Prediction and benefits of minimal disease activity in patients with psoriatic arthritis and active skin disease in the ADEPT trial

Objectives: To determine the proportion of patients with psoriatic arthritis in the Adalimumab Effectiveness in Psoriatic Arthritis trial achieving minimal disease activity (MDA) and its individual components at 1 or more visits over 144 weeks, identify baseline predictors of MDA achievement, and evaluate the association of MDA status with independent quality of life (QoL)-related patient-reported outcomes (PROs). Methods: Univariate and multivariate analyses were used to identify the baseline characteristics that predicted achievement of MDA at individual time points (weeks 12 through 144) or sustained MDA (achievement of MDA at 2 consecutive time points 12 weeks apart). The association of independent QoL-related PROs with MDA achievement was evaluated at weeks 24 and 144. Results: In univariate analyses, higher baseline patient assessment of pain, tender joint count (TJC), enthesitis and Health Assessment Questionnaire-Disability Index (HAQ-DI) score were significantly associated with lower likelihood of achieving MDA at later time points. Multivariate analyses confirmed higher baseline HAQ-DI as a significant predictor for failure to achieve MDA at later time points. Achievement of sustained MDA was associated with lower baseline TJC and HAQ-DI score. Achievement of different MDA components appeared to be treatment dependent. MDA achievers had significantly better QoL-related PROs and greater improvements in PROs from baseline to week 24 compared with non-achievers. Conclusions: Higher HAQ-DI score was the most consistent baseline factor that decreased the likelihood of achieving MDA and sustained MDA at later time points. Achieving MDA was associated with better independent QoL-related PROs

Predicting adherence to therapy in rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis: a large cross-sectional study.

Objective: This analysis explored the association of treatment adherence with beliefs about medication, patient demographic and disease characteristics and medication types in rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) to develop adherence prediction models. Methods: The population was a subset from ALIGN, a multicountry, cross-sectional, self-administered survey study in adult patients (n=7328) with six immune-mediated inflammatory diseases who were routinely receiving systemic therapy. Instruments included Beliefs about Medicines Questionnaire (BMQ) and 4-item Morisky Medication Adherence Scale (MMAS-4 Results: A total of 3390 rheumatological patients were analysed (RA, n=1943; PsA, n=635; AS, n=812). Based on the strongest significant associations, the adherence prediction models included type of treatment, age, race (RA and AS) or disease duration (PsA) and medication beliefs (RA and PsA, BMQ-General Conclusions: For the first time, simple medication adherence prediction models for patients with RA, PsA and AS are available, which may help identify patients at high risk of non-adherence to systemic therapies. Trial registration number: ACTRN12612000977875

Innovation and the circular economy: A systematic literature review

The circular economy emerged as an alternative model to the linear system, which now appears to be reaching its physical limitations. To transition to a circular economy, companies must not only be aware of but also engage in more sustainable practices. For such a transition, companies must rethink and innovate their business models and the ways they propose value to their clients while simultaneously considering environmental and social facets. This systematic literature review sought to map out from the company perspective the key topics interrelated with innovation and the circular economy, describing the internal and external factors to consider in such transition processes. Key lines of research were identified, and suggestions for future research and for facilitating movement toward a circular economy are provided. This work contributes to deepening the literature by identifying the priority areas concerning the circular economy and encouraging future research that meets international standards of excellence.info:eu-repo/semantics/publishedVersio

Mitral valve surgery for mitral regurgitation caused by Libman-Sacks endocarditis: a report of four cases and a systematic review of the literature

Libman-Sacks endocarditis of the mitral valve was first described by Libman and Sacks in 1924. Currently, the sterile verrucous vegetative lesions seen in Libman-Sacks endocarditis are regarded as a cardiac manifestation of both systemic lupus erythematosus (SLE) and the antiphospholipid syndrome (APS). Although typically mild and asymptomatic, complications of Libman-Sacks endocarditis may include superimposed bacterial endocarditis, thromboembolic events, and severe valvular regurgitation and/or stenosis requiring surgery. In this study we report two cases of mitral valve repair and two cases of mitral valve replacement for mitral regurgitation (MR) caused by Libman-Sacks endocarditis. In addition, we provide a systematic review of the English literature on mitral valve surgery for MR caused by Libman-Sacks endocarditis. This report shows that mitral valve repair is feasible and effective in young patients with relatively stable SLE and/or APS and only localized mitral valve abnormalities caused by Libman-Sacks endocarditis. Both clinical and echocardiographic follow-up after repair show excellent mid- and long-term results

Administration of M. leprae Hsp65 Interferes with the Murine Lupus Progression

The heat shock protein [Hsp] family guides several steps during protein synthesis, are abundant in prokaryotic and eukaryotic cells, and are highly conserved during evolution. The Hsp60 family is involved in assembly and transport of proteins, and is expressed at very high levels during autoimmunity or autoinflammatory phenomena. Here, the pathophysiological role of the wild type [WT] and the point mutated K409A recombinant Hsp65 of M. leprae in an animal model of Systemic Lupus Erythematosus [SLE] was evaluated in vivo using the genetically homogeneous [NZBxNZW]F1 mice. Anti-DNA and anti-Hsp65 antibodies responsiveness was individually measured during the animal's life span, and the mean survival time [MST] was determined. The treatment with WT abbreviates the MST in 46%, when compared to non-treated mice [p<0.001]. An increase in the IgG2a/IgG1 anti-DNA antibodies ratio was also observed in animals injected with the WT Hsp65. Incubation of BALB/c macrophages with F1 serum from WT treated mice resulted in acute cell necrosis; treatment of these cells with serum from K409A treated mice did not cause any toxic effect. Moreover, the involvement of WT correlates with age and is dose-dependent. Our data suggest that Hsp65 may be a central molecule intervening in the progression of the SLE, and that the point mutated K409A recombinant immunogenic molecule, that counteracts the deleterious effect of WT, may act mitigating and delaying the development of SLE in treated mice. This study gives new insights into the general biological role of Hsp and the significant impact of environmental factors during the pathogenesis of this autoimmune process

International entrepreneurial orientation and the intention to internationalize

This paper presents a conceptual model of international entrepreneurial intention (IEI) through the lens of planned behavior and expectancy-valence theories. Extending the entrepreneurial intentions literature, where attitude to sustainability has started to have an increasingly important influence, to post-launch decisions, we provide an improved theoretical rationale for new venture internationalization, clarify the relationship between entrepreneurial orientation (EO) and IEI, and more closely align the international entrepreneurship literature with mainstream entrepreneurship literature. In this model, IEI is influenced by the entrepreneur’s attitudes to sustainability, learning, risk, work enjoyment, and work effort, moderated by entrepreneur’s perceived feasibility to act entrepreneurially, and determines the firm-level EO, which may culminate in the internationalization of a new or existing venture

Baseline Results from Proof – A 5-Year Observational Study of Long-Term Disease Outcome in Axial Spondyloarthritis

Background Axial spondyloarthritis (axSpA), encompassing ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) without advanced structural lesions in the sacroiliac joints (SIJ), is a relatively new disease concept. The natural disease course of axSpA, including progression of structural damage over time, has not yet been systematically studied in large patient (pt) groups. Objectives To report the baseline data of PROOF, a large study currently being conducted in 29 countries across the world, evaluating long-term outcomes in pts with axSpA classified by ASAS criteria. Methods PROOF is a multi-country prospective observational study evaluating axSpA pts in rheumatology clinical practice over 5 years. Pts with axSpA fulfilling ASAS classification criteria were eligible, if diagnosed ≤12 months prior to study enrolment. Investigator's confidence with the diagnosis of axSpA is ascertained on a numeric rating scale (NRS 0–10) at enrolment and end of follow-up. Assessments of disease activity (BASDAI, ASDAS-CRP), physical function (BASFI), quality of life (SF-12v2), productivity (WPAI-SHP), and pelvic X-ray are scheduled at yearly follow-up visits. X-rays are graded according to NY criteria by local and central readers. Results 2084 pts with axSpA fulfilling ASAS criteria have been enrolled in PROOF study, 1259 pts with AS (60%) and 825 pts with nr-axSpA (40%) according to the investigators. The level of confidence with the diagnosis of axSpA was 8.7±1.8. The imaging criterion was fulfilled by 85% of pts (40% MRI, 51% X-ray, 9% both), 15% of pts were classified through the clinical arm. HLA-B27 was tested in 85% of pts and found to be positive in 68% of cases (70% with AS and 60% with nr-axSpA). Overall, pts were in their mid-thirties, had a long delay in referral to rheumatologist and recently diagnosed axSpA. Comparison of demographic and clinical characteristics between pts with AS and nr-axSpA is shown in Table 1. Pelvic x-rays were reportedly done in 1635 (78%) pts within 6 months of the baseline visit; to date both local and central readers have scored x-rays of 1344 pts (82% of available). Of the 1344 pts, 83.3% retained their classification (AS or nr-axSpA) after the central reading, while 16.7% were classified differently. Based on the kappa value, there was a substantial agreement on the grading of x-rays between the local and central readers: kappa=0.63 (95% CI, 0.59–0.68).Sin financiación12.811 JCR (2016) Q1,1/30 RheumatologyUE

Oxidized low-density lipoprotein (Ox-LDL) but not LDL aggravates the manifestations of experimental antiphospholipid syndrome (APS)

Ox-LDL is thought to play a major role in atherogenesis. The mechanisms mediating the deleterious influences of Ox-LDL include foam cell formation and cell cytotoxicity. The production of anti-Ox-LDL antibodies results in the formation of immune complexes which are taken up at enhanced rate by macrophages, leading to foam cell formation. APS is characterized by repeated venous and arterial thromboembolic phenomena, recurrent fetal loss and thrombocytopenia, associated with the presence of antibodies to negatively charged phospholipids (aPL) (i.e. cardiolipin, phosphatidylserine). Phospholipids bear structural resemblance to LDL, and several studies have indeed proved that aPL display cross-reactivity with anti-Ox-LDL antibodies. In this study we assessed the capacity of oxidized and native forms of LDL to aggravate the clinical picture of experimentally induced APS in naive mice. Mice were actively immunized intradermally with anticardiolipin antibodies and developed a clinical picture resembling APS in humans. Subsequently, the mice were infused with either Ox-LDL, native LDL or PBS, and similar regimens were applied to controls. APS mice infused with Ox-LDL were found to exhibit a significantly more severe form of the disease in comparison with native LDL- and PBS-infused mice, expressed by lower platelet counts (261 000/mm3, 535 000/mm3 and 455 000/mm3, respectively), longer activated partial thromboplastin time (aPTT) (99 ± 12 s, 63 ± 8 s and 74 ± 8 s, respectively) and higher fetal resorption rates (72.7%, 34.4% and 32.6%, respectively). The results of this study show that Ox-LDL, compared with native LDL, aggravates the clinical manifestations of experimental APS and suggest that cross-reactivity of Ox-LDL with phospholipids may provide a pathogenic explanation for this effect