bluuebunny/crossref_metadata_2025_split huggingface dataset:
The pathogenic actinobacterium Rhodococcus equi: what's in a name?
Authors: Vázquez‐Boland José A. , Meijer Wim G. 
Published: May 2019

SummaryRhodococcus equi is the only recognized animal pathogenic species within an extended genus of metabolically versatile Actinobacteria of considerable biotechnological interest. Best known as a horse pathogen, R. equi is commonly isolated from other animal species, particularly pigs and ruminants, and causes severe opportunistic infections in people. As typical in the rhodococci, R. equi niche specialization is extrachromosomally determined, via a conjugative virulence plasmid that promotes intramacrophage survival. Progress in the molecular understanding of R. equi and its recent rise as a novel paradigm of multihost adaptation has been accompanied by an unusual nomenclatural instability, with a confusing succession of names: "Prescottia equi", "Prescotella equi", Corynebacterium hoagii and Rhodococcus hoagii. This article reviews current advances in the genomics, biology and virulence of this pathogenic actinobacterium with a unique mechanism of plasmid‐transferable animal host tropism. It also discusses the taxonomic and nomenclatural issues around R. equi in the light of recent phylogenomic evidence that confirms its membership as a bona fide Rhodococcus.
Job's Unfinalizable Voice: An Addendum to David Burrell's Deconstructing Theodicy
Authors: Williams Trevor B 
Published: May 2019

AbstractModern theodicies often offer definitive explanations for the unsolvable problem of human suffering. This philosophical enterprise was challenged by David B. Burrell's book,Deconstructing Theodicy: Why Job Has Nothing to Say to the Puzzle of Suffering(2008). His observations about the book of Job and the way it militates against theodical speculation are compelling, but there is a missed opportunity with his exegesis of Job 42:6. The Hebrew of Job's last words can be translated in at least five distinct (and legitimate) ways. Using this grammatical characteristic, this paper argues that the ambiguity in 42:6 creates an “unfinalizable” quality that allows sufferers to be unsilenced and participate in the meaning-making process. Situating the addendum with philosophical ruminations on theodicy, the argument turns to an exegetical section that comments on Burrell's discussion in “Denouement and Epilogue” and analyzes the Hebrew grammar of Job 42:1-6. This addendum compliments Burrell's deconstruction of theodicy, adding a further pool of resources for sufferers to remain unsilenced and narrate their own questioning of God.
Increased food utilization indices and decreased proteolytic activity in Helicoverpa armigera larvae fed sublethal Bacillus thuringiensis‐treated diet
Authors: Fathipour Yaghoub , Sedaratian Amin , Bagheri Abdoolnabi , Talaei‐Hassanlouei Reza 
Published: May 2019

AbstractThe cotton bollworm Helicoverpa armigera is one of the most devastating insect pests. A set of protease enzymes allows this species to feed on different host plant species. Control measures in agriculture often involve the application of the pathogenic bacterium Bacillus thuringiensis subsp. kurstaki (Btk). In the present study, the effects of sublethal Btk doses are evaluated with respect to the food utilization indices and proteolytic activities of Helicoverpa armigera. Accordingly, the H. armigera larvae are fed with artificial diet containing sublethal Btk doses (LC5, LC10, LC15, LC20 and LC25) and a Btk‐free diet as control. All but one of the food utilization indices we measured is observed to increase significantly with increasing Btk doses. By contrast, the specific activity of total protease, chymotrypsin and elastase enzymes decrease significantly with an increasing Btk concentration. We conclude that Btk was not toxic to H. armigera larvae and any damage that it causes can be compensated for by H. armigera larvae via various mechanisms. In conclusion, increased nutritional indices in the larvae fed with Btk diet represent an important issue that needs to be considered to avoid the pest establishing Bt resistant populations. Meanwhile, the lack of effect of Btk sublethal concentrations on trypsin enzyme specific activity can bolster this challenge.
Promoting Children Growth and Development: A community‐based cluster randomized controlled trial in rural areas of Indonesia
Authors: Susanto Tantut , Yunanto Rismawan Adi , Rasny Hanny , Susumaningrum Latifa Aini , Nur Kholid Rosyidi Muhammad 
Published: May 2019

AbstractObjectiveThis study examined the influence of the Promote Children's Growth and Development (PCGD) intervention on children's growth and development in rural areas in Indonesia.Design and SampleA community‐based nonblinded cluster randomized controlled trial was conducted. Twelve clusters of villages were matched based on population and randomly assigned to intervention group (six clusters and 72 caregivers dyads) or control group (six clusters and 72 caregivers dyads) with inclusion criteria age 0–72 months and attending integrated health centers (Posyandu). The intervention was conducted for 14 weeks with caregivers.MeasuresThe weight‐for‐age Z‐score (WAZ), height‐for‐age Z‐score (HAZ), weight‐for‐height Z‐score (WHZ), and body mass index‐for‐age Z‐score (BAZ) were calculated using World Health Organization Anthro‐Plus version 1.0.3. A prescreening developmental questionnaire (PSDQ) measured the development of children before and after the intervention.ResultsThe proportion of stunting of HAZ, wasting of WHZ, and deviation development of PSDQ were higher in the control group compared to the intervention group, respectively (22.2% vs. 37.5%), (9.7% vs. 4.2%), and (12.5% vs. 2.8%). Caregivers were more confident promoting children's growth and development after attending 12 sessions of the PCGD intervention.ConclusionThe 12 session PCGD intervention is effective for promoting the growth and development of children of 0–72 months. The PCGD could be considered for implementation in community health centers.
Perceptual Bias and Public Programs: The Case of the United States and Hospital Care
Authors: Meier Kenneth J. , Johnson Austin P. , An Seung‐Ho 
Published: May 2019

AbstractThis article examines whether the public holds biased perceptions of public organizations (in this case, hospitals) in the United States and whether organizations get credit for positive results from program evaluations. Using an experimental design that replicates Hvidman and Andersen's2016Danish study, the study finds no negative public sector biases in the United States, but organizations are not given any credit for positive program evaluations. These results hold in two experimental replications. The implications of the findings for the measurement of public perceptions of government programs and for effective democratic governance are discussed.
The effects of topical dorzolamide 2% and brinzolamide 1%, either alone or combined with timolol 0.5%, on intraocular pressure, pupil diameter, and heart rate in healthy cats
Authors: Slenter Inge J. M. , Djajadiningrat‐Laanen Sylvia C. , Elders Daphne J. , de Gee Reinoud , Koele Linda E. , Vermeer Loes W. , Boevé Michael H. 
Published: May 2019

AbstractObjectiveTo investigate the effects of topical dorzolamide 2% q8h and brinzolamide 1% q8h, administered either alone (A and B, respectively) or in combination with topical timolol 0.5% q12h (C and D, respectively), on the circadian pattern of intraocular pressure (IOP), the pupil size, and heart rate in healthy cats.MethodsIn this prospective, randomized, double‐blinded study, 10 healthy, adult cats were randomly assigned to one of four groups and the eye to be medicated was randomly assigned. IOP, pupil diameter, and heart rate were measured at 3‐hour intervals. A 5 days’ adjustment period was followed by a 5 days’ placebo (baseline) period. Then, all groups of cats received all four treatments (A‐D) according to a Latin square‐based rotating schedule. Five days’ medication periods were alternated with 3 days’ washout periods.ResultsMean baseline IOP was 13.6 ± 2.7 mm Hg. All treatments resulted in a statistically significant decrease in mean IOP in the treated eye: A: −2.33 mm Hg (95% CI: −2.71, −1.94), B: −1.91 mm Hg (95% CI: −2.30, −1.53), C: −2.36 mm Hg (95% CI: −2.74, −1.97), and D: −2.37 mm Hg (95% CI: −2.76, −1.98) and the nontreated eye: A: −0.19 mm Hg (95% CI: −0.28, −0.11), B: −0.18 mm Hg (95% CI: −0.27, −0.10), C −0.31 mm Hg (95% CI: −0.40, −0.23), and D: −0.24 mm Hg (95% CI: −0.32, −0.15). Timolol resulted in an additional, significant decrease in IOP of 4% and 5%, respectively, compared to A and B, and in mild bradycardia and miosis.ConclusionsTopical administration of dorzolamide 2% and brinzolamide 1% q8h significantly decreased IOP in healthy cats. Supplemental timolol 0.5% eye drops q12h resulted in an additional, statistically significant reduction of IOP.
P62 Population pharmacokinetic study of aminophylline in Indian preterm neonates (≤34weeks) with apnoea; a longitudinal observational study
Authors: M S , Lewis L , Mallayasamy S 
Published: May 2019

BackgroundCurrent dosage regimen of aminophylline is similar in both Appropriate for Gestational Age (AGA) and Small for Gestational Age (SGA) preterm neonates.1 In contrast with AGA babies, SGA babies handle drugs in different way. However, developing countries like India has significant proportion of Growth Restricted/SGA babies. Hence, there is a need to develop appropriate dosage regimen in this population. Objective of the current study was set to develop and qualify the Population-Pharmacokinetic (PPK) model for aminophylline in premature neonates in Indian population.2MethodsAminophylline-treated neonates with IV loading dose of 5 mg/kg followed by maintenance dose of 1.5 or 2 mg/kg 8th hourly for Apnoea of Prematurity (AOP) were included. Any other conditions for secondary causes were excluded. Blood samples were collected by adopting sparse sample scheme and estimated by LCMS-MS. PPK model was developed with appropriate covariates.3 Data was analysed by NONMEM vesion 7.3. Non-parametric bootstrap procedure and Visual Predictive Check (VPC) was used to qualify the developed model.ResultsOne compartment, first-order structured model was fitted to the dataset containing 454 observations from 107 neonates. PPK parameters were represented as model estimated values and variability was depicted as% Co-efficient of variation (%CV). Typical population value of CL was 0.011 L/hour with inter-individual variability (IIV) of 59% and V was 0.332 (L/kg) with 31% IIV. Residual error was found to be 19%. Only postnatal age (PNA) had significant effect on V which was assessed by forward addition and backword elimination regression model.ConclusionAGA and SGA had no influence on PK parameters. However, PNA showed to have significant influence on V. Developed nomogram based on the qualified model may be effective and safe for aminophylline therapy in preterm neonates with apnoea.ReferencesShivakumar M, Jayashree P, Najih M, Lewis LES, Bhat Y R, Kamath A, et al. Comparative Efficacy and Safety of Caffeine and Aminophylline for Apnea of Prematurity in Preterm (≤34 weeks) Neonates: A Randomized Controlled Trial. Indian Pediatr 2017 Apr 15;54(4):279–83.U S Department of Health and Human Services, FDA, Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER): Guidance for Industry Population pharmacokinetics; 1991; Feb CP1, 35 pages.Ette EI, Sun H, Ludden TM, Balanced designs in longitudinal Population Pharmacokinetic studies. Journal of Clinical Pharmacology 1998 May; 38(5):417–423.Disclosure(s)Nothing to disclose
P68 Significant oral drug use in critically ill children: rational therapy or a black box?
Authors: Mooij M , Windster J , van Rosmalen J , Hanff L , Tibboel D , de Wildt S 
Published: May 2019

BackgroundThe disposition of orally prescribed drugs in critically ill children may be affected critical illness in in addition to age, resulting in erratic effects and safety. We aimed to study oral drug prescribing in the neonatal and pediatric intensive care unit (NICU and PICU).MethodsA one-year retrospective cohort study of all drug prescriptions, including route of administration for all children admitted to the NICU and PICU of the Erasmus MC-Sophia’s children’s hospital.Results1723 children with 2091 unique admissions received per admission (median [IQR]) 5 (3–10) drugs; 1 (0–2) orally and 3 (1–7) intravenously (IV). During mechanical ventilation 15% and 75% of drugs were given orally and IV, respectively. In non-ventilated patients, 27% of drugs were given orally and 60% IV. The 5 most frequently orally prescribed drugs were: vitamin K, spironolactone, oral probiotics, amphotericin B (prophylaxis) and trimethoprim.DiscussionCritically ill infants receive a considerable proportion of drugs orally. Considering that critical illness may significantly impact intestinal drug absorption, this may expose them to an increased risk of ineffective or unsafe drug therapy.Disclosure(s)Nothing to disclose
P74 Rituximab effect on B cell depletion in paediatric patients with autoimmune diseases: a retrospective dose-response analysis of an observational study
Authors: Pan S , Yu H , Surti A , Cheng I , Marks SD , Brogan PA , Eleftheriou D , Standing JF 
Published: May 2019

BackgroundRituximab is a chimeric IgG1 monoclonal antibody that depletes B cells for the treatment of several conditions including autoimmune diseases. It is not licensed for use in children but administered off-label. This study aimed to quantify the effect of rituximab on B cell depletion in children with autoimmune diseases and to optimise the dosing regimen.MethodsElectronic health record data were collected from a retrospective and anonymised study at Great Ormond Street Hospital in London. Dosing protocols of rituximab were two 750 mg/m2 intravenous infusions or four weekly 375 mg/m2 infusions. Serum concentrations of rituximab were not measured. CD19+ lymphocyte counts were taken before and after rituximab treatment. A turnover mechanism described the life cycle of CD19+ lymphocytes with rituximab increasing the death rate of CD19+ lymphocytes; a negative feedback was added on the production rate to examine the rebound effect. Rituximab was assumed to decay by first-order kinetics.Results258 measurements of CD19+ lymphocyte counts were collected from 39 children with 8 autoimmune diseases. The dose-response model well described the time course of CD19+ lymphocytes following rituximab administration. The elimination half-lives of rituximab and CD19+ lymphocytes were estimated to be 19 and 35 days, respectively, consistent with findings from other studies [1–5]. The rebound increase in CD19+ lymphocytes was found negligible. Methotrexate and cyclophosphamide increased the maximum death rate by 66% and 38% respectively. Age and gender were not significant covariates.Simulations from the model suggested that a single infusion of rituximab of 375 mg/m2 can provide similar six-month suppression of CD19+ lymphocytes to the higher doses currently used. Methotrexate or cyclophosphamide added minimal suppression effect on CD19+ lymphocytes when taken concurrently with rituximab.ConclusionsOur results could be used in future to assess the effect of rituximab biosimilars and to inform biosimilar dosing in paediatric populations.ReferencesNg, et al. J Clin Pharmacol. 2005; 45:792–801Li, et al. Blood. 2007; 110:2371Li, et al. J Clin Pharmacol. 2012; 52:1918–26Fulcher and Basten. Immunol Cell Biol. 1997; 75:446–55Macallan, et al. Blood. 2005; 105:3633–40Disclosure(s)Nothing to disclose
P78 Pharmacokinetics of intravenous and intranasal nalbuphine in infants
Authors: Pfiffner M , Gotta V , Berger-Olah E , Pfister M , Vonbach P 
Published: May 2019

BackgroundNalbuphine is a mixed agonist-antagonist opioid analgesic agent frequently used in paediatrics, and licensed for parenteral use only. Intranasal delivery could be a safe, effective and non-invasive alternative, especially in infants in the acute setting. However, pharmacokinetic (PK) data for this route of administration is completely lacking. The aim of this study was to assess PK of nalbuphine in infants 1–3 months after single intravenous (0.05 mg/kg) and intranasal (0.1 mg/kg) application, respectively.MethodsWe conducted a prospective, single centre, open-label pharmacokinetic study in infants 1–3 months undergoing sepsis workup in the emergency unit. Included infants received alternating nalbuphine as 0.05 mg/kg intravenous bolus or as 0.1 mg/kg intranasal spray. PK samples were taken at 3 pre-defined time points (15, 30 and max. 240 min post-dose before discharge). Area under the concentration-time curve (AUC0-Tlast, and AUC0-infinity for i.v.) was calculated using noncompartmental analysis and was compared between groups using Wilcoxon test. Further parameters derived included maximum concentration (Cmax), time of maximum concentration (Tmax for i.n.) and terminal half-life (t1/2).ResultsA total of 31 patients were included in the analysis. Median age was 55 days [interquartile range 38–63] in the intranasal (N=20) and 42 [37–76] days in the iv group (N=11). Median AUC0-Tlast was 7.6 (5.4–10.4) mcg*h/L following intranasal versus 7.9 (6.0–14.7) mcg*h/L for iv administration (p=0.46). AUC0-Tlast (i.v.) covered 80 [68–83]% of AUC0-infinity. Median Cmax was 4.5 [3.5–5.6] mcg/L (i.n.) versus 6.5 [5.3–15.9] mcg/L (i.v.) (p=0.014), t1/22.4 [1.3–2.8] h (i.n.) versus 1.3 [1.1–1.5] h (i.v.) (p=0.021). Tmax occurred 37 [32–65] min after intranasal administration.ConclusionThis first PK study of intranasal nalbuphine in infants suggests that 0.1 mg/kg i.n. dosing provides similar exposure as 0.05 mg/kg i.v. in infants in terms of AUC, and hence intranasal bioavailability close to 50%.Disclosure(s)Nothing to disclose
P81 Use of systemic antibiotics in Austrian children and adolescents: a survey
Authors: Rauch E , Lagler FB , Herkner H , Strenger V , Male C 
Published: May 2019

BackgroundSeveral surveys that have assessed the use of antibiotic medicines for children and adolescents demonstrate significant heterogeneity in prescription patterns between different countries. The liberal use of antibacterial treatment, particularly unjustified use of broad spectrum antibiotics, is one of the main reasons for increasing rates of antibiotic resistance. We have studied antibiotics prescription frequencies in children and adolescents in Austria covering both primary and hospital care settings, in order to obtain a representative survey for our country.MethodsPrescription data for systemic antibiotics were assessed for the year 2014. For primary care, reimbursement data were obtained from Austrian health insurances. For hospital care, information on medicines dispensed to paediatric wards was obtained from hospital pharmacies. Frequencies of systemic antibiotic use were analyzed by Anatomical Therapeutic Chemical classification system, age groups, care setting, and in relation to all other medicines used. Systemic antibiotics were divided into subgroups, like broad and narrow spectrum penicillins, cephalosporins, tetracyclins, and others.ResultsSystemic antibiotics comprised 24% and 21% of all medicines prescribed to children and adolescents in primary care and hospital care, respectively. The most frequent were broad spectrum antibiotics (32% and 35% of systemic antibiotics prescribed) in both primary and hospital care settings. Macrolides and 2nd generation cephalosporins were more frequently prescribed in primary care setting, whereas ß-lactam antibiotics other than cephalosporins and antibiotics, such as fluorochinolones, aminoglycosides, or linezolid were more frequently used in hospital.ConclusionsThis is the first representative survey investigating the use of systemic antibiotics in children and adolescents in Austria. The study allows comparison of prescription patterns to other European countries: it reveals rather big differences to systemic antibiotics prescription in Italy, the Netherlands and Denmark, whereas prescription patterns are similar in Germany and Austria. Furthermore, this survey provides the basis to assess temporal trends in the future.Disclosure(s)Nothing to disclose
O12 Circulating concentrations of broad-spectrum beta-lactams in children with cancer: beware of glomerular hyperfiltration!
Authors: André P , Diezi L , Decosterd LA , Crisinel PA , Dao K , Diezi M , Asner S , Buclin T 
Published: May 2019

BackgroundBroad-spectrum beta-lactams such as meropenem (MER) and piperacillin-tazobactam (PIP) are commonly prescribed in children with cancer having febrile neutropenia. They are introduced at intensive dosage, unless decreased renal function calls for dose reduction. Recently, glomerular hyperfiltration (HF) was recognized to be frequent among children with cancer during initial cycles of chemotherapy.1 We evaluated the impact of HF on therapeutic exposure to MER and PIP.MethodsWe retrieved retrospectively all MER and PIP plasma levels measured in children with cancer in our hospital between 2012 and 2018. We compared trough levels with usual therapeutic ranges (derived from reference values of minimum inhibitory concentrations). We classified the children according to plasma creatinine and estimated glomerular filtration rate (Schwartz formula) as either altered-normal (< 160 mL/min/1.73 m2) or increased (i.e. HF, ≥160). Neutropenia was defined as absolute neutrophil count < 500 cells/µL.ResultsWe collected 120 concentration values (53 MER, 67 PIP) measured in 50 children with cancer. Among them, 74 (62%) had concomitant creatinine values suggestive of HF, and 80 (67%) were neutropenic. Overall, 67% of trough levels were below usual therapeutic ranges (MER: 2–8 mg/L, PIP 8–30 mg/L). This was more often the case in presence of concomitant HF (MER: 92%, PIP: 83%), often associated with neutropenia. Low exposure was observed not only at initial intensive dosage (MER: 120 mg/kg/day, PIP: 400 mg/kg/day)2 but tended to persist despite dosage readjustment based on concentration monitoring. Moreover, bacteremia was diagnosed in 38 cases.ConclusionCurrent recommended doses of MER and PIP do not provide optimal concentration coverage throughout the dosing interval in a large fraction of children with cancer and febrile neutropenia as a result of HF. Monitoring of beta-lactams should be offered to all children with cancer to ensure best therapeutic success and avoid the development of resistance.ReferencesKwatra NS, Meany HJ, Ghelani SJ, Zahavi D, Pandya N, Majd M. Glomerular hyperfiltration in children with cancer: prevalence and a hypothesis. Pediatr Radiol 2017;47(2):221–226.The Lexicomp Pediatric & Neonatal Dosage Handbook, 21st edition, Lexicomp, USA.Disclosure(s)Nothing to disclose