Childhood obesity treatment: integrating mobile health technology into a paediatric obesity service

Background: The management of childhood obesity is challenging. Aims: Thesis, i) reviews the evidence for lifestyle treatment of obesity, ii) explores cardiometabolic burden in childhood obesity, iii) explores whether changes in body composition predicts change in insulin sensitivity (IS), iv) develops and evaluates a lifestyle obesity intervention; v) develops a mobile health application for obesity treatment and vi) tests the application in a clinical trial. Methods: In Study 1, systematic reviews and meta-analyses of the 12‐month effects of lifestyle and mHealth interventions were conducted. In Study 2, the prevalence of cardiometabolic burden was estimated in a consecutive series of 267 children. In Study 3, body composition was estimated with bioelectrical impedance analysis (BIA) and dual x-ray absorptiometry (DXA) and linear regression analyses were used to estimate the extent to which each methods predicted change in IS. Study 4 describes the development of the Temple Street W82GO Healthy Lifestyle intervention for clinical obesity in children and a controlled study of treatment effect in 276 children is reported. Study 5 describes the development and testing of the Reactivate Mobile Obesity Application. Study 6 outlines the development and preliminary report from a clinical effectiveness trial of Reactivate. Results: In Study 1, meta--‐analyses BMI SDS changed by -0.16 (-0.24,‐0.07, p<0.01) and -0.03 (-0.13, 0.06, p=0.48). In study 2, cardiometabolic comorbidities were common (e.g. hypertension in 49%) and prevalence increased as obesity level increased. In Study 3, BC changes significantly predicted changes in IS. In Study 4, BMI SDS was significantly reduced in W82GO compared to controls (p<0.001). In Study 5, the Reactivate application had good usability indices and preliminary 6‐month process report data from Study 6, revealed a promising effect for Reactivate. Conclusions: W82GO and Reactivate are promising forms of treatment.

Self-cutting and prospective repetition of self-harm: studies of emergency department presentations in Ireland

Background Self-harm places an individual at increased risk of future self-harm and suicide, and indicates distress and maladaptive coping. Those who present to hospital with self-cutting form a significant minority of self-harm patients who are at increased risk of prospective repetition of self-harm and suicide compared with those presenting with intentional overdose. In addition to increased risk, there is emerging evidence of demographic, psychological, clinical, and social differences between those presenting with self-cutting and those presenting with overdose. Aim and Key Objectives The aim of the current doctoral work was to examine in detail the association between presenting with self-cutting and risk of prospective repetition. The objectives were: to identify evidence-based risk factors for repetition of self-harm among those presenting to emergency departments with self-harm; to compare demographic and presentation characteristics and prospective repetition across presentations of self-cutting only, self-cutting plus intentional overdose, and intentional overdose only; to compare prospective repetition and other characteristics within self-cutting presentations based on the type of treatment received; to compare self-cutting and intentional overdose patients on psychological risk and protective factors for repetition; and to examine the lived experience of engaging in repeated overdose and self-cutting. Methods The current doctoral work used a mixed-methods approach and is comprised of one systematic review and four empirical studies. The empirical studies were two registry-based prospective studies of Irish hospital presentations of self-harm, one prospective structured interview study, and one qualitative study using Interpretative Phenomenological Analysis. Results The systematic review identified several consistent and emerging risk factors for repetition of self-harm, compared to which self-cutting had a medium-sized effect. The registry studies demonstrated that the involvement of self-cutting, particularly less medically severe selfcutting, confers an increased risk of 1-month and 12-month repetition among Irish index selfharm presentations. The structured psychological study detected higher hopelessness and lower non-reactivity to inner experience among those presenting with self-cutting, and higher depression among those who repeated self-harm. Repeaters had lower baseline levels of protective psychological factors than non-repeaters and continued to have higher depression and hopelessness at follow-up. Finally, the qualitative study indicated that self-harm is a purposeful action taken in response to an overwhelming situation and is evaluated afterwards in terms of personal and social effects. Chosen method of self-harm seemed to be influenced by the desired outcome of the self-harm act, capability, accessibility and previous experience. Conclusion Despite limitations in terms of recruitment rates, the work presented in this thesis is innovative in examining the issue of the association between self-cutting and repetition from multiple perspectives. No one factor can reliably predict all repetition but self-cutting represents one consistent and easily detected risk factor for repetition. Those who present with self-cutting exhibit significant differences on demographic, clinical, and psychological variables compared with those presenting with intentional overdose, and seem to exhibit a more vulnerable profile. However, those who present with self-cutting do not form a discrete or homogenous group, and self-harm methods and levels of suicidal intent are liable to fluctuate over time.

Group problem-solving skills training for self-harm: randomised controlled trial

Background: Rates of self-harm are high and have recently increased. This trend and the repetitive nature of self-harm pose a significant challenge to mental health services. Aims: To determine the efficacy of a structured group problem-solving skills training (PST) programme as an intervention approach for self-harm in addition to treatment as usual (TAU) as offered by mental health services. Method: A total of 433 participants (aged 18-64 years) were randomly assigned to TAU plus PST or TAU alone. Assessments were carried out at baseline and at 6-week and 6-month follow-up and repeated hospital-treated self-harm was ascertained at 12-month follow-up. Results: The treatment groups did not differ in rates of repeated self-harm at 6-week, 6-month and 12-month follow-up. Both treatment groups showed significant improvements in psychological and social functioning at follow-up. Only one measure (needing and receiving practical help from those closest to them) showed a positive treatment effect at 6-week (P = 0.004) and 6-month (P = 0.01) follow-up. Repetition was not associated with waiting time in the PST group. Conclusions: This brief intervention for self-harm is no more effective than treatment as usual. Further work is required to establish whether a modified, more intensive programme delivered sooner after the index episode would be effective.

Economic evaluations of clinical pharmacy services in Ireland, 2007-2015

Introduction The concept of this thesis was driven by stagnation within the Irish healthcare system. Multiple reports from pharmacy organisations had outlined possible future directions for the profession but progress was minimal, especially in comparison with other countries. The author’s directive was to evaluate the economic impact of a series of clinical pharmacy services (CPS) in hospital and community settings. Methods A systematic review of economic evaluations of clinical pharmacy services in hospital patients was undertaken to gain insight into recent research in the field. Eligible studies were evaluated using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS), to establish the quality, consistency and transparency of relevant research. A retrospective analysis of an internal hospital pharmacy interventions database was conducted. A method first described by Nesbit et al. was implemented to estimate the level of cost avoidance achieved. A cost-effectiveness analysis based on data from a randomised controlled trial of a pharmacist-supervised patient self-testing (PST) of warfarin therapy is presented. Outcome measure was the incremental cost associated with six months of intervention management. A similar cost-effectiveness analysis based on previously published RCT data was used to evaluate a novel structured pharmacist review of medication in older hospitalised patients. Cost-effectiveness analysis was presented in the form of an incremental cost-effectiveness ratio (ICER). An ICER is an additional cost per unit effect, in the case of this study, the cost of preventing an additional non-trivial ADR in hospital. A method described by Preaud et al. was adapted to estimate the clinical and economic benefit gained from vaccination of patients by a community pharmacist in Ireland in 2013/14. Sample demographic data was obtained from a national chain of community pharmacies and applied to overall national vaccination data. Results Systematic review identified twenty studies which were eligible for inclusion. Overall, pharmacist interventions had a positive impact on hospital budgets. Only three studies (15%) were deemed to be “good-quality” studies. No ‘novel’ clinical pharmacist intervention was identified during the course of this review. Analysis of internal hospital database identified 4,257 interventions documented on 2,147 individual patients over a 12 month period. Substantial cost avoidance of €710,000 was generated over a 1 year period from the perspective of the health care provider. Mean cost avoidance of €166 per intervention was generated. The cost of providing these interventions was €82,000. Substantial net cost-benefits of €626,279 and a cost-benefit ratio of 8.64 : 1 were generated based on this evaluation of pharmacist interventions. Results from an evaluation of a novel pharmacist-led form of warfarin management indicated indicated that on a per patient basis, PST was slightly more expensive than established anticoagulant management. On a per patient basis over a six month period, PST resulted in an incremental cost of €59.08 in comparison with routine care. Overall cost of managing a patient through pharmacist-supervised PST for a six month period is €226.45. However, for this increase in cost a clinically significant improvement in care was provided. Patients achieved a significantly higher time in therapeutic range during the PST arm in comparison with routine care, (72 ± 19.7% vs 59 ± 13.5%). Difference in overall cost was minimal and PST was the dominant strategy in some scenarios examined during sensitivity analysis. Structured pharmacist review of medication was determined to be dominant in comparison to usual pharmaceutical care. Even if the healthcare payer was unwilling to pay any money for the prevention of an ADR, the intervention strategy is still likely to be cost-effective (probability of being determined cost-effective = 0.707). Implementation of pharmacist-led influenza vaccination has resulted in substantial clinical and economic benefits to the healthcare system. The majority of patients (64.9%) who availed of this service had identifiable influenza-related risk factors. Of patients with influenza-related risk factors, age ≥65 year was the most commonly cited risk factor. Pharmacist vaccination services averted a total of 848 influenza cases across all age groups during the 2013/2014 influenza season. Due to receipt of vaccination in a pharmacy setting, 444 influenza-related GP visits were prevented. In terms of more serious influenza-associated events, 11 hospitalisations and five influenza-related deaths were averted. Costs averted were approximately €305,000. These were principally wider societal-related costs associated with lost productivity. Conclusion Overall, clinical pharmacy services are adding value to the Irish healthcare system in both hospital and community settings, but provision of additional funding for new services would enable them to offer a great deal more.

Skin microbiome before development of atopic dermatitis: Early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year

Background: Disease flares of established atopic dermatitis (AD) are generally associated with a low-diversity skin microbiota and Staphylococcus aureus dominance. The temporal transition of the skin microbiome between early infancy and the dysbiosis of established AD is unknown. Methods: We randomly selected 50 children from the Cork Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE) longitudinal birth cohort for microbiome sampling at 3 points in the first 6 months of life at 4 skin sites relevant to AD: the antecubital and popliteal fossae, nasal tip, and cheek. We identified 10 infants with AD and compared them with 10 randomly selected control infants with no AD. We performed bacterial 16S ribosomal RNA sequencing and analysis directly from clinical samples. Results: Bacterial community structures and diversity shifted over time, suggesting that age strongly affects the skin microbiome in infants. Unlike established AD, these patients with infantile AD did not have noticeably dysbiotic communities before or with disease and were not colonized by S aureus. In comparing patients and control subjects, infants who had affected skin at month 12 had statistically significant differences in bacterial communities on the antecubital fossa at month 2 compared with infants who were unaffected at month 12. In particular, commensal staphylococci were significantly less abundant in infants affected at month 12, suggesting that this genus might protect against the later development of AD. Conclusions: This study suggests that 12-month-old infants with AD were not colonized with S aureus before having AD. Additional studies are needed to confirm whether colonization with commensal staphylococci modulates skin immunity and attenuates development of AD.