Results from a type two hybrid-effectiveness study to implement a preoperative anemia and iron deficiency screening, evaluation, and management pathway.

BACKGROUND: Implementation of pathways to screen surgical patients for preoperative anemia and iron deficiency remains limited. This study sought to measure the impact of a theoretically informed, bespoke change package on improving the uptake of a Preoperative Anemia and Iron Deficiency Screening, Evaluation, and Management Pathway. STUDY DESIGN AND METHODS: Pre-post interventional study using a type two hybrid-effectiveness design evaluated implementation. Four hundred (400) patient medical record reviews provided the dataset (200 pre- and 200-post implementation). The primary outcome measure was compliance with the pathway. Secondary outcome measures (clinical outcomes) were anemia on day of surgery, exposure to a red blood cell (RBC) transfusion, and hospital length of stay. Validated surveys facilitated data collection of implementation measures. Propensity score-adjusted analyses determined the effect of the intervention on clinical outcomes, and a cost analysis determined the economic impact. RESULTS: For the primary outcome, compliance improved significantly post-implementation (Odds Ratio 10.6 [95% CI 4.4-25.5] p < .000). In secondary outcomes, adjusted analyses point estimates showed clinical outcomes were slightly improved for anemia on day of surgery (Odds Ratio 0.792 [95% CI 0.5-1.3] p = .32), RBC transfusion (Odds Ratio 0.86 [95% CI 0.41-1.78] p = .69) and hospital length of stay (Hazard Ratio 0.96 [95% CI 0.77-1.18] p = .67), although these were not statistically significant. Cost savings of $13,340 per patient were realized. Implementation outcomes were favorable for acceptability, appropriateness, and feasibility. CONCLUSION: The change package significantly improved compliance. The absence of a statistically significant change in clinical outcomes may be because the study was powered to detect an improvement in compliance only. Further prospective studies with larger samples are needed. Cost savings of $13,340 per patient were achieved and the change package was viewed favorably.

Exploring potential anti-inflammatory effects of medicinal cannabis.

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.

Corticosteroids for the management of cancer-related fatigue in adults with advanced cancer.

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.

'What price do you put on your health?': Medical cannabis, financial toxicity and patient perspectives on medication access in advanced cancer.

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.

Quality of life beyond measure: Advanced cancer patients, wellbeing and medicinal cannabis.

Experiences of advanced cancer are assembled and (re)positioned with reference to illness, symptoms and maintaining 'wellbeing'. Medical cannabis is situated at a borderline in this and the broader social domain: between stigmatised and normalised; recreational and pharmaceutical; between perception, experience, discourse and scientific proof of benefit. Yet, in the hyper-medicalised context of randomised clinical trials (RCTs), cancer, wellbeing and medical cannabis are narrowly assessed using individualistic numerical scores. This article attends to patients' perceptions and experiences at this borderline, presenting novel findings from a sociological sub-study embedded within RCTs focused on the use of medical cannabis for symptom relief in advanced cancer. Through a Deleuzo-Guattarian-informed framework, we highlight the fragmentation and reassembling of bodies and propose body-situated experiences of wellbeing in the realm of advanced cancer. Problematising 'biopsychosocial' approaches that centre an individualised disconnected patient body in understandings of wellbeing, experiences of cancer and potential treatments, our findings foreground relational affect and embodied experience, and the role of desire in understanding what wellbeing is and can be. This also underpins and enables exploration of the affective reassembling ascribed to medical cannabis, with particular focus on how it is positioned within RCTs.

Does Cannabidiol Have a Benefit as a Supportive Care Drug in Cancer?

OPINION STATEMENT: Cannabinoids have been purported as having a wide range of therapeutic uses although currently, there is minimal evidence to support these claims. Patients with advanced cancer experience many distressing symptoms, with some turning to medicinal cannabis to help alleviate these. Focus has fallen on cannabidiol (CBD) as a potential treatment for a variety of symptoms in advanced cancer due to the lack of psychoactive side effects and the potential molecular mechanisms of action associated with this cannabinoid. Many cannabinoid products are easily available in the community, and more countries are legalizing or allowing over the counter products. Studies show that CBD is generally well tolerated, but there are many potential drug interactions that have not been well studied. Few studies have specifically looked at the role of CBD in treating cancer symptoms, with most focusing on combination cannabinoid products. There are currently many unknowns associated with CBD, including which symptoms it might be best for, appropriate dosing, and route of administration. This is especially important in advanced cancer where patients often have significant organ dysfunction and frailty that could impact on the pharmacology of CBD. A small pilot study has shown promise for a role of CBD in the psychological symptoms associated with advanced cancer. Further research is currently underway to further clarify the role of CBD in this setting and to understand how best it might help our patients. Currently we advocate that CBD be used in supervised clinical trials, so that efficacy and adverse effects can be closely monitored.

The Management of Nausea and Vomiting Not Related to Anticancer Therapy in Patients with Cancer.

OPINION STATEMENT: In cancer patients, the management of nausea and vomiting that is not directly related to treatment is challenging. Much current practice is based on expert opinion and anecdote. Fortunately, over recent years, a number of quality trials have been undertaken to strengthen the evidence base that guides the care of our patients with these distressing symptoms. Much is still unknown however. In this article, we present the latest literature that addresses some of the outstanding issues.

Practice review: Evidence-based quality use of corticosteroids in the palliative care of patients with advanced cancer.

BACKGROUND: It would be unusual for a patient with advanced cancer not to be prescribed corticosteroids at some stage of their disease course for a variety of specific and non-specific indications. AIM: The aim of this practice review was to provide a pragmatic overview of the evidence supporting current practice and to identify areas in which further research is indicated. DESIGN: A 'state-of-the-art' review approach was used to examine the evidence supporting the use of corticosteroids for the management of cancer-related complications and in symptom control, in the context of known risks and harms to inform quality use of this medicine. We developed 'Do', 'Do not', and 'Don't know' recommendations based on current literature and identified areas for future investigation and research. DATA SOURCES: We searched MEDLINE, EMBASE and the Cochrane library from inception to 14th October 2020. Our initial search limited to reviews, reviews of reviews, randomised controlled trials (RCTs) and controlled trials was supplemented by supporting literature as appropriate. RESULTS: Evidence to support common practice in the use of corticosteroids is lacking for most indications. This is in the context of strong evidence for the potential for significant toxicity and poor quality use of medicine. CONCLUSION: Guidelines recommending the widespread use of corticosteroids should acknowledge the poor evidence base supporting much current dogma. Quality research is essential not only to define the role of corticosteroids in this context but to ensure good prescribing practice.

Stringent Control of Opioids: Sound Public Health Measures, but a Step Too Far in Palliative Care?

PURPOSE OF REVIEW: Opioids are the only class of drug with the proven ability to control severe pain. The introduction of stringent opioid prescribing restrictions has inevitably impacted upon the ability of those prescribing opioids for advanced life-limited disease to practice as previously and could limit the supply of adequate pain relief to patients with cancer. This review considers the evidence that symptom management of patients with advanced cancer contributes to the "opioid problem" and whether there is adequate recognition of the risks involved. RECENT FINDINGS: The literature suggests that the risk of opioid abuse is low in the palliative care population as is the risk of legal consequences for doctors prescribing opioids at the end of life. However, as many patients with cancer are living longer or surviving with chronic pain, palliative care physicians must be cognisant not only of the risks of long term opioid use but also of the risk of opioid misuse. Adherence to evidence or consensus-based guidelines is necessary to avoid inappropriate prescribing. In palliative care, it is appropriate not only to exercise a reasonable degree of opioid control and surveillance, primarily for the good of society, but also to ensure that the ability to treat pain in patients with advanced malignant disease is not compromised.

Assessing quality of life in palliative care settings: head-to-head comparison of four patient-reported outcome measures (EORTC QLQ-C15-PAL, FACT-Pal, FACT-Pal-14, FACT-G7).

PURPOSE: Head-to-head comparison of reliability, validity and responsiveness of four patient-reported outcome measures (PROMS) suitable for assessing health-related quality of life (HRQOL) in palliative care settings: EORTC QLQ-C15-PAL, FACT-G7, FACIT-Pal and short-form FACIT-Pal-14. METHODS: Secondary analysis of two phase III randomised trials: ketamine for chronic cancer pain, octreotide for vomiting in inoperable malignant bowel obstruction. Sub-groups were defined by Australia-modified Karnofsky performance status (AKPS) and participants' global impression of change (GIC). Two aspects of reliability were assessed: internal consistency (Cronbach alpha, α); test-retest reliability (intra-class correlation coefficient (ICC)) of patients with stable AKPS and those who self-reported 'no change' on GIC. Construct validity was assessed via pre-determined hypotheses about sensitivity of PROM scores to AKPS groups and responsiveness of PROM change scores to GIC groups using analysis of variance. RESULTS: FACIT-Pal had better internal consistency (α ranged 0.59-0.80, 15/18 ≥ 0.70) than QLQ-C15-PAL (0.51-0.85, 4/8 ≥ 0.70) and FACT-G7 (0.54-0.64, 0/2 ≥ 0.70). FACIT scales had better test-retest reliability (FACIT-Pal 11/27 ICCs ≥ 0.70, FACT-G7 2/3 ICCs ≥ 0.70) than QLQ-C15-PAL (2/30 ICCs ≥ 0.70, 18/30 ≤ 0.5). Four scales demonstrated sensitivity to AKPS: QLQ-PAL-15 Physical Functioning and Global QOL, FACT-G Functional Wellbeing and FACIT-Pal Trial Outcome Index (TOI). Nine scales demonstrated responsiveness: three in the ketamine trial population (QLQ-C15-PAL Pain, FACIT-Pal-14, FACT-G7), six in the octreotide trial population (QLQ-C15-PAL Fatigue; FACIT-Pal PalCare, TOI, Total; FACT-G Physical Wellbeing and Total). CONCLUSIONS: No PROM was clearly superior, confirming that choosing the best PROM requires careful consideration of the research goals, patient population and the domains of HRQOL targeted by the intervention being investigated.

Systemic corticosteroids for the management of cancer-related breathlessness (dyspnoea) in adults.

BACKGROUND: Dyspnoea is a common symptom in advanced cancer, with a prevalence of up to 70% among patients at end of life. The cause of dyspnoea is often multifactorial, and may cause considerable psychological distress and suffering. Dyspnoea is often undertreated and good symptom control is less frequently achieved in people with dyspnoea than in people with other symptoms of advanced cancer, such as pain and nausea. The exact mechanism of action of corticosteroids in managing dyspnoea is unclear, yet corticosteroids are commonly used in palliative care for a variety of non-specific indications, including pain, nausea, anorexia, fatigue and low mood, despite being associated with a wide range of adverse effects. In view of their widespread use, it is important to seek evidence of the effects of corticosteroids for the management of cancer-related dyspnoea. OBJECTIVES: To assess the effects of systemic corticosteroids for the management of cancer-related breathlessness (dyspnoea) in adults. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, Science Citation Index Web of Science, Latin America and Caribbean Health Sciences (LILACS) and clinical trial registries, from inception to 25 January 2018. SELECTION CRITERIA: We included randomised controlled trials that included adults aged 18 years and above. We included participants with cancer-related dyspnoea when randomised to systemic corticosteroids (at any dose) administered for the relief of cancer-related dyspnoea or any other indication, compared to placebo, standard or alternative treatment. DATA COLLECTION AND ANALYSIS: Five review authors independently assessed trial quality and three extracted data. We used means and standard deviations for each outcome to report the mean difference (MD) with 95% confidence interval (CI). We assessed the risk of bias and quality of evidence using GRADE. We extracted primary outcomes of sensory-perceptual experience of dyspnoea (intensity of dyspnoea), affective distress (quality of dyspnoea) and symptom impact (burden of dyspnoea or impact on function) and secondary outcomes of serious adverse events, participant satisfaction with treatment and participant withdrawal from trial. MAIN RESULTS: Two studies met the inclusion criteria, enrolling 157 participants (37 participants in one study and 120 in the other study), of whom 114 were included in the analyses. The studies compared oral dexamethasone to placebo, followed by an open-label phase in one study. One study lasted seven days, and the duration of the other study was 15 days.We were unable to conduct many of our predetermined analyses due to different agents, dosages, comparators and outcome measures, routes of drug delivery, measurement scales and time points. Subgroup analysis according to type of cancer was not possible.Primary outcomesWe included two studies (114 participants) with data at one week in the meta-analysis for change in dyspnoea intensity/dyspnoea relief from baseline. Corticosteroid therapy with dexamethasone resulted in an MD of lower dyspnoea intensity compared to placebo at one week (MD -0.85 lower dyspnoea (scale 0-10; lower score = less breathlessness), 95% CI -1.73 to 0.03; very low-quality evidence), although we were uncertain as to whether corticosteroids had an important effect on dyspnoea as results were imprecise. We downgraded the quality of evidence by three levels from high to very low due to very serious study limitations and imprecision.One study measured affective distress (quality of dyspnoea) and results were similar between groups (29 participants; very low-quality evidence). We downgraded the quality of the evidence three times for imprecision, inconsistency, and serious study limitations.Both studies assessed symptom impact (burden of dyspnoea or impact on function) (113 participants; very low-quality evidence). In one study, it was unclear whether dexamethasone had an effect on dyspnoea as results were imprecise. The second study showed more improvement for physical well-being scores at days eight and 15 in the dexamethasone group compared with the control group, but there was no evidence of a difference for FACIT social/family, emotional or functional scales. We downgraded the quality of the evidence three times for imprecision, inconsistency, and serious study limitations.Secondary outcomesDue to the lack of homogenous outcome measures and inconsistency in reporting, we could not perform quantitative analysis for any secondary outcomes. In both studies, the frequency of adverse events was similar between groups, and corticosteroids were generally well tolerated. The withdrawal rates for the two studies were 15% and 36%. Reasons for withdrawal included lost to follow-up, participant or carer (or both) refusal, and death due to disease progression. We downgraded the quality of evidence for these secondary outcomes by three levels from high to very low due to serious study limitations, inconsistency and imprecision.Neither study examined participant satisfaction with treatment. AUTHORS' CONCLUSIONS: There are few studies assessing the effects of systemic corticosteroids on cancer-related dyspnoea in adults with cancer. We judged the evidence to be of very low quality that neither supported nor refuted corticosteroid use in this population. Further high-quality studies are needed to determine if corticosteroids are efficacious in this setting.

Oral medicinal cannabinoids to relieve symptom burden in the palliative care of patients with advanced cancer: a double-blind, placebo controlled, randomised clinical trial of efficacy and safety of cannabidiol (CBD).

BACKGROUND: Despite improvements in medical care, patients with advanced cancer still experience substantial symptom distress. There is increasing interest in the use of medicinal cannabinoids, but there is little high quality evidence to guide clinicians. This study aims to define the role of cannabidiol (CBD) in the management of symptom burden in patients with advanced cancer undergoing standard palliative care. METHODS AND DESIGN: This study is a multicentre, randomised, placebo controlled, two arm, parallel trial of escalating doses of oral CBD. It will compare efficacy and safety outcomes of a titrated dose of CBD (100 mg/mL formulation, dose range 50 mg to 600 mg per day) against placebo. There is a 2-week patient determined titration phase, using escalating doses of CBD or placebo to reach a dose that achieves symptom relief with tolerable side effects. This is then followed by a further 2-week assessment period on the stable dose determined in collaboration with clinicians. DISCUSSION: A major strength of this study is that it will target symptom burden as a whole, rather than just individual symptoms, in an attempt to describe the general improvement in wellbeing previously reported by some patients in open label, non controlled trials of medicinal cannabis. Randomisation with placebo is essential because of the well-documented over reporting of benefit in uncontrolled trials and high placebo response rates in cancer pain trials. This will be the first placebo controlled clinical trial to evaluate rigorously the efficacy, safety and acceptability of CBD for symptom relief in advanced cancer patients. This study will provide the medical community with evidence to present to patients wishing to access medicinal cannabis for their cancer related symptoms. TRIAL REGISTRATION NUMBER: ALCTRN12618001220257 Registered 20/07/2018.

A randomized open-label study of guideline-driven antiemetic therapy versus single agent antiemetic therapy in patients with advanced cancer and nausea not related to anticancer treatment.

BACKGROUND: Nausea/vomiting (N/V) not related to anti-cancer treatment is common in patients with advanced cancer. The standard approach to management is to define a dominant cause, and treat with an antiemetic selected through pathophysiologic knowledge of emetic pathways. High rates of N/V control have been reported using both etiology-based guideline-driven antiemetic regimens and an empiric approach using single agents in uncontrolled studies. These different approaches had never been formally compared. METHODS: This randomized, prospective, open label, dose-escalating study used readily available antiemetics in accordance with etiology-based guidelines or single agent therapy with haloperidol. Participants had a baseline average nausea score of ≥3/10. Response was defined as a ≥ 2/10 point reduction on a numerical rating scale of average nausea score with a final score < 3/10 at 72 h. RESULTS: Nausea scores and distress from nausea improved over time in the majority of the 185 patients randomized. For those who completed each treatment day, a greater response rate was seen in the guideline arm than the single agent arm at 24 h (49% vs 32%; p = 0.02), but not at 48 or 72 h. Response rates at 72 h in the intention to treat analysis were 49 and 53% respectively, with no significant difference between arms (0·04; 95% CI: -0·11, 0·19; p = 0·59). Over 80% of all participants reported an improved global impression of change. There were few adverse events worse than baseline in either arm. CONCLUSION: An etiology-based, guideline-directed approach to antiemetic therapy may offer more rapid benefit, but is no better than single agent treatment with haloperidol at 72 h. CLINICAL TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ANZCTRN12610000481077 .

A retrospective audit on usage of Diatrizoate Meglumine (Gastrografin®) for intestinal obstruction or constipation in patients with advanced neoplasms.

BACKGROUND: Intestinal obstruction and constipation are common conditions in patients with advanced neoplasms. Diatrizoate Meglumine has been used in the management of both these conditions without good quality evidence of its effectiveness and safety. AIM: This audit aimed to assess the usage, effectiveness and adverse effects of Diatrizoate Meglumine for intestinal obstruction and constipation in patients with advanced neoplasms. DESIGN: A retrospective chart review was undertaken. Descriptive statistics were utilised. SETTING/PARTICIPANTS: All patients with known advanced neoplasms admitted to Mater Health Services and St Vincent's Private Hospital Brisbane between January 2013 and October 2015; who were administered Diatrizoate Meglumine were included. RESULTS: Seventy-one patients received Diatrizoate Meglumine. The most common diagnoses were ovarian or primary peritoneal neoplasms (33.8%). Diatrizoate Meglumine was most commonly used for intestinal obstruction (59.2%). The median dose used per patient episode was 50 mL (range: 15-500 mL). Thirty-two patients (45%) had imaging 4-24 h post-dose with Diatrizoate Meglumine being present in the large intestine in 75% of these images. Intestinal obstruction or constipation resolved in 90% of patients post-dose. CONCLUSION: Most clinicians used 50 mL of Diatrizoate Meglumine as a single dose and repeated imaging after 4-24 h. Diatrizoate Meglumine was well tolerated and may be effective in resolving intestinal obstruction and constipation in patients with advanced neoplasms. Quality controlled studies are needed to further guide the use of Diatrizoate Meglumine in intestinal obstruction and constipation in patients with advanced neoplasms.

Castrate-resistant prostate cancer: lessons learnt from a pilot study in the palliative care research population.

BACKGROUND: Palliative care patients are inherently difficult to recruit to and retain on studies. Even when patients are recruited, it is hard to complete studies with sufficient data. There is a dearth of literature specific to men with castrate resistant prostate cancer (CRPC) and the clinical trials coordinator/research nurse's perspective in improving trial outcomes in palliative care. Objectives To describe the lessons learnt (by the nursing research team) from a prospective cohort study of men with CRPC and the practical implications for future research in this area. METHODS: A pilot feasibility cohort study that followed patients with CRPC from referral until death. The participants completed questionnaires while the researcher documented treatments, disease status and symptom burden. The recruitment methods, data quality and results were analysed. RESULTS AND DISCUSSION: Several lessons have been learnt with regard to facilitating trial recruitment and design. These lessons are: the importance of building relationships with local urology teams, including all men with the diagnosis of CRPC as documented by a medical oncologist or urologist, reducing questionnaire burden, capturing symptom scores in clinic, actively following up patients by phone, and recording all reasons for drop-out or lost to follow-up. These lessons can now be implemented to improve future studies involving this demographic.

Corticosteroids for adult patients with advanced cancer who have nausea and vomiting (not related to chemotherapy, radiotherapy, or surgery).

BACKGROUND: Nausea is a common symptom in advanced cancer, with a prevalence of up to 70%. While nausea and vomiting can be related to cancer treatments, such as chemotherapy, radiotherapy, or surgery, a significant number of people with advanced cancer also suffer from nausea unrelated to such therapies. Nausea and vomiting may also cause psychological distress, and have a negative impact on the quality of life of cancer patients; similarly to pain, nausea is often under-treated. The exact mechanism of action of corticosteroids on nausea is unclear, however, they are used to manage a number of cancer-specific complications, including spinal cord compression, raised intracranial pressure, and lymphangitis carcinomatosis. They are also commonly used in palliative care for a wide variety of non-specific indications, such as pain, nausea, anorexia, fatigue, and low mood. However, there is little objective evidence of their efficacy in symptom control, and corticosteroids have a wide range of adverse effects that are dose and time dependent. In view of their widespread use, it is important to seek evidence of their effects on nausea and vomiting not related to cancer treatment. OBJECTIVES: To assess the effects of corticosteroids on nausea and vomiting not related to chemotherapy, radiotherapy, or surgery in adult cancer patients. SEARCH METHODS: We searched CENTRAL, MEDLINE Ovid, Embase Ovid, CINAHL EBSCO, Science Citation Index Web of Science, Latin America and Caribbean Health Sciences (LILACS), Conference Proceedings Citation Index - Science Web of Science, and clinical trial registries, from inception to 23rd August 2016. SELECTION CRITERIA: Any double-blind randomised or prospective controlled trial that included adults aged 18 years and over with advanced cancer with nausea and vomiting not related to chemotherapy, radiotherapy, or surgery were eligible for the review, when using corticosteroids as antiemetic treatment. DATA COLLECTION AND ANALYSIS: All review authors independently assessed trial quality and extracted data. We used arithmetic means and standard deviations for each outcome to report the mean difference (MD) with 95% confidence interval (CI). We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS: Three studies met the inclusion criteria, enrolling 451 participants. The trial size varied from 51 to 280 participants. Two studies compared dexamethasone to placebo, and the third study compared a number of additional interventions in various combinations, including metoclopramide, chlorpromazine, tropisetron, and dexamethasone. The duration of the studies ranged from seven to 14 days. We included two studies (127 participants) with data at eight days in the meta-analysis for nausea intensity; no data were available that incorporated the same outcome measures for the third study. Corticosteroid therapy with dexamethasone resulted in less nausea (measured on a scale of 0 to 10, with a lower score indicating less nausea) compared to placebo at eight days (MD 0.48 lower nausea, 95% CI 1.53 lower to 0.57 higher; very low-quality evidence), although this result was not statistically significant (P = 0.37). Frequency of adverse events was not significantly different between groups, and the interventions were well tolerated. Factors limiting statistical analysis included the lack of standardised measurements of nausea, and the use of different agents, dosages, and comparisons. Subgroup analysis according to type of cancer was not possible due to insufficient data. The quality of this evidence was downgraded by three levels, from high to very low due to imprecision, likely selection bias, attrition bias, and the small number of participants in the included studies. AUTHORS' CONCLUSIONS: There are few studies assessing the effects of corticosteroids on nausea and vomiting not related to chemotherapy, radiotherapy, or surgery in adult cancer patients. This review found very low-quality evidence which neither supported nor refuted corticosteroid use in this setting. Further high quality studies are needed to determine if corticosteroids are efficacious in this setting.

Opioid addiction and misuse in adult and adolescent patients with cancer.

In the context of a therapeutic opioid epidemic, particularly in the USA, where increasingly stringent screening for 'at risk' individuals and close monitoring of opioid prescription and use is strongly recommended, the issue of misuse within the cancer population must be addressed. Most patients with advanced cancer will have pain requiring opioid therapy at some stage during their disease course. In the majority, this will provide good pain relief with no short- or longer-term adverse sequelae. A subset will present with substance misuse issues that will influence management and prescribing practice. The potential ethical issues of limiting effective analgesia on the basis of addiction risk or history must be acknowledged. Both a judgemental or 'relaxed' approach to such patients is problematic. Ignoring the situation will not be in the patient's best interest, but an undue focus on this aspect may damage therapeutic relationships with clinicians and adversely affect a holistic approach to care. Clinical practitioners must be aware of the risk factors for opioid misuse and in patients who are not under palliative care consider screening prior to commencing opioids. Clinicians must be able to manage and monitor those identified as having an opioid misuse problem.

Interventional options for the management of refractory cancer pain--what is the evidence?

PURPOSE: Pain is the most common symptom in cancer patients. Standard pain treatment according to the WHO three-step analgesic ladder provides effective pain management in approximately 70-90% of cancer patients. Refractory pain is defined as not responding to "standard" treatments. Interventional analgesic techniques can be used in an attempt to control refractory pain in patients in whom conventional analgesic strategies fail to provide effective pain relief or are intolerable due to severe adverse effects. This systematic review aims to provide the latest evidence on interventional refractory pain management in cancer patients. METHODS: Systematic literature search in Cochrane, EMBASE and PubMed including reviews and randomised controlled trials (RCTs) and non-randomised controlled trials in the absence of reviews. RESULTS: Neuraxial analgesia may play a role in refractory cancer pain management. Paravertebral blocks decrease the incidence of persistent post-surgical pain after breast cancer. Coeliac plexus blocks improve pain scores in refractory pancreatic cancer pain for up to 4 weeks after the intervention with fewer burdensome side effects as compared to opioids. Cordotomy has mainly been studied in mesothelioma, and the case series suggest possible benefit for pain at the expense of a relatively high risk of side effects. CONCLUSIONS: Overall, very few RCTs have been conducted on interventional pain techniques. In reality, it is very difficult to undertake large controlled trials for a number of reasons. Therefore, today's best evidence for practice may be from large case series of comparable patients with careful response and toxicity evaluation and follow-up.

A randomised, double-blind controlled trial of intranasal midazolam for the palliation of dyspnoea in patients with life-limiting disease.

PURPOSE: Anxiety is a major component of breathlessness and is often palliated with benzodiazepines. Midazolam is a short-acting water-soluble benzodiazepine with a rapid onset of action and short half-life. Intranasal midazolam had been shown to be of marked clinical benefit in an uncontrolled pilot study for the control of dyspnoea. A blinded randomised controlled study was therefore undertaken across four Australasian palliative care services. METHODS: All participants received six numbered study nasal spray (SNS) bottles, three of which contained midazolam and three placebo. They were instructed to use one SNS bottle on each day they were breathless, for 6 days within 2 weeks. Dyspnoea scores were recorded before and at set time intervals following the first use of each SNS bottle. RESULTS: Across all SNS bottles, the maximum change of 2.1 on an 11-point numerical rating scale was seen at 60 min. There was no difference in dyspnoea score between the two arms. Approximately 50 % of participants in each arm had a positive response (i.e. ≥2 point change in dyspnoea score from baseline). Anxiety scores at baseline were low. The most common adverse event was local nasal reactions. CONCLUSION: Intranasal midazolam had no clinical benefit over intranasal placebo for the control of dyspnoea. The low level of anxiety at baseline and dose of active drug delivered may have been important factors. Many participants found the SNS bottles to be a challenging mode of drug delivery. This study confirms the importance of placebo-controlled trials for defining best clinical practise.