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Background: Incurable cancer is a major contributor to societal suffering and disability, and palliative rehabilitation is recommended to be integrated within and between cancer services at all healthcare levels. However, little knowledge exists on how integration of palliative rehabilitation in cancer is understood and achieved in clinical practice. INSPIRE (Integrated short-term palliative rehabilitation to improve quality of life and equitable care access in incurable cancer) is a large European-funded project that aims to promote quality of life through a novel rehabilitation model for people disabled by advanced cancer., Aim: To compare the existing integration of palliative rehabilitation in cancer within official documents and in clinical practice across five European countries including United Kingdom, France, Denmark, Norway, and Italy., Methods: Mixed methods study with a concurrent research design, comprising a document analysis (N = 23), stakeholder interviews (N = 22), and an online survey (N = 225). Data from each sub-study were analysed separately before results were merged., Results: There was limited integration of palliative rehabilitation in cancer in official documents and in clinical practice, though some indicators of integration, including participation in multidisciplinary teams and adherence to standardised pathways, were identified in the survey. Notably, integration of palliative rehabilitation in cancer in clinical practice was observed within limited organisations in secondary healthcare systems, without widespread adoption. Although palliative rehabilitation in cancer as a concept was sparingly used by stakeholders, they recognised the need for a comprehensive approach including multidisciplinary teams that aligns with the individual patient's needs and goals. Moreover, the ambiguous distinction between the terms 'palliative rehabilitation' and 'palliative care', insufficient funding, lack of well-defined care pathways and competence gaps among healthcare professionals represented barriers to integration of palliative rehabilitation in cancer into clinical practice., Conclusion: Integration of palliative rehabilitation in cancer was limited in the five EU partnership countries investigated. Clarifying the concept of palliative rehabilitation, including adoption of the concept into official documents and delineating it from palliative care, is essential for more successful integration. This can possibly be achieved by addressing the barriers identified and fostering close collaboration across disciplines., Competing Interests: Declarations Ethics approval and consent to participate All data handling adhered to EU’s General Data Protection Regulation (GDPR) 2018 and the University of Bergen regulations for GDPR and safe data handling. According to the national regulations for medical and health research (the Health Research Act of 2008-06-20 no. 44; •• 4a and 4d), ethical approval was deemed unnecessary by the Regional Ethics Committee (REC West). However, approval from the Norwegian Agency for Shared Services in Education and Research was required, as the interviews were recorded (reference number 414708). The study was registered in University of Bergen’s System for Risk and Compliance (ID F2402). Written and/or oral informed consent was provided by all participants in the interviews and cross-sectional survey. Consent for publication All authors have provided their consent for publication. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Context: Opioids are the mainstay therapy for patients affected by cancer pain. However, about 10%-20% of patients do not benefit from the received analgesic treatment or experience side effects. Genetic variability might account for the variation in individual responses to opioids, both in terms of efficacy and toxicity., Objectives: The aim of this genome-wide association study (GWAS) was to identify genetic markers of opioid toxicity, in terms of nausea-vomiting., Methods: Cancer patients receiving morphine, oxycodone, buprenorphine, and fentanyl were recruited from different European countries. Data about toxicity (nausea-vomiting score, NVS) and other relevant clinical information were collected, as well as genotyping data. Regression analysis between genotypes of 2052 patients and NVS was performed, using appropriate covariates, with REGENIE software., Results: We found 65 variants associated with NVS (P-value < 1.0×10 -5 ). Of note, 14 intronic variants on chromosome 2 were in NPAS2 gene, encoding a circadian transcription factor reported to play a role in another opioid side effect, the alteration of sleep. Some of these variants were previously identified as splicing quantitative trait loci of the NPAS2 gene., Conclusions: This is the first GWAS, performed in more than two thousand individually genotyped patients treated with opioids for cancer pain, that investigated the genetic bases of opioid-induced nausea-vomiting. Although further studies are needed to confirm our findings and to characterize the functional role of the identified variants, our results emphasize the importance of performing large pharmacogenomic studies to identify germline variants associated with opioid response, with the ultimate goal of tailoring cancer pain therapies., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: The decision to administer palliative radiotherapy (RT) to patients with bone metastases (BMs), as well as the selection of treatment protocols (dose, fractionation), requires an accurate assessment of survival expectancy. In this study, we aimed to develop three predictive models (PMs) to estimate short-, intermediate-, and long-term overall survival (OS) for patients in this clinical setting., Materials and Methods: This study constitutes a sub-analysis of the PRAIS trial, a longitudinal observational study collecting data from patients referred to participating centers to receive palliative RT for cancer-induced bone pain. Our analysis encompassed 567 patients from the PRAIS trial database. The primary objectives were to ascertain the correlation between clinical and laboratory parameters with the OS rates at three distinct time points (short: 3 weeks; intermediate: 24 weeks; prolonged: 52 weeks) and to construct PMs for prognosis. We employed machine learning techniques, comprising the following steps: (i) identification of reliable prognostic variables and training; (ii) validation and testing of the model using the selected variables. The selection of variables was accomplished using the LASSO method (Least Absolute Shrinkage and Selection Operator). The model performance was assessed using receiver operator characteristic curves (ROC) and the area under the curve (AUC)., Results: Our analysis demonstrated a significant impact of clinical parameters (primary tumor site, presence of non-bone metastases, steroids and opioid intake, food intake, and body mass index) and laboratory parameters (interleukin 8 [IL-8], chloride levels, C-reactive protein, white blood cell count, and lymphocyte count) on OS. Notably, different factors were associated with the different times for OS with only IL-8 included both in the PMs for short- and long-term OS. The AUC values for ROC curves for 3-week, 24-week, and 52-week OS were 0.901, 0.767, and 0.806, respectively., Conclusions: We successfully developed three PMs for OS based on easily accessible clinical and laboratory parameters for patients referred to palliative RT for painful BMs. While our findings are promising, it is important to recognize that this was an exploratory trial. The implementation of these tools into clinical practice warrants further investigation and confirmation through subsequent studies with separate databases., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Disability related to incurable cancer affects over a million Europeans each year and people with cancer rank loss of function among the most common unmet supportive care needs., Objectives: To test the clinical and cost-effectiveness of an integrated short-term palliative rehabilitation intervention, to optimise function and quality of life in people affected by incurable cancer., Design: This is a multinational, parallel group, randomised, controlled, assessor blind, superiority trial., Methods: The INSPIRE consortium brings together leaders in palliative care, oncology and rehabilitation from partner organisations across Europe, with complementary expertise in health service research, trials of complex interventions, mixed-method evaluations, statistics and economics. Partnership with leading European civil society organisations ensures citizen engagement and dissemination at the highest level. We will conduct a multinational randomised controlled trial across five European countries, recruiting participants to assess the effectiveness of palliative rehabilitation for people with incurable cancer on the primary outcome - quality of life - and secondary outcomes including disability, symptom burden and goal attainment. To support trial conduct and enhance analysis of trial data, we will also conduct: comparative analysis of current integration of rehabilitation across oncology and palliative care services; mixed-method evaluations of equity and inclusivity, processes and implementation for the intervention, at patient, health service and health system levels. Finally, we will conduct an evidence synthesis, incorporating INSPIRE findings, and a Delphi consensus to develop an international framework for palliative rehabilitation practice and policy, incorporating indicators, core interventions, outcomes and integration methods., Scientific Contribution: If positive, the trial could produce a scalable and equitable intervention to improve function and quality of life in people with incurable cancer and reduce the burden of care for their families. It could also upskill the practitioners involved and motivate future research questions. The intervention could be adapted and integrated into different health systems using existing staff and services, with little or no additional cost., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s), 2023.)

Background: Early palliative care (PC) has shown beneficial effects for advanced cancer patients. However, it is still debated what criteria to use to identify patients for PC referral., Aim: To document the initial steps of the development of the Palliative Care Referral System (PCRS), a tool to be used by oncologists in clinical practice., Methods: A multiprofessional working group developed the PCRS based on the results of a scoping literature review on PC referral criteria. PCRS criteria were evaluated by experts via a nominal group technique (NGT). Descriptive statistics were used to summarize expert scores on relevance, appropriateness and perceived feasibility of the criteria proposed. Quotations of participants during the discussion were also reported., Results: Sixteen studies, including PC referral criteria/tools, emerged from the scoping review. Severe symptoms, poor performance status, comorbidities and prognosis were the most commonly used criteria. The PCRS included nine major criteria and nine assessment methods; a scoring procedure was also proposed. Answers to the questionnaire during the NGT showed that five criteria reached full agreement on all items, while four did not, and were then discussed within the group. Participants agreed on the relevance of all criteria and on the appropriateness of methods proposed to assess most of them, while issues were raised about potential feasibility of the overall assessment of the PCRS in clinical practice., Conclusion: The PCRS has been developed as an help for oncologists to timely identify patients for specialized PC referral. Since feasibility emerged as the main concern, implementation strategies have to be tested in subsequent studies., (© 2022. The Author(s).)

Introduction: Early palliative care (PC) in the clinical pathway of advanced cancer patients improves symptom control, quality of life and has a positive impact on overall quality of care. At present, standardised criteria for appropriate referral for early PC in oncology care are lacking. The aim of this project is to develop a set of standardised referral criteria and procedures to implement appropriate early PC for advanced cancer patients (the palliative care referral system, PCRS) and test its impact on user perception of quality of care received, on patient quality of life and on the use of healthcare resources., Setting: Selected oncology clinics and PC outpatient clinic., Methods and Analysis: A scoping literature review and an expert consultation through a nominal group technique will be used to revise existing referral tools and to develop a new one, the PCRS. 25 patients will be enrolled in a pilot study to assess feasibility of the implementation of PCRS; 10 interviews with patients and healthcare professionals will be carried out to evaluate applicability.A pretest-post-test quasiexperimental study involving 150 patients before implementation of the PCRS and 150 patients after implementation will be carried out.Patient satisfaction with care received, quality of life and use of resources, and caregiver satisfaction with care will also be assessed to explore the impact of the intervention., Ethics and Dissemination: Ethical approval for the study has been granted by the Institutional Review board of the Fondazione IRCCS Istituto Nazionale Tumori; approval reference INT201/19.Results will be disseminated through open access publications and through scientific communication presented at national and international conferences., Trial Registration Number: NCT04936568., Competing Interests: Competing interests: AC has received consultant honoraria from Mundipharma, Pfizer/Eli Lilly Italia Spa, Angelini, Shionogi, Molteni and Kyowa Kirin. He has also received research grants from Molteni & C Soc Esercizio Spa and Ipsen. EZ has received consultant honoraria from Amgen. MN has received travel expenses from Celgene, speaker honorarium from Accademia della Medicina and consultant honoraria from EMD Serono, Basilea Pharmaceutica, Incyte and MSD Italia. FDB has received consultant honoraria from Roche, EMD Serono, NMS Nerviano Medical Science, Sanofi, MSD, Novartis and Incyte. He has received speaker honoraria from BMS, Healthcare Research & Pharmacoepidemiology, Merck Group, ACCMED, Nadirex, MSD, Pfizer, Servier, Sanofi, Roche and AMGEN. He has also received research grants from Novartis, Roche, BMS, Celgene, Incyte, NMS, Merck KGAA, Kymab, Pfizer, Tesaro and MSD. AP, PB, MC, SLD, VF, CBe, MB, PS, SP, SA, AR, GT and CBr declare no conflicts of interest., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Among the distraction techniques used for the non-pharmacological management of acute pediatric pain, one of the most performed is clown therapy. Despite the presence in the literature of some systematic reviews that evaluate its effectiveness, none of them examines its outcomes on procedural pain which has therefore been investigated in this study. The literature search for randomized controlled trials (RCTs) was performed on the Cochrane Library, MEDLINE, EMBASE, CINAHL, PsycINFO, Web of Science, and Scopus over a time frame ranging from each database setup date to 31 July 2021. The primary outcome was the procedural pain of children. We used the Cochrane Risk of Bias tool to assess the risk of bias of the included studies. Six RCTs were selected for this review, which included a total of 517 pediatric subjects. Children undergoing clown therapy during the venipuncture or peripheral vein cannulation procedure reported less pain than those exposed to the standard of care (SMD =  -0.55; 95% CI: -1.23, 0.13) but the result was not found to be statistically significant. School-aged children and adolescent reported significantly less pain (SMD =  -0.51; 95% CI: -0.92, -0.09). Compared to the standard of care, children's anxiety was significantly lower with clown therapy (SMD =  -0.97; 95% CI: -1.38, -0.56)., Conclusion: Clown therapy seems effective in reducing procedural pain in children, particularly for older age groups, but due to poor methodological quality and the high risk of bias of the studies included, the results obtained should be considered with caution., What Is Known: • Clown therapy is one of the most used techniques in the non-pharmacological management of acute pediatric pain. • Laughter physiologically stimulates the production of beta-endorphins, substances with an effect similar to opiates., What Is New: • Clown therapy seems effective in reducing procedural pain and anxiety in children. • The intervention in school-age children or adolescents produces a statistically significant decrease in the symptom., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Opioid-induced constipation (OIC) remains an important clinical obstacle despite the availability of several guidelines and pharmacological options for its management. Here, we surveyed common practices and perceptions about OIC among physicians who prescribe opioids in Italy., Methods: The online survey included 26 questions about OIC. Responses were analyzed descriptively and aggregated by physician specialty., Results: A total of 501 physicians completed the survey. Most respondents (67%) did not feel adequately educated about OIC despite general consensus regarding interest in the topic. Overall, 62-75% of physicians regularly evaluated intestinal function or OIC symptoms in patients receiving opioid therapy. The most common method for assessment was patient diary; few physicians used a validated instrument such as the Rome IV criteria. Psychiatrists and addiction specialists showed the lowest interest and poorest practices. Most respondents (78%) preferred macrogol prophylaxis followed by macrogol plus another laxative for first-line treatment of OIC symptoms. Peripheral-acting mu opioid receptor antagonists (PAMORAs) were not widely used among physicians; 61% had never prescribed a PAMORA for OIC., Conclusion: Our findings reveal important differences in clinical practice for OIC across physician specialties. Additional formative efforts are necessary to improve awareness about best practices in OIC., Competing Interests: FC is a speaker and consultant for Angelini, Grunenthal, Malesci, Molteni, Pfizer, and Shionogi. DA has received research grants and consultant fees from Intercept Pharma, Molteni, Shionogi, and Vesta, and is a consultant for Aboca. ATC has received research grants from Molteni, Gruenenthal GmbH, Prostrakan, Amgen, and Ipsen and is a consultant for Kyowa Kirin, Gruenenthal GmbH, Pfizer, Helsinn Healthcare, Molteni, Shionogi, Italfarmaco, Sandoz International GmbH, Angelini Holding S.p.A., Mundipharma, and the Institute de Recherche “Pierre Fabre.” WG has received research grants and other funding from Molteni and Shionogi. FM has received research grants and other funding from Molteni and Shionogi. GM has received research grants and other funding from Molteni and Shionogi. CP has received research grants and other funding from Molteni and Shionogi. GV is Member of the Advisor Boards of Abbott, Dompé, Malesci, Menarini International, Molteni, Mundipharma, Shionogi. Also, he is Member of the Speakers’ Bureau of Berlin-Chemie, Dompé, MAP, Menarini International, MCAC, Molteni, Takeda. He has received funds for research by Dompé, Fondazione Maugeri and Pfizer. He is a Member of the Editorial Board of several scientific journals, and is Editor in Chief of Pain and Therapy. FL has received research grants and other funding from Molteni and Shionogi. The authors report no other conflicts of interest in this work., (© 2021 Coluzzi et al.)

Introduction: Despite the essential utility of opioids for the clinical management of pain, opioid-induced constipation (OIC) remains an important obstacle in clinical practice. In patients, OIC hinders treatment compliance and has negative effects on quality of life. From a clinician perspective, the diagnosis and management of OIC are hampered by the absence of a clear, universal diagnostic definition across disciplines and a lack of standardization in OIC treatment and assessment., Methods: A multidisciplinary panel of physician experts who treat OIC was assembled to identify a list of ten corrective actions-five "things to do" and five "things not to do"-for the diagnosis and management of OIC, utilizing the Choosing Wisely methodology., Results: The final list of corrective actions to improve the diagnosis and clinical management of OIC emphasized a need for: (i) better physician and patient education regarding OIC; (ii) systematic use of diagnostically validated approaches to OIC diagnosis and assessment (i.e., Rome IV criteria and Bristol Stool Scale, respectively) across various medical contexts; and (iii) awareness about appropriate, evidence-based treatments for OIC including available peripheral mu-opioid receptor antagonists (PAMORAs)., Conclusions: Physicians who prescribe long-term opioids should be forthcoming with patients about the possibility of OIC and be adequately versed in the most recent guideline recommendations for its management.

Nausea and vomiting are often associated with opioid analgesia in cancer patients; however, only a subset of patients develop such side effects. Here, we tested the hypothesis that the occurrence of nausea and vomiting is modulated by the genetic background of the patients. Whole exome sequencing of DNA pools from patients with either low (n = 937) or high (n = 557) nausea and vomiting intensity, recruited in the European Pharmacogenetic Opioid Study, revealed a preliminary association of 53 polymorphisms. PCR-based genotyping of 45 of these polymorphisms in the individual patients of the same series confirmed the association for six SNPs in AIM1L, CLCC1, MUC16, PDE3A, POM121L2, and ZNF165 genes. Genotyping of the same 45 polymorphisms in 264 patients of the Italian CERP study, also treated with opioids for cancer pain, instead confirmed the association for two SNPs in ZNF568 and PDE3A genes. Only one SNP, rs12305038 in PDE3A, was confirmed in both series, although with opposite effects of the minor allele on the investigated phenotype. Overall, our findings suggest that genetic factors are indeed associated with nausea and vomiting in opioid-treated cancer patients, but the role of individual polymorphisms may be weak.

This study reports a case series of patients with upper limb neuromotor deficits following pediatric central nervous system tumor and treated with rehabilitative therapy according to action observation therapy (AOT). AOT is based on the "mirror neurons" system and had positive results in various non-oncologic neurologic pathologies. This study is the first experience in the oncology field, and included 6 patients, 4 of whom were fully evaluated at 6-month follow-up. In all patients, therapy showed improvement in all assessment tests. These promising results lead to further studies to confirm their effectiveness.