Introduction We report on the case of a 15 year old young person with a known diagnosis of autism presenting with a rapid and acute regression in functional abilities, decline in expressive speech and bizarre posturing. The symptoms first started during lockdown (April 2020) with anxiety related to school work followed by urinary incontinence, insomnia, muttering to self and incongruent smiling. Initial medical investigations including MRI, lumbar puncture and 24hour EEG were inconclusive, so she was referred to Paediatric Liaison for assessment. Objectives We demonstrate the value of a child psychiatry liaison service being involved with young people in an acute medical hospital Methods This young person had a thorough psychiatric assessment. Results Through daily psychiatric assessment and reviews with the young person, her parent, social care, wider community team, school and Paediatric Inpatient ward in order to expand on the understanding of the young person and develop a case formulation. She was started on oral Olanzapine 2.5mg which was gradually increased to 10mg OD with minimal improvement. Conclusions Childhood Disintegrative Disorder (CDD or Heller’s Syndrome) is a rare pervasive disorder presenting as a loss of previously acquired skills after at least two years of normal development. Despite no longer being included in DSM-V, it is important for Psychiatrists to have a working knowledge of CDD and consider other differentials when assessing young people. Disclosure No significant relationships.
Abstract Germline loss-of-function (LOF) mutations in Elongator complex protein 1 (ELP1) are found in 15-20% of childhood SHH medulloblastoma (MB) and are exceedingly rare in non-SHH-MB or other cancers. ELP1 germline carriers that develop SHH-MB harbor frequent somatic PTCH1 mutations and universally sustain loss-of-heterozygosity of the remaining ELP1 allele through chromosome 9q deletion. ELP1 functions as a scaffolding subunit of the Elongator complex that is required for posttranscriptional modification of tRNAs and maintenance of efficient translational elongation and protein homeostasis. However, the molecular, biochemical, and cellular mechanisms by which ELP1/Elongator LOF contribute to SHH-MB tumorigenesis remain largely unknown. Herein, we report that mice harboring germline Elp1 monoallelic loss (i.e., Elp1+/-) exhibit hallmark features of malignant predisposition in developing cerebellar granule neuron progenitors (GNPs), the lineage-of-origin for SHH-MB. Elp1+/- GNPs are characterized by increased replication stress-induced DNA damage, upregulation of the homologous recombination repair pathway, aberrant cell cycle, and attenuation of p53-dependent apoptosis. CRISPR/Cas9-mediated Elp1 and Ptch1 gene targeting in mouse GNPs reproduces highly penetrant SHH-MB tumors recapitulating the molecular and phenotypic features of patient tumors. Reactivation of the p53 pathway through MDM2 and PAK4 inhibitors promotes selective cell death in patient-derived xenograft tumors (PDX) harboring deleterious ELP1 mutations. Together, our findings reveal that germline Elp1 deficiency heightens genomic instability and survival in GNPs, providing a mechanistic model for the subgroup-restricted pattern of predisposition and malignancy associated with pathogenic ELP1 germline carriers. These results provide rationale for further preclinical studies evaluating drugs that overcome p53 pathway inhibition in ELP1-associated SHH-MB and a renewed outlook for improving treatment options for affected children and their families.*, # Contributed equally
Abstract Introduction/Background Wrist synovitis is associated with more severe disease and less drug-free remission periods, therefore, the objective of this study was to investigate the demographic, disease course, and complexity of wrist disease in children being treated for Juvenile Idiopathic Arthritis (JIA). Description/Method A single-centre, retrospective case note review of all children and adolescents diagnosed with JIA, who received steroid joint injections of their wrists from 2014 to 2019. All patients received standard therapy and underwent regular follow-up at Birmingham Children’s Hospital. Inclusion criteria were those with an established diagnosis of any JIA-subtype according to the International League of Associations for Rheumatology (ILAR) classification. Patients were excluded if (i) the data were incomplete, (ii) they were over the age of 16y at diagnosis, or (iii) the eventual diagnosis was not JIA. Clinical information was gathered from case notes, departmental databases and hospital clinical systems on to a standardised proforma. Information collected were demographics, JIA subtype, immunology, age at diagnosis, disease duration, number of wrist injections and outcome of every wrist MRI performed. All treatments including intraarticular injections were administered by a paediatric Rheumatologist while MRIs were reviewed by an experienced senior Radiologist. Discussion/Results Of all 94 eligible patients, 88 (94%) were included in this study; 71 girls, with a mean age at diagnosis of 6 years (0-15 years). Wrist arthritis was more common in seronegative polyarthritis (40%) and extended oligoarthritis (23%) but least pronounced in Enthesitis-related arthritis (2%). 85 (95.6%) received Methotrexate therapy with a mean of 10 months from time of diagnosis. 77 patients (88%) required a step-up from MTX, with Etanercept (88%) being the most popular option as a first-line biologics, followed by Adalimumab (11%). All patients who had Adalimumab as a first biologics had evidence of uveitis. Wrist disease was present at diagnosis in 60/88 (68%) of our cohort. 66 patients (75%) had bilateral wrist disease. Over one-quarter of patients who developed wrist arthritis within the first year of diagnosis were young children (0-2 years). A second predominate group was adolescent (10-15 years) accounting for 33% of our cohort. The mean (IQR) duration between diagnosis and first clinical evidence of wrist synovitis was 15 months (1–17). Patients had a median of 3 years from diagnosis until development of first radiological evidence of erosive changes. 12 children (14%) from this cohort underwent a laparoscopic synovectomy for their wrist damage between 2017 and 2021, out of which 9 had polyarticular involvement while two had extended and one had persistent oligoarticular arthritis. Half of the patients reported improvement in pain and Health Assessment Questionnaire (HAQ) scores after synovectomy, while three remained stable at 0 score, and 3 had insufficient data. Key learning points/Conclusion Treatment of wrist arthritis can be challenging to both professionals and health care systems, emphasizing the need for clear steps to improve early recognition and treatment. Wrist disease at presentation was relatively common in our cohort and damage once occurred was irreversible with patients continuing to have ongoing disease activity despite optimization of their treatment. Furthermore, MRI as shown in our analysis, can accurately detect early erosive changes and inform management decision.
Against the backdrop of rapid digital technology development, the impact of parental phubbing on adolescents' physical and mental health has garnered increasing attention. Grounded in the Stimulus-Organism-Response (SOR) theoretical model, this study examines the statistical associations linking parental phubbing to adolescents' anxiety levels and participation in physical activity. Data were collected from 550 middle school students using the Parental Phubbing Scale (PPS), the Generalized Anxiety Disorder-7 (GAD-7), the Social Anxiety Disorder Scale-7 (SAD-7), and the Physical Activity Rating Scale-3 (PARS-3). After excluding 41 invalid responses, 509 valid questionnaires were included in the final analysis. The findings reveal that frequent parental phubbing is significantly positively associated with adolescents' generalized anxiety and social anxiety, and negatively associated with their engagement in physical activity. Network analysis further shows that generalized anxiety emerges as a central hub in the network, whereas social anxiety exhibits a distinct suppressive moderating effect. These results highlight the potential harm of shifting family interaction patterns in the digital age and emphasize the need for parents to be mindful of the modeling effects of their device use. Strengthening face-to-face interactions may help promote adolescents' physical and psychological well-being. These findings offer correlational evidence that may inform the establishment of family digital behavior guidelines and the development of intervention strategies to support adolescent health.
Aim The aim of this study is to describe and compare areas of concern for caregivers of children and adolescents with Down syndrome across ages and explore how these areas impact their ability to participate in daily activities. Methods One hundred and seventeen caregivers of children and adolescents with Down syndrome, aged 0-18, participated and completed the About My Child questionnaire. Descriptive analyses of data from the caregivers were carried out. Individual item scores and the mean scores, standard deviations, median and confidence interval of the total Concern and Impact scores were calculated. Item analyses were carried out across age groups (Kruskal-Wallis test) and between children and adolescent groups (Mann-Whitney Test), aiming to explore concerns and impacts at different ages. Results The lowest mean concern score for an age group was 9.27, and the highest was 12.67, with possible scores from 0 to 19. The lowest mean impact score for an age group was 2.80, and the highest was 3.25, with possible scores from 0 to 4. The items with the highest frequency of concern for most age groups were communication, participation in school and community and behaviour. The biggest impacts on participation were reported for the items concerning the use of arms and hands, sleep and hearing. No differences were found across age groups. Interpretation This study found that caregivers of children and adolescents with Down syndrome have concerns about their child that, in total, do not change throughout life.
Abstract Medulloblastoma (MB) patients determined to have a sub-total resection (STR), defined by >1.5cm2 post-surgical tumour residuum, receive intensified treatment regimes, but recently the designation of STR as a high risk feature is being questioned. We aimed to assess the clinical correlates of extent of resection (EOR) and its impact on survival, with particular consideration of EOR in relation to the four MB consensus molecular subgroups (WNT, SHH, Group 3, Group 4). We collected data from 1113 patients (n=419, UK CCLG institutions; n=694, published data) representing the largest ever combined cohort constructed to assess the impact of EOR in medulloblastoma. We performed association analyses and univariate/multivariate survival analysis using Kaplan-Meier, log-rank and Cox proportional hazard modelling, analysing overall survival (OS) cohort-wide and with reference to molecular subgroups and clinical features. Association analysis of the combined cohort evidenced that infant patients were more likely to have STR (p=0.02). In this whole-cohort analysis, EOR was significantly associated with survival in univariate analysis (HR 1.64, 95% CI 1.30-2.07, p=<0.001) but not in multivariate analysis. STR was variably prognostic in sub-cohort analyses of specific demographics and molecular subgroup; worse outcomes were observed in patients <5 years in SHH (p=0.044) and Group 4 (p=0.044). This was true for WNT patients >5 years old at diagnosis (p=0.034) although numbers were small and require validation in even larger cohorts. In this cohort of >1100 MBs, STR was significantly associated with a lower OS in univariate analysis, but this was driven by specific disease contexts (SHH and Group 4 patients <5 years old). STR was not independently prognostic overall or in any setting. We recommended that surgeons should continue to pursue maximal safe resection for all MB patients but suggest that consideration of STR as a high-risk feature should be disease context specific.
Objective Recruiting, enrolling, and retaining families in pediatric obesity clinical trials is challenging. This study examined perceptions of facilitators and barriers related to clinical research, and preferences of specific research formats, in parents of a child with overweight or obesity. Associations between parental research perceptions and sociodemographic and health factors were also explored. Method A descriptive, cross-sectional online survey of 103 parents of children 2 to 17 years with overweight or obesity was conducted between May 2021 and March 2022 in the southeastern US. Barriers and facilitators of research participation, child weight status, child COVID-19 health care and parental COVID-19 stress, demographic characteristics (e.g., child age, child gender, child race/ethnicity, family income, geographic location), and preferences for specific research formats (e.g., telehealth, in person, group sessions, individual sessions, COVID-19 testing, single-dose COVID-19 vaccine, and multiple-dose COVID-19 vaccine) were assessed. Linear regression analyses were conducted. Results Parents endorsed more reasons and benefits for participation than mistrust, social pressure, and reasons against participation. Lower child body mass index was associated with higher perceptions of research participation benefits. Pandemic parental stress was associated with increased social pressure and benefits. Parents of non-Hispanic White and male youth endorsed more mistrust of clinical research. Conclusion Findings can inform future pediatric overweight and obesity clinical research and trial designs to enable equitable recruitment, reduce participation burden, and increase feasibility and sustainability of interventions.
Abstract Background Foot involvement in juvenile idiopathic arthritis (JIA) is common and affects about 60% of children [1]. Often overlooked by patients and practitioners, ankle and foot disability has been poorly studied and there are no accepted clinical practice guidelines for the diagnostic approach, as well as for the therapeutic management. Objectives Our study aimed to evaluate the effect of medical treatments on functional disability related to foot involvement in JIA. Methods We conducted a cross-sectional study including patients with JIA according to the revised ILAR criteria, collected from the rheumatology department of the Kassab National Institute. Sociodemographic and disease data (activity assessed by the Juvenile Arthritis Disease Activity Score 10 (JADAS-10) and therapeutic modalities) were recorded. Ankle and foot involvement were investigated by questioning and physical examination. We used the Oxford ankle foot questionnaire for children (OxAFQ-C); a validated, simple and reproducible score to assess the impact on the quality of life of children with foot problems [2]. This questionnaire encompasses 14 items corresponding to three dimensions: physical, school and play, and emotional. Higher scores represent better functioning. We searched for an association between the different drug treatments for JIA and the OxAFQ-C score. Results The study included 23 patients. The mean age was 13 ± 4 [6–18] years. The sex ratio was 0.42 with a female predominance. The age of the disease was 49 ± 40 months [6–180 months]. The distribution of the different forms of JIA was as follows: oligoarticular (n = 7), enthesitis-related arthritis (n = 6), polyarticular FR + (n = 1), polyarticular FR- (n = 3), psoriatic arthritis (n = 3), systemic (n = 1) and undifferentiated (n = 1). Pain on walking and limitation of the talocrural joint was found in 39% and 30% respectively. The mean JADAS-10 score was 6.72 ± 6.1 [0–20]. Ten patients had high activity. Eighteen patients (78%) were taking level I analgesics and 14 patients (61%) were on non-steroidal anti-inflammatory drugs, 12 of them on demand. Naproxen was the most commonly used drug, followed by diclofenac. Eleven patients (48%) were on a disease-modifying anti-rheumatic drug (csDMARD). Methotrexate (MTX) was prescribed in 30% of cases with a mean dose of 7.91 mg/week [7.5–10]. Only one patient was on sulfasalazine. Four patients (17%) were treated with biologics: Etanercept (n = 3) and Tocilizumab (n = 1). The mean scores of the different domains of (OxAFQ-C) were as follows: 73.52 ± 35.89 [0—100] in the physical domain, 84.2 ± 30 [6.25—100] in the school and play domain, 88.75 ± 24.71 [12.5 – 100] in the emotional domain. There was no statistically significant association between the different domains of the Oxford score and the use of analgesics or NSAIDs (p> 0.05). Similarly, there was no statistically significant association between the different domains of the Oxford score and treatment with biotherapy (p> 0.05). However, patients on MTX had less functional impairment of the feet with a significant improvement in the physical domain (99.26 on MTX vs 62.5 without MTX, p = 0.02, r = 0.6). Conclusion Our work showed that only methotrexate was associated with an improvement in functional foot outcomes in JIA. Further studies are needed to highlight the effect of other therapies, especially biologics. References [1] Arkell-Kautiainen M, Haapasaari J, Kautiainen H, Vilkkumaa I, Mälkiä E, Leirisalo-Repo M. Favourable social functioning and health-related quality of life of patients with JIA in early adulthood. Ann Rheum Dis. 2005; 64(6):875–880 [2] Morris C, Liabo K, Wright P and Fitzpatrick R. Development of the Oxford ankle foot questionnaire: finding out how children are affected by foot and ankle problems. Child: care and health development. 2007; 33(5): 559–68. The implication to policy, practice, research and advocacy More studies are needed regarding the effect of therapeutics on foot involvement in JIA children
Background Patient and public involvement and engagement (PPIE) can increase the relevance and efficiency of research projects. An overview of PPIE approaches and implementation in pediatric research studies is needed to facilitate learning from others' experiences. Objective We aimed to systematically review practices in PPIE across all pediatric health research disciplines regarding characteristics and recruitment of PPIE participants, timepoints and methods used for PPIE, levels of involvement, benefits and barriers of PPIE. Search strategy We searched Pubmed, EMBASE, Cochrane and PsycInfo using a comprehensive set of terms based on the concepts 'Patient and Public Involvement,' 'Health Research' and 'Pediatrics.' Inclusion criteria We included original research articles describing PPIE implementation in pediatric health research published in English or German between 01/2003-10/2024. Data extraction and synthesis Data was extracted using predefined categories and synthesized by narrative summary and thematic synthesis. PPIE reporting quality was assessed using the GRIPP2 short form checklist. Main results Out of 1910 references, we included 37 original research articles, representing 35 studies. PPIE participants were mostly children, adolescents or caregivers involved in all research stages, especially in study design (89%) and recruitment (51%). Key positive impacts of PPIE on research included enhanced recruitment and retention rates and personal benefits for PPIE participants. Barriers to PPIE were financial and time resources required and challenges in recruiting representative PPIE participants. The level of involvement and PPIE reporting quality varied highly between studies. Discussion Common benefits and barriers of PPIE exist across pediatric research disciplines. Reporting quality varied highly between studies. Conclusions PPIE is valuable in pediatric health research. Adherence to guidelines for conducting and reporting PPIE is important to enhance mutual learning. Patient or public contribution PPIE input contributed to the understandability of the lay summary. The findings of this review, together with parent and public input, will inform guidelines for future PPIE activities at the authors' institutions.
Background International studies exploring the enduring effects of early non-familial childhood care on mental health outcomes show varying impacts depending on the quality of care, age of entry, and socio-economic factors. Methods This German longitudinal study, involving 225 families, investigated the impact of early non-familial child care on the development of mental health problems, risk behaviors, and academic as well as vocational achievements in young adulthood (Mage = 22.6 years, SDage = 1.1 years). Results In comparison to parental care, early non-familial childcare was associated with significantly elevated levels of risky behaviors (such as risky sexual behavior, alcohol abuse, and tobacco consumption), low intimate relationship quality, and a higher likelihood of achieving advanced vocational qualifications. Migration background was identified as a relevant moderating factor in an exploratory analysis. An early age of entry into non-familial care was weakly associated with more mental health problems in young adulthood. Conclusion Parental decisions on early non-familial childcare should carefully consider the child's age of entry, the quality of care, and the family's socio-economic context.
