Development of short forms for screening children's dental caries and urgent treatment needs using item response theory and machine learning methods.

OBJECTIVES: Surveys can assist in screening oral diseases in populations to enhance the early detection of disease and intervention strategies for children in need. This paper aims to develop short forms of child-report and proxy-report survey screening instruments for active dental caries and urgent treatment needs in school-age children. METHODS: This cross-sectional study recruited 497 distinct dyads of children aged 8-17 and their parents between 2015 to 2019 from 14 dental clinics and private practices in Los Angeles County. We evaluated responses to 88 child-reported and 64 proxy-reported oral health questions to select and calibrate short forms using Item Response Theory. Seven classical Machine Learning algorithms were employed to predict children's active caries and urgent treatment needs using the short forms together with family demographic variables. The candidate algorithms include CatBoost, Logistic Regression, K-Nearest Neighbors (KNN), Naïve Bayes, Neural Network, Random Forest, and Support Vector Machine. Predictive performance was assessed using repeated 5-fold nested cross-validations. RESULTS: We developed and calibrated four ten-item short forms. Naïve Bayes outperformed other algorithms with the highest median of cross-validated area under the ROC curve. The means of best testing sensitivities and specificities using both child-reported and proxy-reported responses were 0.84 and 0.30 for active caries, and 0.81 and 0.31 for urgent treatment needs respectively. Models incorporating both response types showed a slightly higher predictive accuracy than those relying on either child-reported or proxy-reported responses. CONCLUSIONS: The combination of Item Response Theory and Machine Learning algorithms yielded potentially useful screening instruments for both active caries and urgent treatment needs of children. The survey screening approach is relatively cost-effective and convenient when dealing with oral health assessment in large populations. Future studies are needed to further leverage the customize and refine the instruments based on the estimated item characteristics for specific subgroups of the populations to enhance predictive accuracy.

Oral Health of Women and Children: Progress, Challenges, and Priorities.

INTRODUCTION: Tooth decay remains the most prevalent chronic disease in children and adults, even though it is largely preventable. Studies show that mothers' oral and overall health is linked to children's oral health and pregnancy outcomes. This paper examines achievements during the last 20 years, assesses current challenges, and discusses future priorities. ORAL HEALTH STATUS: Data show a modest improvement in children's oral health during the last 20 years; however, tooth decay still affects more than half of adolescents. According to national survey data, about 26% of working-age adults had untreated tooth decay. Overall, significant oral health disparities by race/ethnicity and income persist. DENTAL SERVICE UTILIZATION: The annual dental visit rate for children in the 2015 Medical Expenditure Panel Survey was 48%. Among children enrolled in Medicaid, dental visit rates increased from 18% in 1993 to nearly 50% in 2018. About 46% of women are estimated to receive teeth cleaning during pregnancy. Over the years, race or ethnicity and income-level differences in dental visits observed in the early 2000s have narrowed substantially in children but not among pregnant women. DISCUSSION: Many effective interventions are available at the community and individual levels but are underutilized. Lack of integration of oral health into the overall health care system and programs, community conditions, poverty, and limited health literacy make it difficult for families to engage in healthy habits, use preventive interventions, and access treatment promptly. CONCLUSION: To further improve oral health, policy and system reforms are needed to address the factors mentioned above. Therefore, we urge the federal Maternal and Child Health Bureau to take steps to convene a workshop to develop a framework for future actions.

Investigating Perceptions of Teachers and School Nurses on Child and Adolescent Oral Health in Los Angeles County.

This study reports the results of focus groups with school nurses and teachers from elementary, middle, and high schools to explore their perceptions of child and adolescent oral health. Participants included 14 school nurses and 15 teachers (83% female; 31% Hispanic; 21% White; 21% Asian; 14% African American; and 13% Others). Respondents were recruited from Los Angeles County schools and scheduled by school level for six one-hour focus groups using Zoom. Audio recordings were transcribed, reviewed, and saved with anonymization of speaker identities. NVivo software (QSR International, Melbourne, Australia) was used to facilitate content analysis and identify key themes. The nurses' rate of "Oral Health Education" comments statistically exceeded that of teachers, while teachers had higher rates for "Parental Involvement" and "Mutual Perception" comments. "Need for Care" was perceived to be more prevalent in immigrants to the United States based on student behaviors and complaints. "Access to Care" was seen as primarily the nurses' responsibilities. Strong relationships between community clinics and schools were viewed by some as integral to students achieving good oral health. The results suggest dimensions and questions important to item development for oral health surveys of children and parents to address screening, management, program assessment, and policy planning.

Using a Machine Learning Algorithm to Predict the Likelihood of Presence of Dental Caries among Children Aged 2 to 7.

BACKGROUND: Dental caries is the most common chronic childhood infectious disease and is a serious public health problem affecting both developing and industrialized countries, yet it is preventable in most cases. This study evaluated the potential of screening for dental caries among children using a machine learning algorithm applied to parent perceptions of their child's oral health assessed by survey. METHODS: The sample consisted of 182 parents/caregivers and their children 2-7 years of age living in Los Angeles County. Random forest (a machine learning algorithm) was used to identify survey items that were predictors of active caries and caries experience. We applied a three-fold cross-validation method. A threshold was determined by maximizing the sum of sensitivity and specificity conditional on the sensitivity of at least 70%. The importance of survey items to classifying active caries and caries experience was measured using mean decreased Gini (MDG) and mean decreased accuracy (MDA) coefficients. RESULTS: Survey items that were strong predictors of active caries included parent's age (MDG = 0.84; MDA = 1.97), unmet needs (MDG = 0.71; MDA = 2.06) and the child being African American (MDG = 0.38; MDA = 1.92). Survey items that were strong predictors of caries experience included parent's age (MDG = 2.97; MDA = 4.74), child had an oral health problem in the past 12 months (MDG = 2.20; MDA = 4.04) and child had a tooth that hurt (MDG = 1.65; MDA = 3.84). CONCLUSION: Our findings demonstrate the potential of screening for active caries and caries experience among children using surveys answered by their parents.

How Do Mothers Living in Socially Deprived Communities Perceive Oral Health of Young Children? A Qualitative Study.

This qualitative study aims to explore and gain an in-depth understanding of the knowledge and perceptions of mothers living in Greater Western Sydney (GWS), one of Australia's most socio-economically disadvantaged regions, regarding the factors that influence oral health of young children. Mother-child dyads (n = 45) were purposively selected from a population-based cohort study in GWS. Semi-structured in-depth interviews were audio-recorded, transcribed verbatim, and subsequently analyzed using thematic analysis. Five main themes emerged from the interviews: (1) beliefs about child oral health and first set of teeth; (2) awareness and attitudes towards oral health services; (3) identification of caries risk and protective factors; (4) broader cultural and social class influences on childhood oral health practices; and (5) the influence of parental self-confidence, self-efficacy, and perceived control. Overall, mothers reported having limited knowledge and awareness on the importance of baby teeth, child's first dental visit, and seeking oral health care. Oral health and preventative practices in children were reported to be influenced by past dental experiences, culture and social class, and parental factors. The empirical findings of this study bring our attention to the critical factors that influence child oral health and the opportunities for co-creating child oral health promotion by targeting mothers.

Developing a Standard Set of Patient-centred Outcomes for Adult Oral Health - An International, Cross-disciplinary Consensus.

OBJECTIVE: To develop a minimum Adult Oral Health Standard Set (AOHSS) for use in clinical practice, research, advocacy and population health. MATERIALS AND METHODS: An international oral health working group (OHWG) was established, of patient advocates, researchers, clinicians and public health experts to develop an AOHSS. PubMed was searched for oral health clinical and patient-reported measures and case-mix variables related to caries and periodontal disease. The selected patient-reported outcome measures focused on general oral health, and oral health-related quality of life tools. A consensus was reached via Delphi with parallel consultation of subject matter content experts. Finally, comments and input were elicited from oral health stakeholders globally, including patients/consumers. RESULTS: The literature search yielded 1,453 results. After inclusion/exclusion criteria, 959 abstracts generated potential outcomes and case-mix variables. Delphi rounds resulted in a consensus-based selection of 80 individual items capturing 31 outcome and case-mix concepts. Global reviews generated 347 responses from 87 countries, and the patient/consumer validation survey elicited 129 responses. This AOHSS includes 25 items directed towards patients (including demographics, the impact of their oral health on oral function, a record of pain and oral hygiene practices, and financial implications of care) and items for clinicians to complete, including medical history, a record of caries and periodontal disease activity, and types of dental treatment delivered. CONCLUSION: In conclusion, utilising a robust methodology, a standardised core set of oral health outcome measures for adults, with a particular emphasis on caries and periodontal disease, was developed.

Colocation Does Not Equal Integration: Identifying and Measuring Best Practices in Primary Care Integration of Children's Oral Health Services in Health Centers.

OBJECTIVE: Improving oral health of low-income and uninsured young children remains challenging because of reluctance of general dentists to care for very young children or participate in Medicaid, limited involvement of primary care providers in children's oral health, and lack of parental awareness of the importance of early oral health care. These barriers can be addressed in health centers (HCs) that are the premier sources of primary care for low-income and uninsured populations and a significant Medicaid provider. Many HCs provide dental services on-site, but literature indicates that medical and dental services often remain siloed with limited interaction among providers in addressing the oral health needs of young patients including risk assessment, education, and caries prevention. Accordingly, we developed a conceptual framework and measuring tool for medical dental integration and sought to examine utility of this tool in a purposive sample of HCs. METHOD: We developed a conceptual framework for integrated oral health delivery and designed a survey to measure this integration. We surveyed 12 HCs in Los Angeles County participating in a project to improve oral health-care capacity for young children after 2 years of implementation. We included measures of risk assessment, preventive interventions, communication and collaborative practice, and buy-in organized in structure and process domains. Two individuals independently scored the responses, and a third reviewed and finalized. We standardized final scores to range from 0 to 100. RESULTS: Overall integration scores ranged from 31% to 73% (mean = 64%). Process scores were higher than structure scores for nearly all HCs. Processes contributing to higher scores included referrals with warm hand-offs, leadership support for medical-dental integration, and involvement in dental quality improvement projects. Structure factors contributing to higher scores included the presence of medical oral health champions, linked electronic health records, and referral protocols. CONCLUSION: We found that high levels of integration could be achieved despite structure and process limitations and sustainable integration depends on leadership and provider commitment and embedding of best practices in daily operations. Further research can illustrate the reliability of our tool and the impact of integration on access.

Children's Oral Health: Progress, Policy Development, And Priorities For Continued Improvement.

Considerable progress has occurred in the US over the past quarter-century in terms of improving children's oral health. Federal and state policies, programs, and partnerships have contributed to improvements in oral health status. Medicaid and Children's Health Insurance Program coverage expansions helped increase the use of dental services, and investments in safety-net facilities and training programs helped expand service delivery and the oral health workforce. Nevertheless, dental caries remains the most common chronic disease of childhood, notable oral health disparities persist, and the adoption of evidence-based innovations remains slow and uneven. This article highlights improvements during the past twenty-five years in US children's oral health and oral health care that stem from major federal and state initiatives, as well as persistent disparities. We offer promising strategies for reducing gaps and suggestions for overcoming challenges to future progress, including renewed emphasis on oral health during early childhood; greater integration in education and clinical service delivery programs; development of standardized quality measures; and data collection systems that support more robust surveillance, program monitoring, and system improvements.

Computerized adaptive testing and short form development for child and adolescent oral health patient-reported outcomes measurement.

OBJECTIVES: To develop computerized adaptive testing (CAT) and short forms of self-report oral health measures that are predictive of both the children's oral health status index (COHSI) and the children's oral health referral recommendation (COHRR) scales, for children and adolescents, ages 8-17. MATERIAL AND METHODS: Using final item calibration parameters (discrimination and difficulty parameters) from the item response theory analysis, we performed post hoc CAT simulation. Items most frequently administered in the simulation were incorporated for possible inclusion in final oral health assessment toolkits, to select the best performing eight items for COHSI and COHRR. RESULTS: Two previously identified unidimensional sets of self-report items consisting of 19 items for the COHSI and 22 items for the COHRR were administered through CAT resulting in eight-item short forms for both the COHSI and COHRR. Correlations between the simulated CAT scores and the full item bank representing the latent trait are r = .94 for COHSI and r = .96 for COHRR, respectively, which demonstrated high reliability of the CAT and short form. CONCLUSIONS: Using established rigorous measurement development standards, the CAT and corresponding eight-item short form items for COHSI and COHRR were developed to assess the oral health status of children and adolescents, ages 8-17. These measures demonstrated good psychometric properties and can have clinical utility in oral health screening and evaluation and clinical referral recommendations.

Development of toolkits for detecting dental caries and caries experience among children using self-report and parent report.

OBJECTIVES: To develop child- and parent-reported toolkits for active caries and caries experience in children and adolescents, ages 8-17. METHODS: A sample of 398 child/parent dyads recruited from 12 dental practices in Los Angeles County completed a computer-assisted survey that assessed oral health perceptions. In addition, children received a dental examination that identified the presence or absence of active caries and caries experience. A Multiple Adaptive Regression Splines model was used to identify a subset of survey items associated with active caries and caries experience. The splines and coefficients were refined by generalized cross-validation. Sensitivity and specificity for both dependent variables were evaluated. RESULTS: Eleven child self-reported items were identified that had sensitivity of 0.82 and specificity of 0.45 relative to active caries. Twelve parent-reported items had a sensitivity of 0.86 and specificity of 0.50. Seven child self-reported items had a sensitivity of 0.86 and specificity of 0.34, and 11 parent-reported items had a sensitivity of 0.86 and specificity of 0.47 for caries experience. CONCLUSIONS: The survey items identified here are useful in distinguishing children with and without active caries and with and without caries experience. This research presents a path towards using children's and their parents' reports about oral health to screen for clinically determined caries and caries exposure. The items identified in this study can be useful when clinical information is unavailable.

Measuring quality: caries-related emergency department visits and follow-up among children.

OBJECTIVE: This study validated two Dental Quality Alliance system-level measures of oral healthcare quality for children - caries-related emergency department (ED) visits and timely follow-up of those visits with a dentist - including formal validation of diagnosis codes used to identify caries-related ED visits and measurement of follow-up care. METHODS: The measures were specified for implementation with administrative claims data and validated using data from the Florida and Texas Medicaid and Children's Health Insurance Programs. Measure specification testing and measure score validation used administrative data for 7,007,765 children. We validated the diagnosis codes in claims data by comparisons with manual reviews of 300 records from a Florida hospital ED and calculation of the kappa statistic, sensitivity, and specificity. RESULTS: Overall agreement in caries-related ED visit classifications between the claims data and record reviews was 87.7 percent with kappa = 0.71, sensitivity = 82 percent, and specificity = 90 percent. The calculated measure scores using administrative data found more than four-fold variation between programs with the lowest and highest caries-related ED visit rates (6.90/100,000 member months and 30.68/100,000 member months). The percentage of follow-up visits within 7 days and 30 days ranged from 22-39 percent and 34-49 percent, respectively. CONCLUSIONS: These National Quality Forum endorsed measures provide valid methodologies for assessing the rate of caries-related ED visits, an important system-level outcome indicator of outpatient prevention and disease management, and the timeliness of follow-up with a dentist. There is significant variation in caries-related ED visits among state Medicaid programs, and most ED visits do not have follow-up with a dentist within 30 days.

Qualitative methods in the development of a parent survey of children's oral health status.

BACKGROUND: Parents' perceptions of their 8-17-year-old children's oral health status were assessed using a sample from diverse dental clinics in Greater Los Angeles County to identify constructs for a survey instrument. METHODS: Focus groups with 29 parents or guardians were conducted to identify themes that informed development of survey items. The draft items were administered to a different group of 32 parents or guardians in cognitive interviews, and revised for subsequent field-testing. RESULTS: Thematic and narrative analyses were performed after the focus groups and key lay-oriented dimensions were uncovered, notably the relationship between oral health, systemic health and the life course. In the cognitive interviews, parents entered multiple responses to questions related to the look of their child's teeth, and their overall perception of tooth color. Parents also assessed their child's fear or discomfort with the dental experience, and other social and psychological concerns related to oral health status. The temporal dimensions of certain items were specified; for example, oral pain and mood items were revised to include duration of the symptom or mood state. As parents tended to confuse oral health maintenance and prevention, these two related concepts were separated into two items. Based on the qualitative work, we revised items in preparation for a field test. CONCLUSIONS: As a PRO measurement study, qualitative research informed a field test survey to assess factors associated with oral health status and the individual's perceptions and subjective views of these constructs for eventual item development for epidemiological and clinical use.

Improving The Oral Health Care Capacity Of Federally Qualified Health Centers.

Despite efforts that increased dental visits at federally qualified health centers (FQHCs) by 65 percent between 2007 and 2014, only 21 percent of FQHC patients received dental services in 2015-not altogether surprising, given that most such facilities do not offer dental services on site. Many of these facilities are part of multisite organizations that offer dental services at other locations; however, sites with co-located dental and medical services often serve only a fraction of their primary care patients. This article describes an initiative, funded by First 5 LA and led by the University of California, Los Angeles (UCLA), designed to improve access to and quality of oral health care for young children at twenty Los Angeles County FQHCs with co-located medical and dental services. The UCLA-First 5 LA Oral Health Program supported infrastructure enhancements, technical assistance, clinical training, quality improvement, health education for parents and caregivers, and related policy analyses. Findings demonstrate a twofold increase in diagnostic and treatment services capacity for young children and a threefold increase in preventive services capacity after two years. Investments in infrastructure, plus support for training and quality improvement focused on medical and dental integration, were crucial to these capacity increases.

Sealants for Preventing and Arresting Pit-and-fissure Occlusal Caries in Primary and Permanent Molars.

BACKGROUND: National Health and Nutrition Examination Survey 2011-2012 data indicated that, in the United States, nearly onefourth of children and over one-half of adolescents experienced dental caries in their permanent teeth. The purpose of this review was to summarize the available clinical evidence regarding the effect of dental sealants for the prevention and management of pit-and-fissure occlusal carious lesions in primary and permanent molars, compared with a control without sealants, with fluoride varnishes, or with other head-to head comparisons. TYPE OF STUDIES REVIEWED: The authors included parallel and split-mouth randomized controlled trials that included at least 2 years of follow-up, which they identified using MEDLINE (via PubMed), Embase, LILACS, the Cochrane Central Register of Controlled Trials, and registers of ongoing trials. Pairs of reviewers independently conducted the selection of studies, data extraction, risk of bias assessments, and quality of the evidence assessments by using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Of 2,869 records screened, the authors determined that 24 articles (representing 23 studies) proved eligible. Moderate-quality evidence suggested that participants who received sealants had a reduced risk of developing carious lesions in occlusal surfaces of permanent molars compared with those who did not receive sealants (odds ratio [OR], 0.15; 95% confidence interval [CI], 0.08-0.27) after 7 or more years of follow-up. When the authors compared studies whose investigators had compared sealants with fluoride varnishes, they found that sealants reduced the incidence of carious lesions after 7 or more years of follow-up (OR, 0.19; 95% CI, 0.07-0.51); however, this finding was supported by low-quality evidence. On the basis of the evidence, the authors could not provide a hierarchy of effectiveness among the studies whose investigators had conducted head-to-head comparisons. The investigators of 2 trials provided information about adverse events, but they did not report any adverse events. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Available evidence suggests that sealants are effective and safe to prevent or arrest the progression of noncavitated carious lesions compared with a control without sealants or fluoride varnishes. Further research is needed to provide information about the relative merits of the different types of sealant materials.

An Innovative Project Breaks Down Barriers to Oral Health Care for Vulnerable Young Children in Los Angeles County.

Despite the high rate of untreated tooth decay, many young children in California under six years of age have never been to a dentist. Numerous and complex barriers to access to oral health care for young children exist, and a multifaceted approach is required to improve receipt of preventive and treatment services that could improve the oral health of this population. This policy brief describes the UCLA-First 5 LA 21st Century Dental Homes Project, which was designed to improve oral health care for young children in 12 Federally Qualified Health Center (FQHC) clinic sites with co-located dental and primary care services and its accessibility in their service areas throughout Los Angeles County. The project funded infrastructure and staffing, provided technical assistance to improve operations, trained clinical personnel to provide oral health care to young children, implemented a quality improvement learning collaborative, trained parents and child care providers in oral hygiene and healthy habits, and disseminated information to promote effective policies. Early data on the project indicated twofold increases in delivery of both diagnostics and treatment visits for young children, and a threefold increase in preventive services for young children during the program.

Sealants for preventing and arresting pit-and-fissure occlusal caries in primary and permanent molars: A systematic review of randomized controlled trials-a report of the American Dental Association and the American Academy of Pediatric Dentistry.

BACKGROUND: National Health and Nutrition Examination Survey 2011-2012 data indicated that, in the United States, nearly one-fourth of children and over one-half of adolescents experienced dental caries in their permanent teeth. The purpose of this review was to summarize the available clinical evidence regarding the effect of dental sealants for the prevention and management of pit-and-fissure occlusal carious lesions in primary and permanent molars, compared with a control without sealants, with fluoride varnishes, or with other head-to head comparisons. TYPE OF STUDIES REVIEWED: The authors included parallel and split-mouth randomized controlled trials that included at least 2 years of follow-up, which they identified using MEDLINE (via PubMed), Embase, LILACS, the Cochrane Central Register of Controlled Trials, and registers of ongoing trials. Pairs of reviewers independently conducted the selection of studies, data extraction, risk of bias assessments, and quality of the evidence assessments by using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Of 2,869 records screened, the authors determined that 24 articles (representing 23 studies) proved eligible. Moderate-quality evidence suggested that participants who received sealants had a reduced risk of developing carious lesions in occlusal surfaces of permanent molars compared with those who did not receive sealants (odds ratio [OR], 0.15; 95% confidence interval [CI], 0.08-0.27) after 7 or more years of follow-up. When the authors compared studies whose investigators had compared sealants with fluoride varnishes, they found that sealants reduced the incidence of carious lesions after 7 or more years of follow-up (OR, 0.19; 95% CI, 0.07-0.51); however, this finding was supported by low-quality evidence. On the basis of the evidence, the authors could not provide a hierarchy of effectiveness among the studies whose investigators had conducted head-to-head comparisons. The investigators of 2 trials provided information about adverse events, but they did not report any adverse events. CONCLUSIONS AND PRACTICAL IMPLICATIONS: Available evidence suggests that sealants are effective and safe to prevent or arrest the progression of noncavitated carious lesions compared with a control without sealants or fluoride varnishes. Further research is needed to provide information about the relative merits of the different types of sealant materials.

Evidence-based clinical practice guideline for the use of pit-and-fissure sealants: A report of the American Dental Association and the American Academy of Pediatric Dentistry.

BACKGROUND: This article presents evidence-based clinical recommendations for the use of pit-and-fissure sealants on the occlusal surfaces of primary and permanent molars in children and adolescents. A guideline panel convened by the American Dental Association (ADA) Council on Scientific Affairs and the American Academy of Pediatric Dentistry conducted a systematic review and formulated recommendations to address clinical questions in relation to the efficacy, retention, and potential side effects of sealants to prevent dental caries; their efficacy compared with fluoride varnishes; and a head-to-head comparison of the different types of sealant material used to prevent caries on pits and fissures of occlusal surfaces. TYPES OF STUDIES REVIEWED: This is an update of the ADA 2008 recommendations on the use of pit-and-fissure sealants on the occlusal surfaces of primary and permanent molars. The authors conducted a systematic search in MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and other sources to identify randomized controlled trials reporting on the effect of sealants (available on the US market) when applied to the occlusal surfaces of primary and permanent molars. The authors used the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the quality of the evidence and to move from the evidence to the decisions. RESULTS: The guideline panel formulated 3 main recommendations. They concluded that sealants are effective in preventing and arresting pit-and-fissure occlusal carious lesions of primary and permanent molars in children and adolescents compared with the nonuse of sealants or use of fluoride varnishes. They also concluded that sealants could minimize the progression of noncavitated occlusal carious lesions (also referred to as initial lesions) that receive a sealant. Finally, based on the available limited evidence, the panel was unable to provide specific recommendations on the relative merits of 1 type of sealant material over the others. CONCLUSIONS AND PRACTICAL IMPLICATIONS: These recommendations are designed to inform practitioners during the clinical decision-making process in relation to the prevention of occlusal carious lesions in children and adolescents. Clinicians are encouraged to discuss the information in this guideline with patients or the parents of patients. The authors recommend that clinicians reorient their efforts toward increasing the use of sealants on the occlusal surfaces of primary and permanent molars in children and adolescents.