Economic Evaluation of Ticagrelor for Secondary Prevention Following Acute Coronary Syndromes

INTRODUCTION AND OBJECTIVES: To estimate the cost-effectiveness and cost-utility of ticagrelor in the treatment of patients with acute coronary syndromes (unstable angina or myocardial infarction with or without ST-segment elevation), including patients treated medically and those undergoing percutaneous coronary intervention or coronary artery bypass grafting. METHODS: A short-term decision tree and a long-term Markov model were used to simulate the evolution of patients' life-cycles. Clinical effectiveness data were collected from the PLATO trial and resource use data were obtained from the Hospital de Santa Marta database, disease-related group legislation and the literature. RESULTS: Ticagrelor provides increases of 0.1276 life years and 0.1106 quality-adjusted life years (QALYs) per patient. From a societal perspective these clinical gains entail an increase in expenditure of €610. Thus the incremental cost per life year saved is €4780 and the incremental cost per QALY is €5517. CONCLUSIONS: The simulation results show that ticagrelor reduces events compared to clopidogrel. The costs of ticagrelor are partially offset by lower costs arising from events prevented. The use of ticagrelor in clinical practice is therefore cost-effective compared to generic clopidogrel.

Intraocular Pressure in Eyes Receiving Intravitreal Antivascular Endothelial Growth Factor Injections

PURPOSE: The aim of the this study was to determine the effect of intravitreal antivascular endothelial growth factor injections on intraocular pressure (IOP) and identify possible risk factors for the development of increased IOP. MATERIALS AND METHODS: This prospective study included a total of 106 eyes receiving intravitreal injection of bevacizumab as treatment for macular edema or active choroidal neovascularization. IOP was measured by Goldmann applanation tonometry immediately before the intravitreal injection and 5 min, 1 h and 15 days after the procedure. The records of the study patients were reviewed for age, gender, history of glaucoma, diabetes mellitus, phakic status, systemic and topical medication and number of previous injections. Subconjunctival reflux was registered. IOP elevation was defined as IOP ≥21 mm Hg and/or a change from baseline of ≥5 mm Hg recorded at least on two or more measurements on the same visit. RESULTS: Mean preoperative IOP was 15.31 ± 3.90 mm Hg and postoperative IOP values were 27.27 ± 11.87 mm Hg (after 5 min), 17.59 ± 6.24 mm Hg (after 1 h) and 16.86 ± 3.62 mm Hg (after 15 days). The IOP variation was statistically significant between pre- and postoperative measurements (p < 0.05). Subconjunctival reflux was recorded in 11.3%, and in this subgroup the IOP at 5 min and at 1 h was lower than preoperative IOP (p < 0.05). CONCLUSIONS: More than one third of the eyes achieved IOPs >30 mm Hg 5 min after injection. Subconjunctival reflux contributed to a lower mean postoperative IOP (p < 0.05). Considerations for the management include prophylactic IOP lowering with medical therapy and/or preinjection ocular decompression for patients with a history of glaucoma or ocular hypertension and switching to an as-needed injection protocol in patients suffering a marked IOP rise in previous injections. © 2015 S. Karger AG, Basel.

Efectividade de um programa de exercício aquático na osteoartrose do joelho

RESUMO: A osteoartrose do joelho é uma condição clínica cuja prevalência tem aumentado nos últimos anos na população idosa. Trata-se de uma condição que pode ser bastante incapacitante para o idoso, gerando um forte impacto social e económico. O exercício aquático tem sido identificado como um factor de promoção da melhoria do quadro clínico nesta população, mas a sua efectividade não está, ainda, determinada. Objectivo: investigar a efectividade, a curto e médio prazo, de um programa de exercício aquático, realizado em grupo, com a duração de 8 semanas, na amplitude articular, dor e rigidez do joelho, e na função física e qualidade de vida, em idosos com osteoartrose do joelho. Metodologia: Recorreu-se a um estudo quase-experimental, double-blind, controlado, sem aleatorização, cuja amostra, constituída por 43 sujeitos, foi selecionada por conveniência. Os sujeitos do grupo experimental (n=22) foram submetidos ao programa de exercício aquático e os do grupo de controlo (n=21) foram submetidos ao programa de exercício no solo. Ambos os programas foram definidos de acordo com as recomendações internacionais para a prática de exercício físico em idosos com osteoartrose (Arthritis Foundation, 2009a, 2009b). Todo o grupo foi avaliado no início do programa, no final do mesmo (8 semanas) e após 6 semanas de follow-up, nos seguintes indicadores: amplitude articular do joelho (através do goniómetro), dor, rigidez, função e qualidade de vida (através do KOOS). Resultados: A amostra deste estudo foi constituída por sujeitos maioritariamente do género feminino (76,7%), com uma média de 72,7 anos (DP=5,49). O programa de exercício aquático implementado demonstrou um aumento da amplitude articular passiva de flexão (p<0,0001) e extensão (p=0,016) do joelho, uma diminuição da dor e da rigidez articular (p<0,0001), um aumento da função nas AVD’s (p<0,0001) e no desporto/lazer (p=0,031), e ainda, um aumento da qualidade de vida (p<0,0001). Contudo, apenas os níveis de amplitude articular passiva de extensão do joelho (p=0,083) e de função no desporto/lazer (p=0,244) se mantiveram ao longo das seis semanas de follow-up. Conclusões: Apesar de algumas limitações, considera-se que este estudo é de grande importância para a comunidade científica e para os fisioterapeutas preocupados com a crescente prevalência da osteoartrose e dos custos associados. O exercício aquático parece ser uma estratégia importante na melhoria do estado de saúde dos idosos com osteoartrose do joelho.----------------- ABSTRACT: The osteoarthritis of the knee is a clinical condition that has been increasing among the elderly population over the past few years. It’s a condition that can be fairly disabling to the elderly individual, and which generates a strong social and economic impact. Aquatic exercise has been named as a promotional factor in the improvement of the clinical picture in this population, but its effectiveness is yet to be determined. Objective: To investigate the effectiveness, in a short and medium term, of an aquatic exercise program undertaken by a group over eight weeks, in the joint amplitude, pain and stiffness of the knee, and in the physical function and quality of life in elderly people who suffer from knee osteoarthritis. Methodology: was used a double-blind, quasi-experimental study with no randomization and its 43 subjects were selected as a matter of convenience. The subjects of the experimental group (n=22) were subjected to an aquatic exercise program and those of the control group (n=21) were subjected to a land-based exercise program. Both programs have followed international recommendations on the practice of physical exercise in elderly people who suffer from osteoarthritis (Arthritis Foundation, 2009a, 2009b). The entire group was evaluated in the beginning and at the end of the program (8 weeks later), and after a 6 week follow-up, in these parameters: knee range of motion (through a goniometer), pain, stiffness, function and quality of life (through KOOS). Results: This sample was predominantly female (76,7%) with a mean age of 72,7 years (SD=5,49). Aquatic exercise resulted in increase of passive joint flexion (p<0,0001) and knee extension (p=0,016), in the decline of pain and stiffness (p<0,0001), in the increase of function in the ADLs (p<0,0001). However, only the knee extension amplitude (p=0,083) and the function in sports/leisure (p=0,244) were kept through the six-week follow-up. Conclusions: Despite some limitations, this study is of great importance to the community and to the physiotherapists concerned with the growing prevalence of osteoarthritis and the associated costs. Aquatic exercise appears to be an important strategy in the improvement of the health condition of patients who suffer from knee osteoarthritis.

The effect of a dialyzable transfer factor (TFd) in the experimental american trypanosomiasis of mice: preliminary report

A dialyzable transfer factor (TFd) was obtained from spleen cells, of mice vaccinated with the avirulent PF strain of Trypanosoma cruzi. This factor reduced significahtly the parasitemia of animals treated before or after the infection with a virulent strain of the same parasite, but does not reduced the mortality rate to a level lower than that of the control mice. It is expected that in a next future, new techniques in the use ofsuch factor will bring better resutts.

Impact of social economic indicators on RSI incidence and success

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

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.

Differences in Nevirapine Biotransformation as a Factor for its Sex-Dependent Dimorphic Profile of Adverse Drug Reactions

OBJECTIVES: Nevirapine is widely used for the treatment of HIV-1 infection; however, its chronic use has been associated with severe liver and skin toxicity. Women are at increased risk for these toxic events, but the reasons for the sex-related differences are unclear. Disparities in the biotransformation of nevirapine and the generation of toxic metabolites between men and women might be the underlying cause. The present work aimed to explore sex differences in nevirapine biotransformation as a potential factor in nevirapine-induced toxicity. METHODS: All included subjects were adults who had been receiving 400 mg of nevirapine once daily for at least 1 month. Blood samples were collected and the levels of nevirapine and its phase I metabolites were quantified by HPLC. Anthropometric and clinical data, and nevirapine metabolite profiles, were assessed for sex-related differences. RESULTS: A total of 52 patients were included (63% were men). Body weight was lower in women (P = 0.028) and female sex was associated with higher alkaline phosphatase (P = 0.036) and lactate dehydrogenase (P = 0.037) levels. The plasma concentrations of nevirapine (P = 0.030) and the metabolite 3-hydroxy-nevirapine (P = 0.035), as well as the proportions of the metabolites 12-hydroxy-nevirapine (P = 0.037) and 3-hydroxy-nevirapine (P = 0.001), were higher in women, when adjusted for body weight. CONCLUSIONS: There was a sex-dependent variation in nevirapine biotransformation, particularly in the generation of the 12-hydroxy-nevirapine and 3-hydroxy-nevirapine metabolites. These data are consistent with the sex-dependent formation of toxic reactive metabolites, which may contribute to the sex-dependent dimorphic profile of nevirapine toxicity.

Diabetes Mellitus as a Risk Factor in Glaucoma's Physiopathology and Surgical Survival Time: A Literature Review

Glaucoma is a multifactorial condition under serious influence of many risk factors. The role of diabetes mellitus (DM) in glaucoma etiology or progression remains inconclusive. Although, the diabetic patients have different healing mechanism comparing to the general population and it has a possible-negative role on surgical outcomes. This review article attempts to analyze the association of both diseases, glaucoma and DM, before and after the surgery. The epidemiological studies, based mainly in population prevalence analyzes, have shown opposite outcomes in time and even in the most recent articles also the association remains inconclusive. On the contrary, the experimental models based on animal induced chronic hyperglycemia have shown an important association of both diseases, explained by common neurodegenerative mechanisms. Diabetic patients have a different wound healing process in the eye viz-a-viz other organs. The healing process is more and it results in lower surgical survival time, higher intraocular pressure (IOP) levels and, therefore, these patients usually need more medication to lower the IOP. Both randomized and nonrandomized retrospective and experimental molecular studies have shown the association between DM and glaucoma. Further studies are needed to get better explanations about outcomes on more recent surgical procedures and with the exponential use of antifibrotics. How to cite this article: Costa L, Cunha JP, Amado D, Pinto LA, Ferreira J. Diabetes Mellitus as a Risk Factor in Glaucoma's Physiopathology and Surgical Survival Time: A Literature Review.

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.

Economic rents, institutions and growth: International aid and natural resources: A comparative analysis

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

(Re)Financing in a capital intensive industry during economic crises

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

O uso do solo como factor de influência na evolução de um sapal. Casos de estudo do Sapal de Corroios e do Sapal de Pancas

Dissertação para obtenção do Grau de Mestre em Engenharia do Ambiente perfil Ordenamento do Território e Impactes Ambientais

The economic value of Portuguese pine and eucalyptus forests

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

A look into the cross-section of industry stock returns

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

Cluster analysis and segmentation of Global M&A transactions

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