Are adults just big kids? Can the newer paediatric weight estimation systems be used in adults?

BACKGROUND: The weight of a patient is an important variable that impacts on their medical care. Although some drugs are prescribed on a so-called 'adult dose' basis, we know that adults come in all shapes and sizes - a 'one-dose-fits-all' approach is not necessarily appropriate. As a measured weight may not always be available, an alternative method of accurately estimating weight is required. OBJECTIVES: To assess and compare the accuracy of weight estimations in adults by patient self-estimation, the Mercy method, Buckley method, Broca index and PAWPER XL-MAC (paediatric advanced weight prediction in the emergency room eXtra length/eXtra large mid-arm circumference) method. METHODS: This was a prospective, cross-sectional study conducted at a tertiary academic hospital in a metropolitan area of Johannesburg, South Africa. Anthropometric variables of height, abdominal circumference, thigh circumference, mid-arm circumference and humeral length were measured. These variables were then applied to the various weight estimation methods and compared with the patient's actual weight. RESULTS: There were 188 adult patients included in the study. None of the methodologies evaluated in this study achieved the recommended >70% of weight estimations within 10% of the patient's actual weight (PW10). The Mercy method was the closest to achieving greater than the recommended 95% for weight estimation falling within 20% of the patient's actual weight (PW20). The PW20 for the Mercy method was 91.5%. The PAWPER XL-MAC and patient self-estimate methods achieved a PW20 of 85.1% and 86.1%, respectively. The Broca and Buckley methods performed poorly overall. CONCLUSIONS: None of the evaluated weight estimation methodologies was accurate enough for use in adult weight estimation. The Mercy and PAWPER XL-MAC methodologies both showed significant promise for use in adult weight estimation, but need further refinement. Although patient self-estimates were similarly accurate to those found in previous studies, they were not an accurate option; self-estimations would remain the first choice if the patient was able to provide such an estimation. The Broca index and Buckley method cannot be recommended owing to their poor performance.

Potential impurities in drug substances: Compound-specific toxicology limits for 20 synthetic reagents and by-products, and a class-specific toxicology limit for alkyl bromides.

This paper provides compound-specific toxicology limits for 20 widely used synthetic reagents and common by-products that are potential impurities in drug substances. In addition, a 15 µg/day class-specific limit was developed for monofunctional alkyl bromides, aligning this with the class-specific limit previously defined for monofunctional alkyl chlorides. Both the compound- and class-specific toxicology limits assume a lifetime chronic exposure for the general population (including sensitive subpopulations) by all routes of exposure for pharmaceuticals. Inhalation-specific toxicology limits were also derived for acrolein, formaldehyde, and methyl bromide because of their localized toxicity via that route. Mode of action was an important consideration for a compound-specific toxicology limit. Acceptable intake (AI) calculations for certain mutagenic carcinogens assumed a linear dose-response for tumor induction, and permissible daily exposure (PDE) determination assumed a non-linear dose-response. Several compounds evaluated have been previously incorrectly assumed to be mutagenic, or to be mutagenic carcinogens, but the evidence reported here for such compounds indicates a lack of mutagenicity, and a non-mutagenic mode of action for tumor induction. For non-mutagens with insufficient data to develop a toxicology limit, the ICH Q3A qualification thresholds are recommended. The compound- and class-specific toxicology limits described here may be adjusted for an individual drug substance based on treatment duration, dosing schedule, severity of the disease and therapeutic indication.

Extensions of effective-medium theory of transport in disordered systems.

The effective-medium theory of transport in disordered systems, whose basis is the replacement of spatial disorder by temporal memory, is extended in several practical directions. Restricting attention to a one-dimensional system with bond disorder for specificity, a transformation procedure is developed to deduce explicit expressions for the memory functions from given distribution functions characterizing the system disorder. It is shown how to use the memory functions in the Laplace domain forms in which they first appear, and in the time domain forms which are obtained via numerical inversion algorithms, to address time evolution of the system beyond the asymptotic domain of large times normally treated. An analytic but approximate procedure is provided to obtain the memories, in addition to the inversion algorithm. Good agreement of effective-medium theory predictions with numerically computed exact results is found for all time ranges for the distributions used except near the percolation limit, as expected. The use of ensemble averages is studied for normal as well as correlation observables. The effect of size on effective-medium theory is explored and it is shown that, even in the asymptotic limit, finite-size corrections develop to the well-known harmonic mean prescription for finding the effective rate. A percolation threshold is shown to arise even in one dimension for finite (but not infinite) systems at a concentration of broken bonds related to the system size. Spatially long-range transfer rates are shown to emerge naturally as a consequence of the replacement of spatial disorder by temporal memories, in spite of the fact that the original rates possess nearest neighbor character. Pausing time distributions in continuous-time random walks corresponding to the effective-medium memories are calculated.

Variational formula for the relaxation time in the Boltzmann equation.

The relaxation time approximation (RTA) is commonly employed in nonequilibrium statistical mechanics to approximate solutions to the Boltzmann equation in terms of an exponential relaxation to equilibrium. Despite its common use, the RTA suffers from the drawback that relaxation times commonly employed are independent of initial conditions. We derive a variational principle for solutions to the Boltzmann equation, which allows us to extend the standard RTA using relaxation times that depend on the initial distribution. Tests of the approach on a calculation of the mobility for a one-dimensional (1D) tight-binding band indicate that our analysis typically provides a better approximation than the standard RTA.

Static pairwise annihilation in complex networks.

We study static annihilation on complex networks, in which pairs of connected particles annihilate at a constant rate during time. Through a mean-field formalism, we compute the temporal evolution of the distribution of surviving sites with an arbitrary number of connections. This general formalism, which is exact for disordered networks, is applied to Kronecker, Erdös-Rényi (i.e., Poisson), and scale-free networks. We compare our theoretical results with extensive numerical simulations obtaining excellent agreement. Although the mean-field approach applies in an exact way neither to ordered lattices nor to small-world networks, it qualitatively describes the annihilation dynamics in such structures. Our results indicate that the higher the connectivity of a given network element, the faster it annihilates. This fact has dramatic consequences in scale-free networks, for which, once the "hubs" have been annihilated, the network disintegrates and only isolated sites are left.

Nature of charge carriers in disordered molecular solids: are polarons compatible with observations?

Polaronic theories for charge transport in disordered organic solids, particularly molecularly doped polymers, have been plagued by issues of internal consistency related to the magnitude of physical parameters. We present a natural resolution of the problem by showing that, in the presence of correlated disorder, polaronic carriers with binding energies Delta approximately 50-500 meV and transfer integrals J approximately 1-20 meV are completely consistent with the magnitudes of field and temperature dependent mobilities observed.

Nasopharyngeal dysmorphology in the syndromes of Apert and Crouzon.

Results of this cephalometric study of the dimensions of the nasopharynx in the syndromes of Apert and Crouzon concur with information previously reported both from this and other centers, enlarging the data base to direct attention to changes in these dimensions with growth of the patient. Alterations of the nasopharyngeal architecture in these syndromes include reduction in pharyngeal height, width, and depth; increased length and thickness of the velum; decreased length of the hard palate; and marked reduction in the posterior cranial base with somewhat less remarkable changes in the anterior cranial base. Increased basilar kyphosis evident in some patients contributes to the reduction in nasopharyngeal space. Most of these deviations are present early in life and tend to become worse as the patient matures. The combination of reduced nasopharyngeal dimensions and reduced patency of the posterior nasal choanae poses the threat of respiratory embarrassment and cor pulmonale, particularly in the young child.

The otologic manifestations of mandibulofacial dysostosis.

Sixteen patients (32 ears) with diagnoses of mandibulofacial dysostosis were reviewed. The characteristic otologic manifestations of the syndrome were delineated, found to be bilateral, and consist of the following: 1. Mild symmetric deformity of the auricle (grade 1 microtia). 2. Agenesis or hypoplastic development of the mastoid and mastoid antrum. 3. Absence of the external auditory canal. 4. Marked narrowing or agenesis of the middle ear cleft. 5. Agenesis or severe malformation of the malleus and incus. When present, the malleus and incus are most often rudimentary, fused to form a conglomerate mass, and ankylosed to either the atretic plate, epitympanum, or both. 6. Stapedial malformations which usually consist of a deformed suprastructure. 7. Frequently the tegmen assumes a more inferior (low lying) position than normal. 8. Occasionally, the facial nerve pursues an abnormal course and is located more anteriorly than would be expected. 9. A normal inner ear. 10. Normal bone conduction with a marked (greater than 50 dB) conductive hearing loss. 11. Marked disparity between the degree of auricular deformity (mild; grade 1 microtia) and the degree of deformity of the remaining first and second branchial arch derivatives that constitute the external and middle ears (severe).