O efeito da descontinuação dos corticóides inalados em doentes com Doença Pulmonar Obstrutiva Crónica — O estudo COPE

RESUMO: Os autores desenharam um estudo duplamente cego para investigar o efeito da descontinuação do propionato de fluticasona (PF) nas exacerbações e qualidade de vida em doentes com DPOC (estudo COPE).Durante 4 meses, 244 doentes com DPOC foram medicados com propionato de fluticasona (1000 (g /dia).A selecção dos doentes baseou se em critérios clínicos e funcionais e idade compreendida entre os 40 e os 75 anos. Após este período de tempo, 123 doentes mantiveram o tratamento com PF e 121 doentes receberam placebo durante 6 meses. As visitas de controlo ocorreram aos 3 e 6 meses, tendo os doentes sido avaliados do ponto de vista funcional e clínico. Os critérios analisados no estudo foram o número, gravidade e intervalo de tempo entre as exacerbações, a qualidade de vida (questionário respiratório de St Georgeâs), parâmetros funcionais respiratórios (espirometria) e tolerância ao esforço (prova de 6 minutos de marcha standardizada).Na análise dos resultados, os autores demonstraram que no grupo medicado com PF, 47% dos doentes sofreram pelo menos uma agudização, em contraste dos 57 % do grupo placebo. No grupo placebo, 21 % dos doentes apresentaram exacerbações recorrentes e rápidas, ao contrário dos 6% de doentes medicados com PF. Em termos de qualidade de vida, uma diferença significativa ocorreu também entre os 2 grupos, a nível do score total, actividade e sintomas.Não se verificaram diferenças na prova de marcha entre os 2 grupos avaliados. O estudo funcional mostrou uma diferença significativa de 38 ml de VEMS pós-broncodilatação, a favor do grupo medicado com FP.Este estudo indica que a descontinuação de PF em doentes com DPOC está associada a um mais rápido início e recorrência de agudização, bem como uma deterioração maior da qualidade de vida. COMENTÃRIO: Estima-se que a DPOC constitua a 5.ª doença mais frequente e a 4.ª causa de morte a nível mundial.Não existindo cura para esta doença, a terapêutica assenta fundamentalmente na broncodilatação e na evicção tabágica.Sabe se que apesar de a DPOC ser uma doença inflamatória crónica das vias aéreas, os corti cóides inalados (CI) não modificam o declínio mais acelerado do VEMS constatado na DPOC.Múltiplos estudos foram efectuados tendo como um dos objectivos determinar a validade da utilização de CI na DPOC, dos quais se salienta:O estudo EUROSCOP revela eficácia reduzida e transitória do budesonido; o estudo ISOLDE mostrou uma pequena redução no declínio do VEMS, um menor número de exacerbações e score sintomático, em doentes com DPOC grave tratados com fluticasona e o estudo COPENHAGEN não demonstrou qualquer beneficio do budesonido na DPOC ligeira e moderada.O projecto GOLD considera os CI como fármacos de 2.ª linha no tratamento da DPOC, mas refere também uma melhoria sintomática, uma redução no número e gravidade das exacerbações e melhoria da qualidade de vida.Este estudo vem exactamente reforçar o efeito benéfico dos CI em doentes com DPOC a nível da qualidade de vida e frequência e gravidade das agudizações, assim como o agravamento destes parâmetros após a suspensão dos CI. Palavras-chave: Corticóides inalados, DPOC, Qualidade de vida, Exacerbaçã

Personality and local brain structure: Their shared genetic basis and reproducibility

Local cortical architecture is highly heritable and distinct genes are associated with specific cortical regions. Total surface area has been shown to be genetically correlated with complex cognitive capacities, suggesting cortical brain structure is a viable endophenotype linking genes to behavior. However, to what extend local brain structure has a genetic association with cognitive and emotional functioning is incompletely understood. Here, we study the genetic correlation between personality traits and local cortical structure in a large-scale twin sample (Human Connectome Project, n ​= ​1102, 22-37y) and we evaluated whether observed associations reflect generalizable relationships between personality and local brain structure two independent age-matched samples (Brain Genomics Superstructure Project: n ​= ​925, age ​= ​19-35y, enhanced Nathan Kline Institute dataset: n ​= ​209, age: 19-39y). We found a genetic overlap between personality traits and local cortical structure in 10 of 18 observed phenotypic associations in predominantly frontal cortices. However, we only observed evidence in favor of replication for the negative association between surface area in medial prefrontal cortex and Neuroticism in both replication samples. Quantitative functional decoding indicated this region is implicated in emotional and socio-cognitive functional processes. In sum, our observations suggest that associations between local brain structure and personality are, in part, under genetic control. However, associations are weak and only the relation between frontal surface area and Neuroticism was consistently observed across three independent samples of young adults

Predictors for adherence to action plans for self-treatment of COPD exacerbations

Introduction/Aim: A minority of patients with chronic obstructive pulmonary disease (COPD) derives benefit fromself-management interventions that include action plans for self-treatment of COPD exacerbations. The aimof this studywas to identify predictors for adherence to action plans for self-treatment of exacerbations in COPD patients. Methods: Self-reported diary data from a subset of COPD patients who participated in a randomized controlled trial (COPE-II study) in the Netherlands was used to assess adherence to COPD action plans within a self-management intervention. Only patients with exacerbations were included. Successful self-treatment was defined as self-initiating a course of oral steroids/antibiotics within 2 days from the start of an exacerbation. A patient was defined as being adherent when in ≥75% of all exacerbations the self-treatment action plan was followed. Patient-level factors that showed a univariate association (P <0.10) with adherence were included in a multivariate logistic regression model to identify the predictors for adherence toCOPD self-treatment action plans (P <0.05). Results: Data from 66 patients (mean age 63.6 ± 8.0;men 56.1%) showed 387 exacerbations within 2 years of follow-up. Adherence to the action plans was observed in 37.9% of the patients and in 216 COPD exacerbations. Multivariate logistic regression analyses showed that being male (OR: 5.1; 95% CI: 1.5-17.3) and having no walking problems (EQ5D mobility, OR: 4.9; 95%CI: 1.5-16.4) were positively associatedwith being adherent to the action plan for self-treatment of COPD exacerbations. Conclusion: Our study results indicate that being male and having no walking problems are predictors for better adherence to COPD exacerbation action plans. This implies that exploring patients' mobility and offering more support to femaleCOPDpatients who are lessmobilemay positively influence the adherence to COPD exacerbation self-treatment action plans. More research is, however, required to confirm this

Candesartan Mediated Amelioration of Cisplatin-Induced Testicular Damage Is Associated with Alterations in Expression Patterns of Nephrin and Podocin

Nephrin and podocin are known to be closely related to the pharmacological effects of angiotensin-II receptor blocker (ARB). The objectives of this study were to investigate the role of nephrin and podocin using cisplatin-induced testicular damage and to evaluate the effect of ARB. At first, we evaluated the effects of cisplatin either alone or in combination with ARB candesartan on changes in expression patterns of nephrin and podocin in the rat testes. We then conducted in vitro studies to investigate the effects of angiotensin using cultured Sertoli cells, line TM4. As a result, the expression of nephrin and podocin was shown to localize around the basal membrane of seminiferous tubules. Treatment with cisplatin resulted in a marked decrease in the expression of nephrin and podocin and induced a shift of both proteins from linear to granular expression patterns, accompanying the increased apoptotic index in the testes; these changes were partially restored by the additional administration of candesartan. In vitro studies with TM4 revealed the angiotensin-II mediated expression changes of nephrin and podocin. These findings suggest that candesartan can prevent cisplatin-induced testicular damage by regulating expression patterns of the nephrin-podocin complex in the testes

An Evaluative Model to Assess the Organizational Efficiency in Training Corporations

In an organisation any optimization process of its issues faces increasing challenges and requires new approaches to the organizational phenomenon. Indeed, in this work it is addressed the problematic of efficiency dynamics through intangible variables that may support a different view of the corporations. It focuses on the challenges that information management and the incorporation of context brings to competitiveness. Thus, in this work it is presented the analysis and development of an intelligent decision support system in terms of a formal agenda built on a Logic Programming based methodology to problem solving, complemented with an attitude to computing grounded on Artificial Neural Networks. The proposed model is in itself fairly precise, with an overall accuracy, sensitivity and specificity with values higher than 90 %. The proposed solution is indeed unique, catering for the explicit treatment of incomplete, unknown, or even self-contradictory information, either in a quantitative or qualitative arrangement

Usability, acceptability, and self-reported impact of an innovative hepatitis C risk reduction intervention for men have sex with men: A mixed methods study

Hepatitis C virus (HCV) elimination among men who have sex with men (MSM) is unlikely to be feasible without effective behavioural interventions. We developed a multilevel intervention to reduce HCV transmission among MSM in Amsterdam. The intervention includes a toolbox to facilitate risk reduction among MSM and support health care professionals in risk reduction counselling. To assess the use of the toolbox and its impact on behavior, we conducted a mixed-methods study. We collected data through online questionnaires (n = 49), and in-depth interviews with MSM at risk of HCV (n = 15) and health care professionals (n = 7). We found that the toolbox has been well received by MSM, increased awareness of HCV risks and has facilitated preventive behaviours and risk-reduction communication with peers. Professionals reported the toolbox to be a useful aid for discussions about HCV risk and risk reduction strategies with their clients