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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).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.• 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.• 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.

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 article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Context Few studies have addressed the impact of previous opioid exposure on the effect of opioids for the treatment of severe cancer pain episodes. Objectives We aimed to test whether previous exposure to higher opioid doses was associated with a reduced analgesic effect of fentanyl sublingual tablets (FST) and subcutaneous morphine (SCM) and whether it had an influence on their relative effect. Methods This is a secondary analysis of a placebo-controlled randomized trial comparing 100 μg FST with 5 mg SCM for the acute treatment of severe cancer pain episodes. The effect of previous opioid exposure (oral morphine equivalent daily dose from 20 to 120 mg) on pain intensity difference (PID) and side effects at 30 and 60 minutes after administration (PID 0–30 minutes, PID 0–60 minutes, and adverse events 30–60 minutes) and on re-medication for inefficacy, was studied by multivariable linear and logistic regression models and statistical tests for interaction. Results A total of 114 patients were enrolled. Results indicate modest and nonstatistically significant effect of previous opioid exposure on all the outcomes examined (P = 0.11, P = 0.35, P = 0.07, and P = 0.52, respectively, for PID 0–30 minutes, re-medication, PID 0–60 minutes, and adverse events 30–60 minutes). Nonstatistically significant tests for interaction for all models indicated a lack of impact of previous opioid exposure on the difference in the analgesic effect between treatments. Conclusion In this study, we could not demonstrate an effect of previous opioid exposure, from 20 to 120 mg oral morphine equivalent daily dose, on the absolute and relative efficacy and tolerability of 100 μg FST and 5 mg SCM for severe cancer pain episodes.

The field report is a personal account of introducing the practice of mindfulness to humanitarian professionals working in East Jerusalem and the West Bank to help them reduce stress and address issues of burnout. Mindfulness refers to the systematic cultivation of awareness that emerges through pay

Purpose Fentanyl sublingual tablets (FST) are a potentially useful alternative to parenteral opioids such as subcutaneous morphine (SCM) to treat severe cancer pain episodes. No direct comparison between FST and SCM is available. The aim of this study was to test noninferiority of FST versus SCM during the first 30 min postadministration. Methods Patients receiving stable opioid therapy and experiencing a severe pain episode were randomly assigned to either 100 µg FST or 5 mg SCM in a double-blind, double-dummy trial. Average pain intensity (PI) assessed on a 0 to 10 numerical rating scale at 10, 20, and 30 min postadministration was the main end point. Analysis of covariance, adjusted by baseline PI, was the main analysis. The noninferiority margin (NIm) for the between-group difference was set at −0.6, that is, equal to one third of the minimum clinically important PI difference of two points. Results A total of 114 patients were randomly assigned to either FST (n = 58) or SCM (n = 56). One patient (in the FST group) withdrew consent before drug administration and was excluded from analysis. Baseline mean PIs were 7.5 in both groups; mean average PIs assessed at 10, 20, and 30 min postadministration were 5.0 and 4.5 for FST and SCM, respectively, with the 95% CI of the between-group difference including the NIm (−0.49; 95% CI, −1.10 to 0.09). Patients taking FST received a second drug dose after 30 min more frequently than did patients taking SCM (51% v 37%, respectively; risk difference, −13%; 95% CI, −30% to 3%). Both treatments were well tolerated, with average follow-up adverse event scores below the response of “A Little.” Ninety-three percent of patients preferred the sublingual administration. Conclusion This trial did not show noninferiority of FST versus SCM within the chosen NIm. Both treatments were safe, and patients preferred the sublingual route of administration. FST provides analgesia with modest to moderate increased risk of lower efficacy compared with SCM.

Context Quality of life (QoL) and depression are important patient-reported outcomes in cancer care. However, the relative importance of depression severity in predicting QoL remains unclear because of few methodologically sound studies. Objectives To examine whether depression contributes to impairment of QoL irrespective of prognostic factors and symptom burden. Methods A total of 563 patients were included from the European Palliative Care Research Collaborative–Computerized Symptom Assessment Study, an international, multi-center, cross-sectional study. The relative importance of prognostic factors (systemic inflammation [modified Glasgow Prognostic Score—mGPS]), co-morbidities and physical performance (Karnofsky Performance Status), symptom burden (loss of appetite, breathlessness, nausea [Edmonton Symptom Assessment Scale], and pain [Brief Pain Inventory]), and depression severity (Patient Health Questionnaire 9) in predicting Global Health/QoL (European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire [EORTC-QLQ-C30]) were assessed using hierarchical multiple regression models. Results Fifty-five percent were women, median age was 64 years, 87% had metastatic disease, median Karnofsky Performance Status was 70, and mean global QoL was 50.5 (SD = 23.3). Worse QoL was associated with increased systemic inflammation (mGPS = 1 β = −0.12, P = 0.003; mGPS = 2 β = −0.09, P = 0.023), lower physical performance (β = 0.17, P < 0.001), reduced appetite (β = −0.15, P < 0.001), breathlessness (β = −0.11, P = 0.004), pain (β = −0.14, P = 0.002), and higher depression severity (β = −0.27, P < 0.001). The full model accounted for 29% of the observed variance in QoL scores. The strongest predictor was depression severity, accounting for 5.8% of the variance. Conclusion Depression severity was the strongest single predictor of poorer QoL in this sample of patients with advanced cancer, after accounting for a wide range of clinically relevant variables. Future studies should investigate the contribution of psychosocial variables on QoL. Our findings emphasize the importance of managing depression to achieve the best possible QoL for these patients. This is a submitted manuscript of an article published by Elsevier Ltd in Journal of Pain and Symptom Management, 10 August 2017.

ObjectivesPalliative care (PC) services and patients differ across countries. Data on PC delivery paired with medical and self-reported data are seldom reported. Aims were to describe (1) PC organisation and services in participating centres and (2) characteristics of patients in PC programmes.MethodsThis was an international prospective multicentre study with a single web-based survey on PC organisation, services and academics and patients' self-reported symptoms collected at baseline and monthly thereafter, with concurrent registrations of medical data by healthcare providers. Participants were patients ≥18 enrolled in a PC programme.Results30 centres in 12 countries participated; 24 hospitals, 4 hospices, 1 nursing home, 1 home-care service. 22 centres (73%) had PC in-house teams and inpatient and outpatient services. 20 centres (67%) had integral chemotherapy/radiotherapy services, and most (28/30) had access to general medical or oncology inpatient units. Physicians or nurses were present 24 hours/7 days in 50% and 60% of centres, respectively. 50 centres (50%) had professorships, and 12 centres (40%) had full-time/part-time research staff. Data were available on 1698 patients: 50% females; median age 66 (range 21–97); median Karnofsky score 70 (10–100); 1409 patients (83%) had metastatic/disseminated disease; tiredness and pain in the past 24 hours were most prominent. During follow-up, 1060 patients (62%) died; 450 (44%) 2 tests showed that hospice/nursing home patients were significantly older, had poorer performance status and had shorter survival compared with hospital-patients (pConclusionsThere is a wide variation in PC services and patients across Europe. Detailed characterisation is the first step in improving PC services and research.Trial registration numberClinicalTrials.gov Identifier: NCT01362816.

Background: Bisphosphonates and denosumab are well-established therapies to reduce the frequency and severity of skeletal-related events in patients with bone metastasis. However, the analgesic effect of these medications on bone pain is uncertain. Aim: To identify, critically appraise and synthesize existing evidence to answer the following questions: ‘In adult patients with metastatic bone pain, what is the evidence that bisphosphonates and denosumab are effective and safe in controlling pain?’ and ‘What is the most appropriate schedule of bisphosphonate/denosumab administration to control bone pain?’. This review also updates the 2002 Cochrane review ‘Bisphosphonates for the relief of pain secondary to bone metastases’. Design: Standard systematic review and narrative synthesis. Data sources: MEDLINE, EMBASE and Cochrane CENTRAL databases were searched for relevant articles published through 31 January 2014. A manual search was also performed. Study inclusion criteria were: a) conducted in adult patients; b) randomized controlled trial or meta-analisys; c) reported efficacy of bisphosphonates or denosumab on pain and/or decribed side effects versus placebo or other bisphosphonate; and d) English language. Results: The database search yielded 1585 studies, of which 43 (enrolling 8595 and 7590 patients, respectively, in bisphosphonate and denosumab trials) met the inclusion criteria. Twenty-two (79%) of the 28 placebo-controlled trials found no analgesic benefit for bisphosphonates. None of the denosumab studies assessed direct pain relief. Conclusion: Evidence to support an analgesic role for bisphosphonates and denosumab is weak. Bisphosphonates and denosumab appear to be beneficial in preventing pain by delaying the onset of bone pain rather than by producing an analgesic effect per se.

The aim of this systematic review was to evaluate the evidence that oral morphine can be recommended as the first choice opioid in the treatment of moderate to severe cancer pain in updating the European Association for Palliative Care opioid recommendations. A systematic literature review was performed to update the 2007 Cochrane review ‘Oral morphine for cancer pain’. The literature search was conducted on MedLine, EMBASE and Cochrane Central Register of Controlled Trials databases. The search strategy, limited in time (from 1 July 2006 to 31 October 2009), was aimed to be as extensive as possible using both text words and MeSH/EMTREE terms; a hand search of the reference lists of identified papers was also performed. Randomized clinical trials, containing data on efficacy and/or side effects of morphine, were identified. Among the papers retrieved from the cited databases and the Cochrane review, 17 eligible studies, for a total of 2053 patients, and a meta-analysis were selected. These studies do not add significant information to the previous Cochrane review confirming the limitation of efficacy and tolerability data on opioid-naïve and non-selected populations of cancer patients treated with morphine and suggesting that oral morphine, oxycodone and hydromorphone have similar efficacy and toxicity in this patient population.

The aim of this systematic review is to evaluate the scientific evidence for the efficacy and side effects of hydromorphone in the management of moderate to severe cancer pain. Randomized and non-randomized clinical trials, reporting data on efficacy and/or side effects of hydromorphone, were identified. Thirteen eligible studies, involving 1208 patients, were selected. Seven studies compared hydromorphone with other opioids (five with morphine, one with oxycodone and one with fentanyl and buprenorphine) and five of them were randomized controlled trials (RCTs). Most of the studies were conducted on patients already receiving opioid treatment, often at stabilized doses, and most had methodological limitations. The RCTs comparing hydromorphone with morphine and oxycodone showed similar analgesic results, while the comparison of side effects showed minor differences, not consistent across studies. Due to clinical and methodological heterogeneity of the studies, a meta-analysis was not performed. In conclusion there is evidence to support the efficacy and tolerability of hydromorphone for moderate to severe cancer pain as an alternative to morphine and oxycodone, while there is no evidence to demonstrate its superiority or inferiority in comparison with morphine as the first choice opioid for the same indication.

This is a personal account of the clinical work done in the Palestinian Territories by a clinical psychologist working with an international medical Non Governmental Organization (NGO). In her interventions the author used mindfulness-based therapy with people who suffered from severe psychological distress due to the political conflict. Such interventions can be therapeutic and heal deep suffering, whilst offering clients coping strategies when possibly facing other traumatic events in a situation of “chronic emergency” such as the one that people have to face in a country that has been under military occupation for over 40 years. Using a case study approach, the author discusses the intervention with two women, one suffering from post-traumatic stress disorder (PTSD) following the loss of her baby after being kept at a military check-point, and the other suffering from depression following the killing of her son. The mindfulness-based intervention allowed them to explore a therapeutic approach which helped them to overcome their symptoms and “get unstuck”.

Image-guided percutaneous ablation methods have proved effective for treatment of benign bone tumors and for palliation of metastases involving the bone. However, the role of these techniques is controversial and has to be better defined in the setting of palliative care.A systematic review of the existing data regarding minimally invasive techniques for the pain management of vertebral bone metastases was performed by experts of the European Palliative Care Research Network.Only five papers were taken into consideration after performing rigorous screening according to inclusion and exclusion criteria (low number of patients, retrospective series, proceedings).According to the present data a recommendation should be made to perform kiphoplasty in patients with vertebral tumors or metastases. However, the strength of this recommendation was based on one randomized controlled study. Several weaknesses and low quality of study design were observed with other techniques.Further randomized controlled trials are required to improve the strength of evidence available to suggest these procedures on large scale. Until then, the balance of evidence favors the use of these procedures in a small select cohort of patients with severe and disabling back pain refractory to medical therapy.

The paper looks at the symbolic communication – the unconscious communication that lies beyond words – and the use of silence in a non-therapeutic setting. I chose to reflect on a brief but meaningful encounter between the free-spirited Vianne and abused village woman Josephine from the film Chocolat by Lasse Hallstrom. I looked at the unfolding of this informal helping process, reflected on the non-verbal communication, the body language and the wise use of silence. The paper also looks at my personal unconscious motives for choosing this exchange.

bcl-6, CD 10 and CD38 are useful markers for identifying 2 molecularly and prognostically distinct profiles of diffuse large B-cell lymphomas (LCLs), defined as germinal-center B-like and activated B-like. We investigated the prognostic role of bcl-6, CD10 and CD38 immunoreactivity in 102 gastrectomized patients with primary gastric lymphomas (PGLs). There were 41 low-grade marginal zone lymphomas of MALT-type (LGML) and 61 diffuse large B-cell lymphomas with (DLCLMLs; n = 31) or without (DLCLs; n = 30) an LGML component. bcl-6, CD10 and CD38 were significantly more commonly expressed in DLCL or DLCML as compared with LGML (50% vs. 48% vs. 17%, p = 0.0002 for bcl-6; 27% vs. 26% vs. 0%, p = 0.0004 for CD10; 45% vs. 48% vs. 13%, p = 0.0005 for CD38, respectively). CD10 immunoreactivity was independently associated with a better survival in diffuse LCL patients (5-year overall survival: 88% +/- 8% vs. 66% +/- 7%; p = 0.04); bcl-6 or CD38 immunoreactivities did not disclose any prognostic implication. Age, presence of LGML component, lactic dehydrogenase serum levels and use of chemotherapy were additional independent prognostic factors. We conclude that CD10 immunoreactivity assessment could be a clear, easy-to-interpret and reliable prognostic factor in PGL. Accordingly, patients with CD10(+) gastric large B-cell lymphomas may be at reduced risk and eligible for clinical trials evaluating more conservative therapeutic options. (C) 2003 Wiley-Liss, Inc.

The aim of the present study is to compare physician clinical assessment with patient-rated evaluations in the classification of cancer pain patients into groups with different pain levels, according to the presence of incident/breakthrough pain, neuropathic pain, and psychological distress. Average pain in the previous 24 hours was used as the dependent variable in multivariate linear regression models, and incident/breakthrough pain, neuropathic pain, and psychological distress were tested as regressors; in the assessment of regressors, physicians used the Edmonton Classification System for Cancer Pain, whereas patients used structured self-assessment questionnaires. The amount of variability in pain intensity scores explained by the 2 sets of regressors, physician and patient rated, was compared using R 2 values. When tested in 2 separate models, patient ratings explained 20.3% of variability (95% confidence interval [CI] = 15.2–25.3%), whereas physician ratings explained 6.1% (95% CI=2.2–9.8%). The higher discriminative capability of patient ratings was still maintained when both regressor sets were introduced in the same model, with R 2 indices of 17.6% (95% CI=13.0–22.2%) for patient ratings vs 3.4% (95% CI=.9–5.9%) for physician ratings. Patients' self-assessment of subjective symptoms should be integrated in future cancer pain classification systems. Perspective Our results indicate that patient-structured assessment of incident/breakthrough pain, neuropathic pain, and psychological distress significantly contributes to the discrimination of cancer patients with different pain levels. The integration of patient self-assessment tools with more objective clinician assessments can improve the classification of cancer pain.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) and paracetamol are used widely in the management of mild to moderate cancer pain and are frequently combined with opioids in the treatment of moderate to severe pain. Aim: To perform a systematic literature review of the evidence of the efficacy and toxicity of NSAIDs or paracetamol added to WHO Step III opioid treatment for cancer pain. Design and data sources: A systematic literature review of MedLine, EMBASE and Cochrane Central register of controlled trials database was carried out using both text words and MeSH/EMTREE terms. Results: Seven eligible papers were retrieved from the new search and five from the Cochrane review. Five of seven studies showed an additive effect of NSAIDs when combined with opioids either by improving analgesia (three studies) or by reducing the opioid dose (two studies). Paracetamol was only marginally effective in one of five trials. The study designs were not adequate to assess differences in side effects between the opioids alone and opioids in combination with NSAIDs or paracetamol. Conclusions: The evidence from the available clinical trials is of limited amount and quality, but it weakly supports the proposal that the addition of an NSAIDs to WHO Step III opioids can improve analgesia or reduce opioid dose requirement. There is insufficient evidence to support the use of paracetamol in combination with Step III opioids. Data on the toxicity of NSAIDs in this indication are insufficient owing to the small number of patients and the short duration of treatment reported in the studies.

Aim of this study was to validate the use of subjective average pain assessment over an 8-h time period to evaluate cancer pain intensity. A sample of 95 consecutive cancer inpatients were asked to score on 0–10 numerical scales the intensity of their pain at hourly intervals, and then, at the 8th hour, to rate their average pain intensity over the last 8 h. Agreement between the average of the 8 hourly measures (8hA) and the single patient-rated average (PA8h) was examined with the intraclass correlation coefficient (ICC) and the absolute difference (AD) between the two measurements. Associations between AD, gender, age older than 70, somatic pain, visceral pain, neuropathic pain, pain on movement and the presence of pain exacerbations during the 8-h period, were also examined. Average pain intensity scores were very similar with the two measurement schedules: 3.4 for 8hA and 3.7 for PA8h, with a median AD of 0.44 points. Only six patients (6.3%) showed ADs higher than 2 points. Also the ICC (0.85) showed a substantial agreement between the two schedules. Among the examined variables, gender, age over 70 years and presence of pain exacerbations showed a significant association with the agreement level. Overall, our results support the validity of a subjective average pain measurement over 8-h period in cancer patients.

In patients with bone metastases, pain may be absent or moderate at rest, but may be exacerbated by different movements or positions. No study has evaluated separately pain at rest and on movement in patients with bone metastases undergoing treatment with zoledronic acid (ZA). The aim of this prospective observational study was to evaluate the reduction in intensity of pain at rest and in movement-related pain after treatment with up to six infusions of ZA 4 mg every 28 days in patients with painful bone metastases due to breast or prostate cancer cared for at the Oncological Units and Pain Therapy and Palliative Care Unit of the NCI of Milano. Pain was assessed by a six-level verbal rating scale (0–5 score) at baseline and on each infusion as well as at follow-up visits (2 weeks after every infusion). The two main endpoints (estimated reduction in pain and movement-related pain) were defined as the difference between the baseline score and the average of all the post-treatment scores for each patient. To allow for the potential confounding effect of analgesic consumption, patients without any increase in analgesic consumption during zoledronic acid treatment were also analyzed as a separate subgroup. Forty-eight patients with breast (34) or prostate cancer (14) were enrolled. At baseline, 100% of the patients had pain on movement, in 65% of them, the intensity ranged from moderate to very severe, in 61% of the patients, the intensity of pain on movement was higher than the intensity of pain at rest (average difference 0.89; 95% CI, 0.5–1.30). The estimated mean intensity reduction of pain at rest and on movement was: (a) 0.62 (95% CI, 0.28–0.98) and 0.79 (95% CI, 0.43–1.14), respectively, during the first 90 days of ZA treatment; (b) 0.59 (95% CI, 0.23–0.96) and 0.86 (95% CI, 0.49–1.23), respectively, during the entire treatment and follow-up period. Analgesic consumption decreased or was stable on average in 31 and 27%, respectively, of available follow-up data. In the 14 patients with decreased or stable analgesic consumption, pain reduction was 0.61 and 1.01, respectively. In this study, at baseline, all the patients with painful bone metastases experience movement-related pain, and during zoledronic acid treatment, a decrease for both pain at rest and on movement was obtained.