Prevalence of delirium in advanced cancer patients in home care and hospice and outcomes after 1 week of palliative care.

AIM: The aim of this study was to assess the prevalence of delirium in advanced cancer patients admitted to different palliative care services in Italy and possible related factors. The secondary outcome was to assess the changes of delirium after 1 week of palliative care. METHODS: A consecutive sample of patients was screened for delirium in period of 1 year in seven palliative care services. General data, including primary tumor, age, gender, concomitant disease, palliative prognostic score (PaP), and Karnofsky status, were collected. Possible causes or factors associated with delirium were looked for. The Edmonton Symptom Assessment Scale was used to assess physical and psychological symptoms and the Memorial Delirium Assessment Scale (MDAS) to assess the cognitive status of patients, at admission (T0) and 1 week after palliative care (T7). RESULTS: Of 848 patients screened, 263 patients were evaluated. Sixty-six patients had only the initial evaluation. The mean Karnofsky status was 34.1 (SD = 6.69); the mean PaP score at admission was 6.9 (SD = 3.97). The mean duration of palliative care assistance, equivalent to survival, was 38.4 days (SD = 48, range 2-220). The mean MDAS values at admission and after 1 week of palliative care were 6.9 (SD = 6.71) and 8.8 (SD = 8.26), respectively. One hundred ten patients (41.8%) and 167 patients (67.3%) had MDAS values ≥ 7 at admission and after 1 week of palliative care, respectively. Age, dehydration, cachexia, chemotherapy in the last three months, and intensity of drowsiness and dyspnea were independently associated with a MDAS > 7. A worsening of drowsiness, the use of opioids, and the use of corticosteroids were independently associated with changes of MDAS from T0 to T7. CONCLUSION: Although the prevalence of delirium seems to be similar to that reported in other acute settings, delirium tended to worsen or poorly responded to a palliative care treatment. Some clinical factors were independently associated with delirium. This information is relevant for decision-making when delirium does not change despite a traditional intervention. Continuous assessment of delirium should be performed in these settings to detect deterioration of cognitive function. Further studies should elucidate whether an earlier approach to palliative care would decrease the prevalence of delirium at a late stage of disease.

'Now I can train myself to be with death': a phenomenological study with young doctors in care homes supported by a palliative care unit during the second wave of the pandemic in Italy.

OBJECTIVE: During the second wave of the COVID-19 pandemic, one of the organisational strategies established by the Italian National Health System was the special units for continuity of care (SUCCs). In the province of Ravenna, those units enrolled novice doctors to care for elderly patients with COVID-19 in care homes (CHs). The local palliative care (PC) unit decided to offer consultations and support to them. This study aimed to comprehend the experience of young doctors who asked for consultations when facing, during their first early years of practice, complex situations. DESIGN: We conducted a qualitative study employing a phenomenological approach and in-depth interviews. PARTICIPANTS: We involved 10 young doctors who worked in Italian SUCC during the pandemic and used a PC consultation support service. RESULTS: What describes our participants' experience is related to four main themes: (1) reducing distances, (2) perceiving medical futility and improvising, (3) being supported to learn how to be with death and (4) narrowed timing to humanise care. The pandemic was, for our participants, a moment of reflection and critique on the skills acquired during the university course. It was a strong experience of human and professional growth that helped them reshape and deepen their role and skills, incorporating the approach of PC into their professional identity. CONCLUSIONS: Integration between specialists and young doctors with an early entry into the workforce during the pandemic in CHs set out a 'shift' to a proactive and creative approach through a new awareness of professional and personal roles in doctor-patient relations. The continuity of care models should be rethought by integrating CHs and PC. Adequate PC training for young doctors (at pregraduate and postgraduate levels) can change doctors' vision and daily practice in assisting patients at the end of life.

Prospective comparison of prognostic scores in palliative care cancer populations.

PURPOSE: Predicting prognosis in advanced cancer aids physicians in clinical decision making and can help patients and their families to prepare for the time ahead. MATERIALS AND METHODS: This multicenter, observational, prospective, nonrandomized population-based study evaluated life span prediction of four prognostic scores used in palliative care: the original palliative prognostic score (PaP Score), a variant of PaP Score including delirium (D-PaP Score), the Palliative Performance Scale, and the Palliative Prognostic Index. RESULTS: A total of 549 patients were enrolled onto the study. Median survival of the entire group was 22 days (95% confidence intervals [95% CI] = 19-24). All four prognostic models discriminated well between groups of patients with different survival probabilities. Log-rank tests were all highly significant (p < .0001). The PaP and D-PaP scores were the most accurate, with a C index of 0.72 (95% CI = 0.70-0.73) and 0.73 (95% CI = 0.71-0.74), respectively. CONCLUSION: It can be confirmed that all four prognostic scores used in palliative care studies accurately identify classes of patients with different survival probabilities. The PaP Score has been extensively validated and shows high accuracy and reproducibility in different settings.

Improving the Integration between Palliative Radiotherapy and Supportive Care: A Narrative Review.

Palliative radiotherapy (PRT) is known to be effective in relieving cancer related symptoms. However, many studies and clinical practice show several barriers hindering its use and worsening the quality of patient support during PRT. Various solutions were proposed to overcome these barriers: training on PRT for supportive and palliative care specialists and training on palliative care for radiation oncologists, and introduction of pathways and organizational models specifically dedicated to PRT. Evidence on innovative organizational models and mutual training experiences is few and sparse. Therefore, the aim of this literature review is to present a quick summary of the information available on improving the PRT quality through training, new pathways, and innovative organizational models. The majority of studies on the integration of PRT with other palliative and supportive therapies present low levels of evidence being mostly retrospective analyses. However, it should be emphasized that all reports uniformly showed advantages coming from the integration of PRT with supportive therapies. To actively participate in the integration of PRT and palliative care, providing comprehensive support to the needs of patients with advanced cancer, radiation oncologists should not only plan PRT but also: (i) assess and manage symptoms and stress, (ii) rapidly refer patients to specialists in management of more complex symptoms, and (iii) participate in multidisciplinary palliative care teams. To this end, improved education in palliative care both in residency schools and during professional life through continuous medical education is clearly needed. In particular, effective training is needed for radiotherapy residents to enable them to provide patients with comprehensive palliative care. Therefore, formal teaching of adequate duration, interactive teaching methods, attendance in palliative care services, and education in advanced palliative care should be planned in post-graduated schools of radiotherapy.

The Path of Cicely Saunders: The "Peculiar Beauty" of Palliative Care.

This paper is aimed at focusing on the writings and the experience of the Hospice movement Founder, Dame Cicely Saunders. The in-depth analysis carried out had the objective of verifying if "the way" of Cicely to understand, live and propose palliative care was still current and "beautiful", so that we can nowadays refer to her fascinating "Original Palliative Care". With "beauty" we mean, on the one hand, a way able to allow a personal path of research of the meaning of the disease and of the care, both for those who care and for those who are cared for. On the other hand, it seems to us that Cicely strongly suggests how this path can not be carried out alone, but is only possible within the context of a network of relationships and support, in a so called "relational autonomy", for the patient, included in a "care ethics". The authors believe that the work extensively documents as the overall approach of Cicely, traditional but always to be rediscovered, is still today the most convincing way of conception and action of palliative care.

Symptom expression in advanced cancer patients admitted to hospice or home care with and without delirium.

The aim of this study is to investigate the relationship between delirium and symptom expression in advanced cancer patients admitted to palliative care services. This is a secondary analysis of a consecutive sample of advanced cancer patients who were admitted to home care and hospices, and prospectively assessed for a period of 10 months. The Edmonton Symptom Assessment Scale (ESAS) and the MDAS (Memorial Delirium Assessment Scale) were measured at admission (T0) and after seven days of home care or hospice care (T7). Of the eight hundred and forty-eight patients screened in the period, 585 were not considered in the analysis for various reasons. The mean age was 72.1 years (SD 13.7), and 146 patients were males (55.5%). The mean Karnofsky status recorded at T0 is 34.1 (SD = 6.69). The mean duration palliative care assistance is 38.4 days (SD = 48, range 2-220). Of 263 patients who had a MDAS available at T0, 110 patients (41.8%) had a diagnosis of delirium. Of them, 167 patients had complete data regarding MDAS measurement, either at T0 and T7. A larger number of patients (n 167, 63.5%) had delirium after a week of palliative care. Patients with delirium are likely to be older, to have a lower Karnofsky level at T0, and to be home care patients. At T0, weakness, nausea, drowsiness, lack of appetite, and well-being are associated with delirium. At T7, weakness, poor appetite, and poor well-being are significantly associated with delirium. 27% of patients who had a normal cognitive status at T0 developed delirium at T7. In patients with delirium, an improvement in the cognitive status corresponds to a significant improvement in weakness, depression, and appetite. Conversely, the occurrence of delirium in patients who had a normal cognitive status at admission significantly increases the level depression, while the level of weakness and appetite decrease. Symptom expression is amplified in patients with delirium admitted to home care or hospices, while patients without delirium can be more responsive to palliative treatments with a significant decrease in intensity of ESAS items.

The prevalence of constipation at admission and after 1 week of palliative care: a multi-center study.

AIM: To assess the prevalence and intensity of constipation in advanced-cancer patients referred to palliative care, and to assess changes after 1 week of specialist palliative care. METHODS: This was a prospective multi-center study in advanced patients for a period of 1 year. At admission (T0), age, gender, primary tumor, concomitant diseases, Karnofsky status, Palliative prognostic score (PaP), Edmonton Symptom Assessment scale (ESAS), Memorial Delirium Assessment Scale (MDAS), and bowel function index (BFI) were collected. In BFI, high values represent severe constipation. The use of medication was also recorded, as well as possible causes of constipation. The same parameters were recorded 1 week after admission for palliative care (T7). RESULTS: A total of 246 patients were screened for constipation. The mean BFI at T0 was 42.4 (SD = 26.92). One hundred and sixty-three patients (66.3%) had a BFI >28. The mean BFI at T7 was 35.7 (SD = 28.8), with a significant decrease from T0 to T7 (p = .000). A significant decrease of BFI in patients with a BFI >28 was reported (p = .000). In patients with a BFI ≤28 there was a significant worsening of constipation (p = .000). In patients with a BFI >28 at T0 there was a significant increase in the use of laxatives at T7 in comparison with patients having a BFI ≤28 (p = .002). In patients with a BFI ≤28 at T0, who had a significant worsening of BFI (Δ > 12), the use of laxatives was significantly lower in comparison to patients who had a BFI >28 (p = .000). In the multivariate analysis, dehydration and the use of benzodiazepines were independently associated with higher BFI scores. CONCLUSION: Constipation is present in approximately two-thirds of patients, and is principally associated with dehydration and the use of benzodiazepines. Patients with normal bowel function at initial assessment may see a worsening in their condition a week later due to lack of prevention or subsequent under-treatment.

Fatty acids by high-performance liquid chromatography and evaporative light-scattering detector.

A high-performance liquid chromatographic (HPLC) separation method with an evaporative light-scattering detector (ELSD) has been developed for the separation and quantitative analysis of fatty acid methyl esters (FAME) in three different oils. Reverse-phased C18 HPLC separation of 13 FAME is achieved using a methanol/water eluent mixture. The retention times (RT) reflect the elution behavior of these compounds on C18 reversed-phase HPLC. The proposed method is tested on: soybean oil (Glycine max L.) as reference sample, rice bran oil (Oryza sativa L.), pumpkin seed oil (Cucurbita pepo L.) and algal oil (Arthrospira platensis Nordst.).

Comparison of the Tolerability Profile of Controlled-Release Oral Morphine and Oxycodone for Cancer Pain Treatment. An Open-Label Randomized Controlled Trial.

CONTEXT: Oxycodone and morphine are recommended as first-choice opioids for moderate/severe cancer pain, but evidence about their relative tolerability has significant methodological limitations. OBJECTIVES: This study was mainly aimed at comparing the risk of developing adverse events (AEs) with controlled-release oral morphine vs. oxycodone; secondary aims were comparing their analgesic efficacy and testing heterogeneity in tolerability across different age and renal function subgroups. METHODS: An open-label multicenter RCT (EudraCT number: 2006-003151-21) was carried out in patients with moderate/severe cancer pain. At baseline, 7 and 14 days, patients scored on 0-10 rating scales (0-10 numerical rating scale) the intensity of pain and of a list of common opioid side effects. The primary end point was the percentage of patients reporting an AE (a worsening ≥ 2 points on any of the listed side effects); tolerability by subgroups and average follow-up pain intensity were compared through regression models. RESULTS: One hundred eighty-seven patients were enrolled (47% of originally planned). Intention to treat (ITT) analysis (N = 185, morphine 94, oxycodone 91) did not show any difference in the risk of developing AEs (risk difference -0.6%, 95% CI -11.0% to 9.9%) nor in analgesia (0-10 numerical rating scale pain intensity difference -0.28, 95% CI -0.83 to 0.27). No evidence of heterogeneity of tolerability across age and renal function patient subgroups emerged. CONCLUSION: This trial failed to show any difference in tolerability and analgesic efficacy of morphine and oxycodone as first-line treatment for moderate/severe cancer pain but results interpretation is difficult due to lack of power, potential bias from open-label design, and concerns about assay sensitivity. These data, however, can significantly contribute to future meta-analyses comparing WHO Step-III opioids and are relevant in designing future randomized studies.

Determination of free phenolic acids in wort and beer by coulometric array detection.

The simultaneous determination of 19 phenolic compounds was performed directly in wort and beer by a combination of reverse-phase high-performance liquid chromatography coupled with coulometric array detection. Chromatographic separation was achieved with an appropriate gradient of flow and a binary solvent based on phosphate buffer, methanol, and acetonitrile in a 45-min run. Eight serial coulometric detectors were used for on-line generation of voltammetric data to resolve coeluting compounds. The method was reliable and sensitive, the regression coefficient of standard calibration curves is 0.972 < or = r < or = 1.000, and the standard deviation value ranges from 0.010 to 0.129 mg/L for wort and from 0.002 to 0.332 mg/L for beer. The mean concentrations of phenolic acids were 22.1 and 33.8 mg/L, respectively, in worts and beers produced in Italy. These amounts represent 5 and 10% of the non-tannic, non-flavonoid phenols in wort and beer, respectively.

Near-infrared reflectance models for the rapid prediction of quality of brewing raw materials.

Calibration models for quickly and reliably predicting moisture content and total nitrogen, both "as is" and "dry matter" on malt, as well as moisture content and total lipids, both "as is" and "dry matter", on maize by means of near-infrared (NIR) spectroscopy were developed. The FT-NIR spectra recorded on the finely ground cereals were correlated to the analytical data by means of the multivariate PLS algorithm. In particular, these models were developed on the raw materials, which are used by the main Italian brewing industries. Validation was carried out both by means of cross-validation and test set validation. Regression coefficients (R(2)) were higher than 97 for both malt and maize moisture content and higher than 85 and 88 for malt total nitrogen and maize total lipids, respectively. The RMSE values (both RMSECV and RMSEP) were lower than 0.1% m/m for both malt and maize moisture contents, whereas they ranged from 0.024 to 0.042% m/m for malt total nitrogen and from 0.042 to 0.055% m/m for maize total lipids. Repeatability was tested by taking into account more than one sample for each calibration and compared, when possible, to those of the standard methods. Repeatability (r(95)) ranged from 0.060 to 0.158% m/m and from 0.020 to 0.055% m/m for malt moisture and total nitrogen contents, respectively, and from 0.094 to 0.160% m/m and from 0.076 to 0.208% m/m for maize moisture and total lipids contents, respectively.

The palliative prognostic score and survival in patients with advanced solid tumors receiving chemotherapy.

PURPOSE: To evaluate the accuracy of the Palliative Prognostic Score (PaP score) in selecting metastatic gastrointestinal or nonsmall-cell lung cancer patients candidate to palliative chemotherapy. MATERIALS AND METHODS: The PaP score was calculated in 173 patients with advanced, pretreated gastrointestinal or nonsmall-cell lung cancer before starting a further line of chemotherapy with palliative aim. Symptom distress score was calculated using the Edmonton Symptom Assessment System (ESAS) before every course of chemotherapy. Univariate analysis of survival was performed using the logrank test; multivariate analysis was performed using the Cox regression model. Symptom distress scores were compared using multivariate analysis of variance test for repeated measures, and overall symptom distress score was compared using analysis of variance test for repeated measures. RESULTS: Overall median survival was 26 weeks; in PaP score class A it was 32 weeks, and in class B 8 weeks (p < 0.0001). No patient was classified in class C. The two-class PaP score resulted in an independent prognostic factor (p = 0.022), as well as Karnofsky performance status (p = 0.002) and colorectal cancer (p = 0.017). A trend towards worsening of symptom distress was observed in the entire population and in class A. The high number of missed data did not permit an adequate analysis in class B. CONCLUSIONS: The PaP score seems to discriminate patients who could benefit by palliative chemotherapy from those who could better benefit by supportive and palliative approach. However, the data are insufficient to validate the use of the PaP score in patients to be treated with palliative chemotherapy, and further trials should be planned to assess its ability to improve the quality of care in oncology and the appropriateness in the choice of palliative chemotherapy.

A validation study of the WHO analgesic ladder: a two-step vs three-step strategy.

GOALS OF WORK: The aims of the present study were to verify whether an innovative therapeutic strategy for the treatment of mild-moderate chronic cancer pain, passing directly from step I to step III of the WHO analgesic ladder, is more effective than the traditional three-step strategy and to evaluate the tolerability and therapeutic index in both strategies. METHODS: Patients aged 18 years or older with multiple viscera or bone metastases or with locally advanced disease were randomized. Pain intensity was assessed using a 0-10 numerical rating scale based on four questions selected from the validated Italian version of the Brief Pain Inventory. Treatment-specific variables and other symptoms were recorded at baseline up to a maximum follow-up of 90 days per patient. RESULTS: Fifty-four patients were randomized onto the study, and pain intensity was assessed over a period of 2,649 days. The innovative treatment presented a statistically significant advantage over the traditional strategy in terms of the percentage of days with worst pain > or =5 (22.8 vs 28.6%, p < 0.001) and > or =7 (8.6 vs 11.2%, p = 0.023). Grades 3 and 4 anorexia and constipation were more frequently reported in the innovative strategy arm, although prophylactic laxative therapy was used less in this setting. CONCLUSIONS: Our preliminary data would seem to suggest that a direct move to the third step of the WHO analgesic ladder is feasible and could reduce some pain scores but also requires careful management of side effects.