Evaluation of the Impact of Corticosteroid Dose on the Incidence of Hyperglycemia in Hospitalized Patients with an Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

PURPOSE: Guidelines recommend systemic corticosteroids for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) albeit in lower doses than studies that cemented corticosteroids' place in therapy. Corticosteroids potentiate hyperglycemia, however it is undetermined how corticosteroid dose impacts hyperglycemia incidence. OBJECTIVES: To establish whether a greater incidence of steroid-induced hyperglycemia (SIHGLY) exists for high- versus low-dose corticosteroids. METHODS: Patients with primary discharge diagnosis 491.21/491.22 in a community hospital were retrospectively reviewed and divided into tertiles based on corticosteroid dosage. Baseline characteristics and primary endpoint were statistically assessed between tertiles using logistic regression analysis. A Cox proportional hazards (CPH) model adjusted for potential covariates. Post hoc analysis for primary outcome and CPH model was run removing non-insulin dependent diabetics because of disproportionate event count. A secondary endpoint used a Kaplan-Meier curve to evaluate time to event between tertiles. RESULTS: Tertile divisions were 125 and 187.5 mg methylprednisolone equivalents. The primary outcome for incidence of SIHGLY was insignificant; post hoc analysis removing non-insulin-dependent diabetics narrowly missed significance between tertiles 1 and 3 (P = .056). CPH analysis found significant differences in SIHGLY between tertiles 1 and 2 (hazard ratio [HR], 1.68; 95% CI, 1.02-2.76) and tertile 1 and 3 (HR, 1.79; 95% CI, 1.13-2.84), further post hoc analysis resulted in a loss of significance for the CPH analysis. Of 21 non-insulin-dependent diabetics, 20 met event status. The Kaplan-Meier analysis results were insignificant. CONCLUSIONS: Study results suggest that a link between larger corticosteroid doses and hyperglycemia incidence may exist, but it requires further study. RESULTS in non-insulin-dependent diabetics provide evidence for increased glucose monitoring upon initiation of corticosteroid therapy.

Residency Program Directors' View on the Value of Teaching.

PURPOSE: There is no standardization for teaching activities or a requirement for residency programs to offer specific teaching programs to pharmacy residents. This study will determine the perceived value of providing teaching opportunities to postgraduate year 1 (PGY-1) pharmacy residents in the perspective of the residency program director. The study will also identify the features, depth, and breadth of the teaching experiences afforded to PGY-1 pharmacy residents. METHODS: A 20-question survey was distributed electronically to 868 American Society of Health-System Pharmacists-accredited PGY-1 residency program directors. RESULTS: The survey was completed by 322 program directors. Developing pharmacy educators was found to be highly valued by 57% of the program directors. Advertisement of teaching opportunities was found to be statistically significant when comparing program directors with a high perceived value for providing teaching opportunities to program demographics. Statistically significant differences were identified associating development of a teaching portfolio, evaluation of Advanced Pharmacy Practice Experiences students, and delivery of didactic lectures with program directors who highly value developing pharmacy educators. CONCLUSIONS: Future residency candidates interested in teaching or a career in academia may utilize these findings to identify programs that are more likely to value developing pharmacy educators. The implementation of a standardized teaching experience among all programs may be difficult.

A Cross-sectional Analysis Investigating Organizational Factors That Influence Near-Miss Error Reporting Among Hospital Pharmacists.

OBJECTIVE: Underreporting near-miss errors undermines hospitals' ability to improve patient safety. The objective of this analysis was to determine the extent to which punitive work climate, inadequate error feedback to staff, or insufficient preventative procedures are associated with decreased frequency of near-miss error reporting among hospital pharmacists. METHODS: Survey data were obtained from the Agency of Healthcare Research and Quality 2010 Hospital Survey on Patient Safety Culture. Near-miss error reporting was defined using a Likert scale response to the question, "When a mistake is made, but is caught and corrected before affecting the patient, how often is this reported?" Work climate, error feedback to staff, and preventative procedures were defined similarly using responses to survey questions. Multivariate ordinal regressions estimated the likelihood of agreeing that near-miss errors were rarely reported, conditional upon perceived levels of punitive work climate, error feedback, or preventative procedures. RESULTS: Pharmacists disagreeing that procedures were sufficient and that feedback on errors was adequate were more likely to report that near-miss errors were rarely reported (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.7-3.8; OR, 3.5; 95% CI, 2.5-5.1). Those agreeing that mistakes were held against them were equally likely as those disagreeing to report that errors were rarely reported (OR, 0.84; 95% CI, 0.61-1.1). CONCLUSIONS: Inadequate error feedback to staff and insufficient preventative procedures increase the likelihood that near-miss errors will be underreported. Hospitals seeking to improve near-miss error reporting should improve error-reporting infrastructures to enable feedback, which, in turn, would create a more preventative system that improves patient safety.

Associations between communication climate and the frequency of medical error reporting among pharmacists within an inpatient setting.

OBJECTIVE: Although error-reporting systems enable hospitals to accurately track safety climate through the identification of adverse events, these systems may be underused within a work climate of poor communication. The objective of this analysis is to identify the extent to which perceived communication climate among hospital pharmacists impacts medical error reporting rates. METHODS: This cross-sectional study used survey responses from more than 5000 pharmacists responding to the 2010 Hospital Survey on Patient Safety Culture (HSOPSC). Two composite scores were constructed for "communication openness" and "feedback and about error," respectively. Error reporting frequency was defined from the survey question, "In the past 12 months, how many event reports have you filled out and submitted?" Multivariable logistic regressions were used to estimate the likelihood of medical error reporting conditional upon communication openness or feedback levels, controlling for pharmacist years of experience, hospital geographic region, and ownership status. RESULTS: Pharmacists with higher communication openness scores compared with lower scores were 40% more likely to have filed or submitted a medical error report in the past 12 months (OR, 1.4; 95% CI, 1.1-1.7; P = 0.004). In contrast, pharmacists with higher communication feedback scores were not any more likely than those with lower scores to have filed or submitted a medical report in the past 12 months (OR, 1.0; 95% CI, 0.8-1.3; P = 0.97). CONCLUSIONS: Hospital work climates that encourage pharmacists to freely communicate about problems related to patient safety is conducive to medical error reporting. The presence of feedback infrastructures about error may not be sufficient to induce error-reporting behavior.

Single particle inductively coupled plasma-mass spectrometry: a performance evaluation and method comparison in the determination of nanoparticle size.

Sizing engineered nanoparticles in simple, laboratory systems is now a robust field of science; however, application of available techniques to more complex, natural systems is hindered by numerous challenges including low nanoparticle number concentrations, polydispersity from aggregation and/or dissolution, and interference from other incidental particulates. A new emerging technique, single particle inductively coupled plasma-mass spectrometry (spICPMS), has the potential to address many of these analytical challenges when sizing inorganic nanoparticles in environmental matrices. However, to date, there is little beyond the initial feasibility studies that investigates the performance characteristics and validation of spICPMS as a nanoparticle sizing technique. This study compares sizing of four silver nanoparticle dispersions (nominal diameters of 40, 60, 80, and 100 nm) by spICPMS to four established sizing techniques: dynamic light scattering, differential centrifugal sedimentation, nanoparticle tracking analysis, and TEM. Results show that spICPMS is able to size silver nanoparticles, across different sizes and particle number concentrations, with accuracy similar to the other commercially available techniques. Furthermore, a novel approach to evaluating particle coincidence is presented. In addition, spICPMS size measurements were successfully performed on nanoparticles suspended in algal growth media at low concentrations. Overall, while further development of the technique is needed, spICPMS yields important advantages over other techniques when sizing nanoparticles in environmentally relevant media.

Relative efficacy of antilipemic agents in non­high-density lipoprotein cholesterol reduction.

The investigators sought to summarize the percentage reduction in non­high-density lipoprotein cholesterol (non-HDL-C) achieved with various antilipemic regimens and to determine whether certain antilipemic regimens have been proven more effective in lowering non-HDL-C. A search of MEDLINE, International Pharmaceutical Abstracts, and Iowa Drug Information Service Database from 1970 to May 2011 was performed. Criteria were used to exclude studies not published in English, studies with methodology limitations, and studies with variables that may affect efficacy beyond the antilipemic agent administered. Only randomized, controlled trials comparing medications approved by the Food and Drug Administration were reviewed to determine whether significant differences in percentage reduction in non-HDL-C had been observed between different medication regimens. A total of 51 trials reported data that could be used to determine the range of percentage reduction in non-HDL-C achieved by select antilipemic regimens. Of these 51 trials, 38 provided head-to-head comparisons of antilipemic regimens. Rosuvastatin and atorvastatin are the most potent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in lowering non-HDL-C. Adding ezetimibe, fibric acid derivatives, and omega-3 fatty acids to antilipemic monotherapy may result in further reduction in non-HDL-C. Subjects with certain characteristics (eg, nonwhite) were not prevalent in these studies.

Asenapine: a clinical review of a second-generation antipsychotic.

BACKGROUND: Schizophrenia and bipolar disorder are both prevalent types of psychiatric illness in the United States. As second-generation antipsychotics have become a more viable first-line treatment option, their use has been associated with a new era of adverse events (AEs), most notably metabolic and cardiovascular concerns. Although treatment options for schizophrenia and bipolar disorder have arguably improved, there continues to be a need for medications that achieve and maintain desired efficacy with minimal AEs. OBJECTIVES: This article serves as a comprehensive review of the pharmacologic profile of the second-generation antipsychotic asenapine, as well as a review of its efficacy and safety profiles based on the findings from clinical trials in schizophrenia and bipolar disorder. METHODS: Searches of Ovid MEDLINE, EMBASE, and IDIS were conducted (January 1996 to November 2011) to identify clinical studies and other primary literature sources with the following search terms: asenapine, bipolar disorder, antipsychotic, psychosis, dopamine, and schizophrenia. Only studies of asenapine and placebo and/or active-comparator arms were included. RESULTS: The literature search yielded 67 unique articles, including review articles, which were excluded. The efficacy of asenapine was reported in 3 clinical studies in patients with schizophrenia, 1 each in acute and long-term settings, measured as significant changes in Positive and Negative Syndrome Scale scores over 6 and 52 weeks. Asenapine also had reported efficacy in the prevention of relapse in schizophrenia during a 26-week extension study. In addition, efficacy of asenapine was reported in 2 studies in acute mania as well as extension phases of both 9 and 40 weeks, as determined by significant changes in Young Mania Rating Scale scores. The most commonly reported AEs in these studies were somnolence (13%-24%), extrapyramidal symptoms (EPS) (7%-12%), and dizziness (11%). CONCLUSIONS: The findings from multiple studies have suggested that asenapine is efficacious in the acute treatment of schizophrenia. Asenapine has reported long-term efficacy for this indication and the potential to reduce the incidence of relapse. Asenapine efficacy was also reported in the treatment of acute manic or mixed states associated with bipolar I disorder. Asenapine had an acceptable safety profile across the different disease states studied, although it was not devoid of metabolic and EPS-related AEs.

Novel features of ARS selection in budding yeast Lachancea kluyveri.

BACKGROUND: The characterization of DNA replication origins in yeast has shed much light on the mechanisms of initiation of DNA replication. However, very little is known about the evolution of origins or the evolution of mechanisms through which origins are recognized by the initiation machinery. This lack of understanding is largely due to the vast evolutionary distances between model organisms in which origins have been examined. RESULTS: In this study we have isolated and characterized autonomously replicating sequences (ARSs) in Lachancea kluyveri - a pre-whole genome duplication (WGD) budding yeast. Through a combination of experimental work and rigorous computational analysis, we show that L. kluyveri ARSs require a sequence that is similar but much longer than the ARS Consensus Sequence well defined in Saccharomyces cerevisiae. Moreover, compared with S. cerevisiae and K. lactis, the replication licensing machinery in L. kluyveri seems more tolerant to variations in the ARS sequence composition. It is able to initiate replication from almost all S. cerevisiae ARSs tested and most Kluyveromyces lactis ARSs. In contrast, only about half of the L. kluyveri ARSs function in S. cerevisiae and less than 10% function in K. lactis. CONCLUSIONS: Our findings demonstrate a replication initiation system with novel features and underscore the functional diversity within the budding yeasts. Furthermore, we have developed new approaches for analyzing biologically functional DNA sequences with ill-defined motifs.

Determining transport efficiency for the purpose of counting and sizing nanoparticles via single particle inductively coupled plasma mass spectrometry.

Currently there are few ideal methods for the characterization of nanoparticles in complex, environmental samples, leading to significant gaps in toxicity and exposure assessments of nanomaterials. Single particle-inductively coupled plasma-mass spectrometry (spICPMS) is an emerging technique that can both size and count metal-containing nanoparticles. A major benefit of the spICPMS method is its ability to characterize nanoparticles at concentrations relevant to the environment. This paper presents a practical guide on how to count and size nanoparticles using spICPMS. Different methods are investigated for measuring transport efficiency (i.e., nebulization efficiency), an important term in the spICPMS calculations. In addition, an alternative protocol is provided for determining particle size that broadens the applicability of the technique to all types of inorganic nanoparticles. Initial comparison, using well-characterized, monodisperse silver nanoparticles, showed the importance of having an accurate transport efficiency value when determining particle number concentration and, if using the newly presented protocol, particle size. Ultimately, the goal of this paper is to provide improvements to nanometrology by further developing this technique for the characterization of metal-containing nanoparticles.

The homeobox protein CEH-23 mediates prolonged longevity in response to impaired mitochondrial electron transport chain in C. elegans.

Recent findings indicate that perturbations of the mitochondrial electron transport chain (METC) can cause extended longevity in evolutionarily diverse organisms. To uncover the molecular basis of how altered METC increases lifespan in C. elegans, we performed an RNAi screen and revealed that three predicted transcription factors are specifically required for the extended longevity of mitochondrial mutants. In particular, we demonstrated that the nuclear homeobox protein CEH-23 uniquely mediates the longevity but not the slow development, reduced brood size, or resistance to oxidative stress associated with mitochondrial mutations. Furthermore, we showed that ceh-23 expression levels are responsive to altered METC, and enforced overexpression of ceh-23 is sufficient to extend lifespan in wild-type background. Our data point to mitochondria-to-nucleus communications to be key for longevity determination and highlight CEH-23 as a novel longevity factor capable of responding to mitochondrial perturbations. These findings provide a new paradigm for how mitochondria impact aging and age-dependent diseases.

Influence of stability on the acute toxicity of CdSe/ZnS nanocrystals to Daphnia magna.

The acute toxicity of polymer-coated CdSe/ZnS quantum dots (QDs) to Daphnia magna was investigated using 48-h exposure studies. The principal objective was to relate the toxicity of QDs to specific physical and chemical aspects of the QD. As such, two different CdSe core diameters, 2 nm QDs (green-emitting) and 5 nm QDs (red-emitting), and two different surface coatings, polyethylene oxide (PEO) and 11-mercaptoundecanoic acid (MUA) were studied. The QDs were characterized before and after the 48-h exposure using fluorescence, ultrafiltrations (3 kDa), and inductively coupled plasma-atomic emission spectrometry (ICP-AES) metal analysis. In addition, flow field flow fractionation-inductively coupled plasma-mass spectrometry (Fl FFF-ICP-MS) was used as a more extensive characterization technique to determine particle size and composition as well as identify other potential constituents in the QD solutions. The more stable QDs (PEO) were found to be less acutely toxic than the QDs with accelerated dissolution (MUA), suggesting QD stability has significant impact on the nanoparticles' short-term toxicity. The emergence of dissolved Cd(2+) in solution indicates that the toxicity of the MUA QDs is likely due to Cd poisoning, and a mass-based dose response occurred as a consequence of this mode of action. Alternatively, the PEO QDs caused acute toxicity without observed particle dissolution (i.e., no detectable metals were solubilized), suggesting an alternative mode of toxic action for these nanoparticles. Results of the present study suggest that using particle number, instead of mass, as a dose metric for the PEO QDs, produces markedly different conclusions, in that smaller core size does not equate to greater toxicity.

Synchrotron X-ray 2D and 3D elemental imaging of CdSe/ZnS quantum dot nanoparticles in Daphnia magna.

The potential toxicity of nanoparticles to aquatic organisms is of interest given that increased commercialization will inevitably lead to some instances of inadvertent environmental exposures. Cadmium selenide quantum dots (QDs) capped with zinc sulfide are used in the semiconductor industry and in cellular imaging. Their small size (<10 nm) suggests that they may be readily assimilated by exposed organisms. We exposed Daphnia magna to both red and green QDs and used synchrotron X-ray fluorescence to study the distribution of Zn and Se in the organism over a time period of 36 h. The QDs appeared to be confined to the gut, and there was no evidence of further assimilation into the organism. Zinc and Se fluorescence signals were highly correlated, suggesting that the QDs had not dissolved to any extent. There was no apparent difference between red or green QDs, i.e., there was no effect of QD size. 3D tomography confirmed that the QDs were exclusively in the gut area of the organism. It is possible that the QDs aggregated and were therefore too large to cross the gut wall.

Impact of health literacy on health outcomes in ambulatory care patients: a systematic review.

OBJECTIVE: To examine the relationship between low health literacy and disease state control and between low health literacy medication adherence in the primary care setting. DATA SOURCES: The following databases were searched for relevant articles from date of inception to April 2008: The Cochrane Database of Systematic Reviews, Cumulative Index to Nursing & Allied Health Literature, EMBASE, Education Resources Information Center, PsycINFO, International Pharmaceutical Abstracts, and Iowa Drug Information Service. MEDLINE was searched from 1966 to April 2008. Key words included literacy, health literacy, health education, educational status, disease outcomes, health outcomes, adherence, medication adherence, and patient compliance. Additional articles were identified by reviewing reference sections of retrieved articles. STUDY SELECTION AND DATA EXTRACTION: Studies using a validated measure of health literacy and performing statistical analysis to evaluate the relationship between health literacy and disease state control or medication adherence were evaluated. DATA SYNTHESIS: Eleven evaluations, including 10 discrete studies, met eligibility criteria. Six studies evaluated the relationship between health literacy and disease state control, 3 evaluated health literacy and medication adherence, and 1 study evaluated health literacy and both outcomes. A quality rating of poor, fair, or good was assigned to each study based on the study question, population, outcome measures, statistical analysis, and results. Eight studies had good quality, 1 was fair, and 2 were poor. Two high-quality studies demonstrated statistically significant relationships with health literacy, 1 with disease state control and 1 with medication adherence. Limitations of the other studies included inadequate sample size, underrepresentation of patients with low health literacy, use of less objective outcome measures, and insufficient statistical analysis. CONCLUSIONS: There may be a relationship between health literacy and disease state control and health literacy and medication adherence. Future research, with adequate representation of patients with low health literacy, is needed to further define this relationship and explore interventions to overcome the impact that low health literacy may have on patient outcomes.

High yield selective acylation of polyamines: proton as protecting group.

An advance in the selective acylation of polyamines having identical or similar amine functions is reported. While nucleophilicity differences between the various amine functions are slight, the corresponding conjugate acids exhibit pKa values over a significant range. We have used proton as polyamine protecting group: the monoamine resulting from single deprotonation of a polyammonium compound has allowed for high yields of selective acylation.