Genes significantly associated with lineage II food isolates of Listeria monocytogenes.

BACKGROUND: Listeria monocytogenes is a widespread foodborne pathogen that can cause listeriosis, a potentially fatal infection. L. monocytogenes is subdivided into four phylogenetic lineages, with the highest incidence of listeriosis occurring within lineage I followed by lineage II. Strains of L. monocytogenes differ in their phenotypic characteristics, including virulence. However, the genetic bases for these observed differences are not well understood, and current efforts to monitor L. monocytogenes in food consider all strains to be equally virulent. We use a comparative genomics approach to identify genes and single nucleotide polymorphisms (SNPs) in 174 clinical and food isolates of L. monocytogenes that potentially contribute to virulence or the capacity to adapt to food environments. RESULTS: No SNPs are significantly associated with food or clinical isolates. No genes are significantly associated with food or clinical isolates from lineage I, but eight genes consisting of multiple homologues are associated with lineage II food isolates. These include three genes which encode hypothetical proteins, the cadmium resistance genes cadA and cadC, the multi-drug resistance gene ebrB, a quaternary ammonium compound resistance gene qac, and a regulatory gene. All eight genes are plasmid-borne, and most closed L. monocytogenes plasmids carry at least five of the genes (24/27). In addition, plasmids are more frequently associated with lineage II food isolates than with lineage II clinical isolates. CONCLUSIONS: We identify eight genes that are significantly associated with food isolates in lineage II. Interestingly, the eight genes are virtually absent in lineage II outbreak isolates, are composed of homologues which show a nonrandom distribution among lineage I serotypes, and the sequences are highly conserved across 27 closed Listeria plasmids. The functions of these genes should be explored further and will contribute to our understanding of how L. monocytogenes adapts to the host and food environments. Moreover, these genes may also be useful as markers for risk assessment models of either pathogenicity or the ability to proliferate in food and the food processing environment.

Enrichment dynamics of Listeria monocytogenes and the associated microbiome from naturally contaminated ice cream linked to a listeriosis outbreak.

BACKGROUND: Microbiota that co-enrich during efforts to recover pathogens from foodborne outbreaks interfere with efficient detection and recovery. Here, dynamics of co-enriching microbiota during recovery of Listeria monocytogenes from naturally contaminated ice cream samples linked to an outbreak are described for three different initial enrichment formulations used by the Food and Drug Administration (FDA), the International Organization of Standardization (ISO), and the United States Department of Agriculture (USDA). Enrichment cultures were analyzed using DNA extraction and sequencing from samples taken every 4 h throughout 48 h of enrichment. Resphera Insight and CosmosID analysis tools were employed for high-resolution profiling of 16S rRNA amplicons and whole genome shotgun data, respectively. RESULTS: During enrichment, other bacterial taxa were identified, including Anoxybacillus, Geobacillus, Serratia, Pseudomonas, Erwinia, and Streptococcus spp. Surprisingly, incidence of L. monocytogenes was proportionally greater at hour 0 than when tested 4, 8, and 12 h later with all three enrichment schemes. The corresponding increase in Anoxybacillus and Geobacillus spp.indicated these taxa co-enriched in competition with L. monocytogenes during early enrichment hours. L. monocytogenes became dominant after 24 h in all three enrichments. DNA sequences obtained from shotgun metagenomic data of Listeria monocytogenes at 48 h were assembled to produce a consensus draft genome which appeared to have a similar tracking utility to pure culture isolates of L. monocytogenes. CONCLUSIONS: All three methods performed equally well for enrichment of Listeria monocytogenes. The observation of potential competitive exclusion of L. mono by Anoxybacillus and Geobacillus in early enrichment hours provided novel information that may be used to further optimize enrichment formulations. Application of Resphera Insight for high-resolution analysis of 16S amplicon sequences accurately identified L. monocytogenes. Both shotgun and 16S rRNA data supported the presence of three slightly variable genomes of L. monocytogenes. Moreover, the draft assembly of a consensus genome of L. monocytogenes from shotgun metagenomic data demonstrated the potential utility of this approach to expedite trace-back of outbreak-associated strains, although further validation will be needed to confirm this utility.

A LuxR-type repressor of Burkholderia cenocepacia inhibits transcription via antiactivation and is inactivated by its cognate acylhomoserine lactone.

Burkholderia cenocepacia is an opportunistic human pathogen that encodes two LuxI-type acylhomoserine lactone (AHL) synthases and three LuxR-type AHL receptors. Of these, cepI and cepR form a cognate synthase/receptor pair, as do cciI and cciR, while cepR2 lacks a genetically linked AHL synthase gene. Another group showed that a cepR2 mutant overexpressed a cluster of linked genes that appear to direct the production of a secondary metabolite. We found that these same genes were upregulated by octanoylhomoserine lactone (OHL), which is synthesized by CepI. These data suggest that several cepR2-linked promoters are repressed by CepR2 and that CepR2 is antagonized by OHL. Fusions of two divergent promoters to lacZ were used to confirm these hypotheses, and promoter resections and DNase I footprinting assays revealed a single CepR2 binding site between the two promoters. This binding site lies well upstream of both promoters, suggesting an unusual mode of repression. Adjacent to the cepR2 gene is a gene that we designate cepS, which encodes an AraC-type transcription factor. CepS is essential for expression of both promoters, regardless of the CepR2 status or OHL concentration. CepS therefore acts downstream of CepR2, and CepR2 appears to function as a CepS antiactivator.

The effects of musical practice on the well-being, mental health and social support of student, amateur, and professional musicians in Canada during the COVID-19 pandemic.

This pan-Canadian study investigates the effects of musical practice on the well-being, mental health, and social support of Canadian musicians during the COVID-19 pandemic. Using a survey questionnaire, data was collected from 1,618 participants aged 14 and above during the first wave of the pandemic up to the first half of 2022. The survey included standardized questionnaires to self-assess well-being (WHO-5), mental health (MHC-SF), and social support (SPS-10 measures social support). Results show that increased musical practice frequency correlates with improved well-being and mental health, particularly among amateurs. Professional musicians and those at a post-secondary level exhibit lower well-being scores, likely due to pandemic-related challenges. Factors such as age, gender, sports engagement, and participation in social clubs or volunteer work significantly influenced outcomes. While sports engagement was associated with higher scores on well-being, mental health and social support, no significant differences were found among participants engaged in artistic hobbies. As for involvement in social clubs or volunteer work, benefits were reported on two of the three outcomes. Overall, the findings suggest that regular amateur musical practice, especially in group settings, alongside engagement in sports and social activities, may have promoted well-being, mental health, and social support among musicians during the challenging period of the COVID-19 pandemic.

Saturation mutagenesis of a CepR binding site as a means to identify new quorum-regulated promoters in Burkholderia cenocepacia.

Burkholderia cenocepacia is an opportunistic pathogen of humans that encodes two genes that resemble the acylhomoserine lactone synthase gene luxI of Vibrio fischeri and three genes that resemble the acylhomoserine lactone receptor gene luxR. Of these, CepI synthesizes octanoylhomoserine lactone (OHL), while CepR is an OHL-dependent transcription factor. In the current study we developed a strategy to identify genes that are directly regulated by CepR. We systematically altered a CepR binding site (cep box) upstream of a target promoter to identify nucleotides that are essential for CepR activity in vivo and for CepR binding in vitro. We constructed 34 self-complementary oligonucleotides containing altered cep boxes, and measured binding affinity for each. These experiments allowed us to identify a consensus CepR binding site. Several hundred similar sequences were identified, some of which were adjacent to probable promoters. Several such promoters were fused to a reporter gene with and without intact cep boxes. This allowed us to identify four new regulated promoters that were induced by OHL, and that required a cep box for induction. CepR-dependent, OHL-dependent expression of all four promoters was reconstituted in Escherichia coli. Purified CepR bound to each of these sites in electrophoretic mobility shift assays.

Children's feelings about piano performances across a year of study.

Solo performance is a common experience for children learning to play an instrument, yet the research literature on these experiences is limited, with a focus on older children and adolescents. The purpose of this study was to examine younger children's feelings about performance over the course of a year of study. Forty-one children were interviewed about their piano lessons and performance experiences at the end of two consecutive semesters of study. They also responded to a pictorial scale on their feelings about performance at each interview and again at two piano recitals. Results indicate that children are remarkably consistent in their feelings about performing in piano recitals, with few significant changes over time and context. Correlation analyses indicate changes in the relationships between feelings about performance and certain study variables over time-in particular age, liking of lessons, liking of performing, practice time, and perception of being good at piano. In the fall term, gender and age are significant predictors of feelings about performance, with younger children and boys feeling most positive. In the spring, the findings shift and the only significant predictor is children's liking of piano lessons. Implications and directions for further research are discussed.

Liraglutide: once-daily GLP-1 agonist for the treatment of type 2 diabetes.

WHAT IS KNOWN AND OBJECTIVE: The prevalence of diabetes is increasing worldwide. Over the recent years, new discoveries have led to the development of new pharmacological agents targeting the incretin hormones gastric inhibitory peptide (GIP) and glucagon-like peptide-1 (GLP-1). These agents, called incretin-mimetics, are the newest agents added to the diabetes treatment options. The purpose of this article is to review the relevant literature on the chemistry, pharmacology, pharmacokinetics, metabolism, clinical trials, safety, drug interactions and place in therapy of liraglutide in the treatment of type 2 diabetes. METHODS: An extensive search of the literature was performed with liraglutide and NN2211 as key terms. This article presents a review of the literature related to the chemistry, pharmacology, pharmacokinetics, drug interactions and safety and efficacy of liraglutide. RESULTS AND DISCUSSION: Liraglutide, a subcutaneously administered GLP-1 agonist, displays phamacodynamic and pharmacokinetic properties that allow for once-daily administration. The agent has been shown to be efficacious as monotherapy, as well as in combination with glimperide, metformin and/or rosiglitazone, reducing glycoslyated haemoglobin (A1C) between 0·84% and 1·5%. The primary adverse event reported with liraglutide is transient nausea. WHAT IS NEW AND CONCLUSION: Liraglutide has been well studied in dual and triple combination therapies with sulfonylureas, metformin and rosiglitazone and appears safe and effective. For patients who cannot tolerate first-line agents, metformin, insulin and sulfonylureas, liraglutide is a reasonable treatment option.

CETP genotype and concentrations of HDL and lipoprotein subclasses in African-American men.

Aim: To assess the association between the CETP Taq1B and I405V polymorphisms with levels of lipoprotein subclasses in African-American (AA) men with and without Type 2 diabetes (T2DM). Patients & methods: AA men, over 30 years of age, with (n = 54) or without T2DM (n = 50), and not receiving lipid-lowering agents, underwent advanced lipid analysis and genotyping. Results & conclusion: In the total patient population Taq1B B2-allele carriers had significantly higher levels of large HDL subclasses (HDL-2b [p = 0.017] and HDL-L [p = 0.019]), lower levels of small-HDL subclasses (HDL-3a [p = 0.004] and HDL-3b [p = 0.031]), and lower levels of LDL subclasses (LDL-IVa [p = 0.012] and LDL-IIIb [p = 0.009]). The only significant genotype-diabetes interaction occurred with the HDL-2a subclass (p = 0.015). No statistically significant associations were seen with I405V genotype. Our observations of lower levels of small-HDL and higher levels of large-HDL suggest that a potentially important HDL subclass-CETP relationship exists.

Time-Motion Analysis of Nurses Utilizing Insulin Pen Devices Compared to Vial and Syringe in an Inpatient Setting.

OBJECTIVE: To compare the time taken and steps completed by nurses in the process of insulin preparation and administration using the pen device compared to the vial and syringe method. METHODS: Observational and exploratory study utilizing a time-motion analysis of nurses' administration of insulin using the pen versus vial and syringe delivery methods. Nurses were observed, video-recorded, and timed during insulin preparation and administration using each delivery method. The steps performed by nurses were observed against recommended processes for preparing and administering insulin, and the percentage of nurses completing each step was noted. RESULTS: A total of 137 (94%) nurses participated. Nurses took less time preparing and administering insulin with the pen device compared with the vial and syringe method (79 ± 18 seconds vs 88 ± 20 seconds, respectively, P < .001). The overall average completion rate of steps with the pen device was 90% ± 7% compared to 88% ± 7% with the vial and syringe method. CONCLUSION: The time taken by nurses to prepare and administer insulin was lower with the pen device compared with vial and syringe. Furthermore, areas were identified for potential nursing education to enhance safe and appropriate use of insulin with both delivery methods.

The safety of metformin in heart failure.

OBJECTIVE: To examine the evidence regarding the safety of metformin in heart failure. DATA SOURCES: Searches in MEDLINE and International Pharmaceutical Abstracts were performed (1966-February 2007). Search terms included metformin, heart failure, lactic acidosis, clinical trials, and insulin resistance. STUDY SELECTION AND DATA EXTRACTION: Published studies and case reports that evaluated the causal link between metformin and lactic acidosis in patients with heart failure were selected for review. DATA SYNTHESIS: There were no case reports of patients who had metformin-associated lactic acidosis when heart failure was the only contraindication. Two large retrospective studies showed that metformin does not increase the risk of lactic acidosis in patients with heart failure. However, these retrospective analyses did not account for many important confounding variables. A reduction in mortality rates in metformin users with New York Heart Association Class III and IV heart failure was observed in one small (N = 94) prospective trial. CONCLUSIONS: Results from 3 trials suggest that metformin may be safe to use in heart failure. Large prospective trials are needed to provide conclusive evidence regarding metformin's safety. Until then, use of metformin in heart failure patients should not be recommended routinely. If it is used in patients with heart failure, they should be monitored closely for signs of lactic acidosis.

Professional Stereotypes of Interprofessional Education Naive Pharmacy and Nursing Students.

Objective. To assess and compare interprofessional education (IPE) naive pharmacy and nursing student stereotypes prior to completion of an IPE activity. Methods. Three hundred and twenty-three pharmacy students and 275 nursing students at Mercer University completed the Student Stereotypes Rating Questionnaire. Responses from pharmacy and nursing students were compared, and responses from different level learners within the same profession also were compared. Results. Three hundred and fifty-six (59.5%) students completed the survey. Pharmacy students viewed pharmacists more favorably than nursing students viewed pharmacists for all attributes except the ability to work independently. Additionally, nursing students viewed nurses less favorably than pharmacy students viewed nurses for academic ability and practical skills. There was some variability in stereotypes between professional years. Conclusion. This study confirms the existence of professional stereotypes, although overall student perceptions of their own profession and the other were generally positive.

Reduced-dose influenza vaccine.

OBJECTIVE: To evaluate the effectiveness and safety of reduced-dose trivalent inactivated influenza vaccine in adults. DATA SOURCES: A MEDLINE search was conducted (1966-May 2006) using the key search terms inactivated, trivalent, influenza vaccine, dose, and intradermal. DATA SYNTHESIS: Four recent studies evaluated the safety and effectiveness of reduced-dose, inactivated, trivalent influenza vaccine. Reduced doses had immunogenicity similar to that of standard dose vaccination in healthy individuals less than 60 years old. Intramuscular administration caused fewer local adverse effects compared with the other routes of administration. The differences in vaccine administration and dosing used in these studies limit the comparison of their results. CONCLUSIONS: The Centers for Disease Control and Prevention does not recommend vaccinating with reduced-dose influenza vaccine. If reduced-dose vaccination is to be employed during times of vaccine shortage, it should be administered only to healthy adults under the age of 60, and the intramuscular route is preferred.

Spatiotemporal Analysis of Microbiological Contamination in New York State Produce Fields following Extensive Flooding from Hurricane Irene, August 2011.

Although flooding introduces microbiological, chemical, and physical hazards onto croplands, few data are available on the spatial extent, patterns, and development of contamination over time postflooding. To address this paucity of information, we conducted a spatially explicit study of Escherichia coli and Salmonella contamination prevalence and genetic diversity in produce fields after the catastrophic flooding that occurred in New England during 2011. Although no significant differences were detected between the two participating farms, both random forest and logistic regression revealed changes in the spatial pattern of E. coli contamination in drag swab samples over time. Analyses also indicated that E. coli detection was associated with changes in farm management to remediate the land after flooding. In particular, E. coli was widespread in drag swab samples at 21 days postflooding, but the spatial pattern changed by 238 days postflooding such that E. coli was then most prevalent in close proximity to surface water features. The combined results of several population genetics analyses indicated that over time postflooding E. coli populations on the farms (i) changed in composition and (ii) declined overall. Salmonella was primarily detected in surface water features, but some Salmonella strains were isolated from soil and drag swab samples at 21 and 44 days postflooding. Although postflood contamination and land management responses should always be evaluated in the context of each unique farm landscape, our results provide quantitative data on the general patterns of contamination after flooding and support the practice of establishing buffer zones between flood-contaminated cropland and harvestable crops in produce fields.

Pramlintide in the treatment of type 1 and type 2 diabetes mellitus.

BACKGROUND: Amylin is a 37-amino acid peptide neurohormone that is cosecreted with insulin from the pancreatic beta cells in response to meals. It lowers serum glucose by decreasing glucagon release, slowing gastric emptying, and decreasing food intake. Pramlintide, a synthetic amylin analogue, is approved by the US Food and Drug Administration for use with mealtime insulin in patients with type 1 diabetes and patients with type 2 diabetes who are using mealtime insulin only or the combination of insulin and metformin and/or a sulfonylurea. OBJECTIVE: This article reviews the available literature on pramlintide with respect to its mechanism of action, pharmacokinetics and pharmacodynamics, clinical efficacy in type 1 and type 2 diabetes, safety and tolerability, dosing, contraindications, and drug interactions. METHODS: MEDLINE (1966-April 2005), Iowa Drug Information Service (1966-April 2005), and International Pharmaceutical Abstracts (1970-April 2005) were searched for clinical trials and therapeutic reviews published in the English language. The search terms were pramlintide and amylin. The bibliographies of identified articles were reviewed for additional references. All relevant studies were included in the review. RESULTS: Six studies, ranging in duration from 4 to 52 weeks, examined the effect of administering pramlintide with premeal insulin in patients with type 1 diabetes. In these trials, pramlintide 120 to 270 microg/d reduced glycosylated hemoglobin (HbA(1c)) by 0.1 % to 0.67%, 1-hour postprandial glucose (PPG) by 4.4 to 7 mmol/L, and 2-hour PPG by 3.6 to 4.8 mmol/L. Five studies, also ranging from 4 to 52 weeks' duration, examined the effect of administering premeal pramlintide in patients with type 2 diabetes. In these trials, pramlintide 90 to 450 microg/d reduced HbA(1c) by 0.3% to 0.62%, 1-hour PPG by 4.8 mmol/L, and 2-hour PPG by 3.4 mmol/L. The principal adverse events reported in clinical trials were nausea and hypoglycemia. The incidence of hypoglycemia in the first 4 weeks of therapy was 2 to 4 times greater with pramlintide compared with placebo; thus, the manufacturer recommends reducing the dose of premeal insulin by 50% when starting pramlintide. Close monitoring of blood glucose levels is recommended when initiating pramlintide therapy. CONCLUSIONS: Use of pramlintide in addition to insulin in patients with type 1 and type 2 diabetes was associated with modest reductions in HbA(1c). The primary adverse effects of pramlintide therapy were nausea and hypoglycemia.

The impact of outpatient diabetes management on serum lipids in urban African-Americans with type 2 diabetes.

OBJECTIVE: Treating dyslipidemia in diabetic patients is essential, particularly among minority populations with increased risk of complications. Because little is known about the impact of outpatient diabetes management on lipid outcomes, we examined changes in lipid profiles in urban African-Americans who attended a structured diabetes care program. RESEARCH DESIGN AND METHODS: A retrospective analysis of initial and 1-year follow-up lipid values was conducted among patients selected from a computerized registry of an urban outpatient diabetes clinic. The independent effects of lipid-specific medications, glycemic control, and weight loss on serum total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels were evaluated by analysis of covariance and multiple linear regression. RESULTS: In 345 patients (91% African-American and 95% with type 2 diabetes), HbA(1c) decreased from 9.3% at the initial visit to 8.2% at 1 year (P < 0.001); total and LDL cholesterol and triglyceride levels were significantly lower, and HDL cholesterol was higher. After stratifying based on use of lipid-specific therapy, different outcomes were observed. In 243 patients not taking dyslipidemia medications, average total cholesterol, LDL cholesterol, and triglyceride concentrations at 1 year were similar to initial values, whereas in 102 patients receiving pharmacotherapy, these lipid levels were all lower at 1 year relative to baseline (P < 0.001). Mean HDL cholesterol increased regardless of lipid treatment status (P < 0.001). After adjusting for other variables, changes in LDL cholesterol concentration were associated only with use of lipid-specific agents (P = 0.003), whereas improved HbA(1c) and weight loss had no independent effect. Lipid therapy, improved glycemic control, and weight loss were not independently related to changes in HDL cholesterol and therefore could not account for the positive changes observed. Use of lipid-directed medications, improvement in glycemic control, and weight loss all resulted in significant declines in triglyceride levels but only improved HbA(1c) and weight loss had an independent effect. CONCLUSIONS: Among urban African-Americans, diabetes management led to favorable changes in HDL cholesterol and triglyceride levels, but improved glycemic control and weight loss had no independent effect on LDL cholesterol concentration. Initiation of pharmacologic therapy to treat high LDL cholesterol levels should be considered early in the course of diabetes management to reach recommended targets and reduce the risk of cardiovascular complications in this patient population.

Dipeptidyl peptidase-4 inhibitor use in patients with type 2 diabetes and cardiovascular disease or risk factors.

OBJECTIVES: Management of cardiovascular (CV) risk is an essential aspect of diabetes care, and acceptable CV risk is a requirement for antidiabetes medications. Dipeptidyl peptidase-4 (DPP-4) inhibitors effectively reduce glycated hemoglobin, with a low risk of hypoglycemia and weight gain. The purpose of this review is to discuss the use of DPP-4 inhibitors in patients with type 2 diabetes mellitus (T2DM) and CV disease or risk factors. METHODS: A PubMed search (January 2013-June 2015) was conducted to identify prospective trials, meta-analyses, pooled analyses and cohort studies evaluating CV outcomes with DPP-4 inhibitors. RESULTS: Meta-analyses, pooled analyses and retrospective cohort studies in patients with T2DM suggest no increased CV risk and possible CV benefit compared with some antidiabetes medications. The three published, long-term, prospective, randomized, double-blind CV outcomes trials in patients with CV disease or risk factors found no increased rate of major CV events in patients treated with alogliptin, saxagliptin or sitagliptin versus placebo as add-on to standard-of-care. However, the analysis of the components of the secondary end point of the saxagliptin study showed an increased number of hospitalizations for heart failure (HF) in treated patients versus placebo. A post hoc analysis of the alogliptin study showed no increase in HF hospitalization in treated patients with a history of HF versus placebo, but did show an increase in alogliptin-treated patients with no baseline HF history. Sitagliptin showed no increased risk for HF hospitalization versus placebo in the overall cohort. Two CV outcomes trials for linagliptin are ongoing. CONCLUSION: The majority of available data from CV outcomes trials suggest a neutral effect of DPP-4 inhibitors on major CV events.

Evaluation of Rapid Molecular Detection Assays for Salmonella in Challenging Food Matrices at Low Inoculation Levels and Using Difficult-to-Detect Strains.

Assays for detection of foodborne pathogens are generally initially evaluated for performance in validation studies carried out according to guidelines provided by validation schemes (e.g., AOAC International or the International Organization for Standardization). End users often perform additional validation studies to evaluate the performance of assays in specific matrices (e.g., specific foods or raw material streams of interest) and with specific pathogen strains. However, these types of end-user validations are typically not well defined. This study was conducted to evaluate a secondary end user validation of four AOAC-validated commercial rapid detection assays (an isothermal nucleic acid amplification, an immunoassay, and two PCR-based assays) for their ability to detect Salmonella in two challenging matrices (dry pet food and dark chocolate). Inclusivity was evaluated with 68 diverse Salmonella strains at low population levels representing the limit of detection (LOD) for each assay. One assay detected all strains at the LOD, two assays detected multiple strains only at 10 times the LOD, and the fourth assay failed to detect two strains (Salmonella bongori and S. enterica subsp. houtenae) even at 1,000 times the LOD; this assay was not further evaluated. The three remaining assays were subsequently evaluated for their ability to detect five selected Salmonella strains in food samples contaminated at fractional levels. Unpaired comparisons revealed no significant difference between the results for each given assay and the results obtained with the reference assay. However, analysis of paired culture-confirmed results revealed assay false-negative rates of 4 to 26% for dry pet food and 12 to 16% for dark chocolate. Overall, our data indicate that rapid assays may have high false-negative rates when performance is evaluated under challenging conditions, including low-moisture matrices, strains that are difficult to detect, injured cells, and low inoculum levels.

Aggrenox((R)) versus other pharmacotherapy in preventing recurrent stroke.

Stroke is the third leading cause of death in the US with recurrent events a high likelihood in those who survive an initial event. The long-term goal of therapy is to prevent the recurrence of stroke and other atherosclerotic events. Aspirin has been the first-line agent for stroke prevention for a long time. As new antiplatelet agents have been introduced, their role in the secondary prevention of stroke remains to be defined. In particular, the role of the combination of aspirin and modified-release dipyridamole (Aggrenox, Boehringer Ingelheim Corp.), the newest product, in the secondary prevention of stroke, remains unknown. The purpose of this manuscript is to review the evidence of these antiplatelet agents in the secondary prevention of stroke and arrive at a conclusion specifically regarding the role of Aggrenox. Clinical studies which examined stroke as a single primary outcome or as one event in a combined primary outcome will be reviewed.

Nurses' perceptions and satisfaction with the use of insulin pen devices compared with insulin vial and syringes in an inpatient setting.

BACKGROUND: The purpose of this study was to compare nurses' perceptions and satisfaction with the use of insulin pen devices versus vial and syringes for insulin delivery in an inpatient setting. MATERIALS AND METHODS: The study used a descriptive design using self-report surveys. Nurses rated their perceptions on a 4-point Likert scale (from 1=strongly disagree to 4=strongly agree) on the ease of use, ease to teach patients, confidence and comfort in use, perceived time efficiency, safety of use, risk of needle sticks, and overall satisfaction and preference with use of each insulin delivery device. RESULTS: In total, 139 (95%) nurses from nine nursing units at one hospital participated in this study. Compared with vial and syringe, nurses felt insulin pens were easier to use to measure insulin dose (mean±SD, 3.7±0.5 vs. 3.1±0.7; P<0.001), were easier to teach patients to use (3.5±0.6 vs. 2.8±0.7; P<0.001), provided more confidence in measuring insulin dose (3.7±0.5 vs. 3.4±0.6, P<0.001), saved on administration and preparation time (3.6±0.5 vs. 2.3±0.8; P<0.001), reduced the risk of giving a wrong dose of insulin (3.2±0.8 vs. 2.2±0.7; P<0.001), and reduced the risk of needle sticks (3.5±0.7 vs. 2.1±0.8; P<0.001). Overall, a majority of nurses preferred the use of insulin pens to vial and syringes in an inpatient setting (83% vs. 15%; P<0.05). CONCLUSIONS: Nurses felt more comfortable and confident with the use of insulin pens compared with vial and syringes and perceived insulin pens to be a safer alternative for both patients and themselves.

National estimates of insulin-related hypoglycemia and errors leading to emergency department visits and hospitalizations.

IMPORTANCE: Detailed, nationally representative data describing high-risk populations and circumstances involved in insulin-related hypoglycemia and errors (IHEs) can inform approaches to individualizing glycemic targets. OBJECTIVE: To describe the US burden, rates, and characteristics of emergency department (ED) visits and emergency hospitalizations for IHEs. DESIGN, SETTING, AND PARTICIPANTS: Nationally representative public health surveillance of adverse drug events among insulin-treated patients seeking ED care (National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project) and a national household survey of insulin use (the National Health Interview Survey) were used to obtain data from January 1, 2007, through December 31, 2011. MAIN OUTCOMES AND MEASURES: Estimated annual numbers and estimated annual rates of ED visits and hospitalizations for IHEs among insulin-treated patients with diabetes mellitus. RESULTS: Based on 8100 National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance cases, an estimated 97,648 (95% CI, 64,410-130,887) ED visits for IHEs occurred annually; almost one-third (29.3%; 95% CI, 21.8%-36.8%) resulted in hospitalization. Severe neurologic sequelae were documented in an estimated 60.6% (95% CI, 51.3%-69.9%) of ED visits for IHEs, and blood glucose levels of 50 mg/dL (to convert to millimoles per liter, multiply by 0.0555) or less were recorded in more than half of cases (53.4%). Insulin-treated patients 80 years or older were more than twice as likely to visit the ED (rate ratio, 2.5; 95% CI, 1.5-4.3) and nearly 5 times as likely to be subsequently hospitalized (rate ratio, 4.9; 95% CI, 2.6-9.1) for IHEs than those 45 to 64 years. The most commonly identified IHE precipitants were reduced food intake and administration of the wrong insulin product. CONCLUSIONS AND RELEVANCE: Rates of ED visits and subsequent hospitalizations for IHEs were highest in patients 80 years or older; the risks of hypoglycemic sequelae in this age group should be considered in decisions to prescribe and intensify insulin. Meal-planning misadventures and insulin product mix-ups are important targets for hypoglycemia prevention efforts.