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

CareSearch: finding and evaluating Australia's missing palliative care literature

BACKGROUND: Palliative care is an evolving specialty with a growing evidence base. However, evidence is less accessible than it could be with a lower than average conversion of conference abstracts to articles in peer-reviewed journals and the need for more accessible tools to support evidence-based practice (EBP) in palliative care. The CareSearch project involved identifying, collecting and evaluating Australia's "grey" palliative care literature and identifying international published literature missing from the electronic indexing systems. The literature was then catalogued and made publicly available through the CareSearch website. RESULTS: To date over 2,500 items have been included in the CareSearch database and can be accessed and searched through a publicly available website. Nearly 2,000 items are conference abstracts and 178 are theses or government, organisational and planning documents. A further 410 items relate to articles from palliative journals that are not indexed on a major bibliographic database. The website also provides tools and facilities to support palliative care practice and research. CONCLUSION: CareSearch is a new evidence resource for palliative practitioners, educators and researchers. The palliative community now has access to a more comprehensive literature base as well as a resource that supports the integration of knowledge into practice. This specialised data repository enables users to access information on the body of work that has shaped palliative care development and prevents the potential loss or duplication of research work. It also provides a template for other emerging disciplines to use in capturing their literature and evidence

Development of a subject search filter to find information relevant to palliative care in the general medical literature

Purpose: The research developed and validated palliative care search filters for use in the general biomedical literature. Methods: Four general medical journals were hand-searched to identify articles relevant to palliative care, forming a “gold standard” reference set. Searches comprising Medical Subject Headings (MeSH) and text-words were created for use in Ovid MEDLINE, and retrieved references were compared to the gold standard. Sensitivity, specificity, accuracy, and precision rates were calculated. Results: By hand-searching 20,501 articles published in the 4 journals during the 3-year study period (1999–2001), reviewers identified 773 items relevant to palliative care (3.8%). A master search combining 9 MeSH descriptors with 3 text-words achieved 45.4% sensitivity, 99.3% specificity, 73% precision, and 97.3% accuracy. Efforts to increase the sensitivity by modifying 3 relevant published but unvalidated searches did not improve the yield, except in 1 case which resulted in an improved sensitivity of 56.9% but was offset by reduced specificity (92.1%), precision (22%), and accuracy (90.8%). Conclusions: The study confirmed that literature relevant to palliative care is difficult to identify in general medical journals. While the filter developed in this research represents the best trade-off between sensitivity, specificity, accuracy, and precision, the sensitivity is unacceptably low. Further research, such as frequency analysis of text-words and MeSH terms, is required to increase the sensitivity of searching in this subset of the literature

Specialist palliative care needs of whole populations: a feasibility study using a novel approach

330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, USA, VA, 2231

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

Abstract 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 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.</p

Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea

Objective To determine the efficacy of oral morphine in relieving the sensation of breathlessness in patients in whom the underlying aetiology is maximally treated. Design Randomised, double blind, placebo controlled crossover study. Setting Four outpatient clinics at a hospital in South Australia. Participants 48 participants who had not previously been treated with opioids (mean age 76, SD 5) with predominantly chronic obstructive pulmonary disease (42, 88%) were randomised to four days of 20 mg oral morphine with sustained release followed by four days of identically formulated placebo, or vice versa. Laxatives were provided as needed. Main outcome measures Dyspnoea in the morning and evening as shown on a 100 mm visual analogue scale, quality of sleep, wellbeing, performance on physical exertion, and side effects as measured at the end of the four day treatment period. Results 38 participants completed the study; three withdrew because of definite and two because of possible side effects of morphine (nausea, vomiting, and sedation). Participants reported significantly different dyspnoea scores when treated with morphine: an improvement of 6.6 mm (95% confidence interval 1.6 mm to 11.6 mm) in the morning and of 9.5 mm (3.0 mm to 16.1 mm) in the evening (P = 0.011 and P = 0.006, respectively). During the period in which they were taking morphine participants also reported better sleep (P = 0.039). More participants reported distressing constipation while taking morphine (9 v 1, P = 0.021) in spite of using laxatives. All other side effects were not significantly worse with morphine, although the study was not powered to address side effects. Conclusions Sustained release, oral morphine at low dosage provides significant symptomatic improvement in refractory dyspnoea in the community setting