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1
Havercroft, William G. « Exploration of marginal structural models for survival outcomes ». Thesis, University of Bristol, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.684750.
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A marginal structural model parameterises the distribution of an outcome given a treatment intervention, where such a distribution is the fundamental probabilistic representation of the causal effect of treatment on the outcome. Causal inference methods are designed to consistently estimate aspects of these causal distributions, in the presence of interference from non-causal associations which typically occur in observational data. One such method, which involves the application of inverse probability of treatment weights, directly targets the parameters of marginal structural models. The asymptotic properties and practical applicability of this method are well established, but little attention has been paid to its finite-sample performance. This is because simulating data from known distributions which are entirely suitable for such investigations generally presents a significant challenge, especially in scenarios where the outcome is survival time. We illuminate these issues, and propose and implement certain solutions, considering separately the cases of static (pre-determined) and dynamic (tailored) treatment interventions. In so doing, we explore both theoretical and practical aspects of marginal structural models for survival outcomes, and the associated inference method.
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Cavalli, Maide Maria. « Predicting survival outcomes in Myeloma using surrogate markers ». Doctoral thesis, Università di Catania, 2013. http://hdl.handle.net/10761/1394.
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BACKGROUND: OS should be considered the gold standard before adopting a particular treatment strategy as standard of care in Multiple Myeloma Phase III randomized clinical study but the use of OS as trial endpoint results in long trial duration. The primary objective of our project was to investigate whether there was a required minimum PFS difference between two arms in phase III randomized controlled trials (RCTs) that can be used as a predictor of benefit in overall survival (OS). Secondary objectives were to explore if there was a minimum threshold for VGPR rate and CR rate difference between two arms that will predict OS benefit in RCTs.
DESIGN AND METHOD: We performed a PUBMED search to identify potentially relevant randomized controlled trials (RCTs) between January 1992 to January 2012. We also scanned references of abstracts presented at the American Society of Hematology (ASH) between January 2005 to August 2012; this was supplemented by manual searches of others clinical trials. We used both absolute differences in the survival improvement (in months) and response rates between the two arms, as well as proportional improvements for the purpose of analysis. Descriptive statistics were used to summarize the minimum threshold PFS, CR AND VGPR median differences respectively.
RESULTS: Assessment of all publications resulted in identification of 75 RCTs. Of the 75 RCTs studied, 17 (22%) had statistically significant improvement in OS on intent to treat analysis (p-value ¡Ü 0.05) .We found that the minimum improvement in median PFS/TTP required to produce a significant improvement in OS was at least 2.5 months or more. This number varied depending on the stage of the disease and the type of treatment . CR improvements appeared to be widely variable, ranging from -5% (arm with survival improvement having worse CR rate by -5%) to 36%, with no particular pattern relative to type of therapy administered and the minimum threshold needed for survival benefit. VGPR rates were reported only in 5 of the 18 trials and therefore could not be accurately computed.
CONCLUSION: The current data is still immature to consider PFS improvement a pivotal surrogate marker of OS. We are limited by lack of data on Multiple Myeloma clinical trials showing OS significance.
3
Lehr, Carli J. « Extremes of Age Decrease Survival After Lung Transplant ». Case Western Reserve University School of Graduate Studies / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=case152909506004063.
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Ramchandani, Ritesh. « Rank-Based Methods for Survival Data With Multiple Outcomes ». Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845423.
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In clinical studies of survival, additional endpoints on patients may be collected over the course of the study that give additional insight into a treatment's effect. We propose three methods to analyze right censored survival data in the presence of multiple outcomes. In order to make limited parametric assumptions on the data-generating mechanisms, the methods are based on Wilcoxon-type rank statistics. Each method is applied to a recent clinical trial of Ceftriaxone in patients with amyotrophic lateral sclerosis.
In chapter 1, we modify the Gehan-Wilcoxon test for survival to account for auxiliary information on intermediate disease states (e.g. progression) that subjects may pass through before failure. We use multi-state modeling to compute expected ranks for each subject conditional on their last observed disease states and censoring time, and these ranks form the basis of our test statistic. Simulations demonstrate that the proposed test can improve power over the log-rank and generalized Wilcoxon tests in some settings while maintaining the nominal type 1 error rate.
In chapter 2, we propose an estimator for an accelerated failure time model based on the test statistic proposed in chapter 1. We use the statistic as an estimating equation for a parameter that accelerates the time to each subsequent disease state. The estimator incorporates the intermediate states in a manner relevant to the survival outcome, yielding interpretable treatment and covariate effects that consider the entire trajectory of the patient. Simulations demonstrate that the estimator is unbiased, and that the proposed standard error estimator is near the empirical value.
In chapter 3, we aim to assess the treatment effect globally across any types of multiple endpoints. The test we propose is based on a simple scoring mechanism applied to each pair of subjects for each endpoint. The scores for each pair of subjects are then reduced to a summary score, and a rank-sum test is applied to the summary scores. This can be seen as a generalization of several other global rank tests in the literature. Additionally, for certain statistics we describe optimal weighting schemes with respect to statistical power, and provide a method of selecting outcome weights adaptively.Biostatistics
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Meier, Amalia Sophia. « Discrete proportional hazards models for uncertain outcomes / ». Thesis, Connect to this title online ; UW restricted, 2001. http://hdl.handle.net/1773/9579.
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Kernell, Kristina. « Cardiac disease in pregnancy and consequences for reproductive outcomes, comorbidity and survival ». Doctoral thesis, Linköpings universitet, Avdelningen för kliniska vetenskaper, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-134854.
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Background Advances in medical treatment during the last 50 years have resulted in more individuals with congenital heart disease (CHD) and Marfan syndrome reaching childbearing age. The substantial physiological changes during pregnancy result in a high-risk situation, and pregnancy is a major concern in women with these conditions. Aims To describe the socio-demographic characteristics, birth characteristics and reproductive patterns of individuals with CHD and women with Marfan syndrome. To investigate obstetric and neonatal outcomes in the firstborn children of individuals with CHD and women with Marfan syndrome. To study long-term cardiovascular outcomes after childbirth in women with Marfan´syndrome. Methods The studies are population-based register studies. The study population in the first paper included all women born between 1973 and 1983 who were alive and resident in Sweden at the age of 13 (494 692 women, of whom 2 216 were women with CHD). In the second paper, the same definition of the study population was chosen, except that it involved all men born between 1973 and 1983 (522 216 men, of whom 2 689 men with CHD). The third and fourth papers involved a study population of all Swedish women born between 1973 and 1993 who were still living in Sweden at age 13. This population consisted of 1 017 538 women, 273 of whom had been diagnosed with Marfan syndrome. Results and conclusions The individuals studied were more often born preterm, and were small-for-gestational age babies. They were more likely to have been born by cesarean section. In women with CHD, these characteristics were repeated in their firstborn children. No increased risks were found in children of men with CHD or in children of women with Marfan syndrome. There was no increased risk of aortic dissection in women with Marfan syndrome during pregnancy compared to women with Marfan syndrome who did not give birth. Higher frequencies of cardiac arrhythmia and valvular heart disease were found after childbirth in women with Marfan syndrome. Pregnancy in women with CHD is a high-risk situation associated with increased risk of adverse neonatal outcomes for the expected child. Pregnancy in women without CHD, but where the father has CHD is not so associated with increased risk of adverse obstetric or neonatal outcomes. Pregnancy in women with Marfan syndrome is not associated with adverse outcomes for the expected child.
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Dodd, Susanna. « Modelling departure from randomised treatment in randomised controlled trials with survival outcomes ». Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/2006887/.
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Randomised controlled trials are considered the gold standard study design, as random treatment assignment provides balance in prognosis between treatment arms and protects against selection bias. When trials are subject to departures from randomised treatment, however, simple but naïve statistical methods that purport to estimate treatment efficacy, such as per protocol or as treated analyses, fail to respect this randomisation balance and typically introduce selection bias. This bias occurs because departure from randomised treatment is often clinically indicated, resulting in systematic differences between patients who do and do not adhere to their assigned intervention. There exist more appropriate statistical methods to adjust for departure from randomised treatment but, as demonstrated by a review of published trials, these are rarely employed, primarily due to their complexity and unfamiliarity. The focus of this research has been to explore, explain, demonstrate and compare the use of causal methodologies in the analysis of trials, in order to increase the accessibility and comprehensibility by non-specialist analysts of the available, but somewhat technical, statistical methods to adjust for treatment deviations. An overview of such methods is presented, intended as an aid to researchers new to the field of causal inference, with an emphasis on practical considerations necessary to ensure appropriate implementation of techniques, and complemented by a number of guidance tools summarising the necessary clinical and statistical considerations when carrying out such analyses. Practical demonstrations of causal analysis techniques are then presented, with existing methods extended and adapted to allow for complexities arising from the trial scenarios. A particular application from epilepsy demonstrates the impact of various statistical factors when adjusting for skewed time-varying confounders and different reasons for treatment changes on a complicated time to event outcome, including choice of model (pooled logistic regression versus Cox models for inverse probability of censoring weighting methods, compared with a rank-preserving structural failure time model), time interval (for creating panel data for time-varying confounders and outcome), confidence interval estimation method (standard versus bootstrapped) and the considerations regarding use of spline variables to estimate underlying risk in pooled logistic regression. In this example, the structural failure time model is severely limited by its restriction on the types of treatment changes that can be adjusted for; as such, the majority of treatment changes are necessarily censored, introducing bias similar to that in a per protocol analysis. With inverse probability weighting adjustment, as more treatment changes and confounders are accounted for, treatment effects are observed to move further away from the null. Generally, Cox models seemed to be more susceptible to changes in modelling factors (confidence interval estimation, time interval and confounder adjustment) and displayed greater fluctuations in treatment effect than corresponding pooled logistic regression models. This apparent greater stability of logistic regression, even when subject to severe overfitting, represents a major advantage over Cox modelling in this context, countering the inherent complications relating to the fitting of spline variables. This novel application of complex methods in a complicated trial scenario provides a useful example for discussion of typical analysis issues and limitations, as it addresses challenges that are likely to be common in trials featuring problems with nonadherence. Recommendations are provided for analysts when considering which of these analysis methods should be applied in a given trial setting.
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Kitajima, Toshihiro. « Impact of graft thickness reduction of left lateral segment on outcomes following pediatric living donor liver transplantation ». Kyoto University, 2019. http://hdl.handle.net/2433/242356.
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Rahman, M. S. « Validation measures for prognostic models for independent and correlated binary and survival outcomes ». Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1367069/.
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Prognostic models are developed to guide the clinical management of patients or to assess the performance of health institutions. It is essential that performances of these models are evaluated using appropriate validation measures. Despite the proposal of several validation measures for survival outcomes, it is still unclear which measures should be generally used in practice. In this thesis, a simulation study was performed to investigate a range of validation measures for survival outcomes in order to make practical recommendations regarding their use. Measures were evaluated with respect to their robustness to censoring and their sensitivity to the omission of important predictors. Based on the simulation results, from the discrimination measures, Gonen and Heller's K statistic can be recommended for validating a survival risk model developed using the Cox proportional hazards model, since it is both robust to censoring and reasonably sensitive to predictor omission. Royston and Sauerbrei's D statistic can be recommended provided that the distribution of the prognostic index is approximately normal. Harrell's C-index was affected by censoring and cannot be recommended for use with data with more than 30% censoring. The calibration slope can be recommended as a measure of calibration since it is not affected by censoring. The measures of predictive accuracy and explained variation (Graf et al's integrated Brier Score and its R-square version, and Schemper and Henderson's V) cannot be recommended due to their poor performance in the presence of censored data. In multicentre studies patients are typically clustered within centres and are likely to be correlated. Typically, random effects logistic and frailty models are fitted to clustered binary and survival outcomes, respectively. However, limited work has been done to assess the predictive ability of these models. This research extended existing validation measures for independent data, such as the C-index, D statistic, calibration slope, Brier score, and the K statistic for use with random effects/frailty models. Two approaches: the `overall' and `pooled cluster-specific' are proposed. The `overall' approach incorporates comparisons of subjects both within-and between-clusters. The `pooled cluster-specific' measures are obtained by pooling the cluster-specific estimates based on comparisons of subjects within each cluster; the pooling is achieved using a random effects summary statistics method. Each approach can produce three different values for the validation measures, depending on the type of predictions: conditional predictions using the estimates of the random effects or setting these as zero and marginal predictions by integrating out the random effects. Their performances were investigated using simulation studies. The `overall' measures based on the conditional predictions including the random effects performed reasonably well in a range of scenarios and are recommended for validating models when using subjects from the same clusters as the development data. The measures based on the marginal predictions and the conditional predictions that set the random effects to be zero were biased when the intra-cluster correlation was moderate to high and can be used for subjects in new clusters when the intra-cluster correlation coefficient is less than 0.05. The `pooled cluster-specific' measures performed well when the clusters had reasonable number of events. Generally, both the `overall' and `pooled' measures are recommended for use in practice. In choosing a validation measure, the following characteristics of the validation data should be investigated: the level of censoring (for survival outcome), the distribution of the prognostic index, whether the clusters are the same or different to those in the development data, the level of clustering and the cluster size.
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Underhill, Andrea T. « Gender differences in traumatic brain injury outcomes survival, functional independence, and employment status / ». Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2008. https://www.mhsl.uab.edu/dt/2008p/underhill.pdf.
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Mubanga, Mwenya. « Investigation of the management of tuberculous pericarditis (IMPI) registry : survival and outcomes sub-study ». Master's thesis, University of Cape Town, 2012. http://hdl.handle.net/11427/6024.
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Karaesmen, Ezgi. « Genetic Associations with Survival Outcomes after Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation ». The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1587686582370275.
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Gupta, Ruta. « Factors that Predict and Improve the Survival Outcomes of Head and Neck Cancer Patients ». Thesis, The University of Sydney, 2020. https://hdl.handle.net/2123/24601.
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The body of work included in this thesis aims at developing evidence-based strategies using a variety of pathology tools to improve the diagnostic and prognostic accuracy for head and neck cancer patients. Head and neck cancer patients are one of the most underserved subgroup of cancer patients. The studies span a spectrum of pathology methods including cost effective techniques such as standardised macroscopic examination of the resected specimen, and identification and assessment of tumour characteristics using the routine haematoxylin and eosin stained tissue sections that can be undertaken in any part of the world. These publications have contributed towards international standardisation of head and neck cancer specimen examination and attempt to minimise inter-observer variability so that head and neck cancer patients receive similar diagnostic, prognostic and predictive information globally.
Advanced techniques such as specialized immunohistochemical staining based on the antigenic properties of the tumour and sophisticated in situ hybridization tests based on the genetic characteristics of the tumour have also been evaluated. These analyses have validated novel tools such as fluorescent in situ hybridisation that improve diagnostic accuracy in challenging head and neck lesions.
Development of internationally unique resources such as head and neck cancer biobank with cognate clinicopathologic database as well as compute environment was required to harness cutting edge next generation sequencing technology. These studies investigate the molecular characteristics of the tumour to enhance prognostic stratification and to identify therapeutic options for head and neck cancer patients. The work is ongoing, and I hope will bring the survival revolution we are seeing in melanoma and lung cancer to the underserved head and neck malignancies.
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Tsampalieros, Anne. « Inter-centre Variation in the Management of Kidney Transplant Recipients and Its Impact on Clinical Outcomes ». Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37266.
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Introduction: There is an increasing number of Canadians living with end stage renal disease (ESRD). Kidney transplantation is currently the best treatment for ESRD but long-term outcomes remain suboptimal. Identifying factors associated with better outcomes may lead to interventions or practice change that could improve patient survival or quality of life. The objectives of this thesis were to: i) systematically review the literature to examine centre variation in kidney transplantation outcomes and identify centre and provider level factors that may contribute to variation in outcomes; ii) describe differences that may exist at the patient, centre and provider level at the time of kidney transplantation across the six transplant centres in Ontario, Canada; iii) examine variation in graft and patient survival rates across transplant centres in Ontario; and iv) examine whether patient, centre and provider level characteristics contribute to variation in graft and survival rates across transplant centres.
Methods: The first objective of this thesis was met by conducting a systematic review of the literature according to a predefined protocol. The last three objectives of the thesis were met by conducting a population based retrospective cohort study using administrative data from Ontario. Differences at the patient, centre and provider level were described at the time of kidney transplantation. Outcomes of interest included total graft loss; graft loss with follow-up censored at death; death with graft function; and total mortality. All outcomes were assessed at one year post transplantation and at the end of study follow up. Cox proportional hazards regression was used to obtain hazard ratios (HR) for each centre relative to the average across all centres. The independent effect of centre volume and provider characteristics on outcomes was also examined.
Results: The systematic review identified 24 eligible studies. Outcomes included graft survival (n=24) and patient survival (n=9). The main characteristics evaluated were centre volume (n=17) and provider volume (n=2). Centre variation in graft survival was described in 80% (12/15) of studies, while less than half of studies (8/17) found a significant association between volume and graft survival. The population based retrospective cohort included 5092 adults (≥18 years) who received a primary solitary kidney transplant across 6 transplant centres in Ontario between January 1st 2000 and December 31st 2013. Variation in patient, centre and provider level factors existed across centres at the time of transplantation. At the end of study follow-up, case-mix adjusted HRs for total graft loss ranged from 0.84 (95% CI 0.53-1.33) to 1.16 (95% CI 1.00-1.34) across centres (p-value for between centre variation 0.46). After adjusting for centre and provider factors, differences across centres persisted. Centre volume, provider experience and provider type were not independently associated with either short or long-term outcomes (all p>0.05) with the exception of graft loss with follow-up censored at death.
Discussion: This thesis suggests that there is variation in clinical outcomes across transplant centres in Ontario which is not explained by patient factors, centre volume or provider characteristics at the time of transplantation. Additionally centre volume, provider type and experience were not independently associated with outcomes. Future prospective studies with a larger sample size of transplant centres that examine follow-up care after discharge from hospital (e.g. frequency of visits) are required to better understand this phenomenon.
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Reece, Mifanwy Mary. « Comparing outcomes of laparoscopic and open complete mesocolic excision for colon cancer ». Thesis, The University of Sydney, 2021. https://hdl.handle.net/2123/27398.
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Background
Laparoscopic colon cancer surgery has been demonstrated to have improved short-term outcomes including lower complication rates and a shorter recovery time compared to open surgery. In many high-quality trials, oncological outcomes are largely equivalent between the two surgical approaches. Complete mesocolic excision (CME) is the surgical technique that involves excision of the colonic tumour within an intact mesocolic envelope to avoid intra-operative spillage of tumour cells, together with high ligation of colonic vessels in order to completely disrupt any potential metastatic pathways and perform adequate lymphadenectomy. The introduction of this technique at Concord hospital has been demonstrated to improve survival using historical controls. In addition, some centres perform a central vascular ligation (CVL) to excise the most proximal draining lymph nodes, with some evidence that this may improve survival. This procedure is similar to the extent of the left-sided resections performed at Concord Hospital, whereas right-sided resections are less extensive at Concord than at centres that perform CME + CVL. Laparoscopic CME + CVL has also been shown to have similar oncologic outcomes to open surgery. None of the studies comparing laparoscopic and open colon cancer surgery have utilised a competing risks analysis, instead utilising Kaplan-Meier analyses which can exaggerate the results in a survival analysis.
Aims
The primary aim of this study is to examine the survival outcomes of patients undergoing laparoscopic colon cancer resections compared to open procedures. The primary outcomes will be overall survival, competing risks incidence of colon cancer-specific death and competing risks incidence of colon cancer recurrence. Secondary outcomes will include pathology results (as surrogate markers of surgical quality and oncological outcomes) and peri-operative outcomes to enable a thorough comparison of short-term outcomes between the two surgical approaches.
Methodology
Data were collected from the Concord Hospital Colorectal Cancer Database from January 2007 to December 2014. Patients undergoing colon cancer surgery for an index colonic adenocarcinoma were eligible for inclusion. Patients were followed up for a minimum of five years. Laparoscopic cases that were converted to open surgery were included in the laparoscopic group for analysis. Kaplan-Meier analysis was used for overall survival and a competing risks analysis was used for colon-cancer specific death and cancer recurrence.
Results
A total of 677 patients who underwent a colon cancer resection were included (424 laparoscopic and 253 open). The conversion rate was 9%. Laparoscopy was less likely to be selected for urgent resections, left-sided or large tumours or for patients with distant metastatic disease. Whilst patients with adverse histological features were less likely to have undergone a laparoscopic operation, these features were not independently associated with surgical access technique. Mean lymph node yield was significantly lower for laparoscopic operations (18.78 vs 21.89) however there was no difference in the proportion of specimens with a minimum of 12 lymph nodes. Overall complication rates were lower following laparoscopy and LOS was 2.9 days shorter but there was no difference in 30-day mortality.
Five-year overall survival following laparoscopic and open surgery was 71.3% and 52.7% respectively, however on multivariable analysis surgical access was not independently associated with survival. Although statistically significant in the bivariate models, surgical access was not related to competing risks incidence of death due to colon cancer or recurrence in the multivariable models. Patients with ≥T3 tumours, tumours with nodal involvement or with distant metastatic disease or who experienced a postoperative venous thromboembolism had an increased risk of colon cancer-specific death. Patients with ≥T3 tumours, with nodal involvement or who had post-operative sepsis had a higher risk of recurrence.
Conclusion
Laparoscopic colon cancer surgery has many short-term benefits compared to open surgery. Given that long-term oncological outcomes were similar between groups, where feasible, laparoscopy should be considered for all patients undergoing colon cancer surgery.
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Fidler, Miranda Marie. « Long-term adverse outcomes following five-year survival of cancer diagnosed before 40 years age ». Thesis, University of Birmingham, 2016. http://etheses.bham.ac.uk//id/eprint/6638/.
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Purpose: Survival from childhood, teenage, and young adult cancer has increased substantially, with approximately 80% now surviving at least five-years. However, curative treatments are often associated with adverse late effects. This thesis investigated the risk of late adverse health and social outcomes following five-year survival of cancer diagnosed before age 40 years using the British Childhood Cancer Survivor Study (BCCSS) and Teenage and Young Adult Cancer Survivor Study (TY ACSS). Material and Methods: The BCCSS is a population-based cohort of 34,489 five-year survivors of childhood (< 15 years) cancer diagnosed from 1940-2006 in Great Britain. The TY ACSS is a population-based cohort of 200,945 five-year survivors of teenage and young adult (15-39 years) cancer diagnosed from 1971-2006 in England and Wales. Results: Some survivors were found to have increased risks of premature mortality, subsequent primary neoplasms, hospitalizations, poor quality-of-life, and psychosocial limitations. However, for premature mortality, the number of excess deaths is decreasing among those more recently diagnosed for several causes-of-death. Conclusions: Survivors of cancer diagnosed before age 40 are at an increased risk of a range of adverse late effects compared to that expected. The findings reported in this thesis will be useful for risk stratification, updating clinical guidelines, and informing survivors and clinicians.
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Cheung, Li Chien. « Mixture models for left- and interval-censored data and concordance indices for composite survival outcomes ». Thesis, The George Washington University, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10259297.
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For cost-effectiveness and efficiency, many large-scale general-purpose cohort studies are being assembled within health-care providers who use electronic health records. Two key features of such data are that incident disease is interval-censored between irregular visits and pre-existing (prevalent) disease is left-censored. Because prevalent disease is not always immediately diagnosed, some disease diagnosed at later visits are actually undiagnosed prevalent disease. I consider prevalent disease as a point mass at time zero for clinical applications where there is no interest in time of prevalent disease onset. I demonstrate that the naive Kaplan-Meier cumulative risk estimator underestimates risks at early time points and overestimates later risks. I propose a general family of mixture models that we call prevalence-incidence models. Parameters for parametric prevalence-incidence models, such as the logistic regression and Weibull survival (logistic-Weibull) model, are estimated by direct likelihood maximization or EM algorithm. Non-parametric methods are proposed to calculate cumulative risks for cases without covariates. I compare naive Kaplan-Meier, logistic-Weibull, and non-parametric estimates of cumulative risk in the cervical cancer screening program at Kaiser Permanente Northern California. Kaplan-Meier methods provided poor estimates while the logistic-Weibull model was a close fit to the non-parametric. My findings support use of logistic-Weibull models over Kaplan-Meier methods to develop risk estimates for informing U.S. risk-based cervical cancer screening guidelines. Harrell's c index is widely used to measure the accuracy in predicting univariate survival outcomes. However, survival outcomes relating to a disease of interest may show up in multiple endpoints of interest. I propose two extensions of Harrell's c index for composite survival outcomes that account for frequencies of occurrences and the severity/importance of the outcomes. A weighted C index is proposed for a disease process with multiple equally important endpoints, and a most severe comparable C index is proposed for a disease process with a rare primary outcome and a correlated secondary outcome. Asymptotic properties are derived based on theorems for U-statistics. In the simulation studies, my extensions gain efficiency and power in identifying true prognostic variables. I illustrate these novel concordance indices using the Epidemiology of Diabetes Intervention and Complications (EDIC) and the Diabetes Prevention Program (DPP) trials. In EDIC, the prognosis of diabetes patients at risk for multiple equally important microvascular complications are evaluated using the weighted C index. In DPP, patients with impaired glucose resistance (IGR) who may either progress to type II diabetes or regress to normal glucose resistance (NGR). The proposed most severe comparable index better evaluates the accuracy in predicting diabetes risk with the help of auxiliary NGR outcomes.
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Spirko, Lauren Nicole. « Variable Selection and Supervised Dimension Reduction for Large-Scale Genomic Data with Censored Survival Outcomes ». Diss., Temple University Libraries, 2017. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/466860.
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StatisticsPh.D.
One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes, providing insight into the disease's process. With the rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of thousands of genes and proteins resulting in enormous data sets where the number of genomic variables (covariates) is far greater than the number of subjects. It is also typical for such data sets to have a high proportion of censored observations. Methods based on univariate Cox regression are often used to select genes related to survival outcome. However, the Cox model assumes proportional hazards (PH), which is unlikely to hold for each gene. When applied to genes exhibiting some form of non-proportional hazards (NPH), these methods could lead to an under- or over-estimation of the effects. In this thesis, we develop methods that will directly address t
Temple University--Theses
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Ramroth, Johanna Rankin. « Radiotherapy dose-fractionations and outcomes in cancer patients ». Thesis, University of Oxford, 2017. http://ora.ox.ac.uk/objects/uuid:8c5a99de-7d8c-4b19-9a91-e6cf4efa7bd2.
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Radiotherapy cures many cancers, but the optimum total doses and fractionations used to treat different cancer types remain uncertain. While conventional fractionation (≈2 Gy per fraction) is common in many countries, UK practice has been highly variable. This thesis compared different curative-intent radiotherapy dose-fractionations used in non-small cell lung and breast cancer. These two cancers together make up over a quarter of UK cancer incidence and mortality, and radiotherapy can increase cure rates of both cancers. Two studies were conducted: (A) A meta-analysis of randomised radiotherapy trials in non-small cell lung cancer and (B) A cohort study of non-small cell lung and breast cancer radiotherapy in the Thames Valley. For the meta-analysis, a systematic search was conducted. Eligible studies were randomised comparisons of two or more radiotherapy regimens. Median survival ratios were calculated for each comparison and pooled. 3,795 patients in 25 randomised comparisons of radiotherapy dose were studied. When radiotherapy was given alone, the higher dose within-trial resulted in increased survival (median survival ratio 1.13, 95% confidence interval 1.04-1.22). When radiotherapy was given with concurrent chemotherapy, the higher dose within-trial resulted in decreased survival (median survival ratio 0.83, 95% confidence interval 0.71-0.97). For the cohort study, multiple Public Health England data sources were combined to obtain information on radiotherapy, patient characteristics, and outcomes. Multivariable Cox regressions were conducted separately by cancer site. 324 non-small cell lung, 8,879 invasive breast, and 477 ductal carcinoma in situ patients were studied. In analyses of both non-small cell lung and invasive breast cancer, increasing radiotherapy dose was associated with improved survival in some treatment centres, while in other centres the opposite was true. These opposite trends by treatment centre were unlikely to be explained by chance, and they suggest that differences in patient selection were driving results. There were insufficient events among ductal carcinoma in situ patients to assess associations. Findings from the meta-analysis support consideration of further radiotherapy dose escalation trials, making use of modern methods to reduce toxicity. Findings from the cohort study suggest that it is not possible to use observational studies to examine causal effects of radiotherapy dose-fractionation. This thesis therefore shows the continued importance of conducting sufficiently large randomised trials to ascertain optimal dose-fractionation in radiotherapy.
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Webster, Elizabeth Natalie. « Health care Facilities as a Predictor of Breast Cancer Survival Rates ». ScholarWorks, 2018. https://scholarworks.waldenu.edu/dissertations/6145.
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The disparity between survival rates for Black and White women with breast cancer is well documented and has been examined in terms socioeconomics, environment, tumor type, and genetics. However, there is little examination of the role of health care facilities in cancer disparities. Health care facilities are representative of societal norms and beliefs that include location, quality of care, finance, policies, and staffing; therefore, they are a proxy for social justice and social change. The purpose of this study was to examine correlations between health care facility type; social determinants of cancer such as poverty, culture, and social justice; and breast cancer survival rates. Using the social determinants of cancer theoretical framework, the breast cancer survival rate of 4,087 Black and White women in Georgia between the ages of 45 and 69 was studied. The relationship between breast cancer survival and predictors including race, income, health care facility type, grade, and tumor type (4 sub-variables) were examined using the Kaplan-Meier Method, log-rank test, and Cox proportional hazard model. The log-rank test suggested no statistically significant difference in the survival functions among patients in different health care facilities (Ï?2(2) = 0.0150, p = 0.9926). The Cox proportional hazard model suggested no statistically significant relationship between breast cancer survival and health care facility type, after controlling for other predictors (Ï?2(2) = 0.3647, p = 0.8333). This result indicates that healthcare facilities do not influence breast cancer survival rates, however, given the persistent health outcome disparities further research in the area is warranted.
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Hsieh, Jeff Ching-Fu. « Bayesian statistical models for understanding health-related outcomes for women screened for breast cancer ». Thesis, Queensland University of Technology, 2016. https://eprints.qut.edu.au/100033/1/Jeff%20Ching-Fu_Hsieh_Thesis.pdf.
Texte intégralRésumé :
This thesis aims to understand the effects of women's residential location on breast cancer outcomes associated with screening, with a focus on women living in Queensland, Australia. It examines the spatial survival inequalities in health outcomes among these women by means of Bayesian spatial models and presents the inequalities with thematic maps across the state. The thesis investigated the spatial inequalities of various patient demographic, clinical and geographic factors as well as the intended use of cancer treatment among women with screen-diagnosed breast cancer.
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Kvederienė, Rūta. « The impact of emergency care on severe pediatric trauma outcomes ». Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2012. http://vddb.laba.lt/obj/LT-eLABa-0001:E.02~2012~D_20121227_085948-00813.
Texte intégralRésumé :
Trauma is the main cause of death in paediatric population worldwide. Lithuania has the highest trauma-related mortality in the European Union (EU). Lithuanian standardised injury death rate is 150.9 per 100000 inhabitants while in comparison the mean standardised injury death rate in the EU is 41.4, and the lowest one is in the Netherlands (26.4 injury death rate per 100000 inhabitants). The aim of this study was to analyze the impact of pre-hospital and in-hospital emergent trauma care on severe pediatric trauma outcomes, performing a prospective observational clinical trial in the Vilnius University Children’s Hospital and Vilnius Pre-hospital Emergency Service Center. Trauma registry fields were defined in details and validated during this study. The recommended quality indicators were defined and used for pre-hospital pediatric trauma care and in-hospital emergent management evaluation. The study results showed that the level of pre-hospital care is associated statistically significantly with trauma outcomes: higher pre-hospital care level caused better trauma outcome assessed according to the Glasgow Outcome Scale. The longer time until the first key emergency intervention in hospital was associated statistically significantly with the worse trauma outcomes. Calculation of the Probability of survival (Ps) according to Trauma Score Injury Severity Score model (TRISS) revealed unexpected death (Ps > 50 %) rate 74%. The reasons for fatal outcome in the patient group with... [to full text]Traumos yra pagrindinė vaikų, paauglių ir jaunų suaugusiųjų mirties priežastis. Stebimas didžiulis skirtumas Europos Sąjungos (ES) šalyse lyginant mirštamumą nuo traumų. Lietuvoje didžiausias ES standartizuotas traumų mirčių dažnis (150.9 mirtys dėl traumų 100.000 gyventojų). Palyginimui: ES šalių vidurkis yra 41.4 mirtys dėl traumos 100.000 gyventojų, mažiausias standartizuotas traumų mirčių dažnis yra Olandijoje – 26.4 mirtys 100.000 gyventojų. Toks skirtumas nurodo potencialią galimybę sumažinti mirčių dėl traumų skaičių, naudojant visas priemones: tiek traumų prevenciją, tiek skubios pagalbos prieinamumą ir kokybę. Darbo tikslas – išanalizuoti vaikų, patyrusių sunkias traumas, ikihospitalinės pagalbos ir skubiosios pagalbos ligoninėje laiko bei apimties įtaką traumų išeitims, atliekant perspektyvinį tyrimą Vilniaus Universiteto Santariškių klinikų Vaikų ligoninėje bei Vilniaus Greitosios medicinos pagalbos stotyje. Rezultatai parodė, kad pagalbos lygis ikihospitaliniu laikotarpiu susijęs su išeitimi: pacientams, gavusiems aukštesnio lygio pagalbą traumos išeitys pagal Glazgo išeičių skalę buvo geresnės. Ilgesnis laikas nuo paciento atvežimo į ligoninę iki pirmos skubiosios intervencijos statistiškai patikimai koreliavo su blogesne traumos išeitimi. Apskaičiavus išgyvenamumo tikimybę (Ps) pagal traumos skalės pažeidimų sunkumo modelį (TRISS), 74 proc. mirčių dėl traumų pateko į netikėtų mirčių (Ps > 50 proc.) kategoriją. Kiekviena netikėta mirtis, identifikuota naudojant... [toliau žr. visą tekstą]
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Dolgin, Natasha H. « Frailty and Outcomes in Liver Transplantation : A Dissertation ». eScholarship@UMMS, 2016. https://escholarship.umassmed.edu/gsbs_diss/817.
Texte intégralRésumé :
In recent years, the transplant community has explored and adopted tools for quantifying clinical insight into illness severity and frailty. This dissertation work explores the interplay between objective and subjective assessments of physical health status and the implications for liver transplant candidate and recipient outcomes. The first aim characterizes national epidemiologic trends and the impact of Centers for Medicare and Medicaid quality improvement policies on likelihood of waitlist removal based on the patient being too frail to benefit from liver transplant (“too sick to transplant”). This aim includes more than a decade (2002–2012) of comprehensive national transplant waitlist data (Scientific Registry of Transplant Recipients (SRTR)). The second aim will assess and define objective parameters of liver transplant patient frailty by measuring decline in lean core muscle mass (“sarcopenia”) using abdominal CT scans collected retrospectively at a single U.S. transplant center between 2006 and 2015. The relationship between these objective sarcopenia measures and subjective functional status assessed using the Karnofsky Functional Performance (KPS) scale are described and quantified. The third aim quantifies the extent to which poor functional status (KPS) pre-transplant is associated with worse post-transplant survival and includes national data on liver transplantations conducted between 2005 and 2014 (SRTR). The results of this dissertation will help providers in the assessment of frailty and subsequent risk of adverse outcomes and has implications for strategic clinical management in anticipation of surgery. This research will also to serve to inform national policy on the design of transplant center performance measures.
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Dolgin, Natasha H. « Frailty and Outcomes in Liver Transplantation : A Dissertation ». eScholarship@UMMS, 2004. http://escholarship.umassmed.edu/gsbs_diss/817.
Texte intégralRésumé :
In recent years, the transplant community has explored and adopted tools for quantifying clinical insight into illness severity and frailty. This dissertation work explores the interplay between objective and subjective assessments of physical health status and the implications for liver transplant candidate and recipient outcomes. The first aim characterizes national epidemiologic trends and the impact of Centers for Medicare and Medicaid quality improvement policies on likelihood of waitlist removal based on the patient being too frail to benefit from liver transplant (“too sick to transplant”). This aim includes more than a decade (2002–2012) of comprehensive national transplant waitlist data (Scientific Registry of Transplant Recipients (SRTR)). The second aim will assess and define objective parameters of liver transplant patient frailty by measuring decline in lean core muscle mass (“sarcopenia”) using abdominal CT scans collected retrospectively at a single U.S. transplant center between 2006 and 2015. The relationship between these objective sarcopenia measures and subjective functional status assessed using the Karnofsky Functional Performance (KPS) scale are described and quantified. The third aim quantifies the extent to which poor functional status (KPS) pre-transplant is associated with worse post-transplant survival and includes national data on liver transplantations conducted between 2005 and 2014 (SRTR). The results of this dissertation will help providers in the assessment of frailty and subsequent risk of adverse outcomes and has implications for strategic clinical management in anticipation of surgery. This research will also to serve to inform national policy on the design of transplant center performance measures.
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Wahlgren, Thomas. « High dose rate brachytherapy boost for localized prostate cancer : clinical and patient-reported outcomes/ ». Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-931-9/.
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O'Daniel, Alyson J. « SOCIAL CATEGORIES AND HEALTH CARE OUTCOMES : AFRICAN AMERICAN WOMEN AND HIV SURVIVAL IN THE URBAN SOUTH ». UKnowledge, 2010. http://uknowledge.uky.edu/gradschool_diss/92.
Texte intégralRésumé :
This ethnographic research examines the daily life and institutional conditions under which low-income Black women in urban North Carolina perceived and attended to HIV health-related needs. I focus specifically on the interplay among women’s living conditions, programmatic service needs, and their strategies for navigating the local system of care to explore and refine the categorical label “low income.” I found that there were significant differences among study participants in terms of their monthly incomes and financial resources, housing quality and status, and personal experiences with incarceration and substance abuse. The economic differences among women translated into social differences within the context of federally-funded AIDS care programs. Social differences were realized as the differential ability to transform programmatic services enrollment into beneficial social networks. Ultimately, financially stable women were better positioned than their more economically vulnerable counterparts to reap the economic and social benefits of programmatic services eligibility and enrollment. It is in this context that I explore federally-funded AIDS care services as one social field through which processes of class unfold and articulate with processes of race and gender.
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Fong, Sze-un Calvin. « Long-term outcomes of cataract surgery : visual acuity, survival, and incidence and progression of ocular pathology ». Thesis, The University of Sydney, 2014. http://hdl.handle.net/2123/11434.
Texte intégralRésumé :
Purpose: To assess long-term visual and survival outcomes and incidence of ocular pathology after cataract surgery in an older surgical cohort. Methods: The Australian Prospective Cataract Surgery and Age-related Macular Degeneration study is a cohort study of 2029 cataract surgery patients, aged ≥64 years, who were recruited largely at Westmead Hospital in 2004-2007 and were followed annually for five years postoperatively. Results: The majority of patients (86%) had pinhole visual acuity ≥6/12 two years after phacoemulsification surgery. Correction of cataract-related visual impairment via cataract surgery was associated with 30% lower mortality risk, compared to surgical patients with visual impairment remaining after surgery. The three-year cumulative incidences of early and late age-related macular degeneration (AMD) after surgery were 11% and 1%, respectively, and postoperative status was not associated with increased incidence of AMD. In addition, the three-year cumulative incidences of epiretinal membranes and posterior capsule opacification were 11% and 39%, respectively, in eyes after cataract surgery. Conclusions: This cohort study documents that improved vision is sustained for at least two postoperative years; cataract surgery is not associated with subsequent development of AMD; and correcting visual impairment resulting from cataract via cataract surgery is associated with improved survival of older persons.
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Budryk, Michal, et Alice Schmuck. « How to Handle an Internal Venture ? : The Effect of Relatedness on the Outcomes of Corporate Venturing ». Thesis, Uppsala universitet, Företagsekonomiska institutionen, 2014. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-226610.
Texte intégralRésumé :
This paper uses event history analysis to investigate the effects of relatedness on three different outcomes of corporate venturing, identified as retention, termination, and spin-off. For this purpose, relatedness is defined as the degree to which the venture’s activity matches or overlaps with the parent’s activity. Drawing from literature on relational fit, we argue that highly related ventures would be retained, moderately related ones spun off, and unrelated ones would be probable candidates for termination. However, highly related ventures may be likely to pose internal threat to the parent, and consequently be candidates for termination for political reasons as well. This raises the average level of relatedness of terminated ventures above the average of spin-offs. The empirical findings derived from a sample consisting of 78 ventures launched and developed by a number of companies across the Swedish economy give support to our expectations. The highly related ventures were found to be either terminated or retained, moderately related ones were likely to be spun off, and unrelated ones typically faced termination. This supports our hypothesis that relatedness has an impact on how the internal venture is dealt with. We follow with implications for the practice of corporate venturing management.
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Sarnowski, Adam. « Management of the Open Apex Using a Bioceramic Apical Barrier : Success and Survival Rates at Virginia Commonwealth University ». VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5765.
Texte intégralRésumé :
Purpose: The aim of this study was to assess the outcome of treatment of teeth with open apices managed by the orthograde placement of a bioceramic apical barrier as well as to identify potential outcome factors for this type of treatment. Methods: Patient records were pooled from graduate resident cases completed at Virginia Commonwealth University between January 1, 2010 and May 31, 2018. A total of 515 patients were identified using relevant ADA codes and a key word search within the patient record database. A total of 104 patients (119 teeth) had an open apex that had NSRCT utilizing a bioceramic apical barrier, with 32 of the patients (36 teeth) returning for follow-up. Results: Of the 36 examined teeth (30.8% recall rate),72% were considered healed. 92% were considered healed or healing. No predictive variable analyzed had a significant effect on the outcome. Conclusion: Overall, these results indicate that a bioceramic apical barrier technique is a promising treatment option for obturating teeth with open apices during NSRCT.
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Dunn, Janet Audrey. « Development of an improved staging system to predict both survival and specific disease outcomes in multiple myeloma ». Thesis, University of Birmingham, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.412762.
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Hannon, James G. « Place Needs and Client Outcomes of Wilderness Experience Programs in Maine : A Descriptive-Interpretive Approach ». Fogler Library, University of Maine, 2004. http://www.library.umaine.edu/theses/pdf/HannonJG2004.pdf.
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Strand, Linn Beate. « The influence of ambient temperature on birth outcomes in Brisbane, Australia ». Thesis, Queensland University of Technology, 2011. https://eprints.qut.edu.au/47005/1/Linn_Beate_Strand.pdf.
Texte intégralRésumé :
Lately, there has been increasing interest in the association between temperature and adverse birth outcomes including preterm birth (PTB) and stillbirth. PTB is a major predictor of many diseases later in life, and stillbirth is a devastating event for parents and families. The aim of this study was to assess the seasonal pattern of adverse birth outcomes, and to examine possible associations of maternal exposure to temperature with PTB and stillbirth. We also aimed to identify if there were any periods of the pregnancy where exposure to temperature was particularly harmful.
A retrospective cohort study design was used and we retrieved individual birth records from the Queensland Health Perinatal Data Collection Unit for all singleton births (excluding twins and triplets) delivered in Brisbane between 1 July 2005 and 30 June 2009. We obtained weather data (including hourly relative humidity, minimum and maximum temperature) and air-pollution data (including PM10, SO2 and O3) from the Queensland Department of Environment and Resource Management.
We used survival analyses with the time-dependent variables of temperature, humidity and air pollution, and the competing risks of stillbirth and live birth. To assess the monthly pattern of the birth outcomes, we fitted month of pregnancy as a time-dependent variable. We examined the seasonal pattern of the birth outcomes and the relationship between exposure to high or low temperatures and birth outcomes over the four lag weeks before birth. We further stratified by categorisation of PTB: extreme PTB (< 28 weeks of gestation), PTB (28–36 weeks of gestation), and term birth (≥ 37 weeks of gestation). Lastly, we examined the effect of temperature variation in each week of the pregnancy on birth outcomes.
There was a bimodal seasonal pattern in gestation length. After adjusting for temperature, the seasonal pattern changed from bimodal, to only one peak in winter. The risk of stillbirth was statistically significant lower in March compared with January. After adjusting for temperature, the March trough was still statistically significant and there was a peak in risk (not statistically significant) in winter.
There was an acute effect of temperature on gestational age and stillbirth with a shortened gestation for increasing temperature from 15 °C to 25 °C over the last four weeks before birth. For stillbirth, we found an increasing risk with increasing temperatures from 12 °C to approximately 20 °C, and no change in risk at temperatures above 20 °C. Certain periods of the pregnancy were more vulnerable to temperature variation. The risk of PTB (28–36 weeks of gestation) increased as temperatures increased above 21 °C. For stillbirth, the fetus was most vulnerable at less than 28 weeks of gestation, but there were also effects in 28–36 weeks of gestation. For fetuses of more than 37 weeks of gestation, increasing temperatures did not increase the risk of stillbirth. We did not find any adverse affects of cold temperature on birth outcomes in this cohort.
My findings contribute to knowledge of the relationship between temperature and birth outcomes. In the context of climate change, this is particularly important. The results may have implications for public health policy and planning, as they indicate that pregnant women would decrease their risk of adverse birth outcomes by avoiding exposure to high temperatures and seeking cool environments during hot days.
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Hamilton, Neil D. « Influences of first-line oral monotherapy on outcomes in Pulmonary Arterial Hypertension in association with Connective Tissue Disease ». Thesis, University of Bradford, 2013. http://hdl.handle.net/10454/7322.
Texte intégralRésumé :
Background
Pulmonary arterial hypertension (PAH) is a rare progressive disease with no known cure. Of various aetiologies, PAH in association with connective tissue disease (PAH-CTD) is the most rapidly progressive and difficult to treat. Management of PAH has evolved significantly in the past ten years since the introduction of oral therapies. Evidence for the efficacy of these agents outside randomised controlled trials is limited, but guidelines exist.
Aim
To measure the impact of first-line monotherapy with bosentan or sildenafil and the introduction of prescribing guidelines on outcomes in PAH-CTD.
Methods
Following a retrospective analysis of consecutive, incident, treatment-naive PAH-CTD cases identified by the ASPIRE registry, influences on outcome measures have been compared. First-line monotherapy episodes for 247 patients was analysed against four distinct endpoints: change in exercise capacity, WHO functional class, time on monotherapy and all-cause mortality.
Results
Treatment with bosentan or sildenafil resulted in clinical stability at 2 years for nearly 1/4 patients. No difference was identified between the groups in terms of either exercise capacity or WHO functional class. Sildenafil patients were found to remain on monotherapy longer than those prescribed bosentan. Patients prescribed sildenafil have improved survival over those treated with bosentan. Unexpected baseline differences in between groups may confound the results as the haemodynamics of the bosentan patients were more severe.
Conclusions
A significant number of patients with PAH-CTD remain clinically stable on monotherapy at 2 years. Both agents seem equally effective in this aggressive form of PAH. A novel endpoint “TOM” may be of value in future research assessing response to treatment.
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Kabaso, Mushota. « Using simulation and survival analysis to forecast outcomes and economic costs of the antiretroviral therapy programme in Zambia ». Thesis, University of Southampton, 2015. https://eprints.soton.ac.uk/385233/.
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Morsheimer, Megan. « Survival, virological and immunological outcomes of HIV-infected children accessing ART at South African primary health care clinics ». Master's thesis, University of Cape Town, 2013. http://hdl.handle.net/11427/10991.
Texte intégralRésumé :
Includes bibliographical references.South Africa faces the world’s largest pediatric HIV epidemic. Combination antiretroviral therapy (ART) is the only effective treatment for HIV virus suppression. Pediatric HIV care has traditionally been provided in academic research and tertiary care facilities, however efforts to improve ART availability for children are ongoing through decentralization. Tygerberg Hospital physicians with training in pediatric HIV management are providing care in seven community-based primary health care (PHC) clinics in the greater Cape Town region. ART initiation and ongoing ART management for those down-referred from tertiary and district level facilities are provided. The HIV-related outcomes of this cohort have yet to be reported.
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Licht, Amanda Abigail. « Private incentives, public outcomes : the role of target political incentives in the success of foreign policy ». Diss., University of Iowa, 2010. https://ir.uiowa.edu/etd/700.
Texte intégralRésumé :
When do foreign influence attempts succeed in obtaining concessions from targeted states, and why do they so often fail? Powerful states employ a broad range of foreign policy tools in their dealings with other countries, but their ability to successfully exert power varies. This project seeks an explanation for the patchy record of foreign aid and economic sanctions in the political incentives of targeted leaders. Understanding the process of foreign policy success and failure requires considering both the effect of intervention on leader survival and the domestic cost of providing concessions. In both respects, the type of sanction interacts with targets' domestic context. Dynamic trends in leadership experience and political support, strength of political opposition, and regime type condition both the probability of sanctions' effectively tapping into target incentives and the difficulty of providing concessions.
My framework and analyses push beyond standard conceptualizations of leader incentives and foreign policy in several ways. The theory unites positive and negative strategies rather than treating them as divergent phenomena. I also break the traditional dichotomy of democratic and autocratic regimes, modeling dynamic political processes and explicitly incorporating the political opposition. I pursue a multi-stage modeling technique which more faithfully represents the strategic encounters between sending and targeted states and furthers our understanding of the interplay between external demands and domestic political incentives.
The findings suggest many strategies utilized for targeting aid and economic sanctions may be faulty. Sending states' best bet for achieving concession may be to target leaders whose place in office is very secure, yet empirically they pursue the opposite strategy. Contrary to much theory in the literature, I also find that even ineffective negative sanctions can achieve success provided the target faces few domestic challenges. The probability of concession also increases when states demand concessions of a diffuse and symbolic nature, rather than changes to the status quo which would hurt a private domestic interest. A strong political opposition magnifies the relative ease of public-costs concessions, suggesting that challenging parties compete for the favor of elites rather than championing the public interest.
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Hamilton, Neil David. « Influences of first-line oral monotherapy on outcomes in Pulmonary Arterial Hypertension in association with Connective Tissue Disease ». Thesis, University of Bradford, 2013. http://hdl.handle.net/10454/7322.
Texte intégralRésumé :
Background Pulmonary arterial hypertension (PAH) is a rare progressive disease with no known cure. Of various aetiologies, PAH in association with connective tissue disease (PAH-CTD) is the most rapidly progressive and difficult to treat. Management of PAH has evolved significantly in the past ten years since the introduction of oral therapies. Evidence for the efficacy of these agents outside randomised controlled trials is limited, but guidelines exist. Aim To measure the impact of first-line monotherapy with bosentan or sildenafil and the introduction of prescribing guidelines on outcomes in PAH-CTD. Methods Following a retrospective analysis of consecutive, incident, treatment-naive PAH-CTD cases identified by the ASPIRE registry, influences on outcome measures have been compared. First-line monotherapy episodes for 247 patients was analysed against four distinct endpoints: change in exercise capacity, WHO functional class, time on monotherapy and all-cause mortality. Results Treatment with bosentan or sildenafil resulted in clinical stability at 2 years for nearly 1/4 patients. No difference was identified between the groups in terms of either exercise capacity or WHO functional class. Sildenafil patients were found to remain on monotherapy longer than those prescribed bosentan. Patients prescribed sildenafil have improved survival over those treated with bosentan. Unexpected baseline differences in between groups may confound the results as the haemodynamics of the bosentan patients were more severe. Conclusions A significant number of patients with PAH-CTD remain clinically stable on monotherapy at 2 years. Both agents seem equally effective in this aggressive form of PAH. A novel endpoint “TOM” may be of value in future research assessing response to treatment.
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Claggett, Brian Lee. « Statistical Methods for Clinical Trials with Multiple Outcomes, HIV Surveillance, and Nonparametric Meta-Analysis ». Thesis, Harvard University, 2012. http://dissertations.umi.com/gsas.harvard:10440.
Texte intégralRésumé :
Central to the goals of public health are obtaining and interpreting timely and relevant information for the benefit of humanity. In this dissertation, we propose methods to monitor and assess the spread HIV in a more rapid manner, as well as to improve decisions regarding patient treatment options. In Chapter 1, we propose a method, extending the previously proposed dual-testing algorithm and augmented cross-sectional design, for estimating the HIV incidence rate in a particular community. Compared to existing methods, our proposed estimator allows for shorter follow-up time and does not require estimation of the mean window period, a crucial, but often unknown, parameter. The estimator performs well in a wide range of simulation settings. We discuss when this estimator would be expected to perform well and offer design considerations for the implementation of such a study. Chapters 2 and 3 are concerned with obtaining a more complete understanding of the impact of treatment in randomized clinical trials in which multiple patient outcomes are recorded. Chapter 2 provides an illustration of methods that may be used to address concerns of both risk-benefit analysis and personalized medicine simultaneously, with a goal of successfully identifying patients who will be ideal candidates for future treatment. Riskbenefit analysis is intended to address the multivariate nature of patient outcomes, while “personalized medicine” is concerned with patient heterogeneity, both of which complicate the determination of a treatment’s usefulness. A third complicating factor is the duration of treatment use. Chapter 3 features proposed methods for assessing the impact of treatment as a function of time, as well as methods for summarizing the impact of treatment across a range of follow-up times. Chapter 4 addresses the issue of meta-analysis, a commonly used tool for combining information for multiple independent studies, primarily for the purpose of answering a clinical question not suitably addressed by any one single study. This approach has proven highly useful and attractive in recent years, but often relies on parametric assumptions that cannot be verified. We propose a non-parametric approach to meta-analysis, valid in a wider range of scenarios, minimizing concerns over compromised validity.
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Wang, Jiajia. « Assessment of the effects of maternal exposure to heatwave on birth outcomes in Brisbane, Australia ». Thesis, Queensland University of Technology, 2014. https://eprints.qut.edu.au/76289/1/Jiajia_Wang_Thesis.pdf.
Texte intégralRésumé :
Even though heatwave events have become more frequent and intense in most regions around the world, little is known about the impact of heatwave on birth outcomes. This thesis uses a population-based study design to investigate the relationship between maternal heatwave exposure and adverse birth outcomes in Brisbane, Australia. This study found that heatwave exposure at any stage of pregnancy can be harmful to fetal growth, and further increase the risk of adverse birth outcomes. Both short- and long-term effects of heatwave on adverse birth outcomes were found. The findings in this thesis may have significant public health implications.
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Khaddam, Sinan M. D. « Difference in outcomes between central airway lesions requiring stents and lesions that donot in patients with NSCLC ». University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1553513958608363.
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Hall, Thomas Charles. « A randomised control trial investigating the effects of parenteral fish oil on survival outcomes in critically ill patients with sepsis ». Thesis, University of Leicester, 2015. http://hdl.handle.net/2381/32336.
Texte intégralRésumé :
Introduction: Sepsis is a leading cause of mortality in critically ill patients on the intensive care unit (ITU). Death from sepsis in the ITU is frequently preceded by the development of multiple organ failure as a result of uncontrolled inflammation. Treatment with omega-3 (fish oil) has been demonstrated to attenuate the effects of uncontrolled inflammation and may be clinically beneficial in reducing morbidity from organ dysfunction. Method: A randomised control trial investigating the effects of parenteral omega-3 (OmegavenTM), given early in the course of sepsis, was carried out in a single institution. Consecutive patients diagnosed with sepsis were entered into the study. Patients were randomised to receive either parenteral fish oil and standard medical care or standard medical care only. The primary outcome measure was a reduction in organ dysfunction using the SOFA score as a surrogate marker. The secondary outcome measures were mortality, length of stay, mean C-reactive protein (CRP), days free of organ dysfunction/failure and fatty acid (FA) analysis. Results: Sixty patients were included in the study. The baseline demographics were matched for the two cohorts. Patients treated with parenteral fish oil were associated with a significant reduction in new organ dysfunction (delta-SOFA 2.2±2.2 vs. 1.0±1.5, p=0.005 and maximum-SOFA 10.1±4.2 vs. 8.1±3.2, p=0.041) and mean CRP (186.7±78 vs. 141.5±62.6, p=0.019). There was no significant reduction in the length of ITU and total hospital stay between cohorts. Patients treated with fish oil in the strata of less severe sepsis had a significant reduction in mortality (p=0.042). Conclusion: The treatment of critically ill septic patients with parenteral fish oil is safe. N-3 FAs are rapidly taken up by circulating white cells. It is associated with a significant reduction in organ dysfunction and CRP. It may be associated with a reduction in mortality in patients with less severe sepsis. A multi-centre trial is justified as a result of this trial.
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Nishizaki, Daisuke. « Laparoscopic versus open surgery for locally advanced rectal cancer : five-year survival outcomes in a large, multicenter, propensity score matched cohort study ». Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/265186.
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Talikowska, Milena. « The relationship between the quality of cardiopulmonary resuscitation (CPR) performed by paramedics and survival outcomes from out-of-hospital cardiac arrest (OHCA) ». Thesis, Curtin University, 2017. http://hdl.handle.net/20.500.11937/65985.
Texte intégralRésumé :
This thesis investigated the quality of cardiopulmonary resuscitation (CPR) provided by St John Ambulance Western Australia (SJA-WA) paramedics to victims of out-of-hospital cardiac arrest in Perth, Western Australia. Chest compression depth was identified as a key metric that required optimisation. The study also found a significant and inverse association between chest compression fraction and return of spontaneous circulation (ROSC). A paramedic survey identified reasons for the underutilisation of the Q-CPR feedback device in clinical practice.
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Olsson, Christian. « Thoracic Aortic Surgery : Epidemiology, Outcomes, and Prevention of Cerebral Complications ». Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-6899.
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Martel, Guillaume. « Evaluating Surgical Outcomes : A Systematic Comparison of Evidence from Randomized Trials and Observational Studies in Laparoscopic Colorectal Cancer Surgery ». Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/20534.
Texte intégralRésumé :
Background: Laparoscopic surgery for colorectal cancer is a novel healthcare technology, for which much research evidence has been published. The objectives of this work were to compare the oncologic outcomes of this technology across different study types, and to define patterns of adoption on the basis of the literature.
Methods: A comprehensive systematic review of the literature was conducted using 1) existing systematic reviews, 2) randomized controlled trials (RCTs), and 3) observational studies. Outcomes of interest were overall survival, and total lymph node harvest. Outcomes were compared for congruence. Adoption was evaluated by means of summary expert opinions in the literature.
Results: 1) Existing systematic reviews were of low to moderate quality and displayed evidence of overlap and duplication. 2) Laparoscopy was not inferior to open surgery in terms of oncologic outcomes in any study type. 3) Oncologic outcomes from RCTs and observational studies were congruent. 4) Expert opinion in the literature has been supportive of this technology, paralleling the publication of large RCTs.
Conclusions: The evaluation of laparoscopic surgery for colorectal cancer in RCTs and observational studies suggests that it is not inferior to open surgery. Adoption of this technology has paralleled RCT evidence.
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Valentine, Thomas Robert. « Illness Perceptions and Psychological and Physical Health Outcomes in Non-Small Cell Lung Cancer : A Self-Regulatory Model Approach ». The Ohio State University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=osu1594830809190808.
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Derwall, Matthias, Anne Brücken, Christian Bleilevens, Andreas Ebeling, Philipp Föhr, Rolf Rossaint, Karl B. Kern, Christoph Nix et Michael Fries. « Doubling survival and improving clinical outcomes using a left ventricular assist device instead of chest compressions for resuscitation after prolonged cardiac arrest : a large animal study ». BioMed Central Ltd, 2015. http://hdl.handle.net/10150/610308.
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INTRODUCTION: Despite improvements in pre-hospital and post-arrest critical care, sudden cardiac arrest (CA) remains one of the leading causes of death. Improving circulation during cardiopulmonary resuscitation (CPR) may improve survival rates and long-term clinical outcomes after CA. METHODS: In a porcine model, we compared standard CPR (sCPR; n =10) with CPR using an intravascular cardiac assist device without additional chest compressions (iCPR; n =10) following 10 minutes of electrically induced ventricular fibrillation (VF). In a separate crossover experiment, 10 additional pigs were subjected to 10 minutes of VF and 6 minutes of sCPR; the iCPR device was then implanted if a return of spontaneous circulation (ROSC) was not achieved using sCPR. Animals were evaluated in respect to intra- and post-arrest hemodynamics, survival, functional outcome and cerebral and myocardial lesions following CPR. We hypothesized that iCPR would result in more frequent ROSC and better functional recovery than sCPR. RESULTS: iCPR produced a mean flow of 1.36 ± 0.02 L/min, leading to significantly higher coronary perfusion pressure (CPP) values during the early period of CPR (22 ± 10 mmHg vs. 9 ± 5 mmHg, P ≤0.01, 1 minute after start of CPR; 20 ± 11 mmHg vs. 10 ± 7 mmHg, P =0.03, 2 minutes after start of CPR), resulting in high ROSC rates (100% in iCPR vs. 50% in sCPR animals; P =0.03). iCPR animals showed significantly lower serum S100 levels at 10 and 30 minutes following ROSC (3.5 ± 0.6 ng/ml vs. 7.4 ± 3.0 ng/ml 30 minutes after ROSC; P ≤0.01), as well as superior clinical outcomes based on overall performance categories (2.9 ± 1.0 vs. 4.6 ± 0.8 on day 1; P ≤0.01). In crossover experiments, 80% of animals required treatment with iCPR after failed sCPR. Notably, ROSC was still achieved in six of the remaining eight animals (75%) after a total of 22.8 ± 5.1 minutes of ischemia. CONCLUSIONS: In a model of prolonged cardiac arrest, the use of iCPR instead of sCPR improved CPP and doubled ROSC rates, translating into improved clinical outcomes.
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Ozcan, Berkay. « The effects of marital transitions and spousal characteristic on economic outcomes ». Doctoral thesis, Universitat Pompeu Fabra, 2008. http://hdl.handle.net/10803/7251.
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My dissertation aims to improve our understanding of why and how couple dynamics and marital transitions affect four critical economic outcomes: household savings, labour supply, transition to self-employment and income distribution. In all of my papers, behavior of the couple is at the center. First chapter analayzes the likelihood of starting a business and examines at the influence of marriage, its duration and the characteristics of the spouse on the probability to make a transition to entrepreneurship. In the second chapter, I take advantage of Irish Divorce Law introduced in 1996 as quasi-natural experiment for the rise in the risk of divorce and explain its effects on household savings behavior. The third chapterturns its attention to labour supply behaviour of the men on women experiencing a risk in the marital stability. Similarly, the last paper is also concerned about entry and exits from marriage, but it considers these phenomena together with the rise in female employment. Consequently, this chapter sheds light to the mechanisms through which changes in family types and labor supply decisions of women are actually leading to higher or lower inequality. Generally, my dissertation covers both substantive and methodological issues on several fields from inequality research to family demographics and entrepreneurship.Esta tesis tiene el objetivo de ampliar y perfeccionar nuestra comprensión de por qué y cómo la dinámica de pareja afecta cuatro críticos resultados económicos que están directamente realacionados con la desigualdad y la estratificación. Estos resultados son, respectivamente; ser autónomo, la oferta de trabajo, el ahorro de los hogares y la distribución del ingreso. A lo largo de la tesis, con la dinámica de pareja, concibo dos conceptos: en primer lugar implica formar parte de una pareja (es decir, tener una esposa/o con ciertas características) versus ser soltero/a y transiciones entre estos dos estados. Y la segunda se refiere a los cambios en el comportamiento de los esposos debido a un cambio de contexto, como un aumento en el riesgo de disolución de la pareja. Por consiguiente, analiza las implicaciones de estos dos conceptos en cada una de estas variables económicas. La tesis se utiliza una serie de grandes conjuntos de datos longitudinales de diferentes países (p.e. PSID, GSOEP, PHCE, Living in Ireland Survey) y estratégias econométricas. Estas características incluyen el análisis de supervivencia, las estimaciones de diff-en-diff, simulaciones y descomposiciones.
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Abu, Hawa Ozien. « Religiosity and Patient Activation and Health Outcomes among Hospital Survivors of an Acute Coronary Syndrome ». eScholarship@UMMS, 2019. https://escholarship.umassmed.edu/gsbs_diss/1025.
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Background: Religious involvement is widespread and may influence patient engagement with their healthcare (patient activation) and health outcomes. This dissertation examined the association between religiosity and patient activation, changes in health-related quality of life (HRQOL), readmissions, and survival after hospitalization for acute coronary syndrome (ACS).
Methods: We recruited 2,174 patients hospitalized for ACS in Georgia and Central Massachusetts (2011-2013) in a prospective cohort study. Participants self-reported three items assessing religiosity – strength/comfort from religion, petition prayers for health, and awareness of intercessory prayers by others. Patient activation was measured using the 6-item Patient Activation Measure. Generic HRQOL was assessed with the SF-36®v2 physical and mental component summary scores. Disease-specific HRQOL was evaluated with the Seattle Angina Questionnaire Quality of Life subscale. Unscheduled readmissions were validated from medical records. Mortality status was obtained from national and state vital statistics.
Results: After adjustment for several sociodemographic, psychosocial, and clinical variables, reports of strength/comfort from religion and receipt of intercessions were associated with high activation. Praying for one’s health was associated with low activation. Prayers for health were associated with clinically meaningful increases in disease-specific and physical HRQOL. Neither strength/comfort from religion, petition, nor intercessory prayers were significantly associated with unscheduled 30-day readmissions and two-year all-cause mortality.
Conclusions: Most ACS survivors acknowledge religious practices for their health. Religiosity was associated with patient activation and changes in HRQOL. These findings suggest that religiosity may influence patient engagement in their healthcare and recovery after a life-threatening illness, buttressing the need for holistic approach in patient management.
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Yao, Siyuan. « Impact of imbalanced graft-to-spleen volume ratio on outcomes following living donor liver transplantation in an era when simultaneous splenectomy is not typically indicated ». Kyoto University, 2020. http://hdl.handle.net/2433/253139.
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