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Background Ketamine at subanaesthetic dosages ([less than or equal to]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. Objective 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. Methods This was a single arm, open-label, phase II feasibility study (Australian New Zealand Clinical Trial Registry Number-ACTRN12618001586202). We recruited adults ([greater than or equal to] 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. Results 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 [greater than or equal to] 50% reduction in baseline Montgomery-Åsberg Depression Rating Scale, meeting feasibility criteria set a priori. There were no clinically relevant harms encountered. Conclusions 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.

The routine measurement of patient-reported outcomes in cancer clinical care using electronic patient-reported outcome measures (ePROMs) is gaining momentum worldwide. However, a deep understanding of the mechanisms underpinning ePROM interventions that could inform their optimal design to improve health outcomes is needed. This study aims to identify the implicit mechanisms that underpin the effectiveness of ePROM interventions and develop program theories about how and when ePROM interventions improve health outcomes. A realist synthesis of the literature about ePROM interventions in cancer clinical care was performed. A conceptual framework of ePROM interventions was constructed to define the scope of the review and frame the initial program theories. Literature searches of Ovid MEDLINE, Ovid Embase, Scopus, and CINAHL, supplemented by citation tracking, were performed to identify relevant literature to develop, refine, and test program theories. Quality appraisal of relevant studies was performed using the Mixed Methods Appraisal Tool. Overall, 61 studies were included in the realist synthesis: 15 (25%) mixed methods studies, 9 (15%) qualitative studies, 13 (21%) descriptive studies, 21 (34%) randomized controlled trials, and 3 (5%) quasi-experimental studies. In total, 3 initial program theories were developed regarding the salient components of ePROM interventions-remote self-reporting, real-time feedback to clinicians, and clinician-patient telecommunication. The refined theories posit that remote self-reporting enables patients to recognize and report symptoms accurately and empowers them to communicate these to clinicians, real-time feedback prompts clinicians to manage symptoms proactively, and clinician-patient telephone interactions and e-interactions between clinic encounters improve symptom management by reshaping how clinicians and patients communicate. However, the intervention may not achieve the intended benefit if ePROMs become a reminder to patients of their illness and are not meaningful to them and when real-time feedback to clinicians lacks relevance and increases the workload. The key to improving health outcomes through ePROM interventions is enabling better symptom reporting and communication through remote symptom self-reporting, promoting proactive management of symptoms through real-time clinician feedback, and facilitating clinician-patient interactions. Patient engagement with self-reporting and clinician engagement in responding to feedback are vital and may reinforce each other in improving outcomes. Effective ePROM interventions might fundamentally alter how clinicians and patients interact between clinic encounters.

ObjectivesTo estimate the economic impact of delirium in the Australian population in 2016–2017, including financial costs, and its burden on health.Design, setting and participantsA cost of illness study was conducted for the Australian population in the 2016–2017 financial year. The prevalence of delirium in 2016–2017 was calculated to inform cost estimations. The costs estimated in this study also include dementia attributable to delirium.Main outcome measuresThe total and per capita costs were analysed for three categories: health systems costs, other financial costs including productivity losses and informal care and cost associated with loss of well-being (burden of disease). Costs were expressed in 2016–2017 pound sterling (£) and Australian dollars ($A).ResultsThere were an estimated 132 595 occurrences of delirium in 2016–2017, and more than 900 deaths were attributed to delirium in 2016–2017. Delirium causes an estimated 10.6% of dementia in Australia. The total costs of delirium in Australia were estimated to be £4.3 billion ($A8.8 billion) in 2016–2017, ranging between £2.6 billion ($A5.3 billion) and £5.9 billion ($A12.1 billion). The total estimated costs comprised financial costs of £1.7 billion and the value of healthy life lost of £2.5 billion. Dementia attributable to delirium accounted for £2.2 billion of the total cost of delirium.ConclusionsThese findings highlight the substantial burden that delirium imposes on Australian society—both in terms of financial costs associated with health system expenditure and the increased need for residential aged care due to the functional and cognitive decline associated with delirium and dementia. To reduce the substantial well-being costs of delirium, further research should seek to better understand the potential pathways from an episode of delirium to subsequent mortality and reduced cognitive functioning outcomes.

This multi-site, double blind, parallel arm, fixed dose, randomised placebo controlled phase III study compared megestrol acetate 480 mg/day with dexamethasone 4 mg/day for their net effects on appetite in people with cancer anorexia. Patients with advanced cancer and anorexia for ≥ 2 weeks with a score ≤ 4 (0–10 numeric rating scale (NRS) 0 = no appetite, 10 = best possible appetite) were recruited. Participants received megestrol 480 mg or dexamethasone 4 mg or placebo daily for up to 4 weeks. Primary outcomes were at day 7. Responders were defined as having a ≥ 25% improvement in NRS over baseline. There were 190 people randomised (megestrol acetate n = 61; dexamethasone n = 67, placebo n = 62). At week 1 (primary endpoint), 79·3% in the megestrol group, 65·5% in the dexamethasone group and 58·5% in the placebo group ( p  = 0.067) were responders. No differences in performance status or quality of life were reported. Treatment emergent adverse events were frequent (90·4% of participants), and included altered mood and insomnia. Hyperglycemia and deep vein thromboses were more frequent when on dexamethasone than the other two arms. There was no difference in groups between the three arms, with no benefit seen over placebo with anorexia improving in all arms. Trail registration: The trial was registered on 19/08/2008 with the Australian New Zealand Clinical Trials Registry (ACTRN12608000405314).

Key Summary Points Aim To review the published literature on the cost of delirium. Findings Every study has found that delirium increases the cost of care in every setting, in hospital, after discharge at home and in long-term care. Message Delirium results in increased financial and social costs which, when considered with the impacts on morbidity and mortality, support the call to urgently improve prevention, screening, diagnosis and treatment of delirium. Purpose Delirium is common with serious short- and long-term sequelae. However, there are no licensed treatments internationally and relatively little biomedical discovery with the target of finding a cure, with the invisibility or underestimation of the economic implications as a potential driver for this inertia. Methods We conducted a narrative review of published literature in English quantitatively evaluating the financial and social costs of delirium to the health and care systems, patients and their carers. Results Delirium increases the cost of the index hospitalisation as well as increasing the need for post-acute care and the demands on unpaid, often older, carers. Delirium may cause as much as 10% of all cases of dementia and the ongoing need for care of these people with dementia doubles the cost of delirium. Prevention of delirium not only reduces the cost of delirium but also may decrease subsequent rate of dementia. Conclusion The high cost of delirium itself as well as the resultant dementia warrants greater efforts to prevent delirium and discover effective treatment.

Background: Delirium is a serious neuropsychiatric syndrome frequently experienced by palliative care inpatients. This syndrome is under-recognized by clinicians. While screening increases recognition, it is not a routine practice. Aim and design: This systematic review aims to examine methods, quality, and results of delirium prevalence and incidence studies in palliative care inpatient populations and discuss implications for delirium screening. Data sources: A systematic search of the literature identified prospective studies reporting on delirium prevalence and/or incidence in inpatient palliative care adult populations from 1980 to 2012. Papers not in English or those reporting the occurrence of symptoms not specifically identified as delirium were excluded. Results: Of the eight included studies, the majority (98.9%) involved participants (1079) with advanced cancer. Eight different screening and assessment tools were used. Delirium incidence ranged from 3% to 45%, while delirium prevalence varied, with a range of: 13.3%–42.3% at admission, 26%–62% during admission, and increasing to 58.8%–88% in the weeks or hours preceding death. Studies that used the Diagnostic and Statistical Manual–Fourth Edition reported higher prevalence (42%–88%) and incidence (40.2%–45%), while incidence rates were higher in studies that screened participants at least daily (32.8%–45%). Hypoactive delirium was the most prevalent delirium subtype (68%–86% of cases). Conclusion: The prevalence and incidence of delirium in palliative care inpatient settings supports the need for screening. However, there is limited consensus on assessment measures or knowledge of implications of delirium screening for inpatients and families. Further research is required to develop standardized methods of delirium screening, assessment, and management that are acceptable to inpatients and families.

Breathlessness action plans guide people to self-manage acute-on-chronic breathlessness episodes using non-pharmacological strategies to help breathing and overcome panic. We aimed to identify plans available for people with chronic obstructive pulmonary disease (COPD) and describe their development, content, quality, use, and evidence for benefit. Two descriptive methodologies were used, overseen by a team of people with COPD and carers/support persons, clinicians and researchers: 1) A scoping review (academic databases, internet) identified English-language plans and research; 2) An online survey of plan-users and clinicians about their plan-related experience and perceived benefits. Each plan underwent appraisal by a person with COPD/support person and clinician/researcher using the Patient Education Materials Assessment Tool (PEMAT), content analysis and reading grade assessment. Of 69 plans identified, 88% (n=61/69) included breathing techniques, 78% (n=54/69) positioning, 65% (n=45/69) airflow, 36% (n=25/69) relaxation/distraction, 30% (n=21/69) stopping/slowing, 22% (n=15/69) remaining calm, 13% (n=13/69) reassurance, 7% (n=5/69) support from others and 4% (n=3/69) loosening clothing. The 48 plans that could be PEMAT-analysed scored an average of 64% for understandability and 68% for actionability. Their median reading grade was 8.2 (inter-quartile range 2.2). We identified efficacy support from only one pre/post study and feasibility/acceptability from qualitative data in two feasibility trials, each focusing on a different plan. In the survey, 67% (n=31/46) of plan-users self-reported avoiding calling an ambulance over the past year by using their plan. 93% (n=94/101) of clinicians perceived patient benefit in the form of increased confidence/reduced anxiety, 60% (n=61/101) reduced frequency of episodes, 53% (54/101) reduced need for ambulance/emergency department, and 41% (41/101) increased activities of daily living, while 4% (4/101) were unsure of any benefit. Despite multiple plans being available, few studies have assessed acceptability or efficacy. Further research is needed to evaluate net effects on self-management, breathlessness-related outcomes and healthcare usage.

Ketamine at subanaesthetic dosages ([less than or equal to]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 ([greater than or equal to] 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 [greater than or equal to] 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 The majority of cancer patients and cancer care clinicians-CCCs (e.g., oncologists) believe that exercise is an important adjunct therapy that should be embedded in standard practice. Yet, CCCs do not routinely discuss exercise with their patients, nor do they regularly refer them to exercise professionals (e.g., exercise physiologists-EPs). This study evaluated the feasibility and acceptability of an evidence-based approach to improving exercise communication between CCCs and their patients, including an exercise referral pathway. Methods Implementation and testing of the Exercise Communication and Referral Pathway (ECRP) occurred in Sydney, Australia. The ECRP included a brief oncology-initiated communication exchange with patients, CCC exercise referral to an EP, followed by EP-initiated telephone consultation with patients concerning tailored exercise advice. Participant perceptions concerning the feasibility and applicability of the ECPR were evaluated. Semi-structured interviews were conducted with CCCs (n = 3), cancer patients (n = 21), and an EP (n = 1). Inductive thematic analysis was undertaken. Results Analysis generated three themes: (1) Navigating the role of CCCs in the ECRP, suggesting that oncology-initiated communication is a cue to action, however there was a lack of role clarity regarding exercise referral; (2) Implementing Patient-Orientated Care within a Standardised Pathway, highlighting the need for tailored information and advice for patients that reflects individual disease, socio-cultural, and environmental factors, and; (3) Taking Steps Towards Action, revealing the need for structural (e.g., EP initiated contact with patients) and policy changes (i.e., changes to Medicare, direct oncologist referral) to engage patients and better integrate exercise as part of standard care. Conclusions Findings provide important insights into improving oncology-patient exercise communication and developing an exercise referral pathway to increase engagement and patient reach. However, individual (e.g., experience, knowledge) and contextual factors (e.g., time, resources) need consideration when implementing an ECRP. Trial registration This trial was prospectively registered with the Australian New Zealand Clinical (#ACTRN12620000358943) on March 13, 2020.

Purpose This umbrella review aimed to summarise and synthesize the evidence on the outcomes reported and used to assess the value and or efficacy of geriatric assessments (GAs) for older adults with cancer. Methods Six electronic databases, PsycINFO, MEDLINE, Embase, CINAHL, Cochrane Library and Web of Science databases, were searched to identify systematic reviews with or without meta-analyses that described the value or outcomes of GAs for older adults with cancer. Results Twenty-six systematic reviews were included, of which six included a meta-analysis of the data. Thirteen associations and or outcomes were identified. Overall geriatric impairments predicted or were associated with majority of identified outcomes. However, the type of domains associated with outcomes differed within and across reviews. Only treatment toxicity was statistically significantly lower for patients allocated to the GA intervention group compared to standard care. Systematic reviews without meta-analyses demonstrated a positive impact of GA with management on treatment completion, communication and care planning and patient satisfaction with care. Conclusion There is evidence demonstrating the predictive value of GAs for older adults with cancer. GAs seems to be beneficial for older adults with cancer across some outcomes, with strong evidence demonstrating the impact of GA with management for treatment toxicity. However, there is mixed or limited evidence demonstrating the effect of GA in other treatment modalities, and on quality of life and economic outcomes.