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BACKGROUND: Most estimates of rheumatoid arthritis (RA) prevalence, including all official figures in Australia and many other countries, are based on self-report. Self-report has been shown to overestimate RA, but the 'gold standard' of reviewing individual medical records is costly, time-consuming and impractical for large-scale research and population monitoring. This study provides an algorithm to estimate RA cases using administrative data that can be adjusted for use in multiple contexts to provide the first approximate RA cohort in Australia that does not rely on self-report. METHODS: Survey data on self-reported RA and medications from 25 467 respondents of the Australian Longitudinal Study on Women's Health (ALSWH) were linked with data from the national medication reimbursement database, hospital and emergency department (ED) episodes, and Medicare Benefits codes. RA prevalence was calculated for self-reported RA, self-reported RA medications, dispensed RA medications, and hospital/ED RA presentations. Linked data were used to exclude individuals with confounding autoimmune conditions. RESULTS: Of 25 467 survey respondents, 1367 (5·4%) women self-reported disease. Of the 26 840 women with hospital or ED presentations, 292 (1·1%) received ICD-10 codes for RA. There were 1038 (2·8%) cases by the medication database definition, and 294 cases (1·5%) by the self-reported medication definition. After excluding individuals with other rheumatic conditions, prevalence was 3·9% for self-reported RA, 1·9% based on the medication database definition and 0·5% by self-reported medication definition. This confirms the overestimation of RA based on self-reporting. CONCLUSIONS: We provide an algorithm for identifying individuals with RA, which could be used for population studies and monitoring RA in Australia and, with adjustments, internationally. Its balance of accuracy and practicality will be useful for health service planning using relatively easily accessible input data.
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Antirreumáticos , Artrite Reumatoide , Bases de Dados Factuais , Autorrelato , Humanos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/diagnóstico , Feminino , Austrália/epidemiologia , Prevalência , Pessoa de Meia-Idade , Antirreumáticos/uso terapêutico , Estudos Longitudinais , Idoso , Adulto , AlgoritmosRESUMO
OBJECTIVES: This study aims to compare methods of constructing a composite score for the Flare-OA-16 self-reported questionnaire. METHODS: Participants with knee and hip osteoarthritis (OA) completed a validated 16-item questionnaire assessing five domains of flare. Three estimation methods were compared: (i) second-order confirmatory factor analysis (CFA); (ii) logistic regression, according to the participant's self-report of flare (yes/no); and (iii) Rasch method, with weighted scores in each dimension. The distribution (floor effect [FF] and ceiling effect [CF]) were described and the known-group validity (by self-reported flare) tested by Wilcoxon rank-sum test. Similarity between the scores was analyzed by intraclass correlation coefficient (ICC) and their performance against self-report compared by areas under ROC curves (AUC). Intrascore test-retest reliability at 14 days was assessed by ICC. RESULTS: In a sample of 381 participants, 247 reported having a flare. CFA showed fit indices (comparative fit index [CFI] = 0.95; root mean square error of approximation [RMSEA] = 0.08) and estimated composite mean score = 4.33(SD = 2.85) (FF = 14.9%, CF = 0%). For the logistic regression estimation, the mean composite score was 6.48 (SD = 3.13) (FF = 0%; CF = 0%). With Rasch model, the mean composite score was 4.35 (SD = 2.60) (FF = 14.9%; CF = 0%). Similarity analysis indicated a greater concordance between CFA and Rasch scores (ICC = 0.98) than between logistic regression score and the two others (ICC = 0.88 with Rasch score and 0.90 with CFA score). The AUC indicated similar performance of all methods: logistic model (AUC = 0.89 [0.85-0.92]), CFA, and Rasch model (AUC = 0.86 [0.82-0.90]). The difference between groups was significant (P < .05) for scores estimated by CFA (3.98), Rasch model (4.95), and logistic regression (4.30). The reproducibility was ICC = 0.84 (0.75-0.90) for Rasch and CFA scores and ICC = 0.78(0.66-86) for logistic model. CONCLUSION: Three alternatives explored to build a composite score showed similar construct validity. Some metric superiority (better score distribution and reproducibility) of the Rasch model is promising for the detection of occurrence and assessment of severity of a flare in OA.
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BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is key for policy making. Low back pain is the leading cause of disability in terms of years lived with disability (YLDs). Due to sparse data, a current limitation of GDB is that a uniform severity distribution is presumed based on 12-Item Short Form Health Survey scores derived from US Medical Expenditure Panel Surveys (MEPS). We present a novel approach to estimate the effect of exposure to health interventions on the severity of low back pain by country and over time. METHODS: We extracted treatment effects for ten low back pain interventions from the Cochrane Database, combining these with coverage data from the MEPS to estimate the hypothetical severity in the absence of treatment in the USA. Severity across countries was then graded using the Health Access and Quality Index, allowing estimates of averted and avoidable burden under various treatment scenarios. FINDINGS: We included 210 trials from 36 Cochrane systematic reviews in the network analysis. The pooled effect sizes (measured as a standardised mean difference) for the most effective intervention classes were -0·460 (95% uncertainty interval -0·606 to -0·309) for a combination of psychological and physical interventions and -0·366 (-0·525 to -0·207) for surgery. Globally, access to treatment averted an estimated 17·6% (14·8 to 23·8) of the low back pain burden in 2020. If all countries had provided access to treatment at a level estimated for Iceland with the highest Health Access and Quality Index score, an extra 9·1% (6·4 to 11·2) of the burden of low back pain could be avoided. Even with full coverage of optimal treatment, a large proportion (65·9% [56·9 to 70·4]) of the low back pain burden is unavoidable. INTERPRETATION: This methodology fills an important shortcoming in the GBD by accounting for low back pain severity variations over time and between countries. Assumptions of unequal treatment access increased YLD estimates in resource-poor settings, with a modest decrease in countries with higher Health Access and Quality Index scores. Nonetheless, the large proportion of unavoidable burden indicates poor intervention efficacy. This method, applicable to other GBD conditions, provides policy makers with insights into health gains from improved treatment and underscores the importance of investing in research for new interventions. FUNDING: Bill and Melinda Gates Foundation and Queensland Health.
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Carga Global da Doença , Acessibilidade aos Serviços de Saúde , Dor Lombar , Índice de Gravidade de Doença , Humanos , Dor Lombar/terapia , Dor Lombar/epidemiologiaRESUMO
BACKGROUND AND OBJECTIVE: Although paracetamol (acetaminophen) combined with other analgesics can reduce pain intensity in some pain conditions, its effectiveness in managing low back pain and osteoarthritis is unclear. This systematic review investigated whether paracetamol combination therapy is more effective and safer than monotherapy or placebo in low back pain and osteoarthritis. METHODS: Online database searches were conducted for randomised trials that evaluated paracetamol combined with another analgesic compared to a placebo or the non-paracetamol ingredient in the combination (monotherapy) in low back pain and osteoarthritis. The primary outcome was a change in pain. Secondary outcomes were (serious) adverse events, changes in disability and quality of life. Follow-up was immediate (≤ 2 weeks), short (> 2 weeks but ≤ 3 months), intermediate (> 3 months but < 12 months) or long term (≥ 12 months). A random-effects meta-analysis was conducted. Risk of bias was assessed using the original Cochrane tool, and quality of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Twenty-two studies were included. Pain was reduced with oral paracetamol plus a non-steroidal anti-inflammatory drug (NSAID) at immediate term in low back pain (paracetamol plus ibuprofen vs ibuprofen [mean difference (MD) - 6.2, 95% confidence interval (CI) -10.4 to -2.0, moderate evidence]) and in osteoarthritis (paracetamol plus aceclofenac vs aceclofenac [MD - 4.7, 95% CI - 8.3 to - 1.2, moderate certainty evidence] and paracetamol plus etodolac vs etodolac [MD - 15.1, 95% CI - 18.5 to - 11.8; moderate certainty evidence]). Paracetamol plus oral tramadol reduced pain compared with placebo at intermediate term for low back pain (MD - 11.7, 95% CI - 19.2 to - 4.3; very low certainty evidence) and osteoarthritis (MD - 6.8, 95% CI - 12.7 to -0.9; moderate certainty evidence). Disability scores improved in half the comparisons. Quality of life was infrequently measured. All paracetamol plus NSAID combinations did not increase the risk of adverse events compared to NSAID monotherapy. CONCLUSIONS: Low-to-moderate quality evidence supports the oral use of some paracetamol plus NSAID combinations for short-term pain relief with no increased risk of harm for low back pain and osteoarthritis compared to its non-paracetamol monotherapy comparator.
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Acetaminofen , Analgésicos não Narcóticos , Anti-Inflamatórios não Esteroides , Quimioterapia Combinada , Dor Lombar , Osteoartrite , Acetaminofen/uso terapêutico , Acetaminofen/administração & dosagem , Acetaminofen/efeitos adversos , Humanos , Osteoartrite/tratamento farmacológico , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/efeitos adversos , Analgésicos não Narcóticos/uso terapêutico , Analgésicos não Narcóticos/administração & dosagem , Analgésicos não Narcóticos/efeitos adversos , Dor Lombar/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Qualidade de Vida , Ibuprofeno/administração & dosagem , Ibuprofeno/uso terapêutico , Ibuprofeno/efeitos adversos , Dor nas Costas/tratamento farmacológicoRESUMO
Importance: Knee osteoarthritis is disabling, with few effective treatments. Preliminary evidence suggested that krill oil supplementation improved knee pain, but effects on knee osteoarthritis remain unclear. Objective: To evaluate efficacy of krill oil supplementation, compared with placebo, on knee pain in people with knee osteoarthritis who have significant knee pain and effusion-synovitis. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled clinical trial in 5 Australian cities. Participants with clinical knee osteoarthritis, significant knee pain, and effusion-synovitis on magnetic resonance imaging were enrolled from December 2016 to June 2019; final follow-up occurred on February 7, 2020. Interventions: Participants were randomized to 2 g/d of krill oil (n = 130) or matching placebo (n = 132) for 24 weeks. Main Outcomes and Measures: The primary outcome was change in knee pain as assessed by visual analog scale (range, 0-100; 0 indicating least pain; minimum clinically important improvement = 15) over 24 weeks. Results: Of 262 participants randomized (mean age, 61.6 [SD, 9.6] years; 53% women), 222 (85%) completed the trial. Krill oil did not improve knee pain compared with placebo (mean change in VAS score, -19.9 [krill oil] vs -20.2 [placebo]; between-group mean difference, -0.3; 95% CI, -6.9 to 6.4) over 24 weeks. One or more adverse events was reported by 51% in the krill oil group (67/130) and by 54% in the placebo group (71/132). The most common adverse events were musculoskeletal and connective tissue disorders, which occurred 32 times in the krill oil group and 42 times in the placebo group, including knee pain (n = 10 with krill oil; n = 9 with placebo), lower extremity pain (n = 1 with krill oil; n = 5 with placebo), and hip pain (n = 3 with krill oil; n = 2 with placebo). Conclusions and Relevance: Among people with knee osteoarthritis who have significant knee pain and effusion-synovitis on magnetic resonance imaging, 2 g/d of daily krill oil supplementation did not improve knee pain over 24 weeks compared with placebo. These findings do not support krill oil for treating knee pain in this population. Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12616000726459; Universal Trial Number: U1111-1181-7087.
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Euphausiacea , Óleos de Peixe , Osteoartrite do Joelho , Idoso , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Artralgia/tratamento farmacológico , Artralgia/etiologia , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Imageamento por Ressonância Magnética , Óleos/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/complicações , Medição da Dor , Sinovite/tratamento farmacológico , Sinovite/etiologia , Óleos de Peixe/uso terapêuticoRESUMO
OBJECTIVE: Dyadic coping, the process of coping that transpires between couples challenged by one partner's illness, is an important predictor of disease adjustment and patient well-being. However, the extent of dyadic coping in rheumatoid arthritis (RA) remains unclear. This study examines the effect of dyadic coping on psychological distress and relationship quality from the perspectives of both participants with RA and their spouses. METHODS: Participants and their spouses were invited to participate in an online survey study if they were aged ≥ 18 years and had lived together for more than a year. The survey included the Chronic Pain Grade Scale, Dyadic Coping Inventory, Depression Anxiety Stress Scale, and Dyadic Adjustment Scale. Participants and spouses completed the survey independently. The actor-partner interdependence model was used to analyze the dyadic data. RESULTS: One hundred sixty-three couples participated. Our findings showed that participants who reported higher supportive dyadic coping reported lower depression, anxiety, and stress, and higher relationship quality, whereas participants who reported higher negative dyadic coping reported higher depression, anxiety, and stress, and lower relationship quality. Spouses who reported higher supportive dyadic coping reported higher relationship quality, but no effect on depression, anxiety, and stress was observed. In contrast, spouses who reported higher negative dyadic coping reported higher levels of depression, anxiety, and stress, and lower relationship quality. CONCLUSION: Participants' and spouses' perceptions of supportive and negative dyadic coping closely influenced their psychological distress and relationship quality. Further, having a partner with RA also seemed to affect the spouse, especially when there was a negative dyadic coping pattern.
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Endothelial Protein C Receptor (EPCR) is a key regulator of the activated protein C anti-coagulation pathway due to its role in the binding and activation of this protein. EPCR also binds to other ligands such as Factor VII and X, γδ T-cells, plasmodium falciparum erythrocyte membrane protein 1, and Secretory group V Phospholipases A2, facilitating ligand-specific functions. The functions of EPCR can also be regulated by soluble (s)EPCR that competes for the binding sites of membrane-bound (m)EPCR. sEPCR is created when mEPCR is shed from the cell surface. The propensity of shedding alters depending on the genetic haplotype of the EPCR gene that an individual may possess. EPCR plays an active role in normal homeostasis, anti-coagulation pathways, inflammation, and cell stemness. Due to these properties, EPCR is considered a potential effector/mediator of inflammatory diseases. Rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus are autoimmune/inflammatory conditions that are associated with elevated EPCR levels and disease activity, potentially driven by EPCR. This review highlights the functions of EPCR and its contribution to rheumatic diseases.
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Importance: A high proportion of patients who sustain a fracture have multimorbidity. However, the association of multimorbidity with postfracture adverse outcomes, such as subsequent fractures and premature mortality, has not been widely explored. Objective: To examine the association of multimorbidity and self-rated health with subsequent fractures and mortality after fracture. Design, Setting, and Participants: This prospective cohort study included participants from New South Wales, Australia, in the Sax Institute's 45 and Up Study (n = 267â¯357). Participants were recruited from July 2005 to December 2009 and followed up from the date of the incident fracture until subsequent fracture, death, or the end of the study (April 2017), whichever occurred first, with questionnaire data linked to hospital admission and medication records. Data analysis was reported between March and September 2023. Exposures: Charlson Comorbidity Index (CCI) score and self-rated health (SRH). Main Outcomes and Measures: The main outcomes were subsequent fracture or mortality after an incident fracture. Associations between SRH measures and subsequent fracture and mortality were also assessed. All analyses were stratified by sex given the different fracture and mortality risk profiles of females and males. Results: Of 25â¯280 adults who sustained incident fractures, 16â¯191 (64%) were female (mean [SD] age, 74 [12] years) and 9089 (36%) were male (mean [SD] age, 74 [13] years). During a median follow-up time of 2.8 years (IQR, 1.1-5.2 years), 2540 females (16%) and 1135 males (12%) sustained a subsequent fracture and 2281 females (14%) and 2140 males (24%) died without a subsequent fracture. Compared with a CCI score of less than 2, those with a CCI score of 2 to 3 had an increased risk of subsequent fracture (females: hazard ratio [HR], 1.16 [95% CI, 1.05-1.27]; males: HR, 1.25 [95% CI, 1.09-1.43]) and mortality (females: HR, 2.19 [95% CI, 1.99-2.40]; males: HR, 1.89 [95% CI, 1.71-2.09]). Those with a CCI score of 4 or greater had greater risks of subsequent fracture (females: HR, 1.33 [95% CI, 1.12-1.58]; males: HR, 1.48 [95% CI, 1.21-1.81]) and mortality (females: HR, 4.48 [95% CI, 3.97-5.06]; males: HR, 3.82 [95% CI 3.41-4.29]). Self-rated health was also significantly associated with subsequent fracture and mortality. Those reporting the poorest health and quality of life had the highest subsequent fracture risks, and their mortality risks were even higher. Conclusions and Relevance: In this cohort study, both CCI and SRH measures were associated with increased risk of subsequent fractures and mortality after fracture, underscoring the importance of managing the care of patients with comorbidities who sustain a fracture.
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Fraturas Ósseas , Multimorbidade , Humanos , Masculino , Feminino , Idoso , Estudos Prospectivos , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/mortalidade , New South Wales/epidemiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou maisRESUMO
OBJECTIVES: To identify barriers, facilitators, and strategies for future implementation of the OMERACT-Adherence Core Outcome Set (COS) in medication adherence trials for rheumatic conditions. METHODS: Preliminary Delphi survey findings were discussed at OMERACT 2023, utilising the Consolidated Framework for Implementation Research 2 to identify implementation barriers, facilitators, and solutions. RESULTS: Implementation strategies included simplifying the COS definitions, making it adaptabile for clinical practice and drug trials, adherence trial training workshops, and collaborating with key stakeholders such as payers and other COS developers. CONCLUSION: Ongoing collaboration with individuals and organisations within and beyond rheumatology ensures broader applicability of OMERACT-Adherence COS.
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Antirreumáticos , Adesão à Medicação , Doenças Reumáticas , Reumatologia , Humanos , Doenças Reumáticas/tratamento farmacológico , Antirreumáticos/uso terapêutico , Técnica Delphi , Ensaios Clínicos como Assunto , Avaliação de Resultados em Cuidados de SaúdeRESUMO
OBJECTIVE: To gain consensus on the definitions and descriptions of the domains of the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials evaluating shared decision making (SDM) interventions. METHODS: Following the OMERACT Handbook methods, our Working Group (WG), comprised of 90 members, including 17 patient research partners (PRPs) and 73 clinicians and researchers, had six virtual meetings in addition to email exchanges to develop draft definitions and descriptions. The WG then conducted an international survey of its members to gain consensus on the definitions and descriptions. Finally, the WG members had virtual meetings and e-mail exchanges to review survey results and finalize names, definitions and descriptions of the domains. RESULTS: WG members contributed to developing the definitions. Fifty-two members representing four continents and 13 countries completed the survey, including 15 PRPs, 33 clinicians and 37 researchers. PRPs and clinicians/researchers agreed with all definitions and descriptions with agreements ranging from 87% to 100%. Respondents suggested wording changes to the names, definitions and descriptions to better reflect the domains. Discussions led to further simplification and clarification to address common questions/concerns about the domains. CONCLUSION: Our WG reached consensus on the definitions and descriptions of the domains of the core domain set for rheumatology trials of SDM interventions. This step is crucial to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core Outcome Measurement Set. CLINICAL SIGNIFICANCE: The current study provides consensus-based definitions and descriptions for the domains of the OMERACT core domain set for shared decision making interventions from patients/caregivers, clinicians and researchers. This is a crucial step to understand each domain and provides the foundation to identify instruments to measure each domain for inclusion in the Core Outcome Measurement Set for trials of SDM interventions.
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Reumatologia , Humanos , Consenso , Tomada de Decisão Compartilhada , Avaliação de Resultados em Cuidados de SaúdeRESUMO
OBJECTIVE: To describe the evolution of the OMERACT Fellows Program (OM FP) and to evaluate the innovative changes implemented in the 2023 program. METHODS: The OM FP, the first of its kind in global rheumatology, was developed in 2000 to mentor early career researchers in methods and processes for reaching evidence-driven consensus for outcome measures in clinical studies. The OM FP has evolved through continuing iterations of face to face and online feedback. Key new features delivered in 2023 included e-learning modules, virtual introductory pre-meetings, increased networking with Patient Research Partners (PRPs), learning opportunities to give and receive personal feedback, ongoing performance feedback during the meeting from Fellow peers, PRPs, senior OMERACTers (members of the OMERACT community) and Emerging Leader mentors, involvement in pitching promotions, two-minute Lightning Talks in a plenary session and an embedded poster tour. An online survey was distributed after the meeting to evaluate the program. RESULTS: OM FP has included 208 fellows from 16 countries across 4 continents covering 47 different aspects of rheumatology outcomes since its inception. Over 50 % have remained engaged with OMERACT work. In 2023, 18 Fellows attended and 15 (83 %) completed the post-meeting survey. A dedicated OM FP was deemed important by all respondents, and 93 % would attend the meeting in future. The PRP/Fellow Connection Carousel and Lightning Talks were rated exceptional by 93 %. Key components to improve included clarification of expectations, overall workload, the Emerging Leaders Mentoring Program, and the content and duration of daily summary sessions. CONCLUSION: The innovations in the 2023 OM FP were well received by the majority of participants and supports early career rheumatology researchers to develop collaborations, skills and expertise in outcome measurement. Implementation of feedback from Fellows will enhance the program for future meetings, continuing to facilitate learning and succession planning within OMERACT.
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Reumatologia , Humanos , Mentores , Avaliação de Resultados em Cuidados de Saúde , Consenso , PesquisadoresRESUMO
OBJECTIVE: To determine the effect of zoledronic acid (ZA) on the risk of total knee replacement (TKR) in patients with symptomatic knee osteoarthritis and without severe joint space narrowing (JSN). METHODS: We included 222 participants (mean age 62 years, 52% female) from the two-year Zoledronic Acid for Osteoarthritis Knee Pain trial (113 received 5 mg of ZA annually and 109 received placebo) conducted between November 2013 and October 2017. Primary TKR were identified until February 22, 2022. The effect of ZA on TKR risk was evaluated using Cox proportional hazard regression models. Because the treatment effect failed the proportional hazards assumption, a time-varying coefficients analysis for treatment was conducted by splitting the study into two periods (ie, within and after two years of randomization). RESULTS: Over a mean follow-up of seven years, 39% and 30% of participants had any TKR in the ZA and placebo groups, and 28% and 18% had TKR in the study knee, respectively. Use of ZA was associated with a higher risk of TKR in any knee (hazard ratio [HR] 4.2, 95% confidence interval [CI] 1.2-14.7) and showed a trend in the study knee (HR 6.8, 95%CI 0.9-53.9) during the trial. In the posttrial period, the risk of TKR was similar in the ZA and the placebo groups for any knee (HR 1.2, 95%CI 0.5-1.8) and the study knee (HR 1.4, 95%CI 0.5-2.2). CONCLUSION: These results suggest that ZA is not protective against TKR in patients with symptomatic knee osteoarthritis and without severe JSN.
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Artroplastia do Joelho , Conservadores da Densidade Óssea , Osteoartrite do Joelho , Ácido Zoledrônico , Humanos , Ácido Zoledrônico/uso terapêutico , Ácido Zoledrônico/administração & dosagem , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/diagnóstico por imagem , Feminino , Pessoa de Meia-Idade , Masculino , Método Duplo-Cego , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/administração & dosagem , Idoso , Modelos de Riscos Proporcionais , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Resultado do Tratamento , Administração IntravenosaRESUMO
OBJECTIVES: To generate candidates for contextual factors (CFs) for each CF type (i.e., Effect Modifying Contextual Factors (EM-CFs), Outcome Influencing Contextual Factors (OI-CFs), and Measurement Affecting Contextual Factors (MA-CFs)) considered important within rheumatology. METHODS: We surveyed OMERACT working groups and conducted a Special Interest Group (SIG) session at the OMERACT 2023 meeting, where the results were reviewed, and additional CFs suggested. RESULTS: The working groups suggested 44, 49, and 21 generic EM-CFs, OI-CFs, and MA-CFs, respectively. SIG participants added 49, 44, and 55 factors, respectively. CONCLUSION: Candidate CFs were identified, next step is a consensus-based set of endorsed (important) CFs.
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Avaliação de Resultados em Cuidados de Saúde , Reumatologia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , ConsensoRESUMO
Endothelial protein C receptor (EPCR) is a receptor for the natural anti-coagulant activated protein C (aPC). It mediates the anti-inflammatory and barrier-protective functions of aPC through the cleavage of protease-activated receptor (PAR)1/2. Allergic contact dermatitis is a common skin disease characterized by inflammation and defective skin barrier. This study investigated the effect of EPCR and 3K3A-aPC on allergic contact dermatitis using a contact hypersensitivity (CHS) model. CHS was induced using 1-Fluoro-2,4-dinitrobenzene in EPCR-deficient (KO) and matched wild-type mice and mice treated with 3K3A-aPC, a mutant form of aPC with diminished anti-coagulant activity. Changes in clinical and histological features, cytokines, and immune cells were examined. EPCRKO mice displayed more severe CHS, with increased immune cell infiltration in the skin and higher levels of inflammatory cytokines and IgE than wild-type mice. EPCR, aPC, and PAR1/2 were expressed by the skin epidermis, with EPCR presenting almost exclusively in the basal layer. EPCRKO increased the epidermal expression of aPC and PAR1, whereas in CHS, their expression was reduced compared to wild-type mice. 3K3A-aPC reduced CHS severity in wild-type and EPCRKO mice by suppressing immune cell infiltration/activation and inflammatory cytokines. In summary, EPCRKO exacerbated CHS, whereas 3K3A-aPC could reduce the severity of CHS in both EPCRKO and wild-type mice.
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Dermatite Alérgica de Contato , Proteína C , Proteínas Recombinantes , Animais , Camundongos , Proteína C/metabolismo , Receptor de Proteína C Endotelial/metabolismo , Receptor PAR-1/metabolismo , Transdução de Sinais , Citocinas/farmacologia , Dermatite Alérgica de Contato/tratamento farmacológicoRESUMO
Importance: The relationship between self-reported walking limitation, a proxy of muscle function, and fracture risk has not been investigated. Objective: To examine the association between a self-reported walking limitation of 1000 m or less and 5-year risk of fracture. Design, Setting, and Participants: This prospective cohort study compared individuals with various degrees of walking ability limitation at 1000 m (a little limitation and a lot of limitation) and those without limitation (no limitation) accounting for age, falls, prior fractures, and weight. Participants from the ongoing population-based Sax Institute 45 and Up Study were followed from recruitment (2005-2008) for 5 years (2010-2013). Data analysis was conducted from July 2020 to September 2023. Exposure: Self-reported walking limitation. Main Outcomes and Measures: Incident fracture and site-specific fractures (hip, vertebral, and nonhip nonvertebral [NHNV] fractures). Results: Among the 266â¯912 participants enrolled in the 45 and Up Study, 238â¯969 were included, with 126â¯015 (53%) women (mean [SD] age, 63 [11] years) and 112â¯954 (47%) men (mean [SD] age, 61 [11] years). Approximately 20% reported a degree of limitation in walking 1000 m or less at baseline (39â¯324 women [24%]; 23â¯191 men [21%]). During a mean (SD) follow-up of 4.1 (0.8) years, 7190 women and 4267 men experienced an incident fracture. Compared with participants who reported no walking limitations, a little limitation and a lot of limitation were associated with higher risk of fracture (a little limitation among women: hazard ratio [HR], 1.32; 95% CI, 1.23-1.41; a little limitation among men: HR, 1.46; 95% CI, 1.34-1.60; a lot of limitation among women: HR, 1.60; 95% CI, 1.49-1.71; a lot of limitation among men: HR, 2.03; 95% CI, 1.86-2.22). Approximately 60% of fractures were attributable to walking limitation. The association was significant for hip, vertebral, and NHNV fracture and ranged between a 21% increase to a greater than 219% increase. Conclusions and Relevance: In this cohort study of 238â¯969 participants, self-reported walking limitations were associated with increased risk of fracture. These findings suggest that walking ability should be sought by clinicians to identify high-risk candidates for further assessment.
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Fraturas Ósseas , Autoavaliação (Psicologia) , Adulto , Masculino , Humanos , Feminino , Idoso , Pessoa de Meia-Idade , Austrália/epidemiologia , Estudos de Coortes , Estudos Prospectivos , Academias e Institutos , Fraturas Ósseas/epidemiologiaRESUMO
OBJECTIVES: Shared decision making (SDM) is a central tenet in rheumatic and musculoskeletal care. The lack of standardization regarding SDM instruments and outcomes in clinical trials threatens the comparative effectiveness of interventions. The Outcome Measures in Rheumatology (OMERACT) SDM Working Group is developing a Core Outcome Set for trials of SDM interventions in rheumatology and musculoskeletal health. The working group reached consensus on a Core Outcome Domain Set in 2020. The next step is to develop a Core Outcome Measurement Set through the OMERACT Filter 2.2. METHODS: We conducted a scoping review (PRISMA-ScR) to identify candidate instruments for the OMERACT Filter 2.2 We systematically reviewed five databases (Ovid MEDLINE®, Embase, Cochrane Library, CINAHL and Web of Science). An information specialist designed search strategies to identify all measurement instruments used in SDM studies in adults or children living with rheumatic or musculoskeletal diseases or their important others. Paired reviewers independently screened titles, abstracts, and full text articles. We extracted characteristics of all candidate instruments (e.g., measured construct, measurement properties). We classified candidate instruments and summarized evidence gaps with an adapted version of the Summary of Measurement Properties (SOMP) table. RESULTS: We found 14,464 citations, read 239 full text articles, and included 99 eligible studies. We identified 220 potential candidate instruments. The five most used measurement instruments were the Decisional Conflict Scale (traditional and low literacy versions) (n=38), the Hip/Knee-Decision Quality Instrument (n=20), the Decision Regret Scale (n=9), the Preparation for Decision Making Scale (n=8), and the CollaboRATE (n=8). Only 44 candidate instruments (20%) had any measurement properties reported by the included studies. Of these instruments, only 57% matched with at least one of the 7-criteria adapted SOMP table. CONCLUSION: We identified 220 candidate instruments used in the SDM literature amongst people with rheumatic and musculoskeletal diseases. Our classification of instruments showed evidence gaps and inconsistent reporting of measurement properties. The next steps for the OMERACT SDM Working Group are to match candidate instruments with Core Domains, assess feasibility and review validation studies of measurement instruments in rheumatic diseases or other conditions. Development and validation of new instruments may be required for some Core Domains.
Assuntos
Tomada de Decisão Compartilhada , Doenças Musculoesqueléticas , Avaliação de Resultados em Cuidados de Saúde , Doenças Reumáticas , Humanos , Reumatologia/normas , Participação do PacienteRESUMO
OBJECTIVES: To describe associations between MRI markers with knee symptoms in young adults. METHODS: Knee symptoms were assessed using the WOMAC scale during the Childhood Determinants of Adult Health Knee Cartilage study (CDAH-knee; 2008-2010) and at the 6- to 9-year follow-up (CDAH-3; 2014-2019). Knee MRI scans obtained at baseline were assessed for morphological markers (cartilage volume, cartilage thickness, subchondral bone area) and structural abnormalities [cartilage defects and bone marrow lesions (BMLs)]. Univariable and multivariable (age, sex, BMI adjusted) zero-inflated Poisson (ZIP) regression models were used for analysis. RESULTS: The participants' mean age in CDAH-knee and CDAH-3 were 34.95 (s.d. 2.72) and 43.27 (s.d. 3.28) years, with 49% and 48% females, respectively. Cross-sectionally, there was a weak but significant negative association between medial femorotibial compartment (MFTC) [ratio of the mean (RoM) 0.99971084 (95% CI 0.9995525, 0.99986921), P < 0.001], lateral femorotibial compartment (LFTC) [RoM 0.99982602 (95% CI 0.99969915, 0.9999529), P = 0.007] and patellar cartilage volume [RoM 0.99981722 (95% CI 0.99965326, 0.9999811), P = 0.029] with knee symptoms. Similarly, there was a negative association between patellar cartilage volume [RoM 0.99975523 (95% CI 0.99961427, 0.99989621), P = 0.014], MFTC cartilage thickness [RoM 0.72090775 (95% CI 0.59481806, 0.87372596), P = 0.001] and knee symptoms assessed after 6-9 years. The total bone area was negatively associated with knee symptoms at baseline [RoM 0.9210485 (95% CI 0.8939677, 0.9489496), P < 0.001] and 6-9 years [RoM 0.9588811 (95% CI 0.9313379, 0.9872388), P = 0.005]. The cartilage defects and BMLs were associated with greater knee symptoms at baseline and 6-9 years. CONCLUSION: BMLs and cartilage defects were positively associated with knee symptoms, whereas cartilage volume and thickness at MFTC and total bone area were weakly and negatively associated with knee symptoms. These results suggest that the quantitative and semiquantitative MRI markers can be explored as a marker of clinical progression of OA in young adults.
Assuntos
Doenças Ósseas , Doenças das Cartilagens , Cartilagem Articular , Osteoartrite do Joelho , Feminino , Humanos , Adulto Jovem , Criança , Masculino , Osteoartrite do Joelho/complicações , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética , Cartilagem/patologia , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Doenças Ósseas/complicações , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologiaRESUMO
OBJECTIVES: Endothelial protein C receptor (EPCR) is highly expressed in synovial tissues of patients with RA, but the function of this receptor remains unknown in RA. This study investigated the effect of EPCR on the onset and development of inflammatory arthritis and its underlying mechanisms. METHODS: CIA was induced in EPCR gene knockout (KO) and matched wild-type (WT) mice. The onset and development of arthritis was monitored clinically and histologically. T cells, dendritic cells (DCs), EPCR and cytokines from EPCR KO and WT mice, RA patients and healthy controls (HCs) were detected by flow cytometry and ELISA. RESULTS: EPCR KO mice displayed >40% lower arthritis incidence and 50% less disease severity than WT mice. EPCR KO mice also had significantly fewer Th1/Th17 cells in synovial tissues with more DCs in circulation. Lymph nodes and synovial CD4 T cells from EPCR KO mice expressed fewer chemokine receptors CXCR3, CXCR5 and CCR6 than WT mice. In vitro, EPCR KO spleen cells contained fewer Th1 and more Th2 and Th17 cells than WT and, in concordance, blocking EPCR in WT cells stimulated Th2 and Th17 cells. DCs generated from EPCR KO bone marrow were less mature and produced less MMP-9. Circulating T cells from RA patients expressed higher levels of EPCR than HC cells; blocking EPCR stimulated Th2 and Treg cells in vitro. CONCLUSION: Deficiency of EPCR ameliorates arthritis in CIA via inhibition of the activation and migration of pathogenic Th cells and DCs. Targeting EPCR may constitute a novel strategy for future RA treatment.
Assuntos
Artrite Experimental , Artrite Reumatoide , Animais , Humanos , Camundongos , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Células Dendríticas/metabolismo , Receptor de Proteína C Endotelial/metabolismo , Membrana Sinovial/patologia , Células Th17/metabolismoRESUMO
Denosumab (Dmab) is increasingly prescribed worldwide. Unlike bisphosphonates (BPs), its effect on mortality has yet to be well explored. This study examined the association between Dmab and all-cause mortality compared with no treatment in subjects with a fracture and BPs in subjects without a fracture. The study population was from the Sax Institute's 45 and Up Study (n = 267,357), a prospective population-based cohort with questionnaire data linked to hospital admissions (Admitted Patients Data Collection [APDC] data were linked by the Centre for Health Record Linkage), medication records (Pharmaceutical Benefits Scheme [PBS] provided by Services Australia), and stored securely (secure data access was provided through the Sax Institute's Secure Unified Research Environment [SURE]). The new-user cohort design with propensity-score (PS) matching was implemented. In the fracture cohort, Dmab and oral BP users were matched 1:2 to no treatment (Dmab: 617 women, 154 men; oral BPs: 615 women, 266 men). In the no-fracture cohort, Dmab users were matched 1:1 with oral BPs and zoledronic acid (Zol) users (Dmab:oral BPs: 479 men, 1534 women; Dmab:Zol: 280 men, 625 women). Mortality risk was measured using sex-specific pairwise multivariable Cox models. In the fracture cohort, compared with no treatment, Dmab was associated with 48% lower mortality in women (hazard ratio [HR] = 0.52, 95% confidence interval [CI] 0.36-0.72) but not in men. Oral BPs were associated with 44% lower mortality in both sexes (women HR = 0.56, 95% CI 0.42-0.77; men HR = 0.56, 95% CI 0.40-0.78). In the no-fracture cohort, compared with BPs, Dmab was associated with 1.5- to 2.5-fold higher mortality than oral BPs (women HR = 1.49, 95% CI 1.13-1.98; men HR = 2.74; 95% CI 1.82-4.11) but similar mortality to Zol. Dmab in women and oral BPs were associated with lower post-fracture mortality than no treatment. However, Dmab users had generally higher mortality than oral BP users in those without fractures. © 2023 American Society for Bone and Mineral Research (ASBMR).