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Resumo Fundamento O choque cardiogênico (CC) refratário está associado com altas taxas de mortalidade, e o uso de oxigenação por membrana extracorpórea venoarterial (VA-ECMO, do inglês venoarterial extracorporeal membrane oxygenation) como uma opção terapêutica tem gerado discussões. Nesse sentido, sua custo-efetividade, principalmente em países de baixa e média renda como o Brasil, continua incerto.Objetivos: Conduzir uma análise de custo-efetividade na perspectiva do Sistema Único de Saúde (SUS) para avaliar a custo-efetividade de VA-ECMO combinado com o tratamento padrão em comparação ao tratamento padrão isolado em pacientes adultos com CC refratário. Métodos Acompanhamos uma coorte de pacientes com CC refratário tratados com VA-ECMO em centros de assistência terciária do sul brasileiro. Coletamos dados de desfechos e custos hospitalares. Realizamos uma revisão sistemática para complementar nossos dados e usamos o modelo de Markov para estimar a razão de custo-efetividade incremental (RCEI) por ano de vida ajustado pela qualidade (QALY) e por ano de vida ganho. Resultados Na análise do caso-base, a VA-ECMO gerou uma RCEI de Int$ 37 491 por QALY. Análises de sensibilidade identificaram o custo de internação, o risco relativo de sobrevida, e a sobrevida do grupo submetido à VA-ECMO como principais variáveis influenciando os resultados. A análise de sensibilidade probabilística mostrou um benefício do uso de VA-ECMO, com uma probabilidade de 78% de custo-efetividade no limiar recomendado de disposição a pagar. Conclusões Nosso estudo sugere que, dentro do SUS, VA-ECMO pode ser uma terapia custo-efetiva para o CC refratário. Contudo, a escassez de dados sobre a eficácia e de ensaios clínicos recentes que abordem seus benefícios em subgrupos específicos de pacientes destaca a necessidade de mais pesquisas. Ensaios clínicos rigorosos, incluindo perfis diversos de pacientes, são essenciais para confirmar a custo-efetividade com uso de VA-ECMO e assegurar acesso igualitário a intervenções médicas avançadas dentro dos sistemas de saúde, especialmente em países com desigualdades socioeconômicas como o Brasil.

(1) Background: Nanocellulose is an innovative engineered nanomaterial with an enormous potential for use in a wide array of industrial and biomedical applications and with fast growing economic value. The expanding production of nanocellulose is leading to an increased human exposure, raising concerns about their potential health effects. This study was aimed at assessing the potential toxic and genotoxic effects of different nanocelluloses in two mammalian cell lines; (2) Methods: Two micro/nanocelluloses, produced with a TEMPO oxidation pre-treatment (CNFs) and an enzymatic pre-treatment (CMFs), and cellulose nanocrystals (CNCs) were tested in osteoblastic-like human cells (MG-63) and Chinese hamster lung fibroblasts (V79) using the MTT and clonogenic assays to analyse cytotoxicity, and the micronucleus assay to test genotoxicity; (3) Results: cytotoxicity was observed by the clonogenic assay in V79 cells, particularly for CNCs, but not by the MTT assay; CNF induced micronuclei in both cell lines and nucleoplasmic bridges in MG-63 cells; CMF and CNC induced micronuclei and nucleoplasmic bridges in MG-63 cells, but not in V79 cells; (4) Conclusions: All nanocelluloses revealed cytotoxicity and genotoxicity, although at different concentrations, that may be related to their physicochemical differences and availability for cell uptake, and to differences in the DNA damage response of the cell model.

ABSTRACT Background: Brazil’s public health system, the largest in the world, faces great challenges in establishing access to specialized care for all Brazilians. “Regula Mais Brasil” is a structuring project from the Ministry of Health that aims to optimize the referral process for specialized care throughout Brazil and uses telemedicine to support primary care physicians. The high demand for support and referrals in the neurology specialty raises questions about what the difficulties and doubts in managing these patients are and whether the training of the coordinating physician influences the orientation and outcome of referral. Methods: In a retrospective analysis on a database, all teleconsultations in the neurology specialty were evaluated. The diagnoses were categorized using the ICD-10 and according to the specialty of the coordinating teleconsultant for multiple comparisons. Results: In total, 1687 teleconsultations were conducted between January 10 and December 2, 2019, in the cities of Belo Horizonte and Porto Alegre and in the Federal District. The most frequent area of doubt for doctors was about epilepsy. After discussion via telemedicine, 25% of the referrals were avoided and the specialty of the teleconsultant physician did not impact the decision made: 72.3, 72.6 and 66.5%, in relation to approval by neurologists, family doctors and other experts, respectively. Conclusion: Increasing access to specialists, not only for patients but also for doctors, helps in achieving early resolution of issues of greater difficulty for primary healthcare doctors, thus resulting in lower numbers of referrals.

OBJECTIVES: This observational, cross-sectional study based aimed to test whether heart failure (HF)-disease management program (DMP) components are influencing care and clinical decision-making in Brazil. METHODS: The survey respondents were cardiologists recommended by experts in the field and invited to participate in the survey via printed form or email. The survey consisted of 29 questions addressing site demographics, public versus private infrastructure, HF baseline data of patients, clinical management of HF, performance indicators, and perceptions about HF treatment. RESULTS: Data were obtained from 98 centers (58% public and 42% private practice) distributed across Brazil. Public HF-DMPs compared to private HF-DMP were associated with a higher percentage of HF-DMP-dedicated services (79% vs 24%; OR: 12, 95% CI: 94-34), multidisciplinary HF (MHF)-DMP [84% vs 65%; OR: 3; 95% CI: 1-8), HF educational programs (49% vs 18%; OR: 4; 95% CI: 1-2), written instructions before hospital discharge (83% vs 76%; OR: 1; 95% CI: 0-5), rehabilitation (69% vs 39%; OR: 3; 95% CI: 1-9), monitoring (44% vs 29%; OR: 2; 95% CI: 1-5), guideline-directed medical therapy-HF use (94% vs 85%; OR: 3; 95% CI: 0-15), and less B-type natriuretic peptide (BNP) dosage (73% vs 88%; OR: 3; 95% CI: 1-9), and key performance indicators (37% vs 60%; OR: 3; 95% CI: 1-7). In comparison to non- MHF-DMP, MHF-DMP was associated with more educational initiatives (42% vs 6%; OR: 12; 95% CI: 1-97), written instructions (83% vs 68%; OR: 2: 95% CI: 1-7), rehabilitation (69% vs 17%; OR: 11; 95% CI: 3-44), monitoring (47% vs 6%; OR: 14; 95% CI: 2-115), GDMT-HF (92% vs 83%; OR: 3; 95% CI: 0-15). In addition, there were less use of BNP as a biomarker (70% vs 84%; OR: 2; 95% CI: 1-8) and key performance indicators (35% vs 51%; OR: 2; 95% CI: 91,6) in the non-MHF group. Physicians considered changing or introducing new medications mostly when patients were hospitalized or when observing worsening disease and/or symptoms. Adherence to drug treatment and non-drug treatment factors were the greatest medical problems associated with HF treatment. CONCLUSION: HF-DMPs are highly heterogeneous. New strategies for HF care should consider the present study highlights and clinical decision-making processes to improve HF patient care.

BACKGROUND:Chagas disease is a neglected chronic condition caused by Trypanosoma cruzi, with high prevalence and burden in Latin America. Ventricular arrhythmias are common in patients with Chagas cardiomyopathy, and amiodarone has been widely used for this purpose. The aim of our study was to assess the effect of amiodarone in patients with Chagas cardiomyopathy. METHODOLOGY:We searched MEDLINE, Embase and LILACS up to January 2018. Data from randomized and observational studies evaluating amiodarone use in Chagas cardiomyopathy were included. Two reviewers selected the studies, extracted data and assessed risk of bias. Overall quality of evidence was accessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). PRINCIPAL FINDINGS:We included 9 studies (3 before-after studies, 5 case series and 1 randomized controlled trial). Two studies with a total of 38 patients had the full dataset, allowing individual patient data (IPD) analysis. In 24-hour Holter, amiodarone reduced the number of ventricular tachycardia episodes in 99.9% (95%CI 99.8%-100%), ventricular premature beats in 93.1% (95%CI 82%-97.4%) and the incidence of ventricular couplets in 79% (RR 0.21, 95%CI 0.11-0.39). Studies not included in the IPD analysis showed a reduction of ventricular premature beats (5 studies), ventricular tachycardia (6 studies) and ventricular couplets (1 study). We pooled the incidence of adverse side effects with random effects meta-analysis; amiodarone was associated with corneal microdeposits (61.1%, 95%CI 19.0-91.3, 5 studies), gastrointestinal events (16.1%, 95%CI 6.61-34.2, 3 studies), sinus bradycardia (12.7%, 95%CI 3.71-35.5, 6 studies), dermatological events (10.6%, 95%CI 4.77-21.9, 3 studies) and drug discontinuation (7.68%, 95%CI 4.17-13.7, 5 studies). Quality of evidence ranged from moderate to very low. CONCLUSIONS:Amiodarone is effective in reducing ventricular arrhythmias, but there is no evidence for hard endpoints (sudden death, hospitalization). Although our findings support the use of amiodarone, it is important to balance the potential benefits and harms at the individual level for decision-making.

Implantable cardiac pacing systems are a safe and effective treatment for symptomatic irreversible bradycardia. Under the proper indications, cardiac pacing might bring significant clinical benefit. Evidences from literature state that the action of the artificial pacing system, mainly when the ventricular lead is located at the apex of the right ventricle, produces negative effects to cardiac structure (remodeling, dilatation) and function (dissinchrony). Patients with previously compromised left ventricular function would benefit the least with conventional right ventricle apical pacing, and are exposed to the risk of developing higher incidence of morbidity and mortality for heart failure. However, after almost 6 decades of cardiac pacing, just a reduced portion of patients in general would develop these alterations. In this context, there are not completely clear some issues related to cardiac pacing and the development of this cardiomyopathy. Causality relationships among QRS widening with a left bundle branch block morphology, contractility alterations within the left ventricle, and certain substrates or clinical (previous systolic dysfunction, structural heart disease, time from implant) or electrical conditions (QRS duration, percentage of ventricular stimulation) are still subjecte of debate. This review analyses contemporary data regarding this new entity, and discusses alternatives of how to use cardiac pacing in this context, emphasizing cardiac resynchronization therapy.

Introdução: Diabete melito (DM) é uma condição prevalente na população em geral, que parece aumentar o risco de insuficiência cardíaca (IC). Entretanto, a prevalência de DM em pacientes brasileiros com insuficiência cardíaca não é conhecida, e o impacto do DM no tratamento da IC ainda não está claro.Objetivo: Avaliar a prevalência de DM em pacientes ambulatoriais com insuficiência cardíaca, e sua correlação com características clínicas e com o tratamento da IC.Métodos: Foram incluídos 402 pacientes com IC em acompanhamento ambulatorial entre agosto de 2008 e setembro de 2009. Os pacientes foram comparados com relação às características clínicas, remodelamento cardíaco e tratamento da IC.Resultados: A prevalência de DM na amostra estudada foi de 31%. Os pacientes com DM tinham idade maior e maior prevalência de etiologia isquêmica. Os parâmetros ecocardiográficos não diferiram entre os grupos, mas a pressão sistólica da artéria pulmonar (PSAP) foi maior nos pacientes diabéticos. O tratamento da insuficiência cardíaca foi similar entre pacientes com e sem DM. Entre os diabéticos, cerca da metade dos pacientes tinham controle glicêmico adequado, e os principais tratamentos utilizados foram as drogas metformina e insulina.Conclusões: A prevalência de DM foi elevada nesta população de pacientes ambulatoriais com insuficiência cardíaca, sendo associado a etiologia isquêmica e comorbidades. Apesar de não haver associação com outras características de gravidade da doença, remodelamento cardíaco ou com o IC, pacientes diabéticos tinham níveis mais elevados de PSAP. A repercussão clínica e prognóstica destes achados merece ser avaliada em estudos prospectivos futuros.

Linfoma não-Hodgkin sistêmico pode afetar o miocárdio, particularmente em pacientes imunocomprometidos. Quando presentes, sinais e sintomas são geralmente inespecíficos, tornando o diagnóstico de envolvimento cardíaco muito difícil antes da autópsia. Arritmias ventriculares também são pouco usuais nesse cenário. Descrevemos um caso de linfoma não-Hodgkin miocárdico secundário, que se apresentou com taquicardia ventricular monomórfica sustentada e espessamento do septo interventricular basal. Completa remissão das lesões miocárdicas foi observada após o término da quimioterapia de segunda linha, sem recorrências posteriores de arritmias em oito meses.

Introdução: A relação entre consumo excessivo de álcool e risco aumentado para desenvolvimento de miocardiopatia alcoólica é universalmente conhecida. No entanto, permanece não esclarecida qual é a dose de exposição ao álcool e o tempo de consumo necessários para o desenvolvimento dessa doença. Adicionalmente, não existem dados definitivos sobre o consumo leve a moderado de álcool e incidência de insuficiência cardíaca, tanto na população hígida como em pacientes assintomáticos com disfunção sistólica. Objetivo: Identificar as evidências disponíveis na literatura sobre a associação entre o consumo moderado de álcool e a insuficiência cardíaca na população em geral e em pacientes assintomáticos com disfunção ventricular sistólica. Métodos: A busca de evidências foi realizada mediante pesquisa nos bancos de dados PubMed, LILACS e Cochrane e foi restrita a estudos de coorte prospectivo. Resultados: Foram encontrados sete estudos (cinco estudos realizados na população em geral e dois estudos realizados em pacientes assintomáticos com disfunção ventricular sistólica) sugerindo existir uma correlação inversa entre consumo moderado de álcool e risco de insuficiência cardíaca na população geral. Esses achados são mais consistentes para pacientes com insuficiência cardíaca de etiologia isquêmica. Entre pacientes assintomáticos com disfunção sistólica, o consumo moderado parece não interferir na evolução para insuficiência cardíaca clínica. Conclusões: As evidências disponíveis na literatura sugerem que o consumo de álcool em doses moderadas está associado com redução de risco de insuficiência cardíaca clínica, tanto na população geral como em pacientes assintomáticos com disfunção ventricular estabelecida.

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Background: Heart failure (HF) is a growing problem for healthcare systems worldwide. Sodium and fluid restriction are non-pharmacological treatments recommended for patients with HF by several guidelines over the years, even without consensus., Objective: To evaluate the effects of sodium and fluid restriction in patients with HF., Methods: We searched MEDLINE, Embase, and Cochrane CENTRAL databases up to June 2020 and screened the reference lists of relevant articles. We included randomized controlled trials evaluating sodium and/or fluid restriction in patients with HF. We assessed three independent comparisons: (a) sodium restriction versus control; (b) fluid restriction versus control; and (c) sodium and fluid restriction versus control. Main outcomes of interest were all-cause mortality and hospitalization. Two independent reviewers selected studies and extracted data. We pooled the results using random-effects meta-analysis. We used the RoB 2.0 and the GRADE framework to assess risk of bias and quality of evidence., Results: We included 16 studies totaling 3545 patients in our meta-analysis. Daily sodium intake was 1.5-2.4 g for the intervention group and >2.7 g for the control group, and daily fluid intake was 0.8-1.5 L for the intervention group and free oral fluid intake for the control group. Sodium restriction increased mortality (relative risk 1.92, 95% confidence interval 1.51 to 2.45, moderate quality of evidence) and hospitalization (relative risk 1.63, 1.11 to 2.40, low quality of evidence). Fluid restriction reduced mortality (relative risk 0.32, 0.13 to 0.82, low quality of evidence) and hospitalization (relative risk 0.46, 0.27 to 0.77, n = 331, low quality of evidence). The combination of sodium and fluid restriction did not significantly affect the risk of mortality (relative risk 0.92, 0.49 to 1.73, low quality of evidence) or the risk of hospitalization (relative risk 0.94, 0.75 to 1.19, low quality of evidence)., Conclusion: The combination of sodium and fluid restriction in clinical trials resulted in a null effect although results in the opposite direction were observed for each intervention independently. Combined sodium and fluid restriction are usually recommended for patients with HF. Our findings of sodium restriction harm, risk of mortality and hospitalization are consistent with publications from several clinical trial and physiologic explanations. A well-designed clinical trial nested by an implementation study is urgent for definitive sodium range recommendation, specially considering the change of currently guidelines, pushing up the cut-off of sodium restriction range., Competing Interests: Declaration of competing interest The methodological coordination for the development of these study was funded by the Institutional Development Program of the Brazilian Unified Health System (PROADI-SUS) together with Hospital Moinhos de Vento., (Copyright © 2022 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Aims: Although loop diuretics are widely used to treat heart failure (HF), there is scarce contemporary data to guide diuretic adjustments in the outpatient setting., Methods and Results: In a prospective, randomized and double-blind protocol, we tested the safety and tolerability of withdrawing low-dose furosemide in stable HF outpatients at 11 HF clinics in Brazil. The trial had two blindly adjudicated co-primary outcomes: (i) symptoms assessment quantified as the area under the curve (AUC) of a dyspnoea score on a visual-analogue scale evaluated at 4 time-points (baseline, Day 15, Day 45, and Day 90) and (ii) the proportion of patients maintained without diuretic reuse during follow-up. We enrolled 188 patients (25% females; 59 ± 13 years old; left ventricular ejection fraction = 32 ± 8%) that were randomized to furosemide withdrawal (n = 95) or maintenance (n = 93). For the first co-primary endpoint, no significant difference in patients' assessment of dyspnoea was observed in the comparison of furosemide withdrawal with continuous administration [median AUC 1875 (interquartile range, IQR 383-3360) and 1541 (IQR 474-3124), respectively; P = 0.94]. For the second co-primary endpoint, 70 patients (75.3%) in the withdrawal group and 77 patients (83.7%) in the maintenance group were free of furosemide reuse during follow-up (odds ratio for additional furosemide use with withdrawal 1.69, 95% confidence interval 0.82-3.49; P = 0.16). Heart failure-related events (hospitalizations, emergency room visits, and deaths) were infrequent and similar between groups (P = 1.0)., Conclusions: Diuretic withdrawal did not result in neither increased self-perception of dyspnoea nor increased need of furosemide reuse. Diuretic discontinuation may deserve consideration in stable outpatients with no signs of fluid retention receiving optimal medical therapy., Clinicaltrials.gov Identifier: NCT02689180., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Systemic non-Hodgkin's lymphoma can affect the myocardium, particularly in immunocompromised patients. When present, symptoms and signs are usually nonspecific, making the diagnosis of cardiac involvement very difficult before an autopsy. Ventricular arrhythmias are also unusual in this setting. We describe a case of secondary myocardial non-Hodgkin's lymphoma presenting with sustained monomorphic ventricular tachycardia and thickening of the basal interventricular septum. Complete remission of myocardial lesions was observed after completion of second-line chemotherapy treatment, without further recurrences of arrhythmias in eight months.