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Library›Open textbooks›Implementing the Creating Learning Environments for Compassionate Care (CLECC) programme in acute hospital settings: a pilot RCT and feasibility study›Context

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Implementing the Creating Learning Environments for Compassionate Care (CLECC) programme in acute hospital settings: a pilot RCT and feasibility study · Context

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CC BY 4.0 · NIHR Journals Library · approximately 23 min read

The study reported here aimed to assess the feasibility of implementing the Creating Learning Environments for Compassionate Care (CLECC) programme, a practice development programme aiming to promote compassionate care for older people in acute hospital settings, and to assess the feasibility of conducting a cluster randomised trial (CRT) with associated process and economic evaluations to measure and explain the effectiveness of CLECC.

In this chapter, we describe the background to the study, focusing in particular on the policy and practice context of the UK NHS. We also introduce the CLECC intervention, drawing on the international research literature to illustrate the rationale for designing and deploying this particular intervention.

In April 2013, the National Institute for Health Research (NIHR) Health Services and Delivery Research programme invited applications for funding research to support NHS organisations in responding to the Francis Inquiry analysis of care failures at Mid Staffordshire NHS Foundation Trust.1,2 Acknowledging that all NHS organisations could learn from ‘key system weaknesses’ identified in the Francis Inquiry, the call specifically invited applications for ‘robust evaluations of interventions to improve the leadership, organisational culture and quality of frontline care’ (p. 1).3 This report details a study funded through that call.

The NHS context

The need to strengthen the delivery of compassionate care in UK health and social care services, in particular to older patients, has been consistently identified as a high priority by policy-makers in recent years.4 In addition to a series of investigations into high-profile failures, substantial and significant variations in the quality of hospital care for older people have been highlighted.1,5 Variation exists between hospitals, but also between wards within hospitals and between staff within wards. Training, staffing levels, leadership, motivation and organisational culture are all implicated in failures of care. Although these issues are widely reported in the UK, there is evidence to suggest that they are relevant internationally.6,7

Care failures at the Mid Staffordshire NHS Foundation Trust in the late 2000s, and the inquiries that followed, were a watershed moment for the NHS. Over a period of some years, patient care in many wards and departments at the trust had been of very low quality, with, for instance, patients left in soiled bed clothes for lengthy periods, assistance not provided for patients who could not eat without help, and indifferent and unkind treatment by staff of patients, often older patients, and their families. Two inquiries led by Sir Robert Francis QC examined the causes of the lack of care and high mortality rates. The first inquiry focused on patient care at the trust and offered recommendations for improving practice at the trust.2 The second inquiry focused on the systems of governance underpinning the care failures and offered recommendations for the NHS as a whole.1 In the recommendations from the second inquiry, Francis called for a fundamental change in culture across the NHS towards a culture that puts patients first. Several of these recommendations focused on promoting compassionate nursing care. These recommendations focused on how to identify and promote desirable attributes (knowledge, skills, attitudes) in individual nurses. Many other recommendations focus on the systems needed to promote high-quality care and the responsibilities that should be held by key groups and organisations such as trust boards, NHS regulators, professional bodies and educational institutions. Although there is little detail about desirable systems and processes at a ward-team level, recommendations from both inquiries provide an outline of such measures to counteract the potential for the care failures encountered at the Mid Staffordshire NHS Foundation Trust. These include providing mechanisms through which health-care professionals can raise concerns about patient care with colleagues and with senior managers; the ongoing provision of training, support and supervision to nursing staff; and investing in ward leader roles that work alongside team members, providing role modelling and mentorship.

There have been significant changes to UK health-care provision since the establishment of the NHS in 1948. The improvement in medical treatments during this time has contributed to people living longer with more complex health conditions. Acute hospital inpatient beds are now predominantly populated by older people with multiple health conditions. However, recent years in particular have seen the adult social care system and pressures on primary care services affecting secondary care. Acute hospitals have struggled to meet their performance and financial targets. During the time that this study was taking place, health and social care in England was in the midst of unprecedented demand and financial challenges, with NHS providers having overspent by £2.45B by the end of 2015/16.8

It has been acknowledged that an increase in staffing numbers is required and a safe staffing guideline for nurses working on wards in acute hospitals has been published.9 Although this was supported by the creation of 24,000 new nursing posts between 2012 and 2015, an increase of 8.1%, demand has outstripped supply with a deficit of 8.5% of the funded establishment recorded in April 2015.10 This deficit is worse in adult acute nursing, with reported vacancies amounting to 9.7% of the establishment. It is common practice for wards to run with staff vacancies and for the staff complement to be made up of staff from nursing agencies. Recruitment drives targeted at overseas nurses have regained popularity, but this too is a temporary fix, with European Union nurses choosing to exercise their free movement rights.11

Through the development and tightening of systems for financial control and performance management, the NHS has seen an intensification of health-care work through higher patient numbers and time-based targets.12–14 Use of staff without professional qualifications is increasing and nursing staff job satisfaction is low. As we developed this study, anecdotal evidence from a number of NHS acute hospitals indicated that the leadership and team practices, such as role modelling, mutual support, reflective learning and dialogue, required to support nursing staff in their caring role15 were unlikely to be in place in most care settings.

Approach and definition of key terms

The literature is both confused and confusing in the way that compassion is used as a term. There are four key components of the narrative of compassion in nursing, and we have found these helpful to guide our thinking in this study about what compassion is.16 The first is a set of ideas about the moral attributes of a ‘compassionate’ nurse, including wisdom, humanity, love and empathy.17–19 These moral attributes are expressed through a kind of situational awareness in which vulnerability and suffering are perceived and acknowledged.19,20 These perceptions underpin participation of the nurse in responsive action that is aimed at relieving suffering and ensuring dignity, and which involves the nurse in a participatory relationship in which the nurse exercises relational capacity 19,21–23 through which empathy is experienced and a caring pastoral relationship is constructed.15,24,25

Our systematic review of research reporting older patients’ experiences of hospital care highlights the importance of this caring relationship to shaping experiences.6 Older people want nurses, and others, to use social interactions to see the person behind the patient (‘see who I am’), to establish a warm and human connection (‘connect with me’) and to establish understanding and involvement (‘involve me’).6 A later review focusing on nurses’ experiences indicates that registered nurses strive to achieve the caring relationship that is valued by patients, indicating that a perceived lack of compassion in nursing may not be attributable to a lack of the necessary moral attributes or situational awareness on the part of individual nurses. The findings reflected that nurses’ relational capacity and capacity for responsive action can depend on ward-level conditions, and that there is a greater tendency for nurses with low relational capacity to avoid relationships with patients and to burnout, in spite of aspirations to a higher standard of care.15 This study builds on these findings through the development and evaluation of an intervention targeted at improving the capacity of nurses to respond to patient vulnerability and suffering, specifically their relational capacity and capacity for responsive action.

The links between positive patient experiences, leadership, work team climate and the well-being of individual staff are becoming evident through research and so interventions that focus on developing these elements (leadership, work team climate, staff well-being) would appear to be worthwhile to support the development and exercise of relational capacity. A NIHR study on culture change and quality of acute hospital care for older people found that more positive patient and carer assessments of care were correlated with higher staff ratings of a supportive team climate and a shared philosophy of care.26 In addition, ward leadership was a strong indicator of team members sharing a philosophy of care and feeling highly supported, a finding that, together with the qualitative data, highlighted the vital role of the ward manager in shaping a positive team climate for care.26 These findings were mirrored in a second NIHR study that highlighted the key role of the ward leader in shaping the local ward climate of care, the importance of staff well-being, and, in particular, staff experiences of good local work-group climate, co-worker support, job satisfaction, positive organisational climate and support, and supervisor support as antecedents of positive patient experiences.27

Creating Learning Environments for Compassionate Care

Parts of this section are reproduced from Bridges J, Fuller A. Creating learning environments for compassionate care: a programme to promote compassionate care by health and social care teams. Int J Older People Nurs 2015;10:48–58,28 with permission from John Wiley & Sons. © 2014 John Wiley & Sons Ltd. CLECC is a team-based implementation programme focused on developing leadership and team practices that enhance team capacity to provide compassionate care. Its objectives are to:

  1. create an expansive workplace learning environment that supports work-based opportunities for the development of relational practices across the work team
  2. develop and embed sustainable manager and team relational practices, such as dialogue, reflective learning and mutual support
  3. optimise and sustain leader and team capacity to develop and support the relational capacity of individual team members
  4. embed compassionate approaches in staff–service user interaction and practice, and continue to improve compassionate care following the end of programmed activities.

The CLECC intervention was designed for use by ward nursing teams in inpatient settings for older people, but is potentially transferable for use in other settings. The implementation programme takes place over a 4-month period but it is designed to lead to a longer-term period of service improvement. By envisaging the workplace as a learning environment and the work team as a community of practice, CLECC brings a distinctive approach to promoting compassionate care. It uses insights from workplace learning research to develop practices that enhance the capacity of the manager and work team to provide compassionate care within a complex and dynamic organisational context.

Fuller and Unwin’s research on workplace learning and workforce development in a range of public and private sector industries demonstrates the importance of identifying and analysing both the organisational and pedagogical features that characterise diverse workplaces as learning environments.29 They argue that this approach allows workplaces (e.g. hospital wards) to be located on the ‘expansive–restrictive’ continuum. Those at the expansive end are characterised by a range of features including the following: the knowledge and skills of the whole workforce (not just the most highly qualified or senior staff) are valued; managers facilitate workforce and individual development; teamwork is valued; innovation is important; the team has shared goals focusing on the continual improvement of services (or products); there is recognition of and support for learning from ‘each other’; learning new knowledge and skills is highly valued; and the importance of planned time for off-the-job reflective learning is recognised. It follows that an expansive approach to workforce development is more likely to facilitate the integration of personal and organisational development. This has important implications for the design of learning interventions as it requires workplace learning to be perceived as something that both shapes and is shaped by the work organisation itself rather than as a separately existing activity. Such an understanding highlights the importance of interventions that situate and integrate individual and team learning in the everyday life of the workplace (in this case the clinical unit/ward/team setting) as well as providing opportunities for off-the-job provision to foster reflection, consolidate learning and deepen understanding, thereby enhancing ownership and sustainability of new practices.

Our synthesis of qualitative research highlights the importance of the relational aspects of care to shaping older people’s hospital experiences.6 Being compassionate requires ‘relational capacity’ in practitioners, that is, capacity to experience empathy and to engage in a caring relationship.24 Our research also shows that nurses’ relational capacity can depend on ward-level conditions, and that there is a greater tendency for nurses with low relational capacity to avoid relationships with patients and to burnout, in spite of aspirations to a higher standard of care.15 CLECC uses workplace learning principles to develop practices that enhance the capacity of the manager and work team to support the ongoing relational capacity of its individual members. This leadership and team capacity are key characteristics of the ward-level conditions needed to support nurses’ relational work15 and thus improve patient experiences, and are an important foundation for team activities, such as using service user feedback constructively.30 By envisaging the workplace as a learning environment and the work team as a community of practice, CLECC brings a distinctive approach to promoting compassionate care, which enhances the capacity of the manager and work team to provide compassionate care within a complex and dynamic organisational context.29,31 An overview of this programme theory for CLECC is shown in Figure 1 .

FIGURE 1 Overview of CLECC programme theory. Reproduced from Bridges J, Fuller A. Creating learning environments for compassionate care: a programme to promote compassionate care by health and social care teams. Int J Older People Nurs 2015;10:48–58,28 with permission from John Wiley & Sons. © 2014 John Wiley & Sons Ltd. (Figure not reproduced here; see the original article.)

During the 4-month implementation programme, CLECC learning activities are led by a senior (UK band 7) practice development nurse (PDN) or practitioner with strong influencing and interpersonal skills.28 The PDN delivers the study days, facilitates cluster and reflective discussions, facilitates the action-learning sets and co-ordinates the peer observations of practice (see the following subsections for more detail on each of these activities). This individual is not part of the hierarchy of the ward team and this enables a distinction between CLECC activities and performance management. The activities themselves are characteristic of a practice development approach.32 CLECC operates at two key levels: team and team manager. A focus on the team aims to develop team capacity to support team members to provide compassionate care. An equivalent focus on the leadership capacity of the team manager (in ward settings this is the ward manager) aims to develop their role in leading the team, role modelling good practice and enhancing and embedding the desired team practices.

Although the programme draws on elements that have been piloted in other programmes, it is novel in combining these elements with an explicit focus on establishing reforms to routine practice and organisational resources that establish the basis for sustained changes in compassionate care. Although the implementation process is a key element, the essence of the programme is the ongoing processes of peer observation, daily cluster discussions, weekly reflective discussion and the use of evidence-based guidelines. Table 1 sets out a typical schedule for the implementation programme.

TABLE 1 The CLECC implementation programme schedule
ActivityMonth
1234
Ward leader action-learning setsSession 1/setting up set, setting ground rulesSession 2/workplace climate/team values/valuing staffSession 3/enhancing team capacity for compassionate careSession 4/influencing senior managers
Team learning and service user feedback planIntroduce and discussDiscussion and draft by ward leaderFinalise, identify resources needed to support, presentSenior manager feeds back response to team plan
Peer observations of practiceIdentify care-makersTrain care-makersObservations of practiceFeedback on observations of practice
Study daysTeam analysis of workplace climate/values clarification–––
Cluster discussionsOngoingOngoingOngoingOngoing
Reflective discussions‘I feel valued at work when . . .’ exerciseTeam values clarification exercise; BPOP activitiesBPOP framework activities; team learning and service user feedback plan discussionsReflections on feedback from observations of practice

Action-learning sets

The crucial role of the ward leader in influencing the caring culture and the work culture is well documented, with strong and visible leadership identified as an essential requirement for the delivery of dignified care.26,33 In CLECC, ward leaders attend four 4-hour action-learning sets during the implementation programme. Action-learning sets have been used in other projects, including other development projects focused on dignity in care and/or care for older people, to provide an extended reflective space for individuals in a key position of influence to explore and develop their leadership role.34–36

The CLECC action-learning sets follow the McGill and Beaty model37 for action-learning, that is, sets are made up of between four and eight members and are facilitated by an experienced facilitator. Set members may or may not work in the same organisation but often have similar work roles. Participants bring work problems of their own choosing to the session and other set members aid them in reflecting on the issue and drawing up an action plan to address it. In addition, each of the action-learning sessions is themed to encourage a focus on issues related to the manager’s role in supporting the delivery of compassionate care. The first session focuses on establishing relationships among set members and agreeing ground rules. The themes for subsequent sessions are: (session 2) workplace climate/team values/valuing staff, (session 3) enhancing team capacity for compassionate care, and (session 4) influencing senior managers. Reflecting on the results of other programme activities supports discussion in these themes. For instance, during the team study days, all staff will have been invited to complete a questionnaire on perceptions of ward climate. Reflecting on the results of these questionnaires in addition to the results of the ‘I feel valued when . . .’ exercise (see Reflective discussions ) is encouraged in the second action-learning set.36 In addition to this reflective learning set, participants facilitate each other in developing practical ways of dealing with some of the issues that arise during the programme, these issues being informed by the findings relating to ward leader strategies in an earlier dignity in care project.38 Participants are encouraged to use the sets to devise a personal plan associated with their current and future role in promoting compassionate care, including planning clinical supervision sessions for themselves with a selected mentor and/or negotiating ongoing action-learning set access.

In addition to action-learning sets, ward leaders are also facilitated to further develop their relationship with their line manager as a way of accessing additional support. This includes a 1-hour meeting every 2 weeks during the 4-month implementation programme. These meetings provide an opportunity for the line manager to learn about the project and to explore opportunities to participate.

Team learning

Interventions to improve care quality at a ward or unit level may succeed, even if the wider organisation has features that inhibit service improvement on a wider scale.26 Ward-level conditions can strongly influence nurses’ capacity to build and sustain therapeutic relationships with patients.15 Other work suggests that the work team can function as a buffer to stressors from the wider organisation, but that the team’s capacity to do so depends on the extent to which the group perceives its role as supportive of the relational work of individual members.39 Social structures and relationships within the team and the capacity of team members to support each other are a primary influence on how individuals learn emotional abilities and how tacit emotional knowledge is transferred.40 Dialogue and reflection within the team, particularly with a focus on sharing experiences and narratives, appear to be linked with the development of individual emotional abilities, but these activities depend on the extent to which the workplace provides an environment in which staff feel safe to participate.40 Other work indicates that expecting staff to, for example, use patient feedback constructively in the absence of team preparation to hear the patient feedback is unlikely to lead to service improvements.30 A strong focus of the intervention is on the development of shared team goals and expectations, team dialogue, reflection and role modelling. Early activities in the intervention reflect a focus on developing a sense of security within the team,41 with dialogue and reflective learning activities providing the forum for the development of individual and team relational capacity, and the creation by the team of sustainable practices and plans to support ongoing capacity through:

  • commitment and role modelling by senior staff in the team – providing information, opportunities for discussion and involvement in goal-setting and decision-making
  • creating facilitated collective and reflective ‘spaces’ through
    • mid-shift scheduled 5-minute cluster discussions, using trigger questions or observations as behavioural nudges in team members’ planned work with patients
    • twice-weekly longer reflective group meetings, which should draw on a variety of toolkit materials to prompt dialogue and reflective learning, and give staff a regular opportunity to stand back from the demands of their operational practice
  • building relationships in the team, using activities including team analysis of workplace climate
  • critical reflections by the team on caring for and supporting each other, on team relational capacity and on delivery of compassionate care
  • team values – the clarification and development of a shared vision
  • developing shared ownership of compassionate care and understanding about how learning in the workplace can contribute to improved individual and team practice and ‘expansive outcomes’
  • development of a team learning plan, including a plan for hearing and responding to patient feedback.

Teams can be unidisciplinary or interdisciplinary, but an inclusive approach is essential, so for instance, use of CLECC with a nursing team includes the participation of all nursing staff, namely the ward manager, registered nurses, care assistants/health-care support workers and nursing students.

Peer observations of practice

Two staff volunteers from the team were selected to become ‘care-makers’, with their primary role being to undertake peer observations of practice for feedback to their colleagues. Care-makers receive 4 hours of training in peer observations of practice and undertake 8 hours of observation each during the programme. Peer observations are conducted using the Quality of Interactions Schedule (QuIS)42 and findings are fed back at reflective discussion meetings (see Reflective discussions ) with the help of the PDN. The results from the care-makers’ observations of practice on the ward are shared to trigger discussions about how to build on existing good practice and improve practice when this is needed.

Study days

On each ward, three or four full study days are delivered by the PDN during the first month of the programme to enable all ward members to attend one study day. The purpose of the day is to prepare staff for the workplace elements (including cluster and reflective discussions) of the programme by providing opportunities to experience some of the techniques; to develop an understanding of underlying concepts; and to recognise an active role in their personal and team learning journey. Elements of the programme for classroom training are shown in Box 1 .

Introduction to the BPOP framework.43

Life shield activity and group discussion: ‘See who I am’.

Questionnaires and discussion on ward climate, dialogue and reflective learning on the ward.

Values clarification exercise about compassionate care.44

Videos, stories and discussion with service users: ‘Involve me’.

Introduction to workplace learning activities and discussion on how to implement/support/sustain.

Cluster discussions

Mid-shift cluster discussions commence during the first month (following the delivery of study days) and run daily throughout the implementation period. These 5-minute cluster discussions are facilitated initially by the PDN and all nursing staff on the ward at the time of the cluster discussion are encouraged to join the group discussion. The discussion focuses on establishing how the individual staff are at that moment in that context and provides opportunities for the group to offer help and support to members when difficulties are identified. Similar strategies have been used in other projects focused on developing dignity in care/compassionate care.36,45

Reflective discussions

Twice a week, members of the team on duty at the time scheduled for a reflective discussion (usually the afternoon) arrange their work to enable their attendance at a group meeting facilitated by the PDN. To enable all staff on a shift to participate, two sessions may need to be held on the same day, both attended by the ward leader. This interaction is held in a comfortable meeting room on or near to the place of care, but away from the immediate distractions of care delivery. The meeting is for all team members, including senior members of the team and temporary team members, such as student nurses. The meetings involve a variety of group work tasks, some of which are repeated to enable the maximum number of team members to take part, whereas others will be unique. Tasks are aimed at opening up dialogue and reflective learning among those present, and so are selected to prompt personal reflections and narratives about experiences on the ward. They include:

  • ‘I feel valued at work when . . .’ – those present are invited to complete this sentence to trigger discussions about valuing and supporting each other36
  • team values clarification about compassionate care – drawing on collated results of the values clarification exercise in classroom sessions to develop shared vision36,44
  • drawing on collated results of ward climate analyses to identify factors that need to be supported or changed36
  • peer observations of practice – the results from the care-makers’ observations of practice on the ward are shared to trigger discussions about how to build on existing good practice and improve practice when this is needed36
  • the Best Practice for Older People (BPOP) framework – using resources and questions/prompts from the BPOP framework is an essential guide to generating discussion46
  • a team learning plan – working with managers to draw up a team learning plan focusing on compassionate care and using patient feedback.

Best Practice for Older People framework

The BPOP framework is a set of evidence-based UK guidelines for nurses working with older people in acute settings.43,46 Its successful use in development projects aimed at service improvement indicates that it is useful in guiding the practice of health and social care professionals working with other client groups (i.e. not just nurses working with older people). One example of this wider use is the City University Dignity in Care project at two London hospitals.36,47 A resource has been published for use alongside the BPOP framework, providing teams with trigger questions and guidance aimed at generating dialogue and reflective learning in the team, and opening up conversations in which team members give and receive support and help with difficult matters, such as talking to patients about dying.46 In CLECC, this resource is used to identify areas for support, action and learning in the team, and to inform the development of strategies to address these areas. Examples of trigger questions in this resource are:

  • What kind of patients are most difficult to communicate with, and why?
  • What kind of patients are most difficult to involve, and why?
  • What subjects are hardest to talk to patients about, and why?
  • What kind of relatives are most difficult to involve, and why?

The implementation stage of the programme takes 4 months, and during this time ward leaders and their teams develop a team learning plan that includes inviting and responding to patient feedback, and puts in place measures for continuing to develop and support manager and team practices that underpin the delivery of compassionate care. The team learning plan is presented to a senior trust manager, together with a case for support, and the relevant manager is invited to visit the ward team to discuss the plan and respond in person to the proposals.

In summary, the focus of the intervention is on creating an ‘expansive’ environment that supports work-based opportunities for the development of shared goals, dialogue, reflective learning, mutual support and role modelling for all members of the team at an individual and a group level.29 The programme theory states that such an environment should facilitate staff to engage with and learn from service user experiences and their own emotional responses, share positive strategies and support, and optimise and sustain personal and team relational capacity to embed compassionate approaches in staff–service user interaction and practice. Expansive outcomes are theorised to include high-quality interactions between service users and staff, and between care team members, positive care experiences reported by service users and staff reports of high empathy with patients and carers.

Introduction to the study

Findings from our systematic review, reported in Chapter 2 , highlight the lack of definitive evaluation research on compassionate nursing care. Responding to a general absence of strong evidence for the effectiveness of service improvements related to compassion, and building on compelling evidence indicating that a strategy targeted at improving leadership and local ward team climate could improve patient experiences, the study reported here is a foundational step in addressing the need for well-designed and rigorous evaluation to understand what works best in improving care and patient experiences.

This study, conducted in two English hospitals during 2015–16 and reported in the chapters that follow, aimed to assess the feasibility of implementing CLECC and of conducting a CRT with associated process and economic evaluations to measure and explain its effectiveness. Conducting the study provided an important opportunity to assess the feasibility of a programme with unique characteristics designed to address the issues identified in other studies, and to design an evaluation that includes an assessment of its effectiveness. The process and economic evaluations aimed to provide important information about CLECC’s workability, its integration into practice and to lay the foundations for establishing its value for money. The findings reported below (see Chapters 7–10 ) provide the basis for planning a larger, multicentre evaluation aimed at producing evidence that can be generalised more widely to other NHS acute care providers and, together with a refined intervention package, will be a valuable resource for change and improvement for NHS managers, practitioners and educators.

Literature review →

Attribution. Jackie Bridges; Ruth M Pickering; Hannah Barker; Rosemary Chable; Alison Fuller; Lisa Gould et al. (2018). Implementing the Creating Learning Environments for Compassionate Care (CLECC) programme in acute hospital settings: a pilot RCT and feasibility study. NIHR Journals Library. Copyright © Queen’s Printer and Controller of HMSO 2018. This work was produced by Bridges et al. under the terms of a commissioning contract issued by the Secretary of State for Health and Social Care. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising. Applications for commercial reproduction should be addressed to: NIHR Journals Library, National Institute for Health Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK. Licensed under CC BY 4.0. NCBI Bookshelf NBK525482. CC BY 4.0. Original source ↗. Text reproduced from the Bookshelf XML without changing wording; figures, images and supplements are not reproduced.

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