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Background: Radiotherapy (RT) reduces pain in about 60% of patients with painful bone metastases, leaving many patients without clinical benefit. This study assesses predictors for RT effectiveness in patients with painful bone metastases.Materials and Methods: We included adult patients receiving RT for painful bone metastases in a multicenter, multinational longitudinal observational study. Pain response within 8 weeks was defined as ≥2-point decrease on a 0-10 pain score scale, without increase in analgesics; or a decrease in analgesics of ≥25% without increase in pain score. Potential predictors were related to patient demographics, RT administration, pain characteristics, tumor characteristics, depression and inflammation (C-reactive protein [CRP]). Multivariate logistic regression analysis with multiple imputation of missing data were applied to identify predictors of RT response.Results: Of 513 eligible patients, 460 patients (90 %) were included in the regression model. 224 patients (44%, 95% confidence interval (CI) 39%-48%) responded to RT. Better Karnofsky performance status (Odds ratio (OR) 1.39, CI 1.15-1.68), breast cancer (OR 2.54, CI 1.12-5.73), prostate cancer (OR 2.83, CI 1.27-6.33) and soft tissue expansion (OR 2.00, CI 1.23-3.25) predicted RT response. Corticosteroids were a negative predictor (OR 0.57, CI 0.37-0.88). Single and multiple fraction RT had similar response. The discriminative ability of the model was moderate; C-statistic 0.69.Conclusion: This study supports previous findings that better performance status and type of cancer diagnosis predicts analgesic RT response, and new data showing that soft tissue expansion predicts RT response and that corticosteroids is a negative predictor for RT response in patients with painful bone metastases. [ABSTRACT FROM AUTHOR]

Context: Patients with cancer often experience distressing symptoms such as anxiety or dyspnea, which can be managed with benzodiazepines; however, concerns regarding the impact of these drugs on survival may dissuade prescribing and compliance.Objectives: We aimed to identify and appraise studies examining benzodiazepine use and survival in adults with cancer, to investigate the relationship and context of use.Methods: Systematic review of the international literature prepared according to preferred reporting items for systematic reviews. Comprehensive searches of the MEDLINE, Embase, PsycINFO, Cochrane Library, and AMED databases using medical subject heading and free-text search combinations with no date or language restrictions were undertook. Handsearching of references was conducted. Risk of bias of the included studies was assessed using Grading of Recommendations Assessment, Development, and Evaluation criteria.Results: Two thousand two hundred fifty-seven unique records were identified, with 18 meeting inclusion criteria, representing 4117 patients. All studies were very low quality. No study found an increase in mortality in association with benzodiazepine use, whereas two demonstrated an increase.Conclusion: Existing evidence shows no association between benzodiazepine use in patients with cancer and decreased survival. None of the studies evaluated the association between benzodiazepine use and survival in earlier stages of cancer, and the quality of studies retrieved signifies a need for further robust studies to draw more definitive conclusions. Further investigation in patients with cancer using well-designed, high-quality research with survival as a primary outcome should be conducted. [ABSTRACT FROM AUTHOR]

Introduction: Patients with cluster headache (CH), the most common trigeminal autonomic cephalalgia, often face delayed diagnosis, misdiagnosis and mismanagement.Objectives: To identify, appraise and synthesise clinical studies on the delays in diagnosis and misdiagnosis of CH in order to determine its causes and help the management of this condition.Methods: The systematic review was prepared, conducted and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis. It was registered with International Prospective Register of Systematic Reviews. A systematic search of different electronic databases (Medline, EMBASE, PsycINFO, PubMed, CINAHL, BNI, HMIC, AMED, HBE and Cochrane Library) was carried out in May 2017. Reference lists of relevant articles were hand searched.Results: The search identified 201 unique studies. Fifteen studies met the inclusion criteria of which 13 case series studies and two survey studies. Nine studies assessed the delays in diagnosis and misdiagnosis of CH, five studies the delays in diagnosis and one study the misdiagnosis of CH. The studies included 4661 patients. Delays in diagnosis, misdiagnosis and mismanagement have been reported in many European countries, Japan and in the USA with well-developed health services. The patients with CH often visited many different clinicians, surgeons and dentists and received multiple diagnosis prior to being correctly diagnosed.Conclusion: This systematic review shows that the delays in the diagnosis of CH are a widespread problem, the time to diagnosis still vary from country to country and both patients and physicians are responsible for the delays in diagnosis. [ABSTRACT FROM AUTHOR]

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 fi eld. Both non-opioid and opioid analgesia as well as coanalgesics (adjuvants) are reviewed. Within non-opioid analgesia the risks of non-steroidal antiinfl ammatory 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. [ABSTRACT FROM AUTHOR]

Context: Opioids are prescribed to manage moderate-to-severe pain and can be used with older adults; however, they may lead to several adverse effects, including cognitive impairment.Objectives: To identify, appraise, and synthesize evidence on the impact of opioids on cognition in older adults with cancer/chronic noncancer pain, and screening tools/neuropsychological assessments used to detect opioid-induced cognitive impairment.Methods: A systematic literature review following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (international prospective register of systematic reviews registration: CRD42018092943). MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Library, and Web of Science were searched up to December 2018. Randomized controlled trials, quasi-experimental studies, and observational studies of adults aged 65 years and older with cancer/chronic noncancer pain taking opioids were included. A narrative synthesis was conducted.Results: From 4036 records, 10 met inclusion criteria. Five studies used one screening tool, and five studies used a range of neuropsychological assessments; assessing 14 cognitive domains. Most studies demonstrated no effect of opioid use on cognitive domains, whereas four studies showed mixed effects. In particular, attention, language, orientation, psychomotor function, and verbal working/delayed episodic memory were worsened. Changes to cognitive function were predominantly observed in studies with higher mean doses of opioids (120-190.7mg oral morphine equivalent daily dose).Conclusion: Both improvements and impairments to cognition were observed in studies with higher mean opioid doses. In clinical practice, a brief screening tool assessing attention, language, orientation, psychomotor function, and verbal working/delayed episodic memory may be beneficial to detect worsening cognition in older adults with chronic pain using opioids. [ABSTRACT FROM AUTHOR]

Background: Radiation therapy (RT) results in pain relief for about 6 of 10 patients with cancer induced bone pain (CIBP) caused by bone metastases. The high number of non-responders, the long median time from RT to pain response and the risk of adverse effects, makes it important to determine predictors of treatment response. Clinical features such as cancer type, performance status and pain intensity, and biomarkers for osteoclast activity are proposed as predictors of response to RT. However, results are inconsistent and there is a need for better predictors of RT response. A similar argument can be stated for the development of cachexia; there are currently no predictors that can identify patients who will develop cachexia later in the cancer disease trajectory. Experimental and preclinical studies show that pain, depression and cachexia are related to inflammation. However, it is not known if inflammatory biomarkers can predict CIBP, depression or development of cachexia. Methods: This multicenter, multinational longitudinal observational study will include 600 adult patients receiving RT for CIBP. Demographic data, clinical variables, osteoclast and inflammatory biomarkers will be assessed before start of RT, and 3, 8, 16, 24 and 52 weeks after last course of RT. The primary aim of the study is to identify potential predictors for pain relief from RT. Secondary aims are to explore potential predictors for development of cachexia, the longitudinal relationship between pain intensity and depression, and if inflammatory biomarkers are associated with changes in pain intensity, cachexia and depression during one-year follow up. Discussion: The immediate clinical implication of the PRAIS study is to identify potential predictive factors for a RT response on CIBP, and thereby reduce non-efficacious RT. Patient benefits are fewer hospital visits, reduced risk of adverse effects and more individualized pain treatment. The long-term clinical implication of the PRAIS study is to improve the knowledge about inflammation in relation to CIBP, cachexia and depression and potentially identify associations and mechanisms that can be targeted for treatment. Trial registration: ClinicalTrials.gov NCT02107664, date of registration April 8, 2014 (retrospectively registered). Trial sponsor: The European Palliative Care Research Centre (PRC), Department of Clinical and Molecular Medicine, NTNU, Faculty of medicine and Health Sciences, Trondheim, N-7491, Norway. [ABSTRACT FROM AUTHOR]

Context: Somatostatin analogues are commonly used to relieve symptoms in malignant bowel obstruction (MBO) but are more expensive than other antisecretory agents.Objectives: To evaluate the evidence of effectiveness of somatostatin analogues compared with placebo and/or other pharmacologic agents in relieving vomiting in patients with inoperable MBO.Methods: MEDLINE, EMBASE, CINAHL, and The Cochrane Controlled Trials Register databases were systematically searched; reference lists of relevant articles were hand searched. Cochrane risk of bias tool was used.Results: The search identified 420 unique studies. Seven randomized controlled trials (RCTs) met the inclusion criteria (six octreotide studies and one lanreotide); 220 people administered somatostatin analogues and 207 placebo or hyoscine butylbromide. Three RCTs compared a somatostatin analogue with placebo and four with hyoscine butylbromide. Two adequately powered multicenter RCTs with a low Cochrane risk of bias reported no significant difference between somatostatin analogues and placebo in their primary end points. Four RCTs with a high/unclear Cochrane risk of bias reported that somatostatin analogues were more effective than hyoscine butylbromide in reducing vomiting.Conclusion: There is low-level evidence of benefit with somatostatin analogues in the symptomatic treatment of MBO. However, high-level evidence from trials with low risk of bias found no benefit of somatostatin analogues for their primary outcome. There is debate regarding the clinically relevant study end point for symptom control in MBO and when it should be measured. The role of somatostatin analogues in this clinical situation requires further adequately powered, well-designed trials with agreed clinically important end points and measures. [ABSTRACT FROM AUTHOR]

Purpose: The importance and effectiveness of palliative care (PC) in intensive care units (ICU) are known. Less is known about the implementation and integration of ICU-based PC interventions. This systematic review aims to use a modified implementation research logic model (IRLM) to identify, map, and synthesise evidence on implementation of ICU-PC (primary and/or specialist) interventions., Methods: This systematic review used an adapted Smith's IRLM to understand relationships between implementation factors-determinants (barriers and facilitators), strategies, and mechanisms-and report intervention characteristics and outcomes. Searches up to 2nd December 2023, of MEDLINE, Embase, Cochrane, CINAHL, and PsycINFO, combined PC, intensive care, and implementation terms., Results: 84 studies (8 process evaluations, 76 effectiveness studies) were included. Published evidence on ICU-PC interventions is substantial, but reporting on implementation factors is variable and often lacking, especially for patient and family-related determinants and for all aspects of mechanisms. Main facilitators for implementation are adequate resources and collaboration between PC and ICU teams. Main barriers to implementation are lack of resources, negative perceptions of PC, and high ICU acuity. Implementation strategies include auditing resources, building stakeholder collaboratives, creating adaptable interventions, utilising champions, and supporting education. Mechanisms most commonly worked by facilitating collaborative working., Conclusion: This review provides recommendations for ICUs when designing (stakeholder involvement, ICU-PC collaboration, assessment of culture and resources); implementing (targeted and adapted strategies, champions, and education); and evaluating/reporting (collect effectiveness and implementation data, including mechanisms) ICU-PC interventions. Use of implementation structures and patient/family involvement are both needed and important to be included., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The COVID-19 pandemic impacted the Foundation Programme for doctors in the United Kingdom. Foundation doctors were working under increased pressure and significant changes were made to their training., Aims: The aim of this study is to explore the educational impact the COVID-19 pandemic had on foundation doctors and to understand how this resulted in doctors choosing to take time away from structured training programmes within the United Kingdom to make up for lost educational opportunities., Methods: In this phenomenological research, semi-structured interviews were carried out with post-foundation doctors who had completed their training during the pandemic. The data collected from these interviews were coded to carry out a thematic analysis., Results: All 12 participants reported that their formalised teaching had been cancelled, and due to the pandemic, many doctors felt that service provision was prioritised over their postgraduate education. Some doctors had positive experiences of informal teaching; however, many felt they missed out on educational opportunities. Doctors acknowledged that this was a contributing factor when deciding to take time out of training. This also resulted in doctors seeking educational opportunities outside of training., Discussion: The pandemic created many educational challenges for foundation doctors; this has contributed to doctors deciding to take time away from training. In some cases, due to a focus on service provision and their 'lost education', doctors are using time away from training to address their own specific educational needs. The impact of this 'lost education' requires further research and needs to be considered when doctors do apply to speciality training., (© 2023 The Authors. The Clinical Teacher published by Association for the Study of Medical Education and John Wiley & Sons Ltd.)

Background: Delirium is a complex condition, stressful for all involved. Although highly prevalent in palliative care settings, it remains underdiagnosed and associated with poor outcomes. Guideline-adherent delirium care may improve its detection, assessment and management., Aim: To inform a future definitive study that tests whether an implementation strategy designed to improve guideline-adherent delirium care in palliative care settings improves patient outcomes (reduced proportion of in-patient days with delirium)., Design: With Patient Involvement members, we conducted a feasibility study to assess the acceptability of and engagement with the implementation strategy by hospice staff (intervention), and whether clinical record data collection of process (e.g. guideline-adherent delirium care) and clinical outcomes (evidence of delirium using a validated chart-based instrument;) pre- and 12-weeks post-implementation of the intervention would be possible., Setting/participants: In-patient admissions in three English hospices., Results: Between June 2021 and December 2022, clinical record data were extracted from 300 consecutive admissions. Despite data collection during COVID-19, target clinical record data collection ( n  = 300) was achieved. Approximately two-thirds of patients had a delirium episode during in-patient stay at both timepoints. A 6% absolute reduction in proportion of delirium days in those with a delirium episode was observed. Post-implementation improvements in guideline-adherent metrics include: clinical delirium diagnosis 15%-28%; delirium risk assessment 0%-16%; screening on admission 7%-35%., Conclusions: Collection of data on delirium outcomes and guideline-adherence from clinical records is feasible. The signal of patient benefit supports formal evaluation in a large-scale study., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Higher specialty trainees are expected to achieve clinical and non-clinical skills during training in preparation for a consultant role. However, evidence from many specialties from different countries suggests that new consultants are less prepared in non-clinical skills. The transition from trainee to a consultant phase can be challenging. The study aims to identify if new UK Palliative Medicine consultants, within 5 years of their appointment, feel prepared in clinical and non-clinical skills after completing specialty training and understand the support available for them., Method: An online survey, designed using previous literature, was distributed via the Association for Palliative Medicine email and social media. Five-point Likert scales and drop-down options to record preparedness were used. Ethics approval was obtained., Results: Forty-four participants from different UK regions completed the survey; 80% were female. The majority felt very/extremely prepared in audit (84%), clinical skills (71%), interaction with colleagues (70%). Majority moderate preparation was human resources (50%), organisation structure (68%) and leadership (52%). Most were not at all or slightly prepared in financial management (70%) and in complaint management (43%). The majority (75%) reported that departmental colleagues gave the most support in stressful situations but almost 49% did not have formal support., Conclusion: New palliative medicine consultants require support with some non-clinical roles such as management of complaints and finances. This is consistent with findings from other specialties. New consultants would benefit from formal support. Future research could focus on how trainees could be supported to gain more experience in non-clinical domains., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Malignant bowel obstruction is a distressing complication of cancer, causing pain, nausea and vomiting, and often has a poor prognosis. Severe and rapidly developing symptoms, a lack of robust clinical guidelines and the need for multidisciplinary input make treatment decision-making challenging. Sharing decision-making with people with malignant bowel obstruction and their caregivers can be difficult, and inconsistent communication creates serious deficiencies in care by amplifying patients' distress and uncertainty. Little attention has been paid to the implicit influences on this process-for example, the role of discipline-related norms and the beliefs of decision-makers. This study will explore how these processes work and develop interventions to improve shared decision-making., Methods and Analysis: Exploring Pathways to Optimise Care (EPOC) is a three-phase study set within a critical realist framework: (i) realist review, to develop explanatory theory describing collaborative decision-making in the management of malignant bowel obstruction; (ii) an in-depth interview study using modified grounded theory to explore the active ingredients of this collaboration in practice settings; and (iii) the presentation to stakeholders (practitioners, patients and caregivers) of integrated results from Phase I (theory developed from the literature) and Phase II (theory developed from current practice) as a basis for intervention mapping. We aim to produce recommendations to address the challenges, and to develop a set of tools to (i) aid interaction around shared decision-making and (ii) aid interprofessional interaction around the management of this condition. Registration details: The realist review is registered with PROSPERO (CRD42022308251)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Bravington et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: To describe the current, real-world use of non-steroidal anti-inflammatory drugs for pain and the associated benefits and harms., Methods: A prospective, multicentre, consecutive cohort pharmacovigilance study conducted at 14 sites across Australia, Aotearoa/New Zealand and the UK including hospital, hospice inpatient and outpatient services. Pain scores and harms were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events at baseline, 2 days and 14 days. Ad-hoc safety reporting continued until day 28., Results: Data were collected from 92 patients between March 2018 and October 2021. Most patients had cancer (91%) and were coprescribed opioids (90%). At 14 days, 83% of patients had benefit from non-steroidal anti-inflammatory drugs and 22% had harm. The most common harms were nausea (8%), vomiting (3%), acute kidney injury (3%) and non-gastrointestinal bleeding (3%); only 2% were severe and no patients ceased their non-steroidal anti-inflammatory drugs due to toxicity. Overall, 65% had benefit without harm and 3% had harm without benefit., Conclusions: Most patients benefited from non-steroidal anti-inflammatory drugs with only one in five patients experiencing tolerable harm. This suggests that short-term use of non-steroidal anti-inflammatory drugs in patients receiving palliative care is safer than previously thought and may be underused., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: We declare no competing interests.

The UK has a significant and growing population of older adults with frailty and complex healthcare needs, necessitating innovative care solutions. This study aimed to explore patients' and carers' experiences of a novel integrated service that was set up to address the increasing healthcare needs of older people living with frailty. A qualitative study that combined free-text survey questions with in-depth interviews. This study is part of a larger non-randomized trial of the service, with evaluation of wellbeing and quality of life at baseline, 2 to 4 weeks, and 10 to 14 weeks. Patients (aged 65 and above) with an electronic Frailty Index in the severe range and their informal family carers participated in this study. Data were collected between April 2019 and March 2020. Free text survey responses and interview data were subjected to reflexive thematic analyses. Four themes were generated: the overall experience of the service; interactions within the service; treatment and interventions; and outcomes due to the service. Most participants wanted further follow-up and more extensive integration with other services. Most participants described their overall experience positively, especially the available time to address their full range of concerns, but opportunities to integrate the service more fully and to extend follow-up remain., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Fliss Murtagh is a UK National Institute for Health and Care Research (NIHR) Senior Investigator. The remaining authors declared no potential conflicts of interests, (© The Author(s) 2023.)

Background: Malignant bowel obstruction is experienced by 15% of people with advanced cancer, preventing them from eating and drinking and causing pain, nausea and vomiting. Surgery is not always appropriate. Management options include tube or stent drainage of intestinal contents and symptom control using medication. Published literature describing palliative interventions uses a broad range of outcome measures, few of which are patient-relevant. This hinders evidence synthesis, and fails to consider the perspectives of people undergoing treatment., Aims: To develop a Core Outcome Set for the assessment of inoperable malignant bowel obstruction with clinician, patient and caregiver involvement, using COMET methodology (Core Outcome Measures in Effectiveness Trials)., Methods: A systematic review of clinical trials and observational studies, a rapid review of the qualitative literature and in-depth patient and clinician interviews were conducted to identify a comprehensive list of outcomes. Outcomes were compared and consolidated by the study Steering Group and Patient and Public Involvement contributors, and presented to an international clinical Expert Panel for review. Outcomes from the finalised list were rated for importance in a three-round international Delphi process: results of two survey rounds were circulated to respondents, and two separate consensus meetings were conducted with clinicians and with patients and caregivers via virtual conferencing, using live polling to reach agreement on a Core Outcome Set., Results: 130 unique outcomes were identified. Following the independent Expert Panel review, 82 outcomes were taken into round 1 of the Delphi survey; 24 outcomes reached criteria for critical importance across all stakeholder groups and none reached criteria for dropping. All outcomes rated critically important were taken forward for re-rating in round 2 and all other outcomes dropped. In round 2, all outcomes were voted critically important by at least one stakeholder group. Round 2 outcomes were presented again at online consensus meetings, categorised as high ranking (n = 9), middle ranking (n = 7) or low ranking (n = 8). Stakeholders reached agreement on 16 core outcomes across four key domains: Symptom control, Life impact, Treatment outcomes, and Communication and patient preferences., Conclusion: Use of this Core Outcome Set can help to address current challenges in making sense of the evidence around treatment for inoperable malignant bowel obstruction to date, and underpin a more robust future approach. Clearer communication and an honest understanding between all stakeholders will help to provide a basis for responsible decision-making in this distressing situation in clinical practice., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bravington et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Psychological distress is common in patients with cancer; interfering with physical and psychological wellbeing, and hindering management of physical symptoms. Our aim was to systematically review published evidence on non-pharmacological interventions for cancer-related psychological distress, at all stages of the disease., Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review was registered on PROSPERO (CRD42022311729). Searches were made using eight online databases to identify studies meeting our inclusion criteria. Data were collected on outcome measures, modes of delivery, resources and evidence of efficacy. A meta-analysis was planned if data allowed. Quality was assessed using the Mixed Methods Appraisal Tool (MMAT)., Results: Fifty-nine studies with 17,628 participants were included. One third of studies included mindfulness, talking or group therapies. Half of all studies reported statistically significant improvements in distress. Statistically significant intervention effects on distress were most prevalent for mindfulness techniques. Four of these mindfulness studies had moderate effect sizes (d = -0.71[95% CI: -1.04, -0.37] p < 0.001) (d = -0.60 [95% CI: -3.44, -0.89] p < 0.001) (d = -0.77 [CI: -0.146, -1.954] p < 0.01) (d = -0.69 [CI: -0.18, -1.19] p = 0.008) and one had a large effect size (d = -1.03 [95% CI: -1.51, -0.54] p < 0.001). Heterogeneity of studies precluded meta-analysis. Study quality was variable and some had a high risk of bias., Conclusions: The majority of studies using a mindfulness intervention in this review are efficacious at alleviating distress. Mindfulness-including brief, self-administered interventions-merits further investigation, using adequately powered, high-quality studies., Systematic Review Registration: This systematic review is registered on PROSPERO, number CRD42022311729., (© 2023. Crown.)

Opinion Statement: Opioids are an important treatment in managing cancer pain. Uncontrolled pain can be detrimental to function and quality of life. Common adverse effects of opioids such as sedation, constipation and nausea are well recognised, but opioid effects on the endocrine and immune systems are less apparent. The evidence for the immunomodulatory effects of opioids suggest that some opioids might be immunosuppressive and that their use might be associated with reduced survival and increased rates of infection in patients with cancer. However, the quality of this evidence is limited. Opioid-induced endocrinopathies, in particular opioid-induced hypogonadism, may also impact cancer survival and impair quality of life. But again, evidence in patients with cancer is limited, especially with regard to their management. There are some data that different opioids influence immune and endocrine function with varying outcomes. For example, some opioids, such as tramadol and buprenorphine, demonstrate immune-sparing qualities when compared to others. However, most of this data is preclinical and without adequate clinical correlation; thus, no opioid can currently be recommended over another in this context. Higher opioid doses might have more effect on immune and endocrine function. Ultimately, it is prudent to use the lowest effective dose to control the cancer pain. Clinical presentations of opioid-induced endocrinopathies should be considered in patients with cancer and assessed for, particularly in long-term opioid users. Hormone replacement therapies may be considered where appropriate with support from endocrinology specialists., (© 2023. The Author(s).)

Purpose of Review: Tapentadol is the first of a new class of analgesics, having synergistic µ-opioid receptor agonist and noradrenaline reuptake inhibitory actions. It has been widely researched in many areas of pain, often in noninferiority studies against potent opioids. This review describes all randomized and recent nonrandomized studies of tapentadol in adults with cancer pain., Recent Findings: Tapentadol has been shown to be at least as effective as morphine and oxycodone in five randomized (two of which were multicenter and double-blind) and a range of nonrandomized trials, although caution is needed when interpreting these results. It is effective in both opioid-naive patients and those already taking opioids. By having a lower µ-opioid receptor binding affinity, it has fewer opioid-related toxicities such as constipation and nausea. A recent randomized trial comparing tapentadol to tapentadol plus duloxetine in patients with chemotherapy-induced peripheral neuropathy shows similar improvement in both groups in a range of pain relieving and quality of life measures, with similar adverse effects., Summary: Tapentadol has been shown in a range of studies to be an effective analgesic and thus should be considered as an alternative to morphine and oxycodone, especially when opioid toxicities are an issue., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Palliative medicine physicians may be at higher risk of burnout due to increased stressors and compromised resilience during the COVID-19 pandemic. Burnout prevalence and factors influencing this among UK and Irish palliative medicine physicians is unknown., Aim: To determine the prevalence of burnout and the degree of resilience among UK and Irish palliative medicine physicians during the COVID-19 pandemic, and associated factors., Design: Online survey using validated assessment scales assessed burnout and resilience: The Maslach Burnout Inventory Human Services Survey for Medical Personnel [MBI-HSS (MP)] and the Connor-Davidson Resilience Scale (CD-RISC). Additional tools assessed depressive symptoms, alcohol use, and quality of life., Setting/participants: Association of Palliative Medicine of UK and Ireland members actively practising in hospital, hospice or community settings., Results: There were 544 respondents from the 815 eligible participants (66.8%), 462 provided complete MBI-HSS (MP) data and were analysed. Of those 181/462 (39.2%) met burnout criteria, based on high emotional exhaustion or depersonalisation subscales of the MBI-HSS (MP). A reduced odds of burnout was observed among physicians who worked ⩽20 h/week (vs 31-40 h/week, adjusted odds ratio (aOR) 0.03, 95% confidence interval (CI) 0.002-0.56) and who had a greater perceived level of clinical support (aOR 0.70, 95% CI 0.62-0.80). Physicians with higher levels of depressive symptoms had higher odds of burnout (aOR 18.32, 95% CI 6.75-49.73). Resilience, mean (SD) CD-RISC score, was lower in physicians who met burnout criteria compared to those who did not (62.6 (11.1) vs 70.0 (11.3); p  < 0.001)., Conclusions: Over one-third of palliative medicine physicians meet burnout criteria. The provision of enhanced organisational and colleague support is paramount in both the current and future pandemics.

Opioids are commonly used for pain management in patients with cancer. They have a range of unwanted effects, including some that potentially influence cancer growth. This article reviews the data assessing the effects of opioids on survival in patients with cancer. Many studies assessing this show an association between opioids and decreased survival. This effect is present even at very low doses of opioids. These studies do not assess causality, so it is not known if it is a direct effect of opioids on survival. As the control groups are not matched to the opioid group it might be that opioids are being used to control pain and patients receiving opioids have more aggressive cancers and it is the underlying cancer which is causing the decreased survival. Furthermore, although some studies allude to different opioids having different effects on survival, often all opioids are pooled in analysis. Future work needs to try to ascertain causality and differentiate between different opioids, pain, and cancer-mediated effects on survival in specific cancer types. Until then, opioids should continue to be used in patients with cancer as part of measures to optimise comfort and quality of life.

Background: Bereaved people need a supportive response from those around them. Knowing children's and surviving parents' needs following parental death is the first step to ensuring a supportive response. However, no systematic review has reported on this phenomenon., Aim: To systematically identify and synthesise qualitative literature exploring support experiences of parentally bereaved children and surviving parents., Methods: Systematic review with thematic synthesis, following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. MEDLINE, Embase, PsycINFO, CINAHL and the British Nursing Database were searched for relevant papers to September 2021. Included studies were appraised for quality and thematically synthesised using Thomas and Harden's thematic synthesis framework., Results: Fifteen qualitative studies from nine countries were included. There were four analytical themes from the children's perspectives (1) Openness of communication with children about death and dying, (2) Children's challenges of managing change, (3) Navigating emotions, and (4) Children's acceptability, access and engagement with support. There were three analytical themes from the parents' perspectives: (1) Adjusting as a parent, (2) Supporting their children, and (3) Parent's acceptability, access and engagement with support., Conclusions: Following a parental death, open and honest communication and involvement in what is happening within the family will help children cope. Both children and parents suppress emotions and avoid conversations to protect each other and those around them. A taboo around death exists and constrains the support some families receive. Childhood bereavement is a public health issue, with a need for professionals and communities to better understand and respond to the needs of bereaved families.CRD42020166179., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Malignant bowel obstruction, a complication of certain advanced cancers, causes severe symptoms which profoundly affect quality of life. Clinical management remains complex, and outcome assessment is inconsistent., Aim: To identify outcomes evaluating palliative treatment for inoperable malignant bowel obstruction, as part of a four-phase study developing a core outcome set., Design: The review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA); PROSPERO (ID: CRD42019150648). Eligible studies included at least one subgroup with obstruction below the ligament of Treitz undergoing palliative treatment for inoperable malignant bowel obstruction. Study quality was not assessed because the review does not evaluate efficacy., Data Sources: Medline, Embase, the Cochrane Database, CINAHL, PSYCinfo Caresearch, Open Grey and BASE were searched for trials and observational studies in October 2021., Results: A total of 4769 studies were screened, 290 full texts retrieved and 80 (13,898 participants) included in a narrative synthesis; 343 outcomes were extracted verbatim and pooled into 90 unique terms across six domains: physiological, nutrition, life impact, resource use, mortality and survival. Prevalent outcomes included adverse events (78% of studies), survival (54%), symptom control (39%) and mortality (31%). Key individual symptoms assessed were vomiting (41% of studies), nausea (34%) and pain (33%); 19% of studies assessed quality of life., Conclusions: Assessment focuses on survival, complications and overall symptom control. There is a need for definitions of treatment 'success' that are meaningful to patients, a more consistent approach to symptom assessment, and greater consideration of how to measure wellbeing in this population.

Background: Real-world effectiveness of interventions in palliative care need to be systematically quantified to inform patient/clinical decisions. Neuropathic pain is prevalent and difficult to palliate. Tricyclic antidepressants have an established role for some neuropathic pain aetiologies, but this is less clear in palliative care., Aim: To describe the real-world use and outcomes from amitriptyline or nortriptyline for neuropathic pain in palliative care., Design: An international, prospective, consecutive cohort post-marketing/phase IV/pharmacovigilance/quality improvement study of palliative care patients with neuropathic pain where the treating clinician had already made the decision to use a tricyclic antidepressant. Data were entered at set times: baseline, and days 7 and 14. Likert scales graded benefits and harms., Setting/participants: Twenty-one sites (inpatient, outpatient, community) participated in six countries between June 2016 and March 2019. Patients had clinician-diagnosed neuropathic pain., Results: One hundred and fifty patients were prescribed amitriptyline (110) or nortriptyline (40) of whom: 85% had cancer; mean age 73.2 years (SD 12.3); mean 0-4 scores for neuropathic pain at baseline were 1.8 (SD 1.0). By day 14, doses of amitriptyline were 57 mg (SD 21) and nortriptyline (48 mg (SD 21). Fifty-two (34.7%) patients had pain improvement by day 14 (amitriptyline (45/110 (43.3%); nortriptyline (7/40 (18.9%)). Thirty-nine (27.7%) had new harms; (amitriptyline 29/104 (27.9%); nortriptyline 10/37 (27.0%); dizziness ( n  = 23), dry mouth ( n  = 20), constipation ( n  = 14), urinary retention ( n  = 10)). Benefits without harms occurred (amitriptyline (26/104 (25.0%); nortriptyline (4/37 (10.8%))., Conclusions: Benefits favoured amitriptyline while harms were similar for both medications.

Background: Malignant bowel obstruction occurs in up to 50% of people with advanced ovarian and 15% of people with gastrointestinal cancers. Evaluation and comparison of interventions to manage symptoms are hampered by inconsistent evaluations of efficacy and lack of agreed core outcomes. The patient perspective is rarely incorporated., Aim: To synthesise the qualitative data regarding patient, caregiver and healthcare professionals' views and experience of malignant bowel obstruction to inform the development of a core outcome set for the evaluation of malignant bowel obstruction., Design: A qualitative systematic review was conducted, with narrative synthesis. The review protocol was registered prospectively (https://www.crd.york.ac.uk/prospero, CRD42020176393)., Data Sources: MEDLINE, EMBASE, CINAHL, PsycINFO and Scopus databases were searched for studies published between 2010 and 2021. Reference lists were screened for further relevant publications, and citation tracking was performed., Results: Nine papers were included, reporting on seven studies which described the views and experiences of malignant bowel obstruction through the perspectives of 75 patients, 13 caregivers and 62 healthcare professionals. Themes across the papers included symptom burden, diverse experiences of interventions, impact on patient quality of life, implications and trajectory of malignant bowel obstruction, mixed experience of communication and the importance of realistic goals of care., Conclusion: Some of the most devastating sequelae of malignant bowel obstruction, such as pain and psychological distress, are not included routinely in its clinical or research evaluation. These data will contribute to a wider body of work to ensure the patient and caregiver perspective is recognised in the development of a core outcome set.

Cluster headache (CH), a severe primary headache, is often misdiagnosed and mismanaged. The aim of this study was to develop and evaluate a screening tool to aid the diagnosis of CH. We developed a novel 12-item screening tool. This was comprised of four components: (1) images depicting headache pain; (2) pain descriptors; (3) key questions that could differentiate between CH and migraine; and (4) a visual analogue pain scale. The total possible questionnaire score ranged from 3-32. Patients with CH and migraines (control group) were recruited prospectively from a headache centre in the North of England, UK. Two-hundred and ninety-six patients were included in the study: 81 CH patients, 36 of which suffer with episodic CH and 45 with chronic CH; 215 migraine patients, 92 of which suffer with episodic migraine and 123 with chronic migraine. The mean questionnaire score was higher in CH patients versus migraine patients (28.4 versus 19.5). At a cut-off score of >25 out of 32, the screening tool had a sensitivity of 86.4% and a specificity of 92.0% in differentiating between CH and migraine. The screening tool could be a useful instrument to aid the diagnosis of a CH. The images depicting headache pain do not clearly discriminate between CH and migraine., Competing Interests: Availability of data and material: The datasets used and/or analysed during this study are available from the corresponding author upon request.

Purpose: Older people with dementia are at risk of adverse events associated with potentially inappropriate prescribing., Aim: to describe (1) how international tools designed to identify potentially inappropriate prescribing have been used in studies of older people with dementia, (2) the prevalence of potentially inappropriate prescribing in this cohort and (3) advantages/disadvantages of tools METHODS: Systematic literature review, designed and reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). MEDLINE, EMBASE, PsychInfo, CINAHL, the Cochrane Library, the Social Science Citation Index, OpenGrey, Base, GreyLit, Mednar and the National Database of Ageing Research were searched in April 2016 for studies describing the use of a tool or criteria to identify potentially inappropriate prescribing in older people with dementia., Results: Three thousand three hundred twenty-six unique papers were identified; 26 were included in the review. Eight studies used more than one tool to identify potentially inappropriate prescribing. There were variations in how the tools were applied. The Beers criteria were the most commonly used tool. Thirteen of the 15 studies using the Beers criteria did not use the full tool. The prevalence of potentially inappropriate prescribing ranged from 14 to 74% in older people with dementia. Benzodiazepines, hypnotics and anticholinergics were the most common potentially inappropriately prescribed medications., Conclusions: Variations in tool application may at least in part explain variations in potentially inappropriate prescribing across studies. Recommendations include a more standardised tool usage and ensuring the tools are comprehensive enough to identify all potentially inappropriate medications and are kept up to date.

Background: Benzodiazepines and Z-drugs are commonly used in patients with cancer for the management of symptoms such as anxiety, agitation and dyspnoea. Clinical staff, patients and relatives have concerns about the impact of these drugs on survival. This potentially decreases prescribing leading to suboptimal symptom control. The aim of this systematic review was to find and assimilate the evidence assessing the association of benzodiazepines and Z-drugs with survival in patients with cancer, to assist in clinical decision-making regarding the use of these drugs in cancer patients., Methods: Systematic review with narrative synthesis designed and conducted according to the recommendations set out in Preferred Reporting Items for Systematic Reviews and MetaAnalyses-Protocol (PRISMA-P) and PRISMA statements. The review protocol was registered on the PROSPERO prior to commencing the searches. The electronic databases MEDLINE, EMBASE, PsychINFO, Cochrane Library, AMED were searched and hand-searches were performed. Screening, extraction and quality assessment were performed in duplicate., Results: A total of 2257 unique records were identified, 116 full-text articles assessed for eligibility, 18 met the inclusion criteria. These contained data on 4117 patients with cancer. All studies were low or very-low quality. Most studies were conducted in patients in the last days/weeks of life. No study found an association between benzodiazepines and survival in patients with cancer., Conclusions: There is no evidence demonstrating an association between benzodiazepines and survival in patients with cancer. These results should be interpreted with caution as all studies were low/very low quality, most did not report or account for other medications and did not have survival as a primary outcome. No study assessed the effect of long-term benzodiazepines on survival. Therefore, definitive conclusions regarding survival impact of benzodiazepine in patients with cancer can be made. Further investigation using high-quality long-term randomised control trials with survival as a primary endpoint are needed.

Symptom management is an important part of both palliative care and end-of-life care. This article will examine the recent research evidence about drugs commonly used for symptom management in adult patients receiving palliative care. In particular, the management of symptoms where recent palliative care-based evidence has changed recommended practice will be reviewed. This includes: breathlessness, delirium, nausea and vomiting in bowel obstruction, opioid-induced constipation and upper respiratory tract secretions. For each symptom, a review of recent pharmacological evidence has been undertaken, with emphasis on potential important changes to physicians' practice., (© Royal College of Physicians 2018. All rights reserved.)

Background: Communication between parents and their children about parental life-limiting illness is stressful. Parents want support from health-care professionals; however, the extent of this support is not known. Awareness of family's needs would help ensure appropriate support., Aim: To find the current literature exploring (1) how parents with a life-limiting illness, who have dependent children, perceive health-care professionals' communication with them about the illness, diagnosis and treatments, including how social, practical and emotional support is offered to them and (2) how this contributes to the parents' feelings of supporting their children., Design: A systematic literature review and narrative synthesis., Data Sources: Embase, MEDLINE, PsycINFO, CINAHL and ASSIA ProQuest were searched in November 2015 for studies assessing communication between health-care professionals and parents about how to talk with their children about the parent's illness., Results: There were 1342 records identified, five qualitative studies met the inclusion criteria (55 ill parents, 11 spouses/carers, 26 children and 16 health-care professionals). Parents wanted information from health-care professionals about how to talk to their children about the illness; this was not routinely offered. Children also want to talk with a health-care professional about their parents' illness. Health-care professionals are concerned that conversations with parents and their children will be too difficult and time-consuming., Conclusion: Parents with a life-limiting illness want support from their health-care professionals about how to communicate with their children about the illness. Their children look to health-care professionals for information about their parent's illness. Health-care professionals, have an important role but appear reluctant to address these concerns because of fears of insufficient time and expertise.

Objectives: Numerous in vitro studies have evaluated the influence of opioids on many biological and immunological processes. The concentrations that have been used in these studies span a large range and often do not reflect levels that are present in the relevant patient groups. This article reviews the literature concerning the concentrations of opioids that are detected in patients so that the concentrations of opioids that are used for in vitro studies can better reflect those that are present clinically. This will enable scientists and clinicians to more effectively model and interpret potentially relevant clinical effects from in vitro studies., Methods: Data on the concentrations of six commonly used opioids from clinical studies in adults were collected by searching PubMed (Medline)., Results: A total of 42 relevant studies were included in the review. Concentrations of the opioids from previous clinical studies were mostly between 1 and 10 ng/mL for buprenorphine, 1 and 10 ng/mL for fentanyl, 50 and 500 ng/mL for methadone, 25 and 250 ng/mL for morphine, 10 and 100 ng/mL for oxycodone, and 100 and 1,000 ng/mL for Tramadol and were dependent on the patient group and indication under investigation., Conclusions: Concentrations of opioids used in vitro should include those that are present in the relevant clinical setting if the effects of opioids detected in vitro are to be of potential relevance to the clinical setting. Therefore, it is essential that these concentrations in the relevant clinical context(s) are known.

Introduction: Constipation is a common adverse effect of opioids. As an example, constipation is reported in 52% of people with advanced malignancy, and this figure rises to 87% in people who are terminally ill and taking opioids. There is no reason to believe that people with chronic non-malignant disease who are prescribed opioids will be any less troubled by this adverse effect., Methods and Outcomes: We conducted a systematic overview and aimed to answer the following clinical question: What are the effects of opioid antagonists for constipation in people prescribed opioids? The population we studied included people with any condition, although most studies were in people with cancer pain. We searched Medline, Embase, The Cochrane Library, and other important databases up to May 2014 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review)., Results: At this update, searching of electronic databases retrieved 162 studies. After deduplication and removal of conference abstracts, 84 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 47 studies and the further review of 37 full publications. Of the 37 full articles evaluated, two systematic reviews and one RCT were included at this update. We performed a GRADE evaluation for three PICO combinations., Conclusions: In this systematic overview we categorised the efficacy for three interventions based on information relating to the effectiveness of alvimopan, methylnaltrexone, and naloxone.