Paediatrics (RCH) - Theses

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    Asymptomatic thrombosis following the use of central venous catheters in children
    Jones, Sophie Elizabeth ( 2017)
    Central venous catheters (CVCs) are the major cause of thrombosis in acutely unwell neonates and children. This thesis reports the outcomes of a prospective study of 189 children in a paediatric intensive care unit (PICU) that aimed to determine the frequency of asymptomatic CVC-related thrombosis during hospital admission, and the incidence of residual CVC-related thrombosis and clinically significant post thrombotic syndrome (PTS) two years following CVC placement. The study also sought to identify risk factors predictive of CVC-related thrombosis and clinically significant PTS and determine the utility of ultrasound screening for asymptomatic CVC-related thrombosis in acutely unwell children. This study is distinct from previous work as children in this cohort identified to have asymptomatic CVC-related thrombosis were not treated and were followed for two years to determine the natural history of asymptomatic thrombosis. The incidence of asymptomatic CVC-related thrombus during hospital admission was 21.2% (n=31), despite over 80% of the cohort having received thromboprophylaxis. One child had a symptomatic CVC-related thrombosis. Sixteen children had new or residual thrombus identified on the follow-up ultrasound, performed a mean of 26 months post CVC placement. Of 126 PTS assessments completed at follow-up, 10.3% of children were diagnosed with mild PTS as classified by both the Manco-Johnson instrument and Modified Villalta scale. Only two children were identified to have clinically significant PTS (Manco-Johnson instrument only), one of whom had a symptomatic CVC-related thrombosis. Whilst over one fifth of the cohort had asymptomatic CVC-related thrombosis, only one of these children developed clinically significant PTS. There were no clinical embolic phenomenon or deaths attributable to CVC-related thrombosis. These findings suggest that ultrasound screening for asymptomatic CVC-related thrombosis is not indicated in children in PICU as, despite no treatment (in all but one child), the incidence of any thrombosis-associated morbidity was extremely low. In addition, the study’s findings support previous evidence that thromboprophylaxis provides no protection against CVC-related thrombosis in children. Neither D-dimer nor Factor VIII were predictive of CVC-related thrombosis. However, this study identified that children with femoral CVCs had a significantly higher incidence of residual thrombosis and thrombosis-associated morbidity. Children with femoral CVCs were also significantly more likely to have a higher PIM2 probability of death, cardiac arrest, hypotension, elevated D-dimer and Factor VIII compared to children with jugular CVCs. Whether the placement of the CVC in the femoral veins or the apparent higher acuity of this sub-group of patients is the mediator of increased risk (residual thrombosis and morbidity) compared to jugular CVC placement remains unclear. This study contributes novel insights into the natural history of asymptomatic CVC-related thrombosis, demonstrating a very low morbidity associated with jugular CVC placement. This study informs future clinical research targeting children most at risk of long-term CVC-related thrombosis associated morbidity. Specifically, further investigation of similar cohorts of children to those in whom femoral CVC placement occurred in this study is needed to elucidate risk factors for poor outcomes and the potential for a risk stratified approach to the treatment of asymptomatic CVC related thrombosis.
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    Quality of life assessment in children requiring oral anticoagulant therapy
    Jones, Sophie Elizabeth ( 2011)
    The absence of robust evidence regarding the management and clinical outcomes of anticoagulant therapy in children challenges interpretation of the risks and benefits of long-term anticoagulation therapy for children. Decisions about treatment increase in complexity in light of the potential burden of treatment on children and families. Quality of life (QoL) is a recognised and validated measure of the burden of treatments for children; yet, there is a lack of data about the impact of long-term warfarin therapy on QoL for children and families. This thesis describes the first study to evaluate the impact of a home international normalised ratio (INR) self-testing (home ST) program on the QoL of children and their families. The aim of the study was to determine if participation in a home ST program improves QoL for children requiring long-term warfarin therapy and their families. Parents of children requiring long-term warfarin therapy and children aged eight to 18 years participated in the QoL study. Three validated QoL questionnaires, the Pediatric Quality of life Inventory Generic Core Scale™, the Pediatric Quality of Life Family Impact Module™ and the KIDCLOT Pediatric Anticoagulation Quality of Life © inventory were employed to measure QoL. Questionnaires were completed before commencing home ST and six to 12 months later. Participants answered four open-ended questions when completing the questionnaires for the second time. Fifty-six families entered the home ST program during the study period. The children were aged between 2 and 17 years. Fifty-five parents and 35 children completed QoL questionnaires. Results of INRs tested at home were collected. The percentage of time the children’s INRs were in their target therapeutic range was 71.3%, which is comparable to many published paediatric studies of home ST. Parents reported statistically significant improvements in QoL for themselves, their family and their child, across all questionnaires following the commencement of home ST (mean difference in score p ≤ 0.003 on all questionnaires). The children’s scores of their own QoL also improved; however, this improvement was not significant. Parents’ report of their children’s QoL was significantly lower than the children’s report of QoL on all questionnaires at both time points. As well as being the first validated baseline QoL data in an Australian population of children requiring oral anticoagulant therapy, this study reports QoL for the largest cohort of children requiring warfarin therapy worldwide. The employment of both quantitative and qualitative methods to assess QoL enhanced understanding about the impact of home ST on QoL. This study has demonstrated that home ST in a population of children requiring long-term warfarin therapy is safe, efficacious and improves the QoL of children and parents. This study confirms home ST successfully reduced the burden of therapy and maintained excellent clinical outcomes. The results of this study not only identify the impact of warfarin therapy upon QoL in children, but offer an alternative evaluation strategy to sensitively measure the impact of interventions in this population. Accurate QoL assessments ensure children’s and families’ values are integrated with the current evidence for best clinical practice.