Matching the Statistical Model to the Research Question for Dental Caries Indices with Many Zero Counts.

Marginalized zero-inflated count regression models have recently been introduced for the statistical analysis of dental caries indices and other zero-inflated count data as alternatives to traditional zero-inflated and hurdle models. Unlike the standard approaches, the marginalized models directly estimate overall exposure or treatment effects by relating covariates to the marginal mean count. This article discusses model interpretation and model class choice according to the research question being addressed in caries research. Two data sets, one consisting of fictional dmft counts in 2 groups and the other on DMFS among schoolchildren from a randomized clinical trial comparing 3 toothpaste formulations to prevent incident dental caries, are analyzed with negative binomial hurdle, zero-inflated negative binomial, and marginalized zero-inflated negative binomial models. In the first example, estimates of treatment effects vary according to the type of incidence rate ratio (IRR) estimated by the model. Estimates of IRRs in the analysis of the randomized clinical trial were similar despite their distinctive interpretations. The choice of statistical model class should match the study's purpose, while accounting for the broad decline in children's caries experience, such that dmft and DMFS indices more frequently generate zero counts. Marginalized (marginal mean) models for zero-inflated count data should be considered for direct assessment of exposure effects on the marginal mean dental caries count in the presence of high frequencies of zero counts.

Common risk factor approach to address socioeconomic inequality in the oral health of preschool children--a prospective cohort study.

BACKGROUND: Dental caries remains the most prevalent chronic condition in children and a major contributor to poor general health. There is ample evidence of a skewed distribution of oral health, with a small proportion of children in the population bearing the majority of the burden of the disease. This minority group is comprised disproportionately of socioeconomically disadvantaged children. An in-depth longitudinal study is needed to better understand the determinants of child oral health, in order to support effective evidence-based policies and interventions in improving child oral health. The aim of the Study of Mothers' and Infants' Life Events Affecting Oral Health (SMILE) project is to identify and evaluate the relative importance and timing of critical factors that shape the oral health of young children and then to seek to evaluate those factors in their inter-relationship with socioeconomic influences. METHODS/DESIGN: This investigation will apply an observational prospective study design to a cohort of socioeconomically-diverse South Australian newborns and their mothers, intensively following these dyads as the children grow to toddler age. Mothers of newborn children will be invited to participate in the study in the early post-partum period. At enrolment, data will be collected on parental socioeconomic status, mothers' general and dental health conditions, details of the pregnancy, infant feeding practice and parental health behaviours and practices. Data on diet and feeding practices, oral health behaviours and practices, and dental visiting patterns will be collected at 3, 6, 12 and 24 months of age. When children turn 24-30 months, the children and their mothers/primary care givers will be invited to an oral examination to record oral health status. Anthropometric assessment will also be conducted. DISCUSSION: This prospective cohort study will examine a wide range of determinants influencing child oral health and related general conditions such as overweight. It will lead to the evaluation of the inter-relationship among main influences and their relative effect on child oral health. The study findings will provide high level evidence of pathways through which socio-environmental factors impact child oral health. It will also provide an opportunity to examine the relationship between oral health and childhood overweight.

Management of pediatric ureterolithiasis in the emergency room: A single institution review and new management pathway.

INTRODUCTION/BACKGROUND: Urolithiasis is an increasingly common condition seen in children with an annual incidence of 2-3% in children under 18, and up to 10% in adolescents. Treatment of stones varies including observation, IV hydration, pain management, medical expulsive therapy (MET), or surgery. Though well-studied and often used in adults, MET (alpha-adrenergic antagonists to facilitate passage of ureteral stones), is not routinely prescribed in pediatric patients. OBJECTIVE: The goals of this study were to review a quaternary children's hospital's emergency room frequency of MET utilization for ureterolithiasis as well as evaluate the clinical outcomes of children who were prescribed MET compared to those treated with pain control alone. STUDY DESIGN: A retrospective review was performed of children 2 months to 18 years with ureterolithiasis who presented to a quaternary children's hospital ED from 2011 to 2017. The primary outcome was the frequency of MET prescribed. Secondary outcomes included the following comparisons in patients who received MET and analgesics with those who received analgesics alone: hospital admission rate, length of hospitalization, emergency room re-presentation rate, surgical intervention, spontaneous stone passage, urology consultation, how the urology consult affected MET utilization, referral to outpatient urology and nephrology clinics, and CT utilization in the ED. Comparisons were performed utilizing Fischer's exact and t-tests. RESULTS: 139 patients were included with a mean age of 14 years (SD 4.14), 42% male. There was no difference between age, gender, stone size, return to the ED, serum creatinine, or length of hospitalization (if admitted) between patients who were and were not placed on MET. The rate of stone passage was significantly higher for those placed on MET (45%) versus not (20%) (p = 0.0022). Urology was consulted for 93% of the cases where children were prescribed MET, compared with only 52% of cases where MET was not prescribed (p = <0.0001). DISCUSSION: In our experience MET was significantly underutilized in patients where urology was not involved. This is similar to a study by Itano et al. which found urology consultation in the ED significantly increased use of tamsulosin for ureterolithiasis in adults. Children with ureterolithiasis placed on MET had a significantly higher rate of stone passage compared to children managed by pain control alone. CONCLUSION: Given the benefits of MET to increase the rate of spontaneous stone passage it may be considered first line therapy for treatment of children with ureterolithiasis.

Effects of binding factors on structural elements in F-actin.

Understanding the dynamics of the actin filament is essential to a detailed description of their interactions and role in the cell. Previous studies have linked the dynamic properties of actin filaments (F-actin) to three structural elements contributing to a hydrophobic pocket, namely, the hydrophobic loop, the DNase I binding loop, and the C-terminus. Here, we examine how these structural elements are influenced by factors that stabilize or destabilize F-actin, using site-directed spin-labeled (SDSL) electron paramagnetic resonance (EPR), fluorescence, and cross-linking techniques. Specifically, we employ cofilin, an actin destabilizing protein that binds and severs filaments, and phalloidin, a fungal toxin that binds and stabilizes F-actin. We find that cofilin shifts both the DNase I binding loop and the hydrophobic loop away from the C-terminus in F-actin, as demonstrated by weakened spin-spin interactions, and alters the environment of spin probes on residues of these two loops. In contrast, although phalloidin strongly stabilizes F-actin, it causes little or no local change in the environment of the loop residues. This indicates that the stabilizing effect of phalloidin is achieved mainly through constraining structural fluctuations in F-actin and suggests that factors and interactions that control these fluctuations have an important role in the cytoskeleton dynamics.

Logistic regression for dichotomized counts.

Sometimes there is interest in a dichotomized outcome indicating whether a count variable is positive or zero. Under this scenario, the application of ordinary logistic regression may result in efficiency loss, which is quantifiable under an assumed model for the counts. In such situations, a shared-parameter hurdle model is investigated for more efficient estimation of regression parameters relating to overall effects of covariates on the dichotomous outcome, while handling count data with many zeroes. One model part provides a logistic regression containing marginal log odds ratio effects of primary interest, while an ancillary model part describes the mean count of a Poisson or negative binomial process in terms of nuisance regression parameters. Asymptotic efficiency of the logistic model parameter estimators of the two-part models is evaluated with respect to ordinary logistic regression. Simulations are used to assess the properties of the models with respect to power and Type I error, the latter investigated under both misspecified and correctly specified models. The methods are applied to data from a randomized clinical trial of three toothpaste formulations to prevent incident dental caries in a large population of Scottish schoolchildren.

Nonfluoride caries-preventive agents: executive summary of evidence-based clinical recommendations.

BACKGROUND: In this article, the authors present evidence-based clinical recommendations regarding the use of nonfluoride caries preventive agents. The recommendations were developed by an expert panel convened by the American Dental Association (ADA)Council on Scientific Affairs. The panel addressed several questions regarding the efficacy of nonfluoride agents in reducing the incidence of caries and arresting or reversing the progression of caries. TYPES OF STUDIES REVIEWED: A panel of experts convened by the ADA Council on Scientific Affairs, in collaboration with ADA Division of Science staff, conducted a MEDLINE search to identify all randomized and nonrandomized clinical studies regarding the use of non fluoride caries-preventive agents. RESULTS: The panel reviewed evidence from 50 randomized controlled trials and 15 nonrandomized studies to assess the efficacy of various nonfluoride caries-preventive agents. CLINICAL IMPLICATIONS: The panel concluded that certain nonfluoride agents may provide some benefit as adjunctive therapies in children and adults at higher risk of developing caries. These recommendations are presented as a resource for dentists to consider in the clinical decision-making process. As part of the evidence based approach to care, these clinical recommendations should be integrated with the practitioner's professional judgment and the patient's needs and preferences.

Hydrophobic loop dynamics and actin filament stability.

It has been postulated that the hydrophobic loop of actin (residues 262-274) swings out and inserts into the opposite strand in the filament, stabilizing the filament structure. Here, we analyzed the hydrophobic loop dynamics utilizing four mutants that have cysteine residues introduced at a single location along the yeast actin loop. Lateral, copper-catalyzed disulfide cross-linking of the mutant cysteine residues to the native C374 in the neighboring strand within the filament was fastest for S265C, followed by V266C, L267C, and then L269C. Site-directed spin labeling (SDSL) studies revealed that C265 lies closest to C374 within the filament, followed by C266, C267, and then C269. These results are not predicted by the Holmes extended loop model of F-actin. Furthermore, we find that disulfide cross-linking destroys L267C and L269C filaments; only small filaments are observed via electron microscopy. Conversely, phalloidin protects the L267C and L269C filaments and inhibits their disulfide cross-linking. Combined, our data indicate that, in solution, the loop resides predominantly in a "parked" position within the filament but is able to dynamically populate other conformational states which stabilize or destabilize the filament. Such states may be exploited within a cell by filament-stabilizing and -destabilizing factors.

Conformational dynamics of loop 262-274 in G- and F-actin.

According to the original Holmes model of F-actin structure, the hydrophobic loop 262-274 stabilizes the actin filament by inserting into a pocket formed at the interface between two protomers on the opposing strand. Using a yeast actin triple mutant, L180C/L269C/C374A [(LC)(2)CA], we showed previously that locking the hydrophobic loop to the G-actin surface by a disulfide bridge prevents filament formation. We report here that the hydrophobic loop is mobile in F- as well as in G-actin, fluctuating between the extended and parked conformations. Copper-catalyzed, brief air oxidation of (LC)(2)CA F-actin on electron microscopy grids resulted in the severing of thin filaments and their conversion to amorphous aggregates. Disulfide, bis(methanethiosulfonate) (MTS), and dibromobimane (DBB) cross-linking reactions proceeded in solution at a faster rate with G- than with F-actin. Cross-linking of C180 to C269 by DBB (4.4 A) in either G- or F-actin resulted in shorter and less stable filaments. The cross-linking with a longer MTS-6 reagent (9.6 A) did not impair actin polymerization or filament structure. Myosin subfragment 1 (S1) and tropomyosin inhibited the disulfide cross-linking of phalloidin-stabilized F-actin. Electron paramagnetic resonance measurements with nitroxide spin-labeled actin revealed strong spin-spin coupling and a similar mean interspin distance ( approximately 10 A) in G- and in F-actin, with a broader distance distribution in G-actin. These results show loop 262-274 fluctuations in G- and F-actin and correlate loop dynamics with actin filament formation and stability.