Dupilumab treatment in paediatric atopic dermatitis (2 to 18 years): Spanish multicentre retrospective real-life study.

BACKGROUND: Moderate-to-severe atopic dermatitis (AD) can be difficult to manage in paediatric patients, with few licensed treatments in this age group. Dupilumab is approved for AD in children older than 6 months. OBJECTIVES: To assess the effectiveness and safety of dupilumab in a real-life cohort of paediatric AD patients in Spain. METHODS: A multicentre, retrospective real-life study on the effectiveness and safety of dupilumab in patients aged 2 to 18 years old with moderate-to-severe AD was conducted. Demographic and clinical characteristics were analysed, and effectiveness (EASI, IGA, DLQI, NRS itch), safety, and drug survival measures were assessed. A comparison of our results with other real-world outcomes and with clinical trials was made. RESULTS: Data from 243 patients from 19 centres was collected, with a mean follow-up of 85 weeks. Dupilumab exhibited significant effectiveness, with marked reductions in severity scores from week 4. By week 16, 79.4% of patients reached EASI75 and 40.5% reached EASI90. Mean percentage reduction in EASI was 79.7%. Increasing improvements were observed until week 52, with 85.8% and 49.6% achieving EASI75 and EASI90, respectively. Forty-three patients developed adverse events (AE) (43/243, 17.7%), being the most frequent ocular surface diseases (20/243, 8.2%), injection site reactions (8/243, 3.3%) and facial redness (7/243, 2.9%). Drug survival was high (96.9% and 93.1% after 1 and 2 years of follow-up, respectively), with only 19 (19/243, 7.8%) patients interrupting treatment: 7 (7/243, 2.9%) due to AE, 2 (2/243, 0.82%) due to secondary failure, 5 (5/243, 2.1%) were lost to follow-up and 5 (5/243, 2.1%) entered remission and stopped treatment. CONCLUSION: Real-life use of dupilumab in paediatric AD showcased sustained effectiveness, high drug survival, and acceptable safety profiles. Longer-term studies are crucial for AE surveillance and how to manage disease remission.

Improving patient-centered mental health promotion in primary care in vulnerable communities through mindfulness training in Rio de Janeiro, Brazil.

Introduction: Brazilian Primary Health Care (PHC) is responsible for all-sanitary actions for a community-based population, including health promotion and mental health care. Mindfulness Based Health Promotion (MBHP) is an intervention that can promote self-care and psychosocial support in PHC. Objective: To discuss the effects of mindfulness based psychosocial group interventions for health promotion in primary care units in Rio de Janeiro, Brazil. Methods: The intervention was based on the MBHP model adapted for SUS. Nine groups were held in Rio de Janeiro. A quali-quanti research was held with two parts: (a) quantitative study, pre and after the 8 weeks intervention, evaluating the effect on mindfulness and self-compassion and their association with levels of anxiety, depression, and quality of life. (b) Qualitative research using Focus Groups with the participants to investigate their experience at the end of the mindfulness groups. Results and discussion: Sixty-two participants finished the 9 groups where 86% were women, mostly between 30 and 59 years of age and low income, and around 80% under regular medical care in PHC in SUS. In the studied sample 80% had at least one chronic health condition under treatment, including 42% with anxiety and 35% with depression. The effects included significant improvement in Anxiety and Depression and in Quality of Life, mainly in the psychological but also in the physical and interrelation domains. The qualitative study showed that most patients joined the group on the recommendation of health professionals for managing physical and mental health symptoms. Patients reported being able to use the practices taught in the sessions to manage symptoms such as insomnia and emotionally distressing situations in their daily lives. Including family members in mindfulness practices was a strategy to negotiate not only a space at home to meditate, but also to obtain a different approach to health problems. Participants pointed to mindfulness as a complementary therapeutic option to medication and psychotherapy. Conclusion: Mindfulness-Based Intervention have shown to be a feasible, well-accepted and efficacious method of offering psychosocial support and promoting well-being for low-income patients in primary care in LAMIC.

Barriers That Interfere with Access to Tuberculosis Diagnosis and Treatment across Countries Globally: A Systematic Review.

This study evaluated the barriers that interfere with access to diagnosis and treatment of tuberculosis (TB) from the perspective of the patient and health professionals globally. Using the PICo acronym, the question we asked was "What are the barriers that interfere with access to tuberculosis diagnosis and treatment (I) from the perspective of patients and/or health professionals (P) across countries globally (Co)?". We searched the following databases: EMBASE, Scopus, MEDLINE, Latin American and Caribbean Literature in Health Sciences (LILACS), and Web of Science. On Rayyan, duplicates were removed and extraction was done afterward by two authors independently, followed by a tiebreaker. Using a Critical Appraisal Tool proposed by the Joanna Briggs Institute, the methodological quality of the article was assessed. From 36 published articles, the barriers to tuberculosis diagnosis as obtained from our study include information scarcity/low TB knowledge, exorbitant cost of transport, sample collection challenges, long distance to health facility, gender limitations, lack of decentralized diagnostic services, payment for diagnosis and testing, medication side effects, multiple visits during therapy, delayed diagnosis, poor human resources, low knowledge of medical practitioners, concerns regarding the efficacy of treatment, poor facility coordination, poor socioeconomic factors, fear and stigmatization of TB, and wrong initial diagnosis. The review of studies on TB diagnosis and treatment barriers evidences the diverse barriers to the eradication of tuberculosis. Eliminating these barriers is an onus that lies on policy makers, citizens, and health workers alike, with the joint aim of reducing the global TB burden.

The COVID-19 pandemic in Brazil: space-time approach of cases, deaths, and vaccination coverage (February 2020 - April 2024).

OBJECTIVE: To assess the evolution of the COVID-19 pandemic in Brazil and its macro-regions, considering disease incidence and mortality rates, as well as identifying territories with still rising disease indices and evaluating vaccine coverage and population adherence to COVID-19 immunization. METHODS: An ecological study conducted in Brazil with COVID-19 cases and deaths reported between February 2020 and April 2024, obtained through the Coronavirus Panel. Historical series were constructed from incidence and mortality rates to assess the pandemic's evolution, and temporal trends were estimated using the Seasonal Trend Decomposition using Loess (STL) method. The Spatial Variation in Temporal Trends (SVTT) technique was employed to identify clusters with significant variations in temporal trends. Vaccination was analyzed considering the percentage of vaccinated and unvaccinated population in each municipality of the country. RESULTS: Brazil recorded a total of 38,795,966 cases and 712,038 deaths from COVID-19 during the study period. Incidence and mortality rates showed three waves of the disease, with a fourth wave of smaller amplitude. Four clusters with significant case growth and two with increased deaths were identified. Vaccine coverage varied among municipalities, with some regions showing low vaccination rates and others with high immunization adherence. CONCLUSION: The study provided a comprehensive overview of coronavirus behavior in Brazil, and its results highlight the ongoing importance of vaccination and the need to direct efforts and resources to areas of higher risk.

Smoking, mortality, access to diagnosis, and treatment of lung cancer in Brazil.

INTRODUCTION: Lung cancer (LC) is a relevant public health problem in Brazil and worldwide, given its high incidence and mortality. Thus, the objective of this study is to analyze the distribution of smoking and smoking status according to sociodemographic characteristics and disparities in access, treatment, and mortality due to LC in Brazil in 2013 and 2019. METHOD: Retrospective study of triangulation of national data sources: a) analysis of the distribution of smoking, based on the National Survey of Health (PNS); b) investigation of LC records via Hospital-based Cancer Registry (HCR); and c) distribution of mortality due to LC in the Mortality Information System (SIM). RESULTS: There was a decrease in the percentage of people who had never smoked from 2013 (68.5%) to 2019 (60.2%) and in smoking history (pack-years). This was observed to be greater in men, people of older age groups, and those with less education. Concerning patients registered in the HCR, entry into the healthcare service occurs at the age of 50, and only 19% have never smoked. While smokers in the population are mainly Mixed-race, patients in the HCR are primarily White. As for the initial stage (I and II), it is more common in White people and people who have never smoked. The mortality rate varied from 1.00 for people with higher education to 3.36 for people without education. Furthermore, White people have a mortality rate three times higher than that of Black and mixed-race people. CONCLUSION: This article highlighted relevant sociodemographic disparities in access to LC diagnosis, treatment, and mortality. Therefore, the recommendation is to strengthen the Population-Based Cancer Registry and develop and implement a nationwide LC screening strategy in Brazil since combined prevention and early diagnosis strategies work better in controlling mortality from the disease and continued investment in tobacco prevention and control policies.

Multi-platform whole genome sequencing for tuberculosis clinical and surveillance applications.

Whole genome sequencing (WGS) of Mycobacterium tuberculosis offers valuable insights for tuberculosis (TB) control. High throughput platforms like Illumina and Oxford Nanopore Technology (ONT) are increasingly used globally, although ONT is known for higher error rates and is less established for genomic studies. Here we present a study comparing the sequencing outputs of both Illumina and ONT platforms, analysing DNA from 59 clinical isolates in highly endemic TB regions of Thailand. The resulting sequence data were used to profile the M. tuberculosis pairs for their lineage, drug resistance and presence in transmission chains, and were compared to publicly available WGS data from Thailand (n = 1456). Our results revealed isolates that are predominantly from lineages 1 and 2, with consistent drug resistance profiles, including six multidrug-resistant strains; however, analysis of ONT data showed longer phylogenetic branches, emphasising the technologies higher error rate. An analysis incorporating the larger dataset identified fifteen of our samples within six potential transmission clusters, including a significant clade of 41 multi-drug resistant isolates. ONT's extended sequences also revealed strain-specific structural variants in pe/ppe genes (e.g. ppe50), which are candidate loci for vaccine development. Despite some limitations, our results show that ONT sequencing is a promising approach for TB genomic research, supporting precision medicine and decision-making in areas with less developed infrastructure, which is crucial for tackling the disease's significant regional burden.

Atopic Dermatitis: Fertility, Pregnancy, and Treatment Perspectives.

Hormonal and immunologic changes during pregnancy can contribute to the development of different dermatoses, the most common of which is atopic eruption of pregnancy (AEP). Of atopic dermatitis (AD) cases during pregnancy, 80% are new-onset presentations, while 20% represent recurrences or exacerbations of preexisting disease. Evidence on the effects of previous AD on fertility is limited. Different factors influence women's desire to conceive in this setting, and it has been hypothesized that barrier defects and systemic inflammation could contribute to biologic infertility, although more data are needed. Clinical practice suggests a tendency toward undertreatment in pregnant woman due to concerns about potential effects on obstetric and fetal outcomes. However, pregnant women should be offered adequate and safe treatments, preferably on an individual basis. The aim of this review was to summarize the evidence on disease course in pregnant women with AD and the challenges associated with its diagnosis and management. We also review the current evidence on the use of conventional and novel systemic therapies for AD in this population.

Single-cell multi-omics analysis of COVID-19 patients with pre-existing autoimmune diseases shows aberrant immune responses to infection.

In COVID-19, hyperinflammatory and dysregulated immune responses contribute to severity. Patients with pre-existing autoimmune conditions can therefore be at increased risk of severe COVID-19 and/or associated sequelae, yet SARS-CoV-2 infection in this group has been little studied. Here, we performed single-cell analysis of peripheral blood mononuclear cells from patients with three major autoimmune diseases (rheumatoid arthritis, psoriasis, or multiple sclerosis) during SARS-CoV-2 infection. We observed compositional differences between the autoimmune disease groups coupled with altered patterns of gene expression, transcription factor activity, and cell-cell communication that substantially shape the immune response under SARS-CoV-2 infection. While enrichment of HLA-DRlow CD14+ monocytes was observed in all three autoimmune disease groups, type-I interferon signaling as well as inflammatory T cell and monocyte responses varied widely between the three groups of patients. Our results reveal disturbed immune responses to SARS-CoV-2 in patients with pre-existing autoimmunity, highlighting important considerations for disease treatment and follow-up.

Assessment of potential predictive factors of dupilumab response in patients with moderate-to-severe atopic dermatitis.

BACKGROUND: Dupilumab has shown to be an effective and safe treatment for patients with moderate-to-severe atopic dermatitis (AD). OBJECTIVE: To evaluate the predictive factors of response (PRF) in patients with moderate-to-severe AD treated with dupilumab. METHODS: Observational, retrospective and multicentre study conducted on adult patients diagnosed with moderate-to-severe AD treated with dupilumab, with a post-treatment follow-up of at least 16 weeks. The primary endpoints were EASI-75 and the IGA scale at week 52. RESULTS: A total of 198 patients were included in the analysis. Mean age was 38 ± 15.1 years and 116 (58.6%) were men. The most prevalent AD-predominant phenotypes were flexural eczema (45.3%), head-and-neck eczema (18.2%) and erythroderma (17.7%). At week 52, 140 (86.4%) patients achieved EASI-75 and 119 (93.0%) achieved an improvement in ≥2 points from baseline in IGA score. Women were 3.6 times more likely to achieve EASI-75 response than men (Odds ratio: 3.58; p = 0.020). While increased body mass index significantly reduced the probability of obtaining an improvement of ≥2 points in the IGA scale at week 52 (odds ratio: 0.88; p = 0.049). CONCLUSIONS: Dupilumab was an effective treatment in patients with moderate-to-severe AD. Additionally, sex and body mass index were significantly associated with achieving EASI-75 and an improvement of ≥2 points in the IGA scale, respectively, at week 52.

Smoking, mortality, access to diagnosis, and treatment of lung cancer in Brazil / Tabagismo, mortalidade, acesso ao diagnóstico e tratamento de câncer de pulmão no Brasil

ABSTRACT INTRODUCTION Lung cancer (LC) is a relevant public health problem in Brazil and worldwide, given its high incidence and mortality. Thus, the objective of this study is to analyze the distribution of smoking and smoking status according to sociodemographic characteristics and disparities in access, treatment, and mortality due to LC in Brazil in 2013 and 2019. METHOD Retrospective study of triangulation of national data sources: a) analysis of the distribution of smoking, based on the National Survey of Health (PNS); b) investigation of LC records via Hospital-based Cancer Registry (HCR); and c) distribution of mortality due to LC in the Mortality Information System (SIM). RESULTS There was a decrease in the percentage of people who had never smoked from 2013 (68.5%) to 2019 (60.2%) and in smoking history (pack-years). This was observed to be greater in men, people of older age groups, and those with less education. Concerning patients registered in the HCR, entry into the healthcare service occurs at the age of 50, and only 19% have never smoked. While smokers in the population are mainly Mixed-race, patients in the HCR are primarily White. As for the initial stage (I and II), it is more common in White people and people who have never smoked. The mortality rate varied from 1.00 for people with higher education to 3.36 for people without education. Furthermore, White people have a mortality rate three times higher than that of Black and mixed-race people. CONCLUSION This article highlighted relevant sociodemographic disparities in access to LC diagnosis, treatment, and mortality. Therefore, the recommendation is to strengthen the Population-Based Cancer Registry and develop and implement a nationwide LC screening strategy in Brazil since combined prevention and early diagnosis strategies work better in controlling mortality from the disease and continued investment in tobacco prevention and control policies.

RESUMO INTRODUÇÃO O câncer de pulmão (CP) é um relevante problema de saúde pública no Brasil e no mundo, dada sua alta incidência e mortalidade. Assim, objetiva-se analisar a distribuição do tabagismo e da carga tabágica segundo características sociodemográficas e disparidades no acesso, no tratamento e na mortalidade por CP no Brasil, em 2013 e 2019. MÉTODO Estudo retrospectivo de triangulação de fontes de dados de abrangência nacional: a) análise da distribuição do tabagismo, baseada na Pesquisa Nacional de Saúde (PNS); b) investigação dos registros de CP, via Registros Hospitalares de Câncer (RHC); e c) distribuição da mortalidade por CP, no Sistema de Informação sobre Mortalidade (SIM). RESULTADOS Verificou-se redução do percentual de pessoas que nunca fumaram de 2013 (68,5%) para 2019 (60,2%), assim como da carga tabágica (anos-maço). Esta foi observada maior em homens em pessoas de faixas etárias mais avançadas e de menor escolaridade. Em relação aos pacientes registrados no RHC, a entrada no serviço de saúde se dá a partir de 50 anos, e apenas 19% nunca fumaram. Ao passo que os fumantes na população são majoritariamente pardos, os pacientes no RHC são em maioria brancos. Quanto ao estadiamento inicial (I e II), é mais frequente em pessoas brancas e que nunca fumaram. A taxa de mortalidade apresentou variação de 1,00, para pessoas com ensino superior, a 3,36, entre pessoas sem instrução, assim como pessoas brancas têm uma taxa de mortalidade três vezes maior que a de pessoas negras e pardas. CONCLUSÃO Este artigo apontou relevantes disparidades sociodemográficas no acesso ao diagnóstico, tratamento e mortalidade do CP. Assim, recomenda-se: fortalecer o Registro de Câncer de Base Populacional; desenvolver e implementar estratégia de screening de CP no Brasil, uma vez que a realização de estratégias de prevenção e diagnóstico precoce combinadas funcionam melhor no controle da mortalidade pela doença; e investimento contínuo nas políticas de prevenção e controle do tabagismo.

Lung Cancer Screening in Brazil Comparing the 2013 and 2021 USPSTF Guidelines.

Importance: It is estimated that, from 2023 to 2025, lung cancer (LC) will be the second most frequent cancer in Brazil, but the country does not have an LC screening (LCS) policy. Objective: To compare the number of individuals eligible for screening, 5-year preventable LC deaths, and years of life gained (YLG) if LC death is averted by LCS, considering 3 eligibility strategies by sociodemographic characteristics. Design, Setting, and Participants: This comparative effectiveness research study assessed 3 LCS criteria by applying a modified version of the LC-Death Risk Assessment Tool (LCDRAT) and the LC-Risk Assessment Tool (LCRAT). Data are from the 2019 Brazilian National Household Survey. Participants included ever-smokers aged 50 to 80 years. Data analysis was performed from February to May 2023. Exposures: Exposures included ever-smokers aged 50 to 80 years, US Preventive Services Task Force (USPSTF) 2013 guidelines (ever-smokers aged 55 to 80 years with ≥30 pack-years and <15 years since cessation), and USPSTF 2021 guidelines (ever-smokers aged 50 to 80 years with 20 pack-years and <15 years since cessation). Main Outcomes and Measures: The primary outcomes were the numbers of individuals eligible for LCS, the 5-year preventable deaths attributable to LC, and the number of YLGs if death due to LC was averted by LCS. Results: In Brazil, the eligible population for LCS was 27 280 920 ever-smokers aged 50 to 80 years (13 387 552 female [49.1%]; 13 249 531 [48.6%] aged 50-60 years; 394 994 Asian or Indigenous [1.4%]; 3 111 676 Black [11.4%]; 10 942 640 Pardo [40.1%]; 12 830 904 White [47.0%]; 12 428 536 [45.6%] with an incomplete middle school education; and 12 860 132 [47.1%] living in the Southeast region); 5 144 322 individuals met the USPSTF 2013 criteria for LCS (2 090 636 female [40.6%]; 2 290 219 [44.5%] aged 61-70 years; 66 430 Asian or Indigenous [1.3%]; 491 527 Black [9.6%]; 2 073 836 Pardo [40.3%]; 2 512 529 [48.8%] White; 2 436 221 [47.4%] with an incomplete middle school education; and 2 577 300 [50.1%] living in the Southeast region), and 8 380 279 individuals met the USPSTF 2021 LCS criteria (3 507 760 female [41.9%]; 4 352 740 [51.9%] aged 50-60 years; 119 925 Asian or Indigenous [1.4%]; 839 171 Black [10.0%]; 3 330 497 Pardo [39.7%]; 4 090 687 [48.8%] White; 4 022 784 [48.0%] with an incomplete middle school education; and 4 162 070 [49.7%] living in the Southeast region). The number needed to screen to prevent 1 death was 177 individuals according to the USPSTF 2013 criteria and 242 individuals according to the USPSTF 2021 criteria. The YLG was 23 for all ever-smokers, 19 for the USPSTF 2013 criteria, and 21 for the USPSTF 2021 criteria. Being Black, having less than a high school education, and living in the North and Northeast regions were associated with increased 5-year risk of LC death. Conclusions and Relevance: In this comparative effectiveness study, USPSTF 2021 criteria were better than USPSTF 2013 in reducing disparities in LC death rates. Nonetheless, the risk of LC death remained unequal, and these results underscore the importance of identifying an appropriate approach for high-risk populations for LCS, considering the local epidemiological context.

Evaluation of the apical sealing of an eggshell hydroxyapatite-based sealer.

Background: The success of endodontic treatment can be influenced by the type of endodontic sealer used, as certain sealers may be prone to apical microleakage, leading to treatment failure. The limitations of currently available sealers necessitate the development of new materials to improve the success rate of endodontic treatment. Therefore, the objective of this study was to assess the apical microleakage of newly developed hydroxyapatite-based endodontic sealers, including one derived from eggshells, and compare them with other commercially available sealers. Material and Methods: Eighty-five extracted human upper anterior teeth were selected for this study. The teeth were divided into 5 experimental groups and 2 control groups. The experimental groups were designated as follows: (1) HPSINT - obturated with gutta-percha cone and synthetic hydroxyapatite-based sealer, (2) BIOC - obturated with gutta-percha cone and Bio C-Sealer sealer, (3) AHPLUS-BC - obturated with gutta-percha cone and AHPLUS Bioceramic sealer, (4) AHP - obturated with gutta-percha cone and AHPLUS sealer, and (5) HPO - obturated with gutta-percha cone and sealer based on hydroxyapatite extracted from eggshells. Additionally, there were positive and negative control groups consisting of instrumented teeth filled with gutta-percha cones without any sealer and instrumented teeth without any filling, respectively. Methylene blue dye penetration was used to assess apical microleakage. Descriptive statistical analysis and Shapiro-Wilk normality test were applied to the observed results. As the samples followed a normal distribution, the ANOVA test was applied. Results: The control groups confirmed the validity of the experimental method, while the experimental groups showed varying degrees of dye penetration. The group obturated with Bio C-Sealer exhibited the highest mean apical microleakage, while AHPLUS Bioceramic sealer demonstrated lower mean than AHPLUS sealer and sealer based on hydroxyapatite extracted from eggshells (p<0.05). Finally, there was no difference between the synthetic hydroxyapatite-based sealer and AHPLUS Bioceramic sealer, AHPLUS sealer and sealer based on hydroxyapatite extracted from eggshells (p>0.05). No significant difference was observed between the hydroxyapatite-based sealers and the AHPLUS-BC sealer. Conclusions: The results of this study suggest that the newly developed hydroxyapatite-based endodontic sealers, including the one derived from eggshells, may have a lower risk of apical microleakage compared to other commercially available sealers. These findings highlight the potential of hydroxyapatite-based sealers to improve the success rate of endodontic treatment. Further research and clinical studies are warranted to validate these results and explore the long-term effects of these novel sealers. Key words:Endodontic treatment, apical microleakage, endodontic sealer, hydroxyapatite, eggshell-derived sealer.

[Tuberculosis in the Brazilian prison system: scenarios via Joinpoint, from 2007 to 2019]. / Tuberculose no sistema prisional brasileiro: cenários via Joinpoint entre 2007 e 2019.

This study describes and compares tuberculosis (TB) data among persons deprived of liberty and the general Brazilian population, from 2007 to 2019, using the Joinpoint tool to observe changes in trends. This study focuses on women and older adults, for HIV testing, and on the number of detainees according to prison capacity. This is a retrospective, quantitative, and analytical study, which uses methods of regression of time series data from secondary data of unrestricted access collected from the Brazilian Information System for Notifiable Diseases (SINAN), Brazilian Institute of Geography and Statistics (IBGE), and from analytical reports made available by the Brazilian National Penitentiary Department (DEPEN). The results show a considerably higher increase in the prevalence of TB in persons deprived of liberty in all perspectives analyzed; increased HIV testing; and a debatable trend of stability in the number of detainees according to prison capacity. When analyzing trends in prevalence, services, and determinants, it is curious to see the temporal non-coincidence in most cases. Clearly, national policies against TB do not have the same effect within prisons and even the National Policy for Comprehensive Health Care for People Deprived of Liberty in the Prison System (PNAISP) showed restricted effects in view of the health situation herein analyzed. Despite working with secondary data of variable reliability, comparisons were reached that can impact health decisions and actions. Although lacking complete and definitive answers, it was possible to launch a new point-of-view on the evolution of questions for which reflection is essential.

Este estudo descreveu e comparou dados de tuberculose (TB) entre pessoas privadas de liberdade e população geral brasileira, de 2007 a 2019, utilizando a ferramenta Joinpoint para observação de mudanças de tendências. Apresenta um recorte para mulheres e idosos, para testagem para HIV e para número de custodiados por vaga. Trata-se de um estudo retrospectivo, quantitativo e analítico, que utiliza métodos de regressão de dados de séries temporais a partir de dados secundários de acesso irrestrito coletados do Sistema de Informação de Agravos de Notificação (SINAN), do Instituto Brasileiro de Geografia e Estatística (IBGE) e de relatórios analíticos disponibilizados pelo Departamento Penitenciário Nacional (DEPEN). Os resultados retratam aumento da prevalência de TB consideravelmente maior em pessoas privadas de liberdade em todas as perspectivas analisadas; aumento nas testagens para HIV; e discutível tendência de estabilidade na quantidade de custodiados por vaga. Ao se analisar tendências de prevalências, serviços e determinantes, é curioso ver a não coincidência temporal na maioria dos casos. Ficou claro que as políticas nacionais de combate à TB não têm o mesmo efeito dentro das prisões e mesmo a Política Nacional de Atenção Integral à Saúde das Pessoas Privadas de Liberdade no Sistema Prisional (PNAISP) mostrou efeitos restritos diante da situação de saúde aqui analisada. Apesar de trabalhar com dados secundários de confiabilidade variável, alcançaram-se comparações que podem impactar decisões e ações de saúde. Ainda que carente de respostas completas e definitivas, pôde-se lançar um novo olhar à evolução de questões sobre as quais a reflexão é imprescindível.

El presente estudio describió y comparó los datos de tuberculosis (TB) entre las personas privadas de libertad y la población general brasileña, de 2007 a 2019, utilizando la herramienta Joinpoint para observar los cambios en las tendencias. Presenta un límite para mujeres y ancianos, para las pruebas para VIH y para el número de internos por vacante. Se trata de un estudio retrospectivo, cuantitativo y analítico, que utiliza métodos de regresión de datos de series temporales a partir de datos secundarios de acceso no restringido recolectados del Sistema de Información de Agravios de Notificación (SINAN), Instituto Brasileño de Geografía y Estadística (IBGE) e informes analíticos disponibles por el Departamento Penitenciario Nacional (DEPEN). Los resultados muestran un aumento de la prevalencia de TB considerablemente mayor en personas privadas de libertad en todas las perspectivas analizadas; un aumento en las pruebas de VIH, y una tendencia discutible a la estabilidad en la cantidad de internos por vacante. Al analizar las tendencias de las prevalencias, los servicios y determinantes, es curioso ver la no coincidencia temporal en la mayoría de los casos. Quedó claro que las políticas nacionales de combate a la TB no tienen el mismo efecto dentro de las prisiones y incluso la Política Nacional de Atención Integral a la Salud de las Personas Privadas de Libertad en el Sistema Penitenciario (PNAISP) mostró efectos restringidos frente a la situación de salud aquí analizada. A pesar de trabajar con datos secundarios de confiabilidad variable, se lograron comparaciones que pueden afectar las decisiones y acciones de salud. Aunque se carezca de respuestas completas y definitivas, se ha podido dar una nueva mirada a la evolución de cuestiones sobre los que es imprescindible reflexionar.

Association between urinary concentrations of toxic metals/metalloids and oxidative stress in Brazilians living in areas affected by the Fundão dam failure.

The Fundão Dam failure has been the most significant environmental disaster in Brazil. The catastrophe released large amounts of mining waste into the environment, including toxic metals/metalloids, which are recognized to induce carcinogenic effects. The urinary levels of 8-hydroxy-2'-deoxyguanosine (8OHdG), a widely accepted oxidative stress and carcinogenesis biomarker, provide a potential tool for assessing the disaster's health implications. This study investigated the association between urinary levels of some toxic metals/metalloids and 8OHdG in Brazilian individuals living in areas affected by the Fundão dam failure. Urinary concentrations of arsenic (As), cadmium (Cd), mercury (Hg), nickel (Ni), and lead (Pb) were determined using inductively coupled plasma mass spectrometry, while 8OHdG was analyzed by liquid chromatography-tandem mass spectrometry. Non-parametric bootstrap regression was used to estimate the associations between the urinary levels of toxic elements and 8OHdG. The results showed that except for Hg, urinary concentrations of all metals/metalloids analyzed here exceeded the reference ranges for the Brazilian population. The regression analysis revealed that As (0.337; CI 95%: 0.203; 0.474), Cd (0.268; CI 95%: 0.036; 0.520), and Ni (0.296; CI 950.108; 0.469) were positively associated with creatinine-adjusted urinary 8OHdG levels. Associations were not found for Hg (0.0122; CI 95%: -0.155; 0.183) and Pb (0.201; CI 95%: -0.040; 0.498). The current findings suggest that high exposure to toxic metals/metalloids might increase 8OHdG levels with potential adverse health effects. This study is the first one in which the relationship between toxic metals/metalloids and oxidative stress biomarkers is investigated in populations affected by environmental disasters. Further prospective studies are necessary to monitor exposure levels and explore additional health impacts.

Detection of insecticide resistance markers in Anopheles funestus from the Democratic Republic of the Congo using a targeted amplicon sequencing panel.

Vector control strategies have been successful in reducing the number of malaria cases and deaths globally, but the spread of insecticide resistance represents a significant threat to disease control. Insecticide resistance has been reported across Anopheles (An.) vector populations, including species within the An. funestus group. These mosquitoes are responsible for intense malaria transmission across sub-Saharan Africa, including in the Democratic Republic of the Congo (DRC), a country contributing > 12% of global malaria infections and mortality events. To support the continuous efficacy of vector control strategies, it is essential to monitor insecticide resistance using molecular surveillance tools. In this study, we developed an amplicon sequencing ("Amp-seq") approach targeting An. funestus, and using multiplex PCR, dual index barcoding, and next-generation sequencing for high throughput and low-cost applications. Using our Amp-seq approach, we screened 80 An. funestus field isolates from the DRC across a panel of nine genes with mutations linked to insecticide resistance (ace-1, CYP6P4, CYP6P9a, GSTe2, vgsc, and rdl) and mosquito speciation (cox-1, mtND5, and ITS2). Amongst the 18 non-synonymous mutations detected, was N485I, in the ace-1 gene associated with carbamate resistance. Overall, our panel represents an extendable and much-needed method for the molecular surveillance of insecticide resistance in An. funestus populations.

Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers.

A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10-5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate -0.006 kg/m2, 95% CI -0.009 to -0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient.

Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high-incidence country.

Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population-based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non-genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision-recall curve (AUC-PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC-PRC for the Baseline Model (0.44%, 95%CI 0.42-0.46) increased by 0.22 (95%CI 0.15-0.29) when non-genetic factors were included, and by 0.25 (95%CI 0.20-0.30) when incorporating non-genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104-131) decreased to 92 (95%CI 60-128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59-110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non-genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.

Drugs for rheumatoid arthritis provided by the Unified Health System in 2019 in Brazil: a cohort study. / Medicamentos para artrite reumatoide fornecidos pelo Sistema Único de Saúde em 2019 no Brasil: estudo de coorte.

This study analyzes supply characteristics and factors associated with the treatment of rheumatoid arthritis in Brazil, with a focus on disease course-modifying biological drugs (bioDMARDs). A retrospective study was conducted with secondary data from the Outpatient Information System of the Unified Health System. Patients aged 16 years or older who were treated in 2019 were eligible. The analyses were performed with exposure factors in relation to the outcomes: bioDMARD use and population size. The study included 155,679 patients, 84.6% of whom were women. There was a greater exchange of bioDMARDs and a greater supply of rheumatologists in the larger municipalities (more than 500,000 inhabitants). Almost 40% of the patients used bioDMARDs, and they showed greater adherence to treatment (57.0% versus 64%, p=0.001). The dispensing of bioDMARDs occurred in more than one-third of the patients treated for rheumatoid arthritis (RA) in Brazil and was associated with a higher percentage of availability of rheumatologists and larger population size.

Este artigo tem como objetivo analisar características do fornecimento e fatores associados ao tratamento da artrite reumatoide no Brasil, com foco nos medicamentos biológicos modificadores do curso da doença (MMCDbio). Foi realizado um estudo retrospectivo com dados secundários do Sistema de Informação Ambulatorial do Sistema Único de Saúde. Foram incluídos pacientes com 16 anos ou mais, atendidos nos doze meses do ano de 2019. As análises foram feitas com fatores de exposição em relação aos desfechos: uso de MMCDbio e porte populacional. O estudo incluiu 155.679 pacientes, sendo 84,6% mulheres. Observou-se maior troca de MMCDbio e maior provisão de médicos reumatologistas nos municípios de maior porte (mais de 500 mil habitantes). Quase 40% dos pacientes utilizaram MMCDbio e estes apresentaram maior adesão ao tratamento (57,0% versus 64%, p=0,001). A dispensação de MMCDbio ocorreu para mais de um terço dos pacientes tratados para AR no Brasil e esteve associada ao maior percentual de disponibilidade de médicos reumatologistas e ao maior porte populacional dos municípios.