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Patient-reported outcomes (PROs) are assessment tools coming directly from patients about their feelings, perceptions, health-related functions, and treatment effects without interpretation by health-care providers. There is a global interest for more "patient-centered care" and PROs in rheumatology. Assessment of disease impact through patient-reported outcome (PRO) measures is a key element for clinical care and clinical research in Takayasu's arteritis (TAK). Currently there are no disease-specific PRO measures to assess quality of life for patients with TAK. Impaired health-related quality of life (HRQoL), functional status, increased anxiety, and depression were shown in patients with TAK in a few studies with generic PRO instruments such as the Short Form-36. However, it is difficult to capture disease-specific effects on patients' daily life and quality of life with these generic tools. There are ongoing efforts of Outcome Measures in Rheumatology (OMERACT) Vasculitis Working Group to develop disease-specific outcome measures in TAK.

To compare the efficacy of abatacept to that of placebo for the treatment of Takayasu arteritis (TAK).In this multicenter trial, patients with newly diagnosed or relapsing TAK were treated with abatacept 10 mg/kg intravenously on days 1, 15, and 29 and week 8, together with prednisone administered daily. At week 12, patients in remission underwent a double-blinded randomization to continue to receive abatacept monthly or switch to placebo. Patients in both study arms received a standardized prednisone taper, reaching a dosage of 20 mg daily at week 12, with discontinuation of prednisone at week 28. All patients remained on their randomized assignment until meeting criteria for early termination or until 12 months after enrollment of the last patient. The primary end point was duration of remission (relapse-free survival).Thirty-four eligible patients with TAK were enrolled and treated with prednisone and abatacept; of these, 26 reached the week 12 randomization and underwent a blinded randomization to receive either abatacept or placebo. The relapse-free survival rate at 12 months was 22% for those receiving abatacept and 40% for those receiving placebo (P = 0.853). Treatment with abatacept in patients with TAK enrolled in this study was not associated with a longer median duration of remission (median duration 5.5 months for abatacept versus 5.7 months for placebo). There was no difference in the frequency or severity of adverse events, including infection, between the treatment arms.In patients with TAK, the addition of abatacept to a treatment regimen with prednisone did not reduce the risk of relapse.

The aim of this study was to develop and validate case-finding algorithms for granulomatosis with polyangiitis (Wegener's, GPA), microscopic polyangiitis (MPA), and eosinophilic GPA (Churg-Strauss, EGPA).Two hundred fifty patients per disease were randomly selected from two large healthcare systems using the International Classification of Diseases version 9 (ICD9) codes for GPA/EGPA (446.4) and MPA (446.0). Sixteen case-finding algorithms were constructed using a combination of ICD9 code, encounter type (inpatient or outpatient), physician specialty, use of immunosuppressive medications, and the anti-neutrophil cytoplasmic antibody type. Algorithms with the highest average positive predictive value (PPV) were validated in a third healthcare system.An algorithm excluding patients with eosinophilia or asthma and including the encounter type and physician specialty had the highest PPV for GPA (92.4%). An algorithm including patients with eosinophilia and asthma and the physician specialty had the highest PPV for EGPA (100%). An algorithm including patients with one of the diagnoses (alveolar hemorrhage, interstitial lung disease, glomerulonephritis, and acute or chronic kidney disease), encounter type, physician specialty, and immunosuppressive medications had the highest PPV for MPA (76.2%). When validated in a third healthcare system, these algorithms had high PPV (85.9% for GPA, 85.7% for EGPA, and 61.5% for MPA). Adding the anti-neutrophil cytoplasmic antibody type increased the PPV to 94.4%, 100%, and 81.2% for GPA, EGPA, and MPA, respectively.Case-finding algorithms accurately identify patients with GPA, EGPA, and MPA in administrative databases. These algorithms can be used to assemble population-based cohorts and facilitate future research in epidemiology, drug safety, and comparative effectiveness. Copyright © 2016 John WileySons, Ltd.

Background: Patients with vasculitis (VS) have complex organ- and life-threatening disease manifestations due to autoimmune-mediated inflammatory vascular damage and an increased risk of cardiovascular disease (CVD). Accurate biomarkers do not exist for VS. Cells release extracellular vesicles (EVs) in the setting of activation, injury, or death. In patients with diabetes mellitus and CVD, the effects of the inflammatory cascade, platelets and endothelium, positively correlate with levels of EVs bearing receptors for CD3, CD41, or CD105, and negatively correlate with levels of circulating endothelial progenitor cells (CPCs). Because VS is characterized by systemic inflammation, platelet activation and endothelial damage, this group of diseases may have unique effects on EVs and CPCs. This study evaluated a high dimensional flow cytometry approach to profiling EVs and CPCs in plasma to discern a biomarker pattern in VS. Methods: Levels of CPCs and EVs were measured with a panel of cell surface markers in 10 VS patients and 5 age-similar healthy controls (HC). Data were acquired on a modified Becton Dickinson FACSCanto. Results: Although no significant increase in CPCs in VS compared with HC was detected, the standard deviation of CPC levels in VS was more than double that in HC (SD=574 vs. 165, p=0.081), suggesting heterogeneity in the VS group. EV subsets with lower concentrations in VS, compared with HC, included: Annexin + CD3 + double-positive T Lymphocyte (p=0.026) and CD105 + CD64 + double-positive activated Macrophage (p=0.030). CD144 + CD105 + double-positive endothelial EVs were only detected in a subset of VS and not in HC. CD31 + CD41a + double-positive platelet EVs were increased in VS compared with HC (894 (580) vs. 416 (128), p=0.004). Conclusion: This proof of concept study discovered a distinct EV pattern that correlates with a diagnosis of VS, suggesting that cell- and vesicle-based assays could be useful biomarkers in evaluating VS. This pattern is different from that found in patients with diabetes mellitus and CVD. Larger studies could seek to elucidate correlations between CPCs and disease activity and identify a unique EV signature for VS with increased risk for CVD.

PurposeThe purpose of this paper is to profile the characteristics, attributes and growth orientations of Lebanese entrepreneurs, including the relationships, roles, and contributions that family and culture make and play in the development of private small and medium‐sized enterprises.Design/methodology/approachDrawing on a sample of 112 entrepreneurs, psychographic motives, demographic attributes, and business activities are revealed. A series of 112 in‐depth personal interviews was conducted over a 12 month period between May 2006 and 2007. The entrepreneurial profile questionnaire (EPQ) was utilized as a data collection instrument. The EPQ was designed to survey the effect of individual, societal, and environmental factors on entrepreneurship and family business development by collecting a combination of demographic information and extensive detail related to characteristics and orientations.FindingsThe findings suggest that entrepreneurs are motivated by the need for independence and flexibility. Entrepreneurs were found to rely heavily on family member participation to establish, develop, and grow their enterprises. The majority of the entrepreneurs surveyed employ at least one family member on a full‐time basis. Entrepreneurs were also found to use family finances as the primary source of start‐up capital. Family participation in the form of employment and investment was found to have a positive impact on entrepreneurial growth intentions and expansion plans.Originality/valueThe paper offers insights into family contributions to entrepreneurial development in Lebanon.

Purpose – The purpose of this paper is to explore relationships between different governance configurations and firm survival. The objective is to describe the alternative mechanisms through which the owning family takes a stake in the governance of the firm.Design/methodology/approach – The governance systems of 116 family enterprises in Lebanon are examined. The study integrates family, ownership, leadership and the business itself constituting the four structural elements of a family firm's governance system. Then, the study tests four hypotheses whether the family, the ownership, the leadership and the business dimensions influence positively firm survival/longevity. The other hypotheses tested concern the advisory services and the legal form of the board, and how that might affect the survival/longevity of the family firm.Findings – This integrative view allows observation of interactions among the different structures, and the establishment of a coordinating governing structure. Hypotheses testing r...

Objective.Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of linked multisystem life- and organ-threatening diseases. The Outcome Measures in Rheumatology (OMERACT) vasculitis working group has been at the forefront of outcome development in the field and has achieved OMERACT endorsement of a core set of outcomes for AAV. Patients with AAV report as important some manifestations of disease not routinely collected through physician-completed outcome tools; and they rate common manifestations differently from investigators. The core set includes the domain of patient-reported outcomes (PRO). However, PRO currently used in clinical trials of AAV do not fully characterize patients’ perspectives on their burden of disease. The OMERACT vasculitis working group is addressing the unmet needs for PRO in AAV.Methods.Current activities of the working group include (1) evaluating the feasibility and construct validity of instruments within the PROMIS (Patient-Reported Outcome Measurement Information System) to record components of the disease experience among patients with AAV; (2) creating a disease-specific PRO measure for AAV; and (3) applying The International Classification of Functioning, Disability and Health to examine the scope of outcome measures used in AAV.Results.The working group has developed a comprehensive research strategy, organized an investigative team, included patient research partners, obtained peer-reviewed funding, and is using a considerable research infrastructure to complete these interrelated projects to develop evidence-based validated outcome instruments that meet the OMERACT filter of truth, discrimination, and feasibility.Conclusion.The OMERACT vasculitis working group is on schedule to achieve its goals of developing validated PRO for use in clinical trials of AAV.

Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome-wide association analysis of Takayasu arteritis.Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis.We identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 × 10(-9)), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 × 10(-8)), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 × 10(-10)). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 × 10(-8)). In addition, we identified candidate susceptibility genes with suggestive levels of association (P1 × 10(-5)) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B.Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.

Published small case series suggest that inflammatory bowel disease [IBD; Crohn's disease (CD) or ulcerative colitis (UC)] and vasculitis co-occur more frequently than would be expected by chance.To describe this association by an analysis of a large cohort of carefully studied patients and through a systematic literature review.Patients with both IBD and vasculitis enrolled in the Vasculitis Clinical Research Consortium (VCRC) Longitudinal Studies, followed in Canadian Vasculitis research network (CanVasc) centers and/or in the University of Toronto's IBD clinic were included in this case series. A systematic literature review of patients with IBD and vasculitis involved a PubMed search through February 2014. The main characteristics of patients with Takayasu arteritis (TAK) and IBD were compared to those in patients with TAK without IBD followed in the VCRC.The study identified 32 patients with IBD and vasculitis: 13 with large-vessel vasculitis [LVV; 12 with TAK, 1 with giant cell arteritis (GCA); 8 with CD, 5 with UC]; 8 with ANCA-associated vasculitis [AAV; 6 granulomatosis with polyangiitis (GPA), 2 with eosinophilic granulomatosis with polyangiitis (EGPA)]; 5 with isolated cutaneous vasculitis; and 6 with other vasculitides. Patients with LVV and AAV were mostly female (18/21). The diagnosis of IBD preceded that of vasculitis in 12/13 patients with LVV and 8/8 patients with AAV. The review of the literature identified 306 patients with IBD and vasculitis: 144 with LVV (133 TAK; 87 with IBD preceding LVV), 19 with AAV [14 GPA, 1 EGPA, 4 microscopic polyangiitis (MPA)], 66 with isolated cutaneous vasculitis, and 77 with other vasculitides. Patients with IBD and TAK were younger and had more frequent headaches, constitutional symptoms, or gastrointestinal symptoms compared to those patients in the VCRC who had TAK without IBD.These findings highlight the risk of vasculitis, especially TAK, in patients with IBD (both CD and UC).

This article explores the characteristics of Lebanese family businesses using a sample of 114 firms and tests various propositions regarding the relationships between correlates of effective succession planning and longevity. Successful family businesses in Lebanon exhibit a variety of responses to the variables that are conducive to success. The findings indicate that older firms are more inclined to use a participatory decision-making process, as evidenced by more reliance on advisory boards. A significantly larger proportion of older firms relative to younger ones holds family meetings and has formal redemption and liquidity plans. Firms in our sample are characterized by liberal attitudes: more than 75% consider female ownership acceptable and more than two-thirds of the firms respond positively to potential female CEOs.

Objective. Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome-wide association analysis of Takayasu arteritis. Methods. Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study. The Turkish cohort consisted of 559 patients and 489 controls, and the North American cohort consisted of 134 patients and 1,047 controls of European ancestry. Genotyping was performed using the Omni1-Quad and Omni2.5 genotyping arrays. Genotyping data were subjected to rigorous quality control measures and subsequently analyzed to discover genetic susceptibility loci for Takayasu arteritis. Results. We identified genetic susceptibility loci for Takayasu arteritis with a genome-wide level of significance in IL6 (rs2069837) (odds ratio [OR] 2.07, P = 6.70 x 10(-9)), RPS9/LILRB3 (rs11666543) (OR 1.65, P = 2.34 x 10(-8)), and an intergenic locus on chromosome 21q22 (rs2836878) (OR 1.79, P = 3.62 x 10(-10)). The genetic susceptibility locus in RPS9/LILRB3 lies within the leukocyte receptor complex gene cluster on chromosome 19q13.4, and the disease risk variant in this locus correlates with reduced expression of multiple genes including the inhibitory leukocyte immunoglobulin-like receptor gene LILRB3 (P = 2.29 x 10(-8)). In addition, we identified candidate susceptibility genes with suggestive levels of association (P < 1 x 10(-5)) with Takayasu arteritis, including PCSK5, LILRA3, PPM1G/NRBP1, and PTK2B. Conclusion. Our findings indicate novel genetic susceptibility loci for Takayasu arteritis and uncover potentially important aspects of the pathophysiology of this form of vasculitis.

Background: The target sample size for clinical trials often necessitates a multicenter (center of excellence, CoE) approach with associated added complexity, cost, and regulatory requirements. Alternative recruitment strategies need to be tested against this standard model. Objectives: The aim of our study was to test whether a Web-based direct recruitment approach (patient-centric, PC) using social marketing strategies provides a viable option to the CoE recruitment method. Methods: PC recruitment and Web-based informed consent was compared with CoE recruitment for a randomized controlled trial (RCT) of continuing versus stopping low-dose prednisone for maintenance of remission of patients with granulomatosis with polyangiitis (GPA). Results: The PC approach was not as successful as the CoE approach. Enrollment of those confirmed eligible by their physician was 10 of 13 (77%) and 49 of 51 (96%) in the PC and CoE arms, respectively (P=.05). The two approaches were not significantly different in terms of eligibility with 34% of potential participants in the CoE found to be ineligible as compared with 22% in the PC arm (P=.11) nor in provider acceptance, 22% versus 26% (P=.78). There was no difference in the understanding of the trial as reflected in the knowledge surveys of individuals in the PC and CoE arms. Conclusions: PC recruitment was substantially less successful than that achieved by the CoE approach. However, the PC approach was good at confirming eligibility and was as acceptable to providers and as understandable to patients as the CoE approach. The PC approach should be evaluated in other clinical settings to get a better sense of its potential. [J Med Internet Res 2017;19(2):e50]

Granulomatosis with polyangiitis (Wegener's; GPA) is a necrotizing granulomatous vasculitis that can affect any organ system; however, central nervous system involvement is uncommon. We present 2 cases where central diabetes insipidus was the presenting manifestation of GPA. Pituitary involvement was documented by magnetic resonance imaging. Both patients were female and responded to combination therapy of prednisone and cyclophosphamide. We also review the literature for all reported cases of pituitary involvement in GPA. We conclude that pituitary involvement in GPA seems more common in females and may be the initial presenting clinical feature and may occur in the absence of systemic disease. Early recognition and treatment may prevent pituitary necrosis and irreversible damage.

This study aims to compare the severity and outcomes of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) between Hispanics and Caucasians living in the same geographical area. All patients diagnosed with AAV at two academic institutions in Chicago from January 2006 to December 2012 were retrospectively and prospectively identified. Disease activity was measured with the Birmingham Vasculitis Activity Score (BVAS), and disease damage was measured with the Vasculitis Damage Index (VDI). Student's t test and chi-square tests were employed; p ≤ 0.05 was considered significant. Seventy patients with AAV were identified; 15 patients were excluded. Fifty-five patients were included in the study: 23 Hispanics and 32 Caucasians, 35 patients with granulomatosis with polyangiitis (Wegener's), 12 with microscopic polyangiitis, 7 with eosinophilic granulomatosis with polyangiitis, and 1 with renal-limited vasculitis. Compared to Caucasians, Hispanics had a higher BVAS at presentation (16.3 ± 7.6 versus 10.7 ± 7.5, p = 0.006), a higher VDI at presentation (2.90 ± 1.50 versus 2.06 ± 1.30, p = 0.030), and a cumulative VDI (3.90 ± 1.70 versus 2.50 ± 1.90, p = 0.010). Renal involvement was more common among Hispanics (85 % of Hispanics versus 48 % of Caucasians, p = 0.01). Seventy percent of Hispanics had acute renal failure (mean creatinine = 3.37 ± 4.4 mg/dl) of whom seven (50 %) required dialysis, versus 25 % of Caucasians (mean creatinine = 1.78 ± 1.57 mg/dl, p = 0.03) and only two requiring dialysis. Compared to Caucasians, Hispanics with AAV present with more severe disease and higher damage indices. Larger studies are required to confirm these findings and delineate the respective roles of environment and genetics in the pathogenesis of the disease.

Family businesses are the engine that drives socioeconomic development and wealth creation around the world, and entrepreneurship is a key driver of family businesses. The ability to build and keep the business running over generations is a major element of family business continuity and is influential in strategic execution, innovation, and growth. Entrepreneurial family businesses are a primary source of job creation (Shanker & Astrachan, 1996) in market economies where resources are allocated via supply and demand. In Lebanon, family businesses constitute 85% of the private sector, accounting for 1.05 million of 1.24 million jobs (Fahed-Sreih, 2006). The family unit is usually the only intact institution capable of sustaining entrepreneurial activities in Lebanon following civil war.

Motives for Entrepreneurship: The Case of Lebanese Family Businesses

Objective To study the effect of the innate cytokine macrophage migration inhibitory factor (MIF) on the susceptibility and severity of systemic lupus erythematosus (SLE) in a multinational population of 1,369 Caucasian and African American patients. Methods. Two functional polymorphisms in the MIF gene, a -794 CATT5-8 microsatellite repeat (rs5844572) and a -173 G/C single-nucleotide polymorphism (rs755622), were assessed for association with SLE in 3,195 patients and healthy controls. We also measured MIF plasma levels in relation to genotypes and clinical phenotypes, and assessed Toll-like receptor 7 (TLR-7)-stimulated MIF production in vitro. Results. Both Caucasians and African Americans with the high-expression MIF haplotype -794 CATT(7)/ -173* C had a lower incidence of SLE (in Caucasians, odds ratio [OR] 0.63, 95% confidence interval [95% CI] 0.53-0.89, P = 0.001; in African Americans, OR 0.46, 95% CI 0.23-0.95, P = 0.012). In contrast, among patients with established SLE, reduced frequencies of low-expression MIF genotypes (-794 CATT(5)) were observed in those with nephritis, those with serositis, and those with central nervous system (CNS) involvement when compared to patients without end-organ involvement (P = 0.023, P = 0.005, and P = 0.04, respectively). Plasma MIF levels and TLR-7-stimulated MIF production in vitro reflected the underlying MIF genotype of the studied groups. Conclusion. These findings suggest that MIF, which has both proinflammatory properties and macrophage and B cell survival functions, exerts a dual influence on the immunopathogenesis of SLE. Highexpression MIF genotypes are associated with a reduced susceptibility to SLE and may contribute to an enhanced clearance of infectious pathogens. Once SLE develops, however, low-expression MIF genotypes may protect from ensuing inflammatory end-organ damage.