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- Gawel, Danuta, et al.
(författare)
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A validated single-cell-based strategy to identify diagnostic and therapeutic targets in complex diseases
- 2019
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Ingår i: Genome Medicine. - : Springer Science and Business Media LLC. - 1756-994X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Genomic medicine has paved the way for identifying biomarkers and therapeutically actionable targets for complex diseases, but is complicated by the involvement of thousands of variably expressed genes across multiple cell types. Single-cell RNA-sequencing study (scRNA-seq) allows the characterization of such complex changes in whole organs. Methods: The study is based on applying network tools to organize and analyze scRNA-seq data from a mouse model of arthritis and human rheumatoid arthritis, in order to find diagnostic biomarkers and therapeutic targets. Diagnostic validation studies were performed using expression profiling data and potential protein biomarkers from prospective clinical studies of 13 diseases. A candidate drug was examined by a treatment study of a mouse model of arthritis, using phenotypic, immunohistochemical, and cellular analyses as read-outs. Results: We performed the first systematic analysis of pathways, potential biomarkers, and drug targets in scRNA-seq data from a complex disease, starting with inflamed joints and lymph nodes from a mouse model of arthritis. We found the involvement of hundreds of pathways, biomarkers, and drug targets that differed greatly between cell types. Analyses of scRNA-seq and GWAS data from human rheumatoid arthritis (RA) supported a similar dispersion of pathogenic mechanisms in different cell types. Thus, systems-level approaches to prioritize biomarkers and drugs are needed. Here, we present a prioritization strategy that is based on constructing network models of disease-associated cell types and interactions using scRNA-seq data from our mouse model of arthritis, as well as human RA, which we term multicellular disease models (MCDMs). We find that the network centrality of MCDM cell types correlates with the enrichment of genes harboring genetic variants associated with RA and thus could potentially be used to prioritize cell types and genes for diagnostics and therapeutics. We validated this hypothesis in a large-scale study of patients with 13 different autoimmune, allergic, infectious, malignant, endocrine, metabolic, and cardiovascular diseases, as well as a therapeutic study of the mouse arthritis model. Conclusions: Overall, our results support that our strategy has the potential to help prioritize diagnostic and therapeutic targets in human disease.
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| 4. |
- Lovén Wickman, Ulrica, 1966-, et al.
(författare)
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Development of a self-care questionnaire for clinical assessment in patients with inflammatory bowel disease
- 2018
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Ingår i: Presented at the 13th Congress of ECCO, Vienna, Austria, February 14-17, 2018.
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Konferensbidrag (refereegranskat)abstract
- BACKGROUNDPatients with inflammatory bowel disease (IBD) have lifelong needs to learn how to manage their symptoms and life situation. The range of actions that patients take in order to manage daily life and maintain health, is defined as self-care. Assessment of self-care may facilitate patient consulting in IBD health care, with the intention to support and strengthen individual efforts to improve their self-care. There is a lack of measures to assess self-care in patients with IBD. The aim of this study was to develop and evaluate the IBD Self-Care questionnaire for assessment of self-care among patients with IBD.METHODSQualitative and quantitative methods were used to develop the IBD self-care questionnaire. The development and evaluation process was performed in three-phases; (1) item generation based on an interview study on self-care in patients with IBD (n = 20), (2) content validation assessed with Content Validity Index (CVI) by an expert panel (n = 6) and patients (n = 100), ranking and selection of the items, and cognitive interviews to determine the usability of the questionnaire and (3) final evaluation through a pilot study (n = 93) and a test–retest (n = 50) after three weeks. An expert review group with three nurses and one physician continuously discussed the result during the development process.RESULTSA total of 91 patients with Crohn's disease and 102 with ulcerative colitis participated. The final IBD Self-Care questionnaire consisted of 22 items. The assessment of content validity indicated that the items were adequate and easy to understand. Reliability was confirmed with a conformity of 75–100%, in test–retest statistics.CONCLUSIONAn IBD-specific self-care questionnaire was developed with structured methods. The evaluation indicated good validity and reliability. The questionnaire may be a useful tool to assess patients’ with IBD ability of self-care in daily practice. However, the results need to be confirmed in further evaluations of larger IBD populations.
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| 5. |
- Lovén Wickman, Ulrica, 1966-, et al.
(författare)
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Development of a self-care questionnaire for clinical assessment of self-care in patients with inflammatory bowel disease : A psychometric evaluation.
- 2019
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Ingår i: International Journal of Nursing Studies. - : Elsevier. - 0020-7489 .- 1873-491X. ; 89, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with inflammatory bowel disease have lifelong needs to learn how to manage their symptoms and life situation. The range of actions that patients take in order to manage daily life and maintain health is referred to as self-care. Assessment of self-care in patients with inflammatory bowel disease could allow targeted support and education by health care professionals. There are no existing measures assessing self-care in patients with inflammatory bowel disease.OBJECTIVES: The aim was to develop and evaluate the self-care questionnaire for assessment of self-care among patients with inflammatory bowel disease.METHODS: Qualitative and quantitative methods were used to develop the inflammatory bowel disease self-care questionnaire. The development and evaluation process was performed in three phases: (1) item generation based on interviews with patients with inflammatory bowel disease (n = 20), (2) content validation in a panel of experts (n = 6) and patients (n = 100) assessed with the content validity index, cognitive interviews and quantifying and ranking the items to determine the usability of the questionnaire, and (3) final evaluation through a pilot study (n = 93) with test-retest evaluation (n = 50). An expert review group of three nurses and one physician continuously discussed the result during the development process.RESULTS: A total of 91 patients with Crohn's disease and 102 with ulcerative colitis participated. The final self-care questionnaire consists of 22 items. Assessment of content validity indicated that the items were adequate and easy to understand. Test-retest reliability was confirmed with intraclass correlations above 0.6 after a three week interval, for all items except one.CONCLUSION: An inflammatory bowel disease-specific self-care questionnaire was developed using structured methods. The evaluation indicated good validity and reliability. The questionnaire may be a useful tool to assess the ability of patients with inflammatory bowel disease to perform routine self-care.
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| 6. |
- Lovén Wickman, Ulrica, 1966-, et al.
(författare)
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Self-care among patients with inflammatory bowel disease : an interview study
- 2016
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Ingår i: Gastroenterology Nursing. - : Lippincott Williams & Wilkins. - 1042-895X .- 1538-9766. ; 39:2, s. 121-128
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory bowel disease (IBD) is a chronic disease of unknown etiology. The disease occurs early in life and the burden of symptoms is significant. Patients need to perform self-care to handle their symptoms, but knowledge about what kind of self-care patients do is limited and these individuals need to learn how to manage the symptoms that arise. The aim of this study was to explore self-care among patients with IBD. Twenty adult patients with IBD, 25–66 years of age, were interviewed. Data were analyzed by performing a qualitative content analysis. Four categories with 10 subcategories emerged from the analysis of the interviews. The self-care patients perform consists of symptom recognition (subcategories: physiological sensations and psychological sensations), handling of symptoms (subcategories: adapting the diet, using medical treatment, stress management, and using complementary alternative medicine), planning life (subcategories: planning for when to do activities and when to refrain from activities), and seeking new options (subcategories: seeking knowledge and personal contacts). Self-care consists of symptom recognition, handling life through planning, and accommodating the existing situation with the ultimate goal of maintaining well-being. Being one step ahead facilitates living with IBD. A decision to actively participate in care of a chronic illness is a prerequisite for self-care. Healthcare professionals must consider patients' potential for and desire for self-care when giving advice on self-care activities. Doing so may help people better cope with IBD.
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- Lovén Wickman, Ulrica, 1966-, et al.
(författare)
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Self-care among patients with inflammatory bowel disease - an interview study
- 2014
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Ingår i: Presented at the 9th Congress of ECCO: Inflammatory Bowel Diseases, Copenhagen, Denmark, February 20-22, 2014.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease of unknown etiology. The disease occurs early in life and the burden of symptoms is the main problem. Patients need to perform self-care to handle their symptoms but knowledge about what kind of self-care patients do is limited and these typically young individuals need to learn how to manage the symptoms that arise.Methods Twenty adult patients with IBD, 26-66 years of age were interviewed. A qualitative content analysis was performed.Results Four categories with ten sub-categories emerged from the analyses of the interviews. The self-care patients perform consist of symptom recognition (subcategories: physiological sensations and psychological sensations), handling of symptoms (subcategories: adapting the diet, using medical treatment, stress management and using complementary or alternative medicine), planning life (subcategories: planning for when to do activities and when to refrain from activities) and seeking new options (subcategories: seeking knowledge and personal contacts).Conclusions Patients with IBD manage their lives through a broad range of self-care activities. Self-care consists of recognition, handling, planning and seeking new options to increase personal well-being. Being one step ahead facilitates the ability to live a full life. Key words: content analysis, crohns disease, inflammatory bowel disease, self-care, ulcerative colitis.
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| 9. |
- Stjernman, Henrik
(författare)
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Crohn’s Disease in Sickness and in Health : Studies of Health Assessment Strategies and Impact on Health-Related Quality of Life
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims. Crohn’s disease (CD) is a chronic inflammatory bowel disease (IBD) with potentially deleterious effects on well-being and daily-life functioning. A complete picture of health status in CD therefore comprises both disease activity (DA) and health-related quality of life (HRQL). Several measures of DA and HRQL in CD have been developed. Some have gained prominence as standard endpoints in clinical trials, but none has been validated in Swedish CD patients and their use in clinical practice has been limited. A conceptual health status model of five dimensions (Biological variables, Symptoms, Function, Worries, and Well-being) has been proposed for IBD health assessment, enabling the construction of the Short Health Scale (SHS), a four-item questionnaire intended to facilitate assessment and interpretation of HRQL in IBD.The aims of this thesis were: (1) to evaluate the Swedish versions of the Inflammatory Bowel Disease Questionnaire (IBDQ) and the Rating Form of IBD Patient Concerns (RFIPC); (2) to evaluate the Short Health Scale; (3) to study the relationship between DA and HRQL variables by identifying determinants of DA outcome and by validating the SHS health status model; (4) to describe the spectrum of disease-related worries and repercussions on general HRQL in a context of social variables, sickness, and disability.Methods. The thesis is based on clinical variables and HRQL data measured in a population-based cohort of 505 CD patients, consecutively included in conjunction with their regular outpatient visits at three hospitals (Jönköping, Örebro, Linköping). The HRQL questionnaires were evaluated regarding construct validity, reliability, and responsiveness. Multivariate analyses were used to investigate the relationship between Crohn’s Disease Activity Index (CDAI) and physician-assessed DA. The SHS health status model was validated with structural equation modelling (SEM). Disease-related worries and concerns, general HRQL, social variables, sickness, and work disability were compared with data from background population or patients with ulcerative colitis (UC).Results. The IBDQ had good validity, reliability, and responsiveness, but the original dimensional structure was not supported. The RFIPC was valid, and reliable, but less sensitive to change in disease activity. The SHS had the highest completion rate and proved adequate psychometric properties. The CDAI correlated weakly with the physician’s appraisal of disease activity, being more influenced by subjective health perception than objective disease activity. SEM showed that the SHS model had a good fit to measured data, explaining >98% of the covariance of the variables. Worries and general HRQL impairment were greater in CD than in UC, especially for women. Disease complications and impaired life achievements elicited most worries. CD patients had lower educational level. Female patients were more often living single. The rates of long-term sickness and disability were doubled compared with background population, with worse outcome for women.Conclusions. The IBDQ, the RFIPC, and the SHS all demonstrated adequate psychometric properties. The SHS was easier to administer and provided a more comprehensive picture of subjective health status. The weak correlation between CDAI and physician-assessed DA was explained by a strong influence of subjective variables on CDAI, stressing the importance of assessing DA and HRQL separately. The SHS health status model was further supported by SEM. CD has tangible effects on subjective health perception, worries and work capacity, especially for women.
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| 10. |
- Stjernman, Henrik, et al.
(författare)
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Evaluation of the inflammatory bowel disease questionnaire in Swedish patients with Crohn's disease
- 2006
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:8, s. 934-943
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Health-related quality of life (HRQoL) is an important measure of inflammatory bowel disease (IBD) health outcome. The Inflammatory Bowel Disease Questionnaire (IBDQ) comprising 32 items grouped into four dimensions is a widely used IBD-specific HRQoL instrument. The purpose of this study was to evaluate the validity, reliability and responsiveness of the Swedish translation of the IBDQ in patients with Crohn's disease (CD). MATERIAL AND METHODS: Four hundred and forty-eight patients with CD completed the IBDQ and three other HRQoL questionnaires (Rating Form of IBD Patient Concerns; Short Form-36; and the Psychological General Well-Being Index) in connection with their regular visit at the outpatient clinic. Disease activity was assessed by the physician on a 4-point Likert scale. Thirty-two patients who were stable in remission completed the questionnaires a second time, 4 weeks later. A total of 418 patients repeated all measurements after 6 months. RESULTS: The dimensional scores were highly correlated with other measures of corresponding aspects of HRQoL and were significantly better in remission than in relapse. High test-retest correlations indicated good reliability. Responsiveness was confirmed in patients whose disease activity changed over time. However, high correlations between the dimensions, poor correlations between items within each dimension, and factor analysis all indicated that the original grouping of the items is not valid for Swedish CD patients. CONCLUSIONS: Although the Swedish IBDQ has good external validity, reliability and responsiveness for patients with CD, our results did not support the original grouping of the items.
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