Prevalence, severity and impacts of breathlessness in Indian adults: An exploratory, nationally representative, cross-sectional online survey.

There are no known estimates of the prevalence, severity and impacts from breathlessness in low- and middle-income countries. This study aimed to explore the prevalence, severity, self-attributed underlying conditions and impacts of breathlessness limiting exertion in community-dwelling adults in India. This exploratory, population-based online survey recruited a pre-planned sample of 3,000 adult respondents stratified by age, sex and rurality (quotas as per the 2011 Indian National Census). Measures included: demographics; breathlessness limiting exertion (modified Medical Research [mMRC] scale); health-related quality of life (EQ-5D-5L); and disability (World Health Organisation's Disability Assessment Schedule 2.0 12-item questionnaire [WHODAS-12]). Respondents (n = 3,046) had a mean age of 38 years (SD 15); 57% were male, 59% lived in rural areas and 33% had completed 12th grade. Breathlessness limiting exertion (mMRC ≥1) was reported by 44%, mostly attributed to poor nutrition (28%), lung conditions excluding tuberculosis (17%) or anaemia (13%). Compared to those without breathlessness, a higher proportion of people with breathlessness (mMRC ≥1) reported problems across all EQ-5D-5L dimensions. Most people reporting breathlessness (81%) indicated the symptom had adversely affected their normal activities. Disability scores (WHODAS-12 total and individual domains) increased as breathlessness worsened. To conclude, in India, conservative estimates indicate 626 million people live with breathlessness of whom 52 million people live with severe breathlessness. The symptom is associated with poorer health-related quality of life and marked disability, including reduced ability to perform daily activities.

Oxycodone initiation in Australia (2014-2018): Sociodemographic factors and preceding health service use.

AIMS: Oxycodone is the most commonly prescribed strong opioid in Australia. This study describes health service antecedents and sociodemographic factors associated with oxycodone initiation. METHODS: Population-based new user cohort study linking medicine dispensings, hospitalizations, emergency department visits, medical services and cancer notifications from New South Wales (NSW) for 2014-2018. New users had no dispensings of any opioid in the preceding year. We analysed health service use in the 5 days preceding initiation and proportion of people on treatment over 1 year and fitted an area-based, multivariable initiation model with sociodemographic covariates. RESULTS: Oxycodone accounted for 30% of opioid initiations. Annually, 3% of the NSW population initiated oxycodone, and 5-6% were prevalent users; the new user cohort comprised 830 963 people. Discharge from hospital (39.3%), therapeutic procedures (21.4%) and emergency department visits (19.7%) were common; a hospital admission for injury (6.0%) or a past-year history of cancer (7.2%) were less common. At 1 year after initiation, 4.6% of people were using oxycodone. In the multivariable model, new use of oxycodone increased with age and was higher for people outside major cities, for example, an incidence rate ratio of 1.43 (95% confidence interval 1.36-1.51) for inner regional areas relative to major cities; there was no evidence of variation in rates of new use by social disadvantage. CONCLUSION: About half of new oxycodone use in NSW was preceded by a recent episode of hospital care or a therapeutic procedure. Higher rates of oxycodone initiation in rural and regional areas were not explained by sociodemographic factors.

Malnutrition, sarcopenia and cachexia: exploring prevalence, overlap, and perceptions in older adults with cancer.

BACKGROUND: Older adults with cancer are a growing population requiring tailored care to achieve optimum treatment outcomes. Their care is complicated by under-recognised and under-treated wasting disorders: malnutrition, sarcopenia, and cachexia. We aimed to investigate the prevalence, overlap, and patients' views and experiences of malnutrition, sarcopenia, and cachexia, in older adults with cancer. METHODS: Mixed-methods study with cross-sectional study and qualitative interviews. Interviews were thematically analysed through a phenomenological lens, with feedback loop analysis investigating relationships between themes and findings synthesised using modified critical interpretative synthesis. FINDINGS: n = 30 were screened for malnutrition, sarcopenia, and cachexia, n = 8 completed semi-structured interviews. Eighteen (60.0%) were malnourished, 16 (53.3%) sarcopenic, and 17 (56.7%) cachexic. One or more condition was seen in 80%, and all three in 30%. In univariate analysis, Rockwood clinical frailty score (OR 2.94 [95% CI: 1.26-6.89, p = 0.013]) was associated with sarcopenia, reported percentage meal consumption (OR 2.28 [95% CI: 1.24-4.19, p = 0.008]), and visible wasting (OR 8.43 [95% CI: 1.9-37.3] p = 0.005) with malnutrition, and percentage monthly weight loss (OR 8.71 [95% CI: 1.87-40.60] p = 0.006) with cachexia. Screening tools identified established conditions rather than 'risk'. Nutritional and functional problems were often overlooked, overshadowed, and misunderstood by both patients and (in patients' perceptions) by clinicians; misattributed to ageing, cancer, or comorbidities. Patients viewed these conditions as both personal impossibilities, yet accepted inevitabilities. CONCLUSION: Perceptions, identification, and management of these conditions needs to improve, and their importance recognised by clinicians and patients so those truly 'at risk' are identified whilst conditions are more remediable to interventions.

"You're the only thing he comes out [of his room] for": A qualitative study of engagement between Laughter Care Specialists and families of people with dementia in long-term care.

OBJECTIVES: Family involvement in the lives of people who have dementia and live in long-term care is important, but family members may face challenges communicating and connecting with their loved one as dementia progresses. A type of therapeutic humor (Laughter Care) delivered by trained specialists aims to engage people with dementia who reside in long-term care through creative play and laughter. This study aimed to explore the perceptions of Laughter Care Specialists (LCSs) regarding families' engagement with the program. METHODS: Semi-structured interviews were conducted with LCSs (n = 8) and analyzed inductively using thematic analysis. RESULTS: Family members were reported to initially have varied degrees of openness toward Laughter Care, but often become more accepting after observing positive engagement with the person with dementia. Family members were perceived to benefit from the program through witnessing the person with dementia enjoy joyous and light interactions, learn new ways of communicating and connecting with the person with dementia, and engage in positive interactions at end of life. SIGNIFICANCE OF RESULTS: Laughter Care may provide family members with novel ways of communicating and connecting with people who have dementia at end of life as well as comfort into bereavement.

Factors most strongly associated with breathlessness in a population aged 50-64 years.

Background: Breathlessness is a troublesome and prevalent symptom in the population, but knowledge of related factors is scarce. The aim of this study was to identify the factors most strongly associated with breathlessness in the general population and to describe the shapes of the associations between the main factors and breathlessness. Methods: A cross-sectional analysis was carried out of the multicentre population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) of adults aged 50 to 64 years. Breathlessness was defined as a modified Medical Research Council breathlessness rating ≥2. The machine learning algorithm extreme gradient boosting (XGBoost) was used to classify participants as either breathless or nonbreathless using 449 factors, including physiological measurements, blood samples, computed tomography cardiac and lung measurements, lifestyle, health conditions and socioeconomics. The strength of the associations between the factors and breathlessness were measured by SHapley Additive exPlanations (SHAP), with higher scores reflecting stronger associations. Results: A total of 28 730 participants (52% women) were included in the study. The strongest associated factors for breathlessness were (in order of magnitude): body mass index ( SHAP score 0.39), forced expiratory volume in 1 s (0.32), physical activity measured by accelerometery (0.27), sleep apnoea (0.22), diffusing lung capacity for carbon monoxide (0.21), self-reported physical activity (0.17), chest pain when hurrying (0.17), high-sensitivity C-reactive protein (0.17), recent weight change (0.14) and cough (0.13). Conclusion: This large population-based study of men and women aged 50-64 years identified the main factors related to breathlessness that may be prevented or amenable to public health interventions.

Low-Dose Morphine Does Not Cause Sleepiness in COPD: A Secondary Analysis of a Randomized Trial.

RATIONALE: Regular, low-dose, sustained-release morphine is frequently prescribed for persistent breathlessness in chronic obstructive pulmonary disease (COPD). However, effects on daytime sleepiness, perceived sleep quality and daytime function have not been rigorously investigated. OBJECTIVES: Determine the effects of regular, low-dose, sustained-release morphine on sleep parameters in COPD. METHODS: Pre-specified secondary analyses of validated sleep questionnaire data from a randomized trial of daily, low-dose, sustained -release morphine versus placebo over four weeks commencing at 8mg or 16mg/day with blinded up-titration over two weeks to a maximum of 32mg/day. Primary outcomes for these analyses were week-1 Epworth Sleepiness Scale (ESS) and Karolinska Sleepiness Scale (KSS) responses on morphine versus placebo. Secondary outcomes included Leeds Sleep Evaluation Questionnaire (LSEQ) scores (end of weeks 1 and 4), KSS and ESS beyond week-1 and associations between breathlessness, morphine, and questionnaire scores. MEASUREMENTS AND MAIN RESULTS: 156 people were randomized. Week-1 sleepiness scores were not different on morphine versus placebo (∆ESS [95%CI] versus placebo: 8mg group: -0.59 [-1.99, 0.81], p=0.41; 16mg group: -0.72 [-2.33, 0.9], p=0.38; ∆KSS versus placebo: 8mg group: 0.11 [-0.7, 0.9], p=0.78; 16mg group: -0.41 [-1.31, 0.49], p=0.37). This neutral effect persisted at later timepoints. In addition, participants who reported reduced breathlessness with morphine at 4 weeks also had improvement in LSEQ domain scores including perceived sleep quality and daytime function. CONCLUSIONS: Regular, low-dose morphine does not worsen sleepiness when used for breathlessness in COPD. Individual improvements in breathlessness with morphine may be related to improvements in sleep.

Creating more comparable cohorts in observational palliative care studies: A proposed framework to improve applicability and replicability of research.

BACKGROUND: Palliative care is characterised by heterogeneous patient and caregiver populations who are provided care in different health systems and a research base including a large proportion of observational, mostly retrospective studies. The inherent diversity of palliative care populations and the often inadequate study descriptions challenge the application of new knowledge into practice and reproducibility for confirmatory studies. Being able to define systematically study populations would significantly increase their generalisability and effective translation into practice. PROPOSAL: Based on an informal consensus process by active palliative care researchers challenged by this problem and a review of the current evidence, we propose an approach to creating more comparable cohorts in observational (non-randomised) palliative care studies that relies on defining the study population in relation to a fixed, well-defined event from which analyses are built ('anchoring'). In addition to providing a detailed and complete description of the study population, anchoring is the critical step in creating more comparable cohorts in observational palliative care studies. Anchoring can be done with respect to a single or multiple data points, and can support both prospective and retrospective data collection and analysis. DISCUSSION: Anchoring the cohort to reproducible data points will help create more comparable cohorts in palliative care whilst mitigating its inherent heterogeneity. This, in turn, will help optimise the generalisability, applicability and reproducibility of observational palliative care studies to strengthen the evidence base and improve practice.

Assessment and Management of Sleep Disturbance in Palliative Care Settings.

Background: Sleep disturbances, including insomnia, sleep-disordered breathing, and circadian rhythm disorders with potential consequences including excessive daytime somnolence and worsening fatigue, are prevalent yet largely under-measured and therefore under-managed problems in people receiving palliative care. This has the potential to negatively affect the person's functioning and quality of life. Objectives: We aimed to review the current practice of assessment and management of sleep disturbances in people with life-limiting illnesses in Australian and New Zealand palliative care settings, and to define areas for improvement in assessment and management of sleep disturbances and further research. Design: A cross-sectional, online survey was conducted with palliative care health professionals (PCHPs) to explore current approaches to routine assessment of sleep disturbances and PCHPs' awareness of, and perceived access to, evidence-based resources for assessing and managing sleep disturbances in their local settings. Results: Fifty-four PCHPs responded to the survey, including allied health professionals (44%), palliative care nurses (26%), and physicians (19%). Over 70% of PCHPs endorsed routine verbal screening of sleep symptoms, and >90% recommended management with basic behavioral strategies. However, none of PCHPs used validated patient-reported outcome measures for sleep, and <10% of PCHPs demonstrated awareness or use of sleep-specific interventions (including medications). Only 40% reported they had access to sleep specialist services for patients. Conclusion: Our findings provide a useful snapshot of current approaches to managing sleep disturbances in palliative care. Gaps in current practice are highlighted, including the lack of structured, clinical assessment, referral pathways, and PCHPs' perceived lack of access to targeted interventions for sleep disturbances.

Nurses' encounters with patients having end-of-life dreams and visions in an acute care setting - A cross-sectional survey study.

AIM: This study aimed to estimate the proportion of acute care nurses witnessing end-of-life dreams and visions or having these reported by a patient or relative, and to canvass their related attitudes and beliefs. DESIGN: A cross-sectional survey study was conducted from February 2023 to May 2023. SETTING/PARTICIPANTS: Participants were medical and surgical nurses from a 200-bed acute care hospital in metropolitan Australia. RESULTS: Fifty-seven nurses participated from a workforce of 169 (34% response rate), of whom 35 (61%) reported they had encountered end-of-life dreams and visions. The nature of end-of-life dreams and visions encountered was similar to those reported in previous studies by patients and clinicians. Nurses generally held positive attitudes towards end-of-life dreams and visions but identified an unmet need for education and training on this aspect of end-of-life care. CONCLUSION: Our results suggest that nurses in acute care encounter end-of-life dreams and visions in a similar proportion to oncology and long-term care but lower than in palliative care settings. Education and training regarding end-of-life dreams and visions are needed to ensure the provision of comprehensive, patient-centred end-of-life care. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. IMPACT: Research in sub-acute and long-term care settings suggests that end-of-life dreams and visions are a common accompaniment to the dying process. No research has yet focused on the acute care setting, despite this being the place of death for the majority of people in most high-income countries. This study demonstrates that acute care nurses encounter end-of-life dreams and visions in similar proportions to oncology and long-term care nurses but lower than palliative care nurses. Acute care nurses would benefit from education and training regarding end-of-life dreams and visions to enable the provision of holistic person-centred end-of-life care. REPORTING METHOD: This study was reported using the STROBE Checklist for cross-sectional studies.

Screening for End-of-Life in Acute Hospitals: A Cross-Sectional Survey.

BACKGROUND: Patients are frequently admitted to hospital in the last year of life. Actively recognising patients at this stage gives the opportunity to plan future care. METHODS: We performed a cross-sectional survey of all acute medical and surgical inpatients at one tertiary hospital. Two simple screening tools, the indicators for a palliative approach and the surprise question identified a group of patients at greatly increased risk of dying over the next year. RESULTS: The one-year mortality of the study group was 27%, however was 52% and 65% for those identified at risk by the indicators for a palliative approach and surprise question tools. The surprise question had an area under the receiver operator curve value of .84. CONCLUSION: These screening tools could be used to help clinicians identify hospital inpatients that would benefit from advance care planning and a tailored approach to their care.

Palliative care symptoms and problems in a culturally and linguistically diverse population: large retrospective cohort study.

OBJECTIVES: Migrant Australians with cancer have higher unmet needs and poorer health-related quality of life. Less is known about their palliative care experience. We aimed to assess comparative symptom distress and problem severity for culturally and linguistically diverse Australians with cancer in palliative care. METHODS: This was a retrospective, consecutive cohort study using data from the Palliative Care Outcomes Collaboration, which routinely collects standardised symptom assessments nationally at point-of-care. Adults with a cancer diagnosis who died 01/01/2016-31/12/2019 were included. The presence/absence of patient-reported symptom distress and clinician-rated problem severity were compared between people who preferred English and people who preferred another language using logistic regression models. We also compared people who preferred English and the four most common non-English languages in the dataset: Chinese, Greek, Italian and Slavic. RESULTS: A total of 53 964 people with cancer died within the study period, allowing analysis of 104 064 assessments. People preferring non-English languages were less likely to report symptoms (pain: OR=0.89 (0.84 to 0.94); all other symptoms except fatigue OR<1 and CIs did not contain 1). Except for family/carer problems (OR=1.24 (1.12 to 1.31)), linguistically diverse people were less likely to report problems. Variation was seen between non-English language groups. CONCLUSIONS: We did not find evidence of comparatively worse symptom distress or problem severity for nearly all scores for culturally and linguistically diverse Australians. Better symptom management or differential reporting may explain this. It is important to examine this further, including assessing differences within cultural and linguistic groups to ensure the delivery of high-quality palliative care.

Non-steroidal anti-inflammatory drugs for pain in hospice/palliative care: an international pharmacovigilance study.

OBJECTIVES: To describe the current, real-world use of non-steroidal anti-inflammatory drugs for pain and the associated benefits and harms. METHODS: A prospective, multicentre, consecutive cohort pharmacovigilance study conducted at 14 sites across Australia, Aotearoa/New Zealand and the UK including hospital, hospice inpatient and outpatient services. Pain scores and harms were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events at baseline, 2 days and 14 days. Ad-hoc safety reporting continued until day 28. RESULTS: Data were collected from 92 patients between March 2018 and October 2021. Most patients had cancer (91%) and were coprescribed opioids (90%). At 14 days, 83% of patients had benefit from non-steroidal anti-inflammatory drugs and 22% had harm. The most common harms were nausea (8%), vomiting (3%), acute kidney injury (3%) and non-gastrointestinal bleeding (3%); only 2% were severe and no patients ceased their non-steroidal anti-inflammatory drugs due to toxicity. Overall, 65% had benefit without harm and 3% had harm without benefit. CONCLUSIONS: Most patients benefited from non-steroidal anti-inflammatory drugs with only one in five patients experiencing tolerable harm. This suggests that short-term use of non-steroidal anti-inflammatory drugs in patients receiving palliative care is safer than previously thought and may be underused.

Pregnancy-associated gynecological cancer in New South Wales, Australia 1994-2013: A population-based historical cohort study.

INTRODUCTION: Pregnancy-associated gynecological cancer (PAGC) refers to cancers of the ovary, uterus, fallopian tube, cervix, vagina, and vulva diagnosed during pregnancy or within 12 months postpartum. We aimed to describe the incidence of, and perinatal outcomes associated with, invasive pregnancy-associated gynecological cancer. MATERIAL AND METHODS: We conducted a population-based historical cohort study using linked data from New South Wales, Australia. We included all women who gave birth between 1994 and 2013, with a follow-up period extending to September 30, 2018. Three groups were analyzed: a gestational PAGC group (women diagnosed during pregnancy), a postpartum PAGC group (women diagnosed within 1 year of giving birth), and a control group (women with control diagnosis during pregnancy or within 1 year of giving birth). We used generalized estimation equations to compare perinatal outcomes between study groups. RESULTS: There were 1 786 137 deliveries during the study period; 70 women were diagnosed with gestational PAGC and 191 with postpartum PAGC. The incidence of PAGC was 14.6/100 000 deliveries and did not change during the study period. Women with gestational PAGC (adjusted odds ratio [aAOR] 6.81, 95% confidence interval [CI] 2.97-15.62) and with postpartum PAGC (aOR 2.65, 95% CI 1.25-5.61) had significantly increased odds of a severe maternal morbidity outcome compared with the control group. Babies born to women with gestational PAGC were more likely to be born preterm (aOR 3.11, 95% CI 1.47-6.59) and were at increased odds of severe neonatal complications (aOR 3.47, 95% CI 1.45-8.31) compared with babies born to women without PAC. CONCLUSIONS: The incidence of PAGC has not increased over time perhaps reflecting, in part, the effectiveness of cervical screening and early impacts of human papillomavirus vaccination programs in Australia. The higher rate of preterm birth among the gestational PAGC group is associated with adverse outcomes in babies born to these women.

Australian population norms for health-related quality of life measured using the EQ-5D-5L, and relationships with sociodemographic characteristics.

BACKGROUND: Measuring health related quality-of-life (HRQoL) of the general population is essential to establish a reference for health outcome evaluations. This study sought to establish EQ-5D-5L population norms in Australia and to investigate the heterogeneity of HRQoL between sociodemographic variables. METHODS: A cross-sectional study comprising of a representative sample of Australia's general population (n = 9958) aged 18 or older. Recruitment quotas were set for the Australian census population by age, sex, state/territory of residence and rurality. Participants were recruited by Qualtrics through its database of over 800,000 registered panel members and asked to value their own state of health using the EQ-5D-5L domains and the EuroQol-Visual Analogue Scale (EQ-VAS). An Australian value set developed using Discreet Choice Experiment was used to calculate utility scores. RESULTS: The estimated mean EQ-5D-5L index for Australia's general population was 0.86 (standard deviation [SD] 0.19), and the EQ-VAS score was estimated as 73.2 (SD 21.7). 23.9% of the study population reported being in the best health state (11,111). Younger people, current smokers, people who are unemployed and people with more financial stress reported a lower EQ-5D-5L index score (p < 0.001). Residents in the major cities, inner regional and outer regional Australia reported higher health utility scores than those residing in remote and very remote Australia. CONCLUSIONS: This is the first Australian study to apply the EQ-5D-5L in a nationally representative sample. The EQ-5D-5L Australian population norms obtained can be used as reference scores for future population health evaluations and comparisons. The findings facilitate a national reference for clinical, economic, and policy decision-making processes and provide a fuller understanding of the Australian population's HRQoL.

What Aspects of Quality of Life are Important from Palliative Care Patients' Perspectives? A Framework Analysis to Inform Preference-Based Measures for Palliative and End-of-Life Settings.

BACKGROUND AND OBJECTIVE: Preference-based outcome measures are commonly applied in economic analyses to inform healthcare resource allocation decisions. Few preference-based outcome measures have been specifically developed for palliative and end-of-life settings. This study aimed to identify which quality-of-life domains are most important to Australians receiving specialised palliative care services to help determine if the development of a new condition-specific preference-based outcome measure is warranted. METHODS: In-depth face-to-face interviews were conducted with 18 participants recruited from palliative care services in South Australia. Data were analysed using a framework analysis drawing on findings from a systematic review of international qualitative studies investigating the quality-of-life preferences of patients receiving palliation (domains identified included cognitive, emotional, healthcare, personal autonomy, physical, preparatory, social, spiritual). Participants identified missing or irrelevant domains in the EQ-5D and QLU-C10D questionnaires and ranked the importance of domains. RESULTS: A priori domains were refined into cognitive, environmental, financial, independence, physical, psychological, social and spiritual. The confirmation of the eight important quality-of-life domains across multiple international studies suggests there is a relatively high degree of convergence on the perspectives of patients in different countries. Four domains derived from the interviews are not covered by the EQ-5D and QLU-C10D (cognitive, environmental, financial, spiritual), including one of the most important (spiritual). CONCLUSIONS: Existing, popular, preference-based outcome measures such as the EQ-5D do not incorporate the most important, patient-valued, quality-of-life domains in the palliative and end-of-life settings. Development of a new, more relevant and comprehensive preference-based outcome measure could improve the allocation of resources to patient-valued services and have wide applicability internationally.

Breast screening participation and degree of spread of invasive breast cancer at diagnosis in mental health service users: A population linkage study.

BACKGROUND: Women living with mental health conditions may not have shared in improvements in breast cancer screening and care. No studies have directly examined the link between reduced screening participation and breast cancer spread in women using mental health (MH) services. METHODS: Population-wide linkage of a population cancer register, BreastScreen register, and mental health service data set in women aged 50 to 74 years in New South Wales, Australia, from 2008 to 2017. Incident invasive breast cancers were identified. Predictors of degree of spread (local, regional, metastatic) at diagnosis were examined using partial proportional odds regression, adjusting for age, socioeconomic status, rurality, and patterns of screening participation. RESULTS: A total of 29 966 incident cancers were identified and included 686 (2.4%) in women with MH service before cancer diagnoses. More than half of MH service users had regional or metastatic spread at diagnosis (adjusted odds ratio, 1.63; 95% CI, 1.41-1.89). MH service users had lower screening participation; however, advanced cancer was more common even when adjusting for screening status (adjusted odds ratio, 1.53; 95% CI, 1.32-1.77). Advanced cancer was more common in women with severe or persistent MH conditions. CONCLUSIONS: Low screening participation rates explain only small part of the risk of more advanced breast cancer in women who use MH services. More study is needed to understand possible mechanisms contributing to more advanced breast cancer in women living with MH conditions. Health systems need strategies to ensure that women living with MH conditions enjoy population gains in breast cancer outcomes.

Participant Safety in Multisite, Randomized, Double-Blind, Placebo-Controlled Clinical Trials in Hospice/Palliative Care: Data from the Contracted Studies of the Australian National Palliative Care Clinical Studies Collaborative.

Objective: To describe the harms in all arms of six consecutive multi-site, double-blind, placebo-controlled randomised clinical trials. Background: Controversies surround conduct of phase III clinical trials in palliative care. Concerns include risks to participants' safety, use of placebo arms, participants' burden, and justification when therapies are already widely used. Methods: This study collates safety data of the first six studies of the Australian national Palliative Care Clinical Studies Collaborative. On an intention-to-treat basis, all harms are described using standard international definitions, their severity, outcomes, and level of attribution. Results: Studies recruited 1,232 participants: 65/1,232 (5.3%) participants had serious adverse events of which none had a definite (blinded) attribution, all of which settled with ceasing the intervention; 49/1,232 (4.0%) participants had adverse events. No participants on placebo arms had adverse or serious adverse events with definite (blinded) attribution. Discussion: These studies are safe for participants and generate knowledge to support informed patient decision making.