PALLiative care in ONcology (PALLiON): A cluster-randomised trial investigating the effect of palliative care on the use of anticancer treatment at the end of life.

BACKGROUND: Effects on anticancer therapy following the integration of palliative care and oncology are rarely investigated. Thus, its potential effect is unknown. AIM: To investigate the effects of the complex intervention PALLiON versus usual care on end-of-life anticancer therapy. DESIGN: Cluster-randomised controlled trial (RCT), registered at ClinicalTrials.gov (No. NCT01362816). The complex intervention consisted of a physician education program enhancing theoretical, clinical and communication skills, a patient-centred care pathway and patient symptom reporting prior to all consultations. Primary outcome was overall use, start and cessation of anticancer therapy in the last 3 months before death. Secondary outcomes were patient-reported outcomes. Mixed effects logistic regression models and Cox proportional hazard were used. SETTING: A total of 12 Norwegian hospitals (03/2017-02/2021). PARTICIPANTS: Patients ⩾18 years, advanced stage solid tumour, starting last line of anticancer therapy, estimated life expectancy ⩽12 months. RESULTS: A total of 616 (93%) patients were included (intervention: 309/control:307); 63% males, median age 69, 77% had gastrointestinal cancers. Median survival time from inclusion was 8 (IQR 3-14) and 7 months (IQR 3-12), and days between anticancer therapy start and death were 204 (90-378) and 168 (69-351) (intervention/control). Overall, 78 patients (13%) received anticancer therapy in the last month (intervention: 33 [11%]/control: 45 [15%]). No differences were found in patient-reported outcomes. CONCLUSION: We found no significant differences in the probability of receiving end-of-life anticancer therapy. The intervention did not have the desired effect. It was probably too general and too focussed on communication skills to exert a substantial influence on conventional clinical practice.

The prognostic value of patient-reported outcomes in allogeneic hematopoietic stem cell transplantation: exploratory analysis of a randomized nutrition intervention trial.

Whether patient-reported outcomes (PROs) can predict overall survival (OS) and non-relapse mortality (NRM) among recipients of allogeneic stem cell transplantation (allo-HSCT), is unclear. We performed an exploratory analysis of the prognostic value of patient-reported outcomes (PROs) among 117 recipients of allogeneic stem cell transplantation (allo-HSCT) who participated in a randomized nutrition intervention trial. Cox proportional hazards models were used to investigate possible associations between PROs collected pre-allo-HSCT (baseline) using scores from the EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30) and 1-year overall survival (OS), whereas logistic regression was used to study associations between these PROs and 1-year non-relapse mortality (NRM). Multivariable analyses indicated that only the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) and the European Bone Marrow Transplantation (EBMT) risk score were associated with 1-year OS. In the multivariable model including clinical-sociodemographic factors for 1-year NRM, our analysis showed that living alone (p=0.009), HCT-CI (p=0.016), EBMT risk score (p=0.002), and stem cell source (p=0.046) could be associated with 1-year NRM. Moreover, in the multivariable model, our analysis showed that only appetite loss from the QLQ-C30 was associated with 1-year NRM (p=0.026). In conclusion, in this specific setting, our analysis suggests that the commonly used HCT-CI and EBMT risk scores could be predictive for both 1-year OS and 1-year NRM, whereas baseline PROs in general were not.

Seven-year trajectories of body weight, quality of life and comorbidities following Roux-en-Y gastric bypass and sleeve gastrectomy.

BACKGROUND/OBJECTIVES: There is limited long-term data comparing the outcomes of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) for severe obesity, both with respect to body weight, quality of life (QOL) and comorbidities. We aimed to determine 7-year trajectories of body mass index (BMI), QOL, obesity-related comorbidities, biomarkers of glucose and lipid metabolism, and early major complications after SG and RYGB. SUBJECTS/METHODS: Patients scheduled for bariatric surgery at two Norwegian hospitals, preferentially performing either SG or RYGB, were included consecutively from September 2011 to February 2015. Data was collected prospectively before and up to 7 years after surgery. Obesity-specific, generic and overall QOL were measured by the Impact of Weight on Quality of Life-Lite, Short-Form 36 and Cantril's ladder, respectively. Comorbidities were assessed by clinical examination, registration of medication and analysis of glucose and lipid biomarkers. Outcomes were examined with linear mixed effect models and relative risk estimates. RESULTS: Of 580 included patients, 543 (75% women, mean age 42.3 years, mean baseline BMI 43.0 kg/m2) were operated (376 SG and 167 RYGB). With 84.2% of participants evaluable after 5-7 years, model-based percent total weight-loss (%TWL) at 7 years was 23.4 after SG versus 27.3 after RYGB (difference 3.9%, p = 0.001). All levels of QOL improved similarly after the two surgical procedures but remained below reference data from the general population at all timepoints. Remission rates for type 2 diabetes, dyslipidemia, obstructive sleep-apnea and gastroesophageal reflux disease (GERD) as well as the rate of de novo GERD significantly favored RYGB. SG had fewer major early complications, but more minor and major late complications combined over follow-up. CONCLUSION: In routine health care, both SG and RYGB are safe procedures with significant long-term weight-loss, improvement of QOL and amelioration of comorbidities. Long-term weight-loss and remission rates of main obesity-related comorbidities were higher after RYGB.

Total late effect burden in long-term lymphoma survivors after high-dose therapy with autologous stem-cell transplant and its effect on health-related quality of life.

Lymphoma survivors after high-dose therapy with autologous stem-cell transplant (HDT-ASCT) are at risk of several late effects, which might impair their health-related quality of life (HRQoL). We assessed the total late effect burden in this population, and how it affects HRQoL. All lymphoma survivors treated with HDT-ASCT as adults in Norway between 1987 and 2008 were identified, and 271 (68%) attended both a comprehensive clinical assessment and completed a questionnaire. Severity of 45 conditions in 12 organ-system categories were graded as mild, moderate, severe or life-threatening, according to a modified version of CTCAEv4.03. At a median of 8 years after HDT-ASCT, 98% of survivors had at least one moderate or more severe late effect and 56% had severe or life-threatening late effects. Fourteen percent had low, 39% medium and 47% high late effect burden, defined as having moderate or more severe late effects in 0-1, 2-3 and >3 organsystems, respectively. Female sex, increasing age, B-symptoms at diagnosis and >1 treatment line prior to HDT-ASCT were independently associated with having high late effect burden. The survivors had significantly poorer physical and mental HRQoL assessed by the Short Form-36 compared to age- and sex-matched controls. The prevalence of poor physical and mental HRQoL increased with higher late effect burden (both P<0.001), and the low burden group had better physical HRQoL than controls (P<0.001). In conclusion, lymphoma survivors after HDT-ASCT have impaired HRQoL, seemingly driven by a high late effect burden. This highlights the importance of prevention, regular assessments for early detection and treatment of late effects and modifiable risk factors.

Zopiclone versus placebo for short-term treatment of insomnia in patients with advanced cancer-a double-blind, randomized placebo-controlled clinical multicenter phase IV trial.

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.

Pretreatment patient-reported cognitive function in patients with diffuse glioma.

PURPOSE: Cognitive function is frequently assessed with objective neuropsychological tests, but patient-reported cognitive function is less explored. We aimed to investigate the preoperative prevalence of patient-reported cognitive impairment in patients with diffuse glioma compared to a matched reference group and explore associated factors. METHODS: We included 237 patients with diffuse glioma and 474 age- and gender-matched controls from the general population. Patient-reported cognitive function was measured using the cognitive function subscale in the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire. The transformed scale score (0-100) was dichotomized, with a score of ≤ 75 indicating clinically important patient-reported cognitive impairment. Factors associated with preoperative patient-reported cognitive impairment were explored in a multivariable regression analysis. RESULTS: Cognitive impairment was reported by 49.8% of the diffuse glioma patients and by 23.4% in the age- and gender-matched reference group (p < 0.001). Patients with diffuse glioma had 3.2 times higher odds (95% CI 2.29, 4.58, p < 0.001) for patient-reported cognitive impairment compared to the matched reference group. In the multivariable analysis, large tumor volume, left tumor lateralization, and low Karnofsky Performance Status score were found to be independent predictors for preoperative patient-reported cognitive impairment. CONCLUSIONS: Our findings demonstrate that patient-reported cognitive impairment is a common symptom in patients with diffuse glioma pretreatment, especially in patients with large tumor volumes, left tumor lateralization, and low functional levels. Patient-reported cognitive function may provide important information about patients' subjective cognitive health and disease status and may serve as a complement to or as a screening variable for subsequent objective testing.

Surgery for brain metastases-impact of the extent of resection.

BACKGROUND: Surgical resection of brain metastases improves symptoms and survival in selected patients. The benefit of gross total resection is disputed, as most patients are believed to succumb from their non-CNS tumor burden. We investigated the association between overall survival and residual tumor after surgery for single brain metastases. METHODS: We reviewed adults who underwent surgery for a single brain metastasis at a regional referral center (2011-2018). Gross total resection was defined as no visible residual tumor on cerebral MRI 12-48 h postoperatively. RESULTS: We included 373 patients. The most common primary tumors were lung cancer (36%) and melanoma (24%). We identified gross total resection in 238 patients (64%). Median overall survival was 11.0 months, 8.0 (6.2-9.8) months for patients with subtotal resection and 13.0 (9.7-16.3) months for patients with gross total resection. In a multivariate regression analysis including preoperative prognostic factors, gross total resection was associated with longer overall survival (HR: 0.66, p = 0.003). Postoperative radiotherapy administered within 6 weeks did not significantly alter the hazard ratio estimates for grade of resection. CONCLUSIONS: Our study suggests improved survival with gross total resection compared to subtotal resection. The importance of extent of resection in surgery for brain metastases should not be discarded.

Translation and validation of Sinhala version of modified EORTC QLQ-OH15 in oral cancer patients who receive radiotherapy with or without chemotherapy in Sri Lanka.

BACKGROUND: The recognition of patient-reported outcomes for oral cancer is important in improving patients' quality of life. The aim of this study was to translate and validate the modified Sinhala version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Oral Health Module (EORTC QLQ-OH15). METHODS: A cross-sectional study was conducted to validate the EORTC QLQ-OH15 that was modified after adding two questions to the original questionnaire. The two questions added were 'difficulty in opening the mouth wide' and 'trouble with talking' which affect oral health related quality of life (OHRQOL) of oral cancer patients receiving radiotherapy. The Sinhala translated modified EORTC QLQ-OH15 and already validated the core questionnaire EORTC QLQ-C30 were self-completed by 85 adult oral cancer patients who received initial anti-cancer treatment with radiotherapy with or without chemotherapy. Content and face validity were examined by an expert panel. Construct validity was confirmed by using factor analysis, multi-trait scaling analysis, and known group comparison. Reliability was assessed by internal consistency, test-retest reliability by Wilcoxon Signed Ranks Test and intra class correlation coefficient. Responsiveness to change was assessed. RESULTS: The majority of participants (58%) were aged 50-69 years and 84% were males. Nearly 32% had cancer of the anterior two thirds of the tongue. Of the sample, 66% received chemo radiotherapy. Thirteen items were included for the factor analysis. They were loaded for four factors. Three scales 'Eating problem', 'Gum and Speech problem' and 'Soreness' loaded with 5, 4 and 3 items respectively and single item 'teeth' to a one factor with the total variance explained was 72.74%. Mann-Whitney U tests for all three scales were statistically significant confirming the ability of the modified EORTC QLQ-OH15 to detect expected differences in OHRQOL in clinically different groups. Cronbach's alpha for all the scales were more than 0.8. Wilcoxon Matched Paired Sign Rank Test showed highly significant results (p < 0.05) for all three scales revealing high responsiveness. CONCLUSIONS: The modified Sinhala version of the EORTC QLQ-OH15 is a valid, reliable tool that can be used to measure OHRQOL in oral cancer patients who receive radiotherapy with or without chemotherapy.

Overall survival after initial radiotherapy for brain metastases; a population based study of 2140 patients with non-small cell lung cancer.

BACKGROUND: Brain metastases (BM) occur in about 30% of all patients with non-small cell lung cancer (NSCLC). BM treatment guidelines recommend more frequent use of stereotactic radiotherapy (SRT). Overall, studies report no difference in overall survival (OS) comparing SRT to whole-brain radiotherapy (WBRT). We examined survival after radiotherapy for BM in a population-based sample from the South-Eastern Norway Regional Health Authority treated 2006-2018. METHODS: We reviewed electronic medical records of 2140 NSCLC patients treated with SRT or WBRT for BM from 2006-2018. Overall survival (OS) was compared to predicted survival according to the prognostic systems DS-GPA and Lung-molGPA. RESULTS: Use of SRT increased during the period, from 19% (2006-2014) to 45% (2015-2018). Median OS for all patients was 3.0 months, increasing from 2.0 (2006) to 4.0 (2018). Median OS after SRT was 7.0 months (n = 435) and 3.0 months after WBRT (n = 1705). Twenty-seven percent of SRT patients and 50% of WBRT patients died within 90 days after start of RT. Age ≥70, male sex, KPS ≤70, non-adenocarcinoma histology, ECM present, multiple BM, and WBRT were associated with shorter survival (p < .001). Actual mOS corresponded best with predicted mOS by DS-GPA and Lung-molGPA for the SRT group. CONCLUSION: Overall survival after radiotherapy (RT) for BM improved during the study period, but only for patients treated with SRT. Survival after WBRT remains poor; its use should be questioned. DS-GPA and Lung-molGPA seem most useful in predicting prognosis considered for SRT.

Surgery for brain metastases - real-world prognostic factors' association with survival.

BACKGROUND: Surgical resection of brain metastases (BM) improves overall survival (OS) in selected patients. Selecting those patients likely to benefit from surgery is challenging. The Graded Prognostic Assessment (GPA) and the diagnosis-specific Graded Prognostic Assessment (ds-GPA) were developed to predict survival in patients with BM, but not specifically to guide patient selection for surgery. Our aim was to evaluate the feasibility of preoperative GPA/ds-GPA scores and assess variables associated with OS. METHODS: We retrospectively reviewed first-time surgical resection of BM from solid tumors at a Norwegian regional referral center from 2011 to 2018. RESULTS: Of 590 patients, 51% were female and median age was 63 years. Median OS was 10.3 months and 74 patients (13%) died within three months after surgery. Preoperatively tumor origin was unknown in 20% of patients. A GPA score could be calculated for 92% of the patients preoperatively, but could not correctly predict survival. A ds-GPA score could be calculated for 46% of patients. Multivariable regression analysis revealed shorter OS in patients with higher age, worse functioning status, colorectal primary cancer compared to lung cancer, presence of extracranial metastases, and more than four BM. Patients with preoperative progressive extracranial disease or synchronous BM had shorter OS compared to patients with stable extracranial disease. CONCLUSION: Ds-GPA could be calculated in less than half of patients preoperatively and GPA poorly identified patients which had minimal benefit of surgery. Including status of extracranial disease improve prognostication and therefore selection to surgery for brain metastases.

The short-term impact of methylprednisolone on patient-reported sleep in patients with advanced cancer in a randomized, placebo-controlled, double-blind trial.

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).

Psychometric properties of the updated EORTC module for assessing quality of life in patients with lung cancer (QLQ-LC29): an international, observational field study.

BACKGROUND: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) assesses quality of life (QOL) in patients with lung cancer and was the first EORTC module developed for use in international clinical trials. Since its publication in 1994, major treatment advances with possible effects on QOL have occurred. These changes called for an update of the module and its international psychometric validation. We aimed to investigate the scale structure and psychometric properties of the updated lung cancer module, QLQ-LC29, in patients with lung cancer. METHODS: This international, observational field study was done in 19 hospitals across 12 countries. Patients aged older than 18 years with a confirmed diagnosis of lung cancer and no other previous primary tumour, and who were mentally fit with sufficient language skills to understand and complete the questionnaire were included. Patients were asked during a hospital visit to fill in the paper versions of the core questionnaire EORTC QLQ-C30 plus QLQ-LC29, and investigators selected half of these patients to complete the questionnaire again 2-4 weeks later. Our primary aim was to assess the scale structure and psychometric properties of EORTC QLQ-LC29. We analysed scale structure using confirmatory factor analysis; reliability using Cronbach's α value (internal consistency) and intra-class coefficient (test-retest reliability); sensitivity using independent t tests stratified by Karnofsky performance status; and responsiveness to change over time by ANOVA. This study is registered with ClinicalTrials.gov, NCT02745691. FINDINGS: Between April 12, 2016, and Sept 26, 2018, 523 patients with a confirmed diagnosis of either non-small-cell lung cancer (n=442) or small-cell lung cancer (n=81) were recruited. Confirmatory factor analysis provided a solution composed of five multi-item scales (coughing, shortness of breath, fear of progression, hair problems, and surgery-related symptoms) plus 15 single symptom or side-effect items: χ2=370·233, root mean square error of approximation=0·075, and comparative-fit index=0·901. Cronbach's α for internal consistencies of all multi-item scales were above the threshold of 0·70. Intra-class coefficients for test-retest reliabilities ranged between 0·82 and 0·97. Three (shortness of breath, fear of progression, and hair problems) of the five multi-item scales showed responsiveness to change over time (p values <0·05), as did nine of 15 single symptom items. Four (coughing, shortness of breath, fear of progression, and surgery-related symptoms) of the five multi-item scales and ten of the 15 single symptom items were sensitive to known group differences (ie, lower vs higher Karnofsky performance status). INTERPRETATION: Results determined the psychometric properties of the updated lung cancer module, which is ready for use in international clinical studies. FUNDING: EORTC Quality of Life Group.

The relationship between pain, analgesics and survival in patients with advanced cancer; a secondary data analysis of the international European palliative care Cancer symptom study.

PURPOSE: Opioids reduce cancer-related pain but an association with shorter survival is variably reported. AIM: To investigate the relationship between pain, analgesics, cancer and survival within the European Palliative Care Cancer Symptom (EPCCS) study to help inform clinical decision making. METHODS: Secondary analysis of the international prospective, longitudinal EPCCS study which included 1739 adults with advanced, incurable cancer receiving palliative care. In this secondary analysis, for all participants with date of death or last follow up, a multilevel Weibull survival analysis examined whether pain, analgesics, and other relevant variables are associated with time to death. RESULTS: Date of death or last follow-up was available for 1404 patients (mean age 65.7 [SD:12.3];men 50%). Secondary analysis of this group showed the mean survival from baseline was 46.5 (SD:1.5) weeks (95% CI:43.6-49.3). Pain was reported by 76%; 60% were taking opioids, 51% non-opioid analgesics and 24% co-analgesics. Opioid-use was associated with decreased survival in the multivariable model (HR = 1.59 (95% CI:1.38-1.84), p < 0.001). An exploratory subgroup analysis of those with C-reactive protein (CRP) measures (n = 219) indicated higher CRP was associated with poorer survival (p = 0.001). In this model, the strength of relationship between survival and opioid-use weakened (p = 0.029). CONCLUSION: Opioid-use and survival were associated; this relationship weakened in a small sensitivity-testing subgroup analysis adjusting for CRP. Thus, the observed relationship between survival and opioid-use may partly be due to tumour-related inflammation. Larger studies, measuring disease activity, are needed to confirm this finding to more accurately judge the benefits and risks of opioids in advanced progressive disease.

Sleep quality in hospitalized patients with advanced cancer: an observational study using self-reports of sleep and actigraphy.

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 Ë‚ 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.

Symptoms in the general Norwegian adult population - prevalence and associated factors.

BACKGROUND: Patients´ own perceptions and evaluations of symptoms, functioning and other health-related factors, i.e. Patient Reported Outcomes (PROs), are important elements for providing good patient care. Symptoms are subjective and best elicited by the patient orally or by using PRO measures (PROMs), be it on paper, or as electronic assessment tools. Reference values on frequently used PROMs facilitate the interpretation of scores for use in clinics and research settings, by comparing patient data with relevant samples from the general population. Study objectives were to (1) present reference values for the M.D. Anderson Symptom Inventory (MDASI) (2) examine the occurrence and intensity of symptoms assessed by the MDASI in a general Norwegian adult population sample, and (3) examine factors associated with higher symptom burden defined as the sum score of all symptoms, and factors associated with symptoms` interference on functions. METHODS: In 2015, MDASI was sent by mail as part of a larger survey, to a representative sample of the general Norwegian adult population (N = 6165). Medical comorbidities were assessed by the Self-Administered Comorbidity Questionnaire. Depression was self-reported on the Patient Health Questionnaire 9 (PHQ-9). Linear multivariable regression analysis was used to examine for factors associated with MDASI sum score and factors associated with symptoms' interference on functions. RESULTS: The response rate was 36%. More women (54%) than men (46%) responded. Mean age was 55 years (SD 14). The most frequent symptoms were fatigue (59.7%), drowsiness (56.2%) and pain (56.1%). Fatigue, pain and disturbed sleep had the highest mean scores. The presence of one or more comorbidities, increasing PHQ-9 score and lower level of education were associated with higher MDASI sum score (p < 0.001). The MDASI sum score and the PHQ-9 score were positively associated with all interference items (p < 0.001) except for walking (p = 0.22). CONCLUSION: This study provides the first Norwegian reference values for MDASI. The presence of one or more comorbidities, higher level of depressive symptoms and lower level of education were significantly associated with higher MDASI sum score. These covariates must be controlled for when using the reference values.

Norwegian reference data on the Fatigue Questionnaire and the Patient Health Questionnaire-9 and their interrelationship.

BACKGROUND: Population-based reference data on frequently used questionnaires are important for comparative purposes. Due to changes in health and lifestyles, such data should be updated every other decade. The objectives of this study were to establish Norwegian population-based reference data on the Fatigue Questionnaire (FQ) and the Patient Health Questionnaire-9 (PHQ-9) on depression, to compare the FQ-scores with our previous reference data from 1996, and to explore the relationship between the scores on these two instruments. METHODS: In 2015, a representative sample of 6,012 Norwegians aged 18-80 years was mailed a questionnaire including the FQ and the PHQ-9, and 36% responded. Complete FQ-scores were delivered by 2,041 subjects, and complete PHQ-9 scores by 2,086 subjects. The scores are displayed according to sex and 10-year age groups. RESULTS: Few 2015 mean scores of mental, physical, and total fatigue differed significantly from those of 1996, and the same was found for the prevalence rates of chronic fatigue. The exception was a significantly lower prevalence in 2015 of mean fatigue scores and prevalence of chronic fatigue in females ≥ 60 years. The prevalence of major depressive episode (MDE) based on the PHQ-9 sum score cut-off ≥ 10 was 5.9% for males and 9.8% for females, and 2.5% and 3.8% using a DSM-based algorithm with at least five endorsed criteria including either anhedonia or depressed mood. The correlation between the FQ and the PHQ-9 was 0.59, implying 36% shared variance. CONCLUSIONS: This study showed considerable interrelationship between the FQ and the PHQ-9 constructs. The reference data show that scores on the FQ have only improved significantly in persons aged 60 or more years between 1996 and 2015. Our prevalence findings of MDE based on the PHQ-9 are in accordance with the findings from other countries. The FQ and the PHQ-9 should be used together in epidemiological and clinical studies.

Usability testing of EirV3-a computer-based tool for patient-reported outcome measures in cancer.

PURPOSE: Eir version 3 (V3) is an electronic tool for administration of patient-reported outcome measures (Eir-Patient) that immediately presents patient scores on the physician's computer (Eir-Doctor). Perceived usability is an important determinant for successful implementation. The aim of this study was to answer the following research question evaluated at the cancer outpatient clinics, in the patients' home, and at general practitioners' (GPs) offices: What are the number, type, and severity of usability issues evaluated by the patient (Eir-Patient module) and by the physician (Eir-Doctor module)? METHODS: A usability evaluation using observations, think-aloud sessions, individual interviews and focus group interviews in cancer patients and their physicians was conducted. Identified usability issues were graded on a severity scale from 1 (irritant) to 4 (unusable). RESULTS: Overall, 73 Eir registrations were performed by 37 patients, and used by 17 physicians in clinical consultations. All patients were able to complete the Eir-Patient symptom registration. Seventy-two usability issues were identified. None of them were graded as unusable. For the Eir-Patient module, 62% of the identified usability issues was graded as irritant (grade 1), 18% as moderate (grade 2), and 20% as severe (grade 3). For the Eir-Doctor module, 46% of the identified usability issues were graded as irritant, 36% as moderate and 18% as severe. CONCLUSIONS: In the updated Eir version, issues in the severe and moderate categories have been changed, to optimize the usability of using real-time PROMs in clinical practice.

Pilot testing of the first version of the European Association for Palliative Care basic dataset: A mixed methods study.

BACKGROUND: Inadequate description of palliative care cancer patients in research studies often leads to results having limited generalizability. To standardize the description of the sample, the European Association for Palliative Care basic data set was developed, with 31 core demographic and disease-related variables. AIM: To pilot test the data set to check acceptability, comprehensibility and feasibility. DESIGN: International, multi-centre pilot study at nine study sites in five European countries, using mixed methods. SETTING/PARTICIPANTS: Adult cancer patients and staff in palliative care units, hospices and home care. RESULTS: In all, 191 patients (544 screened) and 190 health care personnel were included. Median time to fill in the patient form was 5 min and the health care personnel form was 7 min. Ethnicity was the most challenging item for patients and requires decisions at a national level about whether or how to include. Health care personnel found weight loss, principal diagnosis, additional diagnoses and stage of non-cancer diseases most difficult to respond to. Registration of diagnoses will be changed from International Statistical Classification of Diseases and Related Health Problems, 10th version code to a predefined list, while weight loss and stage of non-cancer diseases will be removed. The pilot study has led to rewording of items, improvement in response options and shortening of the data set to 29 items. CONCLUSION: Pilot testing of the first version of the European Association for Palliative Care basic data set confirmed that patients and health care personnel understand the questions in a consistent manner and can answer within an acceptable timeframe. The pilot testing has led to improvement, and the new version is now subject to further testing.

A prospective study examining cachexia predictors in patients with incurable cancer.

BACKGROUND: Early intervention against cachexia necessitates a predictive model. The aims of this study were to identify predictors of cachexia development and to create and evaluate accuracy of a predictive model based on these predictors. METHODS: A secondary analysis of a prospective, observational, multicentre study was conducted. Patients, who attended a palliative care programme, had incurable cancer and did not have cachexia at baseline, were amenable to the analysis. Cachexia was defined as weight loss (WL) > 5% (6 months) or WL > 2% and body mass index< 20 kg/m2. Clinical and demographic markers were evaluated as possible predictors with Cox analysis. A classification and regression tree analysis was used to create a model based on optimal combinations and cut-offs of significant predictors for cachexia development, and accuracy was evaluated with a calibration plot, Harrell's c-statistic and receiver operating characteristic curve analysis. RESULTS: Six-hundred-twenty-eight patients were included in the analysis. Median age was 65 years (IQR 17), 359(57%) were female and median Karnofsky performance status was 70(IQR 10). Median follow-up was 109 days (IQR 108), and 159 (25%) patients developed cachexia. Initial WL, cancer type, appetite and chronic obstructive pulmonary disease were significant predictors (p ≤ 0.04). A five-level model was created with each level carrying an increasing risk of cachexia development. For Risk-level 1-patients (WL < 3%, breast or hematologic cancer and no or little appetite loss), median time to cachexia development was not reached, while Risk-level 5-patients (WL 3-5%) had a median time to cachexia development of 51 days. Accuracy of cachexia predictions at 3 months was 76%. CONCLUSION: Important predictors of cachexia have been identified and used to construct a predictive model of cancer cachexia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01362816 .

Quality of life in persons with hearing loss: a study of patients referred to an audiological service.

Objective: To investigate the relationship between hearing loss (HL) and general quality of life (QoL) in adults seeking hearing aids (HAs). Design: The patients completed the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire's general part and a questionnaire measuring self-assessed communication ability (Abbreviated Profile of hearing Aid Benefit-APHAB). These responses were compared with EORTC scores from a general population and patients with former head and neck cancer. Study sample: One-hundred and fifty-eight adults with HL were recruited prior to hearing aid (HA) fitting with one half seeking renewal of their HA. Results: General QoL scores among patients with HL were similar to those in the general population, but higher than in many chronic serious diseases. Patients with unilateral HL reported slightly worse social function and more fatigue than patients with bilateral HL. Self-assessed communication ability correlated with general QoL scores. Also, we found that best ear pure tone average (PTA), cognitive and physical QoL function predicted APHAB scores. Conclusion: In the investigated HL group, general QoL scores seem to be relatively close to those seen in the general population.