Who are the patients with tuberculosis who are diagnosed in emergency facilities? An analysis of treatment outcomes in the state of São Paulo, Brazil.

OBJECTIVE: Early tuberculosis diagnosis and treatment are determinants of better outcomes and effective disease control. Although tuberculosis should ideally be managed in a primary care setting, a proportion of patients are diagnosed in emergency facilities (EFs). We sought to describe patient characteristics by place of tuberculosis diagnosis and determine whether the place of diagnosis is associated with treatment outcomes. A secondary objective was to determine whether municipal indicators are associated with the probability of tuberculosis diagnosis in EFs. METHODS: We analyzed data from the São Paulo State Tuberculosis Control Program database for the period between January of 2010 and December of 2013. Newly diagnosed patients over 15 years of age with pulmonary, extrapulmonary, or disseminated tuberculosis were included in the study. Multiple logistic regression models adjusted for potential confounders were used in order to evaluate the association between place of diagnosis and treatment outcomes. RESULTS: Of a total of 50,295 patients, 12,696 (25%) were found to have been diagnosed in EFs. In comparison with the patients who had been diagnosed in an outpatient setting, those who had been diagnosed in EFs were younger and more socially vulnerable. Patients diagnosed in EFs were more likely to have unsuccessful treatment outcomes (adjusted OR: 1.54; 95% CI: 1.42-1.66), including loss to follow-up and death. At the municipal level, the probability of tuberculosis diagnosis in EFs was associated with low primary care coverage, inequality, and social vulnerability. In some municipalities, more than 50% of the tuberculosis cases were diagnosed in EFs. CONCLUSIONS: In the state of São Paulo, one in every four tuberculosis patients is diagnosed in EFs, a diagnosis of tuberculosis in EFs being associated with poor treatment outcomes. At the municipal level, an EF diagnosis of tuberculosis is associated with structural and socioeconomic indicators, indicating areas for improvement

Ciclosporina A reduz a secreção de muco das vias aéreas e o transporte mucociliar de ratos

OBJETIVO: Avaliar os efeitos da ciclosporina A sobre a produção de muco das células caliciformes e sobre o transporte mucociliar in situ de ratos. MÉTODOS: Vinte e um ratos machos Wistar foram distribuídos em três grupos: Controle (n=5), Salina (n=8) e Ciclosporina A (n=8). Após 30 dias de terapia, os ratos foram mortos e os pulmões removidos da cavidade torácica. Amostras de muco foram coletadas e a medida da transportabilidade in vitro foi realizada através de um modelo de palato de rã. A velocidade do transporte mucociliar foi medida através da observação direta do deslocamento de partículas aderidas ao muco do epitélio ciliado brônquico. Por fim, efetuamos a quantificação das mucinas estocadas nas células caliciformes do epitélio respiratório. RESULTADOS: O valor médio da concentração sangüínea da ciclosporina no momento do sacrifício dos ratos foi de 1.246,57 ± 563,88 ng/ml. A transportabilidade do muco in vitro foi estatisticamente menor (p < 0.001) no grupo tratado com ciclosporina. Da mesma forma, houve um decréscimo na velocidade de transporte mucociliar nos animais imunossuprimidos em relação aos que receberam o placebo (p = 0.02). Houve diminuição significativa na quantidade de muco ácido (p = 0,01) e neutro (p = 0,02) produzidos pelas células caliciformes nos animais tratados com ciclosporina. A correlação entre a porcentagem de muco e a transportabilidade in vitro foi positiva e significante (r = 0.706, p < 0.001), assim como entre a porcentagem do muco e o transporte mucociliar in situ (r = 0.688, p = 0.001). CONCLUSÃO: O presente estudo mostra que a ciclosporina A age no sistema mucociliar causando um sério prejuízo através da redução na produção de muco ácido e neutro pelas células caliciformes como também a diminuição da velocidade de transporte mucociliar in situ e a transportabilidade do muco in vitro.PURPOSE: To assay the effects of cyclosporin A on mucus secretion from goblet cells and on mucociliary transport in situ in rats. METHODS: Twenty-one male Wistar rats were assigned to 3 groups: control (n = 5), saline (n = 8), and cyclosporin A (n = 8). After 30 days of drug therapy, the rats were killed, and the lungs were removed from the thoracic cavity. Mucus samples were collected, and the transport rate was evaluated in vitro using a bullfrog palate model. Mucociliary transport was timed in situ by direct view of particles trapped on the mucus moving across the respiratory tract. Finally, the amount of stored mucins in the goblet cells of the respiratory epithelium was measured. RESULTS: Drug dosage measurements showed that cyclosporine blood concentration at the moment the rats were killed was 1246.57 ± 563.88 ng/mL. The in vitro transport rate was significantly lower (P < .001) in the cyclosporin A-treated group. Also, the in-situ mucociliary transport rate was decreased in all cyclosporin A-treated animals when compared to the saline group (P = .02). Mucus quantity measurements showed a significant decrease on both acid (P = .01) and neutral (P = .02) mucus production from goblet cells in the animals submitted to cyclosporin A therapy. The correlation between the percentage of total mucus and in vitro transport rate was positive and significant (r = 0.706, P < .001), as was the correlation between the percentage of total mucus and the in situ mucociliary transport rate (r = 0.688, P = .001). CONCLUSION: This study shows that cyclosporin A plays an important role in the impairment of the mucociliary clearance in rats by reducing both acid and neutral mucus production from goblet cells and causing a decrease in the mucociliary transport velocity

Determinants of short- and long-term treatment outcomes, survival and causes of death of adult patients with tuberculosis in São Paulo State

Introdução: A tuberculose (TB) é uma doença infecciosa que permanece um importante problema de saúde pública no mundo atual. Apesar de avanços no combate à TB, atualmente ainda existem muitos desafios para seu controle. No Brasil, a incidência de TB é alta e está entre os 22 países mais afetados pela doença no mundo. O Estado de São Paulo tem atualmente o maior número de casos absolutos de TB no Brasil e as metas estabelecidas quanto ao desfecho do tratamento ainda não foram atingidas. Assim, o presente projeto analisou os dados do Programa de TB do Estado de São Paulo com o intuito de melhor entender os determinantes dos desfechos do tratamento da TB. Objetivos: i) Avaliar se diferentes classificações da TB de acordo com o sítio da doença estão associadas aos desfechos do tratamento e quantificar se as diferentes classificações impactam na avaliação do desempenho dos programas nacionais quanto aos resultados dos desfechos do tratamento; ii) Descrever o perfil epidemiológico dos pacientes com TB que são diagnosticados em serviços de urgência/emergência, avaliar se estes pacientes tem pior prognóstico e determinar quais variáveis ao nível municipal podem predizer os diagnósticos nestes serviços; iii) Descrever a sobrevida a longo-prazo de pacientes com diagnóstico de TB e compará-la com a população brasileira, descrever as causas de morte a curto e longo-prazo e identificar se variáveis que representam vulnerabilidade social, fatores externos e comorbidades estão associadas à mortalidade por causas específicas. Métodos: Trata-se de estudo de coorte, com análise secundária de base de dados. Incluíram-se pacientes com diagnóstico clínico e/ou microbiológico de TB, sem tratamento prévio, que foram notificados ao Centro de Vigilância Epidemiológica (CVE) do Estado de São Paulo (base TbWeb), no período entre 2010 e 2013. Para os desfechos a longo-prazo, utilizaram-se dados do Sistema de Informações sobre Mortalidade (SIM), através da vinculação de registros. Para cada objetivo, utilizaram-se a descrição sumária de variáveis, modelos de regressão logística para desfechos binários e modelos de tempo até o evento para sobrevida, ajustados para variáveis de confusão. Resultados: Esta tese é composta pela compilação de três artigos. Artigo 1: Analisaram-se 62.178 pacientes de 2010 a 2013 e observou-se que uma classificação anatômica estendida foi associada com desfechos indesejáveis, incluindo morte. Pacientes com a forma pulmonar e extrapulmonar concomitantes tiveram desfechos semelhantes comparando-os aos pacientes com a forma pulmonar, enquanto aqueles com a forma extrapulmonar tiveram melhores desfechos e os com as formas miliar/disseminada piores desfechos. Reportar os desfechos das formas pulmonares e extrapulmonares individualmente se mostrou com menor viés quando comparado à forma sugerida atualmente de reportar os desfechos das duas formas conjuntamente. Artigo 2: Analisaram-se 50.295 pacientes com busca espontânea aos serviços de saúde. Observou-se que 25% dos pacientes foram diagnosticados em serviços de urgência/emergência, que estes pacientes eram mais jovens e mais vulneráveis socialmente, e que tiveram piores desfechos do tratamento quando comparados aos pacientes diagnosticados na atenção primária. Alguns municípios tiveram maior proporção de diagnósticos nos serviços de urgência/emergência, fato que foi associado à baixa cobertura municipal da atenção primária e maior desigualdade e vulnerabilidade sociais. Artigo 3: Analisaram-se 15.501 pacientes diagnosticados no ano de 2010 e por meio da vinculação de registros se obteve a sobrevida dos mesmos até 2015. Durante um seguimento médio de 5 anos, observouse que 2.660 (17,1%) pacientes foram a óbito. Comparado à população brasileira, com pareamento por idade, sexo e ano, a razão de mortalidade padronizada geral foi de 5,652 (95% IC, 5,431-5,881), atingindo seu pico para pacientes com idade entre 35 e 45 anos e durante o primeiro ano após o diagnóstico. Causas infecciosas foram responsáveis por 45% dos óbitos, entretanto outras causas tiveram maior importância entre pacientes sem coinfecção TB-HIV e após o primeiro ano de diagnóstico. Aproximadamente um terço dos óbitos tiveram menção à TB no atestado de óbito, seja como causa básica ou causa associada. População em situação de rua, uso de álcool ou drogas foram associados independentemente a óbitos por causas infecciosas, respiratórias, cardiovasculares e causas externas ou mal definidas. Diabetes mellitus não foi associada a óbitos por causas infecciosas ou tuberculose, porém foi associada a óbitos por causas cardiovasculares. Conclusões: O sítio clínico acometido pela TB foi associado ao desfecho do tratamento e uma classificação estendida além de pulmonar/extrapulmonar parece descrever melhor o risco de desfechos indesejáveis. Um em cada quatro pacientes tem o diagnóstico de TB nos serviços de urgência/emergência e tiveram piores desfechos do tratamento. O diagnóstico em serviços de urgência/emergência parece ser um fenômeno ligado à vulnerabilidade. Os pacientes diagnosticados com TB têm elevada mortalidade, não somente durante o tratamento, mas também a longo-prazo. Vulnerabilidade social, fatores externos e comorbidades são associados a diferentes causas de óbito. A epidemiologia pode contribuir para o melhor entendimento dos desfechos de pacientes com TB no Estado de São Paulo, informando objetivamente pontos para melhora e planejamento de ações específicasIntroduction: Tuberculosis (TB) is an infectious disease that remains a major public health problem worldwide. Despite advances towards TB elimination, there are still many challenges to its control. The incidence of TB is high in Brazil and we are among the 22 high-burden countries list from the World Health Organization (WHO). In this context, São Paulo State has the highest number of absolute TB cases in Brazil and the treatment outcome goals established by the WHO have not yet been reached. This project analysed data from the São Paulo State TB Program in order to better understand the determinants of TB treatment outcomes. Objectives: i) To assess whether different TB anatomical classifications are associated with treatment outcomes and to quantify whether different classifications impact on the evaluation of national programs performance regarding treatment outcomes; ii) To describe the epidemiological profile of patients with TB who are diagnosed in emergency facilities, to evaluate if these patients have a worse prognosis and to determine which variables at the municipal level can predict the diagnoses in emergency facilities; iii) To describe the long-term survival of patients diagnosed with TB and compare it with the expected survival in the source population, to describe the causes of death in the short- and long-term and to identify if variables of social vulnerability, external factors and comorbidities are associated with cause-specific mortality. Methods: This is a cohort study with analysis of routine data. Patients with clinical and/or microbiological diagnosis of TB, without previous treatment, who were notified to the Centro de Vigilância Epidemiológica (CVE) of São Paulo State (TbWeb database), between 2010 and 2013 were included. For the long-term outcomes, data from the Mortality Information System (SIM) was retrieved through a record linkage approach. For each objective, there was a summary description of variables and were applied logistic regression models for binary outcomes and time to event analysis for survival, adjusted for potential confounding. Results: This thesis consists of the compilation of three articles. Article 1: A total of 62,178 patients were analysed from 2010 to 2013 and it was observed that an extended anatomic classification was associated with undesirable outcomes, including death. Patients with concomitant pulmonary and extrapulmonary forms had similar outcomes compared with patients with the pulmonary form, while those with extrapulmonary forms had better outcomes and those with miliary/disseminated forms had worse outcomes. Reporting the outcomes of the pulmonary and extrapulmonary forms individually was shown to be less biased when compared with the currently recommendation of reporting the outcomes of the two forms together. Article 2: A total of 50,295 patients spontaneously seeking medical attention were analysed. It was observed that 25% of patients were diagnosed in emergency facilities, that these patients were younger and more socially vulnerable, and that they had worse treatment outcomes compared with patients diagnosed in primary care units. Some municipalities had a greater proportion of diagnoses in the emergency facilities, a fact that was associated with low coverage of primary care and greater social inequality and vulnerability. Article 3: A total of 15,501 patients diagnosed in 2010 were analysed and followed-up through record linkage until 2015. During an average follow-up of 5 years, we observed that 2,660 (17.1%) patients died. Compared to the Brazilian population, matched by age, sex and calendar year, the standardized mortality ratio was 5.652 (95% CI, 5.431-5.881), reaching its peak for patients aged 35-45 years and during the first year after diagnosis. Infectious causes were responsible for 45% of deaths, however other causes increased their relative importance among patients without TBHIV coinfection and overall after the first year of diagnosis. One every three deaths had tuberculosis cited in the death certificate. Homelessness, alcohol and drug use were independently associated with deaths from infectious, respiratory, cardiovascular and external or ill-defined causes. Diabetes mellitus was not associated with deaths due to infectious or tuberculosis, but it was associated with deaths due to cardiovascular events. Conclusions: The clinical anatomical site affected by TB was associated with treatment outcome and an extended classification beyond pulmonary/extrapulmonary appears to better describe the risk of undesirable outcomes. One in four patients had a diagnosis of TB in emergency facilities and had worse treatment outcomes. Diagnosis in emergency facilities appears to be a phenomenon related to vulnerability. Patients diagnosed with TB have high mortality, both at short- and long-term after diagnosis. Social vulnerability, external factors and comorbidities are associated with different causes of death. Epidemiology may contribute to a better understanding of the outcomes of TB patients in the São Paulo State, objectively providing data to support improvement in some areas and planning of specific action

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Who are the patients with tuberculosis who are diagnosed in emergency facilities? An analysis of treatment outcomes in the state of São Paulo, Brazil

ABSTRACT Objective: Early tuberculosis diagnosis and treatment are determinants of better outcomes and effective disease control. Although tuberculosis should ideally be managed in a primary care setting, a proportion of patients are diagnosed in emergency facilities (EFs). We sought to describe patient characteristics by place of tuberculosis diagnosis and determine whether the place of diagnosis is associated with treatment outcomes. A secondary objective was to determine whether municipal indicators are associated with the probability of tuberculosis diagnosis in EFs. Methods: We analyzed data from the São Paulo State Tuberculosis Control Program database for the period between January of 2010 and December of 2013. Newly diagnosed patients over 15 years of age with pulmonary, extrapulmonary, or disseminated tuberculosis were included in the study. Multiple logistic regression models adjusted for potential confounders were used in order to evaluate the association between place of diagnosis and treatment outcomes. Results: Of a total of 50,295 patients, 12,696 (25%) were found to have been diagnosed in EFs. In comparison with the patients who had been diagnosed in an outpatient setting, those who had been diagnosed in EFs were younger and more socially vulnerable. Patients diagnosed in EFs were more likely to have unsuccessful treatment outcomes (adjusted OR: 1.54; 95% CI: 1.42-1.66), including loss to follow-up and death. At the municipal level, the probability of tuberculosis diagnosis in EFs was associated with low primary care coverage, inequality, and social vulnerability. In some municipalities, more than 50% of the tuberculosis cases were diagnosed in EFs. Conclusions: In the state of São Paulo, one in every four tuberculosis patients is diagnosed in EFs, a diagnosis of tuberculosis in EFs being associated with poor treatment outcomes. At the municipal level, an EF diagnosis of tuberculosis is associated with structural and socioeconomic indicators, indicating areas for improvement

The value of antibody-coated bacteria in tracheal aspirates for the diagnosis of ventilator-associated pneumonia: a case-control study

ABSTRACT Objective: Ventilator-associated pneumonia (VAP) is the leading type of hospital-acquired infection in ICU patients. The diagnosis of VAP is challenging, mostly due to limitations of the diagnostic methods available. The aim of this study was to determine whether antibody-coated bacteria (ACB) evaluation can improve the specificity of endotracheal aspirate (EA) culture in VAP diagnosis. Methods: We conducted a diagnostic case-control study, enrolling 45 patients undergoing mechanical ventilation. Samples of EA were obtained from patients with and without VAP (cases and controls, respectively), and we assessed the number of bacteria coated with FITC-conjugated monoclonal antibodies (IgA, IgM, or IgG) or an FITC-conjugated polyvalent antibody. Using immunofluorescence microscopy, we determined the proportion of ACB among a fixed number of 80 bacteria. Results: The median proportions of ACB were significantly higher among the cases (n = 22) than among the controls (n = 23)-IgA (60.6% vs. 22.5%), IgM (42.5% vs. 12.5%), IgG (50.6% vs. 17.5%), and polyvalent (75.6% vs. 33.8%)-p < 0.001 for all. The accuracy of the best cut-off points for VAP diagnosis regarding monoclonal and polyvalent ACBs was greater than 95.0% and 93.3%, respectively. Conclusions: The numbers of ACB in EA samples were higher among cases than among controls. Our findings indicate that evaluating ACB in EA is a promising tool to improve the specificity of VAP diagnosis. The technique could be cost-effective and therefore useful in low-resource settings, with the advantages of minimizing false-positive results and avoiding overtreatment

Reclassifying the spectrum of septic patients using lactate: severe sepsis, cryptic shock, vasoplegic shock and dysoxic shock

Objetivo: A definição atual de sepse grave e choque séptico inclui um perfil heterogêneo de pacientes. Embora o valor prognóstico de hiperlactatemia seja bem estabelecido, ela está presente em pacientes com ou sem choque. Nosso objetivo foi comparar o prognóstico de pacientes sépticos estratificando-os segundo dois fatores: hiperlactatemia e hipotensão persistente. Métodos: Este estudo é uma análise secundária de um estudo observacional conduzido em dez hospitais no Brasil (Rede Amil - SP). Pacientes sépticos com valor inicial de lactato das primeiras 6 horas do diagnóstico foram incluídos e divididos em 4 grupos segundo hiperlactatemia (lactato >4mmol/L) e hipotensão persistente: (1) sepse grave (sem ambos os critérios); (2) choque críptico (hiperlactatemia sem hipotensão persistente); (3) choque vasoplégico (hipotensão persistente sem hiperlactatemia); e (4) choque disóxico (ambos os critérios). Resultados: Foram analisados 1.948 pacientes, e o grupo sepse grave constituiu 52% dos pacientes, seguido por 28% com choque vasoplégico, 12% choque disóxico e 8% com choque críptico. A sobrevida em 28 dias foi diferente entre os grupos (p<0,001), sendo maior para o grupo sepse grave (69%; p<0,001 versus outros), semelhante entre choque críptico e vasoplégico (53%; p=0,39) e menor para choque disóxico (38%; p<0,001 versus outros). Em análise ajustada, a sobrevida em 28 dias permaneceu diferente entre os grupos (p<0,001), sendo a maior razão de risco para o grupo choque disóxico (HR=2,99; IC95% 2,21-4,05). Conclusão: A definição de pacientes com sepse inclui quatro diferentes perfis, se considerarmos a presença de hiperlactatemia. Novos estudos são necessários para melhor caracterizar pacientes sépticos e gerar conhecimento epidemiológico, além de possível adequação de tratamentos dirigidos