One evidence base; three stories: do opioids relieve chronic breathlessness?

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/. The efficacy of low-dose systemic opioids for chronic breathlessness was questioned by the recent Cochrane review by Barnes et al We examined the reasons for this conflicting finding and re-evaluated the efficacy of systemic opioids. Compared with previous meta-analyses, Barnes et al reported a smaller effect and lower precision, but did not account for matched data of crossover trials (11/12 included trials) and added a risk-of-bias criterion (sample size). When re-analysed to account for crossover data, opioids decreased breathlessness (standardised mean differences -0.32; -0.18 to -0.47; I2=44.8%) representing a clinically meaningful reduction of 0.8 points (0-10 numerical rating scale), consistent across meta-analyses

Researching minoritised communities in palliative care: An agenda for change

Background: Palliative care access, experiences and outcomes of care disadvantage those from ethnically diverse, Indigenous, First nation and First people communities. Research into this field of inquiry raises unique theoretical, methodological, and moral issues. Without the critical reflection of methods of study and reporting of findings, researchers may inadvertently compromise their contribution to reducing injustices and perpetuating racism. Aim: To examine key evidence of the place of minoritised communities in palliative care research to devise recommendations that improve the precision and rigour of research and reporting of findings. Methods: Narrative review of articles identified from PubMed, CINAHL and Google Scholar for 10 years augmented with supplementary searches. Results: We identified and appraised 109 relevant articles. Four main themes were identified (i) Lack of precision when working with a difference; (ii) ‘black box epidemiology’ and its presence in palliative care research; (iii) the inclusion of minoritised communities in palliative care research; and (iv) the potential to cause harm. All stymie opportunities to ‘level up’ health experiences and outcomes across the palliative care spectrum. Conclusions: Based on the findings of this review palliative care research must reflect on and justify the classification of minoritised communities, explore and understand intersectionality, optimise data quality, decolonise research teams and methods, and focus on reducing inequities to level up end-of-life care experiences and outcomes. Palliative care research must be forthright in explicitly indentifying instances of structural and systemic racism in palliative care research and engaging in non-judgemental debate on changes required

What influenced people with chronic or refractory breathlessness and advanced disease to take part and remain in a drug trial? A qualitative study.

BACKGROUND: Recruitment and retention in clinical trials remains an important challenge, particularly in the context of advanced disease. It is important to understand what affects retention to improve trial quality, minimise attrition and reduce missing data. We conducted a qualitative study embedded within a randomised feasibility trial and explored what influenced people to take part and remain in the trial. METHODS: We conducted a qualitative study embedded within a double-blind randomised trial (BETTER-B[Feasibility]: BETter TreatmEnts for Refractory Breathlessness) designed using a person-centred approach. Participants with cancer, chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), or chronic heart failure (CHF), with a modified Medical Research Council dyspnoea scale grade of 3/4 were recruited from three UK sites. A convenience subsample completed qualitative interviews after the trial. Interviews were analysed using thematic analysis. Results were considered in relation to the core elements of person-centred care and our model of the person-centred trial. RESULTS: In the feasibility trial 409 people were screened for eligibility, and 64 were randomised. No participant was lost to follow-up. Twenty-two participants took part in a qualitative interview. Eleven had a diagnosis of COPD, 8 ILD, 2 CHF and 1 lung cancer. The participants' median age was 71 years (range 56-84). Sixteen were male. Twenty had completed the trial, and two withdrew due to adverse effects. The relationship between patient and professional, potential for benefit, trial processes and the intervention all influenced the decision to participate in the trial. The relationship with the research team and continuity, perceived benefit, and aspects relating to trial processes and the intervention influenced the decision to remain in the trial. CONCLUSIONS: In this feasibility trial recruitment targets were met, attrition levels were low, and aspects of the person-centred approach were viewed positively by trial participants. Prioritisation of the relationship between the patient and professional; person-centred processes, including home visits, assistance with questionnaires, and involvement of the carer; and enabling people to participate by having processes in line with individual capabilities appear to support recruitment and retention in clinical trials in advanced disease. We recommend the integration of a person-centred approach in all clinical trials. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN32236160. Registered on 13 June 2016

Symptom prevalence of patients with fibrotic interstitial lung disease: A systematic literature review

© 2018 The Author(s). Background: Those affected by advanced fibrotic interstitial lung diseases have limited treatment options and in the terminal stages, the focus of care is on symptom management. However, quantitatively, little is known about symptom prevalence. We aimed to determine the prevalence of symptoms in Progressive Idiopathic Fibrotic Interstitial Lung Disease (PIF-ILD). Methods: Searches on eight electronic databases including MEDLINE for clinical studies between 1966 and 2015 where the target population was adults with PIF-ILD and for whom the prevalence of symptoms had been calculated. Results: A total of 4086 titles were screened for eligibility criteria; 23 studies were included for analysis. The highest prevalence was that for breathlessness (54-98%) and cough (59-100%) followed by heartburn (25-65%) and depression (10-49%). The heterogeneity of studies limited their comparability, but many of the symptoms present in patients with other end-stage disease were also seen in PIF-ILD. Conclusions: This is the first quantitative review of symptoms in people with Progressive Idiopathic Fibrotic Interstitial Lung Diseases. Symptoms are common, often multiple and have a comparable prevalence to those experienced in other advanced diseases. Quantification of these data provides valuable information to inform the allocation of resources

To What Extent Do the NRS and CRQ Capture Change in Patients' Experience of Breathlessness in Advanced Disease? Findings From a Mixed-Methods Double-Blind Randomized Feasibility Trial.

CONTEXT: Chronic or refractory breathlessness is common and distressing. To evaluate new treatments, outcome measures that capture change in patients' experience are needed. OBJECTIVES: To explore the extent to which the numerical rating scale (NRS) worst and average, and the Chronic Respiratory Questionnaire capture change in patients' experience during a trial of mirtazapine for refractory breathlessness. METHODS: Convergent mixed-methods design embedded within a randomized trial comprising 1) semi-structured qualitative interviews (considered to be the gold standard) and 2) outcome measure data collected pre- and post-intervention. Data were integrated, exploring examples where findings agreed and disagreed. Adults with advanced cancer, chronic obstructive pulmonary disease, interstitial lung disease, or chronic heart failure, with a modified Medical Research Council dyspnea scale grade 3 or 4 were recruited from three U.K. sites. RESULTS: Data were collected for 22 participants. Eleven had a diagnosis of chronic obstructive pulmonary disease, eight interstitial lung disease, two chronic heart failure, and one cancer. Median age was 71 (56-84) years. Sixteen participants were men. Changes in the qualitative data were commonly captured in the NRS (worst and average) and the Chronic Respiratory Questionnaire. The NRS worst captured change most frequently. Improvement in the emotional domain was associated with physical changes, improved confidence, and control. CONCLUSION: This study found that the NRS using the question "How bad has your breathlessness felt at its worst over the past 24 hours?" captured change across multiple domains, and therefore may be an appropriate primary outcome measure in trials in this population. Future work should confirm the construct validity of this question

Safety of benzodiazepines and opioids in interstitial lung disease: A national prospective study

Copyright ©ERS 2018 Safety concerns are a barrier to prescribing benzodiazepines (BDZs) and opioids in interstitial lung disease (ILD). We therefore examined the association of BDZs and opioids on risk of admission to hospital and death. We conducted a population-based longitudinal cohort study of fibrotic ILD patients starting long-term oxygen therapy in Sweden between October 2005 and December 2014. Effects of BDZs and opioids on rates of admission to hospital and mortality were analysed using Fine-Gray and Cox regression while adjusting for potential confounders. We included 1603 patients (61% females). BDZs were used by 196 (12%) patients and opioids were used by 254 (15%) patients. There was no association between BDZs and increased admission. Treatment with high- versus low-dose BDZs was associated with increased mortality (subdistribution hazard ratio (SHR) 1.46, 95% CI 1.08-1.98 versus 1.13, 95% CI 0.92-1.38). Opioids showed no association with increased admission. Neither low-dose opioids (30 mg·day −1 oral morphine equivalent) (SHR 1.18, 95% CI 0.96-1.45) nor high-dose opioids (>30 mg·day −1 oral morphine equivalent) (SHR 1.11, 95% CI 0.89-1.39) showed association with increased mortality. This first ever study to examine associations between BDZ and opioid use and harm in ILD supports the use of opioids and low-dose BDZs in severely ill patients with respiratory compromise

Mirtazapine for chronic breathlessness? A review of mechanistic insights and therapeutic potential

Introduction: Chronic breathlessness is a common and distressing symptom of advanced disease with few effective treatments. Central nervous system mechanisms are important in respiratory sensation and control. Consequently, drugs which may modify processing and perception of afferent information in the brain, may have a role. Antidepressants have been proposed, however current evidence is limited. Of potentially suitable antidepressants, mirtazapine is an attractive option given its tolerability profile, low cost and wide availability, along with additional potential benefits.Areas covered: The paper provides an overview of the physiology of breathlessness, with an emphasis on central mechanisms, particularly the role of fear circuits and the associated neurotransmitters. It provides a potential rationale for how mirtazapine may improve chronic breathlessness and quality of life in patients with advanced disease. The evidence was identified by a literature search performed in PubMed through to October 2018.Expert commentary: Currently, there is insufficient evidence to support the routine use of antidepressants for chronic breathlessness in advanced disease. Mirtazapine is a promising candidate to pursue, with definitive randomised controlled trials required to determine its efficacy and safety in this setting

Implementation of the Needs Assessment Tool for Interstitial Lung Disease Patients (NAT:ILD): Facilitators and Barriers

A Needs Assessment Tool (NAT) was developed previously to help clinicians identify the supportive/palliative needs of people with interstitial lung disease (ILD) (NAT:ILD). This letter presents barriers and facilitators to clinical implementation. Data from (1) a focus group of respiratory clinicians and (2) an expert consensus group (respiratory and palliative clinicians, academics, patients, carers) were analysed using Framework Analysis. Barriers related to resources and service reconfiguration, and facilitators to clinical need, structure, objectiveness, flexibility and benefits of an ‘aide-memoire’. Identified training needs included communication skills and local service knowledge. The NAT:ILD was seen as useful, necessary and practical in everyday practice

Holistic services for people with advanced disease and chronic breathlessness: a systematic review and meta-analysis

Background: Breathlessness is a common, distressing symptom in people with advanced disease and a marker of deterioration. Holistic services that draw on integrated palliative care have been developed for this group. This systematic review aimed to examine the outcomes, experiences and therapeutic components of these services. Methods: Systematic review searching nine databases to June 2017 for experimental, qualitative and observational studies. Eligibility and quality were independently assessed by two authors. Data on service models, health and cost outcomes were synthesised, using meta-analyses as indicated. Data on recipient experiences were synthesised thematically and integrated at the level of interpretation and reporting. Results: From 3239 records identified, 37 articles were included representing 18 different services. Most services enrolled people with thoracic cancer, involved palliative care staff and comprised 4-6 contacts over 4-6 weeks. Commonly used interventions included breathing techniques, psychological support and relaxation techniques. Meta-analyses demonstrated reductions in Numeric Rating Scale distress due to breathlessness (n=324; mean difference (MD) '2.30, 95% CI '4.43 to '0.16, p=0.03) and Hospital Anxiety and Depression Scale (HADS) depression scores (n=408, MD '1.67, 95% CI '2.52 to '0.81, p<0.001) favouring the intervention. Statistically non-significant effects were observed for Chronic Respiratory Questionnaire (CRQ) mastery (n=259, MD 0.23, 95% CI '0.10 to 0.55, p=0.17) and HADS anxiety scores (n=552, MD '1.59, 95% CI '3.22 to 0.05, p=0.06). Patients and carers valued tailored education, self-management interventions and expert staff providing person-centred, dignified care. However, there was no observable effect on health status or quality of life, and mixed evidence around physical function. Conclusion: Holistic services for chronic breathlessness can reduce distress in patients with advanced disease and may improve psychological outcomes of anxiety and depression. Therapeutic components of these services should be shared and integrated into clinical practice. Registration number: CRD42017057508