Breastfeeding Duration and Childhood Caries: A Cohort Study.

This cohort study was conducted in Khon Kaen, Thailand, to test the hypothesis that a longer breastfeeding duration increases the risk for dental caries in primary teeth. We collected information on infant feeding practices and potential confounders using a structured questionnaire to interview mothers or caregivers during the second trimester of pregnancy and after birth at 21 days and at 3, 12, 18, 24, and 36 months. Regardless of other liquids and foods, full breastfeeding was defined as feeding breast milk but not formula, while any breastfeeding was feeding breast milk with or without formula. Two calibrated dentists measured dental caries when the children were 3-4 years of age using the decayed, missing, and filled surfaces (dmfs) index following the World Health Organization criteria. Negative binomial regression with a generalized linear model was used to estimate relative risks (RRs) and 95% confidence intervals (CIs) using dmfs as an outcome. Log-binomial regression was performed to model the caries prevalence. Of 556 children, 88.1% had dental caries with a mean dmfs of 14.2. Full breastfeeding for 6-11 months was significantly associated with a lower dmfs (adjusted RR 0.77, 95% CI 0.63, 0.93) and a lower caries prevalence (adjusted RR 0.45, 95% CI 0.22, 0.90). The frequency of sleeping while breast- or bottle-feeding increased the caries risk in a dose-response manner. There was no association between duration of any breastfeeding and dental caries. In conclusion, full breastfeeding for 6-11 months may protect against dental caries in primary teeth. Prolonged breastfeeding was not associated with dental caries in this population.

Adverse birth outcomes and childhood caries: a cohort study.

OBJECTIVES: To examine the association between adverse birth outcomes and dental caries in primary teeth. METHODS: This study included children in Khon Kaen, Thailand, who participated in the Prospective Cohort Study of Thai Children. Preterm was defined as a birth at <37 weeks gestation, low birthweight (LBW) as birthweight <2500 g, and small-for-gestational age (SGA) as birthweight <10th percentile of expected weight for gestational age. Two calibrated dentists measured dental caries in primary teeth when the children were 3-4 years old using decayed, missing and filled surfaces (dmfs) index following the World Health Organization criteria. We used negative binomial regression with generalize linear models to estimate relative risks (RRs) and their 95% confidence intervals (CIs), adjusted for confounding factors. Of 758 children with gestational age data and 833 with birthweight data, the 544 (follow-up rate of 71.8% in preterm and 65.3% in LBW) who had dental data available were included in the analysis. RESULTS: Dental caries was observed in 480 children (88.2%), with a mean dmfs of 14.3 (standard deviation 12.8). The adjusted RR for dental caries was 0.61 (95% CI 0.43, 0.85) for preterm, 0.89 (95% CI 0.67, 1.21) for LBW, and 0.96 (95% CI 0.74, 1.26) for SGA. CONCLUSIONS: There was an inverse association between preterm and childhood caries. LBW and SGA were not associated with dental caries in this population.

Prevalence of pain in the orofacial regions in patients visiting general dentists in the Northwest Practice-based REsearch Collaborative in Evidence-based DENTistry research network.

BACKGROUND: This study aimed to measure prevalence of pain in the orofacial regions and determine association with demographics, treatment history, and oral health conditions in dental patients visiting clinics in the Northwest Practice-based REsearch Collaborative in Evidence-based DENTistry (PRECEDENT) research network. METHODS: Data were recorded in a survey with systematic random sampling of patients (n = 1,668, 18 to 93 years old, 56% female) visiting 100 general dentists in the Northwest PRECEDENT research network. Prevalence ratios (PR) of orofacial pain by each variable were estimated by generalized estimating equations for Poisson regression. RESULTS: The prevalence of orofacial pain during the past year was 16.1% (95% confidence interval [CI], 13.4-18.9), of which the most prevalent pain locations were dentoalveolar (9.1%; 95% CI, 7.0-11.2) and musculoligamentous tissues (6.6%; 95% CI, 4.5-8.7). Other locations included soft tissues (0.5%; 95% CI, 0.2-0.8) and nonspecific areas (0.6%; 95% CI, 0.2-1.0). The prevalence of dentoalveolar but not musculoligamentous pain decreased with age. When comparing the 18- to 29-year-old patients, dentoalveolar pain decreased significantly in 45- to 64-year-old patients (PR, 0.59; 95% CI, 0.4-0.9) and in those 65 years or older (PR, 0.5; 95% CI, 0.3-0.9). Sex significantly affected the prevalence of musculoligamentous but not dentoalveolar pain. Women (PR, 3.2; 95% CI, 2.0-5.1) were more likely to have musculoligamentous pain. The prevalence of dentoalveolar and musculoligamentous pain did not vary significantly by ethnicity. Dentoalveolar pain was reported more frequently in patients who did not receive dental maintenance (PR, 2.9; 95% CI, 2.1-4.2) and those visiting community-based public health clinics (PR, 2.2; 95% CI, 1.2-3.7). CONCLUSIONS: One in 6 patients visiting a general dentist had experienced orofacial pain during the past year. Dentoalveolar and musculoligamentous pains were the most prevalent types of pain. PRACTICAL IMPLICATIONS: Pain in the muscles and temporomandibular joints was reported as frequently as that in the teeth and surrounding tissues in patients visiting general dentists. Although the dental curriculum is concentrated on the diagnosis and management of pain and related conditions from teeth and surrounding tissues, it is imperative to include the training for other types of orofacial pain, particularly those from temporomandibular joint and musculoligamentous tissues.

Associations of periodontitis and oral manifestations with CD4 counts in human immunodeficiency virus-pregnant women in Thailand.

OBJECTIVES: To investigate the associations of CD4 count with chronic periodontitis and human immunodeficiency virus (HIV)-related oral lesions in pregnant HIV-infected Thai women. STUDY DESIGN: Two hundred ninety-two HIV-infected pregnant women were interviewed for health information and examined for their periodontal condition and HIV-related oral lesions during weeks 16-34 of gestation. Logistic regression, t tests and Chi-squared tests were used to examine the associations of CD4 count with oral lesions and periodontal conditions. RESULTS: One hundred thirty-three women (45.6%) had at least 1 tooth with a periodontal pocket over 4 mm. Thirty-eight (17.76%) subjects had oral candidiasis and 53 subjects (24.77%) had oral hairy leukoplakia (OHL). Low CD4 count was significantly associated with periodontitis at odds ratio (OR) = 2.06 with 95% confidence interval (CI) = [1.00-4.27], P = .05. A significant association was found for low CD4 count with OHL with OR = 3.57, 95% CI = [1.34-9.46], P = .01. CONCLUSIONS: Chronic periodontitis and OHL were associated with CD4 count lower than 200 cells/mm(3) in HIV-infected women.

The summer institute in clinical dental research methods: still going and growing after twenty years.

The first Summer Institute in Clinical Dental Research Methods, a faculty development program at the University of Washington, was offered in the summer of 1992 for sixteen participants. The primary objective of the program was to give clinical faculty members in dentistry an introduction to and an understanding of the fundamental principles and methods used in good clinical research. In the twentieth offering of the institute in 2011, there were thirty-five participants, and over the twenty institutes, there has been a cumulative total of 463 participants who have come from thirty U.S. states as well as forty-three countries outside the United States. The curriculum has expanded from the initial offering of biostatistics, clinical epidemiology, behavioral research methods, and ethics in clinical research to now include clinical trials, grantsmanship, data analysis, an elective in molecular biology, and a team project that provides participants with hands-on experience in research proposal development as members of an interdisciplinary team. Enrollment has doubled since the first year, yet exit evaluations of the program content have remained consistently high (rated as very good to excellent). One of the indicators of program quality is that at least 50 percent of recent participants indicated that they attended because the program was recommended by colleagues who had attended. There seems to be an ever-increasing pool of dental faculty members who are eager to learn more about clinical research methodology through the institute despite the intensive demands of full-time participation in a six-week program.

Increased risks of preterm birth and a low-birth-weight baby in Thai human immunodeficiency virus-positive pregnant women with periodontitis.

BACKGROUND: Many studies have investigated the risks of adverse neonatal outcomes associated with the presence of periodontitis in non-human immunodeficiency virus (HIV)-infected pregnant women. To the best of our knowledge, there has been no study to investigate the risk of neonatal outcomes associated with periodontitis in HIV-infected pregnant women. The aim of this study is to measure the risk of having adverse neonatal outcomes: preterm delivery (<37 weeks of gestation), low birth weight (<2500 g at birth), and preterm and low-birth-weight baby (<37 weeks of gestation and <2500 g at birth) associated with the presence of periodontitis in HIV-infected women. METHODS: A total of 292 HIV-infected pregnant women were interviewed for demographic information and medical history and were examined for their periodontal status during weeks 16 to 34 of gestation. Follow-up sessions were done after the delivery to record the baby's data. Periodontitis defined by various criteria were evaluated as exposures. Binomial regression (generalized linear model) was used to examine the risk ratios (RRs). Logistic regression, t tests, and χ2 test were used to examine the associations of periodontitis with adverse neonatal outcomes. RESULTS: Forty women had preterm delivery, 39 women delivered a low-birth-weight baby, and 22 women gave birth to a baby that was preterm and low birth weight. We found significant elevated risks of having preterm delivery as RR = 3.08, 95% confidence interval (CI) = 1.29 to 7.38, low birth weight RR = 2.55, 95% CI = 1.04 to 2.65, and preterm and low birth weight as RR = 4.08, 95% CI = 1.55 to 10.76 in women who had at ≥1 5-mm periodontal pocket. CONCLUSION: This study found a positive risk of adverse neonatal outcomes in HIV-infected pregnant women who had moderate periodontitis.

What's in a dental practice-based research network? Characteristics of Northwest PRECEDENT dentists, their patients and office visits.

OBJECTIVES: The authors conducted a study to describe the general dentists, practices, patients and patient care patterns of the dental practice-based research network (PBRN) Northwest Practice-based REsearch Collaborative in Evidence-based DENTistry (PRECEDENT). METHODS: Northwest PRECEDENT is a dental PBRN of general and pediatric dentists and orthodontists from five U.S. states in the Northwest: Idaho, Montana, Oregon, Utah and Washington. The authors collected data from general dentists in Northwest PRECEDENT (n = 101) regarding the diagnosis and treatment of oral diseases in a survey with a systematic random sample of patients (N = 1,943) visiting their practices. They also obtained demographic data from the general dentists and their patients. RESULTS: The authors found that 50 percent of the general dentists were 51 to 60 years of age, 14 percent were female and 76 percent were non-Hispanic white. More than one-half (55 percent) of the dentists had practiced dentistry for more than 20 years, 83 percent had private solo practices and 32 percent practiced in rural community settings. The majority (71 percent) of patients visiting the dental practices was in the age range of 18 to 64 years, 55 percent were female and 84 percent were non-Hispanic white. In terms of reasons for seeking dental care, 52 percent of patients overall visited the dentist for oral examinations, checkups, prophylaxis or caries-preventive treatment. In the preceding year, 85 percent of the patients had received prophylaxis, 49 percent restorative treatments, 34 percent caries-preventive treatments and 10 percent endodontic treatments. CONCLUSIONS: Northwest PRECEDENT general dentists are dispersed geographically and are racially and ethnically diverse, owing in part to efforts by network administrators and coordinators to enroll minority dentists and those who practice in rural areas. Estimates of characteristics of dentists and patients in Northwest PRECEDENT will be valuable in planning future studies of oral diseases and treatments.

Urinary porphyrin excretion in children with mercury amalgam treatment: findings from the Casa Pia Children's Dental Amalgam Trial.

Increases in the urinary concentrations of pentacarboxyl- and coproporphyrins and the appearance of the atypical precoproporphyrin have been defined in relation to mercury (Hg) body burden in animal studies, and this change in the porphyrin excretion pattern has been described as a biomarker of occupational Hg exposure and toxicity in adult human subjects. In the present studies, urinary porphyrins were determined in relation to Hg exposure in children and adolescents, 8-18 yr of age, over the 7-yr course of a clinical trial designed to evaluate the neurobehavioral and renal effects of dental amalgam in children. Subjects were randomized to either dental amalgam or composite resin treatments. Urinary porphyrins and creatinine concentrations were measured at baseline and annually in all subjects. Results were evaluated using linear regression analysis. No significant differences between treatment groups (amalgam versus composite) were found when comparing all subjects for any of the porphyrins of interest. However, incipent amalgam treatment-specific increases were observed in the mean concentrations of penta-, precopro- and coproporphyrins especially when the analyses were restricted to younger subjects (8 to 9 yr old at baseline), and these increases were most apparent during yr 2 through 3 of follow-up, the period of highest mercury exposure from amalgam treatment. Based on the mean number of amalgam fillings received by children in this group (17.8), the renal Hg concentration associated with incipient increases in urinary porphyrins was estimated to be approximately 2.7 microg/g renal cortex. This value corresponds to an observed mean urinary Hg concentration of 3.2 microg/g creatinine, which is approximately fivefold less than that at which renal damage from Hg exposure is estimated to occur in children. These findings are consistent with growing evidence supporting the sensitivity of urinary porphyrins as a biological indicator of subclinical Hg exposure in children.

Urinary porphyrin excretion in normal children and adolescents.

BACKGROUND: Urinary porphyrins are diagnostic of various metabolic disorders and xenobiotic exposures, but comprehensive normative data for urinary porphyrin concentrations in children are currently unavailable. METHODS: Subjects were participants in a prospective, randomized, controlled clinical trial of dental materials safety, 8 to 12 y at inception, who were followed longitudinally for 7 y after baseline with an extensive battery of neurobehavioral, neurological, renal function and urinary porphyrin assessments. Porphyrins were quantified by HPLC. Linear regression analyses were used to measure associations of porphyrin levels with age and gender. RESULTS: Mean concentrations, 95% confidence intervals, and 10th, 50th, and 90th percentiles for all 5 typically excreted urinary porphyrins are presented by year of age and by gender. Unadjusted urinary concentrations (microg/l) of all 5 porphyrins remained relatively constant throughout the age range of 8-18 y for both males and females. In contrast, creatinine-adjusted urinary porphyrin concentrations (microg/g) declined significantly throughout this age range in both genders. Boys had significantly higher pentacarboxyl- and copro-porphyrin levels compared with girls both before and after creatinine adjustment. CONCLUSIONS: Normative longitudinal data provided herein may facilitate the clinical assessment of pediatric metabolic disorders and may be of particular relevance in evaluating porphyrin changes as a biological indicator of disease or xenobiotic exposures among children and adolescents.

The serial use of child neurocognitive tests: development versus practice effects.

When serial neurocognitive assessments are performed, 2 main factors are of importance: test-retest reliability and practice effects. With children, however, there is a third, developmental factor, which occurs as a result of maturation. Child tests recognize this factor through the provision of age-corrected scaled scores. Thus, a ready-made method for estimating the relative contribution of developmental versus practice effects is the comparison of raw (developmental and practice) and scaled (practice only) scores. Data from a pool of 507 Portuguese children enrolled in a study of dental amalgams (T. A. DeRouen, B. G. Leroux, et al., 2002; T. A. DeRouen, M. D. Martin, et al., 2006) showed that practice effects over a 5-year period varied on 8 neurocognitive tests. Simple regression equations are provided for calculating individual retest scores from initial test scores.

Biomarkers of kidney integrity in children and adolescents with dental amalgam mercury exposure: findings from the Casa Pia children's amalgam trial.

Mercury is toxic to the kidney, and dental amalgam is a source of mercury exposure. Few studies have evaluated the effects of dental amalgam on kidney function in a longitudinal context in children. Here, we evaluated urinary concentrations of glutathione S-transferases (GSTs) alpha and pi as biomarkers of renal proximal and distal tubular integrity, respectively, and albumin as a biomarker of glomerular integrity in children and adolescents 8-18 years of age over a 7-year course of dental amalgam treatment. Five hundred seven children, 8-12 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral and renal effects of dental amalgam in children. Subjects were randomized to either dental amalgam or resin composite treatments. Urinary GSTs alpha and pi, albumin, and creatinine concentrations were measured at baseline and annually in all subjects. Results were evaluated using linear regression analysis. GST-alpha concentrations were similar between treatment groups and in each sex and race (white vs. non-white) group in each follow-up year. GST-pi levels tended upward over the course of follow-up by four- to six-fold. This increase was seen in all groups irrespective of the treatment, race, or gender. Females had GST-pi levels approximately twice those of males at all ages. Albumin concentrations were constant throughout the follow-up period and did not differ by treatment, although females had 39% higher albumin levels than males. Additionally, we found no significant effects of amalgam treatment on the proportion of children with microalbuminuria (>30 mg/g creatinine). These findings are relevant within the context of children's health risk assessment as relates to the safety of mercury exposure from dental amalgam on kidney function. These data also provide normative values for sensitive indices of renal functional integrity that may serve in the evaluation of children and adolescents with renal disorders.

Preparing practicing dentists to engage in practice-based research.

BACKGROUND: The authors describe an educational program designed to prepare practicing dentists to engage in practice-based research in their practices--a trend receiving more emphasis and funding from the National Institute of Dental and Craniofacial Research (NIDCR). METHODS: The Northwest Practice-based REsearch Collaborative in Evidence-based DENTistry (PRECEDENT), an NIDCR-funded network of which the authors are members, developed a one-day educational program to educate practitioners in principles of good clinical research. The program has four components built around the following questions: "What is the question?"; "What are the options?"; "How do you evaluate the evidence?"; and "How do you conduct a study?" RESULTS: The intensive one-day program initially offered in early 2006, which concluded with applications of research principles to research topics of interest to practitioners, was well-received. Despite their admission that the research methodology by itself was not of great interest, the dentists recognized the importance of the background material in equipping them to conduct quality studies in their practices. CONCLUSIONS: Dentists interested in participating in practice-based research view training in research methodology as helpful to becoming better practitioner-investigators. The PRECEDENT training program seemed to reinforce their interest. PRACTICE IMPLICATIONS: As dentistry evolves to become more evidence-based, more and more of the evidence will come from practice-based research. This training program prepares practicing dentists to become engaged in this trend.

Longitudinal urinary creatinine excretion values among preadolescents and adolescents.

To present longitudinal urinary creatinine excretion data for developmentally normal children 9-17 years of age. Only extremely limited data have been presented of a longitudinal nature for this age group. Overall, 507 children who participated in a prospective, randomized, controlled trial of dental materials safety were followed longitudinally for 7 years with renal measures, including creatinine excretion. Urinary creatinine means, confidence intervals, and 10th, 50th, and 90th percentiles are presented by year of age for the entire group, by sex, and by race (whites, blacks). Urinary creatinine excretion increases with age for both sexes and for both races (P<0.0001). No significant sexual difference were observed, although a race difference occurs, with blacks showing higher excretion levels than whites (P=0.0003). We present longitudinal urinary creatinine excretion data for ages 9-17 in which creatinine excretion increases with age throughout the time period. No sexual differences are observed, although blacks excrete significantly higher levels of urinary creatinine than do whites.

The contribution of dental amalgam to urinary mercury excretion in children.

BACKGROUND: Urinary mercury concentrations are widely used as a measure of mercury exposure from dental amalgam fillings. No studies have evaluated the relationship of these measures in a longitudinal context in children. OBJECTIVE: We evaluated urinary mercury in children 8-18 years of age in relation to number of amalgam surfaces and time since placement over a 7-year course of amalgam treatment. METHODS: Five hundred seven children, 8-10 years of age at baseline, participated in a clinical trial to evaluate the neurobehavioral effects of dental amalgam in children. Subjects were randomized to either dental amalgam or resin composite treatments. Urinary mercury and creatinine concentrations were measured at baseline and annually on all participants. RESULTS: Treatment groups were comparable in baseline urinary mercury concentration (approximately 1.5 microg/L). Mean urinary mercury concentrations in the amalgam group increased to a peak of approximately 3.2 microg/L at year 2 and then declined to baseline levels by year 7 of follow-up. There was a strong, positive association between urinary mercury and both number of amalgam surfaces and time since placement. Girls had significantly higher mean urinary mercury concentrations than boys throughout the course of amalgam treatment. There were no differences by race in urinary mercury concentration associated with amalgam exposure. CONCLUSIONS: Urinary mercury concentrations are highly correlated with both number of amalgam fillings and time since placement in children. Girls excrete significantly higher concentrations of mercury in the urine than boys with comparable treatment, suggesting possible sex-related differences in mercury handling and susceptibility to mercury toxicity.

Survival and reasons for failure of amalgam versus composite posterior restorations placed in a randomized clinical trial.

BACKGROUND: Failure of dental restorations is a major concern in dental practice. Replacement of failed restorations constitutes the majority of operative work. Clinicians should be aware of the longevity of, and likely reasons for the failure of, direct posterior restorations. In a long-term, randomized clinical trial, the authors compared the longevity of amalgam and composite. SUBJECTS, METHODS AND MATERIALS: The authors randomly assigned one-half of the 472 subjects, whose age ranged from 8 through 12 years, to receive amalgam restorations in posterior teeth and the other one-half to receive resin-based composite restorations. Study dentists saw subjects annually to conduct follow-up oral examinations and take bitewing radiographs. Restorations needing replacement were failures. The dentists recorded differential reasons for restoration failure. RESULTS: Subjects received a total of 1,748 restorations at baseline, which the authors followed for up to seven years. Overall, 10.1 percent of the baseline restorations failed. The survival rate of the amalgam restorations was 94.4 percent; that of composite restorations was 85.5 percent. Annual failure rates ranged from 0.16 to 2.83 percent for amalgam restorations and from 0.94 to 9.43 percent for composite restorations. Secondary caries was the main reason for failure in both materials. Risk of secondary caries was 3.5 times greater in the composite group. CONCLUSION: Amalgam restorations performed better than did composite restorations. The difference in performance was accentuated in large restorations and in those with more than three surfaces involved. CLINICAL IMPLICATIONS: Use of amalgam appears to be preferable to use of composites in multisurface restorations of large posterior teeth if longevity is the primary criterion in material selection.

The association of dental caries with blood lead in children when adjusted for IQ and neurobehavioral performance.

UNLABELLED: Associations between childhood lead exposures and dental caries in children have been reported for over 30 years, with widely varying findings and conclusions, and using measures of lead exposure which ranged from food sources and water to tooth, hair or blood lead concentrations. OBJECTIVES: This study examined the relationship of lead exposure and dental caries in a population of normatively healthy children. METHODS: This cross-sectional study used a population of 507 children aged 8-12 who were participating in a clinical trial of dental materials to examine the relationship between lead and caries. Blood lead concentrations and dental caries were examined for association in both primary and permanent teeth. Because it is possible that neurobehavioral status could be associated with both lead exposure and dental caries prevalence, we also examined neurobehavioral status of the subjects. RESULTS: A gender-specific association (males only) between lead exposure and dental caries was found in primary teeth only. Neurobehavioral measures and IQ were not associated with caries status in this population. CONCLUSIONS: This study did not support neurobehavioral status as mediating any association between lead exposure and caries in a normatively healthy population. A gender-specific association between lead and caries not previously reported was found in primary teeth, and no biological explanation for this has been suggested. We conclude that this study provides only weak evidence, if any, for an association of low-level lead exposure with dental caries.

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.

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.