Emerging research suggests a link between attention deficit hyperactivity disorder (ADHD) and central sensitization (CS), a condition characterized by heightened sensitivity to pain and sensory stimuli. This study aimed to measure the severity of CS symptoms in children with ADHD and in their parents; compare results with those of a neurotypical group; and explore associations between CS symptoms and pain intensity as well as potential familial patterns. Participants included 37 children with ADHD (mean age = 11.54 years; 62.2% male) and 29 neurotypical children (mean age = 13.07 years; 58.6% male). Children completed the Central Sensitization Inventory (CSI) - Child and Adolescent Version and rated their pain intensity at the time of assessment and over the past week. One parent per child completed the adult version of the CSI. Children with ADHD reported significantly higher CSI-indexed CS symptom scores than those in the comparison group (p < 0.001). In categorical analyses, neurotypical children were significantly more likely to fall into the subclinical (lowest symptom) CS range (adjusted p < 0.005). Children with ADHD also reported significantly greater pain intensity both currently (p = 0.016) and over the past week (p = 0.003). Stronger correlations between CSI-indexed CS and self-reported pain were observed in the ADHD group, particularly for current pain (ρ = 0.66, p = 0.002). Parents of children with ADHD also had elevated CS scores (p = 0.003), with the majority falling in the severe range. A moderate correlation between parent and child CSI-indexed CS scores was observed across the entire sample (ρ = 0.47, p = 0.002), while a strong correlation between parents' CS scores and their own medical conditions was found only in the ADHD group (ρ = 0.66, p = 0.002). Children with ADHD, and their parents, reported elevated CSI-indexed CS symptoms and pain intensity, suggesting that CS symptoms may represent a clinically relevant feature in some ADHD presentations. These findings support the value of considering sensory and pain-related assessments in ADHD evaluations and highlight the need for further research into potential mechanisms and integrative interventions that may improve outcomes and reduce functional impairment in pediatric neuropsychiatric conditions. Not applicable.
To evaluate the performance of the point-of-care i-STAT device for creatinine measurement in Ugandan children with sickle cell anemia (SCA), and to determine the clinical impact of hydroxyurea-associated assay interference. This secondary analysis was nested within a randomized clinical trial involving 248 Ugandan children with SCA. The mean age at enrollment was 32 months, and 115/248 (46.2%) initiated hydroxyurea during 12 months of follow-up as part of routine clinical care. At enrollment, creatinine values measured by i-STAT and reference laboratory testing were clinically comparable. At follow-up, children receiving hydroxyurea had significantly higher creatinine values measured by i-STAT than by reference laboratory testing (mean difference + 0.19 mg/dL; p = 0.006), with several i-STAT results falling within the clinically abnormal range. No such discrepancy was observed among children not receiving hydroxyurea. In a subset of samples, serum hydroxyurea concentrations measured by high-performance liquid chromatography accounted for 73% of the variability in i-STAT creatinine values. These findings demonstrate clinically meaningful interference of hydroxyurea with enzymatic point-of-care creatinine testing, which may result in misclassification of kidney function and inappropriate clinical decision-making in children with SCA receiving hydroxyurea. gov identifier: NCT03528434 (date registered: May 7th, 2018).
The COVID-19 pandemic significantly impacted the mental health of children and adolescents, particularly those from low-income families and adolescent girls. The long-term effects remain unclear. This study assessed the mental health measured by emotional and behavioural problems and quality of life (QoL) among German children and adolescents, emphasising socio-economic status and gender differences. The help-seeking behaviour among families of children with mental health problems was also examined. A nationwide representative online survey was conducted in April/May 2024. N = 1,530 children and adolescents (ages 8-17) and their parents participated. The self- and parent-report survey assessed behavioural and emotional problems (Strength and Difficulties Questionnaire). QoL (KIDSCREEN-10 Index) was rated in self-report. Parents reported on past help-seeking behaviour within and outside of school via items constructed for the present study. Behavioural and emotional problems (21.1% in self-report, 22.4% in parental report) and low QoL (27.3%) were higher than pre-pandemic levels. Children from low-income families were particularly affected. Of all parents, 23.7% reported a need for help due to their child's mental health issues in the last 12 months, with 28.4% of these parents not seeking professional support. Among those who sought help, most contacted multiple services, with teachers, psychotherapists and general practitioners being the most frequently contacted services. Families who secured a therapy placement waited an average of 12 weeks for an initial appointment and 18 weeks to begin therapy. Behavioural and emotional problems as well as low QoL seem to stabilise at a rate higher than the pre-pandemic baseline, indicating a need for ongoing monitoring, adjustment to the mental health system and further research on correlates and causes of this stabilisation.
This study aimed to evaluate the efficacy of a novel endoscopic approach using argon plasma coagulation (APC) for the treatment of congenital pyriform sinus fistulas (CPSF) in children. A retrospective analysis was conducted on 30 pediatric patients with PSF who were treated at Fujian Children's Hospital (Fujian Branch of Shanghai Children's Medical Center) between 2021 and 2025. All patients underwent neck color Doppler ultrasound and electronic laryngoscopy, with systematically analyzed of the results. Postoperative follow-up was performed at multiple time points. All 30 procedures were successfully completed, with no cases of pharyngeal fistula, dysphagia, or infection around or beyond the fistula tract. During the follow-up period, ranging from 2 weeks to 3 years, no recurrence was observed. Endoscopy-assisted argon plasma coagulation is a promising treatment for CPSF in children, offering advantages including minimal trauma, reduced bleeding, and clear visualization. This method appears safe and effective for infants and children with CPSF and warrants wider clinical adoption.
Differences in body composition during childhood can influence long-term health, with notable links to cardiometabolic disorders in later life. While genetic associations with body composition traits are well-studied, less is known about the role of epigenetic mechanisms, particularly in low- and middle-income countries where the burden of cardiometabolic disease is high. We investigated links between DNA methylation and three compartments of body composition: fat mass, lean mass, and bone measures using data from children enrolled in the Epigenetic Mechanisms linking Pre-conceptional nutrition and Health Assessed in India and Sub-Saharan Africa (EMPHASIS) study. We conducted an epigenome-wide association study of 11 body composition traits assessed through dual-energy X-ray absorptiometry in children from India (mean [range] age = 5.8 [5-7] years; n = 686) and The Gambia (age = 9.0 [7-9] years; n = 284), with blood DNA methylation measured at ~ 800,000 CpGs sites on the Illumina EPIC array. Cohort-specific analysis identified 8 unique differentially methylated CpGs associated with traits across all three body composition compartments (p < 3.6 × 10-8), with none overlapping both cohorts. Cross-cohort meta-analysis revealed four CpGs associated with lean mass and bone area mapping to SOCS3 and ZBTB16. Region-level analyses identified 29 differentially methylated regions (DMRs) in India and 18 in The Gambia. 29 DMRs were identified in the meta-analysis, 25 of which were not detected in either cohort individually. Many DMRs were associated with more than one body composition trait. We report novel DNA methylation signatures associated with body composition traits in children from two low- and middle-income countries. Identified loci map to genes linked to inflammatory signalling, energy metabolism and cellular stress response pathways, highlighting a potential role for epigenetic mechanisms in shaping early-life body composition.
Immune-inflammatory dysregulation is increasingly implicated in the pathogenesis of autism spectrum disorder (ASD). Umbilical cord blood mononuclear cells (UCB-MNCs), with their immunomodulatory effects, represent a promising therapeutic avenue by potentially alleviating neuroinflammation. This study aimed to evaluate the safety and efficacy of multiple intravenous infusions of allogeneic UCB-MNCs in children with ASD and peripheral immune dysregulation. In this single-center, double-blind, randomized, placebo-controlled trial (RCT), 34 children (aged 3 to 8 years) diagnosed with ASD were randomly assigned to receive intravenous infusion of allogeneic UCB-MNCs (3 × 10⁸ cells per infusion) (n = 17) or placebo (n = 17) four times with 1-week interval, alongside their existing rehabilitation therapy, and followed up for 13 weeks. The primary endpoint were the Total score of the Social Responsiveness Scale-2 (SRS-2). Additional endpoints was changes of the five domains of the SRS-2, the Vineland Adaptive Behavior Scales-3 (Vineland-3), the Childhood Autism Rating Scale (CARS), Aberrant Behavior Checklist (ABC), Swanson, Nolan, and Pelham Rating Scale-IV (SNAP-IV), Self-Rating Anxiety Scale (SAS) and safety. At final follow-up, the UCB-MNCs group demonstrated a significantly greater reduction in the SRS-2 Total scores (LS Mean Difference = - 6.03, 95% confidence interval [CI]: - 11.93 to - 0.14, P = 0.045) and Social Cognition domain (LS Mean Difference = - 9.95, 95% confidence interval [CI]: - 15.90 to - 4.00, P = 0.002) scores compared to the placebo group. No major allogeneic UCB-MNCs transplantation-related adverse events occurred. Allogeneic UCB-MNCs transplantation demonstrated preliminary safety and potential efficacy in improving specific aspects of symptoms in children with ASD and peripheral immune dysregulation. Trial registration This study was registered on ChiCTR.org.cn (Identifier: ChiCTR2400082762). Date registered 12 April 2024. https://www.chictr.org.cn/index.html.
Caregiver-reported drop/fall from caregiver hold is a common history in children presenting with extremity injuries, but distinguishing accidental injury from clinician-suspected inflicted injury remains challenging. This study examined clinical and radiographic injury patterns associated with clinician classification as suspected inflicted versus accidental at the index presentation. This single-center cross-sectional study included consecutive children younger than 12 years presenting to the orthopedic emergency room after a reported drop/fall from caregiver hold between 16 June and 31 December 2025. Cases were classified at presentation as clinician-suspected inflicted drop/fall or accidental drop/fall based on structured medico-legal assessment. Injury-pattern variables were analyzed as study variables. Group comparisons used chi-square/Fisher's exact tests and the Mann-Whitney U test. Associations with clinician-suspected inflicted classification were examined using univariable logistic regression and a pre-specified exploratory multivariable Firth penalized logistic regression model. Fifty-eight children were included: 18/58 (31.0%) were classified as clinician-suspected inflicted drop/fall and 40/58 (69.0%) as accidental drop/fall. Clinician-suspected inflicted cases were older and more frequently had father reported as the caregiver. Bruising, displaced fractures, and multiple injuries/fractures were more frequent in clinician-suspected inflicted cases than in accidental cases. The combined pattern of bruising plus displaced fracture was observed in 12/18 (66.7%) clinician-suspected inflicted cases and 0/40 accidental cases in this sample, a zero-cell finding requiring cautious interpretation and external validation.In the pre-specified exploratory Firth penalized logistic regression model, father as the reported caregiver, bruising, and multiple injuries/fractures remained associated with clinician-suspected inflicted classification, rather than with independently confirmed abuse. In this single-center cohort, selected clinical and radiographic injury patterns were associated with clinician-suspected inflicted classification after caregiver-reported drop/fall from caregiver hold. Because abuse was not independently confirmed, these findings should be interpreted as risk indicators to support early safeguarding triage and careful documentation, not as stand-alone evidence of abuse or intent. Because clinician classification was not independent of routinely available clinical and radiographic findings, incorporation bias may have affected the observed associations. Bidirectional misclassification between accidental and clinician-suspected inflicted classifications may also have occurred. The absence of a full skeletal survey and uniformly documented complete examination may have led to missed occult injuries.
This qualitative study explored the social isolation experiences reported by mothers of autistic children in Yazd, Iran. Twenty-two mothers of autistic children aged 4-12 years participated in semi-structured interviews conducted in Yazd, Iran. Data were analyzed inductively using conventional content analysis. The reporting of the study was strengthened using the COREQ checklist, including additional details on the interviewer, recruitment, interview procedures, coding, trustworthiness, and consistency between the thematic table and the Results section. One main theme, social isolation, was developed from participants' accounts. Three categories were identified: stigma and social judgment, inadequate formal and informal support, and caregiving burden and defensive withdrawal. The twelve subcategories reported in the thematic table are now aligned with the Results section. Participants' accounts suggested that social isolation was linked mainly to stigmatizing social responses, community misunderstanding, limited family and service support, therapy-related demands, and mothers' protective withdrawal from social settings. In this sample of 22 mothers in Yazd, social isolation appeared to be shaped by the interaction between autism-related caregiving demands and the surrounding social and cultural environment. The findings support the need for culturally sensitive public awareness, family education, and accessible support services. Because this was a single-city qualitative study based on mothers' self-reported experiences, the findings should be transferred cautiously to other Iranian or international contexts.
Most studies confirm the effectiveness of virtual reality (VR) in alleviating pain and fear during pediatric venipuncture, with limited evidence regarding physiological stress markers and dynamic assessment. This study aims to investigate the effects of VR technology on pain, fear, and physiological responses in children, as well as family satisfaction during intravenous cannulation. This single-blind randomized controlled trial was conducted in the Pediatrics Department of Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China. A total of 188 children requiring intravenous cannulation procedures and their families were allocated into: the control group (n = 96), which received the conventional verbal comfort; and the experimental group (n = 92), which wore VR headsets. The primary outcomes were dynamic fear/pain scores assessed by nurses and self-reported by patients, which were surveyed using the Children's Emotional Manifestation Scale (CEMS) and the Children's Fear Scale (CFS)/the Face, Legs, Activity, Crying, and Consolability scale (FLACC) and the Wong-Baker FACES Pain Rating Scale (Wong-Baker), respectively. The secondary outcomes were dynamic heart rate (HR) and peripheral oxygen saturation (SpO2) measurement, and family satisfaction levels. The pre-specified time points were pre-intervention, immediately post-intervention, at tourniquet application, at venipuncture, and one minute after venipuncture. Results were reported following the Consolidated Standards of Reporting Trials 2025 guidelines. VR significantly reduced children's fear at two pre-venipuncture time points (nurse-assessed CEMS and child-reported CFS; partial η2 = 0.072 and 0.053, both p < 0.05). There were no significant group effects in nurse-assessed FLACC and child-reported Wong-Baker pain scores across three venipuncture time points. However, a significant time-by-group interaction was observed for nurse-assessed FLACC scores (partial η2 = 0.028, p = 0.006). Notably, nurse-assessed FLACC scores were lower than child-reported Wong-Baker scores in both control and experimental groups (Mean Diff.=-1.04 to -2.10, all p < 0.001). The dynamic changes in HR and SpO2 across five time points were lower within the experimental group (partial η2 = 0.106 and 0.045, both p < 0.01). Partial correlation analysis revealed that family satisfaction responded to children's pain, fear, and physiological stress in a "process-sensitive" pattern in the control group but an "outcome-oriented" pattern in the experimental group. In this trial, VR distraction effectively reduced procedural fear (but not pain) during venipuncture. However, the nurse assessment appears to suggest that the effects of VR distraction and conventional intervention on pain experience may vary over time. These findings underscore the importance of multidimensional pain/fear assessment in pediatrics. Our study confirms that VR distraction can significantly reduce fear in children undergoing intravenous cannulation, though pain scores were not significantly lowered. Multidimensional assessment (including subjective fear measures) is therefore important. VR may improve the patient and family experience of painful procedures. We recommend further trials with larger samples to confirm these findings and refine VR interventions. Chinese Clinical Trial Registry, ChiCTR2500113849 (Registration Date: Dec. 3, 2025; Retrospectively registered).
Angelman syndrome is a neurodevelopmental disorder caused by loss of maternal UBE3A expression. With promising therapies now in clinical trials, there is a pressing need for reliable and translatable biomarkers. Elevated delta power in electroencephalography (EEG) recordings is a hallmark of Angelman syndrome and a promising biomarker, but traditional measures of delta power conflate true delta oscillations with broadband spectral shifts, limiting interpretability and utility. We sought to investigate whether separating out periodic and aperiodic contributions to delta power would yield more interpretable biomarkers. We applied spectral parameterization to EEG recordings from children with Angelman syndrome (n = 95) and typically developing children (n = 185), and to cortical local field potential recordings from Ube3a mutant mice (n = 39) and littermate controls (n = 47) across postnatal development. We related periodic and aperiodic features to Bayley developmental scores in children, and to performance on a motor-based behavioral battery in mice. Here we show that elevated delta power reflects a combination of increased periodic delta oscillations as well as elevated aperiodic slope and offset in both humans and mice. Periodic delta power predicts cognitive ability in children, while aperiodic features predict motor deficits in mice. These features also follow divergent developmental trajectories in both species, suggesting distinct underlying mechanisms. Aperiodic spectral features represent a translatable biomarker for Angelman syndrome. Periodic and aperiodic components of the delta phenotype show separable behavioral and developmental signatures, and their complementary use offers improved precision for biomarker-based evaluation in preclinical and clinical research. Angelman syndrome is a rare genetic disorder affecting movement, speech, cognition, and sleep. As new therapies enter clinical trials, reliable measures of brain function are needed to determine whether treatments are effective. Children with Angelman syndrome show elevated slow brain waves in EEG recordings, but this commonly used measure actually reflects two distinct signals: rhythmic slow oscillations and a broader shift in background brain activity. We separated these two signals in EEG recordings from children with Angelman syndrome and in a mouse model of the disorder. Each component was linked to different behavioral features and followed different developmental trajectories. Together, these findings provide more precise tools for tracking Angelman syndrome and evaluating emerging treatments in both patients and preclinical models.
To identify and compare barriers and enablers influencing physical activity in adults and parent-proxy responses for children with type 1 diabetes in the UK. A cross sectional survey was distributed via BreakthroughT1D (formerly JDRF) networks between December 2022 and January 2023. The survey included closed and open-ended questions on physical activity behaviours and influencing factors. Responses were collected from adults with type 1 diabetes and parent-proxy responses for children with type 1 diabetes. Quantitative data were analysed using descriptive statistics and two-proportion z-tests. Free-text responses were analysed thematically. Barriers and enablers were synthesised using the COM-B model and socioecological framework to identify behavioural determinants and intervention targets. 311 responses were analysed (182 adults; 129 parent proxies for children). Stigma and negative comments were reported by nearly three-quarters of both groups. Adults more frequently reported clinical and motivational barriers: fear of hypoglycaemia (53%) and lack of motivation (39%). Adults reported significantly less healthcare provider support for physical activity (24%) compared with parent-proxy responses for children (57%). Parent-proxy responses for children more frequently reported external barriers, including lack of education among coaches (31%). This is one of the first UK-based studies to comprehensively compare barriers and enablers across age groups. Stigma in physical activity and sports settings emerges as a major, under-recognised barrier requiring urgent attention. Multilevel interventions are required, targeting individual knowledge and motivation alongside systemic changes. These should include mandatory diabetes education for coaches and teachers, policy enforcement to address discrimination and enhanced healthcare provider support for physical activity.
The 2024 international pediatric sepsis consensus definition has undergone a paradigm shift from a systemic inflammatory response syndrome (SIRS)-based framework to the organ dysfunction-centered Phoenix Sepsis Criteria (PSC). We aimed to evaluate the diagnostic concordance, predictive performance for 28-day pediatric intensive care unit (PICU) mortality, and phenotypic overlap between these two pediatric sepsis definitions. This single-center retrospective cohort study included 1034 children aged > 1 month to < 18 years with confirmed or suspected infection who were directly admitted to the PICU of Children's Hospital of Chongqing Medical University between January 1, 2020, and November 21, 2023. All patients were independently evaluated for sepsis using both the 2005 International Pediatric Sepsis Consensus Conference (IPSCC) SIRS criteria and the 2024 PSC. Diagnostic agreement was assessed using the Kappa coefficient. Binary logistic regression was employed to establish association models between factors and phenotypes, as well as between factors and PICU 28-day mortality. Predictive performance was compared using the C-statistic. Among 1034 patients, 613 (59.3%) met the Sepsis-SIRS criteria with a 28-day PICU mortality of 15.2% (93/613), 744 (72.0%) met the Sepsis-Phoenix criteria with a mortality of 16.3% (121/744), 489 (47.3%) met both criteria with a mortality of 18.6% (91/489), and 166 (16.1%) met neither criterion with a mortality of 2.4% (4/166). Agreement between the two criteria was poor (kappa = 0.202, 95% CI: 0.143-0.261). After adjusting for clinically relevant confounders, the PSC remained a strong independent predictor of 28-day mortality (adjusted OR = 5.123, 95% CI: 2.128-12.333, p < 0.001), whereas the SIRS criteria showed no independent predictive value (adjusted OR = 0.937, 95% CI: 0.523-1.678, p = 0.827). The PSC demonstrated significantly superior discriminatory ability compared with the SIRS criteria (C-statistic = 0.809 vs. 0.589, p < 0.001). Notably, 20.2% of SIRS-positive patients were not classified as sepsis by the Phoenix Criteria, and this subgroup had an extremely low mortality of 1.6%, reflecting higher specificity of the PSC. The SIRS and PSC identify partially overlapping populations with distinct risk stratification, showing poor diagnostic concordance. The PSC has superior independent predictive performance for PICU 28-day mortality and may be considered for prognostic assessment of infected children in the PICU setting. Importantly, historical study results based on the SIRS criteria should be extrapolated cautiously to PSC-defined populations.
Understanding how disability prevalence differs between social and medical models across socioeconomic contexts helps inform policies aimed at improving the well-being of children with disabilities. Additionally, consistent data collection methods are essential to support the shift from medical to social models of disability. This study examined associations between two measures of disability: parent-reported functional limitations based on the Washington Group/UNICEF Child Functioning Module (CFM) and medically documented impairments. We analyzed data from Türkiye's 2022 child survey, which provided a comprehensive assessment of parent-reported functional limitations and medically documented impairments in 14,705 children aged 0-17 from 9,010 households. Using principal component analysis and logistic regression, we identified and tested associations between the two measures. Disability prevalence was 2% based on medically documented impairments but rose to 14.1% when using the CFM, highlighting significant discrepancies across measures. The CFM responses suggested three distinct sub-populations: (1) physical, sensory, and cognitive domains, (2) social domains, and (3) emotional domains, with each group displaying unique socioeconomic characteristics. Additionally, children with medical disability reports were three times more likely to report symptoms of depression or anxiety than those without such reports, underscoring the importance of integrating functional and clinical measures for a comprehensive understanding of disability. The findings indicate that the CFM's functional approach provided a complementary perspective to the medical model, offering global comparability and a fuller profile of childhood disability. This dual-model approach supports disability-inclusive policies by capturing a broader spectrum of functional needs, thereby aiding resource allocation and public awareness initiatives.
Promoting mental health and psychological well-being from early childhood is a growing priority in global education policy. Bullying has emerged as a major threat to children's well-being, and while most school-based interventions begin in late childhood or adolescence, research suggests that bullying-related behaviors and peer exclusion emerge as early as preschool. Yet, to date, no bullying prevention program has been rigorously evaluated from the beginning of schooling. This study aims to fill this gap by evaluating Vivre Ensemble-Fri for Mobberi (VE-FFM), a comprehensive, developmentally tailored bullying prevention and social-emotional learning (SEL) program implemented in French primary schools from preschool through elementary school. We will conduct a two-arm cluster-randomized controlled trial involving 210 French public schools and approximately 5250 children, recruited at age 3 and followed for 7 years. Schools will be randomly allocated to either the intervention group (VE-FFM) or a wait-list control group continuing with teaching-as-usual. VE-FFM is a universal, whole-school program targeting students, professionals, and families. It focuses on building inclusive peer communities and strengthening children's social-emotional skills through structured group discussions, well-being activities, and SEL workshops. Primary outcomes include bullying and peer victimization. Secondary outcomes include psychological well-being, mental health difficulties, empathy, social skills, academic performance, teacher-child relationship quality, school belonging, subjective unsafety, perception of school kindness, and teacher job satisfaction. Data will be collected at six timepoints using teacher- and child-rated measures. Implementation fidelity will be monitored through teacher logs and recorded classroom sessions. This trial is the first to evaluate the long-term impact of a bullying prevention and SEL program beginning at preschool level. By embedding the intervention into the full span of early schooling, VE-FFM may produce stronger and more lasting effects than shorter-term interventions implemented at later stages. Results will inform educational and mental health policy by providing evidence on the effectiveness of early, community-based approaches to preventing bullying and promoting mental well-being. DRKS; DRKS00037553. Registered on 2025/09/11.
To develop a Core Outcome Set suitable for adults and children for use in studies of Dental Behaviour Support (DBS) techniques, including non-pharmacological DBS, sedation and General Anaesthesia research. Two systematic reviews generated a preliminary list of candidate outcomes that were shared with Key Stakeholders (KSG) and Public Patient Involvement (PPI) groups, who shortlisted outcomes for further exploration. Patients, carers, clinicians, and researchers were invited to participate in a Delphi panel. A modified e-Delphi was used to generate prioritisation and consensus across outcomes. A subsequent series of consensus meetings with panellists, patient groups and professional stakeholder groups determined the final outcomes within the COS. Twenty-three candidate outcomes were rated by 88 panellists in Round 1. The attrition rate between Rounds 1 and 3 was 21.6%. Thirty-four to 32 panellists attended the consensus meetings. The BeSiDe core outcome set for Dental Behaviour Support consisted of nine outcomes: acceptability, adverse effect, anxiety, behavioural response, cost, pain, therapeutic alliance, time and treatment completion. An additional subset of three core outcomes for use in pharmacological DBS studies was agreed upon: recovery, sedation effect and physiological monitoring. Each outcome was presented with a plain-language label and description to support consistent interpretation across stakeholders. A core outcome set to be used across all DBS studies was produced covering both adults and children, with supplementary additional outcomes available to use in studies exploring only pharmacological DBS approaches. The list is for use in research, though there is obvious transferability to clinical practice. COMET Initiative database (Study ID: 2101), registered September 2022.
Anaphylaxis is a potentially life-threatening systemic hypersensitivity reaction. While triggers, clinical manifestations, and severity are influenced by age and sociocultural factors, most evidence regarding the impact of comorbidities and cofactors comes from adult studies. This study aimed to characterize the triggers, clinical features, and outcomes of pediatric anaphylaxis in a tertiary care center, with a particular emphasis on risk factors for severity. We retrospectively reviewed records from August 2023-August 2024 at the European Allergy Academy and Clinical Immunology Center of Excellence in Istanbul. Children aged 0-18 years (n = 100) with anaphylaxis as defined by the 2020 World Allergy Organization (WAO) criteria were included. Demographic, clinical, and follow-up data were collected. The updated 2024 (WAO) grading system was used to classify severity. Of the 3,959 records, 100 children fulfilled the inclusion criteria. A female predominance was noted in those ≤ 4 years, with males predominating thereafter. Medications were the leading trigger, followed by food, venom, and idiopathic causes. Foods were more prevalent among outpatients, and drugs were more prevalent among inpatients. Comorbidities were more common in hospital-onset anaphylaxis. Atopy was more common in food-induced anaphylaxis, whereas infections and polypharmacy were more common in drug-induced cases. Food-related reactions with endogenous factors were typically milder, whereas drug-related reactions-especially in older patients with polypharmacy or hospital-onset-tended to be more severe. Biphasic reactions were associated with delayed presentation, elevated WBC/ANC, and older age. Intramuscular adrenaline was administered in 95% of the patients, but prehospital autoinjector use was rare. Our findings underscore the need for early recognition and management, systematic evaluation of contributing factors, risk-adapted monitoring, and individualized follow-up in pediatric anaphylaxis patients.
The overall survival of children with newly diagnosed acute myeloid leukemia (AML) in high-income countries has increased to 80% over the past decades. Nevertheless, a significant subset of patients experiences relapse and treatment is associated with both short- and long-term toxicities. The CHIP-AML22 protocol includes an updated standard-of-care treatment for children with AML within the NOPHO-DB-SHIP consortium. Targeted therapies are offered to specific subsets of patients and measures to reduce toxicity are being investigated. CHIP-AML22 is a multinational complex clinical trial in newly diagnosed de novo AML patients up to and including 18 years of age, sponsored by the Princess Máxima Center. The primary aim is to improve event-free survival. To achieve this, (1) FLT3-ITD+/NPM1wt patients can participate in a linked-trial assessing safety and efficacy of quizartinib, in addition to conventional chemotherapy during induction and consolidation therapy and as continuation monotherapy after allogeneic hematopoietic stem cell transplantation; (2) a randomization study is incorporated on the use of two doses of 3 mg/m2 gemtuzumab ozogamicin during induction therapy in CD33-positive patients; and (3) updated criteria are used for the identification of high-risk patients, based both on flow measurable residual disease (MRD) and (cyto)genetic profiling. The design allows for introduction of new treatment options in the future. Furthermore, a randomization is included aiming to demonstrate non-inferiority in disease-free survival after two versus three consolidation courses in standard-risk patients. Additionally, the use of the cardioprotective drug dexrazoxane is recommended in all patients. Interim analyses will be conducted to assess safety and efficacy in the linked trial and randomization studies. Based on power calculations, we aim to recruit a total of 905 patients in the Master protocol and 60 patients in the linked Quizartinib trial. The risk-based approach and use of targeted therapies in CHIP-AML22 illustrate a shift toward more personalized treatment. Besides improving event-free survival, this study aims to contribute to the international consensus on strategies to reduce toxicity for all patients. The design of this study provides a dynamic framework, allowing for the potential introduction of emerging therapeutic options in the future. CHIP-AML22 Master protocol: EU CT 2023-504999-25-00, Clinicaltrials.gov NCT05994690. Registered on 16-08-2023 Quizartinib linked-trial: EU CT 2023-505000-27-01, Clinicaltrials.gov NCT06262438. Registered on 16-02-2024.
Food insecurity (FI) is associated with poorer physical and mental health outcomes, exacerbation of chronic diseases, and decreased access to healthcare. Children experiencing FI face additional risks, including lower psychosocial functioning and reduced academic achievement. Although national initiatives call for integrating nutrition support services into healthcare, clinical workflows for FI screening and referral remain inconsistently implemented and difficult to sustain. The goal of this study is to refine, adapt, and optimize a comprehensive FI screening and referral program, and identify effective implementation strategies for pediatric healthcare systems. We will use a RollOut Implementation and Optimization (ROIO) trial design to iteratively implement and refine the implementation strategies for our FI screening and referral program (I-FRESH: Implementing Food Referrals for Equity and Sustained Health) across 4 pediatric clinics. I-FRESH includes: (1) FI screening; (2) assessment of family needs and readiness to access services; (3) referral and navigation support to community nutrition programs; and (4) follow-up to assess fit, utilization, and ongoing needs. The Pragmatic, Robust Implementation and Sustainability Model (PRISM) will guide adaptation and evaluation of contextual determinants, while RE-AIM will guide assessment of outcomes (implementation feasibility and acceptability, fidelity, adoption, reach, effectiveness, and maintenance). We will identify several implementation strategies to increase the likelihood that I-FRESH can be successfully implemented and sustained in a pediatric healthcare system. We will enroll 240 participants and assess preliminary effectiveness on family‑level food security and pediatric nutrition‑related health outcomes (e.g. weight status, blood pressure, lipids, HbA1c, liver function tests). The information gathered in this trial will be utilized in the development of a fully powered Type 2 Hybrid Effectiveness-Implementation Trial that will test the effectiveness of the identified implementation strategies and impact of the FI program on clinical outcomes. By integrating PRISM and RE-AIM within an iterative ROIO design, this study will generate a scalable, contextresponsive implementation model for addressing FI in pediatric healthcare settings. Findings will inform sustainable strategies that link families to highquality nutrition support programs and improve nutritionrelated health outcomes for lowincome children. NCT06661538.
To investigate the retinal microcirculation changes in children with anisometropic amblyopia through multimodal assessment and explore its correlation with neurophysiological dysfunction. This prospective cross-sectional study recruited 68 treatment-naïve children (aged 4-14 years) with primary monocular anisometropic amblyopia. The fellow healthy eye served as the control. Macular microvascular parameters, including foveal avascular zone (FAZ) area and superficial capillary plexus (SCP) perfusion density, were quantified using optical coherence tomography angiography (OCTA). Pattern visual evoked potentials (P-VEP) assessed P100 latency and amplitude. Central macular thickness (CMT) and retinal nerve fiber layer (RNFL) thickness were measured. Correlations and multiple linear regression analyses were performed to identify predictors of best-corrected visual acuity (BCVA) in amblyopic eyes. Compared to fellow eyes, amblyopic eyes exhibited significant microcirculatory impairment: reduced SCP perfusion density (central: 0.27 vs. 0.29, P < 0.001; full: 0.44 vs. 0.46, P < 0.05), enlarged FAZ area (0.30 vs. 0.26 mm², P = 0.035), and increased CMT (141.00 vs. 131.50 μm, P < 0.05) and RNFL thickness (113.00 vs. 110.00 μm, P < 0.001). P-VEP revealed prolonged P100 latency (119.0 vs. 109.5 ms, P < 0.001) and decreased amplitude (12.8 vs. 19.25 µV, P < 0.001). SCP perfusion density correlated negatively with P100 latency (ρ=-0.341, P = 0.004), and SCP vessel density correlated negatively with CMT (ρ=-0.363, P = 0.002) and FAZ area (ρ=-0.424, P < 0.001). Multiple linear regression analysis (adjusted R²=0.625, P < 0.001) identified RNFL thickness (β = -0.546, P < 0.001) as a significant negative predictor of BCVA (logMAR), while SCP full perfusion density (β = 0.375, P < 0.001) and axial length (β = 0.237, P = 0.007) were significant positive predictors. Anisometropic amblyopia is marked by a neurovascular mismatch, manifested through simultaneous retinal hypoperfusion, paradoxical thickening of structures, and delayed neural conduction. The combined OCTA-P-VEP assessment provides a comprehensive biomarker framework. RNFL thickness, SCP perfusion density, and axial length emerge as key independent predictors of visual acuity, suggesting complex interplays between structure, perfusion, and function.
Aging is marked by changes in DNA methylation (DNAm) including an increase in randomness or entropy in the epigenome. Here, we computed epigenetic entropy using DNAm data from the Women's Health Initiative (WHI) ancillary study AS315 (n = 2192), and tested for replication in WHI ancillary studies, BA23 (n = 1989) and AS311 (n = 868). We investigated how different metrics of epigenetic stochasticity relate to demographic variables, health, and mortality risk, and how these compare to machine-learning based models of aging such as the DunedinPACE. Epigenetic entropy had robust and consistent negative associations with income and education in the WHI. Notably, low income was related to increased stochasticity and higher methylation in DNA regions that are targeted by the polycomb proteins-key regulators of cellular memory and embryonic development. While higher income was associated with reduced entropy scores and lower DunedinPACE in White women, this effect of income was diminished in Black and Hispanic women, and on average, Black and Hispanic women had relatively higher stochastic variability. Painting a complex picture, our analysis of the polycomb regions in a small cohort of children showed significant positive associations with parental income. Additionally, in the WHI, higher DunedinPACE predicted higher mortality risk, while the maintenance of methylation at enhancer regions was associated with improved survival. These findings indicate close ties between social and economic factors and aspects of epigenetic aging, and highlight the polycomb targeted CpGs as potential sensors of the social environment and related exposures across demographic groups.