Background: The purpose of this study is to determine whether precursor events are associated with a post-operative composite outcome in a low-medium risk cardiac surgical population. These precursor events may be promising targets for strategies aimed at quality improvement. Methods: This study was a case control design where the outcome of major adverse events (MACE) was assessed in patients exposed to four intra-operative precursor events. Cases and controls were matched 1:1 using propensity score matching, Univariate comparison of ?1 precursor event in the matched groups was performed. Results: The primary outcome of ?1 precursor event occurred significantly more frequently in the MACE patient group vs the non-MACE patients group (33% vs. 24%; p=0.015). The individual events of bleeding and difficulty weaning from CPB were significantly higher in the MACE group whereas incomplete revascularization/repair and repair/regrafting were not. Conclusion: Quality improvement techniques aimed at mitigating the consequences of precursor events may improve surgical outcomes for these patients.

This thesis reports the results of a prospective multicentred case-control study of mesothelioma carried out in South Africa. The objectives of the study were: 1) to examine asbestos exposure of cases in detail with respect to source, risk occupations, fibre type and duration; 2) to determine relative risks for level (certainty) of exposure (definite, probable, possible, unlikely), for category of exposure (occupational, environmental), and for fibre type and skin colour; 3) to determine whether cases without recall of exposure were exposed to other non-asbestos putative agents; 4) to investigate the possible protective effect of certain dietary components. Previous studies of mesothelioma in South Africa had, with the exception of one incidence study, focused on particular occupational or case material, exposure data had been gathered in a non-systematic way, often indirectly from surrogates, and non-asbestos agents had not been investigated. In this case-control study these issues are all addressed. In addition, special efforts were made to minimise potential sources of bias (e.g. interviewer bias) and so to furnish reliable effect estimates. The study incorporated the following methodological features: 1) a prospective approach to gather exposure and dietary information directly from the cases and controls in life and so avoid the use of surrogates for this information; 2) the study was multicentred with study teams established in six cities, each with a major referral hospital, to maximise nation-wide coverage; 3) information was gathered with interviewers blind (at least at the beginning of the study) to study objectives and case control status at the time of the interview; 4) rigorous pathologic review was used to establish the diagnosis of mesothelioma; 5) two controls were selected for each case, a cancer and a non-cancer patient matched for hospital, sex, age and skin colour; 6) in analysis the case control datasets were treated separately (i.e cases and cancer controls, and cases and non-cancer controls were treated as two separate datasets). One hundred and twenty three cases were accepted into the study. No case was documented with purely chrysotile exposure nor exposure to a putative non-asbestos cause of the tumour without some evidence of asbestos exposure. A minimum of 22 cases (18%) had exclusively environmental exposure, 20 were from the NW Cape (a crocidolite mining region). Fifty eight percent had occupational exposure, three of whom had mined amosite. The relative risks associated environmental exposure in the NW Cape were larger than for environmental exposure in the NE Transvaal: 21.9 versus 7.1 for the cancer control dataset and 50.9 versus 12.0 for the medical control dataset. Increasing consumption of carotene rich fruit was found to be protective for mesothelioma when adjusted for asbestos exposure. The results confirm the high disease burden due to occupational exposure, the importance of environmental exposure in the crocidolite mining area of the NW Cape, the relative paucity of cases linked to amosite, the rarity of chrysotile cases, and are consistent with the view that there is a fibre gradient in mesotheliomagenic potential for South African asbestos with crocidolite > amosite > chrysotile. The evidence for a protective effect of carotene rich fruit is new in the South African context.

OBJECTIVE: To evaluate whether the use of salmeterol is associated with an increased risk of an asthma-related hospitalization or emergency care among asthma patients. METHODS: The data for this study were extracted from the Medstat MarketScan® claims databases occurring between 01/01/00 and 12/31/01. A nested case-control study design was employed. A cohort representing asthma patients was identified in 2000. Among the study cohort, hospitalized cases were identified as those who had the firsttime asthma-related hospitalization in 2001, and were matched to select controls by age (± 5 years), sex, and the number of ambulatory visits for asthma (5:1 control to case ratio). A similar process was applied to evaluating an asthma-related emergency department (ED) visit. The odds of prior salmeterol exposure among cases compared to controls were estimated using conditional multiple logistic regressions. The covariates of interest comprised age, prior hospital admission or ED visit for asthma, number of canisters of inhaled short-acting β₂ agonists and use of other asthma medications. RESULTS: A total of 35,312 subjects were eligible to be the study cohort. In addition, 285 and 640 subjects were identified as hospitalized and ED cases, respectively. The non-significant association was found when the prior salmeterol exposure was treated as a dichotomized variable. However, it was found that one unit increase in the number of canisters of salmeterol was associated with a seven percent decrease in the risk of a hospital admission for asthma (p <0.001). Additionally, current use of salmeterol was associated with a 48 percent decrease in the risk of an asthma-related hospitalization (OR = 0.52; p <0.001). The protective effect of salmeterol did not exist for those with recent or past use of salmeterol. Similar findings were observed for the ED visit outcome. CONCLUSIONS: The use of salmeterol was not found to be associated with an increased risk of an asthma-related hospital admission or ED visit. Conversely, one unit increase in the number of canisters of salmeterol and current use of salmeterol, respectively, were found to decrease the risk in an asthma-related hospitalization or ED visit among asthma patients.

Thesis (Ph. D.)--University of Washington, 1995. / Vita. Includes bibliographical references (leaves [175]-192).

This project discusses some of the methodologies developed over the years to estimate attributable risk among exposed persons and the attributable risk in the entire population (also called Etiologic Fraction). It provides a general framework for estimating attributable risk among the exposed (denoted lambda_e). By making use of the recent observation that the two measures of attributable risk can be linked through the prevalence of the risk factor among the cases (denoted V_x), an estimate of population attributable risk (denoted lambda) for matched case-control studies is determined. Using the methodology developed recently by Kuritz and Landis (1987), this project provides explicit formulas for estimating the attributable risk among the exposed and the population attributable risk, and their large sample variances. This has been done both in situations where exactly R controls have been matched to a case and for a variable number of controls per case. The methodologies are illustrated with data from some case-control studies reported in the literature. Asymptotic relative efficiencies of different matching designs computed in terms of the costs of gathering cases and controls, are presented, together with some recommendations on what design is considered optimal. / Thesis / Master of Science (MSc)

It is widely believed that risks of many complex diseases are determined by genetic susceptibilities, including environmental exposures, and their interaction. Chatterjee and Carroll (2005) have recently developed an efficient retrospective maximum-likelihood method for analysis of case-control studies that exploits an assumption of gene-environment independence and leaves the distribution of the environmental covariates to be completely nonparametric. We generalize the semiparametric maximum-likelihood approach to situations when some of the environmental covariates are measured with error and allow genetic information to be missing on some subjects, e.g., unphased haplotypes. Profile likelihood techniques and an EM algorithm are developed, resulting in a relatively simple procedure for parameter estimation. We prove consistency and derive the resulting asymptotic covariance matrix of parameter estimates when variance of measurement error is known and when it is estimated using replications. The performance of the proposed method is illustrated using simulation studies emphasizing the case when genetic information is in the form of a haplotype and missing data arises from haplotype-phase ambiguity and missing genetic data. Inference is performed via a likelihood-ratio type procedure, one that we show has better small-sample performance thanWald-type inferences. An application of this method is illustrated using a case-control study of an association of calcium intake with early stages of colorectal tumor development.

Intravascular brachytherapy is the primary treatment for coronary in-stent restenosis. We hypothesized that differences in dose delivered to target may contribute to treatment failures. We compared dose distribution between arteries that developed recurrent restenosis (treatment failures) and those that remained patent at nine-months (treatment success). A cohort of 207 patients receiving brachytherapy for coronary in-stent restenosis with four radiation delivery devices was followed to identify treatment failures and successes. This cohort was examined to establish which patient and lesion characteristics had an effect on outcome. A nested case-control construct was then used in which treatment failures (n=14) were compared 1:2 to treatment successes (n=28) matched by two variables: radiation delivery system and angiographic pattern of in-stent restenosis. At baseline, the groups had similar patient and lesion characteristics. The dose absorbed by 90% of the artery encompassed by the external elastic membrane (D90EEM) was calculated using intravascular ultrasound (IVUS) images taken at 2-mm intervals along the treated lesion. Dose calculations were performed using dose kernel integration techniques; the dose kernels were generated from Monte Carlo simulations. The mean D90EEM minimum dose in treatment failures was 7.46±1.98 Gy, while for treatment success the mean D90EEM minimum dose was significantly higher: 8.87±1.13 Gy (p=0.007). Using a dose threshold of 8.4 Gy, a D90EEM minimum dose < 8.4 Gy occurred in 13 (93%) patients with treatment failure, but in only 9 (32%) with treatment success (p<0.001). No confounding variables were found to be statistically significant. In conclusion, current brachytherapy dose prescriptions result in significant inter- and intra-lesion variation in dose at the EEM. Arteries that receive < 8.4 Gy at any point along the EEM are more likely to be treatment failures. IVUS guided dosimetry may be critical to assure adequate dose regardless of radiation delivery system.

Thesis (MSc (School of health systems and public health))--University of Pretoria, 2009. / Summary in English. Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 1998. / Vita. Includes bibliographical references (leaves [84]-91).

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (p. 137-144).