Medicinal Cannabis (MedCan 3): a randomised, multicentre, double-blind, placebo-controlled trial to assess THC/CBD (1:20) to relieve symptom burden in patients with cancer-a study protocol for a randomised controlled trial.

BACKGROUND: Distressing symptoms are common in advanced cancer. Medicinal cannabinoids are commonly prescribed for a variety of symptoms. There is little evidence to support their use for most indications in palliative care. This study aims to assess a 1:20 delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) cannabinoid preparation in the management of symptom distress in patients with advanced cancer undergoing palliative care. METHODS AND DESIGN: One hundred and fifty participants will be recruited across multiple sites in Queensland, Australia. A teletrial model will facilitate the recruitment of patients outside of major metropolitan areas. The study is a pragmatic, multicenter, randomised, placebo-controlled, two-arm trial of escalating doses of an oral 1:20 THC/CBD medicinal cannabinoid preparation (10 mg THC:200 mg CBD/mL). It will compare the efficacy and safety outcomes of a titrated dose range of 2.5 mg THC/50mgCBD to 30 mg THC/600 mg CBD per day against a placebo. There is a 2-week patient-determined titration phase, to reach a dose that achieves symptom relief or intolerable side effects, with a further 2 weeks of assessment on the final dose. The primary objective is to assess the effect of escalating doses of a 1:20 THC/CBD medicinal cannabinoid preparation against placebo on change in total symptom distress score, with secondary objectives including establishing a patient-determined effective dose, the effect on sleep quality and overall quality of life. Some patients will be enrolled in a sub-study which will more rigorously evaluate the effect on sleep. DISCUSSION: MedCan-3 is a high-quality, adequately powered, placebo-controlled trial which will help demonstrate the utility of a THC:CBD 1:20 oral medicinal cannabis product in reducing total symptom distress in this population. Secondary outcomes may lead to new hypotheses regarding medicinal cannabis' role in particular symptoms or in particular cancers. The sleep sub-study will test the feasibility of using actigraphy and the Insomnia Severity Index (ISI) in this cohort. This will be the first large-scale palliative care randomised clinical trial to utilise the teletrial model in Australia. If successful, this will have significant implications for trial access for rural and remote patients in Australia and internationally. TRIAL REGISTRATION: ANZCTR ACTRN12622000083796 . Protocol number 001/20. Registered on 21 January 2022. Recruitment started on 8 August 2022.

Attitudes to End-of-Life Care and Voluntary Assisted Dying Amongst Members of the Australian Jewish community.

The implementation of voluntary assisted dying (VAD) in the Australian State of Victoria in 2019 has stimulated discussions about end-of-life care and dying in many communities. Various attempts have been made to represent the attitudes of the Jewish community, a distinct culturally and linguistically diverse (CALD) group, in terms that suggest a unified set of opinions that opposes VAD policies. This research aimed to explore attitudes to VAD in the context of end-of-life care held by members of the Victorian Jewish community. A descriptive qualitative methodological design was employed. Ten Victorians who identify as Jewish were recruited and participated in in-depth, semi-structured interviews. Reflexive thematic analysis was carried out on the transcripts to identify key themes, attitudes and preferences in relation to end-of-life care, death and dying, and VAD. Three themes were identified: "complexity and variation", "similarities", and "factors influencing attitudes to VAD and end-of-life care". A significant degree of diversity was apparent, ranging from highly supportive of VAD to advocacy for a total repeal of the policy. The results indicate that images of how Victorian Jewish individuals feel towards VAD based on essentialised notions about the community and belief systems are not supported by the evidence. In reality, considerable diversity of attitudes exists towards VAD and end-of-life care. We conclude that it is important that policymakers and members of the broader society avoid stereotypes that falsely characterise this specific community and, by implication, other CALD groups, particularly in terms that ignore internal diversity regarding belief systems, social attitudes and ethical perspectives.

Quantifying the Need for Specialist Palliative Care Management in Patients With Systemic Sclerosis.

OBJECTIVE: The importance of early integration of palliative care in the management of complex multisystem diseases has been recognized. In this study, we aimed to quantify the need for specialist palliative care in patients with systemic sclerosis (SSc). METHODS: Using data from 875 patients enrolled in the Australian Scleroderma Cohort Study, we defined the need for palliative care as a high symptom burden at two or more consecutive study visits, at ≥50% of overall study visits, or at the study visit immediately before death. Symptoms of interest included breathlessness, fatigue, pain, depression, anxiety, constipation, and diarrhea. Logistic regression analyses evaluated the association between individual symptoms and SSc manifestations. Linear regression analysis evaluated the relationship between palliative care needs and quality of life (QoL) and function. RESULTS: Almost three-quarters of patients (72.69%) met the threshold for specialist palliative care needs. Severe fatigue (54.17%) was most common, followed by breathlessness (23.66%) and severe constipation (21.14%). Concurrent severe symptoms were frequently observed. Severe breathlessness (coefficient [coef] -7.95, P < 0.01) and pain (coef -7.70, P < 0.01) were associated with the largest reductions in physical QoL. Severe mood symptoms were associated with the greatest reduction in mental QoL (coef -12.91, P < 0.01). Severe pain (coef 0.56, P < 0.01), breathlessness (coef 0.49, P < 0.01), and mood symptoms (coef 0.40, P < 0.01) had a significant impact on function. CONCLUSION: SSc is frequently associated with multiple severe symptoms that may be amenable to palliative care intervention. Given the strong association between symptom burden and impaired QoL targeted, effective symptom management in parallel with standard-of-care treatments may improve overall patient outcomes.

Palliative Approach Remains Lacking in Terminal Hospital Admissions for Chronic Disease Across Rural Settings: Multisite Retrospective Medical Record Audit.

INTRODUCTION/AIM: Despite clear benefit from palliative care in end-stage chronic diseases, access is often limited, and rural access largely undescribed. This study sought to determine if a palliative approach is provided to people with chronic disease in their terminal hospital admission. METHODS: Multisite, retrospective medical record audit, of decedents with a primary diagnosis of chronic lung, heart, or renal failure, or multimorbidity of these conditions over 2019. RESULTS: Of 241 decedents, across five clinical sites, 143 (59.3%) were men, with mean age 80.47 years (SD 11.509), and diagnoses of chronic lung (n = 56, 23.2%), heart (n = 56, 23.2%), renal (n = 24, 10.0%) or multimorbidity disease (n = 105, 43.6%), and had 2.88 (3.04SD) admissions within 12 months. Outpatient chronic disease care was evident (n = 171, 73.7%), however, contact with a private physician (n = 91, 37.8%), chronic disease program (n = 61, 25.3%), or specialist nurse (n = 17, 7.1%) were less apparent. "Not-for-resuscitation" orders were common (n = 139, 57.7%), however, advance care planning (n = 71, 29.5%), preferred place of death (n = 18, 7.9%), and spiritual support (n = 18, 7.5%) were rarely documented. Referral to and input from palliative services were low (n = 74, 30.7% and n = 49, 20.3%), as was review of nonessential medications or blood tests (n = 86, 35.7%, and n = 78, 32.4%). Opioids were prescribed in 45.2% (n = 109). Hospital site and diagnosis were significantly associated with outpatient care and palliative approach (P<0.001). CONCLUSIONS: End-of-life planning and specialist palliative care involvement occurred infrequently for people with chronic disease who died in rural hospitals. Targeted strategies are necessary to improve care for these prevalent and high needs rural populations.

What are the cost and resource implications of voluntary assisted dying and euthanasia?

ObjectivesVoluntary assisted dying (VAD) legislation has now been passed in all Australian states. Although VAD has been operating in many settings worldwide for a considerable time, the specific costs associated with VAD seem unclear. The aim of this study was therefore to outline the common resource implications associated with VAD.MethodsA rapid literature review and grey literature search were undertaken.ResultsWe found a paucity of empirically informed detail regarding the actual costs required to implement VAD. Hence, we tabulated a list of potential costs that could be used for subsequent evaluation and a future research agenda.ConclusionsThere is a lack of publicly available information related to the costs associated with implementing VAD. Given that this is a significant change in policy and many multidisciplinary practitioners may be directly or indirectly involved in VAD it is important that associated costs are clearly outlined so that appropriate resources can be allocated.

Introducing palliative care in advanced cancer: a systematic review.

BACKGROUND: Negative perceptions about palliative care (PC), held by patients with cancer and their families, are a barrier to early referral and the associated benefits. This review examines the approaches that support the task of introducing PC to patients and families and describes any evaluations of these approaches. METHODS: A systematic review with a systematic search informed by the Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines was performed on the online databases MEDLINE, PsychInfo and CINAHL from May 2022 to July 2022. Identified studies were screened by title and abstract, and included if they were empirical studies and described an approach that supported the introduction of PC services for adult patients. A narrative-synthesis approach was used to extract and present the findings. RESULTS: Searches yielded 1193 unique manuscripts, which, following title and abstract screening, were reduced to 31 papers subject to full-text review, with a final 12 studies meeting eligibility criteria. A diverse range of included studies described approaches used to introduce palliative care, which may be broadly summarised by four categories: education, clinical communication, building trust and rapport and integrative system approaches. CONCLUSION: While educational approaches were helpful, they were less likely to change behaviours, with focused communication tasks also necessary to facilitate PC introduction. An established relationship and trust between patient and clinician were foundational to effective PC discussions. A framework to assist clinicians in this task is likely to be multidimensional in nature, although more quantitative research is necessary to establish the most effective methods and how they may be incorporated into clinical practice.

The COVID-19 Pandemic: Bereavement Experiences Between Hospital and Home Deaths in Palliative Care.

BACKGROUND: Australian COVID-19 public health measures reduced opportunities for people to communicate with healthcare professionals and be present at the death of family members/friends. AIM: To understand if pandemic-specific challenges and public health measures during the COVID-19 pandemic impacted end-of-life and bereavement experiences differently if the death, supported by palliative care, occurred in a hospital or at home. DESIGN: A cross-sectional online survey was completed by bereaved adults during 2020-2022. Analyses compared home and in-patient palliative care deaths and bereavement outcomes. Additional analyses compared health communication outcomes for those identified as persons responsible or next of kin. SETTING/PARTICIPANTS: Of 744 bereaved people; 69% (n = 514) had a death in hospital and 31% (n = 220) at home. RESULTS: The COVID-19 public health measures influenced people's decision to die at home. Compared to hospital deaths, the home death group had higher levels of grief severity and grief-related functional impairment. Only 37% of bereaved people received information about bereavement and support services. 38% of participants who were at least 12 months postdeath scored at a level suggestive of possible prolonged grief disorder. Levels of depression and anxiety between the two groups were not significantly different. CONCLUSIONS: These findings highlight the need for health services to recognize bereavement as fundamental to palliative and health care and provide pre- and post death grief and bereavement care to ensure supports are available particularly for those managing end-of-life at home, and that such supports are in place prior to as well as at the time of the death.

Opioid Switch Dosing in Chronic Cancer Pain: A Prospective Longitudinal Study.

Background: Opioid switching is common, however, conversion tables have limitations. Guidelines suggest postswitch dose reduction, yet, observations show opioid doses may increase postswitch. Objectives: To document the opioid conversion factor postswitch in cancer, and whether pain and adverse effect outcomes differ between switched opioid groups. Design/Setting: This multicenter prospective longitudinal study included people with advanced cancer in Australia. Clinical data (demographics, opioids) and validated instruments (pain, adverse effects) were collected twice, seven days apart. Results: Opioid switch resulted in dose increase (median oral morphine equivalent daily dose 90 mg [interquartile range {IQR} 45-184] to 150 mg [IQR 79-270]), reduced average pain (5.1 [standard deviation {SD} 1.7] to 3.8 [SD 1.6]), and reduced adverse effects. Hydromorphone dose increased 2.5 times (IQR 1.0-3.6) above the original conversion factor used. Conclusions: Opioid switching resulted in overall dose increase, particularly when switching to hydromorphone. Higher preswitch dosing may require higher dose conversion ratios. Dose reduction postswitch risks undertreatment and may not be always appropriate.

Pilot Implementation of the Responding to Urgency of Need in Palliative Care (RUN-PC) Triage Tool.

CONTEXT: Specialist palliative care services must balance provision of needs-based care within resource restraints. The Responding to Urgency of Need in Palliative Care (RUN-PC) Triage Tool is a novel, evidence-based, 7-item prioritization tool, with recommended response times for any given score. OBJECTIVES: To investigate the acceptability and appropriateness of the RUN-PC Triage Tool implemented into clinical practice. METHODS: A single-arm, multisite, prospective implementation pilot conducted at 12 community/inpatient palliative care services, using Quality Improvement methodology with Plan-Do-Study-Act cycles. Data collected for each triage episode included demographics, scoring, user feedback and clinical outcomes. Group differences were tested by chi-squared, Wilcoxon Rank Sum or Kruskal Wallis tests. RESULTS: A total of 5418 triage episodes were captured, 1509 with outcome data. Referrals to inpatient services were of higher acuity than those to community (median score 24 vs. 14). Whilst high numerical scores were unusual, a significant proportion of cases were clinically urgent. Admissions occurred within recommended response times in over 80% of triage episodes; 5.8% of referred patients died before being admitted. Users reported the tool was easy to complete (99.3% of applications), rarely requiring additional time (0.07%), and appropriate in its triage determination (96.0% of applications). CONCLUSION: The RUN-PC Triage Tool is feasible to implement, with high clinician acceptability and virtually no additional time required. The recommended response times are feasible and highlight target areas for improvement. Implementation of the tool enables palliative care services to better characterize their referral population and, in turn, improve transparency around access to care.

Therapeutic misunderstandings in modern research.

Clinical trials play a crucial role in generating evidence about healthcare interventions and improving outcomes for current and future patients. For individual trial participants, however, there are inevitably trade-offs involved in clinical trial participation, given that trials have traditionally been designed to benefit future patient populations rather than to offer personalised care. Failure to understand the distinction between research and clinical care and the likelihood of benefit from participation in clinical trials has been termed the 'therapeutic misconception'. The evolution of the clinical trials landscape, including greater integration of clinical trials into healthcare and development of novel trial methodologies, may reinforce the significance of the therapeutic misconception and other forms of misunderstanding while at the same time (paradoxically) challenging its salience. Using cancer clinical trials as an exemplar, we describe how methodological changes in early- and late-phase clinical trial designs, as well as changes in the design and delivery of healthcare, impact upon the therapeutic misconception. We suggest that this provides an impetus to re-examine the ethics of clinical research, particularly in relation to trial access, participant selection, communication and consent, and role delineation.

Effect of gene variants on opioid dose, pain and adverse effect outcomes in advanced cancer: an explorative study.

Aim: Associations between gene variants and opioid net effect are unclear. We conducted an exploratory pharmacogenetic analysis of 35 gene variants and opioid response in advanced cancer. Patients & methods: This multi-center prospective cohort study included clinical data, questionnaires (pain and adverse effects) and DNA (blood). Negative binomial regression and logistic regression were used. Results: Within 54 participants, eight statistically significant associations (p = 0.002-0.038) were observed between gene variants and opioid dose, pain scores or adverse effects, the majority being within the neuroimmune TLR4 pathway (IL1B [rs1143634], IL2 [rs2069762], IL6 [rs1800795], BDNF [rs6265]) and ARRB2 pathway (ARRB2 [rs3786047], DRD2 [rs6275]). Conclusion: Neuroimmune pathway genes may contribute to differences in opioid response in cancer and may be included in future similar studies.