Clinical profiles and treatment outcomes of outpatients with interstitial lung disease and mechanic's hands: A retrospective and observational cohort.

Idiopathic inflammatory myopathies, especially antisynthetase syndrome, often appear outside of the muscles as interstitial lung disease (ILD). Another typical finding is the presence of mechanic's hands. The aim of the present study was to describe the clinical, functional, tomographic, and serological data of patients with ILD and mechanic's hands and their response to treatment and survival rates. This is a retrospective study of ILD with concurrent myopathy. Among the 119 patients initially selected, 51 had mechanic's hands. All the patients were screened for anti-Jo-1 antibodies. An expanded panel of myopathy autoantibodies was also performed in 27 individuals. Of the 51 patients, 35 had 1 or more antibodies. The most common were anti-Jo-1, anti-PL-7, and anti-PL-12, while of the associated antibodies, anti-Ro52 was present in 70% of the 27 tested individuals. A significant response to treatment was characterized by an increase in predicted forced vital capacity (FVC) of at least 5% in the last evaluation done after 6 to 24 months of treatment. A decrease in predicted FVC of at least 5%, the need for oxygen therapy, or death were all considered treatment failures. All patients were treated with corticosteroids, and 71% with mycophenolate. After 24 months, 18 patients had an increase in FVC, 11 had a decrease, and 22 remained stable. After a median follow-up of 58 months, 48 patients remained alive and three died. Patients with honeycombing on high-resolution chest tomography (log-rank = 34.65; P < .001) and a decrease in FVC ≥5% (log-rank = 18.28, P < .001) had a poorer survival rate. Patients with ILD and mechanic's hands respond well to immunosuppressive treatment.

Connective tissue disease-associated interstitial lung disease.

Connective tissue disease-associated interstitial lung disease (CTD-ILD) represents a group of systemic autoimmune disorders characterized by immune-mediated organ dysfunction. Systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myositis, and Sjögren's syndrome are the most common CTDs that present with pulmonary involvement, as well as with interstitial pneumonia with autoimmune features. The frequency of CTD-ILD varies according to the type of CTD, but the overall incidence is 15%, causing an important impact on morbidity and mortality. The decision of which CTD patient should be investigated for ILD is unclear for many CTDs. Besides that, the clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. A significant proportion of patients will present with a more severe and progressive disease, and, for those, immunosuppression with corticosteroids and cytotoxic medications are the mainstay of pharmacological treatment. In this review, we summarized the approach to diagnosis and treatment of CTD-ILD, highlighting recent advances in therapeutics for the various forms of CTD.

Relative incidence of interstitial lung diseases in Brazil.

OBJECTIVE: To assess the relative frequency of incident cases of interstitial lung diseases (ILDs) in Brazil. METHODS: This was a retrospective survey of new cases of ILD in six referral centers between January of 2013 and January of 2020. The diagnosis of ILD followed the criteria suggested by international bodies or was made through multidisciplinary discussion (MDD). The condition was characterized as unclassifiable ILD when there was no specific final diagnosis following MDD or when there was disagreement between clinical, radiological, or histological data. RESULTS: The sample comprised 1,406 patients (mean age = 61 ± 14 years), and 764 (54%) were female. Of the 747 cases exposed to hypersensitivity pneumonitis (HP)-related antigens, 327 (44%) had a final diagnosis of HP. A family history of ILD was reported in 8% of cases. HRCT findings were indicative of fibrosis in 74% of cases, including honeycombing, in 21%. Relevant autoantibodies were detected in 33% of cases. Transbronchial biopsy was performed in 23% of patients, and surgical lung biopsy, in 17%. The final diagnoses were: connective tissue disease-associated ILD (in 27%), HP (in 23%), idiopathic pulmonary fibrosis (in 14%), unclassifiable ILD (in 10%), and sarcoidosis (in 6%). Diagnoses varied significantly among centers (c2 = 312.4; p < 0.001). CONCLUSIONS: Our findings show that connective tissue disease-associated ILD is the most common ILD in Brazil, followed by HP. These results highlight the need for close collaboration between pulmonologists and rheumatologists, the importance of detailed questioning of patients in regard with potential exposure to antigens, and the need for public health campaigns to stress the importance of avoiding such exposure.

On the Nuisance Parameter Elimination Principle in Hypothesis Testing.

The Non-Informative Nuisance Parameter Principle concerns the problem of how inferences about a parameter of interest should be made in the presence of nuisance parameters. The principle is examined in the context of the hypothesis testing problem. We prove that the mixed test obeys the principle for discrete sample spaces. We also show how adherence of the mixed test to the principle can make performance of the test much easier. These findings are illustrated with new solutions to well-known problems of testing hypotheses for count data.

Relative incidence of interstitial lung diseases in Brazil / Incidência relativa de doenças pulmonares intersticiais no Brasil

ABSTRACT Objective: To assess the relative frequency of incident cases of interstitial lung diseases (ILDs) in Brazil. Methods: This was a retrospective survey of new cases of ILD in six referral centers between January of 2013 and January of 2020. The diagnosis of ILD followed the criteria suggested by international bodies or was made through multidisciplinary discussion (MDD). The condition was characterized as unclassifiable ILD when there was no specific final diagnosis following MDD or when there was disagreement between clinical, radiological, or histological data. Results: The sample comprised 1,406 patients (mean age = 61 ± 14 years), and 764 (54%) were female. Of the 747 cases exposed to hypersensitivity pneumonitis (HP)-related antigens, 327 (44%) had a final diagnosis of HP. A family history of ILD was reported in 8% of cases. HRCT findings were indicative of fibrosis in 74% of cases, including honeycombing, in 21%. Relevant autoantibodies were detected in 33% of cases. Transbronchial biopsy was performed in 23% of patients, and surgical lung biopsy, in 17%. The final diagnoses were: connective tissue disease-associated ILD (in 27%), HP (in 23%), idiopathic pulmonary fibrosis (in 14%), unclassifiable ILD (in 10%), and sarcoidosis (in 6%). Diagnoses varied significantly among centers (c2 = 312.4; p < 0.001). Conclusions: Our findings show that connective tissue disease-associated ILD is the most common ILD in Brazil, followed by HP. These results highlight the need for close collaboration between pulmonologists and rheumatologists, the importance of detailed questioning of patients in regard with potential exposure to antigens, and the need for public health campaigns to stress the importance of avoiding such exposure.

RESUMO Objetivo: Avaliar a frequência relativa de casos incidentes de doenças pulmonares intersticiais (DPI) no Brasil. Métodos: Levantamento retrospectivo de casos novos de DPI em seis centros de referência entre janeiro de 2013 e janeiro de 2020. O diagnóstico de DPI seguiu os critérios sugeridos por órgãos internacionais ou foi feito por meio de discussão multidisciplinar (DMD). A condição foi caracterizada como DPI não classificável quando não houve um diagnóstico final específico após a DMD ou houve discordância entre dados clínicos, radiológicos ou histológicos. Resultados: A amostra foi composta por 1.406 pacientes (média de idade = 61 ± 14 anos), sendo 764 (54%) do sexo feminino. Dos 747 casos expostos a antígenos para pneumonite de hipersensibilidade (PH), 327 (44%) tiveram diagnóstico final de PH. Houve relato de história familiar de DPI em 8% dos casos. Os achados de TCAR foram indicativos de fibrose em 74% dos casos, incluindo faveolamento, em 21%. Autoanticorpos relevantes foram detectados em 33% dos casos. Biópsia transbrônquica foi realizada em 23% dos pacientes, e biópsia pulmonar cirúrgica, em 17%. Os diagnósticos finais foram: DPI associada à doença do tecido conjuntivo (em 27%), PH (em 23%), fibrose pulmonar idiopática (em 14%), DPI não classificável (em 10%) e sarcoidose (em 6%). Os diagnósticos variaram significativamente entre os centros (c2 = 312,4; p < 0,001). Conclusões: Nossos achados mostram que DPI associada à doença do tecido conjuntivo é a DPI mais comum no Brasil, seguida pela PH. Esses resultados destacam a necessidade de uma estreita colaboração entre pneumologistas e reumatologistas, a importância de fazer perguntas detalhadas aos pacientes a respeito da potencial exposição a antígenos e a necessidade de campanhas de saúde pública destinadas a enfatizar a importância de evitar essa exposição.

Connective tissue disease-associated interstitial lung disease / Doença pulmonar intersticial associada a doença do tecido conjuntivo

ABSTRACT Connective tissue disease-associated interstitial lung disease (CTD-ILD) represents a group of systemic autoimmune disorders characterized by immune-mediated organ dysfunction. Systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myositis, and Sjögren's syndrome are the most common CTDs that present with pulmonary involvement, as well as with interstitial pneumonia with autoimmune features. The frequency of CTD-ILD varies according to the type of CTD, but the overall incidence is 15%, causing an important impact on morbidity and mortality. The decision of which CTD patient should be investigated for ILD is unclear for many CTDs. Besides that, the clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. A significant proportion of patients will present with a more severe and progressive disease, and, for those, immunosuppression with corticosteroids and cytotoxic medications are the mainstay of pharmacological treatment. In this review, we summarized the approach to diagnosis and treatment of CTD-ILD, highlighting recent advances in therapeutics for the various forms of CTD.

RESUMO Doença pulmonar intersticial associada à doença do tecido conjuntivo (DPI-DTC) representa um grupo de distúrbios autoimunes sistêmicos caracterizados por disfunção de órgãos imunomediada. Esclerose sistêmica, artrite reumatoide, miosite inflamatória idiopática e síndrome de Sjögren são as DTC mais comuns que apresentam acometimento pulmonar, bem como pneumonia intersticial com achados autoimunes. A frequência de DPI-DTC varia de acordo com o tipo de DTC, mas a incidência total é de 15%, causando um impacto importante na morbidade e mortalidade. A decisão sobre qual paciente com DTC deve ser investigado para DPI não é clara para muitas DTC. Além disso, o espectro clínico pode variar desde achados assintomáticos em exames de imagem até insuficiência respiratória e morte. Parte significativa dos pacientes apresentará doença mais grave e progressiva, e, para esses pacientes, imunossupressão com corticosteroides e medicamentos citotóxicos são a base do tratamento farmacológico. Nesta revisão, resumimos a abordagem do diagnóstico e tratamento de DPI-DTC, destacando os recentes avanços na terapêutica para as diversas formas de DTC.

Sleep parameters in patients with chronic hypersensitivity pneumonitis: a case-control study.

OBJECTIVE: To compare patients with chronic hypersensitivity pneumonitis (cHP) and controls with normal spirometry in terms of their sleep characteristics, as well as to establish the prevalence of obstructive sleep apnea (OSA) and nocturnal hypoxemia. Secondary objectives were to identify factors associated with OSA and nocturnal hypoxemia; to correlate nocturnal hypoxemia with the apnea-hypopnea index (AHI) and lung function, as well as with resting SpO2, awake SpO2, and SpO2 during exercise; and to evaluate the discriminatory power of sleep questionnaires to predict OSA. METHODS: A total of 40 patients with cHP (cases) were matched for sex, age, and BMI with 80 controls, the ratio of controls to cases therefore being = 2:1. The STOP-Bang questionnaire, the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index, the Berlin questionnaire and the Neck circumference, obesity, Snoring, Age, and Sex (NoSAS) score were applied to all cases, and both groups underwent full-night polysomnography. RESULTS: The patients with cHP had longer sleep latency, lower sleep efficiency, a lower AHI, a lower respiratory disturbance index, fewer central apneas, fewer mixed apneas, and fewer hypopneas than did the controls. The patients with cHP had significantly lower nocturnal SpO2 values, the percentage of total sleep time spent below an SpO2 of 90% being higher than in controls (median = 4.2; IQR, 0.4-32.1 vs. median = 1.0; IQR, 0.1-5.8; p = 0.01). There were no significant differences between cases with and without OSA regarding the STOP-Bang questionnaire, NoSAS, and ESS scores. CONCLUSIONS: The prevalence of OSA in cHP patients (cases) was high, although not higher than that in controls with normal spirometry. In addition, cases had more hypoxemia during sleep than did controls. Our results suggest that sleep questionnaires do not have sufficient discriminatory power to identify OSA in cHP patients.

Brain activation during fear extinction recall in unmedicated patients with obsessive-compulsive disorder.

Specific brain activation patterns during fear conditioning and the recall of previously extinguished fear responses have been associated with obsessive-compulsive disorder (OCD). However, further replication studies are necessary. We measured skin-conductance response and blood oxygenation level-dependent responses in unmedicated adult patients with OCD (n = 27) and healthy participants (n = 22) submitted to a two-day fear-conditioning experiment comprising fear conditioning, extinction (day 1) and extinction recall (day 2). During conditioning, groups differed regarding the skin conductance reactivity to the aversive stimulus (shock) and regarding the activation of the right opercular cortex, insular cortex, putamen, and lingual gyrus in response to conditioned stimuli. During extinction recall, patients with OCD had higher responses to stimuli and smaller differences between responses to conditioned and neutral stimuli. For the entire sample, the higher the response delta between conditioned and neutral stimuli, the greater the dACC activation for the same contrast during early extinction recall. While activation of the dACC predicted the average difference between responses to stimuli for the entire sample, groups did not differ regarding the activation of the dACC during extinction recall. Larger unmedicated samples might be necessary to replicate the previous findings reported in patients with OCD.

Sleep parameters in patients with chronic hypersensitivity pneumonitis: a case-control study / Parâmetros do sono em pacientes com pneumonite de hipersensibilidade crônica: estudo de caso-controle

ABSTRACT Objective: To compare patients with chronic hypersensitivity pneumonitis (cHP) and controls with normal spirometry in terms of their sleep characteristics, as well as to establish the prevalence of obstructive sleep apnea (OSA) and nocturnal hypoxemia. Secondary objectives were to identify factors associated with OSA and nocturnal hypoxemia; to correlate nocturnal hypoxemia with the apnea-hypopnea index (AHI) and lung function, as well as with resting SpO2, awake SpO2, and SpO2 during exercise; and to evaluate the discriminatory power of sleep questionnaires to predict OSA. Methods: A total of 40 patients with cHP (cases) were matched for sex, age, and BMI with 80 controls, the ratio of controls to cases therefore being = 2:1. The STOP-Bang questionnaire, the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index, the Berlin questionnaire and the Neck circumference, obesity, Snoring, Age, and Sex (NoSAS) score were applied to all cases, and both groups underwent full-night polysomnography. Results: The patients with cHP had longer sleep latency, lower sleep efficiency, a lower AHI, a lower respiratory disturbance index, fewer central apneas, fewer mixed apneas, and fewer hypopneas than did the controls. The patients with cHP had significantly lower nocturnal SpO2 values, the percentage of total sleep time spent below an SpO2 of 90% being higher than in controls (median = 4.2; IQR, 0.4-32.1 vs. median = 1.0; IQR, 0.1-5.8; p = 0.01). There were no significant differences between cases with and without OSA regarding the STOP-Bang questionnaire, NoSAS, and ESS scores. Conclusions: The prevalence of OSA in cHP patients (cases) was high, although not higher than that in controls with normal spirometry. In addition, cases had more hypoxemia during sleep than did controls. Our results suggest that sleep questionnaires do not have sufficient discriminatory power to identify OSA in cHP patients.

RESUMO Objetivo: Comparar pacientes com pneumonite de hipersensibilidade crônica (PHc) e controles com espirometria normal quanto às características do sono, bem como estabelecer a prevalência de apneia obstrutiva do sono (AOS) e hipoxemia noturna. Os objetivos secundários foram identificar fatores associados à AOS e hipoxemia noturna; correlacionar a hipoxemia noturna com o índice de apneias e hipopneias (IAH), função pulmonar, SpO2 em repouso, SpO2 em vigília e SpO2 durante o exercício; e avaliar o poder discriminatório de questionários do sono para predizer AOS. Métodos: Um total de 40 pacientes com PHc (casos) foram emparelhados por sexo, idade e IMC com 80 controles (2:1). O questionário STOP-Bang, a Escala de Sonolência de Epworth (ESE), o Índice de Qualidade do Sono de Pittsburgh, o questionário de Berlim e o escore Neck circumference, obesity, Snoring, Age, and Sex (NoSAS, circunferência do pescoço, obesidade, ronco, idade e sexo) foram aplicados a todos os casos, e ambos os grupos foram submetidos a polissonografia de noite inteira. Resultados: Os pacientes com PHc apresentaram maior latência do sono, menor eficiência do sono, menor IAH, menor índice de distúrbio respiratório, menos apneias centrais, menos apneias mistas e menos hipopneias do que os controles. Os pacientes com PHc apresentaram SpO2 noturna significativamente menor; a porcentagem do tempo total de sono com SpO2 < 90% foi maior que nos controles (mediana = 4,2; IIQ: 0,4-32,1 vs. mediana = 1,0; IIQ: 0,1-5,8; p = 0,01). Não houve diferenças significativas entre os casos com e sem AOS quanto à pontuação no questionário STOP-Bang, no NoSAS e na ESE. Conclusões: A prevalência de AOS em pacientes com PHc (casos) foi alta, embora não tenha sido maior que a observada em controles com espirometria normal. Além disso, os casos apresentaram mais hipoxemia durante o sono do que os controles. Nossos resultados sugerem que os questionários do sono não têm poder discriminatório suficiente para identificar AOS em pacientes com PHc.

Modeling Overdispersed Dengue Data via Poisson Inverse Gaussian Regression Model: A Case Study in the City of Campo Grande, MS, Brazil.

Dengue fever is a tropical disease transmitted mainly by the female Aedes aegypti mosquito that affects millions of people every year. As there is still no safe and effective vaccine, currently the best way to prevent the disease is to control the proliferation of the transmitting mosquito. Since the proliferation and life cycle of the mosquito depend on environmental variables such as temperature and water availability, among others, statistical models are needed to understand the existing relationships between environmental variables and the recorded number of dengue cases and predict the number of cases for some future time interval. This prediction is of paramount importance for the establishment of control policies. In general, dengue-fever datasets contain the number of cases recorded periodically (in days, weeks, months or years). Since many dengue-fever datasets tend to be of the overdispersed, long-tail type, some common models like the Poisson regression model or negative binomial regression model are not adequate to model it. For this reason, in this paper we propose modeling a dengue-fever dataset by using a Poisson-inverse-Gaussian regression model. The main advantage of this model is that it adequately models overdispersed long-tailed data because it has a wider skewness range than the negative binomial distribution. We illustrate the application of this model in a real dataset and compare its performance to that of a negative binomial regression model.

Latency to treatment seeking in patients with obsessive-compulsive disorder: Results from a large multicenter clinical sample.

This study aimed to identify the factors associated with a delay in treatment-seeking among patients with obsessive-compulsive disorder (OCD), a disabling neuropsychiatric disorder. To achieve this purpose, we conducted a cross-sectional study examining latency to treatment (LTT) and its associated correlates in 863 patients with OCD. We defined LTT as the time lag between the awareness of discomfort and/or impairment caused by symptoms and the beginning of OCD-specific treatment. To determine the socio-demographic and clinical characteristics associated with LTT, we built an interval-censored survival model to simultaneously assess the relationship between all variables, representing the best fit to our data format. The results of our study showed that approximately one-third of OCD patients sought treatment within two years of symptom awareness, one-third between two and nine years, and one-third after ten or more years. Median LTT was 4.0 years (mean = 7.96, SD = 9.54). Longer LTT was associated with older age, early onset of OCD symptoms, presence of contamination/cleaning symptoms and full-time employment. Shorter LTT was associated with the presence of aggression symptoms and comorbidity with hypochondriasis. The results of our study confirm the understanding that LTT in OCD is influenced by several interdependent variables - some of which are modifiable. Strategies for reducing LTT should focus on older patients, who work in a full-time job, and on individuals with early onset of OCD and contamination/cleaning symptoms.

Algal-Derived Halogenated Sesquiterpenes from Laurencia dendroidea as Lead Compounds in Schistosomiasis Environmental Control.

Schistosomiasis has been controlled for more than 40 years with a single drug, praziquantel, and only one molluscicide, niclosamide, raising concern of the possibility of the emergence of resistant strains. However, the molecular targets for both agents are thus far unknown. Consequently, the search for lead compounds from natural sources has been encouraged due to their diverse structure and function. Our search for natural compounds with potential use in schistosomiasis control led to the identification of an algal species, Laurencia dendroidea, whose extracts demonstrated significant activity toward both Schistosoma mansoni parasites and their intermediate host snails Biomphalaria glabrata. In the present study, three seaweed-derived halogenated sesquiterpenes, (-)-elatol, rogiolol, and obtusol are proposed as potential lead compounds for the development of anthelminthic drugs for the treatment of and pesticides for the environmental control of schistosomiasis. The three compounds were screened for their antischistosomal and molluscicidal activities. The screening revealed that rogiolol exhibits significant activity toward the survival of adult worms, and that all three compounds showed activity against S. mansoni cercariae and B. glabrata embryos. Biomonitored fractioning of L. dendroidea extracts indicated elatol as the most active compound toward cercariae larvae and snail embryos.

Prognostic features of sarcoidosis course in a Brazilian cohort.

OBJECTIVE: To identify predictive features associated with the course of sarcoidosis at initial evaluation and to develop a predictive score. METHODS: This was a retrospective study involving pulmonary sarcoidosis patients, classified as having a self-limited or persistent course of disease, comparing data between the outcomes by univariate analysis. Features related to persistent disease were selected by multivariate analysis and a prognostic score was designed. RESULTS: The sample comprised 200 patients (mean age = 49 years). The median duration of symptoms to diagnosis was 12 months, and delayed diagnosis (> 12 months) was found in 43% of the cases. The most common radiological stage was II; 37% had reduced FVC. Relevant systemic involvement was detected in 37% of the patients. Treatment for tuberculosis was prescribed in 44 patients prior to sarcoidosis diagnosis. Treatment for sarcoidosis was required in 77% of the sample, and the disease course was persistent in 115 cases. Excluding 40 patients with fibrotic disease, prognostic factors to persistent disease were parenchymal involvement, delayed diagnosis, dyspnea, relevant systemic involvement, and reduced FVC. On the basis of the analysis, a 3-letter scoring system (A, B and C) was developed according to the selected factors. The positive predictive values for persistent course for A (≤ 1 point) and C scores (≥ 4 points) were 12.5% and 81.8%, respectively. CONCLUSIONS: A score can be derived by selected features at initial evaluation, allowing the prediction of outcomes in a significant number of sarcoidosis patients.

Adaptive Significance Levels in Tests for Linear Regression Models: The e-Value and P-Value Cases.

The full Bayesian significance test (FBST) for precise hypotheses is a Bayesian alternative to the traditional significance tests based on p-values. The FBST is characterized by the e-value as an evidence index in favor of the null hypothesis (H). An important practical issue for the implementation of the FBST is to establish how small the evidence against H must be in order to decide for its rejection. In this work, we present a method to find a cutoff value for the e-value in the FBST by minimizing the linear combination of the averaged type-I and type-II error probabilities for a given sample size and also for a given dimensionality of the parameter space. Furthermore, we compare our methodology with the results obtained from the test with adaptive significance level, which presents the capital-P P-value as a decision-making evidence measure. For this purpose, the scenario of linear regression models with unknown variance under the Bayesian approach is considered.

Algal-derived halogenated Sesquiterpenes from Laurencia dendroidea as lead compounds in Schistosomiasis environmental control

Schistosomiasis has been controlled for more than 40 years with a single drug, praziquantel, and only one molluscicide, niclosamide, raising concern of the possibility of the emergence of resistant strains. However, the molecular targets for both agents are thus far unknown. Consequently, the search for lead compounds from natural sources has been encouraged due to their diverse structure and function. Our search for natural compounds with potential use in schistosomiasis control led to the identification of an algal species, Laurencia dendroidea, whose extracts demonstrated significant activity toward both Schistosoma mansoni parasites and their intermediate host snails Biomphalaria glabrata. In the present study, three seaweed-derived halogenated sesquiterpenes, (−)-elatol, rogiolol, and obtusol are proposed as potential lead compounds for the development of anthelminthic drugs for the treatment of and pesticides for the environmental control of schistosomiasis. The three compounds were screened for their antischistosomal and molluscicidal activities. The screening revealed that rogiolol exhibits significant activity toward the survival of adult worms, and that all three compounds showed activity against S. mansoni cercariae and B. glabrata embryos. Biomonitored fractioning of L. dendroidea extracts indicated elatol as the most active compound toward cercariae larvae and snail embryos.

Prognostic features of sarcoidosis course in a Brazilian cohort / Características prognósticas da evolução da sarcoidose em uma coorte brasileira

ABSTRACT Objective: To identify predictive features associated with the course of sarcoidosis at initial evaluation and to develop a predictive score. Methods: This was a retrospective study involving pulmonary sarcoidosis patients, classified as having a self-limited or persistent course of disease, comparing data between the outcomes by univariate analysis. Features related to persistent disease were selected by multivariate analysis and a prognostic score was designed. Results: The sample comprised 200 patients (mean age = 49 years). The median duration of symptoms to diagnosis was 12 months, and delayed diagnosis (> 12 months) was found in 43% of the cases. The most common radiological stage was II; 37% had reduced FVC. Relevant systemic involvement was detected in 37% of the patients. Treatment for tuberculosis was prescribed in 44 patients prior to sarcoidosis diagnosis. Treatment for sarcoidosis was required in 77% of the sample, and the disease course was persistent in 115 cases. Excluding 40 patients with fibrotic disease, prognostic factors to persistent disease were parenchymal involvement, delayed diagnosis, dyspnea, relevant systemic involvement, and reduced FVC. On the basis of the analysis, a 3-letter scoring system (A, B and C) was developed according to the selected factors. The positive predictive values for persistent course for A (≤ 1 point) and C scores (≥ 4 points) were 12.5% and 81.8%, respectively. Conclusions: A score can be derived by selected features at initial evaluation, allowing the prediction of outcomes in a significant number of sarcoidosis patients.

RESUMO Objetivo: Identificar características preditivas associadas à evolução da sarcoidose na avaliação inicial e desenvolver um escore preditivo. Métodos: Estudo retrospectivo com pacientes com sarcoidose pulmonar, classificados como tendo evolução autolimitada ou persistente da doença, comparando dados entre os desfechos por meio de análise univariada. Características relacionadas à doença persistente foram selecionadas por meio de análise multivariada, e foi desenvolvido um escore prognóstico. Resultados: A amostra foi composta por 200 pacientes (média de idade = 49 anos). A mediana da duração dos sintomas até o diagnóstico foi de 12 meses, e houve diagnóstico tardio (> 12 meses) em 43% dos casos. O estádio radiológico mais frequente foi o II; 37% apresentavam redução da CVF. Envolvimento sistêmico relevante foi detectado em 37% dos pacientes. Tratamento para tuberculose foi prescrito em 44 pacientes antes do diagnóstico de sarcoidose. Tratamento para sarcoidose foi necessário em 77% da amostra, e a evolução da doença foi persistente em 115 casos. Com a exclusão de 40 pacientes com doença fibrótica, os fatores prognósticos para doença persistente foram comprometimento parenquimatoso, diagnóstico tardio, dispneia, comprometimento sistêmico relevante e redução da CVF. Com base na análise, foi desenvolvido um sistema de pontuação por letras (A, B e C) de acordo com os fatores selecionados. Os valores preditivos positivos para evolução persistente para as pontuações A (≤ 1 ponto) e C (≥ 4 pontos) foram de 12,5% e 81,8%, respectivamente. Conclusões: É possível derivar um escore por meio de características selecionadas na avaliação inicial, permitindo a predição de desfechos em um significativo número de pacientes com sarcoidose.

Atlas de Medicina Legal: um Recurso para a Aprendizagem em um Curso de Direito / Atlas of Forensic Medicine: a Resource for Learning in a Course of Law

O presente trabalho tem como objetivo elaborar um de aprendizagem para o curso de Medicina Legal propondo o estabelecimento de inovações no desenho dos métodos de aprendizagem dos alunos do terceiro período do curso de Direito de uma universidade privada no Estado do Rio de Janeiro. O material elaborado foi um Atlas de Medicina Legal, que propõe a expansão da possibilidade de aprendizagem através de exposição a imagens aos graduandos em Direito, como processo de apreensão dos apontamentos essenciais da Medicina Legal, normalmente restrita a atividades presenciais, limitando possibilidades do debate, essencial no estudo e o alcance do efetivo conhecimento pelos discentes. O material proposto demanda que os alunos utilizem as informações sobre a origem de cada um dos conceitos apresentados no Atlas sobre Medicina Legal, formem o primeiro conjunto de dados empíricos que ratifica o potencial dessa nova abordagem. Esta proposta se soma aos procedimentos já tradicionais de leitura e avaliação para fins de aprendizagem. Um resultado associado ao procedimento proposto foi a possibilidade do professor também avaliar o seu plano de ensino, verificando como os alunos poderão articular e concentrar os conceitos apresentados pelas imagens, formulando, ao final, um atlas com todo o conteúdo aplicado em sala de aula, além da complementação pesquisada, formulando e instruindo uma associação do meio jurídico à Medicina Legal.

Epidemiology of Invasive Fungal Diseases in Patients with Hematologic Malignancies and Hematopoietic Cell Transplantation Recipients Managed with an Antifungal Diagnostic Driven Approach.

Patients with hematologic malignancies and hematopoietic cell transplant recipients (HCT) are at high risk for invasive fungal disease (IFD). The practice of antifungal prophylaxis with mold-active azoles has been challenged recently because of drug-drug interactions with novel targeted therapies. This is a retrospective, single-center cohort study of consecutive cases of proven or probable IFD, diagnosed between 2009 and 2019, in adult hematologic patients and HCT recipients managed with fluconazole prophylaxis and an antifungal diagnostic-driven approach for mold infection. During the study period, 94 cases of IFD occurred among 664 hematologic patients and 316 HCT recipients. The frequency among patients with allogeneic HCT, autologous HCT, acute leukemia and other hematologic malignancies was 8.9%, 1.6%, 17.3%, and 6.4%, respectively. Aspergillosis was the leading IFD (53.2%), followed by fusariosis (18.1%), candidiasis (10.6%), and cryptococcosis (8.5%). The overall 6-week mortality rate was 37.2%, and varied according to the host and the etiology of IFD, from 28% in aspergillosis to 52.9% in fusariosis. Although IFD occurred frequently in our cohort of patients managed with an antifungal diagnostic driven approach, mortality rates were comparable to other studies. In the face of challenges posed by the use of anti-mold prophylaxis, this strategy remains a reasonable alternative.

Piecewise Modeling the Accumulated Daily Growth of COVID-19 Deaths: The Case of the State of São Paulo, Brazil.

The pandemic scenery caused by the new coronavirus, called SARS-CoV-2, increased interest in statistical models capable of projecting the evolution of the number of cases (and associated deaths) due to COVID-19 in countries, states and/or cities. This interest is mainly due to the fact that the projections may help the government agencies in making decisions in relation to procedures of prevention of the disease. Since the growth of the number of cases (and deaths) of COVID-19, in general, has presented a heterogeneous evolution over time, it is important that the modeling procedure is capable of identifying periods with different growth rates and proposing an adequate model for each period. Here, we present a modeling procedure based on the fit of a piecewise growth model for the cumulative number of deaths. We opt to focus on the modeling of the cumulative number of deaths because, other than for the number of cases, these values do not depend on the number of diagnostic tests performed. In the proposed approach, the model is updated in the course of the pandemic, and whenever a "new" period of the pandemic is identified, it creates a new sub-dataset composed of the cumulative number of deaths registered from the change point and a new growth model is chosen for that period. Three growth models were fitted for each period: exponential, logistic and Gompertz models. The best model for the cumulative number of deaths recorded is the one with the smallest mean square error and the smallest Akaike information criterion (AIC) and Bayesian information criterion (BIC) values. This approach is illustrated in a case study, in which we model the number of deaths due to COVID-19 recorded in the State of São Paulo, Brazil. The results have shown that the fit of a piecewise model is very effective for explaining the different periods of the pandemic evolution.

Transbronchial biopsy in chronic hypersensitivity pneumonitis.

INTRODUCTION: The diagnosis of chronic hypersensitivity pneumonitis (CHP) is based on relevant exposure, tomographic findings and, in some cases, pathological data. The role of bronchoscopy is uncertain, especially in the fibrotic form of CHP. AIM: To analyze the yield of transbronchial biopsy (TBBx) in patients with CHP according to tomographic findings and to evaluate the importance of bronchoalveolar lavage (BAL) in the diagnostic approach. METHODS: This retrospective study analyzed patients with CHP who underwent TBBx in São Paulo, Brazil. The TBBx findings were classified as characteristic (granulomas and/or multinucleated giant cells, associated or not with peribronchiolar infiltration of lymphocytes and plasma cells and bronchiolocentric distribution) and supportive (data indicative of small airway injury: peribronchiolar metaplasia, organizing pneumonia, and intra-alveolar foamy macrophages). RESULTS: One hundred nine patients were included. The presence of characteristic findings of HP was seen in 16 patients (14.7%), and supportive findings were seen in 32 patients (29.4%), with a total yield of 44%. Pathological characteristic findings were more common in cases without fibrosis on high-resolution computed tomography (HRCT) (27.3% vs. 9.2%, p= 0.014), whereas the presence of supportive findings was more common in fibrotic HP (38.1% vs. 9.1%, p= 0.002). Fifty-two patients had differential cytology in BAL fluid. Lymphocytosis (> 20%) was present in 51.9% of the patients. There was no difference in the median lymphocyte count according to nonfibrotic and fibrotic tomographic findings on HRCT. CONCLUSION: TBBx and BAL fluid cytology have a role in CHP diagnosis.