PMS48 Cost-Effectiveness of Tocilizumab for The Management of Inadequately Responding Rheumatoid Arthritis Patients

Weiner, LawrencePrimer pla de l'obra. Tres grans paral·lelepípedes de formigó, amb aparença de sarcòfags.Repartits al llarg de l'avinguda. Tots porten uns versos, escrits el 1845, quan tenia 15 anys, pel premi Nobel Frederic Mistral

Theoretical Characterization of the Interface in a Nonequilibrium Lattice System

The influence of nonequilibrium bulk conditions on the properties of the interfaces exhibited by a kinetic Ising--like model system with nonequilibrium steady states is studied. The system is maintained out of equilibrium by perturbing the familiar spin--flip dynamics at temperature T with completely--random flips; one may interpret these as ideally simulating some (dynamic) impurities. We find evidence that, in the present case, the nonequilibrium mechanism adds to the basic thermal one resulting on a renormalization of microscopic parameters such as the probability of interfacial broken bonds. On this assumption, we develop theory for the nonequilibrium "surface tension", which happens to show a non--monotonous behavior with a maximum at some finite T. It ensues, in full agreement with Monte Carlo simulations, that interface fluctuations differ qualitatively from the equilibrium case, e.g., the interface remains rough at zero--T. We discuss on some consequences of these facts for nucleation theory, and make some explicit predictions concerning the nonequilibrium droplet structure.Comment: 10 pages, 7 figures, submitted to Phys. Re

Clinical characteristics and patient-reported outcomes in patients with inadequately controlled rheumatoid arthritis despite ongoing treatment

Background Despite the wide array of treatments available for rheumatoid arthritis (RA), some patients continue to report unmet clinical needs. We investigated the extent of inadequate disease control in patients with RA. Methods Data were drawn from the Adelphi 2014 RA Disease-Specific Program in France, Germany, Italy, Spain and the UK. Rheumatologists provided patient demographics, comorbidities, satisfaction with RA control and other clinical details. Patients reported their level of satisfaction and completed the EuroQoL 5-Dimensions Health Questionnaire and Work Productivity and Activity Impairment Questionnaire. Patients had been on their current therapy 653 months and had 28-joint disease activity scores (DAS28) reported. Adequately controlled (DAS28 643.2) and inadequately controlled (DAS28 >3.2) patient cohorts were compared using univariate tests. Results Of 1147 patients, 74% were women, the mean age was 52 years and the mean time since RA diagnosis was 7 years. Twenty-seven percent of patients had inadequately controlled RA, whereas 73% had adequately controlled RA. Inadequately controlled patients were more affected clinically versus adequately controlled patients; 69% vs 13% had moderate/severe RA, the current level of pain was 4.6 vs 2.3, and 67% vs 41% experienced flares, respectively (all p<0.0001). Inadequately controlled patients had higher rates of depression (16% vs 5%; p<0.0001), worse health state, greater work and activity impairment, and lower satisfaction rates among the patients and their physicians than the adequately controlled cohort. Conclusion RA was insufficiently controlled in over a quarter of patients despite their current therapy and this had a negative impact on the patients

Clinical activity of ipilimumab for metastatic uveal melanoma: a retrospective review of the Dana-Farber Cancer Institute, Massachusetts General Hospital, Memorial Sloan-Kettering Cancer Center, and University Hospital of Lausanne experience.

BACKGROUND: Uveal melanoma exhibits a high incidence of metastases; and, to date, there is no systemic therapy that clearly improves outcomes. The anticytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) antibody ipilimumab is a standard of care for metastatic melanoma; however, the clinical activity of CTLA-4 inhibition in patients with metastatic uveal melanoma is poorly defined. METHODS: To assess ipilimumab in this setting, the authors performed a multicenter, retrospective analysis of 4 hospitals in the United States and Europe. Clinical characteristics, toxicities, and radiographic disease burden, as determined by central, blinded radiology review, were evaluated. RESULTS: Thirty-nine patients with uveal melanoma were identified, including 34 patients who received 3 mg/kg ipilimumab and 5 who received 10 mg/kg ipilimumab. Immune-related response criteria and modified World Health Organization criteria were used to assess the response rate (RR) and the combined response plus stable disease (SD) rate after 12 weeks, after 23 weeks, and overall (median follow-up, 50.4 weeks [12.6 months]). At week 12, the RR was 2.6%, and the response plus SD rate was 46.%; at week 23, the RR was 2.6%, and the response plus SD rate was 28.2%. There was 1 complete response and 1 late partial response (at 100 weeks after initial SD) for an immune-related RR of 5.1%. Immune-related adverse events were observed in 28 patients (71.8%) and included 7 (17.9%) grade 3 and 4 events. Immune-related adverse events were more frequent in patients who received 10 mg/kg ipilimumab than in those who received 3 mg/kg ipilimumab. The median overall survival from the first dose of ipilimumab was 9.6 months (95% confidence interval, 6.3-13.4 months; range, 1.6-41.6 months). Performance status, lactate dehydrogenase level, and an absolute lymphocyte count ≥ 1000 cells/μL at week 7 were associated significantly with survival. CONCLUSIONS: In this multicenter, retrospective analysis of 4 hospitals in the United States and Europe of patients with uveal melanoma, durable responses to ipilimumab and manageable toxicity were observed

Citizen Science 2.0 : Data Management Principles to Harness the Power of the Crowd

Citizen science refers to voluntary participation by the general public in scientific endeavors. Although citizen science has a long tradition, the rise of online communities and user-generated web content has the potential to greatly expand its scope and contributions. Citizens spread across a large area will collect more information than an individual researcher can. Because citizen scientists tend to make observations about areas they know well, data are likely to be very detailed. Although the potential for engaging citizen scientists is extensive, there are challenges as well. In this paper we consider one such challenge – creating an environment in which non-experts in a scientific domain can provide appropriate and accurate data regarding their observations. We describe the problem in the context of a research project that includes the development of a website to collect citizen-generated data on the distribution of plants and animals in a geographic region. We propose an approach that can improve the quantity and quality of data collected in such projects by organizing data using instance-based data structures. Potential implications of this approach are discussed and plans for future research to validate the design are described

Quaternion-Octonion Unitary Symmetries and Analogous Casimir Operators

An attempt has been made to investigate the global SU(2) and SU(3) unitary flavor symmetries systematically in terms of quaternion and octonion respectively. It is shown that these symmetries are suitably handled with quaternions and octonions in order to obtain their generators, commutation rules and symmetry properties. Accordingly, Casimir operators for SU(2)and SU(3) flavor symmetries are also constructed for the proper testing of these symmetries in terms of quaternions and octonions

Strange Meson Enhancement in PbPb Collisions

The NA44 Collaboration has measured yields and differential distributions of K+, K-, pi+, pi- in transverse kinetic energy and rapidity, around the center-of-mass rapidity in 158 A GeV/c Pb+Pb collisions at the CERN SPS. A considerable enhancement of K+ production per pi is observed, as compared to p+p collisions at this energy. To illustrate the importance of secondary hadron rescattering as an enhancement mechanism, we compare strangeness production at the SPS and AGS with predictions of the transport model RQMD.Comment: 11 pages, including 4 figures, LATE

Barriers to genetic testing in clinical psychiatry and ways to overcome them: from clinicians’ attitudes to sociocultural differences between patients across the globe

Genetic testing has evolved rapidly over recent years and new developments have the potential to provide insights that could improve the ability to diagnose, treat, and prevent diseases. Information obtained through genetic testing has proven useful in other specialties, such as cardiology and oncology. Nonetheless, a range of barriers impedes techniques, such as whole-exome or whole-genome sequencing, pharmacogenomics, and polygenic risk scoring, from being implemented in psychiatric practice. These barriers may be procedural (e.g., limitations in extrapolating results to the individual level), economic (e.g., perceived relatively elevated costs precluding insurance coverage), or related to clinicians’ knowledge, attitudes, and practices (e.g., perceived unfavorable cost-effectiveness, insufficient understanding of probability statistics, and concerns regarding genetic counseling). Additionally, several ethical concerns may arise (e.g., increased stigma and discrimination through exclusion from health insurance). Here, we provide an overview of potential barriers for the implementation of genetic testing in psychiatry, as well as an in-depth discussion of strategies to address these challenges

Dust Devil Tracks

Dust devils that leave dark- or light-toned tracks are common on Mars and they can also be found on the Earth’s surface. Dust devil tracks (hereinafter DDTs) are ephemeral surface features with mostly sub-annual lifetimes. Regarding their size, DDT widths can range between ∼1 m and ∼1 km, depending on the diameter of dust devil that created the track, and DDT lengths range from a few tens of meters to several kilometers, limited by the duration and horizontal ground speed of dust devils. DDTs can be classified into three main types based on their morphology and albedo in contrast to their surroundings; all are found on both planets: (a) dark continuous DDTs, (b) dark cycloidal DDTs, and (c) bright DDTs. Dark continuous DDTs are the most common type on Mars. They are characterized by their relatively homogenous and continuous low albedo surface tracks. Based on terrestrial and martian in situ studies, these DDTs most likely form when surficial dust layers are removed to expose larger-grained substrate material (coarse sands of ≥500 μm in diameter). The exposure of larger-grained materials changes the photometric properties of the surface; hence leading to lower albedo tracks because grain size is photometrically inversely proportional to the surface reflectance. However, although not observed so far, compositional differences (i.e., color differences) might also lead to albedo contrasts when dust is removed to expose substrate materials with mineralogical differences. For dark continuous DDTs, albedo drop measurements are around 2.5 % in the wavelength range of 550–850 nm on Mars and around 0.5 % in the wavelength range from 300–1100 nm on Earth. The removal of an equivalent layer thickness around 1 μm is sufficient for the formation of visible dark continuous DDTs on Mars and Earth. The next type of DDTs, dark cycloidal DDTs, are characterized by their low albedo pattern of overlapping scallops. Terrestrial in situ studies imply that they are formed when sand-sized material that is eroded from the outer vortex area of a dust devil is redeposited in annular patterns in the central vortex region. This type of DDT can also be found in on Mars in orbital image data, and although in situ studies are lacking, terrestrial analog studies, laboratory work, and numerical modeling suggest they have the same formation mechanism as those on Earth. Finally, bright DDTs are characterized by their continuous track pattern and high albedo compared to their undisturbed surroundings. They are found on both planets, but to date they have only been analyzed in situ on Earth. Here, the destruction of aggregates of dust, silt and sand by dust devils leads to smooth surfaces in contrast to the undisturbed rough surfaces surrounding the track. The resulting change in photometric properties occurs because the smoother surfaces have a higher reflectance compared to the surrounding rough surface, leading to bright DDTs. On Mars, the destruction of surficial dust-aggregates may also lead to bright DDTs. However, higher reflective surfaces may be produced by other formation mechanisms, such as dust compaction by passing dust devils, as this may also cause changes in photometric properties. On Mars, DDTs in general are found at all elevations and on a global scale, except on the permanent polar caps. DDT maximum areal densities occur during spring and summer in both hemispheres produced by an increase in dust devil activity caused by maximum insolation. Regionally, dust devil densities vary spatially likely controlled by changes in dust cover thicknesses and substrate materials. This variability makes it difficult to infer dust devil activity from DDT frequencies. Furthermore, only a fraction of dust devils leave tracks. However, DDTs can be used as proxies for dust devil lifetimes and wind directions and speeds, and they can also be used to predict lander or rover solar panel clearing events. Overall, the high DDT frequency in many areas on Mars leads to drastic albedo changes that affect large-scale weather patterns

Factors influencing the use of biologic therapy and adoption of treat-to-target recommendations in current european rheumatology practice

Objective: The aim of this study was to identify factors that influence treatment adjustments and adoption of a treat-to-target (T2T) strategy in patients with rheumatoid arthritis (RA) in European practices. Methods: Cross-sectional data were drawn from the Adelphi 2014 RA Disease Specific Programme. Treatment patterns and clinical characteristics were investigated in patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) vs non-bDMARDs. For the T2T analysis, patients were subdivided into two subsets (RA diagnosis <2 or 652 years) and compared according to the approach used (no target = no T2T approach; pragmatic = target different from remission; and aspirational = target set as remission). Results: Data from 2,536 patients were analyzed (mean age: 52.76 years and mean time since RA diagnosis: 6.05 years). Of the 1,438 patients eligible to receive bDMARDs, 55% did not receive them. Initiation of bDMARDs in a bDMARD-na\uefve patient was prompted by worsening of the disease. In the RA diagnosis <2 years subset, a T2T approach was not adopted in 58% of the patients, whereas 8% and 34% adopted a pragmatic and aspirational approach, respectively. In the RA diagnosis 652 years subset, 45%, 19%, and 36% of the patients adopted a no target, pragmatic, and aspirational approach, respectively. Physician satisfaction with RA control was lower in the RA diagnosis <2 years subset than in the RA diagnosis 652 years subset (65% vs 77% satisfied, respectively; P<0.0001). Conclusion: This analysis shows that the use of bDMARDs remains suboptimal and that a T2T strategy is not universally adopted