Stem cells are specialised precursor cells that can replace aged or damaged cells and thereby maintain healthy tissue function. Stem cell therapy is increasingly used as a treatment for knee osteoarthritis, despite the lack of clarity around the mechanism by which stem cell therapy may slow down disease progression in osteoarthritis, and uncertainty regarding its benefits and harms. To assess the benefits and harms of stem cell injections for people with osteoarthritis of the knee. A secondary objective is to maintain the currency of the evidence, using a living systematic review approach. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase on 15 September 2023, unrestricted by date or language of publication. We also searched ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) for relevant trial protocols and ongoing trials. We included randomised controlled trials (RCTs), or trials using quasi-randomised methods of participant allocation, comparing stem cell injection with placebo injection, no treatment or usual care, glucocorticoid injection, other injections, exercise, drug therapy, surgical interventions, and supplements and complementary therapies in people with knee osteoarthritis. Two review authors selected studies for inclusion, extracted trial characteristics and outcome data, assessed risk of bias and assessed the certainty of evidence using the GRADE approach. The primary comparison was stem cell injection compared with placebo injection. The primary time point for pain, function and quality of life was three to six months, and the end of the trial period for participant-reported success, joint structure changes and adverse event outcomes. Major outcomes were pain, function, quality of life, global assessment of success, radiographic joint progression, withdrawals due to adverse events and serious adverse events. We found 25 randomised trials (1341 participants) comparing stem cell injections with placebo injection (eight trials), no treatment or usual care (analgesia, weight loss and exercise) (two trials), glucocorticoid injection (one trial), hyaluronic acid injection (seven trials), platelet-rich plasma injections (two trials), oral acetaminophen (paracetamol) (one trial), non-steroidal anti-inflammatory drugs plus physical therapy plus hyaluronic acid injection (one trial) and stem cell injection plus intra-articular co-intervention versus co-intervention alone (three trials) in people with osteoarthritis of the knee. Trials were predominantly small, with sample sizes ranging from 6 to 252 participants, with only two trials having more than 100 participants. The average age of participants across trials ranged from 51 to 66 years, and symptom duration varied from one to 10 years. Placebo-controlled trials were largely free from bias, while most trials without a placebo control were susceptible to performance and detection biases. Here, we limit reporting to the main comparison, stem cell injection versus placebo injection. Compared with placebo injection, stem cell injection may slightly improve pain and function up to six months after treatment. Mean pain (0 to 10 scale, 0 no pain) was 4.5 out of 10 points with placebo injection and 1.2 points better (2.5 points better to 0 points better) with stem cell injection (I2 = 80%; 7 studies, 445 participants). Mean function (0 to 100 scale, 0 best function) was 46.3 points with placebo injection and 14.2 points better (25.3 points better to 3.1 points better) with stem cell injection (I2 = 82%; 7 studies, 432 participants). We are uncertain whether stem cell injections improve quality of life or increase the number of people who report treatment success compared to placebo injection, because the certainty of the evidence was very low. Mean quality of life was 45.3 points with placebo injection and 22.8 points better (18.0 points worse to 63.7 points better) with stem cell injection (I2 = 96%; 2 studies, 288 participants) at up to six months follow-up. At the end of follow-up, 89/168 participants (530 per 1000) in the placebo injection group reported treatment success compared with 126/180 participants (683 per 1000) in the stem cell injection group (risk ratio (RR) 1.29, 95% CI 1.10 to 1.53; I2 = 0%; 4 trials, 348 participants). We downgraded the evidence to low certainty for pain and function due to indirectness (as the source, method of preparation and dose of stem cells varied across studies), and suspected publication bias (up to three larger RCTs have been conducted but withdrawn prior to reporting of results). For quality of life and treatment success, we further downgraded the evidence to very low certainty due to imprecision in addition to indirectness and suspected publication bias. We are uncertain of the potential harms associated with stem cell injection, as there were very low event rates for serious adverse events. At the end of follow-up, 5/219 participants (23 per 1000) in the placebo injection group experienced serious adverse events compared with 4/242 participants (16 per 1000) in the stem cell injection group (RR 0.72, 95% CI 0.20 to 2.64; I2 = 0%; 7 trials, 461 participants) and there were no reported withdrawals due to adverse events. We downgraded the evidence to very low certainty due to indirectness, suspected publication bias and imprecision. Radiographic progression was not assessed in any of the included studies. Compared with placebo injections and based upon low-certainty evidence, stem cell injections for people with knee osteoarthritis may slightly improve pain and function. We are uncertain of the effects of stem cell injections on quality of life or the number who report treatment success. Although the putative benefits of stem cell therapies for osteoarthritis include potential regenerative effects on damaged tissues, particularly articular cartilage, we remain uncertain of the effect of stem cell injections on structural progression in the knee (measured by radiographic appearance). There is also uncertainty regarding the safety of stem cell injections. Serious adverse events were infrequently reported, although all invasive joint procedures (including injections) carry a small risk of septic arthritis. The risk of other important harms, including potential concerns related to the use of a therapy with the theoretical capacity to promote cell growth, or to the use of allogeneic cells, remains unknown.
Fractures related to osteoporosis and low bone mineral density lead to substantial morbidity, mortality, and cost to individuals and health systems. Here we present the most up-to-date global, regional, and national estimates of the contribution of low bone mineral density to the burden of fractures from falls and additional categories of injuries from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021. The burden of low bone mineral density was estimated from 1990 to 2020 in terms of years lived with disability (YLDs), disability-adjusted life years (DALYs), and deaths, for individuals aged 40 years and older, using data from population-based studies from 48 countries or territories (169 unique sources). Mean standardised femoral neck bone mineral density values were estimated by GBD location, age, and sex by meta-regression. Based on a separate meta-analysis of population-based studies from nine countries (12 unique sources), we also estimated the pooled relative risk of fractures per unit decrease in bone mineral density (g/cm2). The population-attributable fraction for low bone mineral density was calculated by comparing the observed distributions of standardised femoral neck bone mineral density to an age-specific and sex-specific counterfactual distribution, defined as the 99th percentile of five rounds of the National Health and Nutrition Examination Survey in the USA, by 5-year age group and sex. Hospital and emergency department data were used to derive the incidence of fractures for six categories of injury (road injuries, other transport injuries, falls, non-venomous animal contact, exposure to mechanical forces, and physical interpersonal violence) using ICD codes. Deaths due to fractures were estimated as the proportion of in-hospital deaths due to the specified injury causes for which a fracture (nature of injury code) was more severe than the cause of injury code. YLDs and DALYs attributable to low bone mineral density by cause of injury were also determined according to previous GBD methods. In 2020, 8·32 million (95% UI 5·58-10·84) YLDs, 17·2 million (14·1-20·2) DALYs, and 477 000 (411 000-536 000) deaths were attributable to low bone mineral density globally in individuals aged 40 years and older. Between 1990 and 2020, global YLDs, DALYs, and deaths attributable to low bone mineral density increased by 91·8% (88·5-95·1), 89·8% (81·5-99·0), and 127·1% (108·5-144·5), respectively. Over this period, the age-standardised global rates of YLDs, DALYs, and deaths attributable to low bone mineral density showed modest decreases. In 2020, falls accounted for 76·2% (95% UI 74·2-78·3) of YLDs, 65·2% (62·9-67·6) of DALYs, and 71·0% (67·4-72·8) of deaths attributable to low bone mineral density, and road injuries largely accounted for the remaining amount: 12·4% (11·1-13·6) of YLDs, 24·6% (22·5-27·1) of DALYs, and 23·1% (21·6-26·2) of deaths. As a proportion of all fall-related burden, low bone mineral density accounted for 26·6% (23·2-28·7) of YLDs, 25·6% (22·1-27·4) of DALYs, and 40·6% (35·4-44·0) of deaths in 2020. Of all road injury-related burden, 12·6% (10·8-13·5) of YLDs, 6·3% (5·4-6·9) of DALYs, and 8·9% (7·6-9·6) of deaths were attributable to low bone mineral density. In men, road injuries accounted for the largest proportion of DALYs attributable to low bone mineral density in those aged 40-59 years and the largest proportion of deaths in those aged 40-64 years. In women, road injuries were the leading cause of DALYs attributable to low bone mineral density in those aged 40-44 years and the leading cause of deaths attributable to low bone mineral density in those aged 40-54 years. In older age groups among both men and women, falls were the leading cause of the burden attributable to low bone mineral density. Low bone mineral density is a crucial modifiable risk factor for fractures, which are an important cause of morbidity and mortality particularly in ageing populations. This analysis highlights low bone mineral density as a cause of health loss not just from falls, but also from road injuries. Gates Foundation.
Rheumatoid arthritis (RA) impacts quality of life causing disability and increased mortality. Treatment decisions are complex and require individualization. Shared decision making (SDM) is the first principle of RA treat-to-target guidelines, but uptake is suboptimal. We aim to evaluate the effectiveness of a multicomponent SDM intervention on RA disease activity and explore the early implementation of the intervention within three geographically diverse rheumatology services. The RAiSeD trial uses a stepped-wedge, cluster-randomized trial design at three U.S. Veterans Health Administration rheumatology clinics, targeted to enroll more than 400 patients and over 45 clinicians. The multicomponent SDM intervention consists of three parts: (1) rheumatology clinician training and a pocket card on SDM and fostering choice awareness ("acknowledging when there is more than one sensible option available to address a patient's situation"), (2) RA patient activation using the AskShareKnow questions, and (3) a point-of-care decision aid (RA Choice) and medication summary guide. We will conduct a mixed-methods outcomes and process evaluation. Outcomes will be evaluated during a pre-intervention (usual care) and intervention period. The primary outcome is disease activity as measured by the validated Clinical Disease Activity Index (CDAI), with secondary outcomes of RA knowledge and medication adherence. SDM will be measured by two brief, validated patient-reported measures. A subgroup of clinic visits will be audio-recorded and clinicians' efforts to involve patients in SDM will be assessed. The implementation process will be evaluated using stakeholder interviews and field notes at each of the three sites. This study is the first multi-site trial of a multicomponent intervention to facilitate SDM among veterans with RA. We expect to improve uptake of SDM across geographically distinct rheumatology clinics and hypothesize that patients exposed to the interventions will have a greater decrease in disease activity and an increase in knowledge of RA medications compared to usual care. Insights gained from this study will inform broader dissemination and implementation of SDM across VA rheumatology clinics and beyond, with the goal of improving quality of care for all persons with RA. ClinicalTrials.gov NCT05530694. Registered on September 7, 2022.
Upadacitinib (UPA), an oral Janus kinase inhibitor, has shown efficacy with an acceptable safety profile in rheumatoid arthritis (RA) clinical trials. To assess the real-world effectiveness and safety of UPA in adults with moderate-to-severe RA in the UPHOLD observational study. Co-primary endpoints were: (i) proportion of patients achieving disease activity score in 28 joints using C-reactive protein (DAS28[CRP]) remission (< 2.6) at 6 months; and (ii) proportion of those patients maintaining remission at 12 months. Additional analyses included proportions of patients achieving and maintaining DAS28(CRP) low disease activity (LDA; ≤ 3.2), other composite measures of disease activity, and subgroup analyses by therapy strategy and prior treatment. Treatment-emergent adverse events (TEAEs) in the full analysis set (FAS; patients receiving ≥ 1 UPA dose) were reported through August 10, 2023. Co-primary and selected secondary endpoints were analyzed by modified non-responder imputation (mNRI) in modified (m)FAS1 (FAS patients who completed 6 months of treatment and had DAS28[CRP] data available, and those who discontinued before 6 months) and mFAS2 (mFAS1 patients who achieved remission at 6 months, completed 12 months of treatment, and had DAS28[CRP] data available, and those who discontinued between 6 and 12 months); and as observed (AO) in patients with non-missing data. Of 1719 participants, 1717 were enrolled; 1701 comprised the FAS. Overall, 400/1719 (23.3%) patients discontinued before 12 months. Of mFAS1 patients, 499 (mNRI: 499/1074 [46.5%]; AO: 499/902 [55.3%]) achieved DAS28(CRP) remission at 6 months; of mFAS2 patients, 269 (mNRI: 269/340 [79.1%]; AO: 269/317 [84.9%]) maintained remission at 12 months. DAS28(CRP) remission or LDA rates were consistent regardless of whether UPA was initiated and maintained as monotherapy or combination therapy. Similar responses were observed across prior treatment subgroups. Among selected TEAEs of special interest, herpes zoster and serious infection occurred at 3.12 and 2.62 events/100 patient-years, respectively. No new safety signals were identified. UPA demonstrated real-world effectiveness in moderate-to-severe RA, with approximately half of patients achieving DAS28(CRP) remission at 6 months and most maintaining remission through 12 months. The real-world benefit-risk profile of UPA remains favorable and is consistent with phase 3 clinical trial data. NCT04497597.
To investigate the practices of doctors in the diagnosis and treatment of adult SAPHO syndrome. A cross-sectional study was conducted by distributing online questionnaires to physicians across five hospitals, specifically targeting departments involved in the diagnosis and treatment of adult SAPHO syndrome, including rheumatology, dermatology, and orthopedics. A total of 103 clinical physicians participated in the survey.The three most commonly observed clinical features of adult SAPHO syndrome were elevated ESR and CRP (82/84), focal swelling and fever (73/84), and new lesions found on imaging (70/84). The primary diagnostic tools utilized were Whole body bone imaging (76.2%) and CT scans (60.1%), with less frequent use of MRI (22.6%) and positron emission tomography-computed tomography (PET-CT) (9.6%). Notably, only 14% of physicians reported never performing disease activity monitoring. Nearly all respondents (98%) selected nonsteroidal anti-inflammatory drugs (NSAIDs) as the first-line treatment. Additionally, 81% of physicians opted for target synthetic disease-modifying antirheumatic drugs (tsDMARDs), 78.6% for steroids, 71.4% for biological disease-modifying antirheumatic drugs (bDMARDs), 66.7% for conventional synthetic disease-modifying antirheumatic drugs (csDMARDs, and only 18.5% chose bisphosphonates (pamidronate and zoledronate). While Whole body bone imaging and CT scans are widely used for the early diagnosis of adult SAPHO syndrome, there is a gap in the utilization of MRI and the practice of disease activity monitoring. Physicians prefer commonly used rheumatic drugs, but there remains limited application of bisphosphonates. Highlight • Our study first systematically investigated Chinese physicians' perspectives on the diagnosis and treatment of adult SAPHO syndrome. • We pointed out that the utilization of imaging tools (such as MRI) and bisphosphonates was low, suggesting that the diagnostic strategy needs to be optimized. • This study may aid the research of SAPHO syndrome at home and abroad, providing references.
Dissemination and implementation of socially prescribed community-based programmes for individuals with rheumatic conditions remain rare. However, such programmes can help overcome key barriers, including limited access to evidence-based psychological interventions, individuals' preference for psychosocial care outside of rheumatology clinics and the prevention of isolation and loneliness. This study presents a qualitative process evaluation of a community-based Acceptance and Commitment Therapy (ACT) group intervention, delivered as part of a psychosocial service within a support organization for individuals with rheumatic conditions. We conducted 12 semi-structured qualitative interviews following participants' completion of five in-person ACT group sessions. Reflexive thematic analysis was used to assess acceptability and explore how participants conceptualized ACT's processes of change. Four key themes emerged, offering practical considerations for planning and delivering ACT groups for individuals with rheumatic conditions: (1) the process of finding peace through mindfulness while managing practice-related difficulties, (2) recognizing the importance of making values-consistent choices, (3) navigating an ambivalent relationship with pain and (4) the dual nature of the group experience-both comforting and awkward. Findings highlight the implications of programme duration in planning ACT groups for individuals with rheumatic conditions in the community. The study suggests that acceptance and mindfulness may be time-bound and context-sensitive processes, influenced by the fluctuating symptomatology of rheumatic conditions. Mindfulness is best developed step by step, starting with body awareness, understanding symptoms and slowly bringing mindfulness into daily life. Pain acceptance should focus more on facilitating momentary patterns of activity engagement, rather than willingness towards the fluctuating symptoms.
Needs assessments in patients with juvenile idiopathic arthritis (JIA) have revealed a need for disease information, self-management skills, and peer support. We previously developed and tested the acceptability of an in-person and videoconference-based self-management program (SMP) to address these needs. The aim of this pilot randomized controlled trial (RCT; the VISTA-JIA trial) is to evaluate the feasibility and preliminary effectiveness of a virtual group-based SMP for adolescents with JIA in comparison to a waitlist control group. A total of 100 participants with confirmed JIA (aged 12-17 years) will be recruited from 5 Canadian pediatric rheumatology centers and randomized 1:1 to the intervention or waitlist control groups. Adolescents in the intervention group will receive the virtual SMP. Those randomized to the control group will receive standard of care alone and will later be eligible for the SMP. The SMP includes JIA disease education, self-management strategies, and peer support. Four 60- to 90-minute sessions will be conducted over 8 weeks with a group size of 4-6 participants. The primary feasibility outcome will be adherence to the SMP (defined as completion of all 4 sessions by at least 80% of participants). Other secondary feasibility outcomes will include recruitment and withdrawal rates, the proportion of completed questionnaires, engagement and satisfaction with the SMP measured through a semistructured virtual interview, and intervention fidelity (consistent content and technology delivery). Secondary preliminary effectiveness outcomes will be assessed by completing 5 validated questionnaires at pre- and postprogram time points: (1) the Medical Issues, Exercise, Pain, and Social Support Questionnaire to assess perceived ability to manage JIA (self-management); (2) the Children's Arthritis Self-Efficacy Scale to assess self-efficacy; (3) the Pediatric Quality of Life Inventory 3.0 Rheumatology-Teen Module to assess health-related quality of life; (4) the PROMIS (Patient-Reported Outcomes Measurement Information System) Pediatric Pain Interference Scale to assess pain interference; and (5) Readiness for Adult Care in Rheumatology to assess transition readiness. Descriptive statistics and nonparametric tests will be used to analyze the data. The study setup is complete at all centers, including training of the facilitators, revising and finalizing education sessions, participant's handout guide, and fidelity checklist. Recruitment began in January 2024 and is expected to conclude by December 2025. Feasibility outcomes, including adherence and engagement, as well as preliminary effectiveness, will be analyzed post intervention. This is the first evidence-based, virtual, interactive, group-structured JIA SMP in Canada. This SMP will address needs for disease information, self-management skills, and peer support in adolescents with JIA. The results of this pilot study will inform a full-scale RCT focused on the efficacy and cost-effectiveness of the program with the goal of integration in routine clinical practice across Canada. ClinicalTrials.gov NCT06184100; https://clinicaltrials.gov/study/NCT06184100. DERR1-10.2196/69539.
Golimumab is a safe and effective treatment for patients with rheumatoid arthritis. Biosimilars to the reference product (RP; Simponi®) may make treatment more accessible. The aim of this study was to assess the efficacy of AVT05, a golimumab biosimilar, and RP, each used in combination with methotrexate, in participants with moderate-to-severe rheumatoid arthritis. This was a 52-week, randomized, double-blind, two-arm, parallel-group, active-controlled study. Participants were randomized 1:1 to receive AVT05 (n = 251) or RP (n = 251), 50 mg subcutaneously once every 4 weeks to Week 12 inclusive. Randomization was stratified by the baseline Disease Activity Score-28 for Rheumatoid Arthritis using C-Reactive Protein (DAS28-CRP) [≤ 5.1 and > 5.1]. The primary endpoint was the change from baseline in DAS28-CRP at Week 16. At Week 16, responder participants (DAS28-CRP decreased by > 0.6 from baseline and disease activity DAS28-CRP ≤ 5.1) initially enrolled in the AVT05 arm continued to receive AVT05 every 4 weeks. Responder participants initially randomized to RP were re-randomized 1:1 to either continue receiving RP or switch to AVT05. Non-responders were discontinued from the study drug. Change from baseline in DAS28-CRP response criteria at weeks 4, 8, 12, 24, 32, 40, 48, and 52 and percentage of subjects achieving American College of Rheumatology 20/50/70 at weeks 4, 8, 12, 16, 24, 32, 40, 48, and 52 were assessed as secondary endpoints. Safety and immunogenicity endpoints were also assessed. At Week 16, the least squares mean (standard error) change from baseline in DAS28-CRP in AVT05 and RP was - 2.89 (0.058) and - 2.98 (0.058), respectively. The two-sided 95% confidence interval of the least squares mean difference (0.09; standard error 0.082) was entirely contained within the prespecified equivalence margin of - 0.6, 0.6 (- 0.07, 0.25), supporting a demonstration of comparative efficacy. Two sensitivity analyses (one [S1] without exclusion of any data because of intercurrent events, and one [S2] excluding data following intercurrent events or relevant protocol deviations) supported the robustness of the primary endpoint estimates (S1 95% confidence interval - 0.07, 0.25; S2 95% confidence interval - 0.07, 0.25). There were no notable differences in subgroup analyses. Secondary efficacy analyses were consistent with the primary endpoint, including in participants who switched treatments. Overall safety profiles showed no clinically meaningful differences between treatments, including in participants who switched treatments. Immunogenicity profiles were comparable between treatment arms at all timepoints, including in participants who switched treatments. Analysis of the change in DAS28-CRP from baseline to Week 16 supported the assessment of comparative efficacy between AVT05 and RP golimumab. Secondary efficacy endpoints were consistent with this, including in participants who switched. AVT05 had a safety and immunogenicity profile similar to that observed for RP at all timepoints, including in participants who switched treatments. The trial is registered at ClinicalTrials.gov (ClinicalTrials.gov identifier: NCT05842213) and the EU Clinical Trials Register (EudraCT Number: 2022-001825-63).
Managing rheumatic diseases requires teamwork, but referral patterns and challenges remain poorly understood. This study explored rheumatologists' perspectives on referral patterns in the Gulf countries. We conducted a web-based, 21-question cross-sectional survey between November and December 2024, collecting data on rheumatologists' demographics, referral patterns, influencing factors, and satisfaction. Participants were recruited through email invitations, WhatsApp groups and snowball sampling. Statistical analyses included descriptive and inferential methods, such as subgroup comparisons and logistic regression, to identify predictors of referral frequency and satisfaction. A total of 149 rheumatologists participated, with 58.4% being consultants. Approximately 55% had up to 10 years of post-training experience. The primary referral method was electronic health records (EHR) (84.8%). In the three months preceding the survey, 36.3% made 0-10 referrals, while 35.6% made over 20. Dermatology (85.5%) and physiotherapy (79.5%) were the most referred specialties, aligning with psoriatic arthritis and systemic lupus erythematosus as the most referred diseases. Most rheumatologists (78%) often or always followed up on referrals, and 37.4% reported moderate changes in their referral decision-making over time. Key influences on referral decisions included patient-, practice-, and diagnostic-related factors. Patient gender preference had no impact. Multidisciplinary meetings (78.2%), access to updated clinical guidelines (76.5%), attending multidisciplinary continuing medical education or training programs (67.2%), and improved EHR referral systems (64.7%) were the top resources for improving referrals. Satisfaction post-referral was affected by various factors such as patients' experiences post-referral (61.5%), and healthcare professionals' responsiveness to their questions (54.2%). Logistic regression analysis showed that age, employment status, practice setting, and geographical location were associated with referral decisions. This study is the first to provide valuable insights into referral practices among Gulf rheumatologists, identifying key influencing factors and areas for improvement. Findings suggest that enhancing EHR systems, multidisciplinary meetings, and clinical guidelines can optimize referrals and interdisciplinary care.
Patients with RA are at an increased risk for serious infections, but less is known about more common, non-serious infections. We aimed to assess the frequency and characteristics of non-serious infections and their effect on medication interruptions, quality of life, and disease flares. We remotely recruited adults with RA from July 2022 to July 2023 through a community rheumatology practice-based research network. Participants joined the ArthritisPower Registry (now PatientSpot) and completed a baseline survey and up to six monthly follow-up surveys, focused on patient-reported outcomes (PROs), infections, medication interruptions, and disease flares. The impact of infections was evaluated by comparing survey measures in those with vs without an infection. We recruited 351 patients with RA who contributed 1674 monthly observations. Patients reported 523 infections (31% of observations), most frequently upper respiratory infections. Although few infections led to emergency department visits or hospitalizations, infections frequently led to missed work (37%) or RA treatment interruptions (26%). RA treatment interruptions were more common in those with vs without health-care encounters or antibiotic use (38% vs 12%) and in more severe vs less severe infections (47% vs 20%). Infections were associated with worse scores for fatigue but not function, depression, or social participation. Frequency of disease flares was greater in those with an infection who interrupted RA treatment, especially in patients receiving tumor necrosis factor (TNF) inhibitors. Infections are common in patients with RA and frequently lead to medication interruptions. These infections are associated with greater fatigue and impaired work productivity and may contribute to more disease flares.
To describe the prejudices, attitudes and stereotypes that health professionals, mainly in general medicine, family medicine, internal medicine, rheumatology, mental health, nursing and physiotherapy, have towards fibromyalgia. Systematic review. Pubmed, Web of Science, Scopus, CINAHL and PsycINFO. The search was carried out on 17 June 2024. Original articles and case reports, whose subject matter was related to the main purpose of this work, and published in the last ten years, were included. Data extraction was performed by two reviewers. Methodological quality was assessed using the critical appraisal tools for non-randomized studies of the Joanna Briggs Institute (JBI). A total of 19 studies were included. The delay in diagnosis, the lack of training in the management of this condition, and the subjectivity of its symptoms make fibromyalgia a significant challenge for healthcare professionals. A stereotypical patient profile is described, which contributes to fibromyalgia being perceived as a low-prestige disease, lacking an organic basis that legitimizes it. Health professionals highlight the lack of adequate training to diagnose and treat fibromyalgia. People suffering from this disease are often seen as difficult patients, whose credibility is constantly questioned and stigmatised. This study identifies the factors that cause discordance between professionals and patients, in order to optimise clinical practice. Describir los prejuicios, las actitudes y los estereotipos que tienen los profesionales de la salud, principalmente, de medicina general, medicina de familia, medicina interna, reumatología, salud mental, enfermería y fisioterapia, hacia la fibromialgia. Revisión sistemática. Pubmed, Web of Science, Scopus, CINAHL y PsycINFO. Se realizó la búsqueda el 17 de junio de 2024. Se incluyeron los artículos originales y reporte de casos, cuya temática fuera afín al propósito principal de este trabajo, y publicados en los últimos 10 años. Dos revisores realizaron la extracción de datos. Se valoró la calidad metodológica con las herramientas de evaluación crítica para estudios no aleatorizados del Joanna Briggs Institute (JBI). Fueron incorporados un total de 19 estudios. El retraso en el diagnóstico, la ausencia de formación en la atención hacia esta patología, así como la subjetividad de su sintomatología, hacen que la fibromialgia sea un gran desafío para los profesionales de la salud. Se describe un prototipo estereotipado de paciente, que convierte la fibromialgia en una enfermedad de prestigio inferior, sin base orgánica que la legitime. Los profesionales de la salud señalan la falta de formación adecuada para diagnosticar y tratar la fibromialgia. Las personas que padecen esta enfermedad suelen ser consideradas pacientes difíciles, cuya credibilidad se cuestiona constantemente y están marcadas por el estigma. Este trabajo identifica los factores que generan discordancia tanto en profesionales como en los propios afectados para optimizar la práctica clínica.
Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of rare systemic autoimmune rheumatic diseases. Despite advances in treatment, the definition of remission and low disease activity (LDA) in IIM remains inconsistent and lacks consensus and validation. This review summarizes existing published definitions, achievement rates, and predictive factors of remission/LDA in adult IIM, focusing on dermatomyositis (DM), polymyositis (PM), anti-synthetase syndrome (ASyS), and immune-mediated necrotizing myopathies (IMNM). Our literature review revealed a wide variability in remission definitions, incorporating physician assessment, muscle strength, laboratory normalization, and medication tapering or discontinuation. Some studies defined "remission on medication", while others required complete treatment cessation. Most definitions required a minimum duration of six months. Organ-specific remission (including for the skin, lung, and muscle domains) was inconsistently addressed. LDA has been less extensively studied in IIM, with the myositis disease activity assessment visual analog scales (MYOACT) being the only measure applied to DM. Remission rates varied widely, with stricter criteria yielding lower rates. Factors associated with remission included younger age, early immunosuppressive treatment, non-severe muscle involvement, the absence of myositis-specific autoantibodies (MSA), although some studies reported positivity for certain MSA were associated with remission. Conversely, remission was less likely for patients with PM, overlap myositis, and those positive for anti-TIF1-γ or Ku autoantibodies. Standardized remission criteria incorporating physician assessment, patient assessment, organ-specific parameters, laboratory assessments, and sustained remission duration are essential for harmonizing clinical and research evaluations in IIM. Establishing uniform definitions will improve therapeutic outcome assessments and facilitate meaningful comparisons in clinical trials and real-world practice.
Inflammatory rheumatic diseases (IRDs) are chronic autoimmune conditions that affect a variety of organs and systems. These disorders have a major impact on hand function, restricting independence in daily activities and lowering quality of life. They are characterized by significant reductions in the hand's fine motor skills, grip strength, and coordination capacities. These impairments in hand function have a detrimental influence on physical capability, psychological adjustment, and occupational productivity. Since IRDs are chronic and progressive, early detection, continuous follow-up, and multifaceted rehabilitation strategies are essential. Self-report measures and performance-based assessments are utilized to evaluate hand function. Furthermore, imaging techniques, including ultrasonography, magnetic resonance imaging, and dual-energy computed tomography, provide an objective evaluation of subclinical inflammation and structural damage. Rehabilitation approaches, as a complement to medical care, play an important role in maintaining and enhancing hand function. Multicomponent therapies, including exercise, splinting, occupational therapy, manual therapy, massage, and patient education, are beneficial for preserving functional gains. Future research is anticipated to concentrate on discovering biomarkers for early diagnosis, creating sensor-based digital evaluation tools and telerehabilitation programs, and developing individualized, AI-powered rehabilitation procedures. These developments will make a substantial contribution to preserving hand function and enhancing the quality of life for IRD patients.
Patient-reported outcomes (PROs) in systemic rheumatic diseases (SRDs) are in the forefront of clinical research. However, a comprehensive evaluation of PROs in pivotal trials supporting SRD drug approval is lacking. This study aims to systematically characterize the use of PROs in pivotal trials supporting the US Food and Drug Administration (FDA) approval of SRDs treatments and to assess the quality of reporting. We reviewed the pivotal trials supporting the approval of SRD indications by FDA since July 2013 to assess the use of PROs, including specific PRO measures (PROMs) and types of endpoints designated. Quality of PRO reporting was assessed according to a modified ISOQoL criteria. From July 1st, 2013, to June 30th, 2024, the FDA approved 43 new SRD indications based on 67 pivotal trials, with 58 trials included in the final analysis. PROs served as multiple types of endpoints in most trials. All 58 reviewed trials utilized PROs as secondary or exploratory endpoints. The numbers of trials that employed PROs as components of primary endpoints, co-primary endpoints, and key secondary endpoints, were 47(81.0%), 4(6.9%), 45(77.6%), respectively. Notably, the inclusion of PROs as components of composite primary endpoints or co-primary endpoints (100% vs. 8.3%, P < 0.001) and key secondary endpoints (93.5% vs. 16.7%, P < 0.001) were significantly higher in inflammatory arthritis compared to other SRDs. Regarding PROM types, 37 trials (63.8%) reported both generic and disease-specific PROMs, covering a broad range of domains. Quality of PRO reporting, influenced by disease type and the presence of additional PRO reports, was moderate to poor in 45 trials (81.8%). Key reporting elements, such as the PRO hypothesis, mode of PROMs completion, and extent and reasons for missing PRO data, were documented in fewer than 30% of the trials. PROs significantly impact SRDs drug approval decisions, especially for inflammatory arthritis. However, the overall quality of PRO reporting in pivotal trials of SRDs is suboptimal and needs improvement. Our study provides a comprehensive summary of PRO application in SRDs trials, highlighting the need for strengthening PRO utilization in non-arthritis SRDs and improving PRO reporting quality in future studies.
Radiographic joint space width (JSW) and MRI-based cartilage thickness are key imaging biomarkers in knee osteoarthritis (OA), yet their weak correlation complicates cross-modality interpretation. This mismatch may potentially be explained by differences in patient posture and joint loading, as radiographs are typically obtained in a weight-bearing and flexed position, whereas MRI scans are acquired in a non-weight-bearing and extended position. Using a 0.25 T rotatable MRI scanner, 21 individuals with OA were scanned in four positions, extended and flexed in non-weight-bearing and weight-bearing conditions, to reflect typical clinical imaging conditions and functional joint motion and loading. Three-dimensional JSW and cartilage thickness maps of the tibia and femur were generated, registered to canonical surfaces, and analyzed vertex-wise using statistical parametric mapping. Spearman correlations between JSW and cartilage thickness were calculated for each position. JSW narrowed under weight-bearing, particularly medially, and showed a posterior shift with flexion, especially laterally. Femoral cartilage responded more to positional changes than tibial cartilage, showing posterior thinning and anterior thickening under weight-bearing flexion. Correlations between JSW and cartilage thickness strengthened while weight-bearing, especially posteriorly, but weakened anteriorly and laterally during flexion. Overall, moving from non-weight-bearing extension (MRI positioning) to weight-bearing flexion (radiograph positioning) improved JSW-cartilage correlations in the tibia and posterior femur. JSW and cartilage thickness are strongly influenced by joint loading and flexion. Weight-bearing flexion improves JSW-cartilage correspondence posteriorly but reduces it anteriorly. These findings primarily inform interpretation and standardization of imaging endpoints across modalities and imaging conditions; translation to routine clinical practice is currently limited by scanner availability and the modest magnitude of cartilage thickness differences.
This study aimed to assess the prevalence of female sexual dysfunction (FSD) and its association with clinical characteristics in female patients with Sjögren's syndrome (SS). In this cross-sectional study, 158 female patients with SS admitted to the Department of Rheumatology and Immunology of three Grade-III Class-A hospitals in Beijing between January 2021 and December 2023 were included. The general clinical data, sexual function feelings, medication use, psychological status, and socioeconomic factors of the patients were collected with a standardised questionnaire and assessed. Of the 158 patients, 124 (78.5%) were diagnosed with FSD based on Female Sexual Function Index scores <26.5. The mean age and course of disease were significantly higher in the FSD group than in the non-FSD group (p < 0.05), with a higher proportion of patients aged ≥40 years in the former (71.8%) than the latter (11.8%). After adjusting for potential confounding factors, including medication use, psychological status and socioeconomic factors, the association between SS and FSD remained significant (p < 0.05). In the FSD group, decreased libido (79.0%), difficulty in sexual arousal (71.8%), difficulty in vaginal lubrication (66.1%), orgasmic disorder (77.4%), decreased sexual satisfaction (81.5%) and dyspareunia (75.0%) were commonly reported. The findings of this study suggest that early identification and intervention of FSD for female patients with SS is essential to improve their quality of life. Sjögren’s syndrome (SS) has been associated with a range of extraglandular manifestations, including fatigue, joint pain and neurologic disorders. There is a growing body of evidence suggesting that women with SS experience a higher prevalence of female sexual dysfunction (FSD), which can significantly impact their quality of life. This study provides empirical data on the prevalence and characteristics of FSD in women with SS, highlighting the specific areas of sexual function affected. By identifying FSD as a significant issue in women with SS, this study calls for increased awareness and recognition of sexual health in clinical practice. It may influence future research to develop and evaluate targeted interventions for FSD in patients with SS, potentially improving treatment outcomes and patient satisfaction. Policymakers may consider the findings when formulating guidelines for the comprehensive care of patients with SS, ensuring that sexual health is included in the services provided.
Rheumatoid arthritis (RA) is a global health concern with increasing prevalence. Despite recommendations for regular disease activity assessments, their implementation in routine clinical practice remains challenging. The Medical Support System for Rheumatoid Arthritis (MiRAi) is an offline, semi-automated system that calculates disease activity indices by integrating patient and clinician inputs from electronic health records (EHRs). This study evaluated the association between MiRAi implementation and the frequency of disease activity assessments in patients with RA. We conducted a retrospective cohort study of patients with RA treated at a tertiary hospital in Japan between April 2022 and March 2023. We included all adult outpatients (aged ≥18 years) with RA diagnosed according to the 2010 ACR/EULAR [American College of Rheumatology/European Alliance of Associations for Rheumatology] classification criteria. The hospital introduced MiRAi in June 2022 and achieved full deployment by October 2022. MiRAi calculated the clinical disease activity index (CDAI) and the modified health assessment questionnaire (mHAQ) through automated extraction of joint counts, patient global assessment, and functional status from structured EHR fields. Primary outcomes included the frequency of CDAI and mHAQ assessments. We administered a structured post-implementation survey to assess rheumatologists' perceptions of MiRAi. Physicians used MiRAi for 236/884 (26.7%) patients with RA. Patients with documented CDAI and mHAQ scores increased from 29 (5.9%) in June 2022 to 81 (19.0%) in November 2022, representing a 3.2-fold increase. Among surveyed rheumatologists (n=10), 5 (50%) reported the regular use of MiRAi. Physicians who regularly used MiRAi (n=5) cited improved accuracy in disease assessment and enhanced treatment decision-making. Non-users and occasional users (n=5) identified three primary barriers: limited familiarity with MiRAi, time constraints, and discrepancies between clinical judgment and MiRAi-generated outputs. Despite MiRAi's availability, only 168 (19%) patients underwent quantitative disease activity assessment by the study end. Among 15 patients with high disease activity (CDAI >22), physicians recorded 3 treatment modifications and 2 intra-articular steroid injections. MiRAi implementation increased disease activity assessment frequency by 3.2-fold over 6 months; however, physician adoption remained at 26.7%, below the 80% target for routine care. Future implementation strategies should address identified barriers through system integration, structured user training, and workflow optimization to achieve guideline-concordant care for patients with RA.
To develop evidence-based Pan American League of Associations for Rheumatology (PANLAR) recommendations for the treatment of oligoarthritis category in juvenile idiopathic arthritis (oligo-JIA) patients. A panel of pediatric rheumatologists from Latin-America (LATAM) generated clinically meaningful questions related to the treatment of oligo-JIA patients, using Population, Intervention, Comparator, and Outcome (PICO) format. Following Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology, a team of methodologists conducted a systematic literature review, extracted, summarized intervention effect estimates, and graded the evidence quality. LATAM pediatric rheumatology experts' panel voted each PICO question, which required a minimum agreement of 70% among the voting members and developed recommendations. Seven recommendations and 4 expert opinion were developed. Short-term course of NSAID and intra-articular corticosteroids was recommended as initial therapy in those with minimal disease activity with no risk factors for poor prognosis. The initiation of a nbDMARD was recommended in patients with high disease activity and risk factors for poor prognosis. For patients who achieve inactive disease state, treatment with DMARD should be maintained for a minimum of 12 months after remission. We proposed sulfasalazine or leflunomide in patients with methotrexate intolerance, or in the presence of contraindication or unavailability of bDMARD. For oligo-JIA patients with high disease activity or uveitis, anti-TNF agents are recommended as the first choice among bDMARD. Regular physical activity was also recommended for these patients. The first PANLAR oligo-JIA treatment guidelines provide evidence-based guidance for health care providers, treating patients with oligo-JIA in LATAM.
Enthesitis is increasingly recognized as a key manifestation of psoriatic disease (PsD). However, how best to assess enthesitis remains a point of discussion due to limitations of the existing assessment tools, including their inability to differentiate between inflammatory and noninflammatory enthesitis as well as a high placebo response in clinical trials. At the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2024 annual meeting, a debate was held to address whether traditional clinical enthesitis indices should be discontinued for PsD. Dr. Sibel Aydin advocated for their discontinuation, emphasizing that clinical indices often capture "enthesalgia" (pain at the entheseal sites overlapping with pain disorders like fibromyalgia) rather than true inflammatory enthesitis. These clinical indices may lack specificity for detecting inflammation, which can lead to inaccurate assessments. Further, studies show high reports of placebo response when using clinical indices, suggesting their limitations in discriminating active disease from noninflammatory pain mechanisms. Aydin advocated for prioritizing emerging imaging tools over traditional clinical indices. Dr. Atul Deodhar argued against discontinuation of traditional clinical enthesitis indices, highlighting that despite limitations, these indices have been used successfully in multiple randomized controlled trials, leading to approval of numerous treatment options for psoriatic arthritis. Although promising, alternative imaging modalities like ultrasound to evaluate inflammation come with their own challenges, including operator dependency, variability in interpretation, and lack of regulatory approval as a standardized outcome measure. This report presents both perspectives, analyzing the evidence and implications for the future of enthesitis assessment in clinical practice.
Knee osteoarthritis (OA) is the most common chronic arthritis and is a leading cause of pain and disability. Chronic care model (CCM) has been proved successful in Hong Kong primary care setting. This study aims to assess the clinical effectiveness of a CCM, named Assessment and Management Program on Knee Osteoarthritis (RAMP-Knee OA), compared to usual care in adults with knee OA. The study is a 52-week, two-arm, parallel, open-label randomized clinical trial, evaluating the clinical efficacy of RAMP-Knee OA (N = 114) versus usual care (N = 114) on self-reported knee pain and other secondary outcomes. Measurement instruments will be tested at baseline, 16, 32, and 52 weeks. The primary outcome will be the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC; 5-point Likert) pain at 52 weeks. Secondary outcomes include a set of biopsychosocial parameters: Physical function will be measured subjectively by WOMAC function subscale and objectively by the 30-second chair and stand performance test. Lower limb muscle mass will be measured by bioimpedance analysis. Physical activity level will be measured by the Chinese International Physical Activity Questionnaire (Short form). Self-management efficacy will be measured by Pain-Self Efficacy questionnaire. Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) will be used to measure anxiety and depression, respectively. Insomnia will be measured by the 7-item Insomnia Severity Index (ISI), and loneliness will be measured by the 6-item De Jong Gierveld Loneliness Scale. EuroQuol-5D questionnaire will be used to measure health-related quality of life. Both primary and secondary outcomes at different points will be conducted using analysis of covariance, adjusting for baseline values. Secondary analyses include adjustments for potential confounders and exploration of interaction effects of treatment and the potential moderators. The findings will address the evidence-to-practice gap for the implementation of a CCM that incorporates a comprehensive risk assessment, care protocol, self-management support, and scheduled health assessments in Hong Kong. ClinicalTrials.gov, 1 NCT06283147. Registered on 22 February 2024.