Core Outcome Sets in Child Health: A Systematic Review.

Importance: Developing core outcome sets is essential to ensure that results of clinical trials are comparable and useful. A number of core outcome sets in pediatrics have been published, but a comprehensive in-depth understanding of core outcome sets in this field is lacking. Objective: To systematically identify core outcome sets in child health, collate the diseases to which core outcome sets have been applied, describe the methods used for development and stakeholder participation, and evaluate the methodological quality of existing core outcome sets. Evidence Review: MEDLINE, SCOPUS, Cochrane Library, and CINAHL were searched using relevant search terms, such as clinical trials, core outcome, and children, along with relevant websites, such as Core Outcome Measures in Effectiveness Trials (COMET). Four researchers worked in teams of 2, performed literature screening and data extraction, and evaluated the methodological quality of core outcome sets using the Core Outcome Set-Standards for Development (COS-STAD). Findings: A total of 77 pediatric core outcome sets were identified, mainly developed by organizations or researchers in Europe, North America, and Australia and mostly from the UK (22 [29%]) and the US (22 [29%]). A total of 77 conditions were addressed; the most frequent International Classification of Diseases, 11th Revision category was diseases of the digestive system (14 [18%]). Most of the outcomes in pediatric core outcome sets were unordered (34 [44%]) or presented in custom classifications (29 [38%]). Core outcome sets used 1 or more of 8 development methods; the most frequent combination of methods was systematic review/literature review/scoping review, together with the Delphi approach and consensus for decision-making (10 [14%]). Among the 6 main types of stakeholders, clinical experts were the most frequently involved (74 [100%]), while industry representatives were rarely involved (4 [5%]). Only 6 core outcome sets (8%) met the 12 criteria of COS-STAD. Conclusions and Relevance: Future quality of pediatric core outcome sets should be improved based on the standards proposed by the COMET initiative, while core outcome sets methodology and reporting standards should be extended to pediatric populations to help improve the quality of core outcome sets in child health. In addition, the COMET outcome taxonomy should also add items applicable to children.

Off-label use of drugs in pediatrics: a scoping review.

To explore the current state of research on off-label drug use in children and identify the existing research gaps in this topic. Six literature databases were searched to identify studies focusing exclusively on off-label drug use in children (aged < 18 years) published in Chinese or English between 2016 and 2021. We also searched clinicaltrials.gov for pediatric clinical trials conducted in the same period and compared the numbers of studies on off-label use and clinical trials for the most commonly reported drugs and drug types. Our search revealed 568 studies on off-label drug use. Almost half of the studies (n = 240) were cross-sectional. A total of 212 specific drugs or drug types were addressed in 361 studies, the most frequent being antipsychotic agents (n = 12), dexmedetomidine (n = 10), and rituximab (n = 8). Antipsychotic agents were also the most common type of drug examined in clinical trials in children. We identified a total of 435 different types of off-label use, the top three being unapproved indication (n = 157), population (n = 96), or age (n = 36). Only about one-third of the studies reported collecting informed consent (n = 195) or having ethics committee approval (n = 166).    Conclusions: Off-label use of antipsychotics in children is widely reported in the literature. We suggest pediatric researchers to consider the number of studies on off-label use and existing clinical trials on different drugs when selecting target drugs for new studies and systematic reviews. What is Known: • There exist a large number of studies on off-label drug use in children. What is New: • This is the first scoping review of studies on off-label drug use in children. • Off-label use of antipsychotic agents is widely reported.

Guideline for the management of pediatric off-label use of drugs in China (2021).

BACKGROUND: The "Law on Doctors of the People's Republic of China," which was officially implemented on March 1, 2022, emphasizes the requirements for rational drug use and the necessity for appropriate management of off-label drug use. The safety and ethical considerations related to off-label drug use are different in children than in adults. There is so far no management guideline for pediatric off-label use of drugs in China, and the applicability of foreign guidelines is limited. Establishing a localized evidence-based management guideline for pediatric off-label use of drugs to support the national legislation and clinical practice is of critical importance. METHODS: We established a guideline working group, including experts from a broad range of disciplines and developed recommendations following the guidance of the World Health Organization Handbook and the Chinese Medical Association. The following themes were identified by questionnaires and expert interviews to be of great concern in the management of off-label drug use in children: general principles and characteristics of management of pediatric off-label drug use; establishment of expert committees; evidence evaluation; risk-benefit assessment; informed consent; monitoring and assessment of the risk; and monitoring and patient education. Two rounds of Delphi surveys were organized to determine the final recommendations of this guideline. We graded the recommendations based on the body of evidence, referring to the evaluation tool of the Evidence-based management (EBMgt) and the Oxford Center for Evidence-Based Medicine: Level of Evidence (March 2009). RESULTS: We developed the first guideline for the management of pediatric off-label use of drugs in China. CONCLUSIONS: The guideline is to offer guidance for pediatricians, pharmacists, medical managers, policymakers, and primary care physicians on how to manage off-label drug use in pediatrics and to provide recommendations for Chinese healthcare policy in the future.

Analysis of the Spectrum and Characteristics of Pediatric Cancer Based on Hospital Information Systems in China.

PURPOSE: The purpose of this study was to use the hospital information system to analyze the cancer profile and compare demographics, hospitalization, status of surgery and treatment cost of various cancer categories based on the electronic health record (EHR) of outpatient children with tumors in Shanghai, China. PATIENTS AND METHODS: Information was collected from 3834 inpatients aged 0-18 who were diagnosed with malignant tumors in all 17 hospitals with pediatric wards in the Pudong New District of Shanghai from 2011 to 2016. All patients were classified according to the International Classification of Childhood Cancer-3 (ICCC-3). The chi-squared test was used to compare demographics, hospitalization information, status of surgery and treatment cost according to inpatients' cancer category. RESULTS: In both the malignant non-solid tumor and solid tumor groups, males and those aged 0-4 years were the dominant groups. Lymphocytic leukemia was the most common cancer in all inpatients (n=994, 25.93%), and the acute myeloid leukemia had the longest length of stay of inpatients (median=26.00 days). In both the non-solid and solid tumor groups, patients who received only one type of surgery had an advantage. The highest proportion of patients who had undergone surgery was found in non-Hodgkin lymphoma patients. In terms of total cost, surgical cost and medicine cost, the expenditure of central nervous system tumor patients was the highest. Astrocytoma had the highest total cost. CONCLUSION: Leukemia is common in children with cancer in Pudong and should be given attention. Because the highest financial burden falls on patients with central nervous system tumors and acute myeloid leukemias, the government should take immediate and targeted measures for these cancers in particular.

Antibiotic burden of school children from Tibetan, Hui, and Han groups in the Qinghai-Tibetan Plateau.

BACKGROUND: Given their geographical proximity but differences in cultural and religious dietary customs, we hypothesize that children from the three main ethnic populations (Han, Hui, and Tibetan) residing in the Qinghai-Tibetan Plateau region differs in their non-iatrogenic antibiotic loads. METHODS: To determine the antibiotic burden of the school children unrelated to medical treatment, we quantified the antibiotic residues in morning urine samples from 92 Han, 72 Tibetan, and 85 Muslim Hui primary school children aged 8 to 12 years using high-performance liquid chromatography-tandem mass spectrometry, and performed correlation analysis between these data and concurrent dietary nutrition assessments. RESULTS: Sixteen of the 18 targeted antibiotics (4 macrolides, 3 ß-lactams, 2 tetracyclines, 4 quinolones, 3 sulfonamides, and 2 aminoanols) were identified in the urine samples with an overall detection frequency of 58.63%. The detection frequency of the six antibiotic classes ranged from 1.61% to 32.53% with ofloxacin showing the single highest frequency (18.47%). Paired comparison analysis revealed significant differences in antibiotic distribution frequency among groups, with Tibetans having higher enrofloxacin (P = 0.015) and oxytetracycline (P = 0.021) than Han children. Norfloxacin (a human/veterinary antibiotic) was significantly higher in the Hui children than in the Han children (P = 0.024). Dietary nutrient intake assessments were comparable among participants, showing adequate levels of essential vitamins and minerals across all three ethnic groups. However, significant differences in specific foods were observed among groups, notably in lower fat consumption in the Hui group. CONCLUSIONS: The introduction and accumulation of antibiotic residues in school children through non-iatrogenic routes (food or environmental sources) poses a serious potential health risk and merits closer scrutiny to determine the sources. While the exact sources of misused or overused antibiotics remains unclear, further study can potentially correlate ethnicity-specific dietary practices with the sources of contamination.