Source: Dissertation Abstracts International, Volume: 70-07, Section: B, page: 4057. Adviser: Elaine Symanski. Includes bibliographical references.

Background and Significance: Narcolepsy is a chronic neurological disorder. These patients experience various psychiatric and physical comorbid diseases and mortality at an increased rate compared to the general population. Additionally, patients with narcolepsy experience approximately a doubling of various annual healthcare related facility visits, transactions, and costs comparatively. Narcolepsy with cataplexy is generally believed to be more prevalent than narcolepsy without cataplexy. However, incidence and prevalence estimates of narcolepsy (with or without cataplexy) vary widely with few large epidemiological studies conducted worldwide and none in the U.S evaluating these proportions in both children and adults utilizing a large health care claims database. One of the main mechanisms underlying narcolepsy, the destruction of hypocretin neurons, is not clear. Two of the more noted hypotheses for this pathology are autoimmune and infection based triggers in allele carrier patients. These have been highlighted since narcolepsy diagnoses increased following the late 2000s influenza vaccinations, especially across Europe. Specific influenza and streptococcal infections have also been considered. Large U.S. healthcare claims database investigations of the association between specific infections and development of narcolepsy were not found in the published scientific literature. Our goals were to enhance the knowledge regarding the epidemiology and possible infection triggers of narcolepsy. The information gained may aid in the overall understanding of the condition, the possible vulnerable populations, and lead to hypotheses regarding which subpopulations research should be focused upon and those triggers that may be avoided or reduced in exposure. Methods: The Truven Health MarketScan Commercial Dissertation Database (THMCDD) was used to estimate prevalence and incidence of narcolepsy, with and without cataplexy, by age groups, gender, and region among patients under age 66 with continuous enrollment for years 2008-2010. THMCDD contains health claims information for over 18 million people. Prevalence was expressed as cases/100,000 persons. Average annual incidence (using varying criteria for latency between the diagnostic tests, polysomnograph coupled with MSLT, and the diagnosis) was expressed as new cases/100,000 persons/year. Subsequently, we conducted a case-control study to assess the differences in respiratory infections between patients with incident narcolepsy diagnosis and controls. Continuously enrolled patients under age 66 were included. Cases of narcolepsy occurring from July 1, 2009 through December 31, 2010 were included based on two diagnosis criteria (using varying criteria for latency between diagnosis and the diagnostic tests). Non-narcolepsy controls were frequency matched on look-back time by assigning an index date equal to a case diagnosis date. Occurrence of prior respiratory infections was compared between cases and controls based on narcolepsy criteria and four different time periods pre-index date. Infections were grouped into 9 types based on pathogen and clinical manifestation. Results: From 2008 through 2010, there were 8,444,517 continuously enrolled patients and 6,703 diagnosed with narcolepsy (prevalence overall:79.4/100,000; without cataplexy:65.4/100,000; with cataplexy: 14.0/100,000). Based on the 3 definitions of incidence, overall average annual incidence was 7.67, 7.13, and 4.87/100,000 persons/year. Incidence for narcolepsy without cataplexy was generally several times higher than narcolepsy with cataplexy. Prevalence and incidence were approximately 50% greater for females compared to males across most age groups. Prevalence was highest among the 21-30 age group, with incidence highest among enrollees in their early 20s and late teens. Regionally, the North Central U.S. had the highest prevalence and incidence, while the West was the lowest. For the case-control study, Adjusted odds ratio (aOR) increases were statistically significant for Group 5 (acute respiratory infections), Group 8 (other pneumonias, bronchopneumonia, etc.) and Group 9 (influenzas) across various time periods pre-index date and for both narcolepsy criteria. Overall, the most significant aORs were for acute respiratory infections during the 3 to 15 months pre-index date for both narcolepsy diagnosis criteria (aOR=1.73, 95% 1.52 to 1.98 and aOR=1.83, 95% CI 1.57 to 2.19). The aORs for acute respiratory infections were approximately 50% greater among females than males. Conclusion: We observed higher prevalence and incidence of narcolepsy compared to most previous studies. Females were associated with approximately 50% increased proportions compared to males. We also found that the greatest prevalence and incidence of narcolepsy occurred in patients in their early 20s, and those residing in the North Central region of the U.S. Perhaps most striking was the observation of much greater proportions of narcolepsy without cataplexy compared to narcolepsy with cataplexy. In the case-control assessment, we found increased occurrences of acute respiratory infections, pneumonias, and influenza prior to incident narcolepsy diagnosis, compared to controls. Generally, these rates appeared higher for females than males and occurred for both narcolepsy diagnosis criteria. Additionally, these associations were observed in the infection assessment periods 3 to 15 months and 6 to 18 months prior to incident narcolepsy diagnosis. Increased awareness and early notification among healthcare providers for signs and symptoms of narcolepsy is critical in helping this population of patients manage this burdensome condition. Also, the identification of potential narcolepsy triggers by certain infections may aid in the understanding of the disease. These findings may have implications in the understanding of mechanisms and causation of other acute onset neurological disorders. Our observations of consistently increased risk of incident narcolepsy related to recent previous viral respiratory infections and the inconsistent results for bacterial infections require additional study to confirm these findings.

We investigated the association of Bell's palsy (BP) with the subsequent risk of Parkinson's disease (PD) using a case-control study design. We matched 196 incident cases of PD in Olmsted County, MN, to 196 general population controls with same age (±1 year) and sex, and we reviewed the complete medical records of cases and controls in a medical records-linkage system to detect BP. Six of the 196 patients with PD and none of the 196 controls were diagnosed with BP before PD (exact binomial probability, P = 0.02). The median age at occurrence of BP was 49.5 years (range, 15-84 years) and the median time between BP and the onset of PD was 27.5 years (range, 2-54 years). The findings were similar using a standardized incidence ratio (SIR) approach, but were not statistically significant. This initial association between BP and PD awaits replication.

Controlling norovirus transmission in units with immunocompromised patients is challenging. We present a cluster of norovirus cases that occurred on a stem-cell transplant unit and the prevention efforts that were implemented to limit the outbreak. Protocols developed to control this cluster may provide a model for other facilities. / National Institutes of Health / Revisión por pares

No description available.

Poliomyelitis is a foremost cause of paralysis among preventable diseases among children and adolescents globally. It is caused by persistent infection with poliovirus (PV). The PV infection does not always cause paralysis. A lack of immunization always increases the risk of paralytic polio. Genetic factors also been shown to affect the risk of developing the disease. The aim of this thesis is to investigate whether there are any genetic associations to paralytic poliomyelitis. This is based on a model for understanding its nature as a complex disease, where many genes are involved in contributing to the disease state. This is a population-based case-control study to identify genetic loci that influence disease risk. The study examined the association of genetic variation in single nucleotide polymorphisms (SNPs) across the genome with paralytic poliomyelitis susceptibility in the United States and Canadian survivors of poliomyelitis population, using a genome-wide association study (GWAS) approach. No association was observed. Loci that have been previously implicated were not found to affect the susceptibility to poliomyelitis in this study. The thesis consists of four chapters. Chapter 1 describes the epidemiology, pathogenesis and management of poliomyelitis. Chapter 2 gives an overview of the genomics of infectious diseases in general. Chapter 3 introduces the study population and presents the genome-wide analysis and associations with logistic regression to identify loci explore genes that might be associated with paralytic poliomyelitis and presents results. Chapter 4 discusses the implications of the results and explains future directions. / Thesis / Master of Science (MSc)

Thesis (M.P.H.)--University of Texas Health Science Center at Houston, School of Public Health, 2008. / Source: Masters Abstracts International, Volume: 47-01, page: . Advisers: Robert E. Roberts; Michele Forman. Includes bibliographical references.

Thesis (Ph. D.)--University of Texas Health Science Center at Houston, School of Public Health, 2007. / "December 2007." Source: Dissertation Abstracts International, Volume: 68-11, Section: B, page: 7220. Adviser: Stephen C. Waring. Includes bibliographical references (leaves 39-44).

No description available.

The aims of the studies underlying this thesis were to assess the exposure to quartz in Swedish iron foundries and to determine the cancer morbidity for Swedish foundry workers. A cohort of 3,045 foundry workers and a final measurement database of 2,333 number of samples was established. The exposure measurements showed high levels of respirable quartz, in particular for fettlers and furnace and ladle repair workers with individual 8 hr TWA (GM=0.041 and 0.052 mg/m3; range 0.004-2.1 and 0.0098-0.83 mg/m3). In our database, the quartz concentrations as 8hr TWAs of current and historical data varied between 0.0018 and 4.9 mg/m3, averaging 0.083 mg/m3, with the highest exposures for fettlers (0.087 mg/m3) and furnace and ladle repair workers (0.42 mg/m3). The exposure for workers using respirators assuming full effect when used were assessed quantitatively, revealing workers with actual exposure exceeding the occupational exposure limits. Overall cancer morbidity was not increased, but the incidence of lung cancer was significantly elevated (SIR 1.61; 95 % CI 1.20-2.12). In the cohort study, significant associations between lung cancer and cumulative quartz exposure were detected for quartz doses of 1-2 mg/m3 * year (SIR 2.88; 95 % CI 1.44-5.16) and >2 mg/m3 * year (SIR 1.68; 95 % CI 1.07- 2.52). These findings were not confirmed in the case-control analysis. The agreement between the estimated exposure in our early historical model and the development model showed a regression coefficient of 2.42, implying an underestimation of the historical exposure when using the development model data. The corresponding comparison between the development and the validation model based on our survey data showed a B of 0.31, implying an overestimation of present exposures when using data from the validation model. The main conclusions of the thesis are that certain foundry workers are still exposed to high levels of quartz, and the overall excess lung cancer could not be confirmed in the exposure-response analysis.