Clinical genetics and public policies : how should rare diseases be managed?

The implementation of a specific policy for rare diseases in the Brazilian Unified Health System presents challenges in terms of its rationale. Recognizing the importance of rarity in the context of public health means understanding genetics as one of the dimensions of disease and accepting that Brazil is undergoing a period of transition in health indicators. Although most rare diseases lack pharmacological treatment and genetic counseling constitutes the best strategy for their prevention, the cost of “orphan drugs” and their consequent lack of cost-effectiveness are still claimed as hurdles to the implementation of public policies in this field. Epidemiological aspects should not be used as isolated criteria for prioritization in public policies

Spatio-Temporal Variations of Microphytobenthos in the Botafogo and Siri estuaries (norteast - Brazil)

Variações espaço-temporais da biomassa do microfitobentos foram investigadas nos estuários dos rios Botafogo e Siri em Pernambuco, Brasil. As amostragens foram realizadas em baixa-mar (bimestralmente) de fevereiro a dezembro de 2003. Em cada estuário foram determinadas três estações de amostragem no médio- e no infralitoral. Fortes variações espaciais e temporais foram verificadas nas concentrações tanto de clorofila-a como de feopigmentos. No estuário do Botafogo, a clorofila-a teve 34% do total da sua variação explicada pela análise de regressão múltipla (MRA) baseada nas concentrações de nitrogênio e de fósforo, enquanto no estuário do Siri somente 16% dessa variação foi explicada pela MRA baseada na concentração de nitrogênio. Feopigmentos apresentou 39% de sua variação total explicada pela MRA baseada na concentração de nitrogênio e na salinidade no estuário do Botafogo; enquanto no Siri a MRA explicou 58% da variação total baseada somente na concentração de nitrogênio. Nitrogênio foi discriminado como o fator mais importante para explicar as variações do microfitobentos no estuário do rio Botafogo. Os resultados do presente trabalho ressaltam o papel dos nutrientes e sugerem que ambos estuários apresentam evidências de eutrofização.Spatio-temporal variations of microphytobenthic biomass were investigated in the Botafogo and Siri estuaries, Pernambuco - Brazil. Samples were taken during low water (bi-monthly) from February to December, 2003. Three sampling stations were located in each estuary, in both midlittoral and sublittoral areas. Clear spatial and temporal variations were found for both chlorophyll-a and phaeopigment concentrations. In Botafogo, chlorophyll-a had 34% of total variation explained by MRA from nitrogen and phosphorus concentrations, while only 16% of total variation was thus explained from nitrogen concentration in the Siri estuary. Phaeopigments had 39% of total variation explained by MRA from nitrogen concentration and salinity in the Botafogo estuary and 58% of total variation was similarly explained from nitrogen concentration in the Siri estuary. Nitrogen was discriminated by the b coefficients as the most important factor in the explanation of the microphytobenthic pigments variations in the Botafogo estuary. The data of this study emphasize the role of nutrients and suggest that both estuaries show evidence of eutrophication

The economic burden of Chagas disease: A systematic review

Economic burden; Chagas diseaseCàrrega econòmica; Malaltia de ChagasCarga económica; Enfermedad de ChagasBackground Chagas disease (CD) is a neglected disease affecting millions worldwide, yet little is known about its economic burden. This systematic review is part of RAISE project, a broader study that aims to estimate the global prevalence, mortality, and health and economic burden attributable to chronic CD and Chronic Chagas cardiomyopathy. The objective of this study was to assess the main costs associated with the treatment of CD in both endemic and non-endemic countries. Methods An electronic search of the Medline, Lilacs, and Embase databases was conducted until 31st, 2022, to identify and select economic studies that evaluated treatment costs of CD. No restrictions on place or language were made. Complete or partial economic analyses were included. Results Fifteen studies were included, with two-thirds referring to endemic countries. The most commonly investigated cost components were inpatient care, exams, surgeries, consultation, drugs, and pacemakers. However, significant heterogeneity in the estimation methods and presentation of data was observed, highlighting the absence of standardization in the measurement methods and cost components. The most common component analyzed using the same metric was hospitalization. The mean annual hospital cost per patient ranges from $25.47 purchasing power parity US dollars (PPP-USD) to$18,823.74 PPP-USD, and the median value was $324.44 PPP-USD. The lifetime hospital cost per patient varies from$209,44 PPP-USD for general care to $14,351.68 PPP-USD for patients with heart failure. Discussion Despite the limitations of the included studies, this study is the first systematic review of the costs of CD treatment. The findings underscore the importance of standardizing the measurement methods and cost components for estimating the economic burden of CD and improving the comparability of cost components magnitude and cost composition analysis. Finally, assessing the economic burden is essential for public policies designed to eliminate CD, given the continued neglect of this disease.This study was funded by Novartis Pharma AG as part of a research collaboration with the World Heart Federation, project number CLCZ696D2010R. The World Heart Federation funded the Universidade Federal de Minas Gerais to lead this project. During this study, P.P. received salaries from World Heart Federation, and Y.G. and M.Q. received salaries from Norvartis Pharma AG. A.L.P.R. is supported in part by National Council for Scientific and Technological Development (CNPq) (310790/2021-2 and 465518/2014-1) and by Minas Gerais Research Funding Foundation (FAPEMIG) (PPM-00428-17 and RED-00081-16). M.V.A. and K.V.M.S.N. acknowledge CNPq for the research productivity scholarships (processes 309252/2021-0 and 303459/2022-0, respectively). K.V.M.S.N. is also supported in part by FAPEMIG (PPM-00604-17). A.S.M.S. receives resources from CNPq (381587/2018-5). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Anemia and use of erythropoietin in hemodialysis patients at Hospital de Clínicas de Porto Alegre

Anemia é freqüente em pacientes com insuficiência renal crônica e deve-se, principalmente, à diminuição da síntese endógena de eritropoetina. Desde a década de 1980, o uso da eritropoetina recombinante tornou-se o tratamento de escolha da anemia nesses pacientes. Realizamos um estudo com os pacientes em hemodiálise na Unidade de Hemodiálise do Hospital de Clínicas de Porto Alegre, tendo encontrado uma porcentagem de 82,6% desses indivíduos em uso de eritropoetina recombinante (epoetina). A dose semanal média de epoetina observada foi de 10.260 UI. A hemoglobina média dos pacientes foi de 10,3 g/ dL; quando avaliamos a variação entre os valores médios de Hb dos pacientes em uso dessa medicação, entre os meses de setembro de 2005 e fevereiro de 2006, não houve significância na mesma.Anemia is a very common finding in the course of chronic renal failure; the main cause of this pathology is reduced production of endogenous erythropoietin. Since the 1980’s, the use recombinant human erythropoietin has become the treatment of choice for anemia in this group of patients. We conducted a study with hemodialysis patients in the Hemodialysis Unit at Hospital de Clínicas de Porto Alegre, a university hospital in southern Brazil. We found that 82.6% of the patients were using recombinant erythropoietin (epoetin). The average weekly epoetin dose was 10,260 IU. Mean hemoglobin value was 10.3 g/dL and there was no significant difference between the mean hemoglobin values of the patients using this drug from September 2005 to February 2006

99mTc-thymine scintigraphy may be a promising method in the diagnosis of breast cancer

OBJECTIVE: Mammography has been established as the gold standard for the detection of breast cancer, and imaging techniques such as ultrasonography, magnetic resonance imaging, scintigraphy and positron emission tomography may be useful to improve its sensitivity and specificity. The objective of this study with breast scintigraphy was to evaluate the uptake of 99mTc-thymine in mammary lesions. METHODS: A total of 45 patients were included in this study. Thirty-three patients (73%) were subjected to surgery or percutaneous biopsy, providing histopathological data. The other 12 patients who remained under surveillance received clinical examinations and biannual mammography with a normal follow-up of at least three years, the data from which were used for comparison with the scintimammography results. RESULTS: The majority of patients (64.4%) had clinically impalpable lesions with a mammogram diagnosis of microcalcifications, impalpable nodules, or focal asymmetry. Of the studied lesions, 87% were smaller or equal to 20 mm in diameter, and 22% had malignant histopathological findings. Scintigraphy with 99mTc-thymine had a sensitivity of 70%, a specificity of 85.7%, positive and negative predictive values of 58.3% and 90.9%, respectively, and an accuracy of 82.2%. CONCLUSIONS: The results of this study are consistent with those previously reported by other authors. The good specificity and high negative predictive value of this technique and the absence of uptake in the heart indicate that it may be a promising complementary method in clinical practice and that it may contribute to reducing unnecessary benign biopsies

Challenges in the Identification of New Thermolabile Psychoactive Substances: the 25I-NBOH case

The continuous emergence of NPS over the last years poses a series of novel challenges for forensic analysts. Most of those new compounds are synthesized with minimal chemical modifications to the structure of already known chemicals in order to avoid regulations. Some of these new compounds may undergo chemical changes during analysis leading to misidentification and detrimental legal consequences. GC–MS is one of the most widely used analytical techniques employed by forensic laboratories all over the world for drug analysis. Nevertheless, thermolabile NPS, such as 25I-NBOH can generate artefacts in the traditional GCMS analysis. In this paper, we describe the fragmentation mechanism of the 25I-NBOH into a major peak corresponding to 2C-I and a minor one corresponding to the associated orthophenolic benzyl ether (o-PBE), which exact identity is directly linked with the solvent used for the analysis. Also, a series of method adjustments is displayed, encompassing variation on the injector temperature, split ratio and flow ratio, although with no success to prevent 25I-NBOH thermo degradation in the GC injector. Furthermore, differential scanning calorimetry and thermogravimetric analysis demonstrated that 25I-NBOH´s thermal stability is due to a smaller temperature window between fusion and decomposition points. Finally, we perform derivatization experiments and demonstrate how to overcome 25I-NBOH degradation in the GC/MS analysis

Scientific evidence on hepatitis Delta in Brazil: integrative literature review

Objective: Describe the level of scientific evidence on infections by the hepatitis Delta virus (HDV) in Brazil. Methods: Integrative literature review, with research in the databases of the Medical Literature Analysis and Retrieval System Online, Latin American and Caribbean Center on Health Sciences Information, Scientific Eletronic Library Online and Scopus, with analysis focusing on the leveling of the methodological rigor according to the model of Melnyk and Fineout-Overholt. Results: The search revealed an average of two publications a year between 1987 and 2017. We selected 33 articles, the majority (91%) presented level of evidence VI. The publications were concentrated in the area of tropical medicine (46%) and virology (15%). The authors of 85% of the studies were medical professionals and the most common design was the descriptive/cross-sectional (69.6%). Conclusion: Scientific literature on HDV infections in Brazil is focused on prevalence studies, showing incipiency regarding the production of studies with stricter guidelines, such as clinical trials.Objetivo: Descrever o nível de evidência científica sobre a infecção por vírus da hepatite Delta (VHD) no Brasil. Métodos: Revisão integrativa da literatura, com buscas realizadas nas bases de dados do Medical Literature Analysis and Retrieval System Online, Literatura Latino-americana e do Caribe em Ciências da Saúde, Scientific Eletronic Library Online e Scopus, com análise centrada no nivelamento do rigor metodológico de acordo com o modelo de Melnyk e Fineout-Overholt. Resultados: A busca revelou uma média de duas publicações por ano no intervalo entre 1987 e 2017. Foram selecionados 33 artigos, tendo a maioria (91%) apresentado nível de evidência VI. As publicações ficaram concentradas em periódicos da área de medicina tropical (46%) e virologia (15%). Dos trabalhos, 85% tinha profissional médico com autor e o delineamento mais encontrado foi o descritivo/transversal (69,6%). Conclusão: A produção científica sobre a infecção por VHD no Brasil está centrada em estudos de prevalência, mostrando-se incipiente quanto à produção de estudos com delineamentos mais rígidos como ensaios clínicos.Univ Fed Acre, Multidisciplinary Ctr, Cruzeiro Do Sul, AC, BrazilUniv Fed Acre, Ctr Hlth & Sports Sci, Rio Branco, AC, BrazilUniv Fed Sao Paulo, Escola Paulista Enfermagem, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Enfermagem, Sao Paulo, SP, BrazilWeb of Scienc

Liquid vs Solid Culture Medium to Evaluate Proportion and Time to Change in Management of Suspects of Tuberculosis-A Pragmatic Randomized Trial in Secondary and Tertiary Health Care Units in Brazil.

BACKGROUND: The use of liquid medium (MGIT960) for tuberculosis (TB) diagnosis was recommended by WHO in 2007. However, there has been no evaluation of its effectiveness on clinically important outcomes. METHODS AND FINDINGS: A pragmatic trial was carried out in a tertiary hospital and a secondary health care unit in Rio de Janeiro City, Brazil. Participants were 16 years or older, suspected of having TB. They were excluded if only cerebral spinal fluid or blood specimens were available for analysis. MGIT960 technique was compared with the Lowenstein-Jensen (LJ) method for laboratory diagnosis of active TB. Primary outcome was the proportion of patients who had their initial medical management changed within 2 months after randomisation. Secondary outcomes were: mean time for changing the procedure, patient satisfaction with the overall treatment and adverse events. Data were analysed by intention-to-treat. Between April 2008 and September 2011, 693 patients were enrolled (348 to MGIT, 345 to LJ). Smear and culture results were positive for 10% and 15.7% of participants, respectively. Patients in the MGIT arm had their initial medical management changed more frequently than those in the LJ group (10.1% MGIT vs 3.8% LJ, RR 2.67 95% CI 1.44-.96, p = 0.002, NNT 16, 95% CI 10-39). Mean time for changing the initial procedure was greater in LJ group at both sites: 20.0 and 29.6 days in MGIT group and 52.2 and 64.3 in LJ group (MD 33.5, 95% CI 30.6-36.4, p = 0.0001). No other important differences were observed. CONCLUSIONS: This study suggests that opting for the MGIT960 system for TB diagnosis provides a promising case management model for improving the quality of care and control of TB. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN79888843