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Introduction: Morphine may decrease the intensity of chronic breathlessness but data from a large randomised controlled trial (RCT) are lacking. This first, large, parallel-group trial aimed to test the efficacy and safety of regular, low-dose, sustained-release (SR) morphine compared with placebo for chronic breathlessness.Methods: Multisite (14 inpatient and outpatient cardiorespiratory and palliative care services in Australia), parallel-arm, double-blind RCT. Adults with chronic breathlessness (modified Medical Research Council≥2) were randomised to 20 mg daily oral SR morphine and laxative (intervention) or placebo and placebo laxative (control) for 7 days. Both groups could take ≤6 doses of 2.5 mg, 'as needed', immediate-release morphine (≤15 mg/24 hours) as required by the ethics review board. The primary endpoint was change from baseline in intensity of breathlessness now (0-100 mm visual analogue scale; two times per day diary) between groups. Secondary endpoints included: worst, best and average breathlessness; unpleasantness of breathlessness now, fatigue; quality of life; function; and harms.Results: Analysed by intention-to-treat, 284 participants were randomised to morphine (n=145) or placebo (n=139). There was no difference between arms for the primary endpoint (mean difference -0.15 mm (95% CI -4.59 to 4.29; p=0.95)), nor secondary endpoints. The placebo group used more doses of oral morphine solution during the treatment period (mean 8.7 vs 5.8 doses; p=0.001). The morphine group had more constipation and nausea/vomiting. There were no cases of respiratory depression nor obtundation.Conclusion: No differences were observed between arms for breathlessness, but the intervention arm used less rescue immediate-release morphine.Trial Registration Number: ACTRN12609000806268. [ABSTRACT FROM AUTHOR]

Objectives: Breathlessness ‘crises’ in people with chronic respiratory conditions are a common precipitant for emergency department (ED) presentations, many of which might be avoided through improved selfmanagement and support. This study sought insights from people with experience of ED ‘near misses’ where they considered going to the ED but successfully selfmanaged instead. Design and methods: A qualitative approach was used with a phenomenological orientation. Participants were eligible if they reported breathlessness on most days from a diagnosed respiratory condition and experience of ≥1 ED near miss. Recruitment was through respiratory support groups and pulmonary rehabilitation clinics. Semistructured interviews were conducted with each participant via telephone or face-to-face. Questions focused on ED-related decision-making, information finding, breathlessness management and support. This analysis used an integrative approach and independent coding by two researchers. Lazarus and Cohen’s Transactional Model of Stress and Coping informed interpretive themes. Results: Interviews were conducted with 20 participants, 15 of whom had chronic obstructive pulmonary disease. Nineteen interviews were conducted via telephone. Analysis identified important factors in avoiding ED presentation to include perceived control over breathlessness, self-efficacy in coping with a crisis and desire not to be hospitalised. Effective coping strategies included: taking a project management approach that involved goal setting, monitoring and risk management; managing the affective dimension of breathlessness separately from the sensory perceptual and building three-way partnerships with primary care and respiratory services. Conclusions: In addition to teaching non-pharmacological and pharmacological management of breathlessness, interventions should aim to develop patients’ generic selfmanagement skills. Interventions to improve self-efficacy should ensure this is substantiated by transfer of skills and support, including knowledge about when ED presentation is necessary. Complementary initiatives are needed to improve coordinated, person-centred care. Future research should seek ways to break the cyclical relationship between affective and sensory-perceptual dimensions of breathlessness. [ABSTRACT FROM AUTHOR]

Introduction Delirium is a common, serious and potentially preventable condition with devastating impact on the quality of life prompting a proliferation of interventional trials. Core outcome sets aim to standardise outcome reporting by identifying outcomes perceived fundamental for measurement in trials of a specific interest area. Our aim is to develop international consensus on two core outcome sets for trials of interventions to prevent and/or treat delirium, irrespective of study population. We aim to identify additional core outcomes specific to the critically ill, acutely hospitalised patients, palliative care and older adults. Methods and analysis We will conduct a systematic review of published and ongoing delirium trials (1980 onwards) and one-on-one interviews of patients who have experienced delirium and family members. These data will inform Delphi round 1 of a two-stage consensus process. In round 2, we will provide participants their own response, summarised group responses and those of patient/family participants for rescoring. We will randomise participants to receive feedback as proportion scoring the outcome as critical or as group mean responses. We will hold a consensus meeting using nominal group technique to finalise outcomes for inclusion. We will repeat the Delphi process and consensus meeting to select measures for each core outcome. We will recruit 240 Delphi participants giving us 80% power to detect a 1.0-1.5 point (9-point scale) difference by feedback method between rounds. We will analyse differences for subsequent scores, magnitude of opinion change, items retained and level of agreement. Ethics and dissemination We are obtaining research ethics approvals according to local governance. Participation will be voluntary and data deidentified. Support from three international delirium organisations will be instrumental in dissemination and core outcome set uptake. We will disseminate through peer-reviewed open access publications and present at conferences selected to reach a wide range of knowledge users. [ABSTRACT FROM AUTHOR]

Introduction Chronic breathlessness is highly prevalent and distressing to patients and families. No medication is registered for its symptomatic reduction. The strongest evidence is for regular, low-dose, extended-release (ER) oral morphine. A recent large phase III study suggests the subgroup most likely to benefit have chronic obstructive pulmonary disease (COPD) and modified Medical Research Council breathlessness scores of 3 or 4. This protocol is for an adequately powered, parallel-arm, placebo-controlled, multisite, factorial, block-randomised study evaluating regular ER morphine for chronic breathlessness in people with COPD. Methods and analysis The primary question is what effect regular ER morphine has on worst breathlessness, measured daily on a 0-10 numerical rating scale. Uniquely, the coprimary outcome will use a FitBit to measure habitual physical activity. Secondary questions include safety and, whether upward titration after initial benefit delivers greater net symptom reduction. Substudies include longitudinal driving simulation, sleep, caregiver, health economic and pharmacogenetic studies. Seventeen centres will recruit 171 participants from respiratory and palliative care. The study has five phases including three randomisation phases to increasing doses of ER morphine. All participants will receive placebo or active laxatives as appropriate. Appropriate statistical analysis of primary and secondary outcomes will be used. Ethics and dissemination Ethics approval has been obtained. Results of the study will be submitted for publication in peer-reviewed journals, findings presented at relevant conferences and potentially used to inform registration of ER morphine for chronic breathlessness. [ABSTRACT FROM AUTHOR]

Objective: To determine the accessibility and currency of delirium guidelines, guideline summary papers and evaluation studies, and critically appraise guideline quality. Design: 1. Systematic literature search for formal guidelines (in English or French) with focus on delirium assessment and/or management in adults (≥18 years), guideline summary papers and evaluation studies. 2. Full appraisal of delirium guidelines published between 2008 and 2013 and obtaining a 'Rigour of Development' domain screening score cutoff of >40% using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Data sources: Multiple bibliographic databases, guideline organisation databases, complemented by a grey literature search. Results: 3327 database citations and 83 grey literature links were identified. A total of 118 retrieved delirium guidelines and related documents underwent full-text screening. A final 21 delirium guidelines (with 10 being >5 years old), 12 guideline summary papers and 3 evaluation studies were included. For 11 delirium guidelines published between 2008 and 2013, the screening AGREE II 'Rigour' scores ranged from 3% to 91%, with seven meeting the cut-off score of >40%. Overall, the highest rating AGREE II domains were 'Scope and Purpose' (mean 80.1%, range 64-100%) and 'Clarity and Presentation' (mean 76.7%, range 38-97%). The lowest rating domains were 'Applicability' (mean 48.7%, range 8-81%) and 'Editorial Independence' (mean 53%, range 2-90%). The three highest rating guidelines in the 'Applicability' domain incorporated monitoring criteria or audit and costing templates, and/or implementation strategies. Conclusions: Delirium guidelines are best sourced by a systematic grey literature search. Delirium guideline quality varied across all six AGREE II domains, demonstrating the importance of using a formal appraisal tool prior to guideline adaptation and implementation into clinical settings. Adding more knowledge translation resources to guidelines may improve their practical application and effective monitoring. More delirium guideline evaluation studies are needed to determine their effect on clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Breathlessness remains a highly prevalent and distressing symptom for many patients with progressive life-limiting illnesses. Evidence-based interventions for chronic breathlessness are limited, and there is an ongoing need for high-quality research into developing management strategies for optimal palliation of this complex symptom. Previous studies have suggested that selective serotonin reuptake inhibitors such as sertraline may have a role in reducing breathlessness. This paper presents the protocol for a large, adequately powered randomised study evaluating the use of sertraline for chronic breathlessness in people with progressive life-limiting illnesses. Methods and analysis: A total of 240 participants with modified Medical Research Council Dyspnoea Scale breathlessness of level 2 or higher will be randomised to receive either sertraline or placebo for 28 days in this multisite, double-blind study. The dose will be titrated up every 3 days to a maximum of 100 mg daily. The primary outcome will be to compare the efficacy of sertraline with placebo in relieving the intensity of worst breathlessness as assessed by a 0-100 mm Visual Analogue Scale. A number of other outcome measures and descriptors of breathlessness as well as caregiver assessments will also be recorded to ensure adequate analysis of participant breathlessness and to allow an economic analysis to be performed. Participants will also be given the option of continuing blinded treatment until either study data collection is complete or net benefit ceases. Appropriate statistical analysis of primary and secondary outcomes will be used to describe the wealth of data obtained. Ethics and dissemination: Ethics approval was obtained at all participating sites. Results of the study will be submitted for publication in peer-reviewed journals and the key findings presented at national and international conferences. [ABSTRACT FROM AUTHOR]

Objective Hospice/palliative care patients may differ from better studied populations, and data from other populations cannot necessarily be extrapolated into hospice/palliative care clinical practice. Pharmacovigilance studies provide opportunities to understand the harms and benefits of medications in routine practice. Gabapentin, a γ-amino butyric acid analogue antiepileptic drug, is commonly prescribed for neuropathic pain in hospice/palliative care. Most of the evidence however relates to nonmalignant, chronic pain syndromes (diabetic neuropathy, postherpetic neuralgia, central pain syndromes, fibromyalgia). The aim of this study was to quantify the immediate and short-term clinical benefits and harms of gabapentin in routine hospice/palliative care practice. Design Multisite, prospective, consecutive cohort. Population 127 patients, 114 of whom had cancer, who started gabapentin for neuropathic pain as part of routine clinical care. Settings 42 centres from seven countries. Data were collected at three time points--at baseline, at day 7 (and at any time; immediate and short-term harms) and at day 21 (clinical benefits). Results At day 21, the average dose of gabapentin for those still using it (n=68) was 653 mg/24 h (range 0-1800 mg) and 54 (42%) reported benefits, of whom 7 (6%) experienced complete pain resolution. Harms were reported in 39/127 (30%) patients at day 7, the most frequent of which were cognitive disturbance, somnolence, nausea and dizziness. Ten patients had their medication ceased due to harms. The presence of significant comorbidities, higher dose and increasing age increased the likelihood of harm. Conclusions Overall, 42% of people experienced benefit at a level that resulted in continued use at 21 days. [ABSTRACT FROM AUTHOR]

Background: In December 2013, a partnership between five local health districts and a non-governmental organisation implemented the Palliative Care Home Support Packages (PEACH) Program. The PEACH Program aims to support palliative care clients in their last days of life at their own home. This study sought to evaluate the quality of care delivered by the service from the perspective of clients' primary carers., Methods: A letter was sent to carers of clients 6-10 weeks after the client's death, inviting them to participate in an anonymous survey. The survey measured the level of satisfaction on various aspects of the service using FAMCARE and Likert scales, and invited for comments about the care received and suggestions for improvement., Results: Out of 17 aspects of care provided by the PEACH Program, 13 were scored with 'exceptional' or 'acceptable performance'. The highest satisfaction was observed in meeting clients' physical needs and providing pain relief. The most dissatisfaction was observed in addressing spiritual matters, family conferences and information about treatment side effects. Ninety-five per cent of responses were either 'satisfied' or 'very satisfied' with the overall care provided at home during the last week of the client's life., Conclusion: The results of this research provide further evidence to the field of what constitutes a good home death and the support mechanisms required to enable this. The results also have strong implications on how local services provided by the PEACH Program are delivered in the future., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: We aimed to identify and evaluate: (1) treatment-emergent adverse events (TEAE (worse or new since baseline)) and the subgroup of severe TEAEs in a placebo-controlled 7-day randomised trial of regular, low-dose, sustained-release oral morphine for chronic breathlessness and (2) clinical characteristics associated with TEAE., Methods: Safety analysis of trial data. Adults with chronic breathlessness (modified Medical Research Council breathlessness score ≥2) due to heart or lung disease, or cancer, not on regular opioids were eligible. Symptoms associated with opioids (TEAE of special interest) were systematically sought using Common Terminology Criteria for Adverse Events (CTCAE) grading. Other harms could be reported at any time. The relationship between characteristics and presence of ≥1 TEAE of special interest was explored using univariable logistic regression analyses., Results: 1449/5624 (26%) Adverse Events from 279 participants were TEAE of which 150/1449 (10%) were severe (CTCAE grades 3-5). 1086/5624 (75%) were events of special interest of which 41/1086 (4%) were severe. Compared with placebo, morphine was not associated with more TEAE or severe TEAE of special interest (TEAE: OR 0.53, 95% CI 0.21 to 1.38, p=0.20; severe TEAE: OR 0.96, 95% CI 0.27 to 3.41, p=0.95) nor with CTCAE severity grade (χ 2 =4.39, p=0.50). Among the 26/150 (17%) with severe TEAEs, study withdrawal was more common in the morphine arm (18/26 (69%) morphine arm; 8/26 (30%) placebo arm). None of the severe TEAEs was a respiratory harm., Conclusions: Severe morphine-associated toxicity was uncommon and not associated with study arm. Clinical consequences were minor and self-limiting., Trial Registration Number: ACTRN126000806268., Competing Interests: Competing interests: DC has received an unrestricted research grant from Mundipharma, is an unpaid member of an advisory board for Helsinn Pharmaceuticals and has consulted Mayne Pharma and received intellectual property payments from them. MJJ has received consulting institutional payments from Mayne Pharma. No other authors have any conflicting interests with the content of this manuscript., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Although palliative care is an important public healthcare issue worldwide, the current situation in the Asia-Pacific region has not been systematically evaluated., Objectives: This survey aimed to clarify the current status of palliative care in the Asia-Pacific region., Methods: Questionnaires were sent to a representative physician of each member country/region of the Asia Pacific Hospice Palliative Care Network (APHN). The questionnaire examined palliative care service provision, information regarding physician certification in palliative care, the availability of essential drugs for palliative care listed by the International Association for Hospice and Palliative Care (IAHPC) and the regulation of opioid-prescribing practice., Results: Of the 14 member countries/regions of the APHN, 12 (86%) responded. Some form of specialist palliative care services had developed in all the responding countries/regions. Eight member countries/regions had physician certifications for palliative care. Most essential drugs for palliative care listed by the IAHPC were available, whereas hydromorphone, oxycodone and transmucosal fentanyl were unavailable in most countries/regions. Six member countries/regions required permission to prescribe and receive opioids., Conclusions: The development of palliative care is in different stages across the surveyed countries/regions in the Asia-Pacific region. Data from this survey can be used as baseline data for monitoring the development of palliative care in this region., (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/.)

Objectives: Loss of appetite is prevalent in palliative care and distressing for patients and families. Therapies include corticosteroids or progestogens. This study explores the net effect of dexamethasone on anorexia., Methods: Prospective data were collected when dexamethasone was started for anorexia as part of routine care. The National Cancer Institute's Common Toxicity Criteria for Adverse Events (NCICTCAE) Likert scales assessed severity of anorexia and immediate and short-term harms at 2 time points: baseline and 7 days., Results: This study (41 sites, 8 countries) collected data (July 2013 to July 2014) from 114 patients (mean age 71 (SD 11), 96% with cancer). Median Australian-modified Karnofsky Performance Scale was 50% (range 20-70). Mean baseline NCICTCAE anorexia score was 2.7 (SD 0.6; median 3). 6 patients died by day 7. Of 108 evaluable patients, 74 (68.5%; 95% CI 59.0% to 76.7%) reported ≥1 reduction anorexia scores by day 7, of whom 30 were 0. Mean dexamethasone dose on day 7 was 4.1 mg/day (SD 3.4; median 4; range 0-46 mg). 24 patients reported ≥1 harms (32.4% CI 22.6% to 44.1%; insomnia n=10, depression n=7, euphoria n=7 and hyperglycaemia n=7). Of 24 patients with no benefit, 10 reported ≥1 harms., Conclusions: This study shows positive and negative effects of 7 days of dexamethasone as an appetite stimulant in patients with advanced life-limiting illnesses. Identifying clinicodemographic characteristics of people most at risk of harms with no benefit is a crucial next step. Longer term follow-up will help to understand longer term and cumulative harms., (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/)