Anticipatory prescribing in community end-of-life care in the UK and Ireland during the COVID-19 pandemic: online survey.

BACKGROUND: Anticipatory prescribing (AP) of injectable medications in advance of clinical need is established practice in community end-of-life care. Changes to prescribing guidelines and practice have been reported during the COVID-19 pandemic. AIMS AND OBJECTIVES: To investigate UK and Ireland clinicians' experiences concerning changes in AP during the COVID-19 pandemic and their recommendations for change. METHODS: Online survey of participants at previous AP national workshops, members of the Association for Palliative Medicine of Great Britain and Ireland and other professional organisations, with snowball sampling. RESULTS: Two hundred and sixty-one replies were received between 9 and 19 April 2020 from clinicians in community, hospice and hospital settings across all areas of the UK and Ireland. Changes to AP local guidance and practice were reported: route of administration (47%), drugs prescribed (38%), total quantities prescribed (35%), doses and ranges (29%). Concerns over shortages of nurses and doctors to administer subcutaneous injections led 37% to consider drug administration by family or social caregivers, often by buccal, sublingual and transdermal routes. Clinical contact and patient assessment were more often remote via telephone or video (63%). Recommendations for regulatory changes to permit drug repurposing and easier community access were made. CONCLUSIONS: The challenges of the COVID-19 pandemic for UK community palliative care has stimulated rapid innovation in AP. The extent to which these are implemented and their clinical efficacy need further examination.

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.

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.

Breathlessness and inflammation: potential relationships and implications.

PURPOSE OF REVIEW: Breathlessness 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 FINDINGS: There 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. SUMMARY: There 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.

Service delivery of complex interventions for refractory breathlessness.

PURPOSE OF REVIEW: The review considers the evidence for different service models existing for helping people manage the chronic, irreversible breathlessness that accompanies advanced disease. RECENT FINDINGS: Many 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. SUMMARY: Breathlessness severity gives a better guide to a patient's 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.

Use of Salivary Diurnal Cortisol as an Outcome Measure in Randomised Controlled Trials: a Systematic Review.

BACKGROUND: Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is associated with diverse adverse health outcomes, making it an important therapeutic target. Measurement of the diurnal rhythm of cortisol secretion provides a window into this system. At present, no guidelines exist for the optimal use of this biomarker within randomised controlled trials (RCTs). PURPOSE: The aim of this study is to describe the ways in which salivary diurnal cortisol has been measured within RCTs of health or behavioural interventions in adults. METHODS: Six electronic databases (up to May 21, 2015) were systematically searched for RCTs which used salivary diurnal cortisol as an outcome measure to evaluate health or behavioural interventions in adults. A narrative synthesis was undertaken of the findings in relation to salivary cortisol methodology and outcomes. RESULTS: From 78 studies that fulfilled the inclusion criteria, 30 included healthy participants (38.5 %), 27 included patients with physical disease (34.6 %) and 21 included patients with psychiatric disease (26.9 %). Psychological therapies were most commonly evaluated (n = 33, 42.3 %). There was substantial heterogeneity across studies in relation to saliva collection protocols and reported cortisol parameters. Only 39 studies (50 %) calculated a rhythm parameter such as the diurnal slope or the cortisol awakening response (CAR). Patterns of change in cortisol parameters were inconsistent both within and across studies and there was low agreement with clinical findings. CONCLUSIONS: Salivary diurnal cortisol is measured inconsistently across RCTs, which is limiting the interpretation of findings within and across studies. This indicates a need for more validation work, along with consensus guidelines.

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.

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

PURPOSE OF REVIEW: To review the science of breathlessness and demonstrate how current therapeutic interventions for breathlessness target the known underlying mechanisms. RECENT FINDINGS: There 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. SUMMARY: Therapies 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.

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.