Influence of age on the occurrence of adverse events in rheumatic patients at the onset of biological treatment : Data from the BIOBADASER III register

To assess whether age, at the beginning of biologic treatment, is associated with the time a first adverse event (AE) appears in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA). All patients in the BIOBADASER registry diagnosed with RA, AS, and PsA, and classified as young ( 75 years old) at start of biological treatment were included. Factors associated with the appearance of a first AE using adjusted incidence rate ratios (IRR) (Poisson regression) were analyzed. Survival to first AE was studied by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression. 2483 patients were included: 1126 RA, 680 PsA, and 677 AS. Age group stratification was as follows: 63 young, 2127 adults, 237 elderly, and 56 very elderly. Regression model revealed an increased probability of suffering a first AE at age 65 years or older [IRR elderly: 1.42 (CI95% 1.13-1.77)]. Other characteristics associated with AE were female gender, the use of DMARDs, including methotrexate, the presence of comorbidities, and the time of disease duration. Factors that had the greatest impact on survival over a first AE were age > 75 years [HR 1.50 (1.01-2.24)] and female gender [HR 1.42 (1.22-1.64)]. Age at the start of treatment and female gender are key factors associated with the appearance of a first AE with biologics. Other factors related to patient status and treatment were also associated with a first AE in rheumatic patients treated with biologics

Inflating in a Better Racetrack

We present a new version of our racetrack inflation scenario which, unlike our original proposal, is based on an explicit compactification of type IIB string theory: the Calabi-Yau manifold P^4_[1,1,1,6,9]. The axion-dilaton and all complex structure moduli are stabilized by fluxes. The remaining 2 Kahler moduli are stabilized by a nonperturbative superpotential, which has been explicitly computed. For this model we identify situations for which a linear combination of the axionic parts of the two Kahler moduli acts as an inflaton. As in our previous scenario, inflation begins at a saddle point of the scalar potential and proceeds as an eternal topological inflation. For a certain range of inflationary parameters, we obtain the COBE-normalized spectrum of metric perturbations and an inflationary scale of M = 3 x 10^{14} GeV. We discuss possible changes of parameters of our model and argue that anthropic considerations favor those parameters that lead to a nearly flat spectrum of inflationary perturbations, which in our case is characterized by the spectral index n_s = 0.95.Comment: 20 pages, 7 figures. Brief discussion on the non-gaussianity of this model, one more figure of the field trajectories added as well as other minor changes to the tex

Common variations in estrogen-related genes are associated with severe large-joint osteoarthritis: a multicenter genetic and functional study

OBJECTIVE: Several lines of evidence suggest that estrogens influence the development of osteoarthritis (OA). The aim of this study was to explore the association of two common polymorphisms within the aromatase (CYP19A1) and estrogen receptor (ER) alpha (ESR1) genes with severe OA of the lower limbs. METHODS: The rs1062033 (CYP19A1) and rs2234693 (ESR1) single nucleotide polymorphisms were genotyped in 5528 individuals (3147 patients with severe hip or knee OA, and 2381 controls) from four centres in Spain and the United Kingdom. Gene expression was measured in femoral bone samples from a group of patients. RESULTS: In the global analysis, both polymorphisms were associated with OA, but there was a significant sex interaction. The GG genotype at rs1062033 was associated with an increased risk of knee OA in women [odds ratio (OR) 1.23; P=0.04]. The CC genotype at rs2234693 tended to be associated with reduced OA risk in women (OR 0.76, P=0.028, for knee OA; OR=0.84, P=0.076 for hip OA), but with increased risk of hip OA in men (OR 1.28; P=0.029). Women with unfavourable genotypes at both loci had an OR of 1.61 for knee OA (P=0.006). The rs1062033 genotype associated with higher OA risk was also associated with reduced expression of the aromatase gene in bone. CONCLUSIONS: Common genetic variations of the aromatase and ER genes are associated with the risk of severe OA of the large joints of the lower limb in a sex-specific manner. These results are consistent with the hypothesis that estrogen activity may influence the development of large-joint OA

Replication of PTPRC as genetic biomarker of response to TNF inhibitors in patients with rheumatoid arthritis

Genetic biomarkers could be useful for orienting treatment of patients with rheumatoid arthritis (RA), but none has been convincingly validated yet. Putative biomarkers include 14 single nucleotide polymorphisms that have shown association with response to TNF inhibitors (TNFi) in candidate gene studies and that we assayed here in 755 RA patients. Three of them, in the PTPRC, IL10 and CHUK genes, were significantly associated with response to TNFi. The most significant result was obtained with rs10919563 in PTPRC, which is a confirmed RA susceptibility locus. Its RA risk allele was associated with improved response (B=0.33, P=0.006). This is the second independent replication of this biomarker (P=9.08 × 10 -8 in the combined 3003 RA patients). In this way, PTPRC has become the most replicated genetic biomarker of response to TNFi. In addition, the positive but weaker replication of IL10 and CHUK should stimulate further validation studies. © 2016 Macmillan Publishers Limited

Anticoagulant selection in relation to the SAMe-TT2R2 score in patients with atrial fibrillation: The GLORIA-AF registry

Aim: The SAMe-TT2R2 score helps identify patients with atrial fibrillation (AF) likely to have poor anticoagulation control during anticoagulation with vitamin K antagonists (VKA) and those with scores >2 might be better managed with a target-specific oral anticoagulant (NOAC). We hypothesized that in clinical practice, VKAs may be prescribed less frequently to patients with AF and SAMe-TT2R2 scores >2 than to patients with lower scores. Methods and results: We analyzed the Phase III dataset of the Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF), a large, global, prospective global registry of patients with newly diagnosed AF and ≥1 stroke risk factor. We compared baseline clinical characteristics and antithrombotic prescriptions to determine the probability of the VKA prescription among anticoagulated patients with the baseline SAMe-TT2R2 score >2 and ≤ 2. Among 17,465 anticoagulated patients with AF, 4,828 (27.6%) patients were prescribed VKA and 12,637 (72.4%) patients an NOAC: 11,884 (68.0%) patients had SAMe-TT2R2 scores 0-2 and 5,581 (32.0%) patients had scores >2. The proportion of patients prescribed VKA was 28.0% among patients with SAMe-TT2R2 scores >2 and 27.5% in those with scores ≤2. Conclusions: The lack of a clear association between the SAMe-TT2R2 score and anticoagulant selection may be attributed to the relative efficacy and safety profiles between NOACs and VKAs as well as to the absence of trial evidence that an SAMe-TT2R2-guided strategy for the selection of the type of anticoagulation in NVAF patients has an impact on clinical outcomes of efficacy and safety. The latter hypothesis is currently being tested in a randomized controlled trial. Clinical trial registration: URL: https://www.clinicaltrials.gov//Unique identifier: NCT01937377, NCT01468701, and NCT01671007. © 2020 Hellenic Society of Cardiolog