The preventative role of exogenous melatonin administration to patients with advanced cancer who are at risk of delirium: study protocol for a randomized controlled trial.

BACKGROUND: Delirium is a very common and distressing neuropsychiatric syndrome in palliative care. Increasing age, the presence of dementia and advanced cancer are well-known predisposing risk factors for delirium development. Sleep-wake cycle disturbance is frequently seen during delirium and melatonin has a pivotal role in the regulation of circadian rhythms. Current evidence across various settings suggests a potential preventative role for melatonin in patients at risk of delirium, but no studies are currently reported in patients with advanced cancer. The aim of this article is to describe the design of a feasibility study that is being conducted to inform a larger randomized, placebo-controlled, double-blind trial (RCT) to evaluate the role of exogenously administered melatonin in preventing delirium in patients with advanced cancer. METHODS/DESIGN: Adult patients with a cancer diagnosis who are admitted to the palliative care unit will be randomized into a treatment or placebo group. The pharmacological intervention consists of a single daily dose of immediate-release melatonin (3 mg) at 21:00 ± 1 h, from day 1 to day 28 of admission. The primary objective of this initial study is to assess the feasibility of conducting the proposed RCT by testing recruitment and retention rates, appropriateness of study outcome measures, acceptability of study procedures and effectiveness of the blinding process. The primary outcome measure of the proposed larger RCT is time to first inpatient incident episode of delirium. We also plan to collect data on incident rates of delirium and patient-days of delirium, adjusting for length of admission. DISCUSSION: The outcomes of this feasibility study will provide information on recruitment and retention rates, protocol violation frequency, effectiveness of the blinding process, acceptability of the study procedures, and safety of the proposed intervention. This will inform the design of a fully powered randomized controlled trial to evaluate the preventative role of melatonin administration in patients with advanced cancer. TRIAL REGISTRATION: Registered with ClinicalTrials.gov: NCT02200172 Registered on 21 July 2014. Health Canada protocol number: BRI-MELAT-2013 (Final approved protocol version (Version 3): 18 June 2014) (Notice of Amended Authorization (NOA) received 14 November 2014).

Designing clinically valuable telehealth resources: processes to develop a community-based palliative care prototype.

BACKGROUND: Changing population demography and patterns of disease are increasing demands on the health system. Telehealth is seen as providing a mechanism to support community-based care, thus reducing pressure on hospital services and supporting consumer preferences for care in the home. OBJECTIVE: This study examined the processes involved in developing a prototype telehealth intervention to support palliative care patients involved with a palliative care service living in the community. METHODS: The challenges and considerations in developing the palliative care telehealth prototype were reviewed against the Center for eHealth Research (CeHRes) framework, a telehealth development model. The project activities to develop the prototype were specifically mapped against the model's first four phases: multidisciplinary project management, contextual inquiry, value specification, and design. This project has been developed as part of the Telehealth in the Home: Aged and Palliative Care in South Australia initiative. RESULTS: Significant issues were identified and subsequently addressed during concept and prototype development. The CeHRes approach highlighted the implicit diversity in views and opinions among participants and stakeholders and enabled issues to be considered, resolved, and incorporated during design through continuous engagement. CONCLUSIONS: The CeHRes model provided a mechanism that facilitated "better" solutions in the development of the palliative care prototype by addressing the inherent but potentially unrecognized differences in values and beliefs of participants. This collaboration enabled greater interaction and exchange among participants resulting in a more useful and clinically valuable telehealth prototype.

Community pharmacists: a forgotten resource for palliative care.

Timely access to medicines within the community is important for palliative patients where their preferred place of care is the home environment. The objective of this observational study is to establish baseline data to quantify the issue of poor access to medicines for symptom control in the last few days of life. The list of 13 medicines was generated from medicine use within a metropolitan palliative care unit. A survey was designed to determine which of these 13 medicines community pharmacies stock, the expiry date of this stock, awareness of palliative care patients by community pharmacists and basic demographic characteristics of the community pharmacies. Surveys were distributed, by post, to all community pharmacies in South Australia. The response rate was 23.7%, and was representative of all socioeconomic areas. Each pharmacy stocked a median of 3 medicines (range 0-12) with 1 in 8 pharmacies having none of the 13 medicines listed in the survey. When the data was combined to identify the range of medicines from all pharmacies within a geographical postcode region, the median number of medicines increased to 5 medicines per postcode. Just over 1 in 5 pharmacies reported learning about the palliative status of a patient through another health practitioner. Community pharmacies remain an underused resource to support timely access to medicines for community-based palliative patients. Palliative care services and government agencies can develop new strategies for better access to medicines that will benefit community patients and their carers.

The role of ondansetron in the management of cholestatic or uremic pruritus--a systematic review.

CONTEXT: Pruritus associated with hepatic or renal failure can be a troublesome symptom, refractory to treatment and associated with significant physical and emotional distress and a reduction in quality of life for patients already burdened with chronic disease. Serotonin has been implicated as a possible pathological mediator, and, therefore, 5HT(3) antagonists have been suggested as a possible therapeutic intervention. OBJECTIVES: This review of the literature systematically explores the role of ondansetron in the management of cholestatic or uremic pruritus. METHODS: Electronic databases were systematically searched for randomized controlled trials examining the role of ondansetron in cholestatic or uremic pruritus between 1966 and 2008. RESULTS: Five randomized controlled trials were included in this systematic review: three for cholestatic pruritus and two for uremic pruritus. All trials examined ondansetron vs. placebo, with differing treatment protocols. Overall, three studies showed no benefit to ondansetron over placebo; however, two studies in cholestatic pruritus showed small reductions in pruritus with questionable clinical significance. CONCLUSION: Ondansetron was demonstrated to have negligible effect on cholestatic or uremic pruritus on the basis of a limited number of studies.

Planning phase III multi-site clinical trials in palliative care: the role of consecutive cohort audits to identify potential participant populations.

GOALS OF WORK: Multiple sites enable more successful completion of adequately powered phase III studies in palliative care. Audits of the frequency and distribution of the symptoms of interest can better inform research planning by determining realistic recruitment goals for each site. The proposed studies are to improve the evidence-base for registration and subsidy applications for frequently encountered symptoms where current pharmacological interventions are being used 'off-licence'. METHODS: Six services participated in a standardised, retrospective, consecutive cohort audit of five symptoms of their inpatient populations to inform the design of double blind randomised controlled phase III studies to which each site would recruit simultaneously. The audit covered all deaths in a 3-month period for people who were referred to a specialist palliative care service who had at least one inpatient admission between referral and death, regardless of when the person was referred to the service. The audits were based around inclusion and exclusion criteria for the proposed studies. MAIN RESULTS: Of the 468 people whose medical records were reviewed, potential study participant rates varied by symptom having accounted for general and specific inclusion and exclusion criteria: pain 17.7%; delirium 5.8%; anorexia 5.1%; bowel obstruction 2.8% and cholestatic itch 0%. For those people with a symptom of interest, it was noted at the beginning of the inpatient admission more than half the time. Of all inpatients, fewer than one third would be eligible to participate in at least one study. CONCLUSIONS: These data provide a baseline estimate of potential people to approach about clinical trials in supportive care but do not account for clinician 'gate-keeping', lack of interest in participating nor withdrawal from the study once initiated. The data are retrospective and therefore, limited by clinical documentation. The audit directly informed an increase in the number of participating sites.