Mental capacity assessment in the multi-professional real world: a qualitative study of six areas of uncertainty.

Background: The Mental Capacity Act 2005 of England and Wales is a ground-breaking piece of legislation with reach into healthcare, social care and legal settings. Professionals have needed to develop skills to assess mental capacity and handle malign influence, but it is unclear how assessments are implemented in real world settings. Our previously reported survey found professionals juggling competing resources in complex systems, often struggling to stay up to date with law.

Training and supervision of physical health professionals to implement mental health care in paediatric epilepsy clinics.

Background: Children and young people with epilepsy are more likely to experience multiple mental health problems than those without chronic physical health conditions, yet they often do not receive evidence-based (or indeed any) psychological interventions. Integrated healthcare is recommended as a solution to address these inequalities, but remains limited in the United Kingdom. This is partly due to the lack of training and availability of ongoing supervision for clinicians to ensure the safe and effective delivery of treatments.

Barriers to initiating and implementing palliative and end-of-life care for children with life-limiting conditions: a mixed-methods study in a UK children's hospital.

Background: To ensure that children with life-limiting conditions (LLC) and their families have access to a palliative care pathway from diagnosis to death and bereavement, a better understanding of the challenges experienced by paediatric healthcare professionals caring for children with LLC is needed.

Aim: To explore the barriers paediatricians face in initiating and implementing palliative and end-of-life care for children with LLC.

Methods: Due to the challenges of COVID-19, the study was performed as a service evaluation using semi-structured interviews and an online questionnaire with consultant paediatricians in general paediatrics, community paediatrics and multiple subspecialties at a UK children's hospital between December 2020 and August 2021.

How I treat infant acute lymphoblastic leukemia.

Infant acute lymphoblastic leukemia (ALL) is an aggressive malignancy that has historically been associated with a very poor prognosis. Despite large cooperative international trials and incremental increases in intensity of therapy, there has been no significant improvement in outcome over the last 3 decades. Using representative cases, we highlight the key differences between KMT2A-rearranged and KMT2A-germ line infant ALL, and how advances in molecular diagnostics are unpicking KMT2A-germ line genetics and guiding treatment reduction.

Delivery of a national prenatal exome sequencing service in England: a mixed methods study exploring healthcare professionals' views and experiences.

Introduction: In October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England, requiring the coordination of care from specialist genetics, fetal medicine (FM) and laboratory services. This mixed methods study explored the experiences of professionals involved in delivering the pES service during the first 2 years of its delivery in the NHS.

Methods: A survey ( = 159) and semi-structured interviews ( = 63) with healthcare professionals, including clinical geneticists, FM specialists, and clinical scientists (interviews only) were used to address: 1) Views on the pES service; 2) Capacity and resources involved in offering pES; 3) Awareness, knowledge, and educational needs; and 4) Ambitions and goals for the future.

Using diffusion MRI to understand white matter damage and the link between brain microstructure and cognitive deficits in paediatric medulloblastoma patients.

Purpose: Survivors of medulloblastoma face a range of challenges after treatment, involving behavioural, cognitive, language and motor skills. Post-treatment outcomes are associated with structural changes within the brain resulting from both the tumour and the treatment. Diffusion magnetic resonance imaging (MRI) has been used to investigate the microstructure of the brain.

Pediatric cervical spine instability: evolving concepts.

The pediatric cervical spine is structurally and biomechanically unique in comparison to adults. Guidelines to assess for cervical spine instability and standard of care treatments in the pediatric population have yet to be delineated. This is due to the rarity of the condition and the lack of multicenter data published on the topic.

"How I would like AI used for my imaging": children and young persons' perspectives.

Objectives: Artificial intelligence (AI) tools are becoming more available in modern healthcare, particularly in radiology, although less attention has been paid to applications for children and young people. In the development of these, it is critical their views are heard.

Materials And Methods: A national, online survey was publicised to UK schools, universities and charity partners encouraging any child or young adult to participate.

One- and Two-year Multidisciplinary Follow-Up of MIS-C at a Tertiary Hospital: A Retrospective Cohort Study.

Background: Although 6-month follow-up of patients with multisystem inflammatory syndrome in children (MIS-C) was reassuring, there is scant data on long-term sequelae, including whether changing variants affect clinical severity and outcomes.

Methods: Children (<18 years of age) admitted to Great Ormond Street Hospital between April 4, 2020, and January 2023, meeting diagnostic criteria for MIS-C were included. Admission and follow-up data were categorized by the predominant SARS-CoV-2 circulating variant in the United Kingdom.

RNA Therapy for Oncogenic NRAS-Driven Nevi Induces Apoptosis.

RAS proteins regulate cell division, differentiation, and apoptosis through multiple downstream effector pathways. Oncogenic RAS variants are the commonest drivers in cancers; however, they also drive many benign lesions predisposing to malignancy, such as melanocytic nevi, thyroid nodules, and colonic polyps. Reversal of these benign lesions could reduce cancer incidence; however, the effects of oncogenic RAS have been notoriously difficult to target with downstream pathway inhibitors.

Added value of postmortem mri in sudden unexpected infant death cases.

We aimed to investigate the potential added value of postmortem MRI (PMMRI) in sudden unexpected infant death (SUID) cases referred to our center between September 2020 and June 2023. Ultimately, 19 SUID cases underwent PMMRI alongside standard autopsy procedures, which included technical examinations such as postmortem CT (PMCT). Four radiologists, two with prior PMMRI experience, provided structured reports following consensus.

Interventional oncology in children: Where are we now?

Paediatric Interventional Oncology (IO) lags behind adult IO due to a scarcity of specific outcome data. The suboptimal way to evolve this field is relying heavily on adult experiences. The distinct tumour types prevalent in children, such as extracranial germ cell tumours, sarcomas, and neuroblastoma, differ strongly from those found in adults, presenting a completely different biological behaviour.

Long-term teduglutide associated with improved response in pediatric short bowel syndrome-associated intestinal failure.

Objectives: Patients with short bowel syndrome-associated intestinal failure (SBS-IF) require long-term parenteral nutrition and/or intravenous fluids (PN/IV) to maintain fluid or nutritional balance. We report the long-term safety, efficacy, and predictors of response in pediatric patients with SBS-IF receiving teduglutide over 96 weeks.

Methods: This was a pooled, post hoc analysis of two open-label, long-term extension (LTE) studies (NCT02949362 and NCT02954458) in children with SBS-IF.

A female patient with Dent disease due to skewed X-chromosome inactivation.

X-linked proximal tubulopathies are rare diseases that predominantly affect men. Women are generally carriers and clinical or biochemical manifestations are usually absent or mild. We present the case of a young woman who presented with a full phenotype of Dent disease type 1 due to a de novo mutation in the gene and a skewed X-chromosome inactivation.

Mitochondrial membrane synthesis, remodelling and cellular trafficking.

Mitochondria are dynamic cellular organelles with complex roles in metabolism and signalling. Primary mitochondrial disorders are a group of approximately 400 monogenic disorders arising from pathogenic genetic variants impacting mitochondrial structure, ultrastructure and/or function. Amongst these disorders, defects of complex lipid biosynthesis, especially of the unique mitochondrial membrane lipid cardiolipin, and membrane biology are an emerging group characterised by clinical heterogeneity, but with recurrent features including cardiomyopathy, encephalopathy, neurodegeneration, neuropathy and 3-methylglutaconic aciduria.

Phase 1/2 AAV5-hRKp.RPGR (Botaretigene Sparoparvovec) Gene Therapy: Safety and Efficacy in RPGR-Associated X-Linked Retinitis Pigmentosa.

Purpose: To assess the safety and efficacy of AAV5-hRKp.RPGR in participants with retinitis pigmentosa GTPase regulator (RPGR)-associated X-linked retinitis pigmentosa (XLRP).

Design: Open-label, phase 1/2 dose escalation/expansion study (ClinicalTrials.

Diagnostic pathway and management of first seizures in infants with Sturge-Weber syndrome.

Aim: Sturge-Weber syndrome (SWS) is a rare neurocutaneous syndrome, frequently associated with pharmaco-resistant, early-onset epilepsy. Optimal seizure control is paramount to maximize neurodevelopment.

Method: A single-centre case series of 49 infants explored early SWS care.

Household material hardship and distress among parents of children with advanced cancer: A report from the PediQUEST Response trial.

Background: The prevalence and characteristics of household material hardship (HMH) in families of children with advanced cancer and its association with parent distress are unknown and herein described.

Methods: Parents of children aged ≥2 years with advanced cancer at five cancer centers completed baseline surveys as part of the PediQUEST Response trial. HMH (housing, energy, and food) was operationalized as binary (≥1 HMH domains), ordinal (zero, one, or two or more HMH domains), and housing based (none, nonhousing [food and/or energy], only housing, or housing + other).

Non-syndromic retinal dystrophy associated with biallelic variation of SUMF1 and reduced leukocyte sulfatase activity.

Biallelic variants in SUMF1 are associated with multiple sulfatase deficiency (MSD), a rare lysosomal storage disorder typically diagnosed in early infancy or childhood, marked by severe neurodegeneration and early mortality. We present clinical and molecular characterisation of three unrelated patients aged 13 to 58 years with milder clinical manifestations due to SUMF1 disease variants, including two adult patients presenting with apparent non-syndromic retinal dystrophy. Whole genome sequencing identified biallelic SUMF1 variants in all three patients; Patient 1 homozygous for a complex allele c.