A novel dried blood spot-LCMS method for the quantification of methotrexate polyglutamates as a potential marker for methotrexate use in children

Objective: Development and validation of a selective and sensitive LCMS method for the determination of methotrexate polyglutamates in dried blood spots (DBS). Methods: DBS samples [spiked or patient samples] were prepared by applying blood to Guthrie cards which was then dried at room temperature. The method utilised 6-mm disks punched from the DBS samples (equivalent to approximately 12 μl of whole blood). The simple treatment procedure was based on protein precipitation using perchloric acid followed by solid phase extraction using MAX cartridges. The extracted sample was chromatographed using a reversed phase system involving an Atlantis T3-C18 column (3 μm, 2.1x150 mm) preceded by Atlantis guard column of matching chemistry. Analytes were subjected to LCMS analysis using positive electrospray ionization. Key Results: The method was linear over the range 5-400 nmol/L. The limits of detection and quantification were 1.6 and 5 nmol/L for individual polyglutamates and 1.5 and 4.5 nmol/L for total polyglutamates, respectively. The method has been applied successfully to the determination of DBS finger-prick samples from 47 paediatric patients and results confirmed with concentrations measured in matched RBC samples using conventional HPLC-UV technique. Conclusions and Clinical Relevance: The methodology has a potential for application in a range of clinical studies (e.g. pharmacokinetic evaluations or medication adherence assessment) since it is minimally invasive and easy to perform, potentially allowing parents to take blood samples at home. The feasibility of using DBS sampling can be of major value for future clinical trials or clinical care in paediatric rheumatology. © 2014 Hawwa et al.

Benefits of electronic vision enhancement systems (EVES) for the visually impaired

PURPOSE: To examine whether objective performance of near tasks is improved with various electronic vision enhancement systems (EVES) compared with the subject's own optical magnifier. DESIGN: Experimental study, randomized, within-patient design. METHODS: This was a prospective study, conducted in a hospital ophthalmology low-vision clinic. The patient population comprised 70 sequential visually impaired subjects. The magnifying devices examined were: patient's optimum optical magnifier; magnification and field-of-view matched mouse EVES with monitor or head-mounted display (HMD) viewing; and stand EVES with monitor viewing. The tasks performed were: reading speed and acuity; time taken to track from one column of print to the next; follow a route map, and locate a specific feature; and identification of specific information from a medicine label. RESULTS: Mouse EVES with HMD viewing caused lower reading speeds than stand EVES with monitor viewing (F = 38.7, P < .001). Reading with the optical magnifier was slower than with the mouse or stand EVES with monitor viewing at smaller print sizes (P < .05). The column location task was faster with the optical magnifier than with any of the EVES (F = 10.3, P < .001). The map tracking and medicine label identification task was slower with the mouse EVES with HMD viewing than with the other magnifiers (P < .01). Previous EVES experience had no effect on task performance (P > .05), but subjects with previous optical magnifier experience were significantly slower at performing the medicine label identification task with all of the EVES (P < .05). CONCLUSIONS: Although EVES provide objective benefits to the visually impaired in reading speed and acuity, together with some specific near tasks, some can be performed just as fast using optical magnification. © 2003 by Elsevier Inc. All rights reserved.

Phenobarbital for neonatal seizures:response rate and predictors of refractoriness

Background : Phenobarbital is the first-line choice for neonatal seizures treatment, despite a response rate of approximately 45%. Failure to respond to acute anticonvulsants is associated with poor neurodevelopmental outcome, but knowledge on predictors of refractoriness is limited. Objective : To quantify response rate to phenobarbital and to establish variables predictive of its lack of efficacy. Methods : We retrospectively evaluated newborns with electrographically confirmed neonatal seizures admitted between January 1999 and December 2012 to the neonatal intensive care unit of Parma University Hospital (Italy), excluding neonates with status epilepticus. Response was categorized as complete (cessation of clinical and electrographic seizures after phenobarbital administration), partial (reduction but not cessation of electrographic seizures with the first bolus, response to the second bolus), or absent (no response after the second bolus). Multivariate analysis was used to identify independent predictors of refractoriness. Results : Out of 91 newborns receiving phenobarbital, 57 (62.6%) responded completely, 15 (16.5%) partially, and 19 (20.9%) did not respond. Seizure type (p = 0.02), background electroencephalogram (EEG; p ≤ 0.005), and neurologic examination (p ≤ 0.005) correlated with response to phenobarbital. However, EEG (p ≤ 0.02) and seizure type (p ≤ 0.001) were the only independent predictors. Conclusion : Our results suggest a prominent role of neurophysiological variables (background EEG and electrographic-only seizure type) in predicting the absence of response to phenobarbital in high-risk newborns.

On the accuracy of nonsurvey regional input-output multipliers: An empirical study

Correct specification of the simple location quotients in regionalizing the national direct requirements table is essential to the accuracy of regional input-output multipliers. The purpose of this research is to examine the relative accuracy of these multipliers when earnings, employment, number of establishments, and payroll data specify the simple location quotients.^ For each specification type, I derive a column of total output multipliers and a column of total income multipliers. These multipliers are based on the 1987 benchmark input-output accounts of the U.S. economy and 1988-1992 state of Florida data.^ Error sign tests, and Standardized Mean Absolute Deviation (SMAD) statistics indicate that the output multiplier estimates overestimate the output multipliers published by the Department of Commerce-Bureau of Economic Analysis (BEA) for the state of Florida. In contrast, the income multiplier estimates underestimate the BEA's income multipliers. For a given multiplier type, the Spearman-rank correlation analysis shows that the multiplier estimates and the BEA multipliers have statistically different rank ordering of row elements. The above tests also find no significant different differences, both in size and ranking distributions, among the vectors of multiplier estimates. ^