Quality of care after acute coronary syndromes in a prospective cohort with reasons for non-prescription of recommended medications

BACKGROUND Adherence to guidelines is associated with improved outcomes of patients with acute coronary syndrome (ACS). Clinical registries developed to assess quality of care at discharge often do not collect the reasons for non-prescription for proven efficacious preventive medication in Continental Europe. In a prospective cohort of patients hospitalized for an ACS, we aimed at measuring the rate of recommended treatment at discharge, using pre-specified quality indicators recommended in cardiologic guidelines and including systematic collection of reasons for non-prescription for preventive medications. METHODS In a prospective cohort with 1260 patients hospitalized for ACS, we measured the rate of recommended treatment at discharge in 4 academic centers in Switzerland. Performance measures for medication at discharge were pre-specified according to guidelines, systematically collected for all patients and included in a centralized database. RESULTS Six hundred and eighty eight patients(54.6%) were discharged with a main diagnosis of STEMI, 491(39%) of NSTEMI and 81(6.4%) of unstable angina. Mean age was 64 years and 21.3% were women. 94.6% were prescribed angiotensin converting enzyme inhibitors/angiotensin II receptor blockers at discharge when only considering raw prescription rates, but increased to 99.5% when including reasons non-prescription. For statins, rates increased from 98% to 98.6% when including reasons for non-prescription and for beta-blockers, from 82% to 93%. For aspirin, rates further increased from 99.4% to 100% and from to 99.8% to 100% for P2Y12 inhibitors. CONCLUSIONS We found a very high adherence to ACS guidelines for drug prescriptions at discharge when including reasons for non-prescription to drug therapy. For beta-blockers, prescription rates were suboptimal, even after taking into account reason for non-prescription. In an era of improving quality of care to achieve 100% prescription rates at discharge unless contra-indicated, pre-specification of reasons for non-prescription for cardiovascular preventive medication permits to identify remaining gaps in quality of care at discharge.

Magma Extraction from the Mantle Wedge at Convergent Margins Through Dikes: A Parametric Sensitivity Analysis

We address under what conditions a magma generated by partial melting at 100 km depth in the mantle wedge above a subduction zone can reach the crust in dikes before stalling. We also address under what conditions primitive basaltic magma (Mg # >60) can be delivered from this depth to the crust. We employ linear elastic fracture mechanics with magma solidification theory and perform a parametric sensitivity analysis. All dikes are initiated at a depth of 100 km in the thermal core of the wedge, and the Moho is fixed at 35 km depth. We consider a range of melt solidus temperatures (800-1100 degrees C), viscosities (10-100 Pa s), and densities (2400-2700 kg m(-3)). We also consider a range of host rock fracture toughness values (50-300 MPa m(1/2)) and dike lengths (2-5 km) and two thermal structures for the mantle wedge (1260 and 1400 degrees C at 100 km depth and 760 and 900 degrees C at 35 km depth). For the given parameter space, many dikes can reach the Moho in less than a few hundred hours, well within the time constraints provided by U series isotope disequilibria studies. Increasing the temperature in the mantle wedge, or increasing the dike length, allows additional dikes to propagate to the Moho. We conclude that some dikes with vertical lengths near their critical lengths and relatively high solidus temperatures will stall in the mantle before reaching the Moho, and these may be returned by corner flow to depths where they can melt under hydrous conditions. Thus, a chemical signature in arc lavas suggesting partial melting of slab basalts may be partly influenced by these recycled dikes. Alternatively, dikes with lengths well above their critical lengths can easily deliver primitive magmas to the crust, particularly if the mantle wedge is relatively hot. Dike transport remains a viable primary mechanism of magma ascent in convergent tectonic settings, but the potential for less rapid mechanisms making an important contribution increases as the mantle temperature at the Moho approaches the solidus temperature of the magma.

Career adaptivity, adaptability, and adapting: A conceptual and empirical investigation

The literature on career adaptation is vast and based on a range of different measurement approaches. The present paper aims to explore how different operationalizations of career adaptability in terms of concern, control, curiosity, and confidence are related from a conceptual and empirical standpoint. Based on a cross-sectional analysis with 1260 German university students, we established that the adaptability resources of concern, control, curiosity, and confidence are significantly related to, but empirically distinct from, measures representing adapting in terms of career planning, career decision-making difficulties, career exploration, and occupational self-efficacy. In a follow-up survey six months later, we found that the career adaptability dimensions partially mediated the effects of adaptivity (i.e., core self-evaluations and proactivity) on planning, decision-making difficulties, exploration, and self-efficacy. Interestingly, in both analyses, there was no clear match between adaptability resources and theoretically corresponding aspects of career adapting in terms of behaviors, beliefs, and barriers. The results suggest that psychological career resources in terms of concern, control, curiosity, and confidence partially mediate the effects of more context-general, trait-like adaptivity on different career-specific behavioral forms of adapting.

Achieving a more realistic assessment of rockfall hazards by coupling three-dimensional process models and field-based tree-ring data

Sound knowledge of the spatial and temporal patterns of rockfalls is fundamental for the management of this very common hazard in mountain environments. Process-based, three-dimensional simulation models are nowadays capable of reproducing the spatial distribution of rockfall occurrences with reasonable accuracy through the simulation of numerous individual trajectories on highly-resolved digital terrain models. At the same time, however, simulation models typically fail to quantify the ‘real’ frequency of rockfalls (in terms of return intervals). The analysis of impact scars on trees, in contrast, yields real rockfall frequencies, but trees may not be present at the location of interest and rare trajectories may not necessarily be captured due to the limited age of forest stands. In this article, we demonstrate that the coupling of modeling with tree-ring techniques may overcome the limitations inherent to both approaches. Based on the analysis of 64 cells (40 m × 40 m) of a rockfall slope located above a 1631-m long road section in the Swiss Alps, we illustrate results from 488 rockfalls detected in 1260 trees. We illustrate that tree impact data cannot only be used (i) to reconstruct the real frequency of rockfalls for individual cells, but that they also serve (ii) the calibration of the rockfall model Rockyfor3D, as well as (iii) the transformation of simulated trajectories into real frequencies. Calibrated simulation results are in good agreement with real rockfall frequencies and exhibit significant differences in rockfall activity between the cells (zones) along the road section. Real frequencies, expressed as rock passages per meter road section, also enable quantification and direct comparison of the hazard potential between the zones. The contribution provides an approach for hazard zoning procedures that complements traditional methods with a quantification of rockfall frequencies in terms of return intervals through a systematic inclusion of impact records in trees.

Accuracy of cartilage-specific 3-Tesla 3D-DESS magnetic resonance imaging in the diagnosis of chondral lesions: comparison with knee arthroscopy

BACKGROUND Arthroscopy is considered as "the gold standard" for the diagnosis of traumatic intraarticular knee lesions. However, recent developments in magnetic resonance imaging (MRI) now offer good opportunities for the indirect assessment of the integrity and structural changes of the knee articular cartilage. The study was to investigate whether cartilage-specific sequences on a 3-Tesla MRI provide accurate assessment for the detection of cartilage defects. METHODS A 3-Tesla (3-T) MRI combined with three-dimensional double-echo steady-state (3D-DESS) cartilage specific sequences was performed on 210 patients with knee pain prior to knee arthroscopy. Sensitivity, specificity, and positive and negative predictive values of magnetic resonance imaging were calculated and correlated to the arthroscopic findings of cartilaginous lesions. Lesions were classified using the modified Outerbridge classification. RESULTS For the 210 patients (1260 cartilage surfaces: patella, trochlea, medial femoral condyle, medial tibia, lateral femoral condyle, lateral tibia) evaluated, the sensitivities, specificities, positive predictive values, and negative predictive values of 3-T MRI were 83.3, 99.8, 84.4, and 99.8 %, respectively, for the detection of grade IV lesions; 74.1, 99.6, 85.2, and 99.3 %, respectively, for grade III lesions; 67.9, 99.2, 76.6, and 98.2 %, respectively, for grade II lesions; and 8.8, 99.5, 80, and 92 %, respectively, for grade I lesions. CONCLUSIONS For grade III and IV lesions, 3-T MRI combined with 3D-DESS cartilage-specific sequences represents an accurate diagnostic tool. For grade II lesions, the technique demonstrates moderate sensitivity, while for grade I lesions, the sensitivity is limited to provide reliable diagnosis compared to knee arthroscopy.

Prevalence and risk factors of methicillin-resistant Staphylococcus aureus in critically-ill hospitalized patients in a tertiary care center in Houston, Texas: An active surveillance pilot project

Objective. The objective of this study is to determine the prevalence of MRSA colonization in adult patients admitted to intensive care units at an urban tertiary care hospital in Houston, Texas and to evaluate the risk factors associated with colonization during a three month active-screening pilot project. Design. This study used secondary data from a small cross-sectional pilot project. Methods. All patients admitted to the seven specialty ICUs were screened for MRSA by nasal culture. Results were obtained utilizing the BD GeneOhm™ IDI-MRSA assay in vitro diagnostic test, for rapid MRSA detection. Statistical analysis was performed using the STATA 10, Epi Info, and JavaStat. Results . 1283/1531 (83.4%) adult ICU admissions were screened for nasal MRSA colonization. Of those screened, demographic and risk factor data was available for 1260/1283 (98.2%). Unresolved results were obtained for 73 patients. Therefore, a total of 1187/1531 (77.5%) of all ICU admissions during the three month study period are described in this analysis. Risk factors associated with colonization included the following: hospitalization within the last six months (odds ratio 2.48 [95% CI, 1.70-3.63], p=0.000), hospitalization within the last 12 months, (odds ratio 2.27 [95% CI, 1.57-3.80], p=0.000), and having diabetes mellitus (odds ratio 1.63 [95% CI, 1.14-2.32], p=0.007). Conclusion. Based on the literature, the prevalence of MRSA for this population is typical of other prevalence studies conducted in the United States and coincides with the continual increasing trend of MRSA colonization. Significant risk factors were similar to those found in previous studies. Overall, the active surveillance screening pilot project has provided valuable information on a population not widely addressed. These findings can aid in future interventions for the education, control, prevention, and treatment of MRSA. ^

INDUCED-PLURIPOTENT STEM-DERIVED NEURONAL PROGENITOR CELLS AS A NOVEL TREATMENT FOR NEURODEGENERATIVE DISEASES

Cellular therapies, as neuronal progenitor (NP) cells grafting, are promising therapies for patients affected with neurodegenerative diseases like Creutzfeldt-Jakob Disease (CJD). At this time there is no effective treatment or cure for CJD. The disease is inevitably fatal and affected people usually die within months of the appearance of the first clinical symptoms. Compelling evidence indicate that the hallmark event in the disease is the conversion of the normal prion protein (termed PrPC) into the disease-associated, misfolded form (called PrPSc). Thus, a reasonable therapeutic target would be to prevent PrP misfolding and prion replication. This strategy has been applied with poor results since at the time of clinical intervention substantial brain damage has been done. It seems that a more effective treatment aimed at patients with established symptoms of CJD would need to stop further brain degeneration or even recover some of the previously lost brain tissue. The most promising possibility to recover brain tissue is the use of NPs that have the potential to replenish the nerve cells lost during the early stages of the disease. Advanced cellular therapies, beside their potential for cell replacement, might be used as biomaterials for drug delivery in order to stimulate cell survival or the resolution the disease. Also, implanted cells can be genetically manipulated to correct abnormalities causing disease or to make them more resistant to the toxic microenvironments present in damaged tissue. In recent years cell engineering has been within the scope of the scientific and general community after the development of technologies able to “de-differentiate” somatic cells into induced-pluripotent stem (IPS) cells. This new tool permits the use of easy-to-reach cells like skin or blood cells as a primary material to obtain embryonic stem-like cells for cellular therapies, evading all ethical issues regarding the use of human embryos as a source of embryonic stem cells. The complete work proposes to implant IPS-derived NP cells into the brain of prion-infected animals to evaluate their therapeutic potential. Since it is well known that the expression of prion protein in the cell membrane is necessary for PrPSc mediated toxicity, we also want to determine if NPs lacking the prion protein have better survival rates once implanted into sick animals. The main objective of this work is to develop implantable neural precursor from IPS coming from animals lacking the prion protein. Specific aim 1: To develop and characterize cellular cultures of IPS cells from prp-/- mice. Fibroblasts from prp-/- animals will be reprogrammed using the four Yamanaka factors. IPS colonies will be selected and characterized by immunohistochemistry for markers of pluripotency. Their developmental capabilities will be evaluated by teratoma and embryoid body formation assays. Specific aim 2: To differentiate IPS cells to a neuronal lineage. IPS cells will be differentiated to a NP stage by the use of defined media culture conditions. NP cells will be characterized by their immunohistochemical profile as well as by their ability to differentiate into neuronal cells. Specific aim 3: Cellular labeling of neuronal progenitors cells for in vitro traceability. In order to track the cells once implanted in the host brain, they will be tagged with different methods such as lipophilic fluorescent tracers and transduction with GFP protein expression.

Recent distribution and accumulation of organic carbon on the continental margin west off Spitsbergen

The study compiles the controlling factors for organic matter sedimentation patterns from a suite of organogeochemical parameters in surface sediments off Spitsbergen and direct seabed observations using a Remotely Operated Vehicle (ROV). In addition we assess its storage rates as well as the potential of carbon sinks on the northwestern margin of the Barents Sea with short sediment cores from a selected fjord environment (Storfjord). While sedimentation in the fjords is mainly controlled by river/meltwater discharge and coastal erosion by sea ice/glaciers resulting in high supply of terrigenous organic matter, Atlantic water inflow, and thus enhanced marine organic matter supply, characterizes the environment on the outer shelf and slope. Local deviations from this pattern, particularly on the shelf, are due to erosion and out washing of fine-grained material by bottom currents. Spots dominated by marine productivity close to the island have been found at the outer Isfjord and west off Prins Karls Forland as well as off the Kongsfjord/Krossfjord area and probably reflect local upwelling of nutrient-rich Atlantic water-derived water masses. Accumulation rates of marine organic carbon as well as reconstructed primary productivities decreased since the middle of the last century. Negative correlation of the Isfjord temperature record with reconstructed productivities in the Storfjord could be explained by a reduced annual duration of the marginal ice zone in the area due to global warming. Extremely high accumulation rates of marine organic carbon between 5.4 and 17.2 g/m**2/yr mark the Storfjord area, and probably high-latitude fjord environments in general, as a sink for carbon dioxide.