Implementation of a Pharmacist-Led Patient-Controlled Analgesia Dosing Service.

PURPOSE: The development and implementation of a pharmacist-led patient-controlled analgesia (PCA) dosing service in a large academic institution are described. SUMMARY: To improve pain management at our institution and expand pharmacy clinical services, a pharmacist-led PCA dosing service was developed and implemented. The service is modeled after established antimicrobial and anticoagulation dosing services at our institution. A core group of pharmacists (service leaders) and a pain physician champion developed a policy and guideline and designed electronic medical record (EMR) tools to support the service. Pharmacists were trained by the service leaders to manage acute pain with fentanyl, hydromorphone, or morphine PCA therapy. Cultural and operational barriers to service implementation were identified and resolved. CONCLUSION: After implementation of the pharmacist-led PCA dosing service, pharmacists at our institution provide PCA pain management services as part of our pharmacy department's standard practice.

Estimating the neutron yield in a deuterium plasma with the JET neutron camera.

The JET neutron camera is a well-established detector system at JET, which has 19 sightlines each equipped with a liquid scintillator. The system measures a 2D profile of the neutron emission from the plasma. A first principle physics method is used to estimate the DD neutron yield that is based on JET neutron camera measurements and is independent of other neutron measurements. This paper details the data reduction techniques, models of the neutron camera, simulations of neutron transport, and detector responses used to this end. The estimate uses a simple parameterized model of the neutron emission profile. The method makes use of the JET neutron camera's upgraded data acquisition system. It also accounts for neutron scattering near the detectors and transmission through the collimator. These components together contribute to 9% of the detected neutron rate above a 0.5 MeVee energy threshold. Despite the simplicity of the neutron emission profile model, the DD neutron yield estimate falls on average within 10% agreement with a corresponding estimate from the JET fission chambers. The method can be improved by considering more advanced neutron emission profiles. It can also be expanded to estimate the DT neutron yield with the same methodology.

NEUTRON RADIATION DAMAGE IN CCD CAMERAS AT JOINT EUROPEAN TORUS (JET).

The neutron and gamma radiations in large fusion reactors are responsible for damage to charged couple device (CCD) cameras deployed for applied diagnostics. Based on the ASTM guide E722-09, the 'equivalent 1 MeV neutron fluence in silicon' was calculated for a set of CCD cameras at the Joint European Torus. Such evaluations would be useful to good practice in the operation of the video systems.

Synthesis and Evaluation of the First Fluorescent Antagonists of the Human P2Y2 Receptor Based on AR-C118925.

The human P2Y2 receptor ( hP2Y2R) is a G-protein-coupled receptor that shows promise as a therapeutic target for many important conditions, including for antimetastatic cancer and more recently for idiopathic pulmonary fibrosis. As such, there is a need for new hP2Y2R antagonists and molecular probes to study this receptor. Herein, we report the development of a new series of non-nucleotide hP2Y2R antagonists, based on the known, non-nucleotide hP2Y2R antagonist AR-C118925 (1), leading to the discovery of a series of fluorescent ligands containing different linkers and fluorophores. One of these conjugates, 98, displayed micromolar affinity for hP2Y2R (p Kd = 6.32 ± 0.10, n = 17) in a bioluminescence-energy-transfer (BRET) assay. Confocal microscopy with this ligand revealed displaceable membrane labeling of astrocytoma cells expressing untagged hP2Y2R. These properties make 98 one of the first tools for studying hP2Y2R distribution and organization.

Drug-like Antagonists of P2Y Receptors-From Lead Identification to Drug Development.

P2Y receptors are expressed in virtually all cells and tissue types and mediate an astonishing array of biological functions, including platelet aggregation, smooth muscle cell proliferation, and immune regulation. The P2Y receptors belong to the G protein-coupled receptor superfamily and are composed of eight members encoded by distinct genes that can be subdivided into two groups on the basis of their coupling to specific G-proteins. Extensive research has been undertaken to find modulators of P2Y receptors, although to date only a limited number of small-molecule P2Y receptor antagonists have been approved by drug/medicines agencies. This Perspective reviews the known P2Y receptor antagonists, highlighting oral drug-like receptor antagonists, and considers future opportunities for the development of small molecules for clinical evaluation.

Identification and management of pain medication abuse and misuse: current state and future directions.

Long-term opioid therapy poses a risk for abuse and misuse in some patients. Identifying which patients may potentially be at risk prior to initiation of therapy, and identifying patients in whom these problems develop during therapy, are significant challenges. Outcome prediction is impeded by the complexity of the problem, where considerable heterogeneity results from psychological and socioeconomic factors, as well as interindividual variation in biological pathways due to genetic and epigenetic factors. Screening tools designed to detect opioid misuse and urine drug testing are both used clinically; scant evidence currently exists to allow the formulation of an algorithm for judicious use of these tools. Moreover, these tools may not be addressing the underlying alterations in biological pathways that occur owing to the development of chronic pain or in response to chronic opioid administration. An evidence-based algorithmic approach to risk mitigation that can be applied in a cost-effective manner to guide therapy is urgently needed.

Neutron spectrometer for ITER using silicon detectors.

High resolution neutron spectrometers provide information about plasma parameters at existing fusion experiments. Such a system may also be employed at ITER. Proton recoil telescopes have classically been used to detect neutrons with good energy resolution but poor efficiency. Using annular silicon detectors, it is possible to greatly increase the solid angle coverage and hence improve efficiency. Based on a simulation (MCNPX) study, the scaling of energy resolution, efficiency, and time to determine an ion temperature to 10% accuracy on foil thickness and detector location is shown. The latter quantity is used to determine the optimum foil thickness and detector geometry for specific plasma temperatures. For a 20 keV deuterium-tritium (DT) plasma, 5.3% resolution with efficiency of 2.9x10(-4) n cm(2) is attainable using the available detectors. This gives a temperature measurement with 10% accuracy in 1.1 ms for a neutron flux of 2x10(9) n cm(-2). Multiple detectors can be used to further increase the efficiency if needed. A system of this kind could be tested in a future DT campaign at, for example, JET.

The spectrum of Trp- mutants isolated as 5-fluoroanthranilate-resistant clones in Saccharomyces bayanus, S. mikatae and S. paradoxus.

5-Fluoroanthranilic acid (FAA)-resistant mutants were selected in homothallic diploids of three Saccharomyces species, taking care to isolate mutants of independent origin. Mutations were assigned to complementation groups by interspecific complementation with S. cerevisiae tester strains. In all three species, trp3, trp4 and trp5 mutants were recovered. trp1 mutants were also recovered if the selection was imposed on a haploid strain. Thus, FAA selection may be more generally applicable than was previously described.