Functional inhibition of mesenchymal stromal cells in acute myeloid leukemia.

Hematopoietic insufficiency is the hallmark of acute myeloid leukemia (AML) and predisposes patients to life-threatening complications such as bleeding and infections. Addressing the contribution of mesenchymal stromal cells (MSC) to AML-induced hematopoietic failure we show that MSC from AML patients (n=64) exhibit significant growth deficiency and impaired osteogenic differentiation capacity. This was molecularly reflected by a specific methylation signature affecting pathways involved in cell differentiation, proliferation and skeletal development. In addition, we found distinct alterations of hematopoiesis-regulating factors such as Kit-ligand and Jagged1 accompanied by a significantly diminished ability to support CD34+ hematopoietic stem and progenitor cells in long-term culture-initiating cells (LTC-ICs) assays. This deficient osteogenic differentiation and insufficient stromal support was reversible and correlated with disease status as indicated by Osteocalcin serum levels and LTC-IC frequencies returning to normal values at remission. In line with this, cultivation of healthy MSC in conditioned medium from four AML cell lines resulted in decreased proliferation and osteogenic differentiation. Taken together, AML-derived MSC are molecularly and functionally altered and contribute to hematopoietic insufficiency. Inverse correlation with disease status and adoption of an AML-like phenotype after exposure to leukemic conditions suggests an instructive role of leukemic cells on bone marrow microenvironment.

Personal factors in systemic sclerosis and their coverage by patient-reported outcome measures. A multicentre European qualitative study and literature review.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease where thickening of the skin can lead to reduced body function and limitations in activities. Severe forms can also affect and seriously damage inner organs. Patient-centred rehabilitation emphasises considerations of patients' background, experience and behavior which highlights the need to know if patient-reported outcome measures (PROMs) include such personal factors. AIM: To identify and describe personal factors in the experiences of functioning and health of persons with SSc and to examine if and to what extent PROMs in SSc research cover these factors. DESIGN: Data from a qualitative study with focus group interviews were analysed. PROMs in SSc research were identified in a literature review between 2008-2013. SETTING: Participants were recruited from outpatient clinics at rheumatology department. POPULATION: Sixty-three patients with SSc from four European countries participated. METHODS: Data from interviews were analysed using a structure of personal factors developed by Geyh et al. Identified PROMs were analysed and linked to main concepts, related to the personal factors, found in the interview data. RESULTS: Nineteen main concepts were related to the area "patterns of experience and behaviour" in the personal factor structure, 16 to "thoughts and beliefs", nine to "feelings", one to "motives" and one to "personal history and biography", respectively. Among the 35 PROMs identified, 15 did not cover any of the identified concepts. Concepts within the area "feelings" were mostly covered by the PROMs. Five of the PROMs covered "patterns of experience and behaviour", while "motives" and "personal history and biography" were not covered at all. Four of the identified PROMs covered concepts within the areas "feelings", "thoughts and beliefs" and "patterns of experience and behaviour" in the same instrument. The Illness Cognition Questionnaire and Illness Behaviour Questionnaire were such PROMs. CONCLUSION: Patterns of experience and behaviour had the highest number of concepts related to personal factors, but few of the PROMs in SSc research covered these factors. Only a few PROMs covered several personal factors areas in the same instrument. CLINICAL REHABILITATION IMPACT: The results would be of value when developing core sets for outcome measurements in SSc.

Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells.

Ineffective hematopoiesis is a major characteristic of myelodysplastic syndromes (MDS) causing relevant morbidity and mortality. Mesenchymal stromal cells (MSC) have been shown to physiologically support hematopoiesis, but their contribution to the pathogenesis of MDS remains elusive. We show that MSC from patients across all MDS subtypes (n=106) exhibit significantly reduced growth and proliferative capacities accompanied by premature replicative senescence. Osteogenic differentiation was significantly reduced in MDS-derived MSC, indicated by cytochemical stainings and reduced expressions of Osterix and Osteocalcin. This was associated with specific methylation patterns that clearly separated MDS-MSC from healthy controls and showed a strong enrichment for biological processes associated with cellular phenotypes and transcriptional regulation. Furthermore, in MDS-MSC, we detected altered expression of key molecules involved in the interaction with hematopoietic stem and progenitor cells (HSPC), in particular Osteopontin, Jagged1, Kit-ligand and Angiopoietin as well as several chemokines. Functionally, this translated into a significantly diminished ability of MDS-derived MSC to support CD34+ HSPC in long-term culture-initiating cell assays associated with a reduced cell cycle activity. Taken together, our comprehensive analysis shows that MSC from all MDS subtypes are structurally, epigenetically and functionally altered, which leads to impaired stromal support and seems to contribute to deficient hematopoiesis in MDS.

Quality of life after spinal cord injury: a comparison across six countries.

STUDY DESIGN: An international cross-sectional study. OBJECTIVE: To examine the quality of life (QoL) of people with spinal cord injury (SCI) across six countries worldwide, controlling for socio-demographic and lesion-related sample characteristics and using a cross-culturally valid assessment. METHODS: Data from 243 persons with SCI from Australia, Brazil, Canada, Israel, South Africa and the United States were analyzed. QoL was measured using five satisfaction items from the World Health Organization Quality of Life Assessment. Cross-culturally valid, Rasch-transformed scores were used for comparison. RESULTS: Analysis of variance showed a significant difference in QoL between countries (F=3.938; df=5; P=0.002). Shorter time since injury, no paid employment and living in Brazil were significant predictors of lower QoL, explaining 13% of variance in linear regression. Using multilevel regression with country as higher-order variable, time since injury and paid employment remained significant predictors and explained 18% of variance in QoL. The intraclass correlation coefficient (0.05) indicates that 5% of the variability can be accounted for by country. CONCLUSION: This study showed QoL differences between countries that could not be explained by differences in demographic and lesion-related characteristics. Results point to the relevance of reintegration of people with SCI into the workforce. Further international comparative research using larger samples is recommended.

Biopsychosocial outcomes in individuals with and without spinal cord injury: a Swiss comparative study.

STUDY DESIGN: Multicentre controlled study. OBJECTIVES: To investigate if individuals with and without spinal cord injury (SCI) differ in biopsychosocial variables according to the International Classification of Functioning, Disability and Health (ICF). SETTING: Participants were recruited through three major SCI rehabilitation centres in Switzerland. METHODS: A convenience sample of people with SCI (N=102) and a matched non-SCI sample (N=73) were compared according to secondary conditions, pain, depressive symptoms, participation, social support, self-efficacy, self-esteem, coping and sense of coherence. Difference tests and multivariate logistic regression analyses to predict the likelihood of group membership were calculated. RESULTS: People with SCI reported more health conditions, higher levels of anxiety and depressive symptoms, worse pain and pain interference, lower level of participation and social support, lower self-efficacy, self-esteem and task- and emotion-oriented coping. The two samples did not differ in satisfaction with social support, in use of avoidance-oriented coping and in sense of coherence. Health conditions, pain interference, participation and age were found to be significant predictors of the likelihood of group membership. In the logistic regression models, the number of health conditions, limitations due to health conditions, pain interference, participation, task-oriented coping and age are significant predictors of group membership, accounting for 55% of variation. CONCLUSION: Health conditions, pain interference and participation seemed to be the areas of biopsychosocial functioning that are substantially influenced by SCI. Potential buffering resources seem to be diminished in individuals with SCI. In rehabilitation practice, prevention of secondary conditions, treatment of pain, enhancement of participation and strengthening resources should be addressed.

International Spinal Cord Injury Quality of Life Basic Data Set.

STUDY DESIGN: Survey of expert opinion, feedback, and development of final consensus. OBJECTIVE: Present the background, purpose, development process and results for the International Spinal Cord Injury (SCI) Quality of Life (QoL) Basic Data Set. SETTING: International. METHODS: A committee of experts was established to select and define data elements to be included in an International SCI QoL Basic Data Set. A draft data set was developed and disseminated to appropriate organizations for comment. All suggested revisions were considered, and a final version of the QoL data set was completed. RESULTS: The QoL data set consists of 3 variables: ratings of satisfaction with general quality of life, satisfaction with physical health, and satisfaction with psychological health. All variables are rated on a scale ranging from 0 (completely dissatisfied) to 10 (completely satisfied). CONCLUSION: Collection of the International SCI QoL Basic Data Set variables should be a part of all future studies of SCI QoL to facilitate comparison of results across published studies from around the world. Additional standardized instruments to assess other aspects of QoL can be administered based on the purpose of a particular study.

Self-efficacy and self-esteem as predictors of participation in spinal cord injury--an ICF-based study.

STUDY DESIGN: A multi-centre cross-sectional study. OBJECTIVE: To examine the relationship of self-efficacy and self-esteem with participation of persons with spinal cord injury (SCI) from a comprehensive bio-psycho-social perspective, based on the conceptual framework of the International Classification of Functioning, Disability and Health (ICF). SETTING: Community-dwelling participants, <5 years post discharge, recruited through three SCI rehabilitation centers in Switzerland. METHODS: Data were collected by means of standardized self-report questionnaires sent to the eligible participants by postal mail. The questionnaires covered the different components of the ICF's bio-psycho-social model, namely health conditions, body functions, participation, environmental and personal factors. Bivariate correlations and multivariate linear regression analyses with participation as the dependent variable have been conducted. RESULTS: In all, 102 persons with SCI answered the survey, response rate 25.9%. Self-esteem (r=0.61) and self-efficacy (r=0.54) correlated highly with participation and were the strongest correlates of participation. They were stronger correlates of participation than symptoms of anxiety, depressive symptoms, pain, health conditions, social support, coping styles or sense of coherence. Participation seemed to be independent of gender, age, level or completeness of injury. Self-efficacy and self-esteem explained together with time since discharge and years of education 48% of the variance in participation adjusting for health condition, depressive symptoms, pain interference and social support. CONCLUSION: Considering self-efficacy and self-esteem within the comprehensive framework of the ICF can contribute to a better understanding of functioning, disability and health in SCI, which in turn may facilitate the development of interventions to support the persons' adjustment and reintegration.

The role of social support and social skills in people with spinal cord injury--a systematic review of the literature.

STUDY DESIGN: Systematic literature review. OBJECTIVES: To examine the current knowledge of how social support and social skills are associated with aspects of health, functioning and quality of life of persons living with spinal cord injury (SCI). METHODS: A systematic literature review was conducted. The literature search was carried out in Pubmed, PsycINFO, ERIC (Educational Resources Information Centre), CINAHL (Cumulative Index to Nursing and Allied Health Literature), Embase and SSCI (Social Sciences Citation Index). Publications were identified according to predefined eligibility criteria; study qualities were evaluated, study results extracted and a narrative synthesis was compiled. RESULTS: In all, 58 publications about social support and SCI were included. Social support was positively related to physical and mental health, pain, coping, adjustment and life satisfaction. Social skills were assessed in 11 studies: social problem solving (n=7), assertiveness (n=3), verbal communication (n=1) and self-monitoring (n=1) were examined. Effective problem-solving skills were related to better mental health outcomes, health prevention behavior and less secondary conditions. Assertiveness was related to higher depression in rehabilitation setting. Interventions targeted at social support or social skills were scarcely studied. Only one study examined the relationship between social skills and social support in SCI. CONCLUSION: Social support is associated with better health and functioning in individuals with SCI. However, the full range of social skills has not yet been studied in people with SCI. Furthermore, the role of social skills in relation to social support, health and functioning remains unclear. Better understanding of social skills and social support in SCI could facilitate the development of targeted and effective interventions to enhance functioning of people with SCI.

Psychological resources in spinal cord injury: a systematic literature review.

STUDY DESIGN: Systematic literature review. OBJECTIVES: The purpose of this study was to gain a systematic overview of the role of psychological resources in the adjustment to spinal cord injury (SCI). METHODS: A systematic literature review was performed. The literature search was conducted in the databases Pubmed, PsycINFO, the Social Sciences Citation Index, the Education Resources Information Center, Embase and the Citation Index of Nursing and Allied Health Literature. The assessed variables, measurement instruments, results and the methodological quality of the studies were extracted, summarized and evaluated. RESULTS: A total of 83 mainly cross-sectional studies were identified. Psychological resources were categorized into seven groups: self-efficacy (SE), self-esteem, sense of coherence (SOC), spirituality, optimism, intellect and other personality characteristics. SE and self-esteem were consistently associated with positive adjustment indicators such as high well-being and better mental health. Interrelations between psychological resources and key rehabilitation outcome variables such as participation were rarely studied. Only a few interventions, which were aimed at strengthening psychological resources were identified. Longitudinal studies suggested that SE, SOC, spirituality and purpose in life were potential determinants of adjustment outcomes in the long term. CONCLUSION: Research on psychological resources in SCI is broad, but fragmented. Associations of psychological resources with mental health and well-being were frequently shown, while associations with participation were rarely studied. Further development of resource-based interventions to strengthen persons with SCI is indicated. This review can serve as guide for clinical practice and can add to the design of future SCI research.

The individual experience of functioning and disability in Switzerland--patient perspective and person-centeredness in spinal cord injury.

STUDY DESIGN: Qualitative, multi-center study. OBJECTIVES: The objective of this study is to explore the aspects of functioning and disability that are relevant to individuals with spinal cord injury (SCI), using a comprehensive approach based on the International Classification of Functioning, Disability and Health (ICF). METHODS: Forty-nine people with SCI from early post-acute and long-term rehabilitation settings participated in nine focus groups. Five open-ended questions based on the ICF were used to initiate discussion about relevant Body Functions and Structures, Activities and Participation, Environmental and Personal Factors. The focus groups were audiotaped and the recording was transcribed verbatim. Qualitative analyses included the identification, extraction and coding of meaningful concepts from the transcribed dialogue. Concepts were coded according to established rules using ICF categories and were summarized semi-quantitatively. RESULTS: In the analysis, 1582 different concepts were identified. For coding one concept, an average of 1.4 ICF categories was used. This resulted in 2235 concept-ICF category links, 1068 in the early post-acute and 1167 in the long-term context, respectively. For the coding, 274 out of the 1454 categories contained in the ICF were used. CONCLUSION: The ICF coding showed the broad range of relevant aspects in the functioning experience of persons with SCI. Besides body limitations (especially paralysis and pain), the most relevant concepts covered mainly barriers in physical environment, assistive devices and social support, as well as the impact on everyday life regarding leisure and work. The resulting list of ICF categories can be helpful in facilitating person-centered clinical care and research.

Outcome parameters in spinal cord injury research: a systematic review using the International Classification of Functioning, Disability and Health (ICF) as a reference.

OBJECTIVES: This study is part of the development of an International Classification of Functioning, Disability and Health (ICF) Core Set for spinal cord injury (SCI). Its specific objectives were to identify outcome parameters reported in published studies on individuals with SCI in the early post-acute and chronic situation, and to identify and quantify the concepts of the reported parameters using the ICF as a reference. METHODS: Electronic searches of Medline, EMBASE, PsycINFO and CINAHL from 2001 to 2005 were carried out. All outcome parameters and their underlying concepts were retrieved from the included studies. These concepts were linked to categories of the ICF using standardized rules. RESULTS: From the 6681 abstracts retrieved, 2205 were randomly selected (33.0%) and 281 studies met the inclusion criteria (12.7%). A total number of 5217 concepts were retrieved from standardized and non-standardized measures, of which 4049 (77.6%) could be linked to 175 different ICF categories: 56 out of 114 Body Functions, 19 out of 56 Body Structures, 62 out of 118 Activities and Participation and 38 out of 74 Environmental Factors categories. Second-level categories reported in >20% of all studies were pain, remunerative employment, health services, systems and policies, school education and higher education. CONCLUSION: The ICF provides a valuable reference to identify and quantify the concepts of measures focusing on SCI in the early post-acute and chronic situation. The findings show a great diversity in the consequences of SCI and underscore the importance of social participation and environment for people with SCI.

Validation of the Brief ICF core set for low back pain from the Norwegian perspective.

AIM: The aim of this study was to identify candidate categories from the International Classification of Functioning, Disability and Health (ICF) to be included in the Brief ICF Core Set for low back pain (LBP) by examining their relation to general health and functionality. METHODS: This was part of an international multicentre study with 118 participating Norwegian patients with LBP. The Comprehensive ICF Core Set for LBP was filled in by health professionals. The patients reported their health-related quality of life in the Medical Outcome Study Short Form 36 (SF-36) and function in the Oswestry Disability Index. Two questions regarding the patient's general health and functioning were completed by the health professionals and the patients themselves. Regression models were developed in order to identify ICF categories explaining most of the variance of the criterion measures. RESULTS: Twelve ICF categories remained as significant explanatory factors according to the eight regression models, four of which were not included in a previously proposed Brief ICF Core Set for LBP. CONCLUSIONS: The present study complements the development of the Brief ICF Core Set for LBP, and indicates a minimum number of categories needed to explain LBP patients' functioning and health. Further elaboration of the Brief ICF Core Set for LBP with multinational data is needed.

Does the International Classification of Functioning, Disability and Health (ICF) core set for low back pain cover the patients' problems? A cross-sectional content-validity study with a Norwegian population.

AIM: The aim of this work was to evaluate the Norwegian form of the International Classification of Functioning, Disability and Health (ICF) Core Set for low back pain patients and investigate the feasibility of the Core Set in clinical practice. METHODS: This was part of an international multicenter study with 118 participating Norwegian patients referred to Departments of Physical Medicine and rehabilitation with low back pain (LBP). The ICF Core Set for LBP was filled in by the health professionals. The patients reported their problems using the Medical Outcome Study Short Form 36 (SF-36) and the Oswestry Low Back Pain Disability Questionnaire (ODI). RESULTS: The ICF Core Set categories capture the problems of the LBP patients, and few categories were reported to be missing. Many problems were reported within body function, and problems within work and employment were captured by the activity and participation component. The environmental factors in ICF were most frequently scored as facilitators, but the same factor could also represent a barrier in other individuals. Health professionals, family and friends were important factors within this domain. Few problems were scored as severe or complete indicating the need of collapsing the qualifier levels. Scoring of the ICF Core Set was feasibly, but rather time-consuming. CONCLUSION: The ICF Core Set for LBP captures the problems of LBP, and adds important aspects to clinical practice in the field of LBP. However, the ICF Core Set for LBP needs further elaboration in order to improve the clinical feasibility.

Content comparison of health-related quality of life measures used in stroke based on the international classification of functioning, disability and health (ICF): a systematic review.

OBJECTIVE: To examine and compare the contents of health-related quality of life (HRQoL) measures used in stroke, based on the ICF as the frame of reference. DESIGN: We conducted a systematic literature review to select current generic and condition-specific HRQoL measures applied in stroke. We examined the contents of the selected measures by linking the concepts within the instruments' items to the ICF. RESULTS: The systematic literature review resulted in the selection of six generic and seven stroke-specific HRQoL measures. Within the selected instruments we identified 979 concepts. To map these concepts, we used 200 different ICF categories. None of the ICF categories is contained in all of the instruments. The most frequently used category is 'b152 Emotional functions' contained in 53 items from 10 instruments. Stroke-specific measures more often address 'Mental functions', while the selected generic instruments more often include Environmental Factors. DISCUSSION: The present study provides an overview on current HRQoL measures in stroke with respect to their covered contents and provides valuable information to facilitate the selection of appropriate instruments for specific purposes in clinical as well as research settings.

Linking osteoarthritis-specific health-status measures to the International Classification of Functioning, Disability, and Health (ICF).

OBJECTIVES: The objective of this study was to link the Western Ontario and McMaster Universities (WOMAC) and Lequesne-Algofunctional indices to the ICF on the basis of linking rules developed specifically to accomplish this aim. The linking process enables the understanding of the relationship between health-status measures and the ICF. METHODS: Since the fifth World Health Organisation/International Liege Against Rheumatism (WHO/ILAR) Task Force and the Outcome Measures in Rheumatology Clinical Trials (OMERACT) group recommend the use of WOMAC and the Lequesne-Algofunctional indices in patients with osteoarthritis of the hip and knee in clinical trials, these two health-status measures have been used in this study. Both health-status measures were linked to the ICF separately by two trained health professionals. Consensus between health professionals was used to decide which ICF category should be linked to each item/concept of the two questionnaires. To resolve disagreements between the two health professionals, a third person trained in the linking rules was consulted. RESULTS: Except for the concept of 'morning stiffness', both health professionals agreed on the ICF category chosen to link all the items/concepts of both questionnaires. Altogether, 29 different ICF categories have been linked. Five ICF categories belong to the ICF component 'body functions', 23 categories to the component 'activities and participation', and one category to 'environmental factors'. Both questionnaires have 10 ICF categories in common. CONCLUSIONS: The results of the linking process reflect both the structure of the two questionnaires studied and the relationship between them, showing that the ICF classification can become the cardinal reference for existing health-status measures.