Can pain be self-managed? Pain change in vulnerable participants to a health education programme.

Chronic pain exerts a significant impact on the quality of life, giving rise to both physical and psycho-social vulnerabilities. It not only leads to direct costs associated with treatments, but also results in indirect costs due to the reduced productivity of affected individuals. Chronic conditions can be improved by reducing modifiable risk factors. Various educational programs, including the Chronic Disease Self-Management Programme (CDSMP), have demonstrated the advantages of enhancing patient empowerment and health literacy. Nevertheless, their efficacy in addressing pain symptoms has received limited attention, especially concerning vulnerable populations. This research aims to assess the effectiveness of the CDSMP in alleviating pain among socio-economically vulnerable participants with chronic conditions. By accounting for a wide range of variables, and using data from the EFFICHRONIC project (EU health programme), we investigated the changes in pain levels after the intervention, among 1070 participants from five European countries. Our analyses revealed a significant reduction in pain following the intervention. This finding supports the notion that training programs can effectively ameliorate pain and alleviate its impact on the quality of life, particularly in vulnerable populations. Younger participants, as well as those with higher education levels and individuals experiencing higher levels of pain at baseline, were more likely to experience a reduction in their pain levels. These findings underscore the importance of recognising the social determinants of health. The study was registered at ClinicalTrials.gov (ISRCTN70517103).

Senescence-regulatory factors as novel circulating biomarkers and therapeutic targets in regenerative medicine for osteoarthritis.

Recent discoveries reveal that the chronic presence of senescent cells in osteoarticular tissues provides a focal point of disease development for osteoarthritis (OA). Nevertheless, senescence-regulatory factors associated with OA still need to be identified. Furthermore, few diagnostic- and prognostic-validated biochemical markers (biomarkers) are currently used in clinics to evaluate OA patients. In the future, alongside imaging and clinical examination, detecting senescence-regulatory biomarkers in patient fluids could become a prospective method for disease: diagnosis, monitoring, progression and prognosis following treatment. This review summarizes a group of circulating OA biomarkers recently linked to senescence onset. Remarkably, these factors identified in proteomics, metabolomic and microRNA studies could also have deleterious or protective roles in osteoarticular tissue homeostasis. In addition, we discuss their potentially innovative modulation in combination with senotherapeutic approaches, for long-lasting OA treatment.

The effect of a community-based group intervention on chronic disease self-management in a vulnerable population.

Introduction: Chronic non-communicable diseases (NCDs) are predominantly related to modifiable health behaviors and account for 74% of global deaths at present. Behavior modification through self-management is a strategy to prevent NCDs. Chronic Disease Self-Management Programs (CDSMPs) have demonstrated improvements in health behaviors, health status, and use of healthcare. Objective: We evaluated the effects of a 6-week CDSMP on self-efficacy, health behaviors, mental health, health-related quality of life (HR-QoL), and health responsibilities among vulnerable populations with chronic disease in Europe. Methods: A prospective cohort study with a 6-month pre-post single-group design was conducted in five European countries. The intervention targeted adults with chronic conditions and low socioeconomic status, as well as their caregivers. The intervention was a 6-week community-based CDSMP in a group setting. Outcomes were measured per self-report questionnaire at baseline and 6-month follow-up: self-efficacy, health behaviors, mental health, HR-QoL, and health responsibilities. Results: Of 1,844 participants, 1,248 (67.7%) completed follow-up and attended ≥4 sessions. For the chronic condition group, the following outcome measures at follow-up significantly improved compared with baseline (all P < 0.002): self-efficacy (SEMCD-6 6.7 vs. 6.4), mental health (PHQ-8 6.3 vs. 7.0), HR-QoL (SF-12 PCS 42.3 vs. 40.2, SF-12 MCS 42.8 vs. 41.4), health utility (EQ-5D-5L 0.88 vs. 0.86), self-rated health (EQ-5D-5L 67.2 vs. 63.9), communication with healthcare providers (2.28 vs. 2.11), understanding information (3.10 vs. 3.02), number of doctor visits (3.61 vs. 4.97), accident and emergency department visits (0.25 vs. 0.48), total nights in a hospital (0.65 vs. 1.13), and perceived medical errors (19.6 vs. 28.7%). No significant changes were detected in dietary habits, physical activity, substance use, and sleep and fatigue. For caregivers without a chronic condition, only doctor visits significantly decreased (1.54 vs. 2.25, P < 0.001). Discussion: This CDSMP was associated with improvement in self-efficacy, depression, HR-QoL, and health responsibilities over 6 months in a diverse European population with a chronic condition. However, additional interventions targeting lifestyle risk factors are needed to improve health outcomes.

Senescence-Driven Inflammatory and Trophic Microenvironment Imprints Mesenchymal Stromal/Stem Cells in Osteoarthritic Patients.

Senescent cells promote progressive tissue degeneration through the establishment of a combined inflammatory and trophic microenvironment. The cellular senescence state has therefore emerged as a central driving mechanism of numerous age-related diseases, including osteoarthritis (OA), the most common rheumatic disease. Senescence hallmarks are detectable in chondrocytes, synoviocytes and sub-chondral bone cells. This study investigates how the senescence-driven microenvironment could impact the cell fate of resident osteoarticular mesenchymal stromal/stem cells (MSCs) that are hence contributing to OA disease progression. For that purpose, we performed a comparative gene expression analysis of MSCs isolated from healthy donors that were in vitro chronically exposed either to interferon-gamma (IFN-γ) or Transforming Growth Factor beta 1 (TGFß1), two archetypical factors produced by senescent cells. Both treatments reduced MSC self-renewal capacities by upregulating different senescence-driven cycle-dependent kinase inhibitors. Furthermore, a common set of differentially expressed genes was identified in both treated MSCs that was also found enriched in MSCs isolated from OA patients. These findings highlight an imprinting of OA MSCs by the senescent joint microenvironment that changes their matrisome gene expression. Altogether, this research gives new insights into OA etiology and points to new innovative therapeutic opportunities to treat OA patients.

Evaluation of mindfulness based stress reduction in symptomatic knee or hip osteoarthritis patients: a pilot randomized controlled trial.

BACKGROUND: To evaluate the efficacy for symptomatic knee and hip osteoarthritis (OA) patients of a mindfulness-based stress reduction (MBSR) program versus usual care. METHODS: Randomized, physician-blind, clinical trial in a monocentric prospective pilot study. Adult participants with symptomatic knee or hip OA were randomized into either intervention or control groups. The intervention group completed the MBSR program for a two-and-a-half-hour weekly session for 8 weeks. Usual care management was similar in both groups. All patients were evaluated at baseline, 3 months and 6 months. The primary objective was to evaluate the change in WOMAC pain score between baseline and 3 months in the MBSR group compared to usual care group. Secondary objectives were to evaluate changes in pain VAS, WOMAC scores, quality of life (SF-36), HAD scores between baseline and 3/6 months. RESULTS: Forty patients were enrolled in the study. No differences in the WOMAC pain score between the two groups were observed in the different time points. A similar pattern was found for the other assessment outcomes. However, a significant pain VAS reduction in favor of the MBSR group between baseline and 6 months (- 29.6 ± 26.6 vs - 9.3 ± 27.3; p = 0.03) has been reached. CONCLUSIONS: Our pilot RCT found contrasting results with no benefit on WOMAC pain and function and a delayed but long-term efficacy in pain VAS following a MBSR program in symptomatic knee or hip OA patients. Future studies with larger sample size are mandatory to confirm these preliminary results. Trial registration The study was registered in ClinicalTrials.gov (NCT03644615, 23/08/2018).

Management of patients with rheumatoid arthritis by telemedicine: connected monitoring. A randomized controlled trial.

OBJECTIVES: Rheumatoid arthritis (RA) is a prevalent and disabling disease that is the source of significant direct and indirect costs. The current recommended therapeutic strategy is based on the rapid introduction of therapy with conventional Disease-Modifying Anti-Rheumatic Drugs (DMARDs) combined with regular disease monitoring by the rheumatologist. The onerous nature of such intense monitoring has motivated the development of new, less demanding strategies such as telemedicine. This study aimed to estimate the cost-effectiveness of the connected monitoring of RA patients initiating a new DMARD therapy versus conventional monitoring. METHODS: An economic evaluation based on a randomized controlled trial of 89 patients was conducted. The patients in the intervention group (n=45) were monitored using a connected monitoring interface on a smartphone, while patients in the control group (n=44) were conventionally monitored. Health outcomes were measured as the gain in quality-adjusted life-years (QALYs), assessed using the EuroQol-5D questionnaire. Resource use and health outcomes were collected alongside the trial and at the six-month follow-up using application data and the related clinical case manager time, visits, hospitalisations, and transport records. These outcomes were valued using externally collected data on unit costs and QALY weights. RESULTS: Compared to conventionally monitored patients, patients receiving connected monitoring had a slightly greater but not significant gain in the average QALY of 0.07. The economic analysis found that connected monitoring resulted in a significant cost reduction of 72€ (2927€ vs. 2999€, P<0.01). The incremental cost-utility ratio of the intervention was equal to -1,029€ per QALY (95% CI: -32,033; +24,625) with a 97.8% chance of being cost-effective at a threshold of 30,000€ per QALY gained. CONCLUSION: Implementing EULAR recommendations for RA patients initiating a DMARD treatment using connected monitoring is more efficient and less expensive than conventional care. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT03005925).

The chronic disease Self-Management Programme: A phenomenological study for empowering vulnerable patients with chronic diseases included in the EFFICHRONIC project.

INTRODUCTION: The Chronic Disease Self-Management Programme (CDSMP) has resulted in improved health outcomes for patients. However, research has focused mainly on those with chronic conditions and has not extensively explored prevention programmes targeting individuals with specific vulnerability profiles. AIM: This study aimed to understand the effects of the CDSMP on the lived experience of vulnerable patients included in the EFFICHRONIC project in France, based on their needs and expectations before and after participation. METHODS: We conducted a qualitative phenomenological semio-pragmatic study based on 37 in-depth interviews with 20 patients (20 before/17 after CDSMP). RESULTS: By transforming existential dimensions (identity, relationship with others and bodily experience), chronic illness generates new needs in the vulnerable person. By resonating with the expectations and needs of participants, the CDSMP induces motivation and a sense of belonging to a community of peers. It has enabled the participants to become actors of their own health until empowerment. Although some limitations are reported, the programme has awakened a desire in the participants to take better care of their health and to develop personal skills with, for some, a desire to become involved in health education. CONCLUSION: Our phenomenological approach highlighted the resonance between the programme (its design and implementation) and the lived experience of patients, as an effective element of empowerment. This necessitates training the facilitators to elicit the lived experience of patients. Furthermore, as a patient-centred approach is required, the facilitators need to learn how to adapt the design of the programme to the singularity of the patient. PATIENT OR PUBLIC CONTRIBUTION: Patients provided the data that were collected through in-depth interviews, and their experiences before and after the programme were analysed.

Adipose tissue-derived stromal vascular fraction for treating hands of patients with systemic sclerosis: a multicentre randomized trial Autologous AD-SVF versus placebo in systemic sclerosis.

OBJECTIVE: To assess the superiority of adipose tissue-derived stromal vascular fraction (AD-SVF) injection into the fingers vs placebo in reducing hand disability in systemic sclerosis (SSc) patients. METHODS: We performed a double-blind, multicentre, phase II trial from October 2015 to January 2018 in France. SSc patients with a Cochin Hand Function Scale (CHFS) ≥20/90 were randomized 1:1 to receive injection of AD-SVF or placebo. AD-SVF was obtained using the automated processing Celution 800/CRS system. The placebo was lactated Ringer's solution. The primary efficacy end point was the change of the CHFS score from baseline to 3 months. Secondary efficacy endpoints included the CHFS score at 6 months, hand function, vasculopathy, hand pain, skin fibrosis, sensitivity of the finger pulps, Scleroderma Health Assessment Questionnaire, patients and physician satisfaction, and safety. RESULTS: Forty patients were randomized. The AD-SVF and placebo groups were comparable for age, sex ratio, disease duration, skin fibrosis of the hands and main cause of hand disability. After 3 months' follow-up, hand function significantly improved in both groups with no between-group difference of CHFS (mean change of -9.2 [12.2] in the AD-SVF group vs -7.6 [13.2] in the placebo group). At 6 months, hand function improved in both groups. CONCLUSION: This study showed an improvement of hand function in both groups over time, with no superiority of the AD-SVF. Considering the limits of this trial, studies on a larger population of patients with homogeneous phenotype and hand handicap should be encouraged to accurately assess the benefit of AD-SVF therapy. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02558543. Registered on September 24, 2015.

Impact of the chronic disease self-management program (CDSMP) on self-perceived frailty condition: the EU-EFFICHRONIC project.

INTRODUCTION: The Chronic Disease Self-Management Program (CDSMP) improves self-efficacy and health outcomes in people with chronic diseases. In the context of the EFFICHRONIC project, we evaluated the efficacy of CDSMP in relieving frailty, as assessed by the self-administered version of Multidimensional Prognostic Index (SELFY-MPI), identifying also potential predictors of better response over 6-month follow-up. METHODS: The SELFY-MPI explores mobility, basal and instrumental activities of daily living (Barthel mobility, ADL, IADL), cognition (Test Your Memory-TYM Test), nutrition (Mini Nutritional Assessment-Short Form-MNA-SF), comorbidities, medications, and socio-economic conditions (social-familiar evaluation scale-SFES). Participants were stratified in three groups according to the 6-month change of SELFY-MPI: those who improved after CDSMP (Δ SELFY-MPI < 0), those who remained unchanged (Δ SELFY-MPI = 0), and those who worsened (Δ SELFY-MPI > 0). Multivariable logistic regression was modeled to identify predictors of SELFY-MPI improvement. RESULTS: Among 270 participants (mean age = 61.45 years, range = 26-93 years; females = 78.1%) a benefit from CDSMP intervention, in terms of decrease in the SELFY-MPI score, was observed in 32.6% of subjects. SELFY-MPI improvement was found in participants with higher number of comorbidities (1-2 chronic diseases: adjusted odd ratio (aOR)=2.38, 95% confidence interval (CI) =1.01, 5.58; ⩾ 3 chronic diseases: aOR = 3.34, 95% CI = 1.25, 8.90 vs no chronic disease), poorer cognitive performance (TYM ⩽ 42: aOR = 2.41, 95% CI = 1.12, 5.19 vs TYM > 42) or higher risk of malnutrition (MNA-SF ⩽ 11: aOR = 6.11, 95% CI = 3.15, 11.83 vs MNA-SF > 11). CONCLUSION: These findings suggest that the CDSMP intervention contributes to decreasing the self-perceived severity of frailty (SELFY-MPI score) in more vulnerable participants with several chronic diseases and lower cognitive performance and nutritional status.

The Challenges of Telemedicine in Rheumatology.

During the past 20 years, the development of telemedicine has accelerated due to the rapid advancement and implementation of more sophisticated connected technologies. In rheumatology, e-health interventions in the diagnosis, monitoring and mentoring of rheumatic diseases are applied in different forms: teleconsultation and telecommunications, mobile applications, mobile devices, digital therapy, and artificial intelligence or machine learning. Telemedicine offers several advantages, in particular by facilitating access to healthcare and providing personalized and continuous patient monitoring. However, some limitations remain to be solved, such as data security, legal problems, reimbursement method, accessibility, as well as the application of recommendations in the development of the tools.

Immunomodulation with IL-17 and TNF-α in spondyloarthritis: focus on the eye and the central nervous system.

Tumor necrosis factor alpha (TNF-α) and interleukin-17 (IL-17) are two pro-inflammatory cytokines involved in the pathophysiology of spondyloarthritis (SpA). Therapies targeting TNF-α or IL-17 are used as a second line among SpA patients failing non-steroidal anti-inflammatory drugs. The choice of such treatment has to take into account the patient's comorbidities. Neurologic diseases are common and their association with SpA deserves to be studied. Therefore, the role of TNF-α and IL-17 cytokines is worth investigating in these neuropsychiatric diseases. This review aimed to explore the role of TNF-α and IL-17 in the pathogenesis of uveitis, multiple sclerosis, neuromyelitis optica, Alzheimer's disease, Parkinson's disease and depression. This update is critical to guide the therapeutic management of these co-morbidities in SpA patients.

Mesenchymal Stromal Cell-Derived Extracellular Vesicles Regulate the Mitochondrial Metabolism via Transfer of miRNAs.

Mesenchymal stromal cells (MSCs) are the most commonly tested adult progenitor cells in regenerative medicine. They stimulate tissue repair primarily through the secretion of immune-regulatory and pro-regenerative factors. There is increasing evidence that most of these factors are carried on extracellular vesicles (EVs) that are released by MSCs, either spontaneously or after activation. Exosomes and microvesicles are the most investigated types of EVs that act through uptake by target cells and cargo release inside the cytoplasm or through interactions with receptors expressed on target cells to stimulate downstream intracellular pathways. They convey different types of molecules, including proteins, lipids and acid nucleics among which, miRNAs are the most widely studied. The cargo of EVs can be impacted by the culture or environmental conditions that MSCs encounter and by changes in the energy metabolism that regulate the functional properties of MSCs. On the other hand, MSC-derived EVs are also reported to impact the metabolism of target cells. In the present review, we discuss the role of MSC-EVs in the regulation of the energy metabolism and oxidative stress of target cells and tissues with a focus on the role of miRNAs.

miR-155 Contributes to the Immunoregulatory Function of Human Mesenchymal Stem Cells.

Objectives: Mesenchymal stem/stromal cells (MSCs) are widely investigated in regenerative medicine thanks to their immunomodulatory properties. They exert their anti-inflammatory function thanks to the secretion of a number of mediators, including proteins and miRNAs, which can be released in the extracellular environment or in the cargo of extracellular vesicles (EVs). However, the role of miRNAs in the suppressive function of MSCs is controversial. The aim of the study was to identify miRNAs that contribute to the immunomodulatory function of human bone marrow-derived MSCs (BM-MSCs). Methods: Human BM-MSCs were primed by coculture with activated peripheral blood mononuclear cells (aPBMCs). High throughput miRNA transcriptomic analysis was performed using Human MicroRNA TaqMan® Array Cards. The immunosuppressive function of miRNAs was investigated in mixed lymphocyte reactions and the delayed type hypersensitivity (DTH) murine model. Results: Upon priming, 21 out of 377 tested miRNAs were significantly modulated in primed MSCs. We validated the up-regulation of miR-29a, miR-146a, miR-155 and the down-regulation of miR-149, miR-221 and miR-361 in additional samples of primed MSCs. We showed that miR-155 significantly reduced the proliferation of aPBMCs in vitro and inflammation in vivo, using the DTH model. Analysis of miRNA-mRNA interactions revealed miR-221 as a potential target gene that is down-regulated by miR-155 both in primed MSCs and in aPBMCs. Conclusion: Here, we present evidence that miR-155 participates to the immunosuppressive function of human BM-MSCs and down-regulates the expression of miR-221 as a possible inflammatory mediator.

Identification of a Novel Serum Proteomic Signature for Primary Sjögren's Syndrome.

Context: Primary Sjögren's syndrome (pSS) is a complex heterogeneous autoimmune disease (AID) which can mimic rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE). Our exploratory study investigated serum biomarkers that may discriminate pSS from RA and SLE. Methods: Serum concentrations of 63 biomarkers involved in immune cell trafficking, inflammatory response, cellular movement, and cell-to-cell signaling were measured in AID patients, included prospectively into the study at the Montpellier University Hospital. A multivariate analysis by multiple logistic regression was performed, and discriminative power assessed using logistic regression adjusted on significant demographic factors. Results: Among the 95 patients enrolled, 42 suffered from pSS, 28 from RA, and 25 from SLE. Statistical analysis showed that concentrations of BDNF (OR = 0.493 with 95% CI [0.273-0.891]; p = 0.0193) and I-TAC/CXCL11 (OR = 1.344 with 95% CI [1.027-1.76]; p = 0.0314) can significantly discriminate pSS from RA. Similarly, greater concentrations of sCD163 (OR = 0.803 with 95% CI [0.649-0.994]; p = 0.0436), Fractalkine/CX3CL1 (OR = 0.534 with 95% CI [0.287-0. 991]; p = 0.0466), MCP-1/CCL2 (OR = 0.839 with 95% CI [0.732-0.962]; p = 0.0121), and TNFa (OR = 0.479 with 95% CI [0.247-0.928]; p = 0.0292) were associated with SLE diagnosis compared to pSS. In addition, the combination of low concentrations of BDNF and Fractalkine/CX3CL1 was highly specific for pSS (specificity 96.2%; positive predictive value 80%) compared to RA and SLE, as well as the combination of high concentrations of I-TAC/CXCL11 and low concentrations of sCD163 (specificity 98.1%; positive predictive value 75%). Conclusion: Our study highlights biomarkers potentially involved in pSS, RA, and SLE pathophysiology that could be useful for developing a pSS-specific diagnostic tool.

Efficacy of tocilizumab in patients with hand osteoarthritis: double blind, randomised, placebo-controlled, multicentre trial.

OBJECTIVE: To evaluate the efficacy of tocilizumab, an antibody against IL-6 receptor, in patients with hand osteoarthritis. METHODS: This was a multicentre, 12-week, randomised, double-blind, placebo-controlled study from November 2015 to October 2018. Patients with symptomatic hand osteoarthritis (pain ≥40 on a 0-100 mm visual analogue scale (VAS) despite analgesics and non-steroidal anti-inflammatory drugs; at least three painful joints, Kellgren-Lawrence grade ≥2) were randomised to receive two infusions 4 weeks apart (weeks 0 and 4) of tocilizumab (8 mg/kg intravenous) or placebo. The primary endpoint was changed in VAS pain at week 6. Secondary outcomes included the number of painful and swollen joints, duration of morning stiffness, patients' and physicians' global assessment and function scores. RESULTS: Of 104 patients screened, 91 (45 to tocilizumab and 46 to placebo; 82% women; mean age 64.4 (SD 8.7) years) were randomly assigned and 79 completed the 12-week study visit. The mean change between baseline and week 6 on the VAS for pain (primary outcome) was -7.9 (SD 19.4) and -9.9 (SD 20.1) in the tocilizumab and placebo groups (p=0.7). The groups did not differ for any secondary outcomes at weeks 4, 6, 8 or 12. Overall, adverse events were slightly more frequent in the tocilizumab than placebo group. CONCLUSION: Tocilizumab was no more effective than placebo for pain relief in patients with hand osteoarthritis.

A randomized prospective open-label controlled trial comparing the performance of a connected monitoring interface versus physical routine monitoring in patients with rheumatoid arthritis.

OBJECTIVES: In RA, telemedicine may allow tight control of disease activity while reducing hospital visits. We developed a smartphone application connected with a physician's interface to monitor RA patients. We aimed to assess the performance of this e-Health solution in comparison with routine practice in the management of patients with RA. METHODS: A six-month pragmatic, randomized, controlled, prospective, clinical trial was conducted in RA patients with high to moderate disease activity starting a new DMARD therapy. Two groups were established: 'connected monitoring' and 'conventional monitoring'. The primary outcome was the number of physical visits between baseline and six months. Secondary outcomes included adherence, satisfaction, changes in clinical, functional and health status scores (Short-Form 12). RESULTS: Of the 94 randomized patients, 89 completed study: 44 in the 'conventional monitoring' arm and 45 in the 'connected monitoring' arm. The total number of physical visits between required baseline and six-month visits was significantly lower in the 'connected monitoring' group [0.42 (0.58) vs 1.93 (0.55); P <0.05]. No differences between groups were observed in the clinical and functional scores. A better quality of life for Short-Form 12 subscores (Role-Physical and Role-Emotional) were found in the 'connected monitoring' group. CONCLUSION: Our results suggest that connected monitoring reduces the number of physical visits while maintaining a tight control of disease activity and improving quality of life in patients with RA starting a new treatment. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03005925.