Asthma is a chronic respiratory disease with a prevalence that has increased worldwide over the past 40 years. Longitudinal cohort studies have been designed to determine associations between early life events and asthma prevalence. One such cohort is the Merthyr Allergy Prevention Study (MAPS). MAPS recruited high risk subjects, before birth, from a deprived population in South Wales. The original study was a randomised controlled trial (RCT) of either normal diet for the first four months of life, or a cows’ milk protein exclusion diet with soya formula milk supplementation if subjects were not breast fed. Subjects were subsequently followed up as part of a cohort study. The findings presented are based on the final follow up at age 23 years. While there was a significant protective effect of breast feeding on wheeze at age 1, there was no evidence of an association with wheeze at age 23 years. The intervention arm of the RCT was associated with an increased risk of asthma and sensitisation at age 23 years. There was tracking of both total serum IgE and positive skin prick test results over the years but there was no clear relationship between these two measures of allergy. Although the prevalence of atopy was low in childhood, there was still a clear association with this and wheeze later in life. Wheeze at age 3 years or older was an important determinant of asthma at age 23 years. There was a significant association between those who wheeze from age of 3 to age 23 years and atopic status at age 7 years. In conclusion we have investigated a birth cohort from a relatively deprived area of South Wales and found characteristics in the first 7 years of life are critical in determining if asthma develops in early adulthood.

Background: Childhood critical illness is characterised by a rapid and potentially catastrophic loss of physiological reserve caused by a wide variety of illnesses and injuries. In the Western world, death from childhood critical illness is rare due to advances in paediatric intensive care (PIC) provision, medicine, technology and public health. However, surviving PIC can expose children and their families to a complex array of physical, psychological and social problems. Physical disability, chronic illness, delirium, and stress symptoms have been reported to manifest in the immediate to short-term (<six months post-PIC). Existing research has focused on quantifying the outcomes and impact of surviving childhood critical illness. Furthermore, decontextualised, pathologised, and uni-dimensional platforms to inquiry are the dominant approaches used. Collectively, this has impeded understanding of how childhood survivors construct and experience long-term (≥ six months post-PIC) psychosocial well-being. Aim: This study aimed to explore how long-term psychosocial well-being is described, experienced and constructed by PIC survivors within the context of their lives. Methods: A longitudinal, qualitative, multiple case study approach was used. Nine case studies were formed around a heterogeneous group of nine child and adolescent PIC survivors of an acute life-threatening critical illness (aged six-16 years), admitted to a single UK Paediatric Intensive Care Unit (PICU) at least six months previously. A further 23 significant others, including family members, health professionals and teachers, were identified by the PIC survivors to participate. Each case, bar one, was explored longitudinally over a six-month period collectively providing a follow-up period of six to 20 months post-PICU discharge. Data were collected from October 2012 until July 2013 and included 42 data collection visits. A flexible toolbox of qualitative methods (interviews and art-based approaches) was used to capture stories and accounts. Collectively, 33 hours of audio data and 427 images were collected. Data were analysed sequentially that provided insights into psychosocial well-being from the individual, within the case, and across cases. Both abductive and inductive analytical approaches were used that included narrative psychological analysis, correspondence and pattern matching, and aggregating of case findings. Findings: Findings from survivor accounts illuminate multifaceted and complex storied experiences. Stories were distinctive, varying in how they were constructed as well as in content, with differing biographical, experiential and aspirational accounts. These remained grounded in survivors’ day-to-day lives involving vibrant imagery of life events, contextual factors and prosperities. However, adversities also featured through reports of amnesia, uncertainties, traumas, contemplation of death and dying, and stigma, which appeared to collectively direct constructions of psychosocial well-being. From exploring within each case study, the context of PIC survivors’ lives appeared complex, featuring ongoing adversities, chaos and change. Stories diverged between survivors and significant others as untold and hidden narratives emerged. However, shared stories also appeared, with a distinct focus on future aspirations and recovery. Shared residual traumas and adversities also featured, with narratives of sacrifice and protection being told, that in turn exposed significant others to additional adversity. Findings from across contexts identified multifarious imagery with interwoven and intricate stories that illuminated the complexity of survivor experiences and lives. However, amongst this chaos, common themes from across PIC survivor stories were evident. Themes included: disrupted lives; exposure to death and dying; mediation between different social worlds and identities; and the focus on getting on with life. Through aggregating instances across whole-cases, the inter-relational nature of long-term psychosocial well-being was highlighted. Collectively, findings identify that PIC survivors construct long-term psychosocial well-being within the context of their lives as a paradox; a state of disruption and flux, and an inter-relational and dynamic entity. Conclusion: Childhood PIC survivors’ stories are complex and identify numerous challenges and adversities that are faced when attempting to readjust to life in the long-term post-PICU. Mediation between psychological and social worlds can expose survivors to both negative and positive well-being. However, biographical, individual, familial, social, and wider societal influences also appear significant in how PIC survivors construct and experience psychosocial well-being in the longer term. These novel insights into this unexplored phenomenon challenge existing theoretical propositions from the literature and provide a platform for further inquiry.

Background: Children with severe neurodisability (ND) commonly suffer with respiratory disease and this is the leading cause of premature death. The nature of this respiratory disease is however, poorly understood. The underlying aetiology is often multifactorial, but aspiration (direct or reflux) is likely to play a key role. Unfortunately, diagnostic tests for reflux or direct aspiration are limited. There is a clinical need for high quality research on children with severe ND to define underlying mechanisms of respiratory disease and guide management. Aims: In this study, the aims were to (i) characterise respiratory symptoms and their relationship with lower airway inflammation in children with severe ND, (ii) explore available bronchial lavage (BAL) biomarkers of reflux aspiration, assessing their validity and their relationship to clinical and airway inflammatory data, (iii) develop a novel assay for the accurate detection/quantification of pepsin in BAL, (iv) investigate the validity of an alpha-amylase assay in paediatric BAL and explore the relationship of alpha-amylase levels with lower airway inflammation and clinical symptoms, and (v) investigate the effects of pH alteration and pepsin exposure on airway epithelial cells (AEC). Methods: Clinical data and BAL samples were collected from children with severe ND at times of stability and respiratory deterioration and also from healthy controls. BAL differential cell counts and cytokine measurements (ELISA) were performed. Lower airway microbial colonisation/infection was assessed. BAL pepsin measurement was attempted using a number of methods, and the feasibility of inhibitor affinity enrichment and LC-MRM-MS techniques to identify and quantify BAL pepsin was explored using SDS PAGE gel and mass spectrometry analysis. BAL alpha-amylase activity was measured using an ethylidene-pNP-G7 based assay. BEAS-2B cells were cultured in monolayer and the cytotoxic/inflammatory effects of pH alteration and pepsin exposure were explored through trypan blue staining and cytokine assays. Results: Children with severe ND have burdensome chronic respiratory symptoms that impact on their quality of life and that of their families’. Symptoms may relate to lower airway inflammatory levels. A trend for greater airway neutrophilia and respiratory symptoms was seen in those with lower airway microbial positivity. Available ‘in house’ pepsin ELISA assays were not robust but Western Blot results indicated a higher frequency of BAL pepsin positivity in ND patients with acute respiratory deterioration. Notably, positivity was also found in some healthy controls, highlighting the need for a quantitative assay. The use of an immobilized inhibitor (pepstatin agarose) to recover pepsin from paediatric BAL samples was shown to be feasible. Subsequent digestion of pepsin and detection by LC-MSMS with selective ion monitoring was demonstrated. Significantly increased BAL alpha-amylase levels were seen in Elective-ND patients compared to healthy controls and furthermore, significant correlations were observed with BAL lower airway inflammatory markers. BEAS-2B cells were sensitive to mild acidification, with up-regulation of TGF Beta-1, IL-6 and IL-8 mRNA expression. A corresponding rise in protein secretion was not necessarily seen and in some cases, was significantly down-regulated. No significant cytotoxicity or decrease in cell viability was observed in any condition. Conclusions: In children with severe ND, chronic respiratory symptoms may be directly related to lower airway inflammation and bacterial colonization. Measurement and quantification of pepsin in BAL (as a marker of reflux aspiration) is difficult. However, an inhibitor affinity enhanced mass spectrometry based technique has potential as a ‘gold-standard’ method for identification and quantification of pepsin in BAL. BAL alpha-amylase activity shows promise as a biomarker of direct aspiration. Mild alterations in airway pH may directly contribute to the pathophysiology of inflammatory airway disease and specifically, reflux-aspiration related lung disease in this group. This requires further study as a potential novel therapeutic target.

Medulloblastoma (MB) is the most common malignant brain tumour in children. MBs arise in the cerebellum, originating from neural stem cells progenitors. It has previously been shown that the lack of integrity of signalling pathways due to genetic alterations play a key role in MB chemosensitivity. An example is the p53 signalling, with p53 mutations and or deletions which are associated with drug resistance. Here, we explored the role of p53 induction by chemotherapeutic drugs such as etoposide in MB and the way to bypass the need for intact p53 to trigger apoptosis. We specifically demonstrated that a downstream miRNA target transcribed by p53, miR-34a, is able to reduce the number of viable cells in cultures of MB cells lacking functional p53, although the effect was limited. Beyond the genetic background of a tumour, it is more and more described that the tumour microenvironment plays a key role in drug resistance. MB is a solid tumour and hence will contain areas deprived in oxygen (hypoxic). It has been widely documented that hypoxia is associated with poor prognosis and resistance to treatment in other cancer models and we here aimed to investigate the specific role of hypoxia in MB response to etoposide. We demonstrated that MB (p53 WT) cell lines became more resistant in chronic but not acute hypoxia and this was associated with a decrease in the recruitment of double strand DNA damage sensing machinery and subsequent impairment to transactivate p53 and transcription of pro-apoptotic genes. A transcriptomic microarray profiling study further revealed that chronic hypoxia induced broad and significant changes in global gene expression affecting many biological pathways including stem cell maintenance, neuronal development and phosphoinositol-3 phosphate kinase.

Background: Disorders of lung development cause death and disability in the young and old: novel insights into developmental regulators can aid therapeutic strategies. The Ca2+ATPase SERCA, already implicated in asthma and cystic fibrosis, appears to play a key role in lung development. SERCA inhibition with cyclopiazonic acid (CPA) in vitro, reduces both airway branching and peristalsis reversibly and dose dependently, whilst also halting myogenesis. It is unclear however, whether changes in branching are mediated via SERCA dependent contractility, or whether SERCA is a direct regulator of airway branching. Aims: (i) to further explore the CPA-induced embryonic lung phenotype by assaying gene expression and cell proliferation; and (ii) to determine effects of genetic perturbation of SERCA function in vivo on airway branching morphogenesis, in the absence of contractility (using a Drosophila model). Methods: Embryonic mouse (E11.5) lung explants were cultured +/- CPA at an air/fluid interface. Standard techniques were used to rear Drosophila and SERCA expression manipulated using conditional, heat-sensitive mutants and RNAi targeted to the trachea. Positively labelled, loss-of-function ‘flip-out’ RNAi and mutant clones were produced using heat-shock induced FLP-recombinase. Gene expression was assayed using real-time RT-PCR and SERCA function assessed using calcium dyes and genetic indicators. Embryonic and larval fly airways were imaged using fluorescent proteins and immunostaining, with live or fixed-sample confocal microscopy. Immunofluorescent staining was used to assess protein expression and cell proliferation. Results: SERCA inhibition with CPA significantly up or down regulated mRNA levels of key genes involved in lung branching morphogenesis, myogenesis and angiogenesis in vitro. CPA treatment also reduced cell proliferation dose-dependently in the lung epithelium and mesenchyme. In the fly embryo, neither conditional SERCA mutants nor targeted RNAi significantly affected tracheal morphology. However, residual SERCA mRNA and protein function was evident at this stage of development. Tracheal maturation, in the form of gas filling was significantly impaired though, in embryos expressing a conditional SERCA mutation. In larvae, development of the dorsal air sac primordium (ASP) was severely disrupted by targeted SERCA RNAi and this phenotype could be reproduced when sufficient numbers of loss-of–function clones were present. SERCA inhibition reduced the number of mitotic cells in the ASP and correspondingly, SERCA deficient clones comprised fewer cells than control counterparts: SERCA regulation of airway cell proliferation was therefore evident across species. Fewer SERCA deficient cells reached the tip of the ASP during morphogenesis compared to controls, whereas a greater proportion remained in the stalk, findings that indicate a cell-autonomous defect in cell migration. Changes in morphology were independent of changes in expression of the key ASP signalling pathways MAP kinase and Notch. Expression of the ASP tip-cell marker escargot was expanded in SERCA deficient larvae, with a number of positive cells being abnormally present in the stalk. This finding could be explained by a failure of these cells to migrate to the tip, alternatively by changes in cell fate. Given key roles of tip cells in morphogenetic signalling, escargot may play a role in SERCA inhibition-induced dysmorphogenesis. Conclusions: SERCA has an essential, conserved role in airway branching morphogenesis across species: this role appears independent of contractility. SERCA regulates cell migration and proliferation processes in the airway, findings that may have wider relevance, e.g. in proliferative disease, metastasis and tissue regeneration. Given evidence in plants and fungi of Ca2+ cycling regulating budding, findings here may indicate a role for SERCA as a generic regulator of iterative branching across biology, with clear implications for further research.

Adverse drug reactions (ADRs) in children are common but their predictors are not fully characterised. It is known that both increasing age and number of concomitant medicines increase ADR risk in children, and there is also some evidence that off-label and unlicensed medicine use may contribute. The purpose of the thesis was to characterise ADRs in children, focusing on known risk factors, which have not been adequately evaluated in the literature. The contribution of off-label and unlicensed prescribing to ADR risk in children was assessed in two large prospective studies. In the first study, which evaluated ADR-related hospital admissions, off-label or unlicensed medicines were more likely to be implicated in an ADR than authorised medicines (relative risk 1.67, 95% CI 1.38, 2.02, p < 0.001). In a multivariate analysis, patients admitted under the care of oncology were more likely to have experienced an ADR (odds ratio (OR) 25.70, 95% CI 14.56, 45.38, p < 0.001). The following risk factors were also associated with increased ADR risk: increasing age (OR 1.04, 95% CI 1.00, 1.08, p = 0.045), number of authorised medicines (OR 1.25, 95% CI 1.16, 1.35, p < 0.001) and number of off-label or unlicensed medicines (OR 1.23, 95% CI 1.10, 1.36, p < 0.001). In a sub-group analysis which excluded oncology patients, age and number of authorised medicines predicted ADR risk (OR 1.05, 95% CI 1.01, 1.09, p = 0.023 and OR 1.33, 95% CI 1.23, 1.44, p < 0.001 respectively) but the number of off-label and unlicensed medicines did not (OR 1.04, 95% CI 0.89, 1.12, p = 0.627). The second prospective study examined ADRs occurring in paediatric inpatients. Again, off-label or unlicensed medicines were more likely to be implicated in an ADR than authorised medicines (OR 2.25, 95% CI 1.95, 2.59, p < 0.001). Medicines licensed in children but given to a child below the minimum age or weight recommended had the greatest risk of being implicated in an ADR. Multivariate analysis showed that increasing age (HR 1.04, 95% CI 1.02, 1.05, p < 0.001) and receipt of a general anaesthetic (HR 5.30, 95% CI 4.42, 6.35, p < 0.001) were positive predictors of ADR risk. Both the number of authorised (HR 1.22, 95% CI 1.17, 1.26, p < 0.001) and the number of off-label or unlicensed (HR 1.27, 95% CI 1.20, 1.34, p < 0.001) medicines were predictors of ADR risk. ADR detection in the above studies was based on intensive surveillance. One possible method of detecting ADRs may be through the ICD-10 clinical coding system but this has not been investigated for paediatrics. Only 31.5% of the 241 ADRs evaluated from the prospective admissions study were coded correctly using at least one ICD-10 code. The clinical coding system could contribute to pharmacovigilance if deficiencies in how ADRs are recorded in the case notes and the clinical coding system can be addressed. An important ADR detected in the admissions study was the occurrence of haemorrhage post-tonsillectomy which has been attributed to the use of dexamethasone. In order to analyse this further, a systematic review and meta-analysis of dexamethasone and non-steroidal anti-inflammatory drug (NSAID) use in paediatric tonsillectomy was undertaken. Although there were a large number of randomised controlled trials and observational studies in this area, analysis of all of these led to the conclusion that there was insufficient evidence to rule out an increased risk of haemorrhage with dexamethasone use whether in combination with NSAID or not (Peto odds ratio for dexamethasone versus another intervention 1.41, 95% CI 0.89, 2.25, p = 0.15). Further, well powered, well designed studies are needed in this area. An important ADR detected in the in-patient study was post-operative nausea and vomiting. More detailed analysis was therefore undertaken to identify the risk factors for post-operative vomiting (POV), with a view to developing a risk score. The following were all identified as predictors of POV risk: age (OR 1.06, 95% CI 1.03, 1.10, p<0.001), duration of anaesthesia (OR 1.00, 95% CI 1.00, 1.01, p <0.001) and the use of intra-operative analgesics (OR 2.22, 95% CI 1.58, 3.12, p < 0.001). However, it was not possible to develop a robust model to predict the risk of POV because of the heterogeneity of the patient groups, the types of surgery, and the different clinical practices between different anaesthetists in terms of anti-emetic (choice, timing and doses). The use of off-label and unlicensed medicines in children is common but necessary and these medicines are frequently associated with ADRs. The rational prescribing of medicines is an important measure in the reduction of ADR risk and a solid evidence-base is a pre-requisite. The aim should be that the minimum number of medicines is used safely and effectively, at the lowest dose possible, for the minimum duration necessary.

Introduction: Perthes’ disease is an idiopathic osteonecrosis of a juvenile hip that frequently precipitates premature osteoarthritis. The year 2010 marked a century since Perthes’ disease was first described, but the aetiology and mechanism remain unknown. The incidence of Perthes’ disease varies widely, and it has been suggested that differential exposure to adverse socioeconomic circumstances may be a key precipitant. This work seeks to further the understanding of the distribution and determinants of Perthes’ disease, by exploring temporal and geographic patterns using a case register from Merseyside, discharge data from Scotland and the world’s largest community disease register. Analytical studies are then used to test hypotheses and investigate a disease mechanism. Methods: The descriptive studies were based on data from the Merseyside Perthes’ Disease Register (1976 – 2008), the General Practice Research Database (1990 – 2008) and hospital discharge data for Scotland (2000 – 2009). A systematic review of the published literature was used to explore international variations in incidence. Two case-control studies were used to test hypotheses. The first used a community population derived from the General Practice Research Database to investigate comorbid disease associations. The second used a hospital population to examine tobacco smoke exposure, anthropometric markers of prenatal androgenisation, hyperactivity and impaired endothelial function as a possible disease mechanism. Results: There was a graduated North-South divide in the UK incidence of Perthes’ disease, with rates in Scotland more than twice those in London. All three descriptive studies demonstrated a sustained fall in disease frequency across the study periods. There was a marked association with area deprivation, which was independent of the urban environment. Internationally a North-South divide persisted with equatorial regions being relatively unaffected by disease, and Northern Europe having the highest disease incidence. The international disease distribution was primarily a function of race, although latitude remained an independent predictor of incidence. Analytic studies revealed an association with congenital genitourinary tract anomalies and an association with asthma. There was no clinically apparent hyperactive tendency, though a more subtle abnormality in behavioural profiles was apparent. Exposure to tobacco smoke was a notable risk factor for Perthes’ disease, which was independent of individual or area deprivation measures. Arterial caliber was reduced amongst cases with a corresponding generalised reduction in arterial flow, though endothelial function appeared normal. Conclusions: Within the UK the incidence of Perthes’ disease is in decline. The geographic distribution suggests that variation in disease incidence is related principally to deprivation, though the underlying determinant(s) remain unclear. Latitude may hold an additional ‘risk’ in the disease aetiology, though the specific component(s) of latitude similarly remain unclear. Additional independent risk factors include sex, ethnicity, genitourinary disease and tobacco smoke exposure. Factors acting early in the development of the child appear to offer important insights into the disease aetiology, with particular interest on the influence of prenatal sex hormones. Reduced arterial caliber may have a role in the disease mechanism, and wider implications to vascular health. The aetiological factor in Perthes’ disease remains elusive, but it is likely that unraveling this enigma will unlock additional secrets relating to the fetal origins of diseases.

Background Prader-Willi Syndrome (PWS) is a complex genetic syndrome associated with hyperphagia and behavioural problems. Recent research suggested a link between hyperphagia and behavioural and emotional problems in PWS such as anger and anxiety. The current study aimed to explore this relationship further. Method Through parental report postal questionnaires, data was collected on the age, gender, weight, hyperphagia and behavioural and emotional problems of 105 children with PWS aged 4-18 years (M: 9.63 years). Results Following preliminary analysis, a series of multiple regressions were performed. Hyperphagic drive significantly predicted antisocial/disruptive behaviour, anxiety, social relating problems, communication disturbances and self-absorbed behaviours. Whilst hyperphagic behaviour did not significantly predict any behavioural/emotional problems. Conclusions This study reinforces research which has suggested an association between hyperphagia and non-food related behaviour in PWS. This has implications for the understanding of PWS and the development of psychological interventions for behavioural and emotional problems.

BACKGROUND: A major component in determining the prognosis for all pediatric cancers is the biology of specific malignancies. However, it has also been found that non-medical factors such as distance between home and treatment center, rural versus urban residence, and socioeconomic status can influence pediatric cancer survival. Relatively few studies have been done in this area. AIMS: This study attempted to evaluate whether there are disparities in pediatric cancer survival outcomes in North Carolina (NC) based on geography. Other demographic characteristics of the patients were also examined, including race, ethnicity, sex, and county of residence. METHODS: A retrospective, single-institution study at the University of North Carolina (UNC) Hospital was performed using a clinical database. Eligibility was limited to patients 0-21 years of age who were diagnosed with acute myeloid leukemia, acute lymphoblastic leukemia, central nervous system tumors, neuroblastoma, rhabdomyosarcoma, or Wilms tumor between the years 2000 and 2018 who were NC residents and treated at UNC Hospital. RESULTS: Distance to the UNC Hospital from a patient’s residence did not have a statistically significant impact on pediatric cancer survival outcomes. However, patients living in non-metropolitan areas had lower survival outcomes when compared to patients residing in metropolitan regions. Patients who were African Americans and “Other” races had lower survival outcomes when compared to Whites. CONCLUSIONS: Although this study indicates no significant association between distance to the UNC Hospital and pediatric cancer survival outcome, patient race and metropolitan classification of a patient’s county of residence appear to be linked with survival disparities.

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Science in Physiotherapy Johannesburg, 2017 / Background: Burns are a significant cause of paediatric injuries, particularly in low and middle-income countries, where more than 90% of burn-related paediatric deaths occur. Physiotherapy is an essential, sometimes painful, component of burn rehabilitation therapy. The popularity of the video game use in burns rehabilitation has grown because, in addition to facilitating range of motion (ROM) in an effort to prevent joint contracture formation, the virtual imaging characteristics of these games provides additional benefit of distraction from pain. Video games provide a more efficient, effective and enjoyable method training, and are a helpful adjunct to rehabilitation. Aim: To investigate the effect of using the Xbox Kinect™ on discharge outcomes and early activity levels of children in the Paediatric Burns Unit (PBU) at Chris Hani Baragwanath Academic Hospital (CHBAH) Methods: This non-equivalent post-test only control group design study took place over a period of time until the total number of children required was achieved for each group. The control group was the first group of children recruited to the study and received standard physiotherapy treatment and rehabilitation. The experimental group was the second group of children recruited to the study who received standard physiotherapy treatment and rehabilitation as well as the Xbox Kinect™. Comparisons were made only after the intervention and analysed. Outcome measures for each participant were ROM, Activities Scale for Kids© participation (ASK©p) and a modified Wong-Baker FACES® enjoyment rating scale. On discharge from the unit, ROM assessments and the modified Wong-Baker FACES® enjoyment rating scale were administered. On follow-up one week post discharge, ROM re-assessments were done and the ASK©p was administered. A questionnaire regarding the use of the Xbox Kinect™ was completed by health professionals working within the PBU. Results: Seventy children were recruited into the study of which the data for 66 were analysed. Thirty five children were part of the control group and 31 were part of the Xbox intervention group. No significant difference was found between groups regarding demographic characteristics, the median age was seven years old and 55% of the participants were male. There was one mortality and five children in total were lost to follow up. The majority burns were as a result of hot water attributing to more than 50% of admissions, followed by flame burns (30%) and electrical burns (12%). This study population showed an overall total burn surface area (TBSA) of nine percent which were superficial partial in depth; this is seen as a minor burn injury. Forty percent were seen to have moderate-severe injury and three children were considered to have severe major burns > 30 % TBSA. We observed a greater proportion of injury involving the lower limbs (23.10%) and upper limbs (21.10%), followed by injury involving the trunk (11.40%), buttocks and genitalia (7.50%) and the head and neck regions (6.80%). There was no difference in length of stay (LoS) or the chance of Intensive Care Unit (ICU) stay between the two groups. In the intervention group 75% of the children received 2 or more Xbox Kinect™ sessions. The Xbox Kinect™ was shown to be significant in achieving higher active range of movement (AROM) at discharge (p< 0.01) and at follow up (p< 0.01), and highlights the advantages it has in providing a more amusing and comfortable option as part of the burns rehabilitation process. By allowing the children to be more engaged in the Xbox Kinect™ experience and games, they were distracted and thus experienced less pain. In this study we found that TBSA% was a predictor of ASK©p scores (p= 0.03), thus the higher the burn percentage the lower the ASK©p scores. We also found that age (p= 0.05) and AROM (p= 0.04) were associated with ASK©p scores, thus the younger the child or a child with reduced AROM would have lower ASK©p scores. Fun and enjoyment (p<0.01) was found to be significant in this study, thus highlighting the fun and enjoyment factor the Xbox Kinect™ offers as part of therapy and as an adjunct to burns rehabilitation. Thirty one questionnaires regarding the value and use of the Xbox Kinect™ were completed by health professionals working within the PBU. Many highlighted the value of fun, enjoyment and distraction the Xbox Kinect™ offered as part of the rehabilitation, as well as assisting in achieving more AROM but also indicated that the Xbox Kinect™ sessions still needed to be supervised and guided. Conclusion: This study was the first study done in South Africa involving video game technology during physiotherapy within the paediatric burns population. The use of the Xbox Kinect™ as seen in this study has proven to be beneficial and a useful adjunct to burns rehabilitation within in the paediatric burns population. This distraction and decline in pain assists in reducing the fear associated with movement these burns children experience and assist in improvements related to activity and ultimately age-appropriate play and activities of daily living (ADLs). / MT2017