The first two chapters of this dissertation focus on the child health outcomes in brief, child diarrheal incidence in India, and child growth measures in Rwanda. The third chapter examines the determinants of timely access to health care in emergency departments in the United States. All three essays are different in their area of interest, data sources, and methodology.ESSAY 1 India has recorded the highest number of child diarrheal deaths at the global level. Oral Rehydration Therapy (ORT) would just provide hydration and few mineral supplements for infected children. However, their malnutrition and weakened immune system cannot be reversed. Malnutrition affects child growth, and causes stunting, and makes them susceptible to other forms of infections. The rotavirus vaccine provides a pseudo-sense of protection from non-rotaviral diarrhea. Preventing diarrhea right away from the source of the infection would be a better solution. Since most diarrheal pathogens are water borne, disinfection treatment of drinking water at the point of use could prevent diarrheal incidence of children and adults as well. Household data from the National Family and Health Survey and their estimators viz., Propensity Score Matching (PSM), and Inverse Probability Weights Regression Adjustment (IPWRA) have been employed to examine the effects of water treatment techniques in households. This chapter attempted a novel approach in studying all the popularly used water treatment techniques currently practiced in India in one study. They have been ranked for multi-value treatment effects model. Water filters with ceramic candles are more effective than other point-of-use water treatment techniques, followed by chlorination, water purifiers, and boiling. ESSAY 2 Rwanda is a sub-Sahara African country affected by genocide with a patriarchal family structure system. Higher poverty and gender imbalance were not alleviated by gender equality being on the political agenda. Despite the highest female representation in the parliament in the world, gender equality and liberty are confined to elite women. Additionally, flawed laws for women's equality made women's empowerment a paradoxical phenomenon. Women at the gross root levels, i.e., community and household, are still dependent or interdependent on men (husband/father). This has been confirmed by the findings in Chapter 3, that is, for most decisions, women are taken jointly with their partners. A minimal percentage of women are autonomous in their decisions and in their home. This study made an attempt to examine the mother’s autonomy in Rwanda and its impact on child health. Mother’s autonomy is negatively related to child’s height and weight for their age. Although the expected association between mother’s autonomy and child height/weight is positive, it would also depend on the historical and cultural context of the country of interest. Instrumental variable analysis is used to study women’s autonomy due to its complex and endogenous nature. Spousal educational difference and marriage-to-birth interval are valid instruments but weakly identified. ESSAY 3 An increasing burden on emergency services that exceeded its resources led to congestion in the emergency department (ED), with patients waiting for physicians on the examination bed and for inpatient bed transfer. This creates a blockage between access to healthcare and emergent patients. ED measures adopted to reduce ED congestion, boarding, and waiting times, such as ambulance diversion management, fast tracking of patients with low acuity, and bed coordination do not effectively control waiting time and boarding. ED crowding is a patient flow, but not necessarily a hospital resource deficiency. This is evident from the findings that even EDs with new treatment spaces still keep patients waiting for an inpatient bed, however, they reported a shorter wait time for the physician. Optimal utilization of nurses by floating them to needy units is effective in timely transfers of patients to inpatient beds compared to EDs without floating nurses.

The Shigella species is responsible for many diarrheal infections and deaths across the world each year, with the largest impact on less industrialized countries, especially in children under 5 years of age. The battle between the lack of a targeted treatment or vaccine and the significant rise of antibiotic resistance in Shigella underscores the importance of fully understanding mechanisms of Shigella virulence. Past research clearly demonstrates that Shigella flexneri strain 2457T utilizes host physiology to regulate pathogenesis, including increasing virulence during exposure to bile salts at concentrations found in the small intestine. This study aimed to further characterize the effects of bile salts exposure in Shigella by focusing on a particular gene induced in the presence of bile salts. Growth curve analyses were performed with S. flexneri wild-type and mutant strains to examine the role of the unknown protein in the growth of Shigella during bile salts exposure. To examine the effects of the mutation on virulence, a Congo red secretion assay was also used as a measure of type-III secretion system function as well as invasion assays, both of which used bile salts in the subculture conditions to mimic small intestinal transit of wild-type and the mutant strain prior to infection in the colon. The mutant displayed no change in growth patterns in comparison to WT in the presence or absence of bile salts. However, the mutant displayed increased protein secretion and invasion rates relative to wild-type. Overall, the data suggest that this bile salts-induced gene encodes a protein that negatively regulates S. flexneri virulence, likely providing protection against a hypervirulent phenotype of Shigella. This work has succeeded in further characterizing an unknown protein that is induced by bile salts, and could provide insight for future therapeutic and vaccine development. / 2025-01-19T00:00:00Z

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24968号 / 医博第5022号 / 新制||医||1069(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 中山 健夫, 教授 佐藤 俊哉, 教授 江木 盛時 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Diarrhea is common during critical illness; however, the etiology, definitions, incidence and risk factors for diarrhea and its impact on patient important outcomes require further investigation. There are many possible etiologies of diarrhea, including iatrogenic causes such as laxative medications, often administered as part of bowel protocols, as well as Clostriodiodes difficile associated diarrhea (CDAD). This thesis includes 6 chapters that address the knowledge gaps in the literature regarding the epidemiology of diarrhea in the intensive care unit (ICU), the impact of bowel protocols on diarrhea, and CDAD in critically ill adults. Chapter 1 provides an introduction to gaps in the literature that are addressed by the studies included in this thesis. Chapter 2 outlines the methodology used to inform the protocol for the Diarrhea, Incidence, Consequences and Epidemiology in the Intensive Care Unit (DICE-ICU) Study. Chapter 3 reports on the findings of DICE-ICU including the incidence, risk factors, definitions, and outcomes of patients who develop diarrhea in the ICU. Chapter 4 provides a content analysis of bowel protocols used in multiple ICUs. Chapter 5 summarizes a nested cohort study addressing the incidence, prevalence, timing, treatments, and outcomes of CDAD in critically ill patients enrolled in the PROSPECT Trial. Chapter 6 summarizes the work and discusses the strengths and limitations, implications and conclusions presented in this PhD thesis. / Thesis / Doctor of Philosophy (PhD)

No description available.

No description available.

Clostridium difficile causes pseudomembranous colitis in humans and a similar ileocecitis in hamsters. This organism can colonize the intestines after antibiotic therapy disrupts the normal intestinal microflora. Once established in the intestines, the organism causes disease by producing two toxins, designated toxin A and toxin B. Only toxin A is active on intestinal epithelium, thus toxin A is the cause of the initial tissue damage in the intestines. In order for a toxin to affect a cell, it must first bind to the cell. Toxin A has been shown to bind to Galα1- 3Galβ 1-4GIcNAc on the intestinal epithelium of hamsters. I provide evidence that toxin A can use this trisaccharide as a functional receptor on cell lines, and that the expression of the carbohydrate receptor increases the sensitivity of the cells to toxin A. Furthermore, the intestinal epithelium of infant hamsters bound less toxin A at 37C than did the adult tissue, and infants are less sensitive to the disease caused by C. difficile than are adults. This provides further evidence that the activity of toxin A is increased by the binding of the toxin to Galα1-3Galβ1- 4GlcNAc. Even though Galα1-3Galβ 1-4GlcNAc was a receptor for toxin A on animal cells, it probably is not a receptor for toxin A in humans, because people do not normally express this carbohydrate. Instead, I found that toxin A bound to the carbohydrate antigens designated I, X, and Y, which are present on the intestinal epithelium of humans. These carbohydrates could be receptors for toxin A. The possible significance of these receptors is discussed. / Ph. D.

A qualitative study was conducted to explore and describe the knowledge and perceptions of parents and caregivers on the causes of diarrhoea among children under five years living in the rural areas of the Eastern Cape Province, South Africa. The aim was to assist in correcting the negative perceptions of the causes of under five child diarrhoea through improved educational interventions. Data were collected through individual, semi-structured and face-to-face interviews from seven participants who were parents and caregivers of under-five children presenting with diarrhoea or admitted for the management of diarrhoea at a specific hospital and thematic analysis was done. The findings revealed that the participants had inadequate knowledge and lacked understanding of diarrhoea and its causes. Participants could not mention all the causes and risk factors associated with diarrhoea. Noteworthy is that the participants’ perceived diarrhoea as a serious condition. The study recommends that the implementation of policies regarding public education and health promotion programmes be targeted at educating parents and caregivers / Health Studies / M.A. (Public Health)

Thesis (D.P.H.)--University of Michigan, 1994.

Thesis (D.P.H.)--University of Michigan, 1994.