Remaking critical care: Place, body work and the materialities of care in the COVID intensive care unit.

In this article, we take forward sociological ways of knowing care-in-practice, in particular work in critical care. To do so, we analyse the experiences of staff working in critical care during the first wave of the COVID-19 pandemic in the UK. This moment of exception throws into sharp relief the ways in which work and place were reconfigured during conditions of pandemic surge, and shows how critical care depends at all times on the co-constitution of place, practices and relations. Our analysis draws on sociological and anthropological work on the material culture of health care and its sensory instantiations. Pursuing this through a study of the experiences of 40 staff across four intensive care units (ICUs) in 2020, we provide an empirical and theoretical elaboration of how place, body work and care are mutually co-constitutive. We argue that the ICU does not exist independently of the constant embodied work of care and place-making which iteratively constitute critical care as a total system of relations.

Evaluating the usefulness of a wordless picture book for adults with intellectual disabilities about the COVID-19 vaccination programme using co-production: The CAREVIS study.

AIM: To explore the usefulness of a co-designed wordless book showing processes of receiving COVID-19 vaccines designed by, and for, adults with intellectual disabilities. METHODS: A qualitative evaluation of the resource using mixed methods. Semi-structured interviews were conducted with people with intellectual disabilities, carers and health professionals about resource content, and use. This was analysed thematically. A survey was circulated to intellectual disabilities networks to understand resource need, use, sharing and content. RESULTS: Understanding the COVID-19 vaccine was a process, not a single event using one resource. A visual resource had a place in facilitating conversations about vaccines between people with intellectual disabilities and carers. Differing perspectives were expressed regarding personal needs, existing awareness of vaccine programmes and communication preferences. Changes were suggested to improve the suggested storyline and relevance around COVID-19 restrictions changing. CONCLUSION: A visual resource may help conversations about the COVID-19 vaccine for people with intellectual disabilities.

Adaptations to research within the intellectual disability population during the COVID-19 pandemic: Lessons learned from the CAREVIS study.

The COVID-19 pandemic resulted in changes in all areas of clinical practice, including clinical research and within the intellectual disability population. While there have been some benefits from this rapid adoption of change, those involved in research have had to overcome a number of additional challenges. These adaptive changes, which have included the use of technology, closure of social spaces, working with specific groups who are more vulnerable to COVID-19, and mask use impairing communication, have had both positive and negative impacts on research. As the pandemic and related restrictions evolve, it is important to examine the changes that have occurred. In the future, the adoption of a hybrid model in research is likely to be a common approach, establishing a balance between technology and in-person interaction.

An aromatherapy massage intervention on sleep in the ICU: A randomized controlled feasibility study.

We conducted a feasibility randomized controlled trial exploring the effect of aromatherapy massage on sleep in critically ill patients. Patients were randomized to receive aromatherapy massage or usual care, and feasibility of recruitment and outcome data completion was captured. Sleep (depth) was assessed through Bispectral Index monitoring and self/nurse-reported Richards-Campbell Sleep Questionnaires, and the Sleep in the ICU Questionnaire. Thirty-four patients participated: 17 were randomized to aromatherapy massage and 17 to control. Five participants who received the intervention completed outcomes for analysis (alongside eight controls). A larger study was deemed unfeasible in this population, highlighting the value of testing feasibility of complex interventions, such as massage for sleep in ICU.

Using patient and care partner experiences to confirm outcomes of relevance for inclusion in a core outcome set for trials of physical rehabilitation in critical illness: A qualitative interview study.

BACKGROUND: Incorporating the perspectives of patients and care partners is crucial in the development of core outcome sets. One effective approach for achieving this involvement is by seeking input to refine the outcomes for consensus. The objectives of the study were to: i) to determine patient and care partner views on outcomes that should be measured in trials of physical rehabilitation interventions across the critical illness recovery continuum; (ii) to map these views with a pre-established list of thirty outcomes for potential inclusion in a core outcome set for these trials; and (iii) to identify any new outcomes that could be considered for inclusion. METHODS: A qualitative semistructured telephone interview study was conducted with a convenience sample of post-critical illness patients and care partners, as part of core outcome set development work. Anonymised interview transcripts were analysed using a framework approach, and exemplary narrative quotes from participants were reported used to illustrate outcome reporting. FINDINGS: Fourteen participants were recruited (male:female ratio = 8:6, age range [minimum-maximum]: 50-80 years, 13 former patients, one spouse). Time since intensive care unit discharge ranged from less than 1 year to 10 years at the time of interview. Participants described a range of outcomes that could be measured in trials of physical rehabilitation after critical illness that mapped closely with the pre-established list. No new outcomes were introduced by participants during the interviews. Experiences described by participants commonly reflected outcomes related to physical ability and performance, functional level, activities of daily living, and emotional and mental wellbeing. Participants spoke to how the different outcomes directly impacted their day-to-day lives and highlighted their priorities centred around resumption of tasks and activities that had value to them at personal, functional, and societal level. CONCLUSION: Qualitative interviews confirmed the relevance of existing outcomes for potential inclusion in a core outcome set for trials of physical rehabilitation interventions across the critical illness recovery continuum. The added significance of our findings is to provide real-world meaning to these outcomes. REGISTRATION: COMET Initiative, ID288, https://www.comet-initiative.org/studies/details/288.

Compassionate, collective or transformational nursing leadership to ensure fundamentals of care are achieved: A new challenge or non-sequitur?

AIMS: This discursive paper draws on three key leadership theories with the aim of outlining how styles of leadership impact the provision of fundamentals of care. DESIGN: Discussion paper. DATA SOURCES: key leadership theories, leadership and fundamentals of care literature. IMPLICATIONS FOR NURSING: The conceptualization of fundamentals of care is viewed through the lens of nursing leadership, and collective, compassionate and transformational leadership theory. The cognitive dissonance that nursing leaders encounter when trying to reconcile organizational, patient and nurses' needs is considered, and the pressure to deliver high-quality fundamentals of care presents a challenge to nurse leaders. CONCLUSION: Leaders must align nursing and patient outcome data to drive forward and prioritize fundamental care. Focusing on key elements of relational leadership styles will ensure a workforce fit to provide fundamental care, which in the current climate must be an organizational and global nursing priority. IMPACT: This discussion attempts to draw together overlapping leadership theories, emphasizes the importance of relational leadership in ensuring the provision of the fundamentals of care and acknowledged the impact of the COVID-19 pandemic on nurses and nursing care, with leadership implications outlined, such as a need for role-modelling, understanding shared values and giving nurses a voice. It will have an impact on nurse leaders, but also on those nurses providing direct care by issuing a challenge for them to confront their own nurse leaders, and to ask that they better resolve competing needs of both the nursing workforce and patients.

Reflective learning conversations model for simulation debriefing: a co-design process and development innovation.

BACKGROUND: Health practitioners must be equipped with effective clinical reasoning skills to make appropriate, safe clinical decisions and avoid practice errors. Under-developed clinical reasoning skills have the potential to threaten patient safety and delay care or treatment, particularly in critical and acute care settings. Simulation-based education which incorporates post-simulation reflective learning conversations as a debriefing method is used to develop clinical reasoning skills while patient safety is maintained. However, due to the multidimensional nature of clinical reasoning, the potential risk of cognitive overload, and the varying use of analytic (hypothetical-deductive) and non-analytic (intuitive) clinical reasoning processes amongst senior and junior simulation participants, it is important to consider experience, competence, flow and amount of information, and case complexity related factors to optimize clinical reasoning while attending group- based post-simulation reflective learning conversations as a debriefing method. We aim to describe the development of a post-simulation reflective learning conversations model in which a number of contributing factors to achieve clinical reasoning optimization were addressed. METHODS: A Co-design working group (N = 18) of doctors, nurses, researchers, educators, and patients' representatives collaboratively worked through consecutive workshops to co-design a post-simulation reflective learning conversations model to be used for simulation debriefing. The co-design working group established the model through a theoretical and conceptual-driven process and multiphasic expert reviews. Concurrent integration of appreciative inquiry, plus/delta, and Bloom's Taxonomy methods were considered to optimize simulation participants' clinical reasoning while attending simulation activities. The face and content validity of the model were established using the Content Validity Index CVI and Content Validity Ratio CVR methods. RESULTS: A Post-simulation reflective learning conversations model was developed and piloted. The model was supported with worked examples and scripted guidance. The face and content validity of the model were evaluated and confirmed. CONCLUSIONS: The newly co-designed model was established in consideration to different simulation participants' seniority and competence, flow and amount of information, and simulation case complexity. These factors were considered to optimize clinical reasoning while attending group-based simulation activities.

Chronic illness and critical care-A qualitative exploration of family experience and need.

BACKGROUND: People with chronic illnesses such as cancer and cardiovascular disease are living longer and often require the support of critical care services. Current health care provision means patients may be discharged home once clinically stable despite still having high care demands including social, emotional, or physical needs. Families are often required to assume caregiving roles. Research into family burden using quantitative methods has increased awareness, however, little qualitative work exists and the development of support interventions for families is required. AIMS: To explore the experience and needs of family members of people with an existing chronic illness who are admitted to the Critical Care Unit (CCU), and to identify the desired components of a family support intervention in the form of a resource toolkit. STUDY DESIGN: A qualitative exploration of family experience and need, and content development for a resource toolkit using focus group methodology. Two focus groups and one face-to-face interview were conducted involving nine adult (≥18 years) family members of adult patients with chronic illness admitted to critical care in the preceding 9 months across two specialist hospitals in the UK. These were digitally recorded, transcribed, and thematically analysed. RESULTS: Four themes were identified: importance of communication, need for support, trauma of chronic illness, and having to provide "Do-it-Yourself" care. The immense responsibility of families to provide care throughout the illness trajectory is highlighted. Understandable information is essential for a family support toolkit. CONCLUSION: Family members often view a critical care episode broadly from diagnosis through to recovery/rehabilitation. Basic communication training skills within critical care should be ensured, alongside coordination of simple solutions. The potential traumatic impact on families should be highlighted early within the pathway, and positive aspects used to harness essential family support. A simple and coordinated approach to a toolkit is preferred. RELEVANCE TO CLINICAL PRACTICE: This study highlights that a critical care experience may impact broadly beyond CCU, and the importance of informing patients and families of this potential experience, prior to or on admission, to aid preparation. Further highlighted is the need for contemporaneous and accurate information from clinicians involved in care. Families report a better experience when there is good collaboration across critical care services and admitting clinical teams. Early involvement of families in overall discharge planning is essential to allow patients and families to adjust and plan for recovery.

Patient Harm and Institutional Avoidability of Out-of-Hours Discharge From Intensive Care: An Analysis Using Mixed Methods.

OBJECTIVES: Out-of-hours discharge from ICU to the ward is associated with increased in-hospital mortality and ICU readmission. Little is known about why this occurs. We map the discharge process and describe the consequences of out-of-hours discharge to inform practice changes to reduce the impact of discharge at night. DESIGN: This study was part of the REcovery FoLlowing intensive CarE Treatment mixed methods study. We defined out-of-hours discharge as 16:00 to 07:59 hours. We undertook 20 in-depth case record reviews where in-hospital death after ICU discharge had been judged "probably avoidable" in previous retrospective structured judgment reviews, and 20 where patients survived. We conducted semistructured interviews with 55 patients, family members, and staff with experience of ICU discharge processes. These, along with a stakeholder focus group, informed ICU discharge process mapping using the human factors-based functional analysis resonance method. SETTING: Three U.K. National Health Service hospitals, chosen to represent different hospital settings. SUBJECTS: Patients discharged from ICU, their families, and staff involved in their care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out-of-hours discharge was common. Patients and staff described out-of-hours discharge as unsafe due to a reduction in staffing and skill mix at night. Patients discharged out-of-hours were commonly discharged prematurely, had inadequate handover, were physiologically unstable, and did not have deterioration recognized or escalated appropriately. We identified five interdependent function keys to facilitating timely ICU discharge: multidisciplinary team decision for discharge, patient prepared for discharge, bed meeting, bed manager allocation of beds, and ward bed made available. CONCLUSIONS: We identified significant limitations in out-of-hours care provision following overnight discharge from ICU. Transfer to the ward before 16:00 should be facilitated where possible. Our work highlights changes to help make day time discharge more likely. Where discharge after 16:00 is unavoidable, support systems should be implemented to ensure the safety of patients discharged from ICU at night.

How COVID-19 has affected staffing models in intensive care: A qualitative study examining alternative staffing models (SEISMIC).

AIMS: To understand how COVID-19 affected nurse staffing in intensive care units (ICUs) in England, and to identify factors that influenced, and were influenced by, pandemic staffing models. DESIGN: Exploratory qualitative study. METHODS: Semi-structured, online interviews conducted July-September 2020 with regional critical care leaders including policy leads (n = 4) and directors/lead nurses (n = 10) across critical care networks in England. FINDINGS: The six themes emerging from the framework analysis illustrate how the pre-pandemic ICU culture influenced ICU staffing models during the pandemic. Changes in staffing impacted on the workforce and the care delivered, whilst it was necessary to learn from, and adjust to, a rapidly changing situation. Variation across and between networks necessitated variation in responses. The overwhelming outcome was that the pandemic has challenged the central tenets of ICU nurse staffing. CONCLUSIONS: Pandemic nurse staffing models resulted in changes to ICU skill-mix and staffing numbers. Factors such as the impact of nurse staffing on care practices and on the workforce need to be taken into account when developing and testing future nurse staffing models for ICU. The extent to which ICUs will return to former staffing models is not yet known but there seems to be an appetite for change. IMPACT: In common with many countries, nurse staffing in English ICUs was adapted to address surge requirements during the COVID-19 pandemic. Findings highlight the challenge COVID-19 presented to pre-pandemic ICU nurse staffing guidelines, the impact on patient and staff well-being and the potential legacy for future staffing models. Study findings have implications for ICU nurse managers, researchers and policy makers: nurse staffing models need to be adaptable to the local context of care and future research should investigate the impact of different models on patients, staff and health service outcomes.

Florence Nightingale's legacy for clinical academics: A framework analysis of a clinical professorial network and a model for clinical academia.

BACKGROUND: Clinical academic nursing roles are rare, and clinical academic leadership positions even more scarce. Amongst the United Kingdom (UK) academia, only 3% of nurses who are employed within universities are clinically active. Furthermore, access to research fellowships and research grant funding for nurses in clinical or academic practice is also limited. The work of Florence Nightingale, the original role model for clinical academic nursing, is discussed in terms of how this has shaped and influenced that of clinical academic nurse leaders in modern UK healthcare settings. We analysed case studies with a view to providing exemplars and informing a new model by which to visualise a trajectory of clinical academic careers. METHODS: A Framework analysis of seven exemplar cases was conducted for a network of Clinical Academic Nursing Professors (n = 7), using a structured template. Independent analysis highlighted shared features of the roles: (a) model of clinical academic practice, (b) infrastructure for the post, (c) capacity-building initiatives, (d) strategic influence, (e) wider influence, (f) local and national implementation initiatives, (g) research area and focus and (h) impact and contribution. FINDINGS: All seven of the professors of nursing involved in this discourse were based in both universities and healthcare organisations in an equal split. All had national and international profiles in their specialist clinical areas and were implementing innovation in their clinical and teaching settings through boundary spanning. We outline a model for career trajectories in clinical academia, and how leadership is crucial. CONCLUSION: The model outlined emphasises the different stages of clinical academic roles in nursing. Nursing as a discipline needs to embrace the value of these roles, which have great potential to raise the standards of healthcare and the status of the profession.

The organisation of nurse staffing in intensive care units: A qualitative study.

AIMS: To examine the organisation of the nursing workforce in intensive care units and identify factors that influence how the workforce operates. BACKGROUND: Pre-pandemic UK survey data show that up to 60% of intensive care units did not meet locally agreed staffing numbers and 40% of ICUs were closing beds at least once a week because of workforce shortages, specifically nursing. Nurse staffing in intensive care is based on the assumption that sicker patients need more nursing resource than those recovering from critical illness. These standards are based on historical working, and expert professional consensus, deemed the weakest form of evidence. METHODS: Focus groups with intensive care health care professionals (n = 52 participants) and individual interviews with critical care network leads and policy leads (n = 14 participants) in England between December 2019 and July 2020. Data were analysed using framework analysis. FINDINGS: Three themes were identified: the constraining or enabling nature of intensive care and hospital structures; whole team processes to mitigate nurse staffing shortfalls; and the impact of nurse staffing on patient, staff and intensive care flow outcomes. Staff made decisions about staffing throughout a shift and were influenced by a combination of factors illuminated in the three themes. CONCLUSIONS: Whilst nurse:patient ratios were clearly used to set the nursing establishment, it was clear that rostering and allocation/re-allocation during a shift took into account many other factors, such as patient and family nursing needs, staff well-being, intensive care layout and the experience, and availability, of other members of the multi-professional team. This has important implications for future planning for intensive care nurse staffing and highlights important factors to be accounted for in future research studies. IMPLICATIONS FOR NURSING MANAGEMENT: In order to safeguard patient and staff safety, factors such as the ICU layout need to be considered in staffing decisions and the local business case for nurse staffing needs to reflect these factors. Patient safety in intensive care may not be best served by a blanket 'ratio' approach to nurse staffing, intended to apply uniformly across health services.

A qualitative exploration of the factors influencing the decision to transfuse elective platelets in cancer care.

OBJECTIVES: To explore factors contributing to decisions to transfuse platelets in cancer care outside guidelines using case study methods. METHODS: Two case studies were examined, using instrumental case study methodology, to qualitatively explore factors that influence the decision to transfuse platelets. Interviews (n=10) were conducted around cases in haematology and critical care. In-depth review of documentary evidence was undertaken and propositions were developed to provide rigour during the investigation. Thematic analysis and triangulation of documents was undertaken to find specific factors, and propositions analysed, as per instrumental case study methods. RESULTS: Both cases emphasised how patient complexity, and individual response to platelet administration, was an influencing factor. Other themes included uncertainty of clinical situations coupled with uncertainty about platelet availability. Other factors worthy of further investigation include the concept of professional safety and the trustworthiness of platelet thresholds against platelet monitoring for bleeding episodes. CONCLUSION: The findings indicated several factors influence decisions to transfuse, including clinical context, and individual ability to trust guidelines and assume any perceived risks.

An immunotherapy survivor population: health-related quality of life and toxicity in patients with metastatic melanoma treated with immune checkpoint inhibitors.

PURPOSE: The immune checkpoint inhibitors (ICIs) have resulted in subgroups of patients with metastatic melanoma achieving high-quality durable responses. Metastatic melanoma survivors are a new population in the era of cancer survivorship. The aim of this study was to evaluate metastatic melanoma survivors in terms of health-related quality of life (HRQoL), immune-related adverse events (irAEs) and exposure to immunosuppressive agents in a large single centre in the UK. METHODS: We defined the survivor population as patients with a diagnosis of metastatic melanoma who achieved a durable response to an ICI and had been followed-up for a minimum of 12 months from initiation of ICI without disease progression. HRQoL was assessed using SF-36. Electronic health records were accessed to collect data on demographics, treatments, irAEs and survival. HRQoL data was compared with two norm-based datasets. RESULTS: Eighty-four metastatic melanoma survivors were eligible and 87% (N = 73) completed the SF-36. ICI-related toxicity of any grade occurred in 92% of patients and 43% had experienced a grade 3 or 4 toxicity. Almost half (49%) of the patients required steroids for the treatment of ICI-related toxicity, whilst 14% required treatment with an immunosuppressive agent beyond steroids. Melanoma survivors had statistically significant lower HRQoL scores with regard to physical, social and physical role functioning and general health compared with the normative population. There was a trend towards inferior scores in patients with previous exposure to ipilimumab compared with those never exposed to ipilimumab. CONCLUSIONS: Our results show that metastatic melanoma survivors have potentially experienced significant ICI-related toxicity and experience significant impairments in specific HRQoL domains. Future service planning is required to meet this population's unique survivorship needs.

Burnout: Caring for critically ill and end-of-life patients with cancer.

BACKGROUND: Critical care and palliative care professionals treat and support seriously ill patients on a daily basis, and the possibility of burnout may be high. The consequences of burnout can include moral injury and distress, and compassion fatigue, which are detrimental to both care and staff. AIMS AND OBJECTIVES: To explore the incidence of moral distress in areas at high risk of burnout in a large cancer centre and to explore possible measures for addressing moral distress. DESIGN: A cross-sectional survey. METHODS: The Maslach Burnout Inventory was administered to critical care, critical care outreach, and palliative care teams in a specialist tertiary cancer centre. Open questions on supportive measures were also included. Burnout data were categorised into three domains of emotional exhaustion, depersonalization and personal accomplishment, and free-text analysis was conducted on the open-question data. RESULTS: A total of 63 professionals responded across the teams (45% response rate). A low level of burnout was observed in the emotional exhaustion domain; depersonalization was higher in the critical care professionals; and overall, personal accomplishment was higher than normative scores. Free-text analysis highlighted three categories of responses: Debriefing, Managing emotional well-being, and Valuing individuals. There was a need to proactively recognize issues; undertake more debriefs; and open forums regarding cases, particularly with difficult deaths. Engaging all professionals, support to deal with families, and mandatory moral distress and resilience training were suggested, alongside a focus on team building through external activities such as group relaxation sessions and walks. CONCLUSIONS: This study demonstrated a relatively low incidence of emotional exhaustion and depersonalization, and a slightly higher sense of personal accomplishment than normative scores despite staff working in an environment where high levels of burnout were expected. RELEVANCE TO CLINICAL PRACTICE: Staff highlighted possible solutions to reduce burnout, which included debriefing, managing emotional well-being, and valuing individuals.

Managing clinical uncertainty: An ethnographic study of the impact of critical care outreach on end-of-life transitions in ward-based critically ill patients with a life-limiting illness.

Rapid response teams, such as critical care outreach teams, have prominent roles in managing end-of-life transitions in critical illness, often questioning appropriateness of treatment escalation. Clinical uncertainty presents clinicians with dilemmas in how and when to escalate or de-escalate treatment. AIMS AND OBJECTIVES: To explore how critical care outreach team decision-making processes affect the management of transition points for critically ill, ward-based patients with a life-limiting illness. METHODS: An ethnographic study across two hospitals observed transition points and decisions to de-escalate treatment, through the lens of critical care outreach. In-depth interviews were carried out to elucidate rationales for practices witnessed in observations. Detailed field notes were taken and placed in a descriptive account. Ethnographic data were analysed, categorised and organised into themes using thematic analysis. FINDINGS: Data were collected over 74 weeks, encompassing 32 observation periods with 20 staff, totalling more than 150 hr. Ten formal staff interviews and 20 informal staff interviews were undertaken. Three main themes emerged: early decision-making and the role of critical care outreach; communicating end-of-life transitions; end-of-life care and the input of critical care outreach. Findings suggest there is a negotiation to achieve smooth transitions for individual patients, between critical care outreach, and parent or ward medical teams. This process of negotiation is subject to many factors that either hinder or facilitate timely transitions. CONCLUSIONS: Critical care outreach teams have an important role in shared decision-making. Associated emotional costs relate to conflict with parent medical teams, and working as lone practitioners. The cultural contexts in which teams work have a significant effect on their interactions and agency. RELEVANCE TO PRACTICE: There needs to be a cultural shift towards early and open discussion of treatment goals and limitations of medical treatment, particularly when facing serious illness. With training and competencies, outreach nurses are well placed to facilitate these discussions.

The lived experience of men with advanced cancer in relation to their perceptions of masculinity: a qualitative phenomenological study.

AIMS AND OBJECTIVES: The aim of this exploratory research was to understand how men experience their advanced cancer in relation to their perceptions of masculinity. BACKGROUND: There are differences in the way men and women experience illness and health care. There are inequalities in incidence and morbidities of many diseases as well as differences in rates of help-seeking behaviours. Theories on masculinity offer some explanation towards this. Men's experiences of advanced cancer in relation to masculinity are under reported, published literature suggests that there are certain issues or men dealing with advanced disease that justify investigation. DESIGN: A Qualitative approach using a Husserlian Phenomenological design was conducted. SAMPLE: Eight men (aged 26-68) all with advanced cancer, defined as advanced or metastatic disease for which the patient had exhausted all standard therapeutic options. METHODS: In-depth interviews were conducted to capture narratives of the experiences of men. Data were analysed using Colaizzi's seven stage framework. RESULTS: Themes included thwarted ambition, changing expectations, protection and provision, stoicism and coping, images of illness versus images of masculinity, importance of being a fighter and loss. CONCLUSION: Findings showed that the experiences of these men were complex and should be handled sensitively. Ideas for gender-specific interventions and further research were developed from the findings in relation to current literature. RELEVANCE TO CLINICAL PRACTICE: A better understanding and awareness of this in this context will help nurses to consider more subtle challenges that these patients may be dealing with that in turn could affect how they cope with the burden of cancer.