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).

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.

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.

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.

X-Linked miRNAs Associated with Gender Differences in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease that predominantly affects women. MicroRNAs have emerged as crucial regulators of the immune system, whose expression is deregulated in RA. We aimed at quantifying the expression level of 14 miRNAs located on the X chromosome and at identifying whether differences are associated with disease and/or sex. A case-control study of 21 RA patients and 22 age- and sex-matched healthy controls was performed on peripheral blood mononuclear cells. The expression level of five miRNAs (miR-221, miR-222, miR-532, miR-106a, and miR-98) was significantly different between RA and controls when stratifying by sex, and the expression level of four miRNAs (miR-222, miR-532, miR-98, and miR-92a) was significantly different between RA females and males. The expression quantitative trait loci (eQTL) analysis revealed a significant gender effect of the FoxP3 promoter polymorphism rs3761548A/C on miR-221, miR-222 and miR-532 expression levels, and of the FoxP3 polymorphism rs2232365A/G on miR-221 expression levels in PBMC of RA patients. These data further support the involvement of the X chromosome in RA susceptibility. X-linked miRNAs, in the context of sex differences, might provide novel insight into new molecular mechanisms and potential therapeutic targets in RA for disease treatment and prevention.

Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial.

UNLABELLED: : Osteoarthritis (OA) is the most widespread musculoskeletal disorder in adults. It leads to cartilage damage associated with subchondral bone changes and synovial inflammation, causing pain and disability. The present study aimed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells (ASCs) in patients with knee OA, as well as clinical efficacy as secondary endpoint. A bicentric, uncontrolled, open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries. From April 2012 to December 2013, 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs. The study design consisted of three consecutive cohorts (six patients each) with dose escalation: low dose (2 × 10(6) cells), medium dose (10 × 10(6)), and high dose (50 × 10(6)). The primary outcome parameter was safety evaluated by recording adverse events throughout the trial, and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index. After 6 months of follow-up, the procedure was found to be safe, and no serious adverse events were reported. Four patients experienced transient knee joint pain and swelling after local injection. Interestingly, patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline. Our data suggest that the intra-articular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients. A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy. SIGNIFICANCE: Although this phase I study included a limited number of patients without a placebo arm, it showed that local injection of autologous adipose-derived stem cells was safe and well tolerated in patients with knee osteoarthritis. This study also provides encouraging preliminary evidence of efficacy. Larger and controlled long-term studies are now mandatory to confirm whether this new strategy of cell therapy can improve pain and induce structural benefit in osteoarthritis.

Adipose mesenchymal stem cells protect chondrocytes from degeneration associated with osteoarthritis.

Our work aimed at evaluating the role of adipose stem cells (ASC) on chondrocytes from osteoarthritic (OA) patients and identifying the mediators involved. We used primary chondrocytes, ASCs from different sources and bone marrow mesenchymal stromal cells (MSC) from OA donors. ASCs or MSCs were co-cultured with chondrocytes in a minimal medium and using cell culture inserts. Under these conditions, ASCs did not affect the proliferation of chondrocytes but significantly decreased camptothecin-induced apoptosis. Both MSCs and ASCs from different sources allowed chondrocytes in the cocultures maintaining a stable expression of markers specific for a mature phenotype, while expression of hypertrophic and fibrotic markers was decreased. A number of factors known to regulate the chondrocyte phenotype (IL-1ß, IL-1RA, TNF-α) and matrix remodeling (TIMP-1 and -2, MMP-1 and -9, TSP-1) were not affected. However, a significant decrease of TGF-ß1 secretion by chondrocytes and induction of HGF secretion by ASCs was observed. Addition of a neutralizing anti-HGF antibody reversed the anti-fibrotic effect of ASCs whereas hypertrophic markers were not modulated. In summary, ASCs are an interesting source of stem cells for efficiently reducing hypertrophy and dedifferentiation of chondrocytes, at least partly via the secretion of HGF. This supports the interest of using these cells in therapies for osteo-articular diseases.

Long-term detection of human adipose-derived mesenchymal stem cells after intraarticular injection in SCID mice.

OBJECTIVE: Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy for several disorders, among them the osteoarticular diseases. For such clinical applications, intraarticular (IA) injection of MSCs may be favored for higher levels of safety and targeting of specific joints. Although the safety of intravenous (IV) administration of MSCs has been reported in a number of clinical trials, the safety and biodistribution of MSCs after IA injection have not been tested. Our objective was to assess the toxicity of clinical-grade human adipose-derived MSCs (AD-MSCs), as well as their biodistribution, after IA injection into SCID mice. METHODS: SCID mice received IA or IV administration of 10(6) human AD-MSCs. Several tissues were recovered at different time points and processed for histologic assessment or real-time polymerase chain reaction (PCR) analysis. A highly sensitive assay was used to monitor the distribution of AD-MSCs, based on amplification of human-specific Alu sequences. RESULTS: Absence of toxicity was observed after AD-MSC infusion. Alu PCR assay revealed a high sensitivity (1 human AD-MSC/10(5) murine cells), with a large linear range (1-5 × 10(4) /10(5) murine cells). Importantly, 15% of the IA-injected AD-MSCs were detectable in the joint for the first month and 1.5% of the AD-MSCs engrafted over the long term, at least 6 months. AD-MSCs were observed in the injected joints and in areas of tissue referred to as stem cell niches, such as the bone marrow, adipose tissue, and muscle. CONCLUSION: These data support the feasibility and safety of using IA delivery of human AD-MSCs in the treatment of rheumatic diseases that affect the joints.