Stein Kaasa

St. Olavs Hospital, Nidaros, Sør-Trøndelag, Norway

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Publications (410)1523 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Both the American Society of Clinical Oncology and the European Society for Medical Oncology strongly endorse integrating oncology and palliative care (PC); however, a global consensus on what constitutes integration is currently lacking. To better understand what integration entails, we conducted a systematic review to identify articles addressing the clinical, educational, research, and administrative indicators of integration. We searched Ovid MEDLINE and Ovid EMBase between 1948 and 2013. Two researchers independently reviewed each citation for inclusion and extracted the indicators related to integration. The inter-rater agreement was high (κ = 0.96, p < .001). Of the 431 publications in our initial search, 101 were included. A majority were review articles (58%) published in oncology journals (59%) and in or after 2010 (64%, p < .001). A total of 55 articles (54%), 33 articles (32%), 24 articles (24%), and 14 articles (14%) discussed the role of outpatient clinics, community-based care, PC units, and inpatient consultation teams in integration, respectively. Process indicators of integration include interdisciplinary PC teams (n = 72), simultaneous care approach (n = 71), routine symptom screening (n = 25), PC guidelines (n = 33), care pathways (n = 11), and combined tumor boards (n = 10). A total of 66 articles (65%) mentioned early involvement of PC, 18 (18%) provided a specific timing, and 28 (28%) discussed referral criteria. A total of 45 articles (45%), 20 articles (20%), and 66 articles (65%) discussed 8, 4, and 9 indicators related to the educational, research, and administrative aspects of integration, respectively. Integration was a heterogeneously defined concept. Our systematic review highlighted 38 clinical, educational, research, and administrative indicators. With further refinement, these indicators may facilitate assessment of the level of integration of oncology and PC. ©AlphaMed Press.
    The Oncologist 12/2014; · 4.10 Impact Factor
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    ABSTRACT: Evidence-based treatment guidelines embedded in computer-based clinical decision support systems (CCDSS) may improve patient-reported outcomes (PRO). We systematically reviewed the literature for content and application of CCDSS, and their effects on PRO. A systematic review in MEDLINE and EMBASE was conducted according to PRISMA standards. Searches were limited to the publication period 1996-May 2014 and the English language. The search terms covered "computerized clinical decision systems" and "patient-reported outcomes". Screening and extraction was done independently by two reviewers according to predefined inclusion (computer and guideline) and exclusion criteria (no trial, no PRO). Study and CCDSS quality was rated according to predefined criteria. The database searches identified 1,331 references. Eighty-seven full-text articles were analyzed. The main reason for exclusion was no PRO as a study outcome measure. Fifteen studies met the inclusion criteria, representing 13,480 patients. Nine studies used a computerized device to fill in data; in four studies, this was used by the patients themselves. Most of the studies presented the data to the clinician at point of care and incorporated international guidelines. Three studies showed a positive effect on PRO, but only on symptoms. Overall, no negative effects were reported. There was no association with study quality or year of study publication. There are marginal positive effects of CCDSS on specific PRO. Factors that facilitate the use and effect are identified. Easy to use systems with difficult to ignore evidence-based advice need to be developed and tested.
    The patient. 11/2014;
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    ABSTRACT: Patients with advanced cancer commonly experience multiple somatic symptoms and declining functioning. Some highly prevalent symptoms also overlap with diagnostic symptom-criteria of depression. Thus, assessing depression in these patients can be challenging. We therefore investigated 1) the effect of different scoring-methods of depressive symptoms on detecting depression, and 2) the relationship between disease load and depression amongst patients with advanced cancer. The sample included 969 patients in the European Palliative Care Research Collaborative-Computer Symptom Assessment Study (EPCRC-CSA). Inclusion criteria were: incurable metastatic/locally advanced cancer and ≥18 years. Biomarkers and length of survival were registered from patient-records. Depression was assessed using the Patient Health Questionnaire (PHQ-9) and applying three scoring-methods: inclusive (algorithm scoring including the somatic symptom-criteria), exclusive (algorithm scoring excluding the somatic symptom-criteria) and sum-score (sum of all symptoms with a cut-off ≥8). Depression prevalence rates varied according to scoring-method: inclusive 13.7%, exclusive 14.9% and sum-score 45.3%. Agreement between the algorithm scoring-methods was excellent (Kappa=0.81), but low between the inclusive and sum scoring-methods (Kappa=0.32). Depression was significantly associated with more pain (OR-range: 1.09-1.19, p<0.001-0.04) and lower performance status (KPS-score, OR-range=0.68-0.72, p<0.001) irrespective of scoring-method. Depression was assessed using self-report, not clinical interviews. The scoring-method, not excluding somatic symptoms, had the greatest effect on assessment outcomes. Increasing pain and poorer than expected physical condition should alert clinicians to possible co-morbid depression. The large discrepancy in prevalence rates between scoring-methods reinforces the need for consensus and validation of depression definitions and assessment in populations with high disease load. Copyright © 2014 Elsevier B.V. All rights reserved.
    Journal of affective disorders. 11/2014; 173C:176-184.
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    ABSTRACT: The study objective was to evaluate whether there are clinical or genetic differences between patients with cancer-induced bone pain (CIBP) and patients with non-CIBP, and, in the CIBP group, in those with good versus poor opioid response.
    The Oncologist 10/2014; · 4.10 Impact Factor
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    ABSTRACT: Neuropathic pain (NP) in cancer patients lacks standards for diagnosis. This study is aimed at reaching consensus on the application of the NeuPSIG criteria to the diagnosis of NP in cancer patients and on the relevance of patient reported outcome (PRO) descriptors for the screening of NP in this population. An international group of 42 experts was invited to participate in a consensus process through a modified two-round internet-based Delphi survey. Relevant topics investigated were: peculiarities of NP in patients with cancer, IASP NeuPSIG diagnostic criteria adaptation and assessment, standardized PRO assessment for NP screening. Median consensus scores (MED) and inter-quartile ranges (IQR), were calculated to measure expert consensus after both rounds. 29 experts answered and good agreement was found on the statement "the pathophysiology of NP due to cancer can be different from non-cancer NP" (MED=9, IQR=2). Satisfactory consensus was reached for the first three NeuPSIG criteria (pain distribution, history and sensory findings) (MEDs>=8, IQRs<=3), but not for the fourth one (diagnostic test/imaging) (MED=6, IQR=3). Agreement was also reached on clinical examination by soft brush or pin stimulation (MEDs>=7 and IQRs<=3) and on the use of PRO descriptors for NP screening (MED=8, IQR=3). Based on the study results a clinical algorithm for NP diagnostic criteria in cancer patients with pain was proposed. Clinical research on PRO in the screening phase and on the application of the algorithm will be needed to examine their effectiveness in classifying NP in cancer patients.
    Pain 10/2014; · 5.64 Impact Factor
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    ABSTRACT: Background. Sarcopenia is a defining feature of cancer cachexia associated with physical decline, poor quality of life and poor prognosis. Thus, maintaining muscle mass is an important aim of cachexia treatment. Many patients at risk for developing cachexia or with cachexia experience side effects of chemotherapy that might aggravate the development of cachexia. However, achieving tumor control might reverse the catabolic processes causing cachexia. There is limited knowledge about muscle mass changes during chemotherapy or whether changes in muscle mass are associated with response to chemotherapy. Patients and methods. In this pilot study, patients with advanced non-small cell lung cancer (NSCLC) receiving three courses of palliative chemotherapy were analyzed. Muscle mass was measured as skeletal muscle cross sectional area (SMCA) at the level of the third lumbar vertebrae using CT images taken before and after chemotherapy. Results. In total 35 patients, 48% women, mean age 67 years (range 56–86), participated; 83% had stage IV disease and 71% were sarcopenic at baseline. Mean reduction in SMCA from pre- to post-chemotherapy was 4.6 cm2 (CI 95% −7.3–−1.9; p < 0.002), corresponding to a 1.4 kg loss of whole body muscle mass. Sixteen patients remained stable or gained SMCA. Of these, 14 (56%) responded to chemotherapy, while two progressed (p = 0.071). Maintaining or gaining SMCA resulted in longer median overall survival (loss: 5.8 months, stable/gain: 10.7 months; p = 0.073). Stage of disease (p = 0.003), treatment regimen (p = 0.023), response to chemotherapy (p = 0.007) and SMCA change (p = 0.040), but not sarcopenia at baseline, were significant prognostic factors in the multivariate survival analyses. Conclusion. Almost half of the patients had stable or increased muscle mass during chemotherapy without receiving any cachexia treatment. Nearly all of these patients responded to the chemotherapy. Increase in muscle mass, but not sarcopenia at baseline, was a significant prognostic factor.
    Acta Oncologica. 09/2014;
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    ABSTRACT: Background. Many cancer patients receive chemotherapy and radiotherapy their last 30 days [end of life (EOL)]. The benefit is questionable and side effects are common. The aim of this study was to investigate what characterized the patients who received chemo- and radiotherapy during EOL, knowledge that might be used to improve practice. Methods. Patients dead from cancer in 2005 and 2009 were analyzed. Data were collected from hospital medical records. When performance status (PS) was not stated, PS was estimated from other information in the records. A Glasgow Prognostic Score (GPS) of 0, 1 or 2 was assessed from blood values (CRP and albumin). A higher score is associated with a shorter prognosis. Results. In total 616 patients died in 2005; 599 in 2009. Among the 723 analyzed, median age was 71; 42% had metastases at diagnosis (synchronous metastases); 53% had PS 2 and 16% PS 3-4 at the start of last cancer therapy. GPS at the start of last cancer therapy was assessable in 70%; of these, 26% had GPS 1 and 35% GPS 2. Overall, 10% received chemotherapy and 8% radiotherapy during EOL. The proportions varied significantly between the different types of cancer. Multivariate analyses revealed that those at age < 70 years, GPS 2, no contact with our Palliative Care Unit and synchronous metastases received most chemotherapy the last 30 days. PS 3-4, GPS 2 and synchronous metastases were strongest associated with radiotherapy the last 30 days. Conclusion. Ten percent received chemotherapy and 8% radiotherapy the last 30 days of life. GPS 2 and synchronous metastases were most significantly associated with cancer therapy the last 30 days of life, indicating that in general, patients with the shortest survival time after diagnosis of cancer received more chemo- and radiotherapy during EOL than other patients.
    Acta oncologica (Stockholm, Sweden) 08/2014; · 2.27 Impact Factor
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    ABSTRACT: Background Despite a high incidence of life-limiting disease, there is a deficit of palliative care outcome evidence in sub-Saharan Africa. Providers of end of life care call for appropriate measurement tools. The objective is to compare four approaches to self-report pain and symptom measurement among African palliative care patients completing the African Palliative Care Association African Palliative Outcome Scale (APCA African POS).Methods Patients were recruited from five services (4 in South Africa and 1 in Uganda). Research nurses cross-sectionally administered POS pain and symptom items in local languages. Both questions were scored from 0 to 5 using 4 methods: verbal rating, demonstrating the score using the hand (H), selecting a face on a visual scale (F), and indicating a point on the Jerrycan visual scale (J). H, F and J scores were correlated with verbal scores as reference using Spearman¿s rank and weighted Kappa. A Receiver Operating Characteristic (ROC) analysis was performed.Results315 patients participated (mean age 43.5 years, 69.8% female), 71.1% were HIV positive and 35.6% had cancer, 49.2% lived in rural areas. Spearman¿s rank correlations for pain scores were: H: 0.879, F: 0.823, J: 0.728 (all p¿<¿0.001); for symptoms H: 0.876, F: 0.808, J: 0.721 (all p¿<¿0.001). Weighted Kappa for pain was H: 0.798, F: 0.719 J: 0.548 and for symptoms: H: 0.818, F: 0.718, J: 0.571. There was lower agreement between verbal and both hand and face scoring methods in the Ugandan sample. Compared to the verbal scale the accuracy of predicting high pain/symptoms was H¿>¿F¿>¿J (0.96¿0.89) in ROC analysis.Conclusions Hands and faces scoring methods correlate highly with verbal scoring. The Jerrycan method had only moderate weighted Kappa. POS scores can be reliably measured using hand or face score.
    Health and Quality of Life Outcomes 08/2014; 12(1):118. · 2.27 Impact Factor
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    ABSTRACT: Corticosteroids are frequently used in cancer pain management despite limited evidence. This study compares the analgesic efficacy of corticosteroid therapy with placebo.
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 07/2014;
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    ABSTRACT: Introduction and aims: Reported prevalence rates of depression in cancer vary considerably, and few studies distinguish between depressive symptoms and a depression diagnosis. Study aims were to study the prevalence of depressive symptoms at the last days of life, their relation with other symptoms and patient and care characteristics. Methods: A stratified sample of all deaths in 2005 was drawn by Statistics Netherlands. Questionnaires on patient and care characteristics of the last phase of life were sent to the physicians (N=6860) who signed the death certificates (response rate 77.8%). We selected adult cancer patients with non-sudden death and who were conscious until death (n=1521). Depressive and other symptoms were scored for the last 24 hours before death from 1 to 5, recoded to 1=no, 2-3=moderate and 4-5=severe. Multivariate multinominal regressions were used to examine which characteristics were associated with depressive symptoms. Results: 72% were 65 years or above, 43% were females. The prevalence of moderate and severe depressive symptoms was 32% and 6% respectively. The regression analysis showed no relationship between moderate and severe depressive symptoms and gender, pain, dyspnoea, and involvement of a spiritual caregiver. Moderate depressive symptoms were associated with older age and having anxiety, confusion, and fatigue (P<0.05). Severe depressive symptoms were associated with having anxiety, involvement of a psychologist or psychiatrist, involvement of a palliative care consultant/ pain specialist, and not being attended by a physician working in elderly care. Conclusions: One-third of the patients experienced moderate depressive symptoms according to attending physicians in the last 24 hours before death. Anxiety was associated with both moderate and severe depressive symptoms. Symptom distress at the end-of-life calls for special attention. Acknowledgment: EURO IMPACT (FP7/2007-2013, grant agreement 264697); ZonMw the Netherlands.
    Palliative Medicine; 06/2014
  • Palliative Medicine 05/2014; 28:463-473. · 2.61 Impact Factor
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    ABSTRACT: Patients with advanced cancer need multiple drugs to control symptoms and to treat cancer and concomitant diseases. At the same time, the goal of treatment changes as life expectancy becomes limited. This results in a risk for polypharmacy, maintained use of unneeded drugs, and drug-drug interactions (DDIs). The aim of the study was to analyze the use of medications, and to identify unneeded drugs as well as drugs and drug combinations with a risk for DDIs in a cohort of advanced cancer pain patients, defined by a need for a World Health Organization (WHO) analgesic ladder step III opioid. All drugs taken within a study day by cancer patients receiving opioids for moderate or severe pain (step III opioids) were analyzed. Non-opioids and adjuvants were analyzed for their use across countries. Unneeded medications as well as drugs and drug combinations with a risk for pharmacodynamic and pharmacokinetic DDIs were identified on the basis of published literature and electronic resources. In total, 2282 patients from 17 centers in 11 European countries were included. They received a mean of 7.8 drugs (range 1-20). Over one-quarter used 10 or more medications. The drugs and drug classes most frequently co-administered with opioids were: proton pump inhibitors, laxatives, corticosteroids, paracetamol (acetaminophen), nonsteroidal anti-inflammatory drugs, metoclopramide, benzodiazepines, anticoagulants, antibiotics, anticonvulsants, diuretics and antidepressants. The use of non-opioids and essential adjuvants varied across countries. Forty-five percent of patients received unnecessary or potentially unnecessary drugs and about 7% were given duplicate or antagonizing agents. Exposures to DDIs were frequent and increased the risk of sedation, gastric ulcerations, bleedings, and neuropsychiatric and cardiac complications. Many patients were exposed to pharmacokinetic DDIs involving CYP450, including 58% who used a step III opioid CYP3A4 substrate, and more than 10% who were given major CYP3A4 inhibitors or inducers. Patients with cancer treated with a WHO step III opioid use a high number of drugs. Non-opioid analgesics and corticosteroids are frequently used, but different patterns of use between countries were found. Many patients receive unneeded drugs and are at risk of serious DDIs. These findings demonstrate that drug therapy in these patients need to be evaluated continuously.
    Journal of pain and symptom management 04/2014; · 2.42 Impact Factor
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    ABSTRACT: Depression is common in patients with advanced cancer; however, it is not often recognized and therefore not treated. The aims of this study were to examine the prevalence of the use of antidepressants (ADs) in an international cross-sectional study sample and to identify sociodemographic and medical variables associated with their use. The study was conducted in patients with advanced cancer from 17 centres across eight countries. Healthcare professionals registered patient and disease-related characteristics. A dichotomous score (no/yes) was used to assess the use of ADs other than as adjuvant for pain. Self-report questionnaires from patients were used for the assessment of functioning and symptom intensity. Of 1051 patient records with complete data on ADs, 1048 were included (M:540/F:508, mean age 62 years, standard deviation [SD] 12). The majority were inpatients, and 85% had metastatic disease. The prevalence of AD use was 14%. Multivariate logistic regression analyses showed that younger age (odds ratio [OR] 2.46; confidence interval [CI] 1.32-4.55), female gender (OR 1.59; CI 1.09-2.33), current medication for pain (OR 2.68; CI 1.65-4.33) and presence of three or more co-morbidities (OR 4.74; CI 2.27-9.91) were associated with AD use for reasons other than pain. Disease-related variables (diagnoses, stage, Karnofsky Performance Status and survival) were not associated with the use of ADs. Female gender, younger age, analgesic use and multiple co-morbidities were associated with the use of ADs. However, information is still limited on which variables guide physicians in prescribing AD medication. Further longitudinal studies including details on psychiatric and medication history are needed to improve the identification of patients in need of ADs. Copyright © 2014 John Wiley & Sons, Ltd.
    Psycho-Oncology 04/2014; · 3.51 Impact Factor
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    ABSTRACT: We investigated the feasibility and acceptance of electronic monitoring of symptoms and syndromes in oncological outpatient clinics using a PALM (handheld computer). The assessment of a combination of symptoms and clinical benefit parameters grouped in four pairs was tested in a pilot phase in advanced cancer patients. Based on these experiences, the software E-MOSAIC was developed, consisting of patient-reported symptoms and nutritional intake and objective assessments (weight, weight loss, performance status and medication for pain, fatigue, and cachexia). E-MOSAIC was then tested in four Swiss oncology centers. In order to compare the methods, patients completed the E-MOSAIC as a paper and a PALM version. Preferences of version and completion times were collected. Assessments were compared using Wilcoxon signed-rank tests , and the test-retest reliability was evaluated. The pilot phase was completed by 22 patients. Most patients and physicians perceived the assessment as useful. Sixty-two patients participated in the feasibility study. Twelve patients reported problems (understanding, optical, tactile), and five patients could not complete the assessment. The median time to complete the PALM-based assessment was 3 min. Forty-nine percent of patients preferred the PALM, 23 % preferred a paper version, and 28 % of patients had no preference. Paper vs. PALM revealed no significant differences in symptoms, but in nutritional intake (p = 0.013). Test-retest (1 h, n = 20) reliability was satisfactory (r = 073-98). Electronic symptom and clinical benefit monitoring is feasible in oncology outpatient clinics and perceived as useful by patients, oncology nurses, and oncologists. E-MOSAIC is tested in a prospective randomized trial.
    Supportive Care in Cancer 04/2014; · 2.09 Impact Factor
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    ABSTRACT: Prevalence rates of depression in patients with advanced cancer vary considerably. This may be due to heterogeneous samples and use of different assessment methods. Adequate sample descriptions and consistent use of measures are needed to be able to generalize research findings and apply them to clinical practice. Our objective was two-fold: First, to investigate which clinically important variables were used to describe the samples in studies of depression in patients with advanced cancer. Second, to examine the methods used for assessing and classifying depression in these studies. PubMed, PsycINFO, Embase, and CINAHL were searched combining search term groups representing "depression", "palliative care", and "advanced cancer" covering 2007-2011. Titles and abstracts were screened, and relevant full-text papers were evaluated independently by two authors. Information on thirty-two predefined variables on cancer disease, treatment, socio-demographics, depression-related factors, and assessment methods was extracted from the papers. After removing duplicates, 916 citations were screened of which 59 papers were retained. Age, gender, and stage of the cancer disease were the most frequently reported variables. Depression-related variables were rarely reported, e.g. antidepressant use (10%), and previous depressive episodes (12%). Only 25% of the studies assessed and classified depression according to a validated diagnostic system. Current practice for describing sample characteristics and assessing depression varies greatly between studies. A more standardized practice is recommended to enhance the generalizability and utility of findings. Stakeholders are encouraged to work towards a common standard for sample descriptions.
    Journal of pain and symptom management 03/2014; · 2.42 Impact Factor
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    ABSTRACT: Systematic knowledge about the prevalence and the treatment effects of cancer pain in patients attending a general oncology outpatient department is limited. The purpose of this study was to investigate the prevalence of pain in a large representative cohort of patients attending a general oncology outpatient department in order to guide further screening, classification, and treatment of pain. A cross-sectional study among patients visiting the outpatient clinic with histologically verified cancer, age ≥18 years, adequate cognitive function, and no surgical procedures last 24 h were included. Pain was assessed by the Brief Pain Inventory and the Alberta Breakthrough Pain Assessment Tool. Three hundred five patients were included. The mean age was 60 years, 94 % had a WHO performance status of 0-1 and 59 % received oncological treatment with a curative intent. The mean score for average pain last 24 h (numerical rating scale, 0-10) and current pain was 1.84 and 1.08, respectively. Twenty-two percent reported pain score of ≥4 as their average pain in the previous 24 h. Twenty-one percent reported breakthrough pain (BTP). In multivariate analyses, sleep, BTP, age, treatment intent, and comorbidity was significantly associated with mean average pain in the previous 24 h and explained 29 % of the variability of average pain in the previous 24 h. Of the patients at an oncology outpatient clinic, 22 % reported clinically significant pain. These findings indicate that all patients are candidates to be screened for pain and, if present, a more detailed pain diagnosis should be established before any interventions can be recommended.
    Supportive Care in Cancer 03/2014; · 2.09 Impact Factor
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    ABSTRACT: Weight loss and cachexia are common, reduce tolerance of cancer treatment and the likelihood of response, and independently predict poor outcome. A group of experts met under the auspices of the European School of Oncology to review the literature and - on the basis of the limited evidence at present - make recommendations for malnutrition and cachexia management and future research. Our focus should move from end-stage wasting to supporting patients' nutritional and functional state throughout the increasingly complex and prolonged course of anti-cancer treatment. When inadequate nutrient intake predominates (malnutrition), this can be managed by conventional nutritional support. In the presence of systemic inflammation/altered metabolism (cachexia), a multimodal approach including novel therapeutic agents is required. For all patients, oncologists should consider three supportive care issues: ensuring sufficient energy and protein intake, maintaining physical activity to maintain muscle mass, and (if present) reducing systemic inflammation. The results of Phase II/III trials based on novel drug targets (e.g. cytokines, ghrelin receptor, androgen receptor, myostatin) are expected in the next two years. If effective therapies emerge, early detection of malnutrition and cachexia will be increasingly important in the hope that timely intervention can improve both patient-centered and oncology outcomes.
    Annals of Oncology 02/2014; · 7.38 Impact Factor
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    ABSTRACT: Significant progress has been made in the field of defining and describing the pathophysiology of wasting conditions such as cachexia. The number of new promising drugs, nutritional therapy alternatives, and exercise/rehabilitation programs is increasing. The purpose of this review is to give an overview of recent clinical findings from intervention studies investigating multimodal anabolic therapies utilizing drug, nutritional, and/or exercise interventions in order to counteract wasting. Anabolic agents such as ghrelin and selective androgen receptor modulators are under late-phase clinical testing and hold promise as new therapies, and their ability to mitigate weight loss and improve muscle mass and physical function is evaluated. In the past 2 years, eight new studies investigating interventions with anabolic potential in wasting have been published, among which three of these studies were multimodal. Targeted anabolic therapies aiming to prevent or reverse wasting might involve a combination of anabolic pharmacologic drugs, nutrition, and physical exercise working concurrently to enhance muscle protein synthesis and reduce breakdown. Some anabolic pharmacological interventions demonstrate the potential to improve muscle mass, but the multimodal interventions seem in greater extent to also demonstrate improvement in physical function.
    Current opinion in clinical nutrition and metabolic care. 02/2014;
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    ABSTRACT: Weight loss limits cancer therapy, quality of life and survival. Common diagnostic criteria and a framework for a classification system for cancer cachexia were recently agreed upon by international consensus. Specific assessment domains (Stores, Intake, Catabolism and Function) were proposed. The aim of this study is to validate this diagnostic criteria (two groups: Model 1) and examine a four group (Model 2) classification system regarding these domains as well as survival. Data from an international patient sample with advanced cancer (n=1070) was analysed. In model 1 the diagnostic criteria for cancer cachexia (weight loss/BMI) were used. Model 2 classified patients into four groups (I-IV) according to weight loss/BMI as a framework for cachexia stages. The cachexia domains, survival and sociodemographic/medical variables were compared across models. 861 patients were included. Model 1 consisted of 399 cachectic and 462 non-cachectic patients. Cachectic patients had significantly higher levels of inflammation, lower nutritional intake and performance status and shorter survival. In model 2, differences were not consistent; appetite loss did not differ between group III&IV, and performance status not between I&II. Survival was shorter in group III and IV compared to other groups. By adding other cachexia domains to the model, survival differences were demonstrated. The diagnostic criteria based on weight loss and BMI distinguish between cachectic and non-cachectic patients concerning all domains (Intake, Catabolism and Function) and is associated with survival. In order to guide cachexia treatment a four-group classification model needs additional domains to discriminate between cachexia stages.
    Annals of Oncology 02/2014; · 7.38 Impact Factor
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    ABSTRACT: This study aimed to investigate whether CYP3A4/5 genetic variants, together with clinical and patient factors, influence serum fentanyl and norfentanyl concentrations and their ratio in cancer pain patients receiving transdermal fentanyl. CYP3A4*22 and CYP3A5*3 polymorphisms were analysed in 620 cancer pain patients receiving transdermal fentanyl (12.5-700 μg/h) from the European Pharmacogenetic Opioid Study. Using stepwise linear regression, CYP3A4/5 genetic variability was examined in combination with patient factors relating to organ drug elimination function and ABCB1 genetics for their association with serum fentanyl and norfentanyl concentrations and metabolic ratio (MR) (norfentanyl : fentanyl). Delivery rate-adjusted serum fentanyl concentrations (0.0012-1.1 nmol/l/μg.h) and MRs (0.08-499) varied widely. Only 43% of variability in serum fentanyl concentrations was accounted for by delivery rate and less than 50% by CYP3A4/5 genotypes and clinical variables (delivery rate, sex, comedications, kidney disease, BMI, serum albumin). CYP3A4*22 and CYP3A5*3 variants, CYP3A inhibitors and variables relating to liver and kidney function (serum albumin, glomerular filtration rate, kidney disease, BMI) were associated with MR, but accounted for only 14% of variability. Serum fentanyl concentrations and MR vary considerably between cancer pain patients on transdermal fentanyl patches. CYP3A4*22 and CYP3A5*3 genotypes, and multiple clinical factors, combine to influence transdermal fentanyl pharmacokinetics, but accounted for only a small proportion of variability in this study. Identification of the remaining factors determining serum fentanyl concentrations, and their relationship to efficacy and adverse effects may aid in improving the safety and effectiveness of transdermal fentanyl.
    Pharmacogenetics and Genomics 01/2014; · 3.61 Impact Factor

Publication Stats

13k Citations
1,523.00 Total Impact Points

Institutions

  • 2002–2014
    • St. Olavs Hospital
      • Department of Medicine
      Nidaros, Sør-Trøndelag, Norway
    • La Maddalena Cancer Center
      Palermo, Sicily, Italy
  • 1998–2014
    • Norwegian University of Science and Technology
      • • Department of Cancer Research and Molecular Medicine
      • • Faculty of Medicine
      Nidaros, Sør-Trøndelag, Norway
    • IEO - Istituto Europeo di Oncologia
      Milano, Lombardy, Italy
    • New England Baptist Hospital
      Boston, Massachusetts, United States
    • University Medical Center Hamburg - Eppendorf
      Hamburg, Hamburg, Germany
  • 2013
    • The University of Edinburgh
      • Edinburgh Cancer Research UK Centre
      Edinburgh, SCT, United Kingdom
  • 2012
    • Sykehuset Telemark
      Skien, Telemark county, Norway
    • Turku University Hospital
      Turku, Province of Western Finland, Finland
  • 2010–2012
    • Cantonal Hospital of Schwyz
      Schwyz, Schwyz, Switzerland
  • 2001–2012
    • NTNU Samfunnsforskning
      Nidaros, Sør-Trøndelag, Norway
    • The Norwegian Medical Association
      Kristiania (historical), Oslo County, Norway
  • 2011
    • University of Bonn
      Bonn, North Rhine-Westphalia, Germany
    • University of Leeds
      • School of Medicine
      Leeds, ENG, United Kingdom
  • 2009–2011
    • Oslo University Hospital
      • Department of Oncology
      Oslo, Oslo, Norway
    • Norwegian Institute of Public Health
      • Department of Pharmacoepidemiology
      Kristiania (historical), Oslo County, Norway
    • Sør-Trøndelag University College
      • Faculty of Technology
      Trondheim, Sor-Trondelag Fylke, Norway
  • 2002–2011
    • University of Aberdeen
      • • Division of Applied Health Sciences
      • • Institute of Applied Health Sciences
      Aberdeen, SCT, United Kingdom
  • 1997–2010
    • University of Oslo
      • • Department of Oncology
      • • Department of Behavioural Sciences in Medicine
      Kristiania (historical), Oslo County, Norway
  • 1995–2010
    • University Hospital of North Norway
      Tromsø, Troms, Norway
  • 2002–2009
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      Milano, Lombardy, Italy
  • 2008
    • Lund University
      • Department of Clinical Sciences
      Lund, Skane, Sweden
  • 2007
    • University of Texas MD Anderson Cancer Center
      • Department of Epidemiology
      Houston, TX, United States
  • 2003–2006
    • Norwegian University of Technology and Science
      Nidaros, Sør-Trøndelag, Norway
    • Nordlandssykehuset Bodoe
      Bodø, Nordland, Norway
  • 2005
    • Azienda Unità Sanitaria Locale Forlì
      Forlì, Emilia-Romagna, Italy
  • 2004
    • Malmö University
      Malmö, Skåne, Sweden
  • 1988–2004
    • Norwegian Cancer Society
      Kristiania (historical), Oslo County, Norway
    • Institutt for samfunnsforskning, Oslo
      Kristiania (historical), Oslo County, Norway
  • 1997–2001
    • Sahlgrenska University Hospital
      • Department of Cardiology
      Goeteborg, Västra Götaland, Sweden
  • 1999
    • IT University of Copenhagen
      København, Capital Region, Denmark
  • 1992
    • University of Helsinki
      • Department of Radiotherapy and Oncology
      Helsinki, Southern Finland Province, Finland
  • 1991
    • Det Norske Veritas
      Kristiania (historical), Oslo County, Norway