2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases.

OBJECTIVES: Fatigue is prevalent in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and recognised as one of the most challenging symptoms to manage. The existence of multiple factors associated with driving and maintaining fatigue, and the evidence about what improves fatigue has led to a multifaceted approach to its management. However, there are no recommendations for fatigue management in people with I-RMDs. This lack of guidance is challenging for those living with fatigue and health professionals delivering clinical care. Therefore, our aim was to develop EULAR recommendations for the management of fatigue in people with I-RMDs. METHODS: A multidisciplinary taskforce comprising 26 members from 14 European countries was convened, and two systematic reviews were conducted. The taskforce developed the recommendations based on the systematic review of evidence supplemented with taskforce members' experience of fatigue in I-RMDs. RESULTS: Four overarching principles (OAPs) and four recommendations were developed. OAPs include health professionals' awareness that fatigue encompasses multiple biological, psychological and social factors which should inform clinical care. Fatigue should be monitored and assessed, and people with I-RMDs should be offered management options. Recommendations include offering tailored physical activity and/or tailored psychoeducational interventions and/or, if clinically indicated, immunomodulatory treatment initiation or change. Patient-centred fatigue management should consider the individual's needs and preferences, their clinical disease activity, comorbidities and other psychosocial and contextual factors through shared decision-making. CONCLUSIONS: These 2023 EULAR recommendations provide consensus and up-to-date guidance on fatigue management in people with I-RMDs.

How is the patient perspective captured in ANCA-associated vasculitis research? An integrative review.

Objective: The aim was to describe how the patient perspective is captured in clinical research on ANCA-associated vasculitis (AAV). Methods: This integrative review included 2149 publications found in four different databases and manual searches. After screening, 156 articles remained. All articles were sorted and categorized, and 77 original articles were analysed further. Results: The patient perspective was captured with patient-reported outcome measures (PROMs), single-item questionnaires, project-specific questionnaires and interviews. The most common aspects measured were health-related quality of life, anxiety and depression, and fatigue, and the least common were lifestyle habits, relationships and self-management. Conclusion: The patient perspective was captured predominantly with generic PROMs and occasionally with a qualitative approach. AVV is a lifelong disease, and the results from this review show that not all aspects of importance to patients are covered with the PROMs used in research. Future studies should include the areas that are the most important for patients.

"I've never experienced this before, I don't know what I need"- a qualitative study on social support and self-care during the first year after an aneurysmal subarachnoid hemorrhage.

PURPOSE: To describe perceived support, support needs and self-care among individuals during the first year after an aneurysmal subarachnoid hemorrhage (aSAH). MATERIAL AND METHODS: The study had a qualitative descriptive design with a deductive approach using the concepts of social support and self-care. The informants (n = 16) had been treated for aSAH at a university hospital in Sweden and were interviewed one year after the event. The interviews were transcribed verbatim and a manifest directed content analysis was performed. RESULTS: The findings revealed great variation in the narratives, both regarding the support received and the support desired, as well as the described self-care abilities. All codes were covered by the predefined categories and subcategories: social support (including esteem/emotional support, informational support, social companionship, instrumental support) and self-care (including self-management, self-monitoring, symptom management, self-efficacy). CONCLUSIONS: Not being offered the support needed aggravated the possibility to manage the new life after aSAH. The confidence in self-care abilities was influenced by symptom control and how much life had changed in comparison to before the aSAH. Educational efforts are suggested to facilitate the transition from hospital discharge and to promote specialized rehabilitation at home and self-care abilities.

Early supported discharge can be beneficial for aneurysmal subarachnoid (aSAH) patients, including a discharge plan with documented responsibility for continuing rehabilitation and information on follow-ups.Generic rehabilitation programs need to be adapted to a person-centered approach due to the large variation in aSAH patients' support needs and self-care abilities.When planning educational efforts for aSAH patients, the use of a workshop format in the company of others affected is suggested, to share experiences and increase the sense of self-efficacy.

"My head feels like it has gone through a mixer" - a qualitative interview study on recovery 1 year after aneurysmal subarachnoid hemorrhage.

PURPOSE: To describe patients' perceived and expected recovery 1 year after aneurysmal subarachnoid hemorrhage (aSAH). MATERIALS AND METHODS: Semi-structured interviews were conducted with 16 persons 1 year after aSAH. Inductive manifest qualitative content analysis was used. RESULTS: The analysis resulted in two categories and seven subcategories. The category "A spectrum of varying experiences of recovery" includes four subcategories describing physical recovery, mental recovery, alterations in social life, and perceived possibilities to return to normality. Some informants felt that life was almost as before, while others described a completely different life, including a new view of self, altered relationships, not being able to return to work, and effects on personal finances. The category "A spectrum of reflections and expectations of recovery" comprises three subcategories depicturing that expectations of recovery were influenced by existential thoughts, describing what they based own expectations of recovery on, and how expectations from others influenced them. CONCLUSIONS: aSAH was perceived as a life-changing event. The changes impacted on informants' view of self and relationships, and they perceived new barriers in their living conditions. Lack of information on expected recovery was expressed and expectations of recovery were at times unrealistic.IMPLICATIONS FOR REHABILITATIONContracting an aneurysmal subarachnoid hemorrhage (aSAH) is a life-changing event with possible impact on a variety of areas in daily life.There is a need for improved information to aSAH survivors and their significant others on the course of the recovery and possible long-term consequences.aSAH survivors may need assistance to balance unrealistic expectations on recovery.

Exploring the educational needs of patients with systemic vasculitis using the educational needs assessment tool.

Objectives: Knowledge and health literacy enable patients to monitor symptoms and disease impact. Educational needs have previously been explored in rheumatology, but scarcely for patients with ANCA-associated vasculitis (AAV). The aim of the study was to assess the educational needs among patients with AAV using the educational needs assessment tool (ENAT). Methods: This was a cross-sectional observational study including adults with AAV. Educational needs were captured by ENAT. Total ENAT (0-117 points, with higher numbers indicating higher educational need) and the seven domains (managing pain, movement, feelings, disease process, treatment, self-management and support systems) were explored regarding sex, age, education, diagnosis, disease duration and disease activity. To compare domains, a percentage response (0-100%) was calculated. Results: One hundred and seventy-eight individuals (50% men; 34% with disease duration ≤2 years) were included. The total ENAT mean was 66.5 (s.d. 26.6; 57%), with domains as follows: disease process, 78%; self-management, 69%; treatments, 64%; feelings, 56%; managing pain, 48%; support systems, 47%; and movement, 41%. Higher educational needs were found among women in the domains movement, feelings and disease process and in total ENAT (all P < 0.04) compared with men. Higher educational needs were also seen in patients with disease duration ≤2 years regarding disease process, self-management and support systems and in total ENAT compared with patients with longer disease duration (all P < 0.03). Conclusion: This study revealed great educational needs among AAV patients. Some groups expressed higher needs (women and those with shorter disease duration). Increased education for patients with AAV might lead to improved self-care and treatment adherence.

Spatial coherence and the persistence of high diversity in spatially heterogeneous landscapes.

Our planet hosts a variety of highly diverse ecosystems. The persistence of high diversity is generally attributed to factors such as the structure of interactions among species and the dispersal of species in metacommunities. Here, we show that large contiguous landscapes-that are characterized by high dispersal-facilitate high species richness due to the spatial heterogeneity in interspecies interactions. We base our analysis on metacommunities under high dispersal where species densities become equal across habitats (spatially coherent). We find that the spatially coherent metacommunity can be represented by an effective species interaction-web that has a significantly lower complexity than the constituent habitats. Our framework also explains how spatial heterogeneity eliminates differences in the effective interaction-web, providing a basis for deviations from the area-heterogeneity tradeoff. These results highlight the often-overlooked case of high dispersal where spatial coherence provides a novel mechanism for supporting high diversity in large heterogeneous landscapes.

First and second cycle nursing students' perceptions of the clinical learning environment in acute care settings - A comparative crossectional study using the CLES+T scale.

BACKGROUND: Research has shown that the clinical learning environment can both facilitate and hinder students' learning. Students' perceptions need to be evaluated, preferably using nationally and internationally validated instruments. In Sweden, there is a lack of research about students' evaluation in acute care settings and from the perspectives of different levels of students. OBJECTIVES: The aim was to explore and compare perceptions of the clinical learning environment of first- and second-cycle nursing students in an acute care setting using the Clinical Learning Environment, Supervision and Nurse Teacher scale (CLES+T). DESIGN: The design involves cross-sectional data collection with comparisons between groups. SETTING AND PARTICIPANTS: Data were collected from a convenience sample of first- and second-cycle students at the end of their clinical placements in an acute care setting at a university hospital. METHODS: A paper version and a web version of the culturally adapted version of CLES+T was filled out by the students. An independent t-test was used to explore the differences between CLES+T scores and distribution methods and educational level. Internal consistency was evaluated using Cronbach's alpha. RESULTS: Overall, the students (N = 179) were satisfied with the clinical learning environment. There was no significant difference in the total score (m = 4.31, SD = 0.63) between first- and second-cycle students except for the subscale of "Premises of nursing on the ward" and the individual items "The ward's nursing philosophy was clearly defined" and "Patients received individual nursing care", showing that the first-cycle students were more satisfied compared to the second-cycle students. The scale demonstrated high internal consistency (α = 0.97 vs. 0.96) for the paper survey and the web survey, respectively. CONCLUSIONS: Our findings provide initial support for the CLES+T as a useful instrument to evaluate the clinical learning environment at different levels of education and in different contexts regardless of distribution method.

Identification and Prediction of Fatigue Trajectories in People With Rheumatoid Arthritis.

OBJECTIVE: We aimed to identify groups demonstrating different long-term trajectories of fatigue among people with rheumatoid arthritis and determine baseline predictors for these trajectories. METHODS: Our study included 2741 people aged 18 to 75 years who were independent in daily living. Data were collected from the Swedish Rheumatology Quality Register and questionnaires at baseline, 14 months, and 26 months. Fatigue was rated on a 100-mm visual analog scale. K-means cluster analysis was used to identify fatigue trajectories. Multinomial logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals for potential predictors of trajectory membership. RESULTS: The mean age was 60 years, 73% of participants were female, and the mean baseline fatigue level was 39. Three distinct fatigue trajectories were identified, representing mild (mean 15, n = 1024), moderate (mean 41, n = 986), and severe (mean 71, n = 731) fatigue. Consistent patterns indicated that poorer health perception (ORs 1.68-18.40), more pain (ORs 1.38-5.04), anxiety/depression (ORs 0.85-6.19), and activity limitation (ORs 1.43-7.39) were associated with more severe fatigue. Those in the severe fatigue group, compared with those in the mild fatigue group, were more likely to be college educated than university educated (OR 1.56) and less likely to maintain physical activity (OR 0.54). Those in the severe fatigue group, compared with those in both the moderate (OR 0.67) and mild (OR 0.59) fatigue groups, were less likely to have one additional adult in the household. CONCLUSION: This study identified stable fatigue trajectories, predicted by health perception, pain, anxiety/depression, activity limitation, educational level, maintained physical activity, and household composition. Interventions aimed at reducing these disabilities and supporting physical activity behaviors may help reduce fatigue.

Spatial heterogeneity enhance robustness of large multi-species ecosystems.

Understanding ecosystem stability and functioning is a long-standing goal in theoretical ecology, with one of the main tools being dynamical modelling of species abundances. With the help of spatially unresolved (well-mixed) population models and equilibrium dynamics, limits to stability and regions of various ecosystem robustness have been extensively mapped in terms of diversity (number of species), types of interactions, interaction strengths, varying interaction networks (for example plant-pollinator, food-web) and varying structures of these networks. Although many insights have been gained, the impact of spatial extension is not included in this body of knowledge. Recent studies of spatially explicit modelling on the other hand have shown that stability limits can be crossed and diversity increased for systems with spatial heterogeneity in species interactions and/or chaotic dynamics. Here we show that such crossing and diversity increase can appear under less strict conditions. We find that the mere possibility of varying species abundances at different spatial locations make possible the preservation or increase in diversity across previous boundaries thought to mark catastrophic transitions. In addition, we introduce and make explicit a multitude of different dynamics a spatially extended complex system can use to stabilise. This expanded stabilising repertoire of dynamics is largest at intermediate levels of dispersal. Thus we find that spatially extended systems with intermediate dispersal are more robust, in general have higher diversity and can stabilise beyond previous stability boundaries, in contrast to well-mixed systems.

Factors associated with self-reported capacity to walk, jog and run in individuals with systemic lupus erythematosus.

OBJECTIVES: This study aims to explore how disease and health-related quality of life (HRQOL) factors are associated with self-reported physical capacity in walking, jogging and running in systemic lupus erythematosus (SLE). PATIENTS AND METHODS: This cross-sectional study is part of an ongoing cohort research project which started in 2014. A total of 198 patients (21 males, 177 females; mean age 51.5±16.1 years; range, 20 to 82 years) with SLE answered a question concerning physical capacity and the answers were categorized as low (can walk less than 2 km) and high (can jog and run at least 2 km) capacity. Additional measurements of disease activity (Systemic Lupus Activity Measure-Revised, SLAM-R), organ damage (Systemic Lupus International Collaborating Clinics-Damage Index, SLICC-DI), physical activity (International Physical Activity Questionnaire-Short Form, IPAQ-SF), exercise during the past year, Hospital Anxiety and Depression Scale (HADS), and HRQOL according to EuroQol five-dimension score and EuroQol visual analog scale (EQ-VAS) were included. The independent variables in the multiple logistic regression analysis were age, body mass index (BMI), disease duration, SLAM-R, SLICC-DI, IPAQ-SF category, sitting hours (IPAQ-SF), and exercise during the past year as well as HADS and EQ-VAS. RESULTS: Patients that reported low physical capacity (n=120) were older (p<0.001), had longer disease duration (p<0.001), had more organ damage (p<0.001), reported that they were less physically active (p=0.003), exercised less during the past year (p=0.001), reported more pain/discomfort and depressive symptom (p<0.001) and had lower overall HRQOL (p<0.001) and mobility and usual activities than those that reported high capacity (n=78). The regression analysis showed that age (median ≤49 vs >49) (Exp) (B): 4.52 (95% confidence interval [CI]: 2.05 to 9.98) (p<0.001), disease duration (median ≤17 vs >17) Exp (B): 2.53 (95% CI: 1.15 to 5.60) (p=0.02), SLICC-DI (median <1 vs ≥1) Exp (B): 3.60 (95% CI: 1.48 to 8.73) (p=0.005), and EQ-VAS (median <72 vs ≥72) Exp (B): 4.63 (95% CI: 2.13 to 10.05) (p<0.001) were significant factors associated with physical capacity (Nagelkerke R Squared=0.46). CONCLUSION: Patients with low physical capacity were less physically active, exercised less and had more pain and depressive symptoms than those that reported a high capacity. However, only age, disease duration, organ damage and overall HRQOL were indicators of low physical capacity. In order to increase physical capacity in the management of SLE, it is important to address overall HRQOL.

Quick Systemic Lupus Activity Questionnaire (Q-SLAQ): a simplified version of SLAQ for patient-reported disease activity.

OBJECTIVES: Most indices of disease activity in SLE combine physicians' assessments and laboratory tests. However, there is also a need to capture patients' perspectives of disease activity. Consequently, we need new, preferably quick and easy instruments to collect this information, which can be very useful for online consultations and registry purposes. We compared patients' assessments of SLE disease impact/activity, as reported by a shorter version of the Quick Systemic Lupus Activity Questionnaire (Q-SLAQ), with physicians' assessments using SLE Activity Measure (SLAM) and SLE Disease Activity Index (SLEDAI-2K) and with the original Systemic Lupus Activity Questionnaire (SLAQ). METHODS: Patients with SLE (n=115), with a disease duration of 15 years (IQR 17), completed the Q-SLAQ prior to physicians' assessments by SLAM and SLEDAI-2K. A second set of patients (n=85) with similar characteristics filled out Q-SLAQ and SLAQ. Spearman's ρ correlations were explored between patients' total Q-SLAQ and subscales (Symptom Score, Patient's Global Disease Activity) and physicians' SLAM and SLEDAI-2K, with and without laboratory items (SLAM-nolab and SLEDAI-2K-nolab) and SLAQ. Corresponding items in Q-SLAQ and SLAM were compared. RESULTS: Correlations between patients' and physicians' assessments were higher for SLAM-nolab (total Q-SLAQ, ρ=0.71; Symptom Score, ρ=0.67; and Patient's Global Disease Activity, ρ=0.68) than for the original SLAM (total Q-SLAQ, ρ=0.53; Symptom Score, ρ=0.50; and Patient's Global Disease Activity, ρ=0.53). Regarding specific symptoms, fatigue (ρ=0.72) and alopecia (ρ=0.71) correlated best, while pulmonary/respiratory symptoms correlated least (ρ=0.19, p=0.039). Physicians assessment with SLEDAI-2K-nolab correlated weakly with patients' assessments (total Q-SLAQ, ρ=0.30; Symptom Score, ρ=0.30; and Patient's Global Disease Activity, ρ=0.36). Bivariate correlations between Q-SLAQ and SLAQ were good (ρ=0.82-0.96). CONCLUSIONS: Q-SLAQ and the original SLAQ performed equally well, demonstrating that the shorter Q-SLAQ can safely be used to monitor patients' perception of disease impact/activity. We also noted an intriguing discrepancy between physicians' and patients' evaluations of pulmonary/respiratory symptoms, which requires further investigations.

Contribution of abnormal BMI to adverse health-related quality of life outcomes after a 52-week therapy in patients with SLE.

OBJECTIVES: To investigate whether abnormal BMI is associated with adverse health-related quality of life (HRQoL) outcome, including severe fatigue, after 52 weeks of standard therapy plus belimumab or placebo in patients with SLE. METHODS: We analysed data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials (n = 1684). Adverse HRQoL was defined as SF-36 scores ≤ the fifth percentile in age- and sex-matched US population-based subjects, and FACIT-F scores <30. We compared BMI groups using the Pearson's χ2 test, and assessed independence with multivariable logistic regression analysis. RESULTS: Overweight (BMI ≥25 kg/m2) and obese (BMI ≥30 kg/m2) patients showed increased likelihood to exhibit adverse SF-36 physical component summary (OR: 1.8; 95% CI: 1.4, 2.3; P <0.001 and OR: 2.4; 95% CI: 1.8, 3.2; P <0.001, respectively) and FACIT-F (OR: 1.3; 95% CI: 1.1, 1.6; P = 0.010 and OR: 1.5; 95% CI: 1.2, 2.0; P = 0.002, respectively) scores at week 52. Underweight was associated with adverse SF-36 mental component summary scores, also after adjustment for sex, ancestry, age, disease duration, disease activity, organ damage and prednisone dose during the study period (OR: 2.1; 95% CI: 1.2, 3.6; P = 0.007). Addition of belimumab to standard therapy independently protected against adverse SF-36 general health (OR: 0.8; 95% CI: 0.6, 1.0; P = 0.025) and FACIT-F < 30 (OR: 0.8; 95% CI: 0.6, 1.0; P = 0.018). CONCLUSION: Overweight and obesity contributed to adverse physical and mental HRQoL outcomes after therapeutic intervention in SLE patients, and underweight contributed to adverse mental HRQoL outcome. A protective effect of belimumab against adverse general health and severe fatigue was implicated.

Impact of overweight and obesity on patient-reported health-related quality of life in systemic lupus erythematosus.

OBJECTIVES: Associations between BMI and health-related quality of life (HRQoL) in SLE have been implied, but data are scarce. We determined the impact of overweight and obesity on HRQoL in a large SLE population. METHODS: We pooled cross-sectional baseline data from the BLISS-52 (NCT00424476) and BLISS-76 (NCT00410384) trials (N = 1684). HRQoL was evaluated using the 36-item Short Form Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale and the European Quality of Life 5-dimension questionnaire (EQ-5D). Comparisons between BMI groups were conducted using the Mann-Whitney U test and adjustments using linear regression. Clinical relevance was determined by minimal clinically important differences (MCIDs). RESULTS: In total, 43.2% of the patients had BMI above normal and 17.4% were obese. Overweight and obese patients reported worse SF-36 physical component summary (PCS), physical functioning, role physical, bodily pain and FACIT-Fatigue scores than normal weight patients. Divergences were greater than corresponding MCIDs and more prominent with increasing BMI. Despite no clinically important difference in SF-36 mental component summary scores across BMI categories, patients experienced progressively diminished vitality and social functioning with increasing BMI. In linear regression analysis, BMI above normal and obesity were associated with worse PCS (standardized coefficient ß = -0.10, P < 0.001 and ß = -0.17, P < 0.001, respectively), FACIT-Fatigue (ß = -0.11, P < 0.001 and ß = -0.16, P < 0.001) and EQ-5D (ß = -0.08, P = 0.001 and ß = -0.12, P < 0.001) scores, independently of demographic and disease-related factors. The impact of BMI on the PCS and FACIT-Fatigue was more pronounced than that of SLE activity. CONCLUSION: Patients with SLE and BMI above normal experienced clinically important HRQoL diminutions in physical aspects, fatigue and social functioning. A survey of potential causality underlying this association is warranted.

Predicting collapse of complex ecological systems: quantifying the stability-complexity continuum.

Dynamical shifts between the extremes of stability and collapse are hallmarks of ecological systems. These shifts are limited by and change with biodiversity, complexity, and the topology and hierarchy of interactions. Most ecological research has focused on identifying conditions for a system to shift from stability to any degree of instability-species abundances do not return to exact same values after perturbation. Real ecosystems likely have a continuum of shifting between stability and collapse that depends on the specifics of how the interactions are structured, as well as the type and degree of disturbance due to environmental change. Here we map boundaries for the extremes of strict stability and collapse. In between these boundaries, we find an intermediate regime that consists of single-species extinctions, which we call the extinction continuum. We also develop a metric that locates the position of the system within the extinction continuum-thus quantifying proximity to stability or collapse-in terms of ecologically measurable quantities such as growth rates and interaction strengths. Furthermore, we provide analytical and numerical techniques for estimating our new metric. We show that our metric does an excellent job of capturing the system's behaviour in comparison with other existing methods-such as May's stability criteria or critical slowdown. Our metric should thus enable deeper insights about how to classify real systems in terms of their overall dynamics and their limits of stability and collapse.

Stability of ecosystems enhanced by species-interaction constraints.

Ecosystem stability is a central question both in theoretical and applied biology. Dynamical systems theory can be used to analyze how growth rates, carrying capacities, and patterns of species interactions affect the stability of an ecosystem. The response to increasing complexity has been extensively studied and the general conclusion is that there is a limit. While there is a complexity limit to stability at which global destabilisation occurs, the collapse rarely happens suddenly if a system is fully viable (no species is extinct). In fact, when complexity is successively increased, we find that the generic response is to go through multiple single-species extinctions before a global collapse. In this paper we demonstrate this finding via both numerical simulations and elaborations of theoretical predictions. We explore more biological interaction patterns, and, perhaps most importantly, we show that constrained interaction structures-a constant row sum in the interaction matrix-prevent extinctions from occurring. This makes an ecosystem more robust in terms of allowed complexity, but it also means singles-species extinctions do not precede or signal collapse-a drastically different behavior compared to the generic and commonly assumed case. We further argue that this constrained interaction structure-limiting the total interactions for each species-is biologically plausible.

The Impact of Belimumab and Rituximab on Health-Related Quality of Life in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: Accumulating evidence supports an impaired health-related quality of life (HRQoL) in patients with systemic lupus erythematosus (SLE). We investigated the effects of 2 biologic treatments on HRQoL of patients with SLE. METHODS: Patients with SLE from the Karolinska University Hospital treated with belimumab (n = 34) or rituximab (n = 35) were included; normative values derived from Swedish population-based controls matched for age and sex were used for the purpose of comparisons. Data were collected prospectively at treatment initiation and at months 3, 6, 12, and 24, using the Short Form 36 (SF-36) health questionnaire, the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) scale, the EuroQol 5-dimension (EQ-5D) instrument, and the Stanford Health Assessment Questionnaire disability index (HAQ DI). RESULTS: Substantial decrements from Swedish norms were observed across all SF-36 domains at baseline. Patients treated with belimumab reported gradual improvements in the SF-36 physical component summary (significant from month 12; P = 0.023) and FACIT-Fatigue (significant by month 24; P = 0.001), no changes in EQ-5D scores, and improvements in HAQ DI by month 6 (P = 0.014). Patients treated with rituximab showed rapid improvements in the SF-36 mental component summary and FACIT-Fatigue by month 3 (P = 0.031 and P = 0.007, respectively), as well as improvements in EQ-5D at month 6 (P = 0.016) and HAQ DI at month 3 (P = 0.033). Based on baseline evaluations, patients receiving antimalarial agents (n = 33) performed better in the SF-36 social functioning (P = 0.022) and mental health (P = 0.023) domains compared to patients who did not receive antimalarial agents (n = 36). CONCLUSION: Our results corroborated previous findings of considerable HRQoL impairments in patients with SLE. Patients' perceptions of HRQoL showed discrepant patterns over time in the 2 treatment groups and could provide additional information along with the clinical evaluation of biologic therapy in SLE. Further survey on the effects of antimalarial agents on the HRQoL of patients with SLE in larger cohorts is merited.

Associations between fatigue and physical capacity in people moderately affected by rheumatoid arthritis.

To explore the contribution of physical capacity in explaining variations in fatigue among people with rheumatoid arthritis (RA). This study included participants recruited for a physical activity intervention. Data were collected from the Swedish Rheumatology Quality Registers, from questionnaires on fatigue, activity limitation, perceived health, pain and anxiety/depression and from physical capacity tests (lower limb function, grip strength, and aerobic capacity). We used logistic regression to estimate the association between severe fatigue (≥ 50, visual analogue scale 0-100) and (A) independent variables related to disease and disease impact and (B) model A plus physical capacity tests. Pooled odds ratio tests compared model fit. Out of the 269 participants (mean age 60 years, mean disease activity score [DAS28] 2.8), severe fatigue was reported by 35%. The three variables which were statistically significantly associated with severe fatigue (p < 0.05) in both models were perceived health, pain and anxiety/depression. Anxiety/depression demonstrated the largest effect size with odds ratios of 2.43 (95% CI 1.20, 4.94) in model A and 2.58 (95% CI 1.25, 5.32) in model B. The likelihood ratio test indicated that model B was a better fit to the data than model A with Χ2 (df 3) = 2.65, p = 0.048. Severe fatigue in people with RA is associated with self-rated health, pain and anxiety/depression rather than with physical capacity. Future studies should be prospective, use multidimensional assessments of fatigue to explore the influence of physical capacity and control for possible influence of comorbidities associated with fatigue.

Kynurenine pathway is altered in patients with SLE and associated with severe fatigue.

OBJECTIVE: Fatigue has been reported as the most disturbing symptom in a majority of patients with SLE. Depression is common and often severe. Together these symptoms cause significant morbidity and affect patients with otherwise relatively mild disease. Tryptophan and its metabolites in the kynurenine pathway are known to be important in several psychiatric conditions, for example, depression, which are often also associated with fatigue. We therefore investigated the kynurenine pathway in patients with SLE and controls. METHODS: In a cross-sectional design plasma samples from 132 well-characterised patients with SLE and 30 age-matched and gender-matched population-based controls were analysed by liquid chromatography tandem mass spectrometry to measure the levels of tryptophan and its metabolites kynurenine and quinolinic acid. Fatigue was measured with Fatigue Severity Scale and depression with Hospital Anxiety and Depression Scale. SLE disease activity was assessed with Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). RESULTS: The kynurenine/tryptophan ratio, as a measure of indoleamine 2,3-dioxygenase (IDO) activity, was increased in patients with SLE. Patients with active disease (SLEDAI ≥6) showed lower tryptophan levels compared with controls (54 µM, SD=19 vs 62 µM, SD=14, p=0.03), although patients with SLE overall did not differ compared with controls. Patients with SLE had higher levels of tryptophan metabolites kynurenine (966 nM, SD=530) and quinolinic acid (546 nM, SD=480) compared with controls (kynurenine: 712 nM, SD=230, p=0.0001; quinolinic acid: 380 nM, SD=150, p=0.001). Kynurenine, quinolinic acid and the kynurenine/tryptophan ratio correlated weakly with severe fatigue (rs =0.34, rs =0.28 and rs =0.24, respectively) but not with depression. CONCLUSIONS: Metabolites in the kynurenine pathway are altered in patients with SLE compared with controls. Interestingly, fatigue correlated weakly with measures of enhanced tryptophan metabolism, while depression did not. Drugs targeting enzymes in the kynurenine pathway, for example, IDO inhibitors or niacin (B12) supplementation, which suppresses IDO activity, merit further investigation as treatments in SLE.

TNF-α and plasma albumin as biomarkers of disease activity in systemic lupus erythematosus.

OBJECTIVES: Composite criteria/indices are presently used to diagnose and monitor patients with systemic lupus erythematosus (SLE). Biomarkers for these purposes would be helpful in clinical practice. We therefore evaluated a large panel of cytokines and basic laboratory tests and investigated their performance as discriminators versus controls and as biomarkers of disease activity (DA). METHODS: We examined 437 patients with SLE, fulfilling American College of Rheumatology-82 criteria, and 322 matched controls. DA was assessed according to both SLE DA Index 2000 (SLEDAI-2K) and SLE Activity Measure (SLAM). British Isles Lupus Activity Group (BILAG) was used to assess renal DA. Additionally, 132 patients self-assessed their Global Disease Activity (PtGDA). Mesoscale Discovery 30-plex cytokine assay and routine blood chemistry was performed on fasting EDTA-plasma. RESULTS: Of 26 tested biomarkers, we identified TNF-α as the superior discriminator between patients with SLE and controls (median=4.5 pg/mL, IQR=3.1-6.2 vs median=2.3 pg/mL, IQR=2.0-2.8). The strongest correlations to SLEDAI-2K and SLAM were obtained with TNF-α (Spearman rho (ρ)=0.32 and ρ=0.34, respectively), partly driven by the nephritis subgroup, and with p-albumin (ρ=-0.33 and ρ=-0.31, respectively). P-albumin was decreased and TNF-α was increased in patients with kidney involvement (renal BILAG A/B vs C/D/E, p=4×10-16 and p=6×10-9 respectively). IP-10 was increased in patients with joint involvement (SLAM item 24≥2 vs ≤1, p=0.0005) but did not differ when comparing patients with active/inactive kidney involvement. The most powerful correlations to PtGDA was observed with p-albumin (ρ=-0.42), IL-6 (ρ=0.30) and TNF-α (ρ=0.29). CONCLUSION: TNF-α and p-albumin both performed well as discriminators between patients with SLE and controls and as proxies for DA according to both rheumatologists' and patients' assessments. In particular, renal DA was well reflected by TNF-α. We propose that the TNF-α and p-albumin merit further investigations as clinically useful biomarkers in SLE. We also observed that the pattern of activated cytokines varies with organ involvement.

Excess atherosclerosis in systemic lupus erythematosus,-A matter of renal involvement: Case control study of 281 SLE patients and 281 individually matched population controls.

BACKGROUND: Systemic lupus erythematosus (SLE), is a heterogeneous disease which predominantly affects young females (90%). SLE is associated with a shorter life expectancy than in the general population. Standardized mortality ratios (SMR) of 2.4 have been reported, which is comparable to diabetes. In modern societies cardiovascular disease (CVD) is the major cause of premature mortality. Accelerated atherosclerosis is generally assumed to be the underlying cause for SLE related CVD. However, previous studies diverge regarding whether atherosclerosis is more common in SLE than in controls. With this in mind and based on own clinical experience we hypothesized that accelerated atherosclerosis is not a general feature of SLE, but prevails in SLE subgroups. METHODS: 281 SLE patients and 281 individually age and sex matched population controls, were investigated clinically. Fasting blood samples and risk factor data were collected. All participants were subject to B-mode ultrasonography of the carotid arteries. Carotid plaque occurrence and mean intima media thickness (mIMT) were recorded. Two SLE subgroups previously described to be at high CVD risk; 1) patients with nephritis and 2) patients with anti-phospholipid antibodies (aPL), and one subgroup reported to be at comparatively lower CVD risk; patients positive for Sjögren´s syndrome antigens A/B (SSA/SSB) antibodies were analyzed separately in comparison with their respective matched controls. RESULTS: Median age was 49 (IQR 36-59) years, 93% were females. Manifest CVD; ischemic heart, cerebro- and peripheral vascular disease, prevailed in patients (12% vs. 1%, p<0.0001). Overall plaque prevalence did not differ (20% vs. 16%), but patients had slightly higher mIMT than controls (0.56 vs. 0.53 mm, p<0.0033). After age adjustment plaques, but not mIMT, remained associated with previous CVD events. Therefore we focused further analyses on plaques, a more robust measure of atherosclerosis. Patients with nephritis (40%), but neither aPL (25%) nor SSA/SSB (40%) positive patients, had more plaques than their respective controls (23% vs. 11%, p = 0.008). Notably, patients with nephritis were younger than other SLE patients (45 vs.49 years, p = 0.02). To overcome the confounding effect of age we performed an age-matched nested case-control analysis, which demonstrated that patients with nephritis had twice as often plaques (23%) as both non-nephritis patients (11%, p = 0.038) and controls (12%, p = 0.035). CONCLUSIONS: In SLE excess carotid plaques are essentially confined to the SLE subgroup with nephritis. This subgroup had plaques twice as often as age-matched non-nephritis SLE patients and population controls. Non-nephritis SLE patients, including the aPL positive subgroup, which has a high CVD risk, had similar prevalence of plaques as controls. To prevent later CVD events, this novel observation calls for risk factor screening and initiation of anti-atherosclerotic treatment selectively in SLE nephritis patients. Preferably at nephritis onset, which is often at a young age. In a general perspective this study demonstrates the importance to perform careful clinical subgroup analyses when investigating heterogeneous, hitherto not clearly defined, conditions like SLE.