Background: Delirium is a common debilitating complication of advanced cancer. Objective: To determine if a multicomponent nonpharmacological delirium prevention intervention was feasible for adult patients with advanced cancer, before a phase III (efficacy) trial. Design: Phase II (feasibility) cluster randomized controlled trial. All sites implemented delirium screening and diagnostic assessment. Strategies within sleep, vision and hearing, hydration, orientation, mobility, and family domains were delivered to enrolled patients at intervention site admission days 1–7. Control sites then implemented the intervention (“waitlist sites”). Setting: Four Australian palliative care units. Measurements: The primary outcome was adherence, with an a priori endpoint of at least 60% patients achieving full adherence. Secondary outcomes were interdisciplinary care delivery, delirium measures, and adverse events, analyzed descriptively and inferentially. Results: Sixty-five enrolled patients (25 control, 20 intervention, and 20 waitlist) had 98% delirium screens and 75% diagnostic assessments completed. Nurses (67%), physicians (16%), allied health (8.4%), family (7%), patients (1%), and volunteers (0.5%) delivered the intervention. There was full adherence for 5% patients at intervention sites, partial for 25%. Both full and partial adherence were higher at waitlist sites: 25% and 45%, respectively. One-third of control site patients (32%) became delirious within seven days of admission compared to one-fifth (20%) at both intervention and waitlist sites ( p = 0.5). Mean (standard deviation) Delirium Rating Scale-Revised-1998 scores were 16.8 + 12.0 control sites versus 18.4 + 8.2 ( p = 0.6) intervention and 18.7 + 7.8 ( p = 0.5) waitlist sites. The intervention caused no adverse events. Conclusion: The intervention requires modification for optimal adherence in a phase III trial.

Introduction: Neurodegenerative conditions, such as Alzheimer’s disease, Parkinson’s disease and motor neurone disease, are progressive and incurable conditions that ultimately lead to a state of total functional incapacitation and death. These conditions are “terminal” and, therefore, should be managed with a palliative care approach. This article highlights some of the issues in caring for patients with end-stage neurodegenerative conditions from a palliative perspective. Methods: This review is based on evidence from pre-existing medical literature on the above subject and the authors’ personal experiences and observations. Conclusion: Patients with end-stage neurodegenerative conditions have needs similar to that of advanced cancer patients. Therefore, the principles and practice of palliative care should be applied to such patients. This may also mean that palliative care training should be undertaken in nursing homes, where a large number of such patients are located.

Ketamine at subanaesthetic dosages (≤0.5mg/kg) exhibits rapid onset (over hours to days) antidepressant effects against major depressive disorder in people who are otherwise well. However, its safety, tolerability and efficacy are not known for major depressive disorder in people with advanced life-limiting illnesses. To determine the feasibility, safety, tolerability, acceptability and any antidepressant signal/activity to justify and inform a fully powered study of subcutaneous ketamine infusions for major depressive disorder in the palliative setting. This was a single arm, open-label, phase II feasibility study (Australian New Zealand Clinical Trial Registry Number—ACTRN12618001586202). We recruited adults (≥ 18-years-old) with advanced life-limiting illnesses referred to four palliative care services in Sydney, Australia, diagnosed with major depressive disorder from any care setting. Participants received weekly subcutaneous ketamine infusion (0.1–0.4mg/kg) over two hours using individual dose-titration design. Outcomes assessed were feasibility, safety, tolerability and antidepressant activity. Out of ninety-nine referrals, ten participants received ketamine and were analysed for responses. Accrual rate was 0.54 participants/month across sites with 50% of treated participants achieving ≥ 50% reduction in baseline Montgomery-Åsberg Depression Rating Scale, meeting feasibility criteria set a priori. There were no clinically relevant harms encountered. A future definitive trial exploring the effectiveness of subcutaneous infusion of ketamine for major depressive disorder in the palliative care setting may be feasible by addressing identified study barriers. Individual dose-titration of subcutaneous ketamine infusions over two hours from 0.1mg/kg can be well-tolerated and appears to produce transient antidepressant signals over hours to days.

Background: Coeliac plexus block (CPB) is an interventional pain management option for patients with pancreatic or other upper abdominal malignancy.Aims: To assess the safety, utilization, and outcomes of CPBs in the local context.Methods and Results: We conducted a retrospective case series of all patients with cancer who underwent CPB at 4 Sydney teaching hospitals from March 2010 to February 2016. We recorded baseline demographic data, details of the injectate, procedural approach and survival, as well as pain scores and analgesic use at 4 time points of interest. Thirty‐nine procedures were performed during the study period. Twenty‐four were performed endoscopically, 14 were performed via a bilateral percutaneous posterior approach by Pain Specialists or Radiologists and 1 was performed intraoperatively by a Surgeon. Patients had experienced pain for a mean of 17 weeks prior to CPB. Prior to CPB, the mean pain score was 8.8 out of 10. The mean pain score was reduced at 48 hours, 2 weeks, and 4 weeks following CPB (P < .01). The mean oral morphine equivalent daily dose prior to CPB was 362 mg which was reduced at 48 hours and 2 weeks but increased at the 4 weeks following CPB. One patient developed a bacteremia but otherwise no complications were observed.Conclusion: CPB is performed by a number of approaches and is well tolerated. The approach selected appears to depend on patient anatomy, preference, and availability of local expertise. Local clinicians could consider CPB earlier in the management of malignant epigastric pain.

Introduction: The aim was to demonstrate the safety and tolerability of cannabidiol (CBD) with Δ9-THC in patients with moderate to severe chronic back or neck pain unresponsive to over-the-counter non-opioid analgesics. Methods: This was a non-randomized, single-arm, open-label study. Participants received escalating doses of an oromucosal-administered combination containing 10 mg/mL of Δ9-THC, 25 mg/mL of CBD. On day 1, patients received once-daily 0.5 mL Cybis® 10:25 (5 mg Δ9-THC plus 12.5 mg CBD daily), escalated at days 8, 15, and 22 to 0.5 mL twice-daily (bd) (10 mg Δ9-THC plus 25 mg CBD daily), 1.0 mL bd (20 mg Δ9-THC plus 50 mg CBD daily), and 1.5 mL bd (30 mg Δ9-THC plus 75 mg CBD daily), respectively. The primary outcome was safety and tolerability, with secondary objectives including pharmacokinetic and efficacy outcomes. Results: 28 patients were enrolled in the study. Their median age was 63.3 years, and half were female. The median history of neck/back pain was 10 years. The pharmacokinetics following single doses of 0.5 mL were variable; however, there were dose-dependent increases in trough levels of CBD and Δ9-THC. Cybis® 10:25 was well tolerated, with the majority of adverse events of mild severity. The most common adverse events were nausea, vomiting, fatigue, dizziness, headache, paresthesia, and anxiety. There were dose-dependent improvements in numerical pain rating scores (p < 0.001), with clinically significant reductions in pain at 1.0 mL bd and 1.5 mL bd doses (28.8% and 34.1% reductions, respectively, p < 0.001). Depressive symptoms and stress had dose-dependent reductions (p = 0.0182, p < 0.01, respectively). Conclusion: In patients with chronic neck/back pain, CBD and Δ9-THC are well tolerated and doses of 1.0 mL bd and 1.5 mL bd showed clinically significant reductions in pain compared to baseline pain scores.