| 1. |
- Sylwander, Charlotte, 1992-, et al.
(författare)
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The impact of chronic widespread pain on health status and long-term health predictors: a general population cohort study
- 2020
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Ingår i: BMC Musculoskeletal Disorders. - London : Springer Science and Business Media LLC. - 1471-2474. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Chronic widespread pain (CWP) has a negative impact on health status, but results have varied regarding gender-related differences and reported health status. The aim was to study the impact of CWP on health status in women and men aged 35-54 years in a sample of the general population. The aim was further to investigate lifestyle-related predictors of better health status in those with CWP in a 12- and 21-year perspective. Method A general population cohort study including 975 participants aged 35-54 years, with a 12- and 21-year follow-up. CWP was measured with a pain mannequin, and the questionnaire included questions on lifestyles factors with SF-36 for measurement of health status. Differences in health status were analysed with independent samples t-test and health predictors with logistic regression analysis. Results The prevalence of CWP was higher in women at all time points, but health status was reduced in both women and men with CWP (p < 0.001) with no gender differences of clinical relevance. At the 12-year follow-up, a higher proportion of women than men had developed CWP (OR 2.04; CI 1.27-3.26), and at the 21-year follow-up, a higher proportion of men had recovered from CWP (OR 3.79; CI 1.00-14.33). In those reporting CWP at baseline, a better SF-36 health status (Physical Functioning, Vitality or Mental Health) at the 12-year follow-up was predicted by male gender, having personal support, being a former smoker, and having no sleeping problems. In the 21-year follow-up, predictors of better health were male gender, a weekly intake of alcohol, and having no sleeping problems. Conclusion Women and men with CWP have the same worsening of health status, but men recover from CWP to a greater extent in the long-term. Being male, having social support, being a former smoker, and having no sleeping problems were associated with better health status in those with CWP.
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| 2. |
- Andersson, Ingemar, 1950-
(författare)
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Rehabilitering vid långvarig smärta
- 2010. - 2
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Ingår i: Smärta och smärtbehandling. - Stockholm : Liber. - 9789147084135 ; , s. 401-409
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 3. |
- Fan, Yue, et al.
(författare)
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Unveiling inflammatory and prehypertrophic cell populations as key contributors to knee cartilage degeneration in osteoarthritis using multi-omics data integration
- 2024
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group Ltd. - 0003-4967 .- 1468-2060. ; 83:7, s. 926-944
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Single-cell and spatial transcriptomics analysis of human knee articular cartilage tissue to present a comprehensive transcriptome landscape and osteoarthritis (OA)-critical cell populations.METHODS: Single-cell RNA sequencing and spatially resolved transcriptomic technology have been applied to characterise the cellular heterogeneity of human knee articular cartilage which were collected from 8 OA donors, and 3 non-OA control donors, and a total of 19 samples. The novel chondrocyte population and marker genes of interest were validated by immunohistochemistry staining, quantitative real-time PCR, etc. The OA-critical cell populations were validated through integrative analyses of publicly available bulk RNA sequencing data and large-scale genome-wide association studies.RESULTS: We identified 33 cell population-specific marker genes that define 11 chondrocyte populations, including 9 known populations and 2 new populations, that is, pre-inflammatory chondrocyte population (preInfC) and inflammatory chondrocyte population (InfC). The novel findings that make this an important addition to the literature include: (1) the novel InfC activates the mediator MIF-CD74; (2) the prehypertrophic chondrocyte (preHTC) and hypertrophic chondrocyte (HTC) are potentially OA-critical cell populations; (3) most OA-associated differentially expressed genes reside in the articular surface and superficial zone; (4) the prefibrocartilage chondrocyte (preFC) population is a major contributor to the stratification of patients with OA, resulting in both an inflammatory-related subtype and a non-inflammatory-related subtype.CONCLUSIONS: Our results highlight InfC, preHTC, preFC and HTC as potential cell populations to target for therapy. Also, we conclude that profiling of those cell populations in patients might be used to stratify patient populations for defining cohorts for clinical trials and precision medicine.
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| 4. |
- Wang, Xi, et al.
(författare)
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Comparison of the major cell populations among osteoarthritis, Kashin-Beck disease and healthy chondrocytes by single-cell RNA-seq analysis
- 2021
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Ingår i: Cell Death and Disease. - : Springer Nature. - 2041-4889. ; 12:6
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Tidskriftsartikel (refereegranskat)abstract
- Chondrocytes are the key target cells of the cartilage degeneration that occurs in Kashin-Beck disease (KBD) and osteoarthritis (OA). However, the heterogeneity of articular cartilage cell types present in KBD and OA patients and healthy controls is still unknown, which has prevented the study of the pathophysiology of the mechanisms underlying the roles of different populations of chondrocytes in the processes leading to KBD and OA. Here, we aimed to identify the transcriptional programmes and all major cell populations in patients with KBD, patients with OA and healthy controls to identify the markers that discriminate among chondrocytes in these three groups. Single-cell RNA sequencing was performed to identify chondrocyte populations and their gene signatures in KBD, OA and healthy cells to investigate their differences as related to the pathogenetic mechanisms of these two osteochondral diseases. We performed immunohistochemistry and quantitative reverse-transcription PCR (qRT-PCR) assays to validate the markers for chondrocyte population. Ten clusters were labelled by cell type according to the expression of previously described markers, and one novel population was identified according to the expression of a new set of markers. The homeostatic and mitochondrial chondrocyte populations, which were identified by the expression of the unknown markers MT1X and MT2A and MT-ND1 and MT-ATP6, were markedly expanded in KBD. The regulatory chondrocyte population, identified by the expression of CHI3L1, was markedly expanded in OA. Our study allows us to better understand the heterogeneity of chondrocytes in KBD and OA and provides new evidence of differences in the pathogenetic mechanisms between these two diseases.
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| 5. |
- Eriksson, Catharina, 1955-
(författare)
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Immunological mechanisms in systemic autoimmunity : autoantibodies and chemokines in systemic lupus erythematosus and during treatment with TNF inhibitors in rheumatoid arthritis
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background. Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease that, without powerful treatment, may lead to irreversible joint damage. During the past decade, anti-cytokine therapy has become available, e.g., infliximab, a chimeric antibody targeting the pro-inflammatory cytokine TNF that has a central role in the inflammatory process in RA patients. Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that may affect all organs and is characterized by a massive antibody production. Chemokines, chemokine receptors and lipoprotein receptor-related protein 1(CD91) are regulators of inflammation in autoimmune diseases and T-cell migration. Objectives. The aim of this study was to get a deeper understanding how TNF blocking treatment influences inflammatory mechanisms and autoantibody formation in RA with special reference to similarities and differences with SLE. Methods. In patients with RA treated with anti-TNF, and in SLE patients (ACR criteria) clinical evaluation was performed and blood samples analyzed. Autoantibodies were analyzed using indirect immunofluorescence, ELISA and multiplex flow cytometry in samples from anti-TNF treated RA patients (n=59) followed longitudinally for 54 weeks, in pre-diseased samples from SLE patients (n=38) and matched population-based controls (n=152). T-cell expression of chemokine receptors and CD91 was analyzed by flow cytometry, whilst serum levels of chemokines were determined using ELISA in anti-TNF treated RA-patients (n=24) followed longitudinally (30 weeks), and cross-sectionally in SLE-patients (n=23). Expression of mRNA for chemokines was analyzed in T-cells from SLE-patients (n=10) using PCR. Results. After treatment with infliximab, RA patients produced ANA, anti-dsDNA and anti-nucleosome antibodies, but not anti-ENA antibodies. Although these antibodies are considered typical for SLE only one patient developed a transient lupus-syndrome. Antibodies against cell nuclear antigens, including ENA, were detected several years before the first clinical symptom of SLE; anti-SSA was the earliest detectable antibody. In RA-patients before infliximab treatment, the T-cell expression of several chemokine receptors was elevated compared with healthy controls. In contrast, only one soluble chemokine, IP-10 was elevated. After treatment the levels of soluble MIP-1β, MCP-1 and IP-10, and the T-cell expression of CCR2 were decreased. In SLE-patients MIP-1β, MCP-1, SDF-1, IP-10 and RANTES in blood were elevated, whilst expression of CXCR5 and CCR6 on T-cells was lower than in healthy controls. T-cell expression of CXCR2 and CCR1 was elevated in active disease (measured as SLEDAI index), whereas the CXCR5 and CCR2 expression was lower in inactive SLE. In SLE patients with nephritis IP-10 was lower and T-cell expression of CXCR3 and CCR3 elevated compared with patients without nephritis. The expression of CD91 was higher on T-cells from patients not responsive to infliximab treatment compared with responders. Conclusion. These findings indicate that anti-TNF (infliximab) treatment in RA-patients has a major impact on the production of autoantibodies and chemokines. The autoantibody profile in infliximab-treated patients was similar to that predating disease onset in SLE patients with the exception of anti-ENA being detectable in SLE, but the development of lupus-syndromes was rare. The expression of CD91 on T-cells may predict responsiveness to infliximab. The expression of chemokine receptors in SLE- patients seemed to be related to disease activity. Anti-nuclear antibodies were detectable years before clinical disease onset in patients who developed SLE suggesting a gradual pathogenic process.
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| 6. |
- Kahn, Robin, et al.
(författare)
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Population-based study of multisystem inflammatory syndrome associated with COVID-19 found that 36% of children had persistent symptoms
- 2022
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Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 111:2, s. 354-62
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Our aim was to describe the outcomes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19. Methods: This national, population-based, longitudinal, multicentre study used Swedish data that were prospectively collected between 1 December 2020 and 31 May 2021. All patients met the World Health Organization criteria for MIS-C. The outcomes 2 and 8weeks after diagnosis are presented, and follow-up protocols are suggested. Results: We identified 152 cases, and 133 (87%) participated. When followed up 2weeks after MIS-C was diagnosed, 43% of the 119 patients had abnormal results, including complete blood cell counts, platelet counts, albumin levels, electrocardiograms and echocardiograms. After 8weeks, 36% of 89 had an abnormal patient history, but clinical findings were uncommon. Echocardiogram results were abnormal in 5% of 67, and the most common complaint was fatigue. Older children and those who received intensive care were more likely to report symptoms and have abnormal cardiac results. Conclusion: More than a third (36%) of the patients had persistent symptoms 8weeks after MIS-C, and 5% had abnormal echocardiograms. Older age and higher levels of initial care appeared to be risk factors. Structured follow-up visits are important after MIS-C.
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| 7. |
- Andersson, Maria L.E., et al.
(författare)
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Cohort profile: the Halland osteoarthritis (HALLOA) cohort-from knee pain to osteoarthritis: a longitudinal observational study in Sweden
- 2022
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Ingår i: Bmj Open. - London : BMJ. - 2044-6055. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The overall objective in this study is to investigate the early development of radiographic knee osteoarthritis (OA) and its association with hand or/and knee OA, metabolic diseases, biomarkers, chronic pain, physical function and daily physical activity types. Participants The Halland osteoarthritis (HALLOA) cohort is a longitudinal cohort study that includes individuals with knee pain in the southwest of Sweden. Enrolment took place from 2017 to 2019. The inclusion criteria were current knee pain, with no former known radiographic knee OA and no cruciate ligament rupture or rheumatological disorder. The participants were recruited: (1) when seeking care for knee pain in primary healthcare or (2) by advertisements in local newspapers. There are 306 individuals included in the study, mean age (SD) 51.7 (8.7) years and 69% are women. The baseline and follow-ups include clinical tests, radiographical examinations, blood samples, metabolic measures, pain pressure thresholds, tests of physical functions, daily physical activity types and patient-reported outcomes. Findings to date There were associations between metabolic factors and radiographic knee OA, even in those with normal body mass index at baseline. In addition, clinical hand OA was positively associated with fasting plasma glucose. We also found that modifiable factors as increased visceral fat and total body fat were associated with increased pain sensitivity among individuals with knee pain. Future plans By studying possible pathophysiological mechanisms of OA over time, we aim to provide new insights on OA progression, identify usable preventive measures helping the clinicians in the management of the disease and improve health for the patients. It is also important to study the development of chronic pain in OA, to get tools to identify individuals at risk and to be able to offer them treatment.
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| 8. |
- Westman, Gabriel, 1977-, et al.
(författare)
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Cerebrospinal fluid biomarkers of brain injury, inflammation and synaptic autoimmunity predict long-term neurocognitive outcome in herpes simplex encephalitis.
- 2021
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Ingår i: Clinical Microbiology and Infection. - : Elsevier. - 1198-743X .- 1469-0691. ; 27:8, s. 1131-1136
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim was to investigate the correlation between biomarkers of brain injury and long-term neurocognitive outcome, and the interplay with intrathecal inflammation and neuronal autoimmunity, in patients with herpes simplex encephalitis (HSE).METHODS: A total of 53 adult/adolescent HSE patients were included from a prospective cohort in a randomized placebo-controlled trial investigating the effect of a 3-month follow-up treatment with valaciclovir. Study subjects underwent repeated serum/cerebrospinal fluid (CSF) sampling and brain magnetic resonance imaging in the first 3 months along with cognitive assessment using the Mattis Dementia Rating Scale (MDRS) at 24 months. CSF samples were analysed for biomarkers of brain injury, inflammation and synaptic autoimmunity. The predefined primary analysis was the correlation between peak CSF neurofilament protein (NFL), a biomarker of neuronal damage, and MDRS at 24 months.RESULTS: Impaired cognitive performance significantly correlated with NFL levels (rho = -0.36, p = 0.020). Development of IgG anti-N-methyl-D-aspartate receptor (NDMAR) antibodies was associated with a broad and prolonged proinflammatory CSF response. In a linear regression model, lower MDRS at 24 months was associated with previous development of IgG anti-N-methyl-D-aspartate receptor (NMDAR) (beta = -0.6249, p = 0.024) and age (z-score beta = -0.2784, p = 0.024), but not CSF NFL, which however significantly correlated with subsequent NMDAR autoimmunization (p = 0.006).DISCUSSION: Our findings show that NFL levels are predictive of long-term neurocognitive outcome in HSE, and suggest a causative chain of events where brain tissue damage increases the risk of NMDAR autoimmunisation and subsequent prolongation of CSF inflammation. The data provides guidance for a future intervention study of immunosuppressive therapy administered in the recovery phase of HSE.
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| 9. |
- Åkerman, Linda, 1983-
(författare)
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Aspects of the Pre-Diabetic Period in Type 1 Diabetes
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 1 diabetes (T1D) is an autoimmune disease characterized by insulin deficiency, due to immune-mediated destruction of beta cells. Current knowledge regarding the period preceding disease onset comes, to a large extent, from studying risk cohorts based on relatives of T1D-patients, as they have an increased disease risk. Among T1D patients in general, however, few have the disease in their immediate family. It is therefore important to study risk cohorts from the general population as well. An ongoing autoimmune reaction can often be seen in the blood long before disease onset, by detection of autoantibodies directed towards beta cell antigens. By autoantibody screening among participants in the ABIS (All Babies in the South-east of Sweden) cohort, we could identify a group of children from the general population with increased risk for T1D, positive for multiple autoantibodies. They were enrolled in a 2-year prospective follow-up aiming to characterize the prediabetic period and to identify factors indicative of progression/non-progression to T1D. We assessed glucose homeostasis and autoantibody titers over time, and searched for risk-biomarkers by analyzing the expression of immune-related genes (Th1-Th2-Th3) in peripheral blood mononuclear cells (PBMC) from these children, in comparison to healthy children and newly diagnosed T1D patients. In the same groups we also compared serum micro RNA (miRNA) profiles, knowing that miRNA molecules have desirable biomarker properties. We found that two specific autoantibodies, IA2A and ZnT8A, were detected at higher concentrations in risk-individuals who progressed to overt T1D during or after the follow-up period, compared to those who still have not. We also observed disturbed glucose homeostasis long before onset in the progressors, but it was seen among those who remain symptom free as well. Further, we found support for the possible role of insulin resistance as an accelerator of the disease process. For gene expression and serum miRNA, few differences were observed between risk-individuals and healthy children overall. However, for PBMC gene expression and serum miRNA both, there were associations to beta cell function and glucose homeostasis, and for miRNA also to islet autoantibodies. Although specific profiles for prediction of disease onset or identification of risk-individuals could not be found, these results are interesting and deserve to be evaluated further. As part of another sub-study within ABIS, the effects of physical activity on glucose homeostasis were assessed in healthy schoolchildren. The level of physical activity, measured by pedometers, was related to insulin resistance and beta cell-stress, and decreased physical activity was associated with increased insulin resistance and load on the insulin-producing beta cells, already at school-age.
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| 10. |
- Sylwander, Charlotte, 1992-
(författare)
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Multiple perspectives on health promotion in individuals with knee pain
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic musculoskeletal pain impacts the individual in multiple aspects of life (biological, psychological, and social). Individuals with knee pain have a higher risk of developingchronic widespread pain and knee osteoarthritis, compared to the general population, and the prevalence of chronic pain is estimated to rise. As a result, there is a global call for more health-promotive research in chronic pain. Hence, this thesis aimed to investigate multiple perspectives on health promotion by studying early factors associated with chronic pain and pain development as well as experiences of health-promoting activities and health literacy in individuals with knee pain. The studies are part of the Halland osteoarthritis (HALLOA) cohort, where 306 individuals with knee pain aged 30-65 years were included. Study I was a cross-sectional descriptive study (n=280), which aimed to investigate pain sensitivity and associations with radiographic knee osteoarthritis, chronic widespread pain, and overweight/obesity. Pain sensitivity was measured with pressure pain thresholds, and overweight was assessed using body mass index, visceral fat area and body fat percentage. Study II was a longitudinal study (n=251), aiming to examine whether or not health status and lifestyle habits have an impact on reporting chronic pain after two years. Lifestyle-related habits were overweight, physical activity, diet, alcohol intake, and tobacco use. Study III was an explorative qualitative study including 22 semi-structured interviews. The study aimed to explore health-promotive activities and was analysed with qualitative content analysis. Study IV had a convergent parallel mixed-methods design (n=221), including 19 interviews, and aimed to understand health literacy among individuals with knee pain. Quantitative variables were health literacy, health status, lifestyle habits, and pain distribution. The findings showed that higher pain sensitivity was associated with being female, having more pain sites, chronic widespread pain, higher body fat and visceral fat area (study I). Additionally, overweight/obesity and lower health status were associated with reporting chronic widespread pain after two years. Conversely, being normal-weighted and reporting better health status was associated with no chronic pain (study II). Striving for balance in everyday life was important to experiencing health among individuals with knee pain, and it was achieved by taking care of the body and managing life stressors (study III). Many reported sufficient health literacy, which was also associated with reporting better general health and less pain. How individuals found or received information, processed it, and took a stand based on trust and motivation, affected their decision-making processes (study IV). This thesis concludes that overweight/obesity and lower health status play an essential role in chronic pain. Health literacy and the everyday life of an individual are important when it comes to health promotion; and it is vital to consider what individuals with knee pain need in a given situation in order to prevent chronic pain.
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| 11. |
- Stening, Kent, 1968-, et al.
(författare)
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Hormonal replacement therapy does not affect self-estimated pain or experimental pain responses in post-menopausal women suffering from fibromyalgia: a double-blind, randomized placebo-controlled trial
- 2011
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Ingår i: Rheumatology. - London : Oxford univesity press. - 1462-0324 .- 1462-0332. ; 50:3, s. 544-551
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. FM is a condition that preferentially affects women. Sex hormones, and in particular oestrogens, have been shown to affect pain processing and pain sensitivity, and oestrogen deficit has been considered a potentially promoting factor for FM. However, the effects of oestrogen treatment in patients suffering from FM have not been studied. Here, we examined the effect of transdermal oestrogen substitution treatment on experimental as well as self-estimated pain in women suffering from FM.Methods. Twenty-nine post-menopausal women were randomized to either 8 weeks of treatment with transdermal 17β-oestradiol (50 µg/day) or placebo according to a double-blind protocol. A self-estimation of pain, a set of quantitative sensory tests measuring thresholds to temperature, thermal pain, cold pain and pressure pain, and a cold pressor test were performed on three occasions: before treatment, after 8 weeks of treatment and 20 weeks after cessation of treatment.Results. Hormonal replacement treatment significantly increased serum oestradiol levels as expected (P < 0.01). However, no differences in self-estimated pain were seen between treatment and placebo groups, nor were there any differences between the two groups regarding the results of the quantitative sensory tests or the cold pressor test at any of the examined time points.Conclusion. Eight weeks of transdermal oestradiol treatment does not influence perceived pain, pain thresholds or pain tolerance as compared with placebo treatment in post-menopausal women suffering from FM.
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| 12. |
- Eriksson, Catharina, 1955-, et al.
(författare)
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Changes in chemokines and their receptors in blood during treatment with the TNF inhibitor infliximab in patients with rheumatoid arthritis
- 2013
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Ingår i: Scandinavian Journal of Rheumatology. - : Informa UK Limited. - 0300-9742 .- 1502-7732. - 9789174591439 ; 42:4, s. 260-265
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Tidskriftsartikel (refereegranskat)abstract
- Background. Chemokines are involved in leucocyte recruitment into inflammatory sites, such as the synovial tissue of patients with rheumatoid arthritis (RA). The release of certain chemokines is augmented by pro-inflammatory cytokines, such as tumor necrosis factor (TNF). Infliximab, a monoclonal antibody against TNF that blocks the biological effects of TNF, is used in the treatment of chronic inflammatory diseases. The effect of blocking TNF activity on chemokines is not fully understood.Aim. The aim of this study was to analyse the effects on chemokines and their receptors on peripheral mononuclear cells of anti-TNF treatment in RA-patients.Material and methods. Twelve patients with established RA who began treatment with infliximab, and nine patients with early RA treated with traditional disease-modifying anti-rheumatic drugs, were followed clinically for 30 weeks and chemokine levels in blood samples and chemokine receptor expression on the surface of T-cells and monocytes analysed. Three SLE-patients, as a small control group of another inflammatory disease, and nine healthy subjects were also included in the study.Result. CXCL10/IP-10 was significantly higher in RA-patients compared with healthy controls and decreased significantly two weeks after infliximab infusion. CCL2/MCP-1 and CCL4/MIP-1β decreased significantly after infliximab treatment although the concentrations were not significantly elevated at baseline compared with controls. There was an inverse correlation between the chemokine cleaving molecule dipeptidyl peptidase-IV/CD26 and CCL5/RANTES. Several chemokine receptors on T-cells were elevated in RA patients at inclusion into the study. The CCR2 expression on T-cells decreased significantly after infliximab treatment.Conclusion. The chemokines CXCL10/IP-10, CCL2/MCP-1 and CCL4/MIP-1β, mainly targeting the Th1 immune response, decreased after treatment with anti-TNF suggesting a more pronounced effect onTh1 activity than on the Th2 mediated response. Several chemokine receptors on blood T-cells were elevated in RA-patients, suggesting that they may be involved in the recruitment of T-lymphocytes from the blood to affected tissues.
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| 13. |
- Law, Lucy, 1987-
(författare)
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Subclinical cardiovascular disease and health related quality of life in patients with radiographic axial spondyloarthritis
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Radiographic axial spondyloarthritis (r-axSpA) is a chronic inflammatory rheumatic disease predominantly affecting the axial skeleton. The global prevalence of r-axSpA is between 0.1-1.4%. The disease is associated with extra-musculoskeletal manifestations (EMMs) such as anterior uveitis (AU), as well as increased risk of cardiovascular disease (CVD)-related comorbidities such as atherosclerosis that significantly contribute to mortality and the burden of disease in patients with r-axSpA. The increased CVD risk is not fully explained by traditional CVD risk factors, and little is known about the difference in CVD risk profiles between the sexes. Moreover, the association of disease related variables and subclinical signs of CVD by ultrasound remain to be comprehensively investigated in a well-characterized and sex stratified patient cohort. Additionally, studies investigating factors related to health-related quality of life (HRQoL) in patients with r-axSpA acknowledge that r-axSpA patients have a lower HRQoL than the general population. However, constancy in study methods and comparison to general population controls, especially stratified by sex, are limited. Objectives: The global aim of this thesis was to explore novel methods relating to the evaluation, detection, and monitoring of factors contributing to the burden of CVD in patients with r-axSpA, and to increase knowledge about HRQoL. More specifically, to study the impact of r-axSpA on HRQoL (Paper 1) and identify novel ultrasound markers of subclinical CVD (Papers 2-4) in patients with r-axSpA, overall, stratified by sex, and compared to controls. Materials and methods: Paper 1: The Short Form-36 (SF-36) questionnaire was used to assess HRQoL in patients with r-axSpA from Western Sweden (n=210, females 42.4%). Each patient was compared to 5 age- and sex-matched persons from the SF-36 Swedish normative population database (n=1055). Papers 2-4: Ultrasound was used to (i) assess bilateral common carotid arterial (CCA) stiffness by calculation of b-stiffness index and circumferential 2D strain (Paper 2); (ii) measure mean bilateral carotid intima media thickness (cIMT) and investigate its relationship with biomarkers of inflammation (Paper 3); and (iii) assess the mean thickness of the epicardial adipose tissue (EAT) deposit and its associations with traditional CVD related risk factors (Paper 4). Papers 2-4 used a well characterized patient group from Northern Sweden (‘Backbone cohort’, n=155, female 31.0%). The control group for paper 2 included 46 age- and sex- matched persons from the local population, with no traditional CVD risk factors. The control group for papers 3 and 4, was derived from the Umeå region Swedish CArdioPulmonary bioImaging Study (SCAPIS) recall study (n= 400, females 51.0%). All results were presented stratified by sex. Uni- and multi-variate regression analysis methods were used to evaluate associations with disease and demographic variables. All studies were of cross-sectional design.Results: Paper 1: Patients exhibited significantly lower HRQoL compared to controls (P<0.001). Upon stratification by sex, both sexes scored significantly lower physical compared to the mental HRQoL scores. Multivariable logistic regression analysis found that patients with a longer disease duration, worse physical function (assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI), high disease activity (measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS)), or who lived alone had significantly lower physical HRQoL. Lower mental HRQoL was associated with fatigue, high ASDAS and living alone. Some differences in sex were also found. Paper 2: Patients had higher mean bilateral CCA b-stiffness index, and lower 2D CCA circumferential strain, compared to controls. Multivariate linear regression analysis found that several disease related parameters, in addition to age, were related to 2D circumferential strain (R2 0.33), whereas only age was related to b-stiffness index (R2 0.19). Paper 3: Linear regression analysis, with various adjustment models, showed that patients had increased cIMT compared to controls. White blood cell (WBC)- and monocyte- count were the only inflammatory biomarkers associated with cIMT. This association was only seen in male patients and remained after adjustments. Paper 4: Mean EAT was thicker in r-axSpA patients overall and stratified by sex compared to controls. No difference in mean EAT was found between the sexes. There were borderline significant associations between EAT thickness and cholesterol levels in male patients.Conclusion: Patients with r-axSpA have decreased HRQoL and increased subclinical indicators of CVD compared to controls. By modifying factors, such as ASDAS-CRP and fatigue, HRQoL may be improved in patients with r-axSpA. Additionally, ultrasound methods are non-invasive, and easily obtainable, offering additional insights into the factors that influence the risk of CVD in r-axSpA patients. Although further studies are required to validate novel ultrasound methods, these techniques represent a powerful approach to non-invasively to detect, monitor, and help manage CVD related comorbidities.
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| 14. |
- Westman, Gabriel, et al.
(författare)
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N-Methyl-D-Aspartate Receptor Autoimmunity Affects Cognitive Performance in Herpes Simplex Encephalitis
- 2016
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Ingår i: Clinical Microbiology And Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 22:11, s. 934-940
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate the prevalence and temporal development of N-methyl-D-aspartate receptor (NMDAR) autoantibodies in relation to neurocognitive performance in patients with herpes simplex encephalitis (HSE). Methods: This prospective observational study enrolled a total of 49 HSE patients within a randomized controlled trial of valacyclovir. Cerebrospinal fluid and serum samples were drawn in the initial stage of disease, after 2 to 3 weeks and after 3 months. Anti-NMDAR IgG was detected with HEK293 cells transfected with plasmids encoding the NMDA NR1 type glutamate receptor. A batch of neurocognitive tests, including the Mattis Dementia Rating Scale (MDRS), Glasgow Coma Scale (GCS), Reaction Level Scale (RLS85), Mini-Mental State Examination (MMSE) and National Institutes of Health (NIH) stroke scale, was performed during 24 months' follow-up. Results: Anti-NMDAR IgG was detected in 12 of 49 participants. None were antibody positive in the initial stage of disease. In ten of 12 positive cases, specific antibodies were detectable only after 3 months. Notably, the development of NMDAR autoantibodies was associated with significantly impaired recovery of neurocognitive performance. After 24 months' follow-up, the median increase in MDRS total score was 1.5 vs. 10 points in antibody-positive and -negative participants (p = 0.018). Conclusions: Anti-NMDAR autoimmunity is a common complication to HSE that develops within 3 months after onset of disease. The association to impaired neurocognitive recovery could have therapeutical implications, as central nervous system autoimmunity is potentially responsive to immunotherapy.
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| 15. |
- Johansson, Åsa, et al.
(författare)
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Precision medicine in complex diseases - : Molecular subgrouping for improved prediction and treatment stratification
- 2023
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Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 1365-2796 .- 0954-6820. ; 294:4, s. 378-396
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Forskningsöversikt (refereegranskat)abstract
- Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop accurate diagnostic tools for treatment recommendations and preventive strategies, and for disease prognosis and prediction, is an important step toward precision medicine. However, for complex diseases, precision medicine is associated with several challenges. There is a significant heterogeneity between patients of a specific disease-both with regards to symptoms and underlying causal mechanisms-and the number of underlying genetic and nongenetic risk factors is often high. Here, we summarize precision medicine approaches for complex diseases and highlight the current breakthroughs as well as the challenges. We conclude that genomic-based precision medicine has been used mainly for patients with highly penetrant monogenic disease forms, such as cardiomyopathies. However, for most complex diseases-including psychiatric disorders and allergies-available polygenic risk scores are more probabilistic than deterministic and have not yet been validated for clinical utility. However, subclassifying patients of a specific disease into discrete homogenous subtypes based on molecular or phenotypic data is a promising strategy for improving diagnosis, prediction, treatment, prevention, and prognosis. The availability of high-throughput molecular technologies, together with large collections of health data and novel data-driven approaches, offers promise toward improved individual health through precision medicine.
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| 16. |
- Hedman, Anna, et al.
(författare)
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Bidirectional relationship between eating disorders and autoimmune diseases
- 2019
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Ingår i: Journal of Child Psychology and Psychiatry. - Stockholm : Blackwell Publishing. - 0021-9630 .- 1469-7610. ; 60:7, s. 803-812
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Immune system dysfunction may be associated with eating disorders (ED) and could have implications for detection, risk assessment, and treatment of both autoimmune diseases and EDs. However, questions regarding the nature of the relationship between these two disease entities remain. We evaluated the strength of associations for the bidirectional relationships between EDs and autoimmune diseases.METHODS: In this nationwide population-based study, Swedish registers were linked to establish a cohort of more than 2.5 million individuals born in Sweden between January 1, 1979 and December 31, 2005 and followed up until December 2013. Cox proportional hazard regression models were used to investigate: (a) subsequent risk of EDs in individuals with autoimmune diseases; and (b) subsequent risk of autoimmune diseases in individuals with EDs.RESULTS: We observed a strong, bidirectional relationship between the two illness classes indicating that diagnosis in one illness class increased the risk of the other. In women, the diagnoses of autoimmune disease increased subsequent hazards of anorexia nervosa (AN), bulimia nervosa (BN), and other eating disorders (OED). Similarly, AN, BN, and OED increased subsequent hazards of autoimmune diseases.Gastrointestinal-related autoimmune diseases such as, celiac disease and Crohn's disease showed a bidirectional relationship with AN and OED. Psoriasis showed a bidirectional relationship with OED. The previous occurence of type 1 diabetes increased the risk for AN, BN, and OED. In men, we did not observe a bidirectional pattern, but prior autoimmune arthritis increased the risk for OED.CONCLUSIONS: The interactions between EDs and autoimmune diseases support the previously reported associations. The bidirectional risk pattern observed in women suggests either a shared mechanism or a third mediating variable contributing to the association of these illnesses.
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| 17. |
- Oliv, Stefan, et al.
(författare)
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Important work demands for reducing sickness absence among workers with neck or upper back pain: a prospective cohort study
- 2019
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background The aim of this study was to investigate what exposure to work demands, physical and psychosocial, is associated with lower levels of sickness absence among workers with neck or upper back pain in different groups, by age, gender, duration of sickness absence and work ability score. Methods This study was a prospective study of 4567 workers with neck or upper back pain. Data on neck or upper back pain, work demand and work ability were obtained from the Swedish Work Environment survey over a 3-year period (2009-2013). Register data on sickness absence, 1 year after each survey was conducted, were obtained from the Swedish health insurance database. Analyses were performed to estimate the association between self-reported work demands and registered sick days > 14 days. The analyses were stratified for gender, age group and work ability score. Results Lower numbers of sick days were found for workers reporting low exposure to lifting >= 15 kg and twisted or forward-leaning work postures. Lower numbers of sick days were found for workers reporting high work control and seated work. The associations were generally stronger in the older age groups for the physical work demands. Conclusions The findings in this study suggest that certain physical work demands and having high control over one's work can result in lower sickness absence, especially among middle-aged and older workers with neck or upper back pain.
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| 18. |
- Hagberg, Niklas, et al.
(författare)
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IFN-α Production by Plasmacytoid Dendritic Cells Stimulated with RNA-Containing Immune Complexes Is Promoted by NK Cells via MIP-1β and LFA-1
- 2011
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 186:9, s. 5085-5094
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Tidskriftsartikel (refereegranskat)abstract
- Several systemic autoimmune diseases display a prominent IFN signature. This is caused by a continuous IFN-α production by plasmacytoid dendritic cells (pDCs), which are activated by immune complexes (ICs) containing nucleic acid. The IFN-α production by pDCs stimulated with RNA-containing IC (RNA-IC) consisting of anti-RNP autoantibodies and U1 small nuclear ribonucleoprotein particles was recently shown to be inhibited by monocytes, but enhanced by NK cells. The inhibitory effect of monocytes was mediated by TNF-α, PGE2, and reactive oxygen species, but the mechanisms for the NK cell-mediated increase in IFN-α production remained unclear. In this study, we investigated the mechanisms whereby NK cells increase the RNA-IC–induced IFN-α production by pDCs. Furthermore, NK cells from patients with systemic lupus erythematosus (SLE) were evaluated for their capacity to promote IFN-α production. We found that CD56dim NK cells could increase IFN-α production >1000-fold after RNA-IC activation, whereas CD56bright NK cells required costimulation by IL-12 and IL-18 to promote IFN-α production. NK cells produced MIP-1α, MIP-1β, RANTES, IFN-γ, and TNF-α via RNA-IC–mediated FcγRIIIA activation. The IFN-α production in pDCs was promoted by NK cells via MIP-1β secretion and LFA-mediated cell–cell contact. Moreover, NK cells from SLE patients displayed a reduced capacity to promote the RNA-IC–induced IFN-α production, which could be restored by exogenous IL-12 and IL-18. Thus, different molecular mechanisms can mediate the NK cell-dependent increase in IFN-α production by RNA-IC–stimulated pDCs, and our study suggests that the possibility to therapeutically target the NK–pDC axis in IFN-α–driven autoimmune diseases such as SLE should be investigated.
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| 19. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 20. |
- Montgomery, Scott, et al.
(författare)
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Hospital admission due to infections in multiple sclerosis patients
- 2013
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Ingår i: European Journal of Neurology. - : Blackwell Publishing. - 1351-5101 .- 1468-1331. ; 20:8, s. 1153-1160
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Multiple sclerosis (MS) patients are at increased infection risk. Here the influences of susceptibility, severity and surveillance bias on infection-related hospital admission are assessed.Methods: Swedish registers identified 20 276 patients with MS, matched with 203 951 people from the general population without MS. Risk of first hospital admission for infection and mortality over 36 years was estimated by Poisson regression.Results: Multiple sclerosis was associated with an increased hospital admission risk for all infections, with an adjusted relative risk (and 95% confidence interval) of 4.26 (4.13-4.40). A proportion of this raised risk was probably due to surveillance and referral bias, although a raised risk remained when MS was compared with other immune-mediated diseases. The 1-month mortality rate following hospital admission for infection was higher in MS patients than in the comparison cohort, with a relative risk of 4.69 (4.21-5.22). There was no clear temporal trend in the results, and risks were higher in males and varied by MS phenotype.Conclusions: Higher hospital admission rates among MS patients for infection are likely to be due to a combination of surveillance bias, cautious medical management and greater susceptibility to severe infections. MS-related functional limitations may increase infection risk and this should be considered in MS management.
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| 21. |
- Kucharski, Daniel, et al.
(författare)
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Moderate-to-high intensity exercise with person-centered guidance influences fatigue in older adults with rheumatoid arthritis
- 2019
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Ingår i: Rheumatology International. - : Springer Science and Business Media LLC. - 0172-8172 .- 1437-160X. ; 39:9, s. 1585-1594
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Tidskriftsartikel (refereegranskat)abstract
- Fatigue is described as a dominant and disturbing symptom of rheumatoid arthritis (RA) regardless of the advances in pharmacological treatment. Fatigue is also found to correlate with depression. The objective was to evaluate the impact of moderate-to-high intensity, aerobic and resistance exercise with person-centered guidance on fatigue, anxiety and depression, in older adults with RA. Comparisons were made between older adults (> 65 years) with RA taking part in a 20-week moderate-to-high intensity exercise at a gym (n = 36) or in home-based exercise of light intensity (n = 38). Assessments were performed at baseline, at 20 weeks, and at 52 weeks. Outcomes were differences in Multidimensional Fatigue Inventory (MFI-20), Visual Analog Scale Fatigue (VAS fatigue), and Hospital Anxiety and Depression Scale (HADS). Analysis of metabolomics was also performed. The subscales "physical fatigue" and "mental fatigue" in MFI-20 and symptoms of depression using HADS depression scale improved significantly at week 20 in the exercise group compared with the control group. Exercise did not influence global fatigue rated by VAS or subscales "reduced motivation", "reduced activity" and "general fatigue" in MFI-20. No significant change was found on the anxiety index of HADS. The improvements in physical fatigue were associated with changes in the metabolism of lipids, bile acids, the urea cycle and several sugars. Moderate-to-high intensity exercise with person-centered guidance decreased fatigue and improved symptoms of depression and were accompanied by metabolic changes in older adults with RA.
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| 22. |
- Wang, Sen, et al.
(författare)
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Roles of glycoprotein glycosylation in the pathogenesis of an endemic osteoarthritis, Kashin–Beck disease, and effectiveness evaluation of sodium hyaluronate treatment
- 2020
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Ingår i: Turkish Journal of Medical Sciences. - : TÜBİTAK (the Scientific and Technological Research Council of Turkey). - 1300-0144 .- 1303-6165. ; 50:4, s. 1028-1037
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Tidskriftsartikel (refereegranskat)abstract
- Background/aim: We aimed to explore the roles of glycoprotein glycosylation in the pathogenesis of Kashin–Beck disease (KBD), and evaluated the effectiveness of sodium hyaluronate treatment.Materials and methods: Blood and saliva were collected from KBD patients before and after the injection of sodium hyaluronate. Normal healthy subjects were included as controls. Saliva and serum lectin microarrays and saliva and serum microarray verifications were used to screen and confirm the differences in lectin levels among the three groups.Results: In saliva lectin microarray, bindings to Sophora japonica agglutinin (SJA), Griffonia (Bandeiraea) simplicifolia lectin I (GSL-I), Euonymus europaeus lectin (EEL), Maackia amurensis lectin II (MAL-II), Sambucus nigra lectin (SNA), Hippeastrum hybrid lectin (HHL), and Aleuria aurantia lectin (AAL) were higher in the untreated KBD patients than in the control group. Increased levels of HHL, MAL-II, and GSL-I in the untreated KBD patients discriminated them in particular from the treated ones. Jacalin was lower in the untreated KBD patients compared to the treated KBD and control groups. In serum lectin microarray, HHL and peanut agglutinin (PNA) were increased in the untreated KBD group in comparison to the control one. AAL, Phaseolus vulgaris agglutinin (E+L) (PHA- E+L), and Psophocarpus tetragonolobus lectin I (PTL-I) were lower in the untreated KBD patients compared to the treated KBD and control groups. Hyaluronate treatment appeared to normalize SNA, AAL, and MAL-II levels in saliva, and HHL, PNA, AAL, PTL-I, and PHA-E+L levels in serum. Saliva reversed microarray verification confirmed significant differences between the groups in SNA and Jacalin, in particular for GSL-I levels, while serum reversed microarray verification indicated that HHL, PNA, and AAL levels returned to normal levels after the hyaluronate treatment. Lectin blot confirmed significant differences in HHL, AAL, and Jacalin in saliva, and HHL, PNA, PHA-E+L, and AAL in serum.Conclusion: HHL in saliva and serum may be a valuable diagnostic biomarker of KBD, and it may be used as follow-up for the hyaluronate treatment.
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| 23. |
- Ning, Yujie, et al.
(författare)
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Comparative analysis of the gut microbiota composition between knee osteoarthritis and Kashin-Beck disease in Northwest China
- 2022
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Ingår i: Arthritis Research & Therapy. - : BioMed Central. - 1478-6362. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Osteoarthritis (OA) and Kashin-Beck disease (KBD) both are two severe osteochondral disorders. In this study, we aimed to compare the gut microbiota structure between OA and KBD patients.Methods: Fecal samples collected from OA and KBD patients were used to characterize the gut microbiota using 16S rDNA gene sequencing. To identify whether gut microbial changes at the species level are associated with the genes or functions of the gut bacteria between OA and KBD groups, metagenomic sequencing of fecal samples from OA and KBD subjects was performed.Results: The OA group was characterized by elevated Epsilonbacteraeota and Firmicutes levels. A total of 52 genera were identified to be significantly differentially abundant between the two groups. The genera Raoultella, Citrobacter, Flavonifractor, g__Lachnospiraceae_UCG-004, and Burkholderia-Caballeronia-Paraburkholderia were more abundant in the OA group. The KBD group was characterized by higher Prevotella_9, Lactobacillus, Coprococcus_2, Senegalimassilia, and Holdemanella. The metagenomic sequencing showed that the Subdoligranulum_sp._APC924/74, Streptococcus_parasanguinis, and Streptococcus_salivarius were significantly increased in abundance in the OA group compared to those in the KBD group, and the species Prevotella_copri, Prevotella_sp._CAG:386, and Prevotella_stercorea were significantly decreased in abundance in the OA group compared to those in the KBD group by using metagenomic sequencing.Conclusion: Our study provides a comprehensive landscape of the gut microbiota between OA and KBD patients and provides clues for better understanding the mechanisms underlying the pathogenesis of OA and KBD.
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| 24. |
- Andersson, Ingemar, 1950-
(författare)
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Långvarig smärta - en introduktion
- 2010. - 2
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Ingår i: Smärta och smärtbehandling. - Stockholm : Liber. - 9789147084135 ; , s. 387-400
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 25. |
- Jonsson, Åsa, 1969-
(författare)
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How to create and analyze a Heart Failure Registry with emphasis on Anemia and Quality of Life
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background and aimsHeart failure (HF) is a major cause of serious morbidity and death in the population and one of the leading medical causes of hospitalization among people older than 60 years. The aim of this thesis was to describe how to create and how to analyze a Heart Failure Registry with emphasis on Anemia and Quality of Life. (Paper I) We described the creation of the Swedish Heart Failure Registry (SwedeHF) as an instrument, which may help to optimize the handling of HF patients and show how the registry can be used to improve the management of patients with HF. (Paper II) In order to show how to analyze a HF registry we investigated the prevalence of anemia, its predictors, and its association with mortality and morbidity in a large cohort of unselected patients with HFrEF included in the SwedeHF, and to explore if there are subgroups of HF patients identifying high--‐risk patients in need of treatment. (Paper III) In order to show another way of analyzing a HF registry we assessed the prevalence of, associations with, and prognostic impact of anemia in patients with HFmrEF and HFpEF. (Paper IV) Finally we examined the usefulness of EQ--‐ 5D as a measure of patient--‐reported outcomes among HF patients using different analytical models and data from the SwedeHF, and comparing results about HRQoL for patients with HFpEF and HFrEF.Methods An observational study based on the SwedeHF database, consisting of about 70 variables, was undertaken to describe how a registry is created and can be used (Paper I). One comorbidity (anemia) was applied to different types of HF patients, HFrEF (EF <40%) (II) and HFmrEF (EF 40--‐49% ) or HFpEF (> 50%) (III) analyzing the data with different statistical methods. The usefulness of EQ--‐5D as measure of patient--‐ reported outcomes was studied and the results about HRQoL were compared for patients with HFpEF and HFrEF (IV).ResultsIn the first paper (Paper I) we showed how to create a HF registry and presented some characteristics of the patients included, however not adjusted since this was not the purpose of the study. In the second paper (Paper II) we studied anemia in patients with HFrEF and found that the prevalence of anemia in HFrEF were 34 % and the most important independent predictors were higher age, male gender and renal dysfunction. One--‐year survival was 75 % with anemia vs. 81 % without (p<0,001). In the matched cohort after propensity score the hazard ratio associated with anemia was for all--‐cause death 1.34. Anemia was associated with greater risk with lower age, male gender, EF 30--‐39%, and NYHA--‐class I--‐II. In the third paper (Paper III) we studied anemia in other types of HF patients and found that the prevalence in the overall cohort in patients with EF > 40% was 42 %, in HFmrEF 38 % and in HFpEF (45%). Independent associations with anemia were HFpEF, male sex, higher age, worse New York Heart Association class and renal function, systolic blood pressure <100 mmHg, heart rate ≥70 bpm, diabetes, and absence of atrial fibrillation. One--‐year survival with vs. without anemia was 74% vs. 89% in HFmrEF and 71% vs. 84% in HFpEF (p<0.001 for all). Thus very similar results in paper II and III but in different types of HF patients. In the fourth paper (Paper IV) we studied the usefulness of EQ--‐5D in two groups of patients with HF (HFpEF and HFrEF)) and found that the mean EQ--‐5D index showed small reductions in both groups at follow--‐up. The patients in the HFpEF group reported worsening in all five dimensions, while those in the HFrEF group reported worsening in only three. The Paretian classification showed that 24% of the patients in the HFpEF group and 34% of those in the HFrEF group reported overall improvement while 43% and 39% reported overall worsening. Multiple logistic regressions showed that treatment in a cardiology clinic affected outcome in the HFrEF group but not in the HFpEF group (Paper IV).Conclusions The SwedeHF is a valuable tool for improving the management of patients with HF, since it enables participating centers to focus on their own potential for improving diagnoses and medical treatment, through the online reports (Paper I). Anemia is associated with higher age, male gender and renal dysfunction and increased risk of mortality and morbidity (II, III). The influence of anemia on mortality was significantly greater in younger patients in men and in those with more stable HF (Paper II, III). The usefulness of EQ--‐5D is dependent on the analytical method used. While the index showed minor differences between groups, analyses of specific dimensions showed different patterns of change in the two groups of patients (HFpEF and HFrEF). The Paretian classification identified subgroups that improved or worsened, and can therefore help to identify needs for improvement in health services (Paper IV).
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