Understanding barriers and facilitators to palliative and end-of-life care research: a mixed method study of generalist and specialist health, social care, and research professionals.

BACKGROUND: Palliative care provision should be driven by high quality research evidence. However, there are barriers to conducting research. Most research attention focuses on potential patient barriers; staff and organisational issues that affect research involvement are underexplored. The aim of this research is to understand professional and organisational facilitators and barriers to conducting palliative care research. METHODS: A mixed methods study, using an open cross-sectional online survey, followed by working groups using nominal group techniques. Participants were professionals interested in palliative care research, working as generalist/specialist palliative care providers, or palliative care research staff across areas of North West England. Recruitment was via local health organisations, personal networks, and social media in 2022. Data were examined using descriptive statistics and content analysis. RESULTS: Participants (survey n = 293, working groups n = 20) were mainly from clinical settings (71%) with 45% nurses and 45% working more than 10 years in palliative care. 75% were not active in research but 73% indicated a desire to increase research involvement. Key barriers included lack of organisational research culture and capacity (including prioritisation and available time); research knowledge (including skills/expertise and funding opportunities); research infrastructure (including collaborative opportunities across multiple organisations and governance challenges); and patient and public perceptions of research (including vulnerabilities and burdens). Key facilitators included dedicated research staff, and active research groups, collaborations, and networking opportunities. CONCLUSIONS: Professionals working in palliative care are keen to be research active, but lack time, skills, and support to build research capabilities and collaborations. A shift in organisational culture is needed to enhance palliative care research capacity and collaborative opportunities across clinical and research settings.

New analgesics in cancer pain.

PURPOSE OF REVIEW: Cancer pain continues to be a significant problem despite the range of analgesic and adjuvant medications available. The purpose of this review is to explore the most recent developments in the management of cancer pain. RECENT FINDINGS: Tapentadol, launched in the United Kingdom in May 2011, represents the last new analgesic entity with a novel mode of action to enter clinical practice for moderate-to-severe pain. Recent evidence describes the benefit of duloxetine for cancer-related neuropathic pain, and parecoxib by continuous subcutaneous infusion for refractory cancer pain. There is interest in the role of cannabinoids in cancer pain management but much of the evidence to date is in chronic noncancer pain. Conflicting evidence complicates the role that biased opioid agonism may offer in terms of alternative analgesics in the future. SUMMARY: There is development of new drugs with clinical utility on the horizon but a need for high-quality, randomized controlled trials specifically assessing efficacy and tolerability in cancer pain.

MASCC multidisciplinary evidence-based recommendations for the management of malignant bowel obstruction in advanced cancer.

PURPOSE: To provide evidence-based recommendations on the management of malignant bowel obstruction (MBO) for patients with advanced cancer. METHODS: The Multinational Association for Supportive Care in Cancer (MASCC) MBO study group conducted a systematic review of databases (inception to March 2021) to identify studies about patients with advanced cancer and MBO that reported on the following outcomes: symptom management, bowel obstruction resolution, prognosis, overall survival, and quality of life. The review was restricted to studies published in English, but no restrictions were placed on publication year, country, and study type. As per the MASCC Guidelines Policy, the findings were synthesized to determine the levels of evidence to support each MBO intervention and, ultimately, the graded recommendations and suggestions. RESULTS: The systematic review identified 17,656 published studies and 397 selected for the guidelines. The MASCC study group developed a total of 25 evidence-based suggestions and recommendations about the management of MBO-related nausea and vomiting, bowel movements, pain, inflammation, bowel decompression, and nutrition. Expert consensus-based guidance about advanced care planning and psychosocial support is also provided. CONCLUSION: This MASCC Guideline provides comprehensive, evidence-based recommendations about MBO management for patients with advanced cancer.

MASCC recommendations on the management of constipation in patients with advanced cancer.

PURPOSE: The Palliative Care Study Group of the Multinational Association for Supportive Care in Cancer formed a subgroup to develop evidence-based recommendations on the management of constipation in patients with advanced cancer. METHODS: These recommendations were developed in accordance with the MASCC Guidelines Policy. A search strategy for Medline was developed, and the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were explored for relevant reviews/trials respectively. The recommendations were categorised by the level of evidence and a "category of guideline" based on the level of evidence (i.e. "recommendation", "suggestion", or "no guideline possible"). RESULTS: The group produced 15 recommendations, with varying levels of evidence and so varying categories of guideline. The recommendations relate to the assessment, the treatment, and the re-assessment of constipation. CONCLUSIONS: These recommendations provide a framework for the management of constipation in advanced cancer, although every patient needs individualised management.

The current evidence base for the feasibility of 48-hour continuous subcutaneous infusions (CSCIs): A systematically-structured review.

BACKGROUND: A continuous subcutaneous infusion (CSCI) is an effective method of multiple drug administration commonly encountered in end of life care when the oral route is compromised. At present, current practice is to limit syringe driver infusion time to a maximum of 24 hours as dictated by available chemical stability data. However, the ability to deliver prescribed medication by a CSCI over 48 hours may have numerous benefits in both patient care and health service resource utilisation. AIM: To examine and present the current evidence base for the stability of 48-hour multiple-drug CSCIs in current clinical practice. DESIGN: A systematically-structured review following PRISMA guidelines. DATA SOURCES: Three electronic databases and the grey literature were searched with no time limits. Empirical studies reporting data on the chemical stability of continuous subcutaneous infusions or solutions stored in polypropylene syringes were included. RESULTS: Twenty-one empirical studies were included in this review reporting chemical compatibility and stability of 32 discrete combinations of twenty-four drugs tested at a variety of different drug concentrations. The majority of combinations reported were assessed as being chemically compatible. The greatest risk of clinically significant chemical degradation was observed with midazolam. Only one study reported the microbiological stability of the solution examined. CONCLUSIONS: There is currently limited evidence for the physical, chemical and microbiological stability of solutions for continuous subcutaneous infusion over a period of 48 hours. More stability data is required before the use of 48-hour CSCIs can be evaluated for use within clinical practice.

Updates in palliative care - overview and recent advancements in the pharmacological management of cancer pain.

Pain is a common symptom in many types of cancer. Interdisciplinary team management, including pain assessment, explanation to the patient/family, treating the reversible, non-pharmacological treatments and reassessment are essential. This article focuses on the pharmacological management of cancer pain, and overviews and updates on the recent advances in this field. Both non-opioid and opioid analgesia as well as coanalgesics (adjuvants) are reviewed. Within non-opioid analgesia the risks of non-steroidal anti-inflammatory drugs (NSAIDs) are considered and recommendations for NSAIDs in patients at risk of gastrointestinal and cardiovascular toxicity are made. For opioid analgesics, side effects of opioids are discussed alongside practical guidance on opioid prescribing and converting between opioids. Newer drugs such as tapentadol are considered in this update. Amitriptyline, duloxetine, gabapentin and pregabalin, and the guidance for their use are reviewed in the coanalgesics (adjuvants) section.

Identification of drug combinations administered by continuous subcutaneous infusion that require analysis for compatibility and stability.

BACKGROUND: A continuous subcutaneous infusion (CSCI) delivered via syringe pump is a method of drug administration used to maintain symptom control when a patient is no longer able to tolerate oral medication. Several classes of drugs, such as opioids, antiemetics, anticholinergics, antipsychotics and benzodiazepines are routinely administered by CSCI alone or in combinations. Previous studies attempting to identify the most-common CSCI combinations are now several years old and no longer reflect current clinical practice. The aim of this work was to review current clinical practice and identify CSCI drug combinations requiring analysis for chemical compatibility and stability. METHODS: UK pharmacy professionals involved in the delivery of care to palliative patients in hospitals and hospices were invited to enter CSCI combinations comprised of two or more drugs onto an electronic database over a 12-month period. In addition, a separate Delphi study with a panel of 15 expert healthcare professionals was completed to identify a maximum of five combinations of drugs used to treat more complex, but less commonly encountered symptoms unlikely to be identified by the national survey. RESULTS: A total of 57 individuals representing 33 separate palliative care services entered 1,945 drug combinations suitable for analysis, with 278 discrete combinations identified. The top 40 drug combinations represented nearly two-thirds of combinations recorded. A total of 23 different drugs were administered in combination and the median number of drugs in a combination was three. The Delphi study identified five combinations for the relief of complex or refractory symptoms. CONCLUSION: This study represents the first step towards developing authoritative national guidance on the administration of drugs by CSCI. Further work will ensure healthcare practitioners have the knowledge and confidence that a prescribed combination will be both safe and efficacious.

Four essential drugs needed for quality care of the dying: a Delphi-study based international expert consensus opinion.

PURPOSE: The majority of dying patients do not have access to necessary drugs to alleviate their most common symptoms, despite evidence of drug efficacy. Our aim was to explore the degree of consensus about appropriate pharmacological treatment for common symptoms in the last days of life for patients with cancer, among physicians working in specialist palliative care. MATERIAL AND METHODS: Within OPCARE9, a European Union seventh framework project aiming to optimize end-of-life cancer care, we conducted a Delphi survey among 135 palliative care clinicians in nine countries. Physicians were initially asked about first and second choice of drugs to alleviate anxiety, dyspnea, nausea and vomiting, pain, respiratory tract secretions (RTS), as well as terminal restlessness. RESULTS: Based on a list of 35 drugs mentioned at least twice in the first round (n=93), a second Delphi round was performed to determine ≤ 5 essential drugs for symptom alleviation in the last 48 hours of life that should be available even outside specialist palliative care. There was ≥ 80% consensus among the participants (n=90) regarding morphine, midazolam, and haloperidol as essential drugs. For RTS, there was consensus about use of an antimuscarinic drug, with 9%-27% of the physicians each choosing one of four different drugs. CONCLUSION: Based on this consensus opinion and other literature, we suggest four drugs that should be made available in all settings caring for dying patients with cancer, to decrease the gap between knowledge and practice: morphine (i.e., an opioid), midazolam (a benzodiazepine), haloperidol (a neuroleptic), and an antimuscarinic.

Complexity in non-pharmacological caregiving activities at the end of life: an international qualitative study.

BACKGROUND: In late-stage palliative cancer care, relief of distress and optimized well-being become primary treatment goals. Great strides have been made in improving and researching pharmacological treatments for symptom relief; however, little systematic knowledge exists about the range of non-pharmacological caregiving activities (NPCAs) staff use in the last days of a patient's life. METHODS AND FINDINGS: Within a European Commission Seventh Framework Programme project to optimize research and clinical care in the last days of life for patients with cancer, OPCARE9, we used a free-listing technique to identify the variety of NPCAs performed in the last days of life. Palliative care staff at 16 units in nine countries listed in detail NPCAs they performed over several weeks. In total, 914 statements were analyzed in relation to (a) the character of the statement and (b) the recipient of the NPCA. A substantial portion of NPCAs addressed bodily care and contact with patients and family members, with refraining from bodily care also described as a purposeful caregiving activity. Several forms for communication were described; information and advice was at one end of a continuum, and communicating through nonverbal presence and bodily contact at the other. Rituals surrounding death and dying included not only spiritual/religious issues, but also more subtle existential, legal, and professional rituals. An unexpected and hitherto under-researched area of focus was on creating an aesthetic, safe, and pleasing environment, both at home and in institutional care settings. CONCLUSIONS: Based on these data, we argue that palliative care in the last days of life is multifaceted, with physical, psychological, social, spiritual, and existential care interwoven in caregiving activities. Providing for fundamental human needs close to death appears complex and sophisticated; it is necessary to better distinguish nuances in such caregiving to acknowledge, respect, and further develop end-of-life care.

Educational interventions by pharmacists to patients with chronic pain: systematic review and meta-analysis.

OBJECTIVE: We hypothesized that educational interventions delivered by pharmacists to patients with chronic pain might improve pain-related outcomes and sought to establish "proof of concept" for this hypothesis. METHODS: We searched electronic databases and published literature for randomized studies that examined an educational intervention in relation to the management of chronic pain that was delivered by a pharmacist to an adult patient. Four studies were included that randomized 400 patients with chronic pain and which followed up patients between 1 and 16 weeks. RESULTS: Patients receiving these interventions experienced statistically significant benefits in the following outcomes compared with controls: a reduction in average pain intensity of 0.5 on a 0 to 10 rating scale, a reduction in adverse effects by more than 50%, and an improvement in satisfaction with treatment equivalent to approximately 1 point on a 0 to 10 rating scale. The interventions neither had effect on reducing interference from pain on daily life, nor on improving self-efficacy. DISCUSSION: Pharmacist-delivered educational interventions seem to reduce adverse events and improve satisfaction, but their clinical benefit on pain intensity is debatable. Our analysis suggests that the role of pharmacists may be important but a deeper understanding and evaluation of the active components of these interventions is needed within clinical trials before wider implementation into clinical practice can be recommended.

Integrated strategies for the successful management of breakthrough cancer pain.

PURPOSE OF REVIEW: To highlight the significant impact breakthrough cancer pain (BTcP) can have on patients' quality of life and to discuss potential management strategies that could improve pain control in clinical practice as well as effective strategies to manage risk. RECENT FINDINGS: BTcP can place a significant physical, psychological and economic burden on patients. Despite advances in the management of cancer pain, through the application of modern, evidence-based, multimodality management and the availability of new treatment options, recent European surveys have indicated that the diagnosis and treatment of BTcP is still suboptimal. A general lack of consensus on its definition alongside poor recognition and inadequate assessment may often lead to undertreatment and poor patient outcomes. Fentanyl preparations that have been developed and licensed specifically for the treatment of BTcP have been shown to work more rapidly and be preferred by patients to traditional rescue medication, such as normal-release oral opioids. SUMMARY: Optimizing the management of BTcP requires an integrated approach, including independent assessment and better use of available treatments while taking into consideration risk management strategies, which will ultimately lead to improved outcomes and quality of life for patients.

The management of cancer-related breakthrough pain: recommendations of a task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland.

A task group of the Science Committee of the Association for Palliative Medicine of Great Britain and Ireland (APM) was convened to produce some up-to-date, evidence-based, practical, clinical guidelines on the management of cancer-related breakthrough pain in adults. On the basis of a review of the literature, the task group was unable to make recommendations about any individual interventions, but was able to make a series of 12 recommendations about certain generic strategies. However, most of the aforementioned recommendations are based on limited evidence (i.e., case series, expert opinion). The task group also proposed a definition of breakthrough pain, and some diagnostic criteria for breakthrough pain.

Use and practice implications of modified-release medicines.

Modified-release drugs have complex formulations and require extra care to ensure safe prescribing and administration. This article discusses the use of modified-release preparations and highlights their practice implications.

NSAIDs: gastroprotection or selective COX-2 inhibitor?

Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are effective adjuvant analgesics commonly encountered in palliative care. However, these drugs are associated with adverse effects that are primarily due to gastrointestinal toxicity, with resultant serious complications such as gastroduodenal perforations, ulcers and bleeds. This toxicity has been attributed to inhibition of cyclooxygenase-1 (COX-1). Factors known to increase this risk of toxicity include age above 65 years, classification of NSAID in terms of COX-1/COX-2 selectivity, previous history of complications and coadministration of aspirin, anticoagulants and corticosteroids. Selective inhibitors of cyclooxygenase-2 (COX-2) were developed in an attempt to reduce this association; trials to date confirm that these drugs do indeed have reduced incidence of gastroduodenal toxicity. Prior to the introduction of the COX-2 selective inhibitors, patients at high risk were often coprescribed a gastroprotective agent (such as misoprostol or a proton pump inhibitor) with a conventional NSAID. This review discusses the merits of both options and devises a treatment strategy for the safe and cost-effective use of these drugs in the palliative care population.