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Biomedical subjects

Stein Kaasa

Publications and source records attributed to Stein Kaasa.

At least 19 recordsLinked to original sources

Patient demographics and centre description in European palliative care units.

Patients in palliative care are elderly, frail and in decline with multisystem disease. These and other factors make palliative care research particularly challenging, and has been one of several reasons why relatively little systematic research has been performed. The European Association for Palliative Care (EAPC) is seeking to emphasise the importance of research. The present project is the first empirical multicentre study organised by the EAPC Research Network, with the aim of identifying the patient population using specialised palliative care, and identifying a network of palliative care services across Europe, able to participate in a multicentre collaboration for research. During a designated week in the autumn of 2000, data on patients were recorded from 143 centres. The survey was carried out by means of two questionnaires, one centre questionnaire and one patient questionnaire. Data were submitted on 3013 patients from 22 different European countries. Almost all patients had cancer (94%), while some had neurological disease (3%). The majority (75%) had been referred to a palliative care service during the six to seven months before the survey was performed. Very few patients had less than one week of expected survival (6%), the majority were expected to live one to six months, while as many as 16% were expected to live more than one year. The majority of the patients (27%) were fully ambulatory--the ability to walk independently without any assistance. The majority of the patients (60%) received care as an outpatient, either at a traditional clinic in an outpatient cancer hospital (12%), in home-care programs from a specialised advisory service (24%), or external nursing care (24%). The population of patients included in this survey was not a sample of dying patients. There were a substantial number of patients with an anticipated life expectancy of more than six months. The study demonstrated a considerable enthusiasm for research in the palliative care community across Europe. The heterogeneity of the sample is evident, and this will need careful consideration for future clinical trials. This calls for an international consensus on how to report on patient characteristics within palliative care research. This is necessary in order to be able to evaluate the representativity of the study population, as well as to compare data between studies. The range of services encountered in the survey highlights the need for the organisational and clinical standards for palliative care, which can be audited.

Adolescent↗

Prevalence of pain in hospitalised cancer patients in Norway: a national survey.

PURPOSE: Pain severely impairs health-related quality of life and is a feared symptom among cancer patients. Unfortunately, patients often do not receive optimal care. We wanted to evaluate the quality of cancer pain treatment in Norwegian hospitals. PATIENTS AND METHODS: A one-day prevalence study targeting hospitalised cancer patients above 18 years of age was performed. A questionnaire based on the Brief Pain Inventory was used, and additional information regarding sex, age, diagnosis, break through pain (BTP), and treatment was included. RESULTS: Fifty two percent of the included patients stated having cancer related pain (n=453), and mean pain during the previous 24 hours for these patients was NRS 3.99 (Numeric Rating scale 1-10). Presence of metastasis, occurrence of BTP, and abnormal skin sensibility in the area of pain were associated with higher pain scores. Forty two percent of all patients used opioids. However, these patients still had higher pain scores, more episodes of BTP, and more influence of the pain on daily life functions than average. Thirty percent of patients with severe pain (NRS>or=5) did not use opioids, and some of these patients did not receive any analgesics at all. CONCLUSION: Although most cancer patients receive an acceptable pain treatment in Norwegian hospitals, there are patients who are not adequately managed. Lack of basic knowledge and individual systematic symptom assessment may be reasons for the underuse of analgesics and the resulting unnecessary suffering among the cancer patients.

Aged↗

Exploring joint effects of genes and the clinical efficacy of morphine for cancer pain: OPRM1 and COMT gene.

Pain is a complex human trait. It is likely that the interaction of multiple genes, each with a small individual effect, along with the effect of environmental factors, influences the clinical efficacy of opioids rather than a single gene alone. Polymorphisms in genes coding for the mu-opioid receptor (A118G) and catechol-O-methyl transferase (Val158Met) may be important modulators of opioid efficacy. We assessed joint effects of the OPRM1 and COMT genes in predicting morphine dose for cancer pain relief. We used genotype and clinical data from a pharmacokinetic study of morphine in 207 inpatients treated with stable morphine dose for at least 3 days by Palliative Medicine Specialists. Results showed significant variation in morphine dose requirement by genotype groups: carriers of COMT Val/Val and Val/Met genotype required 63% and 23%, respectively, higher morphine dose compared to carriers of Met/Met genotype (p=0.02). Carriers of OPRM1 GG genotype required 93% higher morphine dose compared to carriers of AA genotypes (p=0.012). When we explored for joint effects, we found that carriers of the OPRM1 AA and COMT Met/Met genotype required the lowest morphine dose to achieve pain relief (87 mg/24 h; 95%CI=57,116) and those with neither Met/Met nor AA genotype needed the highest morphine dose (147 mg/24 h; 95%CI=100,180). The significant joint effects for the Met/Met and AA genotypes (p<0.012) persisted, even after controlling for demographic and clinical variables in the multivariable analyses. Future studies are needed to further characterize the joint effects of multiple genes, along with demographic and clinical variables, in predicting opioid dose.

Adult↗

Long term methadone for chronic pain: a pilot study of pharmacokinetic aspects.

Methadone is used as an alternative opioid when first line opioids fail to provide adequate pain control. Highly variable morphine:methadone dose ratios make switching challenging and little is known about the pharmacokinetics of long lasting methadone treatment for pain. Twelve patients treated with morphine for chronic non-malignant pain were switched to methadone. Seven of these patients continued with methadone throughout the nine months study period and only minor dose adjustments were performed. Serum concentrations of morphine, methadone and their metabolites were measured at baseline, day one and two, after dose titration and one week, five weeks, three months and nine months after the end of dose titration. Serum concentrations of methadone and its metabolite EDDP did not change significantly from the end of dose titration and during the nine months (repeated measures ANOVA: p=0.88 and p=0.06). Very low correlation between dose ratios and serum concentration ratios between morphine and methadone was observed. Large interindividual differences in serum concentrations and metabolism were observed. Our findings contradict that autoinduction of methadone metabolism takes place during long term treatment and supports that a 3-day opioid switch from morphine to methadone followed by a one week titration seems pharmacologically sound.

Adult↗

Prospective randomised multicenter trial on single fraction radiotherapy (8 Gy x 1) versus multiple fractions (3 Gy x 10) in the treatment of painful bone metastases.

BACKGROUND AND PURPOSE: To investigate whether single-fraction radiotherapy is equal to multiple fractions in the treatment of painful metastases. PATIENTS AND METHODS: The study planned to recruit 1000 patients with painful bone metastases from four Norwegian and six Swedish hospitals. Patients were randomized to single-fraction (8 Gy x 1) or multiple-fraction (3 Gy x 10) radiotherapy. The primary endpoint of the study was pain relief, with fatigue and global quality of life as the secondary endpoints. RESULTS: The data monitoring committee recommended closure of the study after 376 patients had been recruited because interim analyses indicated that, as in two other recently published trials, the treatment groups had similar outcomes. Both groups experienced similar pain relief within the first 4 months, and this was maintained throughout the 28-week follow-up. No differences were found for fatigue and global quality of life. Survival was similar in both groups, with median survival of 8-9 months. CONCLUSIONS: Single-fraction 8 Gy and multiple-fraction radiotherapy provide similar pain benefit. These results, confirming those of other studies, indicate that single-fraction 8 Gy should be standard management policy for these patients.

Aged↗

[Delirium in palliative care].

Delirium has an abrupt onset and represents an emergency. The symptoms of delirium include reduced consciousness, cognitive failure and altered psychomotor activity. In this paper, we present delirium in palliative care based on a literature review and clinical experience. Delirium is the second most common psychiatric condition in cancer patients in general. The exact prevalence in palliative care is unknown. Several factors can precipitate a delirium. The most common factors are probably opioids, dehydration and metabolic disturbances. The assessment must be balanced towards the patient's life expectancy and aims at establishing the diagnosis and identifying precipitating factors. The diagnosis of delirium is easy for those familiar with the diagnostic criteria. The abrupt change in the patients' mental status is the key to correct diagnosis. The assessment can include instruments used in semi-structured interviews. Delirium can probably be prevented. The type and amount of treatment depends upon the patient's life expectancy. Causal treatment is a goal unless the delirium is part of the dying process. Symptom control is generally achieved by haloperidol and regulation of stimuli.

Analgesics, Opioid↗

[The specialist field of palliative medicine].

Palliative medicine means caring for patients with incurable disease and short life expectancy, or, with the British definition, "the study and management of patients with active, progressive, far advanced disease, for whom the prognosis is limited and the focus of care is the quality of life". Palliative medicine is more than care for the dying. Today palliative medicine is regarded as integral to the treatment pathway for all patients with incurable disease. Up to now, mostly cancer patients have been offered specialist palliative care, but the international trend is to include other patient groups, especially patients with degenerative neurological disease and advanced cardiac and pulmonary disease. Palliative medicine is characterized by a focus not primarily on disease control but rather on symptom relief, social support, spiritual care, and maintenance of physical and psychological functioning and wellbeing. To reach these goals, a multi-professional approach is needed, and the doctor in charge must be highly qualified clinically and academically and willing and able to cooperate with colleagues and other healthcare professionals.

Hospices↗

[Palliative medicine-- research and education in a new specialist field].

Palliative medicine has developed into a recognised specialty in medicine, calling for a high level of skills as well as evidence-based clinical guidelines. The undergraduate teaching in medical schools in Norway is fragmented in this area, and national minimum standards are needed. At the graduate level, teaching in palliative medicine should be included in all relevant specialties. Doctors who are fully involved in palliative medicine should have a specialised education. Recently, a Nordic Curriculum in Palliative Medicine was developed and a two-year course initiated; 30 doctors have graduated. There is a need for research in palliative care, both on the basic biological level as well as on the clinical level. National and international collaboration is needed in order to reach these goals. Nationally, there are some research groups that perform excellently. However, there is a need to strengthen research in this area. Chairs in palliative medicine will facilitate such a development and are urgently needed in all medical schools.

Biomedical Research↗

The effect of a physical exercise program in palliative care: A phase II study.

The purpose of this pilot study was to assess the effects of a physical exercise program on physical performance and quality of life (QOL) in a population with incurable cancer and a short life expectancy. Thirty-four patients participated in a 50-minute group exercise program twice a week for 6 weeks. Physical performance was measured by three tests: "6-minute walk test," "timed repeated sit to stand," and "functional reach." Fatigue was measured by the Fatigue Questionnaire. QOL was assessed by the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire. The outcome variables were assessed before and after the intervention. The walk length increased and the "timed repeated sit to stand" was reduced (P < 0.05). Emotional functioning improved and physical fatigue was reduced (P < 0.05). Physical exercise seems to be a feasible way to improve well-being among patients with incurable cancer. Future randomized trials are needed to confirm the results.

Adult↗

Opioid switching from morphine to methadone causes a minor but not clinically significant increase in QTc time: A prospective 9-month follow-up study.

Case reports and retrospective studies suggest that methadone causes an increase in QTc (QT time corrected for heart rate) time and risk of torsades de pointes arrhythmia. No prospective studies in pain patients have been conducted, and data on whether a methadone-induced increase in QTc time persists during long-term treatment have not been reported. Eight chronic nonmalignant pain patients experiencing insufficient pain control or intolerable side effects during treatment with oral morphine switched to oral methadone and were included in this study. Electrocardiograms were obtained at baseline and at follow-up 2 weeks, and 3 and 9 months after the opioid switch. Start of methadone caused a minor but statistically significant increase in QTc time, while fluctuations in QTc during treatment with stable doses of methadone were neither clinically nor statistically significant. We observed no episodes of arrhythmias.

Aged↗

Pain assessment tools: is the content appropriate for use in palliative care?

Inadequate pain assessment prevents optimal treatment in palliative care. The content of pain assessment tools might limit their usefulness for proper pain assessment, but data on the content validity of the tools are scarce. The objective of this study was to examine the content of the existing pain assessment tools, and to evaluate the appropriateness of different dimensions and items for pain assessment in palliative care. A systematic search was performed to find pain assessment tools for patients with advanced cancer who were receiving palliative care. An ad hoc search with broader search criteria supplemented the systematic search. The items of the identified tools were allocated to appropriate dimensions. This was reviewed by an international panel of experts, who also evaluated the relevance of the different dimensions for pain assessment in palliative care. The systematic literature search generated 16 assessment tools while the ad hoc search generated 64. Ten pain dimensions containing 1,011 pain items were identified by the experts. The experts ranked intensity, temporal pattern, treatment and exacerbating/relieving factors, location, and interference with health-related quality of life as the most important dimensions. None of the assessment tools covered these dimensions satisfactorily. Most items were related to interference (231) and intensity (138). Temporal pattern (which includes breakthrough pain), ranked as the second most important dimension, was covered by 29 items only. Many tools include dimensions and items of limited relevance for patients with advanced cancer. This might reduce compliance and threaten the validity of the assessment. New tools should reflect the clinical relevance of different dimensions and be user-friendly.

Humans↗

Randomised trial of in-hospital geriatric intervention: impact on function and morale.

BACKGROUND: In two previous publications, we have shown that treatment of acutely sick, frail elderly patients in a Geriatric Evaluation and Management Unit (GEMU) compared to treatment in the general Medical Wards (MW) reduced mortality and improved the chances of living at home in contrast to living in nursing homes or being dead. OBJECTIVE: The aim of this presentation was to study the impact on function, symptoms of depression and general well-being of treatment in the GEMU as compared to treatment in MW. METHODS: Acutely sick, frail patients aged >or=75 years, admitted as emergencies to the Department of Internal Medicine, were randomised either to treatment in the GEMU (n = 127) or the MW (n = 127). In the GEMU the treatment strategy emphasised comprehensive interdisciplinary assessment of all relevant disorders, prevention of complications and iatrogenic conditions, early mobilisation, rehabilitation and discharge planning. The control group received treatment as usual from the Department of Internal Medicine. After discharge neither group received specific follow-up. Activities of daily living (ADL), instrumental ADL, cognitive function, symptoms of depression and general well-being were assessed 3, 6 and 12 months after discharge from hospital. RESULTS: There was no difference in function, depression or general well-being in the GEMU as compared to the MW group. If the dead were included in the analysis at the highest ADL dependency level, there was better function in the GEMU group at 3 months (p = 0.03). CONCLUSION: Treatment in the GEMU had no measurable beneficial impact on function, morale or symptoms of depression. Taken the previously shown mortality reduction into consideration an additional effect on function was less likely and the overall treatment effect was considered to be positive.

Activities of Daily Living↗

Methodological and structural challenges in palliative care research: how have we fared in the last decades?

The heterogeneity of the palliative care population represents challenges to research methodology, including study design, informed consent (and ethical issues in general), assessment and classification of symptoms and signs, as well as practical issues in the clinic. The aim of this report is to describe and examine the status of palliative care research in Europe by means of a survey and a literature review. Only one European country, the UK, has taken a national initiative to stimulate and promote palliative care research through the supportive and palliative care collaboratives (SUPAC) in 2005. There are few European research groups in palliative care reaching a critical size, several countries do not have academic chairs in palliative care, and there is no clear trend that chairs are emerging in general. There is little public funding for palliative care research. Palliative care researchers need to compete on the 'open market' or rely on private foundations. There has been a steady increase in the number of abstracts for presentation at the EAPC Research Forums, from 200 in 2000, to 480 in 2006. The literature review indicated that the majority of publications are surveys and descriptive/observational studies, and few randomised, controlled, studies were published. In conclusion, the quantity of research seems to be steadily increasing. There may be a need for larger multi-centre studies, and in order to perform such studies, national and international structures, encompassing research above the critical size, with a multi-disciplinary background including both basic scientists and clinicians is required.

Aged↗

Opioid switching from oral slow release morphine to oral methadone may improve pain control in chronic non-malignant pain: a nine-month follow-up study.

Twelve patients with poor pain control or unacceptable side effects during treatment with morphine were switched to methadone and followed for nine months in this open prospective study. Primary outcomes were patient preference for opioid and pain control while physical, cognitive and role functioning were secondary outcomes. The morphine dose was decreased by 1/3 daily and was replaced with an equianalgesic dose of methadone over a three-day period. During switching and a one-week dose titration period, patients were given additional methadone if required. During dose titration one patient experienced sedation requiring naloxone. Four patients were switched back to morphine due to poor pain control, drowsiness or sweating. Seven patients preferred long-term (>nine months) treatment with methadone and reported reduced pain and improved functioning while cognition was not improved. This study brings novel information on the long-term consequences for pain control, health-related quality of life and cognitive functioning with a switch from morphine to methadone in the treatment of chronic non-malignant pain.

Administration, Oral↗

Intranasal midazolam: a comparison of two delivery devices in human volunteers.

Bidirectional nasal drug delivery is a new administration principle with improved deposition pattern that may increase nasal drug uptake. Twelve healthy subjects were included in this open, non-randomized 3-way crossover study: midazolam (3.4 mg) intravenously (1 mg mL (-1)), or nasally by bidirectional or traditional spray (2 x100 microL of a 17 mg mL(-1) nasal midazolam formulation). The primary outcome was bioavailability. Blood samples were drawn for 6 h for determination (gas-chromatography-mass-spectrometry) of midazolam and 1-OH-midazolam. Pharmacokinetic calculations were based on non-compartmental modelling, sedation assessed by a subjective 0-10 NRS-scale, and nasal dimensions by non-invasive acoustic rhinometry. Mean bioavailabilities were 0.68-0.71, and Tmax 15 min for the sprays, which also were bioequivalent (ratio geometric means (90%) CI: 97.6% (90% CI 83.5; 113.9)). Sedation after bidirectional spray followed intravenous sedation closely, while sedation after the traditional spray was less pronounced. A negative correlation between Cmax and smallest cross-sectional area was seen. Adverse effects such as local irritation did not differ significantly between the sprays. Apparently bidirectional delivery did not increase systemic bioavailability of midazolam. We cannot disregard that only the traditional spray caused less sedation than intravenous administration. This finding needs to be confirmed in trials designed for this purpose.

Administration, Intranasal↗