Danish value sets for the EORTC QLU-C10D utility instrument.

PURPOSE: In this study, we developed Danish utility weights for the European Organisation for Research and Treatment of Cancer (EORTC) QLU-C10D, a cancer-specific utility instrument based on the EORTC QLQ-C30. METHODS: Following a standardized methodology, 1001 adult participants from the Danish general population were quota-sampled and completed a cross-sectional web-based survey and discrete choice experiment (DCE). In the DCE, participants considered 16 choice sets constructed from the key 10 dimensions of the QLU-C10D and chose their preferred health state for each one. Utility weights were calculated using conditional logistic regression with correction for non-monotonicity. RESULTS: The sample (n = 1001) was representative of the Danish general population with regard to age and gender. The domains with the largest utility decrements, i.e., the domains with the biggest impact on health utility, were physical functioning (- 0.224), pain (- 0.160), and role functioning (- 0.136). The smallest utility decrements were observed for the domains lack of appetite (- 0.024), sleep disorders (- 0.057), and fatigue (- 0.064). Non-monotonicity of severity levels was observed for the domains sleep disturbances, lack of appetite, and bowel problems. Deviations from monotonicity were not statistically significant. CONCLUSION: The EORTC QLU-C10D is a relatively new multi-attribute utility instrument and is a promising cancer-specific health technology assessment candidate measure. The country-specific Danish utility weights from this study can be used for cost-utility analyses in Danish patients and for comparison with other country-specific utility data.

Early treatment response as predictor of long-term outcome in a clinical cohort of children with ADHD.

This study investigates early onset of treatment response as predictor of symptomatic and functional outcome 3 years after initiation of methylphenidate (MPH) administration in a naturalistic, clinical cohort of children and adolescents with ADHD. Children were followed across an initial 12-week MPH treatment trial and after 3 years, with ratings of symptoms and impairment. Associations between a clinically significant MPH treatment response in week 3 (defined as ≥ 20% reduction in clinician-rated symptoms) and in week 12 (defined as ≥ 40% reduction), and 3-year outcome were tested in multivariate linear regression models, adjusting for sex, age, comorbidity, IQ, maternal education, parental psychiatric disorder, and baseline symptoms and function. We did not have information on treatment adherence or the nature of treatments beyond 12 weeks. 148 children, mean age 12.4 years (range 10-16 years), 77% males, participated in the follow-up. We found a significant decrease in symptom score from baseline [M = 41.9 (SD = 13.2)] to 3-year follow-up [M = 27.5 (SD = 12.7), p < 0.001, and in impairment score from baseline (M = 41.6 (SD = 19.4)] to 3-year follow-up [M = 35.6 (SD = 20.2), p = 0.005]. Treatment responses in week 3 and week 12 were significant predictors of the long-term outcome of symptoms, but not of impairment at 3-year follow-up, when adjusting for other well-known predictors. Early treatment response predicts long-term outcome over and above other well-known predictors. Clinicians should follow-up patients carefully, during the first months of treatment, and detect non-responders, since there might be a window of opportunity to alter the outcome, by changing the treatment strategy.Clinical trial registration: ClinicalTrials.gov, registration number NCT04366609, April 28, 2020 retrospectively registered.

Palliative care need screening and specialised referrals fell during the COVID-19 pandemic: a nationwide register-based study.

OBJECTIVES: Few studies have examined whether access to, and quality of, specialised palliative care changed during the COVID-19 pandemic. This study investigated changes in access to and quality of specialised palliative care during the pandemic in Denmark compared to previously. METHODS: An observational study using data from the Danish Palliative Care Database combined with other nationwide registries was conducted, including 69 696 patients referred to palliative care services in Denmark from 2018 to 2022. Study outcomes included number of referrals and admissions to palliative care, and the proportions of patients fulfilling four palliative care quality indicators. The indicators assessed admissions among referred, waiting time from referral to admission, symptom screening using the European Organisation for Research and Treatment of Cancer Quality of Life Questionaire-Core-15-Palliative Care (EORTC QLQ-C15-PAL) questionnaire at admission, and discussion at multidisciplinary conference. Logistic regression analysed whether the probability of fulfilling each indicator differed between the pandemic period and pre-pandemic, while adjusting for possible confounders. RESULT: Number of referrals and admissions to specialised palliative care were lower during the pandemic. The odds for being admitted within 10 days of referral was higher during the pandemic (OR: 1.38; 95% CI: 1.32 to 1.45) whereas the odds for answering the EORTC questionnaire (0.88; 95% CI: 0.85 to 0.92) and for being discussed at multidisciplinary conference (0.93; 95% CI: 0.89 to 0.97) were lower compared with pre-pandemic. CONCLUSIONS: Fewer patients were referred to specialised palliative care during the pandemic, and fewer were screened for palliative care needs. In future pandemics or similar scenarios, it is important to pay special attention to referral rates and to maintain the same high level of specialised palliative care.

Implementation of clinical guidelines in specialized palliative care-results from a national improvement project: A national register-based study.

BACKGROUND: Knowledge about the process and the results of the implementation of clinical guidelines to improve palliative care is limited. A national project aimed at improving the quality of life of advanced cancer patients admitted to specialized palliative care services in Denmark by implementing clinical guidelines for the treatment of pain, dyspnea, constipation, and depression. AIM: To investigate the degree of clinical guideline implementation by evaluating the proportion of patients treated according to guidelines among those who qualified (i.e. reported severe symptom level) before and after the 44 palliative care services implemented the guidelines, and how often different types of interventions were provided. DESIGN: This is a national register-based study. SETTING/PARTICIPANTS: Data from the improvement project were stored in and later obtained from the Danish Palliative Care Database. Adult patients with advanced cancer admitted to palliative care between September 2017 and June 2019 who answered the EORTC QLQ-C15-PAL questionnaire were included. RESULTS: In total 11,330 patients answered the EORTC QLQ-C15-PAL. The proportions of services that implemented the four guidelines ranged 73%-93%. Among services that had implemented guidelines, the proportion of patients receiving interventions was roughly constant over time reaching between 54% and 86% (lowest for depression). Pain and constipation were frequently treated pharmacologically (66%-72%), whereas dyspnea and depression were frequently treated non-pharmacologically (61% each). CONCLUSIONS: Implementing clinical guidelines was more successful for physical symptoms than for depression. The project generated national data on interventions provided when guidelines were followed, which may be used to understand differences in care and outcomes.

Quality of life and mental health in real-world patients with resected stage III/IV melanoma receiving adjuvant immunotherapy.

INTRODUCTION: Treatment with immune checkpoint inhibitors (ICI) has expanded into the adjuvant setting enhancing the importance of knowledge on the immune-related toxicities and their impact on health-related quality of life (HRQoL). Large phase 3 trials of patients with resected Stage III/IV melanoma found no effect on HRQoL during adjuvant immunotherapy. This study investigates how HRQoL was affected during and after adjuvant immunotherapy in a real-world setting. METHODS: Patients with resected melanoma treated with adjuvant nivolumab from 2018 to 2021 in Denmark were identified using the Danish Metastatic Melanoma Database (DAMMED). The study was performed as a nationwide cross-sectional analysis as a questionnaire consisting of six different validated questionnaires on HRQoL, cognitive function, fatigue, depression, fear of recurrence, and decision regret was sent to all patients in March 2021. To evaluate HRQoL during and after adjuvant treatment, patients were divided into groups depending on their treatment status when answering the questionnaire; patients in active treatment for 0-6 months, patients in active treatment for >6 months, patients who ended treatment 0-6 months ago, and patients who ended treatment >6 months ago. RESULTS: A total of 271/412 (66%) patients completed the questionnaire. Patients who ended therapy 0-6 months ago had the lowest HRQoL and had more fatigue. Patients in active treatment for >6 months had lower HRQoL and more fatigue than patients who started treatment 0-6 months ago. Patients ending therapy >6 months ago had higher HRQoL and less fatigue compared to patients who ended therapy 0-6 months ago. Multivariable analysis showed an association between HRQoL and treatment status, comorbidity, civil status, and employment status. CONCLUSIONS: Adjuvant nivolumab may affect some aspects of QoL, but the influence seems temporary. Patient characteristics, such as civil status, employment status, and comorbidity were associated with HRQoL.

Higher overall admittance of immigrants to specialised palliative care in Denmark: a nationwide register-based study of 99,624 patients with cancer.

BACKGROUND: The population of immigrants in Europe is ageing. Accordingly, the number of immigrants with life-threatening diseases and need for specialised palliative care will increase. In Europe, immigrants' admittance to specialised palliative care is not well explored. AIM: To investigate whether country of origin was associated with admittance to (I) palliative care team/unit, (II) hospice, and/or (III) specialised palliative care, overall (i.e. palliative care team/unit and/or hospice). DESIGN: Data sources for the population cohort study were the Danish Palliative Care Database and several nationwide registers. We investigated the associations between country of origin and admittance to specialised palliative care, overall, and to type of palliative care using logistic regression analyses. SETTING/PARTICIPANTS: In 2010-2016, 104,775 cancer patients died in Denmark: 96% were born in Denmark, 2% in other Western countries, and 2% in non-Western countries. RESULTS: Overall admittance to specialised palliative care was higher for immigrants from other Western (OR = 1.13; 95%CI: 1.03-1.24) and non-Western countries (OR = 1.22; 95%CI: 1.08-1.37) than for the majority population. Similar results were found for admittance to palliative care teams. No difference in admittance to hospice was found for immigrants from other Western countries (OR = 1.04; 95%CI: 0.93-1.16) compared to the majority population, while lower admittance was found for non-Western immigrants (OR = 0.70; 95%CI: 0.60-0.81). CONCLUSION: Admittance to specialised palliative care was higher for immigrants than for the majority population as higher admittance to palliative care teams for non-Western immigrants more than compensated for the lower hospice admittance. This may reflect a combination of larger needs and that hospital-based and home-based services are perceived as preferable by immigrants.

Symptoms of advanced cancer in palliative medicine: a longitudinal study.

OBJECTIVES: This study aimed to examine the symptomatology of patients with advanced cancer at admittance to palliative care services and to investigate how the symptomatology changed during the first month, and whether these changes were associated with various patient characteristics. METHODS: In a longitudinal study in Chile, outpatients with advanced cancer completed the questionnaires European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care and the Hospital Anxiety and Depression Scale. Prevalence and severity of symptoms and problems (S/Ps) at baseline were calculated. Differences in S/P scores from baseline to follow-up were calculated overall and according to patient characteristics. Multiple linear regression was used to study the associations between patient characteristics and changes in S/P scores. RESULTS: At baseline, 201 patients answered the questionnaires and 177 completed the follow-up. Fatigue, pain and sleeping difficulties were the most prevalent S/Ps reported, and also had the highest mean scores at baseline. S/P scores at baseline varied significantly according to sex, age, civil status, residence, children, prior and current antineoplastic treatment. Emotional functioning, pain, sleeping difficulties, constipation and anxiety improved significantly during the first month of palliative care. Residence, cohabitation status, diagnosis and current antineoplastic treatment were associated with changes in S/P scores. CONCLUSIONS: Patients reported moderate-to-severe levels of S/Ps at admittance to palliative care. Several S/Ps improved the first month. Certain patient characteristics were associated with changes in S/P scores. This information may guide clinicians to more effective interventions that can improve the quality of life of patients receiving palliative care.

Nausea at the start of specialized palliative care and change in nausea after the first weeks of palliative care were associated with cancer site, gender, and type of palliative care service-a nationwide study.

PURPOSE: Nausea is a common and distressful symptom among patients in palliative care, but little is known about possible socio-demographic and clinical patient characteristics associated with nausea at the start of palliative care and change after initiation of palliative care. The aim of this study was to investigate whether patient characteristics were associated with nausea at the start of palliative care and with change in nausea during the first weeks of palliative care, respectively. METHODS: Data was obtained from the nationwide Danish Palliative Care Database. The study included adult cancer patients who were admitted to palliative care and died between June 2016 and December 2020 and reported nausea level at the start of palliative care and possibly 1-4 weeks later. The associations between patient characteristics and nausea at the start of palliative care and change in nausea during palliative care, respectively, were studied using multiple regression analyses. RESULTS: Nausea level was reported at the start of palliative care by 23,751 patients of whom 8037 also reported 1-4 weeks later. Higher nausea levels were found for women, patients with stomach or ovarian cancer, and inpatients at the start of palliative care. In multivariate analyses, cancer site was the variable most strongly associated with nausea change; the smallest nausea reductions were seen for myelomatosis and no reduction was seen for stomach cancer. CONCLUSION: This study identified subgroups with the highest initial nausea level and those with the least nausea reduction after 1-4 weeks of palliative care. These latter findings should be considered in the initial treatment plan.

The quality of end-of-life care for Danish cancer patients who have received non-specialized palliative care: a national survey using the Danish version of VOICES-SF.

PURPOSE: About half of Danish patients dying from cancer have never been in contact with specialized palliative care. Non-specialized palliative care in Denmark, i.e., somatic hospital departments, community nurses, and general practitioners, has rarely been described or evaluated. We aim to assess how non-specialized palliative care was evaluated by bereaved spouses, and to test whether distress when completing the questionnaire and ratings of aspects of end-of-life care was associated with satisfaction with place of death and overall quality of end-of-life care. METHODS: Bereaved spouses of 792 cancer patients who had received non-specialized palliative care were invited to answer the Views of Informal Carers-Evaluation of Services-Short Form (VOICES-SF) and the Hospital Anxiety and Depression Scale (HADS) 3-9 months after the patient's death. RESULTS: A total of 280 (36%) of invited spouses participated. In the last 3 months of the patient's life, the quality of all services taken together was rated as good, excellent, or outstanding in 70% of the cases. Satisfaction was associated with respondent's current distress (p = 0.0004). Eighty percent of bereaved spouses believed that the patient had died in the right place. Satisfaction with place of death was associated with place of death (p = 0.012) and the respondent's current distress (p = 0.0016). CONCLUSION: Satisfaction with place of death and overall quality of services was generally high but was rated lower by spouses reporting higher levels of distress when completing the questionnaire. Distress should be taken into account whenever services are evaluated by bereaved relatives.

The quality of end of life care for Danish cancer patients who have received specialized palliative: a national survey using the Danish version of VOICES-SF.

BACKGROUND: National recommendations state that Danish patients with complex palliative needs should have access to specialized palliative care but little is known about the perceived quality of this care or end of life care in general. AIM: To assess how end of life care was evaluated by the bereaved spouses and to investigate whether the perceived quality was associated with (1) quantity of specialized palliative care provided, (2) place of death, and (3) emotional state when completing the questionnaire. DESIGN: The bereaved spouses of 1584 cancer patients who had received specialized palliative care were invited to answer the Views Of Informal Carers - Evaluation of Services - Short Form (VOICES-SF) and the Hospital Anxiety and Depression Scale (HADS) approximately 3-9 months after the patient's death. RESULTS: A total of 787 (50%) of the invited spouses participated. In the last 3 months of the patient's life, the quality of all services taken together was rated as good, excellent, or outstanding in 83% of the cases and it was significantly associated with place of death (p = 0.0051, fewest considered it "fair" or "poor" if the patient died at home). In total, 93% reported that the patient died at the right place although only 74% died at the patient's preferred place. Higher levels of anxiety (p = 0.01) but not depression at the time of questionnaire completion was associated with lower satisfaction with the overall quality of care. CONCLUSION: The quality of care was rated very highly by bereaved spouses of patients receiving specialized palliative care.

Age, cancer site and gender associations with symptoms and problems in specialised palliative care: a large, nationwide, register-based study.

BACKGROUND: Patients referred to specialised palliative care are troubled by symptoms/problems, but more knowledge is needed on the level and frequency of symptoms/problems. It is also uncertain how gender, age and cancer diagnosis, respectively, are associated with symptoms/problems. AIMS: To describe symptoms/problems in patients with cancer at the start of specialised palliative care, and to study how age, gender and cancer diagnosis were associated with symptoms/problems. DESIGN: A register-based study including data from the Danish Palliative Care Database. SETTING/PARTICIPANTS: Patients with cancer who reported their symptoms/problems using the European Organisation for Research and Treatment of Cancer Quality of Life Questionaire-Core-15-Palliative Care (EORTC QLQ-C15-PAL) at the start of specialised palliative care were included. Ordinal logistic regression was performed to test if gender, age and cancer diagnosis were associated with each symptom/problem. RESULTS: 31 771 patients with cancer were included in the study. The most prevalent and severe symptoms/problems were pain, appetite loss, fatigue, poor physical function and poor quality of life. Gender, age and cancer diagnosis were significantly associated with most symptoms/problems. The strongest associations between symptoms/problems and gender and age, respectively, were increased risk of nausea in women, as well as increased risk of poor physical function and reduced risk of sleeplessness and pain with increasing age. Patients with brain/central nervous system cancer had the lowest risk of symptoms but the highest risk of poor physical function. CONCLUSION: At the start of specialised palliative care, patients with cancer experience severe levels of symptoms, poor physical function and poor quality of life. Age, gender and diagnosis were significantly associated with most symptoms/problems, but the strength and direction of the associations differed across symptoms/problems.

Process, content, and experiences of delivering the Carer Support Needs Assessment Tool Intervention (CSNAT-I) in the Danish specialised palliative care setting.

PURPOSE: The Carer Support Needs Assessment Tool Intervention (CSNAT-I) has shown positive effects in the Danish specialised palliative care (SPC) setting. Here, we explore the process, content, and experiences of delivering the CSNAT-I. METHODS: Data were collected during a stepped wedge cluster randomised controlled trial investigating the impact of the CSNAT-I in the Danish SPC setting in 2018-2019. Data were obtained from the CSNAT (tool) completed by caregivers, from health care professionals' (HCPs') written documentation of the CSNAT-I, and from semi-structured interviews with HCPs. RESULTS: The study population consisted of the 130 caregivers receiving a first CSNAT-I within 13 days of study enrolment, the 93 caregivers receiving a second CSNAT-I 15-27 days after enrolment, and the 44 HCPs delivering the intervention. Top three domains of unmet caregiver support needs reported in the CSNAT-I were: "knowing what to expect in the future," "dealing with feelings and worries," and "understanding the illness." These domains together with "knowing who to contact if concerned" and "talking to the patient about the illness" were also the domains most frequently prioritised for discussion with HCPs. According to HCPs, most often support delivered directly by HCPs themselves during the actual contact (e.g., listening, advice, information) was sufficient. Overall, HCPs experienced the CSNAT-I as constructive and meaningful, and difficulties in delivering the intervention were rarely an issue. CONCLUSION: The support needs reported by caregivers confirm the relevance of the CSNAT-I. HCPs' overall experiences of the clinical feasibility and relevance of the CSNAT-I were very positive. ClinicalTrials.gov ID: NCT03466580. Date of registration: March 1, 2018.

Outcomes of a 12-week ecologically valid observational study of first treatment with methylphenidate in a representative clinical sample of drug naïve children with ADHD.

Randomized placebo-controlled trials have reported efficacy of methylphenidate (MPH) for Attention-deficit/hyperactivity disorder (ADHD); however, selection biases due to strict entry criteria may limit the generalizability of the findings. Few ecologically valid studies have investigated effectiveness of MPH in representative clinical populations of children. This independently funded study aims to describe treatment responses and their predictors during the first 12 weeks of MPH treatment using repeated measurements of symptoms and adverse reactions (ARs) to treatment in 207 children recently diagnosed with ADHD. The children were consecutively included from the Child and Adolescent Mental Health Centre, Mental Health Services, The Capital Region of Denmark. The children (mean age, 9.6 years [range 7-12], 75.4% males) were titrated with MPH, based on weekly assessments of symptoms (18-item ADHD-rating scale scores, ADHD-RS-C) and ARs. At study-end 187 (90.8%) children reached a mean end-dose of 1.0 mg/kg/day. A normalisation/borderline normalisation on ADHD-RS-C was achieved for 168 (81.2%) children on the Inattention and/or the Hyperactivity-Impulsivity subscale in week 12, and 31 (15.0%) children were nonresponders, which was defined as absence of normalisation/borderline normalisation (n = 19) or discontinuation due to ARs (n = 12), and eight (3.8%) children dropped out from follow-up. Nonresponders were characterised by more severe symptoms of Hyperactivity-Impulsivity and global impairment before the treatment. ARs were few; the most prominent were appetite reduction and weight loss. A decrease in AR-like symptoms during the treatment period questions the validity of currently available standard instruments designed to measure ARs of MPH. This ecologically valid observational study supports prior randomized placebo-controlled trials; 81.2% of the children responded favourably in multiple domains with few harmful effects to carefully titrated MPH. Clinical trial registration: ClinicalTrials.gov with registration number NCT04366609.

Brazilian Validation of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group (QLG) Computerised Adaptive Tests (CAT) Core.

BACKGROUND: This study aimed to validate the Brazilian version of EORTC CAT Core and compare the Brazilian results with those from the original European EORTC CAT Core validation study. METHODS: After validated translation, 168 cancer patients from Brazil receiving radiation therapy with or without chemotherapy was assessed. Translated EORTC CAT Core and all QLQ-C30 items were administered to patients using CHES (Computer-Based Health Evaluation System) before (T0) and after (T1) treatment initiation. The association between QLQ-C30 and CAT scores and ceiling/floor effects were estimated. Based on estimates of relative validity (cross-sectional, known-group differences and changes over time), relative sample-size requirements for CAT compared to QLQ-C30 were estimated. RESULTS: Correlation coefficients between CAT and QLQ-C30 domains ranged from 0.63 to 0.93; except for dyspnoea, all coefficients were >0.82 (corresponding figures were 0.81-0.93 in the European study). On average across domains, floor/ceiling was reduced by 10% using CAT (9% in the European study) corresponding to a relative reduction of 32% (37% in the European study). Analyses of known-group validity and responsiveness indicated that, on average across domains, the sample-size requirements may be reduced by 17% using CAT rather than QLQ-C30, without loss of power (28% in the European study). The Brazilian sample had less symptom/quality of life impairment than the European sample, which likely explains the lower sample-size reduction using CAT when comparing with the European sample. CONCLUSIONS: The results in the Brazilian cohort were generally similar to those from the European sample and confirm the validity and usefulness of the EORTC CAT Core.

Characteristics of patients reporting symptoms by open-ended questions in specialist palliative care.

INTRODUCTION: Comprehensive symptom assessment may be achieved by combining patient-reported outcome instruments with open-ended questions. The open-ended "Write In three Symptoms/Problems" (WISP) instrument allows patients to report symptoms and problems (S/Ps) not covered by the EORTC QLQ-C15-PAL. This study investigated whether sociodemographic or clinical variables were associated with the reporting of additional S/Ps on WISP. METHODS: Data from the Danish Palliative Care Database included all patients admitted to specialist palliative care in Denmark in 2016 who completed the EORTC QLQ-C15-PAL. The associations between patient characteristics and the reporting of a) any additional symptom/problem and b) each of the ten most prevalent additional S/Ps (oedema, dizziness, cough, sweats, diarrhoea, dry mouth, incontinence, sore mouth, vomiting and dysphagia) were investigated using multiple logistic regression. RESULTS: In total, 1,295 patients reported additional S/Ps on WISP. Reporting any additional symptom/problem was associated with having younger children and living with someone. The reporting of the most prevalent additional S/Ps was associated with cancer diagnosis, having younger children, living with someone and being an outpatient. CONCLUSIONS: This study gives new insights into the characteristics of patients reporting S/Ps that are not assessed by standard measures. The results may assist clinicians in improving palliative care. FUNDING: The salary of the first author was financed by Becas Chile-CONICYT. TRIAL REGISTRATION: not relevant.

Early, integrated palliative rehabilitation improves quality of life of patients with newly diagnosed advanced cancer: The Pal-Rehab randomized controlled trial.

BACKGROUND: Early integration of palliative care into oncology treatment is widely recommended. Palliative rehabilitation has been suggested as a paradigm which integrates enablement, self-management, and self-care into the holistic model of palliative care. AIM: We hypothesized that early integration of palliative rehabilitation could improve quality of life. DESIGN: The Pal-Rehab study (ClinicalTrials.gov NCT02332317) was a randomized controlled trial. The 12-week intervention offered by a specialized palliative care team was two mandatory consultations and the opportunity of participating in an interdisciplinary group program. Supplementary individual consultations were offered, if needed. SETTING/PARTICIPANTS: At Vejle University Hospital, Denmark, adults diagnosed with advanced cancer within the last 8 weeks were randomized 1:1 to standard oncology care or standard care plus intervention. Assessments at baseline and after six and 12 weeks were based on the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30). At baseline participants were asked to choose a "primary problem" from a list of QLQ-C30 domains. The primary endpoint was the change in that "primary problem" measured as area under the curve across 12 weeks (T-scores, European mean value = 50, SD = 10). RESULTS: In all, 288 were randomized of whom 279 were included in the modified intention-to-treat analysis (146 in the standard care group and 133 in the intervention group). The between-group difference for the primary outcome was 3.0 (95% CI [0.0-6.0]; p = 0.047) favoring the intervention. CONCLUSION: Early integration of palliative rehabilitation into standard oncology treatment improved quality of life for newly diagnosed advanced cancer patients. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT02332317, registered on December 30, 2014.

Virtual reality-based relaxation for enhancement of perioperative well-being and quality of life: protocol for a randomised pilot trial.

INTRODUCTION: Patients with cancer undergoing surgery often suffer from reduced quality of life and various forms of distress. Untreated distress can negatively affect coping resources as well as surgical and oncological outcomes. A virtual reality-based stress reduction intervention may increase quality of life and well-being and reduce distress in the perioperative phase for patients with cancer. This pilot trial aims to explore the feasibility of the proposed intervention, assess patient acceptability and obtain estimates of effect to provide data for sample size calculations. METHODS AND ANALYSIS: Patients with colorectal cancer and liver metastasis undergoing elective surgery will be recruited for this single-centre, randomised pilot trial with a three-arm design. A total of 54 participants will be randomised at 1:1:1 ratio to one of two intervention groups or a control receiving standard treatment. Those randomised to an intervention group will either receive perioperative virtual reality-based stress reduction exercises twice daily or listen to classical music twice daily. Primary feasibility outcomes are number and proportions of participants recruited, screened, consented and randomised. Furthermore, adherence to the intervention, compliance with the completion of the quality of life questionnaires and feasibility of implementing the trial procedures will be assessed. Secondary clinical outcomes are measurements of the effectiveness of the interventions to inform sample size calculations. ETHICS AND DISSEMINATION: The study protocol, the patient information and the informed consent form have been approved by the ethics committee of the Ludwigs-Maximilians-University, Munich, Germany (Reference Number: 19-915). Study findings will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: DRKS00020909.

High-dose naloxone: Effects by late administration on pain and hyperalgesia following a human heat injury model. A randomized, double-blind, placebo-controlled, crossover trial with an enriched enrollment design.

Severe chronic postsurgical pain has a prevalence of 4-10% in the surgical population. The underlying nociceptive mechanisms have not been well characterized. Following the late resolution phase of an inflammatory injury, high-dose µ-opioid-receptor inverse agonists reinstate hypersensitivity to nociceptive stimuli. This unmasking of latent pain sensitization has been a consistent finding in rodents while only observed in a limited number of human volunteers. Latent sensitization could be a potential triggering venue in chronic postsurgical pain. The objective of the present trial was in detail to examine the association between injury-induced secondary hyperalgesia and naloxone-induced unmasking of latent sensitization. Healthy volunteers (n = 80) received a cutaneous heat injury (47°C, 420 s, 12.5 cm2). Baseline secondary hyperalgesia areas were assessed 1 h post-injury. Utilizing an enriched enrollment design, subjects with a magnitude of secondary hyperalgesia areas in the upper quartile ('high-sensitizers' [n = 20]) and the lower quartile ('low-sensitizers' [n = 20]) were selected for further study. In four consecutive experimental sessions (Sessions 1 to 4), the subjects at two sessions (Sessions 1 and 3) received a cutaneous heat injury followed 168 h later (Sessions 2 and 4) by a three-step target-controlled intravenous infusion of naloxone (3.25 mg/kg), or normal saline. Assessments of secondary hyperalgesia areas were made immediately before and stepwise during the infusions. Simple univariate statistics revealed no significant differences in secondary hyperalgesia areas between naloxone and placebo treatments (P = 0.215), or between 'high-sensitizers' and 'low-sensitizers' (P = 0.757). In a mixed-effects model, secondary hyperalgesia areas were significantly larger following naloxone as compared to placebo for 'high-sensitizers' (P < 0.001), but not 'low-sensitizers' (P = 0.651). Although we could not unequivocally demonstrate naloxone-induced reinstatement of heat injury-induced hyperalgesia, further studies in clinical postsurgical pain models are warranted.

Effect of the Carer Support Needs Assessment Tool intervention (CSNAT-I) in the Danish specialised palliative care setting: a stepped-wedge cluster randomised controlled trial.

BACKGROUND: The Carer Support Needs Assessment Tool intervention (CSNAT-I) has been shown to improve end-of-life care support for informal caregivers. This study investigated the impact of the CSNAT-I on caregivers of patients recently enrolled in specialised palliative care (SPC) at home in Denmark. METHODS: A stepped-wedge cluster randomised controlled trial with nine clusters (ie, SPC teams). Outcome measures were collected using caregiver questionnaires at baseline (T0) and 2-week (T1) and 4-week (T2) follow-up. RESULTS: A total of 437 caregivers were enrolled (control group, n=255; intervention group, n=182). No intervention effect was found on the primary outcome, caregiver strain at T1 (p=0.1865). However, positive effects were found at T1 and T2 on attention to caregivers' well-being (p<0.0001), quality of information and communication (p<0.0001), amount of information (T1: p=0.0002; T2: p<0.0001), involvement (T1: p=0.0045; T2: p<0.0001), talking about greatest burdens (p<0.0001) and assistance in managing greatest burdens (p<0.0001). The effect sizes of these differences were medium or large and seemed to increase from T1 to T2. At T1, positive effects were found on distress (p=0.0178) and home care responsibility (p=0.0024). No effect was found on the remaining outcomes. CONCLUSION: Although no effect was found on caregiver strain, the CSNAT-I showed positive effects on caregiver distress, home care responsibility and key outcomes regarding caregivers' experience of the interaction with healthcare professionals. TRIAL REGISTRATION NUMBER: NCT03466580.

Correction to: Content validation of the EORTC QLQ-C15-PAL with advanced cancer patients and health care professionals from palliative care services in Chile.

An amendment to this paper has been published and can be accessed via the original article.