Experimental Characterization, Modeling, and Numerical Evaluation of a Novel Friction Damper for the Seismic Upgrade of Existing Buildings.

The paper presents the experimental characterization, the formulation of a numerical model, and the evaluation, by means of non-linear analyses, of a new friction damper conceived for the seismic upgrade of existing building frames. The damper dissipates seismic energy through the friction force triggered between a steel shaft and a lead core prestressed within a rigid steel chamber. The friction force is adjusted by controlling the prestress of the core, allowing the achievement of high forces with small dimensions, and reducing the architectural invasiveness of the device. The damper has no mechanical parts subjected to cyclic strain above their yield limit, thereby avoiding any risk of low-cycle fatigue. The constitutive behavior of the damper was assessed experimentally, demonstrating a rectangular hysteresis loop with an equivalent damping ratio of more than 55%, a stable behavior over repeated cycles, and a low dependency of the axial force on the rate of displacement. A numerical model of the damper was formulated in the OpenSees software by means of a rheological model comprising an in-parallel system of a non-linear spring element and a Maxwell element, and the model was calibrated on the experimental data. To assess the viability of the damper for the seismic rehabilitation of buildings, a numerical investigation was conducted by performing non-linear dynamic analyses on two case-study structures. The results highlight the benefits of the PS-LED in dissipating the largest part of seismic energy, limiting the lateral deformation of the frames, and controlling the increase in structural accelerations and internal forces at the same time.

Efficacy and safety of baricitinib in 446 patients with rheumatoid arthritis: a real-life multicentre study.

OBJECTIVES: Baricitinib, an oral Janus kinase (JAK) 1-2 inhibitor, is currently used along biologic DMARDs (bDMARDs) after the failure of methotrexate (MTX) in rheumatoid arthritis (RA). We investigated the efficacy and safety of baricitinib in real life. METHODS: We prospectively enrolled 446 RA patients treated with baricitinib from 11 Italian centres. Patients were evaluated at baseline and after 3, 6, and 12 months. They were arrayed based on previous treatments as bDMARD-naïve and bDMARD-insufficient responders (IR) after the failure or intolerance to bDMARDs. A sub-analysis differentiated the effects of methotrexate (MTX) and the use of oral glucocorticoids (OGC). RESULTS: Our cohort included 150 (34%) bDMARD-naïve and 296 (66%) bDMARD-IR patients, with 217 (49%) using baricitinib as monotherapy. Considering DAS-28-CRP as the primary outcome, at 3 and 6 months, 114/314 (36%) and 149/289 (51.6%) patients achieved remission, while those in low disease activity (LDA) were 62/314 (20%) and 46/289 (15.9%), respectively; finally at 12 months 81/126 (64%) were in remission and 21/126 (17%) in LDA. At all-timepoints up to 12 months, bDMARDs-naïve patients demonstrated a better clinical response, independently of MTX. A significant reduction in the OGC dose was observed at 3 and 12 months in all groups. The serum positivity for both rheumatoid factors (RF) and anti-citrullinated protein antibodies (ACPA) conferred a lower risk of stopping baricitinib due to inefficacy. Fifty-eight (13%) patients discontinued baricitinib due to adverse events, including thrombotic events and herpes zoster reactivation. CONCLUSIONS: Real-life data confirm the efficacy and safety profiles of baricitinib in patients with RA and provide evidence that drug survival is higher in bDMARDs-naïve and seropositive patients.

Pixel or Paper? Validation of a Mobile Technology for Collecting Patient-Reported Outcomes in Rheumatoid Arthritis.

BACKGROUND: In the management of chronic disease, new models for telemonitoring of patients combined with the choice of electronic patient-reported outcomes (ePRO) are being encouraged, with a clear improvement of both patients' and parents' quality of life. An Italian study demonstrated that ePRO were welcome in patients with rheumatoid arthritis (RA), with excellent matching data. OBJECTIVE: The aim of this study is to evaluate the level of agreement between electronic and paper-and-pencil questionnaire responses. METHODS: This is an observational prospective study. Patients were randomly assigned to first complete the questionnaire by paper and pencil and then by tablet or in the opposite order. The questionnaire consisted of 3 independent self-assessment visual rating scales (Visual Analog Scale, Global Health score, Patient Global Assessment of Disease Activity) commonly used in different adult patients, including those with rheumatic diseases. RESULTS: A total of 185 consecutive RA patients were admitted to hospital and were enrolled and completed the questionnaire both on paper and on electronic versions. For all the evaluated items, the intrarater degree of agreement between 2 approaches was found to be excellent (intraclass correlation coefficient>0.75, P<.001). CONCLUSIONS: An electronic questionnaire is uploaded in a dedicated Web-based tool that could implement a telemonitoring system aimed at improving the follow-up of RA patients. High intrarater reliability between paper and electronic methods of data collection encourage the use of a new digital app with consequent benefit for the overall health care system.

Use of ultrasound in treatment decisions for patients with rheumatoid arthritis: an observational study in Italy.

In rheumatoid arthritis (RA), treatment response is generally assessed using standard clinical disease activity measures. However, ultrasound has become increasingly popular among rheumatologists to monitor disease activity and response. The purpose of this analysis of ECOgraphic evaluation for STaging ARthritis (ECOSTAR) study data was to determine how ultrasound affects clinicians' decisions about changing treatment in RA. ECOSTAR was an observational, cohort study conducted between March 2010 and December 2012 at nine clinical centers in Italy in RA patients being considered for treatment change. After clinical evaluation of each patient, patients underwent diagnostic ultrasound (US) investigations and each patient was given a total echography score using a combination of scores for joint effusion, synovial hypertrophy, and power Doppler. The US results were provided to the clinicians and the influence of US on the clinicians' treatment choices were recorded. Ninety-five patients screened for study inclusion had confirmed RA (mean age 53.9 years; mean disease duration 8.9 years). Therapy changes were made by clinicians according to the hand and wrist joint US scores: score 0 appeared to have no influence on clinicians' decision to modify treatment, scores >0-3 were associated with a numerically higher estimated probability of not changing therapy than changing therapy, and scores >3 had a greater influence on the clinician to modify therapy and an increased probability of the clinician changing therapy versus not changing therapy. Ultrasonography scores appear to influence treatment decisions in patients with RA, with clinicians appearing less likely to alter treatment regimens in patients with low ultrasound scores and more likely to change treatment regimens when higher scores are obtained. Further research is warranted.

Adherence to current recommendations on the use of methotrexate in rheumatoid arthritis in Italy: results from the MARI study.

OBJECTIVES: The aim of this study was to assess how the management of rheumatoid arthritis (RA) with methotrexate (MTX) in Italy is adherent to current national recommendations. METHODS: We performed a cross-sectional and retrospective analysis of data collected from the MARI study, a multicentre survey on Italian patients with RA on treatment with MTX for at least 12 months. Retrospective data included patient's clinical history, previous treatment with MTX, screening tests performed before MTX prescription. Cross-sectional data were collected about current treatment with MTX, concomitant medications, and disease activity. Each proposition of the 2013 Italian recommendations on the use of MTX in RA was reformulated in terms of audit criteria, and adherence to provided indications was evaluated for every patient. RESULTS: Among the 1336 included patients, less than 40% had started treatment with MTX within 3-6 months from the diagnosis and nearly 30% of them were prescribed with an initial dose of MTX between 12.5 and 15 mg/week. Screening for HBV and HCV infection as well as chest x-ray was performed in a proportion of patients around 60% and more than 90% of them underwent lab tests before MTX prescription and regularly throughout the treatment. Folic acid supplementation was given at recommended dosages in a high proportion of patients. CONCLUSIONS: Our survey showed a good adherence of Italian rheumatologists to recommendations regarding safety issues with MTX in RA, but a suboptimal approach in terms of time and dosage of the treatment in the early phases of the disease.

Safety of Abatacept in Rheumatoid Arthritis With Serologic Evidence of Past or Present Hepatitis B Virus Infection.

OBJECTIVE: Rheumatoid arthritis (RA) with concomitant hepatitis B virus (HBV) infection represents a therapeutic challenge due to the risk of HBV reactivation under immunosuppressive treatment. To date there are few data coming from anecdotal case reports that concern HBV reactivation following treatment with abatacept. This observational retrospective study was aimed to assess the safety profile of abatacept in this particular clinical setting. METHODS: Eleven Italian rheumatologic centers provided data from patients with RA and positive HBV serology treated with intravenous abatacept. HBV markers and clinical and laboratory data were checked at followup visits every 3 months. RESULTS: In total, 72 patients were included in the study: 47 inactive carriers, 21 occult carriers, and 4 chronic active carriers for HBV. At baseline all of the patients had normal liver function tests and low or undetectable HBV DNA levels, except for those with chronic active hepatitis. Thirteen patients received prophylaxis with lamivudine, and 4 received treatment with adefovir or tenofovir. At the end of the 24-month followup period, 49 patients were being treated. Data from 316 followup visits showed that abatacept was safe. No patients experienced reactivation of hepatitis B. Treatment withdrawals (23 patients) were due to lack of efficacy, subject decision/lost at followup, or adverse events not related to HBV infection. CONCLUSION: Our study provides reassuring data about the safety profile of abatacept in RA with concomitant HBV infection without universal antiviral prophylaxis. Further prospective studies are needed to confirm these preliminary results.

Feasibility, acceptability and construct validity of EQ-5D in systemic sclerosis.

BACKGROUND: Systemic sclerosis is a chronic disabling disease that is often associated with severe physical and psychological impairment. Nonetheless, health-related quality of life (HRQoL) in patients with systemic sclerosis is often left behind in clinical practice and research. One of the reasons for this lack of evaluation is the current use of tools, such as the short form-36 (SF-36) questionnaire, that are complete but complicated to use in everyday routine. Other self-reported outcome measures such as the health assessment questionnaire (HAQ) are simple, but specifically designed for physical disability. STUDY AIMS AND METHODS: Our aim was to evaluate the feasibility, acceptability and construct validity of EQ-5D, a simple and quick self-assessment tool, and to compare its performance with SF-36 and HAQ. We investigated 119 consecutive patients with systemic sclerosis (94% female; age: median 63 years, interquartile range 53-70 years) at three different rheumatology centres. Acceptability was evaluated from comments made by the patients and feasibility on the basis of the number of patients needing assistance or not answering questions (missing data). Construct validity was based on both convergent and divergent validity between conceptually similar and dissimilar domains, respectively, of the compared instruments. RESULTS: EQ-5D was well accepted by patients. The percentage of patients missing data in at least one EQ-5D domain was 2.5%. Spearman's correlation coefficients between similar dimensions of EQ-5D vs SF-36 and vs HAQ were moderate (≥0.30) to strong (≥0.50); in contrast, correlation coefficients between less comparable dimensions were weak. As expected, the EQ-5D anxiety/depression domain did not correlate with any of the HAQ domains. The EQ-5D visual analogue scale (VAS) concordance with SF-36 general health domain and HAQ total score was strong (≥0.50 for both). Median value for the EQ-5D index (interquartile range) was 0.81 (0.75-0.86). The EQ-5D index had correlation coefficients >0.40 with all SF-36 domains and with all HAQ domains, HAQ total and HAQ VAS. CONCLUSIONS: Our data demonstrate good acceptability, feasibility and construct validity of EQ-5D in patients with systemic sclerosis. We suggest the use of EQ-5D in systemic sclerosis patients as an HRQoL measure in clinical practice, in randomised clinical trials and/or in pharmacoeconomic evaluations.

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.

Interventional ultrasound: a critical overview on ultrasound-guided injections and biopsies.

Over the last decades ultrasound-guided procedures have become increasingly diffused in rheumatology, mainly thanks to the technical advances achieved in the ultrasound (US) field, combined with the greater availability, good portability and reduced cost of US devices, compared to other imaging techniques already used in rheumatology units. The direct visualisation of the tissue under analysis and the real-time imaging performance enabled by US-guidance account for an improved accuracy and directness in needle placement in a number of rheumatology interventions such as tendon and intra-articular injections. Compared with blind procedures, US-guided injections are more accurate and safe and they result in better clinical outcome in terms of joints improvement in function and decreased risk of damages caused by needle misplacement. The accuracy in needle placement of US-guided injections has proven to be important not only in common intra-articular injections, but especially in case of complex anatomical areas like the hip, facet and atlanto-occipital joints, where blinded injections are deemed poorly accurate and thus highly risky. Moreover US guidance can be successfully employed in more complex procedures such as synovial biopsy, portal establishment or arthroscopy, where US can also be combined with other imaging techniques. Overall the employment of US-guided procedures is considered to be safe and well-tolerated, and increases the accuracy and therapeutic effectiveness of the interventions performed. This may pave the way for a more widespread employment of US-guidance in rheumatology units, and new studies could further explore the therapeutic advantages of these procedures.

Clinical and ultrasound evaluation of the response to tocilizumab treatment in patients with rheumatoid arthritis: a case series.

This case series evaluates the clinical and ultrasound response to tocilizumab treatment in patients with rheumatoid arthritis (RA). Six patients with active RA (DAS28 ≥ 3.2) for ≥6 months, refractory to conventional DMARDs or anti-TNF agents, received tocilizumab 8 mg/kg every 4 weeks, as monotherapy or in combination with DMARDs, for 6 months. The following clinical parameters were assessed monthly: number of tender joints (28 and 44 joints), number of swollen joints (28 and 44 joints), DAS28-ESR, DAS28-CRP, VAS score, global health status, health assessment questionnaire, patient global assessment of disease activity, physician global assessment of disease activity, functional assessment of chronic illness therapy (FACIT), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). All patients also underwent a gray-scale ultrasonography (US) assessment with power Doppler evaluation at each visit. All clinical parameters improved during the study, versus baseline. This improvement was statistically significant for most parameters 2 months following tocilizumab initiation and was sustained to the end of the observation period. The number of tender joints (44-joint evaluation), the FACIT score, and ESR and CRP concentrations were significantly improved versus baseline values after the first month of tocilizumab treatment. The course of US evaluations mirrored that of clinical parameters; a faster and more evident response was observed for foot joints, with respect to hand joints. This case series suggested the rapid clinical benefit of tocilizumab. Ultrasound assessment showed that the onset of this effect was faster in the foot joints than in the hand joints.

High rate of disease remission in moderate rheumatoid arthritis on etanercept therapy: data from GISEA, the Italian biologics register.

The aim of this study was to evaluate the clinical outcomes of etanercept in rheumatoid arthritis (RA) patients with moderate or severe disease activity. We analyzed data from the Italian biologics register Gruppo Italiano Studio Early Arthritides (GISEA) to investigate the rate of disease remission and functional improvement, based on the 28-Joint Disease Activity Score (DAS28) and the (Health Assessment Questionnaire (HAQ) score in RA patients with moderate or severe disease activity beginning etanercept therapy. Disease was defined as severe (H-RA) with DAS28 ≥5.1 and moderate (M-RA) with DAS28 ≥3.2 to 5.1 at baseline. Patients were considered in remission if DAS28 was ≤2.6, and HAQ ≤0.5 defined normal function. We enrolled 953 RA patients, 320 with M-RA and 633 H-RA. Age and disease duration were similar in the two cohorts, but H-RA patients had significantly more comorbidities (p < 0.01) and took significantly more disease-modifying antirheumatic drugs (p < 0.001) than M-RA patients. After 1 year, the percentage of patients achieving disease remission and normal function (DAS28 ≤2.6 plus HAQ ≤0.5) was higher in M-RA (21.4 %) than in H-RA patients (14.8 %, p = 0.007), regardless of the disease duration. Additionally, female gender (p = 0.006) and H-RA class (p = 0.002) negatively predicted disease remission at 1 year. However, the drug survival rate did not differ between the two subsets. This study confirms that etanercept was effective in the treatment of active RA, but best response, in terms of disease remission and normal function ability, was greater and easier to attain in M-RA patients. These findings may aid clinicians to choose the best strategy to treat RA.

Use of ultrasound-assisted arthroscopy in rheumatology: an experience in 11 patients with different rheumatic diseases.

The 'real time' capability of ultrasound (US) allows dynamic assessment of joint and tendon movements, which can often aid in the detection of structural abnormalities. The simultaneous use of arthroscopy (AS) and US is therefore a logical progression. Here the results of a series of 11 patients with different rheumatic diseases in whom a combined use of US and AS was adopted are reported.

Improving diagnosis of early inflammatory arthritis : results of a novel triage system.

OBJECTIVES: Early treatment of inflammatory arthritis (IA) leads to reduced disease activity, reduced joint damage, decreased functional impairment and increased chance of remission. However, delay often occurs from referral to rheumatology appointment. This survey evaluated whether a preliminary triage carried out by healthcare workers without formal medical training could be effective in identifying patients with or without early IA. METHODS: Patients were recruited during their first call to our centre, before their first visit. A simple questionnaire, including three questions and aimed at investigating the presence of sign and symptoms of IA was developed. The same survey was administered twice: the first time, during patient's first call to our centre (telephone survey), and the second time, during their first visit with the rheumatologist (Ambulatory visit survey). We compared the outcomes of the survey with the actual diagnosis made by the rheumatologist following standard medical examination. RESULTS: In total 484 patients were included in the study, and 34/484 (7.02%) were confirmed to have early IA. The telephone survey was able to detect the non-early IA patients in 99.5% of cases; the same result was reported for the ambulatory visit survey. The median time required to complete the questionnaire was 1 minute in both surveys. CONCLUSIONS: The adoption of a simple survey, also administered by non-medical personnel, may effectively contribute to the early detection of IA.

Clinical and echocardiographic correlations of exercise-induced pulmonary hypertension in systemic sclerosis: a multicenter study.

BACKGROUND: Patients with systemic sclerosis (SSc) are at risk for developing pulmonary hypertension, which is associated with a poor prognosis. Exercise Doppler echocardiography enables the identification of exercise-induced increase in pulmonary artery systolic pressure (PASP) and may provide a thorough noninvasive hemodynamic evaluation. AIM: The aim of this study was to evaluate the clinical and echocardiographic determinants of exercise-induced increase in PASP in a large population of patients with SSc. METHODS: We selected 164 patients with SSc (age 58 ± 13 years, 91% female) with normal resting PASP (<40 mm Hg) who underwent a comprehensive 2-dimensional and Doppler echocardiography and graded bicycle semisupine exercise Doppler echocardiography. Pulmonary artery systolic pressure, cardiac output, and pulmonary vascular resistance (PVR) were estimated noninvasively. Cutoff values of PASP ≥50 mm Hg and PVR ≥3.0 Wood Units at peak exercise were considered a significant exercise-induced increase in PASP and PVR, respectively. RESULTS: Sixty-nine (42%) patients showed a significant exercise-induced increase in PASP. Among them, peak PVR ≥3 Wood Units was present only in 11% of patients, about 5% of the total population. Univariate analysis showed that age, presence of interstitial lung disease, and both right and left diastolic dysfunction are predictors of peak PASP ≥50 mm Hg, but none of these parameters predict elevated peak PVR. CONCLUSIONS: Exercise-induced increase in PASP occurs in almost one-half of patients with SSc with normal resting PASP. Peak exercise PASP is affected by age, interstitial lung disease, and right and left ventricular diastolic dysfunction and, only in 5% of the patients, is associated with an increase in PVR during exercise, suggesting heterogeneity of the mechanisms underlying exercise-induced pulmonary hypertension in SSc.

Imaging in rheumatology: ultrasafe + ultrasure = ultrasound.

Technological advances in ultrasonography (US) in recent years has allowed for improvements to the imaging quality of gray-scale ultrasound and the development of more advanced forms of this imaging technique such as 3D and Doppler US. These improvements mean that US now has an accepted place in rheumatology not only in diagnosis, but also in the determination of disease progression and pathology and in facilitating guidance of interventional therapies. The increasing use of US-guided intervention by rheumatologists in the last 20 years is evidenced by the almost exponential increase in the number of publications in the relevant subjects.

Tight control applied to the biological therapy of rheumatoid arthritis.

In the last decade, treatment strategies for rheumatoid arthritis (RA) have included the early use of disease-modifying anti-rheumatic drugs, since prompt suppression of disease activity is associated with a reduction in radiological damage. This strategy has now been incorporated into the broader concept of "tight control", defined as a treatment strategy tailored to each patient with RA, which aims to achieve a predefined level of low disease activity or remission within a certain period of time. To pursue this goal, tight control should include careful and continuous monitoring of disease activity, and early therapeutic adjustments or switches should be considered as necessary. It is noteworthy that the key role of tight control of RA has been stressed by the recent EULAR Guidelines. This review discusses the most recent evidence concerning the role of a tight control strategy in the treatment of RA, and on how this strategy should be pursued.

Efficacy of tidal irrigation in Milwaukee shoulder syndrome.

OBJECTIVE: To assess the efficacy of tidal irrigation in patients with Milwaukee shoulder syndrome (MSS). METHODS: Ten patients with clinical diagnosis of MSS underwent ultrasound examination and tidal irrigation followed by instillation of methylprednisolone and tranexamic acid. A single shoulder was treated in 9 cases; in one patient with bilateral shoulder involvement, both shoulders were treated at different times. Six patients had longlasting disease (Group A) unsuccessfully treated with repeated joint fluid aspirations and intraarticular corticosteroid injections. Four patients had recent-onset illness without radiologic damage but with clinical findings similar to classic MSS (Group B), not previously treated with corticosteroid injections with symptoms dating from 3 months or less. Clinical examination including evaluation of adverse events, range of motion, and pain score by a 100 mm horizontal visual analog scale was scheduled just before tidal irrigation and after 2 and 6 months following the procedure in all cases. RESULTS: Short- and longterm safety was excellent in all patients. Group A patients experienced short-lived improvement so that tidal irrigation had to be repeated within 6 to 10 months. No further therapy was necessary in any of the Group B patients during a mean followup of 16.5 months (range 12-24) due to a persistent clinical improvement without clinically detectable joint effusion. CONCLUSION: Closed-needle joint irrigation is a minimally invasive procedure, which led to a significant improvement in both pain and active motion in patients with longstanding symptoms. Patients with recent-onset disease recovered completely.

Autoantibodies to heterogeneous nuclear ribonucleoproteins.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are among the most abundant proteins in the eukaryotic cell nucleus and play a direct role in several aspects of the RNA life including splicing, export of the mature RNAs and translation. To date, approximately 30 proteins have been identified. A growing body of evidence points to hnRNPs as an important target of the autoimmune response in rheumatic diseases. Autoantibodies to A and B proteins of the hnRNP complex have been detected in late 1980s in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). Beyond their role as diagnostic test in clinical practice, these autoantibodies are starting to be regarded as important tools to obtain deeper insight into the pathogenesis of autoimmune rheumatic diseases. Furthermore, new anti-hnRNP antibodies have been recognized in the last ten years extending the spectrum of anti-hnRNP reactivity in different autoimmune disorders.