The intersecting effects of race, wealth, and education on AIDS incidence, mortality, and case-fatality rate: a Brazilian cohort study of 28.3 million individuals.

The relationships between race, education, wealth, their intersections and AIDS morbidity/mortality were analyzed in retrospective cohort of 28.3 million individuals followed for 9 years (2007-2015). Together with several sensitivity analyses, a wide range of interactions on additive and multiplicative scales were estimated. Race, education, and wealth were each strongly associated with all of the AIDS-related outcomes, and the magnitude of the associations increased as intersections were included. A significantly higher risk of illness (aRR: 3.07, 95%CI:2.67-3.53) and death (aRR: 4.96, 95%CI:3.99-6.16) from AIDS was observed at the intersection of Black race, lower educational attainment, and less wealth. A higher case-fatality rate (aRR: 1.62, 95%CI:1.18-2.21) was also seen for the same intersectional group. Historically oppressed groups lying at the intersections of race, education, and wealth, had a considerably higher risk of illness and death from AIDS. AIDS-related interventions will require the implementation of comprehensive intersectoral policies that follow an intersectionality perspective.

Syphilis in pregnancy and adverse birth outcomes: A nationwide longitudinal study in Brazil.

OBJECTIVE: The present study aimed to evaluate the association between syphilis in pregnancy and low birth weight, small for gestational age, and preterm birth. METHODS: This longitudinal study used Brazilian National Information System for livebirths (SINASC) linked to the gestational syphilis cases from Notifiable Diseases Information System (SINAN) from 2011 to 2017. Descriptive statistics and logistic regression were used to compare the birth outcomes of pregnant women with and without syphilis. The study protocol was approved by the Research Ethics Committee of the Institute of Collective Health of the Federal University of Bahia (CAAE: registration no. 18022319.4.0000.5030). RESULTS: A total of 17 930 817 live births were included in the study. Of these, 155 214 (8.7/1000) were exposed to syphilis during pregnancy. Maternal syphilis increased the odds of low birth weight (aOR 1.88, 95% CI: 1.85-1.91), small for gestational age (aOR 1.53, 95% CI: 1.51-1.56), and preterm birth (aOR 1.35, 95% CI: 1.33-1.37). Higher odds were observed for pregnant women with VDRL titer ≥64 and untreated maternal syphilis when compared to mothers without syphilis. Analysis stratified by prenatal care showed higher odds for all adverse birth outcomes for mothers attending ≤6 prenatal appointments. CONCLUSION: Our findings showed a strong association between gestational syphilis and adverse birth outcomes with increased odds observed among women with higher VDRL titers, lack of treatment, and fewer prenatal appointments. These results highlight the need for adequate screening and treatment for gestational syphilis during pregnancy to mitigate the risk of adverse birth outcomes.

Estimation and probabilistic projection of age- and sex-specific mortality rates across Brazilian municipalities between 2010 and 2030.

BACKGROUND: Mortality rate estimation in small areas can be difficult due the low number of events/exposure (i.e. stochastic error). If the death records are not completed, it adds a systematic uncertainty on the mortality estimates. Previous studies in Brazil have combined demographic and statistical methods to partially overcome these issues. We estimated age- and sex-specific mortality rates for all 5,565 Brazilian municipalities in 2010 and forecasted probabilistic mortality rates and life expectancy between 2010 and 2030. METHODS: We used a combination of the Tool for Projecting Age-Specific Rates Using Linear Splines (TOPALS), Bayesian Model, Spatial Smoothing Model and an ad-hoc procedure to estimate age- and sex-specific mortality rates for all Brazilian municipalities for 2010. Then we adapted the Lee-Carter model to forecast mortality rates by age and sex in all municipalities between 2010 and 2030. RESULTS: The adjusted sex- and age-specific mortality rates for all Brazilian municipalities in 2010 reveal a distinct regional pattern, showcasing a decrease in life expectancy in less socioeconomically developed municipalities when compared to estimates without adjustments. The forecasted mortality rates indicate varying regional improvements, leading to a convergence in life expectancy at birth among small areas in Brazil. Consequently, a reduction in the variability of age at death across Brazil's municipalities was observed, with a persistent sex differential. CONCLUSION: Mortality rates at a small-area level were successfully estimated and forecasted, with associated uncertainty estimates also generated for future life tables. Our approach could be applied across countries with data quality issues to improve public policy planning.

Do social protection programmes affect the burden of breast and cervical cancer? A systematic review.

Background: Socioeconomic conditions are strongly associated with breast and cervical cancer incidence and mortality patterns; therefore, social protection programmes (SPPs) might impact these cancers. This study aimed to evaluate the effect of SPPs on breast and cervical cancer outcomes and their risk/protective factors. Methods: Five databases were searched for articles that assessed participation in PPS and the incidence, survival, mortality (primary outcomes), screening, staging at diagnosis and risk/protective factors (secondary outcomes) for these cancers. Only peer-reviewed quantitative studies of women receiving SPPs compared to eligible women not receiving benefits were included. Independent reviewers selected articles, assessed eligibility, extracted data, and assessed the risk of bias. A harvest plot represents the included studies and shows the direction of effect, sample size and risk of bias. Findings: Of 17,080 documents retrieved, 43 studies were included in the review. No studies evaluated the primary outcomes. They all examined the relationship between SPPs and screening, as well as risk and protective factors. The harvest plot showed that in lower risk of bias studies, participants of SPPs had lower weight and fertility, were older at sexual debut, and breastfed their infants for longer. Interpretation: No studies have yet assessed the effect of SPPs on breast and cervical cancer incidence, survival, or mortality; nevertheless, the existing evidence suggests positive impacts on risk and protective factors.

The effect of conditional cash transfers on tuberculosis incidence and mortality is determined by ethnoracial and socioeconomic factors: a cohort study of 54 million individuals in Brazil.

Background: Conditional Cash Transfers (CCT) are the world's most widely implemented interventions for poverty alleviation. Still, there is no solid evidence of the CCT effects on the reduction of the burden of Tuberculosis (TB) in marginalized and extremely vulnerable populations. We estimated the effect of the Bolsa Família Program (BFP), the largest CCT in the world, on TB incidence, mortality, and case-fatality rate using a nationwide cohort of 54.5 million individuals during a 12-year period in Brazil. Methods: We selected low-income individuals who entered in the 100 Million Brazilians Cohort and were linked to nationwide TB registries between 2004 to 2015, and compared BFP beneficiaries and non-beneficiaries using a quasi-experimental impact evaluation design. We employed inverse probability of treatment weighting (IPTW) multivariable Poisson regressions, adjusted for all relevant socioeconomic, demographic, and healthcare confounding variables - at individual and municipal level. Subsequently, we evaluated BFP effects for different subpopulations according to ethnoracial factors, wealth levels, sex, and age. We also performed several sensitivity and triangulation analyses to verify the robustness of the estimates. Findings: Exposure to BFP was associated with a large reduction in TB incidence in the low-income individuals under study (adjusted rate ratio [aRR]:0.59;95%CI:0.58-0.60) and mortality (aRR:0.69;95%CI:0.65-0.73). The strongest BFP effect was observed in Indigenous people both for TB incidence (aRR:0.37;95%CI:0.32-0.42), and mortality-aRR:0.35;95%CI:0.20-0.62), and in Black and Pardo people (Incidence-aRR:0.58;95%CI:0.57-0.59; Mortality -aRR:0.69;95%CI:0,64-0,73). BFP effects showed a clear gradient according to wealth levels and were considerably stronger among the extremely poor individuals for TB incidence (aRR:0.49, 95%CI:0.49-0.50) and mortality (aRR:0.60;95%CI:0.55-0.65). The BFP effects on case-fatality rates were also positive, however without statistical significance. Interpretation: CCT can strongly reduce TB incidence and mortality in extremely poor, Indigenous, Black and Pardo populations, and could significantly contribute to achieving the End TB Strategy targets and the TB-related Sustainable Development Goals.

Wildfire, deforestation and health in tropical rainforest areas: a scoping review protocol.

INTRODUCTION: Wildfires and deforestation potentially have direct effects on multiple health outcomes as well as indirect consequences for climate change. Tropical rainforest areas are characterised by high rainfall, humidity and temperature, and they are predominantly found in low-income and middle-income countries. This study aims to synthesise the methods, data and health outcomes reported in scientific papers on wildfires and deforestation in these locations. METHODS AND ANALYSIS: We will carry out a scoping review according to the Joanna Briggs Institute's (JBI) manual for scoping reviews and the framework proposed by Arksey and O'Malley, and Levac et al. The search for articles was performed on 18 August 2023, in 16 electronic databases using Medical Subject Headings terms and adaptations for each database from database inception. The search for local studies will be complemented by the manual search in the list of references of the studies selected to compose this review. We screened studies written in English, French, Portuguese and Spanish. We included quantitative studies assessing any human disease outcome, hospitalisation and vital statistics in regions of tropical rainforest. We exclude qualitative studies and quantitative studies whose outcomes do not cover those of interest. The text screening was done by two independent reviewers. Subsequently, we will tabulate the data by the origin of the data source used, the methods and the main findings on health impacts of the extracted data. The results will provide descriptive statistics, along with visual representations in diagrams and tables, complemented by narrative summaries as detailed in the JBI guidelines. ETHICS AND DISSEMINATION: The study does not require an ethical review as it is meta-research and uses published, deidentified secondary data sources. The submission of results for publication in a peer-reviewed journal and presentation at scientific and policymakers' conferences is expected. STUDY REGISTRATION: Open Science Framework (https://osf.io/pnqc7/).

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.

Gut microbiome signature and nasal lavage inflammatory markers in young people with asthma.

Background: Asthma is a complex disease and a severe global public health problem resulting from interactions between genetic background and environmental exposures. It has been suggested that gut microbiota may be related to asthma development; however, such relationships needs further investigation. Objective: This study aimed to characterize the gut microbiota as well as the nasal lavage cytokine profile of asthmatic and nonasthmatic individuals. Methods: Stool and nasal lavage samples were collected from 29 children and adolescents with type 2 asthma and 28 children without asthma in Brazil. Amplicon sequencing of the stool bacterial V4 region of the 16S rRNA gene was performed using Illumina MiSeq. Microbiota analysis was performed by QIIME 2 and PICRUSt2. Type 2 asthma phenotype was characterized by high sputum eosinophil counts and positive skin prick tests for house dust mite, cockroach, and/or cat or dog dander. The nasal immune marker profile was assessed using a customized multiplex panel. Results: Stool microbiota differed significantly between asthmatic and nonasthmatic participants (P = .001). Bacteroides was more abundant in participants with asthma (P < .05), while Prevotella was more abundant in nonasthmatic individuals (P < .05). In people with asthma, the relative abundance of Bacteroides correlated with IL-4 concentration in nasal lavage samples. Inference of microbiota functional capacity identified differential fatty acid biosynthesis in asthmatic compared to nonasthmatic subjects. Conclusion: The stool microbiota differed between asthmatic and nonasthmatic young people in Brazil. Asthma was associated with higher Bacteroides levels, which correlated with nasal IL-4 concentration.

Comparing the effect of imputation reference panel composition in four distinct Latin American cohorts.

Genome-wide association studies have been useful in identifying genetic risk factors for various phenotypes. These studies rely on imputation and many existing panels are largely composed of individuals of European ancestry, resulting in lower levels of imputation quality in underrepresented populations. We aim to analyze how the composition of imputation reference panels affects imputation quality in four target Latin American cohorts. We compared imputation quality for chromosomes 7 and X when altering the imputation reference panel by: 1) increasing the number of Latin American individuals; 2) excluding either Latin American, African, or European individuals, or 3) increasing the Indigenous American (IA) admixture proportions of included Latin Americans. We found that increasing the number of Latin Americans in the reference panel improved imputation quality in the four populations; however, there were differences between chromosomes 7 and X in some cohorts. Excluding Latin Americans from analysis resulted in worse imputation quality in every cohort, while differential effects were seen when excluding Europeans and Africans between and within cohorts and between chromosomes 7 and X. Finally, increasing IA-like admixture proportions in the reference panel increased imputation quality at different levels in different populations. The difference in results between populations and chromosomes suggests that existing and future reference panels containing Latin American individuals are likely to perform differently in different Latin American populations.

Recent changes in growth trajectories: a population-based cohort study of over 5 million Brazilian children born between 2001 and 2014.

Background: There is limited evidence on recent trends in childhood growth trajectories in Low-/middle-income countries. We investigated how age-trajectories for height and Body Mass Index (BMI) have changed among Brazilian children born in two different time periods after 2000. Methods: We used a population-based cohort (part of the "Cohort of 100-Million Brazilians") created by the linkage of three Brazilian administrative databases: the Cadastro Único of the Federal Government, the National System of Live Births and the National Nutritional and Food Surveillance System. We included longitudinal data on 5,750,214 children who were 3 to <10 years of age and born between 2001 and 2014 (20,209,133 observations). We applied fractional polynomial models with random-effects to estimate mean height and BMI trajectories for children. Findings: Compared to children born in 2001-2007, the cohort born in 2008-2014 were on average taller, by a z-score of 0.15 in boys and 0.12 in girls. Their height trajectories shifted upwards, by approximately 1 cm in both sexes. Levels of BMI increased little, by a z-score of 0.06 (boys) and 0.04 (girls). Mean BMI trajectories also changed little. However, the prevalence of overweight/obesity increased between cohorts, e.g., from 26.8% to 30% in boys and 23.9%-26.6% in girls aged between 5 and <10 years. Interpretation: An increase of 1 cm in mean height of Brazilian children during a short period indicates the improvement in maternal and child health, especially those from low-income families due to the new health and welfare policies in Brazil. Although mean BMI changed little, the prevalence of child overweight/obesity slightly increased and remained high. Funding: This work was supported by National Council for Scientific and Technological Development - CNPq; Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES; National Institute for Health Research (NIHR) Great Ormond Street Hospital Biomedical Research Centre; Society for the Study of Human Biology; Fundação de Amparo à Pesquisa do Estado de Minas Gerais - FAPEMIG; Departamento de Ciência e Tecnologia da Secretaria de Ciência, Tecnologia, Inovação e Complexo da Saúde do Ministério da Saúde - Decit/SECTICS/MS. The study also used resources from the Centre for Data and Knowledge Integration for Health (CIDACS), which receives funding from the Bill & Melinda Gates Foundation, the Wellcome Trust, the Health Surveillance Secretariat of the Ministry of Health and the Secretariat of Science and Technology of the State of Bahia (SECTI-BA).

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.

The rising trends of self-harm in Brazil: an ecological analysis of notifications, hospitalisations, and mortality between 2011 and 2022.

Background: Self-harm is considered an important public health issue and is comprised by a wide range of definitions and behaviours. It is estimated that suicide affects more than 700,000 individuals every year, although, globally, there is a lack of evidence on other self-harm behaviour, such as attempted suicide. The objective of this study is to report and examine temporal trends of notifications, hospitalisations related to self-harm and suicide rates in Brazil between 2011 and 2022, as well as investigating differences in sociodemographic characteristics, methods, and region. Methods: This ecological study used secondary, Brazilian Health Information System data between 2011 and 2022. Self-harm notifications were collected from the Notifiable Diseases Information System (SINAN); self-harm hospitalisations from the Hospital Information System (SIH), and suicide data from the Mortality Information System (SIM). We calculated self-harm notifications, hospitalisations, and suicide rates by sex, age, race, region, and overall. We assessed time-related trends using Joinpoint regression analyses. Findings: From 2011 to 2022, 720,480 self-harm notifications, 104,458 self-harm hospitalisations, and 147,698 suicides were recorded in Brazil. In this period, self-harm notifications (AAPC: 21.13 (CI: 17.50, 25.33)) and suicide (AAPC: 3.70 (CI: 3.05, 4.38)) have increased in the country. Male adults (25-59 years old) and the elderly (>60 years old) continue to be the groups most affected by suicide, with respective rates of 9.59 and 8.60/100,000 in 2022. However, the largest percentage increases have been seen in young people (AAPC: 6.14 (CI: 4.57, 7.88)). The Indigenous population had the highest self-harm notification (103.72, 10,000) and suicide (16.58/100,000) rates, but the lowest hospitalisation rates (1.14/100,000) in 2022), compared to the overall population (70.06, 7.27, and 4.69/100,000, respectively, in 2022). Interpretation: The observed trend of increased self-harm notifications and suicide rates suggests the need for a greater allocation of resources to strategies to prevent self-harm and suicide. The Indigenous population seems to be the group with less access to healthcare. Funding: Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under award number R01MH128911-01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Evaluating the relationship between conditional cash transfer programme on preterm births: a retrospective longitudinal study using the 100 million Brazilian cohort.

BACKGROUND: Preterm births increase mortality and morbidity during childhood and later life, which is closely associated with poverty and the quality of prenatal care. Therefore, income redistribution and poverty reduction initiatives may be valuable in preventing this outcome. We assessed whether receipt of the Brazilian conditional cash transfer programme - Bolsa Familia Programme, the largest in the world - reduces the occurrence of preterm births, including their severity categories, and explored how this association differs according to prenatal care and the quality of Bolsa Familia Programme management. METHODS: A retrospective cohort study was performed involving the first live singleton births to mothersenrolled in the 100 Million Brazilian Cohort from 2004 to 2015, who had at least one child before cohort enrollment. Only the first birth during the cohort period was included, but born from 2012 onward. A deterministic linkage with the Bolsa Familia Programme payroll dataset and a similarity linkage with the Brazilian Live Birth Information System were performed. The exposed group consisted of newborns to mothers who received Bolsa Familia from conception to delivery. Our outcomes were infants born with a gestational age < 37 weeks: (i) all preterm births, (ii) moderate-to-late (32-36), (iii) severe (28-31), and (iv) extreme (< 28) preterm births compared to at-term newborns. We combined propensity score-based methods and weighted logistic regressions to compare newborns to mothers who did and did not receive Bolsa Familia, controlling for socioeconomic conditions. We also estimated these effects separately, according to the adequacy of prenatal care and the index of quality of Bolsa Familia Programme management. RESULTS: 1,031,053 infants were analyzed; 65.9% of the mothers were beneficiaries. Bolsa Familia Programme was not associated with all sets of preterm births, moderate-to-late, and severe preterm births, but was associated with a reduction in extreme preterm births (weighted OR: 0.69; 95%CI: 0.63-0.76). This reduction can also be observed among mothers receiving adequate prenatal care (weighted OR: 0.66; 95%CI: 0.59-0.74) and living in better Bolsa Familia management municipalities (weighted OR: 0.56; 95%CI: 0.43-0.74). CONCLUSIONS: An income transfer programme for pregnant women of low-socioeconomic status, conditional to attending prenatal care appointments, has been associated with a reduction in extremely preterm births. These programmes could be essential in achieving Sustainable Development Goals.

Association of interpregnancy interval with adverse pregnancy outcomes according to the outcomes of the preceding pregnancy: a longitudinal study with 4.7 million live births from Brazil.

Background: Earlier studies have proposed a link between the Interpregnancy Interval (IPI) and unfavorable birth outcomes. However, it remains unclear if the outcomes of previous births could affect this relationship. We aimed to investigate whether the occurrence of adverse outcomes-small for gestational age (SGA), preterm birth (PTB), and low birth weight (LBW)-at the immediately preceding pregnancy could alter the association between IPI and the same outcomes at the subsequent pregnancy. Methods: We used a population-based linked cohort from Brazil (2001-2015). IPI was measured as the difference, in months, between the preceding birth and subsequent conception. Outcomes included SGA (<10th birthweight percentile for gestational age and sex), LBW (<2500 g), and PTB (gestational age <37 weeks). We calculated risk ratios (RRs), using the IPI of 18-22 months as the reference IPI category, we also stratified by the number of adverse birth outcomes at the preceding pregnancy. Findings: Among 4,788,279 births from 3,804,152 mothers, absolute risks for subsequent SGA, PTB, and LBW were higher for women with more adverse outcomes in the preceding delivery. The RR of SGA and LBW for IPIs <6 months were greater for women without previous adverse outcomes (SGA: 1.44 [95% Confidence Interval (CI): 1.41-1.46]; LBW: 1.49 [1.45-1.52]) compared to those with three previous adverse outcomes (SGA: 1.20 [1.10-1.29]; LBW: 1.24 [1.15-1.33]). IPIs ≥120 months were associated with greater increases in risk for LBW and PTB among women without previous birth outcomes (LBW: 1.59; [1.53-1.65]; PTB: 2.45 [2.39-2.52]) compared to women with three adverse outcomes at the index birth (LBW: 0.92 [0.78-1.06]; PTB: 1.66 [1.44-1.88]). Interpretation: Our study suggests that women with prior adverse outcomes may have higher risks for adverse birth outcomes in subsequent pregnancies. However, risk changes due to differences in IPI length seem to have a lesser impact compared to women without a prior event. Considering maternal obstetric history is essential in birth spacing counseling. Funding: Wellcome Trust225925/Z/22/Z.

Income determines the impact of cash transfers on HIV/AIDS: cohort study of 22.7 million Brazilians.

Living with extremely low-income is an important risk factor for HIV/AIDS and can be mitigated by conditional cash transfers. Using a cohort of 22.7 million low-income individuals during 9 years, we evaluated the effects of the world's largest conditional cash transfer, the Programa Bolsa Família, on HIV/AIDS-related outcomes. Exposure to Programa Bolsa Família was associated with reduced AIDS incidence by 41% (RR:0.59; 95%CI:0.57-0.61), mortality by 39% (RR:0.61; 95%CI:0.57-0.64), and case fatality rates by 25% (RR:0.75; 95%CI:0.66-0.85) in the cohort, and Programa Bolsa Família effects were considerably stronger among individuals of extremely low-income [reduction of 55% for incidence (RR:0.45, 95% CI:0.42-0.47), 54% mortality (RR:0.46, 95% CI:0.42-0.49), and 37% case-fatality (RR:0.63, 95% CI:0.51 -0.76)], decreasing gradually until having no effect in individuals with higher incomes. Similar effects were observed on HIV notification. Programa Bolsa Família impact was also stronger among women and adolescents. Several sensitivity and triangulation analyses demonstrated the robustness of the results. Conditional cash transfers can significantly reduce AIDS morbidity and mortality in extremely vulnerable populations and should be considered an essential intervention to achieve AIDS-related sustainable development goals by 2030.

Ethnoracial disparities in childhood growth trajectories in Brazil: a longitudinal nationwide study of four million children.

BACKGROUND: The literature contains scarce data on inequalities in growth trajectories among children born to mothers of diverse ethnoracial background in the first 5 years of life. OBJECTIVE: We aimed to investigate child growth according to maternal ethnoracial group using a nationwide Brazilian database. METHODS: A population-based retrospective cohort study employed linked data from the CIDACS Birth Cohort and the Brazilian Food and Nutrition Surveillance System (SISVAN). Children born at term, aged 5 years or younger who presented two or more measurements of length/height (cm) and weight (kg) were followed up between 2008 and 2017. Prevalence of stunting, underweight, wasting, and thinness were estimated. Nonlinear mixed effect models were used to estimate childhood growth trajectories, among different maternal ethnoracial groups (White, Asian descent, Black, Pardo, and Indigenous), using the raw measures of weight (kg) and height (cm) and the length/height-for-age (L/HAZ) and weight-for-age z-scores (WAZ). The analyses were also adjusted for mother's age, educational level, and marital status. RESULTS: A total of 4,090,271 children were included in the study. Children of Indigenous mothers exhibited higher rates of stunting (26.74%) and underweight (5.90%). Wasting and thinness were more prevalent among children of Pardo, Asian, Black, and Indigenous mothers than those of White mothers. Regarding children's weight (kg) and length/height (cm), those of Indigenous, Pardo, Black, and Asian descent mothers were on average shorter and weighted less than White ones. Regarding WAZ and L/HAZ growth trajectories, a sharp decline in average z-scores was evidenced in the first weeks of life, followed by a period of recovery. Over time, z-scores for most of the subgroups analyzed trended below zero. Children of mother in greater social vulnerability showed less favorable growth. CONCLUSION: We observed racial disparities in nutritional status and childhood growth trajectories, with children of Indigenous mothers presenting less favorable outcomes compared to their White counterparts. The strengthening of policies aimed at protecting Indigenous children should be urgently undertaken to address systematic ethnoracial health inequalities.

Identifying biologically implausible values in big longitudinal data: an example applied to child growth data from the Brazilian food and nutrition surveillance system.

BACKGROUND: Several strategies for identifying biologically implausible values in longitudinal anthropometric data have recently been proposed, but the suitability of these strategies for large population datasets needs to be better understood. This study evaluated the impact of removing population outliers and the additional value of identifying and removing longitudinal outliers on the trajectories of length/height and weight and on the prevalence of child growth indicators in a large longitudinal dataset of child growth data. METHODS: Length/height and weight measurements of children aged 0 to 59 months from the Brazilian Food and Nutrition Surveillance System were analyzed. Population outliers were identified using z-scores from the World Health Organization (WHO) growth charts. After identifying and removing population outliers, residuals from linear mixed-effects models were used to flag longitudinal outliers. The following cutoffs for residuals were tested to flag those: -3/+3, -4/+4, -5/+5, -6/+6. The selected child growth indicators included length/height-for-age z-scores and weight-for-age z-scores, classified according to the WHO charts. RESULTS: The dataset included 50,154,738 records from 10,775,496 children. Boys and girls had 5.74% and 5.31% of length/height and 5.19% and 4.74% of weight values flagged as population outliers, respectively. After removing those, the percentage of longitudinal outliers varied from 0.02% (<-6/>+6) to 1.47% (<-3/>+3) for length/height and from 0.07 to 1.44% for weight in boys. In girls, the percentage of longitudinal outliers varied from 0.01 to 1.50% for length/height and from 0.08 to 1.45% for weight. The initial removal of population outliers played the most substantial role in the growth trajectories as it was the first step in the cleaning process, while the additional removal of longitudinal outliers had lower influence on those, regardless of the cutoff adopted. The prevalence of the selected indicators were also affected by both population and longitudinal (to a lesser extent) outliers. CONCLUSIONS: Although both population and longitudinal outliers can detect biologically implausible values in child growth data, removing population outliers seemed more relevant in this large administrative dataset, especially in calculating summary statistics. However, both types of outliers need to be identified and removed for the proper evaluation of trajectories.

Risk of death following chikungunya virus disease in the 100 Million Brazilian Cohort, 2015-18: a matched cohort study and self-controlled case series.

BACKGROUND: Chikungunya virus outbreaks have been associated with excess deaths at the ecological level. Previous studies have assessed the risk factors for severe versus mild chikungunya virus disease. However, the risk of death following chikungunya virus disease compared with the risk of death in individuals without the disease remains unexplored. We aimed to investigate the risk of death in the 2 years following chikungunya virus disease. METHODS: We used a population-based cohort study and a self-controlled case series to estimate mortality risks associated with chikungunya virus disease between Jan 1, 2015, and Dec 31, 2018, in Brazil. The dataset was created by linking national databases for social programmes, notifiable diseases, and mortality. For the matched cohort design, individuals with chikungunya virus disease recorded between Jan 1, 2015, and Dec 31, 2018, were considered as exposed and those who were arbovirus disease-free and alive during the study period were considered as unexposed. For the self-controlled case series, we included all deaths from individuals with a chikungunya virus disease record, and each individual acted as their own control according to different study periods relative to the date of disease. The primary outcome was all-cause natural mortality up to 728 days after onset of chikungunya virus disease symptoms, and secondary outcomes were cause-specific deaths, including ischaemic heart diseases, diabetes, and cerebrovascular diseases. FINDINGS: In the matched cohort study, we included 143 787 individuals with chikungunya virus disease who were matched, at the day of symptom onset, to unexposed individuals using sociodemographic factors. The incidence rate ratio (IRR) of death within 7 days of chikungunya symptom onset was 8·40 (95% CI 4·83-20·09) as compared with the unexposed group and decreased to 2·26 (1·50-3·77) at 57-84 days and 1·05 (0·82-1·35) at 85-168 days, with IRR close to 1 and wide CI in the subsequent periods. For the secondary outcomes, the IRR of deaths within 28 days after disease onset were: 1·80 (0·58-7·00) for cerebrovascular diseases, 3·75 (1·33-17·00) for diabetes, and 3·67 (1·25-14·00) for ischaemic heart disease, and there was no evidence of increased risk in the subsequent periods. For the self-controlled case series study, 1933 individuals died after having had chikungunya virus disease and were included in the analysis. The IRR of all-cause natural death within 7 days of symptom onset of chikungunya virus disease was 8·75 (7·18-10·66) and decreased to 1·59 (1·26-2·00) at 57-84 days and 1·09 (0·92-1·29) at 85-168 days. For the secondary outcomes, the IRRs of deaths within 28 days after disease onset were: 2·73 (1·50-4·96) for cerebrovascular diseases, 8·43 (5·00-14·21) for diabetes, and 2·38 (1·33-4·26) for ischaemic heart disease, and there was no evidence of increased risk at 85-168 days. INTERPRETATION: Chikungunya virus disease is associated with an increased risk of death for up to 84 days after symptom onset, including deaths from cerebrovascular diseases, ischaemic heart diseases, and diabetes. This study highlights the need for equitable access to approved vaccines and effective anti-chikungunya virus therapeutics and reinforces the importance of robust vector-control efforts to reduce viral transmission. FUNDING: Brazilian National Research Council (CNPq), Fundação de Amparo à Pesquisa do Estado da Bahia, Wellcome Trust, and UK Medical Research Council. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

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.

Combining Digital and Molecular Approaches Using Health and Alternate Data Sources in a Next-Generation Surveillance System for Anticipating Outbreaks of Pandemic Potential.

Globally, millions of lives are impacted every year by infectious diseases outbreaks. Comprehensive and innovative surveillance strategies aiming at early alert and timely containment of emerging and reemerging pathogens are a pressing priority. Shortcomings and delays in current pathogen surveillance practices further disturbed informing responses, interventions, and mitigation of recent pandemics, including H1N1 influenza and SARS-CoV-2. We present the design principles of the architecture for an early-alert surveillance system that leverages the vast available data landscape, including syndromic data from primary health care, drug sales, and rumors from the lay media and social media to identify areas with an increased number of cases of respiratory disease. In these potentially affected areas, an intensive and fast sample collection and advanced high-throughput genome sequencing analyses would inform on circulating known or novel pathogens by metagenomics-enabled pathogen characterization. Concurrently, the integration of bioclimatic and socioeconomic data, as well as transportation and mobility network data, into a data analytics platform, coupled with advanced mathematical modeling using artificial intelligence or machine learning, will enable more accurate estimation of outbreak spread risk. Such an approach aims to readily identify and characterize regions in the early stages of an outbreak development, as well as model risk and patterns of spread, informing targeted mitigation and control measures. A fully operational system must integrate diverse and robust data streams to translate data into actionable intelligence and actions, ultimately paving the way toward constructing next-generation surveillance systems.