Challenges of safety culture in Surgical Center: mixed methods study.

OBJECTIVE: to analyze the safety attitudes of health and support areas professionals working in Surgical Center. METHOD: sequential explanatory mixed methods study. The quantitative stage covered 172 health and support professionals in eight Surgical Centers of a hospital complex. The Safety Attitudes Questionnaire/Surgical Center was applied. In the subsequent qualitative stage, 16 professionals participated in the Focus Group. Photographic methods were used from the perspective of ecological and restorative thinking, and data analysis occurred in an integrated manner, through connection. RESULTS: the general score, by group of Surgical Centers, based on the domains of the Safety Attitudes Questionnaire/Surgical Center, reveals a favorable perception of the safety climate, with emphasis on the domains Stress Perception, Communication in the Surgical Environment, Safety Climate and Perception of Professional Performance. The overall analysis of the domain Communication and Collaboration between Teams appears positive and is corroborated by data from the qualitative stage, which highlights the importance of interaction and communication between healthcare teams as fundamental for daily work. CONCLUSION: the perception of safety attitudes among health and support professionals was positive. The perception of the nursing team stands out as closer or more favorable to attitudes consistent with the safety culture.

Immunohistochemical and histopathological analyses of cutaneous innervation to improve the diagnostic efficacy in hansen disease skin lesion.

BACKGROUND: The diagnosis of Hansen disease (HD) can be difficult when acid-fast bacilli are not detected in the patient's skin sample. OBJECTIVE: To demonstrate that detailed morphological analysis of nonspecific inflammatory and/or noninflammatory alterations in dermal nerves as well as skin adnexa in leprosy-suspected biopsy samples could improve the efficacy of histopathological diagnosis. METHODS: Patients with one to five skin lesions were enrolled in the study and classified into three groups by skin histopathology findings: Hansen disease (HD, n = 13), other diseases (OD, n = 11), and inconclusive cases (INC, n = 11). We quantified dermal nerve damage via the nerve lesion index (NLI) and PGP9.5-immunoreactive axon quantitative index in dermal nerves (AQI). We also measured inflammatory involvement of adnexa in cutaneous samples as indirect evidence of HD. RESULTS: We observed a higher median endoneurial inflammatory infiltrate NLI (HD = 0.5; INC = 0; OD = 0; p < 0.001) and more frequent inflammatory involvement of skin adnexa in samples of the HD group compared with those of the INC and OD groups (HD = 7; INC = 1; OD = 0). However, samples from the INC and OD groups also showed inflammatory and noninflammatory damage of dermal nerves, with 2 or more kinds of alterations in nerves in the same sample (respectively: INC = in 1 and 2 samples; OD = in 3 and 5 respectively). The quantification of PGP9.5-immunoreactive axons in dermal nerves revealed no difference between the groups. CONCLUSION: A detailed morphological analysis of cutaneous nerves in lesions with a suspicion of HD enabled us to select patients with nonspecific inflammatory or non-inflammatory lesions in the dermal nerves in the INC and OD groups, so they may be clinically monitored aiming at a possible future diagnosis of the disease. These INC and OD patients cannot have the HD diagnosis definitely excluded, and HD may coexist with another disease as a comorbidity.

ANTECEDENTES: A hanseníase pode ter o seu diagnóstico histopatológico dificultado quando bacilos álcool-ácido resistentes não são encontrados nas amostras de pele dos pacientes. OBJETIVO: Demonstrar que uma análise morfológica detalhada de alterações histopatológicas dos nervos dérmicos pode aumentar a eficácia diagnóstica. MéTODOS: Foram selecionadas amostras de pele de pacientes com uma a cinco lesões suspeitas de hanseníase. Os casos selecionados foram classificados conforme achados histopatológicos: hanseníase (HD, n = 13), casos inconclusivos (INC, n = 11), e outras doenças (OD, n = 11). Quantificamos as lesões dos nervos cutâneos por meio do índice de lesão de nervos (nerve lesion index, NLI, em inglês) e do índice quantitativo de axônios (axon quantitative index, AQI, em inglês) imunorreativos a PGP9.5 nos nervos cutâneos. Também medimos o envolvimento inflamatório dos anexos em amostras de pele como evidência indireta de hanseníase. RESULTADOS: Foram observadas no grupo HD medianas mais altas do NLI com relação a infiltrados inflamatórios endoneurais (HD = 0,5; INC = 0; OD = 0; p < 0,001) e mais alta frequência de acometimento inflamatório de anexos cutâneos (HD = 7; INC = 1; OD = 0). Entretanto, as amostras dos grupos INC e OD também mostraram comprometimento inflamatório e não inflamatório dos nervos cutâneos, com 2 ou mais tipos de alterações de nervos na mesma amostra (respectivamente: INC = 1 e 2; OD = 3 e 5). Não houve diferença significativa na quantidade de axônios endoneurais imunorreativos a PGP9.5 entre os grupos. CONCLUSãO: A análise morfológica detalhada dos nervos cutâneos em lesões suspeitas de hanseníase permitiu selecionar pacientes com lesões inespecíficas inflamatórias ou não inflamatórias nos nervos dérmicos nos grupos INC e OD, para que sejam monitorados clinicamente visando um possível diagnóstico futuro da doença. Esses pacientes INC e OD não podem ter o diagnóstico de HD definitivamente excluído, e a hanseníase pode coexistir com outra doença como uma comorbidade.

Immunohistochemical and histopathological analyses of cutaneous innervation to improve the diagnostic efficacy in hansen disease skin lesion / Análises imuno-histoquímica e histopatológica da inervação cutânea para aumento da eficácia diagnóstica nas lesões de pele da hanseníase

Abstract Background The diagnosis of Hansen disease (HD) can be difficult when acid-fast bacilli are not detected in the patient's skin sample. Objective To demonstrate that detailed morphological analysis of nonspecific inflammatory and/or noninflammatory alterations in dermal nerves as well as skin adnexa in leprosy-suspected biopsy samples could improve the efficacy of histopathological diagnosis. Methods Patients with one to five skin lesions were enrolled in the study and classified into three groups by skin histopathology findings: Hansen disease (HD, n = 13), other diseases (OD, n = 11), and inconclusive cases (INC, n = 11). We quantified dermal nerve damage via the nerve lesion index (NLI) and PGP9.5-immunoreactive axon quantitative index in dermal nerves (AQI). We also measured inflammatory involvement of adnexa in cutaneous samples as indirect evidence of HD. Results We observed a higher median endoneurial inflammatory infiltrate NLI (HD = 0.5; INC = 0; OD = 0; p < 0.001) and more frequent inflammatory involvement of skin adnexa in samples of the HD group compared with those of the INC and OD groups (HD = 7; INC = 1; OD = 0). However, samples from the INC and OD groups also showed inflammatory and noninflammatory damage of dermal nerves, with 2 or more kinds of alterations in nerves in the same sample (respectively: INC = in 1 and 2 samples; OD = in 3 and 5 respectively). The quantification of PGP9.5-immunoreactive axons in dermal nerves revealed no difference between the groups. Conclusion A detailed morphological analysis of cutaneous nerves in lesions with a suspicion of HD enabled us to select patients with nonspecific inflammatory or non-inflammatory lesions in the dermal nerves in the INC and OD groups, so they may be clinically monitored aiming at a possible future diagnosis of the disease. These INC and OD patients cannot have the HD diagnosis definitely excluded, and HD may coexist with another disease as a comorbidity.

Resumo Antecedentes A hanseníase pode ter o seu diagnóstico histopatológico dificultado quando bacilos álcool-ácido resistentes não são encontrados nas amostras de pele dos pacientes. Objetivo Demonstrar que uma análise morfológica detalhada de alterações histopatológicas dos nervos dérmicos pode aumentar a eficácia diagnóstica. Métodos Foram selecionadas amostras de pele de pacientes com uma a cinco lesões suspeitas de hanseníase. Os casos selecionados foram classificados conforme achados histopatológicos: hanseníase (HD, n = 13), casos inconclusivos (INC, n = 11), e outras doenças (OD, n = 11). Quantificamos as lesões dos nervos cutâneos por meio do índice de lesão de nervos (nerve lesion index, NLI, em inglês) e do índice quantitativo de axônios (axon quantitative index, AQI, em inglês) imunorreativos a PGP9.5 nos nervos cutâneos. Também medimos o envolvimento inflamatório dos anexos em amostras de pele como evidência indireta de hanseníase. Resultados Foram observadas no grupo HD medianas mais altas do NLI com relação a infiltrados inflamatórios endoneurais (HD = 0,5; INC = 0; OD = 0; p < 0,001) e mais alta frequência de acometimento inflamatório de anexos cutâneos (HD = 7; INC = 1; OD = 0). Entretanto, as amostras dos grupos INC e OD também mostraram comprometimento inflamatório e não inflamatório dos nervos cutâneos, com 2 ou mais tipos de alterações de nervos na mesma amostra (respectivamente: INC = 1 e 2; OD = 3 e 5). Não houve diferença significativa na quantidade de axônios endoneurais imunorreativos a PGP9.5 entre os grupos. Conclusão A análise morfológica detalhada dos nervos cutâneos em lesões suspeitas de hanseníase permitiu selecionar pacientes com lesões inespecíficas inflamatórias ou não inflamatórias nos nervos dérmicos nos grupos INC e OD, para que sejam monitorados clinicamente visando um possível diagnóstico futuro da doença. Esses pacientes INC e OD não podem ter o diagnóstico de HD definitivamente excluído, e a hanseníase pode coexistir com outra doença como uma comorbidade.

Challenges of safety culture in Surgical Center: mixed methods study / Desafíos de la cultura de seguridad en Centro Quirúrgico: estudio de métodos mixtos / Desafios da cultura de segurança em Centro Cirúrgico: estudo de métodos mistos

Objective: to analyze the safety attitudes of health and support areas professionals working in Surgical Center. Method: sequential explanatory mixed methods study. The quantitative stage covered 172 health and support professionals in eight Surgical Centers of a hospital complex. The Safety Attitudes Questionnaire/Surgical Center was applied. In the subsequent qualitative stage, 16 professionals participated in the Focus Group. Photographic methods were used from the perspective of ecological and restorative thinking, and data analysis occurred in an integrated manner, through connection. Results: the general score, by group of Surgical Centers, based on the domains of the Safety Attitudes Questionnaire/Surgical Center, reveals a favorable perception of the safety climate, with emphasis on the domains Stress Perception, Communication in the Surgical Environment, Safety Climate and Perception of Professional Performance. The overall analysis of the domain Communication and Collaboration between Teams appears positive and is corroborated by data from the qualitative stage, which highlights the importance of interaction and communication between healthcare teams as fundamental for daily work. Conclusion: the perception of safety attitudes among health and support professionals was positive. The perception of the nursing team stands out as closer or more favorable to attitudes consistent with the safety culture.

Objetivo: analizar las actitudes de seguridad de los profesionales de la salud y de áreas de apoyo que trabajan en el Centro Quirúrgico. Método: estudio explicativo secuencial de métodos mixtos. La etapa cuantitativa abarcó a 172 profesionales de la salud y de apoyo en ocho Centros Quirúrgicos de un complejo hospitalario. Se aplicó el Cuestionario de Actitudes de Seguridad/Centro Quirúrgico. En la etapa cualitativa posterior, participaron del Grupo Focal 16 profesionales. Se utilizaron métodos fotográficos desde la perspectiva del pensamiento ecológico y restaurativo, y el análisis de datos se produjo de manera integrada, por medio de conexión. Resultados: el puntaje general, por grupo de Centros Quirúrgicos, con base en los dominios del Cuestionario de Actitudes de Seguridad/Centro Quirúrgico, revela una percepción favorable del clima de seguridad, con énfasis en los dominios Percepción del Estrés, Comunicación en el Ambiente Quirúrgico, Clima de Seguridad y Percepción del Desempeño Profesional. El análisis global del dominio Comunicación y Colaboración entre Equipos parece positivo y está corroborado por datos de la etapa cualitativa, que resalta la importancia de la interacción y de la comunicación entre los equipos de salud como fundamentales para el trabajo diario. Conclusión: la percepción de las actitudes de seguridad entre los profesionales de la salud y de apoyo fue positiva. Se destaca la percepción del equipo de enfermería como más cercana o favorable a actitudes coherentes con la cultura de seguridad.

Objetivo: analisar as atitudes de segurança de profissionais da saúde e de áreas de apoio atuantes em Centro Cirúrgico. Método: estudo explanatório sequencial de métodos mistos. A etapa quantitativa abrangeu 172 profissionais da saúde e de apoio em oito Centros Cirúrgicos de um complexo hospitalar. Aplicou-se o Questionário de Atitudes de Segurança/Centro Cirúrgico . Na etapa qualitativa subsequente, 16 profissionais participaram do Grupo Focal. Utilizaram-se métodos fotográficos na perspectiva do pensamento ecológico e restaurativo, e a análise dos dados ocorreu de maneira integrada, por conexão. Resultados: o escore geral, por agrupamento de Centros Cirúrgicos, com base nos domínios do Questionário de Atitudes de Segurança/Centro Cirúrgico, revela percepção favorável do clima de segurança, com destaque para os domínios Percepção do Estresse, Comunicação no Ambiente Cirúrgico, Clima de Segurança e Percepção do Desempenho Profissional. A análise global do domínio Comunicação e Colaboração entre as Equipes mostra-se positiva e é corroborada pelos dados da etapa qualitativa, na qual destaca-se a importância da interação e da comunicação entre as equipes de saúde como fundamentais para o trabalho diário. Conclusão: a percepção das atitudes de segurança entre os profissionais da saúde e de apoio foi positiva. A percepção da equipe de enfermagem se destaca como mais próxima ou favorável a atitudes condizentes com a cultura de segurança.

Human N-acetyltransferase 2 (NAT2) gene variability in Brazilian populations from different geographical areas.

Introduction: Several polymorphisms altering the NAT2 activity have already been identified. The geographical distribution of NAT2 variants has been extensively studied and has been demonstrated to vary significantly among different ethnic population. Here, we describe the genetic variability of human N-acetyltransferase 2 (NAT2) gene and the predominant genotype-deduced acetylation profiles of Brazilians. Methods: A total of 964 individuals, from five geographical different regions, were genotyped for NAT2 by sequencing the entire coding exon. Results: Twenty-three previously described NAT2 single nucleotide polymorphisms (SNPs) were identified, including the seven most common ones globally (c.191G>A, c.282C>T, c.341T>C, c.481C>T, c.590G>A, c.803A>G and c.857G>A). The main allelic groups were NAT2*5 (36%) and NAT2*6 (18.2%), followed to the reference allele NAT2*4 (20.4%). Combined into genotypes, the most prevalent allelic groups were NAT2*5/*5 (14.6%), NAT2*5/*6 (11.9%) and NAT2*6/*6 (6.2%). The genotype deduced NAT2 slow acetylation phenotype was predominant but showed significant variability between geographical regions. The prevalence of slow acetylation phenotype was higher in the Northeast, North and Midwest (51.3%, 45.5% and 41.5%, respectively) of the country. In the Southeast, the intermediate acetylation phenotype was the most prevalent (40.3%) and, in the South, the prevalence of rapid acetylation phenotype was significantly higher (36.7%), when compared to other Brazilian states (p < 0.0001). Comparison of the predicted acetylation profile among regions showed homogeneity among the North and Northeast but was significantly different when compared to the Southeast (p = 0.0396). The Southern region was significantly different from all other regions (p < 0.0001). Discussion: This study contributes not only to current knowledge of the NAT2 population genetic diversity in different geographical regions of Brazil, but also to the reconstruction of a more accurate phenotypic picture of NAT2 acetylator profiles in those regions.

Reimagining leprosy elimination with AI analysis of a combination of skin lesion images with demographic and clinical data.

Background: Leprosy is an infectious disease that mostly affects underserved populations. Although it has been largely eliminated, still about 200'000 new patients are diagnosed annually. In the absence of a diagnostic test, clinical diagnosis is often delayed, potentially leading to irreversible neurological damage and its resulting stigma, as well as continued transmission. Accelerating diagnosis could significantly contribute to advancing global leprosy elimination. Digital and Artificial Intelligence (AI) driven technology has shown potential to augment health workers abilities in making faster and more accurate diagnosis, especially when using images such as in the fields of dermatology or ophthalmology. That made us start the quest for an AI-driven diagnosis assistant for leprosy, based on skin images. Methods: Here we describe the accuracy of an AI-enabled image-based diagnosis assistant for leprosy, called AI4Leprosy, based on a combination of skin images and clinical data, collected following a standardized process. In a Brazilian leprosy national referral center, 222 patients with leprosy or other dermatological conditions were included, and the 1229 collected skin images and 585 sets of metadata are stored in an open-source dataset for other researchers to exploit. Findings: We used this dataset to test whether a CNN-based AI algorithm could contribute to leprosy diagnosis and employed three AI models, testing images and metadata both independently and in combination. AI modeling indicated that the most important clinical signs are thermal sensitivity loss, nodules and papules, feet paresthesia, number of lesions and gender, but also scaling surface and pruritus that were negatively associated with leprosy. Using elastic-net logistic regression provided a high classification accuracy (90%) and an area under curve (AUC) of 96.46% for leprosy diagnosis. Interpretation: Future validation of these models is underway, gathering larger datasets from populations of different skin types and collecting images with smartphone cameras to mimic real world settings. We hope that the results of our research will lead to clinical solutions that help accelerate global leprosy elimination. Funding: This study was partially funded by Novartis Foundation and Microsoft (in-kind contribution).

Cultura de segurança em centros cirúrgicos na perspectiva da equipe multiprofissional / Safety culture in surgical centers from the perspective of the multiprofessional team

RESUMO Objetivo avaliar a cultura de segurança a partir da percepção do clima de segurança dos profissionais de saúde que atuam em Centro Cirúrgico. Métodos estudo transversal realizado em oito centros cirúrgicos de um complexo hospitalar. Aplicou-se a versão brasileira validada do Safety Attitudes Questionnaire/Operating Room para uma amostra de conveniência de 172 profissionais de saúde (médicos e de enfermagem) e de apoio. Para a análise empregou-se os testes Qui-quadrado, t de Student e Mann-Whitney. Resultados na avaliação geral, o clima de segurança foi avaliado como positivo. Apenas os profissionais de enfermagem atingiram a mínima pontuação necessária para indicar um resultado positivo no domínio Qualidade da comunicação e colaboração. Os domínios Clima de segurança, Percepção do estresse, Comunicação no ambiente cirúrgico e Percepção do desempenho profissional mostraram-se positivos, enquanto Percepção da gerência e Condição de trabalho apresentaram piores escores. Conclusão a percepção do clima de segurança foi positiva. No entanto, a comunicação apresentou fragilidades apontadas pelos profissionais. Contribuições para a prática: a identificação de domínios que necessitam ser fortalecidos contribui para fomentar uma cultura de segurança nos centros cirúrgicos, repercutindo em melhores resultados assistenciais e ambientes de trabalho para os profissionais.

ABSTRACT Objective to evaluate the safety culture through an observation of the safety climate of health workers from a Surgical Center. Methods cross-sectional study in eight surgical centers from a hospital complex. A validated Brazilian version of the Safety Attitudes Questionnaire/Operating Room was applied to a convenience sample of 172 health and support workers (physicians and nurses). The Chi-squared, Student's t, and Mann-Whitney's tests were used. Results the general evaluation showed a positive safety climate. Only the nursing professionals reached the minimum score that indicates a positive result in the domain Quality of communication and collaboration. The domains Safety climate, Stress recognition, Communication in the surgical environment, and Perception of professional performance showed positive results, while Perception of management and Work conditions had the worst scores. Conclusion the safety climate was positive. Nonetheless, communication showed shortcomings pointed out by the workers. Contributions to practice: identifying domains that need to be improved helps fomenting safety culture in surgical centers, leading to better care outcomes and work environments.

Fatores que interferem no tempo de intervalo entre cirurgias: estudo observacional / Factors that interfere in the interval time between surgeries: an observational study / Factores que interfieren en el intervalo de tiempo entre cirugías: estudio observacional

RESUMO Objetivo: investigar o tempo de intervalo entre as cirurgias e fatores que podem influenciar esse processo. Método: estudo quantitativo, observacional, transversal, desenvolvido em três centros cirúrgicos de um hospital de grande porte do Sul brasileiro. Coleta em janeiro e fevereiro de 2020, por observação do intervalo entre cirurgias guiadas por roteiro. Análise dos dados por estatística descritiva, correlação e análise fatorial. Resultados: o tempo médio de turnover foi 37 minutos. As variáveis: desmontagem (r=0,540, P<0,001 e r=0,406, P<0,001), limpeza (r=0,584, P<0,001) e montagem (r=0,689, P<0,001) relacionaram-se positiva e moderadamente ao turnover. O intervalo foi maior com pacientes de unidades de internação do que de origem ambulatorial, e após cirurgias de pequeno porte era menor do que médio e grande porte. Conclusão: oportunizam-se reflexões sobre processos do centro cirúrgico. Serão úteis no planejamento, implementação e gestão desse setor.

ABSTRACT Objective: to investigate the interval time between surgeries and factors that can influence this process. Method: a quantitative, observational and cross-sectional study carried out in three surgical centers of a large-sized hospital in southern Brazil. Collection took place in January and February 2020, by observing the interval between script-guided surgeries. Data analysis was performed by means of descriptive statistics, correlation and factor analysis. Results: the mean turnover time was 37 minutes. The disassembly (r=0.540, p<0.001 and r=0.406, p<0.001), cleaning (r=0.584, p<0.001) and assembly (r=0.689, p<0.001) variables were positively and moderately related to turnover. The interval was longer with patients coming from hospitalization units than from outpatient services and, after minor surgeries, the time was shorter than in medium-sized and major surgeries. Conclusion: reflections on surgical center processes are provided. They will be useful in planning, implementing and managing this sector.

RESUMEN Objetivo: investigar el intervalo de tiempo entre las cirugías y los factores que pueden influir en este proceso. Método: estudio cuantitativo, observacional, transversal, realizado en tres centros quirúrgicos de un gran hospital del sur de Brasil. La recolección se realizó en enero y febrero de 2020, mediante la observación del intervalo entre cirugías orientada por una guía. El análisis de datos mediante estadística descriptiva, correlación y análisis factorial. Resultados: el tiempo promedio de turnover fue de 37 minutos. Las variables: desmontaje (r=0,540, P<0,001 y r=0,406, P<0,001), limpieza (r=0,584, P<0,001) y montaje (r=0,689, P<0,001) se relacionaron positiva y moderadamente con el turnover. El intervalo fue mayor con los pacientes de las unidades de hospitalización que con los pacientes ambulatorios, y fue menor después de las cirugías de baja complejidad que de las de mediana y gran complejidad. Conclusión: se aportan reflexiones sobre los procesos del centro quirúrgico. Serán útiles en la planificación, implementación y gestión de este sector.

Clinical prediction rules for the diagnosis of neuritis in leprosy.

BACKGROUND: Diagnosing neuritis in leprosy patients with neuropathic pain or chronic neuropathy remains challenging since no specific laboratory or neurophysiological marker is available. METHODS: In a cross-sectional study developed at a leprosy outpatient clinic in Rio de Janeiro, RJ, Brazil, 54 individuals complaining of neural pain (single or multiple sites) were classified into two groups ("neuropathic pain" or "neuritis") by a neurological specialist in leprosy based on anamnesis together with clinical and electrophysiological examinations. A neurologist, blind to the pain diagnoses, interviewed and examined the participants using a standardized form that included clinical predictors, pain features, and neurological symptoms. The association between the clinical predictors and pain classifications was evaluated via the Pearson Chi-Square or Fisher's exact test (p < 0.05). RESULTS: Six clinical algorithms were generated to evaluate sensitivity and specificity, with 95% confidence intervals, for clinical predictors statistically associated with neuritis. The most conclusive clinical algorithm was: pain onset at any time during the previous 90 days, or in association with the initiation of neurological symptoms during the prior 30-day period, necessarily associated with the worsening of pain upon movement and nerve palpation, with 94% of specificity and 35% of sensitivity. CONCLUSION: This algorithm could help physicians confirm neuritis in leprosy patients with neural pain, particularly in primary health care units with no access to neurologists or electrophysiological tests.

Low rate of relapse after twelve-dose multidrug therapy for hansen's disease: A 20-year cohort study in a brazilian reference center.

The World Health Organization has raised concerns about the increasing number of Hansen disease (HD) relapses worldwide, especially in Brazil, India, and Indonesia that report the highest number of recurrent cases. Relapses are an indicator of MDT effectiveness and can reflect Mycobacterium leprae persistence or re-infection. Relapse is also a potential marker for the development or progression of disability. In this research, we studied a large cohort of persons affected by HD treated with full fixed-dose multibacillary (MB) multidrug therapy (MDT) followed for up to 20 years and observed that relapses are a rare event. We estimated the incidence density of relapse in a cohort of patients classified to receive MB regime (bacillary index (BI) > 0), diagnosed between September 1997 and June 2017, and treated with twelve-dose MB-MDT at a HD reference center in Rio de Janeiro, Brazil. We obtained the data from the data management system of the clinic routine service. We linked the selected cases to the dataset of relapses of the national HD data to confirm possible relapse cases diagnosed elsewhere. We diagnosed ten cases of relapse in a cohort of 713 patients followed-up for a mean of 12.1 years. This resulted in an incidence rate of 1.16 relapse cases per 1000 person-year (95% CI = 0.5915-2.076). The accumulated risk was 0.025 in 20 years. The very low risk observed in this cohort of twelve-dose-treated MB patients reinforces the success of the current MDT scheme.

Ambiente da prática profissional de enfermagem em países latino-americanos: scoping review / Environment of the professional nursing practice in latin american countries: a scoping review / Entorno de práctica profesional de enfermería en países de américa latina: scoping review

OBJETIVO: Identificar e mapear a produção literária latino-americana acerca do ambiente da prática profissional de enfermagem no cenário hospitalar com base nos instrumentos Nursing Working Index-Revised e Practice Environment Scale. MÉTODO: Scoping review em cinco bases de dados e outras fontes sobre o tema. A amostra contabilizou 20 artigos, nove Teses e cinco Dissertações publicados na última década. RESULTADO: O Brasil apresentou o maior número de publicações em periódicos, na amostra. Os ambientes mostraram-se favoráveis com a aplicação do Nursing Working Index-Revised e desfavoráveis com a Practice Environment Scale. Entre os domínios destacam-se, com os piores escores, o controle do ambiente e adequação da equipe e de recursos. CONCLUSÃO: A produção literária adquire destaque apenas na última década e aponta para a associação entre ambientes da prática favoráveis e melhores resultados assistenciais.

OBJECTIVE: To identify and map the Latin American literary production about the nursing work environment in the hospital setting based on the Nursing Working Index-Revised and on the Practice Environment Scale. METHOD: A scoping review in five databases and other sources on the topic. The sample included 20 articles, nine Theses and five Dissertations published in the last decade. RESULT: In the sample, Brazil presented the largest number of publications in journals. The environments were favorable with the application of the Nursing Working Index-Revised and unfavorable with the Practice Environment Scale. Among the domains with the worst scores, control over the environment and adequacy of the team and resources stand out. CONCLUSION: The literary production has gained prominence only in the last decade and points to the association between favorable practice environments and better care results.

OBJETIVO: Identificar y mapear la producción literaria latinoamericana sobre el entorno de la práctica profesional de la enfermería en el ámbito hospitalario a partir de los instrumentos Nursing Working Index-Revised y Practice Environment Scale. MÉTODO: Scoping review en cinco bases de datos y otras fuentes sobre el tema. La muestra contó con 20 artículos, nueve Tesis Doctorales y cinco Tesis de Maestría publicadas en la última década. RESULTADO: Brasil tuvo el mayor número de publicaciones en revistas de la muestra. Los entornos fueron favorables con la aplicación del Nursing Working Index-Revised y desfavorables con la Practice Environment Scale. Entre los dominios, con los peores puntajes, se destacan el control del entorno y la adecuación del equipo y los recursos. CONCLUSIÓN: La producción literaria ha ganado notoriedad solo en la última década y apunta a la asociación entre entornos de práctica favorables y mejores resultados de atención.

Presence of Senescent and Memory CD8+ Leukocytes as Immunocenescence Markers in Skin Lesions of Elderly Leprosy Patients.

Leprosy is an infectious disease that remains endemic in approximately 100 developing countries, where about 200,000 new cases are diagnosed each year. Moreover, multibacillary leprosy, the most contagious form of the disease, has been detected at continuously higher rates among Brazilian elderly people. Due to the so-called immunosenescence, characterized by several alterations in the quality of the immune response during aging, this group is more susceptible to infectious diseases. In view of such data, the purpose of our work was to investigate if age-related alterations in the immune response could influence the pathogenesis of leprosy. As such, we studied 87 individuals, 62 newly diagnosed and untreated leprosy patients distributed according to the age range and to the clinical forms of the disease and 25 healthy volunteers, who were studied as controls. The frequency of senescent and memory CD8+ leukocytes was assessed by immunofluorescence of biopsies from cutaneous lesions, while the serum levels of IgG anti-CMV antibodies were analyzed by chemiluminescence and the gene expression of T cell receptors' inhibitors by RT-qPCR. We noted an accumulation of memory CD8+ T lymphocytes, as well as reduced CD8+CD28+ cell expression in skin lesions from elderly patients, when compared to younger people. Alterations in LAG3 and PDCD1 gene expression in cutaneous lesions of young MB patients were also observed, when compared to elderly patients. Such data suggest that the age-related alterations of T lymphocyte subsets can facilitate the onset of leprosy in elderly patients, not to mention other chronic inflammatory diseases.

Increased oxidative stress in elderly leprosy patients is related to age but not to bacillary load.

BACKGROUND: Leprosy continues to be a public health problem in Brazil. Furthermore, detection rates in elderly people have increased, particularly those of multibacillary (L-Lep) patients, who are responsible for transmitting M. leprae. Part of the decline in physiological function during aging is due to increased oxidative damage and change in T cell subpopulations, which are critical in defense against the disease. It is not still clear how age-related changes like those related to oxidation affect elderly people with leprosy. The aim of this work was to verify whether the elderly leprosy patients have higher ROS production and how it can impact the evolution of leprosy. METHODOLOGY/PRINCIPAL FINDINGS: 87 leprosy patients, grouped according to age range and clinical form of leprosy, and 25 healthy volunteers were analyzed. Gene expression analysis of antioxidant and oxidative burst enzymes were performed in whole blood using Biomark's microfluidic-based qPCR. The same genes were evaluated in skin lesion samples by RT-qPCR. The presence of oxidative damage markers (carbonylated proteins and 4-hydroxynonenal) was analyzed by a DNPH colorimetric assay and immunofluorescence. Carbonylated protein content was significantly higher in elderly compared to young patients. One year after multidrug therapy (MDT) discharge and M. leprae clearance, oxidative damage increased in young L-Lep patients but not in elderly ones. Both elderly T and L-Lep patients present higher 4-HNE in cutaneous lesions than the young, mainly surrounding memory CD8+ T cells. Furthermore, young L-Lep demonstrated greater ability to neutralize ROS compared to elderly L-Lep patients, who presented lower gene expression of antioxidant enzymes, mainly glutathione peroxidase. CONCLUSIONS/SIGNIFICANCE: We conclude that elderly patients present exacerbated oxidative damage both in blood and in skin lesions and that age-related changes can be an important factor in leprosy immunopathogenesis. Ultimately, elderly patients could benefit from co-supplementation of antioxidants concomitant to MDT, to avoid worsening of the disease.

In vitro and in vivo comparative performance studies of gadolinium-loaded zeolites and Gd-DOTA as contrast agents for MRI applications.

Gadolinium-based contrast agents (CAs) were synthesized using faujasite zeolite (NaX) and zeolite beta (BEA) and their performances in vitro and in vivo were compared to the widely used commercial CA, gadoteric acid (Gd-DOTA). Magnetic resonance imaging (MRI) relaxometry studies (considering longitudinal [T1 ] and transverse [T2 ] relaxation times) were performed using Gd-DOTA and the zeolitic materials loaded with Gd3+ . The Gd-loaded NaX, which presented large pores and cavities (7.35 and 11.24 Å, respectively), exhibited relaxivity values of around 52 mM-1 s-1 , while BEA, which presented smaller pore and cavity diameters (5.95 and 6.68 Å, respectively) showed lower relaxivity values of ~4.8 mM-1 s-1 . The effect of the Gd-loaded NaX as MRI CA was tested in vivo in Sprague-Dawley rats, employing a 7 T scanner, with comparison to Gd-DOTA MRI angiography. The relaxivity measurements showed that the Gd-loaded NaX (50 mM-1 s-1 ) provided better image contrast than Gd-DOTA (5.1 mM-1 s-1 ). Clearance studies of the CAs using urine and blood showed that both Gd-loaded NaX and Gd-DOTA were eliminated from the body after 2 days, demonstrating the potential of Gd-loaded NaX for use as an MRI CA.

Methotrexate and prednisolone study in erythema nodosum leprosum (MaPs in ENL) protocol: a double-blind randomised clinical trial.

INTRODUCTION: Erythema nodosum leprosum (ENL) is an immunological complication of leprosy. ENL results in morbidity and disability and if it is not treated can lead to death. The current treatment consists of thalidomide or high doses of oral corticosteroids for prolonged periods. Thalidomide is not available in many leprosy endemic countries. The use of corticosteroids is associated with morbidity and mortality. Identifying treatment regimens that reduce the use of corticosteroids in ENL is essential. Methotrexate (MTX) is used to treat many inflammatory diseases and has been used successfully to treat patients with ENL not controlled by other drugs, including prednisolone and thalidomide. We present the protocol of the 'MTX and prednisolone study in ENL' (MaPs in ENL) a randomised controlled trial (RCT) designed to test the efficacy of MTX in the management of ENL. METHODS AND ANALYSIS: MaPs in ENL is an international multicentre RCT, which will be conducted in leprosy referral centres in Bangladesh, Brazil, Ethiopia, India, Indonesia and Nepal. Patients diagnosed with ENL who consent to participate will be randomly allocated to receive 48 weeks of weekly oral MTX plus 20 weeks of prednisolone or 48 weeks of placebo plus 20 weeks of prednisolone. Participants will be stratified by type of ENL into those with acute ENL and those with chronic and recurrent ENL. The primary objective is to determine whether MTX reduces the requirement for additional prednisolone. Patients' reported outcome measures will be used to assess the efficacy of MTX. Participants will be closely monitored for adverse events. ETHICS AND DISSEMINATION: Results will be submitted for publication in peer-reviewed journals. Ethical approval was obtained from the Observational/Interventions Research Ethics Committee of the London School of Hygiene & Tropical Medicine (15762); The Leprosy Mission International Bangladesh Institutional Research Board (in process); AHRI-ALERT Ethical Review Committee, Ethiopia; Ethics Committee of the Managing Committee of the Bombay Leprosy Project; and The Leprosy Mission Trust India Ethics Committee; the Nepal Health and Research Council and Health Research Ethics Committee Dr. Soetomo, Indonesia. This study is registered at www.clinicaltrials.gov. This is the first RCT of MTX for ENL and will contribute to the evidence for the management of ENL.Trial registration numberNCT 03775460.

Psychometric assessment of the EMIC Stigma Scale for Brazilians affected by leprosy.

BACKGROUND: The Stigma Scale of the Explanatory Model Interview Catalogue (EMIC-SS) is a useful option to investigate leprosy-related stigma, but its psychometric qualities are unknown in Brazil. This study investigated the factor structure, the convergent and known-groups validity, and the reliability of the EMIC-SS for Brazilians affected by leprosy. METHODOLOGY: The Brazilian Portuguese version of the EMIC-SS was validated in 180 persons affected by leprosy at a Reference Center in Rio de Janeiro. Confirmatory factorial analysis (CFA) and Cronbach alpha were used to assess the EMIC-SS internal consistency. The Construct validity was tested using Spearman Correlation, Kruskal-Wallis, and Mann-Whitney tests comparing with the Participation Scale, Rosenberg Self-esteem Scale, Beck Depression Inventory, and a Sociodemographic Questionnaire. Test-retest reliability was evaluated with intra-class correlation (ICC). MAIN FINDINGS: CFA confirmed the one- and two-dimensional models of the scale after retaining 12 of the 15 EMIC-SS items. The 12-item EMIC-SS was consistent (α = 0.78) and reproducible (ICC = 0.751, 95% Confidence Interval = 0.657-0.822, p < 0.0001). A significant correlation was observed between the EMIC-SS and the other scales confirming convergent validity. The EMIC-SS and its factors were able to differentiate several hypothesized groups (age, change of occupation, monthly family income, communicating others about the disease, and perception of difficulty to follow treatment) confirming the scale known-groups validity, both in its one and two-dimensional models. CONCLUSIONS/SIGNIFICANCE: Our study found support for the construct validity and reliability of the EMIC-SS as a measure of stigma experienced by people affected by leprosy in Brazil. However, future studies are necessary in other samples and populations with stigmatizing conditions to determine the optimal factor structure and to strengthen the indications of the validated scale.

Macrophage Polarization in Leprosy-HIV Co-infected Patients.

In HIV-infected individuals, a paradoxical clinical deterioration may occur in preexisting leprosy when highly active antiretroviral therapy (HAART)-associated reversal reaction (RR) develops. Leprosy-HIV co-infected patients during HAART may present a more severe form of the disease (RR/HIV), but the immune mechanisms related to the pathogenesis of leprosy-HIV co-infection remain unknown. Although the adaptive immune responses have been extensively studied in leprosy-HIV co-infected individuals, recent studies have described that innate immune cells may drive the overall immune responses to mycobacterial antigens. Monocytes are critical to the innate immune system and play an important role in several inflammatory conditions associated with chronic infections. In leprosy, different tissue macrophage phenotypes have been associated with the different clinical forms of the disease, but it is not clear how HIV infection modulates the phenotype of innate immune cells (monocytes or macrophages) during leprosy. In the present study, we investigated the phenotype of monocytes and macrophages in leprosy-HIV co-infected individuals, with or without RR. We did not observe differences between the monocyte profiles in the studied groups; however, analysis of gene expression within the skin lesion cells revealed that the RR/HIV group presents a higher expression of macrophage scavenger receptor 1 (MRS1), CD209 molecule (CD209), vascular endothelial growth factor (VEGF), arginase 2 (ARG2), and peroxisome proliferator-activated receptor gamma (PPARG) when compared with the RR group. Our data suggest that different phenotypes of tissue macrophages found in the skin from RR and RR/HIV patients could differentially contribute to the progression of leprosy.

Ultra-sensitive detection of Mycobacterium leprae: DNA extraction and PCR assays.

Leprosy urgently needs a precise and early diagnostic tool. The sensitivity of the direct (bacilli staining, Mycobacterium leprae DNA) and indirect (antibody levels, T cell assays) diagnostics methods vary based on the clinical form. Recently, PCR-based M. leprae DNA detection has been shown to differentially diagnose leprosy from other dermatological conditions. However, accuracy can still be improved, especially for use with less invasive clinical samples. We tested different commercial DNA extraction kits: DNeasy Blood & Tissue, QIAamp DNA Microbiome, Maxwell 16 DNA Purification, PowerSoil DNA Isolation; as well as in-house phenol-chloroform and Trizol/FastPrep methods. Extraction was performed on M. leprae-infected mouse footpads and different clinical samples of leprosy patients (skin biopsies and scrapings, lesion, oral and nasal swabs, body hair, blood on FTA cards, peripheral whole blood). We observed that the Microbiome kit was able to enrich for mycobacterial DNA, most likely due the enzymatic digestion cocktail along with mechanical disruption involved in this method. Consequently, we had a significant increase in sensitivity in skin biopsies from paucibacillary leprosy patients using a duplex qPCR targeting 16S rRNA (M. leprae) and 18S rRNA (mammal) in the StepOnePlus system. Our data showed that the presence of M. leprae DNA was best detected in skin biopsies and skin scrapings, independent of the extraction method or the clinical form. For multibacillary patients, detection of M. leprae DNA in nasal swabs indicates the possibility of having a much less invasive sample that can be used for the purposes of DNA sequencing for relapse analysis and drug resistance monitoring. Overall, DNA extracted with the Microbiome kit presented the best bacilli detection rate for paucibacillary cases, indicating that investments in extraction methods with mechanical and DNA digestion should be made.

Emergence of Mycobacterium leprae Rifampin Resistance Evaluated by Whole-Genome Sequencing after 48 Years of Irregular Treatment.

A case of Mycobacterium leprae rifampin resistance after irregular antileprosy treatments since 1971 is reported. Whole-genome sequencing from four longitudinal samples indicated relapse due to acquired rifampin resistance and not to reinfection with another strain. A putative compensatory mutation in rpoC was also detected. Clinical improvement was achieved using an alternative therapy.