MSc (Med), Biostatistics and Epidemiology, Faculty of Health Sciences, University of the Witwatersrand, 2009 / Introduction: Endometrial cancer is a gynaecological cancer that mostly affects women in their sixth and seventh decades of life. It is the fourth most common malignancy in women and ranks eighth among all causes of female cancer in terms of age-adjusted mortality. In developed and numerous developing countries endometrial cancer, as well as other types of cancer in women, is an ever-increasing threat that may be explained, among other reasons, by increased life expectancy and a reduction in fertility or birth rates. Conversely, in South Africa and most other African countries, the previous reasons do not exist, because there is a decline in life expectancy due to increased HIV, low income, and a high fertility rate. International epidemiological studies have established significant relationships between endometrial cancer and risk factors such as the woman’s age, race, early menarche and late menopause, parity, a history of breast or ovarian cancer, the use of endogenous estrogens, concomitant diabetes, family history of breast and ovarian cancer, estrogen therapy, obesity, and the use of tamoxifen. The aim of the study was to identify risk factors associated with endometrial cancer among black South African women. Method: The present case control study comprised black South African women diagnosed with a cancer in Johannesburg, between 1995 and 2005. The study included 592 women aged 27 to 90 years who were admitted to three main public hospitals in the city of Johannesburg with histologically confirmed cancers. 148 cases with endometrial cancer and 444 women with other forms of cancer were analysed. Only newly occurring cases (incident) were included. Women in the control group consisted of those with V cancers not associated with reproductive or hormonal factors, i.e. not cancers of the breast or the female reproductive system. Data handling, cleaning and analysis were done using Stata 9 (STATA). Results: Univariate analysis showed that the risk for endometrial cancer was significantly (P<0.05) affected by: miscarriages, the place of former residence, place of current residence, the use of snuff, wine consumption, age of the youngest child, diabetes, age of menarche, age of menopause, and menstrual status. Smoking was found to be a protective factor for endometrial cancer compared to other cancers. After multivariate adjustment, endometrial cancer risk was significantly (P<0, 05) associated with miscarriages, age at menarche, and earlier completion of childbearing. Smoking remained a protective factor against endometrial cancer. Conclusion: The current study reports similar results to those observed in other international investigations. The risk of endometrial cancer was higher among women who were older, women who experienced miscarriages, and those who fell pregnant early in their reproductive lives. Smoking was a protective factor against endometrial cancer compared to other cancers. However, comparing the cases of endometrial cancer with smoking-associated cancer controls (i.e. lung cancer, oesophageal cancer, and mouth cancer) might have distorted the results. A more appropriate control group for confirming the relationship between smoking and endometrial cancer would be subjects with no cancer. Also, it will be important to evaluate the risk factors for cancer among the other race groups in South Africa.

MSc (Med), Population-Based Field Epidemiology, Faculty of Health Sciences, University of the Witwatersrand / Background Complications of childbirth and pregnancy are leading causes of death among women of reproductive age. Worldwide, developing countries account for ninety-nine percent of maternal deaths. The United Nations’ fifth millennium development goal (MDG-5) is to reduce maternal mortality ratio by three fourths by 2015. Aim The aim of this study is to explore the levels, trends, causes and risk factors associated with maternal mortality as put forward by World Health Organization (WHO) in rural settings of Tanzania. Specific objectives To establish the trend of maternal mortality ratios in Rufiji health and demographic surveillance system (RHDSS) during the period 2002-2006. To determine the main causes of maternal deaths in RHDSS during the period 2002-2006. To determine the risk factors associated with maternal mortality RHDSS during the period 2002-2006. Method Secondary data analysis based on the longitudinal database from Rufiji Health and Demographic Surveillance System was used to study the risk factors and causes of maternal death. Data for a period of 5 years between 2002-2006 was used. A total of 26 427 women v aged 15-49 years were included in the study; 64 died and there were 15 548 live births. Cox proportional hazards regression was used to assess the risk factors associated with maternal deaths. Results Maternal mortality ratio was 412 per 100 000 live births. The main causes of death were haemorrhage (28%), eclampsia (19%) and puerperal sepsis (8%). Maternal age and marital status were associated with maternal mortality. An increased risk of 154% for maternal death was found for women aged 30-39 versus 15-19 years (HR=2.54, 95% CI=1.001- 6.445). Married women had a protective effect of 62% over unmarried ones (HR=0.38, 95% CI=0.176-0.839). These findings were statistically significant at the 5% level. Conclusion This analysis reinforced previous findings pointing to the fact that haemorrhage and eclampsia are the leading causes of maternal mortality in Tanzania and other developing countries. This indicates the need for better antenatal and obstetric care, particularly for women over thirty years of age, as well as implementing health care delivery strategies according to the regional specific risk factors of maternal deaths and not the global factors.

The pioneering work of Ödegaard (1932) was the first to link migration and schizophrenia by reporting rates in Norwegian immigrants in Minnesota as twice that of native Minnesotans and of Norwegians in Norway. However, only in recent decades has an interest in migration and schizophrenia been rekindled as a result of reports of elevated rates of schizophrenia in Afro-Caribbean immigrants in the United Kingdom in the mid- 1960s (Hutchinson & Haasen, 2004). Later studies reported elevated rates in secondgeneration Afro-Caribbean immigrants compared to first-generation (Harrison, Owens, Holton, Neilson, & Boot, 1988). In the United States, Blacks were diagnosed with schizophrenia 2.4 times more often than Whites (Olbert, Nagendra, & Buck, 2018). However, mental health researchers in the United States generally combine all individuals of African descent as African- Americans. This practice obscures the nuances of culture and ethnicity within the Black subgroups as well as the immigrant status of Afro-Caribbeans. This research focused on the Afro-Caribbean immigrants and factors that predict risk for schizophrenia within this population. The process of migration is a complex enterprise that produces stressors and challenges, the effects of which are multifaceted. The social and environmental forces that parallel the process of migration may predispose individuals to severe psychiatric disorders such as schizophrenia. Socio-political dynamics in the host country that marginalize others of different cultural and/or racial persuasions can compound the negative effects of post-migration. Therefore, migration is considered a social determinant of health. Empirical evidence has substantiated that socio-environmental factors such as urbanicity, discrimination or socio-economic deprivation, social support, and goal striving stress are potential contributing factors to the development of psychotic disorders in immigrants. Moreover, evidence has supported that the darker the skin color of the immigrant the greater the risk (Cantor-Graae, 2007). The findings of this study confirmed that for Afro-Caribbean immigrants stressors in the post-migration phase such as discrimination, limited social support, and economic hardship that can be compounded by the number of dependent children were identified as possible predictors of risk for schizophrenia. This risk increased with length of residency and continued into the second-generation. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

The contacts and collisions that are inherent to elite Rugby Union, alongside changes to players’ physical characteristics and match activities, have raised concerns regarding the level of injury burden associated with the professional game. This programme of research was therefore undertaken to investigate injury risk in this setting. The first study of this thesis (Chapter 3) presents a meta-analytic review of injury data relating to senior men’s professional Rugby Union, which shows an overall match incidence rate of 81 per 1000 player hours; this value is high in comparison with other popular team sports. In Chapter 4, the importance of injuries in the context of performance is demonstrated by showing a substantial negative association exists between injury burden and team success measures. Chapter 5 investigates subsequent injury patterns in this population and identifies injury diagnoses with a high risk of early recurrence, whilst also demonstrating that subsequent injuries are not more severe than their associated index injury. Playing professional Rugby Union on an artificial playing surface does not influence overall acute injury risk in comparison with natural grass surfaces (Chapter 6). Chapters 7 and 8 identify intrinsic risk factors for injury (previous injury, match and training loads) for the first time in this setting, and may be used to inform policies on these pertinent issues. Finally, predictive modelling techniques show some potential for predicting the occurrence and severity of injuries, but require further refinement before they can be implemented within elite Rugby Union teams. Overall, this programme of work highlights the importance of injury prevention for all professional Rugby Union stakeholders, addresses the need to use appropriate statistical techniques to account for the dynamic and clustered nature of sport injury data, and demonstrates approaches through which the injury burden associated with elite Rugby Union may be reduced.

Patient-provided data are crucial to achieving the goal of precision medicine. These data, which include family medical history, race and ethnicity, and social and behavioral determinants of health, are essential for disease risk assessment. Despite the well-established importance of patient-provided data, there are many data quality challenges that affect how this information can be used for biomedical research. To determine how to best use patient-provided data to assess disease risk, the research reflected in this dissertation was divided into three overarching aims. In Aim 1, I focused on determining the quality of race and ethnicity, family history and smoking status in clinical databases. In Aim 2, I assessed the impact of various interventions on the quality of these data, including policy changes such as the implementation of the requirements imposed by the Meaningful Use program, and patient-facing tools for collecting and sharing information with patients. In addition to these evaluations, I also developed and evaluated a method “Relationship Inference from the Electronic Health Record” (RIFTEHR), that infers familial relationships from clinical datasets. In Aim 3, I used patient-provided data to assess disease risk both at a population level, by estimating disease heritability, and at an individual level, by identifying high-risk individuals eligible for additional screening for a common disease (diabetes mellitus) and a rare disease (celiac disease). My research uncovered several data quality concerns for patient-provided data in clinical databases. When assessing the impact of interventions on the quality of these data, I found that policy interventions led to more data collection, but not necessarily to better data quality. In contrast, patient-facing tools did increase the quality of the patient-provided data. In the absence of high-quality patient-provided data for family medical history, I developed and evaluated a method for inferring this information from large clinical databases. I demonstrated that electronic health record data can be used to infer familial relationships accurately. Moreover, I showed how the use of clinical data in conjunction with the inferred familial relationships could determine disease risk in two studies. In the first study, I successfully computed disease heritability estimates for 500 conditions, some of which had not been previously studied. In the second study, I identified that screening rates among family members that are considered to be at high-risk for disease development were low for both diabetes mellitus and celiac disease. In summary, the work represented in this dissertation contributes to the understanding of the quality of patient-provided data, how interventions affect the quality of these data, and how novel methods can be applied to troves of existing clinical data to generate new knowledge to support research and clinical care.

No description available.

Cardiovascular diseases (CVD) are the leading cause of death worldwide and the atherosclerotic process that precedes CVD starts during childhood. Physical activity (PA), cardiorespiratory fitness (CRF) and exercise are well known as preventive strategies for CVD. One possible mechanism for such prevention is the role of PA, CRF and exercise on the arterial and autonomic systems. The aim of this thesis was to investigate using observational and experimental studies the role of PA, CRF and exercise on the autonomic and arterial systems of healthy adolescents. Chapter 4 systematically reviewed observational cross-sectional studies and provided level one evidence for a significant and positive association between resting parasympathetic function and moderate-to-vigorous PA in youth. Chapter 4 also indicated that gaps exist in the literature such as the associations between PA intensities, CRF and heart rate variability (HRV). These findings were furthered in Chapter 5 which showed that vigorous PA (VPA) and moderate PA (MPA) were positively related with HRV at rest and cardiac autonomic recovery following exercise in adolescents. In Chapter 6 a high-fat meal was used aiming to increase CVD risk in the postprandial state, and it was demonstrated that PA levels and CRF are not significantly associated with postprandial HRV and arterial stiffness in adolescents. Aiming to investigate possible associations between the vascular and autonomic system, measures of baroreflex sensitivity (BRS) were introduced. Chapter 7 showed that BRS and its autonomic and vascular components present a between-day coefficient of variation lower than 20% whilst within day coefficient of variations were lower than 34% in adolescents. In Chapter 8 acutely following high- and moderate-intensity interval exercise a decrease in blood pressure was observed concomitantly with decreases in BRS. This was mainly mediated by decreases in the autonomic modulation, and the duration of the decreases in blood pressure was higher following high-intensity interval exercise. Chapter 9 extended these findings by demonstrating that the changes in BRS following the ingestion of glucose was not altered by the high or moderate-intensity exercise performed before glucose ingestion. Chapter 10 showed that following four weeks of high-intensity exercise interval training no improvements were observed in BRS and its autonomic and vascular components at rest or acutely following exercise. Collectively, the present thesis contributes significantly to the literature by providing novel evidence in healthy adolescents on the role of PA intensities, CRF and exercise on the arterial and autonomic systems at rest, acutely following exercise and in the postprandial state. The results gathered in this thesis indicate potential of the autonomic and vascular function as targets of CVD risk reduction in youth.

Introduction Non-union (NU) is a fracture that will not unite. With over one million fractures per annum in the UK long bone non-union has serious social and economical implications. There is little epidemiological data available specifically looking at this NU patient cohort. Studies that are bone specific quote rates of non-union as a proportion of their study group but there is no data quantifying the incidence of NU in the population or per fracture. Studies have highlighted risk factors associated with atrophic non-union including age, diabetes, non-steroidals, and cigarette smoking. There is scientific interest regarding how best to classify non-unions and the role of biological agents in treating them. Aims • To quantify the incidence of non-union in a large population and calculate the risk of non-union per fracture according to age, sex and anatomical distribution. • To assess the causes contributing to non-union and outcomes of treatment in a non-union cohort and validate a new non-union scoring system. • To test the treatment potential of a novel molecule (monobutyrin) and a growth factor in a small animal model of non-union. Method • Using the ICD-10 data from the Scottish population as collected by NHS Scotland the incidence of non-union and fractures were calculated. • A cohort of 100 non-union patients were studied for risk factors associated with their non-union, treatment outcome and to assess a new NU classification system. • A rat model of tibial non-union was used to assess the potential of monobutyrin and BMP-2 in treating non-union in an animal model. Results • Fracture non-union is very rarely found in children (1 in 500 fractures) and occurs in up to 1 in 50 adult fractures. Non-union of a fracture has a significantly higher risk in young adults than the elderly by about 3 fold. Osteoporosis may not be a risk for non-union. The tibia and clavicle are the sites with the greatest potential for fracture non-union. • Non-union is multifactorial in two out of three patients. Biomechanical stability, patient host factors and infection must all be considered in every patient. Occult or unexpected recurrent infection is present in up to 10% of patients. When all factors are considered in treatment the outcome is 95% successful with 88% requiring 2 or less procedures to heal the non-union and only a minority requiring adjuvant graft or biological agents. The proposed new classification system is complex and did not clearly identify those patients who would require adjuvant treatment (eg bone grafting or BMP) or those likely to have unsuccessful non-union treatment. • Monobutyrin and BMP-2 when tested on the small animal non-union model did not improve the success rate of union. Conclusions Non-union affects approximately 1000 people per year in Scotland, this figure is not as high as 5-10% of all fractures. It is associated with fractures in young adults and of the clavicle and tibia, treatment can have a very high success rate without the need for adjuvant biological polytherapy when all contributing factors are considered and managed appropriately. A new non-union classification needs to incorporate the multifactorial aspects of non-union without being too complex to use in everyday clinical situations.

nÃo hà / As mortes desencadeadas em crianÃas menores de um ano de vida sÃo influenciadas por fatores biolÃgicos, culturais, demogrÃficos, socioeconÃmicos e assistenciais. Este trabalho teve como objetivo avaliar a evitabilidade dos Ãbitos infantis ocorridos na Secretaria Executiva Regional VI em Fortaleza-CE, em 2008 e 2009. Trata-se de um estudo do tipo ecolÃgico, descritivo e quantitativo, tendo como desfecho a ocorrÃncia do Ãbito infantil. Foram estudados 192 Ãbitos, de uma populaÃÃo de 240. As variÃveis foram agrupadas de acordo com as caracterÃsticas sociodemogrÃficas e maternas. Analisaram-se as mÃdias, medianas e IC95% de variÃveis quantitativas. Para avaliaÃÃo da evitabilidade dos Ãbitos, foram usados os critÃrios propostos pela Lista Brasileira de Mortes EvitÃveis no Sistema Ãnico de SaÃde, apÃs anÃlise pelo Comità Regional de PrevenÃÃo do Ãbito Infantil e Fetal. Em 2008,54% e 2009,52% dos Ãbitos em menores de um ano foram considerados evitÃveis pelo ComitÃ. Comprovou-se que 30% dos Ãbitos de menores de um ano ocorridos em 2008 sÃo reduzÃveis por aÃÃes adequadas de diagnÃstico e tratamento; 26% por adequada atenÃÃo à mulher na gestaÃÃo; 22% por aÃÃes adequadas de promoÃÃo à saÃde; 12% reduzÃveis por adequada atenÃÃo ao recÃm-nascido; 8% por adequada atenÃÃo à mulher no parto, e 2% reduzÃveis por aÃÃes de imunoprevenÃÃo. Dos Ãbitos evitÃveis em 2009, 44% foram classificados como reduzÃveis por adequada atenÃÃo à mulher na gestaÃÃo; 33% por aÃÃes adequadas de diagnÃstico e tratamento; 10% por adequada atenÃÃo ao recÃm-nascido; 7% por aÃÃes adequadas de promoÃÃo à saÃde; e 6% reduzÃveis por adequada atenÃÃo à mulher no parto. Os resultados encontrados podem ser utilizados para o direcionamento de intervenÃÃes efetivas que visem a diminuir a mortalidade infantil, tanto no Ãmbito da Secretaria Executiva Regional VI, como nas demais secretarias do municÃpio de Fortaleza. / Deaths triggered in children less than one year of life are influenced by biological, cultural, demographic, socio-economic and assistance factors. This study describes the epidemiology profile of infant deaths that happened in the 6th Regional Executive Office in Fortaleza-CE, Brazil, in 2008 and 2009 and assesses its avoidability according to the results of the Regional Committee for the Prevention of Infant and Fetal Death (CRPOIF). This is an ecological, descriptive and quantitative study, with the outcome of the occurrence of infant death. 192 deaths were studied in a population of 240. Variables were grouped according to maternal socio-demographic characteristics. For data processing we used the Epi-Info software version 3.5.1, with analysis of means, medians of some variables and adopted the Confidence Interval of 95%. To assess the avoidability of deaths, we used the criteria proposed by the Brazilian List of Preventable Deaths in the National Health System after being reviewed by the committee. In 2008 (54%) and 2009 (52%) of deaths in children under one year of life were considered preventable by the CRPOIF based on this list, and following the classification adopted to analyze the deaths. It was concluded that 30% of deaths of children under one year old in 2008 are avoidable by appropriate actions of diagnosis and treatment, 26% by appropriate care to women in pregnancy, 22% by appropriate actions for health promotion, 12% are avoidable by appropriate care to newborns, 8% by appropriate care to women during childbirth, and 2% reduced through actions of vaccine prevention. From the avoidable deaths in 2009, 44% were reduced through appropriate care to women in pregnancy, 33% by appropriate actions for diagnosis and treatment, 10% by appropriate care to newborns, 7% by appropriate actions to health promotion and 6% reduced through appropriate care to women in childbirth. These results can be used to address effective interventions that aim to reduce infant mortality, both within the 6th Regional Executive Office, as in the other offices of this city.

Scientific interest in the clinical implications, public health importance, and risk factors of anxiety disorders has grown substantially in the past two decades. Despite this, the evidence base on anxiety is insufficient to inform health care planning and policy-making. Further research on the outcomes and risk factors associated with anxiety disorders, and ways of mitigating these risks is needed. One of the aims of this thesis was to provide an overview of the existing literature on the prevalence of anxiety in adults living in countries across the globe, and to describe the prevalence in the context of various health states and life stages. Because generalised anxiety disorder is one of the most common psychiatric conditions in the population, the remainder of the thesis focused on this disorder and aimed to explore its links with health service use and mortality. Risk for this condition was also explored and area deprivation was studied as a possible determinant. Since depression is commonly studied alongside anxiety, the relationship between the residential environment and major depressive disorder was also assessed. Finally, to provide insight into the mitigation of risks of generalised anxiety disorder, a study of coping mechanisms was undertaken. Primary study findings from this thesis are based on the European Prospective Investigation of Cancer in Norfolk, a large, population study of British people over the age of 40. Results from the systematic review showed that anxiety is common in population sub-groups around the world, with women, younger people, and those suffering from chronic physical conditions, such as cancer and cardiovascular disease being particularly affected. Results from the primary studies of the thesis showed that generalised anxiety disorder is associated with increased risk for deaths, though it is not significantly associated with non-psychiatric hospital admissions. Results from the risk factor analyses showed that living in a deprived area is associated with generalised anxiety disorder in women and major depressive disorder in men. The risk mitigation analysis indicated that sense of coherence is an important coping mechanism that can protect against generalised anxiety disorder among women living in disadvantaged circumstances. My work has shown novel associations and attempted to provide a more complete picture of one of the most common psychiatric conditions in the population by focusing on several angles: health outcomes, risk factors, and ways of mitigating risks.