Effect of eardrum perforation and chronic otitis media on the results of infrared tympanic thermometer in adults: A systematic review and meta-analysis.

BACKGROUND: This study was conducted to determine whether tympanic membrane perforation or chronic otitis media affects the results of an infrared tympanic membrane thermometer in adults. METHODS: A literature search was performed using PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar. RESULTS: Four nonrandomized studies were included in the analysis. The temperatures of the bilateral eardrums (one eardrum with normal condition [control group] and the other eardrum with perforation or chronic otitis media [experimental group]) were measured for the same subject in the studies. The mean and standard deviation of the bilateral tympanic membrane temperatures were used to calculate the mean difference (MD) with a corresponding 95% confidence interval (CI). The fixed-effect model was utilized based on the results of the heterogeneity measurement using the Chi2 test and I2 statistic. The results of a meta-analysis in the normal eardrum (control group) and perforated eardrum, chronic suppurative otitis media with tympanic membrane perforation, or chronic otitis media with cholesteatoma (experimental group) were 343 subjects (MD = 0.05; 95% CI = -0.00 to 0.11; P = .06). A meta-analysis of the normal eardrum (control group) and perforated eardrum or chronic suppurative otitis media with tympanic membrane perforation except for cholesteatoma (experimental group) found 296 subjects (MD = 0.05; 95% CI = -0.01 to 0.11; P = .10). CONCLUSION: When the temperatures of the bilateral eardrums were measured using an infrared tympanic membrane thermometer, no difference was observed between the eardrum with perforation or chronic otitis media and the normal eardrum.

Clinical practice guidelines for optimizing bone health in Korean children and adolescents.

The Committee on Pediatric Bone Health of the Korean Society of Pediatric Endocrinology has newly developed evidence-based clinical practice guidelines for optimizing bone health in Korean children and adolescents. These guidelines present recommendations based on the Grading of Recommendations, which includes the quality of evidence. In the absence of sufficient evidence, conclusions were based on expert opinion. These guidelines include processes of bone acquisition, definition, and evaluation of low bone mineral density (BMD), causes of osteoporosis, methods for optimizing bone health, and pharmacological treatments for enhancing BMD in children and adolescents. While these guidelines provide current evidence-based recommendations, further research is required to strengthen these guidelines.

Response to growth hormone according to provocation test results in idiopathic short stature and idiopathic growth hormone deficiency.

PURPOSE: To investigate growth response in children with either idiopathic short stature (ISS) or growth hormone (GH) deficiency (GHD). METHODS: The data of prepubertal GHD or ISS children treated using recombinant human GH were obtained from the LG Growth Study database. GHD children were further divided into partial and complete GHD groups. Growth response and factors predicting growth response after 1 and 2 years of GH treatment were investigated. RESULTS: This study included 692 children (98 with ISS, 443 partial GHD, and 151 complete GHD). After 1 year, changes in height standard deviation score (ΔHt-SDS) were 0.78, 0.83, and 0.96 in ISS, partial GHD, and complete GHD, respectively. Height velocity (HV) was 8.72, 9.04, and 9.52 cm/yr in ISS, partial GHD, and complete GHD, respectively. ΔHt-SDS and HV did not differ among the 3 groups. Higher initial body mass index standard deviation score (BMI-SDS) and midparental height standard deviation score (MPH-SDS) were predictors for better growth response after 1 year in ISS and the partial GHD group, respectively. In the complete GHD group, higher Ht-SDS and BMI-SDS predicted better growth response after 1 year. After 2 years of GH treatment, higher BMI-SDS and MPH-SDS predicted a better growth outcome in the partial GHD group, and higher MPH-SDS was a predictor of good growth response in complete GHD. CONCLUSION: Clinical characteristics and growth response did not differ among groups. Predictors of growth response differed among the 3 groups, and even in the same group, a higher GH dose would be required when poor response is predicted.

Temporal Trends for Diabetes Management and Glycemic Control Between 2010 and 2019 in Korean Children and Adolescents with Type 1 Diabetes.

Purpose: There is increasing use of modern devices in the management of patients with type 1 diabetes (T1D). We investigated temporal trends for diabetes management and outcomes in Korean pediatric T1D patients over 10 years. Methods: We retrospectively collected the data from 752 participants (boys: 311, 41.4%) diagnosed with T1D and aged ≤18 years, with ≥1 year of follow-up between 2010 and 2019 in any of the seven study hospitals in Korea. Results: Over the 10-year study period, use of continuous glucose monitoring (CGM) increased from 1.4% to 39.3%. From 2010 to 2019, there was an increased use of multiple daily insulin injections (MDI; 63.9%-77.0%, respectively) and continuous subcutaneous insulin infusion (CSII; 2.1%-14.0%, respectively), but decreased use of conventional insulin therapy (CIT, 33.9%-9.0%, respectively). Mean glycated hemoglobin (HbA1c) decreased from 8.56% to 8.01% (P < 0.001) and was lower in younger patients, boys, and CGM users (P < 0.001). MDI and CSII users had lower mean HbA1c levels than CIT users (P = 0.003). Regarding the acute complications of T1D, CGM use was associated with lower incidences of diabetic ketoacidosis (P = 0.015); CSII users were likely to experience less severe hypoglycemia (P = 0.008). Conclusions: The use of CSII and CGM increased ∼7- and 30-fold, respectively, over the 10-year study period. The glycemic control of pediatric T1D patients in Korea improved from 2010 to 2019, probably because of increased use of T1D technologies.

A pathogenic PHEX variant (c.1483-1G>C) in a Korean patient with X-linked hypophosphatemic rickets.

X-linked hypophosphatemic rickets is an X-linked dominantly inherited disorder characterized by defects in renal phosphate transport leading to phosphate wasting and hypophosphatemia. In this report, we describe a case of X-linked hypophosphatemic rickets in a patient with a rare pathogenic PHEX variant. The 25-year-old female patient came to our clinic for genetic counseling regarding presumed genetic disease and pregnancy. When she was 9 years old, she had been diagnosed with vitamin D-resistant rickets based on laboratory results and symptoms. She had undergone orthopedic surgery due to bowing leg deformities. Since then, she was intermittently self-prescribing oral phosphate and calcium supplements. At 25 years old, she was diagnosed with X-linked hypophosphatemic rickets with a rare pathogenic PHEX variant (c.1483-1G>C) by next-generation sequencing. This is the second report of the c.1483-1G>C variant to date, and her pathogenicity was confirmed based on the most recent guideline. Traditionally, the disease had been diagnosed mostly based on clinical findings. However, with advancements in genetic testing, genetic confirmation has become an imperative part of diagnostic workup. Herein, we report a 25-year-old female Korean patient diagnosed with X-linked hypophosphatemic rickets harboring a rare pathogenic PHEX variant.

Structure-Activity Relationship Study and Biological Evaluation of 2-(Disubstituted phenyl)-indole-5-propanoic Acid Derivatives as GPR40 Full Agonists.

G-protein-coupled receptor 40 (GPR40) is considered as an attractive drug target for treating type 2 diabetes, owing to its role in the free fatty acid-mediated increase in glucose-stimulated insulin secretion (GSIS) from pancreatic ß-cells. To identify a new chemotype of GPR40 agonist, a series of 2-aryl-substituted indole-5-propanoic acid derivatives were designed and synthesized. We identified two GPR40 agonist lead compounds-4k (3-[2-(4-fluoro-2-methylphenyl)-1H-indol-5-yl]propanoic acid) and 4o (3-[2-(2,5-dimethylphenyl)-1H-indol-5-yl]propanoic acid), having GSIS and glucagon-like peptide 1 secretory effects. Unlike previously reported GPR40 partial agonists that only activate the Gq pathway, 4k and 4o activated both the Gq and Gs signaling pathways and were characterized as GPR40 full agonists. In in vivo efficacy studies, 4o significantly improved glycemic control in both C57BL/6J and db/db mice and increased plasma-active GLP-1 in C57BL/6J mice. Thus, 4o represents a promising lead for further development as a novel GPR40 full agonist against type 2 diabetes.

A national survey of transition from pediatric to adult healthcare providers for adolescents and young adults with type 1 diabetes: perspectives of pediatric endocrinologists in Korea.

PURPOSE: Transition from pediatric to adult healthcare for adolescents and young adults with type 1 diabetes (T1D) increases the risk for poor outcomes. This study aimed to describe the circumstances and clinical practice patterns associated with this transition of care based on a nationwide survey of pediatric endocrinologists in Korea. METHODS: An electronic survey regarding the healthcare transition of T1D patients was administered to 143 pediatric endocrinologists registered in the Korean Society of Pediatric Endocrinology. RESULTS: The response rate was 50.2% (n=72). Among responders, 58.3% (n=42) were females, and 70.8% (n=51) worked in academic medical centers. The main reasons for transfer to adult care were request from a patient or family (69.6%) and age ≥18 years (42.0%). Impediments to transition were a long-lasting therapeutic relationship (72.9%) and lack of adult specialists in T1D care (62.9%). Communication between pediatric and adult endocrinologists was via nonstructured patient summary (68.6%) and telephone or email (27.1%). Responders reported that successful transition requires development of transition protocols (79.2%) and a multidisciplinary team approach for transition care (52.8%). CONCLUSION: Transition care of T1D patients is a challenge to pediatric endocrinologists in Korea. Development of transition care protocols for healthcare providers and improvement of diabetes self-management skills for patients are needed.

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.

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.

PBT-6, a Novel PI3KC2γ Inhibitor in Rheumatoid Arthritis.

Phosphoinositide 3-kinase (PI3K) is considered as a promising therapeutic target for rheumatoid arthritis (RA) because of its involvement in inflammatory processes. However, limited studies have reported the involvement of PI3KC2γ in RA, and the underlying mechanism remains largely unknown. Therefore, we investigated the role of PI3KC2γ as a novel therapeutic target for RA and the effect of its selective inhibitor, PBT-6. In this study, we observed that PI3KC2γ was markedly increased in the synovial fluid and tissue as well as the PBMCs of patients with RA. PBT-6, a novel PI3KC2γ inhibitor, decreased the cell growth of TNF-mediated synovial fibroblasts and LPS-mediated macrophages. Furthermore, PBT-6 inhibited the PI3KC2γ expression and PI3K/ AKT signaling pathway in both synovial fibroblasts and macrophages. In addition, PBT-6 suppressed macrophage migration via CCL2 and osteoclastogenesis. In CIA mice, it significantly inhibited the progression and development of RA by decreasing arthritis scores and paw swelling. Three-dimensional micro-computed tomography confirmed that PBT-6 enhanced the joint structures in CIA mice. Taken together, our findings suggest that PI3KC2γ is a therapeutic target for RA, and PBT-6 could be developed as a novel PI3KC2γ inhibitor to target inflammatory diseases including RA.

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.

Limitations of current screening methods for lipid disorders in Korean adolescents and a proposal for an effective detection method: a nationwide, cross-sectional study.

PURPOSE: To determine the limitations of current screening methods for lipid disorders and to suggest a new method that is effective for use in Korean adolescents. METHODS: Data from the 6th Korea National Health and Nutrition Examination Survey (2013-2015) were analyzed. The diagnostic validity (sensitivity and specificity) of various cardiovascular risk factors currently used for lipid disorder screening was investigated, as was the diagnostic validity of non-HDL-cholesterol ≥145 mg/dL as a screening tool. RESULTS: The prevalence of dyslipidemia and familial hypercholesterolemia (FH) among Korean adolescents was 20.4%±1.0% and 0.8%±0.3%, respectively. The current standard screening methods identified only 5.9%±1.4% and 30.3%±17.2% of the total number of dyslipidemia and FH cases, respectively. The diagnostic sensitivity and specificity of lipid profile analysis for dyslipidemia among obese adolescents were 19.5%±2.3% and 93.6%±0.8% and for FH were 30.3%±17.2% and 91.1%±0.8%, respectively. When adolescents with obesity, hypertension, or a family history of dyslipidemia or cardiocerebrovascular disease for over 3 generations were included in the screening, diagnostic sensitivity increased to 68.4%±2.8% for dyslipidemia and 83.5%±2.7% for FH. Universal screening of all adolescents based on non-HDL-cholesterol levels had sensitivities of 30.2%±2.7% and 100%, and specificities of 99.2%±0.3% and 94%±0.6% for dyslipidemia and FH, respectively. CONCLUSION: New screening methods should be considered for early diagnosis and treatment of lipid disorders in Korean adolescents.

Iodine status and characteristics of Korean adolescents and their parents based on urinary iodine concentration: a nationwide cross-sectional study.

PURPOSE: Iodine is a major component of thyroid hormones. Both deficiency and excess of iodine are major risk factors for thyroid disease, making it important to accurately assess iodine level in the human body. Urinary iodine concentration (UIC) is a commonly used measure of iodine status. However, there is little research on iodine status and related characteristics in Korean adolescents. METHODS: Using data from the sixth Korea National Health and Nutrition Examination Survey (KNHANES VI) for the years 2013-2015, we analyzed UIC and thyroid function test results in adolescents aged 10-18 years and their parents. We also investigated the influence of socioeconomic factors and family history of thyroid disease on iodine status. RESULTS: Mean UIC in Korean adolescents was 963.5±55.7 µg/L. Among evaluated subjects, 6.6%±1.0%, 29.8%±1.7%, and 63.9%±1.9% had low (UIC<100 µg/L), adequate (UIC: 100-299.9 µg/L), and excess (UIC≥300 µg/L) iodine concentrations, respectively. Based on regional trends, the incidence of iodine deficiency exceeded 10% in several regions, even though there was a dominance of regions with excess iodine. Parental UIC, female sex, average monthly income, and expenditure were all found to affect the iodine status of Korean adolescents. CONCLUSION: Although regional differences exist, the iodine status in Korean adolescents is mainly affected by the eating habits of their families and socioeconomic factors. Therefore, monitoring of iodine status is necessary in this population.

Long-term safety and effectiveness of growth hormone therapy in Korean children with growth disorders: 5-year results of LG Growth Study.

PURPOSE: The aim of this registry study was to analyze the long-term safety and effectiveness of recombinant human growth hormone (rhGH) in South Korean pediatric patients (≥2 years of age) with growth hormone deficiency GHD) of idiopathic or organic etiology, idiopathic short stature, Turner syndrome, small for gestational age and chronic renal failure. METHODS: The study patients were followed-up till two years after the epiphyseal closure, with visits scheduled every six months. The outcome measures included the incidence of adverse events (AEs, in particular, neoplasia, glucose intolerance and hypothyroidism), as well as height standard deviation score (Ht SDS) and annual height velocity. The results of the interim analysis of a 5-year accumulated data for 2,024 patients (7,342 patient-years, PY) are presented. RESULTS: A total of 14 neoplasms were diagnosed (191/100,000 PY); 7 out of 9 malignancies were recurrent craniopharyngioma found in patients with organic GHD. Seven cases of glucose intolerance (95/100,000 PY) and 22 cases of hypothyroidism (300/100,000 PY) were detected; about half of the cases (4 and 10 cases each) were considered to be related with rhGH treatment. Most of the growth-retarded patients showed continuous improvement in Ht SDS, with the most prominent effect observed within a year of treatment initiation. The beneficial effect of rhGH on Ht SDS gain was maintained for 2-4 years. CONCLUSIONS: The incidence of AEs of interest in rhGH-treated patients was low, and most of the neoplasms were benign and/or non-related to rhGH. Most patients benefited from the therapy in terms of height increment.

Ease of Use, Preference, and Safety of the Recombinant Human Growth Hormone Disposable Pen Compared with the Reusable Device: A Multicenter, Single-Arm, Open-Label, Switch-Over, Prospective, Phase IV Trial.

PURPOSE: To assess the usability and safety of the disposable pen compared to those of reusable devices in patients receiving recombinant human growth hormone (rhGH) treatment. PATIENTS AND METHODS: This study was a multicenter, single-arm, open-label, switch-over, prospective, Phase IV trial. After screening, eligible patients who were previously treated with rhGH using a reusable device were enrolled to receive treatment with the disposable pen for 8 weeks. The ease of use, preference, and tolerability of the disposable pen compared to those of the reusable device were assessed by the subjects and/or their caregivers using a questionnaire. Adverse events were evaluated by the investigators. RESULTS: Of 116 subjects enrolled in this study, 115 received treatment with the disposable pen and 109 completed the study. The mean age of the subjects was 9.4 years. Compared to the previous reusable device, the disposable pen was assessed as significantly easier to use (mean value 7.88, 95% confidence interval (CI) [7.45-8.30] on a numerical scale ranging from 0 (far less easy) to 10 (far easier)). Furthermore, the percentage of subjects who preferred the disposable pen to the previously used reusable device was 75.7% (95% CI [67.6%-83.8%]). The percentages of subjects who rated pain and discomfort at the injection site as "not at all" were higher after using the disposable pen compared to the reusable device. No specific safety concerns were identified. CONCLUSION: The disposable pen is easier to use than the reusable devices and is preferred by approximately 75% of patients receiving rhGH treatment. Moreover, the disposable pen is safe and acceptable. Therefore, it could be a good alternative to reusable devices. The disposable pen is expected to provide benefits to patients receiving rhGH treatment. CLINICALTRIALSGOV IDENTIFIER: NCT03015909.

[Predictors of Eating Disorders in Adolescents with Type 1 Diabetes]. / 1형 당뇨병 ì²­ì†Œë „ì˜ ì„­ì‹ìž¥ì• ì˜ˆì¸¡ìš”ì¸.

PURPOSE: The purpose of this study was to identify predictors of eating disorders in adolescents with type 1 diabetes, with the goal of providing data in support of nursing interventions to improve their health. METHODS: A total of 136 adolescents aged 13-18 years with type 1 diabetes completed the Diabetes Eating Problem Survey-Revised, Rosenberg Self-Esteem Scale, and the Beck Depression Inventory-II, using structured self-reported questionnaires. The collected data were analyzed using the t-test, x 2 test, and binominal logistic regression with SPSS version 23.0 for Windows. RESULTS: The prevalence of eating disorders in adolescents with type 1 diabetes was 39%. Four significant predictors of eating disorders were identified; absence of body satisfaction (odds ratio [OR]=3.87, 95% confidence interval [CI]=1.55~9.65), depression (OR=2.87, 95% CI=1.13~7.28), female gender (OR=2.67, 95% CI=1.09~6.54), and glycosylated hemoglobin type A1c levels (OR=1.47, 95% CI=1.10~1.97). CONCLUSION: In order to prevent eating disorders among adolescents with type 1 diabetes, programs for managing adolescents' depression and improving their body satisfaction should be developed. Futhermore, more attention should be directed towards programs aiming to prevent eating disorders in female adolescents.

Design of the long-term observational cohort study with recombinant human growth hormone in Korean children: LG Growth Study.

PURPOSE: Regarding recombinant human growth hormone (rhGH) use in the pediatric population, no long-term follow-up data are available for Korean patients. To fill in the gap of knowledge, a registry study (LG Growth Study) was initiated to assess the safety and effectiveness of four types of rhGH products in real-life settings. METHODS: A total of 4,000 children will be registered and prospectively followed up at 6-month intervals until 2 years after epiphyseal closure to collect data on treatment and adverse events, with primary interest in malignancies and growth outcomes. RESULTS: As of 22 March 2017, approximately 50% (2,024) of the target number of patients have been included in the analysis set: growth hormone deficiency, 1,297 (64.1%); idiopathic short stature, 315 (15.6%); small for gestational age, 206 (10.2%); Turner syndrome, 197 (9.7%); and chronic renal failure, 9 (0.4%). At baseline, median age (years) was 8 (interquartile range [IQR], 5-11); 52% (1,048) were boys; and the majority were at Tanner stage I (83% based on breast/external genitalia, 97% on pubic hair). Median height standard deviation score was -2.26 (IQR, -2.69 to -2.0), and median bone age delay (years) was -1.46 (IQR, -2.26 to -0.78). CONCLUSIONS: This registry study will provide the opportunity to assess the risk of malignancies as well as the general safety data in Korean pediatric patients receiving rhGH. In addition, the long-term effectiveness of rhGH and comparative data between different disease entities will provide practical insight on the standard rhGH treatment.

Erratum: The effect of first nocturnal ejaculation timing on risk and sexual behaviors of Korean male adolescents.

[This corrects the article on p. 43 in vol. 22.].