Clinical and Experimental Pediatrics最新文献

Most rare diseases (orphan diseases) still lack approved treatment options despite major advances in research providing the necessary tools to understand their molecular basis and legislation providing regulatory and economic incentives to expedite the development of specific therapies. Addressing this translational gap is a multifaceted challenge, a key aspect of which is the selection of an optimal therapeutic modality to translate advances in rare disease knowledge to potential medicines known as orphan drugs. There are several strategies for developing orphan drugs for rare genetic disorders, including protein replacement therapies, small-molecule therapies (e.g., substrate reduction, chemical chaperone, cofactor, expression modification, and read-through therapies), monoclonal antibodies, antisense oligonucleotides, small interfering RNA or exon skipping therapies, gene replacement and direct genome-editing therapies, mRNA therapy, cell therapy, and drug repurposing. Each strategy has its own strengths and limitations in orphan drug development. Furthermore, numerous hurdles are present in clinical trials of rare genetic diseases because of difficulty with patient recruitment, unknown molecular physiology, the natural history of the disease, ethical concerns regarding pediatric patients, and regulatory challenges. To address these barriers, the rare genetic diseases community, including academic institutions, industry, patient advocacy groups, foundations, payers, and government regulatory and research organizations, must become engaged in discussions about these issues.

The global prevalence of childhood and adolescent obesity, exacerbated by the coronavirus disease 2019 pandemic, affects school-aged children and preschoolers. Early-onset obesity, which carries a high risk of metabolic complications, may contribute to a lower age at the onset of cardiovascular disease. As metabolic diseases such as diabetes, dyslipidemia, and nonalcoholic fatty liver disease observed in adulthood are increasingly recognized in the pediatric population, there is an emphasis on moving disease susceptibility assessments from adulthood to childhood to enable early detection. However, consensus is lacking regarding the definition of metabolic diseases in children. In response, various indicators such as the pediatric simple metabolic syndrome score, continuous metabolic syndrome score, single-point insulin sensitivity estimator, and fatty liver index have been proposed in several studies. These indicators may aid the early detection of metabolic complications associated with pediatric obesity, although further validation studies are needed. Obesity assessments are shifting in perspective from visual obesity to metabolic health and body composition considerations to fill the gap in health impact assessments. Sarcopenic obesity, defined as the muscle- to-fat ratio, has been proposed in pediatric populations and is associated with metabolic health in children and adolescents. The National Health Screening Program for Children in Korea has expanded but still faces limitations in laboratory testing. These tests facilitate timely intervention by identifying groups at a high risk of metabolic complications. Early detection and intervention through comprehensive health screening are critical for mitigating long-term complications of childhood obesity.

Virtual reality (VR) is an emerging method that can be used in many scenarios involving children. VR has been increasingly studied as it has become cheaper, more widely available, and of better quality. In this review of current meta-analyses on the use of VR in children in the medical setting, we examined its role in 5 broad settings where it is used to alleviate pain and anxiety as well as in therapeutic scenarios. The study scope was purposefully broad to highlight a wide range of cases. We searched the ScienceDirect, SpringerLink, Cochrane Library, PubMed, and PMC databases for meta-analyses using VR in pediatric populations in medical settings. The National Institutes of Health quality assessment tool and Quality of Reporting of Meta-analyses statement checklist were used to verify study quality. Six hundred fifty-three articles were retrieved; after the application of the inclusion and exclusion criteria, 11 remained. These meta-analyses included cerebral palsy (4 meta-analyses), attention deficit/hyperactivity disorder (2 meta-analyses), burn care (1 meta-analysis), preoperative anxiety (2 meta-analyses), and needle-involving procedures (2 meta-analyses). The meta-analyses showed broadly positive results, with VR being useful in the areas in which it was applied. This study had several limitations. The meta-analyses consistently highlighted a high level of heterogeneity, making it challenging to draw clear conclusions. Most meta-analyses across all fields yielded encouraging results. However, further studies are required to confirm these findings. Guidelines must be established for future experiments to provide a standard and uniform procedure for reducing the heterogeneity of experimental methods.

Background: Responsive teaching (RT) interventions, which enhance developmental outcomes by improving children's engagement behaviors, are traditionally delivered in person. However, the coronavirus disease 2019 pandemic complicated this approach.

Purpose: This study aimed to evaluate the efficacy and acceptance of online RT in children with developmental disabilities and their parents.

Methods: This pilot study was conducted in Jinju, South Korea, and enrolled parent-child dyads referred to Gyeongsang National University Hospital for developmental concerns between April and September 2022. The children underwent a comprehensive developmental evaluation. The parents received a 5-session RT intervention via ZOOM on a mostly weekly basis. The first 2 sessions involved child development and RT lectures, while the others involved coaching on 3 of the 66 RT strategies. Problem behaviors, parent-child interactions, and parenting stress were assessed pre- versus postintervention using the Korean versions of the Child Behavior Checklist, Maternal/Child Behavior Rating Scale, and Parent Stress Index 4th Edition Short Form, respectively. Acceptability was evaluated using a self-administered questionnaire.

Results: Of the 30 recruited parent-child pairs, 23 (76%) completed the intervention and assessments. The children (mean age, 2.66±0.86 years) included 12 with language delays, 7 with autism spectrum disorder, and 4 with global delays. Predominantly mothers (96%) participated. Online RT significantly improved pivotal behaviors- including joint attention (P=0.04), cooperation (P=0.01), and affect (P=0.01)-and reduced overall problem behaviors (P=0.04). Parents reported less parenting stress (P=0.01), improved interactive behaviors with increased responsiveness (P<0.01), and decreased directiveness (P<0.01). High satisfaction with online RT interventions was also previously reported.

Conclusion: These findings suggest that online RT can improve children's emotional and behavioral outcomes and maternal interaction styles and reduce parenting stress, offering accessible interventions amid challenges such as limited access and pandemics.

Background: Kisspeptin and delta-like 1 homolog (DLK1) are neuropeptides that reportedly play an important role in pubertal timing by activating and inhibiting the hypothalamic-pituitary-gonadal axis, respectively. Consequently, serum kisspeptin and DLK1 levels may be novel biomarkers for differentiating between central precocious puberty (CPP) and premature thelarche (PT) in girls and used to monitor CPP treatment.

Purpose: To compare baseline serum kisspeptin and DLK1 levels in girls with CPP at diagnosis and after treatment to age-matched girls with PT.

Methods: This prospective longitudinal study included girls with precocious puberty and girls with PT who experienced breast development before 8 years of age and peak luteinizing hormone levels of ≥6 versus <6 IU/L after a gonadotropin-releasing hormone (GnRH) stimulation test. Serum kisspeptin and DLK1 levels were determined in both groups at baseline and after 6 months of GnRH analog treatment in the CPP group and analyzed by enzyme-linked immunosorbent assay.

Results: The study divided a total of 48 girls into CPP (n=24; mean age, 7.7±0.7 years) and PT (n=24; mean age, 7.4±0.8 years) groups. The baseline median serum kisspeptin levels were 50.5 pg/mL (range, 38.2-77 pg/mL) and 49.5 pg/mL (range, 39.7-67.6 pg/mL), respectively (P=0.89), while the baseline median serum DLK1 levels were 6.5 ng/mL (range, 5.9-7.5 ng/mL) and 6 ng/mL (4.4-14.4 ng/mL), respectively (P=0.68). After 6 months of GnRH analog treatment in the CPP group, the median serum kisspeptin level was lower (46.4 ng/mL; range, 37.1-60 ng/mL) than that at baseline (P=0.002), while the median serum DLK1 level was higher (7 ng/mL; range, 6.7-8.9) than that at baseline (P=0.002).

Conclusion: Our findings suggest that baseline serum kisspeptin and DLK1 levels are not reliable biomarkers for differentiating between CPP and PT. However, significant changes in serum kisspeptin and DLK1 levels may be used to monitor CPP treatment.

Action-plan is a written set of instructions that helps patient manage their symptoms and respond to worsening of their condition. The action-plan usually includes information on how to recognize, treat, and prevent worsening of symptoms. The plan also helps patient understand when to use their medications, how much to use, and how often to use them as-needed. An action-plan should be developed through a discussion between the patient and the physician, reflecting the patient's severity, preferences, and values and should be regularly updated to reflect changes in the person's condition. In asthma, action-plans and as-needed therapy are already well utilized. Unlike asthma, the importance of an action-plan has been overlooked in allergic rhinitis (AR), but its importance has recently been recognized. AR is a chronic condition that affects people differently, and can cause a range of symptoms, including nasal congestion, runny nose, sneezing, itching, and watery eyes. Therefore, an action-plan and as-needed therapy can help patients manage these symptoms more effectively, reducing the impact on their daily activities and quality of life. Furthermore, it can be tailored to meet the personal needs of each patient, based on the severity of their symptoms, their triggers, and their overall health. Because action-plan can help patients adhere to their treatment regimen by providing clear instructions on when and how to take medication, it can help patients stay on track with their treatment, reducing the likelihood of missed doses and treatment failures. Overall, an action-plan and as-needed therapy are important components of a comprehensive treatment plan for patients with AR. They can help to improve symptom control, prevent complications, and promote adherence to treatment, leading to better outcomes and a higher quality of life.

Iron deficiency (ID) tends to be overlooked compared with anemia. However, its prevalence is estimated to be twice as high as that of ID anemia, and ID without anemia can be accompanied by clinical and functional impairments. The symptoms of ID are nonspecific, such as fatigue and lethargy, but can lead to neurodevelopmental disorders in children, restless legs syndrome, and recurrent infections due to immune system dysregulation. In particular, the risk of ID is high in the context of chronic inflammatory diseases (CIDs) due to the reaction of various cytokines and the resulting increase in hepcidin levels; ID further exacerbates these diseases and increases mortality. Therefore, the diagnosis of ID should not be overlooked through ID screening especially in high-risk groups. Ferritin and transferrin saturation levels are the primary laboratory parameters used to diagnose ID. However, as ferritin levels respond to inflammation, the diagnostic criteria differ among guidelines. Therefore, new tools and criteria for accurately diagnosing ID should be developed. Treatment can be initiated only with an accurate diagnosis. Oral iron is typically the first-line treatment for ID; however, the efficacy and safety of intravenous iron have recently been recognized. Symptoms improve quickly after treatment, and the prognosis of accompanying diseases can also be improved. This review highlights the need to improve global awareness of ID diagnosis and treatment, even in the absence of anemia, to improve the quality of life of affected children, especially those with CIDs.