Defining research priorities and needs in cancer symptoms for adults diagnosed with cancer: an Australian/New Zealand modified Delphi study.

PURPOSE: This study asked consumers (patients, carers) and healthcare professionals (HCPs) to identify the most important symptoms for adults with cancer and potential treatment interventions. METHODS: A modified Delphi study was conducted involving two rounds of electronic surveys based on prevalent cancer symptoms identified from the literature. Round 1 gathered information on participant demographics, opinions and/or experience on cancer symptom frequency and impact, and suggestions for interventions and/or service delivery models for further research to improve management of cancer symptoms. In Round 2, respondents ranked the importance of the top ten interventions identified in Round 1. In Round 3, separate expert panels of consumers and healthcare professionals (HCPs) attempted to reach consensus on the symptoms and interventions previously identified. RESULTS: Consensus was reached for six symptoms across both groups: fatigue, constipation, diarrhoea, incontinence, and difficulty with urination. Notably, fatigue was the only symptom to reach consensus across both groups in Round 1. Similarly, consensus was reached for six interventions across both groups. These were the following: medicinal cannabis, physical activity, psychological therapies, non-opioid interventions for pain, opioids for breathlessness and cough, and other pharmacological interventions. CONCLUSIONS: Consumers and HCPs prioritise differently; however, the symptoms and interventions that reached consensus provide a basis for future research. Fatigue should be considered a high priority given its prevalence and its influence on other symptoms. The lack of consumer consensus indicates the uniqueness of their experience and the need for a patient-centred approach. Understanding individual consumer experience is important when planning research into better symptom management.

The Dilemma of Treating Delirium: the Conundrum of Drug Management.

OPINION STATEMENT: Delirium is a common medical complication in people living with cancer, particularly with more advanced disease. Delirium is associated with significant symptom burden which causes distress and impacts quality of life. As recommended by international guidelines, a high degree of suspicion is needed to ensure delirium is detected early. Attention to collateral history can provide clues to changes in cognition and attention. Non-pharmacological approaches that can be considered essential elements of care are effective in reducing the risk of delirium. Delirium screening using a validated measure is recommended as even expert clinicians can underdiagnose or miss delirium. The diagnostic assessment requires consideration of the cancer diagnosis and comorbidities, in the context of potential reversibility, goals of care, and patient preferences. The gold standard approach based on expert consensus is to institute management for delirium precipitants supported by non-pharmacological essential care, with the support of an interdisciplinary team. Medication management should be used sparingly and for a limited period of time wherever possible for severe perceptual disturbance or agitation which has not improved with non-pharmacological approaches. Clinicians should be familiar with the registered indication for medications and seek informed consent for off-label use. All interventions put in place to manage delirium need to consider net clinical benefit, including harms such as sedation and loss of capacity for meaningful interaction. Clear communication and explanation are needed regularly, with the person with delirium as far as possible and with surrogate decision makers. Delirium can herald a poor prognosis and this needs to be considered and be discussed as appropriate in shared decision-making. Recall after delirium has resolved is common, and opportunity to talk about this experience and the related distress should be offered during the period after recovery.

Efficacy of medicinal cannabis for appetite-related symptoms in people with cancer: A systematic review.

BACKGROUND: Anorexia (loss of appetite) is a prevalent and distressing symptom in people with cancer, with limited effective interventions. Medicinal cannabis has shown promise in improving appetite-related symptoms in people with cancer. AIM: To assess the efficacy of medicinal cannabis for improving appetite-related symptoms in people with cancer, considering measures and outcomes, interventions and toxicity. DESIGN: Systematic review with narrative approach to synthesis and meta-analysis. DATA SOURCES: Databases (MEDLINE, CINAHL, CENTRAL), websites and trials registries were searched from inception to February 2021. Included studies were randomised controlled trials (RCT) in English peer-reviewed journals comparing medicinal cannabis with placebo and/or another intervention. Study quality was assessed using the Cochrane risk of bias tool. RESULTS: Five studies were included that compared medicinal cannabis interventions (dronabinol, nabilone and cannabis extract) either with placebo (n = 4) or megestrol acetate (n = 1). Measures and trial endpoints varied, but efficacy was demonstrated in one trial only, in which dronabinol significantly improved chemosensory perception and other secondary outcomes (taste of food, premeal appetite, proportion of calories consumed as protein) compared with placebo. Cannabis interventions were generally well tolerated across studies, regardless of the product or dose, although the comprehensive measurement of toxicities was limited. CONCLUSION: Evidence from RCTs that medicinal cannabis increases appetite in people with cancer is limited. Measures, outcomes and interventions were variable, and toxicities have not been comprehensively evaluated. Future research should carefully consider biological mechanisms to guide more nuanced selection of endpoints and interventions, including product, dose and administration.

Investigating the benefits and harms of hypodermoclysis of patients in palliative care: A consecutive cohort study.

BACKGROUND: Palliative populations are at risk for dehydration which can cause discomfort, distress and cognitive symptoms. Subcutaneous hydration ('hypodermoclysis') has been used as an alternative administration route to the more invasive intravenous route, but research is lacking on its net clinical effects (harms and benefits) for palliative populations, particularly in real world settings. AIM: To quantify prospectively the net clinical effects of hypodermoclysis in palliative patients with advanced disease who required supplementary fluids. DESIGN: Multisite, multinational consecutive cohort study. SETTING/PARTICIPANTS: Patients receiving hypodermoclysis in an inpatient palliative care setting. RESULTS: Twenty sites contributed data for 99 patients, of which 88 had complete benefits and harms data. The most common primary target symptom for infusion was generalised weakness (18.2%), and the most common non-symptom indication was supplemental hydration (31.8%). Benefits were experienced in 33% of patients in their primary target symptom, and in any symptom in 56.8%. Harms were experienced in 38.7% of patients (42% at Grade 1). Benefits increased with higher performance status, while harms were more frequent in patients with lower performance status (Australia-modified Karnofsky performance status ⩽40). Patients in the terminal phase of their illness experienced the least benefit (15.4% in any indication only) and had more frequent harms (38%). CONCLUSIONS: Hypodermoclysis may improve certain symptoms in patients in palliative care but frequency of harms and benefits may differ at certain timepoints in the illness trajectory. Further research is needed to better delineate which patients will derive the most net clinical benefit from hypodermoclysis.

Outcomes and measures of delirium interventional studies in palliative care to inform a core outcome set: A systematic review.

BACKGROUND: Trials of interventions for delirium in various patient populations report disparate outcomes and measures but little is known about those used in palliative care trials. A core outcome set promotes consistency of outcome selection and measurement. AIM: To inform core outcome set development by examining outcomes, their definitions, measures and time-points in published palliative care studies of delirium prevention or treatment delirium interventions. DESIGN: Prospectively registered systematic review adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. DATA SOURCES: We searched six electronic databases (1980-November 2020) for original studies, three for relevant reviews and the International Clinical Trials Registry Platform for unpublished studies and ongoing trials. We included randomised, quasi-randomised and non-randomised intervention studies of pharmacological and non-pharmacological delirium prevention and/or treatment interventions. RESULTS: From 13/3244 studies (2863 adult participants), we identified 9 delirium-specific and 13 non-delirium specific outcome domains within eight Core Outcome Measures in Effectiveness Trials (COMET) taxonomy categories. There were multiple and varied outcomes and time points in each domain. The commonest delirium specific outcome was delirium severity (n = 7), commonly using the Memorial Delirium Assessment Scale (6/8 studies, 75%). Four studies reported delirium incidence. Non-delirium specific outcomes included mortality, agitation, adverse events, other symptoms and quality of life. CONCLUSION: The review identified few delirium interventions with heterogeneity in outcomes, their definition and measurement, highlighting the need for a uniform approach. Findings will inform the next stage to develop consensus for a core outcome set to inform delirium interventional palliative care research.

Quality of online self-management resources for adults living with primary brain cancer, and their carers: a systematic environmental scan.

BACKGROUND: A primary brain cancer diagnosis is a distressing, life changing event. It adversely affects the quality of life for the person living with brain cancer and their families ('carers'). Timely access to evidence-based information is critical to enabling people living with brain cancer, and their carers, to self-manage the devastating impacts of this disease. METHOD: A systematic environmental scan of web-based resources. A depersonalised search for online English-language resources published from 2009 to December 2019 and designed for adults (> 25 years of age), living with primary brain cancer, was undertaken using the Google search engine. The online information was classified according to: 1) the step on the cancer care continuum; 2) self-management domains (PRISMS taxonomy); 3) basic information disclosure (Silberg criteria); 4) independent quality verification (HonCode); 5) reliability of disease and treatment information (DISCERN Sections 1 and 2); and readability (Flesch-Kincaid reading grade). RESULTS: A total of 119 online resources were identified, most originating in England (n = 49); Australia (n = 27); or the USA (n = 27). The majority of resources related to active treatment (n = 76), without addressing recurrence (n = 3), survivorship (n = 1) or palliative care needs (n = 13). Few online resources directly provided self-management advice for adults living with brain cancer or their carers. Just over a fifth (n = 26, 22%) were underpinned by verifiable evidence. Only one quarter of organisations producing resources were HonCode certified (n = 9, 24%). The median resource reliability as measured by Section 1, DISCERN tool, was 56%. A median of 8.8 years of education was required to understand these online resources. CONCLUSIONS: More targeted online information is needed to provide people affected by brain cancer with practical self-management advice. Resources need to better address patient and carer needs related to: rehabilitation, managing behavioural changes, survivorship and living with uncertainty; recurrence; and transition to palliative care. Developing online resources that don't require a high level of literacy and/or cognition are also required.

Toward best practice methods for delirium biomarker studies: An international modified Delphi study.

BACKGROUND: Delirium is a serious and distressing neurocognitive condition common in people with advanced illness. The understanding of delirium pathophysiology is limited and largely hypothetical. To accelerate empirical understanding of delirium pathophysiology, robust scientific methods for conducting and reporting delirium biomarker studies are urgently needed. The aim of this study was to develop international consensus on the core elements of high-quality delirium biomarker studies. METHODS: A three-round modified Delphi survey was conducted from February to August 2019. Participants were international researchers experienced in conducting delirium studies from a range of settings (hospital, university, research centres). Round one commenced with open-ended questions developed from results from a prior systematic review and the REMARK (REporting recommendations for tumour MARKer prognostic studies) checklist. Responses were qualitatively analysed, and closed statements were developed. Participants then ranked the importance of these statements using a 5-point Likert scale in rounds 2 and 3. A priori consensus was defined as ≥70% participant agreement. Descriptive statistics for each item were computed including the mean Likert scores, SD and median participant scores. RESULTS: Twenty-eight participants completed survey round one, 16 completed round two and 19 completed the final round. Consensus was achieved for a total of 60 items. CONCLUSION: The Delphi survey identified items that expert researchers agreed were important in the conduct of delirium biomarker studies. These reporting items provide a strong platform for improved methodological quality and opportunities to synthesise future delirium biomarker studies.

A systematic review of the overlap of fluid biomarkers in delirium and advanced cancer-related syndromes.

BACKGROUND: Delirium is a serious and distressing neurocognitive disorder of physiological aetiology that is common in advanced cancer. Understanding of delirium pathophysiology is largely hypothetical, with some evidence for involvement of inflammatory systems, neurotransmitter alterations and glucose metabolism. To date, there has been limited empirical consideration of the distinction between delirium pathophysiology and that of the underlying disease, for example, cancer where these mechanisms are also common in advanced cancer syndromes such as pain and fatigue. This systematic review explores biomarker overlap in delirium, specific advanced cancer-related syndromes and prediction of cancer prognosis. METHODS: A systematic review (PROSPERO CRD42017068662) was conducted, using MEDLINE, PubMed, Embase, CINAHL, CENTRAL and Web of Science, to identify body fluid biomarkers in delirium, cancer prognosis and advanced cancer-related syndromes of interest. Studies were excluded if they reported delirium tremens only; did not measure delirium using a validated tool; the sample had less than 75% of participants with advanced cancer; measured tissue, genetic or animal biomarkers, or were conducted post-mortem. Articles were screened for inclusion independently by two authors, and data extraction and an in-depth quality assessment conducted by one author, and checked by two others. RESULTS: The 151 included studies were conducted in diverse settings in 32 countries between 1985 and 2017, involving 28130 participants with a mean age of 69.3 years. Seventy-one studies investigated delirium biomarkers, and 80 studies investigated biomarkers of an advanced cancer-related syndrome or cancer prognosis. Overall, 41 biomarkers were studied in relation to both delirium and either an advanced cancer-related syndrome or prognosis; and of these, 24 biomarkers were positively associated with either delirium or advanced cancer syndromes/prognosis in at least one study. The quality assessment showed large inconsistency in reporting. CONCLUSION: There is considerable overlap in the biomarkers in delirium and advanced cancer-related syndromes. Improving the design of delirium biomarker studies and considering appropriate comparator/controls will help to better understanding the discrete pathophysiology of delirium in the context of co-existing illness.

Inclusion, characteristics and outcomes of people requiring palliative care in studies of non-pharmacological interventions for delirium: A systematic review.

BACKGROUND: Delirium is common, distressing, serious and under-researched in specialist palliative care settings. OBJECTIVES: To examine whether people requiring palliative care were included in non-pharmacological delirium intervention studies in inpatient settings, how they were characterised and what their outcomes were. DESIGN: Systematic review (PROSPERO 2017 CRD42017062178). DATA SOURCES: Systematic search in March 2017 for non-pharmacological delirium intervention studies in adult inpatients. Database search terms were 'delirium', 'hospitalisation', 'inpatient', 'palliative care', 'hospice', 'critical care' and 'geriatrics'. Scottish Intercollegiate Guidelines Network methodological checklists guided risk of bias assessment. RESULTS: The 29 included studies were conducted between 1994 and 2015 in diverse settings in 15 countries (9136 participants, mean age = 76.5 years (SD = 8.1), 56% women). Most studies tested multicomponent interventions (n = 26) to prevent delirium (n = 19). Three-quarters of the 29 included studies (n = 22) excluded various groups of people requiring palliative care; however, inclusion criteria, participant diagnoses, illness severity and mortality indicated their presence in almost all studies (n = 26). Of these, 21 studies did not characterise participants requiring palliative care or report their specific outcomes (72%), four reported outcomes for older people with frailty, dementia, cancer and comorbidities, and one was explicitly focused on people receiving palliative care. Study heterogeneity and limitations precluded definitive determination of intervention effectiveness and only allowed interpretations of feasibility for people requiring palliative care. Acceptability outcomes (intervention adverse events and patients' subjective experience) were rarely reported overall. CONCLUSION: Non-pharmacological delirium interventions have frequently excluded and under-characterised people requiring palliative care and infrequently reported their outcomes.

Talking skin: attitudes and practices around skin infections, treatment options, and their clinical management in a remote region in Western Australia.

INTRODUCTION: Skin infections including scabies and impetigo have a high burden and cause significant morbidity in remote Aboriginal communities in Australia. Nevertheless, there is limited knowledge about community, healthcare practitioner and service provider perspectives on skin infections and treatment preferences. An increased understanding of their respective knowledge, attitudes and practices will contribute to improving healthcare seeking behaviour, improved diagnosis, treatment acceptability and quality of care within remote Aboriginal communities. The aim of this study was to explore Aboriginal parent/carer, healthcare practitioner, and service provider attitudes and practices regarding skin infections in Aboriginal communities in remote communities in the Pilbara, Western Australia. The study documents their perspectives and preferences regarding treatments for skin infections, as well as the perceived barriers and enablers to treatment uptake for scabies and impetigo amongst Aboriginal families in this region. METHODS: A qualitative study consisting of semi-structured interviews and focus group discussions was conducted with parents/carers, healthcare practitioners and community service providers in four remote communities in Western Australia. All interviews and focus group discussions were voice recorded and data were analysed using NVivo software and thematic analysis. RESULTS: Despite the high burden, skin infections were considered normal in these communities, and their impact on child health was under-recognised. Common themes identified by all participants included the inadequacy of health services, the pain of the benzathine penicillin G injection, uncertainty regarding the use of oral antibiotics and topical creams, and the need for health practitioner training and improved communication and resources. CONCLUSION: Documenting carer, service provider and healthcare practitioner perspectives on skin infections provides a more informed understanding of the context in which treatment decisions are made. The ongoing need for culturally appropriate targeted, translational health education; improved treatment guidelines and feasible, painless treatments; and potential for the use of bush medicines for skin infections were themes that emerged.

The effect of comprehensive geriatric assessment on care received, treatment completion, toxicity, cancer-related and geriatric assessment outcomes, and quality of life for older adults receiving systemic anti-cancer treatment: A systematic review.

INTRODUCTION: This systematic review aims to summarise the available literature on the effect of geriatric assessment (multidimensional health assessment across medical, social, and functional domains; "GA") or comprehensive geriatric assessment (geriatric assessment with intervention or management recommendations; "CGA") compared to usual care for older adults with cancer on care received, treatment completion, adverse treatment effects, survival and health-related quality of life. MATERIALS AND METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, and PubMed was conducted to identify randomised controlled trials or prospective cohort comparison studies on the effect of GA/CGA on care received, treatment, and cancer outcomes for older adults with cancer. RESULTS: Ten studies were included: seven randomised controlled trials (RCTs), two phase II randomised pilot studies, and one prospective cohort comparison study. All studies included older adults receiving systemic therapy, mostly chemotherapy, for mixed cancer types (eight studies), colorectal cancer (one study), and non-small cell lung cancer (one study). Integrating GA/CGA into oncological care increased treatment completion (three of nine studies), reduced grade 3+ chemotherapy toxicity (two of five studies), and improved quality of life scores (four of five studies). No studies found significant differences in survival between GA/CGA and usual care. GA/CGA incorporated into care decisions prompted less intensive treatment and greater non-oncological interventions, including supportive care strategies. DISCUSSION: GA/CGA integrated into the care of an older adult with cancer has the potential to optimise care decisions, which may lead to reduced treatment toxicity, increased treatment completion, and improved health-related quality of life scores.

Older Persons' and Their Caregivers' Perspectives and Experiences of Research Participation With Impaired Decision-Making Capacity: A Scoping Review.

BACKGROUND AND OBJECTIVES: Human research ethics statements support the equitable inclusion of diverse groups. Yet older people are underrepresented in clinical research, especially those with impaired decision-making capacity. The aim of this study was to identify the perspectives and experiences of older persons and their caregivers of research participation with impaired decision-making capacity. RESEARCH DESIGN AND METHODS: Scoping review of the literature and online sources in January-February 2019 (updated June 2020) according to Joanna Briggs Institute methodology and PRISMA Extension for Scoping Reviews. English-language peer-reviewed research articles and Australian online narratives were included. Data were tabulated and narratively synthesized. RESULTS: From 4,171 database records and 93 online resources, 22 articles (2000-2019, 82% United States, 16 first authors) and one YouTube webinar (2018) were initially included; updated searches yielded an additional article (2020) and YouTube webinar (2020). Studies were heterogeneous in terminology, methods, and foci, with hypothetical scenarios, quantitative analyses, and examination of proxy consent predominating. Participants (N = 7,331) were older persons (71%), caregivers of older persons with dementia/cognitive impairment (23%), and older persons with dementia/cognitive impairment (6%). Synthesis identified 2 themes: willingness to participate and decision-making approaches. DISCUSSION AND IMPLICATIONS: Research participation by older persons with dementia may be optimized through reducing risks and burdens and increasing benefits for participants, greater consumer input into study development, and shared and supported decision-making. Older persons' and caregivers' perspectives and experiences of research participation with impaired decision-making capacity require investigation in a greater range of countries and conditions other than dementia, and dissemination through more varied media.

Delirium researchers' perspectives of the challenges in delirium biomarker research: A qualitative study.

BACKGROUND: Despite the prevalence and impact of delirium, its pathophysiology remains unclear. In order to advance this field of research, robust scientific methodology is required, yet quality of reporting in this field of research has been highly inconsistent. Delirium biomarker research poses several challenges, none of which have been documented in the literature before. The aim of this study was to explore the perspectives of delirium researchers about key methodological issues in delirium biomarker research. METHODS: Following a Delphi study with delirium experts resulting in 60 recommendations for reporting delirium biomarker studies, semi-structured interviews with international delirium researchers were conducted. Interviews were audio-taped and transcribed verbatim, followed by thematic analysis of the qualitative data. RESULTS: Fifteen participants were interviewed between August and November 2019. Most were male (n = 12; 75%), clinician researchers (n = 13; 86%), and had more than ten years' experience in conducting delirium research (n = 9; 60%). Analysis revealed two major themes and ten sub-themes, outlining key considerations to advance the field of delirium biomarker research. The major themes were: 1) Practical and scientific challenges of delirium biomarker research: stagnation versus driving improved methods and reporting; and 2) Valuing delirium research through investment and collaboration. CONCLUSION: Findings identified a range of factors that contribute to the practical and ethical challenges of conducting delirium biomarker research, which have not previously been explicitly acknowledged or reported. A clear vision for collaborative efforts to enhance research quality for improved impact was also presented by the delirium researchers. This work complements the preceding Delphi and together these studies provide an in-depth understanding of what is needed in the field to inform and improve methods and reporting of delirium biomarker research.

Barriers and Enablers of Health Service Utilisation for Childhood Skin Infections in Remote Aboriginal Communities of Western Australia.

In Australia, children living in remote Aboriginal communities experience high rates of skin infections and associated complications. Prompt presentation to primary care health services is crucial for early diagnosis and treatment. We performed a qualitative study in four remote Aboriginal communities in the Pilbara region of Western Australia to explore factors that affected health service utilisation for childhood skin infections in this setting. The study consisted of semistructured interviews and focus group discussions with parents and carers (n = 16), healthcare practitioners (n = 15) and other community service providers (n = 25). We used Andersen's health service utilisation model as an analytical framework. Our analysis captured a wide range of barriers that may undermine timely use of health services for childhood skin infections. These included general factors that illustrate the importance of cultural competency amongst healthcare providers, patient-centred care and community engagement. Relating specifically to health service utilisation for childhood skin infections, we identified their apparent normalisation and the common use of painful benzathine penicillin G injections for their treatment as important barriers. Health service utilisation in this setting may be enhanced by improving general awareness of the significance of childhood skin infections, actively engaging parents and carers in consultation and treatment processes and strengthening community involvement in health service activities.