Athlete mental health help-seeking: A systematic review and meta-analysis of rates, barriers and facilitators.

Athletes are vulnerable to a range of mental health symptoms, in part due to stressors within the sport environment. An early intervention framework suggests the benefits of routine screening and referral for mental health, however, greater understanding around athlete help-seeking is needed to support referral uptake. This review examined rates of formal help-seeking behaviour as well as barriers and facilitators to help-seeking in sport settings. Relevant studies were retrieved from SportDiscus, PubMed and PsycInfo, with unpublished studies identified through contacting authors. Help-seeking rates were meta-analysed and barriers and facilitators were meta-synthesised. Twenty-two studies were included. Help-seeking rates were reported in 11 studies (N = 3415) and the pooled proportion of help-seeking was 22.4 % (95 % CI 16.2-30.2, I2 = 95.7 %). Barriers were reported in 13 studies and facilitators in six, highlighting a range of sporting-specific factors, such as stigma in relation to athlete identity and sport culture, fear of deselection, and concerns around confidentiality in sport settings, in addition to lack of awareness, low mental health literacy, and negative attitudes to services. Normalising experiences of mental health in sport settings, including through role models, was a key facilitator to help-seeking. Results provide implications for sport organisations to promote help-seeking and athlete mental health, such as through the use of role models, ensuring clarity around confidentiality, stigma reduction interventions, and fostering team cultures that promote mental health. Findings also support the value of sport staff in facilitating help-seeking, and organisational culture changes to foster wellbeing.

Compulsive exercise and its relationship with mental health and psychosocial wellbeing in recreational exercisers and athletes.

OBJECTIVES: Better understanding of compulsive exercise is needed in sports medicine. Whilst compulsive exercise may impact mental health, the limited research exploring the relationship between compulsive exercise and psychosocial outcomes is equivocal. The majority of studies have examined eating disorder populations where the eating disorder pathology might account for distress. This study explores relationships between compulsive exercise and mental health. DESIGN: Cross-sectional observational study. METHODS: Australian recreational exercisers and athletes (N = 1157; Mage 36.4, standard deviation = 12.9, 77 % female) recruited through sporting organisations, clubs, and gyms, completed measures of compulsive exercise, depression, anxiety, stress, life satisfaction, social physique anxiety, and self-esteem. Regression analyses examined relationships between dimensions of compulsive exercise and wellbeing. RESULTS: After adjustment for eating disorder symptoms and sporting level, compulsive exercise was associated with increased risk of clinically-significant anxiety, depression, and stress symptoms. Compulsive exercise was also associated with lower life satisfaction and self-esteem, and higher social physique anxiety. Notably, different dimensions of compulsive exercise had varying relationships with outcomes, and avoidance and rule-driven behaviour and lack of exercise enjoyment were associated with poorer mental health and wellbeing. CONCLUSIONS: Results suggest that compulsive exercise is uniquely associated with a range of psychosocial and mental health outcomes. Results support the need to improve identification and treatment of compulsive exercise in sport and exercise settings. Results highlight that mental health intervention is an important component of treatment, and treatments targeting symptoms related to avoidance and rule-driven behaviour, and anhedonia may be valuable treatment components for those with compulsive exercise.

Plaque Microbiome in Caries-Active and Caries-Free Teeth by Dentition.

OBJECTIVE: Describe associations between dental caries and dental plaque microbiome, by dentition and family membership. METHODS: This cross-sectional analysis included 584 participants in the Center for Oral Health Research in Appalachia Cohort 1 (COHRA1). We sequenced the 16S ribosomal RNA gene (V4 region) of frozen supragingival plaque, collected 10 y prior, from 185 caries-active (enamel and dentinal) and 565 caries-free (no lesions) teeth using the Illumina MiSeq platform. Sequences were filtered using the R DADA2 package and assigned taxonomy using the Human Oral Microbiome Database. RESULTS: Microbiomes of caries-active and caries-free teeth were most similar in primary dentition and least similar in permanent dentition, but caries-active teeth were significantly less diverse than caries-free teeth in all dentition types. Streptococcus mutans had greater relative abundance in caries-active than caries-free teeth in all dentition types (P < 0.01), as did Veillonella dispar in primary and mixed dentition (P < 0.01). Fusobacterium sp. HMT 203 had significantly higher relative abundance in caries-free than caries-active teeth in all dentition types (P < 0.01). In a linear mixed model adjusted for confounders, the relative abundance of S. mutans was significantly greater in plaque from caries-active than caries-free teeth (P < 0.001), and the relative abundance of Fusobacterium sp. HMT 203 was significantly lower in plaque from caries-active than caries-free teeth (P < 0.001). Adding an effect for family improved model fit for Fusobacterium sp. HMT 203 but notS. mutans. CONCLUSIONS: The diversity of supragingival plaque composition from caries-active and caries-free teeth changed with dentition, but S. mutans was positively and Fusobacterium sp. HMT 203 was negatively associated with caries regardless of dentition. There was a strong effect of family on the associations of Fusobacterium sp. HMT 203 with the caries-free state, but this was not true for S. mutans and the caries-active state. KNOWLEDGE TRANSFER STATEMENT: Patients' and dentists' concerns about transmission of bacteria within families causing caries should be tempered by the evidence that some shared bacteria may contribute to good oral health.

Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium.

Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.

Genome-wide Scan of Dental Fear and Anxiety Nominates Novel Genes.

Dental care-related fear and anxiety (DFA) is prevalent, affects oral health care utilization, and is related to poor oral health and decreased quality of life. In addition to learned and cultural factors, genetics is hypothesized to contribute to DFA. Therefore, we performed a genome-wide association study to identify genetic variants contributing to DFA. Adult and adolescent participants were from 4 cohorts (3 from the US-based Center for Oral Health Research in Appalachia, n = 1,144, 1,164, and 535, and the UK-based Avon Longitudinal Study of Parents and Children [ALSPAC], n = 2,078). Two self-report instruments were used to assess DFA: the Dental Fear Survey (US cohorts) and Corah's Dental Anxiety Scale (ALSPAC). Genome-wide scans were performed for the DFA total scores and subscale scores (avoidance, physiological arousal, fear of dental treatment-specific stimuli), adjusting for age, sex, educational attainment, recruitment site, and genetic ancestry. Results across cohorts were combined using meta-analysis. Heritability estimates for DFA total and subscale scores were similar across cohorts and ranged from 23% to 59%. The meta-analysis revealed 3 significant (P < 5E-8) associations between genetic loci and 2 DFA subscales: physiological arousal and avoidance. Nearby genes included NTSR1 (P = 3.05E-8), DMRTA1 (P = 4.40E-8), and FAM84A (P = 7.72E-9). Of these, NTSR1, which was associated with the avoidance subscale, mediates neurotensin function, and its deficiency may lead to altered fear memory in mice. Gene enrichment analyses indicated that loci associated with the DFA total score and physiological arousal subscale score were enriched for genes associated with severe and persistent mental health (e.g., schizophrenia) and neurocognitive (e.g., autism) disorders. Heritability analysis indicated that DFA is partly explained by genetic factors, and our association results suggested shared genetic underpinnings with other psychological conditions.

Consensus Statement on Future Directions for the Behavioral and Social Sciences in Oral Health.

The behavioral and social sciences are central to understanding and addressing oral and craniofacial health, diseases, and conditions. With both basic and applied approaches, behavioral and social sciences are relevant to every discipline in dentistry and all dental, oral, and craniofacial sciences, as well as oral health promotion programs and health care delivery. Key to understanding multilevel, interacting influences on oral health behavior and outcomes, the behavioral and social sciences focus on individuals, families, groups, cultures, systems, societies, regions, and nations. Uniquely positioned to highlight the importance of racial, cultural, and other equity in oral health, the behavioral and social sciences necessitate a focus on both individuals and groups, societal reactions to them related to power, and environmental and other contextual factors. Presented here is a consensus statement that was produced through an iterative feedback process. The statement reflects the current state of knowledge in the behavioral and social oral health sciences and identifies future directions for the field, focusing on 4 key areas: behavioral and social theories and mechanisms related to oral health, use of multiple and novel methodologies in social and behavioral research and practice related to oral health, development and testing of behavioral and social interventions to promote oral health, and dissemination and implementation research for oral health. This statement was endorsed by over 400 individuals and groups from around the world and representing numerous disciplines in oral health and the behavioral and social sciences. Having reached consensus, action is needed to advance and further integrate and translate behavioral and social sciences into oral health research, oral health promotion and health care, and the training of those working to ensure oral health for all.

Dietary Patterns and Risk of a New Carious Lesion Postpartum: A Cohort Study.

Dental caries (cavities), one of the most common infectious diseases, is caused by a number of factors. Oral microbes, dietary practices, sociodemographic factors, and dental hygiene all inform caries risk. Assessing the impact of diet is complicated as individuals eat foods in combinations, and the interactions among the foods may alter caries risk. Our study aimed to prospectively assess the association between dietary patterns and caries risk in the postpartum period, a potentially sensitive period for caries development. We analyzed in-person dental assessments and telephone food frequency questionnaires (FFQs) from 879 Caucasian women participating in the Center for Oral Health Research in Appalachia Cohort 2 (COHRA2) that were collected biannually for up to 6 y. One-week recall of food intake frequency was assessed using a Likert scale. We used principal component analysis to summarize the FFQ data; the top 2 components described 15% and 12% of the variance in FFQ data. The first component was characterized by high consumption of fruits and vegetables, while the second component was heavily influenced by desserts and crackers. We used a modified Poisson model to predict the risk of an increase in the number of decayed, missing, and filled teeth in the postpartum period by 1) dietary patterns and 2) individual foods and beverages at the previous study visit, after controlling for other known risk factors, including history of carious lesions. Eating a dietary pattern high in desserts and crackers was associated with a 20% increase in the number of decayed, missing, and filled teeth in the postpartum period (95% confidence interval, 1.03-1.39). However, this effect was attenuated among those who also consumed a dietary pattern high in fruits and vegetables. Dietary patterns should be considered when devising interventions aimed at preventing dental caries.

Opposition to Early Dental Visit by Dentists: A Qualitative Study on Mothers' Social Networks.

OBJECTIVES: To examine whether information that mothers received from dentists in their social network was consistent with professional recommendations for the first dental visit at age 1 y. METHODS: We performed a cross-sectional qualitative study on mothers in Pennsylvania and West Virginia from 2018 to 2020 to explore how their social networks influence their children's dental service utilization. In-person, semistructured interviews were conducted with 126 mothers of children ages 3 to 5 y. Qualitative data were transcribed, coded, and analyzed using NVivo 12. Two investigators analyzed data using grounded theory and the constant comparative method. RESULTS: Over half of mothers reported a professional relationship with a dentist as part of their social network on children's oral health. Mothers described the following themes: 1) mothers contacted dentists in their social network for child dental information and to schedule their child's first dental visit, 2) mothers described dentists' justifications for the timing of the first dental visit older than age 1 y, 3) mothers described the impact of the dentist declining to see her child, and 4) after the dentist declined to see her child, some mothers did not comply with the dentist's recommendation of delayed child dental visits because they were given alternative information that encouraged early dental visits. CONCLUSIONS: Our findings indicate a need for dentists to reinforce mothers' dental-seeking behavior for young children and adhere to recommendations on the age 1 dental visit. KNOWLEDGE TRANSFER STATEMENT: Qualitative data on mothers' social networks show that dentists play a key role in access to early dental visits, particularly when dentists decline to see the mother's child for visits.

Maternal Oral Health Influences Infant Salivary Microbiome.

Oral microbiomes vary in cariogenic potential; these differences may be established early in life. A major concern is whether mothers transmit cariogenic bacteria to their children. Here we characterize early salivary microbiome development and the potential associations of that development with route of delivery, breastfeeding, and mother's oral health, and we evaluate transmission of microbes between mother and child. We analyzed saliva and metadata from the Center for Oral Health Research in Appalachia. For this cohort study, we sequenced the V6 region of the 16S rRNA gene and used quantitative polymerase chain reaction to detect Streptococcus mitis, Streptococcus sobrinus, Streptococcus mutans, Streptococcus oralis, and Candida albicans in the saliva from mothers and their infants, collected at 2, 9, and 12 mo (Pennsylvania site) and 2, 12, and 24 mo (West Virginia site). Breastfed children had lower relative abundances of Prevotella and Veillonella. If mothers had decayed, missing, or filled teeth, children had greater abundances of Veillonella and Actinomyces. There was little evidence of maternal transmission of selected microbes. At 12 mo, children's microbiomes were more similar to other children's than to their mothers'. Infants' salivary microbiomes became more adult-like with age but still differed with mothers' microbiomes at 12 mo. There was little evidence supporting transmission of selected microbes from mothers to children, but risk of colonization was associated with tooth emergence. Children are likely to acquire cariogenic bacteria from a variety of sources, including foods and contact with other children and adults.

Pilot GWAS of caries in African-Americans shows genetic heterogeneity.

BACKGROUND: Dental caries is the most common chronic disease in the US and disproportionately affects racial/ethnic minorities. Caries is heritable, and though genetic heterogeneity exists between ancestries for a substantial portion of loci associated with complex disease, a genome-wide association study (GWAS) of caries specifically in African Americans has not been performed previously. METHODS: We performed exploratory GWAS of dental caries in 109 African American adults (age > 18) and 96 children (age 3-12) from the Center for Oral Health Research in Appalachia (COHRA1 cohort). Caries phenotypes (DMFS, DMFT, dft, and dfs indices) assessed by dental exams were tested for association with 5 million genotyped or imputed single nucleotide polymorphisms (SNPs), separately in the two age groups. The GWAS was performed using linear regression with adjustment for age, sex, and two principal components of ancestry. A maximum of 1 million adaptive permutations were run to determine empirical significance. RESULTS: No loci met the threshold for genome-wide significance, though some of the strongest signals were near genes previously implicated in caries such as antimicrobial peptide DEFB1 (rs2515501; p = 4.54 × 10- 6) and TUFT1 (rs11805632; p = 5.15 × 10- 6). Effect estimates of lead SNPs at suggestive loci were compared between African Americans and Caucasians (adults N = 918; children N = 983). Significant (p < 5 × 10- 8) genetic heterogeneity for caries risk was found between racial groups for 50% of the suggestive loci in children, and 12-18% of the suggestive loci in adults. CONCLUSIONS: The genetic heterogeneity results suggest that there may be differences in the contributions of genetic variants to caries across racial groups, and highlight the critical need for the inclusion of minorities in subsequent and larger genetic studies of caries in order to meet the goals of precision medicine and to reduce oral health disparities.

Association between obesity in 4- to 7-year-old children and eight types of crime: a hierarchical linear modelling approach.

OBJECTIVE: Evidence of the association between childhood obesity and neighbourhood crime is inconclusive. Most previous studies have included children of all ages, and few have examined different types of crime. The objective of this study was to investigate the association between obesity and eight different types of crime (i.e. commercial robbery, street robbery, assault, other violence, commercial break and enter, residential break and enter, theft of vehicle and theft from vehicle) among 4- to 7-year-old children in a large western Canadian city. METHODS: Cross-sectional, epidemiological study (N = 10,069) using spatial analysis and hierarchical generalized linear modelling. The outcome variable was normal weight or obesity. The exposure variable was the distance between the child's residential postal code and the closest occurrence of each type of crime. RESULTS: Controlling for distance to the closest park, frequency of each type of crime in the child's neighbourhood and neighbourhood factors (proportion of visible minorities, education and median family income), there was no association between any of the crime types and childhood obesity. CONCLUSIONS: Crime did not contribute to obesity in this sample of 4- to 7-year-old children. Replication of this study in other jurisdictions would increase confidence in these results.

Immediately Loaded Fixed Full-Arch Implant-Retained Prosthesis: Clinical Analysis When Using a Moderate Insertion Torque.

PURPOSE: This study uses intentionally tilted implants with a moderate insertion torque to retain an immediately loaded fixed full-arch implant-retained prosthesis using four implants. The aims of this study were to determine the likelihood that this type of implant-retained prosthesis can be predictably provided on the day of implant placement, the survival rate when providing immediate load, and the importance of insertion torque on the survival of the implants. MATERIALS AND METHODS: All implants that were placed after August 1, 2015 and before December 31, 2016 at the ClearChoice Dental Implant Center of Minneapolis were recorded. The performance of these implants was followed to determine the success rate in the category of "intention to treat" where the treatment is provided on the same day as implant placement. Insertion torque was recorded for all implants. Implants were followed to determine survival of the implants and complications observed. RESULTS: Between August 1, 2015 and December 31, 2016, a total of 1,903 implants were placed. These implants were utilized to support 441 prostheses, with 440 actually being restored with a provisional prosthesis on the day of implant placement. Mean follow-up time was 484 days with a maximum of 972 days and a median of 474 days. A total of 36 implants failed to achieve osseointegration, resulting in an overall survival rate of 98.1% with a confidence interval (CI) of 98.7% to 97.5%. Survival was 97.6% in the maxilla and 98.9% in the mandible. Insertion torque of less than 15 Ncm (n = 80, 77 survival), between 15 and 34 Ncm (n = 122, 120 survival), and greater than 35 Ncm (n = 1,701, 1,670 survival) demonstrated no difference in implant survival. CONCLUSION: Based on this study of 1,903 implants placed between August 1, 2015 and December 31, 2016, the following observations were made: (1) this surgical/prosthetic treatment approach succeeded in the "intention to treat" category with 440/441 (99.8%) prostheses inserted on the day of implant surgery; (2) overall implant survival was 98.1%; (3) insertion torque appeared to have no effect on implant survival.

Recruitment & retention program for the NeuroNEXT SMA Biomarker Study: Super Babies for SMA!

BACKGROUND/AIMS: Recruitment and retention of research participants are challenging and critical components of successful clinical trials and natural history studies. Infants with spinal muscular atrophy (SMA) have been a particularly challenging population to study due to their fragile and complex medical issues, poor prognosis and, until 2016, a lack of effective therapies. Recruitment of healthy infants into clinical trials and natural history studies is also challenging and sometimes assumed to not be feasible. METHODS: In 2011, our group initiated a two-year, longitudinal natural history study of infants with SMA and healthy infant controls to provide data to assist in the analysis and interpretation of planned clinical trials in infants with SMA. The recruitment goal was to enroll 27 infants less than 6 months of age with SMA and 27 age-matched healthy infants within the two-year enrollment period. A detailed recruitment and retention plan was developed for this purpose. In addition, a survey was administered to participant families to understand the determinants of participation in the study. RESULTS: All healthy infants were recruited within the study's first year and 26 SMA infants were recruited within the two-year recruitment period. Thirty-eight participant families responded to the recruitment determinants survey. Nearly half of respondents (18/38, 48%) reported that they first heard of the study from their physician or neurologist. The most common reason to decide to enroll their infant (22/38, 58%) and to remain in the study (28/38, 74%) was their understanding of the importance of the study. Thematic recruitment tools such as a study brochure, video on social media, and presentations at advocacy meetings were reported to positively influence the decision to enroll. CONCLUSIONS: A proactive, thematic and inclusive recruitment and retention plan that effectively communicates the rationale of a clinical study and partners with patients, advocacy groups and the local communities can effectively recruit participants in vulnerable populations. Recommendations for the proactive integration of recruitment and retention plans into clinical trial protocol development are provided.

Fear of Pain Questionnaire-9: Brief assessment of pain-related fear and anxiety.

BACKGROUND: Fear and anxiety are important considerations in both acute and chronic pain. Effectively and efficiently measuring fear and anxiety associated with pain in healthcare settings is critical for identifying vulnerable patients. The length and administration time of current measures of pain-related fear and anxiety inhibit their routine use, as screening tools and otherwise, suggesting the need for a shorter, more efficient instrument. METHODS: A 9-item shortened version of the Fear of Pain Questionnaire - III (FPQ-III), the Fear of Pain Questionnaire-9 (FPQ-9), was developed based upon statistical analyses of archival data from 275 outpatients with chronic pain and 275 undergraduates. Additionally, new data were collected from 100 outpatients with chronic pain and 190 undergraduates to directly compare the standard and short forms. Exploratory and confirmatory factor analyses, and other psychometric analyses, were conducted to examine and establish the FPQ-9 as a reliable and valid instrument. RESULTS: The original three-factor structure of the FPQ-III was retained in the shortened version; a confirmatory factor analysis produced good model fit (RMSEA = 0.00, CFI = 1.00, TLI = 1.00, SRMR = 0.03). Results suggested a high degree of correlation between the original FPQ-III and the new FPQ-9 (r = 0.77, p < 0.001). Measures of internal consistency for FPQ-9 subscales were high; correlations with other pain and anxiety instruments suggested concurrent, convergent and divergent validity. CONCLUSIONS: The FPQ-9 is a psychometrically sound alternative to longer instruments assessing fear and anxiety associated with pain, for use in both clinical and research situations that only allow brief screening. SIGNIFICANCE: The FPQ-9 has considerable potential for dissemination and utility for routine, brief screening, given its length (completion time ~2 min; scoring time ~1 min), reading level and psychometric properties.

Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence.

Cigarette smoking is a leading cause of preventable mortality worldwide. Nicotine dependence, which reduces the likelihood of quitting smoking, is a heritable trait with firmly established associations with sequence variants in nicotine acetylcholine receptor genes and at other loci. To search for additional loci, we conducted a genome-wide association study (GWAS) meta-analysis of nicotine dependence, totaling 38,602 smokers (28,677 Europeans/European Americans and 9925 African Americans) across 15 studies. In this largest-ever GWAS meta-analysis for nicotine dependence and the largest-ever cross-ancestry GWAS meta-analysis for any smoking phenotype, we reconfirmed the well-known CHRNA5-CHRNA3-CHRNB4 genes and further yielded a novel association in the DNA methyltransferase gene DNMT3B. The intronic DNMT3B rs910083-C allele (frequency=44-77%) was associated with increased risk of nicotine dependence at P=3.7 × 10-8 (odds ratio (OR)=1.06 and 95% confidence interval (CI)=1.04-1.07 for severe vs mild dependence). The association was independently confirmed in the UK Biobank (N=48,931) using heavy vs never smoking as a proxy phenotype (P=3.6 × 10-4, OR=1.05, and 95% CI=1.02-1.08). Rs910083-C is also associated with increased risk of squamous cell lung carcinoma in the International Lung Cancer Consortium (N=60,586, meta-analysis P=0.0095, OR=1.05, and 95% CI=1.01-1.09). Moreover, rs910083-C was implicated as a cis-methylation quantitative trait locus (QTL) variant associated with higher DNMT3B methylation in fetal brain (N=166, P=2.3 × 10-26) and a cis-expression QTL variant associated with higher DNMT3B expression in adult cerebellum from the Genotype-Tissue Expression project (N=103, P=3.0 × 10-6) and the independent Brain eQTL Almanac (N=134, P=0.028). This novel DNMT3B cis-acting QTL variant highlights the importance of genetically influenced regulation in brain on the risks of nicotine dependence, heavy smoking and consequent lung cancer.

Natural history of infantile-onset spinal muscular atrophy.

OBJECTIVE: Infantile-onset spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality, typically resulting in death preceding age 2. Clinical trials in this population require an understanding of disease progression and identification of meaningful biomarkers to hasten therapeutic development and predict outcomes. METHODS: A longitudinal, multicenter, prospective natural history study enrolled 26 SMA infants and 27 control infants aged <6 months. Recruitment occurred at 14 centers over 21 months within the NINDS-sponsored NeuroNEXT (National Network for Excellence in Neuroscience Clinical Trials) Network. Infant motor function scales (Test of Infant Motor Performance Screening Items [TIMPSI], The Children's Hospital of Philadelphia Infant Test for Neuromuscular Disorders, and Alberta Infant Motor Score) and putative physiological and molecular biomarkers were assessed preceding age 6 months and at 6, 9, 12, 18, and 24 months with progression, correlations between motor function and biomarkers, and hazard ratios analyzed. RESULTS: Motor function scores (MFS) and compound muscle action potential (CMAP) decreased rapidly in SMA infants, whereas MFS in all healthy infants rapidly increased. Correlations were identified between TIMPSI and CMAP in SMA infants. TIMPSI at first study visit was associated with risk of combined endpoint of death or permanent invasive ventilation in SMA infants. Post-hoc analysis of survival to combined endpoint in SMA infants with 2 copies of SMN2 indicated a median age of 8 months at death (95% confidence interval, 6, 17). INTERPRETATION: These data of SMA and control outcome measures delineates meaningful change in clinical trials in infantile-onset SMA. The power and utility of NeuroNEXT to provide "real-world," prospective natural history data sets to accelerate public and private drug development programs for rare disease is demonstrated. Ann Neurol 2017;82:883-891.

Bayesian Analysis of the Association between Family-Level Factors and Siblings' Dental Caries.

We conducted a Bayesian analysis of the association between family-level socioeconomic status and smoking and the prevalence of dental caries among siblings (children from infant to 14 y) among children living in rural and urban Northern Appalachia using data from the Center for Oral Health Research in Appalachia (COHRA). The observed proportion of siblings sharing caries was significantly different from predicted assuming siblings' caries status was independent. Using a Bayesian hierarchical model, we found the inclusion of a household factor significantly improved the goodness of fit. Other findings showed an inverse association between parental education and siblings' caries and a positive association between households with smokers and siblings' caries. Our study strengthens existing evidence suggesting that increased parental education and decreased parental cigarette smoking are associated with reduced childhood caries in the household. Our results also demonstrate the value of a Bayesian approach, which allows us to include household as a random effect, thereby providing more accurate estimates than obtained using generalized linear mixed models.

Dental Care-Related Fear and Anxiety: Distress Tolerance as a Possible Mechanism.

Distress tolerance, the degree to which one is able to cope with and endure negative emotional states, has been broadly applied to understand and treat a variety of health (including behavioral) problems, but little is known about its role in oral health care and specifically dental care-related fear and anxiety, making it a novel construct in the oral health care literature. This cross-sectional study examined distress tolerance as a possible predictor of dental fear and anxiety among a sample of adults with and without diagnoses of dental phobia, investigated possible differences in levels of distress tolerance between adults with and without dental phobia, and determined possible associations between distress tolerance and fear of pain, anxiety sensitivity, and depression. Using 52 volunteers (n = 31, dental phobia group; n = 21, healthy comparison group), this investigation used self-report measures of distress tolerance, fear of pain, anxiety sensitivity, dental fear, and depression. The Anxiety Disorders Interview Schedule, a semi-structured interview, was used to assess for dental phobia and other psychological disorders. Distress tolerance significantly predicted dental fear and anxiety, even after controlling for age, sex, fear of pain, anxiety sensitivity, and depression. In addition, the dental phobia group had lower distress tolerance than the healthy comparison group. Distress tolerance was significantly associated with fear of pain, anxiety sensitivity, and depression. Findings indicate that low distress tolerance plays a unique and distinct role as a possible mechanism in the genesis of dental care-related fear and anxiety and phobia and may exacerbate the experience of other states, including fear of pain and anxiety sensitivity. Knowledge Transfer Statement: Results indicate that patients who have a lower ability to tolerate emotional and physical distress may have higher levels of dental care-related fear and anxiety and even dental phobia, as well as associated sequelae (e.g., avoidance of dental care). Treatment of highly fearful dental patients may helpfully include a focus on increasing distress tolerance.

Exploring the short-term impact of community water fluoridation cessation on children's dental caries: a natural experiment in Alberta, Canada.

OBJECTIVES: Dental caries (tooth decay) is common and can be serious. Dental caries is preventable, and community water fluoridation is one means of prevention. There is limited current research on the implications of fluoridation cessation for children's dental caries. Our objective was to explore the short-term impact of community water fluoridation cessation on children's dental caries, by examining change in caries experience in population-based samples of schoolchildren in two Canadian cities, one that discontinued community water fluoridation and one that retained it. STUDY DESIGN: We used a pre-post cross-sectional design. METHODS: We examined dental caries indices (deft [number of decayed, extracted, or filled primary teeth] and DMFT [number of decayed, missing, or filled permanent teeth]) among grade 2 schoolchildren in 2004/05 and 2013/14 in two similar cities in the province of Alberta, Canada: Calgary (cessation of community water fluoridation in 2011) and Edmonton (still fluoridated). We compared change over time in the two cities. For Calgary only, we had a third data point from 2009/10, and we considered trends across the three points. RESULTS: We observed a worsening in primary tooth caries (deft) in Calgary and Edmonton, but changes in Edmonton were less consistent and smaller. This effect was robust to adjustment for covariates available in 2013/14 and was consistent with estimates of total fluoride intake from biomarkers from a subsample. This finding occurred despite indication that treatment activities appeared better in Calgary. The worsening was not observed for permanent teeth. For prevalence estimates only (% with >0 deft or DMFT), the three data points in Calgary suggest a trend that, though small, appears consistent with an adverse effect of fluoridation cessation. CONCLUSIONS: Our results suggest an increase in dental caries in primary teeth during a time period when community fluoridation was ceased. That we did not observe a worsening for permanent teeth in the comparative analysis could reflect the limited time since cessation. It is imperative that efforts to monitor these trends continue.

Genetic Association of MMP10, MMP14, and MMP16 with Dental Caries.

Matrix metalloproteinases (MMPs), which degrade extracellular proteins as part of a variety of physiological processes, and their inhibitors have been implicated in the dental caries process. Here we investigated 28 genetic variants spanning the MMP10, MMP14, and MMP16 genes to detect association with dental caries experience in 13 age- and race-stratified (n = 3,587) samples from 6 parent studies. Analyses were performed separately for each sample, and results were combined across samples by meta-analysis. Two SNPs (rs2046315 and rs10429371) upstream of MMP16 were significantly associated with caries in an individual sample of white adults and via meta-analysis across 8 adult samples after gene-wise adjustment for multiple comparisons. Noteworthy is SNP rs2046315 (p = 8.14 × 10-8) association with caries in white adults. This SNP was originally nominated in a genome-wide-association study (GWAS) of dental caries in a sample of white adults and yielded associations in a subsequent GWAS of surface level caries in white adults as well. Therefore, in our study, we were able to recapture the association between rs2046315 and dental caries in white adults. Although we did not strengthen evidence that MMPs 10, 14, and 16 influence caries risk, MMP16 is still a likely candidate gene to pursue.