Intentional and unintentional medication nonadherence in psoriasis: the role of patients’ medication beliefs and habit strength [abstract only]

The accurate diagnosis of psoriasis has remained a challenge, as no disease-specific biomarkers have yet been identified. Currently, the diagnosis of chronic inflammatory diseases relies mainly on the assessment of visible symptoms or the histological features of the biopsy. This approach is heavily reliant on the experience of the clinician and, therefore, may lead to misdiagnosis as there are numerous different chronic inflammatory skin diseases that may present similar clinical features. Hence, the need for diagnostic biomarkers is clear. Although different investigations have reported the discovery of potential psoriasis biomarkers, still no accurate and reliable biomarker is available. Rather than searching for a single valid biomarker, we propose that applying a multicomponent bio-marker-based approach would result in a higher degree of success and translation into clinical practice. An extensive review of published studies to identify the most relevant psoriasis-specific biomarker candidates was conducted. This led us to conclude that the expression levels of specific genes in the skin hold the most promise as discriminatory biomarkers, resulting in the selection of five genes, the expression levels of which have been demonstrated to be exclusive for psoriasis vulgaris. We first conducted a preliminary validation study applying support vector machine-based classification and principle component analysis on the skin-derived expression data of 12 patients with psoriasis vulgaris and 12 healthy controls, previously produced in our departments. We then confirmed that the expression levels of the five genes in psoriatic lesions indeed present a unique pattern. Encouraged by these results, we continued to develop a quantitative polymerase chain reaction panel to allow the accurate measurement of expression levels for the five genes to be used in the studies to follow. Although we have yet to confirm these results in the context of other chronic inflammatory skin diseases, the results of previously published studies regarding these five genes are promising. Therefore, we are in the process of collecting additional skin samples from patients with chronic inflammatory disease (including different papulosquamous disorders and atopic dermatitis) to validate the discriminatory power of our panel. These results may further be translated to viable clinical diagnostic tests in the near future. This work was supported by the ERA Chair for Translational Genomics and Personalized Medicine at the University of Tartu

Demography, baseline disease characteristics and treatment history of patients with psoriasis enrolled in a multicentre, prospective, disease-based registry (PSOLAR)*

Summary Background: Psoriasis is associated with several comorbidities and behavioural risk factors. Objectives: To evaluate demographic and disease characteristics in patients enrolled in the Psoriasis Longitudinal Assessment and Registry (PSOLAR). Methods: PSOLAR is a global, prospective, longitudinal, disease-based registry that includes a postmarketing commitment to evaluate safety in patients with psoriasis. Enrolled patients had to be receiving, or be eligible to receive, conventional systemic or biological agents. Demographic/disease characteristics, medical histories, lifestyle risk factors and previous treatments are collected at enrolment. Efficacy and safety data are collected every 6 months for 8 years, and data are extracted annually. Selected parameters are evaluated by age quartile using post hoc analyses. Results: As of 23 August 2012, 11 900 patients were enrolled at 301 sites in North America, Europe and Latin America. Over half of the PSOLAR population (54·7%) is male, with a mean age of 48·6 years and mean body mass index of 30·9 kg m−2 at enrolment. Mean duration of disease at enrolment was 17·5 years, and mean Physician's Global Assessment score was 2·0. Psoriatic arthritis (35·5%) and cardiovascular diseases (38·2%) were highly prevalent. Diabetes mellitus type II was reported in 11·4% of patients. Depression and anxiety were noted in 14·7% and 11·1% of patients, respectively; 79·0% reported any alcohol use and 56·7% reported smoking or a history of smoking. The occurrence of most comorbidities, including cardiovascular disease and risk factors, increased with age. Conclusions: In the PSOLAR population, multiple and age-appropriate comorbidities are associated with psoriasis and may affect the selection of psoriasis treatments. What's already known about this topic? Psoriasis is a complicated disorder, often accompanied by multiple comorbidities. Demographic and disease characteristics of patients with psoriasis reported from large claims datasets may be affected by misclassification bias or coding errors. In clinical trials, many patients are excluded owing to strict inclusion criteria. What does this study add? Data collected by the Psoriasis Longitudinal Assessment and Registry reveal that the demographics and disease characteristics of patients with psoriasis who are receiving, or are candidates for, systemic therapy in actual clinical care resemble those reported in clinical trials. Most comorbidities occur more frequently in older patients, who, in turn, may require more comprehensive overall medical care

Characteristics and outcomes of patients treated with apremilast in the real world: results from the APPRECIATE study

Background APPRECIATE is a multinational, observational, retrospective, cross‐sectional study in patients treated for psoriasis with apremilast, an oral phosphodiesterase 4 inhibitor. Objectives To describe the characteristics of patients with psoriasis treated with apremilast in the clinical setting, to evaluate real‐world outcomes of psoriasis treatment with apremilast and to better understand the perspectives of patients and physicians on treatment outcomes. Methods In six European countries, patients with chronic plaque psoriasis treated in clinical practice who could be contacted 6 (±1) months after apremilast initiation were enrolled. Patient characteristics, Dermatology Life Quality Index (DLQI) and Psoriasis Area and Severity Index (PASI) were obtained from medical records when available. Outcomes were evaluated using patient/physician questionnaires. Results In 480 patients at treatment initiation, mean [median; 95% confidence interval (CI)] PASI and DLQI scores were 12.5 (10.7; 11.6–13.4) and 13.4 (13.0; 11.4–14.2), respectively. At 6 (±1) months, 72.3% of patients (n = 347) continued apremilast treatment [discontinuations: lack of efficacy (13.5%), safety (11.7%), other (2.5%)]. In patients continuing treatment, 48.6% achieved a ≥75% reduction in PASI score; mean (95% CI) DLQI score was 5.7 (4.5–6.9), and mean (SD) Patient Benefit Index score was 2.8 (1.2). Physicians perceived clinical improvement in 75.6% of patients. Physicians’ perspective on overall success of apremilast in meeting expectations correlated with patients’ perception of treatment benefit (r = 0.691). Most commonly reported adverse events (>5% of patients) were diarrhoea, nausea and headache. Conclusions Patients in APPRECIATE reported high disease burden despite more moderate skin involvement than those who enrolled in clinical trials of apremilast. Findings from APPRECIATE demonstrate the real‐world value of apremilast for psoriasis treatment, as 7 of 10 patients continued therapy and showed notable improvement in disease severity and quality of life 6 (±1) months after apremilast initiation

Interdecadal Pacific Oscillation reconstructed from trans-Pacific tree rings: 1350–2004 CE

The interdecadal Pacific Oscillation (IPO) represents the decadal mode of the El Niño-Southern Oscillation phenomenon. As such the IPO is one of the dominant modes of decadal climate variability on both sides of the Pacific Ocean basin. For this paper we utilized a newly developed tree-ring data network comprised of five multi-centennial Vietnamese cypress ring-width chronologies that range from around 11°N–23°N latitude. We combined these data with an average of tree-ring derived drought indices from the North American Drought Atlas over the south central USA, from a box that spans from 27.5°N–35.0°N, 85.0°–110.0°W and contains 55 gridpoints and more than 100 tree ring site chronologies, these 2 locations exhibit rainfall variations that are strongly, negatively correlated with each other and are representative of the influence of the IPO on terrestrial rainfall. The final reconstruction model, weighted most heavily on the three most southerly of the five Vietnamese cypress records, spans from 1350 to 2004, and explains nearly 57% of the variance in the original IPO data for the 5-month season of October–February. The reconstruction model passes all standard statistical tests using a split calibrationverification scheme. We reveal 15 positive and 15 negative phase shifts of the IPO prior to the period of instrumentation, suggesting that the IPO has been active for at least the past seven centuries with varying degrees of intensity. We compare our reconstruction with two related millennial records: the MacDonald and Case (Geophys Res Lett 32(8):L08703, 2005) tree ring-derived reconstruction of the Pacific Decadal Oscillation, and an ice core-derived reconstruction of the IPO from the Law Dome Ice core in Antarctica by Vance et al. (Geophys Res Lett 33(6):L06712, 2015). While there is good general agreement with the latter record, there are three key periods of the past where the two records are out of phase, and we explore the reasons for this disparity. Direct comparison with the related Tripole Index (TPI) shows weaker correlation, likely owing to the stronger relationship between our tree ring data and the equatorial Pacific region relative to the north and south regions of the Pacific that combine to comprise the TPI calculation

Pre-instrumental perspectives on Arkansas River cross-watershed flow variability

We present four reconstruction estimates of Arkansas River baseflow and streamflow using a total of 78 tree-ring chronologies for three streamflow gages, geographically spanning the headwaters in Colorado to near the confluence of the Arkansas-Mississippi rivers. The estimates represent different seasonal windows, which are dictated by the shared limiting forcing of precipitation on seasonal tree growth and soil moisture—and subsequently on the variability of Arkansas River discharge. Flow extremes that were higher and lower than what has been observed in the instrumental era are recorded in each of the four reconstructions. Years of concurrent, cross-basin (all sites) low flow appear more frequently during the 20th and 21st Centuries compared to any period since 1600 A.D., however, no significant trend in cross-basin low flow is observed. As the most downstream major tributary of the Mississippi River, the Arkansas River directly influences flood risk in the Lower Mississippi River Valley. Estimates of extreme high flow in downstream reconstructions coincide with specific years of historic flooding documented in New Orleans, Louisiana, just upstream of the Mississippi River Delta. By deduction, Mississippi River flooding in years of low Arkansas River flow imply exceptional flooding contributions from the Upper Mississippi River catchments

A Microcalorimeter and Bolometer Model

The standard non-equilibrium theory of noise in ideal bolometers and microcalorimeters fails to predict the performance of real devices due to additional effects that become important at low temperature. In this paper we extend the theory to include the most important of these effects, and find that the performance of microcalorimeters operating at 60 mK can be quantitatively predicted. We give a simple method for doing the necessary calculations, borrowing the block diagram formalism from electronic control theory.Comment: 20 pages, 15 figure

Multipixel characterization of imaging CZT detectors for hard X-ray imaging and spectroscopy

We report our in-depth study of Cd-Zn-Te (CZT) crystals to determine an optimum pixel and guard band configuration for Hard X-ray imaging and spectroscopy. We tested 20x20x5mm crystals with 8x8 pixels on a 2.46mm pitch. We have studied different types of cathode / anode contacts and different pixel pad sizes. We present the measurements of leakage current as well as spectral response for each pixel. Our I-V measurement setup is custom designed to allow automated measurements of the I-V curves sequentially for all 64 pixels, whereas the radiation properties measurement setup allows for interchangeable crystals with the same XAIM3.2 ASIC readout from IDEAS. We have tested multiple crystals of each type, and each crystal in different positions to measure the variation between individual crystals and variation among the ASIC channels. We also compare the same crystals with and without a grounded guard band deposited on the crystal side walls vs. a floating guard band and compare results to simulations. This study was carried out to find the optimum CZT crystal configuration for prototype detectors for the proposed Black-Hole Finder mission, EXIST.Comment: To appears in the SPIE 2004 proceedings (5540: Hard X-ray and gamma-ray detector physics V

Mechanisms of Hemolysis-Associated Platelet Activation

Background Intravascular hemolysis occurs after blood transfusion, in hemolytic anemias, and in other conditions, and is associated with hypercoagulable states. Hemolysis has been shown to potently activate platelets in vitro and in vivo, and several mechanisms have been suggested to account for this, including: (i) direct activation by hemoglobin (Hb); (ii) increase in reactive oxygen species (ROS); (iii) scavenging of nitric oxide (NO) by released Hb; and (iv) release of intraerythrocytic ADP. Objective To elucidate the mechanism of hemolysis-mediated platelet activation. Methods We used flow cytometry to detect PAC-1 binding to activated platelets for in vitro experiments, and a Siemens\u27 Advia 120 hematology system to assess platelet aggregation by using platelet counts from in vivo experiments in a rodent model. Results We found that Hb did not directly activate platelets. However, ADP bound to Hb could cause platelet activation. Furthermore, platelet activation caused by shearing of red blood cells (RBCs) was reduced in the presence of apyrase, which metabolizes ADP to AMP. The use of ROS scavengers did not affect platelet activation. We also found that cell-free Hb enhanced platelet activation by abrogating the inhibitory effect of NO on platelet activation. In vivo infusions of ADP and purified (ADP-free) Hb, as well as hemolysate, resulted in platelet aggregation, as shown by decreased platelet counts. Conclusion Two primary mechanisms account for RBC hemolysis-associated platelet activation: ADP release, which activates platelets; and cell-free Hb release, which enhances platelet activation by lowering NO bioavailability

Laboratory Simulation of Charge Exchange - Produced X-Ray Emission from Comets

In laboratory experiments using the engineering spare microcalorimeter detector from the ASTRO-E satellite mission, we recorded the x-ray emission of highly charged ions of carbon, nitrogen, and oxygen, which simulates charge exchange reactions between heavy ions in the solar wind and neutral gases in cometary comae. the spectra are complex and do not readily match predictions. We developed a charge exchange emission model that successfully reproduces the soft x-ray spectrum of comet Linear C/1999 S4, observed with the Chandra X-ray Observatory