Phenotypes of childhood asthma: are they real?

It has been suggested that there are several distinct phenotypes of childhood asthma or childhood wheezing. Here, we review the research relating to these phenotypes, with a focus on the methods used to define and validate them. Childhood wheezing disorders manifest themselves in a range of observable (phenotypic) features such as lung function, bronchial responsiveness, atopy and a highly variable time course (prognosis). The underlying causes are not sufficiently understood to define disease entities based on aetiology. Nevertheless, there is a need for a classification that would (i) facilitate research into aetiology and pathophysiology, (ii) allow targeted treatment and preventive measures and (iii) improve the prediction of long-term outcome. Classical attempts to define phenotypes have been one-dimensional, relying on few or single features such as triggers (exclusive viral wheeze vs. multiple trigger wheeze) or time course (early transient wheeze, persistent and late onset wheeze). These definitions are simple but essentially subjective. Recently, a multi-dimensional approach has been adopted. This approach is based on a wide range of features and relies on multivariate methods such as cluster or latent class analysis. Phenotypes identified in this manner are more complex but arguably more objective. Although phenotypes have an undisputed standing in current research on childhood asthma and wheezing, there is confusion about the meaning of the term 'phenotype' causing much circular debate. If phenotypes are meant to represent 'real' underlying disease entities rather than superficial features, there is a need for validation and harmonization of definitions. The multi-dimensional approach allows validation by replication across different populations and may contribute to a more reliable classification of childhood wheezing disorders and to improved precision of research relying on phenotype recognition, particularly in genetics. Ultimately, the underlying pathophysiology and aetiology will need to be understood to properly characterize the diseases causing recurrent wheeze in children.

Nonparametric location estimators in the randomized complete block design

Several tests for the comparison of different groups in the randomized complete block design exist. However, there is a lack of robust estimators for the location difference between one group and all the others on the original scale. The relative marginal effects are commonly used in this situation, but they are more difficult to interpret and use by less experienced people because of the different scale. In this paper two nonparametric estimators for the comparison of one group against the others in the randomized complete block design will be presented. Theoretical results such as asymptotic normality, consistency, translation invariance, scale preservation, unbiasedness, and median unbiasedness are derived. The finite sample behavior of these estimators is derived by simulations of different scenarios. In addition, possible confidence intervals with these estimators are discussed and their behavior derived also by simulations.

Monitoring of Urinary Calcium and Phosphorus Excretion in Preterm Infants - Comparison of two Methods

OBJECTIVES: Premature babies require supplementation with calcium and phosphorus to prevent metabolic bone disease of prematurity. To guide mineral supplementation, two methods of monitoring urinary excretion of calcium and phosphorus are used: urinary calcium or phosphorus concentration and calcium/creatinine or phosphorus/creatinine ratios. We compare these two methods in regards to their agreement on the need for mineral supplementation. METHODS: Retrospective chart review of 230 premature babies with birthweight <1500 g, undergoing screening of urinary spot samples from day 21 of life and fortnightly thereafter. Hypothetical cut-off values for urine calcium or phosphorus concentration (1 mmol/l) and urine calcium/creatinine ratio (0.5 mol/mol) or phosphorus/creatinine ratio (4 mol/mol) were applied to the sample results. The agreement on whether or not to supplement the respective minerals based on the results with the two methods was compared. Multivariate general linear models sought to identify patient characteristic to predict disagreeing results. RESULTS: 24.8% of cases disagreed on the indication for calcium supplementation, 8.8% for phosphorus. Total daily calcium intake was the only patient characteristic associated with discordant results. CONCLUSIONS: With the intention to supplement the respective mineral, comparison of urinary mineral concentration with mineral/creatinine ratio is moderate for Calcium and good for Phosphorus. The results do not allow to identify superiority of either method on the decision which babies require calcium and/or phosphorus supplements.

Influence of prosthesis type and retention mechanism on complications with fixed implant-supported prostheses: a systematic review applying multivariate analyses

PURPOSE To identify the influence of fixed prosthesis type on biologic and technical complication rates in the context of screw versus cement retention. Furthermore, a multivariate analysis was conducted to determine which factors, when considered together, influence the complication and failure rates of fixed implant-supported prostheses. MATERIALS AND METHODS Electronic searches of MEDLINE (PubMed), EMBASE, and the Cochrane Library were conducted. Selected inclusion and exclusion criteria were used to limit the search. Data were analyzed statistically with simple and multivariate random-effects Poisson regressions. RESULTS Seventy-three articles qualified for inclusion in the study. Screw-retained prostheses showed a tendency toward and significantly more technical complications than cemented prostheses with single crowns and fixed partial prostheses, respectively. Resin chipping and ceramic veneer chipping had high mean event rates, at 10.04 and 8.95 per 100 years, respectively, for full-arch screwed prostheses. For "all fixed prostheses" (prosthesis type not reported or not known), significantly fewer biologic and technical complications were seen with screw retention. Multivariate analysis revealed a significantly greater incidence of technical complications with cemented prostheses. Full-arch prostheses, cantilevered prostheses, and "all fixed prostheses" had significantly higher complication rates than single crowns. A significantly greater incidence of technical and biologic complications was seen with cemented prostheses. CONCLUSION Screw-retained fixed partial prostheses demonstrated a significantly higher rate of technical complications and screw-retained full-arch prostheses demonstrated a notably high rate of veneer chipping. When "all fixed prostheses" were considered, significantly higher rates of technical and biologic complications were seen for cement-retained prostheses. Multivariate Poisson regression analysis failed to show a significant difference between screw- and cement-retained prostheses with respect to the incidence of failure but demonstrated a higher rate of technical and biologic complications for cement-retained prostheses. The incidence of technical complications was more dependent upon prosthesis and retention type than prosthesis or abutment material.