bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing Leadership Capacity for Guideline Use: A Pilot Cluster Randomized Control Trial
Authors: Gifford Wendy A. , Davies Barbara L. , Graham Ian D. , Tourangeau Ann , Woodend A. Kirsten , Lefebre Nancy 
Published: May 2012

ABSTRACTSignificanceThe importance of leadership to influence nurses’ use of clinical guidelines has been well documented. However, little is known about how to develop and evaluate leadership interventions for guideline use.PurposeThe purpose of this study was to pilot a leadership intervention designed to influence nurses’ use of guideline recommendations when caring for patients with diabetic foot ulcers in home care nursing. This paper reports on the feasibility of implementing the study protocol, the trial findings related to nursing process outcomes, and leadership behaviors.MethodsA mixed methods pilot study was conducted with a post‐only cluster randomized controlled trial and descriptive qualitative interviews.Four units were randomized to control or experimental groups. Clinical and management leadership teams participated in a 12‐week leadership intervention (workshop, teleconferences). Participants received summarized chart audit data, identified goals for change, and created a team leadership action.Criteria to assess feasibility of the protocol included: design, intervention, measures, and data collection procedures. For the trial, chart audits compared differences in nursing process outcomes. Primary outcome: 8‐item nursing assessments score. Secondary outcome: 5‐item score of nursing care based on goals for change identified by intervention participants. Qualitative interviews described leadership behaviors that influenced guideline use.ResultsConducting this pilot showed some aspects of the study protocol were feasible, while others require further development. Trial findings observed no significant difference in the primary outcome. A significant increase was observed in the 5‐item score chosen by intervention participants (p = 0.02). In the experimental group more relations‐oriented leadership behaviors, audit and feedback and reminders were described as leadership strategies.ConclusionsFindings suggest that a leadership intervention has the potential to influence nurses’ use of guideline recommendations, but further work is required to refine the intervention and outcome measures. A taxonomy of leadership behaviors is proposed to inform future research.
Conventional and Doppler ultrasound for the differentiation of benign and malignant canine mammary tumours
Authors: Feliciano M. A. R. , Vicente W. R. R. , Silva M. A. M. 
Published: May 2012

Objectives: The aim of this study was to evaluate the sensitivity of conventional and Doppler ultrasound for differentiation of benign and malignant mammary tumours in female dogs.Methods: Mammary tumours were evaluated from 60 animals and divided into two distinct groups, group 1 (benign tumours) and group 2 (malignant tumours). The tumours were assessed by conventional ultrasound, Doppler ultrasound mode, histopathology and immunohistochemical detection of vascular endothelial growth factor.Results: Conventional ultrasound examination was found to be ineffective in separating tumours into the two experimental groups. Similarly, using colour‐flow Doppler ultrasound, no correlation was found between the presence of vascularisation and its characteristics between the two groups. Triplex Doppler ultrasound yielded average maximum velocities of 28·71 cm/s for malignant and 19·91 cm/s for benign tumours, which were significantly different (P=0·01). For vascular endothelial growth factor, an average score of 2·22 was found for group 2 and 1·66 for group 1 (P=0·03). Positive correlations were found between vascular endothelial growth factor and presence of vascularisation (P=0·04 and r=0·3658) and between vascular endothelial growth factor and maximum velocity (P=0·03 and r=0·3913).Clinical Significance: Doppler evaluation may be used to predict malignancy of mammary tumours in bitches.
Clinical evaluation of cochlear hearing status in dogs using evoked otoacoustic emissions
Authors: Gonçalves R. , McBrearty A. , Pratola L. , Calvo G. , Anderson T. J. , Penderis J. 
Published: May 2012

Objectives: Evoked otoacoustic emission testing is the preferred test in human patients for sensorineural deafness screening in neonates and cochlear outer hair cell function monitoring in adults. This study evaluated evoked otoacoustic emission testing for cochlear function assessment in dogs within a clinical setting.Methods: Two populations of anaesthetised dogs were included. In group 1 the evoked otoacoustic emission response was compared to the brainstem auditory evoked response in 10 dogs having hearing assessment. Group 2 comprised 43 presumed normal dogs, in which the suitability of two types of evoked otoacoustic emissions, transient‐evoked and distortion product otoacoustic emissions, were evaluated (brainstem auditory evoked response was not performed in this group).Results: Valid transient‐evoked otoacoustic emission and distortion‐product otoacoustic emission responses were successfully recorded within the clinical setting and correctly identified deaf and hearing ears. Within presumed healthy dogs, normal otoacoustic emission response was demonstrated in more than 80% of dogs using a single, short distortion‐product otoacoustic emission run and in 78% of dogs with valid transient‐evoked otoacoustic emission responses using a series of three repeated transient‐evoked otoacoustic emission short runs.ClinicalSignificance: Transient‐evoked otoacoustic emission and distortion‐product otoacoustic emission testing provided a rapid, non‐invasive frequency‐specific assessment of cochlear function. Transient‐evoked otoacoustic emission and distortion product otoacoustic emission testing is suitable as a screening procedure to detect loss of cochlear function in dogs, although further investigation is needed.
Talking about alcohol consumption: Health campaigns, conversational valence, and binge drinking intentions
Authors: Hendriks Hanneke , de Bruijn Gert‐Jan , van den Putte Bas 
Published: May 2012

Objectives. Although research has shown that whether people talk about health issues influences health campaign effects, no evidence exists on whether conversational valence fulfils a mediating role within health campaign effects. In the context of alcohol consumption, this two‐wave experimental research studies the effects of exposure to an anti‐alcohol message on conversational valence about alcohol. Further, it investigates whether valence subsequently affects alcohol consumption intentions.Design. Eighty‐four undergraduate students, in dyads, were randomly assigned to one of two conditions (anti‐alcohol message vs. no alcohol message exposure).Methods. A baseline measure of the intention to refrain from binge drinking was assessed in advance. Two weeks later, half of the participants were exposed to an anti‐alcohol message, after which all pairs engaged in a conversation about alcohol and binge drinking followed by an assessment of conversational valence and again the intention to refrain from binge drinking.Results. An indirect effect of health message exposure on the intention to refrain from binge drinking through conversational valence was revealed. When participants viewed an anti‐alcohol message, they reported significantly more negative conversations about alcohol. Subsequently, a more negative conversational valence about alcohol increased the intention to refrain from binge drinking.Conclusions. These findings suggest that conversational valence is relevant for health campaign effects. By demonstrating that health messages can influence this valence, important implications arise in terms of health promotion. Future research should focus on how to design effective health campaigns that are able to guide conversational valence in the desired direction.Statement of ContributionWhat is already known on this subject?
Whether people talk about health issues is a relevant intervening variable within the health message – health intention pathway.
The valence of health conversations influences health intentions.
What does this study add?
Not only whether people talk, but also the valence of health conversations is a relevant intervening variable within health campaign effects.
Health message exposure can influence conversational valence. This valence can consequently influence health intentions. Thereby, this study holds important implications for health campaign planners.
Mutations in HIV-1gagandpolCompensate for the Loss of Viral Fitness Caused by a Highly Mutated Protease
Authors: Kožíšek Milan , Henke Sandra , Šašková Klára Grantz , Jacobs Graeme Brendon , Schuch Anita , Buchholz Bernd , Müller Viktor , Kräusslich Hans-Georg , Řezáčová Pavlína , Konvalinka Jan , Bodem Jochen 
Published: May 2012

ABSTRACTDuring the last few decades, the treatment of HIV-infected patients by highly active antiretroviral therapy, including protease inhibitors (PIs), has become standard. Here, we present results of analysis of a patient-derived, multiresistant HIV-1 CRF02_AG recombinant strain with a highly mutated protease (PR) coding sequence, where up to 19 coding mutations have accumulated in the PR. The results of biochemical analysisin vitroshowed that the patient-derived PR is highly resistant to most of the currently used PIs and that it also exhibits very poor catalytic activity. Determination of the crystal structure revealed prominent changes in the flap elbow region and S1/S1′ active site subsites. While viral loads in the patient were found to be high, the insertion of the patient-derived PR into a HIV-1 subtype B backbone resulted in reduction of infectivity by 3 orders of magnitude. Fitness compensation was not achieved by elevated polymerase (Pol) expression, but the introduction of patient-derivedgagandpolsequences in a CRF02_AG backbone rescued viral infectivity to near wild-type (wt) levels. The mutations that accumulated in the vicinity of the processing sites spanning the p2/NC, NC/p1, and p6pol/PR proteins lead to much more efficient hydrolysis of corresponding peptides by patient-derived PR in comparison to the wt enzyme. This indicates a very efficient coevolution of enzyme and substrate maintaining high viral loadsin vivounder constant drug pressure.
A Model for Evaluating Topical Antimicrobial Efficacy against Methicillin-Resistant Staphylococcus aureus Biofilms in Superficial Murine Wounds
Authors: Roche Eric D. , Renick Paul J. , Tetens Shannon P. , Carson Dennis L. 
Published: May 2012

ABSTRACT

A wound biofilm model was created by adapting a superficial infection model. Partial-thickness murine wounds were inoculated with methicillin-resistant
Staphylococcus aureus
(MRSA). Dense biofilm communities developed at the wound surface after 24 h as demonstrated by microscopy and quantitative microbiology. Common topical antimicrobial agents had reduced efficacy when treatment was initiated 24 h after inoculation compared to 4 h after inoculation. This model provides a rapid
in vivo
test for new agents to treat wound biofilm infections.
Adjunctive Daptomycin Attenuates Brain Damage and Hearing Loss More Efficiently than Rifampin in Infant Rat Pneumococcal Meningitis
Authors: Grandgirard Denis , Burri Melchior , Agyeman Philipp , Leib Stephen L. 
Published: May 2012

ABSTRACT
Exacerbation of cerebrospinal fluid (CSF) inflammation in response to bacteriolysis by beta-lactam antibiotics contributes to brain damage and neurological sequelae in bacterial meningitis. Daptomycin, a nonlytic antibiotic acting on Gram-positive bacteria, lessens inflammation and brain injury compared to ceftriaxone. With a view to a clinical application for pediatric bacterial meningitis, we investigated the effect of combining daptomycin or rifampin with ceftriaxone in an infant rat pneumococcal meningitis model.

IMPORTANCE
Eleven-day-old Wistar rats with pneumococcal meningitis were randomized to treatment starting at 18 h after infection with (i) ceftriaxone (100 mg/kg of body weight, subcutaneously [s.c.], twice a day [b.i.d.]), (ii) daptomycin (10 mg/kg, s.c., daily) followed 15 min later by ceftriaxone, or (iii) rifampin (20 mg/kg, intraperitoneally [i.p.], b.i.d.) followed 15 min later by ceftriaxone. CSF was sampled at 6 and 22 h after the initiation of therapy and was assessed for concentrations of defined chemokines and cytokines. Brain damage was quantified by histomorphometry at 40 h after infection and hearing loss was assessed at 3 weeks after infection. Daptomycin plus ceftriaxone versus ceftriaxone significantly (
P
< 0.04) lowered CSF concentrations of monocyte chemoattractant protein 1 (MCP-1), MIP-1α, and interleukin 6 (IL-6) at 6 h and MIP-1α, IL-6, and IL-10 at 22 h after initiation of therapy, led to significantly (
P
< 0.01) less apoptosis, and significantly (
P
< 0.01) improved hearing capacity. While rifampin plus ceftriaxone versus ceftriaxone also led to lower CSF inflammation (
P
< 0.02 for IL-6 at 6 h), it had no significant effect on apoptosis and hearing capacity. Adjuvant daptomycin could therefore offer added benefits for the treatment of pediatric pneumococcal meningitis.
Role of Innate Immune Receptors in Paradoxical Caspofungin ActivityIn Vivoin Preclinical Aspergillosis
Authors: Moretti Silvia , Bozza Silvia , D'Angelo Carmen , Casagrande Andrea , Della Fazia Maria Agnese , Pitzurra Lucia , Romani Luigina , Aversa Franco 
Published: May 2012

ABSTRACTThis study investigated the possible mechanisms underlying the paradoxical caspofungin activityin vivoin preclinical aspergillosis. We evaluated the activity of escalating doses of caspofunginin vivoin different preclinical models of invasive aspergillosis, including mice deficient for selected innate immune receptors. The therapeutic efficacy of caspofungin in experimental invasive aspergillosis was strictly dose dependent, being observed at doses of 0.1 and 1 mg/kg of body weight depending on the experimental models. Paradoxical increase in pulmonary fungal burden as well as inflammatory pathology was observed at the highest dose of caspofungin (5 mg/kg), occurred independently of the so-called Eagle effect and susceptibility to caspofunginin vitro, and was contingent upon the presence of TLR2, Dectin-1, and TLR9. Increased expression of Dectin-1 and TLR9 were observed upon exposure to caspofunginin vitroandin vivo. Together, these findings suggest that the net activity of caspofunginin vivois orchestrated by the activation, directly or indirectly, of multiple innate immune receptors.
Effect of Rifampin and Rifabutin on the Pharmacokinetics of Lersivirine and Effect of Lersivirine on the Pharmacokinetics of Rifabutin and 25-O-Desacetyl-Rifabutin in Healthy Subjects
Authors: Vourvahis Manoli , Davis John , Wang Rong , Layton Gary , Choo Heng Wee , Chong Chew-Lan , Tawadrous Margaret 
Published: May 2012

ABSTRACTLersivirine is a nonnucleoside reverse transcriptase inhibitor (NNRTI) with a unique resistance profile exhibiting potent antiviral activity against wild-type HIV and several clinically relevant NNRTI-resistant strains. Lersivirine, a weak inducer of the cytochrome P450 (CYP) enzyme CYP3A4, is metabolized by CYP3A4 and UDP glucuronosyltransferase 2B7 (UGT2B7). Two open, randomized, two-way (study 1; study A5271008) or three-way (study 2; study A5271043) crossover phase I studies were carried out under steady-state conditions in healthy subjects. Study 1 (n= 17) investigated the effect of oral rifampin on the pharmacokinetics (PKs) of lersivirine. Study 2 (n= 18) investigated the effect of oral rifabutin on the PKs of lersivirine and the effect of lersivirine on the PKs of rifabutin and its active metabolite, 25-O-desacetyl-rifabutin. Coadministration with rifampin decreased the profile of the lersivirine area under the plasma concentration-time curve from time zero to 24 h postdose (AUC24), maximum plasma concentration (Cmax), and plasma concentration observed at 24 h postdose (C24) by 85% (90% confidence interval [CI], 83, 87), 83% (90% CI, 79, 85), and 92% (90% CI, 89, 94), respectively, versus the values for lersivirine alone. Coadministration with rifabutin decreased the lersivirine AUC24,Cmax, andC24by 34% (90% CI, 29, 39), 25% (90% CI, 16, 33), and 58% (90% CI, 52, 64), respectively, compared with the values for lersivirine alone. Neither the rifabutin concentration profile nor overall exposure was affected following coadministration with lersivirine. Lersivirine and rifabutin reduced the 25-O-desacetyl-rifabutin AUC24by 27% (90% CI, 21, 32) andCmaxby 27% (90% CI, 19, 34). Lersivirine should not be coadministered with rifampin, which is a potent inducer of CYP3A4, UGT2B7, and P-glycoprotein activity and thus substantially lowers lersivirine exposure. No dose adjustment of rifabutin is necessary in the presence of lersivirine; an upward dose adjustment of lersivirine may be warranted when it is coadministered with rifabutin.
Efficacy of LFF571 in a Hamster Model of Clostridium difficile Infection
Authors: Trzasko Anna , Leeds Jennifer A. , Praestgaard Jens , LaMarche Matthew J. , McKenney David 
Published: May 2012

ABSTRACT

LFF571 is a novel semisynthetic thiopeptide antibiotic with potent activity against a variety of Gram-positive pathogens, including
Clostridium difficile
.
In vivo
efficacy of LFF571 was compared to vancomycin in a hamster model of
C. difficile
infection (CDI). Infection was induced in Golden Syrian hamsters using a toxigenic strain of
C. difficile
. Treatment started 24 h postinfection and consisted of saline, vancomycin, or LFF571. Cox regression was used to analyze survival data from a cohort of animals evaluated across seven serial experimental groups treated with vancomycin at 20 mg/kg, LFF571 at 5 mg/kg, or vehicle alone. Survival was right censored; animals were not observed beyond day 21. At death or end of study, cecal contents were tested for
C. difficile
toxins A and B. In summary, the data showed that 5 mg/kg LFF571 decreased the risk of death by 79% (
P
< 0.0001) and 69% (
P
= 0.0022) compared with saline and 20 mg/kg vancomycin, respectively. Further analysis of the pooled data indicated that the survival benefit of LFF571 treatment at 5 mg/kg compared to vancomycin at 20 mg/kg was due primarily to a decrease in the risk of recurrence after end of treatment. Animals successfully treated with LFF571 or vancomycin had no detectable
C. difficile
toxin. Overall, LFF571 was more efficacious at the end of the study, at a lower dose, and with fewer recurrences, than vancomycin in the hamster model of CDI. LFF571 is being assessed in humans for safety and efficacy in the treatment of
C. difficile
infections.
High-Dose Daptomycin plus Fosfomycin Is Safe and Effective in Treating Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus Endocarditis
Authors: Miró José M. , Entenza José M. , del Río Ana , Velasco Maria , Castañeda Ximena , Garcia de la Mària Cristina , Giddey Marlyse , Armero Yolanda , Pericàs Juan M. , Cervera Carlos , Mestres Carlos A. , Almela Manuel , Falces Carlos , Marco Francesc , Moreillon Philippe , Moreno Asuncion 
Published: May 2012

ABSTRACT

We describe 3 patients with left-sided staphylococcal endocarditis (1 with methicillin-susceptible
Staphylococcus aureus
[MSSA] prosthetic aortic valve endocarditis and 2 with methicillin-resistant
S. aureus
[MRSA] native-valve endocarditis) who were successfully treated with high-dose intravenous daptomycin (10 mg/kg/day) plus fosfomycin (2 g every 6 h) for 6 weeks. This combination was tested
in vitro
against 7 MSSA, 5 MRSA, and 2 intermediately glycopeptide-resistant
S. aureus
isolates and proved to be synergistic against 11 (79%) strains and bactericidal against 8 (57%) strains. This combination deserves further clinical study.
Antibody Pressure by a Human Monoclonal Antibody Targeting the 2009 Pandemic H1N1 Virus Hemagglutinin Drives the Emergence of a Virus with Increased Virulence in Mice
Authors: O’Donnell Christopher D. , Vogel Leatrice , Wright Amber , Das Suman R. , Wrammert Jens , Li Gui-Mei , McCausland Megan , Zheng Nai-Ying , Yewdell Jonathan W. , Ahmed Rafi , Wilson Patrick C. , Subbarao Kanta 
Published: May 2012

ABSTRACTIn 2009, a novel H1N1 influenza A virus (2009 pH1N1) emerged and caused a pandemic. A human monoclonal antibody (hMAb; EM4C04), highly specific for the 2009 pH1N1 virus hemagglutinin (HA), was isolated from a severely ill 2009 pH1N1 virus-infected patient. We postulated that under immune pressure with EM4C04, the 2009 pH1N1 virus would undergo antigenic drift and mutate at sites that would identify the antibody binding site. To do so, we infected MDCK cells in the presence of EM4C04 and generated 11 escape mutants, displaying 7 distinct amino acid substitutions in the HA. Six substitutions greatly reduced MAb binding (K123N, D131E, K133T, G134S, K157N, and G158E). Residues 131, 133, and 134 are contiguous with residues 157 and 158 in the globular domain structure and contribute to a novel pH1N1 antibody epitope. One mutation near the receptor binding site, S186P, increased the binding affinity of the HA to the receptor. 186P and 131E are present in the highly virulent 1918 virus HA and were recently identified as virulence determinants in a mouse-passaged pH1N1 virus. We found that pH1N1 escape variants expressing these substitutions enhanced replication and lethality in mice compared to wild-type 2009 pH1N1 virus. The increased virulence of these viruses was associated with an increased affinity for α2,3 sialic acid receptors. Our study demonstrates that antibody pressure by an hMAb targeting a novel epitope in the Sa region of 2009 pH1N1 HA is able to inadvertently drive the development of a more virulent virus with altered receptor binding properties. This broadens our understanding of antigenic drift.IMPORTANCEInfluenza viruses accumulate amino acid substitutions to evade the antibody response in a process known as antigenic drift, making it necessary to vaccinate against influenza annually. Mapping human monoclonal antibody (hMAb) epitopes is a necessary step towards understanding antigenic drift in humans. We defined the specificity of an hMAb that specifically targeted the 2009 pH1N1 virus and describe a novel epitope. In addition, we identified a previously unappreciated potential for antibody escape to enhance the pathogenicity of a virus. The escape mutation that we identified within vitroimmune pressure was independently reported by other investigators usingin vivoselection in nonimmune mice. Althoughin vitrogeneration of escape mutants is unlikely to recapitulate antigenic drift in its entirety, the data demonstrate that pressure by a human monoclonal antibody targeting a novel epitope in the hemagglutinin of the 2009 pandemic H1N1 virus can inadvertently drive the development of escape mutants, of which a subset have increased virulence and altered receptor binding properties.