Search

Messenger RNA (mRNA)‐based therapies have emerged as a revolutionary strategy for treating various diseases. In autoimmune diseases like rheumatoid arthritis (RA), targeted mRNA delivery provides a potential intervention to modulate immune responses. However, achieving specific and efficient in vivo modulation of immune regulators, such as the inhibitory Fc gamma receptor, FcγRIIB, on B cells remains challenging. In this study, lipid polymer nanoparticles (LPNs) formulated with AMB‐POC18 lipidoid and poly(ethylene glycol)‐block‐polylactide (PEG‐PLA) are engineered to deliver FcγRIIB mRNA (mFcγRIIB) specifically to splenic B cells for RA treatment. Protein corona analysis indicated that selective adsorption of complement C3 on the LPNs' surface facilitated their targeted delivery to the spleen, enhancing transfection efficiency in B cells following intravenous administration. In a collagen‐induced arthritis mouse model, mFcγRIIB/LPNs effectively upregulated FcγRIIB expression in splenic B cells, significantly reducing autoimmune responses and alleviating RA symptoms. Further mechanistic studies elucidated that increased FcγRIIB expression suppressed B cell activation via the FcγRIIB/Lyn/SHP‐1 signaling pathway. This work underscored the potential of the spleen‐targeted mRNA delivery system for RA therapy, providing a precise and targeted approach to modulate B cell activity and mitigate autoimmune diseases. [ABSTRACT FROM AUTHOR]

Copyright of Osmangazi Journal of Medicine / Osmangazi Tip Dergisi is the property of Eskisehir Osmangazi University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Self-management programs can help patients with rheumatoid arthritis develop strategies to address their disease-related problems. However, accessibility to traditional self-management programs is often limited. Purpose: This study was developed to assess the effectiveness, feasibility, and acceptability of a smartphone-delivered self-management program application (app) for adults with rheumatoid arthritis. Methods: A two-arm (intervention vs. control) randomized controlled trial was used. Adult patients with rheumatoid arthritis were recruited from the rheumatology departments of a medical center. Study enrollment capabilities were limited by current pandemic restrictions. The patients who met the inclusion criteria and agreed to participate (N = 46) were enrolled as participants and randomly assigned either to the intervention group (n = 25), which received instructions on the use of a smartphone app designed to facilitate the self-management of rheumatoid arthritis, or to the control group (n = 21), which received instructions on related self-management only. The outcome variables were assessed at baseline and at 8 and 12 weeks. Differences in between-group outcomes over time were analyzed using generalized estimating equations. Feasibility and acceptability were also evaluated. Data were collected between August 1, 2020, and July 31, 2022. Results: At baseline, no differences were detected between the two groups in terms of the demographic and disease characteristics of concern. Outcome measures for the intervention group improved significantly more than the control group for self-efficacy of pain at 8 weeks (B = 6.39, p < .05) and for both of self-efficacy of pain and self-management behavior at 12 weeks (B = 9.16, p < .05, and B = 4.25, p < .001, respectively). Factors related to app ease of use included limiting pop-ups and windows and having no time restrictions. Most of the participants reported the app as acceptable and easy to use, although challenges relating to using technology limited the usability of the app for some. Conclusions/Implications for Practice: The smartphone app was shown to improve self-efficacy of pain and self-management behaviors. However, an accurate assessment of the effectiveness of the app and generalizability of the findings is limited by the smaller-than-desired sample size due to the COVID-19 pandemic and technological challenges. A greater understanding of how to overcome technological challenges is needed to optimize the delivery of self-management programs via smartphone-based apps. Studies reevaluating this app on a larger sample size should be conducted. [ABSTRACT FROM AUTHOR]

Connective tissue, rheumatological and dermatological conditions affect a large proportion of the pregnant population and have important implications for women and their babies. Some conditions are chronic but may occur de novo in pregnancy whereas some are seen only during pregnancy. Multidisciplinary care is essential to maximise fetal and maternal outcomes, since many of these women require immunosuppressive treatment and close monitoring of their pregnancies. The development of biological therapies has revolutionised treatment of many connective tissue and arthritic diseases, allowing both more targeted treatments and an increase in treatment options. Their impact on fertility is minimal compared to older treatments and hence more women are able to conceive. With new treatments there will always be concerns about safety in pregnancy but concerns around neonatal immunosuppression have largely been unfounded and the benefits of continuing medication are significant. This article uses four cases to illustrate the challenges of management. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiopathogenesis, characterised by persistent joint pain, stiffness and swelling due to inflammation and erosion of the synovial joints. Uncontrolled active RA leads to decreased quality of life, disability, and comorbidity. Despite surgical and pharmacological interventions, many patients with RA continue to experience symptoms such as pain, fatigue and psychological distress such as anxiety and depression. Research shows that these psychological factors in turn, lead to adverse physiological outcomes and negatively affect treatment compliance. In addition, some RA medications have psychological side-effects especially when taken over long periods making psychotherapeutic interventions an important but often overlooked adjuvant treatment option. The focus of psychological treatments in RA is to attain better quality of life including, inter alia, increased self-efficacy, management of psychological distress, enhancing the patient's emotional and cognitive state, and exploring adaptive coping styles. Research demonstrates that Cognitive Behaviour Therapy (CBT) is an effective intervention in ameliorating psychological distress in patients with RA. Ethical and effective adjuvant psychotherapy is an important component in the management of RA patients. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis and rheumatoid arthritis are major causes of pain and disability globally, and exercise is known to be effective at alleviating symptoms and improving physical function. Current Concepts: Knee osteoarthritis is a common degenerative disease, and comprehensive clinical practice guidelines have been established. Most studies strongly recommend appropriate weight management combined with exercise therapy. Aerobic, strength, resistance, isometric, neuromuscular, and balance training have been used. However, the current evidence is insufficient to recommend specific prescriptions regarding the exercise type and dose. Many guidelines group knee and hip osteoarthritis together for exercise recommendations. Evidence supporting the use of exercise for hand osteoarthritis is relatively scarce, and reports on its adverse effects are rare. Weight loss is not recommended for hand osteoarthritis, because its effectiveness has not yet been established. For patients with polyarticular osteoarthritis, exercise is recommended as a core treatment, with systematic land-based exercises being particularly advised. For rheumatoid arthritis, both general exercises and hydrotherapy are recommended to improve joint flexibility, muscle strength, and functional outcomes. Discussion and Conclusion: Exercise is a powerful treatment tool for various types of arthritis. However, further research is required to develop more specific exercise intervention protocols. [ABSTRACT FROM AUTHOR]

Objective: Quality of care (QoC) delivery in rheumatoid arthritis (RA) continues to suffer from various challenges (eg, delay in diagnosis and referral) that can lead to poor patient outcomes. This study aimed to identify good practice interventions that address these challenges in RA care in North America. Methods: The study was conducted in three steps: (1) literature review of existing publications and guidelines (April 2005 to April 2021) on QoC in RA; (2) in‐person visits to >50 individual specialists and health care professionals across nine rheumatology centers in the United States and Canada to identify challenges in RA care and any corresponding good practice interventions; and (3) collation and organization of findings of the two previous methods by commonalities to identify key good practice interventions, followed by further review by RA experts to ensure key challenges and gaps in RA care were captured. Results: Several challenges and eight good practice interventions were identified in RA care. The interventions were prioritized based on the perceived positive impact on the challenges in care and ease of implementation. High‐priority interventions included the use of technology to improve care, streamlining specialist treatment, and facilitating comorbidity assessment and care. Other interventions included enabling patient access to optimal medication regimens and improving patient self‐management strategies. Conclusion: Learnings from the study can be implemented in other rheumatology centers throughout North America to improve RA care. Although the study was completed before the COVID‐19 pandemic, the findings remain relevant. [ABSTRACT FROM AUTHOR]

Purpose: Work ability of people with rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) is reduced, but underexamined as a clinical treatment target. The evidence on vocational interventions indicates that delivery by a single healthcare professional (HCP) may be beneficial. Physiotherapist (PT)-led interventions have potential because PTs are most commonly consulted by RA/axSpA patients in the Netherlands. The aim was to develop a PT-led, vocational intervention for people with RA/axSpA and reduced work ability. Methods: Mixed-methods design based on the Medical Research Council (MRC) framework for developing and evaluating complex interventions, combining a rapid literature review and six group meetings with: patient representatives (n = 6 and 10), PTs (n = 12), (occupational) HCPs (n = 9), researchers (n = 6) and a feasibility test in patients (n = 4) and PTs (n = 4). Results: An intervention was developed and evaluated. Patient representatives emphasized the importance of PTs' expertise in rheumatic diseases and work ability. The potential for PTs to support patients was confirmed by PTs and HCPs. The feasibility test confirmed adequate feasibility and underlined necessity of training PTs in delivery. The final intervention comprised work-focussed modalities integrated into conventional PT treatment (10–21 sessions over 12 months), including a personalized work-roadmap to guide patients to other professionals, exercise therapy, patient education and optional modalities. Conclusion: A mixed-methods design with stakeholder involvement produced a PT-led, vocational intervention for people with RA/axSpA and reduced work ability, tested for feasibility and ready for effectiveness evaluation. [ABSTRACT FROM AUTHOR]

Approximately 90% of patients with arthritis exhibit forefoot deformities, including deformities within the metatarsophalangeal and proximal interphalangeal joints. Current pharmacological treatment with Disease Modifying Antirheumatic Drugs (DMARDs) consists of two groups: synthetic drugs (sDMARDs) and biological drugs (bDMARDs). The objective of our study was to investigate foot anthropometry changes in RA patients based on the administered treatment over a five-year period Method: A longitudinal analysis was conducted with RA patients who were grouped based on their pharmacological treatment. The pharmacological treatment groups were categorized into (I) methotrexate (MTX), (II) MTX plus biological treatments (including all variables), (III) biological treatment alone, and (IV) a miscellaneous group comprising patients with diverse treatments, including patients for whom various drugs had failed or who had not achieved remission with pharmacological treatment. For the anthropometric measurements, a foot measurement platform validated by McPoil et al. was used. Post hoc analyses with Bonferroni correction were performed to identify pairwise differences between the treatment groups while controlling for Type I errors due to multiple comparisons. Results: In the period from 2018 to 2023, significant changes were observed in several foot measurements. For instance, the MTX group showed a statistically significant increase in left heel width (p = 0.026). The MTX group experienced a slight increase in left foot length, while the Biologics and MTX + Bio groups exhibited more substantial increases in both maximum medial arch height and midfoot width. Conclusions: Different RA treatments can have a significant impact on foot structure over a five-year period, showing notable changes in heel width and overall foot morphology. Combined treatments with MTX and biologics potentially offer better management of RA. [ABSTRACT FROM AUTHOR]

Background. Rheumatoid arthritis (RA) has been associated with atrial fibrillation (AF) in observational studies, yet the causal relationship remains elusive. In this study, we employed Mendelian randomization (MR) to investigate the impact of RA on AF risk specifically in East Asian populations. Methods. Utilizing genome‐wide association study (GWAS) data on RA (n = 212,453) and AF (n = 36,792), we applied the following five MR methods: inverse variance weighted (IVW), MR‐RAPS, maximum likelihood, weighted median (WM), and Bayesian weighted Mendelian randomization (BWMR). We evaluated heterogeneity, sensitivity, and pleiotropy. Results. Five genetic instrumental variants for RA were identified. All MR methods consistently indicated a causal association between RA and AF (IVW: OR = 1.20, 95% CI: 1.01–1.41, p < 0.03; MR‐RAPS: OR = 1.21, 95% CI: 1.03–1.42, p < 0.02; maximum likelihood: OR = 1.20, 95% CI: 1.04–1.39, p < 0.01; WM: OR = 1.25, 95% CI: 1.03–1.52, p < 0.03; and BWMR: OR = 1.20, 95% CI: 1.02–1.42, p < 0.03). Sensitivity and pleiotropy analyses confirmed the robustness and validity of the results. Conclusions. This study establishes a causal link between RA and AF in East Asians. Our results underscore the need for in‐depth mechanistic investigations to unravel the underlying pathways. Clinicians should consider AF risk in RA management, emphasizing collaborative care between rheumatologists and cardiologists. Moving forward, future research should explore therapeutic interventions and address the shared biological mechanisms. [ABSTRACT FROM AUTHOR]

Objectives Adult-onset Still's disease (AOSD) is a rare condition characterized by fevers, rash, and arthralgia/arthritis; most doctors treating AOSD in the Netherlands treat <5 patients per year. Currently, there is no internationally accepted treatment guideline for AOSD. The objectives of this study were to conduct a Delphi panel aimed at reaching consensus about diagnostic and treatment strategies for patients with AOSD and to use the outcomes as a basis for a treatment algorithm. Methods The Delphi panel brought together 18 AOSD experts: rheumatologists, internists and paediatricians. The Delphi process consisted of three rounds. In the first two rounds, online lists of questions and statements were completed. In the third round, final statements were discussed during a virtual meeting and a final vote took place. Consensus threshold was set at 80%. Two targeted literature searches were performed identifying the level of evidence of the consensus-based statements. Results Consensus was reached on 29 statements, including statements related to diagnosis and diagnostic tests, definition of response and remission, the therapy, the use of methotrexate and tapering of treatment. The panel consented on reduction of the use of glucocorticoids to avoid side effects, and preferred the use of biologics over conventional treatment. The role of IL-1 and IL-6 blocking agents was considered important in the treatment of AOSD. Conclusion In this Delphi panel, a high level of consensus was achieved on recommendations for diagnosis and therapy of AOSD that can serve as a basis for a treatment guideline. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammatory disease with a higher incidence in older adults. We aimed to analyze the differences in the choice of RA treatment regimens across various age groups. A retrospective cohort study using data from the Ankara Bilkent City Hospital Registry was conducted, involving 3,475 RA patients categorized into three age groups: 18-49, 50-64, and over 65 years. Key variables examined included demographics, comorbidities, and utilization of various treatment modalities, including disease-modifying antirheumatic drugs (DMARDs), tumor necrosis factor-alpha inhibitors (TNFi), targeted synthetic DMARDs (tsDMARDs), and other biological treatments. Statistical analysis was done with Jamovi software. The study found significant differences in drug prescriptions among age groups. Older patients (>65 years) were less likely to be prescribed methotrexate and sulfasalazine but more likely to receive leflunomide and colchicine. A decline in the use of TNFi and tsDMARDs with age was noted, while other biologics were consistently used across all ages. Our findings underscore the impact of age on treatment choices in RA, revealing a tendency towards less aggressive treatment approaches in older patients. We emphasize the importance of re-evaluating current treatment protocols to better accommodate the health needs of the aging RA population and enhance their quality of life. [ABSTRACT FROM AUTHOR]

Background: Recent studies suggest that bacteria may play a role in triggering rheumatoid arthritis. Considering the recent reports on viable but non-culturable cells (VBNC) in the synovial fluid and blood of patients, the role of bacteria has become more prominent. Objective:The present study aimed to use general and specific primers to detect microbiome in the blood of patients with rheumatoid arthritis. Methods: A general primer, called 16S rRNA was used in the present study to detect a wide range of bacteria in the blood of patients with rheumatoid arthritis. Specific primers were designed and used such as nuc and rfbE to trace Staphylococcus aureus and Escherichia coli in patients' blood. Examining 102 blood samples and performing the genomic extraction separately for each sample, PCR was then performed using general and specific primers, and the results were sequenced. The findings were analyzed using descriptive statistics. Results: According to the results, in 102 blood samples of rheumatoid arthritis patients, who were negative for bacteriological culture, there were 74 cases (72.54%) of 16S rRNA gene, and 54 cases (52.9%) of Staphylococcus aureus nuc gene, respectively. Moreover, a specific gene, rfbE, was traced in 12 samples. Conclusion: The findings of the present study indicated the presence of microbiome in the blood of patients with rheumatoid arthritis. Because the blast sequencing results of the PCR product showed a wide range of bacterial genomes. These findings may potentially improve the management of rheumatoid arthritis diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Objective: Patient‐reported outcome (PRO) collection between visits for rheumatoid arthritis (RA) could improve visit efficiency, reducing in‐person visits for patients with stable symptoms while facilitating access for those with symptoms. We examined whether a mobile health PRO application integrated in the electronic health record (EHR) could reduce visit volume for those with RA. Methods: We developed an application for RA that prompted patients every other day to complete brief PRO questionnaires. Results of the application were integrated into the EHR. We tested the application in a controlled interrupted time‐series analysis between 2020 and 2023. Rheumatologists received EHR‐based messages based on PRO results recommending the patient receive a visit earlier or later than scheduled. The primary outcome was monthly visit volume during the year before versus the year after initiation. Results: A total of 150 patients with RA consented and used the application. The median age was 62 years, 83% were female, 7% had fewer than 2 years of disease, and 50% were seropositive; 150 controls were well matched. Among those in the application cohort, the estimated monthly median visit volume in the year before use of the application was 31.2 (95% confidence interval [95% CI] 28.0–34.3); in controls, this was 30.4 (95% CI 27.3–33.6). In the year using the application, the estimated monthly visit volume was 36.8 (95% CI 33.4–40.3) compared to 38.7 (95% CI 35.2–42.3) in controls. The difference in the differences between the cohorts was not statistically significant (−2.7 visits, 95% CI −9.3 to 4.0). No differences were noted in flare rates or visit delays. Conclusion: In this initial trial of a PRO application intervention to improve visit efficiency, we found no association with reduced visit volume. [ABSTRACT FROM AUTHOR]

Objective: Patients with rheumatoid arthritis (RA) may need to access rheumatology care between scheduled visits. WelTel is a virtual care platform that supports secure two‐way text‐messaging between patients and their health care team. The objective of the present study was to explore perspectives and experiences of health care providers (HCPs) and patients related to the use of WelTel as an adjunct to routine care. Methods: Seventy patients with RA were enrolled in a six‐month WelTel pilot project launched in September 2021. Patients received monthly "How are you?" text message check‐ins and could message their health care team during clinic hours to request health advice. The current project is a qualitative study of the WelTel pilot. A subgroup of pilot participants was purposively sampled and invited to participate in interviews. A thematic analysis of transcripts was conducted using a deductive approach leveraging quality of care domains. Results: Thirteen patients (62% female, mean age 62 years, 10 White) completed interviews. Patients' views suggested that text messaging with the rheumatology team supported high‐quality care across multiple quality domains including patient‐centeredness, timeliness, efficiency, safety, effectiveness, equity, and appropriateness. Seven HCPs (57.1% female, one pharmacist and six rheumatologists) completed interviews. HCPs' perspectives varied based on their experience with the WelTel platform. Additional themes reported by HCPs included perceived increased workload and burnout. Conclusions: Patients with RA perceived text‐based messaging as supporting high‐quality care. The impact of increased communications on HCP burnout and workload requires consideration, and future studies should evaluate the effect of texting on patient outcomes. [ABSTRACT FROM AUTHOR]

Talaromycosis is a fungal infection caused by Talaromyces marneffei. The infection was formerly known as penicilliosis. It is the only penicillin species with a dimorphic character and causes systemic mycosis infections in humans. This infection commonly happens in immunocompromised individuals, especially those who are infected with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) or any other immunodeficiency state. The symptoms associated with T. marneffei include fever, weight loss, cough, breathing difficulty, abdominal pain, diarrhea, swollen lymph nodes, and general discomfort. The clinical manifestations impacted by T. marneffei can vary from mild skin lesions to circulatory collapse or respiratory failure. The lungs, liver, and mouth are frequently impacted by talaromycosis in persons who do not have HIV, while it can occasionally spread through the blood and affect the entire body. Here is a case of 70-year-old female patient who had a history of rheumatoid arthritis on steroids, diabetes and hypertension with a recent past history of community-acquired pneumonia treated with intravenous antibiotics from a local hospital. Despite being on appropriate broadspectrum antibiotics, her condition deteriorated, and she was referred here. On admission, she was in sepsis, and she remained sick in spite of being on carbapenems and azithromycin. As she was an immunocompromised host, partial response to initial empiric therapy was considered early transbronchial lung biopsy, which revealed T. marneffei species. She was started on itraconazole oral therapy, to which she responded well and was later discharged. Unfortunately, she got re-admitted on the 25th day with type 1 respiratory failure and shock. The possibility of hospital-acquired infection was considered, and all higher antibiotics, including polymyxin and vancomycin, were initiated in addition to itraconazole therapy and plain amphotericin B as an add-on antifungal therapy; could not revive the patient, and she passed away. This case demonstrates the possibility of T. marneffei infection in any immunocompromised host rather than the fact of its occurrence only in HIV patients and the high mortality associated with it even with reasonable good critical care support. [ABSTRACT FROM AUTHOR]

Background/Aim: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease, and management of it is still a challenge. The present investigation assessed the potential preventive effect of phlorizin on rats with RA. Materials and Methods: A total of 40 healthy Wistar rats were used for this study. Bovine type II collagen and Freund's incomplete adjuvant (1:1 and 1 mg/ml) were administered on days 1 and 8 of the protocol to induce RA in rats; treatment with phlorizin at 60 or 120 mg/kg was started after the 4th week of the protocol, and its effect on inflammation, level of inflammatory cytokines, and expression of proteins were estimated in RA rats. Moreover, an in vitro study was performed on fibroblast-like synoviocytes (FLSs), and the effects of phlorizin on proliferation, apoptosis, and expression of the mechanistic target of rapamycin kinase pathway protein after stimulating these cells with tumor necrosis factor α (TNF-α) were estimated. Results: The data obtained from the study indicate that phlorizin has the potential to mitigate inflammation and enhance weight management in rats with RA induced by bovine type II collagen (CII). The level of inflammatory cytokines in the serum and the expression of protein kinase B (AKT), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and mechanistic target of rapamycin kinase (mTOR) proteins in the joint tissue were reduced in phlorizin-treated rats with RA. In this investigation, phlorizin was shown to reverse the histological abnormalities in the joint tissue of rats with RA. The in-vitro study showed that phlorizin reduced proliferation and had no apoptotic effect on TNF- α-stimulated FLSs. Expression of AKT, PI3K, and mTOR proteins was also down-regulated in phlorizin-treated TNF- α-stimulated FLSs. Conclusion: Phlorizin protects against inflammation and reduces injury to synovial tissues in RA by modulating the AKT/PI3K/mTOR pathway. [ABSTRACT FROM AUTHOR]

Objectives: This research aims to present and assess the Primary Functions of autoinjectors introduced in ISO 11608-1:2022. Investigate the risks in current autoinjector technology, identify and assess risks and benefits associated with Artificial Intelligence (AI) powered autoinjectors, and propose a framework for mitigating these risks. ISO 11608-1:2022 is a standard that specifies requirements and test methods for needle-based injection systems intended to deliver drugs, focusing on design and function to ensure patient safety and product effectiveness. 'KZH' is an FDA product code used to classify autoinjectors, for regulatory purposes, ensuring they meet defined safety and efficacy standards before being marketed. Method: A comprehensive analysis of autoinjectors problems is conducted using data from the United States Food and Drug Administration (FDA) database. This database records medical device reporting events, including those related to autoinjectors, reported by various sources. The analysis focuses on events associated with the product code KZH, covering data from January 1, 2008, to September 30, 2023. This research employs statistical frequency analysis and incorporates pertinent the FDA, United Kingdom, European Commission regulations, and ISO standards. Results: 500 medical device reporting events are assessed for autoinjectors under the KZH code. Ultimately, 188 of these events are confirmed to be associated with autoinjectors, all 500 medical devices were seen to lack AI capabilities. An analysis of these events for traditional mechanical autoinjectors revealed a predominant occurrence of malfunctions (72%) and injuries (26%) among event types. Device problems, such as breakage, defects, jams, and others, accounted for 45% of incidents, while 10% are attributed to patient problems, particularly missed and underdoses. Conclusion: Traditional autoinjectors are designed to assist patients in medication administration, underscoring the need for quality control, reliability, and design enhancements. AI autoinjectors, sharing this goal, bring additional cybersecurity and software risks, requiring a comprehensive risk management framework that includes standards, tools, training, and ongoing monitoring. The integration of AI promises to improve functionality, enable real-time monitoring, and facilitate remote clinical trials, timely interventions, and tailored medical treatments. [ABSTRACT FROM AUTHOR]

Synovitis is the inflammation of a synovial membrane surrounding a joint. Its assessment is an important step in the diagnosis and treatment of rheumatoid arthritis. Joint detection is the first stage of an automated method of assessment of a degree of synovitis, from an Ultrasound (USG) image of a finger joint and its surrounding area. A joint detector consists of three parts: image preprocessing, feature extraction, and classi- fication. Each part contains adjustable parameters that must be set experimentally to ensure the proper operation of the detector. Both the structure of a joint detector and a procedure for finding a near-optimal configuration of the adjustable parameters are described. The optimization process is based on two evaluation measures: Area Under the Receiver Operating Characteristic Curve (AUC) and False Positive Count (FPC). The optimization process decreases the number of pictures with multiple detections, which was the main point of works presented in this paper. This was achieved by increasing the number of components of the homogeneous mixed-SURF descriptor which has the greatest influence on the final result. Non-SURF descriptors achieve poorer classification results. Our research led to the creation of a better joint detector which could positively influence the final results of inflammation level classification [ABSTRACT FROM AUTHOR]

Objective: Chronic fatigue is a major clinical unmet need among patients with rheumatoid arthritis (RA). Current therapies are limited to nonpharmacological interventions, such as personalized exercise programs (PEPs) and cognitive–behavioral approaches (CBAs); however, most patients still continue to report severe fatigue. To inform more effective therapies, we conducted a magnetic resonance imaging (MRI) brain study of PEPs and CBAs, nested within a randomized controlled trial (RCT), to identify their neurobiological mechanisms of fatigue reduction in RA. Methods: A subgroup of patients with RA (n = 90), participating in an RCT of PEPs and CBAs for fatigue, undertook a multimodal MRI brain scan following randomization to either usual care (UC) alone or in addition to PEPs and CBAs and again after the intervention (six months). Brain regional volumetric, functional, and structural connectivity indices were curated and then computed employing a causal analysis framework. The primary outcome was fatigue improvement (Chalder fatigue scale). Results: Several structural and functional connections were identified as mediators of fatigue improvement in both PEPs and CBAs compared to UC. PEPs had a more pronounced effect on functional connectivity than CBAs; however, structural connectivity between the left isthmus cingulate cortex (L‐ICC) and left paracentral lobule (L‐PCL) was shared, and the size of mediation effect ranked highly for both PEPs and CBAs (ßAverage = −0.46, SD 0.61; ßAverage = −0.32, SD 0.47, respectively). Conclusion: The structural connection between the L‐ICC and L‐PCL appears to be a dominant mechanism for how both PEPs and CBAs reduce fatigue among patients with RA. This supports its potential as a substrate of fatigue neurobiology and a putative candidate for future targeting. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis is a chronic systemic inflammatory arthritis disease that affects mainly synovial joints. The incident of RA can lead to the emergence of complications or comorbidities, which then allows patients to receive a variety of therapies that can trigger the incidence of DRPs during the treatment. The prevalence of RA in Indonesia itself in 2018 has reached 7.30%, with the highest percentage occurring in the elderly age group and more prevalent in women. Objective: This study aimed to determine the incidence of DRPs in RA patients in Palembang city hospitals based on the category of DRPs identified as related to drug selection and dose selection problems, as the relationship between demographic factors and the incidence of DRPs. Methods: This research is non-experimental study conducted with a retrospective cross-sectional survey. Data collection was carried out by looking at patient medical record data at X and Y Hospital in Palembang from January 2021 to March 2023. Results: The results showed that the most frequent drps in the drug selection category were drug interactions (72.03%), while in the dose selection category were insufficient dosage regimens (60.74%). The results of bivariate analysis between the incidence of DRPs and gender (p=0.809), age (p=0.879), the number of drugs used (p=0.001), and comorbidities (p=0.089). Conclusion: There is no relationship between demographic factors and comorbidities with the incidence of DRPs, and there is a relationship between the number of drugs and the incidence of DRPs. [ABSTRACT FROM AUTHOR]

Generalized pustular psoriasis (GPP) is a disease that presents with fever and multiple sterile pustules on flushed skin all over the body. GPP should be considered as systemic inflammatory response syndrome (SIRS), and is occasionally associated with respiratory failure. We encountered a case of GPP with organizing pneumonia (OP) during treatment for rheumatoid arthritis (RA). A 74-year-old Japanese woman with RA developed fever and erythema with small pustules on the trunk and extremities. She was diagnosed as GPP and admitted to our hospital. During the clinical course, she suffered hypoxia from OP. Although RA and OP are known to coexist, GPP and OP share the involvement of cytokines such as interleukin 8 in the pathogenesis. These cytokines are therefore also involved in the complications of GPP and OP. [ABSTRACT FROM AUTHOR]

Objective: To explore the clinical judgements of therapists in prescribing the intensity of hand strengthening exercise in rheumatoid arthritis (RA). Methods: Phase I: Eleven therapists knowledgeable in treating patients with RA subjectively identified seven clinical cues. These were incorporated into 54 hypothetical patient case scenarios. Phase II: Therapists with ≥2 years post‐registration experience and current or recent experience in treating patients with RA were asked to assess 69 case scenarios in total (54 + 15 repeats) and judge what intensity of hand strengthening exercise they would prescribe using the OMNI‐Resistance Exercise Scale of perceived exertion. Using responses to the repeated cases, the Cochran‐Weiss‐Shanteau index of expertise was used to identify therapists who prescribed more consistently. Multiple regression was used to determine which clinical cues were most strongly associated with the intensity of exercise prescribed. A sub‐group analysis explored differences between consistent and inconsistent prescribers. Results: Fifty‐three therapists took part. Thirty completed all 69 case scenarios. Across all therapists, the three most important clinical cues associated with lower intensity of exercise prescribed were (1) Patient's reported pain intensity whilst practising the exercise (β = −1.150, p < 0.001), (2) Disease activity (β = −0.425, p < 0.001) and (3) average hand pain over the last week (β = −0.353 p < 0.001). Twelve therapists were categorised as consistent prescribers. This group relied on fewer clinical cues (three vs. seven) when judging what intensity of exercise to prescribe. Conclusion: This study provides insights into how therapists prescribe hand exercises. Intensity of hand strengthening exercise was influenced by three key clinical cues, including pain intensity and disease activity. [ABSTRACT FROM AUTHOR]

Arthritis, a global health burden comprising osteoarthritis and rheumatoid arthritis, demands advanced therapeutic approaches. In this context, flavonoids, a diverse group of naturally occurring compounds abundant in fruits, vegetables, and medicinal plants, have emerged as promising candidates for mitigating the inflammatory processes associated with arthritic conditions. This review aims, first, to provide a comprehensive exploration of the potential of flavonoids, focusing on specific compounds such as quercetin, epigallocatechin-3-gallate (EGCG), apigenin, luteolin, fisetin, silibinin, kaempferol, naringenin, and myricetin. The second section of this review delves into the anti-arthritic activities of these flavonoids, drawing insights from clinical trials and scientific studies. Each flavonoid is scrutinized individually to elucidate its mechanisms of action and therapeutic efficacy in the context of both osteoarthritis and rheumatoid arthritis. The third section of this review highlights the challenges associated with harnessing flavonoids for anti-inflammatory purposes. Bioavailability limitations pose a significant hurdle, prompting the exploration of innovative strategies such as the use of nanoparticles as delivery vehicles. In response to these challenges, the fourth section focuses on the emerging field of flavonoid-based nanoparticles. This includes detailed discussions on quercetin, EGCG, fisetin, and naringenin-based nanoparticles, highlighting formulation strategies and preclinical evidence supporting their potential in arthritis management. The targeted delivery to inflammatory sites and the exploration of synergistic combinations with other compounds are also discussed as promising avenues to enhance the therapeutic impact of flavonoids. This review consolidates current knowledge on flavonoids and their nanoformulations as potential therapeutic interventions for osteoarthritis and rheumatoid arthritis. By addressing challenges and presenting future research directions, this review aims to contribute to the advancement of innovative and effective strategies for alleviating the global burden of arthritis. [ABSTRACT FROM AUTHOR]

Physical therapists (PTs) should know how to best treat patients with inflammatory arthritis. To document interventions chosen by PTs for patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS) and whether choices follow evidence-based practice. Licensed musculoskeletal PTs in Quebec, Canada responded to an online survey. Descriptive statistics illustrated proportions for each treatment choice and inferential statistics explored associations with demographic and practice-related factors. There were 298 PTs who responded to the survey. For both RA and AS respectively, most common interventions were mobility exercises (91.0%; 98.3%) and patient education (90.1%; 92.8%). For both cases, slightly >60% selected strengthening exercises. Passive forms of therapy were chosen by 36% of PTs for RA and 58% for AS. Aerobic exercise was rarely selected. PTs working in the public sector were less likely to use manual therapy for both RA (Odds Ratio (OR) 0.43, 95% confidence interval (CI) 0.22,0.86) and AS (OR 0.46, 95% CI 0.22,0.97). Most PTs chose mobility exercises and patient education, representing evidence-based approaches. Despite current recommendations, strengthening and especially aerobic exercises were not used as much. There is a need to increase awareness regarding the benefits of strengthening and aerobic exercise for these patients. [ABSTRACT FROM AUTHOR]

Depuis une dizaine d'années, les perspectives des patients atteints de polyarthrite rhumatoïde se sont grandement améliorées, en particulier en cas de positivité des auto-anticorps. Pour optimiser l'évolution de la maladie sur le long terme, la communauté cherche à établir si « le plus tôt est bien le mieux » et s'il serait efficace d'instaurer un traitement dans la phase préarthrite de la polyarthrite rhumatoïde. Cette revue évalue le concept de prévention et examine la probabilité prétest de développer une PR pour différents niveaux de risque. Ces niveaux de risque influencent la probabilité post-test des biomarqueurs utilisés et, par conséquent, la précision avec laquelle le risque de polyarthrite rhumatoïde peut être estimé. En outre, de par leur effet sur la précision de la stratification du risque, ces probabilités prétest sont également associées à la probabilité de résultats faux négatifs (ce que Feinstein a qualifié de « tragédie clinico-statistique »). Les critères employés pour évaluer les effets préventifs sont liés soit à l'apparition effective de la maladie, soit à la sévérité des facteurs de risque de développement d'une polyarthrite rhumatoïde. Les résultats d'études de prévention achevées récemment sont discutés à la lumière de ces considérations théoriques. Ils sont variables et n'ont pas permis de démontrer une prévention claire de la polyarthrite rhumatoïde. Certains traitements (p. ex. méthotrexate) ont systématiquement réduit la sévérité des symptômes, le handicap physique et la sévérité de l'inflammation articulaire visible à l'imagerie, tandis que d'autres (hydroxychloroquine, rituximab, atorvastatine) n'ont pas entraîné d'effets durables. La revue propose en conclusion des perspectives concernant la conception de nouvelles études de prévention, ainsi que des éléments et des impératifs à prendre en considération pour qu'il soit possible d'exploiter les résultats dans la pratique clinique des cabinets de rhumatologie recevant des personnes à risque de polyarthrite rhumatoïde. During the last decade, the outlook for patients with rheumatoid arthritis (RA) has improved greatly, especially for patients with autoantibody-positive RA. To further improve long-term disease outcomes, the field has turned to investigating the efficacy of treatment initiated in the pre-arthritic phase of RA, based on the adage "the sooner the better." In this review, the concept of prevention is evaluated and different risk stages are being examined for their pre-test risks of RA development. These risks affect the post-test risk of biomarkers used at these stages and, consequently, the accuracy with which the risk of RA can be estimated. Furthermore, through their effect on accurate risk stratification, these pre-test risks ultimately also associate with the likelihood of false-negative trial results (the so-called 'clinicostatistical tragedy'). Outcome measures to assess preventive effects are evaluated and relate to either the occurrence of disease itself or to the severity of risk factors for RA development. Results of recently completed prevention studies are discussed in the light of these theoretical considerations. The results vary, but clear prevention of RA has not been demonstrated. While some treatments (e.g. methotrexate) persistently reduced symptom severity, physical disability, and the severity of imaging joint inflammation, other treatments were not reported to produce long-lasting effects (hydroxychloroquine, rituximab, atorvastatin). The review concludes with future perspectives regarding the design of new prevention studies and considerations and requirements before findings can be implemented in daily practice in individuals at risk of RA attending rheumatology practices. [ABSTRACT FROM AUTHOR]

Objective: To compare a remotely supervised weight loss and exercise intervention to lifestyle counseling for effects on cardiovascular disease risk, disease activity, and patient‐reported outcomes in older patients with rheumatoid arthritis (RA) and overweight/obesity. Methods: Twenty older (60–80 years), previously sedentary participants with seropositive RA and overweight/obesity were randomized to 16 weeks of either Supervised Weight loss and Exercise Training (SWET) or Counseling Health As Treatment (CHAT). The SWET group completed aerobic training (150 minutes/week moderate‐to‐vigorous intensity), resistance training (two days/week), and a hypocaloric diet (7% weight loss goal). The CHAT control group completed two lifestyle counseling sessions followed by monthly check‐ins. The primary outcome was a composite metabolic syndrome z‐score (MSSc) derived from fasting glucose, triglycerides, high density lipoprotein–cholesterol, minimal waist circumference, and mean arterial pressure. Secondary outcomes included RA disease activity and patient‐reported outcomes. Results: Both groups improved MSSc (absolute change −1.67 ± 0.64 in SWET; −1.34 ± 1.30 in CHAT; P < 0.01 for both groups) with no between‐group difference. Compared with CHAT, SWET significantly improved body weight, fat mass, Disease Activity Score‐28 C‐reactive protein, and patient‐reported physical health, physical function, mental health, and fatigue (P < 0.04 for all between‐group comparisons). Based on canonical correlations for fat mass, cardiorespiratory fitness, and leg strength, component‐specific effects were strongest for (1) weight loss improving MSSc, physical health, and mental health; (2) aerobic training improving physical function and fatigue; and (3) resistance training improving Disease Activity Score‐28 C‐reactive protein. Conclusion: In older patients with RA and overweight/obesity, 16 weeks of remotely supervised weight loss, aerobic training, and resistance training improve cardiometabolic health, patient‐reported outcomes, and disease activity. Less intensive lifestyle counseling similarly improves cardiovascular disease risk profiles, suggesting an important role for integrative interventions in the routine clinical care of this at‐risk RA population. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a progressive, chronic, autoimmune, inflammatory, and systemic condition that primarily affects the synovial joints and adjacent tissues, including bone, muscle, and tendons. The World Health Organization recognizes RA as one of the most prevalent chronic inflammatory diseases. In the last decade, there was an expansion on the available RA therapeutic options which aimed to improve patient's quality of life. Despite the extensive research and the emergence of new therapeutic approaches and drugs, there are still significant unwanted side effects associated to these drugs and still a vast number of patients that do not respond positively to the existing therapeutic strategies. Over the years, several references to the use of flavonoids in the quest for new treatments for RA have emerged. This review aimed to summarize the existing literature about the flavonoids' effects on the major pathogenic/molecular targets of RA and their potential use as lead compounds for the development of new effective molecules for RA treatment. It is demonstrated that flavonoids can modulate various players in synovial inflammation, regulate immune cell function, decrease synoviocytes proliferation and balance the apoptotic process, decrease angiogenesis, and stop/prevent bone and cartilage degradation, which are all dominant features of RA. Although further investigation is necessary to determine the effectiveness of flavonoids in humans, the available data from in vitro and in vivo models suggest their potential as new disease‐modifying anti‐rheumatic drugs. This review highlights the use of flavonoids as a promising avenue for future research in the treatment of RA. [ABSTRACT FROM AUTHOR]

Objective To identify and synthesize patient-related barriers to and enablers of the implementation of high-value physiotherapy (HVP) for chronic pain. Furthermore, to review what patient-related interventions have been used to facilitate the implementation of HVP for chronic pain, as well as their efficacy. Methods We systematically searched the APA PsycInfo, Embase, CINAHL, Medline, Scopus, and PEDro databases for peer-reviewed studies (published in English) of adults with chronic pain. We used the Theoretical Domains Framework of behavior change to synthesize identified themes relating to barriers and enablers. Outcomes from studies reporting on interventions were also qualitatively synthesized. Results Fourteen studies reported on barriers and enablers, 8 of which related to exercise adherence. Themes common to barriers and enablers included perceived efficacy of treatment, interrelationship with the physiotherapist, exercise burden, and the patient's understanding of exercise benefits. Other barriers included fear of movement, fragmented care, and cost. Ten studies explored interventions, 9 of which aimed to improve exercise adherence. Of these, evidence from 4 randomized controlled trials of technology-based interventions demonstrated improved exercise adherence among intervention groups compared with controls. Conclusion Patients with chronic pain experience barriers to HVP, including their beliefs, the nature of their interaction with their physiotherapist, perceived treatment efficacy, and cost. Enablers include rapport with their physiotherapist, achievable exercises, and seamless cost-effective care. Technology-based interventions have demonstrated effectiveness at increasing exercise adherence. Our findings suggest that interventions seeking to enhance implementation of HVP need to consider the multifactorial barriers experienced by patients with chronic pain. Study registration Open Science Framework (https://doi.org/10.17605/OSF.IO/AYGZV). [ABSTRACT FROM AUTHOR]

The aim of article is to provide prompt and brief information on all available types of formulations of tofacitinib citrate. Tofacitinib in the form of tofacitinib citrate belongs to a new class of therapies called Janus kinase (JAK) inhibitors. Tofacitinib citrate is a medication used to treat rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. Tofacitinib is available in the form of a tablet, an extended-release tablet and as an oral solution. Janus kinase inhibitors (JAKi) belong to a new class of oral targeted disease-modifying drugs which have recently revolutionized the therapeutic panorama of rheumatoid arthritis (RA) and other immune-mediated diseases, placing alongside or even replacing conventional and biological drugs. This article elaborates on the information related to patents of tofacitinib citrate for its formulation. A survey data for the marketed formulations of tofacitinib citrate is tabulated. Based on this it is estimated that very less type of formulations pertaining to conventional formulations as tablet or gel is only available in the market. Hence, there is an immediate demand for different type of tofacitinib formulations needed for treatment of extensive cases of arthritis or vitiligo. An extensive literature survey is done on pharmaceutical formulations of tofacitinib citrate. Based on obtained data it was found these researched and developed formulations can be focused and further initiations can be done to make these formulations marketable. Wholesome, this article assists the reader to quickly grab information on marketed formulations and researched formulations of tofacitinib citrate. [ABSTRACT FROM AUTHOR]

Introduction. This study aimed primarily to investigate the effect of a PEMF on proprioception in terms of mechanoreceptor number and function and secondarily to assess the gait quality (sciatic function index) and arthritis severity (paw volume and body weight) in adjuvant-induced arthritis (AIA) RA model. Methods. Twenty-eight healthy adult male Wistar rats were randomly divided into 3 groups: (I) RA experimental model treated with a PEMF (10 animals), (II) positive control (10 animals), and (III) negative control (8 animals). Group I was exposed to a PEMF (0.3 mT 1 h/day for 2 weeks), while Groups II and III were placed in the same setup, except that the PEMF was turned off. The proprioceptive function [as tactile response (TR) / hopping response (HR) / forelimb placing test (FPT)], paw volume (PF), and mechanoreceptor numbers were then tested. Results. There was a significant preservation of mechanoreceptor numbers and proprioception in group I compared to group II, as follows: the number of Ruffini corpuscles mechanoreceptors (p = 0.007) and TR on days 9 and 14 (p = 0.002, 0.012, respectively) with no significant difference compared to group III. Also, PV decreased significantly in group I relative to group II (p = 0.01) with no significant difference for group III. Conclusions. PEMF significantly preserved proprioception receptors and function and decreased inflammation severity in the AIA-RA model. [ABSTRACT FROM AUTHOR]

We analyzed whether commonly used biological medicinal products and/or tyrosine kinase inhibitors with indications for treatment of rheumatologic diseases can be used in patients with concurrent COVID-19 by systematically reviewing scientific articles. The articles were selected according to PRISMA by keywords in the MEDLINE and Central Medical Library - MU Sofia databases for the period January 2020-December 2023. We found 168 scientific publications, of which 9 met the set criteria. Results were evaluated using descriptive methods and the PICOS tool. We found no evidence that the use of BMPs and TKIs in patients with rheumatologic diseases leads to an increased risk of COVID-19 infection and/or a more severe course of SARS-CoV-2 infection. Several cases of prolonged or atypical COVID-19-induced pneumonia have been identified in patients treated with Rituximab. This suggests the need for caution in the use of this medicinal product in patients with COVID-19. The 2022 EULAR recommendations are in the same spirit. [ABSTRACT FROM AUTHOR]

Background: Methotrexate is one of the mainstays for treating rheumatoid arthritis (RA) with a wide range of adverse drug reactions, however, it's the relationship between adverse drug reactions and genetic polymorphism remains to be highlighted, and there is a lack of studies concerning Arabic Iraqi population regarding this aspect. Objective: Evaluate the association between genetic mutations in the MTHFR gene in SNPs (rs1801133G>A and rs1801131T>G) on the adverse drug reaction for RA Iraqi patients. Methods: An observational study, that involved 95 Iraqi RA patients with established RA. Patients were divided according to the occurrence of adverse drug reactions. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was being utilized for MTHFR variants (rs1801133 and rs1801131). The Macrogen Company (Korea) provided the forward and reverse primers in lyophilized form. All PCR procedures are carried out using a PCR thermal cycler (Germany). Results: The study included 95 patients with RA, with a mean age of 43.1 ± 10.6 years, most of the patients were female (85.3%), about 35.8% were smokers, most of the patients had disease low activity (45.2%), followed by moderate (41.1%), high (9.5%), and remission (4.2%). No significant association between individual genetic polymorphism with adverse drug reactions. AG haplotype for rs1801133 rs1801131 polymorphism is associated with reducing the risk of overall adverse drug reactions, meanwhile, GT haplotype for rs1801133, and rs1801131 polymorphism were marginally associated with increased risk of adverse drug reactions. Conclusion: In conclusion, we have successfully found a panel of pharmacogenetic indicators that have the potential to be valuable in predicting the response to methotrexate treatment in patients with rheumatoid arthritis. Haplotypes for rs1801133 rs1801131 polymorphism are associated with reducing or increasing the risk of MTX adverse drug reactions. It is very important to evaluate patients' haplotypes before starting the therapy program so that we can expect the treatment outcome with the most suitable dose and most tolerable one at the same time. [ABSTRACT FROM AUTHOR]

Background: Olokizumab (OKZ) is a monoclonal antibody against the interleukin receptor-6 that has shown promise in recent phase II and III trials in patients of rheumatoid arthritis (RA). This meta-analysis aims to evaluate the efficacy and safety of Olokizumab in managing rheumatoid arthritis. Methods: We searched different databases until March 2023 for randomized controlled trials inspecting the effects of OKZ on various outcomes in RA patients inadequately controlled with anti-TNF or methotrexate. Data were analyzed via Review Manager-v 5.4.1. Relative risks (RR) with 95% confidence intervals were calculated. Results: We evaluated five trials with 2761 patients under four treatment groups: 60mg OKZ administered 2-weekly, 64mg 2-weekly, 64mg 4-weekly, and 120mg 2-weekly. Clinical response as measured by ACR 20, 50, and 70 showed statistically significant improvement with the use of OKZ. A 50% disease improvement was seen across all 4 treatment groups (OKZ 64 mg q2w: RR= 2.96, p<0.0001, OKZ 64mg q4w: RR= 3.06, p=0.0002, OKZ 60 mg q2w: RR=5.06, p=0.007, and OKZ 120mg q2w: RR= 3.63, p=0.04). Moreover, 20% and 70% improvements were also noted with OKZ in doses 64mg 2-weekly and 4-weekly. Disease remission, as indicated by DAS28 <2.6 was also significantly higher than placebo across all groups. Safety data showed comparable mortality rates in treatment and placebo groups (OKZ 64mg q2w: p=0.48, OKZ 64 mg q4w: p=0.93). Conclusion: In conclusion, Olokizumab has shown significant improvement in disease activity compared to placebo with a favourable safety profile. However, further larger and longer-term studies are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Objective: Preliminary evidence suggests that vagus nerve stimulation (VNS) may have some benefit in patients with rheumatoid arthritis (RA); however, prior studies have been small and/or uncontrolled; this study aimed to address that gap. Methods: This randomized, double‐blind, sham‐controlled trial enrolled patients aged 18 to 75 years with active RA who had failed conventional synthetic disease‐modifying antirheumatic drugs (DMARDs) and were naïve to biologic and/or targeted synthetic DMARDs. All patients received an auricular vagus nerve stimulator and were randomized 1:1 to active stimulation or sham. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Secondary endpoints included mean changes in disease activity score of 28 joints with C‐reactive protein (DAS28‐CRP) and Health Assessment Questionnaire‐Disability Index (HAQ‐DI). Results: A total of 113 patients (mean age 54 years; 82% female) enrolled, and 101 patients (89.4%) completed week 12. ACR20 response at week 12 was 25.0% for active stimulation versus 26.9% for sham (difference vs. sham, −1.9; 95% CI, −18.8, 14.9, P = 0.823). The least square mean ± SE change in DAS28‐CRP was −0.95 ± 0.16 for active stimulation and −0.66 ± 0.16 for sham (P = 0.201); in HAQ‐DI it was −0.19 ± 0.06 for active stimulation and −0.02 ± 0.06 for sham (P = 0.044). Adverse events occurred in 17 patients (15%); all were mild or moderate. Conclusion: Auricular VNS did not meaningfully improve RA disease activity. If VNS with other modalities is pursued in the future for the treatment of RA, larger, controlled studies will be needed to understand its utility. [ABSTRACT FROM AUTHOR]

Aims: The study aimed to develop and evaluate the effects of a self‐determination theory‐based, nurse‐led, physical activity programme for postmenopausal women with rheumatoid arthritis. Methods: Between December 2019 and April 2020, this randomized controlled trial recruited 62 postmenopausal women with rheumatoid arthritis from a university‐affiliated hospital in South Korea. The intervention group participated in a self‐determination theory‐based, nurse‐led, physical activity programme that consisted of Tai Chi‐based physical activity, a supportive psychosocial strategy, and interactive counselling for 16 weeks, and the control group continued to undergo their usual care. Results: There were statistically significant group‐by‐time interactions in physical activity and perceived sarcopenia, which favoured the intervention group. Additionally, the intervention group showed significant improvements in the perceived therapeutic efficacy of physical activity, grip strength, walking speed, disease activity score, and health‐related quality of life. Conclusions: The programme developed in this study can be an effective and feasible approach for postmenopausal women with rheumatoid arthritis in improving physical activity, selected osteosarcopenic outcomes, and health‐related quality of life. Further research is required to investigate the long‐term effects of this theory‐based programme for postmenopausal women in diverse settings. Summary statement: What is already known about this topic? Tai Chi‐based physical activity has been known to be a component of self‐management for rheumatoid arthritis. What this paper adds? It highlights the efficacy of a theory‐based, nurse‐led, physical activity programme to improve the quality of life of postmenopausal women with rheumatoid arthritis.The evidenced‐based programme could be transferred to postmenopausal women with rheumatoid arthritis in clinical settings. The implications of this paper: The self‐determination theory‐based, nurse‐led, physical activity programme can improve physical and psychosocial outcomes in postmenopausal women with rheumatoid arthritis.Importantly, this nurse‐led and theory‐based programme is expected to be applicable to postmenopausal women with rheumatoid arthritis in clinical settings, including both hospitals and communities. [ABSTRACT FROM AUTHOR]

Background: Despite the recent advances in the management of inflammatory arthritis, a considerable proportion of arthritis patients remain symptomatic. This cohort has recently been identified as 'difficult to treat' (D2T). In view of the limited evidence base, management of these patients has been a challenge particularly in view of its associated significant economic health burden. A better understanding of the D2T may help recognise or develop new therapeutic targets and facilitate earlier intervention in the disease course to prevent the progression of such condition. The aim of this work is to address the unmet needs in the management of D2T arthritis and develop a comprehensive approach towards the identification and proper assessment of those patients. Results: At the completion of round 3 Delphi process, a total of 20 items were obtained and divided into 5 domains. From 88.9 to 100% of respondents agreed with the recommendations (ranks 7–9). All 20 of the clinical standards that the scientific committee identified were agreed upon in terms of wording, recommendation grade, and level of evidence (i.e. 75% of respondents strongly agreed or agreed). Conclusion: D2T inflammatory arthritis remains a relevant clinical challenge, despite the endorsement of the treat-to-target approach and the availability of a broad range of targeted arthritis medications. This study provided a comprehensive definition of the condition to facilitate the identification of this patients' group. It also highlighted the goals and principles aiming at providing an effective framework for D2T assessment, closely monitor and set up a strategy to intervene in standard clinical practice. [ABSTRACT FROM AUTHOR]

Objective: The inflammatory arthritides (IAs) make up a significant proportion of conditions followed up in rheumatology clinics. These patients require regular monitoring, but this is increasingly difficult with rising patient numbers and demand on clinics. Our objective is to evaluate the clinical impact of electronic patient‐reported outcome measures (ePROMs) as a digital remote‐monitoring intervention on disease activity, treatment decisions, and health care resource use in patients with IA. Methods: Five databases (MEDLINE, Embase, PubMed, Cochrane Library, and Web of Science) were searched, with randomized controlled trials and (nonrandomized) controlled clinical trials included, and meta‐analysis and forest plots conducted for each outcome. Risk of bias was assessed using the Risk of Bias‐2 tool and Risk of Bias in Nonrandomized Studies of Interventions. Results: Eight studies were included with a total of 4,473 patients, with seven studies assessing patients with rheumatoid arthritis. Compared with control, the disease activity in the ePROM group was lower (standardized mean difference [SMD] −0.15; 95% confidence interval [CI] −0.27 to −0.03) and rates of remission/low disease activity were higher (odds ratio1.65; 95% CI 1.02–2.68), but five of eight studies provided additional combined interventions (e.g., disease education). Fewer face to face visits were needed in the remote ePROM group (SMD −0.93; 95% CI −2.14–0.28). Conclusion: Most studies were at high risk of bias with significant heterogeneity in design, but our results suggest there is an advantage in using ePROM monitoring in patients with IAs, with the potential for reduction in health care resource use without detrimental impact in disease outcomes. [ABSTRACT FROM AUTHOR]

Introduction. Rheumatoid arthritis is a form of inflammatory joint disease; sometimes, patients need prolonged cycles of nonsteroidal anti-inflammatory drugs and/or glucocorticoids for symptomatology management in addition to traditional disease-modifying drugs and biologics. On some occasions, doses are increased without improvement of symptoms associated with side effects; this is why, on some occasions, patients seek other types of nonpharmacological therapies, such as alternative therapies. Objective. To establish the effectiveness of alternative therapies such as yoga and acupuncture in rheumatoid arthritis by measuring disease activity with the disease activity score 28. Methods. A systematic review of the literature and meta-analysis was performed; databases such as PubMed and Embase were used to find the best available evidence of randomized clinical trials from 2017 to 2021, two researchers independently screened and extracted the necessary data, and the methodological quality and the risk of bias were assessed through the Cochrane risk-of-bias tool. The articles that applied for meta-analysis were analyzed in Jamovi version 2.2 and EPIDATA version 3.1 software. Results. Eight studies were included for qualitative analysis of which seven were included in the meta-analysis, with 550 rheumatoid arthritis patients, predominantly female. The meta-analysis evidenced a significant effect of yoga and acupuncture interventions in decreasing DAS 28 in patients with rheumatoid arthritis (four RCTs; SMD −2.51 95% CI [−2.89, −2.14], p ≤ 0.001 , I2 25.9%); in the yoga subgroup analysis, there was also evidence of improvement in the evaluated outcome (three RCTs; SMD −0.51 95% CI [−0.71, −0.30], p ≤ 0.001 , I2 0%). Conclusion. It was demonstrated that the practice of yoga and acupuncture in patients with rheumatoid arthritis helped to decrease disease activity through the improvement of pain and joint inflammation; we recommend the implementation of this type of alternative intervention associated with conventional therapies for the management of patients diagnosed with rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Background: Major improvements in the management of rheumatoid arthritis (RA) have made clinical remission an achievable and desirable goal but, despite the relevance gained by a profound disease suppression, many patients with RA still miss clinical remission due to several factors influencing disease activity, including treatment adherence. Objective: To evaluate the effect of adherence to conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) on the achievement of clinical remission in a cohort of patients with new-onset inflammatory arthritis. Study design: A prospective cohort study was conducted using the ELECTRA database, which consists of clinical data from patients followed at the IRCCS Policlinico San Matteo Foundation (Pavia, Italy), linked to regional administrative healthcare databases. Methods: We enrolled patients with new-onset active disease between January 2006 and December 2013 and followed them until their first clinical remission or end of follow-up (December 2015). To assess the association of csDMARD adherence with clinical remission, we estimated the csDMARD proportion of days covered (PDC) during follow-up. PDC was added to the main clinical adjustment covariates as a time-dependent variable in a proportional hazard Cox regression model. Results: The cohort included 324 patients with a mean (SD) age of 58 (13.9) and predominantly female (74.5%). A total of 219 patients (67.6%) achieved clinical remission during follow-up and 85 (26.2%) in the first 6 months (early clinical remission). Cox regression models showed that a 10% increment of PDC increased the probability of achieving clinical remission by 10% (p < 0.001) and the probability of early clinical remission by 21% (p = 0.03). Conclusion: Patients at disease onset with higher adherence to csDMARDs were more likely to achieve clinical remission and early clinical remission. Our study highlighted the importance of close monitoring of patients to increase their likelihood of following therapeutic indications and achieving favorable disease outcomes, such as lower disability. [ABSTRACT FROM AUTHOR]

Aim: To investigate the levels of signal peptide-CUB-EGF domain-containing protein (SCUBE 1 and 3) in rheumatoid arthritis (RA). Materials and Methods: Twenty eight RA patients and 28 healthy volunteers were included in the study. SCUBE-1, SCUBE-3, Vascular Endothelial Growth Factor (VEGF), Matrix Metalloproteinase-9 (MMP-9), CD-40L, Interleukin-6 (IL-6) levels, which are important markers in angiogenesis, were measured twice, at baseline and after the treatment. Results: Compared to the healthy group, only MMP-9, one of the angiogenesis markers, was elevated in the patient group (p>0.05). After treatment, a significant decrease was observed in VEGF levels (p<0.05), while SCUBE-1, SCUBE-3, IL-6, CD-40 and MMP-9 levels remained at similar levels (p>0.05). Conclusion: In our study, RA patients responded to treatment with clinical improvements. Although there were differences in the levels of MMP and VEGF, there was no association with the disease in SCUBE. [ABSTRACT FROM AUTHOR]

Although clinical outcomes of RA have vastly improved in recent years, the disease's mental health impact has seemingly not decreased to the same extent. Even today, learning to live with RA is an active process involving several psychological, cognitive, behavioural and emotional pathways. Consequently, mental health disorders are more common in the context of RA than in the general population, and can be particularly detrimental both to patients' quality of life and to clinical outcomes. However, mental health is a spectrum and represents more than the absence of psychological comorbidity, and supporting patients' psychological wellbeing should thus involve a more holistic perspective than the mere exclusion or specific treatment of mental health disorders. In this viewpoint article, we build on mechanistic and historical insights regarding the relationship between RA and mental health, before proposing a practical stepwise approach to supporting patients' mental health in daily clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) causes structural damage that causes joint deformity including metacarpophalangeal (MCP) joint ulnar drift (UD), thus hindering the pinch strength and the functional ability of the hand. Orthosis or splints are designed to maintain the hand's function, improve joint alignment, restore biomechanical balance, and reduce tissue stress. Limited studies have been done on the effects of dynamic splint on pinch strength and functional ability. Therefore, the purpose of this study was to evaluate and quantify the effects of dynamic MCP splint in treatment of ulnar deviation of RA on pinch strength and functional ability in women. Methods: Twenty women with RA were recruited and completed a 4-week intervention period with dynamic MCP splint. Pinch strength and functional ability score were measured at baseline and after 4 weeks. Results: The results showed a significant improvement in pinch strength (mean ± SD, 11.68 ± 2.14 to 13.53 ± 2.14; P = 0.000) and functional ability score (mean ± SD, 22.70 ± 9.12 to 19.70 ± 8.14; P = 0.000). Conclusion: The results of this study show that the dynamic MCP splint had a positive impact on rheumatoid hands that align the joints in their functional position. The dynamic MCP splint improved the mechanical stability of the hand, thus reducing pain and stress on joints, which in turn improves the pinch strength and functional ability of rheumatoid hand. Clinical Relevance: To increase patient acceptance and use of the splint, the splint designed and used in this study was compact and only covered the affected areas and joints of the hand. Because there was no involvement of the wrist joint and the fingertips were free, the splint was lightweight and allowed the patient to perform activity while wearing it. [ABSTRACT FROM AUTHOR]

Background: Wet cupping (Hijama), a form of alternative medicine, is widely practiced in Middle Eastern countries, especially Saudi Arabia. Although considerable effort has been put into increasing public awareness about the safe and proper practice of wet cupping, studies on the attitudes, knowledge, and awareness levels of the Saudi Arabian public are lacking. Objectives: This study evaluated public attitudes toward the effectiveness, safety, and expected standards of practicing wet cupping. Methods: This cross-sectional study was conducted using an online questionnaire and involved 909 complete responses. The respondents were Saudi adults with a mean age of 30.43 ± 11.4 years (males: 42.1%, females: 57.9%). Results: The study revealed that most participants believed that although wet cupping is a beneficial (84.6%), well-known form of alternative medicine (82.4%) without harmful side effects (63.9%), it is not suitable for treating all diseases (72.3%) or everyone (66.8%). Most participants prefer wet cupping to be done at specialized centers (84.6%) by practitioners with confirmed qualifications (88.6%) using valid and sterile instruments (88.9%). The main demographic factor influencing participant responses was age, which was associated with more positive perceptions. Female, single, college-educated, and middle-aged respondents had more cautious attitudes. Conclusion: Our results indicate that Saudis support the use of wet cupping as an alternative medicine for select diseases and that individuals have adequate awareness of the practice's safety standards to avoid potential risks. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease characterized by pain, swelling, morning stiffness and progressive loss of joint function due to deformation. Caring for a patient with RA requires an interdisciplinary approach that includes doctors, nurses, physiotherapists, psychologists and social workers, as well as the patient's family/legal guardians. Aim of the study: to identify care and therapeutic problems in a patient with rheumatoid arthritis, to establish an individual nursing care plan for a patient with rheumatoid arthritis, and to assess actions taken for the benefit of the patient and his environment. Method material: The study involved a 69-year-old patient with rheumatoid arthritis diagnosed 5 years ago. The patient was hospitalized at the Department of Internal Diseases, Gastroenterology, Endocrinology and Diabetology, Cardinal Stefan Wyszynski Provincial Hospital in Lomza. Results: The disease can have a significant impact on the life of the patient and his caregivers, which is why psychological support is important. Patients with RA may experience pain, fatigue, limited mobility, and emotional problems. Psychological support and nursing care can help the patient cope with the disease and its consequences. Conclusions: A nurse is a key person in the care of a patient with RA. The nurse is responsible for assessing the patient's health condition, monitoring treatment, educating the patient and his family, and providing psychological support. She should have the knowledge and skills necessary to properly care for a patient with RA and should be trained in the diagnosis and treatment of RA, rehabilitation and physiotherapy, patient education and psychological support. The nurse should cooperate with a doctor, a rehabilitator, a psychologist and a social worker in order to provide the patient with comprehensive care. [ABSTRACT FROM AUTHOR]

Introduction: Managing symptoms, resisting functional decline and maintaining health and independence are key motivators for people with Rheumatoid Arthritis (RA) who successfully engage with physical activity (PA). To inform PA support for people with RA the aim was to determine whether the broader RA population share similar beliefs and strategies regarding PA to those who report successful engagement. Methods: A modified two‐stage Delphi approach. 200 patients from four National Health Service rheumatology departments received a postal questionnaire containing statements relating to engagement with PA derived from prior interview data from physically active individuals with RA. Statements rated as agree or strongly agree by >50% of respondents were retained and the same respondents asked to rate and prioritize potential PA intervention components. Ethical approval: Oxford C Research Ethics Committee (ref 13/SC/0418). Results: Questionnaire one received 49 responses (11 males, 37 females, 1 unknown), mean age 65 years (range 29–82). Low levels of PA were reported by 60% of respondents. Questionnaire two responses (n = 36) indicated that a PA intervention should include information about prevention of RA symptoms worsening and benefits of PA for joints; help participants to achieve improved pain management and a feeling of being in control of their RA. For PA maintenance it was important that medication controlled symptoms, and PA instructors understood RA to ensure safety. Conclusions: A key factor to consider when designing a PA intervention for people with RA is that education from a knowledgeable instructor should underpin programme delivery alongside effective medication. Programmes may need tailoring based on demographics; this should be explored in future studies. [ABSTRACT FROM AUTHOR]

Aim: This study investigated the effectiveness of classic and intensive exercise programs in patients with rheumatoid arthritis (RA) and their relationship with disease activity and patient functional well-being. Material and Methods: Sixty patients aged 18 to 65, diagnosed with RA in our clinic, were randomly divided into two groups of 30 each. The first group received an intensive exercise program, while the second group received a classic exercise program. Disease activity was evaluated using erythrocyte sedimentation rate, C-reactive protein, DAS28Sedim, and DAS28Crp. Daily life activities were assessed using the HAQ score and Duruöz hand index. Joint mobility measurements were taken with a goniometer, and muscle strength measurements were taken using a manual dynamometer and pinch meter. Hand and wrist radiographs were taken and evaluated according to Steinbroker stages before exercise therapy. Results: Improvement was observed in both groups' Visual Analog Scale (VAS) and Health Assessment Questionnaire (HAQ) scores, with a significant improvement in VAS scores favoring the intensive exercise group. Conclusions: The study concluded that exercise therapy had positive effects on patients' hand functions, and the intensive exercise program was more effective. [ABSTRACT FROM AUTHOR]

Background/Aim: A real challenge for patients with rheumatoid arthritis (RA) and rheumatologists is primary nonresponse status (PNRS) or secondary nonresponse status (SNRS) to various therapies. Despite their detrimental influence on patient life quality, PNRS and SNRS have no accurate definition and no early predictive criteria for their development exist. Patients with RA under 40 years of age are rare, hence PNRS and SNRS data for this age group are scarce. This study examined the PNRS and SNRS according to sex, age, BMI, therapy type, and duration. Patients and Methods: Retrospectively, 115 patients with RA having PNRS and/or SNRS were stratified by age (22-39, 40-59, and 60-81). The association between body mass index (BMI), proinflammatory cytokines inhibitors, JAK inhibitors, and TNF-alpha inhibitors, sex, age, and PNRS and SNRS was examined. Results: All three proinflammatory cytokine inhibitors (rituximab, tocilizumab, and abatacept) were associated with PNRS and SNRS in women with a high BMI aged 40-59 years. Abatacept-related PNRS and SNRS was significant in women with normal BMI aged 60- 81 years. Adalimumab, infliximab, and golimumab affected SNRS differently in women with normal BMI aged 22-39 years and women with high BMI aged 60-81 years. Etanercept and infliximab were associated with SNRS status in men with highBMI aged 40-59 years. Conclusion: PNRS and SNRS development in patients with RA is significantly influenced by age, sex, and BMI, but most importantly is closely and differentially related to therapy type and duration. [ABSTRACT FROM AUTHOR]

Background/Aim: Regulatory T cells (Treg) play a crucial role in maintaining immune tolerance and preventing autoimmune diseases. Recent data also indicate that type 1 regulatory T (Tr1) and regulatory B (Breg) cells play an inhibitory (i.e., protective) role in autoimmune diseases. Conventional synthetic disease-modifying antirheumatic drugs (csDMARD) are a first-line therapy for rheumatoid arthritis (RA), and our aim was to predict clinical responses of this treatment using immunophenotyping. Materials and Methods: We first detected the presence of immune cells in fresh blood from 16 healthy controls (HC) and 26 patients with RA (14 drug-naive and 12 csDMARD-experienced). Then, we recorded immunophenotypic changes in 14 drug-naive RA (naive RA) patients prior to csDMARD treatment (i.e., day 0) and after receiving treatment for 6 months. The observed changes were also compared with other clinical indicators, including the presence of anti-citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. Results: Naive RA patients had significantly lower Tregs than HC and csDMARD-experienced patients (both p<0.0001) and the number of Tregs correlated with the diagnosis of RA and therapeutic efficacy of csDMARD treatment. Furthermore, lower baseline levels of Treg, memory Treg, Tr1, and higher PD-1+ Marginal B, Breg cells were significantly associated with decreased development of the 28-joint Disease Activity Score (DAS28) (all p<0.05), revealing better medical response. Multiple regression and principal component analysis identified Treg, Tr1, and Breg as potential predictors of csDMARD responses (Area under curve: 0.9; Accuracy: 92.86%). Furthermore, elevated Treg, Tr1, and Breg cells were associated with decreased DAS28, ESR, and CRP (all p<0.05); changes in Treg and Breg cell expression were also more pronounced among double negative anti-CCP and RF in RA patients with better outcomes (p<0.05). Conclusion: Immunophenotyping can be an adjunct clinical tool to identify patients who are poor candidates for csDMARD therapy. Alternative therapeutic interventions in the early stages of disease should be formulated for these patients. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading rapidly across the world, posing a major health concern with the coronavirus disease 2019 (COVID-19). Patients with rheumatoid arthritis (RA) may be at higher risk of infection and disease progression due to impaired autoimmune systems, immunosuppressants, and comorbidities. Therefore, we review the possible immune mechanisms and pathological interactions between COVID-19 and RA, as the uncontrolled immune activation and cytokine response in COVID-19 resemble the immune inflammation of RA. We also discuss the potential mechanisms that may lead to cardiovascular complications as well as the challenges of treating RA patients with COVID-19. While several therapeutic agents are being developed to cure COVID-19, antirheumatic drugs could also be potential options due to the similar proinflammatory cytokines induced in both diseases. Additionally, we discuss the safety and effectiveness of SARS-CoV-2 vaccines and novel therapeutic approaches against RA based on the shared mechanisms between COVID-19 and RA. [ABSTRACT FROM AUTHOR]