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Regulatory agencies must balance patient demands to access new treatments for fatal diseases with limited treatment options while ensuring drug safety and efficacy. However, questionable U.S. regulatory actions resulted in the early approval of AMX0035 to treat amyotrophic lateral sclerosis (ALS) by reconvening advisory commissions to obtain positive decisions and designating the drug as a new molecular entity. Data from one randomized clinical trial suggests minimal delays in disease progression and longer survivability, but debate remains about the lack of confirmatory evidence of effectiveness owing to study limitations. A patient's decision-making process details the experience of using the drug, including perspectives on access, cost, effectiveness, and adverse effects. In line with the "nichebuster" business model, the drugmaker, Amylyx Pharmaceuticals, is charging US$158,000/year/patient and thus forecast to turn a profit on a drug with debatable clinical effectiveness prior to completing a Phase 3 trial. Early marketing approval, despite community demands, is unnecessary and may have reduced access because of the end of a compassionate use program, and the high price tag results in restricted coverage and high out-of-pocket costs. Also, the drug's key ingredients are available as a generic and a supplement.
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Social media platforms such as Instagram are becoming increasingly popular sources for students to access anatomy educational resources. This review used content analysis to examine posts under the hashtag #anatomynotes and is the first to map the characteristics of anatomy education posts on Instagram and determine any temporal changes. Sample posts were gathered from April 2019 and April 2021 and categorized according to the technical format, purpose and author credentials. Engagement was recorded in the form of likes and comments. Overall, posts depicting illustrations remained the most popular format within both time periods. Three-dimensional models saw an increase in popularity with a 62.5% rise. Students remained the most common author type throughout and increased further in 2021 by 25%. Clinician authors and posts focusing on clinical education also increased in 2021 by 17.9% and 227%, respectively. Humor-based posts saw the greatest increase among the post purposes, with 1000% more recorded in 2021. Engagement overall saw a decline with notably significant reductions in average likes per post among all text-based posts (-72%, p < 0.0001), all illustrative posts (-51%, p = 0.0013), and a decline in the presence of comments among all text-based posts (-65.1%, p = 0.0158). These findings highlight that Instagram is a popular platform for facilitating near-peer teaching while increasingly providing a space where students and clinicians can interact. Additionally, it highlights the benefits of the platform for visually focused learners. However, future research should seek to determine whether Instagram can facilitate deeper learning and have an impact on academic and clinical performance.
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Anatomía , Medios de Comunicación Sociales , Humanos , Anatomía/educaciónRESUMEN
Employing a qualitative content analysis of online comments made on YouTube and letters to the editor published in US newspapers, we examine the deployment and neutralization of the evil corporation master frame in debates on two distinct biotechnologies, vaccines and genetically modified organisms. This study builds on previous research by outlining three diagnostic components of the evil corporation master frame: dishonesty, greed, and the contamination of authority. It also finds that supporters of vaccines and genetically modified organisms seek to neutralize the evil corporation master frame through aggressive, defensive, endurance, and redemptive framings. This study provides ideational detail for the ways that controversial biotechnology is constructed. The particularly vexing anti-vaccine movement is not dissimilar from other challenges to mainstream science as disparate movements draw on the same master frame. It also demonstrates how defenses of genetically modified organisms and vaccines tend to reify the anti-corporate stigma that sustains challenges to scientific authority.
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Biotecnología , Opinión Pública , Vacunas , Organismos Modificados Genéticamente , IndustriasRESUMEN
Biomass derived glycolaldehyde was employed as C1 building block for the N-formylation of secondary amines using air as oxidant. The reaction is atom economic, highly selective and proceeds under catalyst free conditions. This strategy can be used for the synthesis of cyclic and acyclic formylamines, including DMF. Mechanistic studies suggest a radical oxidation pathway.
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Acetaldehído , Aminas , Catálisis , OxidantesRESUMEN
Background: About 47% of children < 5 years of age are stunted in Guatemala. In this study, the investigators aimed to compare growth and cognitive outcomes between children in second grade that attended five Guatemala City Municipal Nurseries (GCMN) vs. same sex, grade, and age-matched children. Methods: A cross-sectional design nested in a retrospective cohort was implemented between 2015 and 2019. Children that attended the GCMN and matched controls completed a math test and validated receptive language and fluid intelligence tests. The primary caregivers completed a sociodemographic survey. General and generalized linear mixed effect models were used to compare children that attended the GCMN vs. controls. The models were adjusted by maternal education, sex, asset score, and other relevant covariates. Results: Children that attended the GCMN exhibited greater math and fluid intelligence scores relative to the controls in the adjusted models (ß = 6.48; 95% CI (2.35−10.61)) and (ß = 1.20; 95% CI (0.12−2.29)), respectively. Lower odds of stunting were significant for children who went to any early childcare institution (AOR = 0.28; 95% CI (0.09−0.89)). Conclusions: The importance of integrating nutrition and high-quality early childhood education interventions in cognitive and growth outcomes is highlighted in this study. The GCMN model may be a scalable model in similar low-resource settings.
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Casas Cuna , Niño , Preescolar , Estudios Transversales , Trastornos del Crecimiento , Guatemala/epidemiología , Humanos , Lactante , Inteligencia , Estudios RetrospectivosRESUMEN
Emerging evidence suggests that the nasal microbiome may influence host susceptibility to initial development and severity of respiratory viral infections. While not as extensively studied as the microbiota of the alimentary tract, it is now clearly established that the microbial composition of this niche is influenced by medical, social and pharmacological influences, predisposing some sub-populations to respiratory infections. The resulting specific microbial profiles may explain variance in susceptibility to viral infection. This review summaries the evolution and constituents of the commensal nasal microbiome; the bacterial-virus, bacterial-host and interbacterial interactions which potentiate disease; and considers the effects of interventions such as vaccination and probiotics.
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Nasal pathogen detection sensitivities can be as low as 70% despite advances in molecular diagnostics. This may be linked to the choice of sampling method. A diagnostic test accuracy review for sensitivity was undertaken to compare sensitivity of swabbing to the nasopharynx and extracting nasal aspirates, using the PRISMA protocol, Cochrane rapid review methodology, and QUADAS-2 risk of bias tools, with meta-analysis of included studies. Sensitivities were calculated by a consensus standard of positivity by either method as the 'gold standard.' Insufficient sampling methodology, cross sectional study designs, and studies pooling samples across anatomical sites were excluded. Of 13 subsequently eligible studies, 8 had 'high' risk of bias, and 5 had 'high' applicability concerns. There were no statistical differences in overall sensitivities between collection methods for eight different viruses, and this did not differ with use of PCR, immunofluorescence, or culture. In one study alone, Influenza H1N1(2009) favored nasopharyngeal swabs, with aspirates having 93.3% of the sensitivity of swabs (p > 0.001). Similarly equivocal sensitivities were noted in reports detecting bacteria. The chain of sampling, from anatomical site to laboratory results, features different potential foci along which sensitivity may be lost. A fair body of evidence exists that use of a different sampling method will not yield more respiratory pathogens.
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The Covid-19 pandemic has demanded modifications to undergraduates' learning experiences and promised a more challenging scientific world in which they will live. Bespoke evidence synthesis and critical appraisal skills modules are an opportunity to utilize our information-saturated world to our advantage. This program of study made use of a virtual journal club, structured literature searches, scoping review methods and a variety of online research tools to navigate and critique the literature. The program design is here outlined with sample learning objectives and reference to the resources used.
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Educación Médica/métodos , Enseñanza , COVID-19/epidemiología , Medicina Basada en la Evidencia , Humanos , Periodismo Médico , SARS-CoV-2 , PensamientoRESUMEN
The nasopharyngeal microbiome is a dynamic microbial interface of the aerodigestive tract, and a diagnostic window in the fight against respiratory infections and antimicrobial resistance. As its constituent bacteria, viruses and mycobacteria become better understood and sampling accuracy improves, diagnostics of the nasopharynx could guide more personalized care of infections of surrounding areas including the lungs, ears and sinuses. This review will summarize the current literature from a clinical perspective and highlight its growing importance in diagnostics and infectious disease management.
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Microbiota , Nasofaringe/microbiología , Farmacorresistencia Microbiana , Ambiente , Humanos , Mycobacterium/fisiología , Otitis Media/microbiología , ViromaRESUMEN
It has been previously proposed that pyridines can activate PhICl2 by displacing a chloride and forming the [PhI(Pyr)(Cl)]+ cation as a reactive intermediate. Here we show that pyridine does not displace chloride, but rather forms a weak complex with the iodine via halogen bonding along the C-I bond axis. This interaction is interrogated by NMR, structural, charge density, and theoretical investigations, which all indicate that pyridine does not activate PhICl2 as proposed.
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The COVID-19 pandemic calls into question the institutional structure underlying the pharmaceutical industry. While some have called for medical technologies to be global public goods and patent waivers on pharmaceuticals, much of the industry has pushed back against any attempts that might threaten their monopoly power to set prices. Public acceptance of the role of private companies to control life-saving drugs, as well as of the intellectual property system, informs campaigns guaranteeing universal access to medicines and corporate strategies to shape policy. This study consists of a qualitative content analysis of online comments about news reports of Gilead Science's pricing of remdesivir, a re-purposed drug that shows some positive efficacy against COVID-19 in clinical trials. Analysing elite and public framing about medicine pricing informs our understanding of the social construction of markets. The findings identify hegemonic and counter-hegemonic discourse about innovation, affordability, saving lives, health care savings and international comparisons that stimulate debate and potentially advocacy. As such, the discursive context delineates the possibilities for remediating the normative and material structure of a pharmaceutical system currently geared towards private profit instead of public health needs.
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Adenosina Monofosfato/análogos & derivados , Alanina/análogos & derivados , Tratamiento Farmacológico de COVID-19 , COVID-19 , Accesibilidad a los Servicios de Salud , Pandemias , Adenosina Monofosfato/provisión & distribución , Alanina/provisión & distribución , COVID-19/epidemiología , Ensayos Clínicos como Asunto , Humanos , Investigación CualitativaRESUMEN
Recent scholarship has sought to distinguish between the deeper societal factors that shape the more proximate social determinants of health. One of these socio-structural institutions is global capitalism. While critical scholarship has advanced our understanding of the relationships between capitalist globalization and health, more work is needed to understand the transnational economic, political, and cultural practices that affect various global health issues. This paper argues that the theory of global capitalism provides an important, critical perspective for understanding different phenomena associated with global health. The theory's key concepts of transnational corporations, financialization, consumerism, transnational social classes, and transnational state comprise the conceptual framework. When applied to various global health topics, the theory advances our understanding of the health-related institutional structures of today's global economy, provides a holistic view that integrates various strands of health research, highlights various forms of health activism, and offers new questions for addressing persistent health injustice across the world.
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Capitalismo , Salud Global , Humanos , InternacionalidadRESUMEN
Recent studies of alkali metal N-(α-methylbenzyl)allylamides containing lithium, sodium, and potassium have shown unique rearrangements in NMR experiments. It was found that lithium isomers favored the formation of aza-allyl and aza-enolate complexes that could exist in a solution for a substantial amount of time. As the radius of the metal ion increases going from lithium to potassium, so does the preference for the formation of the imine structure. For sodium, the aza-allyl complex could still be isolated, whereas the imine structure was only found to be stable on the scale of several hours for potassium. In this work, ab initio calculations were used to shed light on this phenomenon. Decomposition of intermolecular interaction energies of the aza-allyl, aza-enolate, and imine complexes showed that for lithium, the formation of aza-allyl and aza-enolate complexes was driven by electrostatic interactions. For potassium, the dispersion component of the metal interaction with the ligand proved to be more important for the stability of the imine structure. The presence of the imine formation in potassium and partially in sodium was found to be due to the reduced electrostatic nature of these larger metals. The assignment of the experimental NMR spectra was further confirmed with the natural bond order (NBO) analysis as well as the partial charge calculations. Analysis of orbital energies, specifically those of the highest occupied molecular orbitals (HOMOs), as well as the deformation energies of each of the ligands, were also considered. Through these procedures, an understanding of the tendency for each metal to have a unique isomerization pathway was gained.
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This study describes the spatial-temporal changes of the proportion of ill-defined causes of death in Brazil (1998-2012) and investigates which demographic and socioeconomic factors affect this proportion. We collected information of the proportion of ill-defined causes of death by age (15-59 years), sex, period, locality, and socioeconomic data. We used a multilevel Poisson model to investigate which factors affect the risk of ill-defined causes of death. Unlike states located in the South and Midwest, we detected clusters with high proportional levels of these deaths in states in the North and Northeast regions. A greater proportion occurred in 1998-2002 (0.09), in the North and Northeast (0.14 and 0.12, respectively), in older age groups (0.09), and in places with poor socioeconomic conditions. The adjusted analysis showed differences in proportion according to the region, age, period, schooling, social inequality, and income. The results indicate that the lower the age group and the better the socioeconomic situation, the lower the risk to register the cause of death as ill-defined. Although over the past years, the quality of Brazil's mortality data has gradually increased, investments towards improving mortality registries cannot be discontinued.
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Causas de Muerte , Modelos Estadísticos , Sistema de Registros , Adolescente , Adulto , Factores de Edad , Brasil/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multinivel , Distribución de Poisson , Factores de Riesgo , Factores Socioeconómicos , Adulto JovenRESUMEN
Clinicians face unique challenges when assessing suspected child abuse cases. The majority of the literature exploring diagnostic decision-making in this field is anecdotal or survey-based and there is a lack of studies exploring decision-making around suspected abusive head trauma (AHT). We aimed to determine factors influencing decision-making and multidisciplinary collaboration in suspected AHT cases, amongst 56 child protection professionals. Semi-structured interviews were conducted with clinicians (25), child protection social workers (10), legal practitioners (9, including 4 judges), police officers (8), and pathologists (4), purposively sampled across southwest United Kingdom. Interviews were recorded, transcribed and imported into NVivo for thematic analysis (38% double-coded). We identified six themes influencing decision-making: 'professional', 'medical', 'circumstantial', 'family', 'psychological' and 'legal' factors. Participants diagnose AHT based on clinical features, the history, and the social history, after excluding potential differential diagnoses. Participants find these cases emotionally challenging but are aware of potential biases in their evaluations and strive to overcome these. Barriers to decision-making include lack of experience, uncertainty, the impact on the family, the pressure of making the correct diagnosis, and disagreements between professionals. Legal barriers include alternative theories of causation proposed in court. Facilitators include support from colleagues and knowledge of the evidence-base. Participants' experiences with multidisciplinary collaboration are generally positive, however child protection social workers and police officers are heavily reliant on clinicians to guide their decision-making, suggesting the need for training on the medical aspects of physical abuse for these professionals and multidisciplinary training that provides knowledge about the roles of each agency.
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Maltrato a los Niños/diagnóstico , Servicios de Protección Infantil , Traumatismos Craneocerebrales/etiología , Personal de Salud/psicología , Relaciones Interprofesionales , Adulto , Niño , Traumatismos Craneocerebrales/diagnóstico , Toma de Decisiones , Diagnóstico Diferencial , Emociones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Abuso Físico/prevención & control , Policia/psicología , Investigación Cualitativa , Trabajadores Sociales/psicología , Incertidumbre , Reino UnidoRESUMEN
The validated Predicting Abusive Head Trauma (PredAHT) tool estimates the probability of abusive head trauma (AHT) based on combinations of six clinical features: head/neck bruising; apnea; seizures; rib/long-bone fractures; retinal hemorrhages. We aimed to determine the acceptability of PredAHT to child protection professionals. We conducted qualitative semi-structured interviews with 56 participants: clinicians (25), child protection social workers (10), legal practitioners (9, including 4 judges), police officers (8), and pathologists (4), purposively sampled across southwest United Kingdom. Interviews were recorded, transcribed and imported into NVivo for thematic analysis (38% double-coded). We explored participants' evaluations of PredAHT, their opinions about the optimal way to present the calculated probabilities, and their interpretation of probabilities in the context of suspected AHT. Clinicians, child protection social workers and police thought PredAHT would be beneficial as an objective adjunct to their professional judgment, to give them greater confidence in their decisions. Lawyers and pathologists appreciated its value for prompting multidisciplinary investigations, but were uncertain of its usefulness in court. Perceived disadvantages included: possible over-reliance and false reassurance from a low score. Interpretations regarding which percentages equate to 'low', 'medium' or 'high' likelihood of AHT varied; participants preferred a precise % probability over these general terms. Participants would use PredAHT with provisos: if they received multi-agency training to define accepted risk thresholds for consistent interpretation; with knowledge of its development; if it was accepted by colleagues. PredAHT may therefore increase professionals' confidence in their decision-making when investigating suspected AHT, but may be of less value in court.
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Actitud del Personal de Salud , Maltrato a los Niños/diagnóstico , Traumatismos Craneocerebrales/etiología , Personal de Salud/psicología , Adulto , Niño , Servicios de Protección Infantil/estadística & datos numéricos , Técnicas de Apoyo para la Decisión , Femenino , Humanos , Masculino , Persona de Mediana Edad , Probabilidad , Investigación Cualitativa , Hemorragia Retiniana/etiología , Reino Unido , Adulto JovenRESUMEN
Abstract This study describes the spatial-temporal changes of the proportion of ill-defined causes of death in Brazil (1998-2012) and investigates which demographic and socioeconomic factors affect this proportion. We collected information of the proportion of ill-defined causes of death by age (15-59 years), sex, period, locality, and socioeconomic data. We used a multilevel Poisson model to investigate which factors affect the risk of ill-defined causes of death. Unlike states located in the South and Midwest, we detected clusters with high proportional levels of these deaths in states in the North and Northeast regions. A greater proportion occurred in 1998-2002 (0.09), in the North and Northeast (0.14 and 0.12, respectively), in older age groups (0.09), and in places with poor socioeconomic conditions. The adjusted analysis showed differences in proportion according to the region, age, period, schooling, social inequality, and income. The results indicate that the lower the age group and the better the socioeconomic situation, the lower the risk to register the cause of death as ill-defined. Although over the past years, the quality of Brazil's mortality data has gradually increased, investments towards improving mortality registries cannot be discontinued.
Resumo Este estudo descreve as mudanças espaço-temporais da proporção de causas mal definidas no Brasil (1998-2012) e seus fatores associados. Coletamos informações da proporção de óbitos por causas mal definidas por idade (15-59 anos), sexo, período, local de residência, além de fatores socioeconômicos. Utilizou-se modelo multinível de Poisson para investigar os fatores associados às causas mal definidas dos óbitos. Ao contrário dos estados do sul e centro-oeste, identificou-se clusters com elevados níveis proporcionais destes óbitos nos estados do norte, nordeste e sudeste. A maior proporção de óbitos mal definidos ocorreu em 1998-2002 (0,09), no norte e nordeste (0,14 e 0,12, respectivamente), nos grupos etários mais velhos (0,09) e nos locais com condições socioeconômicas desfavoráveis. A análise ajustada indicou diferença dos níveis de causas mal definidas de acordo com a região, a idade, o período, a escolaridade, a desigualdade social e a renda. Nossos resultados sugerem que quanto menor a faixa etária e melhores as condições socioeconômicas, menor o risco de óbitos mal definidos. Apesar de nos últimos anos a qualidade dos dados de mortalidade no Brasil ter aumentado, os investimentos na melhoria do registro dos óbitos não podem ser descontinuadas.
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Humanos , Masculino , Femenino , Adolescente , Adulto , Adulto Joven , Sistema de Registros , Modelos Estadísticos , Causas de Muerte , Factores Socioeconómicos , Brasil/epidemiología , Distribución de Poisson , Factores de Riesgo , Factores de Edad , Análisis Multinivel , Persona de Mediana EdadRESUMEN
The aim of this study was to analyze the spatial distribution of the tuberculosis endemic in Rio de Janeiro State from 2002 to 2011. A retrospective study was conducted in the state of Rio de Janeiro from 2002 to 2011. Spatial analysis techniques were used to describe the distribution of tuberculosis incidence in the state. Multilevel Poisson regression model was used to access the relationship of tuberculosis and the following factors: "sex", "age-group" and "diagnostic year" (individual-level factors). Demographic density and municipality were also included in the model as contextual-level factors. A reduction in endemic tuberculosis was observed over the years. The highest incidence rates were concentrated on the south coast of the state, covering Rio de Janeiro City (capital) and neighboring cities. We detected a significant clustering of high TB incidence rates on the south coast of the state and a cluster of low incidence in the northeastern region of state. The risk of tuberculosis was higher in early 2000s, in males and in 40-59 age group. Metropolitan regions are important risk areas for the spread of tuberculosis. These findings could be used to plan control measures according to the characteristics of each region.
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Ciudades , Tuberculosis Pulmonar/epidemiología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Niño , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Distribución de Poisson , Estudios Retrospectivos , Factores de Riesgo , Factores Sexuales , Análisis Espacial , Adulto JovenRESUMEN
Abstract The aim of this study was to analyze the spatial distribution of the tuberculosis endemic in Rio de Janeiro State from 2002 to 2011. A retrospective study was conducted in the state of Rio de Janeiro from 2002 to 2011. Spatial analysis techniques were used to describe the distribution of tuberculosis incidence in the state. Multilevel Poisson regression model was used to access the relationship of tuberculosis and the following factors: "sex", "age-group" and "diagnostic year" (individual-level factors). Demographic density and municipality were also included in the model as contextual-level factors. A reduction in endemic tuberculosis was observed over the years. The highest incidence rates were concentrated on the south coast of the state, covering Rio de Janeiro City (capital) and neighboring cities. We detected a significant clustering of high TB incidence rates on the south coast of the state and a cluster of low incidence in the northeastern region of state. The risk of tuberculosis was higher in early 2000s, in males and in 40-59 age group. Metropolitan regions are important risk areas for the spread of tuberculosis. These findings could be used to plan control measures according to the characteristics of each region.
Resumo O objetivo deste estudo foi analisar a distribuição espacial da tuberculose (TB) endêmica no Rio de Janeiro 2002-2011. Estudo retrospectivo realizado no Estado do Rio de Janeiro, 2002-2011. Técnicas de análise espacial foram utilizadas para descrever a distribuição de incidência de tuberculose no estado. Modelo de regressão multinível de Poisson foi utilizado para acessar a relação de tuberculose e os fatores: "sexo", "faixa etária" e "ano de diagnóstico" (fatores de nível individual). A "Densidade demográfica" e o "município de residência" também foram incluídos no modelo como fatores de nível contextual. Houve redução da tuberculose endêmica ao longo dos anos. As maiores taxas de incidência se concentraram no litoral sul do estado, abrangendo capital e cidades vizinhas. Observamos a formação de cluster significativo com altas taxas de incidência de TB no litoral sul do estado e cluster de baixa incidência na região nordeste do estado. O risco de tuberculose foi maior no início de 2000, no sexo masculino e na faixa etária 40-59. As megacidades são áreas de risco importantes para a disseminação da tuberculose. Estes achados poderiam ser usados para planejar medidas de controle de acordo com as características de cada região.