Cost minimization analysis of different growth hormone pen devices based on time-and-motion simulations

<p>Abstract</p> <p>Background</p> <p>Numerous pen devices are available to administer recombinant Human Growth Hormone (rhGH), and both patients and health plans have varying issues to consider when selecting a particular product and device for daily use. Therefore, the present study utilized multi-dimensional product analysis to assess potential time involvement, required weekly administration steps, and utilization costs relative to daily rhGH administration.</p> <p>Methods</p> <p>Study objectives were to conduct 1) Time-and-Motion (TM) simulations in a randomized block design that allowed time and steps comparisons related to rhGH preparation, administration and storage, and 2) a Cost Minimization Analysis (CMA) relative to opportunity and supply costs. Nurses naïve to rhGH administration and devices were recruited to evaluate four rhGH pen devices (2 in liquid form, 2 requiring reconstitution) via TM simulations. Five videotaped and timed trials for each product were evaluated based on: 1) Learning (initial use instructions), 2) Preparation (arrange device for use), 3) Administration (actual simulation manikin injection), and 4) Storage (maintain product viability between doses), in addition to assessment of steps required for weekly use. The CMA applied micro-costing techniques related to opportunity costs for caregivers (categorized as wages), non-drug medical supplies, and drug product costs.</p> <p>Results</p> <p>Norditropin^®NordiFlex and Norditropin^®NordiPen (NNF and NNP, Novo Nordisk, Inc., Bagsværd, Denmark) took less weekly Total Time (p < 0.05) to use than either of the comparator products, Genotropin^®Pen (GTP, Pfizer, Inc, New York, New York) or HumatroPen^®(HTP, Eli Lilly and Company, Indianapolis, Indiana). Time savings were directly related to differences in new package Preparation times (NNF (1.35 minutes), NNP (2.48 minutes) GTP (4.11 minutes), HTP (8.64 minutes), p < 0.05)). Administration and Storage times were not statistically different. NNF (15.8 minutes) and NNP (16.2 minutes) also took less time to Learn than HTP (24.0 minutes) and GTP (26.0 minutes), p < 0.05). The number of weekly required administration steps was also least with NNF and NNP. Opportunity cost savings were greater in devices that were easier to prepare for use; GTP represented an 11.8% drug product savings over NNF, NNP and HTP at time of study. Overall supply costs represented <1% of drug costs for all devices.</p> <p>Conclusions</p> <p>Time-and-motion simulation data used to support a micro-cost analysis demonstrated that the pen device with the greater time demand has highest net costs.</p

What are Employers Looking for in New Veterinary Graduates? A Content Analysis of UK Veterinary Job Advertisements

As veterinary educators, we have a responsibility to ensure that our graduates are prepared for working life. Veterinary practices, like any other businesses, rely on good employees, and the implications of a poor match between newly employed veterinarian and employing practice could be extremely costly in terms of personal well-being and enjoyment of work as well as the time, financial, and goodwill costs of high staff turnover for the practice. Contemporary veterinary curricula encompass a range of teaching to complement the clinical content; including communication, teamwork, problem solving, and business skills, to support good practice and increase the employability of new graduates. Previous studies have examined the qualities required of early career veterinarians as viewed by educators, recent graduates, pet owners, and practitioners; however, nobody has previously constructed a picture of the employment market for new veterinary graduates by exploring the nature of its recruitment advertising. Three months of UK veterinary job advertisements were examined. Content analysis yielded 10 distinct characteristics desired by employers of early career veterinarians. The most common by far was “enthusiasm,” followed by an interest in a particular area of practice, being an “all-rounder” (i.e., having a broad range of skills), demonstrating good communication skills, teamwork, client care, and independence, as well as being caring, ambitious, and having high clinical standards. While several of these qualities are expected and are specifically taught in veterinary school, the dominance of “enthusiasm” as a specifically desired trait raises interesting questions about the characteristics of veterinary students who we are supporting, encouraging, or maybe even suppressing, during veterinary training

Psychosocial correlates with depressive symptoms six years after a first episode of psychosis as compared with findings from a general population sample

BACKGROUND: Depression is frequently occurring during and after psychosis. The aim of this study was to analyze if the psychosocial characteristics associated with depression/depressive symptoms in the late phase of a first episode psychosis (FEP) population were different compared to persons from the general population. METHODS: A questionnaire was sent out to all individuals six years after their FEP and to a general population sample. Depressive symptoms were recorded using a self-rating scale, the Major Depression Inventory. RESULTS: Formerly FEP persons had a higher representation of depressive symptoms/depression, unemployment, financial problems and insufficient social network. Depressive symptoms/depression were found to be associated with psychosocial problems. An age and gender effect was found in the general population, but not in the FEP sample. When the psychosocial characteristics were taken into account there were no association between having had FEP and depressive symptoms. CONCLUSIONS: The association between having been a FEP patient and depressive symptoms/depression disappeared when negative social aspects were taken into account

Adaptation of gastrointestinal nematode parasites to host genotype: single locus simulation models

Background: Breeding livestock for improved resistance to disease is an increasingly important selection goal. However, the risk of pathogens adapting to livestock bred for improved disease resistance is difficult to quantify. Here, we explore the possibility of gastrointestinal worms adapting to sheep bred for low faecal worm egg count using computer simulation. Our model assumes sheep and worm genotypes interact at a single locus, such that the effect of an A allele in sheep is dependent on worm genotype, and the B allele in worms is favourable for parasitizing the A allele sheep but may increase mortality on pasture. We describe the requirements for adaptation and test if worm adaptation (1) is slowed by non-genetic features of worm infections and (2) can occur with little observable change in faecal worm egg count. Results: Adaptation in worms was found to be primarily influenced by overall worm fitness, viz. the balance between the advantage of the B allele during the parasitic stage in sheep and its disadvantage on pasture. Genetic variation at the interacting locus in worms could be from de novo or segregating mutations, but de novo mutations are rare and segregating mutations are likely constrained to have (near) neutral effects on worm fitness. Most other aspects of the worm infection we modelled did not affect the outcomes. However, the host-controlled mechanism to reduce faecal worm egg count by lowering worm fecundity reduced the selection pressure on worms to adapt compared to other mechanisms, such as increasing worm mortality. Temporal changes in worm egg count were unreliable for detecting adaptation, despite the steady environment assumed in the simulations. Conclusions: Adaptation of worms to sheep selected for low faecal worm egg count requires an allele segregating in worms that is favourable in animals with improved resistance but less favourable in other animals. Obtaining alleles with this specific property seems unlikely. With support from experimental data, we conclude that selection for low faecal worm egg count should be stable over a short time frame (e.g. 20 years). We are further exploring model outcomes with multiple loci and comparing outcomes to other control strategies

Overview of systematic reviews of therapeutic ranges : methodologies and recommendations for practice

BACKGROUND: Many medicines are dosed to achieve a particular therapeutic range, and monitored using therapeutic drug monitoring (TDM). The evidence base for a therapeutic range can be evaluated using systematic reviews, to ensure it continues to reflect current indications, doses, routes and formulations, as well as updated adverse effect data. There is no consensus on the optimal methodology for systematic reviews of therapeutic ranges. METHODS: An overview of systematic reviews of therapeutic ranges was undertaken. The following databases were used: Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts and Reviews of Effects (DARE) and MEDLINE. The published methodologies used when systematically reviewing the therapeutic range of a drug were analyzed. Step by step recommendations to optimize such systematic reviews are proposed. RESULTS: Ten systematic reviews that investigated the correlation between serum concentrations and clinical outcomes encompassing a variety of medicines and indications were assessed. There were significant variations in the methodologies used (including the search terms used, data extraction methods, assessment of bias, and statistical analyses undertaken). Therapeutic ranges should be population and indication specific and based on clinically relevant outcomes. Recommendations for future systematic reviews based on these findings have been developed. CONCLUSION: Evidence based therapeutic ranges have the potential to improve TDM practice. Current systematic reviews investigating therapeutic ranges have highly variable methodologies and there is no consensus of best practice when undertaking systematic reviews in this field. These recommendations meet a need not addressed by standard protocols

Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers

We present a review of the interplay between the evolution of circumstellar disks and the formation of planets, both from the perspective of theoretical models and dedicated observations. Based on this, we identify and discuss fundamental questions concerning the formation and evolution of circumstellar disks and planets which can be addressed in the near future with optical and infrared long-baseline interferometers. Furthermore, the importance of complementary observations with long-baseline (sub)millimeter interferometers and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics Review"; The final publication is available at http://www.springerlink.co

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Mechanism of MicroRNA-Target Interaction: Molecular Dynamics Simulations and Thermodynamics Analysis

MicroRNAs (miRNAs) are endogenously produced ∼21-nt riboregulators that associate with Argonaute (Ago) proteins to direct mRNA cleavage or repress the translation of complementary RNAs. Capturing the molecular mechanisms of miRNA interacting with its target will not only reinforce the understanding of underlying RNA interference but also fuel the design of more effective small-interfering RNA strands. To address this, in the present work the RNA-bound (Ago-miRNA, Ago-miRNA-target) and RNA-free Ago forms were analyzed by performing both molecular dynamics simulations and thermodynamic analysis. Based on the principal component analysis results of the simulation trajectories as well as the correlation analysis in fluctuations of residues, we discover that: 1) three important (PAZ, Mid and PIWI) domains exist in Argonaute which define the global dynamics of the protein; 2) the interdomain correlated movements are so crucial for the interaction of Ago-RNAs that they not only facilitate the relaxation of the interactions between residues surrounding the RNA binding channel but also induce certain conformational changes; and 3) it is just these conformational changes that expand the cavity of the active site and open putative pathways for both the substrate uptake and product release. In addition, by thermodynamic analysis we also discover that for both the guide RNA 5′-end recognition and the facilitated site-specific cleavage of the target, the presence of two metal ions (of Mg2+) plays a predominant role, and this conclusion is consistent with the observed enzyme catalytic cleavage activity in the ternary complex (Ago-miRNA-mRNA). Our results find that it is the set of arginine amino acids concentrated in the nucleotide-binding channel in Ago, instead of the conventionally-deemed seed base-paring, that makes greater contributions in stabilizing the binding of the nucleic acids to Ago

RIC-7 Promotes Neuropeptide Secretion

Secretion of neurotransmitters and neuropeptides is mediated by exocytosis of distinct secretory organelles, synaptic vesicles (SVs) and dense core vesicles (DCVs) respectively. Relatively little is known about factors that differentially regulate SV and DCV secretion. Here we identify a novel protein RIC-7 that is required for neuropeptide secretion in Caenorhabditis elegans. The RIC-7 protein is expressed in all neurons and is localized to presynaptic terminals. Imaging, electrophysiology, and behavioral analysis of ric-7 mutants indicates that acetylcholine release occurs normally, while neuropeptide release is significantly decreased. These results suggest that RIC-7 promotes DCV–mediated secretion