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Evidence-based practice is foundational to high-quality palliative care delivery. However, the clinical trials that compose the evidence base are often methodologically imperfect. Applying their conclusions without critical application to the clinical practice context can harm patients. The tips provided can help clinicians infer judiciously from clinical trial results and avoid credulously accepting findings without critique. We suggest that statistical and mathematical expertise is unnecessary, but rather a keen curiosity about investigators' rationale for certain design choices and how these choices can affect results is key. For a more comprehensive understanding of clinical trials, this article can be used with the authors' corresponding ten tips article that focuses on designing a clinical trial.
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OBJECTIVES: Patients with advanced cancer experience varying physical and psychological symptoms throughout the course of their illness. Depression, anxiety and stress affect overall well-being. This study investigates the correlation between emotional distress and physical symptoms in a cohort of patients with advanced cancer. METHODS: There were 238 patients included in this study. Data from participants in two medicinal cannabis randomised controlled trials were analysed. Patients were aged over 18 years and had advanced cancer. Edmonton Symptom Assessment System, and Depression, Anxiety and Stress Scale (DASS-21) were assessed for all patients at baseline. RESULTS: Moderate-severe depression was reported in 29.8% and moderate-severe anxiety was reported in 47.9% of patients. The emotional subscales of DASS-21 (depression, anxiety, stress) correlated with total symptom distress score (p<0.001) and overall well-being (p<0.001). Depression was correlated with physical symptoms of fatigue, nausea, poor appetite and dyspnoea. Anxiety was correlated with fatigue and dyspnoea. Stress was correlated with fatigue, nausea and dyspnoea. CONCLUSIONS: Depression, anxiety and stress were common in this population. The relationship between physical and psychological well-being is complex. A holistic approach to symptom management is required to improve quality of life in patients with advanced cancer.
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BACKGROUND: Distressing symptoms are common in advanced cancer. Medicinal cannabinoids are commonly prescribed for a variety of symptoms. There is little evidence to support their use for most indications in palliative care. This study aims to assess a 1:20 delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) cannabinoid preparation in the management of symptom distress in patients with advanced cancer undergoing palliative care. METHODS AND DESIGN: One hundred and fifty participants will be recruited across multiple sites in Queensland, Australia. A teletrial model will facilitate the recruitment of patients outside of major metropolitan areas. The study is a pragmatic, multicenter, randomised, placebo-controlled, two-arm trial of escalating doses of an oral 1:20 THC/CBD medicinal cannabinoid preparation (10 mg THC:200 mg CBD/mL). It will compare the efficacy and safety outcomes of a titrated dose range of 2.5 mg THC/50mgCBD to 30 mg THC/600 mg CBD per day against a placebo. There is a 2-week patient-determined titration phase, to reach a dose that achieves symptom relief or intolerable side effects, with a further 2 weeks of assessment on the final dose. The primary objective is to assess the effect of escalating doses of a 1:20 THC/CBD medicinal cannabinoid preparation against placebo on change in total symptom distress score, with secondary objectives including establishing a patient-determined effective dose, the effect on sleep quality and overall quality of life. Some patients will be enrolled in a sub-study which will more rigorously evaluate the effect on sleep. DISCUSSION: MedCan-3 is a high-quality, adequately powered, placebo-controlled trial which will help demonstrate the utility of a THC:CBD 1:20 oral medicinal cannabis product in reducing total symptom distress in this population. Secondary outcomes may lead to new hypotheses regarding medicinal cannabis' role in particular symptoms or in particular cancers. The sleep sub-study will test the feasibility of using actigraphy and the Insomnia Severity Index (ISI) in this cohort. This will be the first large-scale palliative care randomised clinical trial to utilise the teletrial model in Australia. If successful, this will have significant implications for trial access for rural and remote patients in Australia and internationally. TRIAL REGISTRATION: ANZCTR ACTRN12622000083796 . Protocol number 001/20. Registered on 21 January 2022. Recruitment started on 8 August 2022.
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Canabidiol , Dronabinol , Maconha Medicinal , Neoplasias , Cuidados Paliativos , Humanos , Administração Oral , Canabidiol/administração & dosagem , Canabidiol/efeitos adversos , Canabidiol/uso terapêutico , Método Duplo-Cego , Dronabinol/uso terapêutico , Dronabinol/administração & dosagem , Combinação de Medicamentos , Maconha Medicinal/uso terapêutico , Maconha Medicinal/efeitos adversos , Maconha Medicinal/administração & dosagem , Estudos Multicêntricos como Assunto , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Cuidados Paliativos/métodos , Qualidade de Vida , Queensland , Ensaios Clínicos Controlados Aleatórios como Assunto , Carga de Sintomas , Fatores de Tempo , Resultado do TratamentoRESUMO
In the cancer pain setting, ketamine has been typically employed as a co-analgesic for opioid refractory and neuropathic pain. One controversial topic is whether subanesthetic ketamine be considered when managing opioid refractory cancer pain. In this "Controversies in Palliative Care" article, three clinicians independently answer this question. Specifically, each clinician provides a synopsis of the key studies that inform their thought processes, share practical advice on their clinical approach, and highlight the opportunities for future research. Three independent clinicians reported a divergence of opinion regarding the usefulness of subanesthetic ketamine for managing opioid refractory cancer pain. All investigators acknowledged the lack of high-quality trials. All agreed on the need for adequately powered trials, the development of standardized methodology, and the exploration of any patient sub-populations that may benefit from ketamine for cancer related pain.
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Analgésicos Opioides , Analgésicos , Dor do Câncer , Ketamina , Dor Intratável , Humanos , Analgésicos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Dor do Câncer/tratamento farmacológico , Ketamina/uso terapêutico , Dor Intratável/tratamento farmacológico , Cuidados Paliativos/métodosRESUMO
Introduction: Our research group is conducting three large randomized placebo-controlled trials of medicinal cannabis for cancer symptoms. All participants are invited to take part in a posttrial surveillance study. Methods: Participants were given the manufacturers dosing instructions and liberty to titrate to effect. Data were collected on symptoms (Edmonton Symptom Assessment Scale [ESAS] score), perceived benefits, adverse effects, satisfaction with the product, and dose/frequency. Results: Twenty-six percent of eligible participants consented to take part in the surveillance study. Most participants changed their self-titrated dose at least once. Pain, sleep, and mood were the most frequently cited symptoms which improved. Fatigue, nausea, and cognitive impairment were the most frequently mentioned adverse effects. Conclusion: Participants felt confident making changes to their medicinal cannabis dose within the limits suggested by the manufacturer of each product. A number of benefits and adverse effects were ascribed to the product. Benefits were similar to those described in previous studies.
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Maconha Medicinal , Neoplasias , Cuidados Paliativos , Humanos , Maconha Medicinal/uso terapêutico , Maconha Medicinal/efeitos adversos , Masculino , Feminino , Neoplasias/tratamento farmacológico , Pessoa de Meia-Idade , Austrália , Idoso , Adulto , Idoso de 80 Anos ou maisRESUMO
Purpose: This research explores the implementation of a child-centred, co-designed, community-embedded program called 'Young Doctors for Life' (YDFL). YDFL is designed to improve health and wellbeing outcomes for Aboriginal children in the middle childhood years. Focus is given in this paper to the processes of program adaptation of the YDFL to ensure local cultural relevance, drawing on the experiences and perspectives of children, parents, schoolteachers, and the implementation team. Method: Two focus groups with program stakeholders were convened. The first group consisted of three members from the local Aboriginal implementation team, and the second group comprised two members of the program design team. Children (n = 22) and schoolteachers (n = 2) participated in semi-structured interviews. Parent survey data (n = 16) were also collected and included. The data was analysed, guided by the five elements of implementation as outlined in the Hexagon Implementation framework (Capacity; Fit; Need; Usability; Support; and Evidence), which served as a priori themes. Results: YDFL provides a promising example of how programs can be adapted with and for Aboriginal communities to support child health. Successful adaptation and implementation of this program required a co-design approach engaging program designers and the local implementation team. Community collaboration was also essential to identifying and addressing local community goals and aligning new programs with local service and cultural contexts. Conclusion: Health programs to support positive child outcomes are more likely to be successful when they share their focus between the risks and challenges within a community, and the positive, protective factors that can be leveraged to support children to flourish. Stakeholder engagement and community leadership are necessary to achieve meaningful program adaptation and implementation in Aboriginal communities.
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Letramento em Saúde , Criança , Humanos , Grupos Focais , Pais , Inquéritos e Questionários , Povos Aborígenes Australianos e Ilhéus do Estreito de TorresRESUMO
BACKGROUND: The COVID-19 pandemic disrupted the usual provision of healthcare, changing models of care, clinical loads, service provision and patient behaviour. AIMS: This study assesses the impact of COVID-19 on community and inpatient palliative care service provision. METHODS: A retrospective audit and comparison of service use conducted over two defined periods, before and during the COVID-19 pandemic, 2019-2020. FINDINGS: The community palliative care service had a 9% increase in referrals, with a lower proportion of referrals (2.4%) from subacute/palliative care hospitals during the COVID-19 pandemic. Provision of care during the pandemic included less face-to-face contact with patients (24.1% versus 30.2% before), and markedly more contact with patients via videoconference (2.1% versus 0.1% before the pandemic). CONCLUSION: The community specialist palliative care service was busier during the pandemic period, and experienced a shift in mode of care delivery, while the inpatient unit experienced no difference in service use.
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COVID-19 , Humanos , Cuidados Paliativos , Pandemias , Pacientes Internados , Estudos RetrospectivosRESUMO
Cancer pain is the most feared symptom at end of life. Methadone has advantages over other opioids but is associated with significant variability in clinical response, making dosing challenging in practice. OPRM1 is the most studied pharmacogene associated with the pharmacodynamics of opioids, however reports on the association of the A118G polymorphism on opioid dose requirements are conflicting, with no reports including methadone as the primary intervention. This association study on OPRM1 A118G and response to methadone for pain management, includes a review of this genetic factor's role in inter-patient variability. Fifty-four adult patients with advanced cancer were recruited in a prospective, multi-centre, open label dose individualization study. Patient characteristics were not shown to influence methadone response, and no significant associations were observed for methadone dose or pain score. The findings of our review of association studies for OPRM1 A118G in advanced cancer pain demonstrate the importance of taking ancestry into account. While our sample size was small, our results were consistent with European populations, but in contrast to studies in Chinese patients, where carriers of the A118G polymorphism were associated with higher opioid dose requirements. Pharmacogenetic studies in palliative care are challenging, continued contribution will support future genotype-based drug dosing guidelines.
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Dor do Câncer , Neoplasias , Adulto , Humanos , Analgésicos Opioides/uso terapêutico , Dor do Câncer/tratamento farmacológico , Dor do Câncer/genética , Genótipo , Metadona/uso terapêutico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/genética , Manejo da Dor , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Receptores Opioides mu/genéticaRESUMO
OBJECTIVES: Medical cannabinoids have become increasingly popular over the last decade. Preclinical trials suggest cannabinoids, for example, cannabidiol (CBD), may provide an anticancer effect; however, good-quality clinical information supporting this is lacking. We assessed the effect of CBD treatment on disease progression and survival in patients enrolled in a study of CBD versus placebo for symptom management in patients with advanced cancer (MEDCAN-1). METHODS: We reviewed the clinical records of all patients enrolled in the MEDCAN-1 Study (CBD vs placebo) at days 14, 28 and 56 of study follow-up, for evidence of disease progression. The proportion of participants with disease progression by treatment arm at each time point was compared, as was survival between both groups from study entry to the censor date (end of study period) and the effect of treatment arm and disease progression status on survival. RESULTS: Of the 135 patient records assessed, 128 were included in the final analysis. 36% (n=46) had progressive disease documented at day 28, rising to 49.2% (n=63) by day 56. No significant difference in disease progression was noted between the two groups at days 14 (p=0.33), 28 (p=0.67) or 56 (p=0.50). There was no difference in survival between both groups from study entry to censor date (p=0.38). Disease progression at day 14 was highly predictive of mortality (p<0.001). CONCLUSIONS: In this substudy analysis, treatment with CBD oil did not affect disease progression or survival over the course of 56 days in patients with advanced cancer.
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Canabidiol , Progressão da Doença , Neoplasias , Humanos , Canabidiol/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , AdultoRESUMO
BACKGROUND: Many people receiving palliative care have reduced oral intake during their illness, and particularly at the end of their life. Management of this can include the provision of medically assisted hydration (MAH) with the aim of improving their quality of life (QoL), prolonging their life, or both. This is an updated version of the original Cochrane Review published in Issue 2, 2008, and updated in February 2011 and March 2014. OBJECTIVES: To determine the effectiveness of MAH compared with placebo and standard care, in adults receiving palliative care on their QoL and survival, and to assess for potential adverse events. SEARCH METHODS: We searched for studies in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, CANCERLIT, CareSearch, Dissertation Abstracts, Science Citation Index and the reference lists of all eligible studies, key textbooks, and previous systematic reviews. The date of the latest search conducted on CENTRAL, MEDLINE, and Embase was 17 November 2022. SELECTION CRITERIA: We included all relevant randomised controlled trials (RCTs) of studies of MAH in adults receiving palliative care aged 18 and above. The criteria for inclusion was the comparison of MAH to placebo or standard care. DATA COLLECTION AND ANALYSIS: Three review authors independently reviewed titles and abstracts for relevance, and two review authors extracted data and performed risk of bias assessment. The primary outcome was QoL using validated scales; secondary outcomes were survival and adverse events. For continuous outcomes, we measured the arithmetic mean and standard deviation (SD), and reported the mean difference (MD) with 95% confidence interval (CI) between groups. For dichotomous outcomes, we estimated and compared the risk ratio (RR) with 95% CIs between groups. For time-to-event data, we planned to calculate the survival time from the date of randomisation and to estimate and express the intervention effect as the hazard ratio (HR). We assessed the certainty of evidence using GRADE and created two summary of findings tables. MAIN RESULTS: We identified one new study (200 participants), for a total of four studies included in this update (422 participants). All participants had a diagnosis of advanced cancer. With the exception of 29 participants who had a haematological malignancy, all others were solid organ cancers. Two studies each compared MAH to placebo and standard care. There were too few included studies to evaluate different subgroups, such as type of participant, intervention, timing of intervention, and study site. We considered one study to be at high risk of performance and detection bias due to lack of blinding; otherwise, risk of bias was assessed as low or unclear. MAH compared with placebo Quality of life One study measured change in QoL at one week using Functional Assessment of Cancer Therapy - General (FACT-G) (scale from 0 to 108; higher score = better QoL). No data were available from the other study. We are uncertain whether MAH improves QoL (MD 4.10, 95% CI -1.63 to 9.83; 1 study, 93 participants, very low-certainty evidence). Survival One study reported on survival from study enrolment to last date of follow-up or death. We were unable to estimate HR. No data were available from the other study. We are uncertain whether MAH improves survival (1 study, 93 participants, very low-certainty evidence). Adverse events One study reported on intensity of adverse events at two days using a numeric rating scale (scale from 0 to 10; lower score = less toxicity). No data were available from the other study. We are uncertain whether MAH leads to adverse events (injection site pain: MD 0.35, 95% CI -1.19 to 1.89; injection site swelling MD -0.59, 95% CI -1.40 to 0.22; 1 study, 49 participants, very low-certainty evidence). MAH compared with standard care Quality of life No data were available for QoL. Survival One study measured survival from randomisation to last date of follow-up at 14 days or death. No data were available from the other study. We are uncertain whether MAH improves survival (HR 0.36, 95% CI 0.22 to 0.59; 1 study, 200 participants, very low-certainty evidence). Adverse events Two studies measured adverse events at follow-up (range 2 to 14 days). We are uncertain whether MAH leads to adverse events (RR 11.62, 95% CI 1.62 to 83.41; 2 studies, 242 participants, very low-certainty evidence). AUTHORS' CONCLUSIONS: Since the previous update of this review, we have found one new study. In adults receiving palliative care in the end stage of their illness, there remains insufficient evidence to determine whether MAH improves QoL or prolongs survival, compared with placebo or standard care. Given that all participants were inpatients with advanced cancer at end of life, our findings are not transferable to adults receiving palliative care in other settings, for non-cancer, dementia or neurodegenerative diseases, or for those with an extended prognosis. Clinicians will need to make decisions based on the perceived benefits and harms of MAH for each individual's circumstances, without the benefit of high-quality evidence to guide them.
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Neoplasias , Cuidados Paliativos , Adulto , HumanosRESUMO
PURPOSE: Inflammation is thought to play a key role in malignant disease and may play a significant part in the expression of cancer-related symptoms. Cannabidiol (CBD) is a bioactive compound in cannabis and is reported to have significant anti-inflammatory properties. METHOD: Serial C-reactive protein (CRP) levels were measured in all participants recruited to a randomised controlled trial of CBD versus placebo in patients with symptoms related to advanced cancer. A panel of inflammatory cytokines was measured over time in a subset of these patients. RESULTS: There was no difference between the two arms in the trajectory of CRP or cytokine levels from baseline to day 28. CONCLUSION: We were unable to demonstrate an anti-inflammatory effect of CBD in cancer patients. TRIAL REGISTRATION: ANZCTR 26180001220257, registered 20/07/2018.
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Canabidiol , Cannabis , Maconha Medicinal , Neoplasias , Humanos , Maconha Medicinal/farmacologia , Maconha Medicinal/uso terapêutico , Canabidiol/farmacologia , Canabidiol/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Neoplasias/tratamento farmacológicoRESUMO
OBJECTIVES: Drug dependence is becoming increasingly common and meeting palliative care patients with substance use disorders is inevitable. However, data on substance use in these patients are lacking. This study aims to evaluate the prevalence of drug dependence in palliative care patients with advanced cancer and correlate with symptom distress and opioid use. METHODS: Palliative care patients with advanced cancer interested in participation in a medicinal cannabis trial were required to complete Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), Edmonton Symptom Assessment Scale (ESAS) and record of concomitant medications including baseline opioid use as part of the eligibility screen. RESULTS: Of the 182 participants, 167 (92%) reported lifetime alcohol and 132/182 (73%) lifetime tobacco use. No participant reached the threshold criteria for high risk of drug dependence with majority being low risk. There was no correlation between ASSIST score, ESAS and oral morphine equivalent. CONCLUSION: This study identified alcohol and tobacco as the main substances used in this group of patients and that most were of very low risk for drug dependence. This suggests routine drug screening for palliative care patient may not be justified, but the high possibility of questionnaire bias is acknowledged.
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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.
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Neoplasias , Humanos , Adulto , Técnica Delphi , Nova Zelândia , Austrália , Neoplasias/complicações , Neoplasias/terapia , Projetos de Pesquisa , Fadiga/etiologia , Fadiga/terapiaRESUMO
BACKGROUND: Fatigue is the most commonly reported symptom in people with advanced cancer. Cancer-related fatigue (CRF) is pervasive and debilitating, and can greatly impact quality of life (QoL). CRF has a highly variable clinical presentation, likely due to a complex interaction of multiple factors. Corticosteroids are commonly used to improve CRF, but the benefits are unclear and there are significant adverse effects associated with long-term use. With the increasing survival of people with metastatic cancer, the long-term effects of medications are becoming increasingly relevant. Since the impact of CRF can be immensely debilitating and can negatively affect QoL, its treatment warrants further review. OBJECTIVES: To determine the benefits and harms of corticosteroids compared with placebo or an active comparator in adults with advanced cancer and CRF. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Science Citation Index (ISI Web of Science), LILACS, and two clinical trial registries from inception to 18 July 2022. SELECTION CRITERIA: We included randomised controlled trials in adults aged ≥18 years. We included participants with advanced cancer who were suffering from CRF. We included trials that randomised participants to corticosteroids at any dose, by any route, administered for the relief of CRF; compared to placebo or an active comparator, including supportive care or non-pharmacological treatments. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed titles identified by the search strategy; two review authors assessed risk of bias; and two extracted data. We extracted the primary outcome of participant-reported fatigue relief using validated scales and secondary outcomes of adverse events, serious adverse events and QoL. We calculated the risk ratio with 95% confidence intervals (CIs) between groups for dichotomous outcomes. We measured arithmetic mean and standard deviation, and reported the mean difference (MD) with 95% CI between groups for continuous outcomes. We used standardised mean difference (SMD) with 95% CIs when an outcome was measured with different instruments measuring the same construct. We used a random-effects model to meta-analyse the outcome data. We rated the certainty of the evidence using GRADE and created two summary of findings tables. MAIN RESULTS: We included four studies with 297 enroled participants; data were available for only 239 participants. Three studies compared corticosteroid (equivalent ≤ 8 mg dexamethasone) to placebo. One study compared corticosteroid (dexamethasone 4 mg) to an active comparator (modafinil 100 mg). There were insufficient data to evaluate subgroups, such as dose and duration of treatment. One study had a high risk of performance and detection bias due to lack of blinding, and one study had a high risk of attrition bias. Otherwise, we assessed risks of bias as low or unclear. Comparison 1: corticosteroids compared with placebo Participant-reported fatigue relief The was no clear difference between corticosteroids and placebo (SMD -0.46, 95% CI -1.07 to 0.14; 3 RCTs, 165 participants, very low-certainty evidence) for relief of fatigue at one week of the intervention. We downgraded the certainty of the evidence three times for study limitations due to unclear risk of bias, imprecision, and inconsistency. Adverse events There was no clear difference in the occurrence of adverse events between groups, but the evidence is very uncertain (3 RCTs, 165 participants; very low-certainty evidence). Serious adverse events There was no clear difference in the occurrence of serious adverse events between groups, but the evidence is very uncertain (2 RCTs, 118 participants; very low-certainty evidence). Quality of lIfe One study reported QoL at one week using the Edmonton Symptom Assessment System (ESAS) well-being, and found no clear difference in QoL between groups (MD -0.58, 95% CI -1.93 to 0.77). Another study measured QoL using the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs (QoL-ACD), and found no clear difference between groups. There was no clear difference between groups for either study, but the evidence is very uncertain (2 RCTs, 118 participants; very low-certainty evidence). Comparison 2: corticosteroids compared with active comparator (modafinil) Participant-reported fatigue relief There was improvement in fatigue from baseline to two weeks in both groups (modafinil MD 10.15, 95% CI 7.43 to 12.87; dexamethasone MD 9.21, 95% CI 6.73 to 11.69), however no clear difference between the two groups (MD -0.94, 95% CI -4.49 to 2.61; 1 RCT, 73 participants, very low-certainty evidence). We downgraded the certainty of the evidence three times for very serious study limitations and imprecision. Adverse events There was no clear difference in the occurrence of adverse events between groups, but the evidence is very uncertain (1 RCT, 73 participants; very low-certainty evidence). Serious adverse events There were no serious adverse events reported in either group (1 RCT, 73 participants; very low-certainty evidence). Quality of lIfe One study measured QoL at two weeks, using the ESAS-well-being. There was marked improvement in QoL from baseline in both groups (modafinil MD -2.43, 95% CI -2.88 to -1.98; dexamethasone MD -2.16, 95% CI -2.68 to -1.64), however no clear difference between the two groups (MD 0.27, 95% CI -0.39 to 0.93; 1 RCT, 73 participants, very low-certainty evidence). AUTHORS' CONCLUSIONS: There is insufficient evidence to support or refute the use of systemic corticosteroids in adults with cancer and CRF. We included four small studies that provided very low-certainty of evidence for the efficacy of corticosteroids in the management of CRF. Further high-quality randomised controlled trials with larger sample sizes are required to determine the effectiveness of corticosteroids in this setting.
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Neoplasias , Qualidade de Vida , Humanos , Adulto , Adolescente , Modafinila , Corticosteroides/efeitos adversos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Dexametasona/efeitos adversos , Fadiga/tratamento farmacológico , Fadiga/etiologiaRESUMO
INTRODUCTION: Following 2016 legislation permitting limited access to cannabis for research and medicinal purposes, the number of randomized clinical trials (RCTs) investigating the effectiveness of medicinal cannabis (MC) on symptom burden relief in cancer contexts has increased in Australia. This study aimed to understand the perceptions, hopes and concerns of people with advanced cancer regarding the future availability and regulation of MC in Australia. METHODS: This qualitative study draws on semistructured interviews conducted between February 2019 and October 2020 in Brisbane, Australia, as part of an MC RCT substudy. Interviews were undertaken on 48 patients with advanced cancer in palliative care eligible to participate in an MC trial (n = 26 participated in an RCT; n = 2 participated in a pilot study; n = 20 declined). Interviews included a discussion of patients' decision-making regarding trial participation, concerns about MC and perceptions of future availability, including cost. Transcribed interviews were analysed inductively and abductively, informed by constructivist thematic analysis conventions. RESULTS: Overall, participants supported making MC legally accessible as a prescription-only medication. Fear of financial toxicity, however, compromised this pathway. Steep posttrial costs of accessing MC prompted several people to decline trial participation, and others to predict-if found effective-that many would either access MC through alternative pathways or reduce their prescribed dosage to enable affordable access. CONCLUSIONS: These findings suggest that-despite a relatively robust universal healthcare system-Australians are potentially vulnerable to and fearful of financial toxicity. Prevalent in the United States, financial toxicity occurs when disadvantaged cancer patients access necessary but expensive medications with lasting consequences: bankruptcy, ongoing anxiety and cancer worry. Interview transcripts indicate that financial fears-and the systems sustaining them-may pose a threat to RCT completion and to equitable access to legal MC. Such findings support calls for embedding qualitative substudies and community partnerships within RCTs, while also suggesting the importance of subsidisation to overcoming injustices. PATIENT OR PUBLIC CONTRIBUTION: A patient advisory committee informed RCT design. This qualitative substudy foregrounds patients' decision-making, perceptions and experiences.
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Maconha Medicinal , Neoplasias , Humanos , Maconha Medicinal/uso terapêutico , Estresse Financeiro , Austrália , Acessibilidade aos Serviços de Saúde , Neoplasias/tratamento farmacológicoRESUMO
PURPOSE: To determine whether cannabidiol (CBD) oil can improve symptom distress in patients with advanced cancer receiving palliative care. METHODS: Participants were adults with advanced cancer and symptom distress (Edmonton Symptom Assessment Scale [ESAS] total score of ≥ 10/90) who received titrated CBD oil 100 mg/mL, 0.5 mL once daily to 2 mL three times a day, or matched placebo for 28 days. The primary outcome was ESAS total symptom distress score (TSDS) at day 14. Response was defined as a decrease in TSDS by ≥ 6 at day 14. Secondary outcomes were ESAS TSDS over time, individual symptom scores, patient-determined effective dose, opioid use, Global Impression of Change, depression, anxiety, quality of life, and adverse events. RESULTS: Of the 144 patients randomly assigned, the planned sample size of 58 participants on CBD and 63 on placebo reached the primary analysis point (day 14). The unadjusted change in TSDS from baseline to day 14 was -6.2 (standard deviation, 14.5) for placebo and -3.0 (standard deviation, 15.2) for CBD with no significant difference between arms (P = .24). Similarly, there was no detected difference in proportion of responders (placebo: 37 of 63 [58.7%], CBD: 26 of 58 [44.8%], P = .13). All components of ESAS improved (fell) over time with no difference between arms. The median dose of participant-selected CBD was 400 mg per day with no correlation with opioid dose. There was no detectable effect of CBD on quality of life, depression, or anxiety. Adverse events did not differ significantly between arms apart from dyspnea that was more common with CBD. Most participants reported feeling better or much better at days 14 (53% CBD and 65% placebo) and 28 (70% CBD and 64% placebo). CONCLUSION: CBD oil did not add value to the reduction in symptom distress provided by specialist palliative care alone.
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Canabidiol , Neoplasias , Adulto , Humanos , Analgésicos Opioides , Canabidiol/efeitos adversos , Método Duplo-Cego , Neoplasias/tratamento farmacológico , Qualidade de VidaRESUMO
OBJECTIVES: To detail important lessons learnt while conducting several large, medicinal cannabis (MC) randomised clinical trials in a palliative cancer population. METHODS: Investigators involved in these trials had several meetings to agree on the major lessons learnt and how the various challenges could be mitigated in the future. RESULTS: The lessons were sorted into separate categories: patient confidentiality, family dynamics, driving, cost, unfounded beliefs, accessing specific MC products, trial funding, telehealth and COVID-19, and miscellaneous issues. CONCLUSION: Using MC as the intervention arm in such trials entails some unique regulatory, logistical and other challenges. This short report presents key lessons learnt in conducting these randomised controlled trials in a palliative care population for the benefit of future investigators planning similar trials in a similar patient population.
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COVID-19 , Maconha Medicinal , Neoplasias , Medicina Paliativa , Humanos , Maconha Medicinal/uso terapêutico , Cuidados Paliativos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Opioids are the therapeutic agents of choice to manage moderate to severe pain in patients with advanced cancer, however the unpredictable inter-individual response to opioid therapy remains a challenge for clinicians. While studies are few, the KCNJ6 gene is a promising target for investigating genetic factors that contribute to pain and analgesia response. This is the first association study on polymorphisms in KCNJ6 and response to methadone for pain management in advanced cancer. Fifty-four adult patients with advanced cancer were recruited across two study sites in a prospective, open label, dose individualisation study. Significant associations have been previously shown for rs2070995 and opioid response in opioid substitution therapy for heroin addiction and studies in chronic pain, with mixed results seen in postoperative pain. In this study, no associations were shown for rs2070995 and methadone dose or pain score, consistent with other studies conducted in patients receiving opioids for pain in advanced cancer. There are many challenges in conducting studies in advanced cancer with significant attrition and small sample sizes, however it is hoped that the results of our study will contribute to the evidence base and allow for continued development of gene-drug dosing guidelines for clinicians.
Assuntos
Dor Crônica , Neoplasias , Adulto , Humanos , Metadona/uso terapêutico , Analgésicos Opioides/uso terapêutico , Manejo da Dor , Estudos Prospectivos , Dor Crônica/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/genética , Morte , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genéticaRESUMO
BACKGROUND: Clinical trials rarely explore the patient's lived experience. Qualitative research bridges the gap between evidence-based medicine and the patient's journey. OBJECTIVE: The aim of this article is to explore key aspects of the lived experience of patients with end-stage heart failure (ESHF). This will allow clinicians to better engage with patients and carers faced with this condition. DISCUSSION: Psychological and spiritual distress are common in ESHF. Patients with ESHF often feel socially isolated. Inadequate communication from clinical staff is a common negative experience for patients to which they frequently resign themselves. The ambiguous illness trajectory in advanced heart failure makes both general practitioners and cardiologists uncomfortable initiating advance care planning and less sure of their roles in these discussions. Patients have spiritual concerns that they reportedly feel awkward raising during consultation. Attention to these concerns will help build rapport and provide more personalised care for patients with ESHF.