Use of routine data for determination of the population pharmacokinetics and enteral biovailability of phenytoin in neonates and infants with seizures

Objective: To investigate the population pharmacokinetics and the enteral bioavailability of phenytoin in neonates and infants with seizures. Methods: Data (5 mg kg-1 day-1) from 83 patients were obtained retrospectively from the medical records following written ethical approval. A one-compartment model was fitted to the data using NONMEM with FOCE-interaction. Between-subject variability (BSV) and interoccasion variability (IOV) were modelled exponentially together with a log transform-both-sides exponential residual unexplained variance (RUV) model. Covariates in nested models were screened for significance (X2, 1, 0.01). Model validity was determined by bootstrapping with replacement (N=500 samples) from the dataset. Results: The parameters of final pharmacokinetic were: Clearance (L h-1) = 0.826.(current Weight [kg]/70)0.75.(1+0.0692.(Postnatal age [days]-11)); Volume of distribution (L) = 74.2.(current Weight [kg]/70); Enteral bioavailability = 0.76; Absorption rate constant (h-1) = 0.167. BSV for clearance and volume of distribution were 74.2% and 65.6%, respectively. The IOV in clearance was 54.4%. The RUV was 51.1%. Final model parameters deviated from mean bootstrap estimates by

Evaluation of routine microbiological techniques for establishing the diagnosis of catheter-related bloodstream infection caused by coagulase-negative staphylococci

Microbiological diagnosis of catheter-related bloodstream infection (CR-BSI) is often based on isolation of indistinguishable micro-organisms from an explanted catheter tip and blood culture, confirmed by antibiograms. Whether phenotypic identification of coagulase-negative staphylococci (CoNS) allows an accurate diagnosis of CR-BSI to be established was evaluated. Eight patients with a diagnosis of CR-BSI had CoNS isolated from pure blood cultures and explanted catheter tips which were considered as indistinguishable strains by routine microbiological methods. For each patient, an additional three colonies of CoNS isolated from the blood and five from the catheter tip were subcultured and further characterized by antibiogram profiles, analytical profile index (API) biotyping and PFGE. PFGE distinguished more strains of CoNS compared to API biotyping or antibiograms (17, 10 and 11, respectively). By PFGE, indistinguishable micro-organisms were only isolated from pure blood and catheter tip cultures in four out of eight (50%) patients thus supporting the diagnosis of CR-BSI. In another patient, indistinguishable micro-organisms were identified in both cultures; however, other strains of CoNS were also present. The remaining three patients had multiple strains of CoNS, none of which were indistinguishable in the tip and blood cultures, thus questioning the diagnosis of CR-BSI. Phenotypic characterization of CoNS lacked discriminatory power. Current routine methods of characterizing a limited number of pooled colonies may generate misleading results as multiple strains may be present in the cultures. Multiple colonies should be studied using a rapid genotypic characterization method to confirm or refute the diagnosis of CR-BSI. © 2007 SGM.

Clinical outcomes after implantation of a new hydrophobic acrylic toric IOL during routine cataract surgery

PURPOSE: To assess the clinical outcomes after implantation of a new hydrophobic acrylic toric intraocular lens (IOL) to correct preexisting corneal astigmatism in patients having routine cataract surgery. SETTING: Four hospital eye clinics throughout Europe. DESIGN: Cohort study. METHODS: This study included eyes with at least 0.75 diopter (D) of preexisting corneal astigmatism having routine cataract surgery. Phacoemulsification was performed followed by insertion and alignment of a Tecnis toric IOL. Patients were examined 4 to 8 weeks postoperatively; uncorrected distance visual acuity (UDVA), corrected distance visual acuity, manifest refraction, and keratometry were measured. Individual patient satisfaction with uncorrected vision and the surgeon’s assessment of ease of handling and performance of the IOL were also documented. The cylinder axis of the toric IOL was determined by dilated slitlamp examination. RESULTS: The study enrolled 67 eyes of 60 patients. Four to 8 weeks postoperatively, the mean UDVA was 0.15 logMAR G 0.17 (SD) and the UDVA was 20/40 or better in 88% of eyes. The mean refractive cylinder decreased significantly postoperatively, from -1.91 +/- 1.07 D to -0.67 +/- 0.54 D. No significant change in keratometric cylinder was observed. The mean absolute IOL misalignment from the intended axis was 3.4 degrees (range 0 to 12 degrees). The good UDVA resulted in high levels of patient satisfaction. CONCLUSION: Implantation of the new toric IOL was an effective, safe, and predictable method to manage corneal astigmatism in patients having routine cataract surgery.

Conversational interaction in the scanner:mentalizing during language processing as revealed by MEG

Humans are especially good at taking another's perspective-representing what others might be thinking or experiencing. This "mentalizing" capacity is apparent in everyday human interactions and conversations. We investigated its neural basis using magnetoencephalography. We focused on whether mentalizing was engaged spontaneously and routinely to understand an utterance's meaning or largely on-demand, to restore "common ground" when expectations were violated. Participants conversed with 1 of 2 confederate speakers and established tacit agreements about objects' names. In a subsequent "test" phase, some of these agreements were violated by either the same or a different speaker. Our analysis of the neural processing of test phase utterances revealed recruitment of neural circuits associated with language (temporal cortex), episodic memory (e.g., medial temporal lobe), and mentalizing (temporo-parietal junction and ventromedial prefrontal cortex). Theta oscillations (3-7 Hz) were modulated most prominently, and we observed phase coupling between functionally distinct neural circuits. The episodic memory and language circuits were recruited in anticipation of upcoming referring expressions, suggesting that context-sensitive predictions were spontaneously generated. In contrast, the mentalizing areas were recruited on-demand, as a means for detecting and resolving perceived pragmatic anomalies, with little evidence they were activated to make partner-specific predictions about upcoming linguistic utterances.

Knowledge Construction Technology through Hypermedia-Based Intelligent Conversational Channel

There have been multifarious approaches in building expert knowledge in medical or engineering field through expert system, case-based reasoning, model-based reasoning and also a large-scale knowledge-based system. The intriguing factors with these approaches are mainly the choices of reasoning mechanism, ontology, knowledge representation, elicitation and modeling. In our study, we argue that the knowledge construction through hypermedia-based community channel is an effective approach in constructing expert’s knowledge. We define that the knowledge can be represented as in the simplest form such as stories to the most complex ones such as on-the-job type of experiences. The current approaches of encoding experiences require expert’s knowledge to be acquired and represented in rules, cases or causal model. We differentiate the two types of knowledge which are the content knowledge and socially-derivable knowledge. The latter is described as knowledge that is earned through social interaction. Intelligent Conversational Channel is the system that supports the building and sharing on this type of knowledge.

Mapping area variability in social and behavioural difficulties among Glasgow pre-schoolers : linkage of a survey of pre-school staff with routine monitoring data

Funded by The Scottish Government

Pharmacovigilance in children : detecting adverse drug reactions in routine electronic healthcare records. A systematic review

This article is protected by copyright. All rights reserved.

Mapping area variability in social and behavioural difficulties among Glasgow pre-schoolers : linkage of a survey of pre-school staff with routine monitoring data

Funded by The Scottish Government

Pharmacovigilance in children : detecting adverse drug reactions in routine electronic healthcare records. A systematic review

This article is protected by copyright. All rights reserved.