Child Temperament and Early Childhood Caries: A Systematic Review and Meta-Analysis.

Purpose: The purpose of this study was to perform a systematic review to assess current evidence for the association between child temperament and early childhood caries (ECC). Methods: A systematic search was conducted using MEDLINE® through PubMed®, EMBASE®, Scopus®, LILACS, Web of Science™, and EBSCO up to January 2023. Studies measuring ECC and child temperament for children younger than or equal to six years of age using questionnaires, interviews, and surveys through case-control studies, cohort studies, and cross-sectional studies were included. Literature reviews were excluded. Medical subject heading (MeSH) terms like "temperament" and "dental caries" were used by two authors who independently extracted the data, and a third author resolved disagreements. Risk of bias assessment was done using the Newcastle-Ottawa assessment scale for case-control and cohort studies and the Appraisal tool for Cross-Sectional Studies (AXIS). The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations approach (GRADE approach). A chi-square test and I-square index were used to evaluate heterogeneity. Results: A total of 5,072 records were screened, resulting in 15 included studies that yielded data for 6,667 participants; sevenstudies were high, and eight were of moderate quality. Seven studies qualified for meta-analysis, which revealed that persistence did not affectthe presence or absence of ECC. However, there was a strong association between difficult temperament and ECC (odds ratio equals 2.63). Conclusion: A positive association between a child's temperament and early childhood caries exists that is supported by quantitative findings, indicating a connection with very low certainty.

Association of exposures to environmental chemicals estimated through primary teeth biomatrix and health outcomes in children and adolescents - A systematic review.

Children's heightened susceptibility to environmental exposure arises from their underdeveloped detoxification mechanisms and augmented per-unit body-weight absorption capacity for chemical compounds. Primary teeth are an emerging biomatrix, which aid in storing crucial data on early exposure to harmful substances and developmental illnesses. This systematic review aimed to evaluate the association between environmental chemical exposure and health outcomes in children and adolescents using primary teeth as a matrix. The study protocol was registered with PROSPERO (CRD42023428013). The review spanned studies published between 1974 and 2023, identified through an extensive literature search on databases like MEDLINE, EMBASE, LILACS, CINAHL, the Cochrane Oral Health Group Specialized Register, Scopus, and Web of Science. Distiller SR software was used to assess study quality and extract the outcome data. The NTP-OHAT scale assessed evidence quality, and case-control, cross-sectional, and cohort studies in English were included. Comprehensively reviewing 5287 articles resulted in 29 studies being included in the final analysis, comprising 15 cross-sectional, seven case-control, and seven cohort studies. All 29 studies qualified for qualitative analysis. Eleven studies analyzed lead (Pb) effects on health outcomes, four analyzed manganese (Mn), and 14 investigated other element groups. Primary teeth biomatrix assessed various health outcomes: neurobehavior, childhood behaviour, ADHD, birth outcomes, fetal alcohol syndrome disease, inflammatory bowel disease, and dental caries. This study contributes to existing evidence, reinforcing a link between environmental metal exposure and health consequences. The evidence extends to prenatal and postnatal periods, substantiated by primary teeth biomatrix analysis. Lead level fluctuations can influence neuropsychological functioning, potentially causing cognitive impairments. Altered manganese levels correlate with behavioral issues, adverse effects on visuospatial development, and birth weight changes. Primary teeth biomatrices aid fetal alcohol spectrum disorders diagnosis, and correlations between organo-chemical exposure and autism were observed.

Late diagnosis of the X-linked MCT8 deficiency (Allan-Herndon-Dudley syndrome) in a teenage girl with primary ovarian insufficiency.

OBJECTIVES: To report an unusual case of MCT8 deficiency (Allan-Herndon-Dudley syndrome), an X-linked condition caused by pathogenic variants in the SLC16A2 gene. Defective transport of thyroid hormones (THs) in this condition leads to severe neurodevelopmental impairment in males, while heterozygous females are usually asymptomatic or have mild TH abnormalities. CASE PRESENTATION: A girl with profound developmental delay, epilepsy, primary amenorrhea, elevated T3, low T4 and free T4 levels was diagnosed with MCT8-deficiency at age 17 years, during evaluation for primary ovarian insufficiency (POI). Cytogenetic analysis demonstrated balanced t(X;16)(q13.2;q12.1) translocation with a breakpoint disrupting SLC16A2. X-chromosome inactivation studies revealed a skewed inactivation of the normal X chromosome. CONCLUSIONS: MCT8-deficiency can manifest clinically and phenotypically in women with SLC16A2 aberrations when nonrandom X inactivation occurs, while lack of X chromosome integrity due to translocation can cause POI.

Risk of substance use disorders among adolescents and emerging adults with type 1 diabetes: A population-based cohort study.

BACKGROUND: Adolescents and emerging adults with chronic health conditions such as type 1 diabetes mellitus (T1D) are more likely to engage in high-risk behaviors. Previous studies regarding substance use in adolescents and emerging adults with T1D are mostly derived from cross-sectional studies utilizing self-administered questionnaires and are limited by lack of population-based comparison groups. In addition, despite the rising popularity of vaping, little is known about the incidence of vaping in adolescents and emerging adults with T1D. METHODS: We explored the incidence and prospective risk of substance use disorders (SUD) and vaping in adolescents and emerging adults with T1D compared to age and gender matched nondiabetic referents residing in Olmsted County, Rochester, MN. RESULTS: Risk of incident SUD was higher in those with T1D compared to matched referents with alcohol, marijuana, and smoked tobacco being most common substances. When stratified by gender, these differences remained significant in males, but not females. CONCLUSIONS: While further work is needed to delineate the causative relationships between T1D, mental health, and substance abuse, our findings confirm the critical need for substance use screening and mental health support for adolescents and emerging adults with T1D.

Temporal trends in lipid testing among children and adolescents: A population based study.

Unfavorable lipid levels during childhood are associated with subsequent development of atherosclerotic cardiovascular disease. The American Academy of Pediatrics and National Heart, Lung and Blood Institute in 2011 recommended universal lipid screening for children between ages 9-11 years and between ages 17-21 years. The objective of the study was to determine temporal trends in lipid testing among children and young adults in a mid-western population. The Rochester Epidemiology Project database was used to identify lipid testing in ages 2-21 years (n = 51,176) in the Olmsted County population from January 1, 2008 through December 31, 2014. Generalized estimating equations with Poisson distribution were used to test for temporal trends in lipid testing across the age groups. There was modest increase in lipid testing in children in the age groups, 9-11 years and 17-21 years (1.5% in 2008 to 2.2% in 2014, P < 0.001 and 4.4% in 2008 to 4.6% in 2014, P = 0.02, respectively). There was a significant decrease in proportion of 17-21 year olds with elevated total cholesterol (16.2% in 2008 to 11.6% in 2014; P = 0.01) and non-high density lipoprotein cholesterol (22.6% in 2008 to 12.6% in 2014; P < 0.001). In this population-based study, rates of lipid testing increased minimally only in the last six years. Further longitudinal studies are warranted to improve guideline dissemination and address attitudes, practices and barriers to lipid testing in children and young adults.

Effect of Obstructive Sleep Apnea Treatment on Lipids in Obese Children.

Obesity in children is associated with several co-morbidities including dyslipidemia. Obstructive sleep apnea (OSA) is commonly seen in obese children. In adults, diagnosis of OSA independent of obesity is associated with cardiometabolic risk factors including dyslipidemia. There is limited data on the impact of treatment of OSA on lipids in children. The objective of the study was to examine the impact of treatment of OSA on lipids in 24 obese children. Methods: Seventeen children were treated with continuous positive airway pressure (CPAP) and five underwent adenotonsillectomy. Mean apnea hypopnea index prior to treatment was 13.0 + 12.1 and mean body mass index (BMI) was 38.0 + 10.6 kg/m². Results: Treatment of OSA was associated with improvement in total cholesterol (mean change = -11 mg/dL, p < 0.001), and low-density lipoprotein cholesterol (mean change = -8.8 mg/dL, p = 0.021). Conclusion: Obese children should be routinely screened for OSA, as treatment of OSA favorably influences lipids and therefore decreases their cardiovascular risk.

Erythropoiesis-stimulating agents in elderly patients with anemia: response and cardiovascular outcomes.

A specific cause of anemia cannot be identified in many elderly patients. Erythropoiesis-stimulating agents (ESAs) may play a role in treating these patients with anemia of unknown etiology (AUE). This study examines hemoglobin and cardiovascular outcomes among elderly anemic patients treated with ESAs. We conducted a retrospective cohort study that included all anemic patients older than age 60 years who had erythropoietin (EPO) measured between 2005 and 2013 at a single center. Three independent reviewers used defined criteria to assign each patient's anemia to 1 of 4 groups: chronic kidney disease (CKD), myelodysplastic syndrome, AUE, or other etiology. Logistic regression was used to compare treatment response (defined per the International Working Group response criteria in myelodysplasia). Adjusted Cox regression analysis was used to calculate the cardiovascular event hazard ratios associated with ESA treatment. A total of 570 patients met the inclusion criteria, of whom 101 received ESAs. There was a nonstatistically significant but quantitatively better response in AUE (47%) and CKD (54%) compared with other etiologies (22%). The adjusted odds ratio for response in AUE compared with other etiologies was 3.3 (95% confidence interval, 0.838-13.0). A baseline EPO level <200 IU/L independently predicted treatment response. There was no statistically significant difference in cardiovascular events or cardiovascular event-free survival between the treated and untreated groups after adjusting for confounders. Our results suggest that ESAs may effectively treat AUE, and responses may be similar to those in CKD. We could not detect a statistically significant increase in cardiovascular events in the studied cohort.

Relationship between 25(OH)D levels and circulating lipids in African American adolescents.

BACKGROUND: Vitamin D deficiency is commonly seen among African American adolescents. Lipid levels during childhood are excellent predictors of adult dyslipidemia and atherosclerosis. There is a paucity of data on the relationship between 25 hydroxy vitamin D [25(OH)D] levels and lipids among African American adolescents. The objective of this study was to determine if there is an association between 25(OH)D levels and circulating lipids in African American adolescents residing in midwestern United States. METHODS: African American adolescents residing in Rochester, MN (latitude 44°N), USA, underwent measurements of 25(OH)D and lipids following overnight fast. Pearson's correlation test, linear regression model and scatter plots were used to explore the association between 25(OH)D levels and lipids. RESULTS: 25(OH)D levels <30 ng/mL were seen in 21/24 (87%) of the subjects. 25(OH)D levels were inversely correlated with total cholesterol (r=-0.42; p=0.040) and with non-high-density lipoprotein (non-HDL) cholesterol (r=-0.42; p=0.040 ). These associations remained statistically significant after adjustment for age, gender and adiposity. In the multivariate linear regression model, and after adjusting for BMI Z-score, each 1 ng/mL increase in 25(OH)D was associated with a decrease in total cholesterol of 1.38 mg/dL (95% CI: -2.63, -0.14, p=0.030) and with a decrease in non-HDL cholesterol of 1.14 mg/dL (95% CI: -2.09, -0.18, p=0.020). CONCLUSIONS: 25(OH)D levels were inversely correlated with total cholesterol and non-HDL cholesterol levels in African American adolescents residing in midwestern United States. Further studies with larger sample sizes are needed to determine if low vitamin D status in African American adolescents is a potential modifiable risk factor for cardiovascular disease.

Autoimmune Lymphoproliferative Syndrome: A Rare Cause of Disappearing HDL Syndrome.

The term disappearing HDL syndrome refers to development of severe high density lipoprotein cholesterol (HDL-C) deficiency in noncritically ill patients with previously normal HDL-C and triglyceride levels. Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of the immune system due to an inability to regulate lymphocyte homeostasis resulting in lymphadenopathy and hepatosplenomegaly. We describe a 17-year-old boy who was evaluated in the lipid clinic for history of undetectable or low HDL-C and low density lipoprotein cholesterol (LDL-C) levels. Past medical history was significant for ALPS IA diagnosed at 10 years of age when he presented with bilateral cervical adenopathy. He was known to have a missense mutation in one allele of the FAS protein extracellular domain consistent with ALPS type 1A. HDL-C and LDL-C levels had been undetectable on multiple occasions, though lipids had not been measured prior to the diagnosis of ALPS. He had been receiving sirolimus for immunosuppression. The HDL-C and LDL-C levels correlated with disease activity and improved to normal levels during times when the activity of ALPS was controlled. This case highlights the importance of considering ALPS as a cause of low HDL-C and LDL-C levels in a child with evidence of lymphoproliferation.

Erythropoietin Levels in Elderly Patients with Anemia of Unknown Etiology.

BACKGROUND: In many elderly patients with anemia, a specific cause cannot be identified. This study investigates whether erythropoietin levels are inappropriately low in these cases of "anemia of unknown etiology" and whether this trend persists after accounting for confounders. METHODS: This study includes all anemic patients over 60 years old who had erythropoietin measured between 2005 and 2013 at a single center. Three independent reviewers used defined criteria to assign each patient's anemia to one of ten etiologies: chronic kidney disease, iron deficiency, chronic disease, confirmed myelodysplastic syndrome (MDS), suspected MDS, vitamin B12 deficiency, folate deficiency, anemia of unknown etiology, other etiology, or multifactorial etiology. Iron deficiency anemia served as the comparison group in all analyses. We used linear regression to model the relationship between erythropoietin and the presence of each etiology, sequentially adding terms to the model to account for the hemoglobin concentration, estimated glomerular filtration rate (eGFR) and Charlson Comorbidity Index. RESULTS: A total of 570 patients met the inclusion criteria. Linear regression analysis showed that erythropoietin levels in chronic kidney disease, anemia of chronic disease and anemia of unknown etiology were lower by 48%, 46% and 27%, respectively, compared to iron deficiency anemia even after adjusting for hemoglobin, eGFR and comorbidities. CONCLUSIONS: We have shown that erythropoietin levels are inappropriately low in anemia of unknown etiology, even after adjusting for confounders. This suggests that decreased erythropoietin production may play a key role in the pathogenesis of anemia of unknown etiology.

The effect of an automated point of care tool on diagnosis and management of childhood obesity in primary care.

BACKGROUND: Childhood obesity is underdiagnosed in primary care practices. Our study aimed to compare rates of documentation of diagnosis of obesity and counselling for nutrition and physical activity at an academic primary care practice prior to and following implementation of a body mass index (BMI)-based electronic point of care clinical reminder tool. METHODS: We performed a retrospective record review of children aged 2-18 years undergoing well child visits during any of three calendar years (2009, 2011 and 2013). The electronic clinical reminder tool was implemented in September 2010. Records of children with BMI > 95th percentile were electronically searched for terms of documentation of diagnosis of obesity and nutrition and physical activity counselling. Multivariable logistic regression models were used to adjust for potential patient and provider confounders. RESULTS: Among those with BMI ≥ 95th percentile, there was a statistically significant increase in documentation of diagnosis of obesity (45.5% in 2009 vs. 52.4% in 2011; P < 0.001; adjusted odds ratio 1.36; 95% CI 1.13-1.65) and in counselling for physical activity and nutrition (66.8% in 2009 vs. 75.2% in 2011; P < 0.001; adjusted odds ratio 1.33; 95% CI 1.06-1.66) following implementation of the tool. Compared with 2011, there was no statistically significant increase in documentation of obesity (50.4%) or nutrition and physical activity counselling (77.9%) in 2013. CONCLUSIONS: The implementation of a point of care clinical reminder tool was associated with improvement in documentation of diagnosis of obesity and counselling for nutrition and physical activity. Further studies are needed to determine the impact of these automated tools on weight outcomes in children.

Decreased Circulating Levels of Spexin in Obese Children.

CONTEXT: Spexin is a novel peptide that is implicated in obesity and related energy homeostasis in animals and adult humans. Little is known about its role in children. OBJECTIVE: The aim of the current study was to determine the potential role of Spexin in obese children and explore its relationships with various cardiometabolic risk factors. DESIGN AND PARTICIPANTS: This was a cross-sectional study composed of 69 children (51 obese and 18 normal weight; age 15.3 ± 0.26 y). OUTCOME MEASURES: Spexin was measured using a specific enzyme-linked immunosorbent assay. Leptin, total and high-molecular-weight adiponectin, IL-6, high-sensitivity C-reactive protein, glucose, and insulin were also measured. Mann-Whitney U test, Pearson and Spearman rank correlations, logistic regression, and cluster analysis were used for the analysis and interpretation of the data. RESULTS: Spexin levels were significantly lower in obese vs normal-weight children, median(IQR) (0.33 ng/mL [0.27-0.44] vs 0.42 ng/mL [0.33-0.55]; P = .024), but did not correlate with other adipokines and/or insulin and glucose levels. Ordinal categorical variables of Spexin showed a strictly reverse association of obesity with the level of Spexin. Cluster analysis of Spexin and body mass index z score resulted in splitting the participants into normal-weight and obese-weight groups with high accuracy. CONCLUSIONS: Lower circulating levels of Spexin in obese children compared with their normal-weight counterparts and the ability to discriminate obese and normal-weight groups based on Spexin concentration enabled us to suggest a potential role for this novel peptide in childhood obesity. The clinical significance of these findings needs additional investigation.

Erythropoietin in anemia of unknown etiology: A systematic review and meta-analysis.

INTRODUCTION: We conducted a systematic review and meta-analysis of observational studies in order to explore the relationship between erythropoietin (EPO) and hemoglobin in elderly individuals with anemia of unknown etiology (AUE) and other forms of anemia. METHODS: We searched Medline, EMBASE, Web of Science, Biosis Previews, Dissertations, and Theses in addition to meeting abstracts of the European Hematology Association and American Society of Hematology for relevant studies. The meta-analysis was conducted using pooled ratio of means (ROM) through the generic inverse variance method. RESULTS: Six studies were included in the meta-analysis, which confirmed that EPO levels were significantly lower in AUE as compared to iron deficiency anemia (ROM 0.7210; random 95% CI 0.7052 to 0.7372; P-value < 0.00001) and anemia of chronic disease (ROM 0.8995; random 95% CI 0.8362 to 0.9677; P = 0.004). EPO levels in AUE were slightly higher than levels in anemia of chronic kidney disease (ROM 1.0940; random 95% CI 1.0557, 1.1337; P < 0.00001). The heterogeneity (I2) of all analyses was 100%. CONCLUSION: Our findings suggest that erythropoietin levels in AUE, although elevated, remain inappropriately low, particularly when compared with other forms of anemia. This suggests a relative erythropoietin deficiency or a blunted erythroid cell response.