Physical activity guidance in the rheumatology clinic-what matters for patients with rheumatoid arthritis? A qualitative study.

Higher proportions of patients with rheumatoid arthritis (RA) are physically inactive compared to the general population. A barrier to engaging in physical activity (PA) may be lack of consistent PA guidance from health professionals (HPRs). This qualitative study aimed to explore daily PA levels and the patients' perspectives on current and future PA guidance from HPRs. We recruited 20 participants from five rheumatology departments in Denmark. The participants differed in socio-demography and clinical characteristics based on results from an earlier cross-sectional study. The interviews were conducted by telephone, online platforms or face-to-face. Data analysis was based on reflexive thematic analysis. Thirteen participants were female and mean age was 55 years. We generated four themes; (1) Acceptance of the arthritis is a process, which attributed to acknowledging RA as part of life before fully engagement in PA and exercise. (2) Daily physical activity-motivation, barriers and benefits, reflecting the participants' preferred types of activities and motivations and barriers to PA. (3) Physical activity guidance-your own responsibility? This theme reflected how participants missed more comprehensive discussions with HPRs about PA. (4) It is essential how, when and where physical activity guidance is provided, referring to participants' preferences for future PA guidance in the rheumatology clinic. The study emphasizes that an integrated focus on PA should be part of the rheumatology clinic. However, HPRs may need adequate training in how to guide and motivate patients with RA towards increased PA.

Sociodemographic and clinical variables associated with negative illness perception in patients newly diagnosed with rheumatoid arthritis, axial spondyloarthritis, or psoriatic arthritis-a survey based cross-sectional study.

When newly diagnosed with inflammatory arthritis (IA), acquiring self-management skills is beneficial, to enhance quality of life. The personal beliefs and mental representations patients hold about their illness, known as illness perception, significantly influence the development of these skills. Recognizing characteristics that affect illness perception is key to identifying patients requiring additional support for the development of self-management skills. This study aimed at identifying the sociodemographic and clinical characteristics associated with a negative illness perception. This cross-sectional study was based on survey data from patients diagnosed for ≤ 2 years. The Brief Illness Perception Questionnaire (B-IPQ) was used to measure illness perception. After psychometric testing, we divided the B-IPQ into two domains: (1) a control domain and (2) a consequence domain. We performed logistic regression analyses with multiple imputations. A total of 1,360 patients (61% females) were included. Among them, 64%, 20%, and 16% were diagnosed with rheumatoid arthritis, psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA), respectively. Younger patients with lower socioeconomic status, a diagnosis of PsA or axSpA, high disease activity (OR 3.026, CI 2.208;4.147), severe physical disability (OR 4.147. CI 2.883;6.007), severe pain (OR 3.034, CI 1.991;4.622), and severe fatigue (OR 2.612, CI 1.942;3.513) were significantly more likely to report having a negative illness perception. Younger patients with a higher symptom burden, increased disease activity, lower socioeconomic status, and a diagnosis of PsA or axSpA may require additional attention and support in rheumatology clinical practice to aid in the development of their self-management skills.

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.

Fluorescence-Based and Fluorescent Label-Free Characterization of Polymer Nanoparticle Decorated T Cells.

Cells are attractive carriers for the transport and delivery of nanoparticulate cargo. The use of cell-based carriers allows one to enhance control over the biodistribution of drug-loaded polymers and polymer nanoparticles. One key element in the development of cell-based delivery systems is the loading of the cell-based carrier with the nanoparticle cargo, which can be achieved either by internalization of the payload or by immobilization on the cell surface. The surface modification of cells with nanoparticles or the internalization of nanoparticles by cells is usually monitored with fluorescence-based techniques, such as flow cytometry and confocal microscopy. In spite of the widespread use of these techniques, the use of fluorescent labels also poses some risks and has several drawbacks. Fluorescent dyes may bleach, or leach from, the nanoparticles or alter the physicochemical properties of nanoparticles and their interactions with and uptake by cells. Using poly(d,l-lactic acid) nanoparticles that are loaded with Coumarin 6, BODIPY 493/503, or DiO dyes as a model system, this paper demonstrates that the use of physically entrapped fluorescent labels can lead to false negative or erroneous results. The use of nanoparticles that contain covalently tethered fluorescent dyes instead was found to provide a robust approach to monitor cell surface conjugation reactions and to quantitatively analyze nanoparticle-decorated cells. Finally, it is shown that optical diffraction tomography is an attractive, alternative technique for the characterization of nanoparticle-decorated cells, which obviates the need for fluorescent labels.

Covalent and Noncovalent Conjugation of Degradable Polymer Nanoparticles to T Lymphocytes.

Cells are attractive as carriers that can help to enhance control over the biodistribution of polymer nanomedicines. One strategy to use cells as carriers is based on the cell surface immobilization of the nanoparticle cargo. While a range of strategies can be used to immobilize nanoparticles on cell surfaces, only limited effort has been made to investigate the effect of these surface modification chemistries on cell viability and functional properties. This study has explored seven different approaches for the immobilization of poly(lactic acid) (PLA) nanoparticles on the surface of two different T lymphocyte cell lines. The cell lines used were human Jurkat T cells and CD4+ TEM cells. The latter cells possess blood-brain barrier (BBB) migratory properties and are attractive for the development of cell-based delivery systems to the central nervous system (CNS). PLA nanoparticles were immobilized either via covalent active ester-amine, azide-alkyne cycloaddition, and thiol-maleimide coupling, or via noncovalent approaches that use lectin-carbohydrate, electrostatic, or biotin-NeutrAvidin interactions. The cell surface immobilization of the nanoparticles was monitored with flow cytometry and confocal microscopy. By tuning the initial nanoparticle/cell ratio, T cells can be decorated with up to ∼185 nanoparticles/cell as determined by confocal microscopy. The functional properties of the nanoparticle-decorated cells were assessed by evaluating their binding to ICAM-1, a key protein involved in the adhesion of CD4+ TEM cells to the BBB endothelium, as well as in a two-chamber model in vitro BBB migration assay. It was found that the migratory behavior of CD4+ TEM cells carrying carboxylic acid-, biotin-, or Wheat germ agglutinin (WGA)-functionalized nanoparticles was not affected by the presence of the nanoparticle payload. In contrast, however, for cells decorated with maleimide-functionalized nanoparticles, a reduction in the number of migratory cells compared to the nonmodified control cells was observed. Investigating and understanding the impact of nanoparticle-cell surface conjugation chemistries on the viability and properties of cells is important to further improve the design of cell-based nanoparticle delivery systems. The results of this study present a first step in this direction and provide first guidelines for the surface modification of T cells, in particular in view of their possible use for drug delivery to the CNS.

The efficacy of motivational counselling and SMS reminders on daily sitting time in patients with rheumatoid arthritis: a randomised controlled trial.

OBJECTIVES: The aim of this report is to investigate the efficacy of an individually tailored, theory-based behavioural intervention for reducing daily sitting time, pain and fatigue, as well as improving health-related quality of life, general self-efficacy, physical function and cardiometabolic biomarkers in patients with rheumatoid arthritis (RA). METHODS: In this randomised controlled trial 150 patients with RA were randomised to an intervention or a no-intervention control group. The intervention group received three individual motivational counselling sessions and short message service or text messages aimed at reduction of sedentary behaviour during the 16-week intervention period. Primary outcome was change in daily sitting time measured objectively by ActivPAL. Secondary outcomes included change in pain, fatigue, physical function, general self-efficacy, quality of life, blood pressure, blood lipids, haemoglobin A1c, body weight, body mass index, waist circumference and waist-hip ratio. RESULTS: 75 patients were allocated to each group. Mean reduction in daily sitting time was -1.61 hours/day in the intervention versus 0.59 hours/day increase in the control group between-group difference -2.20 (95% CI -2.72 to -1.69; p<0.0001) hours/day in favour of the intervention group. Most of the secondary outcomes were also in favour of the intervention. CONCLUSION: An individually tailored, behavioural intervention reduced daily sitting time in patients with RA and improved patient-reported outcomes and cholesterol levels. TRIAL REGISTRATION NUMBER: NCT01969604; Results.

Effect of intermittent aerobic exercise on sleep quality and sleep disturbances in patients with rheumatoid arthritis - design of a randomized controlled trial.

BACKGROUND: Poor sleep is prevalent in patients with systemic inflammatory disorders, including rheumatoid arthritis, and, in addition to fatigue, pain, depression and inflammation, is associated with an increased risk of co-morbidity and all-cause mortality. Whereas non-pharmacological interventions in patients with rheumatoid arthritis have been shown to reduce pain and fatigue, no randomized controlled trials have examined the effect of non-pharmacological interventions on improvement of sleep in patients with rheumatoid arthritis. The aim of this trial was to evaluate the efficacy of an intermittent aerobic exercise intervention on sleep, assessed both objectively and subjectively in patients with rheumatoid arthritis. METHODS/DESIGN: A randomized controlled trial including 44 patients with rheumatoid arthritis randomly assigned to an exercise training intervention or to a control group. The intervention consists of 18 session intermittent aerobic exercise training on a bicycle ergometer three times a week. Patients are evaluated according to objective changes in sleep as measured by polysomnography (primary outcome). Secondary outcomes include changes in subjective sleep quality and sleep disturbances, fatigue, pain, depressive symptoms, physical function, health-related quality of life and cardiorespiratory fitness. DISCUSSION: This trial will provide evidence of the effect of intermittent aerobic exercise on the improvement of sleep in patients with rheumatoid arthritis, which is considered important in promotion of health and well-being. As such, the trial meets a currently unmet need for the provision of non-pharmacological treatment initiatives of poor sleep in patients with rheumatoid arthritis. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01966835.

Cost-effectiveness of motivational counselling and text reminders in patients with rheumatoid arthritis: results based on a randomised clinical trial.

OBJECTIVE: The aim of this study was to evaluate the cost-effectiveness of an individually tailored intervention consisting of motivational counselling and text message reminders to reduce sedentary behaviour in comparison with usual lifestyle in patients with rheumatoid arthritis (RA). METHODS: RA patients (n=150) were randomised to the intervention or control group. Costs of the intervention and healthcare utilisation during a 22-month follow-up period were reported. Outcomes were objectively measured as 24 hours/7 days sitting time and self-reported Health Assessment Questionnaire (HAQ) and EQ-5D scores at baseline, and 16 weeks, 10 and 22 months after baseline. Cost-effectiveness was reported as incremental cost-effectiveness ratios and statistical uncertainty presented as cost-effectiveness acceptability curves. RESULTS: The intervention cost was estimated at €387 per participant. The mean incremental 22-month healthcare cost was €-1165 (95% bootstrap CI -5613 to 3283). An incremental 20%-point of the participants (CI 10.4% to 29.6%) reduced their daily sitting time more than 50 min and 36%-point reported better HAQ scores (change>0.22). The time-weighted health utilities (quality-adjusted life years (QALYs)) increased by 0.10 (CI 0.02 to 0.18) and 0.11 (CI 0.04 to 0.19) for EQ-5D index and EQ-VAS, respectively. The intervention dominated usual lifestyle by offering better outcomes and lower costs. With a threshold value of €30 000/QALY the intervention has a probability of 95% of being cost-effective. CONCLUSION: This protocolised cost-effectiveness analysis showed that an individually tailored intervention aimed at reducing sedentary behaviour in patients with RA is improving participants' 22-month health status and reducing healthcare costs. These results suggest that the intervention should be implemented in routine rheumatology care. TRIAL REGISTRATION NUMBER: NCT01969604.

Participant evaluation of a behavioral intervention targeting reduction of sedentary behavior in patients with rheumatoid arthritis: a mixed methods study.

Purpose: The "Joint Resources - Sedentary Behavior Study" (JR-SB) revealed significant behavioral and cardio-metabolic effects of reducing daily sedentary behavior replaced by light-intensity physical activity in patients with rheumatoid arthritis. This study explores the participant perception and experiences of the intervention and impact on the participants' health, family and physical activity behavior.Materials and Methods: A mixed-methods study design, including quantitative and qualitative data, was applied. Quantitative data were collected post-intervention using a questionnaire (n = 69) evaluating experiences of participation in the intervention. By maximum variation sampling, 18 participants were recruited to three focus group interviews with discussions of intervention elements. Data from the two sub-studies were collected and analyzed separately, although integrated at the interpretation and reporting level.Results: Based on four overarching themes, results indicated participant satisfaction with the individually tailored, behavioral approach and the focus on light-intensity physical activity rather than higher intensities. Study participation had an additional positive impact on the behaviors of family and social relations. Conversely, the family motivated the participants to achieve their physical activity goals.Conclusions: The study results support the use of individually tailored and behavioral approaches to reduce sedentary behavior, increase light-intensity physical activity and improve physical abilities in patients with rheumatoid arthritis. IMPLICATIONS FOR REHABILITATIONThis paper presents positive participant perception and motivation for an individually tailored, behavioural intervention that aimed to reduce sedentary behaviour replaced by light-intensity physical activity in patients with rheumatoid arthritis.The results indicate that especially the focus on light-intensity physical activity, a consistent focus on the individual's everyday life and continuous support from health professionals motivated the participants to reduce their daily sedentary behaviour - also in the long term.Involvement of participants' family members seems to have influence on their own physical activity behavior as well as on the participants' motivation for changing physical activity behavior.Together with earlier evidence, the results underpin the use of behavioural strategies to support patients with rheumatoid arthritis in achieving their physical activity goals and in improving the abilities needed to manage their everyday lives.

Efficacy and Acceptability of Intermittent Aerobic Exercise on Polysomnography-Measured Sleep in People With Rheumatoid Arthritis With Self-Reported Sleep Disturbance: A Randomized Controlled Trial.

OBJECTIVE: This study's objective was to investigate the efficacy and acceptability of intermittent aerobic exercise training on sleep parameters, fatigue, pain, depressive symptoms, physical function, and cardiorespiratory fitness in people with rheumatoid arthritis (RA). METHODS: Thirty-eight people with RA were assigned to intermittent aerobic exercise training (three sessions/week for 6 weeks; intervention group, n = 17) or usual care (control group, n = 21). The primary outcome was a change in polysomnography-assessed sleep efficiency from baseline to the end of the intervention. Secondary outcomes were sleep quality (Pittsburgh Sleep Quality Index), fatigue (Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire), depression (Center for Epidemiological Studies-Depression), and cardiorespiratory fitness (watt max test). RESULTS: No between-group differences were found in changes in polysomnography-assessed sleep efficiency (0.04; 95% confidence interval [CI]: -0.02 to 0.09, P = 0.17). In the intervention group, sleep efficiency was improved significantly from baseline (0.84; 95% CI: 0.80-0.88) compared with the end of the intervention (6 weeks) (0.88; 95% CI: 0.85-0.92); however, there was no significant difference in the control group. Fatigue and depression measures were significantly lower in the intervention group than in the control group. Between-group differences were overall fatigue (-16.1; 95% CI: -25.1 to -7.0, P = 0.001), physical fatigue (-5.0; 95% CI: -7.3 to -2.7, P = 0.0001), cognitive fatigue (-2.4; 95% CI: -4.2 to 0.6, P = 0.009), living with fatigue (-2.5; 95% CI: -4.5 to -0.5, P = 0.01), and depressive symptoms (-6.8; 95% CI: -12.4 to -1.1, P = 0.02). CONCLUSION: The intervention yielded no significantly better sleep efficiency compared with usual care. However, aspects of fatigue, including physical and cognitive fatigue, and depressive symptoms were significantly improved in the intervention group.

Chemical Cell Surface Modification and Analysis of Nanoparticle-Modified Living Cells.

Cells are promising as carriers that can enhance the delivery of nanomedicines. Cells that carry nanomedicinal cargo, either immobilized on the cell surface or internalized, can allow for highly specific delivery and can enable the transport of nanomedicines across challenging physiological barriers. The effective use of cells as carriers for the transport and delivery of nanomedines requires a careful selection of the chemical strategies that are used to load the cell-based carriers with their cargo. To this end, an in-depth understanding of the impact of various cell-surface modification chemistries on the viability and functional properties of the cells is essential, and techniques are needed that allow characterization of nanoparticle-modified living cells. This article touches upon both of these aspects. The first part of this review will present an overview of contemporary strategies that are available for the cell surface immobilization of nanoparticle cargo. After that, the various techniques that are most frequently used for the characterization of nanoparticle-modified cells will be discussed.

Sustained Long-Term Efficacy of Motivational Counseling and Text Message Reminders on Daily Sitting Time in Patients With Rheumatoid Arthritis: Long-Term Follow-up of a Randomized, Parallel-Group Trial.

OBJECTIVE: To evaluate the 18-month postintervention efficacy following a 4-month individually tailored behavioral intervention on daily sitting time in patients with rheumatoid arthritis (RA). METHODS: In an observer-blinded randomized trial, 150 RA patients were included. During 4 months, the intervention group (n = 75) received 3 motivational counseling sessions and tailored text messages aimed at increasing light-intensity physical activity through reduction of sedentary behavior. The control group (n = 75) maintained their usual lifestyle. The primary outcome was change from baseline to 18 months postintervention in objectively measured daily sitting time (using ActivPAL). Secondary outcomes included changes in clinical patient-reported outcomes and cardiometabolic biomarkers. A mixed-effect repeated measures analysis of covariance model in the intent-to-treat population was applied. RESULTS: At 22 months follow-up from baseline, 12 participants were lost to follow-up. Compared to baseline, sitting time in the intervention group decreased 1.10 hours/day, whereas it increased by 1.32 hours/day in the control group, a between-group difference of -2.43 hours/day (95% confidence interval [95% CI] -2.99, -1.86; P < 0.0001) favoring the intervention group. For most secondary outcomes, between-group differences favored the intervention: visual analog scale (VAS) pain -15.51 mm (95% CI -23.42, -7.60), VAS fatigue -12.30 mm (95% CI -20.71, -3.88), physical function -0.39 Health Assessment Questionnaire units (95% CI -0.53, -0.26), total cholesterol -0.86 mmoles/liter (95% CI -1.03, -0.68), triglycerides -0.26 mmoles/liter (95% CI -0.43, -0.09), and average glucose -1.15 mmoles/liter (95% CI -1.39, -0.91). CONCLUSION: The 4-month postintervention results showed that patients in the intervention reduced their daily sitting time and improved patient-reported outcomes and total cholesterol levels compared to the control group. Eighteen months after intervention, patients in the intervention group were still significantly less sedentary than controls. Findings suggest that a behavioral approach is beneficial for promoting long-term physical activity and health in patients with RA.

Motivational Counseling and Text Message Reminders: For Reduction of Daily Sitting Time and Promotion of Everyday Physical Activity in People with Rheumatoid Arthritis.

Most patients with rheumatoid arthritis tend to be physically inactive and spend more time in sedentary behaviors compared with the general population. This inactive lifestyle can lead to serious health consequences, for example, increased risk of cardiovascular disease. For this reason, there is an interest in increasing participation in physical activity in patients with rheumatoid arthritis. The relatively new approach of reducing sedentary behavior and replacing it with light-intensity physical activity has been shown to be feasible and effective in promoting physical activity in patients with rheumatoid arthritis. However, methods to facilitate this behavior have not yet been fully explored.

Sedentary behaviour in patients with rheumatoid arthritis: A qualitative study.

BACKGROUND: Despite increasing interest in investigating sedentary behaviour (SB) in the general population and in patients with rheumatoid arthritis (RA), there is little documentation of the subjective experiences of SB in patients with RA. This study aimed to examine how patients with RA describe their daily SB. METHODS: Fifteen patients with RA (10 women and 5 men) from 23 to 73 years of age and with a disease duration ranging from 4 to 27 years were interviewed following a semi-structured interview guide. Data were analysed using the content analysis method described by Graneheim. RESULTS: SB appeared in three categories covering: 1) A constant battle between good and bad days; SB could be a consequence of RA in terms of days with pronounced pain and fatigue resulting in many hours of SB. 2) Adaptation to everyday life; living with the unpredictability of RA included constant modification of physical activity level causing increase in SB, especially during periods of disease flare. Prioritizing and planning of SB also functioned as part of self-management strategies. 3) It has nothing to do with my arthritis; for some patients, SB was not related to RA, but simply reflected a way of living independent of the disease. CONCLUSIONS: SB is perceived, motivated, and performed differently in patients with RA. An individually tailored approach may be essential in understanding and encouraging patients' motivation towards sustainable change in SB and activity patterns.

The efficacy of motivational counseling and SMS-reminders on daily sitting time in patients with rheumatoid arthritis: protocol for a randomized controlled trial.

BACKGROUND: Patients with RA (Rheumatoid Arthritis) are more sedentary than the general population. Reduction of Sedentary Behaviour (SB) has been suggested as a mean for improvement of health in patients with chronic diseases and mobility problems. Short-term intervention studies have demonstrated that SB can be reduced by behavioural interventions in healthy populations. However, it remains unexplored whether it is valid for patients with RA also. Therefore, the aim of this trial is to investigate the efficacy of an individually tailored, theory-based motivational counseling intervention on reducing daily sitting time in sedentary patients with RA. Additionally, to explore whether a reduction in daily sitting time is associated with reduced pain and fatigue, self-reported physical function, self-efficacy, improved health-related quality of life (HR-QoL) and cardiovascular biomarker levels, and finally to assess the cost-effectiveness of the intervention. METHODS/DESIGN: For this parallel group randomized trial, 150 patients with RA and at least 5 hours of sitting time per day, will be recruited from a rheumatology outpatient clinic, and block-randomized to the intervention group or the control group receiving usual care. The intervention includes: 1) individual motivational counseling (in total 3 sessions) on reduction of daily sitting time in combination with 2) individual Short Text Message Service (SMS) reminders over a 16-week intervention period. Primary outcome is change in daily sitting time (minutes) from baseline to 16 weeks measured objectively using an ActivPAL® Activity Monitor. Secondary outcomes include fatigue, pain, physical function, HR-QoL, self-efficacy, costs and cost-effectiveness. Furthermore, anthropometric measures will be included as well as measurement of blood pressure and serum lipids. All outcomes are assessed at baseline and repeated after 16 weeks. Follow-up assessments are made at 6 and 18 months post-intervention. DISCUSSION: The intervention is simple, non-invasive and may be implemented at low costs. If the study confirms the positive results expected, the intervention might be implemented in clinical practice and potentially transferred to other clinical populations. TRIAL REGISTRATION: ClinicalTrial.gov registration number: NCT01969604 . Date of registration: 17 October 2013.