Physical diagnostics of cartilage degeneration

Thesis (Ph.D.)--Harvard--Massachusetts Institute of Technology Division of Health Sciences and Technology, February 1999."January 1999."Includes bibliographical references (leaves 219-239).by Steven Treppo.Ph.D

AB0521 COST OF ILLNESS OF ANCA-ASSOCIATED VASCULITIS IN ITALY: DATA LINKAGE ANALYSIS OF MULTIPLE CLINICAL AND ADMINISTRATIVE DATABASES IN THE PROVINCE OF UDINE, ITALY

Background:ANCA-associated vasculitides (AAV) are a group of systemic vasculitis carrying a high risk of hospitalization because the multiorgan involvement, the acute nature of some clinical manifestations, the chronic but very disabling course of some other manifestations and finally the risk of severe infections due to chronic glucocorticoid and immunosuppressor administration. However, data on cost of illness due to AAV are lacking.Objectives:to estimate the cost of illness in patients suffering from AAV in the province of Udine (about 500,000 inhabitants), Friuli Venezia Giulia (FVG), Italy, from year 2010 to 2018.Methods:integration of the information coming from many administrative databases were used to this end. The Regional Health Information System of FVG was used as the source of information for this retrospective cohort study. The system covers the entire regional population and includes various electronic health administrative databases that can be linked with one another on an individual basis through a unique encrypted identifier. In particular, the following databases were matched: the database of the health care beneficiaries (including demographic information and the residential history of all of the subjects living in FVG), the hospital discharge database, the database of exemptions from medical charges, the database of the laboratories. The population under study was selected based on the following inclusion criteria: patients were residents in the province of Udine and they had to carry the exemption code for AAV, including GPA, or EGPA, or MPA. This population was observed from 2010 to 2018.Results:57 patients (201 patient-years) with AAV were identified. They were ANCA-positive in 44/57 (77%). GPA, EGPA and MPA was diagnosed in 18 (31,6%), 15 (26,3%), 11 (19,3%) patients, respectively. The mean age at diagnosis was 54,5 (17,5) years. The disease itself was the main cause of hospitalization in almost half of the hospital discharges (60/126, 47,6%). Four patients died during the observation period due to vasculitis itself (1), pneumonia (2), or haematological malignancy (1). Time to the first event (death or hospitalization) was significantly higher in ANCA-negative AAV patients than in ANCA-positive AAV patients (p=0,03, Log-Rank test), ANCA-positive AAV patients having a three-times higher risk (HR 3,38 95%CI 1,13-10,08, p=0,03). Total estimated cost was € 1,215,078, corresponding to € 6,168 patient-year. Costs for ANCA-positive AAV patients were much higher than those for ANCA-negative AAV patients (€ 1,115,253 vs € 99,825, and € 7058 per person-year vs € 2,559 per person-year, respectively). GPA and MPA showed the highest costs if compared to EGPA [GPA: € 239,168 (€ 5199 per person-year) vs MPA: € 281,502 (€ 4771 per person-year) vs EGPA: € 214,287 (2329 per person-year), respectively]. Costs for hospitalization were the highest [€ 734,957 (€ 3731 per person-year) vs other costs € 480,121 (€ 2437 per person-year)].Conclusion:costs for AAV are very high, confirming the high health care burden of this illness. Management of ANCA-positive patients rather than ANCA-negative patients was burdened by the highest costs. GPA and MPA showed the highest direct costs for hospitalization, which very frequently occurred due to the vasculitis itself.Disclosure of Interests:Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Elena Treppo: None declared, Salvatore De Vita Consultant of: Roche, GSK, Speakers bureau: Roche, GSK, Novartis, Francesca Valent: None declare

Healthcare and economic burden of ANCA-associated vasculitis in Italy: an integrated analysis from clinical and administrative databases

ANCA-associated vasculitides (AAV) comprise a group of systemic vasculitides characterized by inflammation of small-sized blood vessels leading to multi-organ involvement. The worldwide annual incidence of AAV ranges from 1.2 to 3.3 cases per 100 000 individuals with a prevalence of 4.6\u201342.1 cases per 100 000 individuals. The prevalence of AAV is geographically heterogeneous; therefore, regional epidemiological studies can be more informative to improve health care systems. Even though clinicians are aware that the healthcare burden and the risk of hospitalization of AAV appear high, data on hospitalization and cost of illness due to AAV are still scarce or even lacking. This study aims to characterize the economic burden of AAV in Friuli Venezia Giulia (FVG), Italy. Thus, a retrospective study was conducted through the integration of many administrative health databases of the FVG as the source of information. From data integration, we estimated that more than two-thirds of AAV patients showed at least one hospitalization in their medical history, most frequently caused by the disease itself or superimposed infections. Around 10% of patients developed end-stage renal disease. In an 8-year follow-up, the overall healthcare cost was \u20ac 1,215,078, corresponding to \u20ac 6,168 patient-year. ANCA-positive patients showed much higher costs than ANCA-negative patients did. Overall, AAV are rare diseases, but imply very high healthcare costs. Early diagnosis and optimal treatment probably still remain unmet needs for AAV

Rituximab induction and maintenance in ANCA-associated vasculitis: State of the art and future perspectives

Antineutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV) is a group of rare autoimmune diseases characterized by inflammation of the vascular wall. The pathogenesis of AAV is strongly associated with B cell-derived ANCAs; thus, Rituximab (RTX) has become a promising drug in the induction and maintenance treatment of AAV. The purpose of this review is to describe the efficacy and safety of RTX in the induction of remission and maintenance therapy of AAV. Herein, we summarize the randomized controlled trials that have contributed to the refinement of the use of RTX in AAV in the past decades. RTX has been proven to be effective both in new-onset disease and in relapsing disease. Although the optimal duration of AAV maintenance therapy remains unknown, the ANCAs and the B-cell repopulation may offer support for the administration of further RTX cycles (or not). The safety of RTX is comparable with cyclophosphamide, with the advantage of a low risk of malignancy and no concern for fertility. In conclusion, RTX now plays an important role in the induction and maintenance therapy of AAV. Optimizing RTX-based treatment strategies in AAV is one of the main goals of the current research in AAV

Risk of Cancer in Connective Tissue Diseases in Northeastern Italy over 15 Years

Objective: To evaluate cancer risk among individuals with connective tissue disease (CTD) in Friuli Venezia Giulia, northern Italy. Methods: A population-based cohort study was conducted based on data from health records available in the regional healthcare database. Demographic characteristics, hospital discharges, exemption from medical charges, drug prescriptions, were individually matched with data from the population-based cancer registry. Cancer risk was assessed in people diagnosed with the following diseases: systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS), systemic sclerosis (SSc), polymyositis (PM), and dermatomyositis (DM). Results: In all, 2504 patients were followed for a total of 18,006 person-years (median follow-up: 6.8 years). After 5 and 10 years of follow-up, the cumulative cancer incidence was 2.6% and 8.5%, respectively. The most common cancers were breast (n = 34), lung (n = 24), colon–rectum–anus (n = 20), and non-Hodgkin lymphomas (NHL) (n = 20). Overall, no excess cancer risk was noted (SIR = 0.87), whereas the number of observed NHL cases was more than two-fold significantly higher than expected (SIR = 2.52). The subgroup analysis showed a higher risk of NHL among SS patients (SIR = 3.84) and SLE patients (SIR = 2.69). Conversely, the study population showed a decreased risk for breast cancers (SIR = 0.61) and corpus uteri (SIR = 0.21). Conclusions: The incidence of NHL was higher among patients with SS and SLE. Careful surveillance for hematological malignancies in these patients is recommended

Unmet needs in ANCA-associated vasculitis: Physicians’ and patients’ perspectives

In recent years, clinical research has increased significantly and therapies for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis have improved. However, there are still unanswered questions and unmet needs about AAV patients. The purpose of this review is to examine the frontiers of research related to emerging biomarkers eventually predicting relapse, and new therapeutic approaches, not to mention new quality of life assessment tools. Identifying predictors of relapse may help optimize therapeutic strategies, minimize disease recurrence, and reduce treatment-related side effects. In addition, it is important to recognize that patients may suffer long-term consequences of the disease and its treatment, which, although life-saving, is often associated with significant side effects. Our goal, therefore, is to highlight what has been achieved, the pitfalls, and what still needs to be done, comparing the views of physicians and patients

Safety of Biologic-DMARDs in Rheumatic Musculoskeletal Disorders: A Population-Based Study over the First Two Waves of COVID-19 Outbreak

This study aims to explore disease patterns of coronavirus disease (COVID-19) in patients with rheumatic musculoskeletal disorders (RMD) treated with immunosuppressive drugs in comparison with the general population. The observational study considered a cohort of RMD patients treated with biologic drugs or small molecules from September 2019 to November 2020 in the province of Udine, Italy. Data include the assessment of both pandemic waves until the start of the vaccination, between February 2020 and April 2020 (first), and between September 2020 and November 2020 (second). COVID-19 prevalence in 1051 patients was 3.5% without significant differences compared to the general population, and the course of infection was generally benign with 2.6% mortality. A small percentage of COVID-19 positive subjects were treated with low doses of steroids (8%). The most used treatments were represented by anti-TNF agents (65%) and anti-IL17/23 agents (16%). More than two-thirds of patients reported fever, while gastro-intestinal symptoms were recorded in 27% of patients and this clinical involvement was associated with longer swab positivity. The prevalence of COVID-19 in RMD patients has been confirmed as low in both waves. The benign course of COVID-19 in our patients may be linked to the very low number of chronic corticosteroids used and the possible protective effect of anti-TNF agents, which were the main class of biologics herein employed. Gastro-intestinal symptoms might be a predictor of viral persistence in immunosup-pressed patients. This finding could be useful to identify earlier COVID-19 carriers with uncommon symptoms, eventually eligible for antiviral drugs

The mechanical and material properties of elderly human articular cartilage subject to impact and slow loading

Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.Peer reviewedPostprin

Efficacy and Safety of High-Dose Immunoglobulin-Based Regimen in Statin-Associated Autoimmune Myopathy: A Multi-Center and Multi-Disciplinary Retrospective Study

Statin-associated autoimmune myopathy is a rare muscle disorder, characterized by autoantibodies against HMGCR. The anti-HMGCR myopathy persists after statin, and often requires immunosuppressive therapy. However, there is not a standardized therapeutic approach. The purpose of this study is to report the effectiveness of the immunosuppressive treatment employed in a multi-center and multi-disciplinary cohort of patients affected by anti-HMGCR myopathy, in which an immunoglobulin (IVIG)-based treatment strategy was applied. We collected 16 consecutive patients with a diagnosis of anti-HMGCR myopathy, between 2012 and 2019, and recorded data on clinical and laboratory presentation (i.e., muscle strength, serum CK levels, and anti-HMGCR antibody titer) and treatment strategies. Our results highlight the safety and efficacy of an induction therapy combining IVIG with GCs and/or methotrexate to achieve persistent remission of the disease and steroid-free maintenance. Under IVIG-based regimens, clinical improvement and CK normalization occurred in more than two thirds of patients by six months. Relapse rate was low (3/16) and 2/3 relapses occurred after treatment suspension. Nearly 90% of the patients who successfully discontinued GCs were treated with a triple immunosuppressive regimen. In conclusion, an IVIG-based regimen, which particularly includes high-dose immunoglobulin, GCs and methotrexate, can provide a fast remission achievement with GC saving