Validated machine learning tools to distinguish immune checkpoint inhibitor, radiotherapy, COVID-19 and other infective pneumonitis.

BACKGROUND: Pneumonitis is a well-described, potentially disabling, or fatal adverse effect associated with both immune checkpoint inhibitors (ICI) and thoracic radiotherapy. Accurate differentiation between checkpoint inhibitor pneumonitis (CIP) radiation pneumonitis (RP), and infective pneumonitis (IP) is crucial for swift, appropriate, and tailored management to achieve optimal patient outcomes. However, correct diagnosis is often challenging, owing to overlapping clinical presentations and radiological patterns. METHODS: In this multi-centre study of 455 patients, we used machine learning with radiomic features extracted from chest CT imaging to develop and validate five models to distinguish CIP and RP from COVID-19, non-COVID-19 infective pneumonitis, and each other. Model performance was compared to that of two radiologists. RESULTS: Models to distinguish RP from COVID-19, CIP from COVID-19 and CIP from non-COVID-19 IP out-performed radiologists (test set AUCs of 0.92 vs 0.8 and 0.8; 0.68 vs 0.43 and 0.4; 0.71 vs 0.55 and 0.63 respectively). Models to distinguish RP from non-COVID-19 IP and CIP from RP were not superior to radiologists but demonstrated modest performance, with test set AUCs of 0.81 and 0.8 respectively. The CIP vs RP model performed less well on patients with prior exposure to both ICI and radiotherapy (AUC 0.54), though the radiologists also had difficulty distinguishing this test cohort (AUC values 0.6 and 0.6). CONCLUSION: Our results demonstrate the potential utility of such tools as a second or concurrent reader to support oncologists, radiologists, and chest physicians in cases of diagnostic uncertainty. Further research is required for patients with exposure to both ICI and thoracic radiotherapy.

Multimodality local consolidative treatment versus conventional care of advanced lung cancer after first-line systemic anti-cancer treatment: study protocol for the RAMON multicentre randomised controlled trial with an internal pilot.

INTRODUCTION: Lung cancer is the most common cause of cancer death worldwide and most patients present with extensive disease. One-year survival is improving but remains low (37%) despite novel systemic anti-cancer treatments forming the current standard of care. Although new therapies improve survival, most patients have residual disease after treatment, and little is known on how best to manage it. Therefore, residual disease management varies across the UK, with some patients receiving only maintenance systemic anti-cancer treatment while others receive local consolidative treatment (LCT), alongside maintenance systemic anti-cancer treatment. LCT can be a combination of surgery, radiotherapy and/or ablation to remove all remaining cancer within the lung and throughout the body. This is intensive, expensive and impacts quality of life, but we do not know if it results in better survival, nor the extent of impact on quality of life and what the cost might be for healthcare providers. The RAMON study (RAdical Management Of Advanced Non-small cell lung cancer) will evaluate the acceptability, effectiveness and cost-effectiveness of LCT versus no LCT after first-line systemic treatment for advanced lung cancer. METHODS AND ANALYSIS: RAMON is a pragmatic open multicentre, parallel group, superiority randomised controlled trial. We aim to recruit 244 patients aged 18 years and over with advanced non-small-cell lung cancer from 40 UK NHS hospitals. Participants will be randomised in a 1:1 ratio to receive LCT alongside maintenance treatment, or maintenance treatment alone. LCT will be tailored to each patient's specific disease sites. Participants will be followed up for a minimum of 2 years. The primary outcome is overall survival from randomisation. ETHICS AND DISSEMINATION: The West of Scotland Research Ethics Committee (22/WS/0121) gave ethical approval in August 2022 and the Health Research Authority in September 2022. Participants will provide written informed consent before participating in the study. Findings will be presented at international meetings, in peer-reviewed publications, through patient organisations and notifications to patients. TRIAL REGISTRATION NUMBER: ISRCTN11613852.

'The dark before the dawn': the 2021 British Thoracic Society Audit of the treatment of tobacco dependency in acute trusts.

Smoking remains the single largest cause of preventable death, disability and health inequality. Smoking tobacco directly contributes to over 500 000 hospital admissions each year, making hospitals an important location to optimise treatment for tobacco dependency. The third British Thoracic Society Tobacco Dependency Audit was undertaken to determine how effectively national standards for treating tobacco-dependent smokers have been implemented and assess if any progress has been made from previous audits. Data on 14579 patients from 119 hospitals revealed 21% of patients were current smokers, 45% were offered very brief advice and 5% prescribed combination nicotine replacement therapy or varenicline. Only 9% completed a consultation with a specialist tobacco dependency practitioner during their inpatient stay and fewer than 1% of smokers were abstinent at 4 weeks following discharge. Clinical leadership of tobacco dependency services was deficient, and staff were ill equipped in supporting current smokers in their efforts to quit with only 50% of trusts offering regular smoking cessation training. There has been little meaningful improvement from previous audits and there remains woefully inadequate provision of tobacco dependency treatment for patients who smoke. The National Health Service (NHS) Long Term Plan has committed substantial, new funding to the NHS to ensure every patient that smokes admitted to hospital will be offered evidence-based support and treatment for tobacco dependency. The findings of this audit highlight the urgency with which this programme must be implemented to tackle the greatest cause of premature death in the UK and to achieve the wider well-recognised benefits for the healthcare system.

Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion (STRATIFY): protocol of a prospective, multicentre, observational study.

INTRODUCTION: Recurrence rate following radical therapy for lung cancer remains high, potentially reflecting occult metastatic disease, and better staging tools are required. Minimal pleural effusion (mini-PE) is associated with particularly high recurrence risk and is defined as an ipsilateral pleural collection (<1/3 hemithorax on chest radiograph), which is either too small to safely aspirate fluid for cytology using a needle, or from which fluid cytology is negative. Thoracoscopy (local anaesthetic thoracoscopy (LAT) or video-assisted thoracoscopic surgery (VATS)) is the gold-standard diagnostic test for pleural malignancy in patients with larger symptomatic effusions. Staging by Thoracoscopy in potentially radically treatable Lung Cancer associated with Minimal Pleural Effusion (STRATIFY) will prospectively evaluate thoracoscopic staging in lung cancer associated-mini-PE for the first time. METHODS AND ANALYSIS: STRATIFY is a prospective multicentre observational study. Recruitment opened in January 2020. The primary objective is to determine the prevalence of detectable occult pleural metastases (OPM). Secondary objectives include assessment of technical feasibility and safety, and the impact of thoracoscopy results on treatment plans, overall survival and recurrence free survival. Inclusion criteria are (1) suspected/confirmed stages I-III lung cancer, (2) mini-PE, (3) Performance Status 0-2 (4), radical treatment feasible if OPM excluded, (5) ≥16 years old and (6) informed consent. Exclusion criteria are any metastatic disease or contraindication to the chosen thoracoscopy method (LAT/VATS). All patients have LAT or VATS within 7 (±5) days of registration, with results returned to lung cancer teams for treatment planning. Following an interim analysis, the sample size was reduced from 96 to 50, based on a lower-than-expected OPM rate. An MRI substudy was removed in November 2022 due to pandemic-related site setup/recruitment delays. These also necessitated a no-cost recruitment extension until October 2023. ETHICS AND DISSEMINATION: Protocol approved by the West of Scotland Research Ethics Committee (Ref: 19/WS/0093). Results will be published in peer-reviewed journals and presented at international meetings. TRIAL REGISTRATION NUMBER: ISRCTN13584097.

Safety of curative-intent lung cancer surgery in older patients (octogenarians): A contemporary multicentre cohort study.

INTRODUCTION: Despite octogenarians representing an ever-increasing proportion of patients with lung cancer, there is a paucity of evidence describing outcomes after lung resection for these patients. We aimed to evaluate short and mid-term outcomes for octogenarians after lung resection. MATERIALS AND METHODS: A total of 5,470 consecutive patients undergoing lung resection for primary lung cancer from 2012-2019 in two UK centres were included. Primary outcomes were perioperative, 90-day, and one-year mortality in the octogenarian vs. non-octogenarian cohort. Appropriate statistical tests were used to compare outcomes between octogenarian and non-octogenarian patients. Secondary outcomes were post-operative complications and to validate the performance of the Thoracoscore model in the octogenarian cohort. RESULTS: Overall, 9.4% (n=513) of patients were aged ≥80. The rates of 90-day mortality, one-year mortality, and post-operative atrial fibrillation were significantly higher for octogenarians. The one-year mortality rate for octogenarians fell significantly over time (2012-2015: 16.5% vs 2016-2019: 10.2%, p=0.034). Subgroup analysis (2016-2019 only) demonstrated no significant difference in peri-operative, 90-day, or one-year mortality between octogenarian and non-octogenarian patients. Validation of the Thoracoscore model demonstrated modest discrimination and acceptable calibration. DISCUSSION: Mortality for octogenarians fell significantly over time in this study. Indeed, when confined to the most recent time period, comparable rates of both 90-day and one-year mortality for octogenarian and non-octogenarian patients were seen. Whilst preventative strategies to reduce the incidence of post-operative atrial fibrillation in octogenarians should be considered, these findings demonstrate that following appropriate patient selection, octogenarians can safely undergo lung resection for lung cancer.

Endobronchial lymphoma - A rare cause of airway obstruction.

Endobronchial involvement is a very rare manifestation of Non-Hodgkin's Lymphoma, which if left untreated, may cause airway obstruction and lead to respiratory failure. Only a few cases have been reported in the literature. This aim of this case report is to highlight the importance of having a high index of suspicion of endobronchial lymphoma in patients presenting with endobronchial lesions either in isolation or in conjunction with widespread lymphadenopathy.

Invitation strategies and participation in a community-based lung cancer screening programme located in areas of high socioeconomic deprivation.

INTRODUCTION: Although lung cancer screening is being implemented in the UK, there is uncertainty about the optimal invitation strategy. Here, we report participation in a community screening programme following a population-based invitation approach, examine factors associated with participation, and compare outcomes with hypothetical targeted invitations. METHODS: Letters were sent to all individuals (age 55-80) registered with a general practice (n=35 practices) in North and East Manchester, inviting ever-smokers to attend a Lung Health Check (LHC). Attendees at higher risk (PLCOm2012NoRace score≥1.5%) were offered two rounds of annual low-dose CT screening. Primary care recorded smoking codes (live and historical) were used to model hypothetical targeted invitation approaches for comparison. RESULTS: Letters were sent to 35 899 individuals, 71% from the most socioeconomically deprived quintile. Estimated response rate in ever-smokers was 49%; a lower response rate was associated with younger age, male sex, and primary care recorded current smoking status (adjOR 0.55 (95% CI 0.52 to 0.58), p<0.001). 83% of eligible respondents attended an LHC (n=8887/10 708). 51% were eligible for screening (n=4540/8887) of whom 98% had a baseline scan (n=4468/4540). Screening adherence was 83% (n=3488/4199) and lung cancer detection 3.2% (n=144) over 2 rounds. Modelled targeted approaches required 32%-48% fewer invitations, identified 94.6%-99.3% individuals eligible for screening, and included 97.1%-98.6% of screen-detected lung cancers. DISCUSSION: Using a population-based invitation strategy, in an area of high socioeconomic deprivation, is effective and may increase screening accessibility. Due to limitations in primary care records, targeted approaches should incorporate historical smoking codes and individuals with absent smoking records.

Results of the Meso-ORIGINS feasibility study regarding collection of matched benign-mesothelioma tissue pairs by longitudinal surveillance.

OBJECTIVES: To assess key elements of the design for Meso-ORIGINS (Mesothelioma Observational study of RIsk prediction and Generation of paired benign-meso tissue samples, Including a Nested MRI Substudy), an ambitious, UK-wide, prospective study that will collect ≥63 matched benign-mesothelioma tissue pairs through longitudinal surveillance and repeat biopsy of patients with asbestos-associated pleural inflammation (AAPI). DESIGN: A multicentre, mixed-methods feasibility study, comprising a prospective observational element, evaluating recruitment feasibility, technical feasibility of repeat local anaesthetic thoracoscopy (LAT) and patient acceptability, and a retrospective cohort study focused on AAPI-mesothelioma evolution rate, informing sample size. SETTING: 4 UK pleural disease centres (February 2019-January 2020). PARTICIPANTS: Patients with AAPI (history or typical imaging plus appropriate pleural histology) were eligible for both elements. In August 2019, eligibility for the prospective element was broadened, including addition of radiological AAPI for technical feasibility and patient acceptability endpoints only. Retrospective cases required ≥2 years follow-up. OUTCOME MEASURES: A prospective recruitment target was set a priori at 27 histological AAPI cases (or 14 in any 6 months). Technical feasibility and patient acceptability were determined at 6-month follow-up by thoracic ultrasound surrogates and questionnaires, respectively. Retrospective malignant pleural mesothelioma evolution rate was defined by proportion (95% CI). Baseline predictors of evolution were identified using logistic regression. RESULTS: 296 patients with AAPI (39 prospective, 257 retrospective) were recruited/selected. 21/39 prospective recruits were histologically diagnosed (target n=27). Repeat LAT was technically feasible and acceptable in 13/28 (46%) and 24/36 (67%) cases with complete follow-up data. Mesothelioma evolution was confirmed histologically in 36/257 retrospective cases (14% (95% CI 10.3% to 18.8%)) and associated with malignant CT features (OR 4.78 (95% CI 2.36 to 9.86)) and age (OR 1.06 (95% CI 1.02 to 1.12)). CONCLUSIONS: Our initial eligibility criteria were too narrow. Meso-ORIGINS will recruit a broader cohort, including prevalent cases, any biopsy type and patients with malignant CT features. A range of rebiopsy techniques will be allowed, accounting for technical and patient factors. The sample size has been reduced to 500. TRIAL REGISTRATION NUMBER: ISRCTN12840870.

Proposed quality indicators and recommended standard reporting items in performance of EBUS bronchoscopy: An official World Association for Bronchology and Interventional Pulmonology Expert Panel consensus statement.

BACKGROUND: Since their introduction, both linear and radial endobronchial ultrasound (EBUS) have become an integral component of the practice of Pulmonology and Thoracic Oncology. The quality of health care can be measured by comparing the performance of an individual or a health service with an ideal threshold or benchmark. The taskforce sought to evaluate quality indicators in EBUS bronchoscopy based on clinical relevance/importance and on the basis that observed significant variation in outcomes indicates potential for improvement in health care outcomes. METHODS: A comprehensive literature review informed the composition of a comprehensive list of candidate quality indicators in EBUS. A multiple-round modified Delphi consensus process was subsequently performed with the aim of reaching consensus over a final list of quality indicators and performance targets for these indicators. Standard reporting items were developed, with a strong preference for items where evidence demonstrates a relationship with quality indicator outcomes. RESULTS: Twelve quality Indicators are proposed, with performance targets supported by evidence from the literature. Standardized reporting items for both radial and linear EBUS are recommended, with evidence supporting their utility in assessing procedural outcomes presented. CONCLUSION: This statement is intended to provide a framework for individual proceduralists to assess the quality of EBUS they provide their patients through the identification of clinically relevant, feasible quality measures. Emphasis is placed on outcome measures, with a preference for consistent terminology to allow communication and benchmarking between centres.

What is the optimal management of potentially resectable stage III-N2 NSCLC? Results of a fixed-effects network meta-analysis and economic modelling.

Introduction: There is a critical need to understand the optimal treatment regimen in patients with potentially resectable stage III-N2 nonsmall cell lung cancer (NSCLC). Methods: A systematic review of randomised controlled trials was carried out using a literature search including the CDSR, CENTRAL, DARE, HTA, EMBASE and MEDLINE bibliographic databases. Selected trials were used to perform a Bayesian fixed-effects network meta-analysis and economic modelling of treatment regimens relevant to current-day treatment options: chemotherapy plus surgery (CS), chemotherapy plus radiotherapy (CR) and chemoradiotherapy followed by surgery (CRS). Findings: Six trials were prioritised for evidence synthesis. The fixed-effects network meta-analyses demonstrated an improvement in disease-free survival (DFS) for CRS versus CS and CRS versus CR of 0.34 years (95% CI 0.02-0.65) and 0.32 years (95% CI 0.05-0.58) respectively, over a 5-year period. No evidence of effect was observed in overall survival although point estimates favoured CRS. The probabilities that CRS had a greater mean survival time and greater probability of being alive than the reference treatment of CR at 5 years were 89% and 86% respectively. Survival outcomes for CR and CS were essentially equivalent. The economic model calculated that CRS and CS had incremental cost-effectiveness ratios of £19 000/quality-adjusted life-year (QALY) and £78 000/QALY compared to CR. The probability that CRS generated more QALYs than CR and CS was 94%. Interpretation: CRS provides an extended time in a disease-free state leading to improved cost-effectiveness over CR and CS in potentially resectable stage III-N2 NSCLC.

Brain imaging in lung cancer staging: A real-world, multi-centre study of prevalence of brain metastases, impact on treatment and re-modelling of the NICE health economic analysis.

INTRODUCTION: In 2019, the National Institute for Health and Care Excellence (NICE) updated their recommendations with respect to brain imaging in the staging of non-small cell lung cancer (NSCLC) based on an analytic cost-effectiveness model using published data and modelling assumptions from committee experts. In this study, we aimed to re-run this model using real-world multi-centre UK data. MATERIALS AND METHODS: Retrospective data was collected on consecutive patients with radically treatable clinical stage II and III lung cancer from eleven acute NHS Trusts during the calendar year 01/01/2018 to 31/12/2018. Following a written application to the NICE lung cancer guideline committee, we were granted access to the NG122 brain imaging economic model for the purpose of updating the input parameters in line with the real-world findings from this study. RESULTS: A total of 444 patients had data for analysis. The combined prevalence of occult brain metastases was 6.2% (10/165) in stage II and 6% (17/283) in stage III, compared to 9.5% and 9.3% used in the NICE economic model. 30% of patients with clinical stage III NSCLC and occult BMs on pre-treatment imaging went onto complete the planned curative intent treatment of extracranial disease, 60% completed SRS to the brain and 30% completed WBRT. This compares to 0%, 10% and 0% in the NICE assumptions. The health economic analysis concluded that brain imaging was no longer cost-effective in stage II disease (ICERs £50,023-£115,785) whilst brain imaging remained cost-effective for stage III patients (ICERs 17,000-£22,173), with MRI being the most cost-effective strategy. CONCLUSION: This re-running of the NICE health economic model with real-world data strongly supports the NICE guideline recommendation for brain imaging prior to curative-intent treatment in stage III lung cancer but questions the cost-effectiveness of CT brain imaging prior to curative-intent treatment in stage II lung cancer.

Feasibility and outcomes of a real-world regional lung cancer prehabilitation programme in the UK.

BACKGROUND: Prehabilitation, or multimodality patient optimisation before major treatment, has demonstrated meaningful improvements in patients' outcomes. In the setting of lung cancer surgery, postoperative complications and length of hospital stay are reduced, but there is currently limited access to prehabilitation. Prehab4Cancer (P4C) is an innovative regional programme serving all areas of Greater Manchester (GM). METHODS: The lung cancer P4C service commenced in 2019 as a collaboration between the GM Cancer alliance and 12 leisure and community organisations. Patients planning surgical resection could be referred to receive exercise, nutrition, and well-being assessment and interventions before surgery. We evaluated the programme's feasibility, uptake, and outcomes during the 11 months before COVID-19 restrictions. RESULTS: In total, 377 patients were referred to the lung cancer P4C service from all 11 hospitals in GM. Of the patients reached by telephone, 80.0% (n=280/348) attended initial P4C assessment, which occurred a median of 8 days (inter-quartile range [IQR]: 4-14) after referral. In addition, 74.3% (n=280/377) attended for baseline assessment and 47.7% (n=180/377) completed prehabilitation, attending a median of six sessions (IQR: 4-9). Statistically significant improvements in all objective physiological and subjective functional assessments were observed preoperatively, including a mean increase in the incremental shuttle walk test of 50 m (95% confidence interval: 25-74; P<0.001). CONCLUSIONS: The P4C programme demonstrated feasibility at scale, high uptake, and promising impact on the status of patients with lung cancer before surgery. P4C is the first regional prehabilitation service internationally, and this evaluation provides a framework for implementing similar services in other regions.

Patient survey examining the experience of care of a hospital-based opt-out tobacco dependency treatment service (the CURE Project).

INTRODUCTION: Treating tobacco dependency in patients admitted to hospital is a key priority in the National Health Service long-term plan. This service evaluation assessed the perception, needs and experience of care within an opt-out hospital-based tobacco dependency treatment service (the Conversation, Understand, Replace, Experts and Evidence Base (CURE) team) in North-West England. METHODS: A survey was offered to all eligible patients between 1 July 2020 and 30 September 2020. Eligibility criteria were adult patients identified as an active smoker being approached by the CURE team as part of the standard opt-out service model, on a non-covid ward without a high suspicion of COVID-19 infection and able to read and write in English. RESULTS: 106 completed surveys were evaluated. Participants demonstrated high levels of tobacco dependency with an average of 37 years smoking history and 66% describing the onset of cravings within 30 min of hospital admission. The average number quit attempts in the previous 12 months was 1.3 but only 9% had used the most effective National Institute for Health and Care Excellence (NICE) recommended treatments. 100% felt the opt-out service model was appropriate and 96% stated the treatment and support they had received had prompted them to consider a further quit attempt. 82% of participants rated their experience of care as 9/10 or 10/10. Participants wanted a broad range of support post discharge with the most popular option being with their general practitioner. 66% and 65% of participants would have been interested in a vaping kit as stop smoking intervention and support vaping-friendly hospital grounds respectively. CONCLUSION: These results suggest this hospital-based, opt-out tobacco dependency treatment service delivers high-quality experience of care and meets the needs of the patients it serves. It also highlights the opportunity to enhance outcomes by providing access to NICE recommended most-effective interventions (varenicline, vaping and combination nicotine replacement therapy) and providing flexible, individualised discharge pathways.

Regional single-queue scheduling platform for specialist diagnostics in the lung cancer pathway: accelerating cancer recovery from the COVID-19 pandemic.

Lung cancer is the single biggest cause of cancer death. The diagnostic pathway can be complex, including specialist cancer diagnostics that are not performed at every hospital. One such example is endobronchial ultrasound (EBUS), a day-case bronchoscopic procedure used for nodal staging and tissue diagnosis. In this proof-of-concept pilot in Greater Manchester, we tested a novel digital EBUS booking platform. This platform was accessible across multiple acute care trusts and provided visibility of all available EBUS appointments, allowing referring teams to book directly into the appropriate slot. During a 6-month pilot, 193 EBUS procedures were booked through this new single-queue platform. The median waiting times reduced by 2 days from 9 to 7 days (22% reduction and saving approximately 386 days in total) and reduced variation in waiting times by 1 day from 5 to 4 days (20% reduction). 98% of patients who completed an experience of care survey felt the process was 'very well' or 'well' organised and 77% felt the most important factor in deciding where to have their EBUS was the earliest possible appointment regardless of travel. This proof-of-concept pilot has shown improvements in cancer waiting times with significant future potential in delivering specialist cancer diagnostics.

Understanding the implementation strategy of a secondary care tobacco addiction treatment pathway (the CURE project) in England: a strategic behavioural analysis.

OBJECTIVES: The Conversation, Understand, Replace, Experts and evidence-based treatment (CURE) project implemented an evidence-based intervention that offers a combination of pharmacotherapy and behavioural support to tobacco-dependent inpatients. Understanding key characteristics of CURE's implementation strategy, and identifying areas for improvement, is important to support the roll-out of nationwide tobacco dependence services. This study aimed to (1) specify key characteristics of CURE's exiting implementation strategy and (2) develop theoretical-informed and stakeholder-informed recommendations to optimise wider roll-out. DESIGN AND METHODS: Data were collected via document review and secondary analysis of interviews with 10 healthcare professionals of a UK hospital. Intervention content was specified through behaviour change techniques (BCTs) and intervention functions within the Behaviour Change Wheel. A logic model was developed to specify CURE's implementation strategy and its mechanisms of impact. We explored the extent to which BCTs and intervention functions addressed the key theoretical domains influencing implementation using prespecified matrices. The development of recommendations was conducted over a two-round Delphi exercise. RESULTS: We identified six key theoretical domains of influences: 'environmental context and resources', 'goals', 'social professional role and identity', 'social influences', 'reinforcement' and 'skills'. The behavioural analysis identified 26 BCTs, 4 intervention functions and 4 policy categories present within the implementation strategy. The implementation strategy included half the relevant intervention functions and BCTs to target theoretical domains influencing CURE implementation, with many BCTs focusing on shaping knowledge. Recommendations to optimise content were developed following stakeholder engagement. CONCLUSIONS: CURE offers a strong foundation from which a tobacco dependence treatment model can be developed in England. The exiting strategy could be strengthened via the inclusion of more theoretically congruent BCTs, particularly relating to 'environmental context and resources'. The recommendations provide routes to optimisation that are both theoretically grounded and stakeholder informed. Future research should assess the feasibility/acceptability of these recommendations in the wider secondary-care context.