The patent expiry as a major inflection point in a branded Rx drug's life and strategies to counter generic competition - exemplified at Pfizer's blockbuster drug Lipitor in the USA

A large number of expensive, but highly profitable branded prescription drugs will go off-patent in the USA between 2011 and 2015. Their revenues are crucial to fund the immense costs associated with the development of an innovative drug. The rising cost pressure on pharmaceutical stakeholders has increased the demand for more affordable medications, as provided by the branded drug's generic counterpart. Yet, research based incumbents are moving beyond the traditional late lifecycle strategies and deploy more aggressive tactics in order to protect their brands, as seen with Pfizer's Lipitor!. It is doubtful, whether these efforts will help the blockbuster business model to resist current market conditions.

Quality of life of patients with hepatitis C

INTRODUCTION: Self-report on the quality of life (QOL) is increasingly studied in the evaluation of various diseases, especially in chronic ones. However, there are few data in the literature focusing the QOL of patients living with chronic hepatitis C. The objective of this study was to evaluate the QOL in patients with hepatitis C assessed by the World Health Organization Quality of Life Assessment (WHOQOL)-bref scale. METHODS: One hundred and eight hepatitis C patients attending the Outpatient Healthcare Medical Specialties in Tubarão, State of Santa Catarina, Brazil, were contacted from May 2010 to February 2011. Patients answered the WHOQOL-bref scale and a questionnaire about their treatment and risk factors to hepatitis C virus (VHC) infection. RESULTS: Although most of patients with chronic hepatitis C considered their QoL good or very good (58.1%), 47 (44.8%) patients were poorly or very poorly satisfied with their health. About the WHOQOL answers, the environment domain had the highest score (25.15 + 5.77), while the lowest score was the social relationships domain (9.19 + 2.5). There was statistically significant association between household income and quality of life in all domains (p<0.001) and statistically significant association between education and the physical, psychological and social domains of quality of life (p<0.05). CONCLUSIONS: Based on the answers given in WHOQOL-bref, patients with chronic hepatitis C have a generally poor QOL, especially in social relationship domain. Household income and educational level were factors that interfered significantly with patients' QOL assessment.

Protocol for the psychotherapeutic group intervention for facilitating posttraumatic growth in nonmetastatic breast cancer patients

Breast cancer can be perceived as a traumatic event with disturbing effects on psychological domains such as depression, anxiety, and Posttraumatic Stress Disorder. In contrast, growing evidence has shown that posttraumatic growth can occur as a result of coping with breast cancer. Challenging the assumptive world, deliberate rumination, and emotional disclosure are recognized as strong predictors of posttraumatic growth. Group interventions may also increase social support, distress disclosure, and posttraumatic growth. The aim of this study is to evaluate how group-based interventions can facilitate posttraumatic growth and promote improved psychosocial adjustment to breast cancer. This article describes the study protocol and the applied research methods.

Impact of oral health on health-related quality of life : A cross-sectional study

Background: Despite the consensus regarding the existence of a relationship between “impacts on oral health” and “health-related quality of life”, this relationship, considering the latent nature of these variables, is still poorly investigated. Thus, we performed this study in order to determine the magnitude of the impacts of oral health, demographic and symptom/clinical variables on the health-related quality of life in a Brazilian sample of dental patients. Methods: A total of 1,007 adult subjects enrolled in the School of Dentistry of São Paulo State University (UNESP) - Araraquara Campus for dentistry care between September/2012 and April/2013, participated. 72.4 % were female. The mean age was 45.7 (SD = 12.5) years. The Oral Health Impact Profile (OHIP-14) and the Short Form Health Survey (SF-36) were used. The demographic and symptom/clinical variables collected were gender, age, economic status, presence of pain and chronic disease. The impact of studied variables on health-related quality of life were evaluated with a structural equation model, considering the factor “Health” as the central construct. The fit of the model was first analyzed by the evaluation of the goodness of fit indices (χ 2 /df ≤ 2.0, CFI and TLI ≥ 0.90 and RMSEA < 0.10) and the evaluation of the variables’ impact over health-related quality of life was based on the statistical significance of causal paths (β), evaluated by z tests, for a significance level of 5 %. Results: We observed adequate fit of the model to the data (χ 2 /df = 3.55; CFI = 0.95; TLI = 0.94; RMSEA = 0.05). The impacts on oral health explained 28.0 % of the variability of the health-related quality of life construct, while the total variance explained of the model was 39.0 %. For the demographic and symptom/clinical variables, only age, presence of pain and chronic disease showed significant impacts (p < 0.05). Conclusion: The oral health, age, presence of pain and chronic disease of individuals had significant influence on health-related quality of life.

Health-related quality of life in patients with Chagas disease: a review of the evidence

Chagas disease (ChD), a neglected tropical disease caused by infection with the parasite Trypanosoma cruzi (T. cruzi), remains a serious public health issue in Latin America and is an emerging disease in several non-endemic countries, where knowledge of the condition and experience with its clinical management are limited. Regionally, the disease is the major cause of disability secondary to tropical diseases in young adults. Health-related quality of life (HRQoL) impairment is common in patients with ChD, especially in those with Chagas dilated cardiomyopathy, the most severe manifestation of the disease, which frequently leads to heart failure. The aim of this review was to conduct a literature search for studies that have evaluated the determining factors of HRQoL in ChD patients. We included cross-sectional, case-control, cohort, and experimental studies, as well as clinical trials that evaluated the HRQoL in ChD patients aged 18 to 60 years and are presenting an explicit description of statistical analysis. Using a combination of keywords based on Descriptors in Health Sciences (DeCS) and Medical Subject Headings (MeSH) for searches in PubMed and the Scientific Electronic Library Online (SciELO), 148 studies were found. After exclusions, 12 studies were selected for analysis. Three main findings were extracted from these studies: 1) cardiac involvement is associated with a worse HRQoL in ChD patients; 2) HRQoL is associated with the patients' functional capacity; and 3) simple and inexpensive therapeutic measures are effective for improving HRQoL in ChD patients. Hence, ChD patients' functional capacity, the effectiveness of non-surgical conservative treatment, and cardiac involvement are important determining factors for the HRQoL in ChD patients.

Historical trajectories of currently shrinking Portuguese cities: A typology of urban shrinkage

Cities develop according to different patterns, undergoing population growth during some periods and decline (shrinkage) during others. Theories attempting to understand these behaviours include: 1) shrinkage is a natural process in the life cycle of a city, alternating with periods of growth, or 2) shrinkage is an extreme event that places cities into a continuous decline process with no return to population growth. We use retrospective data over a period of 130 years to study 25 Portuguese cities currently facing population decline, and show that both theories coexist in time and space. Five types of shrinking city are revealed: “Persistent Early Shrinkage” due to exodus fromthe rural periphery, “Metropolitan Shrinkage” due to the challenges of urban sprawl, “Recent Shrinkage” in de-industrialisation hotspots, “Cyclic Shrinkage” occurring in political transformation cores, and “Mild Shrinkage” due to life-style disamenity. As diversity of city population trajectories appears to be the norm in both Portugal and other Western European countries, the incorporation of this range into the management of urban transitions is recommended in order to reinforce city resilience.

Life cycle of Trypanosoma cruzi (y strain) in mice

Since 1958, we have studied experimental Chagas' disease (CD) by subcutaneous inoculation of 1,000 blood forms of Trypanosoma cruzi (Y strain) in Balb/C. mice. Evolution of parasitemia remained constant, beginning on the 5th and 6th day of the disease, increasing progressively, achieving a maximum on about the 30th day. After another month, only a few forms were present, and they disappeared from the circulation after the third month, as determined from direct examination of slides and the use of a Neubauer Counting Chamber. These events coincided with the appearance of amastigote nests in the tissues (especially the cardiac ones), starting the first week, and following the Gauss parasitemia curve, but they were not in parallel until the chronic stage. In 1997, we began to note the following changes: Parasites appeared in the circulation during the first week and disappeared starting on the 7th day, and there was a coincident absence of the amastigote nests in the tissues. A careful study verified that young forms in the evolutionary cycle of T. cruzi (epi + amastigotes) began to appear alongside the trypomastigotes in the circulation on the 5th and 7th post-inoculation day. At the same time, rounded, oval, and spindle shapes were seen circulating through the capillaries and sinusoids of the tissues, principally of the hematopoietic organs. Stasis occurs because the diameter of the circulating parasites is greater than the vessels, and this makes them more visible. Examination of the sternal bone marrow revealed young cells with elongated forms and others truncated in the shape of a "C" occupying the internal surface of the blood cells that had empty central portions (erythrocytes?). We hypothesize that there could be a loss of virulence or mutation of the Y strain of Trypanosoma cruzi.

The use of stents in the treatment of traumatic intimal flaps: case report

Treatment of arterial traumatic intimal lesions is controversial due to its unknown natural history. Current therapeutical options include arterial reconstruction and clinical observation. The idea of using stents to correct intimal flaps is based on their use to correct dissections, flaps, and arterial irregularities after angioplasty. We report the successful treatment of a traumatic intimal flap of the superficial femoral artery, caused by gunshot trauma, with a Palmaz stent in the acute period. One year after the operation, a duplex scan revealed normal flow in the artery and complete exclusion of the intimal flap; distal pulses were palpable, and the patient was completely asymptomatic.

The economic impact of the event Volta a Portugal em Bicicleta 2015

This thesis is a Field Lab project requested by the organizer of the Volta a Portugal em Bicicleta 2015, Podium Events. Its purpose is to determine the economic impact of the event for the 21 host economies and Portugal as a whole. The Volta started in Viseu and ended in Lisboa, and lasted for two weeks from the 29th July until the 8th August. Results were computed by accessing data provided by the different economic agents involved in the event (spectators, attendees and organizer), through face-to-face surveys and contact via e-mail. The Volta generated a total economic impact of €76.261.876. Keywords: Cycling,

Has the time for renewables finally arrived? – An event study on EPA’s Clean Power Plan

The recent proposals presented by EPA aimed to reduce the dependency of fossil fuels and to lower current emissions levels, hoping to gradually shift electric generation units to renewable energy sources. Actually, the Final Rule Proposal announcement day exhibited a negative Abnormal Return on Fossil Fuels but the following days had positive Abnormal Returns, mostly due to legislative change perceived by financial markets which eased up implementation periods of the proposed measures in the Final Rule when compared to the Draft Rule. Oppositely, Renewables and Solar Portfolios exhibited negative Cumulative Abnormal Returns over the period surrounding the Final Rule.

The economic impact of the event Volta a Portugal em Bicicleta 2015

This thesis is a Field Lab project requested by the organizer of the Volta a Portugal em Bicicleta 2015, Podium Events. Its purpose is to determine the economic impact of the event for the 21 host economies and Portugal as a whole. The Volta started in Viseu and ended in Lisboa, and lasted for two weeks from the 29th July until the 8th August. Results were computed by accessing data provided by the different economic agents involved in the event (spectators, attendees and organizer), through face-to-face surveys and contact via e-mail. The Volta generated a total economic impact of €76.261.876.

Arshile Gorky: An Armenian in New York

Born in Armenia, the oldest Christian country in the world but nevertheless one of the youngest reinstated republics (1991) after the collapse of the Soviet Union, Arshile Gorky flew to the United States in 1920, where he chose to reinvent himself in the struggle to become an artist. This reinvention meant the creation of a persona with, or behind, which Gorky kept alive the artistic flame inside himself. Gorky became one of the most learned voices lecturing on contemporary European modernist artists and movements of the late nineteenth and early twentieth centuries in the United States (New York) without ever visiting Europe. Moreover, he was able to survive the traumatic events he underwent during the Armenian Genocide (1915-1919) to adapt to his new country and identity, to live through the years of the Depression and, eventually, to become the protagonistof a major artistic breakthrough. This paper proposes an insight into the experience of life and frame of work of this Armenian-American artist, whose simultaneously rich, traumatic, dislocated and reenacted life and work established one of the most fertile links between his middle‑eastern origins, his dreamed of Europe and the particular transit of his American artistic creation.

Fatigue life assessment of endodontic instruments subjected to multi planar curvature

This present study aimed to investigate the fatigue life of unused (new) endodontic instruments made of NiTi with control memory by Coltene™ and subjected to the multi curvature of a mandibular first molar root canal. Additionally, the instrument‟s structural behaviour was analysed through non-linear finite element analysis (FEA). The fatigue life of twelve Hyflex™ CM files was assessed while were forced to adopt a stance with multiple radius of curvature, similar to the ones usually found in a mandibular first molar root canal; nine of them were subjected to Pecking motion, a relative movement of axial type. To achieve this, it was designed an experimental setup with the aim of timing the instruments until fracture while worked inside a stainless steel mandibular first molar model with relative axial motion to simulate the pecking motion. Additionally, the model‟s root canal multi-curvature was confirmed by radiography. The non-linear finite element analysis was conducted using the computer aided design software package SolidWorks™ Simulation, in order to define the imposed displacement required by the FEA, it was necessary to model an endodontic instrument with simplified geometry using SolidWorks™ and subsequently analyse the geometry of the root canal CAD model. The experimental results shown that the instruments subjected to pecking motion displayed higher fatigue life values and higher lengths of fractured tips than those with only rotational relative movement. The finite element non-linear analyses shown, for identical conditions, maximum values for the first principal stress lower than the yield strength of the material and those were located in similar positions to the instrument‟s fracture location determined by the experimental testing results.

Aspectos fundamentais da experiência da vida

A tese que de seguida se esboça assenta sobre uma inquietação fundamental: o facto de cada um dar por si atirado na vida, de, quando cada um dá por si, dar por si a ser vida, etc. Acontece que, logo que se tenta focar mais precisamente de que é de que se trata quando se trata da “vida”, nota-se que esse fenómeno tem habitualmente a forma de um acontecimento anónimo: não se sabe bem a que é que corresponde, que conteúdos tem, que estruturas fundamentais a suportam, etc. Isto é: somos levados pela vida (passamos pela vida, atravessamo-la, estamos expostos a ela, etc.) sem saber exactamente a que é que estamos expostos, o que é que nos leva, sobre que pilares assenta a nossa vivência e a nossa compreensão dela, etc. A tese que se segue não tem a pretensão de deixar definitivamente respondidas estas perguntas; tudo o que faz, na verdade, é meramente proceder a um breve levantamento ou a um registo de algumas das estruturas fundamentais da vida a partir do ângulo da experiência da vida. E, como se espera deixar claro, procurar a resposta a partir do ângulo da experiência (do ângulo da experiência da vida) não é algo acidental ou fortuito. O que se procurará apurar é se não haverá tais laços de afinidade entre “vida” e “experiência” que todas as operações próprias da experiência têm lugar numa vinculação e estão subordinadas às estruturas fundamentais da vida (estruturas que ultrapassam o âmbito da “experiência”) e que, assim também, a vida tenha, de raiz, no modo como nela somos levados e conduzidos, a estrutura ou a forma da “experiência”.