Development and initial validation of a composite disease activity score for systemic juvenile idiopathic arthritis.

OBJECTIVE: To develop a composite disease activity score for systemic JIA (sJIA) and to provide preliminary evidence of its validity. METHODS: The systemic Juvenile Arthritis Disease Activity Score (sJADAS) was constructed by adding to the four items of the original JADAS a fifth item that aimed to quantify the activity of systemic features. Validation analyses were conducted on patients with definite or probable/possible sJIA enrolled at first visit or at the time of a flare, who had active systemic manifestations, which should include fever. Patients were reassessed 2 weeks to 3 months after baseline. Three versions were examined, including ESR, CRP or no acute-phase reactant. RESULTS: A total of 163 patients were included at 30 centres in 10 countries. The sJADAS was found to be feasible and to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha 0.64-0.65), fair ability to discriminate between patients with different disease activity states and between those whose parents were satisfied or not satisfied with illness outcome (P < 0.0001 for both), and strong responsiveness to change over time (standardized response mean 2.04-2.58). Overall, these properties were found to be better than those of the original JADAS and of DAS for RA and of Puchot score for adult-onset Still's disease. CONCLUSION: The sJADAS showed good measurement properties and is therefore a valid instrument for the assessment of disease activity in children with sJIA. The performance of the new tool should be further examined in other patient cohorts that are evaluated prospectively.

The Arabic LupusPRO: A Cross-Cultural Validation of a Disease-Specific Patient-Reported Outcome Tool for Quality of Life in Lupus Patients.

OBJECTIVE: To translate and cross-culturally adapt the Arabic version of LupusPRO v.1.8 and to test its reliability and validity. METHODS: LupusPRO was translated into the Arabic language following a standard procedure with forward-backward translation and was tested in patients with systemic lupus erythematosus (SLE) before use. The Arabic version was administered to 107 Egyptian SLE patients, along with a validated Arabic version of RAND 36-Item Health Survey 1.0 (SF-36). The internal consistency and test-retest reliability were determined. Validity was assessed by correlating LupusPRO scores with SF-36, Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). The conceptual framework of the Arabic LupusPRO was evaluated using confirmatory factor analysis (CFA). RESULTS: Among the 107 SLE patients, 95% were women with a median (range) age of 32 (18-55) years, median (range) SELENA-SLEDAI of 6 (0-23) and median (range) SDI of 0 (0-6). The Cronbach's alpha for the Arabic LupusPRO ranged from 0.71 to 0.98, except for the social support domain (0.65). Test-retest reliability ranged from 0.95 to 0.99. Convergent validity with corresponding domains of SF 36 was satisfactory. For criterion validity, there was a weak but significant correlation between several LupusPRO domains with SELENA-SLEDAI. CFA showed a good model fit. CONCLUSION: The Arabic version of LupusPRO v1.8 is a reliable and valid tool for measuring quality of life among Arabic speaking SLE patients.

Serum and Urinary Interferon-Gamma-Inducible Protein 10 in Lupus Nephritis.

BACKGROUND: Lupus nephritis is a serious manifestation of systemic lupus erythematosus (SLE). The objective of this study was to identify the sensitivity, specificity, and cut-off values of IP-10 in the serum and urine of patients with lupus nephritis compared to renal biopsy, albumin/creatinine ratio, and serum anti-dsDNA. METHODS: Thirty female SLE patients were included. SLEDAI was calculated and blood and urine samples were collected. Patients were divided into 10 SLE patients with renal involvement (six active and four inactive), 10 active SLE, and 10 inactive SLE patients. Ten age-matched healthy (control) were included. Serum and urinary levels of IP-10 were measured by ELISA. Anti-dsDNA, urine albumin/creatinine ratio were performed. RESULTS: Serum and urinary IP-10 in active SLE patients had significantly increased levels as compared to inactive SLE patients (P = 0.015, P = 0.033, respectively). However, there was no difference in serum and urinary levels between active renal and active non-renal patients. Albumin/creatinine ratio is a better marker in differentiating between lupus nephritis and SLE with no renal involvement. Any of serum and urinary IP-10, albumin/creatinine ratio, and anti-dsDNA did not correlate with the class of lupus nephritis in renal biopsy. CONCLUSION: Urinary and serum IP-10 are useful markers of lupus activity, but not indicative of renal activity. Albumin/creatinine ratio is superior in identifying lupus nephritis and renal activity.

OMERACT Core outcome measurement set for shared decision making in rheumatic and musculoskeletal conditions: a scoping review to identify candidate instruments.

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.

Consensus on the definitions and descriptions of the domains of the OMERACT Core Outcome Set for shared decision making interventions in rheumatology trials.

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.

Assessment of Angiopoietin-2 Single Nucleotide Polymorphism in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that destroys joint cartilage and causes disability. Synovial inflammation, with angiogenesis, is an early event in the progression of the disease. Angiopoietin 2 (ANGPT2) is a cytokine with both inflammatory and angiogenic effects. Many genes can influence RA susceptibility and disease activity. The aim is to assess the relationship between ANGPT2 gene polymorphism (rs3020221) and RA. The study was a case-control study that included 212 RA patients and 238 age-and gender-matched healthy volunteers. RA disease activity was assessed using the Disease Activity Score 28 index. Erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and antibody to cyclic citrullinated peptide were measured. ANGPT2 rs3020221 C > T SNP genotyping was done using real-time polymerase chain reaction (PCR). The TT genotype was more frequently represented in RA patients than in healthy controls (18.9% and 7.1%, respectively, p < 0.001) and increased the chance of developing RA four-fold, as compared to other genotypes (OR = 4.00, 95% CI = 2.09-7.63) (p < 0.001). The CT genotype was associated with elevated levels of the inflammatory markers ESR and CRP in RA patients (p = 0.012 and 0.037, respectively) as well as the DAS28 ESR Score (p < 0.001). The presence of the T allele either under the dominant model (for genotypes CT and TT) or the recessive model (for the genotype TT) predicts RA disease. Assessment of ANGPT2 gene polymorphism is useful to predict the patients with susceptibility to RA. The presence of T allele increased the risk of developing RA disease by two folds.

Consensus Evidence-Based Clinical Practice Recommendations for the Diagnosis and Treat-To-Target Management of Osteoporosis in Chronic Kidney Disease Stages G4-G5D and Post-transplantation: An Initiative of Egyptian Academy of Bone Health.

Objective: The aim of this study was to reach a consensus on an updated version of the recommendations for the diagnosis and Treat-to-Target management of osteoporosis that is effective and safe for individuals with chronic kidney disease (CKD) G4-G5D/kidney transplant. Methods: Delphi process was implemented (3 rounds) to establish a consensus on 10 clinical domains: (1) study targets, (2) risk factors, (3) diagnosis, (4) case stratification, (5) treatment targets, (6) investigations, (7) medical management, (8) monitoring, (9) management of special groups, (10) fracture liaison service. After each round, statements were retired, modified, or added in view of the experts' suggestions, and the percent agreement was calculated. Statements receiving rates of 7-9 by more than 75% of experts' votes were considered as achieving consensus. Results: The surveys were sent to an expert panel (n = 26), of whom 23 participated in the three rounds (2 were international experts and 21 were national). Most of the participants were rheumatologists (87%), followed by nephrologists (8.7%), and geriatric physicians (4.3%). Eighteen recommendations, categorized into 10 domains, were obtained. Agreement with the recommendations (rank 7-9) ranged from 80 to 100%. Consensus was reached on the wording of all 10 clinical domains identified by the scientific committee. An algorithm for the management of osteoporosis in CKD has been suggested. Conclusion: A panel of international and national experts established a consensus regarding the management of osteoporosis in CKD patients. The developed recommendations provide a comprehensive approach to assessing and managing osteoporosis for all healthcare professionals involved in its management.

Consensus evidence-based recommendations for treat-to-target management of immunoglobulin A vasculitis.

IgA vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is the most common cause of systemic vasculitis in childhood. Given its potential life-threatening systemic complications, early and accurate diagnosis as well as management of IgAV represent a major challenge for health care professionals. This study was carried out to attain an evidence-based expert consensus on a treat-to-target management approach for IgAV using Delphi technique. The preliminary scientific committee identified a total of 16 key clinical questions according to the patient, intervention, comparison, and outcomes (PICO) approach. An evidence-based, systematic, literature review was conducted to compile evidence for the IgAV management. The core leadership team identified researchers and clinicians with expertise in IgAV management in Egypt upon which experts were gathered from different governorates and health centers across Egypt. Delphi process was implemented (two rounds) to reach a consensus. An online questionnaire was sent to expert panel (n = 26) who participated in the two rounds. After completing round 2, a total of 20 recommendation items, categorized into two sections were obtained. Agreement with the recommendations (rank 7-9) ranged from 91.7-100%. Consensus was reached (i.e. ⩾75% of respondents strongly agreed or agreed) on the wording of all the 20 clinical standards identified by the scientific committee. Algorithms for the diagnosis and management have been suggested. This was an expert, consensus recommendations for the diagnosis and treatment of IgAV and IgA vasculitic nephritis, based on best available evidence and expert opinion. The guideline presented a strategy of care with a pathway to achieve a state of remission as early as possible. PLAIN LANGUAGE SUMMARY: Given its potential life-threatening systemic complications, early and accurate diagnosis of immunoglobulin A vasculitis represents a major challenge for health care professionals. This work provided cornerstone principles for the management of the condition. Adopting PICO approach and implementing Delphi process a consensus was reached on evidence-based treat-to-target treatment recommendations. This will endorse enhancement and consistency of care of this cohort of patients in standard practice.

Endorsement of the OMERACT core domain set for shared decision making interventions in rheumatology trials: Results from a multi-stepped consensus-building approach.

OBJECTIVE: To gain consensus on the Outcome Measures in Rheumatology (OMERACT) core domain set for rheumatology trials of shared decision making (SDM) interventions. METHODS: The process followed the OMERACT Filter 2.1 methodology, and used consensus-building methods, with patients involved since the inception. After developing the draft core domain set in previous research, we conducted five steps: (i) improving the draft core domain set; (ii) developing and disseminating white-board videos to promote its understanding; (iii) conducting an electronic survey to gather feedback on the draft core domain set; (iv) finalizing the core domain set and developing summaries, a plenary session video and discussion boards to promote its understanding; and (v) conducting virtual workshops with voting to endorse the core domain set. RESULTS: A total of 167 participants from 28 countries answered the survey (62% were patients/caregivers). Most participants rated domains as relevant (81%-95%) and clear (82%-93%). A total of 149 participants (n = 48 patients/caregivers, 101 clinicians/researchers) participated in virtual workshops and voted on the proposed core domain set which received endorsement by 95%. Endorsed domains are: 1- Knowledge of options, their potential benefits and harms; 2- Chosen option aligned with each patient's values and preferences; 3- Confidence in the chosen option; 4- Satisfaction with the decision-making process; 5- Adherence to the chosen option and 6- Potential negative consequences of the SDM intervention. CONCLUSION: We achieved consensus among an international group of stakeholders on the OMERACT core domain set for rheumatology trials of SDM interventions. Future research will develop the Core Outcome Measurement Set. CLINICAL SIGNIFICANCE: Prior to this study, there had been no consensus on the OMERACT core domain set for SDM interventions. The current study shows that the OMERACT core domain set achieved a high level of endorsement by key stakeholders, including patients/caregivers, clinicians and researchers.

Endorsement of the domains of knee and hip osteoarthritis (OA) flare: A report from the OMERACT 2020 inaugural virtual consensus vote from the flares in OA working group.

OBJECTIVE: Towards developing an instrument to measure knee and hip osteoarthritis (KHOA) flare, the Outcome Measures in Rheumatology (OMERACT) Flares in OA Working Group first sought to identify and define relevant domains of flare in KHOA. METHODS: Guided by OMERACT Filter 2.1, candidate domains were identified from data generated in interviews, in English or French, with persons with KHOA and health professionals (HPs) who treat OA. The first and second rounds of an online Delphi process with patients and HPs, including researchers, selected relevant domains. The third round provided agreement on the selected domains and their definitions. At the virtual OMERACT 2020 workshop, the proposed domains and their definitions were discussed in facilitated breakout groups with patients and HPs. Participants then voted, with consensus set at ≥70%. RESULTS: Qualitative interviews characterizing OA flare were completed with 29 persons with KHOA and 16 HPs. Content was analyzed and grouped into nine clusters. These candidate domains were included in two Delphi rounds, completed by 91 patients and 165 HPs then 50 patients and 116 HPs, per round, respectively. This resulted in selecting five relevant domains. A final Delphi round, completed by 38 patients and 89 HPs, provided agreement on these domains and their definitions. The OMERACT virtual vote included 27 patients and 106 HPs. The domains and their definitions were endorsed with ≥98% agreement. Domains include: Pain, Swelling, Stiffness, Psychological aspects, and Impact of symptoms, all defined "during flare". CONCLUSION: Using OMERACT methodology, we have developed five domains of KHOA flare that were highly endorsed by patients and HPs.

CD4+CD25-Foxp3+ T cells as a marker of disease activity and organ damage in systemic lupus erythematosus patients.

INTRODUCTION: T regulatory cells (Treg) play an important role in the maintenance of immune cell homeostasis, as it has been reported that CD4+CD25+ T cells suppress the auto-reactive responses in autoimmune diseases such as systemic lupus erythematosus (SLE). The clinical significance of the recently identified population of CD4+CD25-Foxp3+ T cells and whether they are associated with particular organ involvement is still not clear. So, the aim of our study was to evaluate the presence of CD4+CD25-Foxp3+ cells in SLE patients in comparison to healthy controls and to determine whether their frequency is associated with disease activity and particular clinical manifestations in these SLE patients. MATERIAL AND METHODS: The frequency of CD4+CD25-Foxp3+ T cells was analyzed in 56 female SLE patients and 30 healthy female control subjects, using flow cytometry (FACS). CD4+CD25-Foxp3+ T cells were correlated with clinical and laboratory data and the SLE Disease Activity Index (SLEDAI). RESULTS: The level of CD4+CD25-Foxp3+ T cells was significantly increased in SLE patients (15.57 ±4.32%) as compared with the control group (2.46 ±0.65%). A significant correlation was observed for the percentage of CD4+CD25-Foxp3+ T cells with clinical disease activity scores and disease duration (r = 0.6, p < 0.001; r = 0.3, p = 0.02 respectively). It was also positively correlated with renal impairment and hematological involvement. CONCLUSIONS: Systemic lupus erythematosus patients exhibited an altered level of their CD4+Foxp3+ T cells with increased levels of CD4+CD25-Foxp3+ cells.

CD5+ B lymphocytes in systemic lupus erythematosus patients: relation to disease activity.

B cells are essential players in the pathogenic mechanisms of systemic lupus erythematosus (SLE). Although CD5+ B cells have been considered to play a paradoxical role in preventing, rather than inducing autoimmunity, there is no consensus agreement about the proportions of CD5+ B cells population in SLE patients. So, the aim of the present study was to assess blood concentration of CD5+ B cells in patients with SLE and to evaluate their relationship with disease activity and organ damage. We recruited 100 SLE patients and 100 healthy control subjects. Based on SLE disease activity index (SLEDAI), patients were divided into two groups: active SLE (n = 50) and inactive SLE (n = 50). SLE was active when SLEDAI was ≥ 4. The expression of CD5+ B cells was evaluated using flow cytometry to measure the proportions and absolute numbers of the cells. The proportions of CD5+ B cells of total lymphocytes were significantly lower in SLE patients versus controls (4.1 ± 3.9 vs 10.8 ± 5.2%, P = <0.001). CD5+ B cells were significantly decreased in active SLE patients (3.1 ± 2.7%) in comparison to inactive patients (5.2 ± 3.7%) (P = 0.013). CD5+ B cells correlated positively with C3 (r = 0.328, P = 0.020) and C4 (r = 0.355, P = 0.011). CD5+ B cells were significantly decreased in SLE patients compared to healthy controls and they were significantly decreased in active SLE patients in comparison to inactive ones.

Angiopoietin-2 as A Biomarker For Echocardiographic Abnormalities and Carotid Atherosclerosis In Rheumatoid Arthritis Patients.

Atherosclerosis and cardiovascular diseases (CVD) are increasingly recognised complications of rheumatoid arthritis (RA). Angiopoietin 2 (Ang-2) levels have been associated with clinically overt CVD in general population; we assessed serum Ang-2 levels and its correlation with Echocardiographic abnormalities and carotid intima-media thickness in RA patients. 44 RA patients without clinically overt CVD and 44 healthy controls were assessed by questionnaire and clinical examination. Disease activity score (DAS-28) was calculated. Laboratory investigations included measurement of serum Ang-2, Rheumatoid factor (RF), anti-cyclic citrullinated peptide (Anti-CCP), and C reactive protein (CRP). Doppler Echocardiography and Carotid ultrasonography were done to all patients and controls. Mean age of RA patients was 44.4±9.6 and about (86.4%) 38 were females. Mean levels of Ang-2 was higher in RA patients (17.591±13.9 ng/ml) as compared to controls (7.909 ±4.10 ng/ml) P<0.001 and was significantly elevated in RA patients with left ventricular (LV) diastolic dysfunction (23.53±7.75 ng/ml) than those without dysfunction (14.81±15.33ng/ml), P<0.05 and was significantly elevated in RA patients with carotid intima-media thickness (cITM) >0.6mm (21.12±14.79 ng/ml), P<0.005. Serum Ang-2 correlated positively with disease duration, DAS-28, LV posterior wall thickness, E wave velocity and cIMT. In conclusion, serum Ang-2 level is associated with LV diastolic dysfunction and increased carotid intima-media thickness in RA patients and may be useful biomarker for subclinical CVD and atherosclerosis in RA patients.

Assessment of left atrial mechanical functions and atrial electromechanical delay in Juvenile idiopathic arthritis by tissue Doppler echocardiography.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a systemic chronic inflammatory disease. Studies using tissue Doppler imaging (TDI) for the evaluation of cardiac functions of children with JIA are limited. Thus, this study was conducted to evaluate Left ventricular function, left atrial mechanical functions and atrial electromechanical delay in JIA. METHODS: This study was carried out as a across sectional study. A total of 34 patients with active JIA and 34 controls were included. Atrial electromechanical delay and left atrial (LA) mechanical functions in addition to systolic and diastolic left ventricular (LV) functions were measured by using conventional echocardiography and TDI. Assessment of disease activity was done using Juvenile arthritis disease activity score (JADAS-27). RESULTS: JIA patients had abnormal atrial electromechanical coupling as established from prolonged lateral mitral annulus (PA lateral), septal mitral annulus (PA septum), inter-atrial and intra-atrial electromechanical delays compared with healthy controls. Left ventricular filling abnormalities were found characterized by a reduced E/A ratio (1.07 ± 0.56 vs. 1.48 ± 0.16, p = 0.01). E/Em was significantly higher in patients with JIA (7.58 ± 1.79 vs. 4.74 ± 1.45, p = 0.003) denoting impaired diastolic function. Left atrial mechanical functions assessment showed significantly decreased LA passive emptying fraction, increased LA active emptying fraction and LA total emptying volume in JIA patients (p = 0.01, p = 0.01, p = 0.03 respectively). CONCLUSION: Atrial electromechanical coupling intervals, and LA mechanical functions were impaired which can be considered as an early form of subclinical cardiac involvement in JIA patients. Significant diastolic functional abnormalities exist in JIA.