Effectiveness and safety of pamidronate treatment in nonambulatory children with low bone mineral density.

PURPOSE: Nonambulatory pediatric patients may have low bone mineral density (BMD) and increased risk of pathologic fractures. Though bisphosphonate therapy is the mainstream medical intervention in these children, clinical data regarding this treatment are limited. Therefore, this study aimed to evaluate the effectiveness and safety of bisphosphonate therapy in such children. METHODS: We conducted a retrospective study of 21 nonambulatory children (Gross Motor Function Classification System level V) with BMD z-score ≤ -2.0 who were treated with intravenous pamidronate for at least 1 year. These patients received pamidronate every 4 months at a dose of 1.0 to 3.0 mg/kg for each cycle and had regular follow-ups for at least 1 year. The main outcome measures were changes in BMD, risk rate of fracture, biochemical data, and adverse events. RESULTS: The average duration of pamidronate treatment was 2.0±0.9 years, and the mean cumulative dose of pamidronate according to body weight was 7.7±2.5 mg/kg/yr. After treatment, the mean lumbar spine bone mineral content, BMD, and height-for-age-z-score-adjusted BMD z-score (BMDhazZ) significantly improved. The relative risk of fracture after treatment was 0.21 (p=0.0032), suggesting that pamidronate treatment reduced fracture incidence significantly. The increase in the average dose per body weight in each cycle significantly increased the changes in BMDhazZ. CONCLUSION: Pamidronate treatment improved the bone health of nonambulatory children with low bone density without any significant adverse events. Independent of cumulative dosage and duration of treatment, the effectiveness of pamidronate increased significantly with an increase in the average dose per body weight in subsequent cycles.

Bioelectrical impedance parameters add incremental value to waist-to-hip ratio for prediction of metabolic dysfunction associated steatotic liver disease in youth with overweight and obesity.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) presents a growing health concern in pediatric populations due to its association with obesity and metabolic syndrome. Bioelectrical impedance analysis (BIA) offers a non-invasive and potentially effective alternative for identifying MASLD risk in youth with overweight or obesity. Therefore, this study aimed to assess the utility of BIA for screening for MASLD in the youth. Method: This retrospective, cross-sectional study included 206 children and adolescents aged <20 years who were overweight and obese. The correlations between anthropometric measurements and BIA parameters and alanine aminotransferase (ALT) levels were assessed using Pearson's correlation analysis. Logistic regression analysis was performed to examine the associations between these parameters and ALT level elevation and MASLD score. Receiver operating characteristic (ROC) curves were generated to assess the predictive ability of the parameters for MASLD. Results: Pearson's correlation analysis revealed that waist-to-hip ratio (WHR), percentage body fat (PBF), and BIA parameters combined with anthropometric measurements were correlated with ALT level. Logistic regression revealed that WHR, skeletal muscle mass/WHR, PBF-WHR, fat-free mass/WHR, and appendicular skeletal muscle mass/WHR were correlated with ALT level elevation after adjusting for age, sex, and puberty. WHR, PBF-WHR, and visceral fat area (VFA)-WHR were positively correlated with the MASLD score in the total population after adjusting for age, sex, and puberty. PBF-WHR and VFA-WHR were correlated with the MASLD score even in youth with a normal ALT level. The cutoff points and area under the ROC curves were 34.6 and 0.69 for PBF-WHR, respectively, and 86.6 and 0.79 for VFA-WHR, respectively. Discussion: This study highlights the utility of combining BIA parameters and WHR in identifying the risk of MASLD in overweight and obese youth, even in those with a normal ALT level. BIA-based screening offers a less burdensome and more efficient alternative to conventional MASLD screening methods, facilitating early detection and intervention in youth at risk of MASLD.

Comparison of agranulocytosis and anti-neutrophil cytoplasmic antibody-associated vasculitis caused by two antithyroid drugs: A pharmacovigilance study using the WHO international database.

BACKGROUND: Methimazole (MMI) and propylthiouracil (PTU) are commonly used for patients with thyrotoxicosis. Agranulocytosis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is associated with high morbidity and mortality, requiring appropriate interventions. In this study, we compared adverse drug effects associated with MMI and PTU using a real-world large pharmacovigilance database. METHODS: We searched all Individual Case Safety Reports reported to be associated with MMI and PTU, from VigiBase between 1967 and June 2, 2021. We conducted disproportionality analysis (case/non-case analysis) to analyze the difference in reported adverse drug reactions (ADRs) between antithyroid drugs (case) and the entire database (non-cases). We further analyzed information for the cases of agranulocytosis and AAV. RESULTS: Among 11 632 cases of ADRs reported after MMI intake, agranulocytosis occurred in 1633 cases and AAV occurred in 41 cases. For 5055 cases of ADRs reported after PTU intake, agranulocytosis occurred in 459 cases and AAV occurred in 110 cases. Agranulocytosis occurred after a median of 28 days after PTU intake and 33 days after MMI intake. More than 95% of the agranulocytosis cases were classified as serious, but most of them (65.1% for PTU and 70.4% for MMI) were reported to have recovered after dechallenge actions; mostly drug withdrawal. AAV occurred after a median of 668 days after PTU intake, and 1162 days after MMI intake. CONCLUSIONS: This is a pharmacoepidemiological study investigating agranulocytosis and AAV caused by MMI and PTU. Through this research, we could provide more specific insights into a safe prescription of antithyroid drugs in a real-world setting.

Association of Functional Gastrointestinal Disorders with Adolescent Idiopathic Scoliosis.

Numerous adolescents diagnosed with adolescent idiopathic scoliosis (AIS) often manifest symptoms indicative of functional gastrointestinal disorders (FGIDs). However, the precise connection between FGIDs and AIS remains unclear. The study involved adolescents drawn from sample datasets provided by the Korean Health Insurance Review and Assessment Service spanning from 2012 to 2016, with a median dataset size of 1,446,632 patients. The AIS group consisted of individuals aged 10 to 19 with diagnostic codes for AIS, while the control group consisted of those without AIS diagnostic codes. The median prevalence of FGIDs in adolescents with AIS from 2012 to 2016 was 24%. When accounting for confounding factors, the analysis revealed that adolescents with AIS were consistently more prone to experiencing FGIDs each year (2012: adjusted odds ratio (aOR), 1.21 [95% confidence interval (CI), 1.10-1.35], p < 0.001; 2013: aOR, 1.31 [95% CI, 1.18-1.46], p < 0.001; 2014: aOR, 1.24 [95% CI, 1.12-1.38], p < 0.001; 2015: aOR, 1.34 [95% CI, 1.21-1.49], p < 0.001; and 2016: aOR, 1.35 [95% CI, 1.21-1.50], p < 0.001). These findings suggest that AIS is correlated with an elevated likelihood of FGIDs, indicating that AIS may function as a potential risk factor for these gastrointestinal issues. Consequently, it is recommended to provide counseling to adolescents with AIS, alerting them to the heightened probability of experiencing chronic gastrointestinal symptoms.

Prediction of insulin resistance and elevated liver transaminases using serum uric acid and derived markers in children and adolescents.

OBJECTIVE: To investigate the relationship of serum uric acid (Uacid) and derived parameters as predictors of insulin resistance (IR) and elevated liver transaminases in children and adolescents METHODS: Data of 1648 participants aged 10-18 years was analyzed using nationwide survey. Logistic regression analysis was performed with IR and elevated liver transaminases as dependent variables, and odds ratios (ORs) and 95% confidence intervals (CIs) for tertiles 2 and 3 of each parameter in comparison to tertile 1, which served as the reference. Receiver operating characteristic (ROC) curves were generated to assess predictability of the parameters for IR and elevated liver transaminases. RESULTS: Hyperuricemia, IR, and elevated liver transaminases were significantly associated with each other. All Uacid and derived markers showed continuous increase in ORs and 95% CIs for IR and elevated liver transaminases across the tertiles of several biochemical and metabolic variables of interest (all p < 0.001), and were also significantly predictive in ROC curve. Overall, Uacid combined with obesity indices showed higher ORs and area under the curve (AUC) compared to Uacid alone. Uacid-body mass index (BMI) standard deviation score presented the largest AUC for IR. For elevated liver transaminases, Uacid-BMI and Uacid-waist-to-height ratio showed the largest AUC. CONCLUSIONS: Uacid combined with obesity indices are robust markers for prediction of IR and elevated liver transaminases in children and adolescents. Uacid and derived markers have potential as simple markers which do not require fasting for screening of IR and elevated liver transaminases in children and adolescents.

Healthcare professionals' perspectives towards the digitalisation of paediatric growth hormone therapies: expert panels in Italy and Korea.

Introduction: To analyse the perspectives of healthcare professionals (HCPs) regarding the acceptance of digital health solutions for growth hormone (GH) deficiency care. This study identified factors impacting HCPs' intent to use and recommend digital solutions supporting recombinant-human growth hormone (r-hGH) therapy in Italy and Korea with a use case of connected drug delivery system (Aluetta® with Smartdot™) integrated in a platform for GH treatment support (the Growzen™ digital health ecosystem). Methods: Participatory workshops were conducted in Rome, Italy, and Seoul, Korea, to collect the perspectives of 22 HCPs on various predefined topics. HCPs were divided into two teams, each moderated by a facilitator. The workshops progressed in five phases: introduction of the project and experts, capturing views on the current context of digitalisation, perceived usefulness and ease of use of Aluetta® with Smartdot™, exploration of the perception of health technology evolution, and combined team recommendations. Data shared by HCPs on technology acceptance were independently analysed using thematic analysis, and relevant findings were shared and validated with experts. Results: HCPs from both Italy and Korea perceived Aluetta® with Smartdot™ and the Growzen™ based digital health ecosystem as user-friendly, intuitive, and easy-to-use solutions. These solutions can result in increased adherence, a cost-effective healthcare system, and medication self-management. Although technology adoption and readiness may vary across countries, it was agreed that using digital solutions tailored to the needs of users may help in data-driven clinical decisions and strengthen HCP-patient relationships. Conclusion: HCPs' perspectives on the digitalisation in paediatric GH therapies suggested that digital solutions enable automatic, real-time injection data transmission to support adherence monitoring and evidence-based therapy, strengthen HCP-patient relationships, and empower patients throughout the GH treatment process.

2017 Clinical practice guidelines for dyslipidemia of Korean children and adolescents

The Committee on Dyslipidemia of Korean Pediatric and Adolescents of the Korean Society of Pediatric Endocrinology has newly developed evidence-based clinical practice guidelines for dyslipidemia in Korean children and adolescents. These guidelines were formulated with the Grading of Recommendations, which include both the strength of recommendations and the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. These guidelines are based on the 2011 National Heart, Lung, and Blood Institute Guidelines, which focus on the prevention of cardiovascular disease in children and draw from a comprehensive review of evidence. These guidelines contain the definition of and screening process for dyslipidemia and introduce new dietary methods: the Cardiovascular Health Integrated Lifestyle Diet (CHILD)-1, the CHILD-2-low-density lipoprotein cholesterol, and the CHILD-2-triglyceride. Potential drug therapies for dyslipidemia along with their main effects and doses were also included.