"Not wishing to be the white rhino in the crowd" : disability-disclosure at University

This article reports on a qualitative study identifying the drivers for and boundaries to disability-disclosure in interability interactions as experienced by 13 students with physical impairments at five Belgian higher education institutions. Through surveys and in-depth interviews, the study explored whether the students experience, prefer, and expect differences in communication about their impairments with temporarily able-bodied peers, instructors, and staff. Interviews provided insight into the nuances of disclosure and topic avoidance decisions that differ by disclosure target: disabilitydisclosure is mainly a balancing act between fulfilling physical needs and maintaining a normal, positive identity. The visibility of impairments seems to play a minor role in the students’ initial orientation toward disclosing. The functions of disability-disclosure as posited by the Communication Predicament of Disability Model and the CARE-keys to effective interability communication (i.e., Contact, Ask, Respect, Empathy) are discussed as well as the implications of the findings for Communication Accommodation Theory

The economics of debt clearing mechanisms

We examine the evolution of decentralized clearinghouse mechanisms from the 13th to the 18th century; in particular, we explore the clearing of non- or limitedtradable debts like bills of exchange. We construct a theoretical model of these clearinghouse mechanisms, similar to the models in the theoretical matching literature, and show that specific decentralized multilateral clearing algorithms known as rescontre, skontrieren or virement des parties used by merchants were efficient in specific historical contexts. We can explain both the evolutionary self-organizing emergence of late medieval and early modern fairs, and its robustness during the 17th and 18th century

A genome-wide association study identifies risk alleles in plasminogen and P4HA2 associated with giant cell arteritis

Giant cell arteritis (GCA) is the most common form of vasculitis in individuals older than 50 years in Western countries. To shed light onto the genetic background influencing susceptibility for GCA, we performed a genome-wide association screening in a well-powered study cohort. After imputation, 1,844,133 genetic variants were analysed in 2,134 cases and 9,125 unaffected controls from ten independent populations of European ancestry. Our data confirmed HLA class II as the strongest associated region (independent signals: rs9268905, P = 1.94E-54, per-allele OR = 1.79; and rs9275592, P = 1.14E-40, OR = 2.08). Additionally, PLG and P4HA2 were identified as GCA risk genes at the genome-wide level of significance (rs4252134, P = 1.23E-10, OR = 1.28; and rs128738, P = 4.60E-09, OR = 1.32, respectively). Interestingly, we observed that the association peaks overlapped with different regulatory elements related to cell types and tissues involved in the pathophysiology of GCA. PLG and P4HA2 are involved in vascular remodelling and angiogenesis, suggesting a high relevance of these processes for the pathogenic mechanisms underlying this type of vasculitis

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients

Background Patients with acute medical illnesses are at prolonged risk for venous thrombosis. However, the appropriate duration of thromboprophylaxis remains unknown. Methods Patients who were hospitalized for acute medical illnesses were randomly assigned to receive subcutaneous enoxaparin (at a dose of 40 mg once daily) for 10±4 days plus oral betrixaban placebo for 35 to 42 days or subcutaneous enoxaparin placebo for 10±4 days plus oral betrixaban (at a dose of 80 mg once daily) for 35 to 42 days. We performed sequential analyses in three prespecified, progressively inclusive cohorts: patients with an elevated d-dimer level (cohort 1), patients with an elevated d-dimer level or an age of at least 75 years (cohort 2), and all the enrolled patients (overall population cohort). The statistical analysis plan specified that if the between-group difference in any analysis in this sequence was not significant, the other analyses would be considered exploratory. The primary efficacy outcome was a composite of asymptomatic proximal deep-vein thrombosis and symptomatic venous thromboembolism. The principal safety outcome was major bleeding. Results A total of 7513 patients underwent randomization. In cohort 1, the primary efficacy outcome occurred in 6.9% of patients receiving betrixaban and 8.5% receiving enoxaparin (relative risk in the betrixaban group, 0.81; 95% confidence interval [CI], 0.65 to 1.00; P=0.054). The rates were 5.6% and 7.1%, respectively (relative risk, 0.80; 95% CI, 0.66 to 0.98; P=0.03) in cohort 2 and 5.3% and 7.0% (relative risk, 0.76; 95% CI, 0.63 to 0.92; P=0.006) in the overall population. (The last two analyses were considered to be exploratory owing to the result in cohort 1.) In the overall population, major bleeding occurred in 0.7% of the betrixaban group and 0.6% of the enoxaparin group (relative risk, 1.19; 95% CI, 0.67 to 2.12; P=0.55). Conclusions Among acutely ill medical patients with an elevated d-dimer level, there was no significant difference between extended-duration betrixaban and a standard regimen of enoxaparin in the prespecified primary efficacy outcome. However, prespecified exploratory analyses provided evidence suggesting a benefit for betrixaban in the two larger cohorts. (Funded by Portola Pharmaceuticals; APEX ClinicalTrials.gov number, NCT01583218. opens in new tab.

FDG-PET/CT(A) imaging in large vessel vasculitis and polymyalgia rheumatica: joint procedural recommendation of the EANM, SNMMI, and the PET Interest Group (PIG), and endorsed by the ASNC

Large vessel vasculitis (LVV) is defined as a disease mainly affecting the large arteries, with two major variants, Takayasu arteritis (TA) and giant cell arteritis (GCA). GCA often coexists with polymyalgia rheumatica (PMR) in the same patient, since both belong to the same disease spectrum. FDG-PET/CT is a functional imaging technique which is an established tool in oncology, and has also demonstrated a role in the field of inflammatory diseases. Functional FDG-PET combined with anatomical CT angiography, FDG-PET/CT(A), may be of synergistic value for optimal diagnosis, monitoring of disease activity, and evaluating damage progression in LVV. There are currently no guidelines regarding PET imaging acquisition for LVV and PMR, even though standardization is of the utmost importance in order to facilitate clinical studies and for daily clinical practice. This work constitutes a joint procedural recommendation on FDG-PET/CT(A) imaging in large vessel vasculitis (LVV) and PMR from the Cardiovascular and Inflammation & Infection Committees of the European Association of Nuclear Medicine (EANM), the Cardiovascular Council of the Society of Nuclear Medicine and Molecular Imaging (SNMMI), and the PET Interest Group (PIG), and endorsed by the American Society of Nuclear Cardiology (ASNC). The aim of this joint paper is to provide recommendations and statements, based on the available evidence in the literature and consensus of experts in the field, for patient preparation, and FDG-PET/CT(A) acquisition and interpretation for the diagnosis and follow-up of patients with suspected or diagnosed LVV and/or PMR. This position paper aims to set an internationally accepted standard for FDG-PET/CT(A) imaging and reporting of LVV and PMR

Safety and Efficacy of Mepolizumab in Hypereosinophilic Syndrome: An Open-Label Extension Study

Background: A double-blind, placebo-controlled, phase III study (200622) showed that mepolizumab reduces disease flares for patients with uncontrolled FIP1-like-1-platelet-derived growth factor receptor α–negative hypereosinophilic syndrome (HES) and two or more flares in the previous year. Objective: To further characterize the safety, clinical benefit, and pharmacodynamics of mepolizumab. Methods: Eligible patients from both treatment arms of the double-blind study could enter an open-label extension study (205203; NCT03306043) to receive 4-weekly mepolizumab (300 mg subcutaneously) plus background therapy for 20 weeks. Primary end points were safety-based; other end points included flare rates and changes from baseline in mean daily oral corticosteroid (OCS) dose and blood eosinophil count. Results: Of 104 patients who completed the double-blind study, 98% (previous placebo, n = 52; previous mepolizumab, n = 50) enrolled in the open-label extension. Overall, 66 of patients reported adverse events (AEs) (65%), 15 reported treatment-related AEs (15%), and nine reported serious AEs (9%). No events were fatal. The annualized flare rate (95% confidence interval) in the previous placebo and previous mepolizumab groups was 0.37 (0.16-0.86) and 0.14 (0.04-0.49) events/y, respectively. Of 72 patients receiving OCS during weeks 0 to 4, 20 (28%; previous placebo, n = 14; previous mepolizumab, n = 6) achieved 50% or greater reductions in mean daily dose during weeks 16 to 20. At week 20, blood eosinophil count was reduced by 89% in patients previously receiving placebo and remained reduced for those previously receiving mepolizumab. Conclusions: Extended mepolizumab treatment was associated with a positive benefit–risk profile. Continued control of disease flares and blood eosinophil counts, plus reductions in OCS use, were observed with mepolizumab in patients with FIP1-like-1-platelet-derived growth factor receptor α–negative HES

Mepolizumab Reduces Hypereosinophilic Syndrome Flares Irrespective of Blood Eosinophil Count and Interleukin-5

Background: Mepolizumab, an anti-interleukin-5 (IL-5) antibody, reduces disease flares in patients with hypereosinophilic syndrome (HES). Factors predicting treatment response are unknown. Objective: To assess mepolizumab efficacy by baseline blood eosinophil count (BEC) and serum IL-5 level in patients with HES. Methods: This post hoc analysis used data from the phase III study assessing mepolizumab in patients with HES (NCT02836496). Patients 12 years old or older, with HES for 6 or more months, 2 or more flares in the previous year, and BEC ≥1,000 cells/μL at screening were randomized (1:1) to 4-weekly subcutaneous mepolizumab (300 mg) or placebo, plus baseline HES therapy, for 32 weeks. The proportion of patients experiencing 1 or more flares (wk 32), annualized flare rate, and proportion of patients with change from baseline in Brief Fatigue Inventory (BFI) item 3 (wk 32), were analyzed by baseline BEC (<1500/≥1500 to <2500/≥2500 cells/μL). Flare outcomes were assessed by baseline serum IL-5 (<7.81/≥7.81 pg/mL). Results: Across baseline BEC subgroups, mepolizumab reduced the proportion of patients experiencing 1 or more flares by 63% to 90% and flare rate by 58% to 84% (treatment-by-eosinophil interaction P =.76 and P =.90, respectively); patients had improved BFI item 3 score with mepolizumab versus placebo (cells/μL: <1,500: 54% vs 37%; ≥1,500 to <2,500: 47% vs 31%; ≥2,500: 61% vs 0%; treatment-by-eosinophil interaction P =.42). Most patients had undetectable baseline serum IL-5 levels; among these, mepolizumab versus placebo reduced the proportion of patients with 1 or more flares (77%) and flare rate (67%). Conclusions: Mepolizumab was efficacious in the patients with HES studied, irrespective of baseline BEC. Undetectable IL-5 levels should not preclude mepolizumab treatment

Present eternity : quests of temporality in the literary production of the &quot;extr&#234;me contemporain&quot; in France (The Writings of Dominique Fourcade and Emmanuel Hocquard)

The term \uab extr\ueame contemporain \ubb is an expression currently used by scholars to indicate the French literary production of the last 20 years. This term was used in a work of literature for the first time by the French poet Dominique Fourcade in 1986 (\uc9l\ue9gie L apostrophe E.C.) in reference to an epoch, but also to a new sense of experiencing time and space in the so-called \uab age of digital reproducibility \ubb. The aim of this paper is to consider how the change in temporal protocols due to the triumph of Big Optics (Paul Virilio) affects the sense of teleology (destiny) and the quest for experience in French contemporary poetry (in particular, in the genre of the elegy). Including both memory and anticipation, the \uab extr\ueame contemporain \ubb production seems to prefer the \u201ctime of now\u201d, Jetz-zeit in Benjamin\u2019s words, to past or testimony, and speaks to the present, whose responsibility is to give voice to a space where everything is simply allowed to happen