Summary of the II Brazilian Guideline Update on Acute Heart Failure 2009/2011

In the past two years we observed several changes in the diagnostic and therapeutic approach of patients with acute heart failure (acute HF), which led us to the need of performing a summary update of the II Brazilian Guidelines on Acute Heart Failure 2009. In the diagnostic evaluation, the diagnostic flowchart was simplified and the role of clinical assessment and echocardiography was enhanced. In the clinical-hemodynamic evaluation on admission, the hemodynamic echocardiography gained prominence as an aid to define this condition in patients with acute HF in the emergency room. In the prognostic evaluation, the role of biomarkers was better established and the criteria and prognostic value of the cardiorenal syndrome was better defined. The therapeutic approach flowcharts were revised, and are now simpler and more objective. Among the advances in drug therapy, the safety and importance of the maintenance or introduction of beta-blockers in the admission treatment are highlighted. Anticoagulation, according to new evidence, gained a wider range of indications. The presentation hemodynamic models of acute pulmonary edema were well established, with their different therapeutic approaches, as well as new levels of indication and evidence. In the surgical treatment of acute HF, CABG, the approach to mechanical lesions and heart transplantation were reviewed and updated. This update strengthens the II Brazilian Guidelines on Acute Heart Failure to keep it updated and refreshed. All clinical cardiologists who deal with patients with acute HF will find, in the guidelines and its summary, important tools to help them with the clinical practice for better diagnosis and treatment of their patients.

Interethnic diversity of NAT2 polymorphisms in Brazilian admixed populations

Abstract Background N-acetyltransferase type 2 (Nat2) is a phase II drug- metabolizing enzyme that plays a key role in the bioactivation of aromatic and heterocyclic amines. Its relevance in drug metabolism and disease susceptibility remains a central theme for pharmacogenetic research, mainly because of its genetic variability among human populations. In fact, the evolutionary and ethnic-specific SNPs on the NAT2 gene remain a focus for the potential discoveries in personalized drug therapy and genetic markers of diseases. Despite the wide characterization of NAT2 SNPs frequency in established ethnic groups, little data are available for highly admixed populations. In this context, five common NAT2 SNPs (G191A, C481T, G590A, A803G and G857A) were investigated in a highly admixed population comprised of Afro-Brazilians, Whites, and Amerindians in northeastern Brazil. Thus, we sought to determine whether the distribution of NAT2 polymorphism is different among these three ethnic groups. Results Overall, there were no statistically significant differences in the distribution of NAT2 polymorphism when Afro-Brazilian and White groups were compared. Even the allele frequency of 191A, relatively common in African descendents, was not different between the Afro-Brazilian and White groups. However, allele and genotype frequencies of G590A were significantly higher in the Amerindian group than either in the Afro-Brazilian or White groups. Interestingly, a haplotype block between G590A and A803G was verified exclusively among Amerindians. Conclusions Our results indicate that ethnic admixture might contribute to a particular pattern of genetic diversity in the NAT2 gene and also offer new insights for the investigation of possible new NAT2 gene-environment effects in admixed populations.

Alternative management of diabetic ketoacidosis in a Brazilian pediatric emergency department

DKA is a severe metabolic derangement characterized by dehydration, loss of electrolytes, hyperglycemia, hyperketonemia, acidosis and progressive loss of consciousness that results from severe insulin deficiency combined with the effects of increased levels of counterregulatory hormones (catecholamines, glucagon, cortisol, growth hormone). The biochemical criteria for diagnosis are: blood glucose > 200 mg/dl, venous pH <7.3 or bicarbonate <15 mEq/L, ketonemia >3 mmol/L and presence of ketonuria. A patient with DKA must be managed in an emergency ward by an experienced staff or in an intensive care unit (ICU), in order to provide an intensive monitoring of the vital and neurological signs, and of the patient's clinical and biochemical response to treatment. DKA treatment guidelines include: restoration of circulating volume and electrolyte replacement; correction of insulin deficiency aiming at the resolution of metabolic acidosis and ketosis; reduction of risk of cerebral edema; avoidance of other complications of therapy (hypoglycemia, hypokalemia, hyperkalemia, hyperchloremic acidosis); identification and treatment of precipitating events. In Brazil, there are few pediatric ICU beds in public hospitals, so an alternative protocol was designed to abbreviate the time on intravenous infusion lines in order to facilitate DKA management in general emergency wards. The main differences between this protocol and the international guidelines are: intravenous fluid will be stopped when oral fluids are well tolerated and total deficit will be replaced orally; if potassium analysis still indicate need for replacement, it will be given orally; subcutaneous rapid-acting insulin analog is administered at 0.15 U/kg dose every 2-3 hours until resolution of metabolic acidosis; approximately 12 hours after treatment initiation, intermediate-acting (NPH) insulin is initiated at the dose of 0.6-1 U/kg/day, and it will be lowered to 0.4-0.7 U/kg/day at discharge from hospital.

Mastectomia e sexualidade: uma revisão integrativa

Mulheres acometidas pelo câncer mamário são confrontadas com a retirada de uma parte do corpo relacionada à sexualidade. Este estudo teve por objetivo investigar o impacto do câncer de mama e da mastectomia na sexualidade da mulher por meio da análise da produção científica publicada no período de 2000 a 2009. O levantamento bibliográfico foi realizado a partir das bases de dados LILACS, MedLine e PsycINFO. Foram selecionados 29 artigos, que constituíram o corpus do estudo. Os achados foram agrupados por meio de análise de conteúdo. Os resultados evidenciaram que, após a retirada da mama, o desempenho sexual é comprometido, com redução da freqüência de intercurso sexual nos primeiros estágios do tratamento e diminuição da excitação, interesse e satisfação sexual.

Informações para a elaboração de um manual educativo destinado às mulheres com câncer de mama

O objetivo deste estudo foi identificar as informações necessárias para a elaboração de um manual educativo, para auxiliar a mulher no pré-operatório para tratamento do câncer de mama. Para isso, foram entrevistadas mulheres com o diagnóstico de câncer de mama e submetidas ao procedimento cirúrgico pela primeira vez no máximo há seis meses. Foram incluídas 51 mulheres na faixa etária de 25 a 84 anos; 32 tinham companheiro; 26, ensino fundamental incompleto; 24 consideraram sua ocupação como "do lar"; 43,1% foram submetidas à mastectomia; e 82,4% realizaram linfadenectomia axilar. Responderam um instrumento com dados sócio-demográficos e perguntas relativas às informações/orientações recebidas da equipe de saúde sobre tipos de cirurgia, internação, anestesia, uso do dreno e intercorrências. Para a elaboração de material educativo, conhecer esta realidade e as expectativas dos sujeitos é indispensável para que sejam priorizadas as necessidades dos clientes, e não somente as exigências terapêuticas.

Câncer de mama feminino: aspectos clínicos e patológicos dos casos cadastrados de 2005 a 2008 num serviço público de oncologia de Sergipe

OBJETIVOS: conhecer os aspectos clínicos e patológicos dos casos de câncer de mama feminino cadastrados num serviço público de oncologia de Sergipe. MÉTODOS: procurou-se fazer uma associação do estadiamento com as características presentes nos tumores. A coleta de dados foi realizada em 165 prontuários de mulheres cadastradas no período de 2005 a 2008 no ambulatório de oncologia do Hospital Cirurgia, localizado em Aracaju-Sergipe, por meio de formulário de coleta de dados, em 2009. RESULTADOS: identificou-se o carcinoma ductal invasivo como o tipo de neoplasia mamária mais frequente com 80,8% dos casos; 76 (46,1%) neoplasias foram diagnosticadas em estádio avançado (IIB, III e IV) e a mastectomia prevaleceu como tipo de cirurgia utilizado no tratamento independente do estadiamento. Quanto aos receptores hormonais todos apresentaram associação com o grau do estádio e, ainda, notou-se que a positividade do estrogênio e progesterona é fator de proteção para um pior prognóstico. CONCLUSÃO: é notável que os casos de câncer de mama estudados apresentam maior agressividade biológica, cursando com pior prognóstico, considerando o estádio clínico. Fazem-se necessárias ações de detecção precoce voltadas ao câncer de mama na atenção básica de Sergipe para redução da morbi-mortalidade, melhora da sobrevida e qualidade de vida entre as mulheres acometidas por essa neoplasia.

Clinical predictors of long-term outcome in obsessive-compulsive disorder

Background: The purpose of this study was to investigate demographic and clinical factors associated with the long-term outcome of obsessive-compulsive disorder (OCD). Methods: A hundred ninety-six previously untreated patients with DSM-IV criteria OCD completed a 12-week randomized open trial of group cognitive-behavioral therapy (GCBT) or fluoxetine, followed by 21 months of individualized, uncontrolled treatment, according to international guidelines for OCD treatment. OCD severity was assessed using the Yale–Brown Obsessive-Compulsive Scale (Y-BOCS) at different times over the follow-up period. Demographics and several clinical variables were assessed at baseline. Results: Fifty percent of subjects improved at least 35% from baseline, and 21.3% responded fully (final Y-BOCS score < or = 8). Worse prognosis was associated with earlier age at onset of OCD (P = 0.045), longer duration of illness (P = 0.001) presence of at least one comorbid psychiatric disorder (P = 0.001), comorbidity with a mood disorder (P = 0.002), higher baseline Beck-Depression scores (P = 0.011), positive family history of tics (P = 0.008), and positive family history of anxiety disorders (P = 0.008). Type of initial treatment was not associated with long-term outcome. After correction for multiple testing, the presence of at least one comorbid disorder, the presence of a depressive disorder, and duration of OCD remained significant. Conclusions: Patients under cognitive-behavioral or pharmacological treatment improved continuously in the long run, regardless of initial treatment modality or degree of early response, suggesting that OCD patients benefit from continuous treatment. Psychiatric comorbidity, especially depressive disorders, may impair the long-term outcome of OCD patients.

Medication adherence in frail elderly outpatients with dementia

Since drug therapy in the elderly is complex and longterm and aged people commonly present some level of impairment and disability, medication adherence tend to decrease with age. Cognitive function is a key factor associated with medication adherence and professional or caregiver assistance may be necessary to maintain correct drug use. This study aims to analyze frail elderly outpatients aged 80 years or over diagnosed with dementia. The study is cross-sectional and is being conducted at the Ambulatory of Frailty of the University Hospital of the University of São Paulo (AF-UH). It is being based on information collected through an interview conducted with the patient or its caregiver. Medication adherence is assessed by the proportion of the prescribed drugs used in concordance with the prescription. Here it is presented the results of a pilot study. Thirty patients were included in the pilot study of which 23 (76.7%) were female and 7 (23.3%) males. The mean(SD) age, number of dwelling relatives, living children and prescribed drugs was, respectively, 86(5) years, 3(2), 3(2) and 6(3). The AF-UH consultation is the only regular physician encounter for 60.7% of the patients. Out of 30 patients, 5 (16.7%) live alone. Medication is a caregiver responsibility in 22 (73.4%) patients; the others (26.6%) self-administer their medicines. 13 (43.3%) of patients regularly use at least one drug not prescribed. Dementia was present in 8 patients all of which have a caregiver responsible for the management and,or the administration of the medicines; on the other hand, only 4 of the 22 nondemented patients (18.2%) have assistance of a caregiver (p<.001). The mean(SD) number of prescribed drugs was higher in nondemented patients [6.5(2.4)] than in those with dementia[3.5(2.3)] (p=.004). Educational level was similar between caregivers and patients (p=.503) as well as between caregivers of demented and non demented patients (p=.582). Among patients without dementia, those with caregiver assistance pre-presented the same mean(SD) medication adherence [0.93(0.14)] than those without it [0.78(0.28)] (p=.305). When compared to nondemented patients without caregivers, demented patients showed higher medication adherence [1.00(0.00)] (p=.013) since all of them used their drugs as recommended. The lower number of prescribed drugs and caregiver assistance seem to play an important role in the adherence of pharmacotherapy of demented patients in the studied population.

Medication reconciliation and adherence: a call for clinical pharmacist

Introduction and Objectives: With the population ageing, there is a growing number of people who have several comorbidities and make use of a variety of drugs. These factors lead to a greater predisposition to adverse drug events, as well as to medication errors. The clinical pharmacist is the most indicated health professional to target these issues. The aims of this study were to analyze the profile of medication reconciliation and assess the role of the clinical pharmacist regarding medication adherence. Material and Methods: Prospective observational cohort study conducted from Jan-Mar 2013 at the Surgical Clinic of the University Hospital of the University of Sao Paulo. 117 admitted patients - over the age of 18 years, under continuous medication use and with length of hospitalization up to 120h - were included. Discrepancies were classified as intentional/unintentional and according to their risk to cause harm, and interventions were divided into accepted/not accepted. Medication adherence was measured by Morisky questionnaire. Results and Conclusions: Only 30% of hospital prescriptions showed no discrepancies between the medications that the patient was using at home and those which were being prescribed at the hospital and more than one third of those had the potential to cause moderate discomfort or clinical deterioration. One third of total discrepancies were classified as unintentional. About 90% of the interventions were accepted by the medical staff. In addition, about 63% of patients had poor adherence to drug therapy. The study revealed the importance of the medication reconciliation at patient admission, ensuring greater safety and therapeutic efficacy of the treatment during hospitalization, and orienting the patient at discharge, assuring the therapy safety.

Free Rhodium (II) citrate and rhodium (II) citrate magnetic carriers as potential strategies for breast cancer therapy

Abstract Background Rhodium (II) citrate (Rh2(H2cit)4) has significant antitumor, cytotoxic, and cytostatic activity on Ehrlich ascite tumor. Although toxic to normal cells, its lower toxicity when compared to carboxylate analogues of rhodium (II) indicates Rh2(H2cit)4 as a promising agent for chemotherapy. Nevertheless, few studies have been performed to explore this potential. Superparamagnetic particles of iron oxide (SPIOs) represent an attractive platform as carriers in drug delivery systems (DDS) because they can present greater specificity to tumor cells than normal cells. Thus, the association between Rh2(H2cit)4 and SPIOs can represent a strategy to enhance the former's therapeutic action. In this work, we report the cytotoxicity of free rhodium (II) citrate (Rh2(H2cit)4) and rhodium (II) citrate-loaded maghemite nanoparticles or magnetoliposomes, used as drug delivery systems, on both normal and carcinoma breast cell cultures. Results Treatment with free Rh2(H2cit)4 induced cytotoxicity that was dependent on dose, time, and cell line. The IC50 values showed that this effect was more intense on breast normal cells (MCF-10A) than on breast carcinoma cells (MCF-7 and 4T1). However, the treatment with 50 μM Rh2(H2cit)4-loaded maghemite nanoparticles (Magh-Rh2(H2cit)4) and Rh2(H2cit)4-loaded magnetoliposomes (Lip-Magh-Rh2(H2cit)4) induced a higher cytotoxicity on MCF-7 and 4T1 than on MCF-10A (p < 0.05). These treatments enhanced cytotoxicity up to 4.6 times. These cytotoxic effects, induced by free Rh2(H2cit)4, were evidenced by morphological alterations such as nuclear fragmentation, membrane blebbing and phosphatidylserine exposure, reduction of actin filaments, mitochondrial condensation and an increase in number of vacuoles, suggesting that Rh2(H2cit)4 induces cell death by apoptosis. Conclusions The treatment with rhodium (II) citrate-loaded maghemite nanoparticles and magnetoliposomes induced more specific cytotoxicity on breast carcinoma cells than on breast normal cells, which is the opposite of the results observed with free Rh2(H2cit)4 treatment. Thus, magnetic nanoparticles represent an attractive platform as carriers in Rh2(H2cit)4 delivery systems, since they can act preferentially in tumor cells. Therefore, these nanopaticulate systems may be explored as a potential tool for chemotherapy drug development.

Potent Antiretroviral Therapy for Human Immunodeficiency Virus Infection Increases Aortic Stiffness

Background: Highly active antiretroviral therapy for AIDS is known to increase cardiovascular risk, but the effects of potent antiretroviral agents according to gender are unknown. Objective: The present study evaluated the impact of HIV infection treatment on aortic stiffness according to gender. Methods: From university-affiliated hospitals, we recruited 28 AIDS patients undergoing highly active antiretroviral treatment (HAART), 28 treatment-naive HIV-infected patients, 44 patients with type 2 diabetes, and 30 controls. Aortic stiffness was determined by measuring pulse wave velocity (PWV) using a validated and non-invasive automatic device. Results: The crude mean PWV values and 95% confidence intervals (95% CI) for HAART, diabetics, and controls were 9.77 m/s (95% CI 9.17-10.36),, 9.00 m/s (95% CI 8.37-9.63), 9.90 m/s (95% CI 9.32-10.49), and 9.28 m/s (95% CI 8.61-9.95), respectively, for men (P-value for trend = 0.14), and 9.61 m/s (95% CI 8.56-10.66), 8.45 m/s (95% CI 7.51-9.39), 9.83 (95% CI 9.21-10.44), and 7.79 m/s (95% CI 6.99-8.58), respectively, for women (P-value for trend <0.001). Post-hoc analysis revealed a significant difference between the mean PWV values in the HAART group and controls in women (P-value <0.01). After adjusting for other potential covariates, including systolic blood pressure and diabetes, these results did not change. The findings indicate that the impact of HAART treatment on aortic stiffness was amplified in women with hypertension, dyslipidemia, and metabolic syndrome. Conclusion: Potent anti-retroviral agents used in the treatment of HIV infection increases aortic stiffness, mainly among women with higher cardiovascular risk. (Arq Bras Cardiol 2012;99(6):1100-1107)

Modeling the emergence of HIV-1 drug resistance resulting from antiretroviral therapy: Insights from theoretical and numerical studies

The use of antiretroviral therapy has proven to be remarkably effective in controlling the progression of human immunodeficiency virus (HIV) infection and prolonging patient's survival. Therapy however may fail and therefore these benefits can be compromised by the emergence of HIV strains that are resistant to the therapy. In view of these facts, the question of finding the reason for which drug-resistant strains emerge during therapy has become a worldwide problem of great interest. This paper presents a deterministic HIV-1 model to examine the mechanisms underlying the emergence of drug-resistance during therapy. The aim of this study is to determine whether, and how fast, antiretroviral therapy may determine the emergence of drug resistance by calculating the basic reproductive numbers. The existence, feasibility and local stability of the equilibriums are also analyzed. By performing numerical simulations we show that Hopf bifurcation may occur. The model suggests that the individuals with drug-resistant infection may play an important role in the epidemic of HIV. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Drug-targeting in combined cancer chemotherapy: tumor growth inhibition in mice by association of paclitaxel and etoposide with a cholesterol-rich nanoemulsion

Lipid nanoemulsions (LDE) may be used as carriers of paclitaxel (PTX) and etoposide (ETP) to decrease toxicity and increase the therapeutic action of those drugs. The current study investigates the combined chemotherapy with PTX and ETP associated with LDE. Four groups of 10-20 B16F10 melanoma-bearing mice were treated with LDE-PTX and LDE-ETP in combination (LDE-PTX + ETP), commercial PTX and ETP in combination (PTX + ETP), single LDE-PTX, and single LDE-ETP. PTX and ETX doses were 9 mu mol/kg administered in three intraperitoneal injections on three alternate days. In two control groups mice were treated with saline solution or LDE alone. Tumor growth, metastasis presence, cell-cycle distribution, blood cell counts and histological data were analyzed. Toxicity of all treatments was evaluated in mice without tumors. Tumor growth inhibition was similarly strong in all treatment groups. However, there was a greater reduction in the number of animals bearing metastases in the LDE-PTX + ETP group (30 %) in comparison to the PTX + ETP group (82 %, p < 0.05). Reduction of cellular density, blood vessels and increase of collagen fibers in tumor tissues were observed in the LDE-PTX + ETP group but not in the PTX + ETP group, and in both groups reduced melanoma-related anemia and thrombocytosis were observed. Flow cytometric analysis suggested that LDE-PTX + ETP exhibited greater selectivity to neoplastic cells than PTX-ETP, showing arrest (65 %) in the G(2)/M phase of the cell cycle (p < 0.001). Toxicity manifested by weight loss and myelosuppression was markedly milder in the LDE-PTX + ETP than in the PTX + ETP group. LDE-PTX + ETP combined drug-targeting therapy showed markedly superior anti-cancer properties and reduced toxicity compared to PTX + ETP.

DM-1, sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate: a curcumin analog with a synergic effect in combination with paclitaxel in breast cancer treatment

This paper describes a new method for the preparation of sodium 4-[5-(4-hydroxy-3-methoxyphenyl)-3-oxo-penta-1,4-dienyl]-2-methoxy-phenolate, DM-1, and 3-oxo-penta-1,4-dienyl-bis (2-methoxy-phenolate), DM-2. The aim of this work was to evaluate the antitumor effects of DM-1 in adjuvant chemotherapy for breast cancer treatment. Mice bearing mammary adenocarcinomas (Ehrlich ascites tumors) were treated with paclitaxel alone, DM-1 alone, and paclitaxel + DM-1. Tumor samples were used to perform cytological analysis by the Papanicolaou method and apoptosis analysis by annexin V and phosphorylated caspase 3. The paclitaxel + DM-1 group had decreased tumor areas and tumor volumes, and the frequency of metastasis was significantly reduced. This caused a decrease in cachexia, which is usually caused by the tumor. Furthermore, treatment with paclitaxel + DM-1 and DM-1 alone increased the occurrence of apoptosis up to 40% in tumor cells, which is 35% more than in the group treated with paclitaxel alone. This cell death was mainly caused through phosphorylated caspase 3 (11% increase in paclitaxel + DM-1 compared to the paclitaxel group), as confirmed by reduced malignancy criteria in the ascitic fluid. DM-1 emerges as a potential treatment for breast cancer and may act as an adjuvant in chemotherapy, enhancing antitumor drug activity with reduced side effects.

Optimized Duration of Clopidogrel Therapy Following Treatment with the Endeavor Zotarolimus-Eluting Stent in Real-World Clinical Practice (OPTIMIZE) Trial: Rationale and design of a large-scale, randomized, multicenter study

Background Current recommendations for antithrombotic therapy after drug-eluting stent (DES) implantation include prolonged dual antiplatelet therapy (DAPT) with aspirin and clopidogrel >= 12 months. However, the impact of such a regimen for all patients receiving any DES system remains unclear based on scientific evidence available to date. Also, several other shortcomings have been identified with prolonged DAPT, including bleeding complications, compliance, and cost. The second-generation Endeavor zotarolimus-eluting stent (E-ZES) has demonstrated efficacy and safety, despite short duration DAPT (3 months) in the majority of studies. Still, the safety and clinical impact of short-term DAPT with E-ZES in the real world is yet to be determined. Methods The OPTIMIZE trial is a large, prospective, multicenter, randomized (1: 1) non-inferiority clinical evaluation of short-term (3 months) vs long-term (12-months) DAPT in patients undergoing E-ZES implantation in daily clinical practice. Overall, 3,120 patients were enrolled at 33 clinical sites in Brazil. The primary composite endpoint is death (any cause), myocardial infarction, cerebral vascular accident, and major bleeding at 12-month clinical follow-up post-index procedure. Conclusions The OPTIMIZE clinical trial will determine the clinical implications of DAPT duration with the second generation E-ZES in real-world patients undergoing percutaneous coronary intervention. (Am Heart J 2012;164:810-816.e3.)