Background: The paediatric craniocervical junction has anatomical, physiological and biomechanical properties that make this region unique to that of the adult spine, vulnerable to injury, and contribute to the complexity of management. Traditionally, on-lay fusion with external Halo immobilisation has been used. Instrumented fusion offers intra-operative reduction and immediate stability. Methods: A retrospective review of a single surgeon’s prospectively maintained database was conducted for all cases of paediatric patients that had undergone a fusion involving the occipito-atlanto-axial region. Case notes were reviewed and a radiological analysis was done. Results: Sixteen patients were managed with on-lay fusion and external immobilisation and twentyseven patients were managed with internal fixation using screw-rod constructs. The fusion rates were 80% and 90.5% respectively. Allograft bone grafting was found to be a significant risk factor for non-union. Conclusion: The screws can be safely and predictably placed as confirmed on radiological follow-up with a high fusion rate and an acceptable complication rate. Uninstrumented onlay fusion with Halo immobilization remains an acceptable alternative. Allograft in the form of bone croutons or demineralised bone matrix is a significant risk factor for non-union and posterior iliac crest graft should be used preferentially.

京都大学 / 新制・課程博士 / 博士(医学) / 甲第23064号 / 医博第4691号 / 新制||医||1048(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 今中 雄一, 教授 伊達 洋至, 教授 中山 健夫 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Background Pulmonary diseases are the leading causes of mortality globally amongst children under five years of age. Economic evaluations (EEs) guide decision-makers on which health care intervention to adopt to reduce paediatric pulmonary disease burden. Methods We systematically reviewed EEs for paediatric pulmonary diseases published globally between 2010 and 2020. We searched PubMed, Web of Science, MEDLINE, Paediatric Economic Database Evaluation (PEDE), and the Cochrane library. EEs included were specific to paediatric pulmonary diseases in a hospital setting and of children aged from zero to six years old. We extracted data items guided by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. We collected qualitative and quantitative data which we analysed in Microsoft Excel and R Software. Results 22 studies met the inclusion criteria. Seven of the articles were cost-effectiveness analyses, five cost-utility analyses, two cost-minimisation analyses, and eight cost analyses. Fourteen studies were conducted in high-income countries, eight in low-middle-income countries (LMICs). Ten studies were on asthma, nine on pneumonia, two on asthma and pneumonia, and one on tuberculosis. Quality assessment of the articles revealed some methodological inconsistencies across the articles. Conclusion Fewer EEs were conducted in LMICs, yet children from these countries are disproportionately affected by pulmonary diseases. Developing standardised methods for EEs and conducting more EEs and for paediatric pulmonary diseases in LMICs could allow for more evidence-based decision-making.

This study began in 1990 in the Burn Unit of The Red Cross War Memorial Children's Hospital (RCWMCH) in Capetown. It came to our attention that children in the Burn Unit developed respiratory problems. These were complications of fireburns, smoke inhalation, explosions and even hot water scalds. They presented with a wide and confusing array of symptoms and many failed to improve with the symptomatic treatment given. Greater understanding of the pathology was needed in order to investigate and manage these problems correctly. The ultimate aim of this study was to establish a treatment protocol that could be followed by junior staff.

Children with chronic inflammatory disease (CID) are at an increased risk for health complications including mental health issues, cancer, and cardiovascular disease. These complications have been linked to elevated levels of pro-inflammatory cytokines and lifestyle behaviours including low physical activity, and high sedentary time. Physical activity may represent a simple and effective strategy to modulate inflammation and subsequently improve health outcomes. However, the link between cytokines and movement behaviours in children with a CID remains poorly understood. Indeed, no studies to date have examined the link between a broad complement of inflammatory markers and patterns of movement behaviours in children with a CID. Therefore, the objectives of this study were to: (1) examine movement behaviours and inflammation in children with either cystic fibrosis (CF), juvenile idiopathic arthritis (JIA), inflammatory bowel disease (IBD), and type 1 diabetes (T1DM), (2) examine movement behaviours and inflammation in children with a CID compared with healthy controls and (3) examine the association between movement behaviours and inflammation profiles in children with a CID. We hypothesized that (1) children with a CID will have comparable movement profiles and inflammation, (2) children with a CID will have lower physical activity levels and higher levels of pro-inflammatory cytokines relative to healthy counterparts, and (3) children with a CID who are more physically active and engage in less sedentary time will have less inflammation. Boys and girls with a CID and controls wore an ActiGraph GT3X accelerometer around the waist during waking hours for 7 days. Outcomes of interest included, sedentary time, time spent in light physical activity (LPA), moderate-to-vigorous PA (MVPA), and total PA (TPA), determined using Evenson cut-points. After one week a fasted blood sample was collected to determine serum cytokines (TNFα, IL-23, IL-1β, IL-12, IL-6, IL- 17, TGFβ, IL-10) by multiplex assays and C-reactive protein by enzyme linked immunosorbent assay. A total of 132 participants (47% girls; age: 13.3±2.8 years), including JIA (N=27), IBD (N=21), CF (N=14), T1DM (N=18) and healthy controls (N=52), completed the study. Physical activity and inflammatory profiles were comparable between CF, JIA, IBD and T1DM groups. Children with a CID participated in 13.3 fewer mins/day [95% confidence interval 6.9, 101.2] (MVPA (F(1,113)=11.015, p=0.001) of MVPA relative to healthy controls and had comparable cytokine profiles. Physical activity did not predict inflammation in children with a CID. However, we know that physical activity has many beneficial cardiorespiratory and mental health effects. As such, it is still of interest to uncover any potential effects movement behaviours may have on our immune system. / Thesis / Master of Science (MSc) / The purpose of this study was to assess how physical activity, sedentary time, and inflammation are associated. Inflammation is an important part of our immune system that protects us from infection and disease; however, when inflammation goes unchecked, it can cause serious chronic inflammatory disease. We were interested in understanding if children with a chronic inflammatory disease had different levels of physical activity and sedentary time, or different levels of inflammation than healthy children with no medical conditions. We were also interested in understanding if physical activity or sedentary time were related to levels of inflammation in children with a chronic disease. We asked boys and girls between 7 and 17 years old to visit our lab twice. Some of our participants had a medical condition, including chronic kidney disease, cystic fibrosis, juvenile idiopathic arthritis, or inflammatory bowel disease and type 1 diabetes. We also invited a group of children who had no medical condition to participate. During their first visit, we measured their weight, height, pubertal status and gave them a physical activity monitor to wear for 7 days before coming back for their second visit. At their second visit we took a small blood sample that we used to measure immune proteins called cytokines, these proteins act like messengers to tell the immune system what to do. Some of them make inflammation worse, and others help to bring down levels of inflammation. We found that children who had a chronic inflammatory disease participated in less physical activity but had similar levels of sedentary time compared with healthy children. We also found that there were no differences in inflammation between children with a chronic disease and healthy children. Lastly, we found that physical activity and sedentary time were not related to inflammation levels. Although we did not find a relationship between physical activity and inflammation, we know that physical activity has many beneficial cardiorespiratory and mental health effects. As such, it is still of interest to uncover any potential effects movement behaviours may have on health outcomes.

Reference intervals (RIs) are sets of percentiles that outline the range of laboratory test results belonging to healthy individuals. They are essential for the interpretation of laboratory test results. A wide variety of factors affect the validity of RIs. Among them are the statistical methods used to estimate RIs. However, little investigation has gone into the effect that different statistical methods have on the resulting RIs. This is particularly needed as the complexity of paediatric data makes it difficult to estimate RIs. These difficulties, however, can be addressed using appropriate statistical techniques, provided that there is an outline of scenarios under which these techniques are truly “appropriate”. The objective of this thesis is to provide a thorough investigation into the effect of different statistical methods on RIs. A systematic review was first conducted with a focus on paediatric RIs. The results of this review revealed that critical analysis steps are often overlooked due to complicated paediatric data. Even though a guideline addressing the establishment of RIs is available, there is great heterogeneity in the statistical methods chosen to estimate paediatric RIs. An extensive simulation involving the three most commonly used approaches to estimate RIs (the parametric, non-parametric, and robust methods) was also conducted to investigate and compare the performance of the different methods. The simulation results show that, when data follows a Gaussian distribution, or close to it, the parametric method provides the best estimates. The non-parametric method did not provide the best estimates of RIs (compared to the parametric method) unless data was highly skewed and/or large sample sizes were used. In addition, the bias and MSE associated with the parametric method when data follows a Gaussian distribution was mathematically derived, which may lead to the development of a bias corrected and more precise approach in the future. / Thesis / Master of Science (MSc)

Yes / Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention in paediatric patients. Ultrasound is generally the diagnostic imaging modality of choice, followed by CT, where paediatric appendicitis is suspected. However, high operator dependency and diagnostic restrictions related to anatomical and clinical presentation may limit consistency of application. This paper explores whether MRI is a viable alternative to ultrasound as the primary imaging modality. Method: A systematic review of the literature was undertaken. A search of Medline, Cinahl, PubMed Central and Google Scholar was undertaken supplemented by a review of reference lists, author searching and review of NICE evidence base for existing guidelines. Included studies were assessed for bias using the QUADAS-2 quality assessment tool and data were extracted systematically using a purposefully designed electronic data extraction proforma. Results: Seven studies were included in final review. The age range of participants extended from 0 to 19 years. Only one study with a patient age range of 0e14 used sedation. Sensitivity estimates from the included studies ranged from 92% to 100% while specificity ranged from 89% to 100%. A significant variation in the number and type of sequences was noted between the studies. Conclusion: MRI offers high sensitivity and specificity comparable to contrast enhanced CT and greater than ultrasound as reported in the literature. Where accessibility is not a restriction, MRI is a viable alternative to ultrasound in the assessment and diagnosis of paediatric appendicitis. Clinical practice recommendations have been provided to facilitate the translation of evidence into practice.

Gastroschisis is a full thickness abdominal wall defect, usually to the right of the umbilicus, through which a variable amount of viscera herniates, without a covering membrane. Newborns with gastroschisis present challenging problems to paediatric surgeons. The incidence of gastroschisis is rising worldwide. In developed countries, advances in neonatal intensive care have improved survival of patients with gastroschisis. In the few reported studies from Africa, mortality rates of patients with gastroschisis are high. The aim of this study was to evaluate outcome of gastroschisis from a centre in Africa with modern neonatal intensive care facilities. Methods: A retrospective analysis of all neonates admitted with the diagnosis of gastroschisis at Inkosi Albert Luthuli Central Hospital (IALCH) over a 6-year period (2002-2007). Proportions in percentages were used for categorical variables. For continuous variables the mean with standard deviation (SD) were derived. Two sampled t-test was used to show the pvalue for the time to reduction between the non-survivors and survivors with a 95% confidence interval. Results: There was a significant increase in the prevalence of gastroschisis among neonatal surgical admissions from 6.2% in 2003 to 15.2% in 2007. There were more females 53.4%, the majority (71.7% had low birth weight and 64.2% were born prematurely. Although 75% (n=79) of the mothers attended antenatal clinic, antenatal diagnosis by ultrasound was made in only 13 (n=12%)). Most of the babies 90.6% were out-born, with 70.8% delivered by normal vaginal delivery (NVD), and 57.4% of the mothers were primiparous. Primary closure was achieved in 73.5% of the patients. The overall mean (SD) time from birth to primary surgical intervention was 16 (13.04) hours and was higher 17(9.1) hours in those who died compared to survivors 15 (16.0), but the difference was not statistically significant, p=0.4465 and mortality was 43% with sepsis as the leading cause. Staged closure with a plastic silo bag was associated with more than double the mortality as compared to primary closure. Conclusion: The prevalence of gastroschisis among neonatal surgical admissions has increased in accordance with international trends. Due to lack of antenatal diagnosis, most of the babies were out-born resulting into delay in offering surgical treatment. Mortality is still high despite the presence of modern intensive care. / Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2008.

Objectives: To describe the characteristics of children who died and their modes of dying in a South African Paediatric Intensive Care Unit (PICU). Design: Retrospective review of data extracted from the Child Healthcare Problem Identification Programme (Child PIP)and the PICU summary system (admission and death records) on children of any age who died in the PICU between 01 January 2013 and 31 December 2017. Setting: Single-centre tertiary institution. Patients: All children who died during PICU admission were included. Measurements and Main Results: Four-hundred and fifty-one (54% male; median (IQR) age 7 (1-30) months) patients died in PICU on median (IQR) 3 (1-7) days after PICU admission; 103 (22.8%) had a cardiac arrest prior to PICU admission. Mode of death in 23.7% (n=107) was withdrawal of life sustaining therapies; 36.1% (n=163) died after limitation of life sustaining therapies; 22.0% (n=99) died after failed resuscitation and 17.3% (n=78) were diagnosed brain dead. Ultimately, 270 (60%) children died after the decision to limit or withdraw life sustaining therapies. There was no difference in the number of deaths during office and after-hours periods (45.5% vs. 54%; p = 0.07). Severe sepsis (21.9%) was the most common condition associated with death, followed by cardiac disease (18.6%).Ninety-four (20.8%) patients were readmitted to the PICU within the same year; 278 (61.6%) had complex chronic disorders. During the last phase of life, 75.0% (n=342) were on inotropes, 95.9% (n=428) were ventilated, 12.0% (n=45) received inhaled nitric oxide and 10.8% (n=46) renal replacement therapy. Only 1.5% (n=7) of children became organ donors and postmortems were done in 47.2% (n=213) of the patients. Conclusions: Most PICU deaths occurred after a decision to limit or withdraw life-sustaining therapy. Severe sepsis was the most common condition associated with death. Referral for organ donation was extremely rare.

Feeding disorders are psychological conditions that occur during infancy and early childhood, and result in insufficient intake of foods. Existing feeding disorder research identifies a raft of factors associated with predisposition, development and maintenance of feeding disorders, as well as a multitude of potential outcomes for the child and the system around them. However, neither feeding disorders nor their aetiological bases are well defined or uniformly applied in general, academic or clinical domains. Furthermore, the relationships and differences between observable characteristics, diagnostic criteria, and problem perceptions, and the bearing of these on disorder identification and treatment, are under-researched. The numerous definitions and profiles for feeding disorders make comprehension and knowledge gathering very difficult for caregivers and researchers, and thus hinder research and clinical progression in the field. The overarching aim of this thesis was to examine and characterise paediatric feeding disorders. The objective was to characterise and triangulate what feeding disorders are in terms of observable appearance, external perception, and psychometric properties, and better understand what constitutes a feeding disorder from multiple relevant perspectives. A mixed methods approach was taken to the collection and analysis of data, to obtain both depth and breadth of information. The results of the current thesis suggest that feeding disorders are characterised by a variety of behaviours and features within a biopsychosocial model. While physical models of feeding disorders are outdated, the potential for underlying physical contributing factors and resultant physical outcomes was highlighted throughout the current research and should not be ignored. However, overreliance on physicality, under-recognition of psychological processes, and consequent deficits to disorder identification within clinical settings, was also illustrated within the research. Furthermore, significant issues were raised regarding the lack of a consistent and inclusive model of feeding problems and disorders within healthcare systems. Though most clinicians saw feeding on a scale from normal to abnormal and frequently emphasised the value of early identification and treatment, the referral and treatment pathways that were discussed whereby only the most severe or physically affected children were treated, were not consistent with these models. Interviews with mothers highlighted the role of intrinsic child factors within the development of disordered feeding, including challenging behavioural characteristics, sensory sensitivities, difficult temperament, and lack of feeding motivation or avoidance of new foods. The importance of these child factors was supported by psychometric assessment, which identified distinct patterns of child characteristics associated with different types of problematic or disordered feeding, and a strong association between disordered feeding and the parent perception of having a difficult child. Furthermore, video observations of child mealtimes highlighted not only disparity in the amount of food eaten between disordered and non-disordered children, but a considerable deficit in the level of interest, motivation, and engagement with feeding shown by disordered children. Deficits to child feeding motivation pose a problem for parents that is less obvious than extreme emotional reactions, but which can be equally distressing for the parent who views nourishing their child as one of their major responsibilities. This point was reinforced across parent interviews and mealtime observations, and should be a key factor in the identification of families in need of support and intervention. Parent interviews, healthcare professional interviews, and psychometric assessment, all highlighted the considerable presence and role of parent anxiety within feeding disorder development. Parent anxiety was discussed as a potential cause and an outcome of challenging feeding behaviour, exacerbated by the perceived extent of the child s feeding condition and the dearth of support and information about dealing with significant feeding issues. Anxiety was seen by parents and healthcare professionals to influence the feeding strategies used by parents, and without intervention to contribute to a downward spiral of negative feeding interactions. Disordered feeding was also seen to interfere with social interactions, which would otherwise play an important role in the child s feeding and dietary development, and provide social support and guidance for parents. These patterns of problem and disorder perpetuation are liable to persist while general and clinical understanding of feeding disorders is minimal and inconsistent. The findings of the current thesis pose a great variety of potential influences and risk factors for feeding disorder development, supporting an individualistic approach to disorder identification and intervention, and the need for a significant change in the current systems for dealing with feeding disorders. It is essential to take each of the different components into consideration to understand the specific mechanisms underpinning the maintenance of the feeding disorder and aid selection of the most suitable and efficient approach to intervention. The pattern of factors implicated in each individual feeding disorder case will be differentiated according to the child, the parent and the child s general environment. Identification of the full range of children in need of support and intervention is reliant on recognition of the diversity in disorder type, severity and presentation.