Clair Le Boutillier

Background: Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, while deaths related to other non-liver disease areas are declining. Portal hypertension, the primary sequalae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, that lead to hospitalisation and mortality. It remains uncertain whether administering a non-selective beta-blocker (NSBB), specifically carvedilol, at an earlier stage i.e. when oesophageal varices are small, can prevent VH and reduce all-cause decompensation (ACD). Methods/design: The BOPPP trial is a pragmatic, multicentre, placebo-controlled, triple-blinded, randomised controlled trial (RCT) in England, Scotland, Wales and Northern Ireland. Patients aged 18 years or older with cirrhosis and small oesophageal varices that have never bled will be recruited, subject to exclusion criteria. The trial aims to enrol 740 patients across 55 hospitals in the UK. Patients are allocated randomly on a 1:1 ratio to receive either carvedilol 6.25mg (a NSBB) or a matched placebo, once or twice daily, for 36 months, to attain adequate power to determine the effectiveness of carvedilol in preventing or reducing ACD. The primary outcome is time to first decompensating event. It is a composite primary outcome made up of variceal haemorrhage (VH, new or worsening ascites, new or worsening hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, an increase in Child Pugh grade by 1 grade or MELD score by 5 points, and liver-related mortality. Secondary outcomes include progression to medium or large oesophageal varices, development of gastric, duodenal, or ectopic varices, participant quality of life, healthcare costs and transplant-free survival. Discussion: The BOPPP trial aims to investigate the clinical and cost effectiveness of carvedilol in patients with cirrhosis and small oesophageal varices to determine whether this non-selective beta-blocker can prevent or reduce hepatic decompensation. There is clinical equipoise on whether intervening in cirrhosis, at an earlier stage of portal hypertension, with NSBB therapy is beneficial. Should the trial yield a positive result, we anticipate that the administration and use of carvedilol will become widespread with pathways developed to standardise the administration of the medication in primary care. Ethics and dissemination: The trial has been approved by the National Health Service (NHS) Research Ethics Committee (REC) (reference number: 19/YH/0015). The results of the trial will be submitted for publication in a peer-reviewed scientific journal. Participants will be informed of the results via the BOPPP website ( www.boppp-trial.org ) and partners in the British Liver Trust (BLT) organisation. Trial registration: EUDRACT reference number: 2018-002509-78 ISRCTN reference number: ISRCTN10324656

People living with treatable-but-not-curable (TbnC) cancer encounter cancer-related needs. While the NHS long-term plan commits to offering a Holistic Needs Assessment (HNA) and care plan to all people diagnosed with cancer, the content, delivery and timing of this intervention differs across practice. Understanding how people make sense of their cancer experience can support personalised care. A conceptual framework based on personal narratives of living with and beyond cancer (across different cancer types and all stages of the disease trajectory), identified three interlinked themes: Adversity, Restoration and Compatibility, resulting in the ARC framework. Our aim was to use the ARC framework to underpin the HNA to improve the experience of personalised care and support planning for people living with TbnC cancer. We used clinical work experience to operationalise the ARC framework and develop the intervention, called the ARC HNA, and service-level structure, called the ARC clinic. We sought expert input on the proposed content and structure from patients and clinicians through involvement and engagement activities. Delivered alongside standard care, the ARC HNA was piloted with patients on the TbnC cancer (myeloma and metastatic breast, prostate or lung) pathway, who were 6–24 months into their treatment. Iterations were made to the content, delivery and timing of the intervention based on user feedback. Fifty-one patients received the intervention. An average of 12 new concerns were identified per patient, and 96% of patients achieved at least one of their goals. Patients valued the space for reflection and follow-up, and clinicians valued the collaborative approach to meeting patients’ supportive care needs. Compared with routine initial HNA and care plan completion rates of 13%, ARC clinic achieved 90% with all care plans shared with general practitioners. The ARC clinic adopts a novel and proactive approach to delivering HNAs and care plans in a meaningful and personalised way.

Objectives Our aim was to examine the feasibility and implementation of a complex intervention to improve the care of patients with peripheral arterial disease (the LEGS intervention) from the perspective of patients, general practitioners and secondary care clinicians. Design A qualitative study involving semistructured individual interviews with patients and providers to gain an understanding of the feasibility of the LEGS intervention as well the barriers and facilitators to implementation in secondary and primary care. Setting Primary and secondary care settings across two National Health Service Trusts. Participants Twenty-five semistructured telephone interviews were conducted with (1) patients who had received the intervention (n=11), (2) secondary care clinicians responsible for delivering the intervention (n=8) and (3) general practitioners (n=6). Analysis Data were initially analysed using inductive descriptive thematic analysis. The consolidated framework for implementation research was then used as a matrix to explore patterns in the data and to map connections between the three participant groups. Lastly, interpretive analysis allowed for refining, and a final coding frame was developed. Results Four overarching themes were identified: (1) the potential to make a difference, (2) a solution to address the gap in no man’s land, (3), prioritising and making it happen and (4) personalised information and supportive conversations for taking on the advice. The impetus for prioritising and delivering the intervention was further driven by its flexibility and adaptability to be tailored to the individual and to the environment. Conclusions The LEGS intervention can be tailored for use at early and late stages of peripheral arterial disease, provides an opportunity to meet patient needs and can be used to promote shared working across the primary–secondary care interface.

Background: The Beta-blockers Or Placebo for Primary Prophylaxis of oesophageal varices (BOPPP) trial is a 3-year phase IV, multi-centre clinical trial of investigational medicinal product (CTIMP) that aims to determine the effectiveness of carvedilol in the prevention of variceal bleeding for small oesophageal varices in patients with cirrhosis. Early engagement of General Practitioners (GPs) in conversations about delivery of a potentially effective secondary care-initiated treatment in primary care provides insights for future implementation. The aim of this study was to understand the implementation of trial findings by exploring i) GP perspectives on factors that influence implementation beyond the context of the trial and ii) how dose titration and ongoing treatment with carvedilol is best delivered in primary care. Methods: This qualitative study was embedded within the BOPPP trial and was conducted alongside site opening. GP participants were purposively sampled and recruited from ten Clinical Commissioning Groups in England and three Health Boards across Wales. Semi-structured telephone individual interviews were conducted with GPs (n = 23) working in England and Wales. Data were analysed using reflexive thematic analysis. Findings: Five overarching themes were identified: i) primary care is best placed for oversight, ii) a shared approach led by secondary care, iii) empower the patient to take responsibility, iv) the need to go above and beyond and v) develop practice guidance. The focus on prevention, attention to holistic care, and existing and often long-standing relationships with patients provides an impetus for GP oversight. GPs spoke about the value of partnership working with secondary care and of prioritising patient-centred care and involving patients in taking responsibility for their own health. An agreed pathway of care, clear communication, and specific, accessible guidance on how to implement the proposed treatment strategy safely and effectively are important determinants in the success of implementation. Conclusions: Our findings for implementing secondary care-initiated treatment in primary care are important to the specifics of the BOPPP trial but can also go some way in informing wider learning for other trials where work is shared across the primary-secondary care interface, and where findings will impact the primary care workload. We propose a systems research perspective for addressing implementation of CTIMP findings at the outset of research. The value of early stakeholder involvement is highlighted, and the need to consider complexity in terms of the interaction between the intervention and the context in which it is implemented is acknowledged. Trial registration: ISRCTN10324656.

Background: The Community and Hospital cAre Bundle to improve the medical treatment of cLaudIcation and critical limb iSchaemia (CHABLIS) study is a prospective mixed-methods study across NHS hospitals and primary care networks, which aims to determine the feasibility of using a complex intervention in the form of a care bundle, consisting of checklists, leaflets and letters, called the LEGS intervention (LEaflet Gp letter Structured checklist), to improve the care of patients with peripheral arterial disease (PAD). The aim of this qualitative study was to gain an understanding of the acceptability of the provision and delivery of the LEGS intervention, by patients, general practitioners and secondary care clinicians. Engaging stakeholders in these conversations provides insights for future intervention refinement, uptake and implementation. Methods: This qualitative study was embedded within the CHABLIS study. Twenty-five semi-structured telephone interviews were conducted with i) patients who had received the intervention (n=11), ii) secondary care clinicians responsible for delivering the intervention (n=8), and iii) general practitioners (n=6). Data were initially analysed using inductive descriptive thematic analysis. The consolidated framework for implementation research was then used as a matrix to explore patterns in the data and to map connections between the three participant groups. Lastly, interpretive analysis allowed for refining, and a final coding frame was developed. Results: Four overarching themes were identified: i) The potential to make a difference, ii) A solution to address the gap in no man’s land, iii), Prioritising and making it happen and iv) Personalised information and supportive conversations for taking on the advice. The intervention was viewed as an opportunity to meet patient needs, and to develop shared primary and secondary care working practices. The impetus for prioritising and delivering the intervention was further driven by its flexibility and adaptability to be tailored to the individual and to the environment. Conclusions: The LEGS intervention can be tailored for use at early and late stages of PAD, can be provided across primary and secondary care settings, and provides an opportunity to promote shared working across the primary-secondary care interface. Contributions to the literature: Primary and secondary care providers acknowledged the need for an intervention to support them to deliver guideline-based PAD treatment, and to target the intervention earlier in the PAD treatment pathway. A gap was identified in terms of support for patients and providers between the time of diagnosis of early-stage PAD (e.g., claudication) and a subsequent potential diagnosis of advanced PAD. The LEGS intervention can be used to fill this gap by enabling providers to support patients to receive help, education, support, or appropriate medication to address their condition. Patient-provider interactions that promote shared decision-making and that support patient preference are also important determinants in the success of implementation.

Objectives: Individuals with psychosis report that emotion regulation (ER) difficulties are treatment priorities, yet little is known about how targeted ER interventions may help. We evaluated a new eight‐session Dialectical Behavioural Therapy (DBT)–informed skills group specifically adapted for individuals with psychosis: the Managing Emotions Group (MEG) in diverse, inner‐city community services. Method: A mixed‐method design was utilised to assess the feasibility (acceptability and potential clinical impact) of local delivery of MEG. Uptake, completion (≥50% of sessions), post‐session satisfaction ratings, and thematic analysis of qualitative feedback from 12 completers assessed acceptability. Pre–post‐intervention changes in psychological distress, self‐reported ER difficulties, and adaptive ER skill use assessed potential clinical impact. Results: Forty‐eight individuals (81% of attenders) completed the intervention ( M _age = 43, 54% female) of whom 39 completed pre‐ and post‐group measures. Participants reported high satisfaction and meaningful improvements in understanding and managing emotions, with positive impact on daily life. Self‐reported psychological distress, ER difficulties, and adaptive ER skill use significantly improved, with medium‐to‐large pre‐post effects ( d = 0.5–0.7) except lack of emotional clarity ( d = 0.3). Conclusions: MEG was feasible and acceptable, and a future feasibility randomised controlled trial is warranted. Practitioner points: Individuals with psychosis report that support with their emotions is a priority. Brief interventions for emotion regulation difficulties are acceptable to individuals with psychosis and can be feasibly delivered in a local outpatient service. Distress and emotion regulation difficulties and skills improved significantly from pre–post treatment for clients completing the managing emotions group. Further implementation and evaluation are needed to support continued refinement to meet the needs and priorities of individuals with psychosis.

Objective: The success of pharmacological randomised controlled trials (RCTs) depends on the recruitment of the required number of participants. Recruitment to RCTs for patients with cirrhosis and small oesophageal varices raises specific additional challenges. The objectives of the study were 1) to explore patient perspectives on factors that influence RCT recruitment, 2) to understand factors that influence the success of recruitment from a staff perspective, and 3) to identify opportunities for tailored interventions to improve trial recruitment in this context. Methods: The qualitative study was embedded in a multi-centre blinded RCT (BOPPP trial) and was conducted alongside site opening. Semi-structured interviews were conducted with patients who enrolled to participate in the trial (n = 13), patients who declined to take part (n = 5), and staff who were responsible for recruiting participants to the trial (n = 18). An open approach to data collection and analysis was adopted and the Theoretical Domains Framework (TDF) was used to provide a theoretical lens through which to view influences on behaviour. Data was analysed using thematic analysis. Results: The findings consist of 5 overarching themes that outline trial recruitment influences at the patient, staff, team, organisational and trial levels: i) patient risks and benefits ii) staff attitudes, knowledge and capacity, iii) team-based approach, iv) organisational context and v) Trial collective. Patient-generated themes map onto thirteen of the fourteen TDF domains and staff-generated themes map onto all TDF domains. The overarching themes are not mutually exclusive; with evidence of direct interactions between patient and staff-level themes that influence recruitment behaviours. Conclusions: This study uses a theory-informed approach to gain new insights into improving clinical trial recruitment for patients with cirrhosis and small oesophageal varices. Although people with cirrhosis often display decreased healthcare-seeking behaviours, we found that patients used research to empower themselves to improve their health. Pragmatic trials involving unpredictable populations require staff expertise in building trust, and a deep knowledge of the patient group and their vulnerabilities. RCT recruitment is also more successful when research visits align with what staff identified as the natural rhythm of care. Trial registration: ISRCTN10324656; https://clinicaltrials.gov/.

Background The concept of living with and beyond cancer is now emerging in policy and literature. Rather than viewing this notion simply as a linear timeline, developing an agreed understanding of the lived experience of people affected by cancer will aid the development of person‐centred models of care. Methods A systematic review was conducted. The review question was What does the term ‘living with and beyond cancer’ mean to people affected by cancer? The protocol for the review was pre‐registered in the PROSPERO database (PROSPERO CRD42017059860). All included studies were qualitative, so narrative synthesis was used to integrate descriptions and definitions of living with and beyond cancer into an empirically based conceptual framework. Results Out of 2345 papers that were identified and 180 that were reviewed, a total of 73 papers were included. The synthesis consists of three interlinked themes: Adversity ‐ realising cancer, Restoration ‐ readjusting life with cancer and Compatibility ‐ reconciling cancer, resulting in the ARC framework. Conclusions Three themes describe the experience of living with and beyond cancer: Adversity, Restoration and Compatibility. The ARC framework provides an empirically informed grounding for future research and practice in supportive cancer care for this population.