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1.
  • Kalter, J., et al. (author)
  • Effects and moderators of psychosocial interventions on quality of life, and emotional and social function in patients with cancer : An individual patient data meta-analysis of 22 RCTs
  • 2018
  • In: Psycho-Oncology. - : WILEY. - 1057-9249 .- 1099-1611. ; 27:4, s. 1150-1161
  • Research review (peer-reviewed)abstract
    • Objective: This individual patient data (IPD) meta-analysis aimed to evaluate the effects of psychosocial interventions (PSI) on quality of life (QoL), emotional function (EF), and social function (SF) in patients with cancer, and to study moderator effects of demographic, clinical, personal, and intervention-related characteristics. Methods: Relevant studies were identified via literature searches in 4 databases. We pooled IPD from 22 (n = 4217) of 61 eligible randomized controlled trials. Linear mixed-effect model analyses were used to study intervention effects on the post-intervention values of QoL, EF, and SF (z-scores), adjusting for baseline values, age, and cancer type. We studied moderator effects by testing interactions with the intervention for demographic, clinical, personal, and intervention-related characteristics, and conducted subsequent stratified analyses for significant moderator variables.Results: PSI significantly improved QoL (=0.14,95%CI=0.06;0.21), EF ( beta = 0.13,95%CI = 0.05;0.20), and SF (beta = 0.10,95%CI = 0.03;0.18). Significant differences in effects of different types of PSI were found, with largest effects of psychotherapy. The effects of coping skills training were moderated by age, treatment type, and targeted interventions. Effects of psychotherapy on EF may be moderated by cancer type, but these analyses were based on 2 randomized controlled trials with small sample sizes of some cancer types. Conclusions: PSI significantly improved QoL, EF, and SF, with small overall effects. However, the effects differed by several demographic, clinical, personal, and intervention-related characteristics. Our study highlights the beneficial effects of coping skills training in patients treated with chemotherapy, the importance of targeted interventions, and the need of developing interventions tailored to the specific needs of elderly patients.
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  • Gronberg, H, et al. (author)
  • The risk-based STHLM3 model to improve prostate cancer testing in men 50-69 years: Further health, economic, and clinic evaluation
  • 2016
  • In: JOURNAL OF CLINICAL ONCOLOGY. - : American Society of Clinical Oncology (ASCO). - 0732-183X .- 1527-7755. ; 34:2
  • Conference paper (other academic/artistic)abstract
    • 36 Background: Prostate-specific antigen (PSA) is used to screen for prostate cancer but suffers from a high false-positive rate that translates into unnecessary prostate biopsies and over-diagnosis of low-risk prostate cancers. We aimed to develop a model for prostate cancer screening with better test characteristics than PSA. Methods: STHLM3 is a prospective, population-based, paired screen-positive diagnostic study. It investigates whether the predefined STHLM3 model, a combination of 6 plasma protein biomarkers (PSA, free-PSA, intact-PSA, HK2, MIC-1, and MSMB), genetic polymorphisms (232 SNPs), and clinical variables (age, family history, previous biopsies, DRE, and prostate volume) can substantially reduce the proportion of men biopsied while maintaining the same sensitivity to diagnose Gleason score ≥ 7 prostate cancer as PSA ≥3 ng/ml. In addition, a health economic evaluation was performed comparing the STHLM3 model with current clinical practice in Stockholm. Results: 58,818 men without prostate cancer aged 50-69, participated in the STHLM3 study, with 6,700 undergoing subsequent prostate biopsy. The STHLM3 model performed significantly better (p<0.001) than PSA for detecting GS ≥7 cancers, increasing the Area Under the Curve from 0.56 to 0.74. All variables used in the STHLM3 Model were significantly associated with Gleason score ≥7 prostate cancers (p<0.05) in a multiple logistic regression model. Using the same sensitivity as PSA ≥3 ng/ml to diagnose Gleason score ≥7 prostate cancer, the STHLM3 model reduced the number of biopsies by 32% (95% CI 24%-39%) and avoided 44% (95% CI; 35%-54%) of the negative biopsies. The number of Gleason score 6 cancers was reduced by 17% (95% CI; 7%-26%). Positive ICER for the STHLM3 model was seen in all models of the health economic analysis. Conclusions: The STHLM3 model reduces unnecessary biopsies without compromising the ability to diagnose Gleason score ≥7 prostate cancer in a cost-efficient way. This is a significant step towards personalized risk-based prostate cancer diagnostic programs. Clinical trial information: ISRCTN84445406.
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  • Toren, K., et al. (author)
  • Measures of bronchodilator response of FEV1, FVC and SVC in a Swedish general population sample aged 50-64 years, the SCAPIS Pilot Study
  • 2017
  • In: The International Journal of Chronic Obstructive Pulmonary Disease. - : DOVE MEDICAL PRESS LTD. - 1176-9106 .- 1178-2005. ; 12, s. 973-980
  • Journal article (peer-reviewed)abstract
    • Background: Data are lacking from general population studies on how to define changes in lung function after bronchodilation. This study aimed to analyze different measures of bronchodilator response of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and slow vital capacity (SVC). Materials and methods: Data were derived from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) Pilot study. This analysis comprised 1,050 participants aged 50-64 years from the general population. Participants were investigated using a questionnaire, and FEV1, FVC and SVC were recorded before and 15 minutes after inhalation of 400 mu g of salbutamol. A bronchodilator response was defined as the relative change from baseline value expressed as the difference in units of percent predicted normal. Predictors of bronchodilator responses were assessed using multiple linear regression models. Airway obstruction was defined as FEV1/FVC ratio below lower limit of normal (LLN) before bronchodilation, and COPD was defined as an FEV1/FVC ratio below LLN after bronchodilation. Physician-diagnosed asthma was defined as an affirmative answer to " Have you ever had asthma diagnosed by a physician?". Asymptomatic never-smokers were defined as those not reporting physician-diagnosed asthma, physician-diagnosed COPD or emphysema, current wheeze or chronic bronchitis and being a lifelong never-smoker. Results: Among all subjects, the greatest bronchodilator responses (FEV1, FVC and SVC) were found in subjects with asthma or COPD. The upper 95th percentile of bronchodilator responses in asymptomatic never-smokers was 8.7% for FEV1, 4.2% for FVC and 5.0% for SVC. The bronchodilator responses were similar between men and women. In a multiple linear regression model comprising all asymptomatic never-smokers, the bronchodilator response of FEV1 was significantly associated with airway obstruction and height. Conclusion: When the bronchodilator response in asymptomatic never-smokers is reported as the difference in units of predicted normal, significant reversibility of FEV1, FVC and SVC to bronchodilators is 9%, 4% and 5%, respectively.
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  • Torén, Kjell, 1952, et al. (author)
  • Measures of bronchodilator response of FEV1, FVC and SVC in a Swedish general population sample aged 50-64 years, the SCAPIS Pilot Study
  • 2017
  • In: International Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1178-2005. ; 12, s. 973-980
  • Journal article (peer-reviewed)abstract
    • Background: Data are lacking from general population studies on how to define changes in lung function after bronchodilation. This study aimed to analyze different measures of bronchodilator response of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and slow vital capacity (SVC). Materials and methods: Data were derived from the Swedish Cardiopulmonary Bioimage Study (SCAPIS) Pilot study. This analysis comprised 1,050 participants aged 50-64 years from the general population. Participants were investigated using a questionnaire, and FEV1, FVC and SVC were recorded before and 15 minutes after inhalation of 400 mu g of salbutamol. A bronchodilator response was defined as the relative change from baseline value expressed as the difference in units of percent predicted normal. Predictors of bronchodilator responses were assessed using multiple linear regression models. Airway obstruction was defined as FEV1/FVC ratio below lower limit of normal (LLN) before bronchodilation, and COPD was defined as an FEV1/FVC ratio below LLN after bronchodilation. Physician-diagnosed asthma was defined as an affirmative answer to " Have you ever had asthma diagnosed by a physician?". Asymptomatic never-smokers were defined as those not reporting physician-diagnosed asthma, physician-diagnosed COPD or emphysema, current wheeze or chronic bronchitis and being a lifelong never-smoker. Results: Among all subjects, the greatest bronchodilator responses (FEV1, FVC and SVC) were found in subjects with asthma or COPD. The upper 95th percentile of bronchodilator responses in asymptomatic never-smokers was 8.7% for FEV1, 4.2% for FVC and 5.0% for SVC. The bronchodilator responses were similar between men and women. In a multiple linear regression model comprising all asymptomatic never-smokers, the bronchodilator response of FEV1 was significantly associated with airway obstruction and height. Conclusion: When the bronchodilator response in asymptomatic never-smokers is reported as the difference in units of predicted normal, significant reversibility of FEV1, FVC and SVC to bronchodilators is 9%, 4% and 5%, respectively.
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  • Fazelinejad, Somayeh, et al. (author)
  • Fungal biomass and ethanol from lignocelluloses using Rhizopus pellets under simultaneous saccharification, filtration, and fermentation (SSFF)
  • 2016
  • In: Biofuel Research Journal. - 2292-8782. ; 9, s. 372-378
  • Journal article (peer-reviewed)abstract
    • The economic viability of the 2nd generation bioethanol production process cannot rely on a single product but on a biorefinery built around it. In this work, ethanol and fungal biomass (animal feed) were produced from acid-pretreated wheat straw slurry under an innovative simultaneous saccharification, fermentation, and filtration (SSFF) strategy. A membrane unit separated the solids from the liquid and the latter was converted to biomass or to both biomassand ethanol in the fermentation reactor containing Rhizopus sp. pellets. Biomass yields of up to 0.34 g/g based on the consumed monomeric sugars and acetic acid were achieved. A surplus of glucose in the feed resulted in ethanol production and reduced the biomass yield, whereas limiting glucose concentrations resulted in higher consumption of xylose and acetic acid. The specific growth rate, in the range of 0.013-0.015/h, did not appear to be influenced by the composition of the carbon source. Under anaerobic conditions, an ethanol yield of 0.40 g/g was obtained. The present strategy benefits fromthe easier separation of the biomass from the medium and the fungus ability to assimilate carbon residuals in comparison with when yeast is used. More specifically, it allows in-situ separation of insoluble solids leading to the production of pure fungal biomass as a value-added product. (C) 2016 BRTeam. All rights reserved.
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  • Gummesson, Anders, 1973, et al. (author)
  • Non-alcoholic fatty liver disease is a strong predictor of coronary artery calcification in metabolically healthy subjects: A cross-sectional, population-based study in middle-aged subjects
  • 2018
  • In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:8
  • Journal article (peer-reviewed)abstract
    • Objectives This study aims to estimate the relationship between non-alcoholic fatty liver disease (NAFLD) and measures of atherosclerotic cardiovascular disease (ASCVD), and to determine to what extent such relationships are modified by metabolic risk factors. The study was conducted in the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort (n = 1015, age 50-64 years, 51.2% women). NAFLD was defined as computed tomography liver attenuation <= 40 Hounsfield Units, excluding other causes of liver fat. Coronary artery calcification score (CACS) was assessed using the Agatston method. Carotid plaques and intima media thickness (IMT) were measured by ultrasound. Metabolic status was based on assessments of glucose homeostasis, serum lipids, blood pressure and inflammation. A propensity score model was used to balance NAFLD and non NAFLD groups with regards to potential confounders and associations between NAFLD status and ASCVD variables in relation to metabolic status were examined by logistic and generalized linear regression models. NAFLD was present in 106 (10.4%) of the subjects and strongly associated with obesity-related traits. NAFLD was significantly associated with CACS after adjustment for confounders and metabolic risk factors (OR 1.77, 95% CI 1.07-2.94), but not with carotid plaques and IMT. The strongest association between NAFLD and CACS was observed in subjects with few metabolic risk factors (n = 612 [60% of all] subjects with 0-1 out of 7 predefined metabolic risk factors; OR 5.94, 95% CI 2.13-16.6). NAFLD was independently associated with coronary artery calcification but not with measures of carotid atherosclerosis in this cohort. The association between NAFLD and CACS was most prominent in the metabolically healthy subjects.
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  • Hagstrom, Emil, et al. (author)
  • IMPACT OF BODY WEIGHT AT AGE 20 AND WEIGHT GAIN DURING ADULTHOOD ON MIDLIFE CORONARY ARTERY CALCIUM IN 15,000 MEN AND WOMEN : AN INTERIM ANALYSIS OF THE SWEDISH CARDIOPULMONARY BIOIMAGE STUDY
  • 2019
  • In: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 73:9, s. 1692-1692
  • Journal article (other academic/artistic)abstract
    • BackgroundElevated body weight in adolescence is strongly associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, or to weight gain with subsequent high adult weight is not known. Using data from the Swedish CArdioPulmonary bioImage Study (SCAPIS), we investigated the association between weight at age 20, weight gain to midlife and coronary artery calcium score (CACS) at midlife.MethodsIn the first 15,810 participants in SCAPIS (mean age 58 years, 52% women), data on CACS at midlife, self-reported body weight at age 20 and weight at examination in SCAPIS were recorded.ResultsCACS in midlife was significantly higher with increasing weight at age 20 (p<0.001 for both sexes), and then increased with weight gain until midlife at all levels of body weight at age 20 after adjusting for age, height, smoking, alcohol intake, education level, exercise levels and LDL cholesterol. However, the association with weight gain was only significant in men (p = 0.047), not in women (p=0.474). No significant interaction was seen between weight at age 20 and midlife weight with CACS. The effect of weight at age 20 on CACS was significantly more marked in men than in women, as was the effect of weight gain (p<0.001 for both interactions).ConclusionWeight at age 20 and weight gain to midlife were both related to CACS, but much more markedly so in men than in women, indicating a generally larger effect of both early adult weight and further weight gain until midlife on CACS in men, compared to women.
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  • Halvardson, Jonatan, et al. (author)
  • Mutations in HECW2 are associated with intellectual disability and epilepsy
  • 2016
  • In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 53:10, s. 697-704
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: De novo mutations are a frequent cause of disorders related to brain development. We report the results of screening patients diagnosed with both epilepsy and intellectual disability (ID) using exome sequencing to identify known and new causative de novo mutations relevant to these conditions.METHODS: Exome sequencing was performed on 39 patient-parent trios to identify de novo mutations. Clinical significance of de novo mutations in genes was determined using the American College of Medical Genetics and Genomics standard guidelines for interpretation of coding variants. Variants in genes of unknown clinical significance were further analysed in the context of previous trio sequencing efforts in neurodevelopmental disorders.RESULTS: In 39 patient-parent trios we identified 29 de novo mutations in coding sequence. Analysis of de novo and inherited variants yielded a molecular diagnosis in 11 families (28.2%). In combination with previously published exome sequencing results in neurodevelopmental disorders, our analysis implicates HECW2 as a novel candidate gene in ID and epilepsy.CONCLUSIONS: Our results support the use of exome sequencing as a diagnostic approach for ID and epilepsy, and confirm previous results regarding the importance of de novo mutations in this patient group. The results also highlight the utility of network analysis and comparison to previous large-scale studies as strategies to prioritise candidate genes for further studies. This study adds knowledge to the increasingly growing list of causative and candidate genes in ID and epilepsy and highlights HECW2 as a new candidate gene for neurodevelopmental disorders.
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  • Ishola, Mofoluwake M., et al. (author)
  • Simultaneous glucose and xylose utilization for improved ethanol production from lignocellulosic biomass through SSFF with encapsulated yeast.
  • 2015
  • In: Biomass and Bioenergy. - : Pergamon Press. - 0961-9534 .- 1873-2909. ; 77, s. 192-199
  • Journal article (peer-reviewed)abstract
    • Simultaneous glucose and xylose uptake was investigated for ethanol prodn. using the simultaneous saccharification, filtration and fermn. (SSFF) process with pretreated wheat straw as a xylose-rich lignocellulosic biomass. A genetically engineered strain of Saccharomyces cerevisiae (T0936) with the ability to ferment xylose was used for the fermns. SSFF was compared with a conventional method of simultaneous saccharification and fermn. (SSF) for glucose and xylose uptake, ethanol prodn., and cell viability on 10% and 12% suspended solids (SS) basis. With 10% SS, an ethanol yield of 90% of the theor. level was obtained during SSFF with 80% xylose uptake while only 53% ethanol yield was obsd. during the SSF process. Increasing the solid load to 12% resulted in an ethanol yield of 77% of the theor. value and 36% xylose uptake during SSFF while only 27% ethanol yield and no xylose uptake was obsd. during the corresponding SSF process. The SSFF process preserved the viability of the genetically engineered yeast throughout the fermn., even when reused for 2 consecutive cultivations. The results show that the SSFF process does not only enhance effective cell performance but also facilitates simultaneous glucose and xylose utilization, which is important for broad range of biomass utilization for lignocellulosic ethanol prodn. [on SciFinder(R)]
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  • Kullberg, Joel, 1979-, et al. (author)
  • Automated analysis of liver fat, muscle and adipose tissue distribution from CT suitable for large-scale studies
  • 2017
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7
  • Journal article (peer-reviewed)abstract
    • Computed Tomography (CT) allows detailed studies of body composition and its association with metabolic and cardiovascular disease. The purpose of this work was to develop and validate automated and manual image processing techniques for detailed and efficient analysis of body composition from CT data. The study comprised 107 subjects examined in the Swedish CArdioPulmonary BioImage Study (SCAPIS) using a 3-slice CT protocol covering liver, abdomen, and thighs. Algorithms were developed for automated assessment of liver attenuation, visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue, thigh muscles, subcutaneous, subfascial (SFAT) and intermuscular adipose tissue. These were validated using manual reference measurements. SFAT was studied in selected subjects were the fascia lata could be visually identified (approx. 5%). In addition, precision of manual measurements of intra-(IPAT) and retroperitoneal adipose tissue (RPAT) and deep-and superficial SAT was evaluated using repeated measurements. Automated measurements correlated strongly to manual reference measurements. The SFAT depot showed the weakest correlation (r = 0.744). Automated VAT and SAT measurements were slightly, but significantly overestimated (<= 4.6%, p <= 0.001). Manual segmentation of abdominal sub-depots showed high repeatability (CV <= 8.1%, r >= 0.930). We conclude that the low dose CT-scanning and automated analysis makes the setup suitable for large-scale studies.
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  • Musoro, ZJ, et al. (author)
  • Establishing anchor-based minimally important differences (MID) with the EORTC quality-of-life measures: a meta-analysis protocol
  • 2018
  • In: BMJ open. - : BMJ. - 2044-6055. ; 8:1, s. e019117-
  • Journal article (peer-reviewed)abstract
    • As patient assessment of health-related quality of life (HRQOL) in cancer clinical trials has increased over the years, so has the need to attach meaningful interpretations to differences in HRQOL scores between groups and changes within groups. Determining what represents a minimally important difference (MID) in HRQOL scores is useful to clinicians, patients and researchers, and can be used as a benchmark for assessing the success of a healthcare intervention. Our objective is to provide an evidence-based protocol to determine MIDs for the European Organisation for Research and Treatment for Cancer Quality of life Questionnaire core 30 (EORTC QLQ-C30). We will mainly focus on MID estimation for group-level comparisons. Responder thresholds for individual-level change will also be estimated.Methods and analysisData will be derived from published phase II and III EORTC trials that used the QLQ-C30 instrument, covering several cancer sites. We will use individual patient data to estimate MIDs for different cancer sites separately. Focus is on anchor-based methods. Anchors will be selected per disease site from available data. A disease-oriented and methodological panel will provide independent guidance on anchor selection. We aim to construct multiple clinical anchors per QLQ-C30 scale and also to compare with several anchor-based methods. The effects of covariates, for example, gender, age, disease stage and so on, will also be investigated. We will examine how our estimated MIDs compare with previously published guidelines, hence further contributing to robust MID guidelines for the EORTC QLQ-C30.Ethics and disseminationAll patient data originate from completed clinical trials with mandatory written informed consent, approved by local ethical committees. Our findings will be presented at scientific conferences, disseminated via peer-reviewed publications and also compiled in a MID ‘blue book’ which will be made available online on the EORTC Quality of Life Group website as a free guideline document.
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  • Nair, Ramkumar, et al. (author)
  • Dilute phosphoric acid pretreatment of wheat bran for enzymatic hydrolysis and subsequent ethanol production by edible fungi Neurospora intermedia.
  • 2015
  • In: Industrial crops and products (Print). - : Elsevier BV. - 0926-6690 .- 1872-633X. ; 69, s. 314-323
  • Journal article (peer-reviewed)abstract
    • The use of an underutilized and abundant lignocellulosic feedstock residue, wheat bran, was studied for ethanol prodn. using dil. phosphoric acid pretreatment followed by fermn. using edible fungi Neurospora intermedia. Wheat bran was subjected to dil. acid pretreatment at varying acid concns. (0.5-3.0% w/v), temp. (150-210 °C), and reaction time (5-20 min). The interaction of multiple factors showed the optimum pretreatment conditions at acid concn. of 1.75% (w/v), at 190 °C for 10 min. The max. total polysaccharide yield of 0.27 ± 0.01 g/g dry biomass loading, corresponding to 66% of the theor. max. was obsd. Subsequent fermn. with N. intermedia showed 85% of the theor. max. ethanol yield from the untreated bran glucose. The effect of the dil. acid pretreatment on the functional groups of the wheat bran cellulose was detd. with 78% redn. in the cellulose crystallinity index. The validation of the dil. phosphoric acid pretreatment in a demo plant is also reported for the first time. Enzymic hydrolysis of pretreated slurry from the demo plant showed 85% total theor. yield of polysaccharides. Compared to the untreated bran biomass, an increase of 51% was obsd. in the ethanol yield following pretreatment, with a total ethanol yield of 95% theor. max. Higher yield of ethanol is also attributed to the xylose fermenting capability of the fungi. [on SciFinder(R)]
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  • Sackey, H., et al. (author)
  • Self-perceived, but not objective lymphoedema is associated with decreased long-term health-related quality of life after breast cancer surgery
  • 2015
  • In: European Journal of Surgical Oncology. - : Saunders Elsevier. - 0748-7983 .- 1532-2157. ; 41:4, s. 577-584
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: The primary aim was to compare long-term health-related quality of life (HRQoL) in patients undergoing sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND), with or without axillary metastases. Secondary aims were to a) investigate agreement between objectively measured and self-reported lymphoedema and b) compare, with respect to HRQoL, women with objective arm lymphoedema without subjective ratings and those with no objective but subjective ratings of arm lymphoedema.METHODS: The three study groups were defined by axillary surgery: 1) SLNB alone (N = 140), 2) ALND in patients without axillary metastases (N = 125) and 3) ALND in patients with axillary metastases (N = 155). Preoperatively, one and three years postoperatively arm volume was measured and questionnaires regarding self-perceived symptoms of arm lymphoedema and HRQoL were completed (The Swedish Short Form-36 Health Survey, SF-36).RESULTS: Out of the original 516 who had axillary surgery, 420 (81%) completed the study. There were no statistically significant differences in HRQoL between the three study groups. No statistically significant agreement was found between self-perceived and objectively measured arm lymphoedema. Women without self-perceived arm lymphoedema, regardless of objective arm lymphoedema or not, scored higher on all eight SF-36 domains than those who reported self-perceived arm lymphoedema.CONCLUSION: Women reporting self-perceived arm lymphoedema, regardless of objective lymphoedema or not, have a decreased long-term health-related quality of life. This indicates that more attention should be given to the subjective reports of symptom in order to better help these women.
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