Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection.

BackgroundHIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described.MethodsWe measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH.ResultsAmong 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses.ConclusionsHigher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH

Comunidade: objeto coletivo do trabalho das enfermeiras da Estratégia Saúde da Família

Compreender no que concerne a constituição da interação da enfermeira com a comunidade, considerando o(s) sujeito(s) e a(s) finalidade(s) com base na percepção de enfermeiras atuantes na Saúde da Família. Métodos: Estudo exploratório-descritivo utilizando entrevista semiestruturada com análise qualitativa temática com 65 enfermeiras atuantes na Estratégia Saúde da Família, no extremo sul do Brasil, no período de janeiro a julho de 2006. Resultados: Duas abordagens da interação foram evidenciadas: imediata nas entidades coletivas; e mediata, com os demais trabalhadores da equipe. Nas finalidades, emergiram dois objetos de ação: a população na resolutividade e integralidade com enfoque na qualidade da ação, formação de vínculo, prevenção de doenças e promoção da saúde direcionada à autonomia com corresponsabilização; e a equipe na organização do trabalho direcionada à resolutividade da atenção. Conclusões: Enfatiza-se a importância da interação enfermeira-comunidade visando às ações que fortaleçam potencialidades dos indivíduos/grupos e integralidade e resolutividade da assistência pela organização do trabalho.Understanding regarding the establishment of the nurse’s interaction with a community, considering the subject(s), source(s), and purpose(s), based on the perception of nurses working in Family Health. Methods: Exploratory descriptive study with qualitative analysis of themes developed from semi-structured interviews with 65 nurses who worked within the Family Health Strategy in southern Brazil, from January to July 2006. Results: Two approaches for interaction were found: an immediate one in collective entities, and secondarily, with other team members. In the end, two objects of action emerged: on the population in terms of resolution and integrality with focus on quality of action, bond formation, disease prevention and health promotion directed toward autonomy with co-responsibility; and organized team work directed at the resolution of attention. Conclusions: We emphasize the importance of nurse-community interaction in order to develop actions that strengthen capabilities of individuals / groups and completeness of problem solving and assistance for the organization of work.Comprender lo concerniente a la constitución de la interacción de la enfermera con la comunidad, considerando el(los) sujeto(s) y la(s) finalidad(es) con base en la percepción de enfermeras que trabajan en la Salud de la Familia. Métodos: Estudio exploratoriodescriptivo en el que se utilizó la entrevista semi- estructurada con análisis cualitativo temático realizado con 65 enfermeras actuantes en La Estrategia Salud de la Familia, en el extremo sur del Brasil, en el período de enero a julio del 2006. Resultados: Fueron evidenciados dos abordajes de la interacción: inmediata en las entidades colectivas; y mediata, con los demás trabajadores del equipo. En las finalidades, emergieron dos objetos de acción: la población en la resolutividad e integralidad con enfoque en la calidad de la acción, formación de vínculo, prevención de enfermedades y promoción de la salud dirigida a la autonomía con corresponsabilización; y el equipo en la organización Del trabajo dirigida a la resolutividad de la atención. Conclusiones: Se enfatiza la importancia de la interacción enfermera-comunidad con La finalidad de que las acciones fortalezcan las potencialidades de los individuos/grupos y la integralidad y resolutividad de la asistencia por La organización del trabajo

Impact of age at onset and newborn screening on outcome in organic acidurias

To describe current diagnostic and therapeutic strategies in organic acidurias (OADs) and to evaluate their impact on the disease course allowing harmonisation. Datasets of 567 OAD patients from the E-IMD registry were analysed. The sample includes patients with methylmalonic (MMA, n = 164), propionic (PA, n = 144) and isovaleric aciduria (IVA, n = 83), and glutaric aciduria type 1 (GA1, n = 176). Statistical analysis included description and recursive partitioning of diagnostic and therapeutic strategies, and odds ratios (OR) for health outcome parameters. For some analyses, symptomatic patients were divided into those presenting with first symptoms during (i.e. early onset, EO) or after the newborn period (i.e. late onset, LO). Patients identified by newborn screening (NBS) had a significantly lower median age of diagnosis (8 days) compared to the LO group (363 days, p  < 0.001], but not compared to the EO group. Of all OAD patients 71 % remained asymptomatic until day 8. Patients with cobalamin-nonresponsive MMA (MMA-Cbl(-)) and GA1 identified by NBS were less likely to have movement disorders than those diagnosed by selective screening (MMA-Cbl(-): 10 % versus 39 %, p = 0.002; GA1: 26 % versus 73 %, p  < 0.001). For other OADs, the clinical benefit of NBS was less clear. Reported age-adjusted intake of natural protein and calories was significantly higher in LO patients than in EO patients reflecting different disease severities. Variable drug combinations, ranging from 12 in MMA-Cbl(-) to two in isovaleric aciduria, were used for maintenance treatment. The effects of specific metabolic treatment strategies on the health outcomes remain unclear because of the strong influences of age at onset (EO versus LO), diagnostic mode (NBS versus selective screening), and the various treatment combinations used. NBS is an effective intervention to reduce time until diagnosis especially for LO patients and to prevent irreversible cerebral damage in GA1 and MMA-Cbl(-). Huge diversity of therapeutic interventions hampers our understanding of optimal treatmen

Networking across borders for individuals with organic acidurias and urea cycle disorders: the E-IMD consortium

BACKGROUND: Patients with organic acidurias (OAD) and urea cycle disorders (UCD) are at increased risk of disability, impaired quality of life and reduced life expectancy. Clinical care in any one centre is constrained by small patient numbers; and furthermore diagnostic and treatment strategies vary between metabolic centres and countries, resulting in significant inequalities and disparity in patient outcome. AIMS/METHODS: The overall objective of the EU-funded activity 'European registry and network for intoxication type metabolic diseases' (E-IMD) is to collect systematic data to improve the knowledge of these diseases, to develop consensus care guidelines and to provide detailed information materials for families and professionals. RESULTS: Within three years E-IMD has (1) established a network of 87 partners in 25 countries (2) set up a patient registry of more than 1,000 individuals with OAD and UCD, (3) launched a website ( www.e-imd.org ) including detailed information materials in 11 languages, (4) developed guidelines for OAD and UCD, (5) organised two teaching courses and various scientific meetings, (6) extended the IT platform clustering with other inherited metabolic diseases (IMD) and (7) strengthened the collaboration with other international scientific consortia. CONCLUSIONS: E-IMD has made important steps towards improving and sharing knowledge on OAD and UCD and harmonisation of diagnostic and therapeutic strategies. Through the establishment of a modular patient registry, clustering with other IMD and stepwise extension of the network, E-IMD has implemented the core components of a European Reference Network for rare diseases