bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHARMACOKINETIC STUDIES IN NEONATES: IS AN OPPORTUNISTIC SAMPLING STRATEGY SUFFICIENT FOR POPULATION PHARMACOKINETIC MODELLING AND DOSE PREDICTION?
Authors: Leroux Stéphanie , Turner Mark A. , Guellec Chantal Barin-Le , Hill Helen , Anker Johannes N. van den , Kearns Gregory L. , Jacqz-Aigrain Evelyne , Zhao Wei 
Published: December 2015

Background and objectiveThe use of an opportunistic (also called scavenged) sampling strategy in a prospective pharmacokinetic study combined with population pharmacokinetic modelling has been proposed as an alternative strategy to conventional methods for accomplishing pharmacokinetic studies in neonates. However, the reliability of this approach in this particular paediatric population has not been evaluated. The objective of the present study was to evaluate the performance of an opportunistic sampling strategy for a population pharmacokinetic estimation as well as dose prediction, and compare this strategy to a pre-determined pharmacokinetic sampling approach.MethodsThree population pharmacokinetic models were derived for ciprofloxacin from opportunistic blood samples (SC model), pre-determined (i.e., scheduled) samples (TR model) and all samples (full model used to previously characterize ciprofloxacin pharmacokinetics), respectively, using NONMEM software. The predictive performance of developed models was evaluated in an independent group of patients.ResultsPharmacokinetic data from 60 newborns were obtained with a total of 430 samples available for analysis; 265 collected at pre-determined times and 165 that were scavenged from those obtained as part of clinical care. All data sets were fit using a two-compartment model with first order elimination. The SC model could identify the most significant covariates and provided reasonable estimates of population pharmacokinetic parameters (clearance and steady state volume of distribution) as compared to the TR and full models. Their predictive performances were further confirmed in an external validation by Bayesian estimation and showed similar results. Monte Carlo simulation based on AUC0–24/MIC using either the SC or the TR model gave similar dose prediction for ciprofloxacin.ConclusionBlood samples scavenged in the course of caring for neonates can be used to estimate ciprofloxacin pharmacokinetic parameters and therapeutic dose requirements.
JOINT COMMISSION INTERNATIONAL (JCI) IN THE PEDIATRIC INTENSIVE CARE UNIT (PICU): PREVENTING MEDICATION INCIDENTS THROUGH REMOTE CONTROL
Authors: Lazaryan Moran , Berkovitch Sofia , Toledano Michal , Yehoshua Noa Rosenfeld- , Abu-Kishk Ibraim , Berkovitch Matitiahu 
Published: December 2015

IntroductionMany medical centers worldwide try to get JCI accreditation in order to improve safety and quality of patient care. Review of medication orders for appropriateness is one of the JCI standards. This process is usually performed by clinical pharmacists joining physician rounds. However, in many medical centers there is a shortage of pharmacists.ObjectivesTo prospectively investigate the process of remote reviewing of medication orders in the PICU, with a pharmacist located at the pharmacy, without joining physician rounds. To characterize pharmacist recommendations (PR) and decisions taken by the physician.MethodsThe study was carried out from 6.3.14–6.10.14 in the PICU (7 beds). Patient demographics, diagnosis and medications prescribed were recorded.Results186 review forms were filled in by the pharmacist, regarding 117 admissions(109 children). In 57 (30.6%) forms there was at least one PR. Most common PRs concerned significant interactions (34.5%), dose (26.2%), technical inappropriateness (22.6%) and contraindications (8.3%). Out of all PRs, 51.2% were accepted by the physician, 11.9% rejected and in 36.9% there was no comment. The estimated review time for one medical record was 8.9 min (95% CI, 6.9–10.9), as every additional medication prescribed increased the total review time by 0.8 min (95% CI, 0.49–1.11). Using Monte-Carlo simulation, 108.42 min per day were needed to review all medical records in 95% of the cases.ConclusionsHospitals facing budget shortages can perform a daily remote review of several departments by an experienced pharmacist instead of participation in physician rounds, and still have a considerable effect on patient safety.
LEVOSIMENDAN IN TREATMENT OF CONGENITAL AND ACQUIRED HEART DISEASES
Authors: Dinarević Senka , Jonuzi Fedzat , Halimic Mirza , Begic Zijo , Kadić Almira , Gojak Refet 
Published: December 2015

IntroductionLevosimendan as a new generation vasoactive coronary and peripheral dilatation drug, has been recently developed for cardiac decompensation treatment.AimTo evaluate the effects on cardiac function during treatment with Levosimendan in cardiac decompensated severely ill infants and children.MethodsRetrospective-prospective study was performed in Paediatric Clinic CC University of Sarajevo, from 01.01.2013. till 30.12.2014. Study included 7 pts; with congenital/post surgery Tetralogia Fallot/ and acquired heart diseases/dilated cardiomyopathy-myocarditis/pts. Patients were divided into two groups: I Group pre treatment and II Group, post Levosimendan treatment. Parameters evaluated were: age, sex, diagnosis, left ventricle EF /LV EF/pre and post-treatment (EF1 and EF2/and use of inotropic drugs.ResultsThe evaluated variables were: age in I Group of pts /4/ with congenital heart disease: mean 7.5 months/ratio: 6.5–8.5 months of age/and in second with acquired heart diseases /3/, mean: 8.5 years of age/3–14 years/, 3 boys; inotropic drugs used in both Groups of pts: Noradrenalin, Dobutamin, Dopamine and Corotrop which were decreased and stopped in the First Group 2nd day post Levosimendan start and in second Group, 3rd day stopped post Levosimendan start. LV EF evaluated in both Groups; difference of mean EF1 in relation to mean EF2 values, showed statistically significant improvement of LV function /p=0,002/ and decrease in inotropic support.ConclusionLevosimendan has positive effects on myocardial function restoration regardless on congenital or acquired heart diseases in paediatric population as well as in decrease in inotropic support and rapid myocardial cell recovery.
PROSPECTIVE VALIDATION OF A MODEL-BASED DOSING REGIMEN FOR AMIKACIN IN NEONATES: FEASIBLE AND RELEVANT
Authors: Smits Anne , Cock Roosmarijn De , Allegaert Karel , Vanhaesebrouck Sophie , Danhof Meindert , Knibbe Catherijne 
Published: December 2015

IntroductionA neonatal amikacin dosing regimen was previously developed based on a population pharmacokinetic model. The aim of the current study was to prospectively validate this model-derived dosing regimen.MethodsFirst, early (before and after second dose) therapeutic drug monitoring (TDM) observations were evaluated for achieving target trough (<3 mg/L) and peak (>24 mg/L) levels. Secondly, observed concentrations were compared with model-predicted concentrations, whereby the results of an NPDE (normalized prediction distribution error) were considered as well. Subsequently, Monte Carlo simulations were performed. Finally, remaining causes limiting amikacin predictability (prescription errors and disease characteristics of outliers) were explored.ResultsIn 579 neonates [median (range) birth bodyweight 2285 (420–4850) g, postnatal age 2 (1–30) days, gestational age 34 (24–41) weeks], 90.5% of early peak levels reached 24 mg/L and 60.2% of trough levels was <3 mg/L (93.4% ≤5 mg/L). Observations were accurately predicted by the model without bias, which was confirmed by the NPDE. Monte Carlo simulations showed that peak concentrations >24 mg/L were reached in almost all patients. Trough values <3 mg/L were documented in 78–100% and 45–96% of simulated cases, respectively, when ibuprofen was co-administered or not. Suboptimal trough levels were found in patient subgroups with postnatal age <14 days and current weight >2000g.ConclusionsProspective validation of a model-based neonatal amikacin dosing regimen resulted in optimized peak and trough concentrations in almost all patients. Adapted dosing for patients with suboptimal trough levels was proposed. Besides improving dosing individualization, feasibility and relevance of neonatal prospective validation studies was demonstrated.
SLOW INFUSIONS OF GENTAMICIN ARE ASSOCIATED WITH HIGH VARIABILITY IN PEAK GENTAMICIN CONCENTRATIONS IN LOW GESTATION AGE (GA) NEONATES
Authors: Medlicott Natalie , Thomas Louise , Broadbent Roland , Reith David 
Published: December 2015

IntroductionDelayed gentamicin delivery through intravenous lines has been reported.Delay is expected to be greater in smaller neonates when the flow rate of carrier intravenous fluid and dose volumes are low.AimTo investigate the effects of neonate GA and weight on gentamicin peak concentrations after 30 minute infusion or bolus administrations.MethodsNeonates admitted to Dunedin Neonatal Intensive Care Unit in 2008 and 2010 who received gentamicin (2008: 30 minute infusion; 2010: slow bolus) in the first three days of life were included. Peak concentrations were compared and correlations between concentration and weight were investigated over GA bands.ResultsThere were 151 neonates in 2010 and 118 neonates in 2008. Median (range) GA was 38 weeks (24–42) in 2010 and 34.7 weeks (23.4–42.1) in 2008. Median (range) weight was 3.25kg (0.51–5.65) in 2010 and 2.67kg (0.49–5.11) in 2008. Peak gentamicin concentrations (mg/L) were 8.15±0.098 (at 1.2±0.32h) in 2010 and 9.92±0.17 (at 1.34±0.4h) in 2008. A test for equal variances showed peak concentrations were more variable in 2008 (p0.05).ConclusionsPeak concentrations were more variable following 30 minute infusions and were positively correlated with GA or weight for neonates with GA.
GENTAMICIN PHARMACOKINETIC VARIABILITY IS INFLUENCED BY CHOICE OF ADMINISTRATION ROUTE
Authors: Lala Anita , Medlicot Natalie , Broadbent Roland , McCaffrey Frances , Reith David 
Published: December 2015

IntroductionA critically ill neonate may have several routes of venous access available, operating at different flow rates and with different dead-volumes, and therefore with different delivery kinetics.AimsTo determine which lumen of a double lumen umbilical venous catheter (UVC) would be used for administration of intravenous gentamicin to a premature baby and what flush volume would be used.MethodsAn individual self-administered questionnaire was completed by Dunedin Hospital NICU nurses in April-May 2014. The questionnaire consisted of two scenarios describing babies of 24 and 32 weeks gestation, and asked that the site of administration be chosen on a diagram. Secondary information regarding flush volume was also collected and free-text responses encouraged.ResultsThere were 42 nurses employed in Dunedin NICU during this period, of whom 37 (88%) responded. For a 24-week gestation baby, 34 nurses (92%) would administer into the primary lumen (20ga), containing 10% dextrose (0.5 mL/hr), compared to 3 (8%) who would use the secondary lumen (23ga), containing parenteral nutrition fluid (2.1 mL/hr). For a 32-week gestation baby 35 nurses (95%) would administer through the slow-flowing primary lumen. If a peripheral intravenous line (PIV) was present this would be used preferentially by 35 nurses (95%) to reduce the risk of infection. Smaller flush volumes were documented following administration through the UVC compared with PIV (1.17–1.35 mL vs 2.4 mL at 24 weeks and 1.42–1.74 mL vs 3.2 mL at 32 weeks).DiscussionThe variability in intravenous delivery route may be a significant contributor to variability in neonatal gentamicin pharmacokinetics.
Influence of religious organisations’ statements on compliance with a smoke-free law in Bogor, Indonesia: a qualitative study
Authors: Byron M Justin , Cohen Joanna E , Gittelsohn Joel , Frattaroli Shannon , Nuryunawati Ramadhani , Jernigan David H 
Published: December 2015

ObjectiveTo explore the Bogor public's perspective on Muslim organisations’ pronouncements against smoking and the effect of these pronouncements on compliance with a new smoke-free law in the context of a prosmoking social norm.DesignSemistructured focus group discussions were conducted, transcribed, coded using ATLAS.ti software, and analysed using thematic content analysis. Photo elicitation was also used during the focus groups.SettingBogor, Indonesia.Participants11 focus groups (n=89), stratified by age, gender and smoking status, with members of the public (46 male, 43 female, ages 18–50).ResultsThere was limited knowledge of and compliance with both the smoke-free law and the religious pronouncements. In most of the focus groups, smoking was described as a discouraged, but not forbidden, behaviour for Muslims. Participants described the decision of whether to follow the religious pronouncements in the context of individual choice. Some participants felt religious organisations lacked credibility to speak against smoking because many religious leaders themselves smoke. However, some non-smokers said their religion reinforced their non-smoking behaviour and some participants stated it would be useful for religious leaders to speak more about the smoke-free law.ConclusionsReligious organisations’ pronouncements appear to have had a small effect, primarily in supporting the position of non-smokers not to smoke. Participants, including smokers, said their religious leaders should be involved in supporting the smoke-free law. These findings suggest there is potential for the tobacco control community to partner with sympathetic local Muslim leaders to promote common goals of reducing smoking and public smoke exposure. Muslim leaders’ views on smoking would be perceived as more credible if they themselves followed the smoke-free law. Additionally, public health messaging that includes religious themes could be piloted and tested for effectiveness. These findings may also inform similar efforts in other Muslim cities implementing smoke-free laws.
Prevalence and risk factors of retinopathy in patients with or without metabolic syndrome: a population-based study in Shenyang
Authors: Liu Lei , Yue Song , Wu Jingyang , Zhang Jiahua , Lian Jie , Teng Weiping , Huang Desheng , Chen Lei 
Published: December 2015

ObjectiveTo investigate the relationship between metabolic syndrome (MS) and the prevalence of retinopathy.DesignA cross-sectional study was carried out from August 2013 to September 2014 in Fengyutan Sub-District.Primary and secondary outcome measuresA total of 1163 eligible participants attended. All the participants were subjected to stereo fundus photography to detect retinopathy. The discrepancy of prevalence of retinopathy in different participants was described.ResultsThe prevalence of retinopathy was 9.64% in patients with MS and 3.91% in patients without MS. A higher prevalence of retinopathy with proliferative diabetic retinopathy was found in patients with MS. In multiple logistic regression analysis, independent risk factors for any retinopathy in patients with MS were longer diabetes duration (OR 1.07; 95% CI 1.04 to 1.10, per year increase), higher systolic blood pressure (SBP) (OR 1.16; 95% CI 1.09 to 1.29, per 10 mm Hg increase), higher diastolic blood pressure (DBP) (OR 1.24; 95% CI 1.12 to 1.35, per 10 mm Hg increase), higher fasting plasma glucose (OR 1.07; 95% CI 1.02 to 1.11, per 10 mg/dL increase), higher 2 h postprandial plasma glucose (OR 1.17; 95% CI 1.12 to 1.21, per 10 mg/dL increase), and higher haemoglobin A1c (HbA1c) (OR 1.23; 95% CI 1.13 to 1.34, per % increase). Similar independent risk factors, except for DBP, were found for any retinopathy in patients without MS.ConclusionsThe presence of MS components, hyperglycaemia (fasting glucose and HbA1c) and hypertension (SBP and DBP), are significantly associated with the prevalence of retinopathy.
Driving performance in patients with chronic obstructive lung disease, interstitial lung disease and healthy controls: a crossover intervention study
Authors: Skovhus Prior Thomas , Troelsen Thomas , Hilberg Ole 
Published: December 2015

IntroductionCognitive deficits in patients suffering from chronic obstructive pulmonary disease (COPD) have been described and hypoxaemia has been addressed as a possible cause. Cognitive functions in patients with interstitial lung disease (ILD) are not well studied. These patients are taking part in everyday traffic, but little is known regarding their driving performance. This study was conducted to determine the driving performance in patients with COPD and ILD, respectively compared to healthy controls using a driving simulator. Additionally, the effect of oxygen supply was addressed.Methods16 patients with COPD (8 receivers and 8 non-receivers of long-term oxygen therapy (LTOT)), 8 patients with ILD (consisting of idiopathic interstitial pneumonias) and 8 healthy controls were tested in a driving simulator. Each test lasted 45 min. In the oxygen intervention part of the study the patients were randomised to receive oxygen therapy in the first or second test and acted as their own controls.ResultsPatients with COPD had significantly impaired driving performance when comparing SD from the centre of the road and number of off-road events to controls. Patients with COPD receiving LTOT performed significantly worse than those not receiving LTOT when comparing SD and worse than the patients with ILD when comparing SD and off-road events. Patients with ILD performed similarly to controls (SD: LTOT 2.39*; no LTOT 0.69*; ILD 0.37; controls 0.36; *p<0.05. Off-road: LTOT 226.67*; no LTOT 78.92*; ILD 40.00; controls 25.78; *p<0.05). Oxygen therapy had no effect on driving performance.ConclusionsPatients with ILD performed similarly to controls in the driving simulator, whereas patients with COPD showed decreased driving performance, especially those receiving LTOT. Doctors should be aware of this when renewing the driving license of patients with COPD. Oxygen therapy showed no effect on driving performance.Trial registration numberNCT02125916
Review on the degradation and device physics of quantum dot solar cells
Authors: Afshar Elham N. , Rouhi Rasoul , Gorji Nima E. 
Published: December 2015

Briefly, we reviewed the latest progress in energy conversion efficiency and degradation rate of the quantum dot (QD) solar cells. QDs are zero dimension nanoparticles with tunable size and accordingly tunable band gap. The maximum performance of the most advanced QD solar cells was reported to be around 10%. Nevertheless, majority of research groups do not investigate the stability of such devices. QDs are cheaper replacements for silicon or other thin film materials with a great potential to significantly increase the photon conversion efficiency via two ways: (i) creating multiple excitons by absorbing a single hot photon, and (ii) formation of intermediate bands (IBs) in the band gap of the background semiconductor that enables the absorption of low energy photons (two-step absorption of sub-band gap photons). Apart from low conversion efficiency, QD solar cells also suffer from instability under real operation and stress conditions. Strain, dislocations and variation in size of the dots (under pressure of the other layers) are the main degradation resources. While some new materials (i.e. perovskites) showed an acceptable high performance, the QD devices are still inefficient with an almost medium rate of 4% (2010) to 10% (2015).
Field-based structural studies as analogues to sub-surface reservoirs
Authors: Sanderson David J. 
Published: December 2015

Abstract
This paper examines a number of field analogues to structures in the sub-surface, based mainly on examples from SW Britain. Whereas sedimentological analogues are largely interpreted in terms of a clearly defined sequence of depositional events related to stratigraphy, structures can develop throughout the history of the reservoir and their timing is poorly constrained stratigraphically. This leads to fundamental differences in how the two types of analogues are used. The simplest and most direct use of structural analogues comes from comparison of field structures with those sampled in the sub-surface, where they can guide conceptual development of reservoir models. Many examples of this approach exist from the development of stratabound fracture systems to the formation of linked fault systems and fracture networks. Field analogues also play an important role in the study of sub-seismic structures, providing a link to evidence from core. One new area is the application of topology to the study of fault and fracture networks. Not only does this provide insight into fundamental relationships between structures, such as their relative age and connectivity, but it also provides new methods of analysis of great relevance to the spatial variation and scaling of structures.
Genomic Profiling of Penile Squamous Cell Carcinoma Reveals New Opportunities for Targeted Therapy
Authors: McDaniel Andrew S. , Hovelson Daniel H. , Cani Andi K. , Liu Chia-Jen , Zhai Yali , Zhang Yajia , Weizer Alon Z. , Mehra Rohit , Feng Felix Y. , Alva Ajjai S. , Morgan Todd M. , Montgomery Jeffrey S. , Siddiqui Javed , Sadis Seth , Bandla Santhoshi , Williams Paul D. , Cho Kathleen R. , Rhodes Daniel R. , Tomlins Scott A. 
Published: December 2015

Abstract
Penile squamous cell carcinoma (PeSCCA) is a rare malignancy for which there are limited treatment options due to a poor understanding of the molecular alterations underlying disease development and progression. Therefore, we performed comprehensive, targeted next-generation sequencing to identify relevant somatic genomic alterations in a retrospective cohort of 60 fixed tumor samples from 43 PeSCCA cases (including 14 matched primary/metastasis pairs). We identified a median of two relevant somatic mutations and one high-level copy-number alteration per sample (range, 0–5 and 0–6, respectively). Expression of HPV and p16 was detectable in 12% and 28% of patients, respectively. Furthermore, advanced clinical stage, lack of p16 expression, and MYC and CCND1 amplifications were significantly associated with shorter time to progression or PeSCCA-specific survival. Notably, four cases harbored EGFR amplifications and one demonstrated CDK4 amplification, genes for which approved and investigational targeted therapies are available. Importantly, although paired primary tumors and lymph node metastases were largely homogeneous for relevant somatic mutations, we identified heterogeneous EGFR amplification in primary tumor/lymph node metastases in 4 of 14 cases, despite uniform EGFR protein overexpression. Likewise, activating HRAS mutations occurred in 8 of 43 cases. Taken together, we provide the first comprehensive molecular PeSCCA analysis, which offers new insight into potential precision medicine approaches for this disease, including strategies targeting EGFR. Cancer Res; 75(24); 5219–27. ©2015 AACR.