Ciąża bliźniacza przebiegająca w postaci zaśniadu groniastego współwystępującego z żywym płodem: rozpoznanie, postępowanie oraz obserwacja po zakończeniu ciąży

Twin molar pregnancy with a hydatidiform mole and a coexisting live fetus is a rare form of gestational trophoblastic disease associated with an increased risk of obstetric complications and poor perinatal outcome. Prenatal diagnosis is essential for couple counseling and follow-up in Tertiary Reference Centers. Magnetic resonance imaging is important for the diagnostic differentiation of placental mesenchymal dysplasia and exclusion of myometrial invasion. Here we present a case of twin molar pregnancy with a hydatidiform mole and a coexisting live fetus diagnosed at gestational week 14 using two-dimensional (2D) and three-dimensional (3D) ultrasound and magnetic resonance imaging. We also describe the obstetric management and postmolar follow-up.Zaśniad groniasty stanowi łagodną postać ciążowej choroby trofoblastycznej (gestational trophoblastic disease, GTD)(1). W Brazylii ciążowa choroba trofoblastyczna stwierdzana jest 5–10 razy częściej(2) niż w Stanach Zjednoczonych i Europie(3,4). Zaśniad groniasty powstaje w wyniku nieprawidłowego zapłodnienia komórki jajowej i może przybierać dwie formy: zaśniadu groniastego całkowitego lub zaśniadu groniastego częściowego(1). Z klinicznego punktu widzenia taka reprodukcja materiału genetycznego może prowadzić do rozwinięcia się ciążowej neoplazji trofoblastu, która bez wdrożenia właściwego leczenia może skutkować śmiercią kobiety(1–4). Artykuł w wersji polskojęzycznej jest dostępny na stronie http://jultrason.pl/index.php/wydawnictwa/volume-17-no-7

A twin pregnancy with a hydatidiform mole and a coexisting live fetus: prenatal diagnosis, treatment, and follow-up

Twin molar pregnancy with a hydatidiform mole and a coexisting live fetus is a rare form of gestational trophoblastic disease associated with an increased risk of obstetric complications and poor perinatal outcome. Prenatal diagnosis is essential for couple counseling and follow-up in Tertiary Reference Centers. Magnetic resonance imaging is important for the diagnostic differentiation of placental mesenchymal dysplasia and exclusion of myometrial invasion. Here we present a case of twin molar pregnancy with a hydatidiform mole and a coexisting live fetus diagnosed at gestational week 14 using two-dimensional (2D) and three-dimensional (3D) ultrasound and magnetic resonance imaging. We also describe the obstetric management and postmolar follow-up

O DESEMPENHO DO RASTREIO PRECOCE DA PRÉ-ECLÂMPSIA A PARTIR DE FATORES MATERNOS E MARCADORES BIOFÍSICOS NA MATERNIDADE ESCOLA DA UNIVERSIDADE FEDERAL DO RIO DE JANEIRO

A predição da pré-eclâmpsia(PE) de forma eficaz e efetiva  é meta de muitos pesquisadores em todo o mundo. Existem evidências de que a identificação de gestantes de risco, no 1o trimestre da gestação    e subsequente implementação de aspirina em doses diárias de 150 mg, diminui a ocorrência das formas precoces de PE. A Fundação de Medicina Fetal desenvolveu modelo preditivo apresentado como algoritmo a partir de características físicas e da história  materna e de marcadores  biofísicos , que passou a ser utilizado na rotina asistencial. Os objetivos desse estudo são: (1) descrever a distribuição dos escores de risco, para desenvolvimento  da PE; (2) comparar a importância dos fatores de risco e dos marcadores biofísicos entre a população submetida ao rastreio e a população de referência e (3) avaliar o desempenho do teste de rastreio para  PE realizado no 1o trimestre da gestação, a partir de fatores maternos e marcadores biofísicos. O  estudo foi transversal e observacional com inclusão de gestantes que realizaram o rastreio da PE. Os casos foram classificados em PE<34;PE<37 e PE<42,  de acordo com a idade gestacional em que ocorreu o parto.Calculamos as médias e medianas dos  escores de risco para PE nos seguintes grupos e subgrupos: elegíveis; amostra final; excluídos; uso de aspirina; perdas; normais; PE <42; PE< 37  e PE< 34.Comparamos os coeficientes dos fatores maternos da amostra estudada com os da população de referência, assim como o comportamento dos marcadores biofísicos. Calculamos  sensibilidade, especificidade, VPP e VPN, LR+, LR-  e AUC. Os casos elegíveis totalizaram  1934 e a amostra final 1531. Ocorreram 120 casos de PE (7,5%), dos quais foram 26 (1,56%) PE<37 e 11(0,65%) PE<34. A distribuição dos valores de escores de risco foi assimétrica com 15% da amostra estudada de alto risco. As médias das variáveis contínuas idade, peso e altura maternas foram inferiors às da população de referência. A raça negra não se mostrou significativa na ocorrência da PE. O modelo de regressão Gaussiano  demostrou coeficientes com magnitudes diferentes do modelo de referência, enquanto os marcadores biofísicos apresentaram distribuição semelhante. Encontramos os seguintes valores ao se considerar o teste positivo, segundo os critérios da população de referência: sensibilidade:33,3%; valor preditivo positivo:16,9%; razão de verossimilhança positiva: 2,40; especificidade:85,8%; valor preditivo negativo:93,7%;  e razão de verossimilhança negativa: 0,77; AUC:0,7155. Concluímos que (1)A distribuição  dos valores de escore para desenvolvimento de PE<34, PE<37 e PE<42 é assimétrica, com cauda à direita, identificando a maioria da amostra como de baixo risco e com valores do grupo normal significativamente menores do  que os do grupo que  desenvolveu PE. (2) Os fatores maternos apresentaram diferenças na significância e na magnitude da associação, implicando na necessidade de derivação de novo modelo ajustado, para que este seja incorporado na prática clínica. (3) O teste demonstra bom desempenho em afastar o risco para desenvolvimento de PE , mas falha em identificar satisfatoriamente os casos que vão desenvolvê-la, impedindo  a instituição de medidas profiláticas efetivas.Palavras chaves: Pré-eclâmpsia; programas de rastreamento; Reprodutibilidade dos testes; Sensibilidade e especificidade

RESIDÊNCIA MULTIPROFISSIONAL EM SAÚDE PERINATAL DA MATERNIDADE ESCOLA DA UFRJ: REFLEXÕES SOBRE A FORMA DE ENSINAR E PRODUZIR CUIDADO EM SAÚDE PERINATAL

A Residência tem um desafio - sensibilizar os profissionais de saúde e o usuário com relação a uma prática multiprofissional, integrada, que visa à produção de vida e de cuidado. OBJETIVO: realizar formação em serviço integrada, voltada ao modelo humanístico, usuário centrado na área de perinatologia. Metodologia: Relato de experiência de ensino em saúde. Foi proposto as Residentes a elaboração de um projeto para o dia das mães inspirado no vídeo “Reflections of motherhood” (www.reflectionsofmotherhood). A pergunta central que faziam as mães era: “Se pudesse voltar no tempo, o que diria a si mesma no dia em que descobriu que estava grávida?” As mulheres respondiam com uma frase escrita em um quadro e eram fotografadas. A posteriori foi editada um vídeo, gravado em digital versatile disc (DVD) e entregue, como presente de dias das mães. Resultados: Produziu-se cuidado sensível em ato. Significou-se o aprendizado e integrou-se as Residentes, mostrando aos demais profissionais o valor da formação em saúde e em serviço, de uma forma lúdica, tirando o estigma dos plantões, transformando-os em uma oportunidade de produção de vida, no cotidiano do Sistema Único de Saúde. Considerações finais: entrelaçar cada vez mais o mundo do trabalho com a Residência e assim criar um espaço de educação permanente para refletir experiências como esta.Palavras-chave: Residência. Multiprofissional. Perinatal. Educação

Changes in Group B <i>Streptococcus</i> Colonization among Pregnant Women before and after the Onset of the COVID-19 Pandemic in Brazil

Group B Streptococcus (GBS) is a leading cause of neonatal infections. The genitourinary and gastrointestinal tract of pregnant women are the main source of transmission to newborns. This work investigated the prevalence and characterized GBS from pregnant women in Rio de Janeiro, Brazil, comparing the periods before (January 2019 to March 2020; 521) and during (May 2020 to March 2021; 285) the COVID-19 pandemic. GBS was detected in 10.8% of anovaginal samples. Considering scenarios before and during the pandemic, GBS colonization rate significantly decreased (13.8% vs. 5.3%; p = 0.0001). No clinical and sociodemographic aspect was associated with GBS carriage (p > 0.05). A total of 80%, 13.8% and 4.6% GBS strains were non-susceptible to tetracycline, erythromycin and clindamycin, respectively. Serotype Ia was the most frequent (47.7%), followed by V (23.1%), II (18.4%), III (7.7%) and Ib (3.1%). An increasing trend of serotypes Ib and V, as well as of antimicrobial resistance rates, and a decreasing trend of serotypes II and III, were observed after the pandemic onset, albeit not statistically significant (p > 0.05). The reduction in GBS colonization rates and alterations in GBS serotypes and resistance profiles during the pandemic were not due to changes in the sociodemographic profile of the population. Considering that control and preventive measures related to the COVID-19 pandemic onset have impacted other infectious diseases, these results shed light on the need for the continuous surveillance of GBS among pregnant women in the post-pandemic era

Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: an individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts

The Zika Brazilian Cohorts Consortium was supported by the National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq) (grant number 404861/2018-0). The individual studies participating in the ZBC-Consortium were funded by: Wellcome Trust and the United Kingdom’s Department for International Development (grant numbers: 205377/Z/16/Z; 201870/Z/16/Z). European Union’s Horizon 2020 research and innovation programme under ZikaPLAN (grant number 734584). Wellcome Trust - Research Enrichment in Epidemic Situation (grant number 107779/Z/15/Z; with ER1505 & ER1601). Medical Research Council on behalf of the Newton Fund and Wellcome Trust (grant number MC_PC_15088). National Institutes of Health/National Institute of Allergy and Infectious Diseases (grant number RO1/ AI140718). Fondation Christophe et Rodolphe Mérieux. National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq) (grant numbers 443875/2018-9; 440573/2016-5; 441098/2016-9; 305090/2016-0; 307282/2017-1; 304476/2018-8; 465549/2014-4; 440763/2016-9; 309722/2017-9; 306708/2014-0; 440577/2016-0). Coordination for the improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Capes) (grant numbers 88881.130813/2016-01; 88887.116627/2016-01; 88887.136366/2017-00). Ministry of Health of Brazil - Emergency Response in Public Health - Zika virus and Microcephaly (Ministério da Saúde de Brasil - Resposta à Emergência em Saúde Pública – Zika vírus e Microcefalia) (grant number 837058/2016). Department of Science and Technology (Departamento de Ciência e Tecnologia - DECIT) (grant numbers 25000.072811/2016-19; 440839/2016-5). Foundation of Research Support of the State of São Paulo (Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP) (grant numbers 2016/08578-0; 2017/21688-1; 2013/21719-3; 2016/ 15021-1; 2015/12295-0; 2016/05115-9). Foundation of Research Support of the State of Rio de Janeiro (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ) (grant numbers E-26/201.351/2016; E-18/ 2015TXB; E-26/202.862/2018; E 26/010.002477/2016). Foundation of Support for Research and Scientific and Technological Development of Maranhão (Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão – FAPEMA) (grant number 008/2016). Brazilian Ministry of Health (Ministério da Saúde – MS) (grant number 929698560001160-02). Evandro Chagas Institute/Brazilian Ministry of Health (Instituto Evandro Chagas/Ministério da Saúde). Foundation of Research Support of the State of Goiás (Fundação de Amparo à Pesquisa do Estado de Goiás – FAPEG) (number grant 2017/10267000531). Foundation of Research Support of the State of Rio Grande do Sul (Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul – FAPERGS) (grant number 17/2551-0000521-0). Foundation to Support Teaching, Research and Assistance at Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto (Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto) and São Paulo State Department of Health (Secretaria de Saúde do Estado de São Paulo). Support Foundation of Pernambuco Science and Technology (Fundação de Amparo à Ciência e Tecnologia de Pernambuco – FACEPE) (grant numbers APQ-0172-4.01/16; APQ-0192-4.01/17; APQ0793-4.01/17).Federal University of Pernambuco. Postgraduate Program in Tropical Medicine. Recife, PE, Brazil / University of Pernambuco. Post-Graduation in Health Sciences. Recife, PE, Brazil.University of Pernambuco. Post-Graduation in Health Sciences. Recife, PE, Brazil.London School of Hygiene & Tropical Medicine. Department of Infectious Disease Epidemiology. London, UK.Federal University of Pernambuco. Postgraduate Program in Collective Health. Recife, PE, Brazil.University of Pernambuco. Post-Graduation in Health Sciences. Recife, PE, Brazil.University of Amazonas State. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil / Doctor Heitor Vieira Dourado Tropical Medicine Foundation. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil.Ribeirão Preto Medical School. Department of Pediatrics. Ribeirão Preto, SP, Brazil.Ribeirão Preto Medical School. Department of Gynecology and Obstetrics. Ribeirão Preto, SP, Brazil.Ribeirão Preto Medical School. Department of Gynecology and Obstetrics. Ribeirão Preto, SP, Brazil.Ribeirão Preto Medical School. Department of Pediatrics. Ribeirão Preto, SP, Brazil.University of Amazonas State. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil / Doctor Heitor Vieira Dourado Tropical Medicine Foundation. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil.University of Amazonas State. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil / Doctor Heitor Vieira Dourado Tropical Medicine Foundation. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil.Instituto Fernandes Figueira. Clinical Research Unit. Rio de Janeiro, RJ, Brazil.Oswaldo Cruz Foundation. Instituto Fernandes Figueira. Clinical Research Unit. Rio de Janeiro, RJ, Brazil.Oswaldo Cruz Foundation. Instituto Fernandes Figueira. Obstretics. Rio de Janeiro, RJ, Brazil.University of California. David Geffen School of Medicine. Department of Pediatrics. Los Angeles, CA, Estados Unidos.Oswaldo Cruz Foundation. Research Center Aggeu Magalhães. Recife, PE, Brazil.London School of Hygiene & Tropical Medicine. Department of Infectious Disease Epidemiology. London, UK.Oswaldo Cruz Foundation. Research Center Aggeu Magalhães. Recife, PE, Brazil.Altino Ventura Foundation. Department of Ophthalmology. Recife, PE, Brazil / Pernambuco Eyes Hospital. Recife, PE, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Medicine School of São José do Rio Preto. Department of Infectious Disease. São José do Rio Preto, SP, Brazil.Medicine School of São José do Rio Preto. Department of Infectious Disease. São José do Rio Preto, SP, Brazil.Medicine School of São José do Rio Preto. Department of Gynecology and Obstetrics. São José do Rio Preto, SP, Brazil.Medicine School of Jundiaí. Infectious Pediatric Laboratory. Jundiaí, SP, Brazil.Federal University of São Paulo. Department of Fetal Medicine. São Paulo, SP, Brazil.Father Anchieta University Center. Nursing School. Jundiaí, SP, Brazil.Federal University of São Paulo. Paulista School of Medicine. Departament of Obstetrics. São Paulo, SP, Brazil.Federal University of Goiás. Institute of Tropical Pathology and Public Health. Goiânia, GO, Brazil.Health Secretariat of Goiás State. Maternal and Child Hospital. Goiânia, GO, Brazil.Federal University of São Paulo. Paulista School of Medicine. Departament of Obstetrics. São Paulo, SP, Brazil.Health Secretariat of Goiás State. Maternal and Child Hospital. Goiânia, GO, Brazil.Universidade Federal do Rio Grande do Sul. Hospital das Clinicas de Porto Alegre. Departamento de Genética. Porto Alegre, RS, Brazil.City Hall of Tangará da Serra, Municipal Health Department, Tangará da Serra, MT, Brazil.Federal University of Campina Grande. Medical Academic Unit. Campina Grande, PB, Brazil.Federal University of Campina Grande. Medical Academic Unit. Campina Grande, PB, Brazil.Federal University of Rio de Janeiro. Department of Pediatrics. Rio de Janeiro, RJ, Brazil.D’Or Institute for Research & Education. Department of Pediatrics. Rio de Janeiro, RJ, Brazil.Departmentiversity of Rio de Janeiro Maternity School. Department of Obstectrics. Rio de Janeiro, RJ, Brazil.Departmentiversity of Rio de Janeiro Maternity School. Department of Obstectrics. Rio de Janeiro, RJ, Brazil.Reference Maternity Prof. José Maria de Magalhães Netto. Bahia Health Department, Salvador, BA, Brazil.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil.Federal University of Rio de Janeiro. Department of Infecitous Diseases. Rio de Janeiro, RJ, Brazil.Federal University of Rio de Janeiro. Department of Infecitous Diseases. Rio de Janeiro, RJ, Brazil.Oswaldo Cruz Foundation. Gonçalo Moniz Institute. Salvador, BA, Brazil.Oswaldo Cruz Foundation. Leonidas and Maria Deane Institute. Manaus, AM, Brazil.University of Amazonas State. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil / Doctor Heitor Vieira Dourado Tropical Medicine Foundation. Postgraduate Program in Tropical Medicine. Manaus, AM, Brazil / Oswaldo Cruz Foundation. Leonidas and Maria Deane Institute. Manaus, AM, Brazil.Oswaldo Cruz Foundation. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brazil.Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%

Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: an individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts ConsortiumResearch in context

Summary: Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies. Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks. Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association. Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%. Funding: National Council for Scientific and Technological Development - Brazil (Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq); Wellcome Trust and the United Kingdom's Department for International Development; European Union's Horizon 2020 research and innovation program; Medical Research Council on behalf of the Newton Fund and Wellcome Trust; National Institutes of Health/National Institute of Allergy and Infectious Diseases; Foundation Christophe et Rodolphe Mérieux; Coordination for the improvement of Higher Education Personnel (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Capes); Ministry of Health of Brazil; Brazilian Department of Science and Technology; Foundation of Research Support of the State of São Paulo (Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP); Foundation of Research Support of the State of Rio de Janeiro (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ); Foundation of Support for Research and Scientific and Technological Development of Maranhão; Evandro Chagas Institute/Brazilian Ministry of Health (Instituto Evandro Chagas/Ministério da Saúde); Foundation of Research Support of the State of Goiás (Fundação de Amparo à Pesquisa do Estado de Goiás – FAPEG); Foundation of Research Support of the State of Rio Grande do Sul (Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul – FAPERGS); Foundation to Support Teaching, Research and Assistance at Hospital das Clínicas, Faculty of Medicine of Ribeirão Preto (Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto); São Paulo State Department of Health (Secretaria de Saúde do Estado de São Paulo); Support Foundation of Pernambuco Science and Technology (Fundação de Amparo à Ciência e Tecnologia de Pernambuco – FACEPE)