This thesis explores the effects of adverse childhood experience, including childhood abuse and neglect, on adolescents. More specifically, it explores these effects in relation to offending behaviour. A literature review considered research investigating differences between sexual and non-sexual offenders. More consistent differences were identified for adolescents who sexually offend against children, as opposed to those who offend against peers / adults, when compared to other groups of offenders. Studies in this area are, however, subject to methodological limitations. Following this, an empirical research project investigates the prevalence and characteristics of adverse childhood experience in a sample of mixed sex adolescents detained in a medium secure specialist psychiatric hospital, alongside psychopathological traits. Male sexual offenders differed from violent offenders on a number of variables, including experiences of sexual abuse and a diagnosis of a Learning Disability (LD). Then, a single case study is highlighted which investigates and demonstrates the influence of adverse childhood experience and cognitive impairment on vulnerabilities and offending behaviour in an adolescent male detained in the aforementioned secure psychiatric hospital. The effectiveness of the intervention, designed to address this individual’s difficulties with emotional recognition and regulation, is demonstrated by changes in psychometric assessments scores and via clinical observation of behaviour. Finally, a critique is presented of the Coping Responses Inventory – Youth Form (CRI-Y) (Moos, 1993). This is a psychometric measure designed to measure styles of coping in adolescents. It is critically evaluated to demonstrate its psychometric properties, and its validity for clinical settings. This thesis emphasises the importance of considering developmental experience in the onset of offending behaviour, and the importance of engineering more comprehensive, systemic, and targeted early intervention programmes for individuals deemed at risk of committing particular offences or becoming delinquent in adolescence.

Malnutrition is a global health problem that affects infants and young children. It is frequently associated with infections and commonly affects children in developing countries. Malnutrition is the cellular imbalance between the supply of energy from macronutrients and micronutrients and the demand of the body for them in order to achieve normal growth, maintenance, and specific functions. Underweight (mild to moderate) and marasmus, marasmic-kwashiorkor, and kwashiorkor (severe) are the spectrum of malnutrition. Various pathophysiological changes, including fatty changes, abnormal rough endoplasmic reticula and mitochondria, decreased peroxisomes, and decreased quantity and quality of metabolising enzymes, are associated with malnutrition which may significantly influence hepatic drug metabolism. However, the effect of different categories of malnutrition on drug metabolism has not been extensively investigated. This research, therefore, aimed to determine the effect of malnutrition on drug metabolism. The specific objectives are (i) to perform a systematic review of the studies of drug pharmacokinetics in malnourished children, and (ii) to use the caffeine breath test to determine the effects of different types of malnutrition on the metabolising activity of hepatic CYP1A2 enzymes. The systematic review involved literature searches in the MEDLINE and EMBASE databases covering publications between January 1960 and December 2009. Articles describing drug pharmacodynamics and pharmacokinetic parameters in the four categories of malnutrition, limited to children from 0 to 17 years, were sought using both databases and by reference tracking. Altogether, 42 publications evaluated the disposition of 34 drugs in malnourished children. The drug absorption rate (Ka) was reported for eight drugs, of which gentamicin, metronidazole, phenytoin, chloramphenicol, paracetamol, and sulphamethoxazole showed no difference in the values of Ka for malnourished children and the control groups. The AUC of seven drugs did not differ for malnourished children when compared to their control groups but significantly decreased for carbamazepine (p < 0.05) and chloroquine (p < 0.001). By contrast, there was a statistically significant increase in the AUC of six drugs: metronidazole (p < 0.05), caffeine (p < 0.05), paracetamol (p < 0.05), phenobarbitone (p < 0.05), sulphadiazine (p < 0.01), and sulphamethoxazole (p < 0.001). The plasma protein binding of 19 drugs was evaluated in seven in vitro and two in vivo studies. There was a statistically significant decrease in the protein binding of 17 drugs in kwashiorkor when compared to healthy adults (p-values ranged from <0.0005 to <0.05). Nineteen studies evaluated the effects of malnutrition on the volume of distribution (VD) for 14 drugs. For most drugs, malnutrition had no statistically significant effect on VD. However, four drugs: gentamicin, quinine, streptomycin, and theophylline demonstrated contrasting results. The effect of malnutrition on the total clearance (CL) and elimination half-life (t½) of nine drugs that are primarily metabolised in the liver was evaluated in 15 studies. There was a statistically significant decrease in the CL of six drugs: acetanilide (p < 0.025), antipyrine (p < 0.05, p < 0.0025, p < 0.05), caffeine (p < 0.01), sulphamethoxazole, isoniazid (p < 0.01), and metronidazole (p < 0.01). There was a corresponding statistically significant increase in their plasma half-lives. For six drugs that are primarily eliminated by the kidneys, malnutrition has a varying effect on their total CLs. The total CL was significantly increased for penicillin in children with marasmus (p < 0.001), marasmic-kwashiorkor (p < 0.01), and kwashiorkor (p < 0.01), as well as increased for streptomycin in children with kwashiorkor (p < 0.01). By contrast, the total CL was significantly decreased for penicillin in underweight children (p < 0.01). It was also significantly decreased for cefoxitin in children with kwashiorkor (p < 0.025). The significantly decreased total CL of most of the drugs primarily metabolised by the liver may reflect decreased activity of the intrinsic hepatic metabolising enzymes. This would suggest a need to reduce drug dosage in malnourished children. More studies are therefore required to assess the activities of the hepatic metabolising enzymes in malnourished children. Following the systematic review, the caffeine breath test (CBT) identified as a non-invasive approach to study the effects of the four categories of malnutrition on caffeine metabolism. Caffeine is a 1, 3, 7 trimethylxanthine compound that is metabolised in the liver by 1-N, 2-N and 7-N demethylation, and C-8 hydroxylation to 1, 3, 7 trimethyluric acid. CYP1A2 is responsible for the 3-N demethylation of caffeine. The CBT involves oral administration of a non-radioactive stable isotope of caffeine (13C on the 3-methyl group). The caffeine undergoes 3-N demethylation in the liver which is a CYP1A2 dependent reaction. After N-demethylation, the 13C methyl group enters the carbon pool as it is converted to formaldehyde, formate and bicarbonate. The bicarbonate is exhaled as carbon-dioxide. The exhaled labelled 13CO2 is known to correlate with CY1A2 activity. Fifteen children each who were underweight or experiencing marasmus, marasmic-kwashiorkor or kwashiorkor were recruited from Lagos and Kano States in Nigeria. They were studied before and after nutritional rehabilitation. After ingesting labelled caffeine (3mg/kg) at 0900 hours, breath samples were collected in duplicate at -20, -10, -1 minute and every 15 minutes over 2 hours. The cumulative mean percent 13C-caffeine dose exhaled as 13CO2 was measured over 2 hours. Student’s t-test was used to compare the results for each category of malnutrition, before and after nutritional rehabilitation, at 5% level of significance. The mean cumulative percent 13C-caffeine dose recovered (CPDR) in underweight children was 7.56 ± 4.01% and 7.95 ± 3.68% before and after nutritional rehabilitation, respectively, and there was no significant difference in the mean values (p = 0.603). The CPDR significantly increased after nutritional rehabilitation in children with marasmus (from 6.80 ± 3.00% to 7.67 ± 2.81%, p < 0.001), marasmic-kwashiorkor (from 6.61 ± 2.26% to 7.56 ± 2.46%, p < 0.041), and kwashiorkor (from 6.29 ± 1.06% to 7.20 ± 1.80%, p =0.002). It is concluded that the present study may not have been adequately powered to detect a statistically significant difference in the results for underweight children. Such a difference would have been the basis for validating the results in a larger population of underweight children. However, doses of drugs that are metabolised by CYP1A2 enzyme may require modification in severely malnourished children.

Many authors have commented on the perceived gap between psychotherapy research and clinical practice, but with the rise of 'evidence-based practice' over the past decade, this gap has become more problematic. Whilst funders of services increasingly emphasise the importance of practice being informed by the best available research evidence, clinicians have become concerned with the way in which clinical and service-level decisions are based on an overly narrow definition of 'evidence'. Psychodynamic therapists have been especially cautious about 'evidence-based practice', arguing that the methodologies used are not appropriate for this type of therapy. Clinicians working with children have also been concerned that there is limited funding available to evaluate therapy with young people, and that the approaches used are often transposed from studies with adults, without attention to whether they are developmentally appropriate. This PhD by Published Works brings together a series of papers published between 2003 and 2014, which engage with these topics. They address issues of methodology and policy, as well as providing examples of attempts to 'bridge the gap' using both primary research and secondary reviews of the existing literature. The papers are mostly presented in chronological order, and have been organised into three sections. Part one, 'Incorporating qualitative research methods into child psychotherapy', includes three papers that deal conceptually and practically with the issue of identifying appropriate research methods for investigating child psychotherapy. The papers in part two, 'The case study as a method of research in child psychotherapy', examine the traditional method of investigating child psychotherapy, and explore the pros and cons of this approach. The final section, 'Engaging with the evidence-base for psychoanalytic child psychotherapy’, offers an approach to evaluation that draws on a range of methodologies, and thereby engages with evidence-based practice whilst also offering a critique of current approaches.

At a time when health literacy is emerging as a central concern in the health field, this thesis examines whether and how practitioners involved in the promotion of breastfeeding incorporate dimensions of health literacy as described in the current literature. Although there is little evidence that practitioners are familiar with specific definitions of health literacy, their description of practices reflected various facets of health literacy including functional health literacy, interactive and critical health literacy, and health literacy as composed of multiple literacies. This qualitative case study was set in a rural health district in the Canadian province of Nova Scotia where breastfeeding initiation and duration rates are lower than national averages and where health literacy was identified as a community health issue. In-depth face-to-face interviews were conducted with 30 professional and lay practitioners. Practices in one hospital-based and two community-based settings were observed. Data were analyzed for themes using an iterative process of constant comparison. Interview informants and mothers provided feedback on preliminary findings in focus group interviews. Findings reflect an emphasis on the transmission of information to persuade mothers to breastfeed, in contrast to strengthening their capacity to use information in making or acting on choices about how to feed their babies. Practitioners’ discomfort in identifying clients with low literacy skills raises fundamental concerns about the stigma associated with low literacy. A focus on the functional health literacy deficiencies of clients, not on their capacities, appears limiting in addressing the complexities of breastfeeding promotion. There is little evidence of practices which reflect critical health literacy or efforts to reduce structural barriers to breastfeeding. In conclusion, the study suggests that practitioners’ engagement in critical reflection of their breastfeeding promotion practices through the multidimensional frame of health literacy could help to further their practice and the conceptual development of health literacy.

Introduction: The segregation of patients with Cystic Fibrosis, purposefully keeping them apart from one another, has become common practice in order to reduce infections being passed from one CF patient to another. There is sufficient medical evidence to support these measures as an effective method of preventing early deterioration of the lungs, yet, there has been virtually no research exploring the psycho-social impact of such a policy. This study aimed to fill this void and become the first study to explore segregation from the perspectives of young people with cystic fibrosis. Method: A qualitative design was used and eight young people with Cystic Fibrosis, (aged 13-15) were interviewed at The Royal Hospital for Sick Children, NHS Greater Glasgow & Clyde. Following transcription, in-depth analysis using Interpretative Phenomenological Analysis was carried out. Results: Analysis of transcripts led to the identification of three super-ordinate themes; ‘Acceptance of Source’ which refers to participants overall acceptance of being in source isolation, after weighing up the pros and cons, ‘Personal Models of CF’ which refers to both medical and psycho-social perceptions of having CF, and ‘Normalisation’ emerged through descriptions of methods used to help to them feel normal and cope with CF. It is proposed that loss of any one of these factors may have a negative impact on adjustment. Conclusions: Support was found for the practice of segregation however this is not without a psycho-social cost (i.e. loss of opportunity to openly discuss their health with others and have their experiences validated). These young people also appeared to have heightened awareness of the wider impact of the policy upon their parents. Contact with CF others was recognised by these young people as valuable. Innovative solutions are urgently required to address these potential costs. In light of this, a number of clinical recommendations have been made and areas for future research have been outlined.

Juvenile GM2 gangliosidosis (jGM2) is a group of inherited neurodegenerative diseases caused by deficiency of lysosomal β-hexosaminidase A (Hex A) resulting in GM2 ganglioside accumulation in brain. Like many other lysosomal storage diseases (LSDs), no specific treatment currently exists. In order to establish clinical outcomes for the investigation of potential therapies for jGM2, I collected comprehensive information on the natural history of the condition by studying retrospective and prospectively a cohort of 21 patients with the disease, and reviewing previously published reports of 134 patients. Several symptoms at disease onset, symptom latencies, and the survival curve were described. Genotype-phenotype correlations and neuroradiological findings were also studied. Based on pre-clinical results in animal models, we studied substrate reduction therapy (SRT), with miglustat, in a phase I/II clinical trial to assess its pharmacokinetics (PK), safety, tolerability in infantile and jGM2. Miglustat showed a PK profile similar to the one found in adult patients. The drug was found to be safe and well-tolerated in patients with jGM2, with diarrhea and weight loss being the most common drug-related adverse events. The analysis of efficacy showed that SRT was unable to arrest the full neurological progression of the condition; however, relative stabilization of cognitive function was noted, which was consistent with brain MRI findings. Because of the limited efficacy obtained with SRT, enzyme-enhancement therapy was considered to be an attractive alternative therapy for the late onset forms of GM2 gangliosidosis. Screening of a FDA-approved library of approved therapeutic compounds resulted in the identification of pyrimethamine, as a potential pharmacological chaperone for mutant forms of Hex A. Relative enhancements of enzyme activity and protein levels were observed in patient cells treated with therapeutic concentrations of drug. Applying the same principles, ambroxol was identified as a potential PC for mutant glucocerebrosidase (GCC), the lysosomal enzyme that when deficient causes Gaucher disease (GD). Significant increases of residual mutant GCC were observed in cultured patients cells with type 1 GD. In conclusion, principles developed in the course of studies on jGM2 were shown to be useful for the investigation of novel small-molecule therapies for LSDs, associated with significant neurodegeneration.

As Crohn’s disease (CD) is a disease of the gastrointestinal tract, nutrition is very important and is implicated in several aspects of the disease, from aetiology, management, and the long-term health of the patient. Nutritional therapy with EEN is the mainstream approach in the management of active paediatric CD and has a dual effect, inducing clinical remission and providing nutritional support and rehabilitation. Although its efficacy is well established by human trials and clinical experience, the mode of action remains unknown. Initial speculations for a mechanism of action mediated through gut rest, and protein/energy reconstitution have not been established. On the other hand the strong evidence for the role of the indigenous microbiota and micronutrients in disease aetiology and mucosal injury, challenged the researcher to explore whether the action of EEN is mediated through changes in these parameters. This study aimed to assess aspects of the nutritional status of paediatric patients with inflammatory bowel disease (IBD), to appraise the use of nutritional remedies in the same population, and to explore putative mechanisms of action of EEN, the nutritional therapy, with the most robust evidence of clinically efficacy. The first of these studies was a questionnaire survey which assessed the use of special diets, nutritional supplements, herbals, and alternative medicine in a representative sample of paediatric patients with IBD. Use of these treatments was declared by two thirds of the patients with probiotic use and dairy free diet being the commonest forms used. Prevalence of anaemia and predictors of its progress at six and 12 months were assessed in a large retrospective case review study. Anaemia was as high as 73% of patients at diagnosis and haemoglobin concentration improvement at six and 12 post diagnosis was associated with the use of oral iron supplementation, improvement of nutritional status markers, growth, and systemic markers of disease activity. In a mechanistic study the validity of a bedside method, used to assess the body composition of children with CD, was compared against a reference method. The agreement of the two methods was low and the inter-individual bias between them was substantial. The aim of this thesis was to study the effect of EEN on gut microbiota diversity, bacterial metabolic activity, inflammatory response and nutritional status in paediatric patients with active CD. Newly diagnosed children with active CD, and patients with longstanding disease, on clinical relapse, who started treatment with EEN as part of their standard clinical management, were recruited. Four stool samples were collected while on treatment with EEN and one when the patient returned to their normal diet. Bacterial diversity was assessed with molecular microbiology techniques, and bacterial metabolites were measured in serial stool samples and correlated with faecal calprotectin levels, systemic inflammatory markers and clinical activity. A single stool sample was collected from their first-degree relatives and two serial samples from healthy children with no family history of IBD. Significant changes were observed for the metabolic activity of the commensal microbiota during the course of treatment. In particular, faecal butyrate significantly decreased by more than 100%, faecal pH moved into the alkaline range, and a five-fold increase was observed in total sulphide but only in those patients who achieved clinical remission, or in whom faecal calprotectin levels decreased at the end of treatment. No such changes were observed in children who did not achieve complete clinical remission or when the treatment failed. Gut bacterial diversity did not change significantly during treatment, but was significantly lower than in healthy children, who also presented a higher degree of similarity between the two serial samples. Interestingly the gut microbiota of the healthy first degree relatives of CD children had significantly lower bacterial diversity compared with the healthy children but no such difference was observed compared with their CD relatives. The majority of the healthy relatives had also significantly high levels of calprotectin suggesting intestinal inflammation but no clinical presentation of gastrointestinal disease. A secondary outcome of this study was to measure changes in the systemic and gut specific markers of disease activity during treatment. Although systemic markers of disease activity improved to normal levels in the majority of the patients, intestinal inflammation was still ongoing and only one of the 16 children had normal calprotectin levels at the end of EEN. Moreover, only in those patients who achieved clinically complete remission, did calprotectin levels decrease significantly at the end of treatment. From the same cohort of patients three blood samples were also collected before, at the end of treatment and on normal diet. Changes in the concentration of 19 different micronutrients were measured in the serum and some in erythrocytes and correlated with systemic markers of disease activity. Serial changes in anthropometry and body composition were assessed during EEN and correlated with disease activity markers. Body weight increased in all patients at the end of treatment but fat free mass significantly increased only in those patients who entered in clinical remission. Several micronutrients and mainly antioxidants were below the reference range for the majority of patients at the time of treatment initiation. Most of them improved by the end of treatment but the serum concentration of carotenoids further deteriorated with more than 90% of the patients presenting concentration lower than the lower sensitivity level of the assay. A strong association was found between systemic markers of disease activity and antioxidant vitamins, but not with intestinal inflammation. In conclusion, paediatric patients with IBD, and mainly those with CD present with suboptimal protein/energy status, anaemia, and low circulating levels for many antioxidants. Treatment with EEN corrected the majority of these markers of nutritional status but the carotenoid levels deteriorated. Although the improvement in the serum levels of some micronutrients can be an epiphenomenon of the acute phase response, it does not explain the depleted levels of carotenoids at the end of EEN. This may be attributed to the lack of carotenoids in the feeds used in conjunction with excessive utilisation during the active course of the disease. On the other hand, the unhealthy intestinal microenvironment observed, in only those patients who clinically improved at the end of treatment; do not support a prebiotic mode of EEN action, as was proposed by a recent Italian study. These changes may be a secondary phenomenon, associated with changes in gut motility, better absorption of butyrate with disease improvement, or changes in the availability of colonic bacterial substrates. Alternatively these changes may be associated with changes in the microbiota composition and production of so far unknown bacterial bioproducts which may have a causative association with the onset and propagation of intestinal inflammation in CD. These results may have significant implications in manufacturers of clinical nutrition products. Addition of carotenoids may improve the provision of antioxidant micronutrients and a dual nutritional therapy combining EEN with prebiotics, butyrate supplementation, or probiotics may increase the efficacy of the existing formulae. This should be addressed in future studies.

Objectives - To develop and pilot a community-based family programme, ‘Families for Health’, for intervention with overweight and obese children aged 7-11 years. Intervention – ‘Families for Health’ is a 12-week programme, with parallel groups for parents and children, combining support for parenting, lifestyle change, as well as social & emotional development. Design of the Evaluation – Pilot study using mixed-methods comprising: process evaluation; outcome evaluation involving a ‘before and after’ evaluation and triangulation with interview data; economic evaluation (cost-outcome description); users and providers perspectives. Setting – Leisure Centre, Coventry, England Participants – 27 overweight or obese children aged 7-13 years (18 girls, 9 boys) and their parents, from 21 families. Process Evaluation – Two groups were run, and were delivered as planned. Recruitment was difficult, although most effective via the media. Attendance rate was 62%, with 18(67%) children completing the programme. Outcome Evaluation – Primary outcome was change in the BMI z-score from baseline. For 22 children with follow-up data, BMI z-score was significantly reduced by -0.18 (95% CI -0.30 to -0.05, p=0.008) at the end of the programme, and was sustained to 9-months (-0.21) and 2-years (-0.23). There were also significant improvements in the children’s quality-of-life, eating and activity environment, child-parent relationships and parent’s mental health. Fruit and vegetable consumption, participation in moderate/vigorous exercise, and children’s self-esteem did not change significantly. Interview data illustrated the changes made by the families, particularly to their eating environment. User and Provider Perspectives – The group-based parenting approach was received well, providing the ‘tools’ for parents to become ‘agents of change’ in the family. Suggested changes to the programme include providing follow-up sessions and a greater focus on physical activity. Economic Evaluation - Costs to run ‘Families for Health’ were £517 per family or £402 per child, in-line with other group-based obesity management or parenting interventions. Conclusion - ‘Families for Health’ is a promising new intervention for the management of childhood obesity.

Access to health care for children is important. It is dependent on access to health professionals and also parental attitudes towards illness. Children have the right to receive medicines that are scientifically evaluated for both efficacy and safety. Counterfeit and substandard medicines unfortunately result in the death of many children worldwide. There have been particular problems with diethylene glycol which has been used as a solvent in counterfeit medicines. It has also been found in contaminated substandard medicines. It has been responsible for the death of many children in different countries throughout the world. I performed a literature review of all cases of diethylene glycol poisoning that have been published. I have described the clinical signs and symptoms and hope that these findings increase the awareness of diethylene glycol poisoning in children. It is well known that there are clear inequalities in health and access to health care in the UK. This inequity has been particularly noticed amongst certain minority groups. Children of “at risk” groups, such as Asylum Seekers and Refugees, and Gypsies and Travellers, were recognised as having possible barriers in accessing health care and medicines. I conducted a study to explore children’s access to medicines in the East Midlands area in the UK. Alongside determining accessibility to health care the study also wished to explore parental attitudes towards receiving treatment for pain, asthma and epilepsy Both quantitative and qualitative research methodology was used in this study. The research data was gathered with the aid of semi-structured interviews with parents from the “at risk” groups and control parents. Fifty parents from each group were selected and interviewed regarding their children‟s health and their access to health care and medicines. The semi-structured interviews allowed participating parents to state their opinions about any barriers they had encountered to their children receiving medicines. Parents from both “at risk” groups and children from the Traveller group had more health problems than the controls. The attitude of some Gypsy and Traveller parents (11%) not to immunise their children was a significant problem. One in six Refugee parents reported difficulties while obtaining medicines. The two main barriers were language/communication problems and financial difficulties. Both Refugee and Traveller children received fewer OTC medicines than the children of the control group. It was not clear from the interviews whether this was due to financial difficulties or reluctance to use medicines without a doctor having seen the child first. Parents from both “at risk” groups were less likely to give analgesics for treating earache than those in the control group. Parents of Refugee children were more reluctant to tell others about their child’s epilepsy. Access to health care is an essential human right. Children are dependent upon both their parents and the health system for ensuring access to health care. This study has identified problems both within the system and also in relation to parental beliefs that may affect the access to health care and treatment for children. It is important that both of these potential barriers are addressed in order to improve the health of children of “at risk” groups. It is hopeful that the findings in this study will help to identify ways of improving access to health care and medicines for these groups.

Attention Deficit Hyperactivity Disorder (ADHD) is the most commonly diagnosed mental disorder of childhood. Most of the deficits it describes are situated examples of classroom misdemeanour, and yet the school’s complicity in rising diagnostic trends has not been extensively questioned. This study aims to provide this through an ethnographic account of ADHD in the infant classroom. Underscored by Foucault’s analysis of power and discourse, this study aims to describe some of the conditions of school and home which make the application of a diagnosis possible. The project firstly presents textual critique of the dichotomous and categorical channels through which ADHD is currently known. Following this the ethnographic account is presented, the data for which derives mainly from observational work in two schools and interviews with two families. The data explores four problematics in early education and social care; routinisation, gendering, responsibilisation and emotional governance. Together these relations produce binds in the conceptualisation of childhood, schooling and family, through which therapeutic discourse is able to form objects, producing the classroom subject ‘ADHD’. Through this argument I offer the means to re-insert the social and cultural into naturalised and individualised therapeutic narratives. In conclusion I argue for a re-imagination of the manner in which we interrogate choice, and state the case for a more reflexive pedagogical encounter with the construction of others.