Experience sampling methodology study of anxiety and depression in adolescents with epilepsy: The role of metacognitive beliefs and perseverative thinking.

Emotional distress is common in young people with epilepsy (YPwE). According to the Self-Regulatory Executive Function (S-REF) model, maladaptive metacognitive beliefs and perseverative thinking are fundamental in the development and maintenance of emotional distress. As emotional distress and perseverative thinking can highly fluctuate over short intervals in YPwE, it is important to account for this variability when testing the utility of psychological models. Experience sampling methodology (ESM) was therefore used to explore the momentary relationship between metacognitive beliefs, perseverative thinking, and emotional distress in YPwE. Eighteen participants diagnosed with epilepsy (aged 12-17 years) completed the 10-day ESM period. Participants were prompted to complete the ESM assessment five times daily. The ESM assessment assessed participant's momentary levels of metacognitive beliefs, perseverative thinking (i.e., worry and rumination), and emotional distress (i.e., anxiety and depression). A series of multilevel regression analyses indicated that metacognitive beliefs were significantly positively associated with worry, rumination, anxiety and depression. After controlling for worry and rumination, respectively, metacognitive beliefs did not account for additional variance in anxiety or depression. Findings provide preliminary support for the utility of the S-REF model for emotional distress in YPwE. Metacognitive therapy, which is underpinned by the S-REF model, may be an appropriate intervention for emotional distress in YPwE. Future studies should assess the mediational relationship between metacognitive beliefs, perseverative thinking, and emotional distress using time-lagged models.

Genome-wide association studies of toxicity to oxaliplatin and fluoropyrimidine chemotherapy with or without cetuximab in 1800 patients with advanced colorectal cancer.

Chemotherapies administered at normal therapeutic dosages can cause significant side-effects and may result in early treatment discontinuation. Inter-individual variation in toxicity highlights the need for biomarkers to personalise treatment. We sought to identify such biomarkers by conducting 40 genome-wide association studies, together with gene and gene set analyses, for any toxicity and 10 individual toxicities in 1800 patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidine chemotherapy ± cetuximab from the MRC COIN and COIN-B trials (385 patients received FOLFOX, 360 FOLFOX + cetuximab, 707 XELOX and 348 XELOX + cetuximab). Single nucleotide polymorphisms (SNPs), genes and gene sets that reached genome-wide or suggestive significance were validated in independent patient groups. We found that MROH5 was significantly associated with neutropenia in MAGMA gene analyses in patients treated with XELOX (P = 6.6 × 10-7 ) and was independently validated in those receiving XELOX + cetuximab; pooled P = 3.7 × 10-7 . rs13260246 at 8q21.13 was significantly associated with vomiting in patients treated with XELOX (odds ratio = 5.0, 95% confidence interval = 3.0-8.3, P = 9.8 × 10-10 ) but was not independently replicated. SNPs at 139 loci had suggestive associations for toxicities and lead SNPs at five of these were independently validated (rs6030266 with diarrhoea, rs1546161 with hand-foot syndrome, rs9601722 with neutropenia, rs13413764 with lethargy and rs4600090 with nausea; all with pooled P's < 5.0 × 10-6 ). In conclusion, the association of MROH5 with neutropenia and five other putative biomarkers warrant further investigation for their potential clinical utility. Despite our comprehensive genome-wide analyses of large, well-characterised, clinical trials, we found a lack of common variants with modest effect sizes associated with toxicities.

ß-Glucan is a major growth substrate for human gut bacteria related to Coprococcus eutactus.

A clone encoding carboxymethyl cellulase activity was isolated during functional screening of a human gut metagenomic library using Lactococcus lactis MG1363 as heterologous host. The insert carried a glycoside hydrolase family 9 (GH9) catalytic domain with sequence similarity to a gene from Coprococcus eutactus ART55/1. Genome surveys indicated a limited distribution of GH9 domains among dominant human colonic anaerobes. Genomes of C. eutactus-related strains harboured two GH9-encoding and four GH5-encoding genes, but the strains did not appear to degrade cellulose. Instead, they grew well on ß-glucans and one of the strains also grew on galactomannan, galactan, glucomannan and starch. Coprococcus comes and Coprococcus catus strains did not harbour GH9 genes and were not able to grow on ß-glucans. Gene expression and proteomic analysis of C. eutactus ART55/1 grown on cellobiose, ß-glucan and lichenan revealed similar changes in expression in comparison to glucose. On ß-glucan and lichenan only, one of the four GH5 genes was strongly upregulated. Growth on glucomannan led to a transcriptional response of many genes, in particular a strong upregulation of glycoside hydrolases involved in mannan degradation. Thus, ß-glucans are a major growth substrate for species related to C. eutactus, with glucomannan and galactans alternative substrates for some strains.

The discovery and optimization of benzimidazoles as selective NaV1.8 blockers for the treatment of pain.

The voltage gated sodium channel NaV1.8 has been postulated to play a key role in the transmission of pain signals. Core hopping from our previously reported phenylimidazole leads has allowed the identification of a novel series of benzimidazole NaV1.8 blockers. Subsequent optimization allowed the identification of compound 9, PF-06305591, as a potent, highly selective blocker with an excellent preclinical in vitro ADME and safety profile.

The Improving Rural Cancer Outcomes Trial: a cluster-randomised controlled trial of a complex intervention to reduce time to diagnosis in rural cancer patients in Western Australia.

This corrects the article DOI: 10.1038/bjc.2017.310.

The Improving Rural Cancer Outcomes Trial: a cluster-randomised controlled trial of a complex intervention to reduce time to diagnosis in rural cancer patients in Western Australia.

BACKGROUND: Rural Australians have poorer survival for most common cancers, due partially to later diagnosis. Internationally, several initiatives to improve cancer outcomes have focused on earlier presentation to healthcare and timely diagnosis. We aimed to measure the effect of community-based symptom awareness and general practice-based educational interventions on the time to diagnosis in rural patients presenting with breast, prostate, colorectal or lung cancer in Western Australia. METHODS: 2 × 2 factorial cluster randomised controlled trial. Community Intervention: cancer symptom awareness campaign tailored for rural Australians. GP intervention: resource card with symptom risk assessment charts and local cancer referral pathways implemented through multiple academic detailing visits. Trial Area A received the community symptom awareness and Trial Area B acted as the community campaign control region. Within both Trial Areas general practices were randomised to the GP intervention or control. PRIMARY OUTCOME: total diagnostic interval (TDI). RESULTS: 1358 people with incident breast, prostate, colorectal or lung cancer were recruited. There were no significant differences in the median or ln mean TDI at either intervention level (community intervention vs control: median TDI 107.5 vs 92 days; ln mean difference 0.08 95% CI -0.06-0.23 P=0.27; GP intervention vs control: median TDI 97 vs 96.5 days; ln mean difference 0.004 95% CI -0.18-0.19 P=0.99). There were no significant differences in the TDI when analysed by factorial design, tumour group or sub-intervals of the TDI. CONCLUSIONS: This is the largest trial to test the effect of community campaign or GP interventions on timeliness of cancer diagnosis. We found no effect of either intervention. This may reflect limited dose of the interventions, or the limited duration of follow-up. Alternatively, these interventions do not have a measurable effect on time to cancer diagnosis.

Exploring the role of knowledge of condition and psycho-social profiles of young people with epilepsy during transition.

Transitioning from paediatric to adult care can be a particularly challenging time for young people with epilepsy and research has shown that there are a range of factors which may influence a young person's ability to successfully cope with this difficult time. The following study aimed to explore the psychosocial characteristics of this transitioning population, as well as investigate how knowledgeable the young person and their parent/carer are of their own condition throughout transition. Young people with epilepsy were recruited from two specialist epilepsy clinics in the North West and allocated to one of three groups; Group 1 pre-transition, Group 2 transitioning, and Group 3 post-transition. Results found that the young person's knowledge increased significantly throughout transition, whilst parent/carer's knowledge decreased. In addition, anxiety was found to be significantly lower in Group 2 (transitioning group) compared to Group 1 (pre-transition) and Group 3 (post-transition) and a number of significant gender differences were also identified across the groups. The study highlights the importance of considering all relevant psychosocial factors, such as anxiety, gender and the degree of knowledge the individual holds of their own condition during the transition process in order to develop psycho-educational programmes and transition pathways.

The experiences of parenting a child with an acquired brain injury: A meta-synthesis of the qualitative literature.

OBJECTIVE: To systematically review and then synthesize the qualitative literature on the experience of parenting a child with an acquired brain injury (ABI). DESIGN: Systematic literature review and meta-synthesis Methods. A systematic search of the literature was conducted in four databases. Papers which met the inclusion criterion were assessed for quality using the Critical Skills Appraisal Programme (CASP) tool and then synthesized according to Noblit and Hare's (1988) guidelines for meta-ethnography. RESULTS: Of the 4855 papers retrieved, 17 met the inclusion criteria. Synthesis resulted in three themes: (1) Disconnection: Cut off from internal emotions and isolated from others; (2) Seeking understanding and support to manage in an insecure world; and (3) New parent to a different child. CONCLUSIONS: Having a child with an ABI leads to many challenges for parents. These include feeling insecure, isolated from others and struggling to adapt to the different roles required to parent their different child. Clinical implications highlight the need for specialist support that is ongoing after discharge, including specialist knowledge and understanding of ABI and opportunities for peer support.

Review of psychological effects of dog bites in children.

BACKGROUND: Dog bites are a concerning health problem in children and one of the leading causes of non-fatal injuries in this population. Dog attacks not only cause physical injuries but can also lead to long-term psychological problems. A review was performed to investigate the scope of literature on the psychological effects of dog bites on a paediatric population. METHODS: A literature search was performed on Web of Knowledge database between 1982 to June 2023, returning 249 results. 14 primary studies reporting the psychological consequences of dog bites in children or adolescents were classed as eligible and 9 further studies were added from prior knowledge and bibliographical searches. 23 studies involving 1894 participants met the criteria and were included in this review. RESULTS: Of these 23 studies, 8 were case studies or small case series reports (up to n=4), 14 larger descriptive studies and 1 analytical cross-sectional study. There was a mixture of retrospective and prospective data-gathering. The most common psychological consequences of dog bites in children were post-traumatic stress disorder, dog phobia, nightmares and symptoms of anxiety and avoidance behaviours. CONCLUSIONS: Studies on dog bites in a paediatric population with a specific focus on the psychological consequences associated with dog bites and their management are sparse. Future research and practice should more greatly consider the psychological impact on child victims of dog bites and their family members, as well as their management to avoid the development of mental health issues and improve their quality of life. Future research also needs to ascertain the efficacy of using virtual reality in treating children with dog phobia.

Developing a core outcome set for the health outcomes for children and adults with congenital oesophageal atresia and/or tracheo-oesophageal fistula: OCELOT task group study protocol.

INTRODUCTION: Heterogeneity in reported outcomes of infants with oesophageal atresia (OA) with or without tracheo-oesophageal fistula (TOF) prevents effective data pooling. Core outcome sets (COS) have been developed for many conditions to standardise outcome reporting, facilitate meta-analysis and improve the relevance of research for patients and families. Our aim is to develop an internationally-agreed, comprehensive COS for OA-TOF, relevant from birth through to transition and adulthood. METHODS AND ANALYSIS: A long list of outcomes will be generated using (1) a systematic review of existing studies on OA-TOF and (2) qualitative research with children (patients), adults (patients) and families involving focus groups, semistructured interviews and self-reported outcome activity packs. A two-phase Delphi survey will then be completed by four key stakeholder groups: (1) patients (paediatric and adult); (2) families; (3) healthcare professionals; and (4) researchers. Phase I will include stakeholders individually rating the importance and relevance of each long-listed outcome using a 9-point Likert scale, with the option to suggest additional outcomes not already included. During phase II, stakeholders will review summarised results from phase I relative to their own initial score and then will be asked to rescore the outcome based on this information. Responses from phase II will be summarised using descriptive statistics and a predefined definition of consensus for inclusion or exclusion of outcomes. Following the Delphi process, stakeholder experts will be invited to review data at a consensus meeting and agree on a COS for OA-TOF. ETHICS AND DISSEMINATION: Ethical approval was sought through the Health Research Authority via the Integrated Research Application System, registration no. 297026. However, approval was deemed not to be required, so study sponsorship and oversight were provided by Alder Hey Children's NHS Foundation Trust. The study has been prospectively registered with the COMET Initiative. The study will be published in an open access forum.

The tumor multi-omic landscape of endometrial cancers developed on a germline genetic background of adiposity.

High body mass index (BMI) is a causal risk factor for endometrial cancer but the tumor molecular mechanisms affected by adiposity and their therapeutic relevance remain poorly understood. Here we characterize the tumor multi-omic landscape of endometrial cancers that have developed on a background of lifelong germline genetic exposure to elevated BMI. We built a polygenic score (PGS) for BMI in women using data on independent, genome-wide significant variants associated with adult BMI in 434,794 women. We performed germline (blood) genotype quality control and imputation on data from 354 endometrial cancer cases from The Cancer Genome Atlas (TCGA). We assigned each case in this TCGA cohort their genetically predicted life-course BMI based on the BMI PGS. Multivariable generalized linear models adjusted for age, stage, microsatellite status and genetic principal components were used to test for associations between the BMI germline PGS and endometrial cancer tumor genome-wide genomic, transcriptomic, proteomic, epigenomic and immune traits in TCGA. High BMI germline PGS was associated with (i) upregulated tumor gene expression in the IL6-JAK-STAT3 pathway (FDR=4.2×10-7); (ii) increased estimated intra-tumor activated mast cell infiltration (FDR=0.008); (iii) increased single base substitution (SBS) mutational signatures 1 (FDR=0.03) and 5 (FDR=0.09) and decreased SBS13 (FDR=0.09), implicating age-related and APOBEC mutagenesis, respectively; and (iv) decreased tumor EGFR protein expression (FDR=0.07). Alterations in IL6-JAK-STAT3 signaling gene and EGFR protein expression were, in turn, significantly associated with both overall survival and progression-free interval. Thus, we integrated germline and somatic data using a novel study design to identify associations between genetically predicted lifelong exposure to higher BMI and potentially actionable endometrial cancer tumor molecular features. These associations inform our understanding of how high BMI may influence the development and progression of this cancer, impacting endometrial tumor biology and clinical outcomes.

Intravenous immunoglobulin treatment in childhood encephalitis (IgNiTE): a randomised controlled trial.

OBJECTIVE: To investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness. DESIGN: Phase 3b multicentre, double-blind, randomised placebo-controlled trial. SETTING: Twenty-one hospitals in the UK. PARTICIPANTS: Children aged 6 months to 16 years with a diagnosis of acute or subacute encephalitis, with a planned sample size of 308. INTERVENTION: Two doses (1 g/kg/dose) of either IVIG or matching placebo given 24-36 hours apart, in addition to standard treatment. MAIN OUTCOME MEASURE: The primary outcome was a 'good recovery' at 12 months after randomisation, defined as a score of≤2 on the Paediatric Glasgow Outcome Score Extended. SECONDARY OUTCOME MEASURES: The secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and IVIG safety data. RESULTS: 18 participants were recruited from 12 hospitals and randomised to receive either IVIG (n=10) or placebo (n=8) between 23 December 2015 and 26 September 2017. The study was terminated early following withdrawal of funding due to slower than anticipated recruitment, and therefore did not reach the predetermined sample size required to achieve the primary study objective; thus, the results are descriptive. At 12 months after randomisation, 9 of the 18 participants (IVIG n=5/10 (50%), placebo n=4/8 (50%)) made a good recovery and 5 participants (IVIG n=3/10 (30%), placebo n=2/8 (25%)) made a poor recovery. Three participants (IVIG n=1/10 (10%), placebo n=2/8 (25%)) had a new diagnosis of epilepsy during the study period. Two participants were found to have specific autoantibodies associated with autoimmune encephalitis. No serious adverse events were reported in participants receiving IVIG. CONCLUSIONS: The IgNiTE (ImmunoglobuliN in the Treatment of Encephalitis) study findings support existing evidence of poor neurological outcomes in children with encephalitis. However, the study was halted prematurely and was therefore underpowered to evaluate the effect of early IVIG treatment compared with placebo in childhood encephalitis. TRIAL REGISTRATION NUMBER: Clinical Trials.gov NCT02308982; ICRCTN registry ISRCTN15791925.

Interventions and methods to prepare, educate or familiarise children and young people for radiological procedures: a scoping review.

Children attending hospital for radiological procedures can experience uncertainty, anxiety and distress; this can result in sub-optimal experiences for children, poor scan quality and the need for radiological procedures to be rescheduled or sedation to be used. The preparation and education of children before clinical procedures has been shown to have a positive influence on procedural outcomes. This scoping review aimed to locate and examine the evidence relating to non-invasive interventions and methods to prepare, educate and familiarise children for radiological procedures within a healthcare setting. A comprehensive search strategy identified 36 articles. A narrative synthesis approach was adopted to make sense of the key findings. Studies investigated a range of radiological procedures (MRI, plain radiographs, CT, fluoroscopy and Micturating cystourethrogram) using a wide range of interventions (smartphone applications, storybooks, videos, mock scanners) which varied by method, mode of delivery and target audience. The outcomes used to evaluate the value and impact of the interventions are wide, varied and inconsistently applied making it difficult to judge which interventions offer the optimal impact on scan quality, scan completion and children's experiences. This review highlights that there is a need to further understand which specific elements of the non-invasive interventions 'work best' for children. There is a need for consistency on the outcomes measured and for these measures to include child-centred outcomes alongside scan quality and length of radiological procedure.

Parents' experiences of their child's assessment on an epilepsy surgery pathway: A qualitative study.

PURPOSE: Children's epilepsy surgery services (CESS) in the UK aim to improve outcomes for young children by increasing access to surgery. Consideration for surgery is complex and time consuming, yet there is lack of research exploring how this process might impact on families. This study aimed to explore parents' experiences of their child consideration for epilepsy surgery to inform future service development and delivery. METHODS: Semi-structured interviews with parents of children (aged < six years) considered for surgery within the previous three years. Recruitment was through social media and purposive sampling of medical records. Data were analysed using a thematic and iterative approach. RESULTS: 15 parents of 14 children were interviewed (13 mothers and 2 fathers). Initial discussions of epilepsy surgery were described as 'shocking' but also as a source of hope. However, unclear communication between staff and parents, including lack of information about the steps, assessments/investigations and timeframes involved in the process of assessment for surgery led to some feeling 'out of control,' uncertain and in some cases distressed. Parents described examples of positive support from staff, yet many felt they needed additional general and emotional support throughout the epilepsy surgery pathway. CONCLUSIONS: Findings highlight the importance of providing clear and consistent information about the epilepsy surgery assessment to minimise parental distress and help facilitate a sense of control. Recommendations include providing parents with advance warning that surgery will be discussed at their next appointment, improved access to psychosocial and clinical psychological support and a step-by-step guide of the process with realistic timelines.

A genome-wide search for determinants of survival in 1926 patients with advanced colorectal cancer with follow-up in over 22,000 patients.

BACKGROUND: While genome-wide association studies (GWAS) have identified germline variants influencing the risk of developing colorectal cancer (CRC), there has been limited examination of the possible role of inherited variation as a determinant of patient outcome. PATIENTS AND METHODS: We performed a GWAS for overall survival (OS) in 1926 patients with advanced CRC from the COIN and COIN-B clinical trials. For single nucleotide polymorphisms (SNPs) showing an association with OS (P < 1.0 × 10-5), we conducted sensitivity analyses based on the time from diagnosis to death and sought independent replications in 5675 patients from the Study of Colorectal Cancer in Scotland (SOCCS) and 16,964 patients from the International Survival Analysis in Colorectal cancer Consortium (ISACC). We analysed the Human Protein Atlas to determine if ERBB4 expression was associated with survival in 438 patients with colon adenocarcinomas. RESULTS: The most significant SNP associated with OS was rs79612564 in ERBB4 (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 1.16-1.32, P = 1.9 × 10-7). SNPs at 17 loci had suggestive associations for OS and all had similar effects on the time from diagnosis to death. No lead SNPs were independently replicated in the meta-analysis of all patients from SOCCS and ISACC. However, rs79612564 was significant in stage-IV patients from SOCCS (P = 2.1 × 10-2) but not ISACC (P = 0.89) and SOCCS combined with COIN and COIN-B attained genome-wide significance (P = 1.7 × 10-8). Patients with high ERBB4 expression in their colon adenocarcinomas had worse survival (HR = 1.50, 95% CI = 1.1-1.9, P = 4.6 × 10-2). CONCLUSIONS: Genetic and expression data support a potential role for rs79612564 in the receptor tyrosine kinase ERBB4 as a predictive biomarker of survival.

Probing intracellular oxygen by quenched phosphorescence lifetimes of nanoparticles containing polyacrylamide-embedded [Ru(dpp(SO3Na)2)3]Cl2.

Methods for measuring O(2) within living cells that rely on luminescent probes are hampered by several factors: local conditions of hydrophobicity, pH, ionic composition, dielectric constant, and photobleaching by free radical species. Use of a polymer-embedded luminophore should minimize these problems. Here we use a Ru(II) coordination complex embedded within 45 nm hydrodynamic diameter nanoparticles, and demonstrate that both phosphorescence intensity and lifetimes are O(2)-sensitive, both in aqueous suspensions and intracellularly (e.g. 4.06 versus 1.55 microseconds under anaerobic or aerobic conditions, respectively). Electroporation is necessary for incorporation of the nanoparticles into yeasts: it is more effective with the fission yeast, Schizosaccharomyces pombe, than for the budding yeast, Saccharomyces cerevisiae. However, electroporation was not required for particle uptake into a cultured human cell-line (mammary adenosarcoma MCF-7), although the intracellular distribution of the probe is more general to intracellular compartments when electroporation is employed. These procedures did not compromise vitality of cells over periods of 6 h, as judged by retention of structural characteristics evident in Nomarski interference or confocal microscopy images. Spatial resolution of intracellular structures defined by nanoparticle phosphorescence intensity imaging indicates potential usefulness of the application of lifetime imaging techniques for mapping of intracellular O(2) distributions.

Uptake and localisation of rhenium fac-tricarbonyl polypyridyls in fluorescent cell imaging experiments.

The synthesis of a series of rhenium fac tricarbonyl bisimine complexes and their application as lumophores in fluorescence imaging of yeast and human adenocarcinoma cells is reported. A wide range of complexes are synthesised with varying charges and lipophilicities, all of which have photophysical properties which make them suitable as cell imaging agents. After attempts to apply these as imaging agents in various strains of yeast which showed limited uptake, an investigation was undertaken of their applications as imaging agents in mammalian cells. In general the uptake was high and short-term toxicity and photobleaching appear to be low. The patterns of uptake and localisation are correlated with structural and electronic features of the complexes in an attempt to establish ground-rules for the design and application of rhenium complexes in imaging of eukaryotes.

Child and parent experiences of childhood epilepsy surgery and adjustment to life following surgery: A qualitative study.

PURPOSE: Surgical procedures are increasingly used as a treatment option for paediatric patients with refractory epilepsy as seizure relief is often assumed to be associated with positive psychosocial and quality of life outcomes. This study aimed to explore children's and parents' experiences of epilepsy surgery and associated psychosocial outcomes. METHODS: Semi-structured interviews were conducted with parents and their children aged between 7 and 17 years old, who had undergone epilepsy surgery within the previous six months to three years. Analysis of interview data was interpretive and iterative, using the constant comparison approach, to develop a rich understanding of family experiences throughout the surgery journey. RESULTS: Interviews were conducted with 16 participants including seven children (aged 8-15 years) and their nine parents. Epilepsy had significant impact on quality of life for children and parents. Concerns about long term wellbeing, risks to safety and hope for a 'normal' life contributed to the decision to pursue surgery. All participants described improvements in seizure control, alongside improved psychological wellbeing, quality of life, social relationships and family functioning. However, children and their parents experienced difficulties adjusting to a new post-surgical identity and 'missing' aspects of their pre-surgical life with epilepsy. CONCLUSIONS: Epilepsy surgery had a positive impact on participants' lives, but families described difficulties in adjusting to postsurgical changes and leading a 'normal' life. Our findings suggest that families would benefit from additional information and clinical support leading up to epilepsy surgery to help them prepare for and adjust to a life without epilepsy.

Siblings' experiences of their relationship with a brother or sister with a pediatric acquired brain injury.

Primary purpose: Child acquired brain injury has significant impact on the family, including siblings. This study aimed to explore siblings' experiences of their relationship with their brother or sister with acquired brain injury in order to make recommendations for health professionals working with this population.Research design: Semi-structured interviews were conducted with five siblings of children with acquired brain injury aged between 9 and 12 years and analyzed using interpretative phenomenological analysis.Results: The analysis resulted in four themes: (i) Coping with "a nightmare that you live"; (ii) Disconnection from family relationships; (iii) My sibling is different but "still the same underneath all this thing"; and (iv) Changing togetherness.Conclusions: The siblings in this study experienced a high level of distress with the near loss of their brother or sister. This was followed by difficulty in adjusting to the physical and psychological changes in their injured sibling and the impact on their sibling role and relationship. The changes were experienced alongside disruption to family relationships. Important clinical implications include the inclusion of siblings in their injured sibling's care and the provision of information and support for this group.Implications for RehabilitationSiblings of children with an acquired brain injury experience significant challenges while trying to adapt to their changing sibling relationship and feelings of disconnection with their family.This study highlights a need to work systemically with families of childhood brain injury and recognize siblings' important role in their family unit and therefore involve them in their brother/sister's care and rehabilitation.This study also highlights a need to support siblings to cope with the trauma and provide information to validate and understand their experience.