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OBJECTIVE The transition of the young adult with spina bifida (YASB) from pediatric to adult health care is considered a priority by organized pediatrics. There is a paucity of transition programs and related studies. Jacksonville Health and Transition Services (JaxHATS) is one such transition program in Jacksonville, Florida. This study’s purpose was to evaluate the health care access, utilization, and quality of life (QOL) of a group of YASBs who have transitioned from pediatric care. METHODS A survey tool addressing access to health care and quality of health and life was developed based on an established survey. Records of the Spinal Defects Clinic held at Wolfson Children’s Hospital and JaxHATS Clinic were reviewed and YASBs (> 18 and < 30 years old) were identified. RESULTS Ten of the 12 invited YASBs in the Jacksonville area completed the surveys. The mean age of respondents was 25.1 years. All reported regular medical home visits, 8 with JaxHATS and 2 with other family care groups. All reported easy access to medical care and routine visits to spina bifida (SB) specialists; none reported difficulty or delays in obtaining health care. Only 2 patients required emergent care in the last year for an SB-related medical problem. Seven respondents reported very good to excellent QOL. Family, lifestyle, and environmental factors were also examined. CONCLUSIONS In this small group of YASBs with a medical home, easy access to care for medical conditions was the norm, with few individuals having recent emergency visits and almost all reporting at least a good overall QOL. Larger studies of YASBs are needed to evaluate the positive effects of medical homes on health and QOL in this population.

INTRODUCTION: The legal and illicit use of cannabinoid-containing products is accelerating worldwide and is accompanied by increasing abuse problems. Due to legal issues, the USA will be entering a period of rapidly expanding recreational use of cannabinoids without the benefit of needed basic or clinical research. Most clinical cannabinoid research is focused on adults. However, the pediatric population is particularly vulnerable since the central nervous system is still undergoing developmental changes and is potentially susceptible to cannabinoid-induced alterations. RESEARCH DESIGN AND METHODS: This review focuses on the systems medicine of cannabinoids with emphasis on the need for future studies to include pediatric populations and mother-infant dyads. RESULTS AND CONCLUSION: Systems medicine integrates omics-derived data with traditional clinical medicine with the long-term goal of optimizing individualized patient care and providing proactive medical advice. Omics refers to large-scale data sets primarily derived from genomics, epigenomics, proteomics, and metabolomics.

An interprofessional approach to pediatric behavioral care is increasingly important in the care of pediatric patients, who present to healthcare settings with a wide variety of concerns ranging from potty training to depression. Previously, much of the care of these patients have focused on a narrow approach to the problem, based on the expertise of the professional providing care. Faculty from three disciplines: Social Work, Psychology, and Medicine collaborated to design a course for students from these three disciplines to collaborate in attaining three goals: (1) reinforce the importance of multidisciplinary collaboration, (2) share clinical techniques and skills in a simulated interprofessional setting, and (3) practice collaboration within interprofessional teams. We detail the course goals and design and topics covered and discuss implementation of this course. Suggested module content and pedagogical design are discussed, and case examples are detailed with the goal of encouraging the adoption of similar courses.

Social, emotional and behavioural aspects of development are key to children’s overall development. A failure to develop normally in any one of these areas can have far reaching consequences, affecting the child’s ability to learn and to develop relationships with peers, potentially leading to fewer educational qualifications, a lack of future employment, poverty and a range of other outcomes including difficulty forming relationships, mental health issues and increased criminal behaviour (Tremblay et al., 2004; Woodward & Fergusson, 2000; Ttofi, Farrington, & Lasel, 2012; Hodgins, Larm, Ellenbogen, Vitaro, C Tremblay, 2013; Pingault et al., 2013). In Glasgow City, a large proportion of children live in disadvantaged circumstances, including living in households and areas suffering from multiple deprivation, living with parental substance misuse and witnessing domestic and community violence (Glasgow Centre for Population Health, 2013; Taulbut & Walsh, 2013). These risk factors can all impact on children’s social, emotional and behavioural development (Margolin & Gordis, 2000a; Gennetian, Castells, & Morris, 2010; Chronis et al., 2003). Children also tend to be clustered in schools with other children who may share similar demographic characteristics and who have similar levels of difficulties, which may compound or ameliorate the individual’s strengths or weaknesses. This thesis aimed to explore the levels of children’s social, emotional and behavioural difficulties at the start of Primary School (age 4-5) and at Primary 3 (age 7-8) in Glasgow city and to investigate the stability of these over time. Analysis was carried out using a brief behavioural screening questionnaire, Goodman’s Strengths and Difficulties Questionnaire (SDQ)(Goodman, 2013b), which had been completed by nursery staff and class teachers. The thesis also aimed to examine whether Glasgow City is different in its levels of social, emotional and behavioural difficulties compared with other areas of Scotland and the UK. Clustering of difficulties within schools is analysed in order to explore the relationships between peer difficulties and demographics, individual difficulties over time and ultimately, whether schools have an effect on the development of social, emotional and behavioural difficulties during the first three years of school. The results of this study indicate that, between preschool and P3, levels of Conduct Problems, Emotional Symptoms and Hyperactivity/inattention increased, whilst levels of abnormal Pro-social Behaviours decreased and Peer Relationship Problems remained relatively static. Both means and prevalence rates for children in Glasgow City demonstrated similar patterns to UK norms, though levels of Hyperactivity/inattention problems at P3 were higher than in UK 5-10 year olds. Data from the Growing Up in Scotland study were used to investigate whether a ‘Glasgow Effect’ (i.e. an amount of variation that could not be explained solely by demographic differences in the population) existed in children’s social, emotional and behavioural difficulties at preschool age. Children in the Glasgow sample did have higher rates of social, emotional and behavioural difficulties compared with children in the rest of Scotland. However, this difference in difficulties appeared be entirely accounted for by the difference in demographics within the populations in the different areas. There are various factors which might explain this: sampling issues, such as having to use a Greater Glasgow and Clyde sample rather than Glasgow City, may mask any Glasgow Effect, whilst it may be that differential attrition in the GUS cohort may mean that children with problems are missing from the sample. It could also be that sleeper effects are at work, which may emerge in the form of difficulties later in childhood, or that what we are seeing is a ‘Scottish Effect’ rather than a Glasgow Effect, given that most of the previous research in this area compared Glasgow with demographically similar English cities. At this stage however, it appears that results from Glasgow may be generalisable to other areas, once demographics are controlled for. Multilevel modelling of Strengths and Difficulties Questionnaire (SDQ) data from Glasgow City schools was then used to explore what factors were associated with longitudinal increases in SDQ scores between preschool and P3. Results showed significant differences between schools in the unadjusted models, accounting for 11% of variance in change scores. The adjusted model found that having worsening social, emotional and behavioural difficulties in the first three years of school was associated with being male, being from a White-UK background, and having had Looked After status (been under the supervision of the state) by preschool. Being in a school with a small school roll was also associated with an increase in difficulties over this time. School effects were only reduced slightly in this final adjusted model, accounting for 9% of variance between schools, suggesting that variation in the development of social, emotional and behavioural difficulties may differ somewhat between schools during the first three years. It should be noted that numbers of pupils within schools were small in some cases, leading to wide confidence intervals and possibly reducing significance of the results. Having social, emotional or behavioural problems at P3 (above the cut-off on the SDQ for likely difficulties) was also related to a range of factors. Again in the unadjusted model, there was a statistically significant difference in levels of difficulties between schools. The strongest predictor of such problems was having had an abnormal score at preschool. Also important was being male, having been Looked After by preschool and being in a school with a higher proportion of children eligible for free school meals, which is likely to be a proxy for income deprivation. However, once these characteristics were controlled for, there was no statistically significant difference between schools. The ability to identify a group of children prior to the start of school who are at risk of continued social, emotional and behaviour difficulties raises questions about whether a preschool mental health screening test should be put in place. It would be hoped that this would allow children to access the support they need in order to optimise their development, with a suggestion that a universal screen for these types of problems could double or treble the traditionally low numbers of children receiving help (Goodman et al., 2000). However, there are also difficulties with a screening tool of this nature, including the potential for false identification of difficulties, the potentially negative impact of labelling children, the additional burden that this may place of services and finally the current lack of evidence around a potential effective intervention for children of this age (Goodman et al., 2000; Sayal et al., 2010; Wichstrom et al., 2012). In conclusion, children in Glasgow City have similar prevalence rates of social, emotional and behavioural difficulties at preschool, compared with children in the rest of the UK, but these difficulties are markedly worse in Glasgow City by the third year of school. However, the difference in these scores may just be due to Glasgow City having a more disadvantaged population, which in turn impacts on levels of difficulties. Whilst schools were found to make a difference in relation to children moving up or down the spectrum of difficulties in the first three years of school, there was no evidence that schools contributed to the likelihood of children having an ‘abnormal’ score at P3, though again, this lack of significance could be related to the small numbers of pupils within some schools, as well as the over-riding impact of having difficulties earlier in life. More research is required with larger numbers of students within schools in order to see if the lack of variance seen between schools at P3 is real or whether it is a sampling issue related to small numbers and therefore wide confidence intervals within schools. Qualitative work around the outliers and some of the unusual findings, e.g. that children in smaller schools appear to fare worse, would be beneficial in interpreting the findings. It would also be of great benefit to follow these children up to the next stage of data collection at P6, in order to explore what happens to children’s social, emotional and behavioural difficulties by the end of Primary school.

Urinary tract infections (UTI) in young children have been associated with serious long-term complications such as renal scarring, hypertension and renal failure. The presenting symptoms of UTI in children are non-specific. If UTI is not suspected, a urine sample is not obtained, and without this, UTI cannot be diagnosed. There is evidence that the diagnosis is often missed. Most published studies have not systematically sampled urine, and those that have are largely based in US emergency departments and only include highly selected groups of children. The true prevalence of UTI in acutely ill children presenting in UK general practice is therefore unknown. My thesis consists of a literature review discussing the association of childhood UTI with long-term complications, the challenges of diagnosis and the evidence that UTIs are being missed; a systematic review of papers reporting UTI prevalence in children which highlights the need for a study in UK general practice; a pilot study to determine the feasibility of recruiting children and obtaining urine samples in UK general practice; and a prospective cohort study to determine the point prevalence of UTI in 597 presenting children, determine the predictive value of presenting symptoms, signs and risk factors, and describe the clinical outcomes for children with UTI. I found that the prevalence of UTI was 5.9% (95% confidence interval: 4.3-8.0%). This may be sufficiently high to justify increased urine sampling in general practice. A multi-variable logistic regression model identified younger age range, pain on passing urine (dysuria) and urinary frequency as being associated with UTI. I propose a urine sampling strategy for GPs assessing acutely ill children and compare this to suspicion-led sampling and current guidelines. In my discussion I discuss the limitations, generalisability and implications of these findings.

Cardiac arrest in paediatric patients often results in death or survival with severe brain injury. Therapeutic hypothermia, lowering of core body temperature to 32 to 34⁰C may reduce injury to the brain in the period after circulation has been restored. This thesis comprises studies related to the feasibility of performing a randomised controlled trial (RCT) of therapeutic hypothermia for neuroprotection after cardiac arrest in the UK. A systematic Cochrane review of paediatric evidence finds no published RCTs supporting or refuting the use of therapeutic hypothermia after cardiac arrest. Four on-going RCTs are identified which will add to the future evidence base; however, a future UK RCT is recommended. Additional support for a RCT is demonstrated by two UK surveys of paediatric intensive care and emergency care clinicians. Current UK practice is varied and clinical equipoise exists regarding post cardiac arrest temperature management. A national, retrospective study of all admissions to paediatric intensive care after out of hospital (OHCA) and in hospital cardiac arrest (IHCA) shows an overall survival of 76 and 50% respectively. Important differences between IHCA and OHCA populations are identified, recommending separation in a RCT. The incidence rate of cardiac arrest admissions to PICU in the UK is too low to recruit to a UK only RCT, after consideration of sample size requirements. A large, multi-centre, retrospective, observational study of OHCA patients identified multiple factors associated with survival. A survival prediction model, incorporating: pupillary reaction, blood lactate level and duration of cardiac arrest, is described. The model could be used as a tool for stratified randomisation within a RCT. Finally, therapeutic hypothermia is retrospectively compared with standard, normothermic temperature management after OHCA. In a limited population, no difference in survival is found; however, important information on application, logistics and safety of the intervention are evaluated.

Cerebral palsy (CP) affects around every one in 500 children born. It isn’t a particular illness or disease, but an umbrella term used to describe a physical condition that affects movement as a result of injury to the brain. There are several types of CP, the main ones being spastic, athetoid and ataxic. Despite medical advances, there is no cure for CP but there are ranges of treatments from drugs to Botulinum toxin type A injections, massage therapy to surgery. The aim of this study is to look at two of these treatments, namely Botulinum toxin type A injections and physiotherapy to treat spastic CP. Botulinum toxin is widely used to reduce muscle tone in the treatment of spasticity in children with cerebral palsy. The aim of the study is to compare the effects treatment with Botulinum toxin type A and Botulinum toxin type A with additional physical therapy in the management of a group of children with cerebral palsy. Experiments were done at The Prince Sultan Hospital and Al-Hada Armed Forces Hospital in Saudi Arabia. The local Ethics Committee approved the protocol. 47 children were recruited. All had cerebral palsy, diplegia, spasticity of the ankle planter flexors and significant gait abnormalities due to dynamic equinus foot deformity. They were divided into two groups. Both groups had their Gross Motor Function assessed one week before injection and at 4 and 6 weeks after injection. Additional measurements of range of movement and stiffness at the ankle and soleus electromyograms were recorded The soleus EMG was silent during ankle dorsiflexion in 20 children four weeks after injection of Botox. The EMG had returned six weeks after injection in every child. The Gross Motor Function Measurements were not significantly different in the two groups before the injection (p=0.23). The measurements improved significantly over the next six weeks in both groups (p<0.001). The magnitude of the improvement was greater in the group, which received Botulinum toxin type A and physical therapy (means 57.2 + 8.90 before, 64.9 + 9.78 after. Mean + SD) than in the group which received Botulinum toxin type A alone (59.5 + 11.0 before, 62.4 + 11.3 after Mean + SD). Conclusions 1. . The Treatment allocation provided groups, which were comparable pre-treatment in terms of baseline GMFM. 2. . Both treatments showed evidence of improvement in GMFM over the period of the study and particularly at 52 weeks. 3. . Treatment 2 showed a significant average advantage in GMFM over Treatment 1 at all times in the study. 4. . This advantage in average GMFM increased from 4 through to 52 weeks with a clear and significant difference between 4 and 52 weeks. 5. . This average advantage appeared to increase the higher the child’s baseline GMFM.

Since the introduction of glucocorticoids (GCs) in the treatment of rheumatoid arthritis in 1949, GC therapy has been associated with a number of adverse effects. Long-term use of GCs can result in growth retardation during childhood due to their actions on growth plate chondrocytes, although the exact mechanisms involved are unclear. The work of this thesis has investigated the cellular and molecular mechanisms involved in mediating GC effects at the growth plate. Affymetrix microarray has been used to identify and characterise the expression of lipocalin 2, a novel GC-responsive chondrocyte gene which may contribute to GC-induced growth retardation in the growth plate. In vitro and in vivo studies have also been used to examine the role of the cell cycle regulator, p21WAF1/CIP1 in GC-induced growth retardation. Finally, the growth plate sparing effects of a novel GC receptor modulator, AL-438, have also been identified. AL438, has reduced effects on bone growth compared to Dex, but maintains similar anti-inflammatory efficacy. This work has not only determined novel mechanisms of GC-induced growth retardation, but has also advanced the search for novel GC receptor modulators with reduced adverse effects.

Brain tissue, both grey and white matter from the cerebral parietal region and the cerebellum, was obtained from 66 infants dying of sudden infant death syndrome. The fatty acid composition was analysed in these tissues by gas liquid chromatography after extraction and derivatisation. The subjects were divided according to their dietary history, either breast or formula feeding. Formula-fed infants were further subdivided according to the content of -linolenic acid in the formula milk. At the time of this study no formula milks analysed contained long chain polyunsaturated fatty acids. Dietary related differences were found in the accretion of polyunsaturated fatty acids into neural membranes. Docosahexaenoic acid concentrations were higher and conversely n-6 series fatty acids lower in breast-fed than formula-fed infants. In cerebral white matter, nervonic acid, the long-chain fatty acid associated with myelination, appeared in breast-fed in advance of formula-fed infants. Similar dietary related differences in polyunsaturated fatty acid compositions were found in the cerebella cortex and the cerebellar white matter was associated with an earlier accretion of nervonic and lignoceric acids when compared to the cerebrum. Analysis of the phospholipid and glycolipid composition of the cerebral and cerebellar white matter tissues was achieved by means of separation by high performance thin layer chromatography followed by scanning densitometry. The results of this study support the need for breast feeding for a minimum of four months. Formulation of manufactured milks should include long chain polyunsaturated fatty acids and nervonic acid at concentrations similar to those of breast milk.