Objectives: This thesis included 6 manuscripts which focused on the analysis of adverse events following immunization (AEFIs), including general health services utilization (emergency room (ER) visits and hospital admissions) and specific diagnoses (e.g. febrile convulsions). The main objectives of this research were: 1) To demonstrate the utility of the self-controlled case series (SCCS) design coupled with health administrative data for studying the safety of vaccines; 2) Introducing an innovative approach using relative incidence ratios (RIRs) within an SCCS analysis to identify risk factors for AEFIs and to overcome the healthy vaccinee bias; and 3) To demonstrate how SCCS and RIR analyses of health services outcomes in health administrative data can provide important insights into underlying physiological and behavioural mechanisms. Data Sources: This work utilized Ontario health administrative data housed at the Institute for Clinical Evaluative Sciences (ICES). The study included all children born in Ontario, Canada between 2002 and 2011 (over 1 million children). Vaccinations were identified using OHIP fee for service billing codes for general vaccination. Admissions and ER visits for any reason were identified in the Discharge Abstract Database (DAD) and National Ambulatory Care Reporting System (NACRS). Primary reasons for admissions and ER visits were investigated using ICD-10-CA codes reported in the DAD and NACRS databases. Statistical Methods: The self-controlled case series design (SCCS) was used to calculate the relative incidence of admissions, ER visits and other AEFIs. To investigate relative incidence for AEFIs across risk groups of interest, as well as addressing the healthy vaccinee effect bias, RIRs were calculated. RIRs are the ratio of incidence ratios in a subgroup of interest relative to a designated reference group. Results and Conclusions: The combined approach of using the SCCS design and RIRs to identify risk factors and overcome the healthy vaccinee bias proved to be a powerful approach to studying vaccine safety. Future work will be important to characterize the performance and validity of the SCCS + RIR approach in the presence of increasing levels of confounding and differing manifestations of the healthy vaccinee bias, as well as to elucidate the biological and behavioural mechanisms underlying our findings.

Une augmentation au moins transitoire de la ploïdie est un événement fréquent de l'oncogenèse. L'hyperploïdisation déclenche un stress du réticulum endoplasmique (RE) caractérisé par l'hyperphosphorylation du facteur d'initiation eucaryote 2α (eIF2α) qui induit l'exposition consécutive de la calréticuline à la surface cellulaire. La calréticuline exerce un effet « adjuvant » en tant que un signal "mange-moi", pour les cellules dendritiques, entrainant un contrôle immunitaire de la tumeur par les lymphocytes T CD8+. Nous avons étudié la possibilité que l'hyperploïdisation puisse également affecter l'antigénicité des cellules cancéreuses en modifiant l'immunopeptidome. Cependant, la vaccination avec des peptides candidats n’a pas réussi à induire des réponses inhibitrices de la croissance tumorale de cellules hyperploïdes in vivo. Nous concluons donc que l'hyperploïdie augmente principalement l'immunogénicité des cellules cancéreuses en affectant leur adjuvanticité (via l’expression de calréticuline) plutôt que leur antigénicité. Nous montrons de plus que des fibrosarcomes induits par méthylcholanthrène (MCA), développés dans des souris Rag2-/-γc-/- immunodéficientes (mais pas dans des souris sauvages), sont particulièrement hyperploïdes, en corrélation avec une teneur en ADN plus élevée, une augmentation de la surface nucléaire, ainsi que l'hyperphosphorylation de eIF2α,. De telles cellules forment des tumeurs dans les souris Rag2-/-γc-/- (dépourvues de cellules T, B et NK) ainsi que dans les souris Rag2-/- (dépourvues de lymphocytes T et B) sans différence entre les deux souches de souris, suggérant que l'absence de cellules B et T est suffisante pour que ces cellules prolifèrent. Pour mesurer ces paramètres, nous avons développé un outil d'analyse morphométrique applicable à l'immunohistochimie. Cet algorithme identifie et quantifie automatiquement la surface des noyaux et l'intensité de la phosphorylation de eIF2α dans une région d'intérêt périnucléaire. Des analyses comparatives ont validé la précision de cette méthode, qui peut être utilisée pour étudier la ploïdie et le stress du RE dans les cancers in situ. / An at least transient increase of ploidy, usually by whole genome duplication, is a frequent event in oncogenesis. Hyperploidization triggers an endoplasmic reticulum (ER) stress characterized by the hyperphosphorylation of the eukaryotic initiation factor 2α (eIF2α), with leads to the exposure of calreticulin to the cell surface. Calreticulin is acting like an "adjuvant" effect as a "eat me" signal, for dendritic cells, ultimately eliciting immune control by CD8 + T lymphocytes. We investigated the possibility that hyperploidization might also affect the antigenicity of cancer cells by altering the immunopeptidome. However, vaccination with candidate peptides was unable to elicit tumor growth-inhibitory responses against hyperploid cells in vivo. We conclude that hyperploidy increases the immunogenicity of cancer cells mostly through their adjuvanticity (through calreticulin exposure) rather than their antigenicity. We also show that when developed in Rag2 - / - γc - / - immunodeficient mice (but not in WT mice) fibrosarcomas induced by methylcholanthrene (MCA) are particularly hyperploid, correlating with higher DNA content, increased nuclear surface, as well as the hyperphosphorylation of eIF2α. These cells are able to form tumors in Rag2 - / - γc - / - recipients (which lack T, B and NK cells) as well as in Rag2 - / - recipients (which only lack T and B lymphocytes) without any difference between the two strains, suggesting that the absence of B and T cells is enough to allow these cells to grow. To measure these parameters, we developed a morphometric analysis tool that is applicable to immunohistochemistry. This software automatically identifies and quantifies the surface of nuclei and the intensity of eIF2α phosphorylation within a perinuclear region of interest. Comparative analyzes validated the accuracy of this method, which can be used to investigate ploidy and ER stress in cancers in situ.

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Background: Immunization training is essential for nursing students. However, Brigham Young University's (BYU) Nursing Program lacks data regarding the current curriculum's effect on vaccination knowledge and confidence. Purpose: The purpose of the study is to explore BYU nursing students' knowledge and confidence regarding vaccinations. Methods: Nursing students at BYU in the second and fourth semesters were surveyed using pre-and post-test questionnaires designed to measure student nurses' knowledge of and confidence about immunizations. To help evaluate current curricula established immunization content was taught during both the public health course and pediatric course via direct instruction, assigned reading, quizzes, exams, lab, and simulation experiences. Curriculum content varied between a public health course and a pediatric course. Data were collected at the beginning and end of the fall semester of 2019. Results: Seventy-seven students completed both pre and post-assessment questionnaires. After education, students' ability to identity pediatric immunizations increased for several vaccines. Students were more likely to seek evidence-based sources of vaccination information. Students' knowledge of correct biohazard waste disposal and confidence in their ability to administer vaccinations also increased. Additionally, several gaps were identified regarding specific guidelines for vaccination storage, preparation, and administration. Discussion: The data from this study showed several gains and gaps in student knowledge. Student nurses in this study were similar in immunization knowledge and performance to student nurses in current vaccination knowledge literature. Nursing Applications: Nursing faculty can implement immunization education into current curriculum by assessing student knowledge, repeating exposure to immunization content in multiple courses, and utilizing simulation for students to practice challenging immunization conversations. Conclusion: The understanding gained in this study could facilitate positive changes in nursing faculty members' ability to provide exceptional education and produce knowledgeable, confident, and prepared nurses to address vaccination concerns.

Background and Purpose: School nurses have the critical task of overseeing the health and wellness of school-aged students. Utah is 1 of 17 states which allow parents to exempt their children from vaccines. The most common parental reason for exempting children from vaccines is personal choice. With the number of students without vaccinations on the rise, school nurses are tasked with responsibilities related to the spread of vaccine-preventable diseases. However, few studies have explored the role of school nurses in managing a disease outbreak. Therefore, the purpose of this study was to 1) explore the responsibilities of Utah school nurses during a disease outbreak; 2) review disease outbreak training for Utah school nurses; 3) identify groups with which the Utah school nurse would collaborate during a disease outbreak; and 4) identify Utah school nurse concerns while attempting to manage a disease outbreak. Methods: A qualitative descriptive design was used with a semi-structured interview guide for focus groups (3 focus groups, 24 total participants) of Utah school nurses. Qualitative analysis of content and themes was utilized. Results: School nurses' responses revealed their collaborative role and cited strong teamwork with the local health department; lack of standardized disease outbreak training; high student-to-nurse ratios; and concerns with communication with parents and community. Thematic descriptions with illustrative quotes are presented as well as perceived challenges and barriers Utah school nurses faced during a disease outbreak. Conclusion: Utah school nurses face barriers that prevent them from working effectively during a disease outbreak. Most barriers are due to communication difficulties and lack of training for school nurses. Findings of this study have implications for standardized training, funding to decrease the high nurse-to-student ratio and for further education in the community to raise awareness of outbreak guidelines.

Vaccinations are among the greatest accomplishments of public health. However, many parents are choosing not to vaccinate. The purpose of this study was to explore the association between social media influence and parents' decisions to vaccinate their children. The health belief model indicates that individuals' likelihood of engaging in a health-related behavior is determined by their perceptions of susceptibility, severity, benefits, and barriers. The research questions addressed whether there is an association between parents' perception of their children's disease susceptibility and their decisions about vaccination, and whether there is an association between exposure to messaging from social media and parents' decision to vaccinate. A quantitative, cross-sectional research design was used. The primary dependent variable was vaccination choices, and the primary independent variable was exposure to information about vaccination through social media. Data were gathered through a questionnaire administered to 269 White parents residing in Illinois with their own children between the ages of 0 and 18 years living with them. Binomial logistic regression showed that there was not a statistically significant relationship between parents' perception of disease susceptibility and vaccination choice or between parents' vaccination choice and exposure to online antivaccine advertisements. These study findings help in defining an overall picture of vaccine hesitancy in the United States. By focusing on the predictors of this behavior, it may be possible to implement interventions to combat the antivaccine movement with the goal of increasing vaccine compliance among parents.

North West Nigeria has the lowest vaccination rate of the geopolitical regions of the country. The purpose of this cross-sectional study was to examine associations between the parents'/caregivers' biological, cultural, and socioeconomic factors and the completion or noncompletion of routine immunization schedules. Andersen's behavioral model provided the framework for the study. Data were obtained from the 2013 National Demographic Health Survey. Descriptive statistics were calculated for all variables. Chi-square tests were used for categorical predictor variables, simple logistic regression models were used for the age variable, and multiple linear regression models were used for the biological, cultural, and socioeconomic variables to assess the relative importance of factors within each category. Findings indicated a statistically significant association between 4 factors (education, wealth index, religious affiliation, and cost of healthcare) and completion of immunization schedules. Findings may be used to improve the likelihood of immunization of children in North West Nigeria and reduce the levels of childhood morbidity and mortality. Policy makers and immunization programmers can strengthen social services such as women's education, income generation, especially in the agricultural sector and other culturally sensitive interventions with community collaboration to bring the required social change.

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As key members of the school environment, it is important for school employees to be vaccinated. Employees are in direct contact with children in close quarters for long periods of time and such an environment can easily serve as an outbreak center for vaccine-preventable communicable diseases such as measles. Despite the fact that most school employees believe vaccines are safe and effective and many school employees report they are up-to-date with their vaccines, a closer examination reveals discrepancy between belief and behavior. As a vaccine advocate, the school nurse can be influential in providing adult vaccination education for school employees, thus increasing awareness of the importance of adult vaccines and knowing one's vaccination status. Additionally, school nurses might need to meet with school district policymakers to promote vaccine mandates for school employees and to assist in the creation of containment plans in the event of a measles outbreak at school.

Schools are group settings where vaccine-preventable diseases can spread quickly, especially if vaccination rates are suboptimal. Vaccination of school children has been the subject of many studies; however, data are lacking regarding the vaccination status, vaccination perceptions, and potential barriers to vaccination for school employees. Method: A questionnaire was developed to measure school employees' perceptions,awareness of current vaccination status, and potential barriers to vaccinations. This study included a convenience sample of 277 employees from a small urban school district located in central Utah. Results: Adult vaccination knowledge is lacking in the school employee population, with over half believing they were fully vaccinated even though 57.8% had not had an influenza vaccination this season. Many school employees were unaware of their vaccination status for highly virulent diseases such as measles and pertussis. In addition, most subjects believed vaccinations were safe and effective, although they believed vaccinations were more important for children than adults. Almost half of respondents believed vaccine mandates should exist for school employees. Conclusion: Knowledge gaps regarding adult vaccines can be positively influenced by nurses, especially school nurses. These knowledge gaps may be especially important to bridge concerning adults working in the school setting, an environment ideal for the spreading of communicable diseases.