Archives of Disease in Childhood最新文献

Chimeric antigen receptor (CAR) T cell therapy is a promising form of adoptive cell therapy. This process re-engineers patient-derived T cells to express a hybrid receptor targeting a selected tumour-expressed antigen. CAR T cell therapy directed against the CD19 antigen has been highly successful in haematological malignancies that have failed other therapies, particularly relapsed B-cell acute lymphoblastic leukaemia (B-ALL). This review focuses on the numerous real-world aspects of treating children with B-ALL with CD19-targeted CAR T cell therapy. We discuss some of the considerations for clinicians including manufacturing time, administration and care of the patient receiving this novel therapy, toxicities and outcomes. We also discuss the therapeutic uncertainty many physicians now face of when to use CAR T cell therapy in the patient journey, especially when haematopoietic stem cell transplant is being considered.

Objective: To examine the views of adolescents with excess weight and parents of adolescents with excess weight towards weight and weight management.

Design: A qualitative study design using semi-structured phone interviews. The interviews were recorded, transcribed verbatim and analysed using reflexive thematic analysis to interpret the data.

Settings: Parents and adolescents based in the UK and recruited through schools, social media and youth centres.

Participants: Ten parents and 16 adolescents, including four linked parent-child dyads.

Results: Both parents and adolescents reported that adolescents felt societal pressure to achieve an 'ideal body' and that this pressure was the primary motivator for weight loss. All interviewed parents perceived themselves as overweight; however, those who had minimal weight-based shame were more likely to normalise weight discussions, reducing weight shame in their children. Adolescents preferred parents to display healthy behaviours rather than initiate weight-based discussions; however, they wanted to feel supported if the conversations were self-initiated.

Conclusion: Weight is a sensitive issue in intergenerational relationships, primarily driven by feelings of shame. Adolescents feel supported by a 'show not tell' approach from parents, which is more likely in families with less shame. While guidelines encourage clinicians to initiate weight-related conversations, this may not be welcomed by adolescents, although they do want confidence that they could access weight management support if they choose to seek help.

Background: Children and young people (CYP) with bone tumours often experience lengthy intervals prior to diagnosis that can lead to increased morbidity and mortality. Early diagnosis is key to optimising treatment options and long-term outcomes. This review aims to describe symptomatology at diagnosis, in order to develop interventions to accelerate diagnosis.

Methods: A literature search of MEDLINE and EMBASE was conducted for studies published between January 2008 and May 2023, reporting signs and symptoms in CYP with bone tumours. Pooled proportions of symptoms and signs were calculated.

Results: 16 studies (1452 patients; 492 osteosarcoma and 932 Ewing's sarcoma) were included in the analysis. The most prevalent symptoms were pain (64%, 95% CI 52% to 75%) and swelling (22%, 95% CI 6% to 42%). Other symptoms included fever, pain and swelling, history of trauma, pathological fracture, palpable mass, functional limitation, increased volume and limp. Subanalysis identified differences in symptom clusters: osteosarcoma more frequently presented with a history of trauma, pathological fracture, pain on weight-bearing, pain worse at night, pain at rest and weight loss. Ewing's sarcoma was associated with fever, functional limitation and a palpable mass.

Conclusions: These data highlight the differences in presentations between osteosarcoma and Ewing sarcoma, which may account for differences in survival and outcome. This will be used to inform professional and public health interventions through the Child Cancer Smart campaign to accelerate diagnosis for all. This review also highlights the need for a renewed research focus to identify patients earlier in the disease development as a strategy to improve the current static outcomes.

Objective: A process evaluation of the Children and Young People's Health Partnership (CYPHP) model of integrated care for the interpretation of trial findings and building evidence on the implementation of integrated care for children.

Design: A mixed-methods process evaluation.

Setting: CYPHP was implemented at scale across two inner-city London boroughs in South London, England, as a pragmatic cluster-randomised controlled trial involving nearly 98 000 children, with a nested process evaluation.

Participants: Linked data were available from 73 000 participants. Qualitative data collection was through 102 interviews (group and 1:1) and observations.

Interventions: Local child health clinics delivered by paediatricians and general practitioners and a nurse-led early intervention service for children with tracer conditions (asthma, eczema and constipation), decision support, a primary care hotline, self-management support and health promotion.

Main outcome measures: Five domains of the RE-AIM implementation framework: Reach, Effectiveness, Adoption, Implementation and Maintenance.

Results: Implementation varied depending on resource availability, competing priorities and natural changes over time. Successful implementation drivers included cohesive interprofessional and partnership collaboration.

Conclusions: Integrated care for children can be implemented at scale, but variability, particularly low reach, may limit measurable impact at the population level. Significant health system strengthening, implementation plasticity and contextual tailoring are crucial for ensuring the efficacy and sustainability of impactful integrated care for children.

Trial registration number: NCT03461848.

Objective: To examine trends in diagnosis of gender dysphoria and related conditions in children and young people attending primary care practices in England.

Design: Longitudinal analysis of electronic primary care records from the Clinical Practice Research Datalink (CPRD) Aurum database linked to hospital and Index of Multiple Deprivation data.

Setting: Primary care practices in England between 2011 and 2021.

Participants: 3782 patients aged 0-18 years with a recorded history of gender dysphoria/incongruence and matched comparators with autism spectrum conditions or eating disorder.

Main outcome measures: Incidence rates and prevalence of gender dysphoria/incongruence; prescribing rates for medical treatments; co-occurrence of anxiety, depression and self-harm.

Results: Between 2011 and 2021, incidence rates of recorded gender dysphoria/incongruence increased from 0.14 (95% CI 0.08 to 0.20) to 4.4 (95% CI 4.1 to 4.7) per 10 000 person years, and from 2014 the rate increased more rapidly in recorded females than males. There was no significant association between gender dysphoria/incongruence and area level deprivation. Of the 3782 children and young people with a record of gender dysphoria/incongruence, 176 (4.7%) were prescribed puberty suppressing hormones; 302 (8.0%) were prescribed masculinising/feminising hormones; and 1994 (52.7%) had a record of anxiety, depression or self-harm. Compared with matched comparators, those experiencing gender dysphoria/incongruence had similar recorded rates of anxiety and higher rates of depression and self-harm.

Conclusions: Recorded prevalence of gender dysphoria/incongruence increased substantially in children and young people between 2011 and 2021, particularly in recorded females. Levels of anxiety, depression and self-harm were high, indicating an urgent need for better prevention and treatment of mental health difficulties in these patients.

Objective: Complete congenital heart block (CHB) due to anti-Ro/La antibodies in pregnancy can lead to adverse fetal outcomes and neonatal death. National and international guidelines do not recommend specific treatment for women identified with anti-Ro antibodies while pregnant.

Design: Systematic review of studies of pregnant women with anti-Ro/La antibodies undertaking treatment(s) to prevent CHB. Studies solely focused on treating developing or established CHB were excluded.

Main outcome measure: CHB incidence.

Results: Of 1049 articles, 20 studies were eligible, of which 13 were retrospective. Sixteen studies contained usable data comparing various treatments (seven hydroxychloroquine (HCQ), six corticosteroids, two intravenous immunoglobulin (IVIG) and one each on combined HCQ and corticosteroids and plasmapheresis), including 2134 women and 2915 pregnancies. Meta-analysis was not possible due to heterogeneity. HCQ as primary prophylaxis showed protective effect on CHB incidence in four of five studies, whereas for preventing recurrence, only one study had a comparator arm, which showed a protective effect. Corticosteroids showed protective effect on CHB incidence as primary prophylaxis in two of three studies, whereas in recurrence, only one study showed protective effect. The IVIG study with a comparator showed no protective effect on CHB recurrence. Two studies (IVIG and plasmapheresis) had no comparator. The long-term toxicity of treatments was poorly investigated.

Conclusion: HCQ showed the most evidence among various treatment options to prevent CHB in babies of women with anti-Ro/La antibodies. However, included studies had high risk of bias and imprecision. Future studies should be prospective, compare existing treatments and capture adverse effects.PROSPERO registration number CRD42023492934.

Aim: Gender dysphoria (GD) refers to the psychological distress associated with the incongruence between one's sex and one's gender identity. To manage GD, individuals may delay the development of primary and secondary sex characteristics with the use of puberty blockers. In this systematic review, we assess and summarise the certainty of the evidence about the effects of puberty blockers in individuals experiencing GD.

Methods: We searched Medline, Embase, PsychINFO, Social Sciences Abstracts, LGBTQ+ Source and Sociological Abstracts from inception to September 2023. We included observational studies comparing puberty blockers with no puberty blockers in individuals aged <26 years experiencing GD, as well as before-after and case series studies. Outcomes of interest included psychological and physical outcomes. Pairs of reviewers independently screened articles, abstracted data and assessed risk of bias. We performed a meta-analysis and assessed the certainty of a non-zero effect using the grading of recommendations assessment, development and evaluation (GRADE) approach.

Results: We included 10 studies. Comparative observational studies (n=3), comparing puberty blockers versus no puberty blockers, provided very low certainty of evidence on the outcomes of global function and depression. Before-after studies (n=7) provided very low certainty of evidence addressing gender dysphoria, global function, depression, and bone mineral density.

Conclusions: There remains considerable uncertainty regarding the effects of puberty blockers in individuals experiencing GD. Methodologically rigorous prospective studies are needed to understand the effects of this intervention.

Trial registration number: PROSPERO CRD42023452171.

Objective: To explore quality of life outcomes for caregivers of children with childhood dementia including the positive and negative impact of caregiving. The secondary aim was to explore caregivers' perspectives on healthcare services for children with dementia.

Design: Cross-sectional, mixed-methods study with analyses of quantitative and qualitative data collected via online survey.

Setting: Australian tertiary referral children's hospitals, clinics and community advocacy groups.

Patients: 40 caregivers of children with dementia.

Interventions: The survey was developed by a multidisciplinary team of clinicians including paediatric neurologists and behavioural scientists with experience in caring for families with childhood dementias and mixed-methods research.

Main outcome measures: Surveys assessed caregiver-reported health-related quality of life, psychological distress, the impacts of caregiving and perspectives on healthcare services and how they may be improved for children with dementia.

Results: Psychological distress was reported by 72.5%, caregiver stress by 67%, chronic pain or discomfort by 43% and for 87.5% their child's condition had a moderate or severe impact on their ability to do regular daily activities. Caregivers voiced a desire for more integrated care, increased general awareness and education around childhood dementia and a greater need for more trained support services.

Conclusions: Caregivers of children with dementia experience high levels of psychological distress, physical and social consequences. This study highlights the need for integrated care and psychosocial support to efficiently connect children and families with appropriate healthcare services and resources.

Objectives: To determine (1) which maternal and area characteristics are associated with reaching fidelity targets (the expected number of visits mothers should receive at each stage of the programme) in the Family-Nurse Partnership (FNP), and (2) whether achieving these fidelity targets affects outcomes.

Design, setting and population: Cohort study of mothers enrolled in the FNP, aged 13-19 years, giving birth between April 2010 and January 2018 in England. Mothers were linked to their Hospital Episode Statistics and National Pupil Database records.

Outcomes: We described whether mothers reached fidelity targets for each programme stage (pregnancy, infancy and toddlerhood) and explored the characteristics associated with reaching targets. We used generalised linear models to compare child and maternal outcomes between mothers who did and did not reach fidelity targets.

Results: Of the 28 155 mothers enrolled, 58% completed the programme. Fidelity targets were met by 59% of mothers in pregnancy, 65% in infancy and 61% in toddlerhood. The median number of visits was 38 (median 43 hours contact time). Younger mothers, those with a history of unplanned hospital admissions for adversity and those with social care involvement received a greater number of visits. Meeting fidelity targets was associated with a reduction in subsequent births within 18 months and an increase in the number of children with unplanned hospital admissions for maltreatment or injury up to age 2.

Conclusions: Achieving fidelity to the FNP is challenging, but family nurses are able to engage the most vulnerable mothers in the programme. More research is needed to understand whether fidelity to programme targets is a useful measure of mothers' experiences of intensive home visiting.