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Cancer pain intensity (PI) fluctuates, but the relationship between pain flares and background pain with respect to pain management is not settled. We studied how flare and background PIs corresponded with treatment results for background cancer pain. Patients admitted to an acute palliative care unit with average and/or worst PI ≥ 1 on the 11-point numeric rating scale were included. Average and worst PI at admission and average PI at discharge were collected. We examined how the difference and ratio between worst and average PI and average PI at admission, were associated with average PI development during hospitalization. Positive differences between worst and average PI at admission were defined as pain flares. Ninety out of 131 patients had pain flares. The reduction in average PI for patients with flares was 0.9 and for those without, 1.9 (p = 0.02). Patients with large worst minus average PI differences reported the least improvement, as did those with large worst/average PI ratios. Patients with pain flares and average PI ≤ 4 at admission had unchanged average PI during hospitalization, while those with pain flares and average PI > 4 experienced pain reduction (2.1, p < 0.001). Large pain flares, in absolute values and compared to background PI, were associated with inferior pain relief. [ABSTRACT FROM AUTHOR]

Purpose: Insomnia is frequent in patients with advanced cancer, and a variety of pharmacological agents is used to treat this condition. Still, few clinical trials have investigated the effectiveness of pharmacological sleep therapies in this patient group. We aimed to study the short-term effectiveness of zopiclone on sleep quality in patients with advanced cancer who report insomnia. Methods: A randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase IV clinical trial in adult patients with metastatic malignant disease and insomnia. Patients were treated with zopiclone or placebo for six subsequent nights. Primary end point was patient-reported sleep quality during the final study night (NRS 0–10). Secondary end points were patient-reported sleep onset latency (SOL) and total sleep time (TST). Results: Forty-one patients were randomized, with 18 being analyzed in the zopiclone group and 21 in the placebo group. Median age was 66, median Karnofsky performance score was 80, and 56% were male. Mean sleep quality at end of study was 2.9 (CI 2.3 to 3.8) in the zopiclone group and 4.5 (CI 3.6 to 5.4) in the placebo group (p = 0.021). At end of study, SOL was significantly different between the treatment groups: zopiclone 29 min (CI 13 to 51) and placebo 62 min (CI 40 to 87) (p = 0.045). TST was not significantly different across groups: zopiclone 449 min (403 to 496) and placebo 411 min (CI 380 to 440) (p = 0.167). Conclusion: Zopiclone improved short-term patient-reported sleep quality in this cohort of patients with advanced cancer. Trial registration: ClinicalTrials.gov Identifier: NCT02807922. [ABSTRACT FROM AUTHOR]

Simple Summary: This review focuses on sleep in patients with advanced cancer. Cancer patients experience multiple symptoms and they receive concomitant medications. These are all factors that may affect sleep. In this paper, we present recommendations on sleep assessment in patients with advanced cancer and highlight cancer-related factors that may contribute to insomnia. Sleep is an essential aspect of health-related quality of life; therefore, it is important for health care providers to focus on sleep to improve patient care. Patients with advanced cancer experience multiple symptoms, with fluctuating intensity and severity during the disease. They use several medications, including opioids, which may affect sleep. Sleep disturbance is common in cancer patients, decreases the tolerability of other symptoms, and impairs quality of life. Despite its high prevalence and negative impact, poor sleep quality often remains unrecognized and undertreated. Given that sleep is an essential aspect of health-related quality of life, it is important to extend both the knowledge base and awareness among health care providers in this field to improve patient care. In this narrative review, we provide recommendations on sleep assessment in patients with advanced cancer and highlight cancer-related factors that contribute to insomnia. We also present direct implications for health care providers working in palliative care and for future research. [ABSTRACT FROM AUTHOR]

Palliative cancer care patients may live for a long time, but malnutrition worsens the prognosis. Parenteral nutrition (PN) is suitable for replenishing a calorie deficit, but its advantages and tolerance late in the cancer trajectory are debated. We examined symptom development in hospitalized patients with and without PN. A total of 21 palliative cancer care patients receiving PN and 155 palliative cancer care patients not receiving PN during hospitalization in a specialized unit were retrospectively compared. We studied symptom intensity at admission, symptom relief during the hospital stay, and survival. The patients had locally advanced or metastatic cancer, a mean age of 70 years, and their median ECOG performance status was III. Symptom burden at admission was similar in the compared groups. Symptom relief during hospitalization was also similar. However, patients already on PN at admission reported more nausea and patients receiving PN during hospitalization reported better nausea relief compared to patients not receiving this intervention. Overall median survival was less than two months and similar in the compared groups. Based on a limited number of observations and a suboptimal study design, we were not able to demonstrate an increased symptom burden for palliative cancer care patients receiving PN late in the disease trajectory. [ABSTRACT FROM AUTHOR]

Purpose: Although corticosteroids are frequently used in patients with advanced cancer, few studies have examined the impact of these drugs on patient-reported sleep. We aimed to examine the short-term impact of methylprednisolone on patient-reported sleep in patients with advanced cancer. Methods: Patient-reported sleep was a predefined secondary outcome in a prospective, randomized, placebo-controlled, double-blind trial that evaluated the analgesic efficacy of corticosteroids in advanced cancer patients (18+), using opioids, and having pain ≥ 4 past 24 h (NRS 0–10). Patients were randomized to the methylprednisolone group with methylprednisolone 16 mg × 2/day or placebo for 7 days. The EORTC QLQ-C30 (0–100) and the Pittsburgh Sleep Quality Index questionnaire (PSQI) (0–21) were used to assess the impact of corticosteroids on sleep at baseline and at day 7. Results: Fifty patients were randomized of which 25 were analyzed in the intervention group and 22 in the control group. Mean age was 64 years, mean Karnofsky performance status was 67 (SD 13.3), 51% were female, and the mean oral daily morphine equivalent dose was 223 mg (SD 222.77). Mean QLQ-C30 sleep score at baseline was 29.0 (SD 36.7) in the methylprednisolone group and 24.2 (SD 27.6) in the placebo group. At day 7, there was no difference between the groups on QLQ-C30 sleep score (methylprednisolone 20.3 (SD 32.9); placebo 28.8 (SD 33.0), p = 0.173). PSQI showed similar results. Conclusions: Methylprednisolone 16 mg twice daily for 7 days had no impact on patient-reported sleep in this cohort of patients with advanced cancer. Trial registration: Clinical trial information NCT00676936 (13.05.2008) [ABSTRACT FROM AUTHOR]

Purpose: Although patients with advanced cancer report poor sleep quality, few studies have assessed sleep quality with a combination of subjective and objective measures. We aimed to examine sleep quality in hospitalized patients with advanced cancer by combining patient-reported outcome-measures (PROMs) and polysomnography (PSG) or actigraphy.Methods: A one-night prospective observational study of sleep in hospitalized patients with metastatic cancer using WHO step III opioids was conducted. Total sleep time, sleep onset latency, number of awakenings, and wake after sleep onset were assessed by PROMs and actigraphy. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI) (range; 0-21), where higher scores indicate worse sleep quality.Results: Forty patients were monitored. Median age was 70, median oral morphine equivalent dose was 80 mg/24 h (10-1725), median Karnofsky Performance Score was 50 (20-90), and median time to death from inclusion was 38 days (4-319). Mean PSQI score was 6.5 (SD ± 3.4). PROMs and actigraphy of mean (SD) sleep onset latency were 46 (± 64) and 35 min (± 61), respectively, while mean time awake at night was 37 (± 35) and 40 min (± 21). PROMs and actigraphy differed on number of awakenings (mean 2 (± 1) vs. 24 (± 15), p ˂ 0.001). Bland-Altman plots showed large individual differences between PROMs and actigraphy. PSG was not feasible.Conclusions: PROMs and actigraphy documented poor sleep quality, but a lack of agreement across methods. The study demonstrates a need to improve assessment of sleep quality and treatment of sleep disturbance in hospitalized patients with advanced cancer near end of life. [ABSTRACT FROM AUTHOR]

Introduction: Dexmedetomidine, an alpha-2 adrenergic receptor agonist with potential opioid sparing properties, is utilized in palliative medicine, but the knowledge base for this practice is limited. We describe concomitant use of dexmedetomidine and opioids in an acute palliative care unit. Methods: We included all hospitalized palliative cancer care patients treated with dexmedetomidine from January 2019 to January 2021. Demographics, opioid doses, dexmedetomidine indications and dosing, reported effects and adverse responses, as well as treatment lengths were recorded. Results: Three women and six men aged 42–66 years with metastatic cancer and Eastern Cooperative Oncology Group (ECOG) performance status I–IV used dexmedetomidine and opioids concomitantly. Indications for dexmedetomidine were pain (n = 7) and anxiety (n = 2). Dexmedetomidine was administered intravenously in two patients and subcutaneously in seven. All administrations were continuous infusions; initial doses ranged from 240 to 1344 µg/24 h with later doses from 240 to 2440 µg/24 h. Physicians reported relief from pain and anxiety, but two patients required neuraxial pain management during admission. At day 2 of dexmedetomidine treatment, the opioid dose was reduced in six out of nine patients. For all patients with available data at day 7, mean opioid dose was reduced to 74% of the initial dose. When excluding the two patients requiring neuraxial pain management, the corresponding number was 80%. Two patients had transient hypotension, but dexmedetomidine was well tolerated and in no cases withdrawn due to adverse effects. Mean dexmedetomidine treatment length was 40 days. Conclusions: Dexmedetomidine treatment decreased opioid consumption and was well tolerated in a retrospective study of nine palliative cancer care patients. It may represent a treatment option late in the disease trajectory. [ABSTRACT FROM AUTHOR]

Simple Summary: Approximately one-quarter of the patients with advanced cancer acutely admitted to the Palliative Care Unit at St. Olav's University Hospital received intravenous antibiotics. We observed that physiological variables and paraclinical findings in patients with and without infections differed at admission but observed no differences in patient-reported outcome measures. Patients admitted for infection had no shorter life expectancy than patients without infections. We did not observe any difference in the prescription of antibiotics to patients with ongoing anti-cancer therapy (integrated pathway) compared to patients with no ongoing cancer therapy (palliative care pathway). This information increases the knowledge about the use of antibiotic therapy in palliative cancer care. Decision-making for antibiotic therapy in palliative cancer care implies avoiding futile interventions and to identify patients who benefit from treatment. We evaluated patient-reported outcome-measures (PROMs), physiological findings, and survival in palliative cancer care patients hospitalized with an infection. All acute admissions during one year, directly to a University Hospital unit that provided integrated services, were included. Serious infection was defined as a need to start intravenous antibiotics. PROMs, clinical and paraclinical variables, and survival were obtained. Sixty-two of 257 patients received intravenous antibiotic treatment. PROMs were generally similar in the infection group and the non-infection group, both in respect to intensities at admission and improvements during the stay. There were more physiological and paraclinical deviations at admission in patients in the infection group. These deviations improved during the stay. Survival was not poorer in the infection group compared to the non-infection group. Patients in integrated cancer care were as likely to be put on intravenous antibiotics but had longer survival. In integrated oncology and palliative cancer services, patients with an infection had similar outcomes as those without an infection. This argues that the use of intravenous antibiotics is appropriate in many patients admitted to palliative care. [ABSTRACT FROM AUTHOR]

Background: Despite the high prevalence of insomnia in patients with advanced cancer, there are no randomized controlled trials on pharmacological interventions for insomnia in this group of patients. A variety of pharmacological agents is recommended to manage sleep disturbance for insomnia in the general population, but their efficacy and safety in adults with advanced cancer are not established. Thus, there is a need to evaluate the effectiveness of medications for insomnia in order to improve the evidence in patients with advanced cancer. One of the most used sleep medications at present in patients with cancer is zopiclone.Methods: This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. A total of 100 patients with metastatic cancer who report insomnia will be randomly allocated to zopiclone or placebo. The treatment duration with zopiclone/placebo is 6 consecutive nights. The primary endpoint is patient-reported sleep quality during the final study night (night 6) assessed on a numerical rating scale of 0-10, where 0 = Best sleep and 10 = Worst possible sleep. Secondary endpoints include the mean patient-reported total sleep time and sleep onset latency during the final study night (night 6).Discussion: Results from this study on treatment of insomnia in advanced cancer will contribute to clinical decision-making and improve the treatment of sleep disturbance in this patient cohort.Trial Registration: ClinicalTrials.gov, NCT02807922 . Registered on 21 June 2016. [ABSTRACT FROM AUTHOR]

Simple Summary: Circadian rhythms are internal changes that happen roughly over a 24-h period. In patients with cancer, healthy circadian rhythms may become abnormal, and these changes have been linked to more symptoms, poorer quality of life, and shorter survival. Circadian rhythms can be observed in rest and during physical activity, and disorders of this rest–activity rhythm are common. There are many ways to research and report rest–activity rhythms, and currently, there are no formal criteria to diagnose the condition. This study aimed to provide recommendations on how to assess and diagnose the condition. Purpose: Circadian rest–Activity Rhythm Disorders (CARDs) are common in patients with cancer, particularly in advanced disease. CARDs are associated with increased symptom burden, poorer quality of life, and shorter survival. Research and reporting practices lack standardization, and formal diagnostic criteria do not exist. This electronic Delphi (e-Delphi) study aimed to formulate international recommendations for the assessment and diagnosis of CARDs in patients with cancer. Methods: An international e-Delphi was performed using an online platform (Welphi). Round 1 developed statements regarding circadian rest–activity rhythms, diagnostic criteria, and assessment techniques. Rounds 2 and 3 involved participants rating their level of agreement with the statements and providing comments until consensus (defined internally as 67%) and stability between rounds were achieved. Recommendations were then created and distributed to participants for comments before being finalized. Results: Sixteen participants from nine different clinical specialties and seven different countries, with 5–35 years of relevant research experience, were recruited, and thirteen participants completed all three rounds. Of the 164 generated statements, 66% achieved consensus, and responses were stable between the final two rounds. Conclusions: The e-Delphi resulted in international recommendations for assessing and diagnosing CARDs in patients with cancer. These recommendations should ensure standardized research and reporting practices in future studies. [ABSTRACT FROM AUTHOR]

Purpose: To study the use of interventions and symptom relief for adult patients with incurable cancer admitted to an acute palliative care unit providing integrated oncology and palliative care services. Methods: All admissions during 1 year were assessed. The use of interventions was evaluated for all hospitalizations. Patients with assessments for worst and average pain intensity, tiredness, drowsiness, nausea, appetite, dyspnea, depression, anxiety, well-being, constipation, and sleep were evaluated for symptom development during hospitalization. Descriptive statistics was applied for the use of interventions and the paired sample t-test to compare symptom intensities (SIs). Results: For 451 admissions, mean hospital length of stay was 7.0 days and mean patient age 69 years. More than one-third received systemic cancer therapy. Diagnostic imaging was performed in 66% of the hospitalizations, intravenous rehydration in 45%, 37% received antibiotics, and 39% were attended by the multidisciplinary team. At admission and at discharge, respectively, 55% and 44% received oral opioids and 27% and 45% subcutaneous opioids. For the majority, opioid dose was adjusted during hospitalization. Symptom registrations were available for 180 patients. Tiredness yielded the highest mean SI score (5.6, NRS 0–10) at admission and nausea the lowest (2.2). Significant reductions during hospitalization were reported for all assessed SIs (p ≤ 0.01). Patients receiving systemic cancer therapy reported symptom relief similar to those not on systemic cancer therapy. Conclusion: Clinical practice and symptom relief during hospitalization were described. Symptom improvements were similar for oncological and palliative care patients. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to examine the adequacy of treatment for constipation, nausea, depression and poor sleep and the factors associated with inadequate symptom control in cancer patients receiving opioids.Methods: Patients receiving strong opioids for cancer pain were recruited from 17 centres in 11 European countries. By using the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30, 1,938 patients reported their symptoms at four-point scales. Health care providers assessed symptoms at corresponding four-point scales and registered use of medications, demographic and disease-related variables. Symptomatic treatment was scored as 1 if not administered during the past 24 h and as 2 if administered. Adequacy of treatment was evaluated by subtracting the patients' symptom score from the treatment score. Negative scores, caused by either no treatment or ineffective treatment of a symptom, were interpreted as inadequate treatment.Results: Approximately 60% of patients with constipation, depression or poor sleep and 45% of nauseated patients were inadequately treated. Numbers of inadequately treated patients varied between countries. In general, underestimation of symptom intensity by health care providers (p < 0.001), low performance status (p < 0.05) and recent initiation of opioids (p < 0.05) increased the risk of inadequate treatment. The subset of demographic- and disease-related factors associated with inadequate treatment varied between the symptoms investigated.Conclusions: Inadequate treatment, either no treatment or ineffective treatment, was frequent in cancer patients. There were subgroups of patients at particular risk for inadequate treatment, which might need additional attention from health care providers for achievement of adequate symptom control. [ABSTRACT FROM AUTHOR]

Abstract: The purposes of this study were to determine a clinically significant cutpoint for worst pain and to evaluate for differences in the use of pain coping strategies between oncology inpatients with mild (i.e., worst pain intensity scores of ≤4) compared with moderate to severe (i.e., worst pain intensity scores of >4) pain based on results of the cutpoint analysis. Oncology inpatients in pain (n =224) completed the Coping Strategies Questionnaire (CSQ), the Brief Pain Inventory, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Fifty-six percent had moderate to severe pain. Patients in the moderate to severe pain group had significantly poorer Karnofsky Performance Status scores (P =0.04) and significantly lower ratings of overall health (P <0.0001). No differences were found between the two pain groups on any of the subscales of the CSQ, except catastrophizing (P <0.0001). Compared with the mild pain group, patients in the moderate to severe group scored significantly higher on this subscale. In addition, patients in the moderate to severe group used more passive coping strategies (P =0.02). Except for catastrophizing, the number and types of pain coping strategies used by this sample of hospitalized patients do not appear to be influenced by their pain intensity scores. Finally, when the CSQ scores of these hospitalized oncology patients were compared with those found in previous studies of oncology outpatients and patients with chronic noncancer pain, the scores were similar. [Copyright &y& Elsevier]

Context: Patients with advanced cancer commonly suffer from both distressing symptoms and cognitive impairment, but the effect of cognitive impairment on the reliability and validity of symptom self-report is unknown.Objectives: To evaluate the reliability and validity of symptom self-report in cancer outpatients with and without mild to moderate cognitive impairment.Methods: This was an analysis of the longitudinal European Palliative Care Cancer Symptom study of adults with incurable cancer in specialized palliative care (30 centers across 12 countries). Patients who could not comply with the study because of severe cognitive impairment were excluded. Cognitive status on the Mini-Mental State Examination short version and nine symptoms (pain, tiredness, drowsiness, nausea, appetite, breathlessness, depression, anxiety, and well-being) using the revised Edmonton Symptom Assessment System were self-reported at baseline and one-month follow-up. Reliability was analyzed using intraclass correlation coefficients and validity using regression of each symptom with health-related quality of life (HrQoL) measured with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care.Results: A total of 1047 patients were included: mean age of 62.9 years; 54.4% women; main cancer types were of digestive organs (26.6%), breast (21.6%), and lungs (21.2%). Cognitive impairment was present in 181 (17.3%) at baseline and associated with worse self-reported tiredness, drowsiness, appetite, and depression. Reliability (intraclass correlation coefficient) and validity (associations with HrQoL) were similar between people with/without cognitive impairment across the nine symptoms, except breathlessness, which showed a weaker relation to HrQoL in patients with cognitive impairment. Findings were robust in sensitivity analyses and after controlling for potential confounders.Conclusion: In advanced cancer, self-report of nine major symptoms was reliable and valid also in people with mild-to-moderate cognitive impairment.Trial Registration: ClinicalTrials.gov database (NCT01362816). [ABSTRACT FROM AUTHOR]