Protease inhibitors to treat hepatitis C in the Swiss HIV Cohort Study: high efficacy but low treatment uptake.

OBJECTIVES: Direct-acting antiviral agents (DAAs) have become the standard of care for the treatment of chronic hepatitis C virus (HCV) infection. We aimed to assess treatment uptake and efficacy in routine clinical settings among HIV/HCV coinfected patients after the introduction of the first generation DAAs. METHODS: Data on all Swiss HIV Cohort Study (SHCS) participants starting HCV protease inhibitor (PI) treatment between September 2011 and August 2013 were collected prospectively. The uptake and efficacy of HCV therapy were compared with those in the time period before the availability of PIs. RESULTS: Upon approval of PI treatment in Switzerland in September 2011, 516 SHCS participants had chronic HCV genotype 1 infection. Of these, 57 (11%) started HCV treatment during the following 2 years with either telaprevir, faldaprevir or boceprevir. Twenty-seven (47%) patients were treatment-naïve, nine (16%) were patients with relapse and 21 (37%) were partial or null responders. Twenty-nine (57%) had advanced fibrosis and 15 (29%) had cirrhosis. End-of-treatment virological response was 84% in treatment-naïve patients, 88% in patients with relapse and 62% in previous nonresponders. Sustained virological response was 78%, 86% and 40% in treatment-naïve patients, patients with relapse and nonresponders, respectively. Treatment uptake was similar before (3.8 per 100 patient-years) and after (6.1 per 100 patient-years) the introduction of PIs, while treatment efficacy increased considerably after the introduction of PIs. CONCLUSIONS: The introduction of PI-based HCV treatment in HIV/HCV-coinfected patients improved virological response rates, while treatment uptake remained low. Therefore, the introduction of PIs into the clinical routine was beneficial at the individual level, but had only a modest effect on the burden of HCV infection at the population level.

Comportamento da dose glandular versus contraste do objeto em mamografia: determinação de formalismo semi-empírico para diferentes combinações alvo-filtro

OBJETIVO: Verificar o efeito da mudança no contraste do objeto, tempo de exposição e dose de radiação quando diferentes espessuras de filtração de molibdênio (Mo) e ródio (Rh) são empregadas em mamógrafos. MATERIAIS E MÉTODOS: Realizaram-se medidas da exposição na entrada da pele com uma câmara de ionização para diferentes espessuras para os filtros de Mo e Rh. Para determinar a dose glandular média foi utilizado simulador de BR12 (50% tecido adiposo e 50% tecido glandular) de diferentes espessuras (4 cm e 8 cm). Energias na faixa de 24 kVp a 34 kVp foram empregadas e filmes Kodak MinR 2000 foram utilizados. RESULTADOS: Os resultados evidenciaram dados de contraste do objeto, dose glandular e tempo de exposição para diferentes espessuras de filtros adicionais e diferentes tensões. Esses dados indicaram aumento nos valores de contraste do objeto e tempo de exposição, com o aumento da espessura dos filtros. A dose glandular apresentou comportamento com diferentes tendências para cada caso analisado. Equações foram definidas para possibilitar a estimativa do contraste do objeto, dose glandular e tempo de exposição para os casos estudados. CONCLUSÃO: Os resultados possibilitaram a estimativa de equações que auxiliam na verificação do comportamento do contraste do objeto e da dose glandular para simuladores com espessura de 4 cm e 8 cm e para os filtros de Rh e Mo. Dessa forma, torna-se possível estimar a figura de mérito (razão entre o contraste do objeto e a dose glandular), podendo auxiliar na análise da relação risco-benefício dos casos estudados.

Hépatite C: traitement actuel [Hepatitis C: current therapy].

Le traitement de l'hépatite C chronique a été révolutionné par l'introduction de nouveaux antiviraux (directly acting antivirals [DAA]). Ces inhibiteurs de protéase, de la protéine NS5A et de la polymérase peuvent être associés dans des traitements oraux hautement efficaces et bien tolérés sans interféron. Dans cet article, nous fournissons un aperçu du traitement actuel de l'hépatite C chronique avec considération particulière des DAA actuellement autorisés en Suisse. Treatment of chronic hepatitis C is currently being revolutionised, with the introduction of directly acting antivirals (DAA), including protease, NS5A and polymerase inhibitors. These can be combined in interferon-free oral therapies with unprecedented efficacy and good tolerance. Here, we review the current therapy of chronic hepatitis C, with a particular focus on DAA that are approved in Switzerland today.

Role of immune and angiogenic markers in the pathology of endometriosis

Background: Endometriosis is an estrogen-dependent, pro-inflammatory, pro-angiogenic condition that affects 5 to 10% of women of reproductive age. Its defining feature is the presence of endometrium-like tissue in sites outside the uterine cavity, primarily on the pelvic peritoneum and ovaries. The main clinical features are chronic pain, pain during intercourse and infertility. In patients with endometriosis, inflammatory and immune responses, angiogenesis and apoptosis are altered in favour of the survival and replenishment of endometriotic tissue. These basic pathological processes depend on the excessive formation of estrogen and prostaglandins. Recently, new cellular and molecular mechanisms for the resolution of inflammation have been discovered, revealing key roles for lipid mediators such as lipoxins, resolvins and protectins. It is possible that disequilibrium in the expression of these molecules exists in endometriosis. Objective: To compare the expression of two proteins involved in the synthe sis and in the function of lipid mediators; the Arachidonate 15-lipoxygenase (ALOXI5), implicated in the synthesis of lipoxins A4 and B4 and the Formyl peptide receptor 1 (FPRLI), the specific receptor for Lipoxin A4 and B4, between women who suffer from endometriosis and a control group. We wish to demonstrate the cellular localisation of these two molecules and to investigate if their expression is alteted in this pathology. Methods and Materials Using immunohistochemistry we will compare ALOXI5 and FPRLI staining, in endometrium, normal peritoneum and endometriotic lesions. The samples are being collected in the department of Gynaecology and Obstetrics at the Centre Hospitalier Universitaire Lausanne (CHUV). Women attending the department for laparoscopic investigation of pain/infertility, suspected endometriosis or for a hysterectomy, are invited to participate. Approval of the ethics committee (Commission d'Ethique de la recherché clinique) was obtained in March 2009. Clinical samples will only be obtained from subjects having consented. Expected results and interpretation: No published studies investigating the expression of these two molecules in endometriotic lesions exist. A better understanding of the mechanisms underlying this disease will result in the development of new medical therapies and new diagnostic tests, with the aim of ameliorating the quality of life of endometriosis patients.

The forced adoption of a fast-track appraisal process for a breast cancer treatment in UK

Trastuzumab (Herceptin ®, Roche) is approved in UK for the treatment of the metastatic breast cancer since 2001. As of 2005, concomitantly with the publication of 3 studies that showed it produces a 50% reduction of the recurrence rates of breast cancer, trastuzumab started to be prescribed in the earlt adjuvant treatrnent of this disease. Und June 2006, trastuzumab did not have both: 1) regulatory approval and 2) NICE [National Institute for Health and Clinical Excellence] recommendation for the use in early stages of breast cancer. During the period until June 2006, the trastuzumab use in those patients was not reimbursed and because the cost of trastuzumab is equal with the yearly UK average income, most of patients could not self fund their treatrnent. Before the publication of the final NICE guidance, the new data of trastuzumab in early breast cancer raised enormous patient and professional interest and expectations. A great volume of public and professional pressure was generated to transcend a system by which Primary Care Trusts can reimburse a treatment only after a formal guidance was issued. This paper draw on a case study depicting and analyzing the process by which regulatory approval and NICE recommendations were achieved in a record time and how trastuzumab became a standard treatment on early adjuvant breast cancer. According to the data we gathered in this work we were witnessing one of the fastest processes of adoption of a health care technology since the creation of NICE, in 1999. This study addresses the following research question: How and why does the adoption pattern of trastuzumab differ from the rational decision-making model of the reimbursement process in UK? [Author, p. 4]

The First International Workshop on Warning Criteria for Active Slides: technical issues, problems and solutions for managing early warning systems

Early warning systems (EWSs) rely on the capacity to forecast a dangerous event with a certain amount of advance by defining warning criteria on which the safety of the population will depend. Monitoring of landslides is facilitated by new technologies, decreasing prices and easier data processing. At the same time, predicting the onset of a rapid failure or the sudden transition from slow to rapid failure and subsequent collapse, and its consequences is challenging for scientists that must deal with uncertainties and have limited tools to do so. Furthermore, EWS and warning criteria are becoming more and more a subject of concern between technical experts, researchers, stakeholders and decision makers responsible for the activation, enforcement and approval of civil protection actions. EWSs imply also a sharing of responsibilities which is often averted by technical staff, managers of technical offices and governing institutions. We organized the First International Workshop on Warning Criteria for Active Slides (IWWCAS) to promote sharing and networking among members from specialized institutions and relevant experts of EWS. In this paper, we summarize the event to stimulate discussion and collaboration between organizations dealing with the complex task of managing hazard and risk related to active slides.

MEDEX: a general overview

The general objective of the international MEDiterranean EXperiment (MEDEX) was the better understanding and forecasting of cyclones that produce high impact weather in the Mediterranean. This paper reviews the motivation and foundation of MEDEX, the gestation, history and organisation of the project, as well as the main products and scientific achievements obtained from it. MEDEX obtained the approval of World Meteorological Organisation (WMO) and can be considered as framed within other WMO actions, such as the ALPine EXperiment (ALPEX), the Mediterranean Cyclones Study Project (MCP) and, to a certain extent, THe Observing System Research and Predictability EXperiment (THORPEX) and the HYdrological cycle in Mediterranean EXperiment (HyMeX). Through two phases (2000 2005 and 2006 2010), MEDEX has produced a specific database, with information about cyclones and severe or high impact weather events, several main reports and a specific data targeting system field campaign (DTS-MEDEX-2009). The scientific achievements are significant in fields like climatology, dynamical understanding of the physical processes and social impact of cyclones, as well as in aspects related to the location of sensitive zones for individual cases, the climatology of sensitivity zones and the improvement of the forecasts through innovative methods like mesoscale ensemble prediction systems.

Tribosähköiseen ilmiöön perustuvan hiukkaspitoisuusmittarin kehitys

Diplomityön tarkoituksena oli kehittää mikroprosessoriohjattu digitaalinen pölymittarituoteperhe vanhan analogisen hiukkasmittarin tilalle. Työssä käydään läpi mittarin teoreettista perustaa ja kehitysprojektin eri vaiheita sekä tutustutaan hiukkasmittauksen perusteisiin, lainsäädäntöön sekä hiukkasten terveysvaikutuksiin, joista saadaan motivaatiota sille, miksi hiukkasia yleensä kannattaa ja pitää mitata. Työssä tutustutaan myös lainsäädännön mittarilta vaatimiin hyväksyntöihin eri sovelluskohteissa, käytännön mittauksissa esiintyviin haasteisiin sekä käydään läpi hyväk-syntöjen läpäisemiseksi vaaditut testit. Diplomityön lopuksi tutustutaan mittarin kaupalliseen menestykseen, ehdotetaan kehi-tyskohteita ja tutustutaan tribosähköisen mittauksen tulevaisuuden mahdollisuuksiin.

Explosion-proof requirements for Electrical Machines in Chemical, Oil and Gas Industry in Russia and CIS Countries

One of the main industries which form the basis of Russian Economical structure is oil and gas. This industry is also playing a significant role for CIS countries. Oil and gas industry is developing intensively attracting foreign investments. This situation is providing sustainable development of machinery production for hazardous areas. Operating in oil and gas areas is always related with occurrence of explosion gas atmospheres. Machines for hazardous areas must be furnished with additional protection of different types. Explosion protection is regulated with standards according to which equipment must be manufactured. In Russia and CIS countries explosion-proof equipment must be constructed in compliance with GOST standards. To confirm that equipment is manufactured according to standards’ requirements and is safe and reliable it must undergo the approval procedure. Certification in Russia is governed by Federal Laws and legislation. Each CIS country has its own approval certificates and permissions for operating in hazardous areas.

Plan de seguridad y salud para el suministro y montaje del Parque Eólico Rancho Viejo en el T.M. de Medina-Sidonia (Cádiz)

No hace más de 3 años se podía leer en las revistas especializadas que España había pasado a ocupar el tercer puesto en el ranking mundial por potencia eólica instalada. La industria eólica española a su vez ha pasado a ocupar el tercer puesto en la fabricación e instalación de aerogeneradores, con una cuota de mercado del 13%, siendo así un sector con gran capacidad de exportación. Por otra parte, tras diez años de promulgación de la Ley 31/95, de 8 de noviembre, de Prevención de Riesgos Laborales, y después su desarrollo reglamentario, es un hecho incontestable que, pese a todo, y a los ingentes esfuerzos realizados por los distintos actores implicados en la prevención de riesgos laborales (Estado, Comunidades Autónomas, Agentes Sociales, Entidades especializadas, etcetera), existe un sector como el de la construcción que, constituyendo uno de los ejes del crecimiento económico de nuestro país, está sometido a unos riesgos especiales y continúa registrando una siniestralidad laboral muy notoria por sus cifras y gravedad. La legislación de prevención, los manuales sobre las distintas disciplinas preventivas, los libros especializados, los expertos... han abordado ya, con mayor o menor acierto, muchas de las cuestiones generales y específicas que afectan a la seguridad y salud: la evaluación de riesgos, las medidas higiénicas, los equipos de trabajo y equipos de protección individual, la planificación, la formación, los servicios de prevención , los sistemas de gestión de la prevención, las auditorías ... forman parte de los contenidos que se han ido creando en torno a este tema. No obstante, resulta de gran interés la elaboración de un estudio de Seguridad y Salud, en el que partiendo de un desarrollo técnico concreto, pero sobre todo integral, es decir, que comprenda todas las fases para el suministrp e instalación de aerogeneradores para un parque eólico, vayamos desgranando cada uno de los puntos desarrollados en su construcción. Entre las conclusiones más destacadas de este trabajo, se encuentra la definición de las condiciones relativas a la prevención de accidentes y enfermedades laborales durante la ejecución de los trabajos de suministro e instalación de un parque eólico y la gestión de su prevención, las características de las instalaciones preceptivas para higiene y bienestar de los trabajadores, así como directrices básicas mínimas, que deben reflejarse y desarrollarse en el Plan de Seguridad y Salud que las empresas contratistas deberán presentar para su aprobación por el director de obra, antes del comienzo de los trabajos, de forma que sea posible la disminución de accidentes laborales así como evitar las posibles sanciones administrativas y/o penales.

Veus ignorades: representacions socials, subjectivitat i resiliència en persones grans amb pèrdua d’autonomia funcional

Els processos per a l’aprovació i la implementació de la Llei per a l’Autonomia personal i l’Atenció a les Persones en situació de Dependència (LAPAD) han donat lloc a un intens debat polític i social que, coincidint també amb les millores en la provisió de serveis i els avenços mèdics, ha contribuït a un procés de classificació i d’etiquetatge basats en els dèficits de les persones que es troben en aquestes circumstàncies. Aquesta visió anul·la el subjecte i la seva experiència singular i condiciona l’abordatge dels models d’atenció i de cura. L’estudi pretén fer una aproximació a les persones grans amb pèrdua d’autonomia funcional, fent emergir les seves veus, que expressen com perceben, interpreten, afronten i es reajusten a la nova situació. Partint d’un enfocament constructivista, basat en la subjectivitat, es fa un recorregut sobre els models de la discapacitat que han reeixit en l’activitat científica dels darrers anys, els mecanismes de regulació de les pèrdues que defensen les teories del cicle vital i les aportacions que s’han fet sobre el model de la resiliència aplicat a les persones que envelleixen. El resultats de l’estudi mostren com les representacions i els significats que les persones grans atribueixen a la seva experiència s’inscriuen en les seves trajectòries vitals, donant un sentit únic i singular a la forma de viure i de respondre a la pèrdua d’autonomia funcional i les seves conseqüències. Aquelles que expressen una vivència d’integritat respecte de la vida viscuda, amb predomini d’afectes positius envers un mateix i els altres, que conserven l’esperança i el desig de continuar vivint, s’ajusten a les pèrdues de manera més satisfactòria que aquelles que expressen desconfiança i una certa amargor respecte de la pròpia vida. D’això se’n deriva que els espais d’escolta i d’acompanyament poden ser un recurs vàlid i necessari en el qual, a través de la paraula i el testimoni narrat, el subjecte pugui repensar i resignificar les seves experiències.

Development of an instrument to measure the degree of critical patient's satisfaction with nursing care: research protocol

Aim: To investigate and understand patient's satisfaction with nursing care in the intensive care unit to identify the dimensions of the concept of"satisfaction" from the patient's point of view. To design and validate a questionnaire that measures satisfaction levels in critical patients. Background: There are many instruments capable of measuring satisfaction with nursing care; however, they do not address the reality for critical patients nor are they applicable in our context. Design: A dual approach study comprising: a qualitative phase employing Grounded Theory and a quantitative and descriptive phase to prepare and validate the questionnaire. Methods: Data collection in the qualitative phase will consist of: in-depth interview after theoretical sampling, on-site diary and expert discussion group. The sample size will depend on the expected theoretical saturation n = 27-36. Analysis will be based on Grounded Theory. For the quantitative phase, the sampling will be based on convenience (n = 200). A questionnaire will be designed on the basis of qualitative data. Descriptive and inferential statistics will be used. The validation will be developed on the basis of the validity of the content, the criteria of the construct and reliability of the instrument by the Cronbach's alpha and test-retest approach. Approval date for this protocol was November 2010. Discussion: Self-perceptions, beliefs, experiences, demographic, socio-cultural epistemological and political factors are determinants for satisfaction, and these should be taken into account when compiling a questionnaire on satisfaction with nursing care among critical patients.

HIV - recentes avanços na pesquisa de fármacos

The development of new antiretroviral drugs is a dynamic process that is continuously fueled by identification of new molecular targets and new compounds for know targets. The current available drugs can be classified into five categories: nucleoside analogues reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors and entry inhibitors (fusion inhibitors and CCR5 antagonist). In addition, the maturation inhibitors may be considered as potential target for chemotherapeutic intervention. This review presents some anti-HIV agents that have already gone through the advance development process for final approval for the treatment of AIDS.

Biodiversidade: fonte potencial para a descoberta de fármacos

In economic terms, biodiversity transcends the boundaries usually given to conventional industries because it is a valuable source of biological and chemical data of great use to drug discovery. Certainly, the use of natural products has been the single most successful strategy in the discovery of novel medicines, and most of the medical breakthroughs are based on natural products. Half of the top 20 best-selling drugs are natural products, and their total sales amounted to US$ 16 billions shows the importance of natural products, which is evidenced by the new chemical entities (NCE) approved by regulatory authorities around the world in the past decade. Recently, the approval of the alkaloid galanthamine as a medicine to treat Alzheimer's disease shows that natural compounds from plants will continue to reach the market. The huge biological diversity of the Brazilian biomes, by its ability to generate new knowledge and technological innovation can be a fantastic alternative as raw material for drug discovery.

Metsäsääntely Suomessa ja Venäjällä. Näkökulmia kestävään metsätalouteen

Sustainability is the aim of forest management and forest regulation in many countries. Accordingly, forest management has been steered towards more environmentally friendly methods and new regulatory instruments have been introduced. At the same time, wood trade and forest industry have become a global business. Even if the importance of national forest legislation has not decreased, it has been widely acknowledged that national regulation of forest management is no longer sufficient. The movement of goods does not acknowledge boundaries, even though most negative environmental and social consequences stay in the country of origin of wood and other raw materials. As a partial solution to this dilemma, different kinds of regulations have been developed. Various forest certification schemes and wood trade regulation in the EU (995/2010) are examples of efforts to prevent illegal logging and unsustainable forestry. The Finland-based forest industry is to a varying extent dependent on wood trade from Russia. Especially in the 1990‟s, ethical questions concerning import of wood from Russian old growth forests near the Finnish border were widely discussed. Consequently, forest industry enterprises have developed systems to trace the origin of wood and to buy certified wood from Russia. The aim of the research has been to evaluate Finnish and Russian forest regulations in order to investigate what kind of forest management these regulations enhance, and to what extent ecologically sustainable forest management has been integrated into different forms of regulation. I have examined Finnish and Russian forest regulation in four separate articles based on the topics of the Russian Forest Code, forest certification and other voluntary forest protection measures in Russia, Finnish forest certification and Finnish forest legislation. One objective has been to analyse the roles voluntary forest certification plays in promoting sustainable forest management in different countries. In my research, I have mainly concentrated on ecological sustainability and protection of biodiversity, although other aspects of sustainable forest management have been touched upon in different articles. In the following I shall conclude the findings of my research. When the current Russian Forest Code (2006) was being adopted, the main emphasis was not on ecological issues, but on reorganizing forest governance. The role of ecological requirements was even slightly diminished during the legislative reform. There are, nevertheless, still stipulations aiming at ecological sustainability, such as the division of forests into different forest management categories and various protection zones. In 2000, FSC forest certification arrived in Russia, at present covering already 28 million hectares of forests. The PEFC scheme is now in use as well, but to a much lesser extent. If properly implemented, Russian forest certification schemes clearly improve the level of ecological and social sustainability of forestry in Russia. Certification criteria, however, are partly in conflict with the Russian forest legislation and certified enterprises have been forced to pay fines or to negotiate with forest authorities. This clearly indicates that even if Russian forest legislation has otherwise been liberalized to a certain extent, some significant paternalism still exists. Voluntary, hands-on biodiversity protection measures are not valued, and they are not part of the official protection policies as in many other countries. However, there have been some regional solutions to this dilemma. In the Republic of Karelia forest authorities have approved a set of forest biodiversity protection rules created by a local NGO and a forest industry enterprise. By following these local rules, an enterprise can avoid fines for protection measures. The current Finnish Forest Act was adopted in 1996. It brought forest legislation into a new era as some ecological aspects were integrated into forest legislation. The various soft-law forest management recommendations further increased the level of biodiversity protection. My evaluation of the overall legitimacy of the Finnish forest legislation and forest management paradigm revealed, however, several problematic issues. As part of this study I analysed the history of the current forest management paradigm. This analysis revealed the path dependency which still hinders the protection of biodiversity and clearly decreases the general legitimacy of forest management. Due to several historical reasons only even-structured forest management based on clear cuts has for decades been officially approved in Finland. Due to increasing demands of forest owners the legislation is finally being revised. Yet, the official approval of uneven-structured forest management would not be enough to fully improve ecological, social and cultural legitimacy. The latest ecological theories and knowledge of endangered species should be taken into account in the on-going reform of forest legislation as well as the modernisation. Forest legislation is one of the very few spheres of Finnish environmental legislation where openness and participation are still considered a threat. The first Finnish forest certification scheme, PEFC, was established in 2000. It now covers more than 20 million hectares, about 95% of the forests in Finland. PEFC Finland does not require a higher level of biodiversity protection than the recommendations by Tapio (the Development Centre for Forestry), but certification has unified forest management practices and requires more protection measures than mere forest legislation. The study suggests that in Finland PEFC has not functioned as an instrument which would substantially improve the level of forest management. Rather it has supported the status quo of the forest sector. While the ecological and social responsibility of Finland-based forest corporations was one impetus for this research, I want to conclude that there are problems related to forest legislation and non-state regulation in both Finland and Russia. If an enterprise buying wood from Russia buys only certified wood, and carefully avoids wood coming from high conservation value forests that are either ecologically or socially valuable, it can be claimed to be as sustainably produced as in Finland. However, there must be continuous scrutiny of the circumstances. In Russia, the level of the compliance of certification criteria varies considerably, and there are vast unprotected invaluable forest areas. The utilisation of these areas should not be based on short-sighted decisions or lack of consensus among stakeholders.