[Thrombolysis of the middle cerebral artery]

Intravenous thrombolysis (IVT) is the evidence-based treatment of acute ischemic stroke in the first 3 h after symptom onset (IVT 3-4.5 h: off-label use with informed consent of the patient). However, intra-arterial thrombolysis (IAT) results in higher recanalization rates of the middle cerebral artery compared to IVT. Therefore it seems reasonable to apply IAT in addition or instead of IVT up to 6 h after symptom onset.

Rotational atherectomy followed by drug-eluting stent implantation (Rota-DES): a rational approach for complex calcified coronary lesions

Rotational atherectomy has been regaining interest over the last couple of years after it almost has disappeared from most interventional catheterization laboratories for several years due to failure to prove its original concept of improving long term results of percutaneous coronary interventions (PCI) as was repeatedly shown in studies in the 1990s. Its revival coupled the introduction of drug-eluting stents (DES); these devices have led to treating much more complex lesions and high-risk patients by PCI. However, real-world experience suggested that off-label use of DES is associated with a higher rate of early and late stent thrombosis. Therefore, more attention is now being paid to the initial implantation technique of DES including aggressive lesion preparation to facilitate stent delivery and expansion. The limited studies with rot-ablation and DES showed promising results with no long term safety concerns. In these studies, a subtle observation was made suggesting that rot-ablation prior to DES implantation in such lesions may have an add-on effect on long term outcome compared to DES alone. An ongoing multicenter study is investigating such effect among complex calcified coronary lesions. Even if this additive benefit does not prove true, rot-ablation remains an efficient tool for preparing certain lesions to facilitate effective and safe DES implantation. Therefore, interventional training programs should focus on this difficult technique to bridge the gap of experience which resulted from neglecting it for several years. In this regard, dedicated courses at experienced sites as well as medical simulation may be appropriate.

Diagnosis and treatment of peripartum bleeding

Severe peripartum hemorrhage (PPH) contributes to maternal morbidity and mortality and is one of the most frequent emergencies in obstetrics, occurring at a prevalence of 0.5-5.0%. Detection of antepartum risk factors is essential in order to implement preventive measures. Proper training of obstetric staff and publication of recommendations and guidelines can effectively reduce the frequency of PPH and its resulting morbidity and mortality. Therefore, an interdisciplinary expert committee was formed, with members from Germany, Austria, and Switzerland, to summarize recent scientific findings. An up-to-date presentation of the importance of embolization and of the diagnosis of coagulopathy in PPH is provided. Furthermore, the committee recommends changes in the management of PPH including new surgical options and the off-label use of recombinant factor VIIa.

[Safety of treatment with tacrolimus ointment for anterior segment inflammatory diseases]

BACKGROUND: The off-label use of topical tacrolimus (Protopic) for inflammatory external eye diseases is gaining popularity. However, there are no reports on the safety profile of this new treatment option. PATIENTS AND METHODS: We treated six patients with different inflammatory eye diseases with topical tacrolimus (Protopic 0.03 %) as off-label use in addition to the conventional anti-inflammatory treatment. Patients were interviewed for side effects and serum drug concentrations were measured under steady state conditions one hour after topical application of tacrolimus ointment. RESULTS: Two patients reported a slight burning sensation immediately after application, in one patient we found a slight worsening of the dry eye problems. No patient abandoned the treatment due to side effects. Serum drug concentrations remained below the analytical threshold in all cases (< 1.5 ng/ml). CONCLUSIONS: Tacrolimus for the topical treatment of anterior segment inflammatory eye diseases is well tolerated without detectable systemic drug resorption.

Clean intermittent self-catheterization after botulinum neurotoxin type A injections: short-term effect on quality of life

OBJECTIVE: To investigate the hypothesis that the need for clean intermittent self-catheterization after botulinum neurotoxin type A injections is outweighed by the efficacy of this treatment, so that clean intermittent self-catheterization is not a burden for patients with refractory idiopathic detrusor overactivity. METHODS: Women undergoing intradetrusor injections of 200 units botulinum neurotoxin type A for refractory idiopathic detrusor overactivity were evaluated prospectively. Clean intermittent self-catheterization was discussed with all patients and its possible need after botulinum neurotoxin type A treatment. As indicator of quality of life, lower urinary tract symptom distress and effect on daily activities were assessed using the validated Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) before and 4 weeks after receiving botulinum neurotoxin type A injections. RESULTS: Mean age of the 65 women was 51 years, and all voided spontaneously before botulinum neurotoxin type A injections. After botulinum neurotoxin type A treatment, 28 (43%) required clean intermittent self-catheterization. Mean UDI-6 and IIQ-7 scores reduced from 61 to 33 (P<.001) and 62 to 30 (P<.001) in women performing clean intermittent self-catheterization and from 60 to 28 (P<.001) and 64 to 25 (P<.001) in those who did not, respectively. Comparison of quality of life in women performing clean intermittent self-catheterization and in those who did not revealed no significant differences before and after botulinum neurotoxin type A treatment. CONCLUSION: Clean intermittent self-catheterization after botulinum neurotoxin type A intradetrusor injections did not impair quality of life in appropriately informed and selected women in the short term. All patients should be informed of the potential need for clean intermittent self-catheterization after botulinum neurotoxin type A injections, and a willingness to do so should be a prerequisite for this still unlicensed off-label treatment.

Is postmenopausal hormone replacement therapy suitable after a cardio- or cerebrovascular event?

PURPOSE Vascular disease is the leading cause of death in women. One-third of acute events affect women below age 60, when the prevalence of menopausal symptoms is high. This raises the question if hormone replacement therapy (HRT) may be an appropriate treatment for individual women although vascular disease is generally considered a contraindication. METHODS Selective literature search was used for this study. RESULTS In healthy women, HRT increases risks for venous thromboembolism and ischemic stroke, but for cardiovascular disease apparently only beyond 10 years after menopause or 60 years of age. Limited data in women with cardio or cerebrovascular disease have not demonstrated an increased risk for a vascular recurrent event, but for the first year after initiation. In HRT users affected by a cardiovascular event continuation of HRT has not been found to be associated with adverse outcome. Low dose estradiol--preferentially as transdermal patches, if necessary combined with metabolically neutral progestins--appears to convey lower risk. CONCLUSIONS Safety data on HRT in survivors of cardiovascular events or ischemic stroke are limited, but exceptionally increased risk appears to be excluded. If off-label use of HRT is considered to be initiated or continued in women with cardio- or cerebrovascular disease, extensive counseling on the pros and cons of HRT is mandatory.

Is dosing of therapeutic immunoglobulins optimal? A review of a three-decade long debate in europe.

The consumption of immunoglobulins (Ig) is increasing due to better recognition of antibody deficiencies, an aging population, and new indications. This review aims to examine the various dosing regimens and research developments in the established and in some of the relevant off-label indications in Europe. The background to the current regulatory settings in Europe is provided as a backdrop for the latest developments in primary and secondary immunodeficiencies and in immunomodulatory indications. In these heterogeneous areas, clinical trials encompassing different routes of administration, varying intervals, and infusion rates are paving the way toward more individualized therapy regimens. In primary antibody deficiencies, adjustments in dosing and intervals will depend on the clinical presentation, effective IgG trough levels and IgG metabolism. Ideally, individual pharmacokinetic profiles in conjunction with the clinical phenotype could lead to highly tailored treatment. In practice, incremental dosage increases are necessary to titrate the optimal dose for more severely ill patients. Higher intravenous doses in these patients also have beneficial immunomodulatory effects beyond mere IgG replacement. Better understanding of the pharmacokinetics of Ig therapy is leading to a move away from simplistic "per kg" dosing. Defective antibody production is common in many secondary immunodeficiencies irrespective of whether the causative factor was lymphoid malignancies (established indications), certain autoimmune disorders, immunosuppressive agents, or biologics. This antibody failure, as shown by test immunization, may be amenable to treatment with replacement Ig therapy. In certain immunomodulatory settings [e.g., idiopathic thrombocytopenic purpura (ITP)], selection of patients for Ig therapy may be enhanced by relevant biomarkers in order to exclude non-responders and thus obtain higher response rates. In this review, the developments in dosing of therapeutic immunoglobulins have been limited to high and some medium priority indications such as ITP, Kawasaki' disease, Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, myasthenia gravis, multifocal motor neuropathy, fetal alloimmune thrombocytopenia, fetal hemolytic anemia, and dermatological diseases.

Application, tolerance and safety of fondaparinux therapy in a German hospital: a prospective single-centre experience.

INTRODUCTION The pentasaccharide fondaparinux is widely approved for prophylaxis and treatment of thromboembolic diseases and therapy of acute coronary syndrome. It is also used off-label in patients with acute, suspected or antecedent heparin-induced thrombocytopenia (HIT). The aim of this prospective observational cohort study was to document fondaparinux' prescription practice, tolerance and therapy safety in a representative mixed German single-centre patient cohort. PATIENTS AND METHODS Between 09/2008 - 04/2009, 231 consecutive patients treated with fondaparinux were enrolled. Medical data were obtained from patient's records. The patients were clinically screened for thrombosis (Wells score), sequelae of HIT (4T's score), and bleeding complications (ISTH-criteria) and subjected to further assessment (i.e. sonography, HIT-diagnostics), if necessary. The mortality rate was assessed 30 days after therapy start. RESULTS Overall, 153/231 patients had a prophylactic, 74/231 patients a therapeutic, and 4/231 patients a successive prophylactic/therapeutic indication. In 11/231 patients fondaparinux was used due to suspected/antecedent HIT, in 5/231 patients due to a previous cutaneous delayed-type hypersensitivity to heparins. Other indications were rare. Three new/progressive thromboses were detected. No cases of HIT, major bleedings, or fatalities occurred. CONCLUSIONS Fondaparinux was well tolerated and was safe in prophylaxis and therapy; prescriptions mostly followed the current approval guidelines and were rarely related to HIT-associated indications (<5% of prescriptions), which is in contrast to previous study results in the U.S. (>94% of prescriptions were HIT-associated). A trend towards an individualised fondaparinux use based on the compound's inherent properties and the patients' risk profiles, i.e., antecedent HIT, bone fractures, heparin allergy, was observed.

The role of anti-VEGF agents in myopic choroidal neovascularization: Current standards and future outlook

Introduction The global prevalence of pathologic myopia is 0.9-3.1%, and visual impairment is found in 0.1-0.5% of European and 0.2-1.4% of Asian studies. Myopic choroidal neovascularization (mCNV) affects 5.2-11.3% of pathologic myopia patients and is a leading cause of vision impairment in the working-age population. Characteristic morphological changes and visual-acuity decrease are diagnostic features. Vascular-Endothelial-Growth-Factor (VEGF) has been identified as a trigger for pathologic neovascularization in these highly myopic patients. Areas Covered We cover the epidemiology, pathology and diagnostic aspects of mCNV. The history of therapeutic interventions is described, followed by an overview of current standard-of-care (SOC)-blocking VEGF using bevacizumab (off-label), ranibizumab or aflibercept and improving vision up to 13.5-14.4 letters. Despite good efficacy, an unmet medical need remains. We summarize ongoing and future developments of new drugs to treat or potentially cure mCNV. Expert Opinion mCNV is a major global health concern. Early detection and treatment is key for a satisfying outcome. The current SOC, VEGF inhibitors, affords good therapeutic efficacy and reasonable disease stabilization with few intravitreal treatments per year. However, the long-term prognosis is still unsatisfactory, and side-effects like chorioretinal atrophy development are of concern. Therefore, efforts should be intensified to develop more effective therapies.

Expanding Indications of Transcatheter Heart Valve Interventions.

Transcatheter aortic valve replacement (TAVR) has been established as a less invasive alternative to open-heart surgery in inoperable or high-risk patients presenting with symptomatic severe aortic valve stenosis. The feasibility and efficacy of valve-in-valve implantation in degenerated surgical aortic bioprostheses have also been described and can currently be considered a valuable treatment option in patients deemed unsuitable for repeat cardiac surgery. However, the clinical use of TAVR devices is not limited to the treatment of the tricuspid stenotic aortic valve. Several additional indications including treatment of the bicuspid stenotic aortic valve, aortic regurgitation, and valve-in-valve or valve-in-ring implantation in the mitral or tricuspid position as well as treatment of pure mitral, tricuspid, or pulmonary regurgitation have been described. The purpose of the present review is to summarize the available evidence concerning the emerging off-label use of TAVR devices in current clinical practice. Case examples have been selected to highlight the main procedural steps of each particular intervention.

On the Dark Side of Therapies with Immunoglobulin Concentrates: The Adverse Events

Therapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE) profile of IgG concentrates which is, even at life-long need for therapy, excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current good manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times, the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below, we review elements of non-infectious AEs, and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates.

Solución para la delegación de identidad en Sistemas de Gestión de Identidad paneuropeos basada en infraestructuras de certificación y lenguajes formales de asertos de seguridad

La estrategia i2010 de la UE tiene como objetivo garantizar el liderazgo europeo en materia de TIC y poner los beneficios de la Sociedad de la Información al servicio de la economía, la sociedad y la calidad de vida personal, teniendo presente que los éxitos de Europa hasta la fecha se han basado en favorecer la competencia leal en los mercados de las telecomunicaciones y crear un mercado sin fronteras para contenidos y medios de comunicación digitales. En esta línea, la Comisión Europea ha establecido que los distintos estados miembros deben contribuir activamente al desarrollo y uso seguro de los servicios telemáticos entre sus ciudadanos. Más concretamente, atribuye a las Administraciones Públicas, tanto a nivel nacional, regional como local, un papel dinamizador de la Sociedad de la Información que les obliga a ofrecer paulatinamente todos los actos administrativos a los ciudadanos a través de Internet. Como primer paso para el uso seguro de los servicios telemáticos que ofrecen las instituciones públicas se hace preciso dotar a los ciudadanos de una identidad digital que les permita identificarse ante un Proveedor de Servicio o ante otros ciudadanos de manera inequívoca. Por esta razón, la mayoría de países europeos – y otros en el resto del mundo – están promoviendo, sistemas fiables de gestión de identidad electrónica (eIDM), de tal manera que los ciudadanos, las empresas y departamentos gubernamentales (incluso en Estados miembros diferentes) pueden identificar y certificar sus operaciones con precisión, rapidez y sencillez. Sin embargo, la gestión de esta identidad por las Administraciones Públicas supone un importante desafío, acentuado cuando se hace necesaria la interoperabilidad entre Administraciones de diferentes países, puesto que personas y entidades tienen credenciales de identificación diferentes en función de su propio marco jurídico nacional. Consciente del problema, en la Unión Europea se han puesto en marcha una serie de proyectos con el objetivo de conseguir la interoperabilidad de los eIDMs entre las instituciones públicas de diferentes Estados miembros. A pesar de ello, las soluciones adoptadas hasta la fecha son insuficientes porque no prevén todos los posibles casos de interacción del usuario con las instituciones. En concreto, no tienen en cuenta un aspecto muy importante que se ofrece en los distintos sistemas jurídicos nacionales, a saber, la delegación de la identidad, mediante la cual un ciudadano puede autorizar a otro para que actúe en su nombre para acceder a determinados servicios prestados por las instituciones públicas. En esta tesis se realizan un conjunto de aportaciones que dan solución a distintos aspectos de los problemas planteados y que, de forma conjunta, permiten la interoperabilidad y la delegación de identidad en determinados Sistemas de Gestión de Identidad aplicados al entorno de las Administraciones Públicas. En el caso de la delegación, se ha definido un sistema de delegación dinámica de identidad entre dos entidades genéricas que permite solucionar el problema del acceso delegado a los servicios telemáticos ofrecidos por las Administraciones Públicas. La solución propuesta se basa en la generación de un token de delegación, constituido a partir de un Certificado Proxy, que permite a la entidad que delega establecer la delegación de identidad en otra entidad en base a un subconjunto de sus atributos como delegador, estableciendo además, en el propio token de delegación, restricciones en el conjunto de servicios accesibles a la entidad delegada y el tiempo de validez de la delegación. Adicionalmente, se presentan los mecanismos necesarios tanto para poder revocar un token de delegación como para comprobar sin un token de delegación ha sido o no revocado. Para ello se propone una solución para la identificación unívoca de tokens de delegación y la creación de una nueva entidad denominada Autoridad de Revocación de Tokens de Delegación. Entre las características del sistema de delegación propuesto destaca el que es lo suficientemente seguro como para ser utilizado en el entorno de la Administración Pública, que no requiere el uso de mecanismos off‐line para la generación de la delegación y que se puede realizar la delegación de forma instantánea y sin la necesidad de trámites complejos o la participación de un elevado número de entidades. Adicionalmente, el token de delegación propuesto es perfectamente integrable en las infraestructura de clave pública actual lo que hace que, dado que gran parte de las Administraciones Públicas europeas basan sus sistemas de identidad digital en el uso de la PKI y certificados de identidad X.509, la solución pueda ser puesta en marcha en un entorno real sin necesidad de grandes cambios o modificaciones de comportamiento. En lo referente a la interoperabilidad, se realiza un análisis exhaustivo y la correspondiente evaluación de las principales propuestas de Sistemas de Gestión de Identidad orientados a conseguir la interoperabilidad realizadas hasta la fecha en el marco de la Unión Europea y se propone, a alto nivel, una arquitectura de interoperabilidad para la gestión de identidad en las Administraciones Públicas. Dicha arquitectura es lo suficientemente genérica como para poder ser aplicada tanto en el entorno pan‐Europeo como en los entornos nacionales, autonómicos y locales, de tal forma que la interoperabilidad en la gestión de la identidad esté garantizada en todos los niveles de la Administración Pública. Por último, mediante la integración de la solución de delegación dinámica de identidad y la arquitectura de interoperabilidad propuestas se presenta una solución al problema de la delegación en un escenario pan‐Europeo de gestión de identidad, dando lugar a una arquitectura global de interoperabilidad pan‐Europea con soporte a la delegación de identidad. SUMMARY The i2010 European Union Plan aims to ensure European leadership in ICT and to promote the positive contribution that information and communication technologies can make to the economic, social and personal quality of life, bearing in mind that, to date, success in Europe has been based on promoting fair competition in telecommunications markets and on creating a borderless market for contents and digital media. In this line, the European Commission has established that the different member states should contribute actively to the development and secure use of telematic services among their citizens. More specifically, it is attributed to national, regional and local Public Administrations to have a supportive role of the Information Society, requiring them to gradually provide the citizens with Internet‐based access to all administrative procedures acts. As a first step for the secure use of telematic services offered by public institutions, it is necessary to provide the citizens with a digital identity to enable them to identify themselves unequivocally to a Service Provider or to other citizens. For this reason, most European countries ‐ and others in the rest of the world ‐ are promoting reliable systems for managing electronic identity (eIDM), so that citizens, businesses and government departments (even in different Member States) can identify and certify their operations with precision, speed and simplicity. However, the identity management by Public Administrations is a major challenge that becomes more difficult when interoperability between administrations of different countries is needed, due to the fact that individuals and entities have different identification credentials according to their own national legal framework. Aware of the problem, the European Union has launched a series of projects with the aim of achieving interoperability of eIDMs between public institutions of different Member States. However, the solutions adopted to date are insufficient because they do not foresee all possible cases of user interaction with the institutions. In particular, solutions do not take into account a very important aspect that is offered in different national legal systems, namely, the delegation of identity, by which a citizen can authorize another to act on his/her behalf to access certain services provided by public institutions. In this thesis a collection of contributions that provide solution to different aspects of the aforementioned problems are carried out. The solutions, in global, enable interoperability and identity delegation in some of the Identity Management Systems applied to Public Administration environment. In the case of delegation, a dynamic identity delegation system between generic entities is defined. This system makes it possible to solve the problem of delegated access to telematic services offered by Public Administrations. The proposed solution is based on the generation of a piece of information called delegation token. This delegation token, derived from a Proxy Certificate, allows the establishment of identity delegation by an entity that delegates (delegator) in other entity (delegatee) making use of a subset of delegator attributes. It also establishes restrictions on services that can be used by the delegated entity and the expiry date of delegation. In addition to this, the mechanisms necessary to revoke and check the revocation status of a delegation token are presented. To do this, a solution to univocally identify delegation tokens and the creation of a completely new entity, called Token Delegation Revocation Authority, are proposed. The most remarkable characteristics of the proposed delegation system are its security, enough for it to be used in the Public Administration environment, the fact that it does not require off‐line processes in order to generate the delegation, and the possibility of performing the delegation instantaneously and without neither complex processes nor the intervention of a large number of entities. The proposed delegation token can be completely incorporated into current Public Key Infrastructure (PKI). Thus, since most of the European Public Administrations base their digital identity systems on PKI and X.509 identity certificates, the solution can be adopted in a real environment without great changes or performance modifications. Regarding interoperability, an exhaustive analysis and evaluation of most significant proposals on Identity Management Systems that aim to achieve interoperability carried out in the European Union framework until now are performed. A high level identity management interoperability architecture for Public Administrations is also proposed. This architecture is sufficiently generic to be applied to both pan‐European environment and national, regional or local environments, thus interoperability in identity management at all Public Administration levels is guaranteed. Finally, through the integration of the proposed dynamic identity delegation solution and the high level interoperability architecture, a solution to the problem of identity delegation in a pan‐European identity management environment is suggested, leading to a pan‐European global interoperability architecture with identity delegation support.

Desigualdades en salud en poblaciones inmigradas a España. Una revisión de la literatura

Antecedentes/Objetivos: Tras el crecimiento de la inmigración extranjera de la pasada década, este estudio tiene como objetivo analizar la evidencia científica generada en los últimos quince años sobre la salud de la población inmigrante en España que aborda la influencia de determinantes sociales y/o las desigualdades en comparación con la población española. Métodos: Se realizó un estudio de revisión mediante la metodología de scoping review y se efectúo una búsqueda de la literatura científica publicada desde 1998 hasta 2013 en España. Se consultaron las bases de datos de medline y medes. Se combinaron 3 filtros temáticos: a) desigualdades sociales: se utilizó el propuesto por Borrell y Malmusi (Informe SESPAS 2010); b) inmigración: términos MeSH Emigrants and Immigrants, Emigration and Immigration, Transients and Migrants, Ethnic Groups; c) España: se utilizó el desarrollado por Valderas et al. (Rev Esp Cardiol 2006). Se seleccionaron estudios sobre desigualdades sociales en salud con población inmigrante procedente de países tales como Latinoamérica, África, Asia o Europa del Este. Resultados: Se seleccionaron 27 artículos. La mayoría fueron publicados en los años 2009 y 2010 (n = 17). Doce utilizaron encuestas poblacionales de salud de ámbito nacional (n = 6) y autonómicas (n = 6). Un total de 23 se centraron en población adulta mayor de 15 años. Los indicadores más frecuentemente analizados fueron el estado de salud percibido (n = 9) y la salud mental (n = 7). La población inmigrante está expuesta a determinantes sociales más desfavorables que la autóctona (clase social, renta, condiciones de empleo y trabajo, apoyo social, discriminación). A pesar de una menor prevalencia de enfermedades crónicas, parece presentar mayores problemas de salud mental y peor percepción de salud, sobretodo en mujeres y a mayor tiempo de estancia. También se reportan menores prevalencias de tabaquismo y consumo de alcohol, uso de fármacos y menor mortalidad, así como mayor sedentarismo y obesidad, sobre todo en mujeres, y violencia del compañero íntimo. Conclusiones: Los estudios exploran un amplio abanico de indicadores de salud en población adulta e infantil. A pesar de su recién llegada, las peores condiciones de vida se traducen en desigualdades sociales en la salud que afectan a la población inmigrante. Se detectan algunas lagunas de conocimiento y aspectos metodológicos a mejorar. Se hace necesario analizar la evolución de estas desigualdades en el nuevo contexto económico y considerando el previsible deterioro del efecto inmigrante sano.

Utilização de agentes biológicos no tratamento do lúpus eritematoso cutâneo

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Os inibidores orais do fator Xa na prevenção de eventos cerebrovasculares em doentes com fibrilhação auricular não-reumática

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014