Synthesis of Novel Triazine-Based Chalcones and 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as Potential Leads in the Search of Anticancer, Antibacterial and Antifungal Agents.

This study presents the synthesis of four series of novel hybrid chalcones (20,21)a-g and (23,24)a-g and six series of 1,3,5-triazine-based pyrimido[4,5-b][1,4]diazepines (28-33)a-g and the evaluation of their anticancer, antibacterial, antifungal, and cytotoxic properties. Chalcones 20b,d, 21a,b,d, 23a,d-g, 24a-g and the pyrimido[4,5-b][1,4]diazepines 29e,g, 30g, 31a,b,e-g, 33a,b,e-g exhibited outstanding anticancer activity against a panel of 60 cancer cell lines with GI50 values between 0.01 and 100 µM and LC50 values in the range of 4.09 µM to >100 µM, several of such derivatives showing higher activity than the standard drug 5-fluorouracil (5-FU). On the other hand, among the synthesized compounds, the best antibacterial properties against N. gonorrhoeae, S. aureus (ATCC 43300), and M. tuberculosis were exhibited by the pyrimido[4,5-b][1,4]diazepines (MICs: 0.25-62.5 µg/mL). The antifungal activity studies showed that triazinylamino-chalcone 29e and triazinyloxy-chalcone 31g were the most active compounds against T. rubrum and T. mentagrophytes and A. fumigatus, respectively (MICs = 62.5 µg/mL). Hemolytic activity studies and in silico toxicity analysis demonstrated that most of the compounds are safe.

New pyridine-based chalcones and pyrazolines with anticancer, antibacterial, and antiplasmodial activities.

New pyridine-based chalcones 4a-h and pyrazolines 5a-h (N-acetyl), 6a-h (N-phenyl), and 7a-h (N-4-chlorophenyl) were synthesized and evaluated by the National Cancer Institute (NCI) against 60 different human cancer cell lines. Pyrazolines 6a, 6c-h, and 7a-h satisfied the pre-determined threshold inhibition criteria, obtaining that compounds 6c and 6f exhibited high antiproliferative activity, reaching submicromolar GI50 values from 0.38 to 0.45 µM, respectively. Moreover, compound 7g (4-CH3) exhibited the highest cytostatic activity of these series against different cancer cell lines from leukemia, nonsmall cell lung, colon, ovarian, renal, and prostate cancer, with LC50 values ranging from 5.41 to 8.35 µM, showing better cytotoxic activity than doxorubicin. Furthermore, the compounds were tested for antibacterial and antiplasmodial activities. Chalcone 4c was the most active with minimal inhibitory concentration (MIC) = 2 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA), while the pyrazoline 6h showed a MIC = 8 µg/mL against Neisseria gonorrhoeae. For anti-Plasmodium falciparum activity, the chalcones display higher activity with EC50 values ranging from 10.26 to 10.94 µg/mL. Docking studies were conducted against relevant proteins from P. falciparum, exhibiting the minimum binding energy with plasmepsin II. In vivo toxicity assay in Galleria mellonella suggests that most compounds are low or nontoxic.

Low dose post-transplant cyclophosphamide and sirolimus induce mixed chimerism with CTLA4-Ig or lymphocyte depletion in an MHC-mismatched murine allotransplantation model.

Allogeneic hematopoietic cell transplantation (allo-HCT) offers a curative option for patients with certain non-malignant hematological diseases. High-dose post-transplant cyclophosphamide (PT-Cy) (200 mg/kg) and sirolimus (3 mg/kg), (HiC) synergistically induce stable mixed chimerism. Further, sirolimus and cytotoxic T lymphocyte-associated antigen-4 immunoglobulin (CTLA4-Ig), also known as Abatacept (Aba), promote immune tolerance and allograft survival. Here, in a major histocompatibility complex (MHC)-mismatched allo-HCT murine model, we combined Aba and/or T-cell depleting anti-Thy1.2 (Thy) with a lower dose of PT-Cy (50 mg/kg) and Sirolimus (3 mg/kg), (LoC). While mice in the LoC group showed graft rejection, the addition of Thy to LoC induced similar donor chimerism levels when compared to the HiC group. However, the addition of Aba to LoC led to graft acceptance only in younger mice. When Thy was added to the LoC+Aba setting, graft acceptance was restored in both age groups. Engrafted groups displayed significantly reduced frequencies of recipient-specific interferon-γ-producing T cells as well as an increased frequency in regulatory T cells (Tregs) except in the LoC+Aba group. Splenocytes from engrafted mice showed no proliferation upon restimulation with Balb/c stimulators. Collectively, in combination with Aba or Thy, LoC may be considered to reduce graft rejection in patients who undergo allo-HCT.

Income Segregation, Conditional Cash Transfers, and Breast Cancer Mortality Among Women in Brazil.

Importance: Women living in income-segregated areas are less likely to receive adequate breast cancer care and access community resources, which may heighten breast cancer mortality risk. Objective: To investigate the association between income segregation and breast cancer mortality and whether this association is attenuated by receipt of the Bolsa Família program (BFP), the world's largest conditional cash-transfer program. Design, Setting, and Participants: This cohort study was conducted using data from the 100 Million Brazilian Cohort, which were linked with nationwide mortality registries (2004-2015). Data were analyzed from December 2021 to June 2023. Study participants were women aged 18 to 100 years. Exposure: Women's income segregation (high, medium, or low) at the municipality level was obtained using income data from the 2010 Brazilian census and assessed using dissimilarity index values in tertiles (low [0.01-0.25], medium [0.26-0.32], and high [0.33-0.73]). Main Outcomes and Measures: The main outcome was breast cancer mortality. Mortality rate ratios (MRRs) for the association of segregation with breast cancer deaths were estimated using Poisson regression adjusted for age, race, education, municipality area size, population density, area of residence (rural or urban), and year of enrollment. Multiplicative interactions of segregation and BFP receipt (yes or no) in the association with mortality (2004-2015) were assessed. Results: Data on 21 680 930 women (mean [SD] age, 36.1 [15.3] years) were analyzed. Breast cancer mortality was greater among women living in municipalities with high (adjusted MRR [aMRR], 1.18; 95% CI, 1.13-1.24) and medium (aMRR, 1.08; 95% CI, 1.03-1.12) compared with low segregation. Women who did not receive BFP had higher breast cancer mortality than BFP recipients (aMRR, 1.17; 95% CI, 1.12-1.22). By BFP strata, women who did not receive BFP and lived in municipalities with high income segregation had a 24% greater risk of death from breast cancer compared with those living in municipalities with low income segregation (aMRR, 1.24: 95% CI, 1.14-1.34); women who received BFP and were living in areas with high income segregation had a 13% higher risk of death from breast cancer compared with those living in municipalities with low income segregation (aMRR, 1.13; 95% CI, 1.07-1.19; P for interaction = .008). Stratified by the amount of time receiving the benefit, segregation (high vs low) was associated with an increase in mortality risk for women receiving BFP for less time but not for those receiving it for more time (<4 years: aMRR, 1.16; 95% CI, 1.07-1.27; 4-11 years: aMRR, 1.09; 95% CI, 1.00-1.17; P for interaction <.001). Conclusions and Relevance: These findings suggest that place-based inequities in breast cancer mortality associated with income segregation may be mitigated with BFP receipt, possibly via improved income and access to preventive cancer care services among women, which may be associated with early detection and treatment and ultimately reduced mortality.

The intersection of race/ethnicity and socioeconomic status: inequalities in breast and cervical cancer mortality in 20,665,005 adult women from the 100 Million Brazilian Cohort.

OBJECTIVES: There is limited evidence regarding the impact of race/racism and its intersection with socioeconomic status (SES) on breast and cervical cancer, the two most common female cancers globally. We investigated racial inequalities in breast and cervical cancer mortality and whether SES (education and household conditions) interacted with race/ethnicity. DESIGN: The 100 Million Brazilian Cohort data were linked to the Brazilian Mortality Database, 2004-2015 (n = 20,665,005 adult women). We analysed the association between self-reported race/ethnicity (White/'Parda'(Brown)/Black/Asian/Indigenous) and cancer mortality using Poisson regression, adjusting for age, calendar year, education, household conditions and area of residence. Additive and multiplicative interactions were assessed. RESULTS: Cervical cancer mortality rates were higher among Indigenous (adjusted Mortality rate ratio = 1.80, 95%CI 1.39-2.33), Asian (1.63, 1.20-2.22), 'Parda'(Brown) (1.27, 1.21-1.33) and Black (1.18, 1.09-1.28) women vs White women. Breast cancer mortality rates were higher among Black (1.10, 1.04-1.17) vs White women. Racial inequalities in cervical cancer mortality were larger among women of poor household conditions, and low education (P for multiplicative interaction <0.001, and 0.02, respectively). Compared to White women living in completely adequate (3-4) household conditions, the risk of cervical cancer mortality in Black women with 3-4, 1-2, and none adequate conditions was 1.10 (1.01-1.21), 1.48 (1.28-1.71), and 2.03 (1.56-2.63), respectively (Relative excess risk due to interaction-RERI = 0.78, 0.18-1.38). Among 'Parda'(Brown) women the risk was 1.18 (1.11-1.25), 1.68 (1.56-1.81), and 1.84 (1.63-2.08), respectively (RERI = 0.52, 0.16-0.87). Compared to high-educated White women, the risk in high-, middle- and low-educated Black women was 1.14 (0.83-1.55), 1.93 (1.57-2.38) and 2.75 (2.33-3.25), respectively (RERI = 0.36, -0.05-0.77). Among 'Parda'(Brown) women the risk was 1.09 (0.91-1.31), 1.99 (1.70-2.33) and 3.03 (2.61-3.52), respectively (RERI = 0.68, 0.48-0.88). No interactions were found for breast cancer. CONCLUSION: Low SES magnified racial inequalities in cervical cancer mortality. The intersection between race/ethnicity, SES and gender needs to be addressed to reduce racial health inequalities.

Prevalence of adult smokers in Brazilian capitals according to socioeconomic deprivation.

OBJECTIVE: To estimate the prevalence of adult smokers in the 26 capitals and the Federal District according to the Brazilian Deprivation Index (Índice Brasileiro de Privação - IBP). METHODS: Dataset on smoking were obtained from the Surveillance of Risk and Protective Factors for Noncommunicable Diseases by Survey (Vigitel) system for the 26 capitals and the Federal District, in the period from 2010 to 2013. The IBP classifies the census sectors according to indicators such as: income less than ½ minimum wage, illiterate population and without sanitary sewage. In the North and Northeast regions, the census sectors were grouped into four categories (low, medium, high and very high deprivation) and in the South, Southeast and Midwest regions into three (low, medium and high deprivation). Prevalence estimates of adult smokers were obtained using the indirect estimation method in small areas. To calculate the prevalence ratios, Poisson models are used. RESULTS: The positive association between prevalence and deprivation of census sector categories was found in 16 (59.3%) of the 27 cities. In nine (33.3%) cities, the sectors with the greatest deprivation had a higher prevalence of smokers when compared to those with the least deprivation, and in two (7.4%) there were no differences. In Aracaju, Belém, Fortaleza, João Pessoa, Macapá and Salvador, the prevalence of adult smokers was three times higher in the group of sectors with greater deprivation compared to those with less deprivation. CONCLUSION: Sectors with greater social deprivation had a higher prevalence of smoking, compared with less deprivation, pointing to social inequalities.

Increased Liver Enzymes: An Under-Recognized Finding in Maturity-Onset Diabetes of the Young Type 5 (MODY 5).

Maturity-onset diabetes of the young type 5 (MODY 5) is characterized by a single gene mutation in the HNF1B gene. This frequently leads to insulin resistance and presents as young-onset diabetes. Other manifestations can occur in organs expressing hepatocyte nuclear factor-1 beta. This case report highlights family members with MODY 5 presenting with increased liver enzymes with no etiology. The siblings and their mother had a point mutation p.Arg235Trp in HNF1B gene located at 17q12. This variant is associated with autosomal dominant MODY 5 with renal cysts also known as renal cysts and diabetes syndrome.

Tendência temporal da prevalência e mortalidade infantil das anomalias congênitas no Brasil, de 2001 a 2018 / Temporal trends in prevalence and infant mortality of birth defects in Brazil, from 2001 to 2018

Resumo As anomalias congênitas (AC) configuram um relevante problema para a saúde pública global, afetando em média de 3% a 6% dos recém-nascidos em todo o mundo. No Brasil, ocupam a segunda posição entre os principais grupos de causas de óbito infantil. Assim, estudos amplos são necessários para mostrar o impacto das AC na saúde infantil. O presente estudo descreve a tendência temporal da prevalência e da mortalidade infantil por AC entre nascidos vivos (NV) no Brasil e em suas cinco regiões de 2001 a 2018, utilizando dados vinculados entre as bases de dados do Sistema de Informações sobre Nascidos Vivos (SINASC) e do Sistema de Informações sobre Mortalidade (SIM). A prevalência e mortalidade infantil por AC mostrou-se crescente no Brasil na maioria das regiões, principalmente no Norte e no Nordeste. Aquelas do aparelho osteomuscular foram as mais prevalentes ao nascimento (29,8/10.000 NV); as do aparelho circulatório passaram para a segunda posição (12,7/10.000 NV) após a vinculação das bases e representam a primeira causa de morte desse grupo. A técnica de vinculação de dados aplicada corrigiu a prevalência nacional das AC em 17,9% no período analisado, após serem recuperadas as AC notificadas no SIM, mostrando ser uma boa ferramenta para melhorar a qualidade das informações das AC.

Abstract Congenital anomalies (CA) are a relevant problem for global public health, affecting about 3% to 6% of newborns worldwide. In Brazil, these are the second main cause of infant mortality. Thus, extensive studies are needed to demonstrate the impact of these anomalies on births and deaths. The present study describes the temporal trends of prevalence and infant mortality due to CA among live births in Brazil and regions, from 2001 to 2018, using the related data between the Live Birth Information System (SINASC, acronym in Portuguese) and the Mortality Information System (SIM, acronym in Portuguese). The prevalence and infant mortality due to CA has increased in Brazil and in most regions, especially in the Northeast and North. CAs in the musculoskeletal system were the most frequent at birth (29.8/10,000 live births), followed by those in the circulatory system (12.7/10,000 live births), which represented the primary cause of death in this group. The applied linkage technique made it possible to correct the national prevalence of CA by 17.9% during the analyzed period, after retrieving the anomalies reported in SIM, thereby proving to be a good tool to improve the quality of information on anomalies in Brazil.

Impact of cash transfer programs on birth and child growth outcomes: systematic review / Impacto dos programas de transferência de renda nos desfechos de nascimento e crescimento infantil: revisão sistemática

Abstract To investigate the impact of cash transfer (CTs) on birth outcomes, including birth weight, low birth weight and prematurity, as well as child physical growth were included, as assessed by anthropometric indices in children under five years of age. Searching was performed using the PubMed/Medline, Embase, LILACS, Cochrane Library, Scopus and Web of Science databases. Quantitative observational, experimental and quasi-experimental. Eleven studies were included in the review. The majority (81.8%) were carried out in low-and middle-income countries and most involved conditional CTs (63.6%). Four were clinical trials and seven were observational studies. Conditional CTs were found to be associated with a reduction in height-for-age (-0.14; 95%CI -0.27, -0.02); (OR 0.85; 95%CI 0.77-0.94); (OR = 0.44; 95%CI 0.19-0.98), a significantly reduced chance of low weight-for-age (OR = 0.16; 95%CI -0.11-0.43), low weight-for-height (OR = -0.68; 95%CI -1.14, -0.21), and low weight-for-age (OR = 0.27; 95%CI 0.10; 0.71). Unconditional CTs were associated with reduced birth weight (RR = 0.71; 95%CI 0.63-0.81; p < 0.0001) and preterm births (RR = 0.76; 95%CI 0.69-0.84; p < 0.0001). Conditional CTs can positively influence birth outcomes and child growth.

Resumo Investigar o impacto dos programas de tranferência de renda (CTs) nos desfechos ao nascer, incluindo peso ao nascer, baixo peso ao nascer e prematuridade, e crescimento físico infantil, avaliado pelos índices antropométricos de crianças menores de cinco anos. Revisão sistemática realizada nas bases de dados PubMed/Medline, Embase, LILACS, Cochrane Library, Scopus e Web of Science. Foram incluídos estudos quantitativos observacionais, experimentais e quasi-experimentais, com um total de 11 estudos na revisão. A maioria (81,8%) foi realizada em países de baixa e média rendas. Também na modalidade CT condicionais (63,6%). Quatro eram ensaios clínicos, e sete observacionais. Os CT condicionais estiveram associados a uma redução nos índices de altura-para-idade (-0,14; IC95% -0,27, -0,02); (OR 0,85; IC95% 0,77-0,94); (OR = 0,44; IC95% 0,19-0,98), redução significativa na chance de baixo peso-para-idade (OR = 0,16; IC95% -0,11-0,43), baixo peso-para-altura (OR = -0,68; IC95% -1,14, -0,21), e redução de peso para idade (OR = 0,27; IC95% 0,10; 0,71). CTs não condicionais foram associados à redução do baixo peso as nascer (RR = 0,71; IC95% 0,63-0,81; p < 0,0001), e de prematuros (RR = 0,76; IC95% 0,69-0,84; p < 0,0001). Os CTs condicionais podem influenciar positivamente os desfechos ao nascer e o crescimento infantil.

Premature mortality due to noncommunicable diseases in Brazilian capitals: redistribution of garbage causes and evolution by social deprivation strata / Mortalidade prematura por doenças crônicas não transmissíveis em capitais brasileiras: redistribuição de causas garbage e evolução por estratos de privação social

ABSTRACT Objective: To analyze premature mortality due to noncommunicable chronic diseases (NCDs) in Brazilian capitals and the Federal District (DF) after redistribution of garbage causes and the temporal evolution according to social deprivation strata in the 2010 to 2012 and 2017 to 2019 triennia. Methods: Corrections were applied to the Mortality Information System (Sistema de Informação sobre Mortalidade - SIM) data such as the redistribution of garbage codes (GC). Premature mortality rates due to NCDs were calculated and standardized by age. The differences among NCDs mortality rates were analyzed according to the Brazilian Deprivation Index (Índice Brasileiro de Privação - IBP) categories and between the three-year periods. Results: In the capitals as a whole, rates increased between 8 and 12% after GC redistribution and the greatest increases occurred in areas of high deprivation: 11.9 and 11.4%, triennia 1 and 2, respectively. There was variability between the capitals. There was a reduction in rates in all strata of deprivation between the three-year periods, with the greatest decrease in the stratum of low deprivation (-18.2%) and the lowest in the stratum of high deprivation (-7.5%). Conclusion: The redistribution of GC represented an increase in mortality rates, being higher in the strata of greater social deprivation. As a rule, a positive gradient of mortality was observed with increasing social deprivation. The analysis of the temporal evolution showed a decrease in mortality from NCDs between the triennia, especially in areas of lower social deprivation.

RESUMO Objetivo: Analisar a mortalidade prematura por doenças crônicas não transmissíveis (DCNT) nas capitais brasileiras e Distrito Federal (DF) após redistribuição das causas garbage, e a evolução temporal segundo estratos de privação social nos triênios 2010 a 2012 e 2017 a 2019. Métodos: Foram aplicadas correções ao Sistema de Informação sobre Mortalidade (SIM), sendo empregada metodologia para redistribuição das causas garbage (CG). As taxas de mortalidade prematura por DCNT padronizadas por idade foram estimadas. Foram analisadas as diferenças entre as taxas de mortalidade por DCNT segundo categorias do Índice Brasileiro de Privação (IBP) e entre os triênios. Resultados: No conjunto das capitais, as taxas aumentaram entre 8 e 12% após a redistribuição de CG, e os maiores acréscimos ocorreram em áreas de alta privação: 11,9 e 11,4%, triênios 1 e 2, respectivamente. Houve variabilidade entre as capitais. Observou-se redução das taxas em todos os estratos de privação entre os triênios, sendo maior decréscimo no estrato de baixa privação (-18,2%), e menor no estrato de alta privação (-7,5%). Conclusão: A redistribuição de CG representou aumento das taxas de mortalidade, sendo maior nos estratos de maior privação social. Via de regra, observou-se gradiente positivo de mortalidade com o aumento da privação social. A análise da evolução temporal evidenciou decréscimo da mortalidade por DCNT entre os triênios, sobretudo em áreas de menor privação social.

Racial and economic segregation in Brazil: a nationwide analysis of socioeconomic and socio-spatial inequalities / Segregação racial e econômica no Brasil: uma análise nacional das desigualdades socioeconômicas e socioespaciais / Segregación racial y económica en Brasil: un análisis nacional de las desigualdades socioeconómicas y socioespaciales

Abstract This article aims to analyze residential segregation by race (racial segregation) and income (economic segregation) in Brazil and explore its relationship with socioeconomic and socio-spatial factors. Residential segregation was assessed using the dissimilarity index based on the 2010 demographic census and considering urban census tracts since segregation is sociologically considered an urban problem. The results for racial segregation showed that it is more evident in cities in the South and Southeast of Brazil and mainly affects the self-declared black population. The approach used to calculate economic segregation involved examining the income level of different low-income groups. Therefore, we consider families that earned between 0 and 1 minimum wage as the group with the greatest social vulnerability. We did not find significant correlations between racial and income segregation indices with aspects such as urbanization (urban population size). Finally, we present the racial segregation indices stratifying families by income thresholds for the 27 Brazilian capitals and conclude that per capita household income is a preponderant factor for the segregation of the poorest, especially in families whose residents self-identify as black.

Resumo Este artigo tem como objetivo analisar a segregação residencial por raça (segregação racial) e renda (segregação econômica) no Brasil e explorar sua relação com fatores socioeconômicos e socioespaciais. A segregação residencial foi avaliada pelo índice de dissimilaridade baseado no Censo Demográfico de 2010 e considerando setores censitários urbanos, uma vez que a segregação é entendida sociologicamente como um problema urbano. Os resultados mostram que a segregação racial é mais evidente nas cidades do Sul e Sudeste do Brasil, atingindo principalmente a população autodeclarada preta. A abordagem utilizada para calcular a segregação econômica envolveu examinar o nível de renda de diferentes grupos de baixa renda. Portanto, consideramos as famílias que ganham entre 0 e 1 salário mínimo - o grupo de maior vulnerabilidade social. Não encontramos correlações significativas entre os índices de segregação racial e de renda com fatores como a urbanização (tamanho da população urbana). Por fim, apresentamos os índices de segregação racial estratificando as famílias por faixas de renda para as 27 capitais brasileiras e concluímos que a renda domiciliar per capita é fator preponderante para a segregação dos mais pobres, principalmente nas famílias cujos moradores se autodeclaram pretos.

Resumen Este artículo tiene como objetivo analizar la segregación residencial por raza (segregación racial) y renta (segregación económica) en Brasil y explorar su relación con factores socioeconómicos y socioespaciales. La segregación residencial se evaluó utilizando el índice de disimilitud con base en el censo demográfico de 2010 y considerando las secciones censales urbanas ya que la segregación es considerada sociológicamente como un problema urbano. Los resultados para la segregación racial mostraron que esta es más evidente en ciudades del sur y del sudeste de Brasil y que afecta principalmente a la población autodeclarada negra. El enfoque usado para calcular la segregación económica implicó examinar el nivel de ingresos de diferentes grupos de bajos ingresos. Por lo tanto, consideramos que las familias que ganaban entre cero y un salario mínimo son el grupo con mayor vulnerabilidad social. No encontramos correlaciones significativas entre los índices de segregación racial y los de ingresos con factores como la urbanización (tamaño de la población urbana). Finalmente, presentamos los índices de segregación racial estratificando a las familias por umbrales de renta para las 27 capitales brasileñas y concluimos que la renta per cápita de los hogares es un factor preponderante para la segregación de los más pobres, en especial en las familias cuyos habitantes se autodeclaran negros.

Quality of child anthropometric data from SISVAN, Brazil, 2008-2017 / Qualidade dos dados antropométricos infantis do Sisvan, Brasil, 2008-2017

ABSTRACT OBJECTIVE To evaluate the quality of anthropometric data of children recorded in the Food and Nutrition Surveillance System (SISVAN) from 2008 to 2017. METHOD Descriptive study on the quality of anthropometric data of children under five years of age admitted in primary care services of the Unified Health System, from the individual databases of SISVAN. Data quality was annually assessed using the indicators: coverage, completeness, sex ratio, age distribution, weight and height digit preference, implausible z-score values, standard deviation, and normality of z-scores. RESULTS In total, 73,745,023 records and 29,852,480 children were identified. Coverage increased from 17.7% in 2008 to 45.4% in 2017. Completeness of birth date, weight, and height corresponded to almost 100% in all years. The sex ratio was balanced and approximately similar to the expected ratio, ranging from 0.8 to 1. The age distribution revealed higher percentages of registrations from the ages of two to four years until mid-2015. A preference for terminal digits "zero" and "five" was identified among weight and height records. The percentages of implausible z-scores exceeded 1% for all anthropometric indices, with values decreasing from 2014 onwards. A high dispersion of z-scores, including standard deviations between 1.2 and 1.6, was identified mainly in the indices including height and in the records of children under two years of age and residents in the North, Northeast, and Midwest regions. The distribution of z-scores was symmetric for all indices and platykurtic for height/age and weight/age. CONCLUSIONS The quality of SISVAN anthropometric data for children under five years of age has improved substantially between 2008 and 2017. Some indicators require attention, particularly for height measurements, whose quality was lower especially among groups more vulnerable to nutritional problems.

RESUMO OBJETIVOS Avaliar a qualidade dos dados antropométricos de crianças registradas no Sistema de Vigilância Alimentar e Nutricional (Sisvan) no período 2008-2017. MÉTODOS Estudo descritivo sobre a qualidade dos dados antropométricos de crianças menores de 5 anos atendidas nos serviços de atenção primária do Sistema Único de Saúde, a partir das bases de dados individuais do Sisvan. A qualidade dos dados foi avaliada anualmente por meio dos indicadores: cobertura, completude, razão entre sexos, distribuição da idade, preferência por dígitos de peso e estatura, valores de escore-z implausíveis, desvio-padrão e normalidade dos escores-z. RESULTADOS No total, 73.745.023 registros e 29.852.480 crianças foram identificados. A cobertura aumentou de 17,7% em 2008 para 45,4% em 2017. A completude da data de nascimento, peso e estatura correspondeu a quase 100% para todos os anos. A razão entre sexos foi equilibrada e aproximadamente similar a razão esperada, variando entre 0,8 e 1. A distribuição da idade revelou maiores percentuais de registros entre as idades de 2 a 4 anos até meados de 2015. Uma preferência pelos dígitos terminais "zero" e "cinco" foi identificada entre os registros de peso e estatura. As porcentagens de escores-z implausíveis excederam 1% para todos os índices antropométricos, com redução dos valores a partir de 2014. Uma alta dispersão dos escores-z, incluindo desvios-padrão entre 1,2 e 1,6, foi identificada principalmente nos índices incluindo estatura e nos registros de crianças menores de 2 anos e residentes das regiões Norte, Nordeste e Centro-Oeste. A distribuição dos escores-z foi simétrica para todos os índices e platicúrtica para estatura/idade e peso/idade. CONCLUSÕES A qualidade dos dados antropométricos do Sisvan para crianças menores de 5 anos melhorou substancialmente entre 2008 e 2017. Alguns indicadores requerem atenção, sobretudo para medidas de estatura, cuja qualidade foi principalmente inferior entre os grupos mais vulneráveis a agravos nutricionais.

A completeness indicator of gestational and congenital syphilis information in Brazil

ABSTRACT OBJECTIVE To evaluate the quality of information on gestational syphilis (GS) and congenital syphilis (CS) on the Sistema de Informação de Agravos de Notificação (SINAN-Syphilis Brazil - Notifiable Diseases Information System) by compiling and validating completeness indicators between 2007 and 2018. METHODS Overall, care, and socioeconomic completeness scores were compiled based on selected variables, by using ad hoc weights assigned by experts. The completeness scores were analysed, considering the region and area of residence, the pregnant woman's race/colour, and the year of case notification. Pearson's correlation coefficients were used to validate the scores obtained by the weighted average method, compared with the values obtained by principal component analysis (PCA). RESULTS Most selected variables presented a good or excellent degree of completeness for GS and CS, except for clinical classification, pregnant woman's level of education, partner's treatment, and child's race/colour, which were classified as poor or very poor. The overall (89.93% versus 89.69%) and socioeconomic (88.71% versus 88.24%) completeness scores for GS and CS, respectively, were classified as regular, whereas the care score (GS-90.88%, and CS-90.72%) was good, despite improvements over time. Differences in the overall, care and socioeconomic completeness scores according to region, area of residence, and ethnic-racial groups were reported for syphilis notifications. The completeness scores estimated by the weighted average method and PCA showed a strong linear correlation (> 0.90). CONCLUSION The completeness of GS and CS notifications has been improving in recent years, highlighting the variables that form the care score, compared with the socioeconomic scores, despite differences between regions, area of residence, and ethnic-racial groups. The weighted average was a viable methodological alternative easily operationalised to estimate data completeness scores, allowing routine monitoring of the completeness of gestational and congenital syphilis records.

Trajetória acadêmica da Profa. Ana Marlúcia Oliveira: contribuições para o campo da alimentação e nutrição no Brasil / Academic trajectory of Prof. Ana Marlúcia Oliveira: contributions to the field of food and nutrition in Brazil

RESUMO São apresentadas neste artigo as principais contribuições acadêmicas da Profa. Marlúcia Oliveira (AMO) (in memoriam), nutricionista, docente da Escola de Nutrição da Universidade Federal da Bahia, Doutora em Epidemiologia e Pesquisadora A do Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ), no período de 1980 a 2021. A Profa. Ana acumulou, ao longo de sua carreira acadêmica, artigos científicos publicados em periódicos nacionais e internacionais; livro e capítulos de livro de sua autoria; trabalhos apresentados em eventos científicos, além de ter orientado projetos de iniciação científica, dissertações e teses. Coordenou vários projetos de pesquisa no campo da alimentação e nutrição em saúde coletiva, com foco na epidemiologia nutricional. O escopo dos assuntos abordados na sua produção científica expressou a inquietude que a mobilizava em torno da produção de conhecimentos para o enfrentamento dos complexos problemas de saúde e nutrição do Brasil. Sua forma de ser no mundo, acolhendo e cuidando das pessoas que se aproximavam em busca de oportunidades de qualificação, seu exemplo, suas palavras e ensinamentos influenciaram, e ainda influenciam, a trajetória e a formação de nutricionistas e de professores e pesquisadores na Escola de Nutrição da Universidade Federal da Bahia (ENUFBA) e em outras instituições nacionais e internacionais. Trata-se de uma pesquisadora e intelectual brasileira comprometida com a saúde das populações mais vulneráveis e com o combate contra a desnutrição e a fome no nosso país. Sua vasta e fecunda obra nos deixou um legado a ser lembrado e continuado. Alguns dos seus amigos, colegas e colaboradores prestam este tributo à sua memória e ao legado que ela deixou para todos nós e para as próximas gerações.

RESUMO It will be presented the main academic contributions of Professor Ana Marlúcia Oliveira (AMO) (in memoriam), nutritionist, professor at the School of Nutrition at the Federal University of Bahia, Ph.D. in epidemiology and CNPQ Researcher level A, from 1980 to 2021. Professor Ana accumulated, throughout her academic career, scientific articles published in national and international journals; book and book chapters authored by her; papers presented at scientific events, in addition to guiding scientific projects, dissertations and theses. She has coordinated several research projects in the field of food and nutrition in public health, with a focus on nutritional epidemiology. The scope of the subjects addressed in her scientific production expressed the concern that mobilized her around the production of knowledge to face the complex health and nutrition problems in Brazil. Her way of being in the world, welcoming and caring for people who approached her seeking qualification opportunities, her example, words and teachings influenced, and still influence, the trajectory and training of nutritionists, professors and researchers at ENUFBA and other national and international institutions. She was a Brazilian researcher and intellectual committed to the health of the most vulnerable populations and the fight against malnutrition and hunger in our country. Her wide and fruitful work left us a legacy to be remembered and continued. Some of her friends, colleagues and collaborators pay this tribute to her memory, to her example and to the legacy she left for all of us and future generations.

Prevalence of adult smokers in Brazilian capitals according to socioeconomic deprivation / Prevalência de fumantes adultos nas capitais brasileiras, segundo privação socioeconômica

ABSTRACT Objective: To estimate the prevalence of adult smokers in the 26 capitals and the Federal District according to the Brazilian Deprivation Index (Índice Brasileiro de Privação - IBP). Methods: Dataset on smoking were obtained from the Surveillance of Risk and Protective Factors for Noncommunicable Diseases by Survey (Vigitel) system for the 26 capitals and the Federal District, in the period from 2010 to 2013. The IBP classifies the census sectors according to indicators such as: income less than ½ minimum wage, illiterate population and without sanitary sewage. In the North and Northeast regions, the census sectors were grouped into four categories (low, medium, high and very high deprivation) and in the South, Southeast and Midwest regions into three (low, medium and high deprivation). Prevalence estimates of adult smokers were obtained using the indirect estimation method in small areas. To calculate the prevalence ratios, Poisson models are used. Results: The positive association between prevalence and deprivation of census sector categories was found in 16 (59.3%) of the 27 cities. In nine (33.3%) cities, the sectors with the greatest deprivation had a higher prevalence of smokers when compared to those with the least deprivation, and in two (7.4%) there were no differences. In Aracaju, Belém, Fortaleza, João Pessoa, Macapá and Salvador, the prevalence of adult smokers was three times higher in the group of sectors with greater deprivation compared to those with less deprivation. Conclusion: Sectors with greater social deprivation had a higher prevalence of smoking, compared with less deprivation, pointing to social inequalities.

RESUMO Objetivo: Estimar as prevalências de adultos fumante nas 26 capitais e no Distrito Federal segundo o Índice Brasileiro de Privação. Métodos: Os dados sobre tabagismo foram obtidos junto ao sistema de Vigilância de Fatores de Risco e Proteção para Doenças Crônicas por Inquérito (Vigitel) para as 26 capitais e o Distrito Federal, no período de 2010 a 2013. O Índice Brasileiro de Privação classifica os setores censitários segundo indicadores como: renda menor que meio salário mínimo, população não alfabetizada e sem esgotamento sanitário. Nas regiões Norte e Nordeste, os setores censitários foram agrupados em quatro categorias (baixa, média, alta e muito alta privação) e, nas regiões Sul, Sudeste e Centro-Oeste, em três (baixa, média e alta privação). As estimativas de prevalências de adultos fumantes foram obtidas pelo método indireto de estimação em pequenas áreas. Para o cálculo das razões de prevalências, empregram-se modelos de Poisson. Resultados: A associação positiva entre a prevalência e a privação das categorias de setores censitários foi encontrada em 16 (59,3%) das 27 cidades. Em nove (33,3%) cidades, os setores de maior privação apresentaram maior prevalência de fumantes quando comparados aos de menor privação e, em duas (7,4%), não apresentaram diferenças. Em Aracaju, Belém, Fortaleza, João Pessoa, Macapá e Salvador, as prevalências de adultos fumantes foram três vezes maiores no grupo de setores com maior privação em relação aos de menor privação. Conclusão: Setores de maior privação social apresentaram maiores prevalências de tabagismo, comparados com menor privação, apontando desigualdades sociais.

Main and moderated effects of multimorbidity and depressive symptoms on cognition

Objective: Multimorbidity, or the occurrence of two or more chronic conditions, is a global challenge, with implications for mortality, morbidity, disability, and life quality. Psychiatric disorders are common among the chronic diseases that affect patients with multimorbidity. It is still not well understood whether psychiatric symptoms, especially depressive symptoms, moderate the effect of multimorbidity on cognition. Methods: We used a large (n=2,681) dataset to assess whether depressive symptomatology moderates the effect of multimorbidity on cognition using structural equation modelling. Results: It was found that the more depressive symptoms and chronic conditions, the worse the cognitive performance, and the higher the educational level, the better the cognitive performance. We found a significant but weak (0.009; p = 0.04) moderating effect. Conclusion: We have provided the first estimate of the moderating effect of depression on the relation between multimorbidity and cognition, which was small. Although this moderation has been implied by many previous studies, it was never previously estimated.

Mortality inequalities measured by socioeconomic indicators in Brazil: a scoping review.

OBJECTIVE: Summarize the literature on the relationship between composite socioeconomic indicators and mortality in different geographical areas of Brazil. METHODS: This scoping review included articles published between January 1, 2000, and August 31, 2020, retrieved by means of a bibliographic search carried out in the Medline, Scopus, Web of Science, and Lilacs databases. Studies reporting on the association between composite socioeconomic indicators and all-cause, or specific cause of death in any age group in different geographical areas were selected. The review summarized the measures constructed, their associations with the outcomes, and potential study limitations. RESULTS: Of the 77 full texts that met the inclusion criteria, the study reviewed 24. The area level of composite socioeconomic indicators analyzed comprised municipalities (n = 6), districts (n = 5), census tracts (n = 4), state (n = 2), country (n = 2), and other areas (n = 5). Six studies used composite socioeconomic indicators such as the Human Development Index, Gross Domestic Product, and the Gini Index; the remaining 18 papers created their own socioeconomic measures based on sociodemographic and health indicators. Socioeconomic status was inversely associated with higher rates of all-cause mortality, external cause mortality, suicide, homicide, fetal and infant mortality, respiratory and circulatory diseases, stroke, infectious and parasitic diseases, malnutrition, gastroenteritis, and oropharyngeal cancer. Higher mortality rates due to colorectal cancer, leukemia, a general group of neoplasms, traffic accident, and suicide, in turn, were observed in less deprived areas and/or those with more significant socioeconomic development. Underreporting of death and differences in mortality coverage in Brazilian areas were cited as the main limitation. CONCLUSIONS: Studies analyzed mortality inequalities in different geographical areas by means of composite socioeconomic indicators, showing that the association directions vary according to the mortality outcome. But studies on all-cause mortality and at the census tract level remain scarce. The results may guide the development of new composite socioeconomic indicators for use in mortality inequality analysis.

Real-world effectiveness of biological therapy in patients with rheumatoid arthritis: Systematic review and meta-analysis.

Background: The treatment of rheumatoid arthritis (RA), a chronic systemic inflammatory autoimmune disease, is based on disease-modifying anti-rheumatic drugs (DMARDs). Typically, it starts with conventional synthetic DMARDs (csDMARDs), and depending on the patient's response to the treatment and the adverse events experienced, biological DMARDs (bDMARDs) are initiated. bDMARDs are more specific to inflammatory factors than csDMARDs and more efficient in inducing remission and low disease activity. Thus, this study aimed to assess the effectiveness of biological therapy in patients with rheumatoid arthritis in administrative health databases. Methods: PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science databases were searched from inception to 21 October 2021, to identify observational studies that evaluated the effectiveness of biological therapy in patients with rheumatoid arthritis using administrative databases and real-world data. The methodological quality was assessed by the methodological index for non-randomized studies (MINORS). A fixed or random-effects model estimated risk ratios with 95% confidence intervals. The analysis was divided into four groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus TNFi (adalimumab, etanercept, and golimumab versus infliximab); bDMARDs versus Janus kinase inhibitors (JAKi); and bDMARDs monotherapy versus combination therapy (bDMARDs and MTX). Results: Twenty-one records were eligible for inclusion in this systematic review and meta-analysis; seven population-based cohorts, eight prospective, and six retrospective cohort studies. Overall, 182,098 rheumatoid arthritis patients were evaluated. In the meta-analysis, lower effectiveness was observed among TNFi users than in non-TNFi (RR: 0.88; 95% CI: 0.81-0.95; p < 0.01; I2 = 94.0%) and bDMARDs than in JAKi (RR: 0.86; 95% CI: 0.79-0.94; p < 0.01; I2 = 93.0%). Higher effectiveness among adalimumab, etanercept, and golimumab than in infliximab (RR: 1.19; 95% CI: 1.05-1.36; p < 0.01; I2 = 96.0%) was found. No significant differences in the effectiveness of bDMARD monotherapy compared to combination therapy (RR: 0.83; 95% CI: 0.68-1.00; p < 0.01; I2 = 81.0%) was observed. E-value analysis indicated that the estimates were not robust against unmeasured confounding. Conclusion: According to the available real-world data, our results suggest that biological therapy effectively treats patients with rheumatoid arthritis, indicating higher effectiveness with non-TNFi and JAKi than with TNFi. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID#CRD42020190838, identifier CRD42020190838.

Safety of biological therapy in patients with rheumatoid arthritis in administrative health databases: A systematic review and meta-analysis.

Background: Rheumatoid arthritis (RA) is a systemic inflammatory disease that affects the synovial fluid of joints, tendons, and some extra-articular sites. Biologic agents have been highly effective and are comparable in reducing RA symptoms, slowing disease progression, and improving physical function; however, concerns have been raised about the risks of several potential adverse effects. Thus, this study aimed to assess the safety of biological therapy in patients with rheumatoid arthritis in observational studies using administrative health databases. Methods: PubMed, Embase, Lilacs, Ovid, Scopus, and Web of Science were searched from inception to 21 October 2021. The analysis was divided into five groups: tumor necrosis factor inhibitors (TNFi) versus non-TNFi; TNFi versus csDMARDs; bDMARDs versus csDMARDs; abatacept versus bDMARDs; and TNFi versus Janus kinase inhibitors (JAKi). The adverse events were cancer, cardiovascular events, infection, herpes zoster, tuberculosis, and death. The methodological quality of the studies was assessed by the Newcastle-Ottawa Scale. A random-effects model estimated risk ratios with 95% confidence intervals. Results: Thirty-one studies were eligible for inclusion in the present systematic review, published from 2014 to 2021. A total of 1,039,398 RA patients were assessed. The 31 studies evaluated eleven different biological drugs. No significant differences were found regarding safety between TNFi versus non-TNFi (RR 1.08; 95% CI 0.92-1.28; p < 0.01; I2 = 93.0%), TNFi versus csDMARDs (RR 0.91; 95% CI 0.75-1.10; p < 0.01; I2 = 87.0%), bDMARDs versus csDMARDs (RR 0.99; 95% CI 0.82-1.20; p < 0.01; I2 = 93.0%), abatacept versus bDMARDs (RR 0.80; 95% CI 0.54-1.18; p < 0.01; I2 = 90.0%), and TNFi versus JAKi (RR 3.54; 95% CI 0.30-42.09; p = 0.01; I2 = 81.0%). In the subgroup analysis, among studies comparing abatacept to TNFi, a lower risk of cardiovascular events was associated with abatacept (RR 0.37; 95% CI 0.24-0.55). Conclusion: Our results do not suggest an increased risk of adverse events associated with biological therapy in treating RA patients, indicating a lower risk of cardiovascular events with abatacept than TNFi. However, these findings must be interpreted with caution given the limitations of this study and the low/very low certainty of the evidence. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?, identifier [CRD42020190838].