Typescript (photocopy). / Digitized by Kansas Correctional Industries

The incidence of surgical site infection (SSI) in pediatric spinal deformity has been reported to remain high in the United States in spite of efforts made to reduce SSI. The risk of SSI is associated with multiple factors. For example, the heterogeneity of patients with different clinical and surgical characteristics in this population imposes challenges to identify the most beneficial preventive strategies for individual patients. This dissertation sought to advance understanding of risk factors and preventive strategies for SSI in individual pediatric patients undergoing spinal deformity surgery. Although the literature reports various risk factors and preventive strategies associated with SSI, there are no reliable review papers using formal methodology to aggregate evidence. The first aim of the dissertation was to conduct a systematic review and a meta-analysis to assess published literature investigating associations between various risk factors and SSI in pediatric patients undergoing spine surgery. The systematic review and the meta-analysis were conducted among peer-reviewed journals published in English between January 2000 - April 2019 using the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA-P). Studies included pediatric patients with spinal deformity undergoing surgical procedures in North America and were assessed for risk factors of SSI. Of 763 articles identified, thirteen met inclusion criteria after abstract or full manuscript review, and seven studies were rated as average and six as poor based on the quality checklist. The meta-analysis identified obesity/overweight, neuromuscular etiology, gastrostomy tube, non-ambulatory status, pelvic instrumentation, and high estimated blood as significant risk factors for SSI. Because the published literature does not identify which individual patients are at high risk for SSI, the second aim of this dissertation was to create a calculator using prediction modeling including patient, surgical and hospital characteristics to quantify the risk of SSI in individual patients. A retrospective cohort study was conducted using a database from seven centers that included 3,092 pediatric patients (0-21 years of age) with spinal deformity who underwent primary, revision, or definitive spinal fusion from 2004 to 2018. A total of 132 SSI (4.5%) within 90 days after surgery were identified. Candidate risk factors in this study included 31 patient, 12 surgical and 4 hospital factors that were present or determined before the surgery and unlikely to be modifiable. The final prediction model achieved adequate predictive ability (area under the curve [AUC]: 0.76) and included 10 risk factors: overweight/obese, neuromuscular etiology, American Society of Anesthesiologist Physical Status Classification System (ASA) >1, non-ambulatory status, abnormal hemoglobin (HGB) level, high white blood cell (WBC) count, revision surgery, presence of pelvic instrumentation, procedure time for ≥7 hours, and <100 spine surgical case per year per institution. Based on these findings, a risk probability calculator to predict the risk of SSI in individual patients was developed. There are a number of preventive strategies that have been recommended in consensus-based guidelines in the United States. The third aim of this dissertation was to investigate the association between preventive care measures and SSI and predict the reduction of SSI probability in individual patients by these preventive strategies. The database used in Aim 2 was also utilized to investigate the association between preventive care measures and the risk of SSI. Examined preventive strategies were the use of topical vancomycin, povidone-iodine irrigations, multilayered closure, impermeable dressing, the enrollment in Children’s Hospitals’ Solutions for Patient Safety (SPS) program or in the Comprehensive Unit-based Safety Program (CUSP), and adherence to the institutional perioperative antibiotic prophylaxis guideline. None of these preventive strategies were included in the risk model from Aim 2. When the CUSP/SPS enrollment alone was in the model, patients whose procedures were performed when sites were enrolled in the programs had 49.4% decrease in SSI (odds ratio [OR]:0.51, [95% CI: 0.32; 0.81], p=0.005) and AUC of 0.56. When CUSP/SPS enrollment was added to the risk model from Aim 2, the model revealed that patients whose procedures were performed when sites were enrolled in the CUSP/SPS had an average 48.9% decrease in SSI (odds ratio: 0.51, [95% CI: 0.29; 0.82]). The final prediction model demonstrated adequate predictive ability (AUC: 0.77). This dissertation highlighted factors associated with an increased risk of SSI and preventive strategies related to a reduced risk of SSI in pediatric patients undergoing spinal deformity surgery. The results of this study will enable healthcare providers to calculate the risk of SSI and effects of preventive strategies in reducing the risk of SSI in individual patients. In the long term, the information from this study could be used to enhance personalized care in clinical practice to prevent SSI in individual patients as well as to facilitate patient education and shared decision-making.

Thesis (M.Tech.: Chiropractic)-Dept. of Chiropractic, Durban University of Technology, 2007 xi, 38 leaves, Annexures 1-2 / Background: Various congenital spinal anomalies are common findings in the general population. Their clinical significance is controversial with no definitive association been made between any specific congenital spinal anomaly to any clinical features. Project Design: This research study was designed in the form of a quantitative, non-experimental, empirical clinical survey. Method: Data was obtained from thoracic and lumbar spine radiographs contained in the Chiropractic Day Clinic at the Durban University of Technology from 1 January 1997 to 31 December 2005 and from the corresponding patient files. Through the research procedure, 519 thoracic and lumbar spine radiographs were located in the confines of the Chiropractic Day Clinic. Due to the exclusion criteria of a past or present history of trauma to the thoracic or lumbar spine areas, 147 radiographs were excluded. Objectives 1.To determine the period prevalence (1 January 1997 – 31 December 2005) of congenital thoracic and lumbar spine anomalies. 2.To determine if there is any association between the presenting clinical features and the congenital thoracic and lumbar spine anomalies in general. 3.To determine if there is any association between the presenting clinical features and individual congenital thoracic and lumbar spine anomalies. 4.To compare subjects presenting clinical features with reported clinical features from literature.

Dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Chiropractic, Durban University of Technology, 2007. / Background: Various congenital spinal anomalies are common findings in the general population. Their clinical significance is controversial with no definitive association been made between any specific congenital spinal anomaly to any clinical features. Project Design: This research study was designed in the form of a quantitative, non-experimental, empirical clinical survey. Method: Data was obtained from thoracic and lumbar spine radiographs contained in the Chiropractic Day Clinic at the Durban University of Technology from 1 January 1997 to 31 December 2005 and from the corresponding patient files. Through the research procedure, 519 thoracic and lumbar spine radiographs were located in the confines of the Chiropractic Day Clinic. Due to the exclusion criteria of a past or present history of trauma to the thoracic or lumbar spine areas, 147 radiographs were excluded. Objectives 1.To determine the period prevalence (1 January 1997 – 31 December 2005) of congenital thoracic and lumbar spine anomalies. 2.To determine if there is any association between the presenting clinical features and the congenital thoracic and lumbar spine anomalies in general. 3.To determine if there is any association between the presenting clinical features and individual congenital thoracic and lumbar spine anomalies. 4.To compare subjects presenting clinical features with reported clinical features from literature. / M

The present study focuses on the biological functions of the transcription factor EMA/E2F-6, a member of the E2F-family of transcription factors that play an import role in cell cycle progression, differentiation and apoptosis. EMA/E2F-6 functions as a transcriptional repressor by recruiting a large protein complex, that includes polycomb group proteins, to specific target genes in order to silence their expression. To identify the biological functions of EMA/E2F-6 mice lacking this factor were developed and subsequently analysed. EMA/E2F6-/- mice are born with the expected frequency, are fertile and develop normally up to 18 months of age. Then about 25 % of these mice develop a paralysis of the hind limbs and present with a severe primary myelination defect of the spinal cord (and in part of peripheral nerves, too) that is accompanied by a massive infiltration of macrophages. Importantly, the histological findings were also detected in EMA/E2F-6-/- mice lacking clinical symptoms albeit to a lesser extend. With respect to EMA/E2F-6 association with polycomb group (Pc-G) proteins there were no significant findings such as skeletal transformations. In addition, only a mild proliferation defect of T-lymphocytes was observed that, in a more severe form, is typical for Pc-G mutations in the mice. Surprisingly, embryonic fibroblasts from EMA/E2F-6-/- mice have no obvious cell cycle defects. Accordingly, gene expression profiles showed that classical E2F target genes were normally regulated in these cells. However, EMA/E2F-6-/- fibroblasts ubiquitously express genes like alpha-tubulin-3 and -7 that are normally expressed in a strictly testis-specific manner. All EMA/E2F-6-dependent target genes identified contain a conserved E2F-binding site in their promoters that is required both for EMA/E2F-6 binding and regulation.