Pepsin measured in induced sputum - a test for pulmonary aspiration in children?

Purpose The purpose of this study was to investigate if pepsin measured in sputum is a useful marker of pulmonary aspiration secondary to gastroesophageal reflux (GER) in children. It is possible that the induced sputum procedure could cause GER and invalidate the results. The hypothesis stated that healthy children (those without history of respiratory or gastroesophageal symptoms) would not have pepsin detected in induced sputum. Methods Children attending surgical outpatients in the Royal Belfast Hospital for Sick Children (Belfast, Northern Ireland) were recruited. After spirometry, sputum was obtained by induction with hypertonic 3% saline. Spirometry was repeated, and complications were noted. An “in-house” enzyme-linked immunosorbent assay was used to measure pepsin concentration in sputum. The lower limit of detection of pepsin was 1.19 ng/mL. Results Children (n = 21) aged 4 to 16 years were recruited. Twenty children completed the study. No adverse effects were reported. Pepsin was detected in 17 (85%) of 20 sputum samples. Conclusions The act of sputum induction appears to induce physiologic GER in a healthy childhood population. The analysis of pepsin in sputum obtained by sputum induction is therefore not useful in the investigation of reflux-related respiratory disease.

A randomised, controlled trial of conventional versus automated weaning from mechanical ventilation using SmartcareTM/PS

Objective
Preliminary assessment of an automated weaning system (SmartCare™/PS) compared to usual management of weaning from mechanical ventilation performed in the absence of formal protocols.


Design and setting
A randomised, controlled pilot study in one Australian intensive care unit.


Patients
A total of 102 patients were equally divided between SmartCare/PS and Control.

Interventions
The automated system titrated pressure support, conducted a spontaneous breathing trial and provided notification of success (“separation potential”).

Measurements and results
The median time from the first identified point of suitability for weaning commencement to the state of “separation potential” using SmartCare/PS was 20 h (interquartile range, IQR, 2–40) compared to 8 h (IQR 2–43) with Control (log-rank P = 0.3). The median time to successful extubation was 43 h (IQR 6–169) using SmartCare/PS and 40 (14–87) with Control (log-rank P = 0.6). Unadjusted, the estimated probability of reaching “separation potential” was 21% lower (95% CI, 48% lower to 20% greater) with SmartCare/PS compared to Control. Adjusted for other covariates (age, gender, APACHE II, SOFAmax, neuromuscular blockade, corticosteroids, coma and elevated blood glucose), these estimates were 31% lower (95% CI, 56% lower to 9% greater) with SmartCare/PS. The study groups showed comparable rates of reintubation, non-invasive ventilation post-extubation, tracheostomy, sedation, neuromuscular blockade and use of corticosteroids.

Conclusions
Substantial reductions in weaning duration previously demonstrated were not confirmed when the SmartCare/PS system was compared to weaning managed by experienced critical care specialty nurses, using a 1:1 nurse-to-patient ratio. The effect of SmartCare/PS may be influenced by the local clinical organisational context.

Validity of a 1 minute walk test for children with cerebral palsy.

The concurrent validity of a 1 minute walk test at a child's maximum walking speed was assessed in children with bilateral spastic cerebral palsy (BSCP). The distance covered during the 1 minute walk test was compared with the children's gross motor function as assessed by the Gross Motor Function Measure (GMFM). Twenty-four male and 10 female children with CP (mean age 11y, range 4 to 16y) participated in the study. Gross Motor Function Classification System (GMFCS) levels were; level I (n=3), level II (n=17), level III (n=10), and level IV (n=4). Participants had clinical diagnoses of symmetrical diplegia (n=19), asymmetrical diplegia (n=14), and quadriplegia (n=1). Results showed a significant correlation between GMFM score and the distance covered during the 1 minute walk (r=0.92; p<0.001). There was also a significant decrease in the distance walked with increasing GMFCS level (p<0.001). We concluded that the 1 minute walk test is a valid measure for assessing functional ability in children with ambulatory BSCP. Its cost-effectiveness and user friendliness make it a potentially useful tool in the clinical setting. Further study needs to address its reliability and ability to detect change over time.

Development of a Diagnostic Genetic Test for Simplex and Autosomal Recessive Retinitis Pigmentosa

PURPOSE: Retinitis pigmentosa (RP) causes hereditary blindness in adults (prevalence, approximately 1 in 4000). Each of the more than 30 causative genes identified to date are responsible for only a small percentage of cases. Genetic diagnosis via traditional methods is problematic, and a single test with a higher probability of detecting the causative mutation would be very beneficial for the clinician. The goal of this study therefore was to develop a high-throughput screen capable of detecting both known mutations and novel mutations within all genes implicated in autosomal recessive or simplex RP. DESIGN: Evaluation of diagnostic technology. PARTICIPANTS AND CONTROLS: Participants were 56 simplex and autosomal recessive RP patients, with 360 population controls unscreened for ophthalmic disease. METHODS: A custom genechip capable of resequencing all exons containing known mutations in 19 disease-associated genes was developed (RP genechip). A second, commercially available arrayed primer extension (APEX) system was used to screen 501 individual previously reported variants. The ability of these high-throughput approaches to identify pathogenic variants was assessed in a cohort of simplex and autosomal recessive RP patients. MAIN OUTCOME MEASURES: Number of mutations and potentially pathogenic variants identified. RESULTS: The RP genechip identified 44 sequence variants: 5 previously reported mutations; 22 known single nucleotide polymorphisms (SNPs); 11 novel, potentially pathogenic variants; and 6 novel SNPs. There was strong concordance with the APEX array, but only the RP genechip detected novel variants. For example, identification of a novel mutation in CRB1 revealed a patient, who also had a single previously known CRB1 mutation, to be a compound heterozygote. In some individuals, potentially pathogenic variants were discovered in more than one gene, consistent with the existence of disease modifier effects resulting from mutations at a second locus. CONCLUSIONS: The RP genechip provides the significant advantage of detecting novel variants and could be expected to detect at least one pathogenic variant in more than 50% of patients. The APEX array provides a reliable method to detect known pathogenic variants in autosomal recessive RP and simplex RP patients and is commercially available. High-throughput genotyping for RP is evolving into a clinically useful genetic diagnostic tool.

Automated mixed dimensional modelling from 2D and 3D CAD models

The motivation for this paper is to present procedures for automatically creating idealised finite element models from the 3D CAD solid geometry of a component. The procedures produce an accurate and efficient analysis model with little effort on the part of the user. The technique is applicable to thin walled components with local complex features and automatically creates analysis models where 3D elements representing the complex regions in the component are embedded in an efficient shell mesh representing the mid-faces of the thin sheet regions. As the resulting models contain elements of more than one dimension, they are referred to as mixed dimensional models. Although these models are computationally more expensive than some of the idealisation techniques currently employed in industry, they do allow the structural behaviour of the model to be analysed more accurately, which is essential if appropriate design decisions are to be made. Also, using these procedures, analysis models can be created automatically whereas the current idealisation techniques are mostly manual, have long preparation times, and are based on engineering judgement. In the paper the idealisation approach is first applied to 2D models that are used to approximate axisymmetric components for analysis. For these models 2D elements representing the complex regions are embedded in a 1D mesh representing the midline of the cross section of the thin sheet regions. Also discussed is the coupling, which is necessary to link the elements of different dimensionality together. Analysis results from a 3D mixed dimensional model created using the techniques in this paper are compared to those from a stiffened shell model and a 3D solid model to demonstrate the improved accuracy of the new approach. At the end of the paper a quantitative analysis of the reduction in computational cost due to shell meshing thin sheet regions demonstrates that the reduction in degrees of freedom is proportional to the square of the aspect ratio of the region, and for long slender solids, the reduction can be proportional to the aspect ratio of the region if appropriate meshing algorithms are used.