Pharmacovigilance in hospice/palliative care: rapid report of net clinical effect of metoclopramide

Background: Understanding the performance of prescribed medications in day-to-day practice is important to minimize harm, maximize clinical benefits, and, eventually, better target the people who are most likely to benefit, especially in hospice/palliative care where there may be limited time to optimize prescribing. Metoclopramide, a benzamide prokinetic antiemetic, is widely used for a number of indications including nausea, vomiting, hiccups, and reflux. It has recently had a new ‘‘black box’’ warning issued by the Food and Drug Administration in relation to tardive dyskinesia to limit use to 12 weeks. Methods: A consecutive cohort of patients from 12 participating centers in two countries who were having metoclopramide initiated had data collected at three time points—baseline, 2 days (clinical benefit), and day 7 (clinical harm). Additionally, harms could be recorded at any time. Results: Of the 53 people included in the cohort, 23 (43%) reported benefit at 48 hours, but only 18 (34%) of these people were still using it one week after commencing it. For the other 5, the medication was ceased due to harms. The most frequent harms were akathisia (n = 4), headache (n = 4), and abdominal pain (n = 4). Nine people (17%) had no clinical benefit and experienced harms. Conclusion: Overall, one in three people gained net clinical benefit at one week. Limiting effects include sideeffects that need to be sought actively in clinical care

The Australia-modified Karnofsky Performance Status (AKPS) scale: a revised scale for contemporary palliative care clinical practice [ISRCTN81117481]

© 2005 Abernethy et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background : The Karnofsky Performance Status (KPS) is a gold standard scale. The Thorne-modified KPS (TKPS) focuses on community-based care and has been shown to be more relevant to palliative care settings than the original KPS. The Australia-modified KPS (AKPS) blends KPS and TKPS to accommodate any setting of care. Methods : Performance status was measured using all three scales for palliative care patients enrolled in a randomized controlled trial in South Australia. Care occurred in a range of settings. Survival was defined from enrollment to death. Results : Ratings were collected at 1600 timepoints for 306 participants. The median score on all scales was 60. KPS and AKPS agreed in 87% of ratings; 79% of disagreements occurred within 1 level on the 11-level scales. KPS and TKPS agreed in 76% of ratings; 85% of disagreements occurred within one level. AKPS and TKPS agreed in 85% of ratings; 87% of disagreements were within one level. Strongest agreement occurred at the highest levels (70–90), with greatest disagreement at lower levels (≤40). Kappa coefficients for agreement were KPS-TKPS 0.71, KPS-AKPS 0.84, and AKPS-TKPS 0.82 (all p < 0.001). Spearman correlations with survival were KPS 0.26, TKPS 0.27 and AKPS 0.26 (all p < 0.001). AKPS was most predictive of survival at the lower range of the scale. All had longitudinal test-retest validity. Face validity was greatest for the AKPS. Conclusion : The AKPS is a useful modification of the KPS that is more appropriate for clinical settings that include multiple venues of care such as palliative care

Palliative care clinical trials: how nurses are contributing to ethical, integrated and evidence based care of palliative care patients participating in clinical trials

The aim of this paper is to describe the emerging role of the palliative care clinical trials nurse in an era of evidence based practice and increasing clinical trial activity in palliative care settings across Australia. An overview of the current clinical trials work is provided with a focus on three aspects of clinical trials nursing practice which have significant implications for patients: (1) the consent process; (2) integration of clinical trials into multidisciplinary care, and (3) promotion of evidence based practice in palliative care settings. Clinical trials roles provide palliative care nurses with an opportunity to contribute to clinical research, help expand palliative care’s evidence base as well as develop their own research capabilities

No excess harms from sustained-release morphine: A randomised placebo-controlled trial in chronic breathlessness

© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ. Objectives: We aimed to identify and evaluate: (1) treatment-emergent adverse events (TEAE (worse or new since baseline)) and the subgroup of severe TEAEs in a placebo-controlled 7-day randomised trial of regular, low-dose, sustained-release oral morphine for chronic breathlessness and (2) clinical characteristics associated with TEAE. Methods: Safety analysis of trial data. Adults with chronic breathlessness (modified Medical Research Council breathlessness score ≥2) due to heart or lung disease, or cancer, not on regular opioids were eligible. Symptoms associated with opioids (TEAE of special interest) were systematically sought using Common Terminology Criteria for Adverse Events (CTCAE) grading. Other harms could be reported at any time. The relationship between characteristics and presence of ≥1 TEAE of special interest was explored using univariable logistic regression analyses. Results: 1449/5624 (26%) Adverse Events from 279 participants were TEAE of which 150/1449 (10%) were severe (CTCAE grades 3-5). 1086/5624 (75%) were events of special interest of which 41/1086 (4%) were severe. Compared with placebo, morphine was not associated with more TEAE or severe TEAE of special interest (TEAE: OR 0.53, 95% CI 0.21 to 1.38, p=0.20; severe TEAE: OR 0.96, 95% CI 0.27 to 3.41, p=0.95) nor with CTCAE severity grade (χ2=4.39, p=0.50). Among the 26/150 (17%) with severe TEAEs, study withdrawal was more common in the morphine arm (18/26 (69%) morphine arm; 8/26 (30%) placebo arm). None of the severe TEAEs was a respiratory harm. Conclusions: Severe morphine-associated toxicity was uncommon and not associated with study arm. Clinical consequences were minor and self-limiting. Trial registration number: ACTRN126000806268

Double-blind, placebo-controlled, randomized trial of octreotide in malignant bowel obstruction

Context Does octreotide reduce vomiting in cancer-associated bowel obstruction? Objectives To evaluate the net effect of adding octreotide or placebo to standardized therapies on the number of days free of vomiting for populations presenting with vomiting and inoperable bowel obstruction secondary to cancer or its treatment. Methods Twelve services enrolled people with advanced cancer presenting with vomiting secondary to bowel obstruction where surgery or anti-cancer therapies were not indicated immediately. In a double-blind study, participants were randomized to placebo or octreotide (600 μg/24 hours by infusion). Both arms received standardized supportive therapy (infusion of ranitidine [200 mg/24 hours], dexamethasone [8 mg/24 hours], and parenteral hydration [10-20 mL/kg/24 hours]). The primary outcome was patient-reported days free of vomiting at 72 hours. Results In a study that recruited to the numbers identified in its power calculation, 87 participants provided data at 72 hours (45, octreotide arm). Seventeen people (octreotide) and 14 (placebo) were free of vomiting for 72 hours (P = 0.67). Mean days free of vomiting were 1.87 (SD 1.10; octreotide) and 1.69 (SD 1.15; placebo; P = 0.47). An adjusted multivariate regression of the incidence of vomiting over the study showed a reduced number of episodes of vomiting in the octreotide group (incidence rate ratio = 0.40; 95% CI: 0.19-0.86; P = 0.019); however, people in the octreotide arm were 2.02 times more likely to be administered hyoscine butylbromide (P = 0.004), potentially reflecting increased colicky pain. Conclusion Although there was no reduction in the number of days free of vomiting, the multivariate analysis suggests that further study of somatostatin analogues in this setting is warranted

Creating a research culture in a palliative care service environment: A qualitative study of the evolution of staff attitudes to research during a large longitudinal controlled trial (ISRCTN81117481)

Abstract in French availablePublisher versionThis study investigated the impact of a three-year randomized control trial of different models of service provision on palliative care staff associated with the hospice where the trial was being conducted. Eleven open access de-identified qualitative focus groups were held over a period of three years: three months into the trial, one year after its inception, and at the end of the trial. Four staff groups were involved: inpatient hospice nurses, palliative care outreach nurses, medical palliative specialists, and administrative staff and social workers. Initially the impact of the trial produced high levels of staff stress which largely diminished over time, to be replaced by enthusiasm for the changes achieved and sadness that post trial the perceived benefits gained would be lost. When attempting to change a clinical culture to incorporate research, and in particular where increased staff workload is involved, highly interactive levels of communication and valuing of staff input are required to minimize the stress and burden of this imposition

Integration, Coordination and Multidisciplinary Care: What can These Approaches Offer to Australian Primary Health Care?

Australia's population is ageing and the consequential burden of chronic disease increasingly challenges the health system. This has raised interest in, and awareness of, approaches built on multidisciplinary teams and integrated and coordinated care in managing the complex care needs of patient groups such as the chronically ill or frail aged. A systematic investigation of the literature relating to these approaches provided the opportunity to explore the meaning of these terms and their potential application and relevance to the Australian primary health care setting. Five systematic reviews of a sentinel condition and an exemplar approach to coordinated and multidisciplinary care were completed. Common learnings from the individual reviews were identified. The literature suggests that approaches encouraging a coordinated and multidisciplinary plan of care for individual patients and/or particular populations may improve a variety of outcomes. There are many methodological considerations in conducting reviews of complex interventions and in assessing their applicability to the Australian health system

Phase II, double blind, placebo controlled, multi-site study to evaluate the safety, feasibility and desirability of conducting a phase III study of anamorelin for anorexia in people with small cell lung cancer: a study protocol (LUANA trial)

AbstractAnorexia is experienced by most people with lung cancer during the course of their disease and treatment. Anorexia reduces response to chemotherapy and the ability of patients to cope with, and complete their treatment leading to greater morbidity, poorer prognosis and outcomes. Despite the significant importance of cancer-related anorexia, current therapies are limited, have marginal benefits and unwarranted side effects. In this multi-site, randomised, double blind, placebo controlled, phase II trial, participants will be randomly assigned (1:1) to receive once-daily oral dosing of 100mg of anamorelin HCl or matched placebo for 12 weeks. Participants can then opt into an extension phase to receive blinded intervention for another 12 weeks (weeks 13-24) at the same dose and frequency. Adults (≥18 years) with small cell lung cancer (SCLC); newly diagnosed with planned systemic therapy OR with first recurrence of disease following a documented disease-free interval ≥6 months, AND with anorexia (i.e., ≤ 37 points on the 12-item Functional Assessment of Anorexia Cachexia Treatment (FAACT A/CS) scale) will be invited to participate. Primary outcomes are safety, desirability and feasibility outcomes related to participant recruitment, adherence to interventions, and completion of study tools to inform the design of a robust Phase III effectiveness trial. Secondary outcomes are the effects of study interventions on body weight and composition, functional status, nutritional intake, biochemistry, fatigue, harms, survival and quality of life. Primary and secondary efficacy analysis will be conducted at 12 weeks. Additional exploratory efficacy and safety analyses will also be conducted at 24 weeks to collect data over longer treatment duration. The feasibility of economic evaluations in Phase III trial will be assessed, including the indicative costs and benefits of anamorelin for SCLC to the healthcare system and society, the choice of methods for data collection and the future evaluation design. The trial has been registered with the Australian New Zealand Clinical Trials Registry [ACTRN12622000129785] and approved by the South Western Sydney Local Health District Human Research Ethics Committee [2021/ETH11339]

Integration, coordination and multidisciplinary approaches in primary care: a systematic investigation of the literature

Australia's population is ageing and there is an increasing burden of chronic disease putting pressure on the health system. These challenges have raised interest and awareness of primary health care models of care, like the use of integrated, co-ordinated multidisciplinary team approaches. This review looked at the existence and effectiveness of these models in primary health care settings.The research reported in this paper is a project of the Australian Primary Health Care Research Institute, which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research, Evaluation and Development Strategy