398 research outputs found

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

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    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

    North American megadroughts in the Common Era: reconstructions and simulations

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    During the Medieval Climate Anomaly (MCA), Western North America experienced episodes of intense aridity that persisted for multiple decades or longer. These megadroughts are well documented in many proxy records, but the causal mechanisms are poorly understood. General circulation models (GCMs) simulate megadroughts, but do not reproduce the temporal clustering of events during the MCA, suggesting they are not caused by the time history of volcanic or solar forcing. Instead, GCMs generate megadroughts through (1) internal atmospheric variability, (2) sea-surface temperatures, and (3) land surface and dust aerosol feedbacks. While no hypothesis has been definitively rejected, and no GCM has accurately reproduced all features (e.g., timing, duration, and extent) of any specific megadrought, their persistence suggests a role for processes that impart memory to the climate system (land surface and ocean dynamics). Over the 21st century, GCMs project an increase in the risk of megadrought occurrence through greenhouse gas forced reductions in precipitation and increases in evaporative demand. This drying is robust across models and multiple drought indicators, but major uncertainties still need to be resolved. These include the potential moderation of vegetation evaporative losses at higher atmospheric [CO₂], variations in land surface model complexity, and decadal to multidecadal modes of natural climate variability that could delay or advance onset of aridification over the the next several decades. Because future droughts will arise from both natural variability and greenhouse gas forced trends in hydroclimate, improving our understanding of the natural drivers of persistent multidecadal megadroughts should be a major research priority

    Management and outcome of patients with established coronary artery disease: the Euro Heart Survey on coronary revascularization

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    Aims The purpose of the Euro Heart Survey Programme of the European Society of Cardiology is to evaluate to which extent clinical practice endorses existing guidelines as well as to identify differences in population profiles, patient management, and outcome across Europe. The current survey focuses on the invasive diagnosis and treatment of patients with established coronary artery disease (CAD). Methods and results Between November 2001 and March 2002, 7769 consecutive patients undergoing invasive evaluation at 130 hospitals (31 countries) were screened for the presence of one or more coronary stenosis >50% in diameter. Patient demographics and comorbidity, clinical presentation, invasive parameters, treatment options, and procedural techniques were prospectively entered in an electronic database (550 variables+29 per diseased coronary segment). Major adverse cardiac events (MACE) were evaluated at 30 days and 1 year. Out of 5619 patients with angiographically proven coronary stenosis (72% of screened population), 53% presented with stable angina while ST elevation myocardial infarction (STEMI) was the indication for coronary angiography in 16% and non-ST segment elevation myocardial infarction or unstable angina in 30%. Only medical therapy was continued in 21%, whereas mechanical revascularization was performed in the remainder [percutaneous coronary intervention (PCI) in 58% and coronary artery bypass grafting (CABG) in 21%]. Patients referred for PCI were younger, were more active, had a lower risk profile, and had less comorbid conditions. CABG was performed mostly in patients with left main lesions (21%), two- (25%), or three-vessel disease (67%) with 4.1 diseased segments, on average. Single-vessel PCI was performed in 82% of patients with either single- (45%), two- (33%), or three-vessel disease (21%). Stents were used in 75% of attempted lesions, with a large variation between sites. Direct PCI for STEMI was performed in 410 cases, representing 7% of the entire workload in the participating catheterization laboratories. Time delay was within 90 min in 76% of direct PCI cases. In keeping with the recommendations of practice guidelines, the survey identified under-use of adjunctive medication (GP IIb/IIIa receptor blockers, statins, and angiotensin-converting enzyme-inhibitors). Mortality rates at 30 days and 1 year were low in all subgroups. MACE primarily consisted of repeat PCI (12%). Conclusion The current Euro Heart Survey on coronary revascularization was performed in the era of bare metal stenting and provides a global European picture of the invasive approach to patients with CAD. These data will serve as a benchmark for the future evaluation of the impact of drug-eluting stents on the practice of interventional cardiology and bypass surger

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

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    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

    Causes of Death Following PCI Versus CABG in Complex CAD 5-Year Follow-Up of SYNTAX

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    AbstractBackgroundThere are no data available on specific causes of death from randomized trials that have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI).ObjectivesThe purpose of this study was to investigate specific causes of death, and its predictors, after revascularization for complex coronary disease in patients.MethodsAn independent Clinical Events Committee consisting of expert physicians who were blinded to the study treatment subclassified causes of death as cardiovascular (cardiac and vascular), noncardiovascular, or undetermined according to the trial protocol. Cardiac deaths were classified as sudden cardiac, related to myocardial infarction (MI), and other cardiac deaths.ResultsIn the randomized cohort, there were 97 deaths after CABG and 123 deaths after PCI during a 5-year follow-up. After CABG, 49.4% of deaths were cardiovascular, with the greatest cause being heart failure, arrhythmia, or other causes (24.6%), whereas after PCI, the majority of deaths were cardiovascular (67.5%) and as a result of MI (29.3%). The cumulative incidence rates of all-cause death were not significantly different between CABG and PCI (11.4% vs. 13.9%, respectively; p = 0.10), whereas there were significant differences in terms of cardiovascular (5.8% vs. 9.6%, respectively; p = 0.008) and cardiac death (5.3% vs. 9.0%, respectively; p = 0.003), which were caused primarily by a reduction in MI-related death with CABG compared with PCI (0.4% vs. 4.1%, respectively; p <0.0001). Treatment with PCI versus CABG was an independent predictor of cardiac death (hazard ratio: 1.55; 95% confidence interval: 1.09 to 2.33; p = 0.045). The difference in MI-related death was seen largely in patients with diabetes, 3-vessel disease, or high SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries) trial scores.ConclusionsDuring a 5-year follow-up, CABG in comparison with PCI was associated with a significantly reduced rate of MI-related death, which was the leading cause of death after PCI. Treatments following PCI should target reducing post-revascularization spontaneous MI. Furthermore, secondary preventive medication remains essential in reducing events post-revascularization. (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972

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

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    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

    Correlation Between Bulk Material Defects and Spectroscopic Response in Cadmium Zinc Telluride Detectors

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    One of the critical challenges for large area cadmium zinc telluride (CdZnTe) detector arrays is obtaining material capable of uniform imaging and spectroscopic response. Two complementary nondestructive techniques for characterizing bulk CdZnTe have been developed to identify material with a uniform response. The first technique, infrared transmission imaging, allows for rapid visualization of bulk defects. The second technique, x-ray spectral mapping, provides a map of the material spectroscopic response when it is configured as a planar detector. The two techniques have been used to develop a correlation between bulk defect type and detector performance. The correlation allows for the use of infrared imaging to rapidly develop wafer mining maps. The mining of material free of detrimental defects has the potential to dramatically increase the yield and quality of large area CdZnTe detector arrays

    Visualization and assessment of saccular duct and endolymphatic sinus

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    Conclusion: The saccular duct and endolymphatic sinus run in the bony groove, before reaching the orifice of the vestibular aqueduct. We first clinically visualized this sulciform groove using three-dimensional (3D) cone beam CT images. This strategy can be useful to assess the condition of the saccular duct and endolymphatic sinus concerning the longitudinal flow system of endolymph. Objective: To assess the saccular duct and endolymphatic sinus in the endolymphatic system in order to advance clinical studies on inner ear dysfunction. Methods: The sulciform groove of the saccular duct and endolymphatic sinus of human subjects was analyzed by cone beam CT and compared with that of a cadaver. Results: We could obtain reconstructed 3D CT images of the sulciform groove of the saccular duct and endolymphatic sinus using several CT window levels
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