Biomedical subjects

Brian G Leroux

Publications and source records attributed to Brian G Leroux.

16 recordsLinked to original sources

PubMed2006

Statistical models for autocorrelated count data.

A generalized linear mixed model is an increasingly popular choice for the modelling of correlated, non-normal responses in a regression setting. A number of methods are currently available for fitting a generalized linear mixed model including Monte-Carlo Markov-Chain maximum likelihood algorithms, approximate maximum likelihood (PQL), iterative bias correction, and others. Of interest in this paper is to compare the parameter estimation of the various methods in the modelling of a count data set, the incidence of polio in the USA over the period 1970-1983, using a longlinear generalized linear mixed model with an autoregressive correlation structure. Despite the fact that all of these methods are considered valid modelling techniques, we find that parameter estimates and standard errors differ substantially between analyses, particularly in the estimation of the parameters describing the random effects distribution. A small simulation study is helpful in understanding some of these differences. The methods lead to reasonably similar predictions for future observations, with small differences observed in some monthly counts.

Algorithms↗

PubMed2006

Neurobehavioral effects of dental amalgam in children: a randomized clinical trial.

CONTEXT: Dental (silver) amalgam is a widely used restorative material containing 50% elemental mercury that emits small amounts of mercury vapor. No randomized clinical trials have determined whether there are significant health risks associated with this low-level mercury exposure. OBJECTIVE: To assess the safety of dental amalgam restorations in children. DESIGN: A randomized clinical trial in which children requiring dental restorative treatment were randomized to either amalgam for posterior restorations or resin composite instead of amalgam. Enrollment commenced February 1997, with annual follow-up for 7 years concluding in July 2005. SETTING AND PARTICIPANTS: A total of 507 children in Lisbon, Portugal, aged 8 to 10 years with at least 1 carious lesion on a permanent tooth, no previous exposure to amalgam, urinary mercury level <10 microg/L, blood lead level <15 microg/dL, Comprehensive Test of Nonverbal Intelligence IQ > or =67, and with no interfering health conditions. INTERVENTION: Routine, standard-of-care dental treatment, with one group receiving amalgam restorations for posterior lesions (n = 253) and the other group receiving resin composite restorations instead of amalgam (n = 254). MAIN OUTCOME MEASURES: Neurobehavioral assessments of memory, attention/concentration, and motor/visuomotor domains, as well as nerve conduction velocities. RESULTS: During the 7-year trial period, children had a mean of 18.7 tooth surfaces (median, 16) restored in the amalgam group and 21.3 (median, 18) restored in the composite group. Baseline mean creatinine-adjusted urinary mercury levels were 1.8 microg/g in the amalgam group and 1.9 microg/g in the composite group, but during follow-up were 1.0 to 1.5 microg/g higher in the amalgam group than in the composite group (P<.001). There were no statistically significant differences in measures of memory, attention, visuomotor function, or nerve conduction velocities (average z scores were very similar, near zero) for the amalgam and composite groups over all 7 years of follow-up, with no statistically significant differences observed at any time point (P values from .29 to .91). Starting at 5 years after initial treatment, the need for additional restorative treatment was approximately 50% higher in the composite group. CONCLUSIONS: In this study, children who received dental restorative treatment with amalgam did not, on average, have statistically significant differences in neurobehavioral assessments or in nerve conduction velocity when compared with children who received resin composite materials without amalgam. These findings, combined with the trend of higher treatment need later among those receiving composite, suggest that amalgam should remain a viable dental restorative option for children. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00066118.

Child↗

PubMed2006

Close friends', parents', and older siblings' smoking: reevaluating their influence on children's smoking.

A number of longitudinal studies have explored the role of friends', parents', and older siblings' smoking in children's smoking acquisition. A reasonable implication of this previous research is that intervention efforts could be beneficially directed toward countering the potential influence of friends' and possibly older siblings' smoking but not parents' smoking. However, methodological limitations of this previous research motivated our reevaluation of the role of friends', parents', and older siblings' smoking in children's smoking. Close friends' smoking status was assessed when children were in 5th grade, whereas parents' and older siblings' smoking status was assessed when children were in 3rd grade. The outcome, children's daily smoking status, was assessed in 12th grade. The setting was 40 Washington state school districts that participated in the long-term Hutchinson Smoking Prevention Project. Participants were the 4,576 families for whom close friends', parents', and older siblings' smoking status as well as children's smoking status were available. The probability that each close friend's smoking influenced the child to smoke daily was 9% (95% CI = 6%-12%), the probability that each parent's smoking influenced the child to smoke daily was 11% (95% CI = 9%-14%), and the probability that each older sibling's smoking influenced the child to smoke daily was 7% (95% CI = 1%-13%). These results suggest that close friends', parents', and siblings' smoking were similarly important influences on children's smoking. Family-focused interventions could be a valuable future direction of prevention research.

Adolescent↗

PubMed2006

Prospective prediction of children's smoking transitions: role of parents' and older siblings' smoking.

AIMS: To use a novel social epidemic probability model to investigate longitudinally the extent to which parents' and older siblings' smoking predict children's smoking transitions. DESIGN: Parents' and older siblings' smoking status was assessed when children were in 3rd grade (baseline). Three smoking transitions were assessed over the period of child/adolescent smoking acquisition (up to 12th grade): (1) transition from never smoking to trying smoking, (2) transition from trying to monthly smoking and (3) transition from monthly to daily smoking. SETTING: Forty Washington State school districts participating in the long term Hutchinson Smoking Prevention Project (HSPP). PARTICIPANTS AND MEASUREMENTS: Participants were the 5520 families for whom data on both parents' and older siblings' baseline smoking status, as well as on children's smoking transitions, were available. FINDINGS: The probability that a smoking parent influenced their child to make the first transition to trying smoking was 32% (95% CI: 27%, 36%); to make the second transition from trying to monthly smoking, 15% (95% CI: 10%, 19%); and to make the third transition from monthly to daily smoking, 28% (95% CI: 21%, 34%). The probability that an older sibling influenced a child to make the first transition to trying smoking was 29% (95% CI: 17%, 39%); to make the second transition from trying to monthly smoking, 0% (95% CI: 0%, 8%); and to make the third transition from monthly to daily smoking, 20% (95% CI: 4%, 33%). CONCLUSIONS: In contrast to previous research, the results provide new evidence suggesting that family smoking influences both initiation and escalation of children's smoking. Results also quantify, in terms of probabilities, the importance of parents' and older siblings' smoking on children's three major smoking transitions. Parents' smoking, as well as older siblings' smoking, are important behaviors to target in preventing adolescents from making smoking transitions.

Adolescent↗

PubMed2005

Individual differences in initial sensitivity and acute tolerance predict patterns of chronic drug tolerance to nitrous-oxide-induced hypothermia in rats.

RATIONALE: A preventive strategy for drug addiction would benefit from being able to identify vulnerable individuals. Understanding how an individual responds during an initial drug exposure may be useful for predicting how that individual will respond to repeated drug administrations. OBJECTIVES: This study investigated whether individual differences in initial drug sensitivity and acute tolerance can predict how chronic tolerance develops. METHODS: During an initial 3-h administration of 60% nitrous oxide (N(2)O), male Long-Evans rats were screened for N(2)O's hypothermic effect into subsets based on being initially insensitive (II), sensitive with acute tolerance (AT), or sensitive with no intrasessional recovery (NR). Animals in each individual difference category were randomly assigned to receive six 90-min exposures of either 60% N(2)O or placebo gas. Core temperature was measured telemetrically. RESULTS: Rats that exhibited a comparable degree of hypothermia during an initial N(2)O exposure, but differed in acute tolerance development, developed different patterns of chronic tolerance. Specifically, the NR group did not become fully tolerant over repeated N(2)O exposures while the AT group developed an initial hyperthermia followed by a return of core temperature to control levels indicative of full tolerance development. By the second N(2)O exposure, the II group breathing N(2)O became hyperthermic relative to the placebo control group and this hyperthermia persisted throughout the multiple N(2)O exposures. CONCLUSIONS: Individual differences in initial drug sensitivity and acute tolerance development predict different patterns of chronic tolerance. The hypothesis is suggested that individual differences in opponent-adaptive responses may mediate this relationship.

Animals↗

PubMed2005

Childhood friends who smoke: do they influence adolescents to make smoking transitions?

This study investigated longitudinally the extent to which childhood friends who smoke influence adolescents' smoking transitions, and compared that influence with that of parents who smoke. In a sample of 4744 children, results showed that the probability, per close friend, that a smoking close friend influenced the adolescent to make the first transition to trying smoking was 38% (95% CI: 28%, 46%); to make the second transition from trying to monthly smoking, 10% (95% CI: 5%, 15%); and to make the third transition from monthly to daily smoking, 11% (95% CI: 5%, 17%). Compared to parents' smoking, close friends' smoking was 12% (p=0.03) more influential for the first transition, no different for the second transition (p=0.53), and 16% (p=0.01) less influential for the third transition. Results provide new evidence suggesting that childhood close friends who smoke influence not only initiation but also escalation of adolescents' smoking. Results also confirmed the important role of parents' smoking. Targeting both childhood close friends' and parents' smoking would be valuable in prevention research.

Adolescent↗

PubMed2005

Nine-year prediction of adolescent smoking by number of smoking parents.

For scientific and public health reasons, it is important to identify the role of family influences on child smoking acquisition. Using a well-followed (>90%) cohort of 3,012 children and their parents, this study prospectively investigated the influence of smoking by 0 vs. 1 vs. 2 parents when the children were young (3rd grade), on whether the children subsequently became daily smokers. It is the only study to investigate the prediction of child/adolescent smoking at the end of the smoking acquisition period (12th grade) by parental smoking at the start of the period (3rd grade). Logistic regression analyses revealed that having one parent who smokes substantially increases the risk that children will become daily smokers, relative to families where neither parent smokes (OR=1.90, p<.01). There is no evidence that the increased risk depends on parent or child gender. These results suggest the need for public health interventions that inform parents of young children that their own smoking behavior increases their children's risk for future smoking.

Adolescent↗

PubMed2005

Nitrous oxide analgesia in humans: acute and chronic tolerance.

Electrical tooth stimulation was used to investigate whether humans develop tolerance to nitrous oxide (N(2)O) analgesia within a single administration as well as over repeated administrations. In a double-blind cross-over experiment, 77 subjects received a 40-min administration of 38% N(2)O at one session and placebo gas at the other. The sessions were separated by 1 week and the order of gas administration was counterbalanced. Acute analgesic tolerance developed for pain threshold but not for detection threshold. There was no evidence of a hyperalgesic rebound effect following cessation of the N(2)O administration. In a second double-blind experiment, 64 subjects received both 30-min of placebo gas and 30-min of 35% N(2)O, separated by a 35-min gas wash-out period, during each of five sessions. Sensory thresholds were assessed prior to drug or placebo administration (baseline) and between 7-12 and 25-30 min of gas administration. A control group of 16 subjects received only placebo gas at these five sessions. During a sixth session, the experimental procedures were similar to the previous sessions except that the control group received N(2)O for the first time and the experimental group was sub-divided to test for conditioned drug effects. For both detection and pain threshold measures, acute tolerance developed during the initial N(2)O exposure and chronic tolerance developed over repeated administrations. Although chronic tolerance developed, a test for Pavlovian drug conditioning found no evidence of conditioned effects on sensory thresholds. In conclusion, acute and chronic tolerance develop to N(2)O's analgesic effects in humans.

Adolescent↗

PubMed2005

Parental smoking cessation and children's smoking: mediation by antismoking actions.

The present study investigated whether parents' antismoking actions mediated the prospective relationship between parental smoking cessation and children's smoking. Smoking status of parents (predictor) was assessed when their children were in 3rd grade, parental antismoking actions (mediators) were assessed when their children were in 11th grade, and children's smoking status (outcome) was assessed when they were in 12th grade. In 20 Washington state school districts, data were collected from 1,600 children (49% female, 91% White) and from their parents. Results showed that children's odds of daily smoking were reduced by 39% (95% CI = 24%-51%) for those whose parents had quit smoking, compared with those whose parents were current smokers. Asking to sit in nonsmoking sections of public establishments was a significant (p<.01) mediator that explained 64% of the association between parental smoking cessation and children's smoking. However, not allowing smoking in the home and asking others not to smoke around them were not significant mediators (p = .10, and p = .06, respectively). In conclusion, asking to sit in a nonsmoking section of a public establishment substantially mediates the relationship between parental smoking cessation and children's smoking.

Adolescent↗

PubMed2005

Group sequential testing in dental clinical trials with longitudinal data on multiple outcome variables.

In this article, methods are proposed for design and analysis of clinical trials that gather longitudinal data on multiple outcome variables. A valid test of the null hypothesis of no treatment group differences can be obtained for any choice of a working alternative hypothesis and a working covariance matrix for the outcome variables. Increased power can be achieved by accurate modeling of the true treatment effect and covariance structure. Implementation of the procedure is simple using existing software for generalized estimating equations. The procedure is an extension of the 'derived variable' technique (univariate analysis applied to a linear combination of the outcome variables) and also of O'Brien's generalized least squares test. The procedure is extended to allow sequential testing using an arbitrary division of the total type I error rate among repeated hypothesis tests. The methods are illustrated by the design of a study on the safety of dental amalgam fillings, which served as the motivation for the research.

Clinical Trials as Topic↗

PubMed2004

Antismoking parenting practices are associated with reduced rates of adolescent smoking.

BACKGROUND: Although parental smoking is clearly one important influence on children's smoking, it is still unclear what are the many mechanisms by which parents influence their children's smoking. Antismoking actions are one potential mechanism. OBJECTIVE: To determine whether parental antismoking actions including having rules about smoking in one's home, using nonsmoking sections of public establishments, or asking others not to smoke in one's presence are associated with adolescents' adoption of smoking. DESIGN: A cross-sectional survey. SETTING: Rural and suburban communities in western Washington State. PARTICIPANTS: Population-based cohort of 3555 adolescents and their parents. MAIN OUTCOME MEASURE: Daily smoking in 12th grade. RESULTS: Adolescents of parents who report having rules about smoking in one's home, using nonsmoking sections of public establishments, or asking others not to smoke in one's presence were significantly less likely to smoke than adolescents of parents who did not engage in antismoking actions. This association of antismoking action and reduced smoking was found for children of both smoking and nonsmoking parents. CONCLUSION: Parents' antismoking actions may help prevent smoking by their teenaged children.

Adolescent↗

PubMed2003

Conditioned place aversion and self-administration of nitrous oxide in rats.

The rewarding/aversive effects of nitrous oxide (N(2)O) were evaluated using the place conditioning paradigm. Male Long-Evans rats (N=103) received a daily 40-min gas exposure for 8 consecutive days that alternated between two distinct chambers. A control group received placebo gas in both chamber types, while the N(2)O groups (8%, 15%, 30%, and 60% N(2)O) received four consistent pairings of N(2)O with one chamber type and four pairings of placebo gas with the other. A conditioned place aversion was found for the chambers that had been paired with 30% and 60% N(2)O. Place aversions were demonstrated during a 20-min test session on Day 9 when placebo gas was delivered to both chambers, and also during a 20-min test session on Day 10 when N(2)O was delivered to both chambers. A second study evaluated two novel methods of inhalant self-administration, one that used a forced-choice alternating gas environment and one that used a free-choice paradigm. Of four rats tested, two self-administered N(2)O, one rat avoided N(2)O, and one rat's behavior was consistent with neither self-administration nor avoidance. Availability of these methods will facilitate research on the neurobiological mechanisms underlying the rewarding and reinforcing effects of N(2)O and other abused inhalants.

Administration, Inhalation↗

PubMed2003

Nine-year prospective association between older siblings' smoking and children's daily smoking.

PURPOSE: To explore the hypothesis that older siblings' smoking, after controlling for parents' smoking, influences children's smoking. METHODS: Study participants were 2981 students in the control cohort of a school-based smoking prevention randomized trial for whom parents' smoking and older siblings' smoking data were collected at 3rd grade and daily smoking data was assessed 9 years later through a self-report questionnaire at the 12th grade. Data were analyzed using conditional logistic regression and likelihood ratio tests. RESULTS: For families in which no parent smoked, the 12th grade prevalence of daily smoking was 31% when at least one older sibling smoked compared to 18% when no older sibling smoked. For families in which at least one parent smoked, the 12th grade prevalence of daily smoking was 41% when at least one older sibling smoked compared to 29% when no older sibling smoked. There was a substantial increase in the odds (OR = 1.60, p =.004) of children's daily smoking at 12th grade when their older siblings smoked, even after adjusting for parents' smoking. CONCLUSIONS: Older siblings' smoking is associated with increased risk of children's smoking after adjusting for parents smoking. Furthermore, there was no evidence to suggest that the influence of older siblings' smoking was different in families where no parent smoked compared to those where at least one parent smoked. Also, there was no evidence that the influence of older siblings' smoking was different in boys vs. girls.

Adolescent↗

PubMed2003

Nine-year prospective relationship between parental smoking cessation and children's daily smoking.

AIMS: The first prospective investigation of the extent to which parental smoking cessation predicts their children's daily smoking. DESIGN: Parental smoking status was assessed when children were aged 8/9 years and children's smoking status was assessed at age 17/18 years. SETTING: Twenty Washington State school districts in the control group of the Hutchinson Smoking Prevention Project. PARTICIPANTS AND MEASUREMENTS: Questionnaire data were gathered on 3012 children (49% female and 91% Caucasian) and both of their parents in a cohort with a 95% retention rate. FINDINGS: When both parents quit smoking, children's odds of daily smoking were reduced by 39% (95% CI = 15%,56%) compared to when both parents were current smokers.Furthermore, when both parents never smoked then children's odds of daily smoking were reduced by 71% (95% CI = 62%,78%). CONCLUSIONS: Parental smoking cessation is associated with reduced risk of their children's daily smoking. Parents who quit still place children at substantially higher risk compared to parents who never smoked.

Adolescent↗

PubMed2002

Mothers' attitudes and concerns about their children smoking: do they influence kids?

BACKGROUND: The effects of mothers' attitudes and concerns about tobacco use on whether their children take up smoking are largely unknown. This study examined the predictive effects of mothers' attitudes about tobacco and concerns about their children smoking. METHODS: Self-reported data from a large number of 12th-grade students (2,736) and their mothers were used. Mothers' attitudes and concerns were assessed when their children were 3rd graders (age 8), at the start of the smoking acquisition period; their children were then followed prospectively (with attrition of only 5%) for 9 years to the end of the period (12th grade) for the assessment of smoking behavior. RESULTS: In households in which both parents are nonsmokers, strong maternal antismoking attitudes are associated with a statistically significant approximately 50% reduction (P < 0.05) in the prevalence of smoking by adolescent children. In contrast, in households in which one or both parents are current smokers, there was no reduction in adolescent smoking associated with mothers' antismoking attitudes. CONCLUSIONS: Maternal antismoking attitudes when their children are young predict adolescents' adoption of smoking at 12th grade, but only when parental behavior is consistent with these attitudes.

Adolescent↗

PubMed2002

Issues in design and analysis of a randomized clinical trial to assess the safety of dental amalgam restorations in children.

The Casa Pia Study of the Health Effects of Dental Amalgams in Children is a randomized clinical trial designed to assess the safety of low-level mercury exposure from dental amalgam restorations in children. It is being carried out in 507 students (8 to 12 years of age at enrollment) of the Casa Pia school system in Lisbon, Portugal, by an interdisciplinary collaborative research team from the University of Washington (Seattle) and the University of Lisbon, with funding from the National Institute of Dental and Craniofacial Research. Since the goal of the trial is to assess the safety of a treatment currently in use, rather than the efficacy of an experimental treatment, unique design issues come into play. The requirements to identify as participants children who have extensive unmet dental treatment needs and who can be followed for 7 years after initial treatment are somewhat in conflict, since those with the most treatment needs are usually in lower socioeconomic categories and more difficult to track. The identification of a primary study outcome measure around which to design the trial is problematic, since there is little evidence to indicate how health effects from such low-level exposure would be manifested. The solution involves the use of multiple outcomes. Since there are concerns about safety, multiple interim comparisons over time between treatment groups are called for which, in conjunction with the use of multiple outcomes, require an extension of statistical methodology to meet this requirement. Ethical questions that have to be addressed include whether assent of the children participating is required or appropriate, and whether the director of the school system, who is the legal guardian for approximately 20% of the students who are wards of the state and live in school residences, should provide consent for such a large number of children. Approaches taken to address these and other design issues are described.

Child↗