Early Sac Shrinkage Predicts a Low Risk of Late Complications After Endovascular Aortic Aneurysm Repair

BACKGROUND: Aneurysm shrinkage has been proposed as a marker of successful endovascular aneurysm repair (EVAR). Patients with early postoperative shrinkage may experience fewer subsequent complications, and consequently require less intensive surveillance. METHODS: Patients undergoing EVAR from 2000 to 2011 at three vascular centres (in 2 countries), who had two imaging examinations (postoperative and after 6-18 months), were included. Maximum diameter, complications and secondary interventions during follow-up were registered. Patients were categorized according to early sac dynamics. The primary endpoint was freedom from late complications. Secondary endpoints were freedom from secondary intervention, postimplant rupture and direct (type I/III) endoleaks. RESULTS: Some 597 EVARs (71.1 per cent of all EVARs) were included. No shrinkage was observed in 284 patients (47.6 per cent), moderate shrinkage (5-9 mm) in 142 (23.8 per cent) and major shrinkage (at least 10 mm) in 171 patients (28.6 per cent). Four years after the index imaging, the rate of freedom from complications was 84.3 (95 per cent confidence interval 78.7 to 89.8), 88.1 (80.6 to 95.5) and 94.4 (90.1 to 98.7) per cent respectively. No shrinkage was an independent risk factor for late complications compared with major shrinkage (hazard ratio (HR) 3.11; P < 0.001). Moderate compared with major shrinkage (HR 2.10; P = 0.022), early postoperative complications (HR 3.34; P < 0.001) and increasing abdominal aortic aneurysm baseline diameter (HR 1.02; P = 0.001) were also risk factors for late complications. Freedom from secondary interventions and direct endoleaks was greater for patients with major sac shrinkage. CONCLUSION: Early change in aneurysm sac diameter is a strong predictor of late complications after EVAR. Patients with major sac shrinkage have a very low risk of complications for up to 5 years. This parameter may be used to tailor postoperative surveillance.

Low Socioeconomic Status is an Independent Risk Factor for Survival After Abdominal Aortic Aneurysm Repair and Open Surgery for Peripheral Artery Disease

OBJECTIVE/BACKGROUND: The association between socioeconomic status (SES), presentation, and outcome after vascular surgery is largely unknown. This study aimed to determine the influence of SES on post-operative survival and severity of disease at presentation among vascular surgery patients in the Dutch setting of equal access to and provision of care. METHODS: Patients undergoing surgical treatment for peripheral artery disease (PAD), abdominal aortic aneurysm (AAA), or carotid artery stenosis between January 2003 and December 2011 were retrospectively included. The association between SES, quantified by household income, disease severity at presentation, and survival was studied using logistic and Cox regression analysis adjusted for demographics, and medical and behavioral risk factors. RESULTS: A total of 1,178 patients were included. Low income was associated with worse post-operative survival in the PAD cohort (n = 324, hazard ratio 1.05, 95% confidence interval [CI] 1.00-1.10, per 5,000 Euro decrease) and the AAA cohort (n = 440, quadratic relation, p = .01). AAA patients in the lowest income quartile were more likely to present with a ruptured aneurysm (odds ratio [OR] 2.12, 95% CI 1.08-4.17). Lowest income quartile PAD patients presented more frequently with symptoms of critical limb ischemia, although no significant association could be established (OR 2.02, 95% CI 0.96-4.26). CONCLUSIONS: The increased health hazards observed in this study are caused by patient related factors rather than differences in medical care, considering the equality of care provided by the study setting. Although the exact mechanism driving the association between SES and worse outcome remains elusive, consideration of SES as a risk factor in pre-operative decision making and focus on treatment of known SES related behavioral and psychosocial risk factors may improve the outcome of patients with vascular disease.

Validation of Two US Risk Scores for Percutaneous Coronary Intervention in a Single-Center Portuguese Population of Patients with Acute Coronary Syndrome

INTRODUCTION: New scores have been developed and validated in the US for in-hospital mortality risk stratification in patients undergoing coronary angioplasty: the National Cardiovascular Data Registry (NCDR) risk score and the Mayo Clinic Risk Score (MCRS). We sought to validate these scores in a European population with acute coronary syndrome (ACS) and to compare their predictive accuracy with that of the GRACE risk score. METHODS: In a single-center ACS registry of patients undergoing coronary angioplasty, we used the area under the receiver operating characteristic curve (AUC), a graphical representation of observed vs. expected mortality, and net reclassification improvement (NRI)/integrated discrimination improvement (IDI) analysis to compare the scores. RESULTS: A total of 2148 consecutive patients were included, mean age 63 years (SD 13), 74% male and 71% with ST-segment elevation ACS. In-hospital mortality was 4.5%. The GRACE score showed the best AUC (0.94, 95% CI 0.91-0.96) compared with NCDR (0.87, 95% CI 0.83-0.91, p=0.0003) and MCRS (0.85, 95% CI 0.81-0.90, p=0.0003). In model calibration analysis, GRACE showed the best predictive power. With GRACE, patients were more often correctly classified than with MCRS (NRI 78.7, 95% CI 59.6-97.7; IDI 0.136, 95% CI 0.073-0.199) or NCDR (NRI 79.2, 95% CI 60.2-98.2; IDI 0.148, 95% CI 0.087-0.209). CONCLUSION: The NCDR and Mayo Clinic risk scores are useful for risk stratification of in-hospital mortality in a European population of patients with ACS undergoing coronary angioplasty. However, the GRACE score is still to be preferred.

Economic analysis in health care regulation : three essays

ABSTRACT - It is the purpose of the present thesis to emphasize, through a series of examples, the need and value of appropriate pre-analysis of the impact of health care regulation. Specifically, the thesis presents three papers on the theme of regulation in different aspects of health care provision and financing. The first two consist of economic analyses of the impact of health care regulation and the third comprises the creation of an instrument for supporting economic analysis of health care regulation, namely in the field of evaluation of health care programs. The first paper develops a model of health plan competition and pricing in order to understand the dynamics of health plan entry and exit in the presence of switching costs and alternative health premium payment systems. We build an explicit model of death spirals, in which profitmaximizing competing health plans find it optimal to adopt a pattern of increasing relative prices culminating in health plan exit. We find the steady-state numerical solution for the price sequence and the plan’s optimal length of life through simulation and do some comparative statics. This allows us to show that using risk adjusted premiums and imposing price floors are effective at reducing death spirals and switching costs, while having employees pay a fixed share of the premium enhances death spirals and increases switching costs. Price regulation of pharmaceuticals is one of the cost control measures adopted by the Portuguese government, as in many European countries. When such regulation decreases the products’ real price over time, it may create an incentive for product turnover. Using panel data for the period of 1997 through 2003 on drug packages sold in Portuguese pharmacies, the second paper addresses the question of whether price control policies create an incentive for product withdrawal. Our work builds the product survival literature by accounting for unobservable product characteristics and heterogeneity among consumers when constructing quality, price control and competition indexes. These indexes are then used as covariates in a Cox proportional hazard model. We find that, indeed, price control measures increase the probability of exit, and that such effect is not verified in OTC market where no such price regulation measures exist. We also find quality to have a significant positive impact on product survival. In the third paper, we develop a microsimulation discrete events model (MSDEM) for costeffectiveness analysis of Human Immunodeficiency Virus treatment, simulating individual paths from antiretroviral therapy (ART) initiation to death. Four driving forces determine the course of events: CD4+ cell count, viral load resistance and adherence. A novel feature of the model with respect to the previous MSDEMs is that distributions of time to event depend on individuals’ characteristics and past history. Time to event was modeled using parametric survival analysis. Events modeled include: viral suppression, regimen switch due virological failure, regimen switch due to other reasons, resistance development, hospitalization, AIDS events, and death. Disease progression is structured according to therapy lines and the model is parameterized with cohort Portuguese observational data. An application of the model is presented comparing the cost-effectiveness ART initiation with two nucleoside analogue reverse transcriptase inhibitors (NRTI) plus one non-nucleoside reverse transcriptase inhibitor(NNRTI) to two NRTI plus boosted protease inhibitor (PI/r) in HIV- 1 infected individuals. We find 2NRTI+NNRTI to be a dominant strategy. Results predicted by the model reproduce those of the data used for parameterization and are in line with those published in the literature.

Credit risk stress testing: The Portuguese environment, macroeconomic scenarios and the estimation of losses for corporate sectors

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Finance from the NOVA – School of Business and Economics

Comparative analysis of multicriteria decision making methods

Dissertação para obtenção do Grau de Mestre em Engenharia Electrotécnica e de Computadores

Carbon prices. Dynamic analysis of European and Californian markets

Dissertação para obtenção do Grau de Doutor em Alterações Climáticas e Políticas de Desenvolvimento Sustentável

Analysis of molecular biology techniques for the diagnosis of human papillomavirus infection and cervical cancer prevention

The objective of the present study was to evaluate the usefulness of molecular methodologies to access human papillomavirus genome in the genital tract. Samples from 136 women aged 17 to 52 years old obtained from the Dr. Sérgio Franco Laboratories between 2000 and 2001, were analyzed by the hybrid capture assay and amplified by PCR with generic primers MY09/MY11 and specific primers for types 16, 18, 31, 33, 35, 58. Viral genome was detected in 71.3% of the samples by hybrid capture and 75% by amplification. When cytopathology was used as a reference method for screening lesions, hybrid capture (p=0) and amplification (p=0.002) presented positive association. The 3 methods showed absolute agreement when cytopathology confirmed papillomavirus infection and high grade intraepithelial lesion. Disagreements occurred for 10 cases: seven inflammatory cases positive by PCR and negative for hybrid capture and 3 low squamous intraepithelial lesions positive for hybrid capture but negative for amplification. In conclusion, hybrid capture was shown to be sensitive and specific enough for use in clinical routines. Moreover, the evaluation of viral load values obtained by this method were shown to be related to the severity of the lesion and merit further studies to analyze the possible association with risk of progression to malignancy.

Tuberculosis incidence and risk factors among patients living with HIV/AIDS in public health service institutions in Brasilia, Federal District

In order to estimate the incidence of and risk factors for developing tuberculosis, the clinical charts of a retrospective cohort of 281 HIV-positive adults, who were notified to the AIDS Program of the Health Department of Brasilia in 1998, were reviewed in 2003. All the patients were treatment-naive regarding antiretroviral therapy at the time of inclusion in the cohort. Twenty-nine patients were identified as having tuberculosis at the start of the study. Thirteen incident tuberculosis cases were identified during the 60 months of follow-up, with an incidence density rate of 1.24/100 person-years. Tuberculosis incidence was highest among patients with baseline CD4+ T-lymphocyte counts < 200 cells/µl who were not using antiretroviral therapy (incidence = 5.47; 95% CI = 2.73 to 10.94). Multivariate analysis showed that baseline CD4+ T-lymphocyte counts < 200 cells/µl (adjusted hazard ratio [AHR] = 5.09; 95% CI = 1.27 to 20.37; p = 0.02) and non-use of antiretroviral therapy (AHR = 12.17; 95% CI = 2.6 to 56.90; p = 0.001) were independently associated with increased risk of tuberculosis.

Hepatitis C: sexual or intrafamilial transmission? Epidemiological and phylogenetic analysis of hepatitis C virus in 24 infected couples

The role of sexual or intrafamilial transmission of hepatitis C is controversial. A phylogenetic analysis was performed on the non-structural region 5B of the hepatitis C virus (NS5B-HCV). High percentages of homology (mean of 98.3%) were shown between the couples. Twenty (83.3%) of the 24 men but only two of the women (8.3%) reported having had sexually transmitted diseases during their lives. The risk factors for HCV acquisition were blood transfusion (10 couples), use of illegal injected drugs (17), use of inhalants (15), acupuncture (5) and tattoos (5). The shared use of personal hygiene items included toothbrushes between six couples (25%), razor blades between 16 (66.7%), nail clippers between 21 (87.5%) and manicure pliers between 14 (58.3%). The high degree of similarity of the hepatitis C virus genome supports the hypothesis of hepatitis C virus transmission between these couples. The shared use of personal hygiene items suggests the possibility of intrafamilial transmission of infection.

Enhancement of an implemented rating model and impact on existing risk management processes: A hands-on approach from financial supplier risk management within the automotive industry

The purpose of this paper is to conduct a methodical drawback analysis of a financial supplier risk management approach which is currently implemented in the automotive industry. Based on identified methodical flaws, the risk assessment model is further developed by introducing a malus system which incorporates hidden risks into the model and by revising the derivation of the most central risk measure in the current model. Both methodical changes lead to significant enhancements in terms of risk assessment accuracy, supplier identification and workload efficiency.

Co-infection and risk factors of tuberculosis in a Mexican HIV+ population

INTRODUCTION: The situation of tuberculosis (TB) is being modified by the human immunodeficiency virus (HIV), which is increasing the occurrence of new cases and the generation of drug resistant strains, affecting not only the people infected with HIV, but also their close contacts and the general population, conforming a serious public health concern. However, the magnitudes of the factors associated to this co-infection differ considerably in relation to the population groups and geographical areas. METHODS: In order to evaluate the prevalence and risk factors for the co-infection of tuberculosis (TB) in a population with human immunodeficiency virus (HIV+) in the Southeast of Mexico, we made the analysis of clinical and epidemiological variables and the diagnosis of tuberculosis by isolation of mycobacteria from respiratory samples. RESULTS: From the 147 HIV+ individuals analyzed, 12 were culture positive; this shows a prevalence of 8% for the co-infection. The only variable found with statistical significance for the co-infection was the number of CD4-T < 200 cells/mm³, OR 13 (95%, CI 2-106 vs 12-109). CONCLUSIONS: To our knowledge this is the first report describing the factors associated with tuberculosis co -infection with HIV in a population from Southern Mexico. The low number of CD4 T-cells was the only variable associated with the TB co-infection and the rest of the variables provide scenarios that require specific and particular interventions for this population group.

Epidemiological factors related to the transmission risk of Trypanosoma cruzi in a Quilombola community, State of Mato Grosso do Sul, Brazil

INTRODUCTION: This work was an epidemiological investigation of the risk of Trypanosoma cruzi transmission in the rural Quilombola community of Furnas do Dionízio, State of Mato Grosso do Sul, Brazil. METHODS: Of the 71 animals examined, seven were captured (two opossums, Didelphis albiventris; four rats, Rattus rattus; and one nine-banded armadillo, Dasypus novemcinctus) and 64 were domestic (one canine, Canis familiaris; five pigs, Sus scrofa; two bovines, Bos taurus; five caprines, Capra sp.; and 51 ovines, Ovis aries). Parasitological tests were performed to detect parasites in the blood and to identify the morphology of flagellates. These methods included fresh examinations, buffy coat tests and blood cultures. Molecular analysis of DNA for identification of trypanosomatids was performed by polymerase chain reaction (PCR) with primers S35 and S36. RESULTS: The parasitological tests showed flagellates in an opossum and two cattle. The molecular tests showed DNA from T. cruzi in an opossum and a pig. Triatoma sordida was the only triatomine species found in the community, and it colonized households (four specimens) and the surrounding areas (124 specimens). Twenty-three specimens tested positive for flagellates, which were subsequently identified as T. cruzi by PCR. CONCLUSIONS: Data analysis demonstrated that T. cruzi has a peridomestic life cycle that involves both domestic and wild mammals.

Risk factors for Leishmania chagasi infection in an endemic area in Raposa, State of Maranhão, Brazil

INTRODUCTION: Infection with Leishmania chagasi is the most common clinical presentation for visceral leishmaniaisis in endemic areas. The municipality of Raposa is an endemic area in State of Maranhão, Brazil, and have had registration cases of visceral leishmaniasis disease. For this reason, a cross- sectional study was conducted to evaluate the risk factors for infection with L. chagasi detected by Montenegro skin test. METHODS: The sample comprised 96% of the inhabitants of the villages of Maresia, Pantoja, and Marisol located in the municipality of Raposa, corresponding to 1,359 subjects. Data were collected using a questionnaire. Univariate and multivariate logistic regression models were applied to evaluate the association between the variables studied and infection of L. chagasi. RESULTS: The variables associated with infection upon nonadjusted analysis were a straw roof, mud walls, floors of beaten earth, presence of sand flies inside or outside of the dwelling, and bathing outdoors. Adjusted analysis showed that the presence of sand flies inside/outside the dwelling was a risk factor, and age younger than 10 years was a protective factor against asymptomatic infection. CONCLUSIONS: The results highlight the extent to which precarious living conditions of the population strengthen the epidemiological chain of visceral leishmaniasis.

Geographic analysis on the occurrence of human and canine leptospirosis in the city of Maringá, state of Paraná, Brazil

INTRODUCTION: Leptospirosis is a zoonotic disease, the primary hosts of which are wild, synanthropic, and household animals. Humans behave as terminal and accidental hosts. The prevalence of leptospirosis depends on carrier animals that disseminate the agent, on the environmental survival of this agent, and on the contact of susceptible individuals. Each serovar has one or more hosts with different adaptation levels. The focuses of leptospirosis are infected, sick, and asymptomatic animals, which are considered to be sources of environmental infection. This study aimed to determine the risk areas for leptospiral infection in stray dogs and patients diagnosed with leptospirosis from 2006 to 2008 in Maringá, State of Paraná, Brazil. METHODS: Three hundred and thirty-five stray dogs and 25 patients were studied. Serum from both animals and patients was examined by the microscopic serum agglutination test to study anti-leptospiral antibodies. To determine the risk areas and the spatial distribution of the disease, thematic maps were designed. RESULTS: Forty-one (12.2%) dogs positive for one or more leptospire serovars were observed, the most frequent serovars being Pyrogenes (43.9%), Canícola (21.9%), and Copennhageni (19.5%). Among the humans, 2 (8%) were positive for serovars Pyrogenes and Hardjo Prajitno and for Pyrogenes and Cynopteri. CONCLUSIONS: Spatial analysis showed that the risk for dogs and humans in the City of Maringá to become infected with leptospires exists in both the central and the peripheral areas, a fact that reinforces the relevance of this study and of continuous epidemiological and environmental surveillance actions to control the disease in animals and in humans.