Non-mosaic X monosomy (77,X) in a female dog with signs of virilization.

A 14-month-old female Miniature Poodle dog with an enlarged clitoris and asymmetry in the placement of the teats was subjected to clinical, histopathological, and genetic studies. Macroscopically, the uterus and fallopian tubes appeared normal, while both ovaries were diffusely altered. At histology, the ovarian parenchyma was almost completely effaced by a diffuse hyperplasia of theca cells with atretic primary follicles. Chromosome analysis showed pure (non-mosaic) X monosomy (77,X). This finding was confirmed by the highly sensitive droplet digital PCR (ddPCR) approach. Despite the observed virilization, molecular analysis did not show the presence of Y-linked genes (SRY, ZFY, and TSPY1) in the blood cells or ovary tissue. To the best of our knowledge, this is the first case of X monosomy in a dog associated with virilization.

Oral fibroepithelial polyps ("chewing granulomas") in 21 dogs: Histomorphology, immunohistochemical characterization, and clinical outcome.

Oral fibroepithelial polyps (FEPs) are common, benign, nonneoplastic lesions in humans that often develop slowly in sites of local irritation or trauma. This study analyzed 23 oral fibroepithelial polypoid lesions retrieved from 21 dogs (2014-2021). All lesions were pedunculated with usually an irregular/cauliflower-like or rarely smooth surface. FEPs most commonly arose under or lateral to the tongue; other sites included the labial and gingival mucosa, soft palate, and hard palate. All the lesions were characterized by a thick fibrovascular stalk consisting of bundles of fibrocytes and fibroblasts embedded in a collagenous matrix rich in blood vessels. The surface squamous epithelium, when evaluable, was hyperplastic (22/22; 100%) with frequent parakeratotic hyperkeratosis (12/22; 54.5%). Ulceration of variable extent was observed in 13/23 cases (56.5%). Inflammation was associated with 18/23 cases (78.3%), and was mostly lymphoplasmacytic. The connective tissue was consistently immunoreactive for vimentin and generally negative for smooth muscle actin and desmin. All FEPs in cases with available clinical outcome data did not recur after surgical excision. The presence of chronic inflammation and ulceration suggests a causative role of chronic irritation in the pathogenesis of canine oral FEPs. FEPs should be included among the differential diagnoses of proliferative lesions of the oral cavity in dogs.

Acquired myasthenia gravis with concurrent polymyositis and myocarditis secondary to a thymoma in a dog.

Background: Canine thymomas are associated with multiple paraneoplastic syndromes, among which myasthenia gravis (MG) is the most common. Acquired MG is an autoimmune disease characterized by the presence of antibodies against acetylcholine receptors (ACHRs). ACHRs antibodies are the most commonly formed, but the production of antistriational antibodies binding to skeletal and cardiac muscle proteins has also been recorded both in humans and dogs. An association between the occurrence of antistriational antibodies and a severe form of myocarditis, giant cell myocarditis, has been described in humans. Case Description: A 4-year-old mixed-breed dog was referred because of 1 month history of exercise-induced weakness, hypersalivation, and regurgitation. The neurologic examination was indicative of a neuromuscular junction disease, and MG was suspected. A computed tomographic scan examination showed the presence of a megaoesophagus and a thymic mass. Serum antibodies against ACHRs confirmed the diagnosis of MG. Treatment with pyridostigmine was started, and the thymic mass was surgically excised, and a diagnosis of thymoma was confirmed by histology. 24 hours after surgery, the dog developed a third-degree atrioventricular block. Severe arrhythmia and increased troponin serum levels suggested myocarditis which rapidly led to cardiopulmonary arrest. Histopathologic examination of the heart, esophagus and diaphragm revealed a lymphocytic and macrophagic infiltration, consistent with myocarditis and polymyositis. Scattered rare giant multinucleated cells were also detected in the myocardium. Conclusion: To the author's knowledge, this is the first report of thymoma-associated MG with concurrent polymyositis and giant cell-like myocarditis in a dog.

Use of Ultrasonography to Discriminate Psoriatic Arthritis from Fibromyalgia: A Post-Hoc Analysis of the ULISSE Study.

In psoriatic arthritis (PsA) patients with concomitant chronic widespread pain, the differential diagnosis with fibromyalgia syndrome (FMS) can be challenging. We evaluated whether ultrasound (US) examination of entheseal sites can distinguish pain from (PsA) enthesitis versus FMS. PsA and FMS patients underwent clinical evaluation and gray-scale (GS; B-mode) and power Doppler (PD) US examination of the entheses. At least one enthesis with GS- and PD-mode changes was found in 90% and 59.3% of PsA patients (n = 140) and 62.7% and 35.3% of FMS patients (n = 51), respectively. GS and PD identified changes in 49.5% and 19.2% of the 840 PsA entheses and 22.5% and 7.9% of the 306 FMS entheses, respectively. Receiver operating characteristic curve analysis showed an area under the curve of 0.77 and 0.66 for B- and PD-mode, respectively, 3.5 being the best cut-off GS-score to discriminate the two conditions. Multivariate regression showed that Achilles and proximal patellar tendon enthesitis (B-mode) were strongly associated with PsA (odds ratio, ~2). Principal component analysis (B-mode) confirmed that PsA patients have a higher number of involved entheses and patterns of entheseal involvement than FMS patients. US evaluation of the entheses may help differentiate chronic widespread pain from PsA versus FMS.

Canine Dilated Cardiomyopathy: Diffuse Remodeling, Focal Lesions, and the Involvement of Macrophages and New Vessel Formation.

Dilated cardiomyopathy (DCM) is among the most common cardiac diseases in dogs. Its pathogenesis is not fully understood, but myocardial remodeling and inflammation are suspected to be involved. The present study aimed to characterize the pathological processes in canine DCM, investigating morphological changes in association with the expression of relevant cytokines and remodeling markers. The myocardium of 17 dogs with DCM and 6 dogs without cardiac diseases was histologically evaluated, and selected cases were further examined by immunohistochemistry, morphometry, and reverse transcription quantitative PCR. In DCM, the myocardium exhibited subtle but statistically significant diffuse quantitative changes. These comprised increased interstitial collagen deposition and macrophage numbers, as well as an overall reduced proportion of contractile tissue. This was accompanied by a significant increase in myocardial transcription of intracellular adhesion molecule (ICAM) 1, inflammatory cytokines, and remodeling enzymes. Laser microdissection showed that cardiomyocytes transcribed most relevant markers including ICAM-1, tumor necrosis factor α, transforming growth factor ß (TGF-ß), matrix metalloproteinase 2 (MMP-2), tissue inhibitor of MMP (TIMP) 1 and TIMP-2. In addition, there were multifocal cell-rich lesions characterized by fibrosis, neovascularization, macrophage infiltration, and cardiomyocyte degeneration. In these, macrophages were often found to express ICAM-1, TGF-ß, and vascular endothelial growth factor; the former two were also expressed by cardiomyocytes. These results characterize the diffuse myocardial remodeling processes that occur in DCM. The observed multifocal cell-rich lesions might result from reduced tissue perfusion. Macrophages and cardiomyocytes seem to actively contribute to the remodeling processes, which ultimately lead to cardiac dilation and dysfunction. The precise role of the involved cells and the factors initiating the remodeling process still needs to be identified.

Ultrasonographic and Clinical Assessment of Peripheral Enthesitis in Patients with Psoriatic Arthritis, Psoriasis, and Fibromyalgia Syndrome: The ULISSE Study.

OBJECTIVE: The purpose of the ULISSE study was to evaluate the prevalence of clinical and ultrasonographic (US) entheseal involvement in patients with psoriatic arthritis (PsA), psoriasis, and fibromyalgia syndrome (FMS). METHODS: In this cross-sectional multicenter study, patients with PsA and psoriasis (not taking systemic therapy) and FMS underwent a clinical evaluation of the entheses, and a B-mode and power Doppler examination of 6 pairs of entheses. RESULTS: The study analyzed 140 patients with PsA, 51 with psoriasis, and 51 with FMS. Clinical and US examinations were performed in 1960 and 1680 entheses in the PsA group, and 714 and 612 entheses both in the psoriasis group and in the FMS group. In both per-patient and per-enthesis evaluation, the frequency of entheseal tenderness was higher in patients with FMS (92% of the patients and 46% of the entheses, compared with 66%/23% in the PsA group and 59%/18% in the psoriasis group). With US examination, signs of entheseal involvement were more frequent in both the per-patient and per-enthesis evaluation in PsA and psoriasis (about 90% of patients in both the PsA and psoriasis groups and 75% of patients in the FMS group had at least 1 site affected, and 54%, 41%, and 27% of the pairs of entheses in, respectively, PsA, psoriasis, and FMS patients showed at least 1 enthesis involved). CONCLUSION: The ULISSE study indicated that enthesitis is a common feature in patients with PsA, those with psoriasis, and in those with FMS if only clinical examination is used. US entheseal assessment showed findings more consistent with the 3 disorders.

Effectiveness of a telemonitoring intensive strategy in early rheumatoid arthritis: comparison with the conventional management approach.

BACKGROUND: The advent of Internet and World Wide Web has created new perspectives toward interaction between patients and healthcare professionals. Telemonitoring patients with rheumatoid arthritis (RA) is an emerging concept to guide the collaborative management treatment and improve outcomes in patients. The objective of this study was to investigate whether an intensive treatment strategy, according to a telemonitoring protocol, is more effective than conventional management strategy in reaching remission and comprehensive disease control (CDC) after 1 year in early rheumatoid arthritis (ERA) patients. METHODS: Forty-four ERA patients were randomly allocated into two groups: the telemonitoring intensive strategy (TIS) group (group 1) or the conventional strategy (CS) group (group 2). Three patients refused to participate. In group 1 (n = 21), a remote monitoring system of disease activity, in combination with protocolised treatment adjustments aiming for remission was applied. In group 2 (n = 20), patients were treated according to daily clinical practice, with regular evaluation of disease activity, but without protocolised treatment adjustments. A telemedical care called "REmote TElemonitoring for MAnaging Rheumatologic Condition and HEaltcare programmes" (RETE-MARCHE), was developed to perform the remote monitoring. RESULTS: A higher percentage of patients in the TIS group achieved CDAI remission vs patients in the CS group (38.1 % vs 25 % at year 1, p <0.01). Time to achieve remission was significantly shorter in the group 1 than in the group 2, with a median of 20 weeks vs a median over 36-weeks (p <0.001). Concordantly, the patients in group 1 showed a greater improvement (p <0.001), compared with group 2 in terms of functional impairment (71.4 % vs 35 %) and radiological damage progression (23.8 % vs 10 %), resulting in a greater rate of CDC (19.4 % vs 5 %). CONCLUSIONS: According to our results, an intensive treatment strategy by telemonitoring leads to more effective disease remission and more rapid CDC than treatment according to conventional management strategy in ERA. TRIAL REGISTRATION NUMBER: ISRCTN13142685 Date of registration: March, 17(th) 2016.

Web/Internet-based telemonitoring of a randomized controlled trial evaluating the time-integrated effects of a 24-week multicomponent intervention on key health outcomes in patients with fibromyalgia.

OBJECTIVES: The aims of the study were to assess the efficacy of a multicomponent intervention and evaluate the feasibility and user acceptance of an internet-based home telemedical surveillance system for the evaluation of pain and other key health outcomes in patients with fibromyalgia (FM). METHODS: The study involved 76 FM patients who were randomised to usual care or the multicomponent exercise programme, which consisted of 24 twice-weekly sessions of combined aerobic, muscle strength training exercises and education. All the patients completed the revised version of the Fibromyalgia Impact Questionnaire (FIQR) and the self-administered Fibromyalgia Activity Score (FAS). A predefined website allowed authorised users to enter data via a personal computer (PC) and Internet browser. The differences between the groups were assessed using the Mann-Whitney U-test and Fisher's exact test, and the correlations were analysed using Spearman's rank correlation test. RESULTS: The multicomponent intervention led to a clinically relevant difference in improvement in comparison with the standard approach. It markedly improved the FIQR symptom subscale score, significantly increased the time-integrated area under the curve (AUC) of the FAS scores, and led to a greater benefit in terms of fatigue and the quality of sleep. The mean change in the AUC of the total FIQR score closely correlated with the changes in the AUC of the total FAS score. CONCLUSIONS: The multicomponent approach to FM was effective in treating the key symptoms and maintaining the improvements in the short term, and telemonitoring proved to be an easyto-use solution for patient-centred data acquisition.

Construct validity and responsiveness of the simplified version of Ankylosing Spondylitis Disease Activity Score (SASDAS) for the evaluation of disease activity in axial spondyloarthritis.

BACKGROUND: Over the last decade, significant progresses have been achieved in the development and validation of new tools for the evaluation of disease activity in axial spondyloarthritis (SpA). Despite they play a key role in the assessment of these patients, the calculation scores are relatively complex and difficult to be quickly assessed in the busy daily clinical practice. OBJECTIVES: To test the construct validity of the Simplified Ankylosing Spondylitis Disease Activity Score (SADSAS) to define disease activity and compare its internal and external responsiveness with the Ankylosing Spondylitis Disease Activity Score (ASDAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in patients with axial SpA. METHODS: The patient cohort comprised 397 consecutive axial SpA patients who had never been treated with tumor necrosis factor (TNF) blockers. Clinical and laboratory outcome assessments were performed at baseline, and at week 24. The following parameters were evaluated: BASDAI, ASDAS-CRP, ASDAS-ESR, and SASDAS. Construct convergent validity was evaluated by correlating SASDAS with ASDAS CRP/ESR, BASDAI, Bath Ankylosing Spondylitis Functional Index (BASFI) and EuroQol five-dimensional (EQ-5D) questionnaire. One hundred and fifty-six patients were observed longitudinally for 6 months. Responsiveness was assessed after six months of treatment with sulfasalazine (SSZ) or biologics. Internal responsiveness was evaluated by using the effect size (ES) and standardized response mean (SRM). External responsiveness was investigated by receiver operating characteristic (ROC) analysis. Change scores were compared by calculating paired t-test statistic for the difference. RESULTS: In testing for convergent validity a strong correlations (p < 0.0001) were observed between both SASDAS and ASDAS-ESR (r = 0.835), and ASDAS-CRP (r = 0.805). Strong correlations (p < 0.0001) were also found between SASDAS and BASDAI score (r = -0.886), SASDAS and BASFI scores (rho = 0.588) and SASDAS and EQ-5D scores (rho = -0.579). The cross-classification showed a significant overall agreement (defined as the percentage of observed exact agreements) for SASDAS vs ASDAS-ESR (weighted k = 0.704) and for SASDAS vs ASDAS-CRP (k = 0.661). The most efficient composite measure in detecting change was the ASDAS-CRP (ES 1.95 and SRM 0.97). The responsiveness of SASDAS was slightly higher to ASDAS-ESR with an ES of 1.62 and 1.33, and an SRM of 0.88 and 0.71, respectively. The BASDAI appear to be the less responsive (ES = 0.93 and SRM = 0.52). The area under ROC curve of the SASDAS gives similar results to those provided by ASDAS CRP/ESR. The score changes of all combinations were highly correlated (p < 0.0001). CONCLUSIONS: The new SASDAS is a highly effective measure in assessing disease activity and it showed comparable internal and external responsiveness with respect to the ASDAS ESR/CRP response criteria in patients with axial SpA. SASDAS is easy to calculate and, therefore, appear suitable for clinical decision making, epidemiologic research, and clinical trials.

Efficacy and safety of rituximab with and without methotrexate in the treatment of rheumatoid arthritis patients: results from the GISEA register.

INTRODUCTION: Rituximab (RTX) is a monoclonal anti-CD20 antibody approved for the treatment of rheumatoid arthritis (RA) in association with methotrexate (MTX). OBJECTIVES: To evaluate the efficacy and safety of RTX-MTX combination therapy compared with RTX alone in the treatment of RA. METHODS: We analyzed data from a prospective cohort study, the Italian biologic register GISEA, to investigate the efficacy and safety of rituximab. Moreover, the adverse events (AE) and the causes of discontinuation therapy were analyzed. RESULTS: We identified 338 RA patients, 162 treated with RTX and 176 with RTX-MTX. After 52 and 104 weeks of therapy the disease activity score in 28 joints and the Health Assessment Questionnaire Score were available in 168 patients (78 with RTX-MTX and 60 with RTX alone), showing significant reduction without differences among the two groups. AE were reported in 142 patients (42%), for a total of 368 recorded side effects. The majority (90.5%) of AE were mild to moderate in severity. Comparable percentages of severe AE were reported in the 2 groups (9.9% for RTX alone and 9.3% for RTX+MTX). A poor disease control was observed in 14.2% and 13.5% of patients treated with RTX+MTX and RTX, respectively; while 12 patients (4.5% in RTX+MTX, and 2.5% in RTX group) suspended therapy for AE. CONCLUSIONS: RTX showed a good efficacy and safety profile in the real-life management of RA patients regardless of the association with MTX.

Disease activity in psoriatic arthritis: comparison of the discriminative capacity and construct validity of six composite indices in a real world.

OBJECTIVE: To compare, "in a real world," the performance of the most common composite activity indices in a cohort of PsA patients. METHODS: A total of 171 PsA patients were involved. The following variables were evaluated: peripheral joint assessment, patient reported of pain, physician and patient assessments of disease activity, patient general health status, dactylitis digit count, Leeds Enthesitis Index, Health Assessment Questionnaire (HAQ), physical and mental component summary score of the Medical Outcome Survey (SF-36), Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). To measure the disease activity, the Disease Activity Score (DAS28-ESR and DAS28-CRP), Simple Disease Activity Index (SDAI), Composite Psoriatic Disease Activity Index (CPDAI), disease activity in psoriatic arthritis (DAPSA), and Psoriatic Arthritis Disease Activity Score (PASDAS) have been calculated. The criteria for minimal disease activity (MDA) and remission were applied as external criterion. RESULTS: The ROC were similar in all the composite measures. Only the CPDAI showed less discriminative ability. There was a high degree of correlation between all the indices (P < 0.0001). The highest correlations were between DAPSA and SDAI (rho = 0.996) and between DAPSA and DAS28-CRP (rho = 0.957). CPDAI, DAPSA, and PASDAS had the most stringent definitions of remission and MDA category. DAS28-ESR and DAS28-CRP had the highest proportions in remission and MDA. CONCLUSIONS: Although a good concurrent validity and discriminant capacity of six disease activity indices were observed, the proportions of patients classified in the disease activity levels differed. In particular, the rate of patients in remission was clearly different among the respective indices.

Validity of a computer-assisted manual segmentation software to quantify wrist erosion volume using computed tomography scans in rheumatoid arthritis.

BACKGROUND: To investigate the performance of conventional radiography (CR) for the detection of bone erosions of wrist in rheumatoid arthritis (RA) using multidetector computed tomography (CT) as the reference method and to evaluate the validity of a computer-assisted manual segmentation (outlining) technique to quantify erosion volume on CT scans. METHODS: Twenty five RA patients and six controls underwent CT and radiographic evaluation of the dominant wrist on the same day. CT was performed by using a 64 GE light Speed VCT power. Wrists images were evaluated separately and scored for the presence of erosions according to the Outcome Measures in Rheumatology Rheumatoid Arthritis MRI Scoring System (RAMRIS) and the Sharp/van der Heijde scoring method. Measurements of bone erosion volumes were obtained using OsiriX medical imaging software. The mean value of the volumes of the CT bone erosions detected at two readings was used to calculate inter-rater agreement. RESULTS: The overall sensitivity, specificity and accuracy of radiography for detecting erosions were 25.5%, 98.3% and 70.1%, respectively. Using computer-assisted manual segmentation (outlining) technique, erosion volume on CT measurements per subject was ranged from 0.001 cm³ to 2.01 cm³. Spearman's RAMRIS score of each wrist bones in all subjects (n = 25) were correlated with the total erosion volume on CT (p < 0.0001), with the ratio between erosion volume and the corresponding bone volume on a percentage basis (p < 0.0001). The total Sharp/van der Heijde erosion score of the all wrist bones was correlate with the RAMRIS score (p = 0.008). The intraclass correlation coefficients (ICC) for manual segmentation showed high agreement (ICC = 0.901). CONCLUSIONS: Considering CT as the reference method, CR showed very low sensitivity. A close correlation with CT erosion volumes supports the OMERACT RAMRIS erosion score as a semiquantitative measure of joint damage in RA. Although the computer-assisted manual segmentation can be beneficial for diagnostic decision in cross-sectional CT examinations of the wrist in RA, this technique will require further evaluation in terms of responsiveness.

Usability of an innovative and interactive electronic system for collection of patient-reported data in axial spondyloarthritis: comparison with the traditional paper-administered format.

OBJECTIVE: To evaluate the validity, in terms of the patients' acceptance, preference, feasibility and reliability of an innovative, interactive computerized system for collection of patient-reported outcome (PRO) data on axial SpA against the paper-and-pencil version. METHODS: Fifty-five patients with axial SpA completed both the touch screen and the paper-and-pencil set of questionnaires. A computerized touch-screen system, SPEAMonitor, was developed to capture PRO data. Variables recorded included demographic data, patient's assessment of general health status, BASDAI, BASFI, BASMI and acute-phase reactant levels. In order to assess the patient's acceptance of, preference for and feasibility of computer-based questionnaires, the participants filled in an additional questionnaire. The time taken to complete both formats was measured. In a further test-retest study, 25 patients were re-evaluated. RESULTS: The agreement between the paper-administered and computer touch-screen format of the BASFI, BASDAI questionnaires and the Ankylosing Spondylitis Disease Activity Scores was excellent. Intraclass correlation coefficients (ICCs) between data ranged from 0.90 to 0.96. Additionally the test-retest study showed a very good agreement between the scores for the two administrations (ICC ≥ 0.90). Age, computer experience and education level had no significant impact on the results. The computerized questionnaires were reported to be easier to use. The mean time spent completing the questionnaires on a touch screen was 5.1 min and on paper 7.9 min. CONCLUSION: Our newly developed computer-assisted touch-screen questionnaires for PRO in axial SpA were well accepted by patients, with good data quality, reliability and score agreement.

Classical test theory and Rasch analysis validation of the Recent-Onset Arthritis Disability questionnaire in rheumatoid arthritis patients.

Disability has been identified as a core outcome measure in rheumatoid arthritis (RA). The aim of this study was to perform a comprehensive psychometric analysis of the Recent-Onset Arthritis Disability (ROAD) questionnaire in patients with RA. The questionnaire was completed by 583 patients with RA: 196 subjects participating in the NEW INDICES study and 387 subjects who were taking part in a long-term observational study. At confirmatory factor analysis for categorical data, data fit for a three-factor model was adequate to good (non-normed fit index = 0.98, comparative fit index = 0.99, root mean square error of approximation = 0.079, standardized root mean square residual = 0.047), with standardized item-to-factor loadings ranging from 0.60 to 0.90 and a cumulative explained variance of 83 %. The bifactor model of ROAD presented a clean independent cluster structure. The loadings in the unidimensional model were very similar to those on the general factor in the bifactor model. Rasch analysis showed a correct functioning of rating categories, a good fit of the data to the model for all three subscales, and satisfactory separation indexes and respective reliability (for both persons and items). This study, using both classical test theory and Rasch analysis methods, provides psychometric evidence of the reliability and internal and structural validity of ROAD in RA patients. Our results support the use of separate subscores for upper limb function, lower limb function, and activities of daily living/work, and the appropriateness of reporting an overall score (i.e., the mean of the three subscales).

The comparative responsiveness of the patient self-report questionnaires and composite disease indices for assessing rheumatoid arthritis activity in routine care.

OBJECTIVES: This paper aims to evaluate the internal and external responsiveness of the patient self-report questionnaires, comparatively to the traditional composite indices to assess the activity of rheumatoid arthritis (RA) in everyday practice. METHODS: One hundred and ninety-one RA out-patients completed the clinical arthritis activity (PRO-CLARA) index, the rheumatoid arthritis disease activity index (RADAI), the routine assessment of patient index data (RAPID3), and the patient activity score (PAS). Simultaneously, the disease activity score-28 joints based on CRP (DAS28-CRP) and ESR (DAS28-ESR), the simplified disease activity index (SDAI), the clinical disease activity index (CDAI), and the mean overall index for RA (MOI-RA) were computed for each patient. Sensitivity to change was assessed after 6 months of treatment with disease-modifying anti-rheumatic drugs or biologics. Internal responsiveness was evaluated with the effect size (ES) and standardised response mean (SRM). External responsiveness was investigated by receiver operating characteristic (ROC), in categories of respondents, stratified according to the response on an item on change in overall health. In addition, change scores were compared by calculating correlation coefficients. RESULTS: No significant differences in internal and external responsiveness were found between self-report questionnaires and composite indices. The internal responsiveness of the self-report questionnaires and composite measures was wide, with SRM and ES ranging from 1.03 (RADAI) to 1.80 (DAS28-ESR) and higher than that of the each individual measures. The responsiveness of the PRO-CLARA was equal to the DAS28-ESR, DAS28-CRP, SDAI or MOI-RA, but better than the CDAI. The RADAI and PAS were less responsive than the PRO-CLARA and RAPID3. The area under ROC curve of the PRO-CLARA gives identical results to those provided by other comparator composite indices. The score changes of all combinations were highly correlated (p<0.0001). CONCLUSIONS: The self-report questionnaires showed comparable internal and external responsiveness to the composite activity scores and allow for the detection of rheumatoid disease activity. They appear suitable for clinical decision making, epidemiologic research and clinical trials. Further longitudinal studies are needed to validate these encouraging results.

Long-term anti-TNF therapy and the risk of serious infections in a cohort of patients with rheumatoid arthritis: comparison of adalimumab, etanercept and infliximab in the GISEA registry.

OBJECTIVE: To evaluate the risk of serious infections (SIs) in RA patients receiving anti-TNF therapy on the basis of the data included in the GISEA register. METHODS: The study involved 2769 adult patients with long-standing RA (mean age 53.2±13.4 years; mean disease duration 9.0±8.3 years) enrolled in the GISEA register, who had been treated for at least 6 months with TNF inhibitors or had discontinued therapy due to SI: 837 (30%) treated with infliximab (IFN), 802 (29%) with adalimumab (ADA), and 1130 (41%) with etanercept (ETN). RESULTS: 176 patients had experienced at least one of the 226 Sis during the 9 years of treatment with an anti-TNF agent, an overall incidence of 31.8/1000 patient-years (95% CI 25.2-38.3): 23.7/1000 patient-years (95% CI 13.1-34.2) on ADA; 12.8/1000 patient-years (95% CI 6.3-19.4) on ETN and 65.1/1000 patient-years (95% CI 48.4-81.8) on IFN. The risk was higher in the first than in the second year of treatment, but this difference was not statistically significant (p=0.08) (38.9% of the SIs were recorded in the first 12 months of treatment). The risk of SI was significantly different among the three treatment groups (p<0.0001). Multivariate models confirmed that the use of steroids (p<0.046), concomitant DMARD treatment during anti-TNF therapy (p=0.004), advanced age at the start of anti-TNF treatment (p<0.0001), and the use of IFN or ADA rather than ETN (respectively p<0.0001 and p=0.023) were strong and statistically significant predictors of infection. CONCLUSIONS: Anti-TNF therapy is associated with a small but significant risk of SI that is associated with the concomitant use of steroids, advanced age at the start of anti-TNF treatment, and the type of anti-TNF agent.

Relationship between time-integrated disease activity estimated by DAS28-CRP and radiographic progression of anatomical damage in patients with early rheumatoid arthritis.

BACKGROUND: The main aim of the study was to investigate the relationship between persistent disease activity and radiographic progression of joint damage in early rheumatoid arthritis (ERA). METHODS: Forty-eight patients with active ERA was assessed every 3 months for disease activity for 3 years. Radiographic damage was measured by the Sharp/van der Heijde method (SHS). The cumulative inflammatory burden was estimated by the time-integrated values (area under the curve-AUC) of Disease Activity Score 28 joint based on C-reactive protein (DAS28-CRP) in rapid progressors versus non-progressors. Bland and Altman's 95% limits of agreement method were used to estimate the smallest detectable difference (SDD) of radiographic progression. The relationship between clinical and laboratory predictors of radiographic progression and their interactions with time was analysed by logistic regression model. RESULTS: After 3-years of follow-up, radiographic progression was observed in 54.2% (95%CI: 39.8% to 67.5%) of patients and SDD was 9.5 for total SHS. The percentage of patients with erosive disease increased from 33.3% at baseline to 76% at 36 months. The total SHS of the progressors worsened from a median (interquartile range) of 18.5 (15-20) at baseline to 38.5 (34-42) after 3 years (p < 0.0001) whereas non-progressors worsened from a median of 14.5 (13-20) at baseline to 22.5 (20-30) after 3 years (p < 0.001). In the regression model, time-integrated values of DAS28-CRP and anti-CCP positivity have the highest positive predictive value for progression (both at level of p < 0.0001). Radiographic progression was also predicted by a positive IgM-RF (p0.0009), and a high baseline joint damage (p = 0.0044). CONCLUSIONS: These data indicate that the level of disease activity, as measured by time-integrated DAS28-CRP, anti-CCP and IgM-RF positivity and a high baseline joint damage, affects subsequent progression of radiographic damage in ERA.

Psychometric properties of an index of three patient reported outcome (PRO) measures, termed the CLinical ARthritis Activity (PRO-CLARA) in patients with rheumatoid arthritis. The NEW INDICES study.

OBJECTIVES: To evaluate the psychometric properties of an index based on 3 patient reported outcomes measures, termed PRO-CLinical ARthritis Activity (PRO-CLARA), in order to facilitate rapid and easy rheumatoid arthritis (RA) activity assessment in daily routine. METHODS: 196 patients partially or not responding to disease modifying anti-rheumatic drugs (DMARDs), consented to participate in a multicentre cross-sectional study. For the evaluation of the psychometric properties of the PRO-CLARA, this population has been compared to another cohort of 247 outpatients with RA who were participating in a long-term observational study and who satisfying minimal disease activity and remission definitions. All patients completed the PRO-CLARA, combining patient's physical function, self-administered tender joint count and perception of global health status into a single measure of disease activity. Additional comparator composite indices were analysed. Internal consistency was assessed with Cronbach's alpha coefficient. A confirmatory factor analysis was carried out to test factor structure. Concurrent validity was analyzed using Spearman's correlations and cross-tabulations. Discriminant validity to distinguish patients with active and non-active disease was assessed with receiver operating characteristic (ROC) curve analysis. For agreement analysis, kappa statistics were calculated. RESULTS: In testing for internal consistency, we found that Cronbach's alpha for the PRO-CLARA was 0.893, indicating high reliability. PRO-CLARA proved to be significantly correlated to established RA activity assessment tools. The area under ROC curve of the PRO-CLARA gives identical results to those provided by other comparator indices. CONCLUSIONS: The study showed satisfactory psychometric properties of the PRO-CLARA.

Clinical value of single versus composite provocative clinical tests in the assessment of painful shoulder.

OBJECTIVES: The aims of the present study were to investigate the clinical value of the provocative clinical tests and propose a composite index for the assessment of painful shoulder, using ultrasonography (US) as reference method. METHODS: Two hundred three patients with painful shoulder underwent both clinical and US evaluations. The physical examination was carried out performing the Hawkins, Jobe, Patte, Gerber, and Speed tests. Each test was included in a composite index namely, SNAPSHOT (Simple Numeric Assessment of Pain by SHOulder Tests). The US examination was performed by a rheumatologist experienced in US and blinded to clinical findings. Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratio of each clinical test were calculated. The receiver operating characteristic (ROC) curve analysis was used to assess the performance of the composite SNAPSHOT index. RESULTS: Sensitivity was low for the clinical diagnosis of all shoulder abnormalities. The highest sensitivity and smallest negative likelihood ratio were found for the Hawkins (63.88% and 0.50%) and Patte (62.21% and 0.52%) tests. Specificity was good for Speed (76.33%), Gerber (75.42%), and Patte (74.20%) tests. Patte and Speed tests were the most accurate (71.12% and 66.41%, respectively). The calculated area under the ROC curve related to the SNAPSHOT composite index was 0.881 +/- 0.026. With an optimal cut-off point of 3, the sensitivity and specificity were 75.8% and 87.5%, respectively. CONCLUSION: The results of the present study showed that SNAPSHOT is a feasible, informative and quantitative composite index for the assessment of painful shoulder in the clinical setting.

Development and validation of the self-administered Fibromyalgia Assessment Status: a disease-specific composite measure for evaluating treatment effect.

INTRODUCTION: The Fibromyalgia Impact Questionnaire (FIQ) is a composite disease-specific measure validated for fibromyalgia (FM), but it is rarely used in clinical practice. The objective was to develop and analyse the psychometric properties of a new composite disease-specific index (Fibromyalgia Assessment Status, FAS), a simple self-administered index that combines a patient's assessment of fatigue, sleep disturbances and pain evaluated on the basis of the 16 non-articular sites listed on the Self-Assessment Pain Scale (SAPS) in a single measure (range 0 to 10). METHODS: The FAS index was constructed using a traditional development strategy, and its psychometric properties were tested in 226 FM patients (209 women, 17 men); whose disease-related characteristics were assessed by means of an 11-numbered circular numerical rating scale (NRS) for pain, fatigue, sleep disturbances and general health (GH), the tender point score (TPS), the SAPS, the FIQ, and the SF-36. A group of 226 rheumatoid arthritis (RA) patients was used for comparative purposes. Of the 179 FM patients who entered the follow-up study, 152 completed the three-month period and were included in the responsiveness analyses. One hundred and fifty-four patients repeated the FAS questionnaire after an interval of one week, and its test/re-test reliability was calculated. Responsiveness was evaluated on the basis of effect size and the standardised response mean. RESULTS: The FAS index fulfilled the established criteria for validity, reliability and responsiveness. Factor analysis showed that SAPS and fatigue contributed most, and respectively explained 47.4% and 31.2% of the variance; sleep explained 21.3%. Testing for internal consistency showed that Cronbach's alpha was 0.781, thus indicating a high level of reliability. As expected, closer significant correlations were found when FAS was compared with total FIQ (rho = 0.347; P < 0.0001) and the FIQ subscales, particularly job ability, tiredness, fatigue and pain (all P < 0.0001), but the correlation between FAS and the mental component summary scale score (MCS) of the SF-36 (rho = -0.531; P < 0.0001) was particularly interesting. Test/re-test reliability was satisfactory. The FAS showed the greatest effect size. The magnitude of the responsiveness measures was statistically different between FAS (0.889) and the FIQ (0.781) (P = 0.038), and between the SF-36 MCS (0.434) and the SF-36 physical component summary scale score (PCS) (0.321) (P < 0.01). CONCLUSIONS: The self-administered FAS is a reliable, valid and responsive disease-specific composite measure for assessing treatment effect in patients with FM.