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Purpose Various prognostic indexes have been proposed to improve physicians’ ability to predict survival time in advanced cancer patients admitted to palliative care (PC), but no optimal score has still been identified. The study therefore aims to develop and externally validate a new multivariable predictive model in this setting.Methods We developed the model on 1020 cancer patients prospectively enrolled to home care palliative care at VIDAS Milan, Italy, between May 2018 and February 2020 and followed-up to June 2020. The model was then validated among two separate samples of 544 home care and 247 hospice patients. Overall survival was considered as the primary outcome to develop and validate the model; Cox and flexible parametric Royston-Parmar regression models were used.Results Through a four-step modelling process, among 68 clinical factors considered, five predictors were included in the predictive model, i.e., rattle, heart rate, anorexia, liver failure, and the Karnofsky performance status. Patient’s survival probability at various time points was estimated. The predictive model showed a good calibration and moderate discrimination (area under the receiver operating characteristic curve between 0.72 and 0.79) in the home care validation set, but model calibration was suboptimal in hospice patients.Conclusions The new multivariable predictive model for palliative cancer patients’ survival (PACS model) includes clinical parameters routinely at patient’s admission to PC and can be easily used to facilitate immediate and appropriate clinical decisions for PC cancer patients in the home setting.

The Lombardy Region has one of the most widespread and advanced models of Palliative Care (PC) in the country. However, there is a relative lack of updated data referring to the activity of the Lombardy PC network.This work aims to describe the activity carried out in the two main PC care settings (home care and hospice) in 2019 through the analysis of the data sent by each Unit to the Lombardy Region. Data were analysed on a regional basis and considering the 8 Health Protection Agencies (ATS) separately.In 2019, PC activity was provided by 114 home care units (1.14/100,000 inhabitants) and 70 hospice for a total of 812 beds (8.1 beds/100,000 inhabitants). Overall, 25,514 patients were assisted for a total of 29,892 care pathway. 77.6% of the patients assisted were oncologic and about 67% of the patients who died of cancer in Lombardy were intercepted by CP. 54.4% of patients were taken care of in home care, although with a significant difference between cancer patients (58%) and non-cancer patients (42%). In home care, average activation time was 2.8 days and in 81% of cases the assistance was activated within 24-48 hours; in hospice, average activation time was 3.5 days, with 60% of admissions within 24 hours and over 30% with waiting time ≥3 days. The median duration of home palliative care was approximately 21 days (average 40.5), that in hospice was 9 days (average 17.2). In the home care pathways, the prevalent outcome was the death of the patient at home (64%) and hospitalization in hospice (17.2%), while 86% of hospitalizations in hospice ended with death.This accurate report of the Lombardy PC activity indicates that PC satisfy various qualitative indicators of structural and care process identified by national regulations. However, PC still remain predominantly intended for cancer patients, with relatively short duration of care, particularly in the hospice setting.

PURPOSE To evaluate the prescription of preventive medications with questionable usefulness in community dwelling elderly adults with cancer or chronic progressive diseases during the last year of life. METHODS Through the utilization of the healthcare databases of the Lombardy region, Italy, we identified two retrospective cohorts of patients aged 65 years or more, who died in 2018 and had a diagnosis of either a solid cancer (N = 19 367) or a chronic progressive disease (N = 27 819). We estimated prescription of eight major classes of preventive drugs 1 year and 1 month before death; continuation or initiation of preventive drug use during the last month of life was also investigated. RESULTS Over the last year of life, in both oncologic and non-oncologic patients, we observed a modest decrease in the prescription of blood glucose-lowering drugs, anti-hypertensives, lipid-modifying agents, and bisphosphonates, and a slight increase in the prescription of vitamins, minerals, antianemic drugs, and antithrombotic agents (among oncologic patients only). One month before death, the prescription of preventive drugs was still common, particularly for anti-hypertensives, antithrombotics, and antianemics, with more than 60% of patients continuing to be prescribed most preventive drugs and an over 10% starting a therapy with an antithrombotic, an antianemic, or a vitamin or mineral supplement. CONCLUSION These findings support the need for an appropriate drug review and improvement in the quality of drug prescription for vulnerable populations at the end-of-life.

Background: medical oncologists and palliative care physicians have different tasks even if they play a similar role when coping with pain of their patients. In spite of this converging goal, oncologists and palliative care therapists can not have the same approach and impact in managing pain. This study analyzes how pain is treated and which outcomes derive from in 1 461 cancer patients separately cared by oncologists or palliative care physicians.Methods: data derive from an observational, multicentre, prospective, longitudinal study carried out in 110 Italian hospitals. After inclusion, the data were recorded weekly for a 28 days period of follow-up.Results: 876 patients (60%) were cared by oncologists and 585 (40%) by palliative care physicians. The two professional categories tended to similarly manage the drugs of WHO analgesic ladder, while rescue and adjuvant therapies were more frequently used by palliative care physicians. Opioids daily dose increased from 68.3 to 92.5 mg/day (Effect size=0.282) among oncologists and from 70.8 to 107.8 mg/day (Effect size=0.402) among palliative care physicians. The switch of opioids was applied in 12.3% and in 19.1% (p=0.1634), respectively. Pain intensity decreased in both groups but more strongly in the palliative context. The full responders patients were 50% in oncology wards and 58.9% in palliative care (p=0.0588).Conclusions: this study indicates how much oncologists and palliative care physicians differ in managing cancer pain. The observational nature of this study reflects the natural and unaffected choice of the professionals. As intrinsic limit the study only describes their behaviors without a stringent comparative evaluation.

Delirium in end-of-life patients is reported to be between 13% and 42% and up to 80% in the terminal phase. It is a serious clinical situation, often a cause of death due to the frequent ineffectiveness of treatments. This study aimed to assess whether and how much precocity of diagnosis, hitherto little considered, could affect the outcomes and prognosis of delirium in palliative care settings.Patients consecutively admitted to a palliative care unit (PCU) between October 2018 and December 2019, cared for both in hospice and home programs, were analyzed. All patients were subjected to a careful procedure aimed at recognizing the onset of delirium. The first step was the detection of prodromal "sentinel" symptoms related to incoming delirium. PCU staff and family members/caregivers were trained to observe the patients and immediately identify the appearance of even one symptom. The final diagnosis was performed with the 4AT (4 A's test). Patients were then included in the categories of "early" or "slow" diagnosis (cut-off: four hours) depending on the time between sentinel symptom observation and the final diagnosis of delirium.Among 503 admitted patients, 95 developed delirium. Confusion was the most frequent sentinel symptom (49.5%). The early diagnosis was more frequent in hospice than in home care (p-value0.0001). Delirium was positively resolved in 43 patients, of which 25 with an early diagnosis (p-value=0.038). Time to resolution was shorter in the case of early diagnosis (7.1 vs. 13.7 hours in hospice patients; p-value=0.018). Palliative sedation was performed on 25 patients, but only 8 of them had an early diagnosis.Time of diagnosis was important in determining the clinical outcomes of patients in charge of PCU who experienced delirium. The early diagnosis reduced both mortality and the necessity of palliative sedation.

This living and systematic review aimed to provide an updated summary of the available evidence on pain undertreatment prevalence in patients with cancer; correlations with some potential determinants and confounders were also carried out.We updated a systematic review published on 2014, including observational and experimental studies reporting the use of the pain management index (PMI) in adults with cancer and pain, from 2014 to 2020. We conducted searches in PubMed/MEDLINE, Embase, and Google Scholar. We performed univariate and multivariable regression analyses to describe the relationship between PMI and a list of potential explanatory variables.Twenty new papers were identified, yielding a total sample size of 66 studies. The proportion of patients classified as undertreated according to the year of study publication shows a higher decrease from 1994 to 2013 (-13% as relative change) than the most recent years 2014-2020 (-11%). The quality of the included studies has increased over the years (from 80% to 93%). At the multivariable analysis, a statistically significant relationship was confirmed between undertreatment and the year of the publication of the study and with a low-medium economic level of the countries, where the studies were conducted.Despite the improvement when compared to the period 1994-2000, still about 40% of the cases identified received an analgesic treatment inadequate to the intensity of pain, according to the PMI. Despite its intrinsic limitations, PMI continues to be widely used, and it could allow a continuous monitoring of pain management across a different mix of studies and patients.

ObjectivesHospice and home palliative care have been associated to a reduction of aggressive treatments in the end-of-life, but data in the Italian context are scanty. Therefore, we aim to investigate the role of palliative care on indicators of end-of-life intensity of care among patients with cancer in Lombardy, the largest Italian region.MethodsWithin a retrospective study using the healthcare utilisation databases of Lombardy, Italy, we selected all residents who died in 2019 with a diagnosis of cancer. We considered as exposure variables admission to palliative care and time at palliative care admission, and as indicators of aggressive care hospitalisations, diagnostic/therapeutic procedures, in-hospital death, emergency department visits and chemotherapy over a time window of 30 days before death; chemotherapy in the last 14 days was also considered.ResultsOur cohort included 26 539 individuals; of these, 14 320 (54%) were admitted to palliative care before death. Individuals who were admitted to palliative care had an odds ratio (OR) of 0.27 for one hospitalisation, 0.14 for ≥2 hospitalisations, 0.25 for hospital stay ≥12 days, 0.38 for minor diagnostic/therapeutic procedures, 0.18 for major diagnostic/therapeutic procedures, 0.02 for in-hospital death, 0.35 for one emergency department visit, 0.29 for ≥2 emergency department visits and 0.66 for chemotherapy use in the last 30 days; the OR was 0.56 for chemotherapy use in the last 14 days.ConclusionsThis large real-world analysis confirms and further support the importance of palliative care assistance for patients with cancer in the end- of- life; this is associated to a significant reduction in unnecessary treatments.

Introduction Opioids are often used to relieve moderate to severe pain, but their analgesic response may vary. We focused on the absolute lack of analgesic response immediately after beginning opioid treatment, quantifying the proportion of patients with unchanged or worse pain on day 3 (defined as early non-responders (ENRs)) and day 7. Methods This is a post-hoc analysis from a randomized controlled trial involving 498 cancer patients with pain, starting to receive WHO step III opioids. On days 1, 3 and 7 pain intensity (PI) was measured. Results On day 3, 68 (13.7%) patients were ENRs, 53 no change and 15 greater PI compared to baseline. The relationships between pain and clinical characteristics showed no significant differences between ENRs and Early responders (ERs), except for PI at baseline, which was significantly lower in ENRs. ENRs on day 3 were re-assessed on day 7 to explore the patterns of analgesic response: 31.7% of patients remained NRs, 48.3% had become responders, and 20.0% were poor responders. Adverse drug reactions were similar in ERs and ENRs at each visit. Discussion The complete lack of early response to opioids in cancer patients is clinically important and more frequent than expected. Better definition of the mechanism will allow better pain management in cancer and non-cancer patients.

In treating chronic and acute pain, opioids are widely used. Although they do provide analgesia, their usage does come with adverse events (AEs). One of the most burdensome is opioid-induced bowel dysfunction, and more specifically opioid-induced constipation (OIC). The pathogenesis of these AEs is well known as the consequence of the action of opioids on m-receptors in the enteric nervous system. In recent years, medicines counteracting this specific action at the receptors have been registered for clinical use: the peripherally acting μ-opioid receptor antagonists (PAMORAs). The knowledge of their comparative efficacy and tolerability is very important for physicians and patients in opioid therapy. This systematic review of the existing literature on PAMORAs aimed to study the relative clinical advantages and disadvantages. The most important data banks, including "PubMed," "Embase," "CT.gov," "ICTRP" and "CINAHL" were used to find the published material on PAMORAs. The selected publications were examined to systematically analyze the efficacy and safety of the four existing PAMORAs. All of the medications are superior to placebo in reducing OIC. There are few published data on alvimopan used to treat OIC, and it is only indicated for the treatment of post-abdominal surgery ileus. Methylnaltrexone is studied mainly in its subcutaneous (SC) formulation. When used in its oral formulation, it seems more rapid than naloxegol and placebo in the reduction of OIC. Naldemedine is able to produce more spontaneous bowel movements (SBMs) when compared to alvimopan and naloxegol. Tolerability was found to be similar for all of them. In particular, they affect the gastrointestinal tract (GI), with flatulence and diarrhea, especially at high dosages. For some of them, nasopharyngitis and abdominal pain were observed as treatment adverse effects (TEAs). Several cardiovascular TEAs were reported after methylnaltrexone use, but it is not clear whether they were consequences of the drug or related to the general conditions of the patients. Considering the existing data, naloxegol and naldemedine seem to be the best choices, with a higher number of spontaneous bowel movements following naldemedine administration.

Delirium occurs in 50-80% of end-of-life patients but it is often misdiagnosed. Identification of clinical factors potentially associated with delirium onset can lead to a correct early diagnosis. To this aim, we conducted an observational prospective study on patients from an Italian Palliative Care Unit (PCU) in 2018-2019 and evaluated the presence of clinical factors at patients’ admission. We then compared their presence in patients who developed delirium and in those who did not during follow-up. On 503 enrolled patients, 95 (18.9%) developed delirium. In univariate analyses, factors significantly more frequent in patients with delirium were advanced age, care in hospice, very compromised performance status, hypoxia, high number of simultaneous clinical factors, presence of breathlessness, poor well-being, severe drowsiness, and background therapy with haloperidol and drugs acting on CNS. In multivariate analyses, setting of care (odds ratio, OR, 1.68 for hospice versus home care, 95% confidence interval, CI 1.02-2.75; p=0.040), and administration of psychiatric drugs (OR 1.74 for administration versus no administration, 95% CI 1.08-2.81; p=0.023) were significantly associated with the risk of developing delirium, while the associations with age (OR 1.82 for > 80 years versus ≤ 70 years, 95% CI=0.98-3.36; p=0.046) and presence of breathlessness (OR 1.70, 95%, CI 0.99-2.89, p=0.053) were of borderline significance. The study indicates that some clinical factors are associated with the probability of delirium onset. Their evaluation in PC patients could help the healthcare professionals to timely identify the development of delirium in those patients.

Delirium occurs in 50–80% of end-of-life patients but is often misdiagnosed. Identification of clinical factors potentially associated with delirium onset can lead to a correct early diagnosis. To this aim, we conducted a prospective cohort study on patients from an Italian palliative care unit (PCU) admitted in 2018–2019. We evaluated the presence of several clinical factors at patient admission and compared their presence in patients who developed delirium and in those who did not develop it during follow-up. Among 503 enrolled patients, after a median follow-up time of 16 days (interquartile range 6–40 days), 95 (18.9%) developed delirium. Hazard ratios (HR) and corresponding 95% confidence intervals were computed using Cox proportional hazard models. In univariate analyses, factors significantly more frequent in patients with delirium were care in hospice, compromised performance status, kidney disease, fever, renal failure, hypoxia, dehydration, drowsiness, poor well-being, breathlessness, and “around the clock” therapy with psychoactive drugs, particularly haloperidol. In multivariate analyses, setting of care (HR 2.28 for hospice versus home care, 95% CI 1.45–3.60; p

Background: Cancer patients experience multiple symptoms throughout the course of the disease. We aimed to provide a comprehensive analysis of the symptom burden in patients with advanced cancer at admission to specialist palliative care (PC) services and seven days later to estimate the immediate impact of PC intervention. Patient and methods: The analysis was based on an observational, prospective, multicenter study (named DEMETRA) conducted in Italy on new patients accessing network specialist PC centers during the period May 2017&ndash, November 2017. The prevalence and intensity of symptoms were assessed at baseline and after seven days using three tools including the Edmonton Symptom Assessment System (ESAS). Results: Five PC centers recruited 865 cancer patients. Thirty-three different symptoms were observed at the baseline, the most frequent being asthenia (84.9%) and poor well-being (71%). The intensity of the most frequent symptoms according to ESAS ranged from 5.5 for asthenia to 3.9 for nausea. The presence and intensity of physical symptoms increased with increasing levels of anxiety and depression. After seven days, prevalence of nausea and breathlessness as well as intensity of almost all symptoms significantly decreased. Conclusions: The study confirmed the considerable symptom burden of patients with advanced cancer. PC intervention has significantly reduced the severity of symptoms, despite the patients&rsquo, advanced disease and short survival.

Background: Cancer patients experience a number of symptoms throughout the course of the disease. We aimed to provide a comprehensive analysis of the symptom burden in patients with advanced cancer at admission to specialist palliative care (PC) services and seven days later, to estimate the immediate impact of PC intervention.Patient and methods: The analysis was based on an observational, prospective, multicenter study (named DEMETRA) conducted in Italy to outline the profile of patients, families and PC services in different care settings (hospital, hospice and home care). The prevalence and intensity of symptoms were assessed using three tools, including the Edmonton Symptom Assessment System (ESAS).Results: Five PC centers recruited 865 cancer patients. Thirty-three different symptoms were observed at baseline, the most frequent being asthenia (85%) and lack of appetite (71%). Two-thirds of patients experienced six to twelve simultaneous symptoms. The intensity of the most frequent symptoms according to ESAS varied from 5.5 for asthenia to 3.9 for nausea. The presence and intensity of physical symptoms increased with increasing levels of anxiety and depression. After seven days, prevalence decreased significantly only for nausea and breathlessness, while intensity diminished significantly for almost all symptoms. At admission we noted a correlation between patients' symptoms and the care setting. After one week, the symptom intensity was uniformly reduced in all settings.Conclusions: The study confirmed the considerable symptom burden of patients with advanced cancer. PC intervention significantly lessened the severity of symptoms, despite the patients’ advanced disease and short survival.

Opioid switching is a possible strategy for inadequate analgesia or unmanageable side effects. Its effectiveness ranges from 50 to 90% and is still debated. We analyzed the impact of opioid switching in a cancer pain population treated with strong opioids for pain. This is a post hoc analysis from a multicenter, randomized, four-arm, controlled, phase IV clinical trial. Outcome variables included the percentages of switches, the reasons for the switch, the dose changes before and after the switch, depending on the starting opioid, the response in case of inadequate analgesia, and unmanageable toxicity, and the variability of response among and within patients. We analyzed 498 patients. The opioid was switched in 79 patients (15.9%) 87 times, mainly for uncontrolled pain (52.3%), adverse opioid reactions (22.1%), both of these (4.8%), and dysphagia (20.8%). The reasons for switching varied depending on the starting opioid. Pain reduction was good after 51.45% of switches and control of opioid side effects was good after 43.5%. The relief of opioid-induced toxicity varied among adverse events and within each patient. The daily doses were higher after switching oral opioids and lower after transdermal drugs. Half of the patients who underwent switching experienced improved relief of pain or amelioration of opioid toxicity. The switch can help in the management of some cases but with many limits and uncertainties.

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/.

Introduction Opioids are often used to relieve moderate to severe pain, but their analgesic response may vary. We focused on the absolute lack of analgesic response immediately after beginning opioid treatment, quantifying the proportion of patients with unchanged or worse pain on day 3 (defined as early non-responders (ENRs)) and day 7. Methods This is a post-hoc analysis from a randomized controlled trial involving 498 cancer patients with pain, starting to receive WHO step III opioids. On days 1, 3 and 7 pain intensity (PI) was measured. Results On day 3, 68 (13.7%) patients were ENRs, 53 no change and 15 greater PI compared to baseline. The relationships between pain and clinical characteristics showed no significant differences between ENRs and Early responders (ERs), except for PI at baseline, which was significantly lower in ENRs. ENRs on day 3 were re-assessed on day 7 to explore the patterns of analgesic response: 31.7% of patients remained NRs, 48.3% had become responders, and 20.0% were poor responders. Adverse drug reactions were similar in ERs and ENRs at each visit. Discussion The complete lack of early response to opioids in cancer patients is clinically important and more frequent than expected. Better definition of the mechanism will allow better pain management in cancer and non-cancer patients.

Oxycodone-Naloxone (OXN) aims to reduce opioid-related constipation while being successfully analgesic.We evaluated the analgesic response, prevalence, and severity of side effects in 176 cancer patients with moderate to severe pain and treated with OXN. Patients were followed for 28 days and evaluated every seven. Pain intensity, changes of therapy, and adverse drug reactions were recorded at each visit. The primary efficacy endpoint was the proportion of responders (≥30% reduction of pain intensity from baseline to final) and final average pain score ≤4 on a 0-10 scale.Average and worst pain intensity, and breakthrough pain (BTP) prevalence decreased over time and 81.3% of patients were responders. The starting daily dose of OXN was raised from 25.1±13.0 mg to 44.1±29.9 mg, and dose escalation5%/day was observed in 19.4% of patients; 40.8-46.2% and 11.0-17.0% experienced any and severe grade of constipation during the follow-up visit, respectively. Digestive system tumor, thyroid endocrinopathies, psychological irritability, and BTP increased the risk of analgesic non-response.OXN had strong analgesic effect in moderate to severe cancer pain patients: the safety profile is in line with the common adverse effects of opioids and severe constipation was uncommon. This article is protected by copyright. All rights reserved.

Introduction: Palliative care not only focuses on physical ailments associated with the disease, but also considers the psychological, social and spiritual needs of the patients. The aim of this study is to assess the impact of physical activity on palliative care patients, with special regard to the subjective assessment of severity of total pain and quality of life. Materials and methods: The study was conducted on 92 palliative care patients either in a hospice or at home. The tool used to assess the patients was an original questionnaire focusing on the area of their independence and motor abilities. The study attempted to understand whether an appropriate physical activity and the instruction of palliative care patients and their families in the field of independence would improve the quality of life and reduce the intensity of total pain in the patients. Results: All of the patients were at an advanced stage of cancer. The survey at time “0”, conducted before the start of the instructions for patients and their relatives, showed that a majority of patients (47, 51.09%) often experienced limitations during the performance of daily activities. In the fourth visit, conducted one week after the fourth educational session, there was a significant increase in patients who did not experience any limitations in performing their daily activities or experienced them just sometimes. Conclusions: The ultimate effect of the proposed educational program on physical activity was an increase in the quality of life, a reduction in pain and a mood improvement. These results would need confirmation with more extensive studies.

Cancer cachexia (CC) is a debilitating multifactorial syndrome, involving progressive deterioration and functional impairment of skeletal muscles. It affects about 80% of patients with advanced cancer and causes premature death. No causal therapy is available against CC. In the last few decades, our understanding of the mechanisms contributing to muscle wasting during cancer has markedly increased. Both inflammation and oxidative stress (OS) alter anabolic and catabolic signaling pathways mostly culminating with muscle depletion. Several preclinical studies have emphasized the beneficial roles of several classes of nutraceuticals and modes of physical exercise, but their efficacy in CC patients remains scant. The route of nutraceutical administration is critical to increase its bioavailability and achieve the desired anti-cachexia effects. Accumulating evidence suggests that a single therapy may not be enough, and a bimodal intervention (nutraceuticals plus exercise) may be a more effective treatment for CC. This review focuses on the current state of the field on the role of inflammation and OS in the pathogenesis of muscle atrophy during CC, and how nutraceuticals and physical activity may act synergistically to limit muscle wasting and dysfunction.

In order to plan the right palliative care for patients and their families, it is essential to have detailed information about patients&rsquo, needs. To gain insight into these needs, we analyzed five Italian local palliative care networks and assessed the clinical care conditions of patients facing the complexities of advanced and chronic disease. A longitudinal, observational, noninterventional study was carried out in five Italian regions from May 2017 to November 2018. Patients who accessed the palliative care networks were monitored for 12 months. Sociodemographic, clinical, and symptom information was collected with several tools, including the Necesidades Paliativas CCOMS-ICO (NECPAL) tool, the Edmonton Symptom Assessment System (ESAS), and interRAI Palliative Care (interRAI-PC). There were 1013 patients in the study. The majority (51.7%) were recruited at home palliative care units. Cancer was the most frequent diagnosis (85.4%), and most patients had at least one comorbidity (58.8%). Cancer patients reported emotional stress with severe symptoms (38.7% vs. 24.3% in noncancer patients, p = 0.001) and were less likely to have clinical frailty (13.3% vs. 43.9%, p &lt, 0.001). Our study confirms that many patients face the last few months of life with comorbidities or extreme frailty. This study contributes to increasing the general knowledge on palliative care needs in a high-income country.

Background: Scanty data exist on the integration between the analgesic effect of opioids, dose changes, and adverse events in cancer patients. Methods: To provide further information on this issue, we analysed data on 498 advanced-stage cancer patients treated with strong opioids. At baseline and three visits (at days 7, 14, and 21), pain intensity, oral morphine-equivalent daily dose, and the prevalence of major adverse events were measured. The proportion of responders (pain intensity decrease &ge, 30% from baseline) and non-responders, as well as of patients with low or high dose escalation, was calculated. Results: Pain intensity strongly decreased from baseline (pain intensity difference &minus, 4.0 at day 7 and &minus, 4.2 at day 21) in responders, while it was quite stable in non-responders (pain intensity difference &minus, 0.8 at day 7 and &minus, 0.9 at day 21). In low dose escalation patients (82.4% at final visit), daily dose changed from 52.3 to 65.3 mg, in high dose escalation patients (17.6%), it varied from 94.1 to 146.7 mg. Among responders, high dose escalation patients experienced significantly more frequent adverse events compared to low or high dose escalation patients, while no differences were observed in non-responders. Conclusions: The response to opioids results from the combination of three clinical aspects, which are strongly interrelated. These results provide some thoughts to help clinical evaluations and therapeutic decisions regarding opioid use.

Context Opioids are frequently used for the treatment of moderate-to-severe pain and their use may produce a number of unwanted adverse events (AEs). Objectives The objective of this study was to understand the burden of opioid-induced AEs in cancer patients with pain after the introduction of strong opioids (WHO Step III). Methods This is a cohort study derived from a randomized controlled trial involving 498 cancer patients with pain who received strong opioids. During 28-day follow-up, we analyzed frequency, intensity, and changes over time of the main opioid-induced AEs; the influence of previous pain therapy on AEs; and the relationships between the presence of AEs and analgesic response. Results After starting strong opioids, dry mouth, nausea, and vomiting immediately increased and persisted over time, constipation continued to increase, while drowsiness and confusion tended to decrease. Patients previously treated with weak opioids had more frequent and severe AEs. While at all observation points the percentage of patients without AEs was 37%–39%, considering all the five scheduled visits, from Day 3 to Day 28, 17% of patients never experienced any AEs, while 48% of patients had four or more concomitant AEs. Patients with no AEs experienced significantly lower pain intensity. Conclusion Opioid introduction induces various AEs that persist over time and worse patients' symptomatology. Moreover, there seems to be a different expression of the opioid toxicity among patients, and a possible interaction between AEs and the analgesic response. The balance between the opioids analgesic effect and induced toxicity is fundamental in deciding the best management for pain in cancer patients.

BACKGROUND Over the last decades, consumption of opioids for the treatment of pain increased steadily in the United States, Australia, and a few European countries. To date, no study has analysed time trends in opioid consumption across Europe. METHODS We analysed data provided by International Narcotics Control Boards on the consumption of fentanyl, oxycodone, morphine, hydromorphone and pethidine in 40 European countries over the last decade. Trends in total opioid consumption from 1990 to 2016 in 22 selected European countries, the European Union (EU) as a whole, and, for comparison purpose, the United States, were analysed using the joinpoint regression analysis. RESULTS In 2014-2016, opioid use was >10,000 defined daily doses for statistical purposes (s-DDD) per 1,000,000 inhabitants die in Western/Northern countries, whereas it was

A 47‐year‐old man, affected by Schwannomatosis, presented a very severe pain (10/10, NRS) with paroxysmal shooting episodes, allodynia, paresthesia, and dysesthesia; in parallel, the patient had lost weight (from 70 to 49 kg) and experienced fatigue and deep depression. The previous pain prescription, including opioids and antineutopathic drugs, was fully ineffective. We progressively substituted this therapy with 15 drops, 3 times/daily, of THC/CBD in a concentration ratio 5:1, equal to 15 mg of active substance each time, reaching improvement in pain intensity (6/10) and in several other aspects as mood and quality of life

BACKGROUND AND OBJECTIVE Opioid treatments are often prolonged because of the pathology causing pain. We focused on the cognitive functions in patients with chronic pain treated with opioids. This topic is currently controversial, but in practice, the consequences are important in patients' daily lives, social interactions, working ability, and driving. DATABASE AND DATA TREATMENT Medline and Embase databases were searched for eligible articles. We included studies that enrolled patients with chronic noncancer pain, studies with patients receiving opioid treatment, studies with a control group not using opioids, and studies in which cognitive functions were evaluated with specific tests. The cognitive areas examined were as follows: attention, reaction time, executive functions, psychomotor speed, memory, and working memory. From 356 abstracts screened, 9 articles satisfied eligibility criteria and were included in our review: 7 observational and 7 experimental studies. We classified the pain treatments as follows: opioids, other drugs active on the central nervous system (CNS) (antidepressants/anticonvulsants), and treatments not specifically targeted to the CNS. RESULTS Statistically significant differences were seen only with regard to attention between opioids alone and no centrally acting treatment (standardized mean difference [SMD]: -0.53, 95% confidence interval [CI] : -0.91, -0.15; P = 0.007; I2 = 23%) and between opioids combined with antidepressants and/or anticonvulsants and no centrally acting treatment (SMD: -0.62, 95% CI: -1.04, -0.20; P = 0.004; I2 = 0%). No other significant differences were observed. CONCLUSIONS Opioids reduce attention when compared with treatments not targeted on the CNS. If opioids are used together with antidepressants and/or anticonvulsants, this effect increases. SIGNIFICANCE These findings on the neuropsychological effects of opioids could be used to generate strategies to refine pain treatments.

A Roberto,1 MT Greco,2 L Legramandi,3 F Galli,3 M Galli,4 O Corli1 1Pain and Palliative Care Research Unit, Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy, 2Department of Clinical Sciences and Community, University of Milan, Milan, Italy, 3Methodology for Clinical Research Laboratory, Oncology Department, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy, 4Scientific Medical Communication srl, Novara, Italy Background: Opioids are the most important pharmacological treatment for moderate-to-severe cancer pain, but side effects limit their use. Transdermal fentanyl (TDF) and oral prolonged-release oxycodone-naloxone (OXN-PR) are effective in controlling chronic pain, with less constipation compared to other opioids. However, TDF and OXN-PR have never been directly compared.Patients and methods: Cancer patients with moderate-to-severe chronic pain were consecutively enrolled in two prospective 28-day trials, received either TDF or OXN-PR, and were assessed at baseline and after 7, 14, 21, and 28 days. The primary endpoint was 28-day analgesic response rate (average pain intensity decrease ≥30% from baseline). Other outcome measures included opioid daily dose changes over time; need for adjuvant analgesics; number of switches; premature discontinuation; presence and severity of constipation; and other adverse drug reactions. To compare the efficacy and the safety of TDF and OXN-PR, we used the propensity score analysis to adjust for heterogeneity between the two patient groups.Results: Three hundred ten out of 336 patients originally treated (119 TDF and 191 OXN-PR) were included in the comparative analysis. The amount of responders was comparable after TDF (75.3%) and OXN-PR administration (82.9%, not significant [NS]). The final opioid daily dose expressed as morphine equivalent was 113.6 mg for TDF and 44.5 mg for OXN-PR (p5% was less common after OXN-PR (19.3%) than after TDS administration (37.9%, p

Context. Despite the large body of literature on breakthrough cancer pain (BTcP), an accurate estimate of BTcP prevalence is still not available. Objectives. To provide an estimate of BTcP prevalence and investigate the association between different prevalence rates and possible determinants. Methods. We conducted MEDLINE and EMBASE searches for studies published from 1990 to 2012 reporting data on BTcP prevalence in adult cancer populations. Pooled prevalence rates from observational studies with an acceptable methodological quality were computed. The association between BTcP prevalence and possible predictors was investigated using subgroup analyses and meta-regression. Results. Twenty-seven observational studies were identified. When quality criteria were applied, only 19 studies were included in the pooled analysis. The overall pooled prevalence was 59.2%, with high heterogeneity. The lowest prevalence rates were detected in studies conducted in outpatient clinics (39.9%), and the highest prevalence was reported in studies conducted in hospice (80.5%). The association between BTcP prevalence and other determinants such as publication year, age, gender, metastatic disease prevalence, or baseline pain intensity did not reach statistical significance. Conclusion. In the context of a large between-studies heterogeneity, more than one in two patients with cancer pain also experiences BTcP, with some variability according to clinical and organizational variables. J Pain Symptom Manage

Fabio Guerriero,1,2 Anna Roberto,3 Maria Teresa Greco,4 Carmelo Sgarlata,1 Marco Rollone,2 Oscar Corli3 1Department of Internal Medicine and Medical Therapy, Section of Geriatrics, University of Pavia, 2Department of Geriatrics, Agency for Elderly People of Pavia, Santa Margherita Institute, Pavia, 3Department of Oncology, Pain and Palliative Care Research Unit, IRCCS-Mario Negri Institute for Pharmacological Research, 4Unit of Medical Statistics, Biometry and Epidemiology GA Maccacaro, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy Background: Two-thirds of older people suffer from chronic pain and finding valid treatment options is essential. In this 1-yearlong investigation, we evaluated the efficacy and safety of prolonged-release oxycodone–naloxone (OXN-PR) in patients aged ≥70 (mean 81.7) years.Methods: In this open-label prospective study, patients with moderate-to-severe noncancer chronic pain were prescribed OXN-PR for 1 year. The primary endpoint was the proportion of patients who achieved ≥30% reduction in pain intensity after 52 weeks of treatment, without worsening bowel function. The scheduled visits were at baseline (T0), after 4 weeks (T4), and after 52 weeks (T52).Results: Fifty patients completed the study. The primary endpoint was achieved in 78% of patients at T4 and 96% at T52 (P

Background Dealing with cancer pain implies assessing the intensity and other attributes of pain and identifying appropriate outcomes and endpoints to evaluate the effect of treatments. Methods In the context of an observational longitudinal prospective study, 1461 painful cancer patients were evaluated at baseline and weekly over 4 weeks. Four pain intensity (PI) measures (worst, average, least and right now: WP, AP, LP, and PRN), pain relief and patients’ satisfaction with pain treatments were recorded. Starting from these data, we extrapolated the full responder (FR) subjects, whose PI decreased by ≥2 points, or by ≥30%, or who obtained a final score of ≤5 points, according to criteria previously suggested by literature. The receiver operating characteristics (ROC) curve analysis was used to estimate the predictive accuracy. Results All the PI measures decreased from the initial to final visit: the reduction was 1.9 as WP, 1.3, 0.8 and 1.2 as AP, LP and PRN, respectively. The proportion of FR differed from 47.8% to 88.3% depending on PI measures and the criterion adopted. ROC analysis showed an acceptable accuracy of all endpoints and confirmed the cut-offs recommended by the literature. The best criterion corresponded to a PI absolute value of ≤4 points when measured as AP. Conclusions All measures applied seem able to profile the evolution of pain, with some differences. This implies the need of an appropriate choice of outcomes and endpoints according to the goal and objective of the intervention under evaluation.

Objective. This analysis, carried out in the context of a wider observational prospective study, tried to explore whether four World Health Organization/step-III opioids (morphine, oxycodone, fentanyl, and buprenorphine) had different effectiveness when using several different outcomes and endpoints. Design. Cross-sectional and longitudinal design. Setting. Oncologic, palliative, and pain centers in Italy. Patients. Two hundred fifty-eight cancer patients monitored over a 3-week follow-up program. Intervention. Not applicable. Outcome Measures. The analgesic efficacy was assessed using effectiveness endpoints, such as pain intensity, pain intensity difference (PID), proportion of nonresponders (NR) and full-responders (FR) subjects, percentage of switches and dose escalation. Results. Mean values of PID led to differences among opioids ranging from 10% to 30%. FR (PID ≥ 30%) were more frequent in buprenorphine-fentanyl-oxycodone groups than in morphine; NR (PID ≤ 0%) were variable. The percentage of switches resulted three times more frequent when using morphine than buprenorphine (24.4% vs 8.6%). An increase of dose ≥5% a day was observed in 33.3% of fentanyl patients vs 15% of buprenorphine. As a whole, opioids show some different behaviors on the basis of the considered endpoints. Conclusions. The observed results, even if the small sample size and the nature itself of the study do not allow a definitive evaluation of the effectiveness of the drugs, underline a degree of variability among opioids and address toward a correct planning of a comparative randomized clinical trial that is now underway in Italy. For this reason, a confirmative effectiveness randomized controlled trial is required.

The overall aim of the present study was to further develop an evidence-based platform for the content of an international cancer pain classification system. Data from a multicentre, observational longitudinal study of cancer patients were analysed. Analyses were carried out in 2 samples: (A) Cross-sectional data of patients on opioids at inclusion, and (B) patients just admitted to palliative care. Outcome measures in the models we investigated were pain on average, worst pain, and pain relief at inclusion, and at day 14, respectively. Uni- and multivariate regression models were applied to test the explicative power on pain outcomes of a series of known pain domains, including incident pain, psychological distress, neuropathic pain, pain localisation, sleep disturbances, total morphine equivalent daily dose (MEDD), and cancer diagnosis. In the 2 analyses, 1529 (A) and 352 (B) patients were included, respectively. Incident pain, pain localisation, MEDD, use of nonsteroidal antiinflammatory drugs, and sleep were associated with one or more of the pain outcomes in analysis A, while initial pain intensity, initial pain relief, incident pain, localisation of pain, cancer diagnosis, and age were predictors in the longitudinal analysis. Identified domains explained 16% to 24% of the variability of the pain outcome. Initial pain intensity emerged as the strongest predictor of pain outcome after 2 weeks, and incident pain was confirmed to be a relevant domain. The regression models explained only a minor part of the variability of pain outcomes.

Background Transdermal delivery systems containing fentanyl or buprenorphine, despite the relatively lack of comparative studies, have reached an impressive share of the market in several countries. In the context of a wider observational study, we applied the propensity score to test the comparative effectiveness of the two routes of administration (oral vs. transdermal). Methods We applied the propensity score in a subgroup of patients (starting the World Health Organization third step therapy during the scheduled follow-up of 28 days) using pre-planned primary (pain intensity change) and secondary endpoints, such as increase in doses, need for switching and safety profile. Univariate and multivariate analyses were carried out. Results Three-hundred sixty-six eligible cases were analysed. We found a difference among the two groups in terms of variables potentially associated with therapy choice and outcomes. After adjusting for propensity score, results were in favour of transdermal delivery systems for the primary endpoint (odds ratio 1.68; p = 0.04). A similar trend was also present for the other secondary endpoints. Only in the case of nausea and vomiting, patients receiving transdermal delivery systems reported a higher frequency of events. Conclusion The application of the propensity score has helped understand better the actual effectiveness of transdermal delivery systems that are at least equivalent to the oral opioids, and even more effective for pain intensity reduction.

Most patients with advanced or metastatic cancer experience pain and despite several guidelines, undertreatment is well documented. A multicenter, open-label, prospective, non-randomised study was launched in Italy in 2006 to evaluate the epidemiology, patterns and quality of pain care of cancer patients. To assess the adequacy of analgesic care, we used a standardised measure, the pain management index (PMI), that compares the most potent analgesic prescribed for a patient with the reported level of the worst pain of that patient together with a selected list of clinical indicators. A total of 110 centres recruited 1801 valid cases. 61% of cases were received a WHO-level III opioid; 25.3% were classified as potentially undertreated, with wide variation (9.8-55.3%) according to the variables describing patients, centres and pattern of care. After adjustment with a multivariable logistic regression model, type of recruiting centre, receiving adjuvant therapy or not and type of patient recruited (new or already on follow-up) had a significant association with undertreatment. Non-compliance with the predefined set of clinical indicators was generally high, ranging from 41 to 76%. Despite intrinsic limitations of the PMI that may be considered as an indicator of the poor quality of cancer pain care, results suggest that the recourse to WHO third-level drugs still seems delayed in a substantial percentage of patients. This delay is probably related to several factors affecting practice in participating centres and suggests that the quality of cancer pain management in Italy deserves specific attention and interventions aimed at improving patients' outcomes.

The amount and quality of information and awareness in cancer patients’ is a topic frequently debated, but few studies have focussed on terminal patients. This is the objective of the present study that involved two different palliative home-care units in Italy, which recruited 550 terminal cancer patients. Data from patients and their caregivers was prospectively collected with special attention to information patients were provided with when their cancer was diagnosed and patients’ awareness of their current health condition. In the case of the information, 67.0% of patients reported they were previously informed about their diagnosis, but only 58.0% seemed to be aware of their terminal condition. The comparison between the caregivers opinions about the level of information provided to the patients and their present awareness and what the patients really know about their own disease shows a high degree of correspondence. Some variables such as age and education level of patients were associated with patient’s awareness.

Marzia Lazzari,1 Maria Teresa Greco,2,3 Claudio Marcassa,4 Simona Finocchi,1 Clarissa Caldarulo,1 Oscar Corli2 1Emergency Care, Critical Care Medicine, Pain Medicine and Anesthesiology Department, Tor Vergata Polyclinic, University of Rome, Rome, 2Oncology Department, Pain and Palliative Care Research Unit, Mario Negri IRCCS, 3Department of Clinical Sciences and Community, University of Milan, Milan, 4Cardiology, Fondazione Maugeri IRCCS Veruno, Novara, Italy Background: World Health Organization step III opioids are required to relieve moderate-to-severe cancer pain; constipation is one of the most frequent opioid-induced side effects. A fixed combination, prolonged-release oxycodone/naloxone (OXN), was developed with the aim of reducing opioid-related gastrointestinal side effects. The objective of this study was to compare the efficacy and safety of prolonged-release oxycodone (OXY) alone to OXN in opioid-naïve cancer patients with moderate-to-severe pain. Methods: Propensity analysis was utilized in this observational study, which evaluated the efficacy, safety, and quality of life. Results: Out of the 210 patients recruited, 146 were matched using propensity scores and included in the comparative analysis. In both groups, pain intensity decreased by ≈3 points after 60days, indicating comparable analgesic efficacy. Responder rates were similar between groups. Analgesia was achieved and maintained with similarly low and stable dosages over time (12.0–20.4mg/d for OXY and 11.5–22.0mg/d for OXN). Bowel Function Index (BFI) and laxative use per week improved from baseline at 30days and 60days in OXN recipients (-16, P

10089 Background: The prolonged use of opioids is usually associated with the appearance of adverse events as drowsiness, constipation, nausea/vomiting, and dizziness. Some effects are self-limiting over time for the onset of tolerance while others, as constipation, persist. Clinical studies demonstrated that the association oxycodone-naloxone (OXN), reduced the constipation in the presence of unchanged analgesic efficacy. Though, the variability of the analgesic response to OXN is not explained yet. The aim of this study was to evaluate the association between the clinical and genetics factors and analgesics response at OXN. Methods: In this study the cancer patients with moderate to severe pain received OXN and followed for 28 days. At each visit pain intensity modifications of therapy and adverse drug reactions (ADRs) were recorded. The primary efficacy endpoint was the proportion of responders, defined as patients with a decrease of the average pain intensity from baseline to last visit ≥30% and a final average pain score≤4, measured on 0-10 numerical rating scale. Genetic tests to identify SNPs related to opioid response were performed in each patient. Results: 14 centers participated in the study and recruited 206 patients. Among 176 patients analyzed for a primary endpoint the mean age was 68 (SD 10); 56% were male. Average and worst pain intensity decreased from baseline to last visit from 6.2 to 2.9 and from 8.3 to 4.6 respectively. 81% of patients were responders. Digestive system tumors (p = 0.05), concomitant thyroid endocrinopathy (p = 0.023), psychological irritability (p = 0.0029) and breakthrough pain at baseline were found to decrease the risk of positive response. None of the investigated polymorphisms influenced the analgesic response. Moderate to severe intensity ADRs were mainly constipation (26%), drowsiness (19%) and dry mouth (12%). Conclusions: In patients with moderate to severe cancer pain, OXN showed a strong analgesic effect (about 50% pain reduction). In comparison with other studies the induced constipation appears substantially lower. Some clinical factors influence the analgesic response while none genetic polymorphisms modulate the response. Clinical trial information: NCT02293785.

Purpose: Pain is a frequent symptom in cancer patients with substantial impact. Despite the availability of opioids and updated guidelines from reliable leading societies, under-treatment is still very frequent. Materials and methods: We updated a systematic review published in 2008 which showed that, according to the Pain Management Index (PMI), 43.4% of cancer patients were under-treated. This review included observational and experimental studies reporting negative PMI for adults with cancer and pain published from 2007 to 2013 and retrieved through Medline, Embase and Google Scholar. In order to detect any temporal trend and identify potential determinants of under-treatment we compared papers published before and after 2007 with univariate, multivariate and sensitivity analyses. Results: In the new set of 20 papers published from 2007 to 2013 there was a decrease in undertreatment of about 25% (from 43.4 to 31.8%). In the whole sample the proportion of under-treated patients felt from 2007 to 2013, and an association was confirmed between negative PMI, economic level and non-specific setting for cancer pain. Sensitivity analysis confirmed the robustness of results. Conclusion: Analysis of 46 papers published from 1994 to 2013 using the PMI to assess the adequacy of analgesic therapy suggests the quality of pharmacological pain management has improved. However, about one third of patients still do not receive pain medication proportional to their pain intensity., JRC.I.2-Public Health Policy Support

An increasing number of cancer patients live longer, and palliative care has become an important part of their treatment. Symptoms are often inadequately assessed and managed. A significant challenge in clinical trials is to control for the variability of the samples being studied. To overcome this problem, classification systems have been developed in order to characterise and stratify patients by grouping them according to major common characteristics. The lack of agreed methods for the assessment and classification of cancer pain has been clearly indicated in clinical trials and in clinical practice and may be one possible explanation for the inadequate treatment of cancer pain. This was the background to an international expert meeting arranged in September 2009 in Milan, Italy. The primary aims were to produce recommendations on how to assess and classify cancer pain and to recommend a strategy for the further development, validation and implementation of an international cancer pain classification and assessment system. The recommendations consisted of two basic working proposals, nine specific working proposals and seven recommendations for the further development of a cancer pain classification system. Examples of specific working proposals were to include pain intensity, pain mechanism, breakthrough pain and psychological distress as the core domains in this classification of cancer pain and to measure pain intensity with a 0–10 numerical rating scale with ‘no pain’ and ‘pain as bad as you can imagine’ as anchors. The proposed name for this international standard is Cancer Pain Assessment and Classification System (CPACS).

Background: cancer pain is still undertreated as for inappropriate use of opioids, as for reason related to other factors. To increase knowledge of cancer pain, the “Mario Negri” Institute promote a series of initiatives to improve the quality of care and patients’ outcomes.Methods: a series of activities were launched including literature review, clinical studies and training schemes.Results: literature reviews shown a prevalence of undertreatment ranged from 8% to 82% and a raw prevalence of BTcP (Breakthrough Cancer Pain) of 51%. In the outcome research study mean worst pain at baseline was 6.8, and 38.3% received a strong opioids. Prevalence of BTcP was 40.3%, and 33.9% of the patients were not receiving rescue therapy at the study inclusion. About analgesic effectiveness of oral and transdermal opioids (TD), treatments with TD were associated with a lower probability to switch (OR=0.83) and to drop out from the study (OR=0.68).Conclusions: the initiative, still ongoing, has allowed a) the creation of a unit for the study and evaluation of cancer pain, b) the production of clinical evidence about the epidemiology, quality and effects of cancer pain management in Italy, c) the design and promotion of a Randomized Controlled Trial to evaluate the effectiveness of four major opioids.

A recent review article reports that more than one out of two patients with cancer-related pain also suffers from breakthrough pain (BTcP), however, this finding is based on several investigations with inconsistencies in the definition and assessment of the phenomenon. In the study by Davies et al., led in a sample of 1000 European BTcP patients, BTcP was defined by a unique and standardized diagnostic algorithm. A first interesting result of this study is that epidemiological and clinical aspects of BTcP (prevalence, daily numbers of episodes, time to peak, duration, interferences with daily activities) are referred to separately for the main sub-types of BTcP i.e. incident (44% of the sample) and spontaneous (42%). This is an original approach that highlights some dissimilar features—most notably peak and duration - which could imply the use of different therapeutic strategies. For instance, these observed differences could be used to determine which available rescue drugs are likely to be most effective on the basis of their different pharmacokinetic properties. Moreover, as to the treatments referred by the patients, pharmacological intervention was the preferred option in 29% of cases while a non-pharmacological option was selected by 23% of patients. That is quite surprising because a higher rate of pharmacological strategies would be expected. In parallel, other treatment options selected by patients (e.g., rest, position change, movement, heat/cold, complimentary therapies) reveals a range of solutions rarely described in clinical studies. In conclusion, the results from this study increase our knowledge of BTcP and can steer the direction of its management toward a broader spectrum of effective treatments, including non-pharmacological solutions., JRC.I.2-Public Health Policy Support

The antiemetic efficacy of levosulpiride (L) was compared to metoclopramide (M) in a double-blind, randomized, crossover study. Thirty patients with advanced cancer, who were no longer receiving antineoplastic therapy, were randomly assigned to receive either L 75 mg/day or M 30 mg/day. After 7 days, patients were crossed over to the alternate treatment, which was also given for 7 days. The hours with nausea were 1.08 (mean value/day/patient) during treatment with L and 2.01 with M (P = 0.002), independent of the order of administration. The nausea intensity was 0.76 (mean value/day/patient) with L and 1.42 with M (P = 0.0004). Complete control of nausea was obtained in 84.6% of patients receiving L and 42.3% of those treated with M (P = 0.0034). The number of vomiting episodes was 0.38 (mean value/day/patient) during treatment with L and 0.70 with M (P = 0.002), independent of the order of administration. Vomiting disappeared in 81.5% of patients receiving L and 51.8% of those treated with M (P = 0.041). There was a carry-over effect in favor of L. These data indicate that both L and M reduce nausea and vomiting, but L is more effective.