bluuebunny/crossref_metadata_2025_split huggingface dataset:
Augmented Renal Clearance Implies a Need for Increased Amoxicillin-Clavulanic Acid Dosing in Critically Ill Children
Authors: De Cock Pieter A. J. G. , Standing Joseph F. , Barker Charlotte I. S. , de Jaeger Annick , Dhont Evelyn , Carlier Mieke , Verstraete Alain G. , Delanghe Joris R. , Robays Hugo , De Paepe Peter 
Published: September 2015

ABSTRACT

There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added
a priori
to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study [NCT02456974].)
Interactions of Klebsiella pneumoniae with the Innate Immune System Vary in Relation to Clone and Resistance Phenotype
Authors: Pantelidou Iliana-Maria , Galani Irene , Georgitsi Marianna , Daikos George L. , Giamarellos-Bourboulis Evangelos J. 
Published: September 2015

ABSTRACT

Apart from inadequate antimicrobial treatment, specific virulence factors contribute to the high attributable mortality of infections caused by multidrug-resistant (MDR)
Klebsiella pneumoniae
. We explored the roles of MDR and clones as virulence determinants of
K. pneumoniae
and their interaction with innate immunity. Twenty isolates were studied and characterized by resistance phenotype and multilocus sequence type (MLST). Human peripheral blood mononuclear cells (PBMCs) were stimulated for the production of proinflammatory cytokines by live and heat-killed isolates and plasmid DNA; modulation by cellular pathway inhibitors was explored. Survival of 30 mice was recorded after intraperitoneal challenge with susceptible and
K. pneumoniae
carbapenemase (KPC)-producing isolates. Splenocytes of mice were stimulated for the production of pro- and anti-inflammatory cytokines. Isolates were divided into different patterns of production of tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) poststimulation in relation to both the MLST clone and resistance phenotype. The sequence type 383 (ST383) clone producing Verona integron-encoded metallo-β-lactamase (VIM) stimulated high production of both TNF-α and IL-1β. Clone ST17 producing KPC elicited low TNF-α production; this was reversed by Toll-like receptor 9 (TLR9) antagonists, indicating an effect of plasmid DNA. This isolate was linked with early death of mice compared to high-TNF-α-producing isolates. We conclude that KPC-producing isolates seem to be highly virulent in a low-TNF-α-release environment, suggesting an immunoparalysis induction mechanism. KPC plasmids may directly contribute to the immune system stimulation.
Role of Host Cell-Derived Amino Acids in Nutrition of Intracellular Salmonella enterica
Authors: Popp Jasmin , Noster Janina , Busch Kim , Kehl Alexander , zur Hellen Gero , Hensel Michael 
Published: September 2015

ABSTRACT

The facultative intracellular pathogen
Salmonella enterica
resides in a specific membrane-bound compartment termed the
Salmonella
-containing vacuole (SCV). Despite being segregated from access to metabolites in the host cell cytosol,
Salmonella
is able to efficiently proliferate within the SCV. We set out to unravel the nutritional supply of
Salmonella
in the SCV with focus on amino acids. We studied the availability of amino acids by the generation of auxotrophic strains for alanine, asparagine, aspartate, glutamine, and proline in a macrophage cell line (RAW264.7) and an epithelial cell line (HeLa) and examined access to extracellular nutrients for nutrition. Auxotrophies for alanine, asparagine, or proline attenuated intracellular replication in HeLa cells, while aspartate, asparagine, or proline auxotrophies attenuated intracellular replication in RAW264.7 macrophages. The different patterns of intracellular attenuation of alanine- or aspartate-auxotrophic strains support distinct nutritional conditions in HeLa cells and RAW264.7 macrophages. Supplementation of medium with individual amino acids restored the intracellular replication of mutant strains auxotrophic for asparagine, proline, or glutamine. Similarly, a mutant strain deficient in succinate dehydrogenase was complemented by the extracellular addition of succinate. Complementation of the intracellular replication of auxotrophic
Salmonella
by external amino acids was possible if bacteria were proficient in the induction of
Salmonella
-induced filaments (SIFs) but failed in a SIF-deficient background. We propose that the ability of intracellular
Salmonella
to redirect host cell vesicular transport provides access of amino acids to auxotrophic strains and, more generally, is essential to continuously supply bacteria within the SCV with nutrients.
The Fibronectin-Binding Protein EfbA Contributes to Pathogenesis and Protects against Infective Endocarditis Caused by Enterococcus faecalis
Authors: Singh Kavindra V. , La Rosa Sabina Leanti , Somarajan Sudha R. , Roh Jung Hyeob , Murray Barbara E. 
Published: September 2015

ABSTRACT

EfbA is a PavA-like fibronectin adhesin of
Enterococcus faecalis
previously shown to be important in experimental urinary tract infection. Here, we expressed and purified the
E. faecalis
OG1RF EfbA and confirmed that this protein binds with high affinity to immobilized fibronectin, collagen I, and collagen V. We constructed an
efbA
deletion mutant and demonstrated that its virulence was significantly attenuated (
P
< 0.0006) versus the wild type in a mixed inoculum rat endocarditis model. Furthermore,
efbA
deletion resulted in diminished ability to bind fibronectin (
P
< 0.0001) and reduced biofilm (
P
< 0.001). Reintroduction of
efbA
into the original chromosomal location restored virulence, adherence to fibronectin, and biofilm formation to wild-type levels. Finally, vaccination of rats with purified recombinant EfbA protein protected against OG1RF endocarditis (
P
= 0.008
versus
control). Taken together, our results demonstrate that EfbA is an important factor involved in
E. faecalis
endocarditis and that rEfbA immunization is effective in preventing such infection, likely by interfering with bacterial adherence.
LL-37 Immunomodulatory Activity during Mycobacterium tuberculosis Infection in Macrophages
Authors: Torres-Juarez Flor , Cardenas-Vargas Albertina , Montoya-Rosales Alejandra , González-Curiel Irma , Garcia-Hernandez Mariana H. , Enciso-Moreno Jose A. , Hancock Robert E. W. , Rivas-Santiago Bruno 
Published: September 2015

ABSTRACT

Tuberculosis is one of the most important infectious diseases worldwide. The susceptibility to this disease depends to a great extent on the innate immune response against mycobacteria. Host defense peptides (HDP) are one of the first barriers to counteract infection. Cathelicidin (LL-37) is an HDP that has many immunomodulatory effects besides its weak antimicrobial activity. Despite advances in the study of the innate immune response in tuberculosis, the immunological role of LL-37 during
M. tuberculosis
infection has not been clarified. Monocyte-derived macrophages were infected with
M. tuberculosis
strain H37Rv and then treated with 1, 5, or 15 μg/ml of exogenous LL-37 for 4, 8, and 24 h. Exogenous LL-37 decreased tumor necrosis factor alpha (TNF-α) and interleukin-17 (IL-17) while inducing anti-inflammatory IL-10 and transforming growth factor β (TGF-β) production. Interestingly, the decreased production of anti-inflammatory cytokines did not reduce antimycobacterial activity. These results are consistent with the concept that LL-37 can modulate the expression of cytokines during mycobacterial infection and this activity was independent of the P2X7 receptor. Thus, LL-37 modulates the response of macrophages during infection, controlling the expression of proinflammatory and anti-inflammatory cytokines.
Field Science—the Nature and Utility of Scientific Fields
Authors: Casadevall Arturo , Fang Ferric C. 
Published: September 2015

ABSTRACT
Fields are the fundamental sociological units of science. Despite their importance, relatively little has been written about their emergence, composition, structure, and function in the scientific enterprise. This essay considers the nature of fields and their important role in maintaining information and providing normative standards for scientific work. We suggest that fields arise naturally as a consequence of increasing information and scientific specialization. New fields tend to emerge as research communities grow, which may reflect biologically determined optima for the size of human groups. The benefits of fields include the organization of scientists with similar interests into communities that collectively define the next important problems to pursue. In the discipline of microbiology, fields are often organized on the basis of phylogenetic differences between microorganisms being studied. Although fields are essential to the proper functioning of science, their emergence can restrict access by outsiders and sustain dogmas that hinder progress. We suggest mechanisms to improve the functioning of scientific fields and to promote interdisciplinary interaction between fields.
Reservoirs of Extraintestinal Pathogenic
Escherichia coli
Authors: Manges Amee R. , Johnson James R. 
Published: September 2015

ABSTRACT

Several potential reservoirs for the
Escherichia coli
strains that cause most human extraintestinal infections (extraintestinal pathogenic
E. coli
; ExPEC) have been identified, including the human intestinal tract and various non-human reservoirs, such as companion animals, food animals, retail meat products, sewage, and other environmental sources. Understanding ExPEC reservoirs, chains of transmission, transmission dynamics, and epidemiologic associations will assist greatly in finding ways to reduce the ExPEC-associated disease burden. The need to clarify the ecological behavior of ExPEC is all the more urgent because environmental reservoirs may contribute to acquisition of antimicrobial resistance determinants and selection for and amplification of resistant ExPEC. In this chapter, we review the evidence for different ExPEC reservoirs, with particular attention to food and food animals, and discuss the public health implications of these reservoirs for ExPEC dissemination and transmission.
Counting the costs of accreditation in acute care: an activity-based costing approach
Authors: Mumford Virginia , Greenfield David , Hogden Anne , Forde Kevin , Westbrook Johanna , Braithwaite Jeffrey 
Published: September 2015

ObjectivesTo assess the costs of hospital accreditation in Australia.DesignMixed methods design incorporating: stakeholder analysis; survey design and implementation; activity-based costs analysis; and expert panel review.SettingAcute care hospitals accredited by the Australian Council for Health Care Standards.ParticipantsSix acute public hospitals across four States.ResultsAccreditation costs varied from 0.03% to 0.60% of total hospital operating costs per year, averaged across the 4-year accreditation cycle. Relatively higher costs were associated with the surveys years and with smaller facilities. At a national level these costs translate to $A36.83 million, equivalent to 0.1% of acute public hospital recurrent expenditure in the 2012 fiscal year.ConclusionsThis is the first time accreditation costs have been independently evaluated across a wide range of hospitals and highlights the additional cost burden for smaller facilities. A better understanding of the costs allows policymakers to assess alternative accreditation and other quality improvement strategies, and understand their impact across a range of facilities. This methodology can be adapted to assess international accreditation programmes.
Smoking in the home after childbirth: prevalence and determinants in an English cohort
Authors: Orton Sophie , Coleman Tim , Jones Laura L , Cooper Sue , Lewis Sarah 
Published: September 2015

ObjectivesChildren's exposure to secondhand smoke (SHS) is causally linked to childhood morbidity and mortality. Over 38% of English children (aged 4–15) whose parents are smokers are exposed to SHS in the home. Little is known about the prevalence of SHS exposure in the homes of young infants (≤3 months). This study aimed to estimate maternal self-reported prevalence of SHS exposure among infants of women who smoked just before or during pregnancy, and identify factors associated with exposure.SettingPrimary Care, Nottingham, England.ParticipantsCurrent and recent ex-smoking pregnant women (n=850) were recruited in Nottingham, England. Women completed questionnaires at 8–26 weeks gestation and 3 months after childbirth. Data on smoking in the home 3 months after childbirth was available for 471 households.Primary and secondary outcome measuresMaternal-reported smoking in the home 3 months after childbirth.ResultsThe prevalence of smoking in the home 3 months after childbirth was 16.3% (95% CI 13.2% to 19.8%) and after multiple imputation controlling for non-response 18.2% (95% CI 14.0% to 22.5%). 59% of mothers were current smokers; of these, 24% reported that smoking occurred in their home compared to 4.7% of non-smokers. In multivariable logistic regression, mothers smoking ≥11 cigarettes per day were 8.2 times (95% CI 3.4 to 19.6) more likely to report smoking in the home. Younger age, being of non-white ethnicity, increased deprivation and less negative attitudes towards SHS were also associated with smoking in the home.ConclusionsThis survey of smoking in the home 3 months after childbirth found a lower prevalence than has been reported in older children. Interventions to support smoking mothers to quit, or to help them restrict smoking in the home, should target attitudinal change and address inequality relating to social disadvantage, younger age and non-white ethnic groups.
The influence of snoring, mouth breathing and apnoea on facial morphology in late childhood: a three-dimensional study
Authors: Al Ali Ala , Richmond Stephen , Popat Hashmat , Playle Rebecca , Pickles Timothy , Zhurov Alexei I , Marshall David , Rosin Paul L , Henderson John , Bonuck Karen 
Published: September 2015

ObjectiveTo explore the relationship between the prevalence of sleep disordered breathing (SDB) and face shape morphology in a large cohort of 15-year-old children.DesignObservational longitudinal cohort studySettingAvon Longitudinal Study of Parents and Children (ALSPAC), South West of England.ParticipantsThree-dimensional surface laser scans were taken for 4784 white British children from the ALSPAC during a follow-up clinic. A total of 1724 children with sleep disordered breathing (SDB) and 1862 healthy children were identified via parents’ report of sleep disordered symptoms for their children. We excluded from the original cohort all children identified as having congenital abnormalities, diagnoses associated with poor growth and children with adenoidectomy and/or tonsillectomy.Main outcome measuresParents in the ALSPAC reported sleep disordered symptoms (snoring, mouth breathing and apnoea) for their children at 6, 18, 30, 42, 57, 69 and 81 months. Average facial shells were created for children with and without SDB in order to explore surface differences.ResultsDifferences in facial measurements were found between the children with and without SDB throughout early childhood. The mean differences included an increase in face height in SDB children of 0.3 mm (95% CI −0.52 to −0.05); a decrease in mandibular prominence of 0.9° (95% CI −1.30 to −0.42) in SDB children; and a decrease in nose prominence and width of 0.12 mm (95% CI 0.00 to 0.24) and 0.72 mm (95% CI −0.10 to −0.25), respectively, in SDB children. The odds of children exhibiting symptoms of SDB increased significantly with respect to increased face height and mandible angle, but reduced with increased nose width and prominence.ConclusionsThe combination of a long face, reduced nose prominence and width, and a retrognathic mandible may be diagnostic facial features of SBD that may warrant a referral to specialists for the evaluation of other clinical symptoms of SDB.
A retrospective analysis of the effect of discussion in teleconference and face-to-face scientific peer-review panels
Authors: Carpenter Afton S , Sullivan Joanne H , Deshmukh Arati , Glisson Scott R , Gallo Stephen A 
Published: September 2015

ObjectiveWith the use of teleconferencing for grant peer-review panels increasing, further studies are necessary to determine the efficacy of the teleconference setting compared to the traditional onsite/face-to-face setting. The objective of this analysis was to examine the effects of discussion, namely changes in application scoring premeeting and postdiscussion, in these settings. We also investigated other parameters, including the magnitude of score shifts and application discussion time in face-to-face and teleconference review settings.DesignThe investigation involved a retrospective, quantitative analysis of premeeting and postdiscussion scores and discussion times for teleconference and face-to-face review panels. The analysis included 260 and 212 application score data points and 212 and 171 discussion time data points for the face-to-face and teleconference settings, respectively.ResultsThe effect of discussion was found to be small, on average, in both settings. However, discussion was found to be important for at least 10% of applications, regardless of setting, with these applications moving over a potential funding line in either direction (fundable to unfundable or vice versa). Small differences were uncovered relating to the effect of discussion between settings, including a decrease in the magnitude of the effect in the teleconference panels as compared to face-to-face. Discussion time (despite teleconferences having shorter discussions) was observed to have little influence on the magnitude of the effect of discussion. Additionally, panel discussion was found to often result in a poorer score (as opposed to an improvement) when compared to reviewer premeeting scores. This was true regardless of setting or assigned reviewer type (primary or secondary reviewer).ConclusionsSubtle differences were observed between settings, potentially due to reduced engagement in teleconferences. Overall, further research is required on the psychology of decision-making, team performance and persuasion to better elucidate the group dynamics of telephonic and virtual ad-hoc peer-review panels.
Reducing the number and impact of outbreaks of nosocomial viral gastroenteritis: time-series analysis of a multidimensional quality improvement initiative
Authors: Mitchell Caroline , Meredith Paul , Richardson Matthew , Greengross Peter , Smith Gary B 
Published: September 2015

BackgroundNosocomial norovirus infections and their control measures disrupt patient care, increase staff workload and raise healthcare costs.ObjectiveTo determine the impact on outbreaks of nosocomial viral gastroenteritis, staff and patients affected, and bed closures of a multidimensional quality improvement (QI) initiative focused on education; improved patient surveillance; early automated recognition and notification of infection of index patients; and proactive care and control measures.MethodsIn a pragmatic, retrospective, observational study, we compared numbers of suspected/confirmed norovirus outbreaks at Portsmouth Hospitals National Health Service Trust (PHT) with regional and national data, before and after a multidimensional QI initiative. We also compared mean daily bed closures due to norovirus-like symptoms. At PHT only we recorded patient and staff numbers with norovirus-like symptoms, and days of disruption due to outbreaks.ResultsAnnual outbreak numbers fell between 2009–2010 and 2010–2014 by 91% at PHT compared with 15% and 28% for Wessex and England, respectively. After April 2010, recorded outbreaks were 8 (PHT), 383 (Wessex) and 5063 (England). For the winter periods from 2010/2011 to 2013/2014, total bed closures due to norovirus were 38 (PHT; mean 0.5 per week), 3565 (Wessex hospitals; mean 48.8 per hospital per week) and 2730 (England; mean 37.4 per hospital per week). At PHT, patients affected by norovirus-like symptoms fell by 92%, affected staff by 81% and days of disruption by 88%.ConclusionsA multiyear QI programme, including use of real-time electronic identification of patients with norovirus-like symptoms, and an early robust response to suspected infection, resulted in virtual elimination of outbreaks. The ability to identify index cases of infection early facilitates prompt action to prevent ongoing transmission and appears to be a crucial intervention.
Impact of frailty on outcomes after percutaneous coronary intervention: a prospective cohort study
Authors: Murali-Krishnan Rachel , Iqbal Javaid , Rowe Rebecca , Hatem Emer , Parviz Yasir , Richardson James , Sultan Ayyaz , Gunn Julian 
Published: September 2015

BackgroundAverage life expectancy is rising, resulting in increasing numbers of elderly, frail individuals presenting with coronary artery disease and requiring percutaneous coronary intervention (PCI). PCI can be of value for this population, but little is known about the balance of benefit versus risk, particularly in the frail.ObjectiveTo determine the relationship between frailty and clinical outcomes in patients undergoing PCI.MethodsPatients undergoing PCI, for either stable angina or acute coronary syndrome, were prospectively assessed for frailty using the Canadian Study of Health and Ageing Clinical Frailty Scale. Demographics, clinical and angiographic data were extracted from the hospital database. Mortality was obtained from the Office of National Statistics.ResultsFrailty was assessed in 745 patients undergoing PCI. The mean age of patients was 62±12 years and 70% were males. The median frailty score was 3 (IQR 2–4). A frailty score ≥5, indicating significant frailty, was present in 81 (11%) patients. Frail patients required longer hospitalisation after PCI. Frailty was also associated with increased 30-day (HR 4.8, 95% CI 1.4 to 16.3, p=0.013) and 1 year mortality (HR 5.9, 95% CI 2.5 to 13.8, p<0.001). Frailty was a predictor of length of hospital stay and mortality, independent of age, gender and comorbidities.ConclusionsA simple assessment of frailty can help predict mortality and the length of hospital stay, and may therefore guide healthcare providers to plan PCI and appropriate resources for frail patients.