, evidence-based, personalised and transformative; (ii) the organisation has to have a relevant need, have an understanding of the arts, has to have resources, inspiration and commitment from staff members, relevant skillsets and help from outside the organisation; (iii) at a policy level it is important to pay attention to attitude shifts towards the arts, meet rules, guidelines and standards expected from services, highlight gaps in provision, seek out early intervention and treatment options, and consider service delivery changes. The presence of champions at a local level and buy-in from managers, local leaders and policy makers are also needed alongside actively seeking to implement arts initiatives in different settings across geographical spread. Our theoretically-based and experientially-refined study provides the first ever scaling up framework developed for place-based arts initiatives that support the mental health and wellbeing, offering opportunities for spread and adoption of such projects in different organisational contexts, locally, nationally and internationally.

Exploring pathways to optimise care in malignant bowel obstruction (EPOC): Protocol for a three-phase critical realist approach to theory-led intervention development for shared decision-making.

INTRODUCTION: Malignant bowel obstruction is a distressing complication of cancer, causing pain, nausea and vomiting, and often has a poor prognosis. Severe and rapidly developing symptoms, a lack of robust clinical guidelines and the need for multidisciplinary input make treatment decision-making challenging. Sharing decision-making with people with malignant bowel obstruction and their caregivers can be difficult, and inconsistent communication creates serious deficiencies in care by amplifying patients' distress and uncertainty. Little attention has been paid to the implicit influences on this process-for example, the role of discipline-related norms and the beliefs of decision-makers. This study will explore how these processes work and develop interventions to improve shared decision-making. METHODS AND ANALYSIS: Exploring Pathways to Optimise Care (EPOC) is a three-phase study set within a critical realist framework: (i) realist review, to develop explanatory theory describing collaborative decision-making in the management of malignant bowel obstruction; (ii) an in-depth interview study using modified grounded theory to explore the active ingredients of this collaboration in practice settings; and (iii) the presentation to stakeholders (practitioners, patients and caregivers) of integrated results from Phase I (theory developed from the literature) and Phase II (theory developed from current practice) as a basis for intervention mapping. We aim to produce recommendations to address the challenges, and to develop a set of tools to (i) aid interaction around shared decision-making and (ii) aid interprofessional interaction around the management of this condition. Registration details: The realist review is registered with PROSPERO (CRD42022308251).

Supported: Supporting, enabling, and sustaining homecare workers to deliver end-of-life care: A qualitative study protocol.

BACKGROUND: Homecare workers provide essential care at home for people at end-of-life but are often poorly trained and supported. AIM: To explore the experiences and needs of homecare workers and the views of homecare clients and carers, and other community-based health and social care staff about the homecare worker role, including identification of good practice. METHODS: In this qualitative exploratory study, we will conduct 150 semi-structured interviews with homecare workers within three geographic English localities chosen for maximum socio-demographic variation. Eligible participants will be consenting adults providing care services (workers [n = 45], managers [n = 15] community practitioners [n = 30]), receiving care (clients thought to be in the last 6 months of life [n = 30], family carers [n = 15], or commissioners of homecare services supporting end-of-life care [n = 15]. Interviews may adopt a Pictor-guided or standard semi-structured approach according to their preference. Managers and commissioners can contribute to an online focus group if preferred. A range of recruitment strategies will be used, including through homecare agencies, local authorities, local NHS services, charities, voluntary sector groups and social media. Interviews and focus groups will be recorded, transcribed, anonymised, and analysed adopting a case-based approach for each geographic area within-case and then comparison across cases using reflexive thematic analysis. The design and analysis will be informed by Bronfenbrenner's Adapted Ecological Systems theory. This study is registered on the Research Registry (No.8613). CONTRIBUTION: We will provide evidence on ways to improve the experiences and address the needs of homecare workers in relation to caring for people nearing end-of-life. It will offer insight into good practice around supporting homecare workers including responding to their training and development needs. Findings will inform subsequent stages of an evaluation-phase study of a training resource for homecare workers.

Drivers of unprofessional behaviour between staff in acute care hospitals: a realist review.

BACKGROUND: Unprofessional behaviours (UB) between healthcare staff are rife in global healthcare systems, negatively impacting staff wellbeing, patient safety and care quality. Drivers of UBs include organisational, situational, team, and leadership issues which interact in complex ways. An improved understanding of these factors and their interactions would enable future interventions to better target these drivers of UB. METHODS: A realist review following RAMESES guidelines was undertaken with stakeholder input. Initial theories were formulated drawing on reports known to the study team and scoping searches. A systematic search of databases including Embase, CINAHL, MEDLINE and HMIC was performed to identify literature for theory refinement. Data were extracted from these reports, synthesised, and initial theories tested, to produce refined programme theories. RESULTS: We included 81 reports (papers) from 2,977 deduplicated records of grey and academic reports, and 28 via Google, stakeholders, and team members, yielding a total of 109 reports. Five categories of contributor were formulated: (1) workplace disempowerment; (2) harmful workplace processes and cultures; (3) inhibited social cohesion; (4) reduced ability to speak up; and (5) lack of manager awareness and urgency. These resulted in direct increases to UB, reduced ability of staff to cope, and reduced ability to report, challenge or address UB. Twenty-three theories were developed to explain how these contributors work and interact, and how their outcomes differ across diverse staff groups. Staff most at risk of UB include women, new staff, staff with disabilities, and staff from minoritised groups. UB negatively impacted patient safety by impairing concentration, communication, ability to learn, confidence, and interpersonal trust. CONCLUSION: Existing research has focused primarily on individual characteristics, but these are inconsistent, difficult to address, and can be used to deflect organisational responsibility. We present a comprehensive programme theory furthering understanding of contributors to UB, how they work and why, how they interact, whom they affect, and how patient safety is impacted. More research is needed to understand how and why minoritised staff are disproportionately affected by UB. STUDY REGISTRATION: This study was registered on the international database of prospectively registered systematic reviews in health and social care (PROSPERO): https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021255490 .

The handheld fan for chronic breathlessness: Clinicians' experiences and views of implementation in clinical practice.

INTRODUCTION: The handheld fan ('fan') is useful for chronic breathlessness management, however little is known about clinicians' implementation of the fan in clinical practice. AIM: To explore clinicians' experiences and views of fan implementation. METHODS: A qualitative approach, using semi-structured interviews. Participants were purposively sampled from clinicians who had completed an on-line fan implementation survey and were willing to participate. A topic guide was developed using the Theoretical Domains Framework (TDF). Data were analysed using an inductive approach informed by the TDF. FINDINGS: Twelve clinicians participated (doctors n = 4; nurses n = 4; allied health professionals n = 4) from respiratory and palliative care. Analysis generated three major themes: i) Clinician knowledge and skills in fan implementation, ii) environmental constraints on fan use and iii) clinician beliefs about the consequences of fan use. Implementation by clinicians was positively influenced by having a scientific rationale for fan use presented (mechanism of action). Clinicians believed that the fan relieved breathlessness and did not carry a significant infection risk. Opportunity for fan use varied across healthcare settings; key environmental influences were COVID-19 restrictions, lack of access to resources and funding to provide fans, particularly in acute and respiratory services. Clinicians commonly encountered scepticism among patients and colleagues who felt the fan was an implausible intervention for breathlessness. CONCLUSION: Implementation of the fan is motivated by clinician beliefs about patient-benefit, a scientific rationale to counter clinician and patient scepticism, and access to fans in clinic. Funding to allow patients to be supplied with and taught how to use a fan would support uptake. Research is needed to address concerns about infection risk.

BREATHLEssness in INDIA (BREATHE-INDIA)-Study protocol for the co-design of a community breathlessness intervention in India using realist methods and intervention mapping.

BACKGROUND: Breathlessness that persists despite treatment of causal disease(s) is disabling, associated with high therapy-related costs and poor socioeconomic outcomes. Low resource countries bear a disproportionate burden of respiratory problems, often characterised by disabling breathlessness. Low-cost self-management breathlessness-targeted interventions are effective and deliverable in community settings but have been developed in high-income countries. We aim to understand how breathlessness self-management works in 'real life' populations and cultural contexts, to develop programme theory and co-design a prototype intervention to improve persistent breathlessness management in India. METHODS AND ANALYSIS: Using a Realist approach, Intervention Mapping and the Medical Research Council Complex Intervention Framework we will undertake two phases of work supported by our Expert Group (of respiratory, primary, palliative care physicians) and key stakeholder groups (opinion leader clinicians, community health workers and people with lived experiences of breathlessness). 1) Realist review and evaluation to identify and refine evidence and theory for breathlessness self-management, producing intervention and implementation programme theory. We will identify literature through our Expert Group, scoping searches and systematic searches (Medline, Ebscohost, CINAHL, Scopus, Psychinfo). We will map intervention components to 'what works, for whom, and where.' 2) Intervention development using Intervention Mapping to map intervention and implementation programme theory to intervention components, develop materials to support intervention delivery, and co-design a prototype educational intervention ready for early acceptability and delivery-feasibility testing and evaluation planning in India. Use of stakeholder groups is to allow people with experience of breathlessness and/or its management to contribute their views on content developed by our team based upon review of secondary data sources. Experts and Stakeholders are therefore not research subjects but are included as extended members of the study team and will not follow informed consent procedures. Experts and stakeholders will be acknowledge in outputs arising from our project if they wish to be. Our review conduct will be consistent with RAMESES quality standards. DISCUSSION: At the conclusion of our study, we will have co-designed a breathlessness intervention for use in the community setting in India ready for further evaluation of: effectiveness, socioeconomic outcomes, acceptability and transferability to other low resource settings.

How can NHS trusts in England optimise strategies to improve the mental health and well-being of hospital doctors? The Care Under Pressure 3 (CUP3) realist evaluation study protocol.

INTRODUCTION: The growing incidence of mental ill health in doctors was a major issue in the UK and internationally, even prior to the COVID-19 pandemic. It has significant and far-reaching implications, including poor quality or inconsistent patient care, absenteeism, workforce attrition and retention issues, presenteeism, and increased risk of suicide. Existing approaches to workplace support do not take into account the individual, organisational and social factors contributing to mental ill health in doctors, nor how interventions/programmes might interact with each other within the workplace. The aim of this study is to work collaboratively with eight purposively selected National Health Service (NHS) trusts within England to develop an evidence-based implementation toolkit for all NHS trusts to reduce doctors' mental ill health and its impacts on the workforce. METHODS AND ANALYSIS: The project will incorporate three phases. Phase 1 develops a typology of interventions to reduce doctors' mental ill health. Phase 2 is a realist evaluation of the existing combinations of strategies being used by acute English healthcare trusts to reduce doctors' mental ill health (including preventative promotion of well-being), based on 160 interviews with key stakeholders. Phase 3 synthesises the insights gained through phases 1 and 2, to create an implementation toolkit that all UK healthcare trusts can use to optimise their strategies to reduce doctors' mental ill health and its impact on the workforce and patient care. ETHICS AND DISSEMINATION: Ethical approval has been granted for phase 2 of the project from the NHS Research Ethics Committee (REC reference number 22/WA/0352). As part of the conditions for our ethics approval, the sites included in our study will remain anonymous. To ensure the relevance of the study's outputs, we have planned a wide range of dissemination strategies: an implementation toolkit for healthcare leaders, service managers and doctors; conventional academic outputs such as journal manuscripts and conference presentations; plain English summaries; cartoons and animations; and a media engagement campaign.

Interventions to address unprofessional behaviours between staff in acute care: what works for whom and why? A realist review.

BACKGROUND: Unprofessional behaviour (UB) between staff encompasses various behaviours, including incivility, microaggressions, harassment, and bullying. UB is pervasive in acute healthcare settings and disproportionately impacts minoritised staff. UB has detrimental effects on staff wellbeing, patient safety and organisational resources. While interventions have been implemented to mitigate UB, there is limited understanding of how and why they may work and for whom. METHODS: This study utilised a realist review methodology with stakeholder input to improve understanding of these complex context-dependent interventions. Initial programme theories were formulated drawing upon scoping searches and reports known to the study team. Purposive systematic searches were conducted to gather grey and published global literature from databases. Documents were selected if relevant to UB in acute care settings while considering rigour and relevance. Data were extracted from these reports, synthesised, and initial theories tested, to produce refined programme theories. RESULTS: Of 2977 deduplicated records, 148 full text reports were included with 42 reports describing interventions to address UB in acute healthcare settings. Interventions drew on 13 types of behaviour change strategies and were categorised into five types of intervention (1) single session (i.e. one off); (2) multiple session; (3) single or multiple sessions combined with other actions (e.g. training sessions plus a code of conduct); (4) professional accountability and reporting programmes and; (5) structured culture change interventions. We formulated 55 context-mechanism-outcome configurations to explain how, why, and when these interventions work. We identified twelve key dynamics to consider in intervention design, including importance of addressing systemic contributors, rebuilding trust in managers, and promoting a psychologically safe culture; fifteen implementation principles were identified to address these dynamics. CONCLUSIONS: Interventions to address UB are still at an early stage of development, and their effectiveness to reduce UB and improve patient safety is unclear. Future interventions should incorporate knowledge from behavioural and implementation science to affect behaviour change; draw on multiple concurrent strategies to address systemic contributors to UB; and consider the undue burden of UB on minoritised groups. STUDY REGISTRATION: This study was registered on the international database of prospectively registered systematic reviews in health and social care (PROSPERO): https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021255490 .

Health service improvement using positive patient feedback: Systematic scoping review.

BACKGROUND: Healthcare services regularly receive patient feedback, most of which is positive. Empirical studies suggest that health services can use positive feedback to create patient benefit. Our aim was to map all available empirical evidence for how positive patient feedback creates change in healthcare settings. METHODS: Empirical studies in English were systematically identified through database searches (ACM Digital Library, AMED, ASSIA, CINAHL, MEDLINE and PsycINFO), forwards and backwards citation, and expert consultation. We summarise the characteristics of included studies and the feedback they consider, present a thematic synthesis of qualitative findings, and provide narrative summaries of quantitative findings. RESULTS: 68 papers were included, describing research conducted across six continents, with qualitative (n = 51), quantitative (n = 10), and mixed (n = 7) methods. Only two studies were interventional. The most common settings were hospitals (n = 27) and community healthcare (n = 19). The most common recipients were nurses (n = 29). Most outcomes described were desirable. These were categorised as (a) short-term emotional change for healthcare workers (including feeling motivated and improved psychological wellbeing); (b) work-home interactional change for healthcare workers (such as improved home-life relationships); (c) work-related change for healthcare workers (such as improved performance and staff retention). Some undesirable outcomes were described, including envy when not receiving positive feedback. The impact of feedback may be moderated by characteristics of particular healthcare roles, such as night shift workers having less interaction time with patients. Some factors moderating the change created by feedback are modifiable. CONCLUSION: Further interventional research is required to assess the effectiveness and cost-effectiveness of receiving positive feedback in creating specific forms of change such as increases in staff retention. Healthcare managers may wish to use positive feedback more regularly, and to address barriers to staff receiving feedback.

Views and experiences of opioid access amongst palliative care providers and public representatives in a low-resource setting: A qualitative interview study.

Opioids (e.g. morphine) are affordable, effective interventions for cancer-related pain. However, equity of access to this key medication remains a global challenge, particularly in low- and middle-income countries. We aimed to explore views of palliative care providers and public-representatives about opioid analgesia access in two States in India. We conducted a qualitative study using semi-structured interviews. Transcribed audio-recordings were subjected to thematic analysis using a Framework Approach. Palliative care providers and public-representatives were purposively sampled from services reporting consistent opioid availability and prescribing (≥4kg per annum) from Karnataka and Kerala. Twenty participants (doctors (10), nurses (4), pharmacists (2), service managers (2) and public-representatives (2) were interviewed. Three themes were identified: 1) Attitudes and awareness: opioid treatments are perceived as end-of-life (last days/weeks) interventions; fears of addiction and misunderstanding of pain management goals limit access. 2) Expected and unexpected inequities: patients/carers from lower socioeconomic strata accept doctor recommendations if opioids are affordable, more educated patients/families have reservations about opioids, delay access and perceive expensive medicines as better. Non-palliative care specialist doctors have negative entrenched views and require specialist training. 3) Experiential learning-positive experiences can positively alter attitudes (e.g., participants in Kerala report improved attitudes, awareness and understanding influenced by exposure and community awareness, but experience can also reinforce perceptions as end-of-life care. Entrenched negative views are reinforced by poor experiences while positive experiences improve attitudes. To promote access, opioid prescribing must be needs-based rather than prognosis-based. Addressing the lack of training for non-palliative care workforce would help overcome a major barrier.

Modified-release morphine or placebo for chronic breathlessness: the MABEL trial protocol.

Chronic breathlessness, a persistent and disabling symptom despite optimal treatment of underlying causes, is a frightening symptom with serious and widespread impact on patients and their carers. Clinical guidelines support the use of morphine for the relief of chronic breathlessness in common long-term conditions, but questions remain around clinical effectiveness, safety and longer term (>7 days) administration. This trial will evaluate the effectiveness of low-dose oral modified-release morphine in chronic breathlessness. This is a multicentre, parallel group, double-blind, randomised, placebo-controlled trial. Participants (n=158) will be opioid-naïve with chronic breathlessness due to heart or lung disease, cancer or post-coronavirus disease 2019. Participants will be randomised 1:1 to 5 mg oral modified-release morphine/placebo twice daily and docusate/placebo 100 mg twice daily for 56 days. Non-responders at Day 7 will dose escalate to 10 mg morphine/placebo twice daily at Day 15. The primary end-point (Day 28) measure will be worst breathlessness severity (previous 24 h). Secondary outcome measures include worst cough, distress, pain, functional status, physical activity, quality of life, and early identification and management of morphine-related side-effects. At Day 56, participants may opt to take open-label, oral modified-release morphine as part of usual care and complete quarterly breathlessness and toxicity questionnaires. The study is powered to be able to reject the null hypothesis and an embedded normalisation process theory-informed qualitative substudy will explore the adoption of morphine as a first-line pharmacological treatment for chronic breathlessness in clinical practice if effective.

Connecting the science and practice of implementation - applying the lens of context to inform study design in implementation research.

The saying "horses for courses" refers to the idea that different people and things possess different skills or qualities that are appropriate in different situations. In this paper, we apply the analogy of "horses for courses" to stimulate a debate about how and why we need to get better at selecting appropriate implementation research methods that take account of the context in which implementation occurs. To ensure that implementation research achieves its intended purpose of enhancing the uptake of research-informed evidence in policy and practice, we start from a position that implementation research should be explicitly connected to implementation practice. Building on our collective experience as implementation researchers, implementation practitioners (users of implementation research), implementation facilitators and implementation educators and subsequent deliberations with an international, inter-disciplinary group involved in practising and studying implementation, we present a discussion paper with practical suggestions that aim to inform more practice-relevant implementation research.

Improving asthma care through implementation of the SENTINEL programme: findings from the pilot site.

Aim: Short-acting ß2-agonist (SABA) overuse adversely impacts asthma-related outcomes and the environment. The SABA rEductioN Through ImplemeNting Hull asthma guidELines (SENTINEL) programme aims to reduce SABA overuse through supported implementation of an adult asthma guideline, which advocates for a SABA-free maintenance and reliever therapy (MART)-preferred treatment where appropriate, across six primary care networks (PCNs) in the UK. We present findings on patient/disease characteristics, asthma prescribing patterns and exacerbation rates from the pilot PCN. Methods: Patients (aged ≥18 years, prescribed at least one inhaled therapy) and their prescribed asthma treatments were characterised using National Health Service data. Asthma treatments and exacerbations were analysed for three periods: 24‒12 months pre-, 12 months pre- and 12 months post-SENTINEL implementation (November 2020‒January 2021). Results: Of the 2571 registered asthma patients, 33.6% (n=864) underwent an asthma review, of whom 44.7% (n=386) were transitioned to MART. Fewer patients were prescribed three or more SABA canisters per year post-implementation in the overall asthma population (45.4% and 46.2% during 24‒12 months and 12 months pre-implementation, respectively, and 23.9% 12 months post-implementation), and in the two subgroups: 1) those who had an asthma review (74.5% and 83.6% during 24‒12 months and 12 months pre-implementation, respectively, and 26.5% post-implementation); and 2) those transitioned to MART following a review (76.4% and 86.5% during 24‒12 months and 12 months pre-implementation, respectively, and 16.3% post-implementation). A higher proportion of patients were exacerbation-free post-implementation in the overall asthma population and in the two subgroups. At least 71.5% of patients transitioned to MART were still prescribed MART 12 months post-implementation, of whom ≥86.7% were SABA-free. Conclusion: SENTINEL implementation led to reduced SABA prescribing, increased inhaled corticosteroid uptake and fewer asthma exacerbations. MART was considered appropriate for ∼50% of reviewed patients, with improved prescribing patterns sustained post-implementation.

The biological paradigm of psychosis in crisis: A Kuhnian analysis.

The philosophy of Thomas Kuhn proposes that scientific progress involves periods of crisis and revolution in which previous paradigms are discarded and replaced. Revolutions in how mental health problems are conceptualised have had a substantial impact on the work of mental health nurses. However, despite numerous revolutions within the field of mental health, the biological paradigm has remained largely dominant within western healthcare, especially in orientating the understanding and treatment of psychosis. This paper utilises concepts drawn from the philosophy of Thomas Kuhn to explore the impact of what Kuhn terms 'anomalies' within the dominant biological paradigm: the anomaly of the meaningful utterance, the anomaly of complex aetiology and taxonomy and the anomaly of pharmacological inefficacy in recovery. The paper argues that the biological paradigm for understanding psychosis is in crisis and explores the implications for mental health nursing.

Combined KRASG12C and SOS1 inhibition enhances and extends the anti-tumor response in KRASG12C-driven cancers by addressing intrinsic and acquired resistance.

Efforts to improve the anti-tumor response to KRASG12C targeted therapy have benefited from leveraging combination approaches. Here, we compare the anti-tumor response induced by the SOS1-KRAS interaction inhibitor, BI-3406, combined with a KRASG12C inhibitor (KRASG12Ci) to those induced by KRASG12Ci alone or combined with SHP2 or EGFR inhibitors. In lung cancer and colorectal cancer (CRC) models, BI-3406 plus KRASG12Ci induces an anti-tumor response stronger than that observed with KRASG12Ci alone and comparable to those by the other combinations. This enhanced anti-tumor response is associated with a stronger and extended suppression of RAS-MAPK signaling. Importantly, BI-3406 plus KRASG12Ci treatment delays the emergence of acquired adagrasib resistance in both CRC and lung cancer models and is associated with re-establishment of anti-proliferative activity in KRASG12Ci-resistant CRC models. Our findings position KRASG12C plus SOS1 inhibition therapy as a promising strategy for treating both KRASG12C-mutated tumors as well as for addressing acquired resistance to KRASG12Ci.