ABSTRACT Numerous tests employed to predict cardiac and functional status are expensive and not widely accessible for a considerable number of patients, particularly those diagnosed with Chagas disease (CD) residing in remote and endemic regions. To date, there is no knowledge of studies that have validated instruments that address functionality in an expanded way, including the biopsychosocial factors in patients with CD. This study aims to evaluate the psychometric properties of the World Health Organization Disability Assessment Schedule (WHODAS 2.0), in its 12-item shortened version (WHODAS-12) when applied to patients with CD. This is a cross-sectional study of a prospective cohort that follows individuals with CD (SaMi-Trop). Data collection took place between October 2019 and March 2020. In the interviews, sociodemographic information, life habits, clinical information, and indicators of disability measured by WHODAS-12 were collected. Descriptive analysis, internal consistency and construct validity of the instrument were performed. A total of 628 patients with CD were interviewed, most were women (69.5%), their mean age was of 57 years, and most declared an average self-perception of health (43.4%). The 12 items of WHODAS-12 were distributed into three factors, which together account for 61% of the variance. The Kaiser–Meyer–Olkin (KMO) index was 0.90, indicating adequacy of the sample for factor analysis. The internal consistency of the global scale showed alpha = 0.87. The percentage of incapacity was 16.05%, indicating mild incapacity for the evaluated patients. WHODAS-12 is a valid and reliable measure to assess the disability of the Brazilian population with CD.

ABSTRACT The present study aimed to establish a population pharmacokinetic (PopPK) modeling of benznidazole (BZD) in Brazilian patients with chronic Chagas disease. This was part of a Brazilian prospective cohort study with eight patients diagnosed with Chagas disease during the beginning of BZD treatment up to the 60th day. On the 15th day of treatment, a blood sampling was collected and analyzed. A one-compartment PK model was developed using Pmetrics. Patients with an average age of 50.3 (SD: 6.2) years old, 6 female patients and 2 males, 70.2 kg (14.2), receiving a 5 mg/Kg/day dose were included. PK parameters estimated for CL, V and Ka were 6.27 L/h, 38.97 L and 1.66 h-1, respectively. This is the first study to establish a population pharmacokinetic modeling of BZD in Brazilian patients with chronic Chagas disease. Therefore, further studies are needed to obtain the complete characterization of BZD pharmacokinetics.

Resumo A Doença de Chagas (DC) é reconhecida pela Organização Mundial da Saúde como uma das treze doenças tropicais mais negligenciadas do mundo. A autopercepção de saúde é considerada um melhor preditor de mortalidade do que medidas objetivas do estado de saúde, e o contexto em que se vive influencia esse preditor. O objetivo deste estudo foi avaliar a prevalência e os fatores individuais e contextuais associados à pior autopercepção em saúde de pacientes com DC de uma região endêmica do Brasil. É um estudo transversal multinível. Os dados individuais vêm de um corte transversal de um estudo de coorte denominado SaMi-Trop. Os dados contextuais foram coletados a partir de plataformas e sistemas de informações institucionais acessíveis ao público. A variável dependente foi a autopercepção de saúde. A análise foi realizada por meio de regressão logística binária multinível. Participaram do estudo 1.513 pacientes com DC, sendo 335 (22,1%) com pior autopercepção de saúde. Este estudo revelou a influência da organização/oferta do serviço público de saúde brasileiro e de características individuais na autopercepção de saúde de pacientes com DC.

Abstract Chagas disease (CD) is recognized by the World Health Organization as one of the thirteen most neglected tropical diseases in the world. Self-perceived health is considered a better predictor of mortality than objective measures of health status, and the context in which one lives influences this predictor. This study aimed to evaluate the prevalence and individual and contextual factors associated with poor self-rated health among CD patients from an endemic region in Brazil. It is a multilevel cross-sectional study. The individual data come from a cross-section of a cohort study named SaMi-Trop. Contextual data was collected from publicly accessible institutional information systems and platforms. The dependent variable was self-perceived health. The analysis was performed using multilevel binary logistic regression. The study included 1,513 patients with CD, where 335 (22.1%) had Poor self-rated health. This study revealed the influence of the organization/offer of the Brazilian public health service and of individual characteristics on the self-perceived health of patients with CD.

Resumo A Doença de Chagas (DC) é reconhecida pela Organização Mundial da Saúde como uma das treze doenças tropicais mais negligenciadas do mundo. A autopercepção de saúde é considerada um melhor preditor de mortalidade do que medidas objetivas do estado de saúde, e o contexto em que se vive influencia esse preditor. O objetivo deste estudo foi avaliar a prevalência e os fatores individuais e contextuais associados à pior autopercepção em saúde de pacientes com DC de uma região endêmica do Brasil. É um estudo transversal multinível. Os dados individuais vêm de um corte transversal de um estudo de coorte denominado SaMi-Trop. Os dados contextuais foram coletados a partir de plataformas e sistemas de informações institucionais acessíveis ao público. A variável dependente foi a autopercepção de saúde. A análise foi realizada por meio de regressão logística binária multinível. Participaram do estudo 1.513 pacientes com DC, sendo 335 (22,1%) com pior autopercepção de saúde. Este estudo revelou a influência da organização/oferta do serviço público de saúde brasileiro e de características individuais na autopercepção de saúde de pacientes com DC.

Abstract Chagas disease (CD) is recognized by the World Health Organization as one of the thirteen most neglected tropical diseases in the world. Self-perceived health is considered a better predictor of mortality than objective measures of health status, and the context in which one lives influences this predictor. This study aimed to evaluate the prevalence and individual and contextual factors associated with poor self-rated health among CD patients from an endemic region in Brazil. It is a multilevel cross-sectional study. The individual data come from a cross-section of a cohort study named SaMi-Trop. Contextual data was collected from publicly accessible institutional information systems and platforms. The dependent variable was self-perceived health. The analysis was performed using multilevel binary logistic regression. The study included 1,513 patients with CD, where 335 (22.1%) had Poor self-rated health. This study revealed the influence of the organization/offer of the Brazilian public health service and of individual characteristics on the self-perceived health of patients with CD.

ABSTRACT Currently, there are no biomarkers for Chikungunya fever (CHIK) in clinical practice that can accurately predict the severity or chronification of the disease. The aim of this study is to evaluate the existing literature on biomarkers related to the severity and chronification of CHIK. In this sense, a systematic review was conducted based on the PRISMA Statement guideline. Articles that described the association of biomarkers with the evolution of the disease (severity or chronification), published until August 20th 2019 were considered eligible. The search was carried out in the PubMed, Scopus, Virtual Health Library (VHL) and Science Direct databases. After searching the databases, 17 articles were added to the review, and after analyzing the articles, several biomarkers were associated with severity, such as increased levels of IL-6, IP-10, IL-1b, MIG, MCP-1, and reduced levels of RANTES and IL-8 or chronification, such as increased levels of IL-6, TNF-α, MCP-1, IL-12, INF-α, IL-13, INF-γ, GM-CSF, CRP, IL-1a, IL-15, Factor VII, IP-10, IL-10, IL-4, IL-1RA, IL-8, MIP-1α, MIP-1β, ferritin, MIG, ESR, NO, malondialdehyde, and reduced levels of RANTES, ferritin, eotaxin, HGF, IL-27, IL-17A, IL-29, TGF-β, IL-10, and thiols. IL-6, CRP and TNF-α were included in the meta-analysis to assess the relationship with chronification, although they did not reach statistical significance. It was concluded that several biomarkers showed a relationship with severity and chronification of CHIK; the search for these biomarkers can reveal prognostic factors and important therapeutic targets for the treatment of the disease.

ABSTRACT Chagas cardiomyopathy (ChCM) is a severe consequence of Trypanosoma cruzi infection and has a range of electrocardiographic (ECG) and echocardiographic (ECHO) manifestations. There is a need for a standard and parsimonious research cardiac end point that does not rely on expert panel adjudication, and it is not intended to change the ChCM definition. We use data from the REDS-II cohort to propose a simplified cardiac endpoint. A total of 499 T. cruzi-seropositive blood donors were included. All participants underwent a 12-lead ECG, echocardiogram and clinical examination, and those with abnormal findings were reviewed by a panel of cardiologists who classified cases as having Chagas cardiomyopathy or not. We created an exhaustive set of ECG and ECHO finding combinations and compared these with the panel’s classification. We selected the simplest combination that most accurately reproduced the panel’s results. Individual ECG and ECHO variables had low sensitivity for panel-defined cardiomyopathy. The best performing combination was right bundle branch block and/or ECHO evidence of left ventricular hypocontractility. This combination had 98% specificity and 85% sensitivity for panel-defined ChCM. It was not possible to improve the overall accuracy by addition of any other ECG or ECHO variable. Substituting right bundle branch block for the more inclusive finding of QRS interval > 120 ms produced similar results. The combination of prolonged QRS interval and/or left ventricular hypocontractility closely reproduced the REDS-II expert panel classification of Chagas ChCM. In conclusion, the simple and reproducible research endpoint proposed here captures most of the spectrum of cardiac abnormalities in Chagas disease.

ABSTRACT The SaMi-Trop project is a cohort study conducted in 21 municipalities of endemic areas of Chagas disease, including 1,959 patients with chronic Chagas cardiomyopathy. In this article we updated the results of the project, adding information from the second cohort visit. Trypanosoma cruzi-seropositive patients were enrolled from the primary care Telehealth service in Minas Gerais State, Brazil. The eligibility criterium for the second visit was the participation in the baseline evaluation. Of 1,959 participants at the baseline assessment, 1,585 (79.9%) returned after two years for the second evaluation. The mortality rate was 6.7%, but varied from 0.9% to 18.2% when it was stratified by certain clinical characteristics. A lower age-adjusted NT-Pro-BNP level (less than 300) and a prior benznidazole treatment were associated with lower mortality. There was an improvement in most quality of life domain scores. Participants have also reported fewer signs and symptoms and greater use of medication. The second follow-up visit will be complete in Oct 2021.

ABSTRACT Chagas disease (CD) is still a neglected disease. Infected individuals are diagnosed late, being treated in worse clinical conditions. Thus, this study aimed to analyze the prevalence and the factors associated with new confirmed cases of CD identified by serological screening in an endemic region of Minas Gerais State, Brazil. This is an analytical cross-sectional study with data from a project of the Research Center in Tropical Medicine of Sao Paulo- Minas Gerais (SaMi-Trop) conducted in two municipalities. Data collection included a questionnaire with closed questions, a venous blood collection and an ELISA serological test for CD. A total of 2,038 individuals with no previous diagnosis of CD participated in the study. The result of the serological test for CD was adopted as the dependent variable. The independent variables addressed personal issues, health conditions and lifetime housing. A descriptive analysis of individual variables was performed. Subsequently, a bivariate analysis was performed using the Pearson’s chi-square test. Households sheltering individuals positive for CD were georeferenced, and the analysis of spatial distribution was performed using the quartic function to estimate the density of the nucleus. Among the participants, 188 (9.2 %) were positive for CD. The profile of participants with CD was associated with place of residence, age, relative/family member with CD and living conditions. It is noteworthy that there are still patients with CD who are unaware of their diagnosis in both, rural and urban areas.

ABSTRACT Chagas disease (CD) is a neglected tropical highly morbid disease that can have a negative impact on the quality of life (QoL). The purpose of this study was to conduct an integrative review to analyze the QoL of patients with CD in the chronic phase of the disease, as well as the instruments used and the effect of different interventions. The review was carried out based on the criteria and recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guideline (PRISMA) using the PubMed, Scopus, Web of Science and Science Direct databases. An analysis of the reference list of the included articles was also carried out. Publications in all languages have been included. Two independent reviewers selected the eligible articles and extracted the data. A total of 1,479 articles were identified, and after applying the inclusion criteria 18 articles were included. Four different instruments were used to assess QoL and the most used was the Minnesota Living with Heart Failure Questionnaire (MLWHFQ) [33.3% (n = 6)]. Investigations involving intervention showed a positive impact on the patients’ QoL, and the Environment domain had the lowest score. Heterogeneity of instruments and lack of methodology standardization for assessing QoL was observed. QoL proved to be an important indicator for the planning and monitoring of patients with CD, however it is suggested that the instruments for its assessment should be the ones recommended by the validation studies. This process will allow the comparison of data between investigations.

Resumo Introdução Este trabalho discute a possibilidade de utilização de informações sobre a vacinação infantil reportada pelas mães em inquéritos domiciliares para a construção de indicadores de cobertura vacinal no Brasil. Objetivo Avaliar o potencial das informações declaradas pelas mães sobre a imunização das crianças em inquéritos domiciliares como uma fonte para o cálculo do indicador de cobertura vacinal. Método Analisaram-se os indicadores de confiabilidade (precisão) e validade (concordância) entre as informações disponíveis nos cartões de vacina das crianças menores de 2 anos e as informações reportadas pelas mães em pesquisas domiciliares realizadas nos anos de 2013 e 2015 no município de Santo Antônio do Monte, Minas Gerais. Resultados O principal resultado mostra que, em um contexto de alta cobertura, as mães tendiam a informar sobre a vacinação de seus filhos de forma aleatória, ou seja, informações reportadas pelas mães apresentavam baixa validade. Conclusão Embora a coleta de informações dos cartões de vacina das crianças seja um procedimento mais custoso, essa é a forma mais adequada e confiável de se mensurar a cobertura vacinal no contexto brasileiro.

Abstract Background This study discusses the possibility of using information on child vaccination reported by mothers through household surveys to construct indicators of immunization coverage in Brazil. Objective Evaluate the potential of information reported by mothers on the immunization of children in household surveys as a source to calculate a vaccination coverage indicator. Method The indicators of reliability (accuracy) and validity (concordance) between the information available on the vaccination cards of children under two years of age and that reported by mothers in two household surveys conducted in 2013 and 2015 in the municipality of Santo Antônio do Monte, state of Minas Gerais, Brazil. Results The main result shows that, in a context of high coverage, the mothers tended to inform randomly about the vaccination of their children, that is, the information reported by mothers presented low validity. Conclusion Although collecting information from children's vaccination cards is a more costly procedure, it is the most adequate and reliable way to measure vaccination coverage in the Brazilian context.

ABSTRACT The present study aimed to review the existing literature and to evaluate the best dose regimen for benznidazole in adult patients with Chagas disease in the chronic phase. A systematic review was conducted followed by meta-analysis. Searches were performed in four databases, to include studies published until May 2019. The descriptors used were: “Chagas disease”, “benznidazole”, “Drug Therapy”, “Pharmacokinetics”, “Dose-response relationship, drug” and “Chronic disease”. The meta-analysis compared studies using the standard dose of 5 mg/kg/day for 30 or 60 days. A total of 608 articles were found, 23 of which were considered eligible for this review and nine were included in the meta-analysis. The studies selected and analyzed were published between 1996 and 2018, with various benznidazole dose regimens, ranging from 2.5 mg/kg/day to 10 mg/kg/day, for 30 to 80 days of treatment. The results pointed to a great diversity of dose regimens, thus there is no consensus on the optimal dose regimen for benznidazole in the chronic phase of Chagas disease.

ABSTRACT The diagnosis of Chagas disease is based on the detection of Trypanosoma cruzi (T. cruzi)-specific antibodies. Nonetheless, there is concern about the sensitivity of current serological assays due to reports of T. cruzi PCR positivity among seronegative individuals. The aim of this study was to evaluate if T. cruzi seronegative infections occur in endemic areas. We recruited 2,157 individuals that were identified as having Chagas disease in a public health system database of an endemic region in Brazil. All participants were interviewed and 2,091 had a sample collected for serological and PCR testing. From these, 149 (7.1%) had negative serological results. PCR was positive in 610 samples (31.4%) of the 1,942 seropositive samples but in none of the 149 samples from seronegative participants. True T. cruzi seronegative infections seem to be rare (95% CI 0-3.7) and should not be a concern for blood supply, which relies on antibody screening.

Resumo O artigo avalia a linha de cuidado de uma coorte de 260 indivíduos com diabetes mellitus e 295 indivíduos com hipertensão arterial sistêmica antes, durante e após a implantação do Laboratório de Inovações na Atenção às Condições Crônicas (LIACC). Essa intervenção buscou fortalecer a atenção primária à saúde, implantando o modelo de atenção às condições crônicas no município de Santo Antônio do Monte, Minas Gerais, Brasil, entre 2013 e 2014. Trata-se de um estudo observacional longitudinal que utiliza informações clínicas e laboratoriais dos prontuários dos pacientes dessas duas condições crônicas entre 2012 e 2017. Os desfechos avaliados foram baseados nas linhas guias da Secretaria de Estado de Saúde de Minas Gerais. Os resultados evidenciam o LIACC associado à universalização de macroprocessos da atenção primária, como o cadastramento e a classificação do risco familiar. Para pacientes com diabetes houve melhora em diversos marcadores no período, como o aumento da realização de consulta (de 90% em 2012 para 92% em 2017) e diminuição dos pacientes com exames fora das faixas de normalidade. Já para indivíduos com hipertensão, mesmo sendo observado um crescimento acentuado da realização de consultas (de 80% em 2012 para 84% em 2017), as melhorias clínicas foram menos evidentes. Conclui-se que o LIACC se configura como uma promissora intervenção para a melhoria do manejo de pacientes com doenças crônicas na atenção primária à saúde.

Abstract This article evaluates the care of a cohort of 260 individuals with diabetes and 295 individuals with hypertension before, during and after the implementation of the Innovative Care Laboratory for Chronic Conditions (LIACC). This intervention sought to strengthen Primary Health Care by implementing the Chronic Care Model in Santo Antônio do Monte, Minas Gerais, Brazil, between 2013 and 2014. This is a longitudinal observational study that uses clinical and laboratory information from medical records of patients with these two chronic conditions between 2012 and 2017. The outcomes evaluated were based on the guidelines of the Department of Health of Minas Gerais State. The results show the LIACC associated with the universalization of primary care macro-processes such as registration and classification of family risk. For patients with diabetes, there was an improvement in several markers in the period, such as increased consultation (from 90% in 2012 to 92% in 2017) and a decrease in patients with examinations outside the normal range. For individuals with hypertension, although there is a marked increase in medical appointments (from 80% in 2012 to 84% in 2017), clinical improvements were less evident. It can be concluded that LIACC is a promising intervention to improve the management of patients with chronic diseases in Primary Health Care.

Resumen El artículo evalúa la línea de cuidado de una cohorte de 260 individuos con diabetes mellitus y de 295 individuos con hipertensión arterial sistémica antes, durante y después de la implantación del Laboratorio de Innovación en Atención a las Condiciones Crónicas (LIACC). Esta intervención buscó fortalecer la Atención Primaria en Salud implantando el Modelo de Atención a las Condiciones Crónicas en el municipio de Santo Antônio do Monte, Minas Gerais, Brasil, entre 2013 y 2014. Se trata de un estudio observacional longitudinal con informaciones clínicas y de laboratorio de registros médicos de los pacientes con las dos condiciones crónicas entre 2012 y 2017. Los desenlaces evaluados se basaron en las líneas guía de la Secretaría de Salud del estado de Minas Gerais. Los resultados evidencian el LIACC asociado con la universalización de los macroprocesos de atención primaria como el registro y la clasificación del riesgo familiar. Para los pacientes con diabetes se observó una mejora en muchos marcadores en el período, como el aumento de las consultas (de 90 % en 2012 a 92 % en 2017) y la disminución de los pacientes con exámenes fuera de los rangos normales. Aunque para las personas con hipertensión se ha observado un notable aumento en la concreción de las consultas (de 80 % en 2012 a 84 % en 2017), las mejorías clínicas fueron menos pronunciadas. Se concluye que el LIACC es una prometedora intervención para la mejora del manejo de pacientes con enfermedades crónicas en la atención primaria.

Resumo O objetivo deste estudo foi determinar a taxa de mortalidade por câncer de boca e aplicar o Modelo Bayesiano Empírico e a Análise Espacial para suavizar a taxa bruta de mortalidade por câncer de boca e orofaringe. Foi usado o Capítulo II da Classificação Internacional de Doenças (CID-10) para Categorias C00 a C14. Os dados foram extraídos do Sistema de Informações sobre Mortalidade do Brasil (SIM) do Estado de Minas Gerais. As estatísticas descritivas e as taxas brutas de mortalidade foram calculadas para cada município. Posteriormente, foram aplicados os estimadores Bayesianos Empíricos. Em 2012, em Minas Gerais, foram registradas 769 mortes para o câncer de boca e orofaringe, dos quais 607 (78,96%) eram homens e 162 (21,04%) mulheres. Houve uma grande variação na distribuição espacial da taxa de mortalidade bruta. Foi possível identificar aglomeração nas regiões Sul, Central e Norte com maior precisão pelo Estimador Bayesiano Modelo Global e Local. Através dos Modelos Bayesian foi possível mapear aglomeração espacial de mortes por câncer de boca e orofaringe com maior precisão. Assim, pela epidemiologia espacial foi possível obter resultados mais precisos e fornecer subsídios para ações para reduzir a mortalidade por este tipo de câncer.

Abstract The objective of this study was to determine of oral and oropharynx cancer mortality rate and the results were analyzed by applying the Spatial Analysis of Empirical Bayesian Model. To this end, we used the information contained in the International Classification of Diseases (ICD-10), Chapter II, Category C00 to C14 and Brazilian Mortality Information System (SIM) of Minas Gerais State. Descriptive statistics were observed and the gross rate of mortality was calculated for each municipality. Then Empirical Bayesian estimators were applied. The results showed that, in 2012, in the state of Minas Gerais, were registered 769 deaths of patients with cancer of oral and oropharynx, with 607 (78.96%) men and 162 (21.04%) women. There was a wide variation in spatial distribution of crude mortality rate and were identified agglomeration in the South, Central and North more accurately by Bayesian Estimator Global and Local Model. Through Bayesian models was possible to map the spatial clustering of deaths from oral cancer more accurately, and with the application of the method of spatial epidemiology, it was possible to obtain more accurate results and provide subsidies to reduce the number of deaths from this type of cancer.

Resumo O objetivo deste estudo foi determinar a taxa de mortalidade por câncer de boca e aplicar o Modelo Bayesiano Empírico e a Análise Espacial para suavizar a taxa bruta de mortalidade por câncer de boca e orofaringe. Foi usado o Capítulo II da Classificação Internacional de Doenças (CID-10) para Categorias C00 a C14. Os dados foram extraídos do Sistema de Informações sobre Mortalidade do Brasil (SIM) do Estado de Minas Gerais. As estatísticas descritivas e as taxas brutas de mortalidade foram calculadas para cada município. Posteriormente, foram aplicados os estimadores Bayesianos Empíricos. Em 2012, em Minas Gerais, foram registradas 769 mortes para o câncer de boca e orofaringe, dos quais 607 (78,96%) eram homens e 162 (21,04%) mulheres. Houve uma grande variação na distribuição espacial da taxa de mortalidade bruta. Foi possível identificar aglomeração nas regiões Sul, Central e Norte com maior precisão pelo Estimador Bayesiano Modelo Global e Local. Através dos Modelos Bayesian foi possível mapear aglomeração espacial de mortes por câncer de boca e orofaringe com maior precisão. Assim, pela epidemiologia espacial foi possível obter resultados mais precisos e fornecer subsídios para ações para reduzir a mortalidade por este tipo de câncer.

Abstract The objective of this study was to determine of oral and oropharynx cancer mortality rate and the results were analyzed by applying the Spatial Analysis of Empirical Bayesian Model. To this end, we used the information contained in the International Classification of Diseases (ICD-10), Chapter II, Category C00 to C14 and Brazilian Mortality Information System (SIM) of Minas Gerais State. Descriptive statistics were observed and the gross rate of mortality was calculated for each municipality. Then Empirical Bayesian estimators were applied. The results showed that, in 2012, in the state of Minas Gerais, were registered 769 deaths of patients with cancer of oral and oropharynx, with 607 (78.96%) men and 162 (21.04%) women. There was a wide variation in spatial distribution of crude mortality rate and were identified agglomeration in the South, Central and North more accurately by Bayesian Estimator Global and Local Model. Through Bayesian models was possible to map the spatial clustering of deaths from oral cancer more accurately, and with the application of the method of spatial epidemiology, it was possible to obtain more accurate results and provide subsidies to reduce the number of deaths from this type of cancer.