Anna Spathis

Teenage and Young Adult Cancer-Related Fatigue Is Prevalent, Distressing, and Neglected: It Is Time to Intervene. A Systematic Literature Review and Narrative Synthesis

PURPOSE Cancer-related fatigue in adults has been the subject of considerable recent research, confirming its importance as a common and debilitating symptom, and establishing a number of evidence-based interventions. There has, however, been limited focus on the fatigue suffered by teenagers and young adults with cancer, a group recognized as having unique experiences and developmental needs. We have undertaken a systematic review of the literature to provide a comprehensive overview of studies evaluating fatigue in this younger patient group in order to guide clinical practice and future research. METHOD We searched MEDLINE, EMBASE, PsycINFO, and CINAHL databases for literature containing data relating to any aspect of fatigue in patients aged 13-24 at cancer diagnosis or treatment. RESULTS Sixty articles were identified, of which five described interventional clinical trials. Cancer-related fatigue was consistently one of the most prevalent, severe, and distressing symptoms, and it persisted long-term in survivors. It was associated with a number of factors, including poor sleep, depression, and chemotherapy. There was little evidence for the effectiveness of any intervention, although exercise appears to be the most promising. Importantly, fatigue was itself a significant barrier to physical and social activities. CONCLUSION Cancer-related fatigue is a major and disabling problem in young cancer patients. Effective management strategies are needed to avoid compounding the dependence and social isolation of this vulnerable patient group. Future research should focus on providing evidence for the effectiveness of interventions, of which activity promotion and management of concurrent symptoms are the most promising.

The Breathing, Thinking, Functioning clinical model: a proposal to facilitate evidence-based breathlessness management in chronic respiratory disease

Refractory breathlessness is a highly prevalent and distressing symptom in advanced chronic respiratory disease. Its intensity is not reliably predicted by the severity of lung pathology, with unhelpful emotions and behaviours inadvertently exacerbating and perpetuating the problem. Improved symptom management is possible if clinicians choose appropriate non-pharmacological approaches, but these require engagement and commitment from both patients and clinicians. The Breathing Thinking Functioning clinical model is a proposal, developed from current evidence, that has the potential to facilitate effective symptom control, by providing a rationale and focus for treatment.

Service delivery of complex interventions for refractory breathlessness.

Purpose of reviewThe review considers the evidence for different service models existing for helping people manage the chronic, irreversible breathlessness that accompanies advanced disease. Recent findingsMany of the service models that are delivering care have not yet published their results in the scientific literature because these ideas, and the methods to evaluate them, are relatively new. There are three randomized controlled trials published which demonstrate the effectiveness of this approach and one which suggests that more episodes of some intervention components are not necessarily better. SummaryBreathlessness severity gives a better guide to a patients prognosis than physiological measures in many diseases and the general population. Randomized controlled trial evidence confirms that a complex intervention for breathlessness can improve quality of life, reduce symptom impact, and support carers. Some preliminary data suggest prognosis improvement in some people. Integrated care is needed for both rapidly progressive disease, where death is inevitable, and chronic illness, when health improvement is possible.

The brain and breathlessness: Understanding and disseminating a palliative care approach

Almost exactly 50 years ago, the first conference to consider breathlessness as a symptom was convened in Manchester by cardiorespiratory physicians and scientists. Julius Comroe identified that breathlessness not only comprised the sensation itself but also ‘the patient’s reaction to that sensation’ and highlighted its similarity to pain in this regard.1 Since that first historic meeting, progress in the clinical assessment and palliation of pain has been significant, while the chronic refractory breathlessness of advanced disease is still often overlooked; even when detected, it is imperfectly managed, causing unnecessary suffering. We suggest that, in part, this relates to a poor understanding of its underlying neurophysiology – on which the rationale, for a palliative care approach to symptom management, is based. Comroe’s insight into breathlessness as a central nervous system (CNS) phenomenon, and one with both sensory and affective dimensions, was prescient and has now been authoritatively confirmed in neuroimaging studies.2,3 It has been firmly established that breathlessness is a complex experience of the mind and the body, comprising different sensations that can only be perceived by the individual. Affective components drive the accompanying feelings of distress, fear and anxiety, and it is the brain, not the lungs, that generates these phenomena. While the brain has long been recognised as the origin of all sensory phenomena, including breathlessness, in the neuroscientific literature, this insight has not yet been widely integrated into clinical approaches to the symptom. In cardiorespiratory and even palliative medicine, breathlessness is more commonly understood to be mediated in and by the heart, lungs and great vessels. ‘Stimulation of the failing organ’ is often considered the most effective intervention.4 When this fails, little else is tried, and patients and families continue to live with this devastating symptom unrelieved. When there was no evidence to guide clinicians, this could have been excusable. Now, however, the evidence base in the palliation of breathlessness is growing rapidly. The essence of palliative care is to improve patients’ and carers’ quality of life through early identification and impeccable assessment and treatment of symptoms. Palliative care clinicians and researchers therefore need to take the lead in improving the care of breathlessness, as they did with cancer pain, in every setting in collaboration with their colleagues, particularly those in cardiorespiratory medicine and primary care. The recent publication of two palliative medicine randomised controlled trials (RCTs) from specialist services in Cambridge and London, United Kingdom, demonstrating the effectiveness of a complex intervention in relieving suffering and reducing the impact of breathlessness, gives clinicians and commissioners the evidence they need to implement best practice.5,6 They emphatically remove any excuse for failing breathless patients, and their families, any longer. ‘Assessing dyspnoea is the first step in managing it’.7 There is clear evidence that although breathlessness is a very common symptom in advanced illness, its presence and severity are rarely recorded – even in diseases like cancer and chronic obstructive pulmonary disease (COPD) where it occurs in the majority of people. In the past, inadequate tools for assessing breathlessness in clinical practice, coupled with a sense of therapeutic nihilism, were probably contributory factors to this neglect. Now eliciting the presence of breathlessness, recording its severity and treating it should be standard practice. Importantly, increased understanding of the multidimensional nature of breathlessness has led to the development of new accurate scales that assess the sensory and affective components of the sensation, and use of these, such as the Multidimensional Dyspnoea Profile, needs to become part of routine care in all settings.8 Banzett et al.9 describe breathlessness as the first ‘vital symptom’ alongside the traditional vital signs that impact patient outcomes. They have demonstrated that the routine recording of breathlessness severity in acute medical units is quick and easy, and that breathlessness severity has potential as a prognostic indicator of in-hospital mortality and other serious outcomes. Appreciation of the usefulness of breathlessness as an indicator of general disease severity, as well as a contributor to unscheduled use of hospital services, particularly acute admissions out of hours, should enhance the likelihood that breathlessness will become more widely assessed, although this alone would not necessarily lead to effective treatment. 579836 PMJ0010.1177/0269216315579836Palliative MedicineEditorial research-article2015

Selective circadian rhythm disturbance in cerebral lymphoma

We present a patient with cerebral lymphoma who developed a selective circadian rhythm disturbance. Treatment with modafinil led to a considerable improvement in quality of life.

Learning from paediatric palliative care: Lessons for adult practice:

Paediatric palliative care is an emerging subspecialty of paediatrics that has developed over the last decade, relatively distinctly from adult palliative care. In recent years, there have been multiple calls in the paediatric literature for the subspecialty to learn from and emulate its wellestablished adult counterpart.1 Our experience, however, is that the converse is also true. The few adult-trained palliative care specialists working in paediatric services are becoming increasingly aware of useful lessons that can be learned from their paediatric colleagues. Although adult and paediatric palliative care share the same fundamental principles – active, patient-centred care striving to enhance quality of life, there are significant differences in needs and practice. Whereas adult palliative care has traditionally focused on patients with cancer, paediatric services look after children with a diverse range of life-limiting conditions, most commonly genetic/congenital diseases (41%) and neuromuscular conditions (39%). Disease trajectories tend to be long and particularly unpredictable. Emergencies, often respiratory crises, occur relatively frequently and usually respond to active intervention. Prescribing for children is influenced by many factors, including body weight and low acceptability of the subcutaneous route of drug administration. Families carry a particularly heavy burden, as longterm primary care givers. Related psychosocial morbidity, such as depression, divorce and unemployment, is prevalent. Children, unlike adults, tend to continue to develop physically and cognitively throughout their illness, and families expect flexible, responsive support at the location of the child, whether at home, school or hospital. Paediatric hospice admission usually occurs for planned respite care or for symptom management, at any time from diagnosis to death. The dual approach, combining palliation with disease modification, cuts across the conventional transition from active treatment to palliative care. It is clear then that paediatric palliative care differs considerably from its adult counterpart, and can be clinically challenging. We argue that it is the development of the subspecialty in the face of such challenges that has lead to the innovative practice from which adult palliative medicine can learn. Necessity is, indeed, ‘the mother of invention’. As children need home-based care, a close relationship with key professionals, and concurrent disease modification with palliation, this has led to the development of specialist nurses, who can provide care across all healthcare settings at any stage from diagnosis to death. For example, paediatric oncology outreach nurses, POONs, act as key workers providing active treatment, such as chemotherapy, within hospital and at home, as well as home-based palliative care at the end of life. There is evidence that, with such support, 80% of children can die in their preferred place, usually home.2 By contrast, adult specialist nursing care is relatively fragmented. Cancer site-specific nurses and respiratory nurse specialists, for example, have traditionally tended to work in one setting, focusing on early-stage disease and then handing over to palliative care colleagues. Adult specialist nursing teams could emulate the POON model with, for example, cancer site-specific specialist nurses working between hospital, hospice and home from diagnosis to death. Although advance care planning is increasingly promoted for adults, the speed with which medical crises develop, coupled with the role of parents in decisionmaking, has meant that, in the paediatric field, future care planning is particularly well developed and frequently integrated with emergency treatment planning. In the UK for example, the South Central Strategic Health Authority has developed a unified Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) policy, which includes a detailed future care plan for children and young people. Decisions about CPR are more easily discussed within the context of a wider future care planning discussion. In addition, formal symptom management plans (SMPs) are an increasingly established part of paediatric and young adult palliative care practice. A SMP summarises the clinical context and anticipated future problems, and then, for each symptom in turn, gives a detailed plan of current and potential treatment options. The plans are shared, usually electronically, with patients, families and the wider healthcare team, 450124 PMJ

The biological impact of living with chronic breathlessness – A role for the hypothalamic–pituitary–adrenal axis?

Breathlessness is a common and distressing symptom in advanced cardiorespiratory disease, with recognised psychological, functional and social consequences. The biological impact of living with chronic breathlessness has not been explored. As breathlessness is often perceived as a threat to survival, we propose that episodic breathlessness engages the stress-response, as regulated by the hypothalamic-pituitary-adrenal (HPA) axis. Furthermore, we hypothesise that chronic breathlessness causes excessive stimulation of the HPA axis, resulting in dysfunctional regulation of the HPA axis and associated neuropsychological, metabolic and immunological sequelae. A number of observations provide indirect support for this hypothesis. Firstly, breathlessness and the HPA axis are both associated with anxiety. Secondly, similar cortico-limbic system structures govern both breathlessness perception and HPA axis regulation. Thirdly, breathlessness and HPA axis dysfunction are both independent predictors of survival. There is a need for direct observational evidence as well as experimental data to investigate this hypothesis which, if plausible, could lead to the identification of a new biomarker pathway to support breathlessness research.

Correlates between basic science and therapeutic interventions: the theory and the practice.

Purpose of reviewTo review the science of breathlessness and demonstrate how current therapeutic interventions for breathlessness target the known underlying mechanisms. Recent findingsThere is increasing evidence that breathlessness is experienced in multiple dimensions. The underlying mechanisms relate to the perceptual processes involved, the emotional response and the functional impact. The theory that breathlessness is perceived when there is a mismatch between the central drive to breathe and the level of ventilation remains a central concept, providing a useful theoretical framework around which many current therapies have been developed. The sites involved in the corticolimbic processing of breathlessness have been identified, though little is known about the neural pathways involved. SummaryTherapies which aim to reduce the neural respiratory drive include oxygen, exercise and opioids. Interventions which aim to improve ventilation include breathing retraining and positioning. Modulation of respiratory afferent feedback may be achieved using chest wall vibration and fan therapy. Cognitive and behavioural therapies aim to modify the emotional response to breathlessness. Opioids have been shown to modulate breathlessness at the level of the corticolimbic system, as well as the brainstem. Further work is needed to identify other relevant neurotransmitter systems in order to explore new therapies.

Salivary diurnal cortisol profiles in patients suffering from chronic breathlessness receiving supportive and palliative care services: a cross-sectional study

Chronic breathlessness is a common source of psychological and physical stress in patients with advanced or progressive disease, suggesting that hypothalamic-pituitary-adrenal (HPA) axis dysregulation may be prevalent. The aim of this study was to measure the salivary diurnal cortisol profile in patients receiving supportive and palliative care for a range of malignant and non-malignant conditions and to compare the profile of those experiencing moderate-to-severe disability due to breathlessness against that of patients with mild/no breathlessness and that of healthy controls. Saliva samples were collected over two consecutive weekdays at 3, 6, and 12h after awakening in 49 patients with moderate-to-severe breathlessness [Medical Research Council (MRC) dyspnoea grade ≥3], 11 patients with mild/no breathlessness (MRC dyspnoea grade ≤2), and 50 healthy controls. Measures of breathlessness, stress, anxiety, depression, wellbeing and sleep were examined concomitantly. The diurnal cortisol slope (DCS) was calculated for each participant by regressing log-transformed cortisol values against collection time. Mean DCS was compared across groups using ANCOVA. Individual slopes were categorised into one of four categories: consistent declining, consistent flat, consistent ascending and inconsistent. Controlling for age, gender and socioeconomic status, the mean DCS was significantly flatter in patients with moderate-to-severe breathlessness compared to patients with mild/no breathlessness and healthy controls [F (2, 103)=45.64, p<0.001]. Furthermore, there was a higher prevalence of flat and ascending cortisol profiles in patients with moderate-to-severe breathlessness (23.4%) compared to healthy controls (0%). The only variable which correlated significantly with DCS was MRC dyspnoea grade (rs=0.29, p<0.05). These findings suggest that patients with moderate-to-severe breathlessness have evidence of HPA axis dysregulation and that this dysregulation may be related to the functional disability imposed by breathlessness.

Cancer-Related Fatigue in Adolescents and Young Adults After Cancer Treatment: Persistent and Poorly Managed

Cancer-related fatigue is the most prevalent and distressing symptom experienced by adolescents and young adults (AYAs). An electronic survey was undertaken to ascertain current fatigue management and perceptions of its effectiveness. Eighty-five percent of responders (68/80) experienced fatigue, and it was worse more than 1 year after cancer treatment ended, compared to <1 year (p = 0.007). Forty-one percent received no fatigue management. Although advice to exercise was the most frequent intervention, the greatest impact of fatigue was on the ability to exercise and most did not find exercise advice helpful. Early intervention is warranted, supporting AYAs to persevere with increasing activity.