Richella Ryan

Corticosteroid-use in primary and secondary brain tumour patients: a review

Corticosteroids have been effective in the management of cerebral oedema, in the context of brain tumours, for many decades. Though their effectiveness is well-established, this needs to be balanced against their potential to cause significant side effects. There is currently little consensus in the literature about how this should be done. This article reviews the literature, specifically in relation to the role of corticosteroids in primary and secondary brain tumour patients. Areas reviewed include corticosteroid pharmacology, indications, mechanism of action, toxicity profile, prescribing practices, and corticosteroid-sparing agents.

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.

The importance of the feasibility study: Lessons from a study of the hand-held fan used to relieve dyspnea in people who are breathless at rest.

Background: The dyspnea accompanying advanced cardiorespiratory disease is often refractory to palliation. It is disabling, distressing and associated with the diseases most common everywhere in the world. The hand-held fan, used to generate a draught across the face, is a simple, cost-effective, safe, and universally applicable palliative breathlessness intervention, consistently described as valuable in qualitative research. A previous crossover trial confirmed its benefit in patients breathless at rest, but the washout period was uncertain. Aim: To determine the washout period after use of the hand-held fan to inform accurate randomized controlled trial design. Design: An observational methodological study. Breathlessness intensity was measured using 100 mm visual analog scale and numerical rating scale, and “relief of breathlessness” was measured on a 5-point scale. Those benefitting from the fan provided visual analog scale/numerical rating scale scores until (1) scores returned to baseline values or (2) until response had plateaued. The primary outcome measure was the time (in minutes) to reach either component of the primary study endpoint. Settings/participants: Four in-/out-patient hospice/hospital units; participants had chronic refractory breathlessness using the fan. Results: Overall, 31 patients participated (mean age: 74.8 years; range: 49–98 years, standard deviation = 11.5 years); 64% were males. Approximately, half of the sample experienced benefit of moderate effect size. The relative reduction in breathlessness relative to the mean baseline score for the sample was 27% for the visual analog scale and 19% for the numerical rating scale. Conclusion: Feasibility work is essential, even for simple widely employed interventions.

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 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 of unknown primary: addressing the communicative, ethical and medical challenges in clinical practice – a perspective from palliative care and supportive oncology

Abstract Cancer of unknown primary (CUP) constitutes approximately 3–5% of all cancers and is the fourth leading cause of cancer death in females and males in developed countries. Despite its frequency, it remains a poorly understood entity in terms of its behaviour, investigation, management and prognosis. Physicians and allied professionals, especially those in palliative care, face unique ethical, communicative and medical challenges in the context of CUP. These challenges have not been specifically explored in the literature to date. This article illustrates these challenges in the form of a case report and discussion.

Breathlessness and inflammation: potential relationships and implications

Purpose of reviewBreathlessness and chronic inflammation both span a wide range of disease contexts and hold prognostic significance. The possibility of a causal relationship between the two has been hypothesized. The aims of this article are to review the intersections between breathlessness and inflammation in the literature, describe potential mechanisms connecting the two phenomena, and discuss the potential clinical implications of a causal relationship. Recent findingsThere is a very limited literature exploring the relationship between systemic inflammation and breathlessness in chronic obstructive pulmonary disease, heart failure, and cancer. One large study in cancer patients is suggestive of a weak association between self-reported breathlessness and inflammation. Studies exploring the relationship between inflammation and Medical Research Council Dyspnoea grade in chronic obstructive pulmonary disease patients have produced inconsistent findings. Although a causal relationship has not yet been proven, there is evidence to support the existence of potential mechanisms mediating a relationship. This evidence points to a role for the skeletal muscle and stress hormone systems. SummaryThere is much progress to be made in this area. Interventional studies, evaluating the impact of anti-inflammatory interventions on breathlessness, are needed to help determine whether a causal relationship exists. If proven, this relationship might have important implications for both the treatment and impact of breathlessness.

Salivary diurnal cortisol profiles in patients with advanced malignant and non-malignant disease: A cross-sectional study

levelmodeling. Saliva sampleswere collected immediately, 15min, 30min, 45min, 3h, 6h, 9h, and 12h, after waking each day for two consecutive days from 82 healthy elders in Hong Kong (equal number ofmen andwomen,mean age=73.09 yrs). Day, saliva sampling time, and the motivation to strengthen social ties (Network Cultivation) were treated as fixed variables). Cortisol awakening response and diurnal declinewere examined in relation toNetwork Cultivation. Results showed that participants scoring higher onNetwork Cultivation exhibited a stronger cortisol awakening response and a faster diurnal decline in comparison to those who scored lower on Network Cultivation. This pattern of findings suggests that elders who are more socially embedded exhibit a diurnal cortisol profile typically seen in younger people. Development of intervention/education programs to promote social embeddedness in the elderly is warranted.