Toxic effects of mercury, lead and gadolinium on vascular reactivity

Heavy metals have been used in a wide variety of human activities that have significantly increased both professional and environmental exposure. Unfortunately, disasters have highlighted the toxic effects of metals on different organs and systems. Over the last 50 years, the adverse effects of chronic lead, mercury and gadolinium exposure have been underscored. Mercury and lead induce hypertension in humans and animals, affecting endothelial function in addition to their other effects. Increased cardiovascular risk after exposure to metals has been reported, but the underlying mechanisms, mainly for short periods of time and at low concentrations, have not been well explored. The presence of other metals such as gadolinium has raised concerns about contrast-induced nephropathy and, interestingly, despite this negative action, gadolinium has not been defined as a toxic agent. The main actions of these metals, demonstrated in animal and human studies, are an increase of free radical production and oxidative stress and stimulation of angiotensin I-converting enzyme activity, among others. Increased vascular reactivity, highlighted in the present review, resulting from these actions might be an important mechanism underlying increased cardiovascular risk. Finally, the results described in this review suggest that mercury, lead and gadolinium, even at low doses or concentrations, affect vascular reactivity. Acting via the endothelium, by continuous exposure followed by their absorption, they can increase the production of free radicals and of angiotensin II, representing a hazard for cardiovascular function. In addition, the actual reference values, considered to pose no risk, need to be reducedResearch supported by CAPES and CNPq/FAPES/ FUNCITEC (#39767531/07), Brazil, and MCINN (#SAF 2009-07201) and ISCIII (Red RECAVA, #RD06/0014/0011), Spai

Comparative effectiveness of adalimumab and etanercept for rheumatoid arthritis in the Brazilian Public Health System

Aim: Biological disease-modifying antirheumatic drugs (bDMARDs) are used to treat rheumatoid arthritis (RA) with adalimumab and etanercept the most used bDMARDs in Brazil. This open prospective cohort study evaluated their effectiveness and safety among RA patients in the Brazilian Public Health System given their costs. Methods: The Clinical Disease Activity Index was primarily used to assess their effectiveness after 6 and 12 months of follow-up. The Health Assessment Questionnaire and EuroQol-5D were also used. Results: A total of 266 RA patients started treatment with adalimumab or etanercept. Adalimumab was the most widely used bDMARD (70%). In total, 46% achieved remission or low-disease activity at 12 months with no difference in effectiveness between them (p = 0.306). bDMARDs were more effective in patients who had better functionality at treatment onset and had spent longer in education. Conclusion: This real-world study demonstrated that adalimumab and etanercept are equal alternatives for RA treatment and both were well tolerated

Profile of patients with rheumatic diseases undergoing treatment with anti-TNF agents in the Brazilian Public Health System (SUS), Belo Horizonte - MG

The aim of this study was to describe the baseline demographic and clinical characteristics as well as the functional status of a prospective cohort of patients with rheumatic diseases assisted by the Brazilian Public Health System (SUS). Data for 302 patients receiving tumor necrosis factor α inhibitors (anti-TNF agents) was collected through a standard form. Among patients, 229 (75.8%) were female and 155 (51.3%) were Caucasian; the mean age was 50.3 ± 12.8 years, and the mean disease duration was 9.9 ± 8.7 years. Among them 214 patients (70.9%) received adalimumab, 72 (23.8%) etanercept, and 16 (5.3%) infliximab. Mean Health Assessment Questionnaire-Disability Index (HAQ-DI) was 1.37 ± 0.67 for all participants. Poor functional response was associated with female gender, married patients and with a score of &lt; 0.6 on the EuroQoL-5 dimensions (EQ-5D). Significant correlation was found between the HAQ-DI values, disease activity and quality of life (QOL). The results obtained in this study contribute to a better understanding of the clinical and demographic characteristics of patients with rheumatic diseases at the beginning of anti-TNF-agent treatment by SUS. Furthermore, our findings are consistent with another Brazilian and foreign cross-sectional investigations. This knowledge can be of great importance for further studies evaluating the effectiveness of biological agents, as well as, to contribute to improve the well-being of the patients with rheumatic diseases.O objetivo do estudo foi descrever as características demográficas e clínicas iniciais, bem como o estado funcional de uma coorte de pacientes com doenças reumáticas tratados pelo Sistema Único de Saúde (SUS). Dados de 302 pacientes em uso de inibidores do fator de necrose tumoral (agentes anti-TNF) foram coletados por formulário padronizado. Desses, 229 (75.8%) eram mulheres e 155 (51.3%) eram brancos; a idade média foi 50,3 ± 12,8 anos, e a duração média da doença foi de 9,9 ± 8,7 anos. Entre os pacientes 214 (70,9%) usaram adalimumabe, 72 (23,8%) etanercepte e 16 (5,3%) infliximabe. A média do Health Assessment Questionnaire-Disability Index (HAQ-DI) foi 1,37 ± 0,67 para a população total. Pior resposta funcional estava associada com mulheres, pacientes casados e com um valor de EuroQoL-5 dimensions (EQ-5D) < 0.6. Correlação significativa foi obtida entre os valores de HAQ-DI, atividade das doenças e qualidade de vida. Os resultados obtidos no estudo contribuem para o melhor entendimento das características clínicas e demográficas de pacientes com doenças reumáticas iniciando a terapia com agentes anti-TNF pelo SUS. Além disso, nossos achados são consistentes com resultados obtidos em outros estudos transversais nacionais e estrangeiros. Este conhecimento pode ser de grande importância para estudos futuros que avaliem a eficácia de agentes biológicos, assim como, para contribuir para a melhoria do bem-estar das pessoas com doenças reumáticas

Acidose metabólica e o estado nutricional de pacientes em hemodiálise

Introduction: The prevalence of malnutrition in hemodialysis (HD) is high, being a marker of poor prognosis in chronic kidney disease. Metabolic acidosis is common on dialysis, and has been associated with mortality. Objectives: To evaluate metabolic acidosis and the nutritional status of HD patients. Methods: A cross-sectional study was carried out in a single HD center. Data were collected from medical records, and the presence of metabolic acidosis and the nutritional status of the patients were verified by anthropometric and biochemical indicators. Results: The total sample of 63 patients, 54% male and 46% female, with 58.7% between 45 and 64 years. The mean dialysis time was of 5.4 years. The mean value of the body mass index (BMI) was 24.9kg/m2, and the mean value of albumin was 3.9g/dL. The prevalence of metabolic acidosis was of 77.8%. There was a negative linear correlation between bicarbonate and creatinine, without correlation with anthropometric and albumin indicators. Patients malnourished according to the BMI corresponded to 55.5% of the total sample and gained more interdialytic weight. Out of the total sample, 14.2% of the patients were classified as malnourished by the arm circumference index, and albumin &lt; 4.0 g/dL was observed in 49.2% of the patients. Serum creatinine was higher in male patients aged between 45 and 64 years old. No difference in time on hemodialysis was observed regarding age, interdialytic weight gain, laboratory, and anthropometric measures. Conclusion: The prevalence of metabolic acidosis was high, and there was no correlation with the nutritional status. Bicarbonate &lt; 22 mEq/L was correlated with higher creatinine values, but was unrelated to the nutritional status. The nutritional assessment by BMI was in agreement with the Brazilian literature, and albumin indicated elevated malnutrition

Discontinuation, persistence and adherence to subcutaneous biologics delivered via a homecare route to Scottish adults with rheumatic diseases: a retrospective study

ObjectivesTo understand patterns of subcutaneous (SC) biologics use over time in adults with inflammatory rheumatic musculoskeletal diseases receiving a homecare delivery service.DesignRetrospective cohort.SettingPatients in secondary care receiving SC biologics in the largest Scottish Health Board.ParticipantsA new bespoke cohort was created from routine data gathered as part of a health board Homecare Service Database. Patients over 18 years who received a supply of SC biologic from January 2012 to May 2015 with a diagnosis for rheumatoid arthritis (RA), psoriatic arthritis (PsA) or ankylosing spondylitis (AS) were included.Outcomes measuredA standardised framework was applied by measuring discontinuation rates, persistence using Kaplan-Meier analysis and Cox regression and adherence using medication refill adherence (MRA) and compliance rate (CR).Results751 patients were identified (AS: 105, PsA: 227, RA: 419) of whom 89.3% had more than one biologic delivery (median days’ follow-up: AS: 494; PsA: 544; RA: 529) and 83.2% did not switch biologic. For all conditions, approximately half were persistent on their index biologic (52% AS, 54% PsA, 48%RA). Of patients who discontinued treatment, the majority reinitiated with the same biologic (19% AS, 18% PsA and 21% RA). Overall adherence during the period of treatment was over 80% when calculated using MRA (median %MRA: AS: 84.0%, PsA: 85.0%, RA: 82.4%) or CR (median %CR: AS: 96.6%, PsA: 97%, RA: 96.6%).ConclusionUse of linked routine data is a sustainable pathway to enable ongoing evaluation of biologics use. A more consistent approach to studying use (discontinuation, persistence and adherence metrics) should be adopted to enable comparability of studies.</jats:sec

Ten-year kidney transplant survival of cyclosporine- or tacrolimus-treated patients in Brazil

Background: Cyclosporine and tacrolimus are well established immunosuppressants; however little know about long term survival rates. Aim: Compare 10-year graft survival and associated factors among kidney transplant patients within the Brazilian Public Health system (SUS) prescribed either medicine. Methods: Analyze a national cohort of kidney transplant recipients within SUS. Graft loss defined by death or dialysis for more than three months. Kaplan-Meier method used to estimate cumulative probabilities of survival. Cox proportional hazards model used to evaluate factors associated with progression to graft loss. Results: 13,811 patients were included, 5,887 used cyclosporine and 7,924 tacrolimus. A higher risk of graft loss was associated with tacrolimus, a deceased donor, additional years of age, median period of dialysis greater than 47 months, diagnosis of diabetes as the primary cause of chronic kidney disease and transplantation between 2005 and 2009. Conclusions: Among other factors, tacrolimus-based regimens were associated with worse graft survival

Processo para modificar a biomassa de segunda geração e bio-óleo pelo referido processo

DepositadaRefere-se a um processo para modificar a biomassa de segunda geração utilizando tratamentos de hidrólise e acilação combinados à irradiação de micro-ondas, provendo produtos líquidos denominados bio-óleos de acilação (BIOAC) que são mais estáveis e menos polares do que os líquidos designados como bio-óleos obtidos de processos térmicos da biomassa. Portanto, os líquidos produzidos pela presente invenção são parcialmente solúveis em derivados de petróleo e produzem sistemas mais estáveis com este. Logo, são transportados mais facilmente e co-processados junto com cargas de petróleo em diversos processo de refino. A presente invenção se refere ainda ao bio-óleo de acilação (BIOAC) obtido pelo referido processo

Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos : métodos

A Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM) – componente Serviços teve por objetivo caracterizar a organização dos serviços de assistência farmacêutica na Atenção Básica do Sistema Único Saúde. A PNAUM – Serviços foi um estudo transversal, avaliativo, com amostra planejada de 600 municípios, realizado entre 2014 e 2015, composto por uma fase remota, com entrevistas telefônicas com gestores. Desses 600 municípios foram selecionados 300 para um inquérito em serviços de saúde. Foram selecionadas as 27 capitais, 0,5% dos maiores municípios de cada região e realizado um sorteio dos demais municípios. O cálculo do tamanho da amostra representativa nacional considerou três níveis: municípios, serviços de dispensação de medicamentos e usuários. As entrevistas foram realizadas com a utilização de um questionário estruturado específico para: secretário municipal de saúde, responsável pela assistência farmacêutica no município, responsável pela entrega de medicamentos, médico e usuário. Os dados secundários foram obtidos em bases oficiais, na data mais recente de atualização. A PNAUM – Serviços foi a primeira pesquisa de âmbito nacional visando a avaliação e obtenção de indicadores nacionais e regionais acerca de acesso a medicamentos, bem como utilização e uso racional, sob a ótica de variados atores sociais.The Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos –Serviços (PNAUM – National Survey on Access, Use and Promotion of Rational Use of Medicines – Services) aimed to characterize the organization of pharmaceutical services in the Primary Health Care of the Brazilian Unified Health System (SUS). PNAUM – Services is a cross-sectional and evaluative study, with planned sample of 600 cities, held between 2014 and 2015, composed of a remote phase, with telephone interviews with health managers. Of these 600 cities, 300 were selected for a survey on health services. We selected the 27 capitals, the 0.5% largest cities of each region, and the remaining cities were drawn. The estimate of the representative national sample size considered three levels: cities, medicine dispensing services, and patients. The interviews were carried out with a structured questionnaire specific for: municipal secretaries of health, professionals responsible for pharmaceutical services in the city, professionals responsible for the dispensing of medicines, physicians, and patients. The secondary data were obtained in official databases, in the latest update date. PNAUM – Services was the first nationwide research aimed at the assessment and acquisition of national and regional indicators on access to medicines, as well as use and rational use, from the perspective of various social subjects

The use of probiotics as a supplementary therapy in the treatment of patients with asthma : a pilot study and implications

OBJECTIVES: Evaluate the use of probiotics as an additional therapy in the treatment of children and adolescents with asthma in Belo Horizonte, MG-Brazil. METHODS: A pilot longitudinal, experimental and nonrandomized study with 30 patients from six to 17 years old from Belo Horizonte. In the baseline appointment, all patients received beclomethasone, and one group also received a probiotic containing Lactobacillus reuteri (n=14). The patients were reassessed after at least 60 days with the Asthma Control Test, spirometry and self-report of the symptoms they experienced associated with asthma. RESULTS: A predominance of male patients (56.7%) and a mean age of 10.6 years were observed. The groups using probiotics did not differ in terms of sex, age or atopy. In the longitudinal evaluation, an increase in the Asthma Control Test scores and a reduction in the number of symptoms were observed in the probiotic group. There was an increase in the peak expiratory flow among those who used probiotics. CONCLUSIONS: This pilot study supports the hypothesis that the administration of probiotics as a supplementary therapy for the treatment of children and adolescents with asthma improves the clinical condition of the patients. Further studies are needed to confirm the efficacy of probiotics in asthma treatment

Custo-efetividade dos análogos de nucleosídeos/nucleotídeos para hepatite crônica B

OBJECTIVE: To conduct a cost-effectiveness analysis of drug alternatives with rescue therapy in case of relapse due to viral resistance for the treatment of patients with chronic hepatitis B (CHB). METHODS: Hypothetical cohort of patients with CHB, HBeAg-negative, without clinical or histological evidence of cirrhosis, detectable HBV DNA, histological diagnosis of the disease, positive serum HBsAg for longer than six months, high levels of alanine aminotransferase (ALT) (twice as high as the upper limit of normality) and mean age of 40 years. A Markov model was developed for chronic hepatitis B (HBeAg- negative) with a 40-year time horizon. Costs and benefits were discounted at 5%. Annual rates of disease progression, costs due to complications and the efficacy of medicines were obtained from the literature. One-way and probabilistic sensitivity analysis evaluated uncertainties. RESULTS: Initiation of treatments with entecavir resulted in an increase of 0.35 discounted life-years gained compared to lamivudine. The incremental cost-effectiveness ratio was R$16,416.08 per life-years gained. In the sensitivity analysis, the incremental cost-effectiveness ratio was more sensitive to variation in the probability of transition from chronic hepatitis B to compensated cirrhosis, discount rate and medicine prices (± 10$ 16.416,08 por años de vida ganados. En el análisis de sensibilidad el cociente de costo-efectividad incremental fue más sensible a la variación en la probabilidad de transición de hepatitis crónica B para cirrosis compensada, tasa de descuento y precio de los medicamentos (±10%). En el análisis de sensibilidad probabilística, la curva de aceptación mostró que iniciar con entecavir fue la alternativa más costo-efectiva en comparación al uso de lamivudina. CONCLUSIONES: La disponibilidad del entecavir es económicamente atractiva como parte del tratamiento precoz para pacientes con hepatitis crónica B sin co-infección con el VIH.OBJETIVO: Conduzir uma análise de custo-efetividade das alternativas medicamentosas com terapia de resgate na recaída por resistência viral para tratamento de pacientes com hepatite crônica B (HCB). MÉTODOS: Coorte hipotética de pacientes com HCB, HBeAg negativo, sem evidência clínica ou histológica de cirrose, DNA do VHB detectável, diagnóstico histológico da doença, HBsAg positivo no soro por mais de seis meses, elevados níveis de alanina transferase (ALT) (duas vezes maior que o limite superior da normalidade &#91;LSN&#93;) e média de idade de 40 anos. Modelo de Markov foi desenvolvido para a hepatite crônica B (antígeno HBeAg negativo) com horizonte temporal de 40 anos. Custos e benefícios foram descontados em 5%. As taxas anuais de progressão, custos devido a complicações e a eficácia dos medicamentos foram obtidos da literatura. As incertezas foram avaliadas por análises de sensibilidade unidirecional e probabilística. RESULTADOS: Iniciar o tratamento com entecavir resultou em 0,35 ano de vida ganho em relação à lamivudina. A razão de custo-efetividade incremental foi de R$ 16.416,08 por anos de vida ganhos. Na análise de sensibilidade a razão de custo-efetividade incremental foi mais sensível à variação na probabilidade de transição de hepatite crônica B para cirrose compensada, taxa de desconto e preço dos medicamentos (± 10%). Na análise de sensibilidade probabilística, a curva de aceitabilidade mostrou que iniciar com entecavir foi a alternativa mais custo-efetiva na comparação ao uso de lamivudina. CONCLUSÕES: A disponibilidade do entecavir é economicamente atrativa como parte do tratamento precoce para pacientes com hepatite crônica B sem coinfecção com o HIV