Showing papers by "Michael I. Bennett published in 2022"

Oxycodone for cancer-related pain.

Abstract: BACKGROUND Many patients with cancer experience moderate to severe pain that requires treatment with strong opioids, of which oxycodone and morphine are examples. Strong opioids are, however, not effective for pain in all patients, nor are they well-tolerated by all patients. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for patients with cancer pain. OBJECTIVES To assess the effectiveness and tolerability of oxycodone for pain in adults with cancer. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), EMBASE (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), PsycINFO (Ovid) and PubMed to March 2014. We also searched Clinicaltrials.gov, metaRegister of Controlled Trials (mRCT), EU Clinical Trials Register and World Health Organization International Clinical Trials Registry Platform (ICTRP). We checked the bibliographic references of relevant identified studies and contacted the authors of the included studies to find additional trials not identified by the electronic searches. No language, date or publication status restrictions were applied to the search. SELECTION CRITERIA We included randomised controlled trials (parallel-group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults. DATA COLLECTION AND ANALYSIS Two authors independently extracted study data (study design, participant details, interventions and outcomes) and independently assessed the quality of the included studies according to standard Cochrane methodology. Where possible, we meta-analysed the pain intensity data using the generic inverse variance method, otherwise these data were summarised narratively along with the adverse event and patient preference data. The overall quality of the evidence for each outcome was assessed according to the GRADE approach. MAIN RESULTS We included 17 studies which enrolled/randomised 1390 patients with 1110 of these analysed for efficacy and 1170 for safety. The studies examined a number of different drug comparisons. Four studies compared controlled release (CR) oxycodone to immediate release (IR) oxycodone and pooled analysis of three of these studies showed that the effects of CR and IR oxycodone on pain intensity after treatment were similar (standardised mean difference (SMD) 0.1, 95% confidence interval (CI) -0.06 to 0.26; low quality evidence). This was in line with the finding that none of the included studies reported differences in pain intensity between the treatment groups. Three of the four studies also found similar results for treatment acceptability and adverse events in the IR and CR groups; but one study reported that, compared to IR oxycodone, CR oxycodone was associated with significantly fewer adverse events.Six studies compared CR oxycodone to CR morphine and pooled analysis of five of these studies indicated that pain intensity did not differ significantly between the treatments (SMD 0.14, 95% CI -0.04 to 0.32; low quality evidence). There were no marked differences in adverse event rates, treatment acceptability or quality of life ratings.The remaining seven studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None of them found any clear superiority or inferiority of oxycodone for cancer pain, neither as an analgesic agent nor in terms of adverse event rates and treatment acceptability.The quality of this evidence base was limited by the risk of bias of the studies and by small sample sizes for many outcomes. Random sequence generation and allocation concealment were under-reported, and the results were substantially compromised by attrition with data missing from more than 20% of the enrolled/randomised patients for efficacy and from more than 15% for safety. AUTHORS' CONCLUSIONS Overall, the data included within this review suggest that oxycodone offers similar levels of pain relief and adverse events to other strong opioids including morphine, which is commonly considered the gold standard strong opioid. Our conclusions are consistent with other recent reviews and suggest that while the reliability of the evidence base is low, given the absence of important differences within this analysis it seems unlikely that larger head to head studies of oxycodone versus morphine will be justified. This means that for clinical purposes oxycodone or morphine can be used as first line oral opioids for relief of cancer pain.

Conceptualising effective symptom management in palliative care: a novel model derived from qualitative data

Abstract: Pain, breathlessness and fatigue are some of the most challenging symptoms to manage in patients with advanced disease. Specialist palliative care leads to better symptom management, but factors contributing to successful symptom management in this context have not been explored. Our aim was to understand what facilitates effective symptom management in specialist palliative care within UK hospices and investigate what barriers are experienced.This was a grounded theory study using qualitative semi-structured focus groups and interviews. Participants were recruited from multidisciplinary specialist palliative care teams (doctors, nurses, healthcare assistants, physiotherapists, occupational therapists, complementary therapists, social workers and chaplains) working in inpatient, outpatient and community services provided by five hospices in the United Kingdom.We present a novel qualitative data-derived model of effective symptom management in specialist palliative care. We describe a co-ordinated, multi-faceted, sequential approach involving a process of engagement, partnership, decision-making, and delivery. Interventions to manage symptoms are less effective in psychologically distressed patients. Our data highlights that families of patients have a key role in determining effectiveness of symptom management interventions A holistic approach by a co-ordinated, multi-disciplinary team, including support to recognise and minimise psychological distress might facilitate more effective symptom management. Barriers to symptom management include team discordance and lack of understanding about symptom management by patient and families.Shared decision-making between patients and professionals and co-ordination of care by a multi-disciplinary team are key components of effective symptom management. Actions to address psychological distress and evaluate the understanding and expectations of patients and their families would enable more effective symptom management. A more effective multi-disciplinary approach would be facilitated by discussion within teams about role competencies and boundaries.

Does ethnicity affect pain management for people with advanced disease? A mixed methods cross-national systematic review of ‘very high’ Human Development Index English-speaking countries

Abstract: Racial disparities in pain management have been observed in the USA since the 1990s in settings such as the emergency department and oncology. However, the palliative care context is not well described, and little research has focused outside of the USA or on advanced disease. This review takes a cross-national approach to exploring pain management in advanced disease for people of different racial and ethnic groups.Mixed methods systematic review. The primary outcome measure was differences in receiving pain medication between people from different racial and ethnic groups. Five electronic databases were searched. Two researchers independently assessed quality using JBI checklists, weighted evidence, and extracted data. The quantitative findings on the primary outcome measure were cross-tabulated, and a thematic analysis was undertaken on the mixed methods studies. Themes were formulated into a conceptual/thematic matrix. Patient representatives from UK ethnically diverse groups were consulted. PRISMA 2020 guidelines were followed.Eighteen papers were included in the primary outcome analysis. Three papers were rated 'High' weight of evidence, and 17/18 (94%) were based in the USA. Ten of the eighteen (56%) found no significant difference in the pain medication received between people of different ethnic groups. Forty-six papers were included in the mixed methods synthesis; 41/46 (89%) were based in the USA. Key themes: Patients from different ethnically diverse groups had concerns about tolerance, addiction and side effects. The evidence also showed: cultural and social doctor-patient communication issues; many patients with unmet pain management needs; differences in pain assessment by racial group, and two studies found racial and ethnic stereotyping.There was not enough high quality evidence to draw a conclusion on differences in receiving pain medication for people with advanced disease from different racial and ethnic groups. The mixed methods findings showed commonalities in fears about pain medication side effects, tolerance and addiction across diverse ethnic groups. However, these fears may have different foundations and are differently prioritised according to culture, faith, educational and social factors. There is a need to develop culturally competent pain management to address doctor-patient communication issues and patients' pain management concerns.PROSPERO- CRD42020167890 .

Practice review: Evidence-based and effective management of anaemia in palliative care patients

Abstract: Background: Anaemia is a common sequela of advanced disease and is associated with significant symptom burden. No specific guidance exists for the investigation and management of anaemia in palliative care patients. Aim: We aim to offer a pragmatic overview of the approaches to investigate and manage anaemia in advanced disease, based on guidelines and evidence in disease specific patient groups, including cancer, heart failure and chronic kidney disease. Design: Scoping review methodology was used to determine the strength of evidence supporting the investigation and management of anaemia in patients with advanced disease. Data sources: A search for guidelines was performed in 2020. National or international guidelines were examined if they described the investigation or management of anaemia in adult patients with health conditions seen by palliative care services written within the last 5 years in the English language. Searches of MEDLINE, the Cochrane library and WHO guidance were made in 2019 to identify key publications that provided additional primary data. Results: Evidence supports patient-centred investigation of anaemia, results of which should guide targeted intervention. Blanket use of blood transfusion should be avoided, with evidence supporting a more restrictive approach to transfusion. Routine use of oral iron and erythropoetin stimulating agents (ESAs) are not recommended. Insufficient evidence exists to determine the effectiveness of IV iron in this patient group. Conclusion: We advocate early consideration and investigation of anaemia, guided by symptom burden and patient preferences. Correction of reversible causes should be the mainstay of treatment, with a restrictive approach to blood transfusion. Research is required to evaluate the efficacy of IV iron in these patients.

Issues affecting supply of palliative medicines into community pharmacy: A qualitative study of community pharmacist and pharmaceutical wholesaler/distributor perspectives

Abstract: Patient access to medicines in the community at end-of-life (pertaining to the last year of life) is vital for symptom control. Supply of such medicines is known to be problematic, but despite this, studies have failed to examine the issues affecting community pharmacy access to palliative medicines. To identify community pharmacists' and pharmaceutical wholesalers'/distributors' views on supply chain processes and challenges in providing access to medicines during the last year of life, to characterise supply in this UK context. Qualitative design, with telephone interviews analysed using Framework Analysis. Coding frames were developed iteratively with data analysed separately and then triangulated to examine differences in perspectives. Thirty-two interviews (24 community pharmacists and 8 wholesalers/distributors) were conducted. To ensure appropriate palliative medicines were available despite occasional shortages, community pharmacists worked tirelessly. They navigated a challenging interface with wholesalers/distributors, the Drug Tariff to ensure reimbursement, and multiple systems. IT infrastructures and logistics provided by wholesalers/distributors were often helpful to supply into community pharmacies resulting in same or next day deliveries. However, the inability of manufacturers to predict operational issues or accurately forecast demand led wholesalers/distributors to encounter shortages with manufactured stock levels, reducing timely access to medicines. The study identifies for the first time how palliative medicines supply into community pharmacy, can be improved. A conceptual model was developed, illustrating how influencing factors affect responsiveness and speed of medicines access for patients. Work is required to strengthen this supply chain via effective relationship-building and information-sharing, to prevent patients facing disruptions in access to palliative medicines at end-of-life.

Mapping and characterising electronic palliative care coordination systems and their intended impact: A national survey of end-of-life care commissioners

Abstract: Objectives In England, Electronic Palliative Care Coordination Systems (EPaCCS) were introduced in 2008 to support care coordination and delivery in accordance with patient preferences. Despite policy supporting their implementation, there has been a lack of rigorous evaluation of EPaCCS and it is not clear how they have been translated into practice. This study sought to examine the current national implementation of EPaCCS, including their intended impact on patient and service outcomes, and barriers and facilitators for implementation. Methods We conducted a national cross-sectional online survey of end-of-life care commissioning leads for Clinical Commissioning Groups (CCGs) in England. We enquired about the current implementation status of EPaCCS, their role in information sharing and intended impact, and requested routine patient-level data relating to EPaCCS. Results Out of 135 CCGs, 85 (63.0%) responded, with 57 (67.1%) having operational EPaCCS. Use of EPaCCS were confined to healthcare providers with most systems (67%) not supporting information sharing with care homes and social care providers. Most systems (68%) sought to facilitate goal concordant care, although there was inconsonance between intended impacts and monitoring measures used. Common challenges to implementation included healthcare professionals’ limited engagement. Only one-third of patients had an EPaCCS record at death with limited recording of patient preferences. Conclusions Critical gaps exist in engagement with EPaCCS and their ability to facilitate information sharing across care providers. The limited alignment between stated goals of EPaCCS and their monitoring impedes efforts to understand which characteristics of systems can best support care delivery.

Evidence-based management approaches for patients with severe chronic obstructive pulmonary disease (COPD): A practice review

Abstract: Background: Patients with chronic obstructive pulmonary disease (COPD) face limited treatment options and inadequate access to palliative care. Aim: To provide a pragmatic overview of clinical guidelines and produce evidence-based recommendations for severe COPD. Interventions for which there is inconsistent evidence to support their use and areas requiring further research were identified. Design: Practice review of guidelines supported by scoping review methodology to examine the evidence reporting the use of guideline-recommended interventions. Data sources: An electronic search was undertaken in MEDLINE, EMBASE, PsycINFO, CINAHL and The Cochrane Database of Systematic Reviews, complemented by web searching for guidelines and publications providing primary evidence (July 2021). Guidelines published within the last 5 years and evidence in the last 10 years were included. Results: Severe COPD should be managed using a multidisciplinary approach with a holistic assessment. For stable patients, long-acting beta-agonist/long-acting muscarinic antagonist and pulmonary rehabilitation are recommended. Low dose opioids, self-management, handheld fan and nutritional support may provide small benefits, whereas routine corticosteroids should be avoided. For COPD exacerbations, systematic corticosteroids, non-invasive ventilation and exacerbation action plans are recommended. Short-acting inhaled beta-agonists and antibiotics may be considered but pulmonary rehabilitation should be avoided during hospitalisation. Long term oxygen therapy is only recommended for patients with chronic severe hypoxaemia. Short-acting anticholinergic inhalers, nebulised opioids, oral theophylline or telehealth are not recommended. Conclusions: Recommended interventions by guidelines are not always supported by high-quality evidence. Further research is required on efficacy and safety of inhaled corticosteroids, antidepressants, benzodiazepines, mucolytics, relaxation and breathing exercises.

Ethnicity and palliative care: we need better data – five key considerations

Abstract: Complete and valid ethnicity data are essential for monitoring racial and ethnic disparities but consideration needs to be given to collecting data well and using it responsibly. Palliative care could provide leadership in this field. The COVID19 pandemic has revealed the importance of good quality data for demonstrating the extent, nature and impact of ethnic and racial disparities within society. 2 Where it has been available, data on race and ethnicity has long been used to highlight persistent inequalities in healthcare globally. Recent events of historical and political significance have also brought a renewed attention and momentum to these issues, for example, Black Lives Matter and Empire Windrush in the UK. There have been numerous calls for mandatory ethnicity data collection within routine health and social care, and on death certificates, 4 5 which Scotland has already established. However, there has not been a parallel focus on how to get data collection right. Data are powerful, but can be misused. There are a number of practical, methodological and ethical issues which require addressing. Holism is at the core of palliative care, in the approach to a person and their ‘total pain’. Extending this framework to ethnicity data engenders a responsibility across both the collection and usage of data. We outline five key considerations informed by this framework relating to ethnicity data.

Attitudes, Knowledge, and Perceived Barriers Towards Cancer Pain Management Among Healthcare Professionals in Libya: a National Multicenter Survey

Abstract: Cancer pain presents in approximately 66% of patients in advanced stages. Although several guidelines and pharmacological options are available for cancer pain management (CPM), assessment and treatment of cancer pain remain inadequate globally, particularly in developing countries. Lack of knowledge and negative attitudes towards CPM among healthcare professionals (HCPs) are important barriers to CPM. This survey aimed to evaluate nurses' and physicians' knowledge, attitudes, and potential barriers regarding CPM in Libya. This cross-sectional survey involved a convenience sample of 152 oncology nurses and physicians working in six oncology settings in Libya. The response rate was 76%. The Barriers Questionnaire II (BQ-II) was used for data collection (higher scores signify greater attitudinal barriers and poorer knowledge). Data analysis was carried out using Statistical Package for Social Sciences (SPSS), version 26 software. An independent t-test (unadjusted estimate) indicated that Libyan nurses showed higher mean barrier scores (mean = 3.8, SD = 0.7) to CPM than physicians (mean = 2.9, SD = 0.8), p < 0.001. The six most common differences in attitudinal barriers between nurses and physicians were "opioid side effects," "poor tolerance," "strong patient endures pain," "distract the physician," "drug addiction," and "opioids impair immune function," p < 0.001. Multiple regression results (adjusted estimate) indicated that nurses had more barrier scores to CPM than physicians (B = - 0.530, p < 0.05), and participants with higher educational levels were associated with lower barrier scores to CPM (B = - 0.641, p < 0.05). Our results suggest that Libyan oncology HCPs hold perceived barriers, lack of knowledge, and negative attitudes towards CPM. Professional education and training in CPM, addressing phobia and myths on opioid usage, and the benefits and complications of using opioids are likely to result in reduced barriers to CPM in Libya.

Quality of end‐of‐life care with non‐malignant liver disease: Analysis of the VOICES National Survey of Bereaved People

Abstract: Patients with liver disease struggle to access palliative care. We aimed to compare carers' perceptions of end‐of‐life care for decedents with non‐malignant liver disease, malignant liver disease and other non‐malignant diseases, and to identify associated factors in non‐malignant liver disease.

Patient and carer access to medicines at end of life: the ActMed mixed-methods study

Abstract: Patient access to medicines at home during the last 12 months of life is critical for effective symptom control, prevention of distress and unplanned admission to hospital. The limited evidence suggested problems with different components of service delivery and, to the best of our knowledge, the impact of innovations in end-of-life service delivery has remained unevaluated. To provide an evaluation of patient and carer access to medicines at end of life within the context of models of service delivery. The study used a multiphase mixed-methods design, comprising (1) a systematic literature review; (2) an online questionnaire survey of health-care professionals delivering end-of-life care; (3) evaluative mixed-method case studies of service delivery models, including cost and cost-effectiveness analysis; (4) interviews with community pharmacists and pharmaceutical wholesalers and distributors; and (5) an expert consensus-building workshop. Community and primary care end-of-life services in England. Health-care professionals delivering end-of-life care and patients living at home in the last 12 months of life and their carers. A systematic review identified a lack of evidence on service delivery models and patient experiences of accessing medicines at end of life. A total of 1327 health-care professionals completed an online survey. The findings showed that general practitioners remain a predominant route for patients to access prescriptions, but nurses and primary care-based pharmacists are also actively contributing. However, only 42% of clinical nurse specialists and 27% of community nurses were trained as prescribers. The majority (58%) of prescribing nurses and pharmacists did not have access to an electronic prescribing system. Health-care professionals’ satisfaction with access to shared patient records to facilitate medicines access was low, with 39% of health-care professionals either not at all or only slightly satisfied. Respondents perceived that there would be a significant improvement in pain control if access to medicines was greater. Case studies (n = 4) highlighted differences in speed and ease of access to medicines between service delivery models. Health-care professionals’ co-ordination facilitated the access process. The work of co-ordination was frequently burdensome, for example because general practitioner services were hard to access or because the stock of community pharmacy medicines was unreliable. Prescription cost differentials between services were substantial when accounting for the eligible population over the medium term. The supply chain generally ensured stocks of palliative medicines, but this was underpinned by onerous work by community pharmacists navigating multiple complex systems and wholesaler interfaces. Patient records lacked sufficient detail for timelines to be constructed. Commissioners of community pharmacy services and wholesalers and distributors were difficult to recruit. Accessing medicines required considerable co-ordination work. Delays in access were linked to service delivery models that were over-reliant on general practitioners prescribing, unreliable stocks of community pharmacy medicines and clinical nurse specialists’ lack of access to electronic prescribing. Key issues were relationships and team integration, diversifying the prescriber workforce, access to shared records and improved community pharmacy stock. Further research should consider policy and practice action for nursing and pharmacy services to fulfil their potential to help patients access medicines, together with attention to improving co-ordination and shared electronic records across professional service interfaces. This study is registered as CRD42017083563 and the trial is registered as ISRCTN12762104. This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 20. See the NIHR Journals Library website for further project information.

Non-steroidal anti-inflammatory drugs (NSAIDs) in cancer pain: A database analysis to determine recruitment feasibility for a clinical trial

Abstract: Background: Insufficient evidence exists to support or refute use of NSAIDs for managing cancer pain. Palliative physicians support a placebo-controlled trial of NSAIDs as strong opioid adjuncts for cancer-induced bone pain as the most pragmatic design to benefit clinical practice. Aim: We aimed to determine patient numbers receiving palliative radiotherapy for cancer-induced bone pain, estimate the suitability of NSAID prescription and determine survival, guiding future trial feasibility. Design: A retrospective observational database analysis was undertaken using 5 years of routinely collected regional radiotherapy and healthcare data, filtered to achieve a cohort with cancer-induced bone pain. Demographics and survival were linked to available serology and co-morbidity data. Setting/participants: Data was sourced from the regional Leeds Cancer Centre, a tertiary care setting. Patients who underwent palliative single fraction 8 gray (Gy) radiotherapy treatment for cancer-induced bone pain were included, totalling 2411 over 5 years. Results: A mean of 478 patients received palliative radiotherapy for cancer-induced bone pain annually. Median age (IQR) was 70 (62–77); negatively skewed (−0.69). 65.3% died within 1 year of radiotherapy; 48.0% within 6 months. Age was not associated with survival on univariable analysis (HR 0.999 (95% CI 0.996–1.003)). Serology from 1063 patients (44.2%) were available; eGFR was ⩾60 mL/min/1.73 m2 in 83.0%. From available data (1352 pts; 51.6% of sample), 20.2% had a coded co-morbidity contra-indicating NSAIDs. Combining serology and co-morbidities, 68.5% could be considered for NSAID prescription. Conclusions: Patient numbers at a regional radiotherapy centre support the feasibility of trial recruitment. Available serology and co-morbidity data suggest two-thirds may be suitable for NSAID prescription.

Characteristics of good home-based end-of-life care: analysis of 5-year data from a nationwide mortality follow-back survey in England

Abstract: Background Recently, there has been an emphasis on providing good-quality end-of-life care; however, little is known about it and its determinants for patients living at home. Aim To determine what characterises good-quality end-of-life care for patients living at home. Design and setting An observational study using 5-year data from the National Survey of Bereaved People (Views of Informal Carers — Evaluation of Services [VOICES]) in England. Method Analysis was based on data for 63 598 decedents, who were cared for at home in the last 3 months of life. Data were drawn from 110 311 completed mortality follow-back surveys of a stratified sample of 246 763 deaths registered in England between 2011 and 2015. Logistic regression analyses were used to identify independent variables associated with overall quality of end-of-life care and other indicators of end-of-life care quality. Results Patients who received good continuity of primary care (adjusted odds ratio [AOR] 2.03; 95% confidence interval [CI] = 2.01 to 2.06) and palliative care support (AOR 1.86; 95% CI = 1.84 to 1.89) experienced better overall quality of end-of-life care than those who did not, as perceived by relatives. Decedents who died from cancer (AOR 1.05; 95% CI = 1.03 to 1.06) or outside of hospital were more likely to receive good end-of-life care, as perceived by relatives. Being older, female (AOR 1.16; 95% CI = 1.15 to 1.17), from areas with least socioeconomic deprivation, and White (AOR 1.09; 95% CI = 1.06 to 1.12) were associated with better overall end-of-life care, as perceived by relatives. Conclusion Better quality of end-of-life care was associated with good continuity of primary care, specialist palliative care support, and death outside of hospital. Disparities still exist for those from minority ethnic groups and those living in areas of socioeconomic deprivation. Future commissioning and initiatives must consider these variables to provide a more-equitable service.

Evaluation design of the patient-centred pathways of early palliative care, supportive ecosystems and appraisal standard (InAdvance): a randomised controlled trial

Abstract: Abstract Background Palliative care aims to contribute to pain relief, improvement with regard to symptoms and enhancement of health-related quality of life (HRQoL) of patients with chronic conditions. Most of the palliative care protocols, programmes and units are predominantly focused on patients with cancer and their specific needs. Patients with non-cancer chronic conditions may also have significantly impaired HRQoL and poor survival, but do not yet receive appropriate and holistic care. The traditional focus of palliative care has been at the end-of-life stages instead of the relatively early phases of serious chronic conditions. The ‘Patient-centred pathways of early palliative care, supportive ecosystems and appraisal standard’ (InAdvance) project implements and evaluates early palliative care in the daily clinical routine addressing patients with complex chronic conditions in the evolution towards advanced stages. The objective of the current study is to evaluate the acceptability, feasibility, effectiveness and cost-effectiveness of this novel model of palliative care in the relatively early phases in patients with chronic conditions. Methods In this study, a single blind randomised controlled trial design will be employed. A total of 320 participants (80 in each study site and 4 sites in total) will be randomised on a 1:1 basis to the Palliative Care Needs Assessment (PCNA) arm or the Care-as-Usual arm. This study includes a formative evaluation approach as well as a cost-effectiveness analysis with a within-trial horizon. Study outcomes will be assessed at baseline, 6 weeks, 6 months, 12 months and 18 months after the implementation of the interventions. Study outcomes include HRQoL, intensity of symptoms, functional status, emotional distress, caregiving burden, perceived quality of care, adherence to treatment, feasibility, acceptability, and appropriateness of the intervention, intervention costs, other healthcare costs and informal care costs. Discussion The InAdvance project will evaluate the effect of the implementation of the PCNA intervention on the target population in terms of effectiveness and cost-effectiveness in four European settings. The evidence of the project will provide step-wise guidance to contribute an increased evidence base for policy recommendations and clinical guidelines, in an effort to augment the supportive ecosystem for palliative care. Trial registration ISRCTN, ISRCTN24825698 . Registered 17/12/2020.

P-75 Non-steroidal anti-inflammatory drugs (NSAIDs) in cancer pain: testing patient eligibility for recruitment to a clinical trial

Abstract: Introduction Insufficient quality evidence exists to support or refute the use of non-steroidal anti-inflammatory drugs (NSAIDs) in the management of cancer pain. Palliative physicians support a placebo-controlled trial of NSAIDs as strong opioid adjuncts for cancer-induced bone pain (CIBP) as the most pragmatic design to benefit clinical practice. We aimed to determine the number, demographics and co-morbidities of palliative patients receiving radiotherapy for CIBP, guiding the feasibility of a future trial. Method Five years of retrospective radiotherapy data from the regional Leeds Cancer Centre was filtered (94% sensitive, 90% specific) to achieve a palliative cohort with CIBP. Demographics and survival were linked to available serology and co-morbidity data. Linear regression and descriptive statistics were used. Results Over five years, 2411 patients received palliative radiotherapy for CIBP in Leeds (mean 478 patients/year). Median age (IQR) was 70 (62–77); negatively skewed (0.69). More were male (58%). 61.8% died within 1 year of radiotherapy; 46.6% within 6 months. Age did not correlate with survival duration, r(1878) 0.015,p=0.51. A large minority (30.1%) underwent further radiotherapy on subsequent dates. During the 6 months prior to radiotherapy, serology from 1063 (44.2%) patients were available; eGFR was 90 mL/min/1.73m2 in 47.0% and 60 mL/min/ 1.73m2 in 83.0%. Similarly, a minority had markers of impaired synthetic liver function (platelets<150 109/L in 7.9%; bilirubin 21 in 3.4%; INR 1.2 in 20.5%), excluding hypoalbuminaemia (54.1%). From available data (51.6% of sample), 20.2% had a coded co-morbidity contra-indicating NSAID prescription. Combining serological (eGFR>60 mL/min/1.73m2) and contra-indicated co-morbidity data, 68.5% of this population could be considered for NSAID prescription. Conclusions Patient numbers at a single regional radiotherapy centre support the feasibility of trial recruitment. Available serology and co-morbidity data suggest two thirds may be suitable for NSAID prescription. This may be an underestimate, considering data limitations. Concerning survival post radiotherapy, NSAIDs could provide sustained benefit for this population if proven efficacious.

Oxycodone for cancer-related pain.

Abstract: BACKGROUND Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not effective for pain in all people, neither are they well tolerated by all people. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for adults with cancer pain. This is an updated Cochrane review previously published in 2017. OBJECTIVES To assess the effectiveness and tolerability of oxycodone by any route of administration for pain in adults with cancer. SEARCH METHODS For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), Embase (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), and PsycINFO (Ovid) to November 2021. We also searched four trial registries, checked the bibliographic references of relevant studies, and contacted the authors of the included studies. We applied no language, date, or publication status restrictions. SELECTION CRITERIA We included randomised controlled trials (parallel-group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults by examining pain intensity/relief, adverse events, quality of life, and participant preference. DATA COLLECTION AND ANALYSIS Two review authors independently sifted the search, extracted data and assessed the included studies using standard Cochrane methodology. We meta-analysed pain intensity data using the generic inverse variance method, and pain relief and adverse events using the Mantel-Haenszel method, or summarised these data narratively along with the quality of life and participant preference data. We assessed the overall certainty of the evidence using GRADE. MAIN RESULTS For this update, we identified 19 new studies (1836 participants) for inclusion. In total, we included 42 studies which enrolled/randomised 4485 participants, with 3945 of these analysed for efficacy and 4176 for safety. The studies examined a number of different drug comparisons. Controlled-release (CR; typically taken every 12 hours) oxycodone versus immediate-release (IR; taken every 4-6 hours) oxycodone Pooled analysis of three of the four studies comparing CR oxycodone to IR oxycodone suggest that there is little to no difference between CR and IR oxycodone in pain intensity (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.1 to 0.34; n = 319; very low-certainty evidence). The evidence is very uncertain about the effect on adverse events, including constipation (RR 0.71, 95% CI 0.45 to 1.13), drowsiness/somnolence (RR 1.03, 95% CI 0.69 to 1.54), nausea (RR 0.85, 95% CI 0.56 to 1.28), and vomiting (RR 0.66, 95% CI 0.38 to 1.15) (very low-certainty evidence). There were no data available for quality of life or participant preference, however, three studies suggested that treatment acceptability may be similar between groups (low-certainty evidence). CR oxycodone versus CR morphine The majority of the 24 studies comparing CR oxycodone to CR morphine reported either pain intensity (continuous variable), pain relief (dichotomous variable), or both. Pooled analysis indicated that pain intensity may be lower (better) after treatment with CR morphine than CR oxycodone (SMD 0.14, 95% CI 0.01 to 0.27; n = 882 in 7 studies; low-certainty evidence). This SMD is equivalent to a difference of 0.27 points on the Brief Pain Inventory scale (0-10 numerical rating scale), which is not clinically significant. Pooled analyses also suggested that there may be little to no difference in the proportion of participants achieving complete or significant pain relief (RR 1.02, 95% CI 0.95 to 1.10; n = 1249 in 13 studies; low-certainty evidence). The RR for constipation (RR 0.75, 95% CI 0.66 to 0.86) may be lower after treatment with CR oxycodone than after CR morphine. Pooled analyses showed that, for most of the adverse events, the CIs were wide, including no effect as well as potential benefit and harm: drowsiness/somnolence (RR 0.88, 95% CI 0.74 to 1.05), nausea (RR 0.93, 95% CI 0.77 to 1.12), and vomiting (RR 0.81, 95% CI 0.63 to 1.04) (low or very low-certainty evidence). No data were available for quality of life. The evidence is very uncertain about the treatment effects on treatment acceptability and participant preference. Other comparisons The remaining studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None found any clear superiority or inferiority of oxycodone for cancer pain, neither as an analgesic agent nor in terms of adverse event rates and treatment acceptability. The certainty of this evidence base was limited by the high or unclear risk of bias of the studies and by imprecision due to low or very low event rates or participant numbers for many outcomes. AUTHORS' CONCLUSIONS The conclusions have not changed since the previous version of this review (in 2017). We found low-certainty evidence that there may be little to no difference in pain intensity, pain relief and adverse events between oxycodone and other strong opioids including morphine, commonly considered the gold standard strong opioid. Although we identified a benefit for pain relief in favour of CR morphine over CR oxycodone, this was not clinically significant and did not persist following sensitivity analysis and so we do not consider this important. However, we found that constipation and hallucinations occurred less often with CR oxycodone than with CR morphine; but the certainty of this evidence was either very low or the finding did not persist following sensitivity analysis, so these findings should be treated with utmost caution. Our conclusions are consistent with other reviews and suggest that, while the reliability of the evidence base is low, given the absence of important differences within this analysis, it seems unlikely that larger head-to-head studies of oxycodone versus morphine are justified, although well-designed trials comparing oxycodone to other strong analgesics may well be useful. For clinical purposes, oxycodone or morphine can be used as first-line oral opioids for relief of cancer pain in adults.

The pharmacological management of cancer pain

Abstract: This chapter addresses methods and approaches to managing cancer pain. It begins with the assessment and classification of pain, then the principles that underpin effective pain management and the barriers that may prevent this from happening. A systemic approach to prescribing in cancer pain is included, then the chapter goes on to the methods and pharmacological interventions used. This includes non-opioids and weak opioids, and the administration of opioids and managing adverse effects. Switching to strong opioid alternatives or to morphine is explained, and then various opioids and their administration and management are described. Adjuvants, co-analgesics, steroids, anticonvulsants and antidepressants are all covered, and the chapter finishes with the key learning points.

A systematic review of subcutaneous versus intramuscular or intravenous routes of opioid administration on pain outcomes in cancer and post-surgical clinical populations – challenging current assumptions in palliative care practice

Abstract: Objective The objective of this review is to investigate the use of the subcutaneous route of administration of analgesics, common practice within palliative medicine. Design Systematic review using consensus approach, direct comparison of subcutaneous route with intravenous and intramuscular routes. Results The limited available evidence demonstrates non-inferiority of the subcutaneous route in both cancer patients and those post-surgery. Pain management is comparable to other routes. Route-related side effects are rare and systemic side effects are comparable. Conclusion Pain management is a critical role of palliative medicine. The subcutaneous route of administration offers a viable option for the delivery of parenteral analgesia within all settings, including the community. This review supports current practice, demonstrating equivalence with more invasive routes of administration.

P-77 How does age, sex, ethnicity and diagnosis affect the pain reported by palliative care patients in a hospice setting?

Abstract:

Introduction

Palliative care improves the quality of life, well-being and symptom control in patients with advanced disease. Globally only 14% of those in need are thought to receive palliative care. The most common symptom resulting in admission to a palliative care provider is uncontrolled pain. Regular use of symptom assessment measures such as the integrated palliative care outcome scale (IPOS) improves the identification and management of pain. Despite the benefits, the proportion of IPOS completion is around half of what it should be, and these rates are much lower in ethnic minority patients. This study compares the pain scores of patients according to their diagnosis, age, sex and ethnicity.

Methods

This study was an audit of pre-collected retrospective data from St Gemma’s hospice. The IPOS pain scores of 576 inpatients between 2019–20 were included. Exclusion criteria were patients with less than two recorded IPOS scores.

Results

There was a significant increase from initial to final pain in the total sample, non-cancer conditions, females and younger patients. As well as a non-significant greater increase in the pain of ethnic minority patients. Lung cancer patients experienced a non-significant reduction in pain.

Conclusions

High-quality UK based studies are required to expand on the current research demonstrating ethnic inequalities in pain assessment, management and care provision. The gender imbalance may be due to females more openly disclosing their needs, evidence also indicates that female pain is under-documented and overlooked by physicians. The lower pain levels reported by older patients has been attributed to their acceptance of pain as part of the end of life and willingness to reduce their activity levels as a result. The provision of care for chronic, terminal non-cancer diseases can be improved through early and sustained palliative intervention, that is offered without bias, based on clinical need.

Authors Reply to Letter to Editor

Abstract: We would like to thank the authors of the letter, entitled ‘The management of absolute iron deficient anaemia in the palliative care population: A reply to Neoh et al’ for their response to our article. We would like to provide the following in response. In our paper, we do not advocate that oral iron is avoided for treatment of absolute iron deficiency anaemia in the palliative care population. We give moderate weighting (‘solid empirical evidence from one or more papers/recommended in guidelines’) to not routinely using oral iron in managing palliative care patients, not absolute iron deficiency specifically. To support this recommendation, we discuss the effect of inflammation on raising hepcidin levels, with the consequent reduction in oral iron absorption, as is internationally agreed.1 Equally, we note the prevalence of inflammation amongst palliative patients, in the context of cancer and chronic diseases including congestive heart failure (CHF) and chronic kidney disease (CKD).1–4 Lewis et al.5 highlighted the clinical impact of this in CHF patients, in which a significant relationship between higher baseline hepcidin levels and lack of iron repletion orally was noted. Similar evidence exists in oncology cohorts, with ESMO guidelines recommending IV iron in all but those with a ferritin <30 ng/mL and non-inflammatory conditions (CRP <5 mg/L).3,4 The British Society of Gastroenterology (BSG) guidelines acknowledge that parenteral iron replacement therapy may be “preferable from the outset in those with. . .the combination of iron deficiency and anaemia of inflammation”.6 We believe, considering the prevalence of inflammation amongst palliative cohorts, significant doubt regarding the absorption of oral iron remains. We acknowledge the lack of studies in specific palliative care populations, and agree the need for further research to progress understanding in this area. We would challenge the assertion that the majority of participants in the Lewis et al.’s trial had functional iron deficiency. The clear distinction between absolute, functional, and mixed iron deficiency remains challenging biochemically, although serum ferritin of <30 μg/L is generally accepted to be indicative of low body iron stores (absolute iron deficiency).6 In the context of systemic inflammation and its consequent effects on ferritin, it cannot be assumed that a median ferritin of 69 ng/mL (IQR, 40–98) and median transferring saturation (Tsat) of 18% (IQR, 15%–22%) is diagnostic of FID.5,7 Other serological markers are generally required to guide diagnosis, alongside a determination of inflammation or chronic illness clinically.6,7 Guideline recommendations vary concerning thresholds for ferritin and Tsat, adding to the complexity of diagnosis.6,7 For example, it is argued a Tsat of <20% can be indicative of absolute iron deficiency if serum ferritin is 100–300 μg/L, as seen in chronic inflammatory conditions.1,8 Other sources use a Tsat of <16% to support this diagnosis.7 Considering the concern regarding iron doses used by Lewis et al.,5 we would agree that work by Stoffel et al.9,10 would advocate a lower oral iron dose for replacement if oral replacement is being considered. Of note however, the populations in the Stoffel et al.9,10 trials are similarly divergent from general palliative care populations (e.g. age 18–45 years, female patients only recruited). Importantly, those with inflammation (defined as a CRP >5 mg/L) or chronic disease were specifically excluded.9,10 This supports international assertion of the impact of inflammation on oral iron absorption.1 Equally, Stoffel et al.’s9,10 findings support the principle that raised hepcidin levels affect enteral absorption, regardless of mechanism by which it is raised. To conclude, we advocate guideline-supported investigation of anaemia for palliative care patients (acknowledging the complexities of identifying underlying aetiology or aetiologies), tailoring treatment from results. Systemic inflammation is common in the palliative population, impairing enteral iron absorption. Consequently, routine use of oral iron should be avoided. If a trial of oral iron is Authors Reply to Letter to Editor