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IMPORTANCE: Chronic breathlessness is common in people with chronic obstructive pulmonary disease (COPD). Regular, low-dose, extended-release morphine may relieve breathlessness, but evidence about its efficacy and dosing is needed. OBJECTIVE: To determine the effect of different doses of extended-release morphine on worst breathlessness in people with COPD after 1 week of treatment. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, double-blind, placebo-controlled randomized clinical trial including people with COPD and chronic breathlessness (defined as a modified Medical Research Council score of 3 to 4) conducted at 20 centers in Australia. People were enrolled between September 1, 2016, and November 20, 2019, and followed up through December 26, 2019. INTERVENTIONS: People were randomized 1:1:1 to 8 mg/d or 16 mg/d of oral extended-release morphine or placebo during week 1. At the start of weeks 2 and 3, people were randomized 1:1 to 8 mg/d of extended-release morphine, which was added to the prior week's dose, or placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was change in the intensity of worst breathlessness on a numerical rating scale (score range, 0 [none] to 10 [being worst or most intense]) using the mean score at baseline (from days -3 to -1) to the mean score after week 1 of treatment (from days 5 to 7) in the 8 mg/d and 16 mg/d of extended-release morphine groups vs the placebo group. Secondary outcomes included change in daily step count measured using an actigraphy device from baseline (day -1) to the mean step count from week 3 (from days 19 to 21). RESULTS: Among the 160 people randomized, 156 were included in the primary analyses (median age, 72 years [IQR, 67 to 78 years]; 48% were women) and 138 (88%) completed treatment at week 1 (48 in the 8 mg/d of morphine group, 43 in the 16 mg/d of morphine group, and 47 in the placebo group). The change in the intensity of worst breathlessness at week 1 was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, -0.3 [95% CI, -0.9 to 0.4]) or between the 16 mg/d of morphine group and the placebo group (mean difference, -0.3 [95%, CI, -1.0 to 0.4]). At week 3, the secondary outcome of change in mean daily step count was not significantly different between the 8 mg/d of morphine group and the placebo group (mean difference, -1453 [95% CI, -3310 to 405]), between the 16 mg/d of morphine group and the placebo group (mean difference, -1312 [95% CI, -3220 to 596]), between the 24 mg/d of morphine group and the placebo group (mean difference, -692 [95% CI, -2553 to 1170]), or between the 32 mg/d of morphine group and the placebo group (mean difference, -1924 [95% CI, -47 699 to 921]). CONCLUSIONS AND RELEVANCE: Among people with COPD and severe chronic breathlessness, daily low-dose, extended-release morphine did not significantly reduce the intensity of worst breathlessness after 1 week of treatment. These findings do not support the use of these doses of extended-release morphine to relieve breathlessness. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02720822.

OPINION STATEMENT: Delirium is a common medical complication in people living with cancer, particularly with more advanced disease. Delirium is associated with significant symptom burden which causes distress and impacts quality of life. As recommended by international guidelines, a high degree of suspicion is needed to ensure delirium is detected early. Attention to collateral history can provide clues to changes in cognition and attention. Non-pharmacological approaches that can be considered essential elements of care are effective in reducing the risk of delirium. Delirium screening using a validated measure is recommended as even expert clinicians can underdiagnose or miss delirium. The diagnostic assessment requires consideration of the cancer diagnosis and comorbidities, in the context of potential reversibility, goals of care, and patient preferences. The gold standard approach based on expert consensus is to institute management for delirium precipitants supported by non-pharmacological essential care, with the support of an interdisciplinary team. Medication management should be used sparingly and for a limited period of time wherever possible for severe perceptual disturbance or agitation which has not improved with non-pharmacological approaches. Clinicians should be familiar with the registered indication for medications and seek informed consent for off-label use. All interventions put in place to manage delirium need to consider net clinical benefit, including harms such as sedation and loss of capacity for meaningful interaction. Clear communication and explanation are needed regularly, with the person with delirium as far as possible and with surrogate decision makers. Delirium can herald a poor prognosis and this needs to be considered and be discussed as appropriate in shared decision-making. Recall after delirium has resolved is common, and opportunity to talk about this experience and the related distress should be offered during the period after recovery.

Purpose Sleep disturbance is easily overlooked in subspecialty consultations and may remain untreated during and after initial treatment of malignant brain tumours (BT). This study aimed to explore perceptions of healthcare professionals (HCPs) actively engaged in neuro-oncology care towards sleep disturbance in adults with primary or secondary BT and to identify facilitators and barriers to assessment and management of sleep disturbance. Methods A survey was conducted to explore HCPs’ perceptions about their knowledge, skills, and confidence in managing sleep disturbance in people with BT. The survey also explored their beliefs, motivation, and perceived role in managing sleep disturbance, and views on contributing external factors that impacted management. Results Seventy-three interdisciplinary HCPs with average of 9.3 years of clinical experience in neuro-oncology participated. Fifty-five percent of participants were medical or radiation oncologists. Participants reported a high observed prevalence of sleep disturbance, especially in inpatient settings, during initial treatment, and after tumour progression or recurrence. Only 20% of participants reported routinely reviewing sleep-related symptoms during consultations. General symptom screening questions were perceived as helpful to identify sleep disturbance. Almost all respondents (92%) viewed corticosteroids as the most relevant risk factor, followed by psychological distress. The most frequent clinical responses were offering verbal advice and prescribing medication. The lack of time, resources, and training for managing sleep issues were commonly reported barriers. Conclusions Overall, participants perceived sleep disturbance as highly prevalent in neuro-oncology and positively viewed the importance of managing this symptom. Practical barriers to management were reported that future interventions can target.

ContextCurrently, systematic evidence of the prevalence of clinically significant depressive symptoms in people with extremely short prognoses is not available to inform its global burden, assessment, and management.ObjectivesTo determine the prevalence of clinically significant depressive symptoms in people with advanced life-limiting illnesses and extremely short prognoses (range of days to weeks).MethodsA systematic review and meta-analysis (random-effects model) were performed (PROSPERO: CRD42019125119). MEDLINE, Embase, PsycINFO, CINAHL, and CareSearch were searched for studies (1994-2019). Data were screened for the prevalence of clinically significant depressive symptoms (assessed using validated depression-specific screening tools or diagnostic criteria) of adults with advanced life-limiting illnesses and extremely short prognoses (defined by survival or functional status). Quality assessment was performed using the Joanna Briggs Institute Systematic Reviews Checklist for Prevalence Studies for individual studies and Grading of Recommendations Assessment, Development and Evaluation (GRADE) across studies.ResultsThirteen studies were included. The overall pooled prevalence of clinically significant depressive symptoms in adults with extremely short prognoses (n = 10 studies; extremely short prognoses: N = 905) using depression-specific screening tools was 50% (95% CI: 29%-70%; I2 = 97.6%). Prevalence of major and minor depression was 10% (95% CI: 4%-16%) and 5% (95% CI: 2%-8%), respectively. Major limitations included high heterogeneity, selection bias, and small sample sizes in individual studies.ConclusionsClinically, significant depressive symptoms were prevalent in people with advanced life-limiting illnesses and extremely short prognoses. Clinicians need to be proactive in the recognition and assessment of these symptoms to allow for timely intervention.

AIM:Low participation in cancer clinical trials by culturally and linguistically diverse (CALD) patients limits access to cutting-edge treatments and generalizability of results. This is the first study exploring trials knowledge/attitudes and their association with trial participation in Vietnamese- and Anglo-Australian cancer patients. METHODS:Eligible patients diagnosed with cancer in the past 10 years were invited to complete a self-report questionnaire comprising validated measures of: trials knowledge and attitudes, preferred information amount, preferred decision-making involvement, health literacy, and past and future (i.e. hypothetical) trial participation. Multivariable linear regression evaluated correlates of trials knowledge/attitudes. Multinomial logistic regression estimated the relationship between trials knowledge/attitudes and possible future trial participation. RESULTS:Vietnamese-Australian participants (n = 50) had more negative attitudes regarding trials than Anglo-Australians (n = 100; B = -9.28; 95% confidence interval [CI], -17.60 to -0.97; P = 0.029), but similar knowledge (B = -0.91; 95% CI, -2.27 to 0.44; P = 0.18). Future trial participation was associated with positive attitudes (odds ratio [OR] = 1.08; 95% CI, 1.04-1.12; P

Patient-defined factors that are important at the end of life include being physically independent for as long as possible, good symptom control, and spending quality time with friends and family. Hospice care adds to the quality of care and these patient-centered priorities for people with cancer and their families in the last weeks and days of life. Evidence from large observational studies demonstrate that hospice care can improve outcomes directly and support better and more appropriate health care use for people in the last stages of cancer.Team-based community hospice care has measurable benefits for patients, their family caregivers, and health services. In addition to improved symptom control for patients and a greater likelihood of time spent at home, caregiver outcomes are better when hospice care is accessed: informational needs are better met, and caregivers have an improved ability to move on with life after the patient's death compared with people who did not have access to these services.Hospice care continues to evolve as its reach expands and the needs of patients continue to broaden. This is reflected in the transition from hospice being based on excellence in nursing to teams with a broad range of health professionals to meet the complex and changing needs of patients and their families. Additional integration of cancer services with hospice care will help to provide more seamless care for patients and supporting family caregivers during their caregiving and after the death of the patient.

© The Author(s) 2018. Background: Translating research evidence into clinical practice often has a long lag time. Aim: To determine the impact of a phase III randomised controlled trial on palliative care clinicians’ self-reported practice change. Design: Online survey about use of octreotide in managing inoperable malignant bowel obstruction due to cancer or its treatments distributed in November 2016, 2 years after the first publication of the study in a peer-reviewed journal. Demographic, self-reported practice and the reasons underpinning this were collected. Responses were aggregated to ‘practice modified’ or ‘practice not modified’. A multinomial regression model explored predictors of practice change. Setting: Members of the Australian New Zealand Society of Palliative Medicine. Results: Response rate was 20.8% (106/509): 55.6% were aged >50 years, 56.5% were female and 77% had previously prescribed octreotide for this clinical indication. Out of 106 respondents, 52 (49.1%) indicated modified practice (60.9% of those who had previously prescribed octreotide in this setting). In those who reported practice change, most frequently octreotide was now used when other therapies failed; for not changing practice, ‘more confirmatory evidence was needed’ was most often cited. In the regression model, older age (clinician age = 50–59 years; relative risk = 0.147; 95% confidence interval = 0.024–0.918; p = 0.04) and having practices with lower proportions of people treated with octreotide (0%–20%; relative risk = 0.039; 95% confidence interval = 0.002–0.768; p = 0.033) predicted greater self-reported practice change. Conclusion: Clinician-reported change in practice in the survey is seen in the majority of respondents. This suggests that there is a cohort of ‘early adopters’ within palliative care practice as new evidence becomes available.

© Copyright 2017, Mary Ann Liebert, Inc. 2017. Background: Red Blood Cell (RBC) transfusions are commonly used in palliative care. RBCs are a finite resource, transfusions carry risks, and the net effect (benefits and harms) is poorly defined for people with life-limiting illnesses. Objective: To examine the indications and effects of RBC transfusion in palliative care patients. Design: This international, multisite, prospective consecutive cohort study. Setting/Subjects: Palliative care patients undergoing RBC transfusion. Measurements: Target symptoms (fatigue, breathlessness, generalized weakness, or dizziness) were assessed before transfusion and at day 7 by treating clinicians, using National Cancer Center Institute Common Terminology Criteria for Adverse Events. Assessment of harms was made at day 2. Results: One hundred and one transfusions with day 7 follow-up were collected. Median age was 72.0 (interquartile range 61.5-83.0) years, 58% men, and mean Australia-modified Karnofsky Performance Status (AKPS) of 48 (standard deviation [SD] 17). A mean 2.1 (SD 0.6) unit was tranfused. The target symptoms were fatigue (61%), breathlessness (16%), generalized weakness (12%), dizziness (6%), or other (5%). Forty-nine percent of transfusions improved the primary target symptom, and 78% of transfusions improved at least one of the target symptoms. Harms were infrequent and mild. An AKPS of 40%-50% was associated with higher chances of symptomatic benefit in the target symptom; however, no other predictors of response were identified. Conclusions: In the largest prospective consecutive case series to date, clinicians generally reported benefit, with minimal harms. Ongoing work is required to define the optimal patient-and clinician-reported hematological and functional outcome measures to optimize the use of donor blood and to minimize transfusion-Associated risk.

© The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. The high incidence and psychophysiological morbidities of sleep disturbance in cancer have been increasingly recognized. Yet, more detailed understanding of sleep disturbance and options for management have been neglected areas in both clinical care and research. Brain tumor patients have been particularly overlooked. A systematic search of the literature from 1990 to 2015 was performed to review sleep disturbance in adults with primary or secondary brain tumor and their family caregivers. Fifty eligible studies were identified, of which 12 focused on sleep, 37 reported sleep items within a health-related quality of life measure and 1 reported caregivers' sleep. No sleep intervention has been developed or tested for brain tumor patients. Sleep disturbance and somnolence were frequently reported as the most severely rated symptoms within health-related quality of life across the disease course or treatments, along with fatigue. However, sleep-focused studies yielded inconsistent results in small samples of mostly benign brain tumors in long-term remission from total tumor resection. The research using standardized, multifaceted sleep assessments, particularly in patients with malignant brain tumor and caregivers who are undergoing treatment, is seriously lacking. A more systematic examination of sleep disturbance is warranted to inform the development of better symptom management programs in this population.

Copyright © 2017 John Wiley & Sons, Ltd. Prescribing of antipsychotic medications for patients with delirium remains controversial. Concerns exist that these vulnerable and frail patients may be prescribed antipsychotics inappropriately as a substitute for non-pharmacological approaches when identifiable causes are not found or they challenge ward processes. Moreover, recent evidence suggests that antipsychotics may cause more harm than good in the palliative care patient group with delirium. On the other hand, guidelines in the United Kingdom and the Netherlands support prescribing of antipsychotics in certain circumstances, and a large European survey has revealed that antipsychotics tend to be prescribed first line for hyperactive delirium. Never before, therefore, is there a greater need to examine whether indeed these medications are clinically useful for the treatment of delirium. With this in mind, evidence-based arguments for and against prescribing antipsychotics for the treatment of delirium are presented in this debate article. The paper concludes with a moderation piece to help guide clinical practice.

© Mary Ann Liebert, Inc. 2016. Introduction: Delirium has a high mortality rate. Understanding predictors of prognosis in patients with delirium will aid treatment decisions and communication. This study aimed to explore variables associated with death during an established episode of delirium in palliative care when haloperidol treatment had been commenced. Methods: A consecutive cohort of palliative care patients, from 14 centers across four countries, is reported. The outcome of interest was death within 14 days from commencement of haloperidol treatment for delirium. Clinicodemographic variables explored were delirium severity, age, gender, primary life limiting illness, body mass index (BMI), total daily haloperidol dose at baseline (mg), functional status, and comorbidities. Results: One hundred and sixteen palliative care patients where vital status was known were included in the analysis; 45% (n = 52) died within 10 days, and 56% (n = 65) died within 14 days. In multivariate analyses no clinical or demographic variables predicted death, apart from lower BMI in noncancer patients. Conclusion: This study has shown a very high mortality rate within two weeks of commencing haloperidol for delirium in palliative care, with no clear clinical predictors for those with a higher chance of dying. Having a higher BMI offered some benefit in survival, but only in noncancer patients. When delirium occurs in advanced illness, discussion should be initiated about the gravity of the clinical situation.

© 2015, Mary Ann Liebert, Inc. 2015. Many people in our communities live with symptoms for years or decades, something of relevance to hospice/palliative care clinicians and researchers. The proportion of people in the community at large who have a chronic symptom is likely to approximate the proportion of people referred to hospice/palliative care services with that same chronic symptom that pre-dates their life-limiting illness. Such patients may have different responsiveness to, and expectations from, symptomatic therapies, thus requiring more advanced approaches to symptom control. For researchers evaluating the impact of hospice/palliative care services, failing to account for people with long-term refractory symptoms pre-dating their life-limiting illness may systematically underestimate services' benefits. Observational symptom prevalence studies reported in hospice/palliative care to date have not accounted for people with long-term refractory symptoms, potentially systematically overestimating symptoms attributed to life-limiting illnesses. Cross-sectional community prevalence rates of key chronic refractory symptoms largely unrelated to their life-limiting illness reflect the likely prevalence on referral to hospice/palliative care: fatigue (up to 35%); pain (12%-31%); pain with neuropathic characteristics (9%); constipation (2%-29%); dyspnea (4%-9%); cognitive impairment (>10% of people >65 years old; >30% of people >85 years old); anxiety (4%); and depression (lifetime incidence 2%-15%; one year prevalence 3%). Prospective research is needed to establish (1) the prevalence and severity of chronic symptoms that pre-date the diagnosis of a life-limiting illness in people referred to hospice/palliative care services, comparing this to whole-of-population estimates; and (2) whether this group is disproportionately represented in people with refractory symptoms.

The direct burden of people whose goal of care is a palliative approach has not been estimated in the acute care setting. Using a single time point, cross-sectional survey of all inpatient beds, an estimate was generated across a network of three South Australian public hospitals. One in three inpatients had a palliative approach as the goal of care and of these, only one in five had been referred to specialist palliative care services. Those referred were significantly more likely to have cancer and be younger men. Active recognition and documentation that a palliative approach frames the goals of care for this person needs to be incorporated more systematically into clinical practice in the acute care setting. At the same time, triggers for needs-based referral for specialist assessment should be implemented. Specialist palliative care services must also provide direct care for a wider range of patients than just those with cancer. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

Context: Breathlessness reportedly worsens as death approaches for many people, but the differences in intensity and time course between underlying causes are not well described. Objectives: To determine differences in the intensity of breathlessness by diagnosis over time as death approaches in a consecutive cohort seen by a specialist palliative care service. Methods: Patients referred to Silver Chain Hospice Care Service over a period of four years (January 2004 to December 2007) had dyspnea evaluated at every clinical encounter until death. A numeric rating scale (NRS) was used to measure the intensity. Patients were categorized into five clusters (lung cancer, secondary cancer to lung, heart failure, end-stage pulmonary disease, and no identifiable cardiorespiratory cause) at three time points (60-53 [T3], 30-23 [T2], and 7-0 [T1] days before death [T0]). Group differences were assessed using analysis of variance. Joinpoint regression models defined significant changes in mean breathlessness intensity. Results: For 5,862 patients, data were collected an average of 20 times (median: 13; 116,982 data points) for an average of 86 days (median: 48). Breathlessness was significantly higher at all three time points in people with noncancer diagnoses. Breathlessness increased significantly at days 10 and 3 before death for people with cancer (P < 0.001 for both), but remained unchanged, albeit significantly higher for patients with noncancer diagnoses. In the three months leading to death, the prevalence of "no breathlessness" decreased from 50% to 35%, and the proportion of patients with severe breathlessness (>7 out of 10) increased from 10% to 26%. Conclusion: Prevalence of breathlessness increases rapidly at life's end, especially for people with primary lung cancer; the levels of breathlessness became close to those experienced by people with noncancer diagnoses despite symptom control measures. © 2010 U.S. Cancer Pain Relief Committee.