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<p> Cause-specific mortality (CSM), among other global health estimates, has garnered prominence in the contemporary public health field. CSM has been associated with several factors, however, research comparing CSM for prefracking versus postfracking periods is sparse. Hydraulic fracturing or fracking is a technique of extracting oil and gas from deep underground. The purpose of this study was to evaluate the difference among mean CSM scores from 1975 through 2015 in the available cities and counties of residence in Colorado and to determine the impact of gender, marital status, county of residence, and city of residence on CSM scores (prefracking period 1975-1977 versus postfracking period 1999-2015) among adults aged 45-70 years. In this retrospective quantitative study, the socioecological model of health was used to analyze 73,251 cases obtained from the Colorado Department of Public Health and Environment. One-way analysis of variance and multiple regression were used to analyze data. Results showed that Denver County had a higher mean CSM score compared to other counties in Colorado. Regression results revealed a significant but weak association between CSM scores and gender, marital status, city of residence, and county of residence. If gender, marital status, and county of residence can be significant predictors of CSM, this information could have social change implications by influencing decisions regarding CSM and fracking.</p><p>

<p>The Idiopathic Interstitial Pneumonias (IIPs) are complex conditions, with limited treatment options and unknown etiology. Thus, given the complex nature of the disease and the likelihood of genetic heterogeneity, phenotypic and environmental factors must be taken into consideration when searching for genetic components involved in IIP. Families with 2 or more cases of IIP (classified as familial interstitial pneumonia, FIP) provide a unique opportunity to study IIP genetics. Therefore, in order to better define the FIP phenotype, families with a homogeneous pattern of disease diagnosis (IPF only, with all individuals diagnosed with IPF) were compared to families with a heterogeneous phenotype (mixed, with multiple different IIP diagnoses within a single family, including at least one case of IPF). Survival was decreased in the mixed (46%) compared to the IPF only (60%) families (p=0.006) along with the mean age of death (69 IPF only, 64 mixed, p=0.007). Surprisingly, the same results were found when only individual diagnosed with IPF from both types of families were compared (survival 40% vs. 60%, p=0.0003 and age of death 65 vs. 69, p=0.03). Using this same phenotypic classification scheme a whole genome microsatellite screen for FIP was conducted. Two peaks suggestive of linkage to chromosome 11 (LOD=3.3) and chromosome 10 (LOD=2.1) were identified in all 82 families, along with a third peak on chromosome 12 only seen in homogeneous families (LOD=2.5). In order to determine if the two linkage peaks seen in all 82 families were the result of genetic heterogeneity, ordered subset analysis (OSA) was conducted. Applying OSA, which uses family level covariate data to define a more homogeneous subset of families that maximize linkage, low linkage to chromosome 11 maximized linkage to chromosome 10 within a subset of 63 of the 83 families (LOD=3.4) and 27 of the mixed families (LOD=5.1). Furthermore, OSA revealed that families with a lower proportion of smokers among affected individuals contributed significantly to evidence in favor of linkage on chromosome 11 (LOD=4.9). It therefore appears that chromosomes 10 and 11 represent distinct susceptibility factors for FIP. Conducting further fine-mapping of the chromosome 11 region also identified 2 potential candidate genes, MUC2 and MUC5AC. Re-sequencing of both genes followed by selective genotyping of the 10 most interesting SNPs revealed 7 SNPs significantly associated with FIP and 7 SNPs significantly associated with IPF, 6 of which were significant in both FIP and IPF cases as compared to spouse controls. A haplotype consisting of 4 SNPs (1 in MUC2 and 3 in MUC5AC) was also found to be significant in both FIP (p=0.002) and IPF cases (p=0.001). While the SNP in MUC2 is intronic, all 3 MUC5AC SNPs produce amino acid changes. Thus, non-synonymous polymorphisms in MUC5AC are associated with both FIP and IPF.</p> / Dissertation

Background. Several trials of antibiotic use for the secondary prevention of cardiovascular diseases have been performed but individual studies have produced conflicting and inconclusive results. Therefore, we performed a systematic review of published studies to synthesize the evidence. We also examined a large cohort of previously revascularized patients to assess if a small but meaningful benefit of antibiotic exists. / Research question. Whether antibiotic use, compared to non-use, can reduce future cardiovascular events in a population of previously revascularized patients. / Method. A meta-analysis and a nested case control study were both conducted to answer the research question. In the meta-analysis, PubMed and the Cochrane Central Registry of controlled trials were searched for studies published between January 1 1994 and December 31 2004 using keyword 'antibiotic use' and 'cardiovascular diseases'. 232 published papers were initially identified and 12 randomized trials meet our inclusion criteria. The data were combined using a random effects model. A sensitivity analysis with a fixed effects model was also performed. Our nested case control study was conducted on a cohort of all individuals &ge;65 years of age who had a revascularization procedure from 1995 to 2000 and were registered in the Quebec universal health databases. The discharge date of each patient after revascularization was date of cohort entry. The primary endpoint was a composite of death, myocardial infraction and repeat revascularization. For each case, five controls were randomly selected and matched by date of cohort entry and age to the cases. Current users of antibiotics, those whose last prescription overlapped with the index date, were compared to individuals who were not exposed to antibiotics in the year preceding the event. Similarly the risk of recent (1-6 month) and past (6-12 months) antibiotic exposure was estimated. Odds ratios were calculated by using conditional logistic regression and adjusted for potential confounders. / Results. Our meta-analysis identified the 12 studies which randomized 10 231 patients to antibiotic treatment and 10 144 patients to control. The odds ratio for the composite event endpoint of death, myocardial infarction or revascularization was 0.92 (95CI%: 0.84-1.02). A similar result was found using a fixed effect model. No evidence for publication bias was found. Our nested case control study included 6 117 cases and 30 573 controls. The adjusted odds ratios of cardiac events for any current, recent and past antibiotic use were 1.12 [95%CI: 0.98-1.29], 1.21[95%CI: 1.07-1.28] and 1.31 [95%CI: 1.15-1.48], respectively. / Conclusion. No prevention association between antibiotic use and future cardiovascular events was shown either in the meta-analysis or our nested case control study. On the contrary, our nested case control study suggested increased risk long term following antibiotic exposure. One hypothesis to explain these results is that antibiotic exposure is a surrogate marker for a heightened inflammatory status that is associated with later cardiovascular risk.