Bayesian methods in palliative care research: cancer-induced bone pain.

OBJECTIVE: To show how a simple Bayesian analysis method can be used to improve the evidence base in patient populations where recruitment and retention are challenging. METHODS: A Bayesian conjugate analysis method was applied to binary data from the Thermal testing in Bone Pain (TiBoP) study: a prospective diagnostic accuracy/predictive study in patients with cancer-induced bone pain (CIBP). This study aimed to evaluate the clinical utility of a simple bedside tool to identify who was most likely to benefit from palliative radiotherapy (XRT) for CIBP. RESULTS: Recruitment and retention of patients were challenging due to the frail population, with only 27 patients available for the primary analysis. The Bayesian method allowed us to make use of prior work done in this area and combine it with the TiBoP data to maximise the informativeness of the results. Positive and negative predictive values were estimated with greater precision, and interpretation of results was facilitated by use of direct probability statements. In particular, there was only 7% probability that the true positive predictive value was above 80%. CONCLUSIONS: Several advantages of using Bayesian analysis are illustrated in this article. The Bayesian method allowed us to gain greater confidence in our interpretation of the results despite the small sample size by allowing us to incorporate data from a previous similar study. We suggest that this method is likely to be useful for the analysis of small diagnostic or predictive studies when prior information is available.

Properties of Pain Assessment Tools for Use in People Living With Stroke: Systematic Review.

Background: Pain is a common problem after stroke and is associated with poor outcomes. There is no consensus on the optimal method of pain assessment in stroke. A review of the properties of tools should allow an evidence based approach to assessment. Objectives: We aimed to systematically review published data on pain assessment tools used in stroke, with particular focus on classical test properties of: validity, reliability, feasibility, responsiveness. Methods: We searched multiple, cross-disciplinary databases for studies evaluating properties of pain assessment tools used in stroke. We assessed risk of bias using the Quality Assessment of Diagnostic Accuracy Studies tool. We used a modified harvest plot to visually represent psychometric properties across tests. Results: The search yielded 12 relevant articles, describing 10 different tools (n = 1,106 participants). There was substantial heterogeneity and an overall high risk of bias. The most commonly assessed property was validity (eight studies) and responsiveness the least (one study). There were no studies with a neuropathic or headache focus. Included tools were either scales or questionnaires. The most commonly assessed tool was the Faces Pain Scale (FPS) (6 studies). The limited number of papers precluded meaningful meta-analysis at level of pain assessment tool or pain syndrome. Even where common data were available across papers, results were conflicting e.g., two papers described FPS as feasible and two described the scale as having feasibility issues. Conclusion: Robust data on the properties of pain assessment tools for stroke are limited. Our review highlights specific areas where evidence is lacking and could guide further research to identify the best tool(s) for assessing post-stroke pain. Improving feasibility of assessment in stroke survivors should be a future research target. Systematic Review Registration Number: PROSPERO CRD42019160679 Available online at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019160679.

A systematic review examining clinical markers and biomarkers of analgesic response to radiotherapy for cancer-induced bone pain.

INTRODUCTION: Cancer frequently spreads to bone, causing cancer-induced bone pain (CIBP) which affects quality of life. The best treatment is radiotherapy (XRT), but response is variable. The aim of this systematic review was to identify factors that predict analgesic response. MATERIALS AND METHODS: Using PRISMA guidelines, Medline (1946-2018), Embase Classic + Embase (1947-2018) and Cochrane (setup-2018) databases were searched. Eligible studies examined adult patients receiving external beam XRT for CIBP with clinical marker and/or biomarkers evaluated. RESULTS: Twenty-one studies (n = 4490) were included: Urinary markers in three studies (n = 357), genomic biomarkers in one study (n = 107), imaging techniques in five studies (n = 231) and demographics and disease parameters in eight studies (n = 4572). Quantitative sensory testing (n = 23) and physical activity and/or gait (n = 42) have been examined in one study each, while two studies have evaluated grade of spinal instability (n = 276). CONCLUSION: No predictors of analgesic response from XRT in CIBP were identified but several show promise.

The Management of Opioid-Induced Nausea and Vomiting in Patients with Cancer: A Systematic Review.

BACKGROUND: Opioids are the foundation of treatment for cancer pain but can cause side-effects, one of the most common being nausea and vomiting, which can impair quality of life. OBJECTIVE: To evaluate the evidence for the management of opioid-induced nausea and vomiting. This systematic review was undertaken as part of an update of the European Association for Palliative Care's opioid guidelines. DESIGN: Searches of MEDLINE (1966-2017) and EMBASE (1980-2017) were done. Key eligibility criteria were: randomized controlled trials conducted in patients with cancer. The Grading of Recommendations Assessment Development and Evaluations system was applied to formulate recommendations. RESULTS: Fifteen studies were eligible (1524 patients). The studies were grouped as follows: opioid switching (n = 8); the use of antiemetics to treat opioid-induced nausea and vomiting (n = 4); and change of route of administration of the opioid (n = 3). Three recommendations were formulated: A weak recommendation for switching from morphine to oxycodone in cancer patients with nausea (quality D); a weak recommendation for switching from tramadol to either codeine or hydrocodone for pain in cancer patients with nausea (quality D); and a weak recommendation for switching from morphine/oxycodone to methadone using the three-day switch method in patients with increasing pain considered untreatable with further opioid titration and/or with opioid-related side effects (quality C). CONCLUSIONS: This systematic review can make only weak recommendations for the management of opioid-induced nausea and vomiting. There remains a need for high-quality studies before strong recommendations on the management of opioid-induced nausea and vomiting can be made.

Prognostic Tools in Patients With Advanced Cancer: A Systematic Review.

PURPOSE: In 2005, the European Association for Palliative Care made recommendations for prognostic markers in advanced cancer. Since then, prognostic tools have been developed, evolved, and validated. The aim of this systematic review was to examine the progress in the development and validation of prognostic tools. METHODS: Medline, Embase Classic and Embase were searched. Eligible studies met the following criteria: patients with incurable cancer, >18 years, original studies, population n ≥100, and published after 2003. Descriptive and quantitative statistical analyses were performed. RESULTS: Forty-nine studies were eligible, assessing seven prognostic tools across different care settings, primary cancer types, and statistically assessed survival prediction. The Palliative Performance Scale was the most studied (n = 21,082), comprising six parameters (six subjective), was externally validated, and predicted survival. The Palliative Prognostic Score composed of six parameters (four subjective and two objective), the Palliative Prognostic Index composed of nine parameters (nine subjective), and the Glasgow Prognostic Score composed of two parameters (two objective) and were all externally validated in more than 2000 patients with advanced cancer and predicted survival. CONCLUSION: Various prognostic tools have been validated but vary in their complexity, subjectivity, and therefore clinical utility. The Glasgow Prognostic Score would seem the most favorable as it uses only two parameters (both objective) and has prognostic value complementary to the gold standard measure, which is performance status. Further studies comparing all proved prognostic markers in a single cohort of patients with advanced cancer are needed to determine the optimal prognostic tool.

The use of opioids in cancer patients with renal impairment-a systematic review.

PURPOSE: Opioids are recommended for moderate to severe cancer pain; however, in patients with cancer, impaired renal function can affect opioid metabolism. The aim of this systematic review was to evaluate the current evidence for the use of opioids in cancer patients with renal impairment. METHODS: A systematic review was conducted and the following databases were searched: MEDLINE (1966 to 2015), EMBASE (1980 2015) and Cochrane Central Register of Controlled Trials (up to 2015). Eligible studies met the following criteria: patients with cancer pain taking an opioid (defined as per the WHO ladder); >18 years; renal impairment (serum creatinine > normal range (study dependent), creatinine clearance (CrCl) or glomerular filtration rate (GFR) measurements <90 ml/min, or as per the study definition); clinical outcome related to renal impairment. All eligible studies were appraised using the Grading of Recommendation Assessment, Development and Evaluations (GRADE) system. RESULTS: Eighteen studies (n = 2422) were eligible but heterogeneity meant meta-analysis was not possible. Morphine was examined in eight studies (n = 1418), oxycodone in two studies (n = 325), and fentanyl, alfentanil or sufentanil were discussed in six studies in total (n = 442). No recommendations could be formulated on the preferred opioid in patients with renal impairment. CONCLUSION: There is lack of consensus within the existing literature on the relationship between morphine, creatinine levels and morphine-related side effects. Based on the current evidence, morphine should be used with caution; however, more evidence is needed. Fentanyl, alfentanil and sufentanil are recommended in patients with renal impairment based on pharmacokinetics and clinical experience. However, the present systematic review found very little clinical evidence for this. Overall, the quality of the existing evidence on opioid treatment in cancer patients with renal impairment is low. There remains a need for high-quality clinical studies examining opioids in patients with renal impairment.

The characteristics of physical activity and gait in patients receiving radiotherapy in cancer induced bone pain.

BACKGROUND AND PURPOSE: An objective measure of pain relief may add important information to patients' self assessment, particularly after a treatment. The study aims were to determine whether measures of physical activity and/or gait can be used in characterizing cancer-induced bone pain (CIBP) and whether these biomarkers are sensitive to treatment response, in patients receiving radiotherapy (XRT) for CIBP. MATERIALS AND METHODS: Patients were assessed before (baseline) and 6-8weeks after XRT (follow up). The following assessments were done: Brief Pain Inventory (BPI), activPAL™ activity meter, and GAITRite® electronic walkway (measure of gait). Wilcoxon, Mann-Whitney and Pearson statistical analyses were done. RESULTS: Sixty patients were assessed at baseline; median worst pain was 7 and walking interference was 5. At follow up 42 patients were assessed. BPI worst pain, average pain, walking interference and total functional interference all improved (p<0.001). An improvement in functional interference correlated with aspects of physical activity (daily hours standing r=0.469, p=0.002) and gait (cadence r=0.341, p=0.03). The activPAL and GAITRite parameters did not change following XRT (p>0.05). In responder analyses there were no differences in activPAL and GAITRite parameters (p>0.05). CONCLUSION: Assessment of physical activity and gait allow a characterization of the functional aspects of CIBP, but not in the evaluation of XRT.