Preoperative geriatric assessment and tailored interventions in frail older patients with colorectal cancer: a randomized controlled trial.

AIM: Colorectal cancer (CRC) is prevalent in the older population, and surgery is the mainstay of curative treatment. A preoperative geriatric assessment (GA) can identify frail older patients at risk for developing postoperative complications. In this randomized controlled trial we wanted to investigate whether tailored interventions based on a preoperative GA could reduce the frequency of postoperative complications in frail patients operated on for CRC. METHOD: Patients > 65 years scheduled for elective CRC surgery and fulfilling predefined criteria for frailty were randomized to either a preoperative GA followed by a tailored intervention or care as usual. The primary end-point was Clavien-Dindo Grade II-V postoperative complications. Secondary end-points included complications of any grade, reoperation, length of stay, readmission and survival. RESULTS: One hundred and twenty-two patients with a mean age of 78.6 years were randomized. We found no statistically significant differences between the intervention group and the control group for Grade II-V complications (68% vs 75%, P = 0.43), reoperation (19% vs 11%, P = 0.24), length of stay (8 days in both groups), readmission (16% vs 6%, P = 0.12) or 30-day survival (4% vs 5%, P = 0.79). Grade I-V complications occurred in 76% of patients in the intervention group compared with 87% in the control group (P = 0.10). In secondary analyses adjusting for prespecified prognostic factors, there was a statistically significant difference in favour of the intervention for reducing the total number of Grade I-V complications (P = 0.05). CONCLUSION: A preoperative GA and tailored interventions did not reduce the rate of Grade II-V complications, reoperations, readmission or mortality in frail older patients electively operated on for CRC.

Characteristics and implications of attrition in health-related quality of life studies in palliative care.

In a longitudinal study of 297 palliative care patients, 280 patients were followed from inclusion to death. Characteristics and health-related quality of life (HRQL) of the participants and those who later dropped out were compared at inclusion, and 3 and 2 months before their death. At inclusion, the dropouts were older (P = 0.001), had reduced Karnofsky performance score (P < 0.001), received more help from the local authority (P = 0.004) and had reduced HRQL compared with patients who continued in the study and completed the next questionnaire. There were no differences in any of the HRQL parameters between participants and dropouts 3 months before death. Two months before death, differences in HRQL were found, but in favour of the dropouts. Data from patients close to death may be representative of a larger group of patients, whereas initial dropouts may lead to a positive bias of reported HRQL.

Classification of pain in cancer patients--a systematic literature review.

One of the aims of the European Palliative Care Research Collaborative (EPCRC) is to achieve consensus on a classification system for cancer pain. We performed a systematic literature review to identify existing classification systems and domains/items used to classify cancer patients with pain. In a systematic search in the databases Medline and Embase, covering 1986-2006, 692 hits were obtained. 92 papers were evaluated to address pain classification. Six standardised classification systems were identified; three of them systematically developed and partially validated. Both pain characteristics and patient characteristics relevant for cancer pain classification were included in the classification systems. All but one of the standardised systems aim at predicting treatment response or adequacy of treatment. Several domains and items used to describe cancer pain but not formally described as part of a classification system were also identified and systematized. The existing approaches to pain classification in cancer patients are different, mostly not thoroughly validated, and none is widely applied. An internationally accepted classification system for cancer pain could improve research and cancer pain management. This systematic review suggests a need for developing an international consensus on how to classify pain in cancer patients.

Chronic non-malignant pain patients report as poor health-related quality of life as palliative cancer patients.

BACKGROUND: Patients with chronic non-malignant pain (CNMP) conditions are known to report reduced health-related quality of life (HRQoL). The objective of this exploratory study was to compare HRQoL between patients admitted to a multidisciplinary pain centre, palliative cancer (PC) patients and national norms. METHODS: HRQoL data from 288 patients with CNMP admitted to the multidisciplinary pain centre at Trondheim University Hospital were compared with 434 patients with advanced cancer included in a trial of comprehensive palliative care in the hospital palliative medicine unit and national norms. HRQoL was assessed using the EORTC QLQ-C30. Age- and gender-adjusted norm data were calculated and compared between the two groups. RESULTS: Scores from both groups deviated from adjusted norm data on all scales, with poorer functioning and more symptoms. Compared with PC patients, CNMP patients reported a larger deviation (worse scores) on global quality of life, cognitive functioning, pain, sleep disturbances and financial difficulties. Deviations from norm data were similar for physical, social and emotional functioning, diarrhoea, dyspnoea and fatigue. PC patients reported worse scores on role functioning, nausea/vomiting, loss of appetite and constipation. CONCLUSION: CNMP patients admitted to multidisciplinary pain centres report significantly reduced HRQoL, in addition to severe pain. They consider their HRQoL to be as poor as HRQoL reported from dying cancer patients and substantially poorer than national norms. Factors other than the biological severity of the disease seem to be of major importance for self-reported HRQoL.

Quality of life in palliative cancer care: results from a cluster randomized trial.

PURPOSE: To assess the impact of comprehensive palliative care on patients' quality of life. The intervention was based on cooperation between a palliative medicine unit and the community service and was compared with conventional care. PATIENTS AND METHODS: A cluster randomized trial was carried out, with community health care districts defined as the clusters. Patients from these districts who had malignant disease and survival expectancy between 2 to 9 months were entered onto the trial. The main quality-of-life end points were physical and emotional functioning, pain, and psychologic distress assessed monthly by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) questionnaire and Impact of Event scale (IES). In total, 235 intervention patients and 199 controls were included. RESULTS: During the initial 4 months of follow-up, the compliance was good (72%) and comparable among treatment groups. No significant differences on any of the quality-of-life scores were found. At later assessments and for scores that were made within 3 months before death, there was also no consistent tendency in favor of any treatment group on the main outcomes or other EORTC QLQ-C30 scales/items. CONCLUSION: A general program of palliative care may be important to ensure flexibility and to meet the needs of terminally ill patients. However, to achieve improvements on a group level of the various dimensions of quality of life, specific interventions directed toward specific symptoms or problems may have to be defined, evaluated, and included in the program.

Factors affecting grief reactions in close family members to individuals who have died of cancer.

This longitudinal study examined factors related to grief reactions in a systematic and standardized way in 183 close family members to individuals who died of cancer. Grief reactions were measured using the Texas Revised Inventory of Grief (TRIG). A repeated measures MANOVA was used to test and compare the grief reactions of the bereaved for one year after the loss. The female respondents showed stronger grief reactions than the male respondents. The grief reactions increased with age, and those who had lost a younger family member experienced stronger grief reactions than those who had lost an older family member. The relationship to the deceased, the duration of the disease, place of death, aspects of social support such as children living at home, and employment were not related to the grief reactions in the bereaved respondents when controlling for the former factors.

Methods for handling missing data in palliative care research.

Missing data is a common problem in palliative care research due to the special characteristics (deteriorating condition, fatigue and cachexia) of the population. Using data from a palliative study, we illustrate the problems that missing data can cause and show some approaches for dealing with it. Reasons for missing data and ways to deal with missing data (including complete case analysis, imputation and modelling procedures) are explored. Possible mechanisms behind the missing data are: missing completely at random, missing at random or missing not at random. In the example study, data are shown to be missing at random. Imputation of missing data is commonly used (including last value carried forward, regression procedures and simple mean). Imputation affects subsequent summary statistics and analyses, and can have a substantial impact on estimated group means and standard deviations. The choice of imputation method should be carried out with caution and the effects reported.

[Malignant non-Hodgkin's lymphomas. Classification, treatment and survival in a 10-year material]. / Maligne non-Hodgkins lymfomer. Klassifisering, behandling og overlevelse i et tiårsmateriale.

Over a ten year period, 71 cases of malignant non-Hodgkin's lymphomas were treated at the Department of Internal Medicine, Nordland Central Hospital. Of these cases, 41 were low grade malignant non-Hodgkin's lymphomas, while 28 were high grade. 41% presented localized disease. 30% had primary extranodal manifestations. Median age was 68 years. 5-years disease-specific survival was 57%. The results of treatment are judged to be satisfactory when compared with the results from other unselected materials. Improvements can be made on some points. The study revealed possibly too extensive use of surgery in patients with extranodal manifestations, and too extensive use of aggressive chemotherapy in patients with low grade malignancy.

[Diagnosis and treatment of lymphomas. Retrospective quality assessment of a 10-year material]. / Lymfomdiagnostikk og behandling. Retrospektiv kvalitetsvurdering av et tiårsmateriale.

We have performed a quality assessment of staging and treatment of 64 patients with non-Hodgkin's lymphoma treated at the Department of Internal Medicine, Nordland Central Hospital from 1982 to 1991. The assessment was based on defined quality criteria. Journal records of patient history, physical examination and stage were unsatisfactory. Histological examinations, use of laboratory tests and X-ray examinations were appropriate. The choice of chemotherapy for high grade malignancy was adequate, average relative dose-intensity was low. Low utilization of radiotherapy could be explained in most cases by individual patient factors. 5-years disease-specific survival was 54% for all patients and 70% for those presenting with localized disease.

Cluster-randomized trials.

Cluster-randomized trials represent an important experimental design, supplementing ordinary randomized clinical trials. They are particularly relevant when evaluating interventions at the level of clinic, hospital, district or region. They are necessary when it is not feasible to randomize individual patients, and desirable when there may be contamination between clusters. But they also carry serious design and analysis implications, and the use of clusters as the unit of randomization must be justified. Sample sizes will usually need to be greatly increased, an adequate number of clusters is essential, and the statistical analysis must allow for the cluster design. And one should rigorously guard against selection bias.

A palliative-care intervention and death at home: a cluster randomised trial.

BACKGROUND: The Palliative Medicine Unit at University Hospital of Trondheim, Norway, started an intervention programme that aims to enable patients to spend more time at home and die there if they prefer. Close cooperation was needed with the community health-care professionals, who acted as the principal formal caregivers, and a multidisciplinary consultant team coordinated the care. We did a cluster randomised trial to assess the intervention's effectiveness compared with conventional care METHODS: Community health-care districts in and around Trondheim, Norway, were defined as the clusters to be randomised. We enrolled 434 patients (235 assigned intervention and 199 conventional care [controls]) in these districts who had incurable malignant disease and an expected survival of 2-9 months. Main outcomes were place of death and time spent in institutions in the last month of life. FINDINGS: 395 patients died. Of these, more intervention patients than controls died at home (54 [25%] vs 26 [15%], p<0.05). The time spent at home was not significantly increased, although intervention patients spent a smaller proportion of time in nursing homes in the last month of life than did controls (7.2 vs 14.6%, p<0.05). Hospital use was similar in the two groups. INTERPRETATION: The palliative-care intervention enabled more patients to die at home. More resources for care in the home (palliative care training and staff) and an increased focus on use of nursing homes would be necessary, however, to increase time at home and reduce hospital admissions.

Fatigue. Measures and relation to pain.

Fatigue describes reduced capacity to sustain force or power output, reduced capacity to perform multiple tasks over time and simply a subjective experience of feeling exhausted, tired, weak or having lack of energy. Pain and fatigue have several components in common, such as being subjective, prevalent in most patients with cancer and caused by multiple factors of both a physical and psychological nature. In order to explore the relationship between fatigue and pain, data from five studies were used: two random samples from the Norwegian population (n=2323 and n=1965), Hodgkin's disease survivors (n=459), palliative care patients (n=434) and patients with bone metastases (n=94). All patients had completed one or more of the following instruments: EORTC QLQ-C30, SF-36 and/or Fatigue Questionnaire. The level of fatigue was much higher in the two palliative care populations (54.4 and 63.2) as compared to the normal population samples (25.0). Patients with bone metastases had significantly more pain (72.0) than the patients in the palliative care trial (47.4) and norms (20.5). In the two palliative care and bone metastases populations fatigue was almost unchanged over time, while pain was reduced. In the palliative care population a high level of fatigue (80.3) and pain (57.8) was reported 0-1 month before death. The relationship between pain, fatigue and the health-related quality of life domains should be explored in more detail, especially in follow-up studies in order to assess possible changes over time. In addition, the validity of the existing instruments measuring fatigue should be investigated for use in patients with advanced disease and short life expectancy.

Compliance in quality of life data: a Norwegian experience.

Compliance is of extreme importance in assessing quality of life since lost data never can be retrieved. In order to assess this issue in various studies, a cross-sectional study in cured cancer patients, three prospective trials and a normative study were explored. In the cross-sectional study 82 per cent of the patients completed the questionnaires after one reminder. More females than males answered the questionnaires. The compliance rate varied from 99 per cent to 62 per cent in the prospective studies depending upon time after inclusion. It seems that compliance decreases during follow up, primarily because of disease progression. In one of the prospective studies low compliance rate (approximately 30 per cent) was found in the questionnaire assessing religious issues. In the normative study 68 per cent of the population completed the questionnaire. No gender differences were found, but younger males and elderly women were poor compliers. In conclusion, our data support that most patients complete quality of life questionnaires. It seems that patients with inferior education, reduced physical function and with progressive/terminal disease are low compliers. Introduction of the first quality of life questionnaires to the patients is of great importance. Detailed information about the study should be given and the importance of completing the questionnaires should be underlined.

Challenges in palliative care research; recruitment, attrition and compliance: experience from a randomized controlled trial.

Randomized controlled trials (RCTs) in palliative cancer care often experience methodological problems. In this paper we discuss issues of major concern, including recruitment, patient attrition and compliance, arising from an RCT that compared comprehensive palliative care to conventional care. The main criteria for trial entry were incurable malignant disease and a survival expectancy of between 2 and 9 months. Patients' health-related quality of life (HRQL), self-assessed by multi-item questionnaires, was a defined endpoint. The planned number of patients was successfully recruited, although the patients were referred late in the course of their disease so that follow-up tended to be short. Compliance in completing HRQL questionnaires was good up to 1 month before the patient's death; but in the final weeks it was found to drop substantially. Based on our experience, recommendations are given for those planning similar research. Procedures for improving patient recruitment are suggested, stressing the need for local data management, repeated information to referral sources, extensive screening for potentially eligible patients and simple referral routines. Precise inclusion criteria, including prognostic factors other than physicians' estimates of life expectancy, should be used to ensure a sufficient follow-up period. For HRQL assessment, multi-item questionnaires can achieve excellent compliance up to 1 month before patients' death, but in order to evaluate the very final weeks of life we recommend the use of simpler methods.

The first year of grief and bereavement in close family members to individuals who have died of cancer.

Using a systematic and standardized method this longitudinal study examines changes in grief reactions in a sample of close family members (n = 183) to individuals who had died of cancer. The respondents were followed for 1 year after the loss. The study sample originated from a cluster randomized trial evaluating comprehensive palliative care (intervention) against conventional care (control). Hence, we also compared grief reactions among close family members to the patients in the intervention and control groups. Overall, the family members' grief reactions, as measured by the second part of the Texas Revised Inventory of Grief (TRIG), showed a significant decline over the period studied. However, we found no significant differences in grief reactions between the family members to the intervention and control patients at any point in time, and the pattern of change did not differ significantly for the two groups.

Lack of concealment may lead to selection bias in cluster randomized trials of palliative care.

Comprehensive palliative care programs are often implemented on a community level, and to evaluate such interventions, randomization by cluster (community) may be the only feasible method. In trials randomizing individual subjects, the importance of proper concealment has been stressed. In cluster randomized trials, however, concealment of individual patient allocation is often impossible. The following risk of selection bias has been given little attention. In the present study, comparing palliative care to conventional care, community health care districts were defined as clusters and randomized. The patients' treatment assignment was determined by the allocation of the cluster in which they resided, and hence predictable by their address. A biased selection based on practical considerations related to patients' diagnoses and hospital departments was suspected. To explore this, cancer diagnoses were grouped according to local tradition for sharing of treatment responsibility among hospital departments. A significant difference between trial arms in distribution of these groups was revealed and strongly supported our suspicion. The finding carries an important message to future researchers: when using cluster randomization, any evidence of selection bias should be carefully checked and reported.

Quality of life in advanced cancer patients: the impact of sociodemographic and medical characteristics.

Population-based surveys have shown that health-related quality of life (HRQL) is influenced by patients' characteristics such as age, gender, living situation and diagnoses. The present study explores the impact of such factors on the HRQL of severely ill cancer patients. The study sample included 395 cancer patients who participated in a cluster randomised trial of palliative care. Median survival was 13 weeks. HRQL assessments (using the EORTC QLQ-C30 questionnaire) were compared among subgroups of relevant patients' characteristics (ANOVA), and the significance of individual covariates was explored by multivariate linear regression. Most EORTC QLQ-C30 scores showed minor differences between genders. Higher age was associated with less sleeping disturbance, less pain and better emotional functioning. No positive impact of living with a partner was found. Performance status and/or time from assessment to death were significantly associated with most functioning and symptom scores. We concluded that although the overall impact of sociodemographic characteristics may seem less important to HRQL scores among advanced cancer patients than in general populations, age and gender should be allowed for. Performance status and closeness to death also need to be reported.

Use of item response theory to develop a shortened version of the EORTC QLQ-C30 emotional functioning scale.

BACKGROUND: As part of a larger study whose objective is to develop an abbreviated version of the EORTC QLQ-C30 suitable for research in palliative care, analyses were conducted to determine the feasibility of generating a shorter version of the 4-item emotional functioning (EF) scale that could be scored in the original metric. METHODS: We used data from 24 European cancer studies conducted in 10 different languages (n = 8242). Item selection was based on analyses by item response theory (IRT). Based on the IRT results, a simple scoring algorithm was developed to predict the original 4-item EF sum scale score from a reduced number of items. RESULTS: Both a 3-item and a 2-item version (item 21 'Did you feel tense?' and item 24 'Did you feel depressed?') predicted the total score with excellent agreement and very little bias. In group comparisons, the 2-item scale led to the same conclusions as those based on the original 4-item scale with little or no loss of measurement efficiency. CONCLUSION: Although these results are promising, confirmatory studies are needed based on independent samples. If such additional studies yield comparable results, incorporation of the 2-item EF scale in an abbreviated version of the QLQ-C30 for use in palliative care research settings would be justified. The analyses reported here demonstrate the usefulness of the IRT-based methodology for shortening questionnaire scales.