Changes in prescribing patterns of benzodiazepines after training of general practitioners

RESUMO: Introdução: As benzodiazepinas são os fármacos ansiolíticos e hipnóticos mais utilizados. O elevado consumo destes fármacos tem representado uma preocupação devido aos efeitos secundários do seu uso prolongado e dependência. Portugal tem a maior utilização de benzodiazepinas na Europa. Este estudo pretende analisar a alteração do padrão de prescrição de benzodiazepinas após uma intervenção com clínicos gerais. Métodos: A intervenção consistiu numa sessão educacional a um grupo de clínicos gerais. Foi comparado o padrão de prescrição de benzodiazepinas dos médicos intervencionados com o de um grupo de médicos não intervencionado da mesma região e com o de um grupo de médicos não intervencionados de outra região. Analisaram-­‐se as prescrições de 12 meses antes e depois da intervenção. A análise do padrão de prescrição utilizou como metodologia a Dose Diária Definida (DDD) e a Dose Diária Definida por 1000 pacientes por dia (DHD). A análise estatística recorreu a métodos de regressão segmentada. Resultados: Houve uma diminuição no padrão de prescrição de benzodiazepinas no grupo intervencionado após a intervenção (p=0.005). Houve também uma redução no padrão de prescrição no grupo não intervencionada da mesma região (p=0.037) e no grupo não-intervencionado da região diferente (p=0.010). Analisando por género, prescritores do género feminino prescrevem uma quantidade maior de benzodiazepinas. Os clínicos gerais do género feminino intervencionados tiveram a maior redução na prescrição após a intervenção (p=0.008). Discussão: Os dados demonstraram que a intervenção reduziu a prescrição de benzodiazepinas após a intervenção. A diminuição geral do padrão de prescrição poderá ser explicada pelo efeito de Hawthorne ou pela contaminação entre os três grupos de clínicos gerais. Os dados disponíveis não explicam as diferenças nos padrões de prescrição por género. Conclusão: Este estudo demonstra como uma única intervenção tem um impacto positivo na melhoria dos padrões de prescrição. A replicação desta intervenção poderá representar uma oportunidade para alterar a prescrição de benzodiazepinas em Portugal. -----------------------------ABSTRACT: Introduction: Benzodiazepines are the most utilized anxiolytic and hypnotic drugs. The high consumption of benzodiazepines has been a concern due to the reported side effects of long-­‐term use and dependence. Portugal has the highest benzodiazepine utilisation in Europe. This study aims to analyse the change in General Practitioners’ (GPs) benzodiazepine prescription pattern after na intervention period. Methods: An educational session was delivered to a group of intervened GPs. The benzodiazepine prescription pattern of the intervened group was compared to the pattern of a non-­‐intervened matched group from the same region, and to the pattern of another non-­‐intervened matched group from a diferente region. The research time frame was 12 month before and after intervention. The analysis of the prescription trends used the Defined Daily Dose (DDD) and Defined Daily Dose per 1000 patients per day (DHD) methodology. The statistical methods consisted of segmented regression analysis. Results: There was a decrease in benzodiazepine prescription pattern of intervened GPs after intervention (p=0.005). There was also a decrease in benzodiazepine prescription pattern for the non-­‐intervened group from the same region (p=0.037) and for the non-­‐ intervened group from a diferente region (p=0.010). Concerningthe analysis by gender, female gender prescribed a higher amount of benzodiazepines. The intervened female gender prescribers presented the highest decrease in prescription trend after intervention (p=0.008). Discussion: The data demonstrated that the intervention was effective in reducing benzodiazepine prescription after intervention. The general decrease in prescription trend might be explained by a Hawthorne effect or a contamination effect between the three groups of GPs. The available data couldn´t explain the diferences in prescription patterns by gender. Conclusion: This study demonstrates how a single intervention has a positive impact on improving prescription trends. The replication of this intervention might be an opportunity to changing the worrying benzodiazepine utilisation in Portugal.

Sexual dysfunction and dissatisfaction in chronic hepatitis C patients

IntroductionThe prevalence of sexual dysfunction (SD) and dissatisfaction with sexual life (DSL) in patients with chronic hepatitis C virus infection (CHC) was jointly investigated via a thorough psychopathological analysis, which included dimensions such as fatigue, impulsiveness, psychiatric comorbidity, health-related quality of life (HRQL) and sociodemographic and clinical characteristics.MethodsMale and female CHC patients from an outpatient referral center were assessed using the Brief Fatigue Inventory, the Barrat Impulsiveness Scale, the Beck Depression Inventory (BDI), the Hospital Anxiety and Depression Scale, the Hamilton Anxiety Scale (HAM-A), and the World Health Organization Quality of Life Scale-Brief Version (WHOQOL-BREF). Structured psychiatric interviews were performed according to the Mini-International Neuropsychiatric Interview. SD was assessed based on specific items in the BDI (item 21) and the HAM-A (item 12). DSL was assessed based on a specific question in the WHOQOL-BREF (item 21). Multivariate analysis was performed according to an ordinal linear regression model in which SD and DSL were considered as outcome variables.ResultsSD was reported by 60 (57.1%) of the patients according to the results of the BDI and by 54 (51.4%) of the patients according to the results of the HAM-A. SD was associated with older age, female gender, viral genotype 2 or 3, interferon-α use, impulsiveness, depressive symptoms, antidepressant and benzodiazepine use, and lower HRQL. DSL was reported by 34 (32.4%) of the patients and was associated with depressive symptoms, anxiety symptoms, antidepressant use, and lower HRQL.ConclusionsThe prevalence of SD and DSL in CHC patients was high and was associated with factors, such as depressive symptoms and antidepressant use. Screening and managing these conditions represent significant steps toward improving medical assistance and the HRQL of CHC patients.

Synthesis and characterization of C3-symmetric 1,3,5 - Benzenetricarboxamide derived supramolecular systems

The aim of this work was to study the self-assembly process of C3-symmetric molecules. To accomplish this objective 1,3,5 – benzentricarboxamides (BTA) derivatives were obtained. Five C3-symmetric molecules were synthesized in moderate to good yields (39-72%) using azo-benzene, aniline, benzylamine, tryptophan and tyrosine. The aggregation behavior of the BTA derivatives was probed with 1H-NMR spectroscopy, 1H-1H 2D Nuclear Overhauser Effect Spectroscopy (NOESY) and Diffusion Ordered Spectroscopy (DOSY). These experiments allowed to study the influence of H-bonding groups, aromatic rings, unsaturated bonds and the overall geometry in the molecular self-assembly associated with the different structural patterns present on these molecules. The stacking and large molecule behavior where observed in BTA 1, aniline derivative, BTA 4, tyrosine derivative or BTA 5, tryptophan derivative, with several of those discussed functional groups such as unsaturated bonds and H-bonding groups. BTA 5 was used in a few preliminary interaction studies with glucose and ammonium chloride showing interaction with the ammonium ion.

A negociação no mercado a prazo do MIBEL

This master thesis has been developed during the internship in the Supervision Department of Supervision of the Intermediation and Market Structures of CMVM. My collaboration in such department was mainly focused on the derivatives market of the Iberian Electricity Market (MIBEL). MIBEL embodies two organized markets – the derivatives market in Portugal and the spot market in Spain The trading activity in the derivatives market of MIBEL is processed through the trading platform of the regulated market managed by OMIP, however, much of the negotiation is over-the-counter. The aim of this work is to describe the market from a legal and economic perspective and to analyse the evolution of the negotiation, namely the impact of OTC in the regulated market trading. To achieve this, I propose to analyse also MiFID and EMIR rules over derivative contracts and the role of central counterparties, as they both are important to the discussion. In parallel, we found that OTC transactions are considerably higher than those traded in the regulated market managed by OMIP, those findings can be justified by the contractual relationships based on trust already established between the partiesarties. Nevertheless, since 2011 this trend changed by an increase of the registered OTC. Thereafter, although the parties continued to trade bilaterally, these transactions were registered in a central counterparty in order to eliminate the inherent risks related to the OTC derivatives transactions. This change in the negotiation pattern may also be influenced by the mandatory reporting of transactions imposed by EMIR, that requires for some classes of derivatives the centralized clearing and for all other requires the implementation of risk mitigation techniques.

Fractional pennes' bioheat equation: theoretical and numerical studies

In this work we provide a new mathematical model for the Pennes’ bioheat equation, assuming a fractional time derivative of single order. Alternative versions of the bioheat equation are studied and discussed, to take into account the temperature-dependent variability in the tissue perfusion, and both finite and infinite speed of heat propagation. The proposed bioheat model is solved numerically using an implicit finite difference scheme that we prove to be convergent and stable. The numerical method proposed can be applied to general reaction diffusion equations, with a variable diffusion coefficient. The results obtained with the single order fractional model, are compared with the original models that use classical derivatives.

Fractional bioheat equation

In this work we develop a new mathematical model for the Pennes’ bioheat equation assuming a fractional time derivative of single order. A numerical method for the solu- tion of such equations is proposed, and, the suitability of the new model for modelling real physical problems is studied and discussed

Comparison of different numerical methods for the solution of the time-fractional reaction-diffusion equation with variable diffusion coefficient

In this work we perform a comparison of two different numerical schemes for the solution of the time-fractional diffusion equation with variable diffusion coefficient and a nonlinear source term. The two methods are the implicit numerical scheme presented in [M.L. Morgado, M. Rebelo, Numerical approximation of distributed order reaction- diffusion equations, Journal of Computational and Applied Mathematics 275 (2015) 216-227] that is adapted to our type of equation, and a colocation method where Chebyshev polynomials are used to reduce the fractional differential equation to a system of ordinary differential equations

Photolabile protection for amino acids: studies on the release from novel benzoquinolone cages

The synthesis of a novel fused nitrogen heterocycle, benzoquinolone, for evaluation as a photocleavable protecting group is described for the first time, by coupling to model amino acids (alanine, phenylalanine and glutamic acid). Conversion of the phenylalanine ester conjugate to the thionated derivative was accomplished by reaction with Lawesson’s reagent. Photocleavage studies of the carbonyl and thiocarbonyl benzoquinolone conjugates in various solvents and at different wavelengths (300, 350 and 419 nm) showed that the most interesting result was obtained at 419 nm for the thioconjugate, revealing that the presence of the thiocarbonyl group clearly improved the photolysis rates, giving practicable irradiations times for the release of the amino acids (less than 1 minute).

A new competitive implementation of the electromagnetism-like algorithm for global optimization

The Electromagnetism-like (EM) algorithm is a population- based stochastic global optimization algorithm that uses an attraction- repulsion mechanism to move sample points towards the optimal. In this paper, an implementation of the EM algorithm in the Matlab en- vironment as a useful function for practitioners and for those who want to experiment a new global optimization solver is proposed. A set of benchmark problems are solved in order to evaluate the performance of the implemented method when compared with other stochastic methods available in the Matlab environment. The results con rm that our imple- mentation is a competitive alternative both in term of numerical results and performance. Finally, a case study based on a parameter estimation problem of a biology system shows that the EM implementation could be applied with promising results in the control optimization area.

Uma teoria da justiça libertarista: contribuições de Nozick e Steiner

Dissertação de mestrado em Filosofia Política

Pró-fármacos fotoativáveis do péptido AAPV: síntese e avaliação da libertação controlada por luz

Dissertação de mestrado em Bioquímica Aplicada (área de especialização em Biomedicina)

Vanishing spin stiffness in the spin-1/2 Heisenberg chain for any nonzero temperature

Whether at the zero spin density m = 0 and finite temperatures T > 0 the spin stiffness of the spin-1/2 XXX chain is finite or vanishes remains an unsolved and controversial issue, as different approaches yield contradictory results. Here we explicitly compute the stiffness at m = 0 and find strong evidence that it vanishes. In particular, we derive an upper bound on the stiffness within a canonical ensemble at any fixed value of spin density m that is proportional to m2L in the thermodynamic limit of chain length L → ∞, for any finite, nonzero temperature, which implies the absence of ballistic transport for T > 0 for m = 0. Although our method relies in part on the thermodynamic Bethe ansatz (TBA), it does not evaluate the stiffness through the second derivative of the TBA energy eigenvalues relative to a uniform vector potential. Moreover, we provide strong evidence that in the thermodynamic limit the upper bounds on the spin current and stiffness used in our derivation remain valid under string deviations. Our results also provide strong evidence that in the thermodynamic limit the TBA method used by X. Zotos [Phys. Rev. Lett. 82, 1764 (1999)] leads to the exact stiffness values at finite temperature T > 0 for models whose stiffness is finite at T = 0, similar to the spin stiffness of the spin-1/2 Heisenberg chain but unlike the charge stiffness of the half-filled 1D Hubbard model.

The contribution of phenolic acids to the anti-inflammatory activity of mushrooms: Screening in phenolic extracts, individual parent molecules and synthesized glucuronated and methylated derivatives

In the present study, the ethanolic extracts of fourteen edible mushrooms were investigated for their anti-inflammatory potential in LPS (lipopolysaccharide) activated RAW 264.7 macrophages. Furthermore the extracts were chemically characterized in terms of phenolic acids and related compounds. The identified molecules (p-hydroxybenzoic, p-coumaric and cinnamic acids) and their glucuronated and methylated derivatives obtained by chemical synthesis were also evaluated for the same bioactivity, in order to establish structure-activity relationships and to comprehend the effects of in vivo metabolism reactions in the activity of the compounds. The extracts of Pleurotus ostreatus, Macrolepiota procera, Boletus impolitus and Agaricus bisporus revealed the strongest anti-inflammatory potential (EC50 values 96 ± 1 to 190 ± 6 µg/mL, and also the highest concentration of cinnamic acid (656 to 156 µg/g), which was also the individual compound with the highest anti-inflammatory activity. The derivatives of p-coumaric acid revealed the strongest properties, specially the derivative methylated in the carboxylic group (CoA-M1) that exhibited similar activity to the one showed by dexamethaxone used as anti-inflammatory standard; by contrast, the derivatives of p-hydroxybenzoic revealed the lowest inhibition of NO production. All in all, whereas the conjugation reactions change the chemical structure of phenolic acids and may increase or decrease their activity, the glucuronated and methylated derivatives of the studied compounds are still displaying anti-inflammatory activity.

Magnetoliposomes based on manganese ferrite nanoparticles as nanocarriers for antitumor drugs

Manganese ferrite nanoparticles with a size distribution of 26 ± 7 nm (from TEM measurements) were synthesized by the coprecipitation method. The obtained nanoparticles exhibit a superparamagnetic behaviour at room temperature with a magnetic squareness of 0.016 and a coercivity field of 6.3 Oe. These nanoparticles were either entrapped in liposomes (aqueous magnetoliposomes, AMLs) or covered with a lipid bilayer, forming solid magnetoliposomes (SMLs). Both types of magnetoliposomes, exhibiting sizes below or around 150 nm, were found to be suitable for biomedical applications. Membrane fusion between magnetoliposomes (both AMLS and SMLs) and GUVs (giant unilamellar vesicles), the latter used as models of cell membranes, was confirmed by F¨orster Resonance Energy Transfer (FRET) assays, using a NBD labeled lipid as the energy donor and Nile Red or rhodamine B-DOPE as the energy acceptor. A potential antitumor thienopyridine derivative was successfully incorporated into both aqueous and solid magnetoliposomes, pointing to a promising application of these systems in oncological therapy, simultaneously as hyperthermia agents and nanocarriers for antitumor drugs.

Synthesis of new peptide derivatives that self-assemble into nanostructured hydrogels for biomedical applications

Tese de Doutoramento em Ciências (área de especialização em Química)