Micro-costing analysis of guideline-based treatment by direct-acting agents: the real-life case of hepatitis C management in Brazil

Background Eradication of hepatitis C virus (HCV) using direct-acting agents (DAA) has been associated with a financial burden to health authorities worldwide. We aimed to evaluate the guideline-based treatment costs by DAAs from the perspective of the Brazilian Ministry of Health (BMoH). Methods The activity based costing method was used to estimate the cost for monitoring/treatment of genotype-1 (GT1) HCV patients by the following strategies: peg-interferon (PEG-IFN)/ribavirin (RBV) for 48 weeks, PEG-IFN/RBV plus boceprevir (BOC) or telaprevir (TEL) for 48 weeks, and sofosbuvir (SOF) plus daclastavir (DCV) or simeprevir (SIM) for 12 weeks. Costs were reported in United States Dollars without (US$) and with adjustment for purchasing power parity (PPP$). Drug costs were collected at the National Database of Health Prices and an overview of the literature was performed to assess effectiveness of SOF/DCV and SOF/SIM regimens in real-world cohorts. Results Treatment costs of GT1-HCV patients were PPP$43,176.28 (US$ 24,020.16) for PEG-IFN/RBV, PPP$71,196.03 (US$ 39,578.23) for PEG-IFN/RBV/BOC and PPP$86,250.33 (US$ 47,946.92) for PEG-IFN/RBV/TEL. Treatment by all-oral interferon-free regimens were the less expensive approach: PPP$19,761.72 (US$ 10,985.90) for SOF/DCV and PPP$21,590.91 (US$ 12,002.75) for SOF/SIM. The overview reported HCV eradication in up to 98% for SOF/DCV and 96% for SOF/SIM. Conclusion Strategies with all oral interferon-free might lead to lower costs for management of GT1-HCV patients compared to IFN-based regimens in Brazil. This occurred mainly because of high discounts over international DAA prices due to negotiation between BMoH and pharmaceutical industries

Comparison of different delivery systems of DNA vaccination for the induction of protection against tuberculosis in mice and guinea pigs

The great challenges for researchers working in the field of vaccinology are optimizing DNA vaccines for use in humans or large animals and creating effective single-dose vaccines using appropriated controlled delivery systems. Plasmid DNA encoding the heat-shock protein 65 (hsp65) (DNAhsp65) has been shown to induce protective and therapeutic immune responses in a murine model of tuberculosis (TB). Despite the success of naked DNAhsp65-based vaccine to protect mice against TB, it requires multiple doses of high amounts of DNA for effective immunization. In order to optimize this DNA vaccine and simplify the vaccination schedule, we coencapsulated DNAhsp65 and the adjuvant trehalose dimycolate (TDM) into biodegradable poly (DL-lactide-co-glycolide) (PLGA) microspheres for a single dose administration. Moreover, a single-shot prime-boost vaccine formulation based on a mixture of two different PLGA microspheres, presenting faster and slower release of, respectively, DNAhsp65 and the recombinant hsp65 protein was also developed. These formulations were tested in mice as well as in guinea pigs by comparison with the efficacy and toxicity induced by the naked DNA preparation or BCG. The single-shot prime-boost formulation clearly presented good efficacy and diminished lung pathology in both mice and guinea pigs

On the gauge boson's properties in a candidate technicolor theory

The technicolor scenario replaces the Higgs sector of the standard model with a strongly interacting sector. One candidate for a realization of such a sector is two-technicolor Yang-Mills theory coupled to two degenerate flavors of adjoint, massless techniquarks. Using lattice gauge theory the properties of the technigluons in this scenario are investigated as a function of the techniquark mass towards the massless limit. For that purpose the minimal Landau gauge two-point and three-point correlation functions are determined, including a detailed systematic error analysis. The results are, within the relatively large systematic uncertainties, compatible with a behavior very similar to QCD at finite techniquark mass. However, the limit of massless techniquarks exhibits features which could be compatible with a (quasi-)conformal behavior.Comment: 27 pages, 17 figures, 1 table; v2: persistent notational error corrected, some minor modification

Temporal and Spatiotemporal Arboviruses Forecasting by Machine Learning: A Systematic Review

Arboviruses are a group of diseases that are transmitted by an arthropod vector. Since they are part of the Neglected Tropical Diseases that pose several public health challenges for countries around the world. The arboviruses' dynamics are governed by a combination of climatic, environmental, and human mobility factors. Arboviruses prediction models can be a support tool for decision-making by public health agents. In this study, we propose a systematic literature review to identify arboviruses prediction models, as well as models for their transmitter vector dynamics. To carry out this review, we searched reputable scientific bases such as IEE Xplore, PubMed, Science Direct, Springer Link, and Scopus. We search for studies published between the years 2015 and 2020, using a search string. A total of 429 articles were returned, however, after filtering by exclusion and inclusion criteria, 139 were included. Through this systematic review, it was possible to identify the challenges present in the construction of arboviruses prediction models, as well as the existing gap in the construction of spatiotemporal models

Candida bracarensis: Evaluation of virulence factors and its tolerance to Amphotericin B and Fluconazole

Candida bracarensis is an uncommon Candida species found during an epidemiological study of candidiasis performed in Braga, Portugal. Initially, it was identified as C. glabrata, but recently detailed analyses pointed out their differences. So, little information is still available about C. bracarensis virulence factors and antifungal susceptibilities. Therefore, the main goal of this work is to evaluate the ability of C. bracarensis to form biofilms, to produce hydrolytic enzymes (proteases, phospholipases and hemolysins), as well as its susceptibility to amphotericin B and fluconazole. It was shown, for the first time, that all C. bracarensis strains were able to form biofilms and display proteinase and hemolytic activities. Moreover, although planktonic cells presented antifungal susceptibility, amphotericin B and fluconazole were unable to inhibit biofilm formation and eradicate pre-formed biofilms. Due to the propensity of C. bracarensis to display antifungal resistance and virulence attributes, the control of these emerging pathogens is recommended.This work was supported by the projects PTDC/SAU-MIC/119069/2010, PEst-OE/EQB/LA0023/2013, from Fundação para a Ciência e Tecnologia (FCT), Portugal and ‘‘BioHealth—Biotechnology and Bioengineering approaches to improve health quality’’, Ref. NORTE-07-0124FEDER-000027, co-funded by the Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER. The authors also acknowledge the project ‘‘Consolidating Research Expertise and Resources on Cellular and Molecular Biotechnology at CEB/IBB’’, Ref. FCOMP-01-0124-FEDER027462

Depression among women living in the outskirts of São Paulo, Southeastern Brasil

OBJECTIVE: To assess the meaning of depression in women diagnosed with the disorder, and the context of care given by the psychiatrists who follow them up. METHODS: Qualitative study performed in Embu, outskirt of São Paulo, between August 2002 and January 2003. Etnographic observation and in-depth interview were carried out with 16 women diagnosed with depression in primary care, and four psychiatrists. After exhaustive reading, data were grouped into categories and assessed. The assessment of outcomes was based on the concept of culture. RESULTS: Women interviewed are well aware of the disorder, and accept treatment based on medication. For psychiatrists, depression is a term understood by the common sense. All women interviewed identified the onset of the disease from a past event such as: death of a son, violent episodes connected with drug traffic, unemployment, and partners' aggressiveness. Violence was common in the every day life of the interviewed women both inside and outside their homes. CONCLUSIONS: For these women, depression is a way to express their feelings, such as unhappiness in a context of poverty and violence. Psychiatrists go beyond their clinical functions and play an important role on reorganizing the daily life of these women.OBJETIVO: Analisar o significado da depressão para mulheres diagnosticadas com o transtorno e o contexto do atendimento realizado pelos psiquiatras que as acompanham. MÉTODOS: Estudo qualitativo realizado no município de Embu, na Grande São Paulo, entre agosto de 2002 e janeiro de 2003. Foram realizadas observação etnográfica e entrevistas em profundidade com 16 mulheres diagnosticadas com depressão, pacientes de uma Unidade Básica de Saúde, e quatro psiquiatras. Após a leitura exaustiva, os dados foram agrupados em categorias e analisados. A interpretação dos resultados baseou-se no conceito de cultura. RESULTADOS: As entrevistadas tinham ampla noção do transtorno, aceitando o tratamento com medicação. Para os psiquiatras, a depressão é um termo assimilado pelo senso-comum. Todas as entrevistadas identificaram a origem da doença em eventos passados, como: morte de filho, episódios violentos ligados ao tráfico de drogas, desemprego e agressividade do companheiro. A violência era comum no cotidiano das entrevistadas, tanto fora como dentro de casa. CONCLUSÕES: Para essas mulheres, a depressão era uma forma de expressar sentimentos, como a infelicidade num contexto de pobreza e violência. Os psiquiatras extrapolam as suas funções clínicas e têm um papel na reorganização do cotidiano dessas mulheres.Universidade Católica de Santos Programa de Mestrado em Saúde ColetivaUniversidade Federal de São Paulo (UNIFESP) Departamento de PsiquiatriaUNIFESP, Depto. de PsiquiatriaSciEL