Normative Peak Cardiopulmonary Exercise Test Responses in Canadian Adults Aged ≥40 Years.

BACKGROUND: Up-to-date normative reference sets for cardiopulmonary exercise testing (CPET) are important to aid in the accurate interpretation of CPET in clinical or research settings. RESEARCH QUESTION: This study aimed to (1) develop and externally validate a contemporary reference set for peak CPET responses in Canadian adults identified with population-based sampling; and (2) evaluate previously recommended reference equations for predicting peak CPET responses. STUDY DESIGN AND METHODS: Participants were healthy adults who were ≥40 years old from the Canadian Cohort Obstructive Lung Disease who completed an incremental cycle CPET. Prediction models for peak CPET responses were estimated from readily available participant characteristics (age, sex, height, body mass) with the use of quantile regression. External validation was performed with a second convenience sample of healthy adults. Peak CPET parameters that were measured and predicted in the validation cohort were assessed for equivalence (two one-sided tests of equivalence for paired-samples and level of agreement (Bland-Altman analyses). Two one-sided tests of equivalence for paired samples assessed differences between responses in the derivation cohort using previously recommended reference equations. RESULTS: Normative reference ranges (5th-95th percentiles) for 28 peak CPET parameters and prediction models for 8 peak CPET parameters were based on 173 participants (47% male) who were 64 ± 10 years old. In the validation cohort (n = 84), peak CPET responses that were predicted with the newly generated models were equivalent to the measured values. Peak cardiac parameters predicted by the previously recommended reference equations by Jones and colleagues and Hansen and colleagues were significantly higher. INTERPRETATION: This study provides reference ranges and prediction models for peak cardiac, ventilatory, operating lung volume, gas exchange, and symptom responses to incremental CPET and presents the most comprehensive reference set to date in Canadian adults who were ≥40 years old to be identified with population-based sampling.

Nailfold capillaroscopy with USB dermatoscope: A cross-sectional study in healthy adults.

BACKGROUND: Nailfold capillaroscopy (NFC) is a convenient method for studying capillary morphology in the proximal nailfold (PNF) and is used for the evaluation of connective tissue and other diseases affecting the microvasculature. However, capillary density and morphological patterns in healthy individuals are largely unknown and this compromises the evaluation of the microvasculature in disease states. OBJECTIVE: To describe and quantify the morphological characteristics of nailfold capillaries in healthy adult Indians. METHODS: A USB 2.0 dermatoscope (Dinolite AM413ZT) with polarizing light was used to study nailfold capillary characteristics in 50 consecutive healthy adult individuals. NFC was performed on all 10 fingers. Images were assessed for both quantitative and qualitative features. RESULTS: The mean capillary density in healthy Indian adults was 7.63 ± 1.12 capillary/mm. Tortuosity (22%), meandering capillaries (14%) and microhemorrhages (14%) were frequently seen in these individuals. LIMITATION: The small sample size limited a conclusive determination of statistically significant differences in NFC findings with respect to gender and age. CONCLUSION: NFC with a USB dermatoscope is a useful technique for studying the PNF capillaries. The normal PNF capillary density in healthy Indian adults was 7.63 ± 1.12 capillary/mm. Capillary alterations such as tortuosity, meandering capillaries and microhemorrhages are seen in a significant number of healthy individuals.

Performance of diagnostic tests for pulmonary tuberculosis in indigenous populations in Brazil: the contribution of Rapid Molecular Testing.

OBJECTIVE: To evaluate the accuracy of rapid molecular testing as a diagnostic tool and estimate the incidence of smear-positive pulmonary tuberculosis among the indigenous population. METHODS: This is an epidemiological study based on secondary data. We calculated the incidence of smear-positive pulmonary tuberculosis between January 1st, 2011 and December 31, 2016, and the performance of bacilloscopy and rapid molecular testing in diagnosing pulmonary tuberculosis compared to sputum culture (standard test). RESULTS: We included 4,048 cases of indigenous people with respiratory symptoms who provided sputum samples for analysis. Among them, 3.7%, 6.7%, and 3.7% had positive results for bacilloscopy, sputum culture, and rapid molecular testing, respectively. The mean incidence of pulmonary tuberculosis was 269.3/100 thousand inhabitants. Rapid molecular testing had 93.1% sensitivity and 98.2% specificity, compared to sputum culture. Bacilloscopy showed 55.1% sensitivity and 99.6% specificity. CONCLUSIONS: Rapid molecular testing can be useful in remote areas with limited resources and a high incidence of tuberculosis, such as indigenous villages in rural regions of Brazil. In addition, the main advantages of rapid molecular testing are its easy handling, fast results, and the possibility of detecting rifampicin resistance. Together, these attributes enable the early start of treatment, contributing to reduce the transmission in communities recognized as vulnerable to infection and disease.

Subclinical atherosclerosis and cardiovascular markers in patients with lichen planus: A case-control study.

BACKGROUND: Lichen planus is an idiopathic and chronic inflammatory disease that affects the skin and the mucous membranes, and has been associated with an increased risk for cardiovascular diseases. Hyperhomocysteinemia has been regarded as a risk factor for atherosclerosis and cardiovascular diseases. Increased plasma fibrinogen levels are also associated with increased risk of myocardial infarction. OBJECTIVE: The main aim of this study is the evaluation of common carotid artery mean intima media wall thickness, serum fibrinogen and homocysteine levels in patients with lichen planus. METHODS: Forty-three patients with lichen planus and 43 age, gender and body mass index (BMI) matched healthy controls (from general population without the disease) were included in this study. RESULTS: Compared to the healthy controls, patients had statistically significant greater mean intima media wall thickness of the common carotid artery. Moreover, a positive correlation was observed between lichen planus and increased serum homocysteine and c-reactive protein levels. LIMITATIONS: The main limitation of this study is the small sample size due to the time limitation and financial constraints. CONCLUSION: Early diagnosis of atherosclerosis in patients with lichen planus might afford better prophylaxis, including weight control and/or lipid profile monitoring. Measurement of the mean intima media wall thickness of the common carotid artery by duplex high-resolution B-mode ultrasound scanning could be beneficial as a valuable method for early diagnosis of atherosclerosis in lichen planus.

Linking of psoriasis with osteopenia and osteoporosis: A cross-sectional study.

BACKGROUND/PURPOSE: Psoriasis is a multisystem disease which has been related to vitamin-D deficiency through chronic inflammation. This psoriasis-related inflammatory state and vitamin-D deficiency may induce bone mineral density loss. The purpose of this study is to assess the relationship of psoriasis with bone mineral density, by comparing psoriatic patients with healthy controls and patients with osteopenia/osteoporosis. METHODS: A total of 185 subjects were studied; 58 psoriatic patients who had not been under systemic or biological treatment were included. Age, gender, body mass index, phosphocalcic metabolic parameters and hip and lumbar (L4) bone mineral density data were collected. These variables were compared with those collected in 61 healthy controls and 67 patients with osteopenia/osteoporosis. RESULTS: Psoriatic patients showed worse hip and lumbar spine bone mineral density levels than healthy controls (P = 0.001) and better levels than osteoporotic patients (P < 0.001). Multivariate analysis demonstrated a negative association of age and a positive association of body mass index in hip bone mineral density in psoriatic patients. LIMITATIONS: The main limitations are those of cross-sectional studies, such as a lack of follow up period, and a male predominance in the psoriatic group, which is corrected employing a multivariate analysis with an adjusted model for confounding factors. CONCLUSIONS: Bone mineral density levels in psoriatic patients are situated halfway between healthy controls and patients with osteopenia/osteoporosis. In addition, the higher body mass index in patients with psoriasis appears to confer a protective effect against further development of lower bone mineral density.

Ultrasound assessment of enthesis thickness in psoriasis and psoriatic arthritis: A cross-sectional study.

BACKGROUND: The inflammatory involvement of the enthesis in the course of psoriasis is accompanied by structural abnormalities detectable by ultrasound. The most common of these abnormalities is the thickening of the tendon at the insertion site. AIMS: The aim of the present study was to compare the thickness of entheses of patients with psoriatic arthritis, only skin psoriasis, and healthy controls. METHODS: A cross-sectional study was conducted in a cohort of patients affected with either only skin psoriasis or psoriatic arthritis as well as in a control group. Eight entheses sites were scanned by ultrasound bilaterally. The following entheseal characteristics were collected and recorded in a predefined database: entheseal thickness, bone erosions, enthesis calcifications (enthesophytes), presence of blood flow, and presence of bursitis. All the detected entheseal changes were scored, and the data was statistically analyzed. RESULTS: The major differences in enthesis thickness between only skin psoriasis and psoriatic arthritis patients were found at the following sites: (i) olecranon tuberosity, (ii) superior pole of the patella, and (iii) medial epicondyle of femur. The thickness of the medial collateral ligament at the site of the femoral origin was increased in psoriatic arthritis, but not in both only skin psoriasis and healthy controls. The score obtained by adding the thickness of all the 8 examined entheses for each patient showed significant differences among the three groups (psoriatic arthritis: 81.3; only skin psoriasis 74.4; Controls: 67.6; P < 0.0001). Interestingly, we found that in psoriatic arthritis patients, the highest enthesis thickening was seen in entheses affected by bone erosions. LIMITATIONS: The small sample of patients studied is a limiting factor in this study. CONCLUSIONS: Our data demonstrated that the ultrasound measurement of the enthesis thickness enables a distinction between patients with psoriatic arthritis from those with only skin psoriasis. It is a useful method to improve diagnostic accuracy, especially in patients without clear clinical signs of enthesitis.

Performance of diagnostic tests for pulmonary tuberculosis in indigenous populations in Brazil: the contribution of Rapid Molecular Testing / Desempenho de testes para o diagnóstico de tuberculose pulmonar em populações indígenas no Brasil: a contribuição do Teste Rápido Molecular

ABSTRACT Objective: To evaluate the accuracy of rapid molecular testing as a diagnostic tool and estimate the incidence of smear-positive pulmonary tuberculosis among the indigenous population. Methods: This is an epidemiological study based on secondary data. We calculated the incidence of smear-positive pulmonary tuberculosis between January 1st, 2011 and December 31, 2016, and the performance of bacilloscopy and rapid molecular testing in diagnosing pulmonary tuberculosis compared to sputum culture (standard test). Results: We included 4,048 cases of indigenous people with respiratory symptoms who provided sputum samples for analysis. Among them, 3.7%, 6.7%, and 3.7% had positive results for bacilloscopy, sputum culture, and rapid molecular testing, respectively. The mean incidence of pulmonary tuberculosis was 269.3/100 thousand inhabitants. Rapid molecular testing had 93.1% sensitivity and 98.2% specificity, compared to sputum culture. Bacilloscopy showed 55.1% sensitivity and 99.6% specificity. Conclusions: Rapid molecular testing can be useful in remote areas with limited resources and a high incidence of tuberculosis, such as indigenous villages in rural regions of Brazil. In addition, the main advantages of rapid molecular testing are its easy handling, fast results, and the possibility of detecting rifampicin resistance. Together, these attributes enable the early start of treatment, contributing to reduce the transmission in communities recognized as vulnerable to infection and disease.

RESUMO Objetivo: Avaliar a acurácia do teste rápido molecular como ferramenta diagnóstica e estimar a incidência de casos pulmonares positivos entre a população indígena. Métodos: Estudo epidemiológico baseado em dados secundários. Foi calculada a incidência de casos de tuberculose pulmonar positiva entre 1° de janeiro de 2011 e 31 de dezembro de 2016, e o desempenho da baciloscopia e do teste rápido molecular no diagnóstico de tuberculose pulmonar, em comparação à cultura de escarro (teste padrão). Resultados: Foram incluídos 4.048 casos de indígenas considerados sintomáticos respiratórios, que forneceram amostras de escarro para análise. Destes, 3,7%, 6,7% e 3,7% apresentaram resultados positivos para baciloscopia, cultura e teste rápido molecular, respectivamente. A incidência média de tuberculose pulmonar foi de 269,3/100 mil habitantes. A sensibilidade do teste rápido molecular, em relação à cultura, foi 93,1% e a especificidade foi 98,2%. A baciloscopia apresentou sensibilidade 55,1% e especificidade 99,6%. Conclusões: O teste rápido molecular pode ser útil em áreas remotas, com recursos limitados e incidência de tuberculose elevada, como as aldeias indígenas nas áreas rurais do país. Ademais, o teste rápido molecular apresenta como principais vantagens o fácil manuseio, os resultados rápidos e a possibilidade de identificar a resistência à rifampicina. Em conjunto, esses atributos facilitam o início do tratamento precoce, contribuindo para reduzir a transmissão em comunidades reconhecidamente vulneráveis à infecção e à doença.

[Leprosy trends following implementation of an intervention project in a state capital in the North of Brazil, 2002-2016]. / Tendências da hanseníase após implementação de um projeto de intervenção em uma capital da Região Norte do Brasil, 2002-2016.

The project Palmas Free of Leprosy was implemented to improve indicators and deal with the disease, since the capital of Tocantins State is the most hyperendemic state capital in Brazil. This study measures the impact of the project's intervention through trend analysis of the priority indicators in Palmas, from 2002 to 2016. The study was based on an analysis of data from the Brazilian Information System for Notifiable Diseases (SINAN) and reports of applied training courses with problem-solving methodology. The indicators for new leprosy cases in Palmas residents were investigated, and the trends were identified by joinpoint regression analysis to assess the results. In the year the intervention project was implemented (2016), the detection rate for new cases in the overall population was 236.3/100,000 inhabitants, and this indicator showed a significant decrease of -7.5% from 2002 to 2014. From 2014 to 2016, there was a significant increase of 104.6% in overall detection. The detection rate in individuals under 15 years of age also showed a reduction of -4.6%, but in the years 2014, 2015, and 2016 there was an increase of 111.1%, together with detection rates for grades 0, 1, and 2, with 59.3%, 225.2%, and 121.7%, respectively. The proportion of cases detected by contact assessment showed a significant increase of 201.1% from 2014 to 2016. The data proved the effectiveness and potentiality of the project's intervention strategy for the diagnosis and control of leprosy in Palmas. The study provided evidence that timely diagnosis by primary care services results in indicators that reflect the real incidence of cases.

O projeto Palmas Livre da Hanseníase foi implementado para o incremento dos indicadores e o enfrentamento da doença, visto que a capital do Tocantins é a mais hiperendêmica do país. Este estudo mede o impacto da intervenção do projeto por meio da análise da tendência de indicadores prioritários em Palmas, 2002-2016. Baseia-se em análise de dados advindos do Sistema de Informação de Agravos de Notificação (SINAN) e de relatórios de capacitações aplicadas com metodologia de problematização. Os indicadores dos casos novos de hanseníase residentes em Palmas foram investigados, e suas tendências foram identificadas por análise de regressão joinpoint para avaliação dos resultados. No ano de implementação do projeto de intervenção (2016), o coeficiente de detecção de casos novos na população geral foi de 236,3/100 mil habitantes, e esse indicador apresentava decréscimo significativo de -7,5% no período de 2002 a 2014. Nos anos entre 2014 e 2016, houve aumento significativo de 104,6% para a detecção geral. O coeficiente de detecção em menores de 15 anos também apresentava queda de -4,6%, mas nos anos de 2014, 2015 e 2016, houve aumento de 111,1%, juntamente com os coeficientes de detecção de casos com grau 0, 1 e 2, com 59,3%, 225,2% e 121,7%, respectivamente. A proporção de casos detectados por avaliação de contatos teve acréscimo significativo de 201,1% no período de 2014 a 2016. Os dados comprovaram a efetividade e potencialidade da estratégia de intervenção do projeto para as ações de diagnóstico e controle da hanseníase em Palmas. Trouxe evidências de que a agilidade diagnóstica dos serviços de atenção primária resulta em indicadores que refletem a incidência real de casos.

El proyecto Palmas Libre de Hanseniasis se implementó para el incremento de indicadores y combate a la enfermedad, dado que la capital de Tocantins es la más hiperendémica de Brasil. Este estudio mide el impacto de la intervención del proyecto, mediante el análisis de la tendencia de indicadores prioritarios en Palmas, 2002-2016. Se basa en un análisis de datos procedentes del Sistema de Información sobre Enfermedades de Notificación Obligatoria (SINAN por sus siglas en portugués) y de informes de capacitaciones, aplicadas con metodología de problematización. Se investigaron los indicadores de casos nuevos de hanseniasis, en residentes de Palmas, y se identificaron sus tendencias mediante análisis de regresión joinpoint para la evaluación de los resultados. En el año de implementación del proyecto de intervención (2016), el coeficiente de detección de casos nuevos en la población general fue de 236,3/100 mil habitantes, y ese indicador presentaba una disminución significativa de un -7,5%, durante el período de 2002 a 2014. Entre los años de 2014 a 2016, hubo un aumento significativo de un 104,6% en la detección general. El coeficiente de detección en menores de 15 años también presentaba una bajada de -4,6%, pero durante los años de 2014, 2015 y 2016, hubo un aumento de 111,1%, junto a los coeficientes de detección de casos con grado 0, 1 y 2, con un 59,3%, 225,2% y 121,7%, respectivamente. La proporción de casos detectados por la evaluación de contactos tuvo un aumento significativo de un 201,1%, durante el período de 2014 a 2016. Los datos comprobaron la efectividad y potencialidad de la estrategia de intervención del proyecto para las acciones de diagnóstico y control de la hanseniasis en Palmas. Hubo evidencias de que la agilidad diagnóstica de los servicios de atención primaria se traduce en indicadores que reflejan la incidencia real de casos.

Tendências da hanseníase após implementação de um projeto de intervenção em uma capital da Região Norte do Brasil, 2002-2016 / Leprosy trends following implementation of an intervention project in a state capital in the North of Brazil, 2002-2016 / Tendencias de la hanseniasis tras la implementación de un proyecto de intervención en una capital de la región norte de Brasil, 2002-2016

Resumo: O projeto Palmas Livre da Hanseníase foi implementado para o incremento dos indicadores e o enfrentamento da doença, visto que a capital do Tocantins é a mais hiperendêmica do país. Este estudo mede o impacto da intervenção do projeto por meio da análise da tendência de indicadores prioritários em Palmas, 2002-2016. Baseia-se em análise de dados advindos do Sistema de Informação de Agravos de Notificação (SINAN) e de relatórios de capacitações aplicadas com metodologia de problematização. Os indicadores dos casos novos de hanseníase residentes em Palmas foram investigados, e suas tendências foram identificadas por análise de regressão joinpoint para avaliação dos resultados. No ano de implementação do projeto de intervenção (2016), o coeficiente de detecção de casos novos na população geral foi de 236,3/100 mil habitantes, e esse indicador apresentava decréscimo significativo de -7,5% no período de 2002 a 2014. Nos anos entre 2014 e 2016, houve aumento significativo de 104,6% para a detecção geral. O coeficiente de detecção em menores de 15 anos também apresentava queda de -4,6%, mas nos anos de 2014, 2015 e 2016, houve aumento de 111,1%, juntamente com os coeficientes de detecção de casos com grau 0, 1 e 2, com 59,3%, 225,2% e 121,7%, respectivamente. A proporção de casos detectados por avaliação de contatos teve acréscimo significativo de 201,1% no período de 2014 a 2016. Os dados comprovaram a efetividade e potencialidade da estratégia de intervenção do projeto para as ações de diagnóstico e controle da hanseníase em Palmas. Trouxe evidências de que a agilidade diagnóstica dos serviços de atenção primária resulta em indicadores que refletem a incidência real de casos.

Abstract: The project Palmas Free of Leprosy was implemented to improve indicators and deal with the disease, since the capital of Tocantins State is the most hyperendemic state capital in Brazil. This study measures the impact of the project's intervention through trend analysis of the priority indicators in Palmas, from 2002 to 2016. The study was based on an analysis of data from the Brazilian Information System for Notifiable Diseases (SINAN) and reports of applied training courses with problem-solving methodology. The indicators for new leprosy cases in Palmas residents were investigated, and the trends were identified by joinpoint regression analysis to assess the results. In the year the intervention project was implemented (2016), the detection rate for new cases in the overall population was 236.3/100,000 inhabitants, and this indicator showed a significant decrease of -7.5% from 2002 to 2014. From 2014 to 2016, there was a significant increase of 104.6% in overall detection. The detection rate in individuals under 15 years of age also showed a reduction of -4.6%, but in the years 2014, 2015, and 2016 there was an increase of 111.1%, together with detection rates for grades 0, 1, and 2, with 59.3%, 225.2%, and 121.7%, respectively. The proportion of cases detected by contact assessment showed a significant increase of 201.1% from 2014 to 2016. The data proved the effectiveness and potentiality of the project's intervention strategy for the diagnosis and control of leprosy in Palmas. The study provided evidence that timely diagnosis by primary care services results in indicators that reflect the real incidence of cases.

Resumen: El proyecto Palmas Libre de Hanseniasis se implementó para el incremento de indicadores y combate a la enfermedad, dado que la capital de Tocantins es la más hiperendémica de Brasil. Este estudio mide el impacto de la intervención del proyecto, mediante el análisis de la tendencia de indicadores prioritarios en Palmas, 2002-2016. Se basa en un análisis de datos procedentes del Sistema de Información sobre Enfermedades de Notificación Obligatoria (SINAN por sus siglas en portugués) y de informes de capacitaciones, aplicadas con metodología de problematización. Se investigaron los indicadores de casos nuevos de hanseniasis, en residentes de Palmas, y se identificaron sus tendencias mediante análisis de regresión joinpoint para la evaluación de los resultados. En el año de implementación del proyecto de intervención (2016), el coeficiente de detección de casos nuevos en la población general fue de 236,3/100 mil habitantes, y ese indicador presentaba una disminución significativa de un -7,5%, durante el período de 2002 a 2014. Entre los años de 2014 a 2016, hubo un aumento significativo de un 104,6% en la detección general. El coeficiente de detección en menores de 15 años también presentaba una bajada de -4,6%, pero durante los años de 2014, 2015 y 2016, hubo un aumento de 111,1%, junto a los coeficientes de detección de casos con grado 0, 1 y 2, con un 59,3%, 225,2% y 121,7%, respectivamente. La proporción de casos detectados por la evaluación de contactos tuvo un aumento significativo de un 201,1%, durante el período de 2014 a 2016. Los datos comprobaron la efectividad y potencialidad de la estrategia de intervención del proyecto para las acciones de diagnóstico y control de la hanseniasis en Palmas. Hubo evidencias de que la agilidad diagnóstica de los servicios de atención primaria se traduce en indicadores que reflejan la incidencia real de casos.

Social determinants of leprosy in a hyperendemic State in North Brazil.

OBJECTIVE: To identify the socioeconomic, demographic, operational, and health service-related factors associated with the occurrence of leprosy in a hyperendemic State in North Brazil. METHODS: This is an ecological study based on secondary data from the Sistema de Informações de Agravos de Notificação in municipalities of the State of Tocantins from 2001 to 2012. Units of analysis were the 139 municipalities of the State. Negative binomial log linear regression models were used to estimate incidence rate ratios. RESULTS: In bivariate analysis, the incidence rate ratios were significantly higher for municipalities with higher income ratio of the poorest 20.0% (1.47; 95%CI 1.19-1.81) and better Municipal Human Development Index (1.53; 95%CI 1.14-2.06). In multivariate analysis, the incidence rate ratios were significantly higher in municipalities with higher proportion of immigrants (1.31; 95%CI 1.11-1.55) and higher proportion of households with waste collection (1.37; 95%CI 1.11-1.69). There was a significant reduction in the incidence rate ratio with increased coverage of the Bolsa Família Program (0.98; 95%CI 0.96-0.99). CONCLUSIONS: Control programs need to focus on activities in municipalities of greater social vulnerability with intersectoral investment for the improvement of the living conditions of the population. OBJETIVO: Identificar fatores socioeconômicos, demográficos, operacionais e de serviços de saúde associados à ocorrência da hanseníase em um estado hiperendêmico do norte do Brasil. MÉTODOS: Estudo ecológico com dados secundários do Sistema de Informações de Agravos de Notificação em municípios do estado do Tocantins de 2001 a 2012. As unidades de análise foram os 139 municípios do estado. Modelos de regressão log linear binomial negativa foram utilizados para estimar as razões de taxas de incidência. RESULTADOS: Na análise bivariada, a razão de taxa de incidência foi significativamente maior para os municípios com maior razão de renda dos 20,0% mais pobres (1,47; IC95% 1,19-1,81) e melhor Índice de Desenvolvimento Humano Municipal (1,53; IC95% 1,14-2,06). Na múltipla, a razão de taxa de incidência foi significativamente superior em municípios com maior concentração de imigrantes (1,31; IC95% 1,11-1,55) e proporção de domicílios com coleta de lixo (1,37; IC95% 1,11-1,69). Houve redução significativa da razão de taxa de incidência com o aumento da cobertura do programa bolsa família (0,98; IC95% 0,96-0,99). CONCLUSÕES: Os programas de controle precisam focar as atividades em municípios de maior vulnerabilidade social com investimentos intersetoriais para a melhoria das condições de vida da população.

qPCR detection of Mycobacterium leprae in biopsies and slit skin smear of different leprosy clinical forms

Abstract Leprosy, whose etiological agent is Mycobacterium leprae, is a chronic infectious disease that mainly affects the skin and peripheral nervous system. The diagnosis of leprosy is based on clinical evaluation, whereas histopathological analysis and bacilloscopy are complementary diagnostic tools. Quantitative PCR (qPCR), a current useful tool for diagnosis of infectious diseases, has been used to detect several pathogens including Mycobacterium leprae. The validation of this technique in a robust set of samples comprising the different clinical forms of leprosy is still necessary. Thus, in this study samples from 126 skin biopsies (collected from patients on all clinical forms and reactional states of leprosy) and 25 slit skin smear of leprosy patients were comparatively analyzed by qPCR (performed with primers for the RLEP region of M. leprae DNA) and routine bacilloscopy performed in histological sections or in slit skin smear. Considering clinical diagnostic as the gold standard, 84.9% of the leprosy patients were qPCR positive in skin biopsies, resulting in 84.92% sensitivity, with 84.92 and 61.22% positive (PPV) and negative (NPV) predictive values, respectively. Concerning bacilloscopy of histological sections (BI/H), the sensitivity was 80.15% and the PPV and NPV were 80.15 and 44.44%, respectively. The concordance between qPCR and BI/H was 87.30%. Regarding the slit skin smear, 84% of the samples tested positive in the qPCR. Additionally, qPCR showed 100% specificity, since all samples from different mycobacteria, from healthy individuals, and from other granulomatous diseases presented negative results. In conclusion, the qPCR technique for detection of M. leprae using RLEP primers proved to be specific and sensitive, and qPCR can be used as a complementary test to diagnose leprosy irrespective of the clinical form of disease.

qPCR detection of Mycobacterium leprae in biopsies and slit skin smear of different leprosy clinical forms.

Leprosy, whose etiological agent is Mycobacterium leprae, is a chronic infectious disease that mainly affects the skin and peripheral nervous system. The diagnosis of leprosy is based on clinical evaluation, whereas histopathological analysis and bacilloscopy are complementary diagnostic tools. Quantitative PCR (qPCR), a current useful tool for diagnosis of infectious diseases, has been used to detect several pathogens including Mycobacterium leprae. The validation of this technique in a robust set of samples comprising the different clinical forms of leprosy is still necessary. Thus, in this study samples from 126 skin biopsies (collected from patients on all clinical forms and reactional states of leprosy) and 25 slit skin smear of leprosy patients were comparatively analyzed by qPCR (performed with primers for the RLEP region of M. leprae DNA) and routine bacilloscopy performed in histological sections or in slit skin smear. Considering clinical diagnostic as the gold standard, 84.9% of the leprosy patients were qPCR positive in skin biopsies, resulting in 84.92% sensitivity, with 84.92 and 61.22% positive (PPV) and negative (NPV) predictive values, respectively. Concerning bacilloscopy of histological sections (BI/H), the sensitivity was 80.15% and the PPV and NPV were 80.15 and 44.44%, respectively. The concordance between qPCR and BI/H was 87.30%. Regarding the slit skin smear, 84% of the samples tested positive in the qPCR. Additionally, qPCR showed 100% specificity, since all samples from different mycobacteria, from healthy individuals, and from other granulomatous diseases presented negative results. In conclusion, the qPCR technique for detection of M. leprae using RLEP primers proved to be specific and sensitive, and qPCR can be used as a complementary test to diagnose leprosy irrespective of the clinical form of disease.

qPCR detection of Mycobacterium leprae in biopsies and slit skin smear of different leprosy clinical forms

Leprosy, whose etiological agent is Mycobacterium leprae, is a chronic infectious disease that mainly affects the skin and peripheral nervous system. The diagnosis of leprosy is based on clinical evaluation, whereas histopathological analysis and bacilloscopy are complementary diagnostic tools. Quantitative PCR (qPCR), a current useful tool for diagnosis of infectious diseases, has been used to detect several pathogens including Mycobacterium leprae. The validation of this technique in a robust set of samples comprising the different clinical forms of leprosy is still necessary. Thus, in this study samples from 126 skin biopsies (collected from patients on all clinical forms and reactional states of leprosy) and 25 slit skin smear of leprosy patients were comparatively analyzed by qPCR (performed with primers for the RLEP region of M. leprae DNA) and routine bacilloscopy performed in histological sections or in slit skin smear. Considering clinical diagnostic as the gold standard, 84.9% of the leprosy patients were qPCR positive in skin biopsies, resulting in 84.92% sensitivity, with 84.92 and 61.22% positive (PPV) and negative (NPV) predictive values, respectively. Concerning bacilloscopy of histological sections (BI/H), the sensitivity was 80.15% and the PPV and NPV were 80.15 and 44.44%, respectively. The concordance between qPCR and BI/H was 87.30%. Regarding the slit skin smear, 84% of the samples tested positive in the qPCR. Additionally, qPCR showed 100% specificity, since all samples from different mycobacteria, from healthy individuals, and from other granulomatous diseases presented negative results. In conclusion, the qPCR technique for detection of M. leprae using RLEP primers proved to be specific and sensitive, and qPCR can be used as a complementary test to diagnose leprosy irrespective of the clinical form of disease.

Normal threshold values for a monofilament sensory test in sural and radial cutaneous nerves in Indian and Nepali volunteers.

The monofilament test (MFT) is a reliable method to assess sensory nerve function in leprosy and other neuropathies. Assessment of the radial cutaneous and sural nerves, in addition to nerves usually tested, can help improve diagnosis and monitoring of nerve function impairment (NFI). To enable the detection of impairments in leprosy patients, it is essential to know the monofilament threshold of these two nerves in normal subjects. The radial cutaneous, sural, ulnar, median and posterior tibial nerves of 245 volunteers were tested. All nerves were tested at three sites on both left and right sides. Normal monofilament thresholds were calculated per test-site and per nerve. We assessed 490 radial cutaneous and 482 sural nerves. The normal monofilament was 2 g (Filament Index Number (FIN) 4.31) for the radial cutaneous and 4 g (FIN 4.56) for the sural nerve, although heavy manual laborers demonstrated a threshold of 10 g (FIN 5.07) for the sural nerve. For median and ulnar nerves, the 200 mg (FIN 3.61) filament was confirmed as normal while the 4 g (FIN 4.56) filament was normal for the posterior tibial. Age and occupation have an effect on the mean touch sensitivity but do not affect the normal threshold for the radial cutaneous and sural nerves. The normal thresholds for the radial cutaneous and sural nerves are determined as the 2 g (FIN 4.31) and the 4 g (FIN 4.56) filaments, respectively. The addition of the radial cutaneous and sural nerve to sensory nerve assessment may improve the diagnosis of patients with impaired sensory nerve function.

Assessing clinical significance of treatment outcomes using the DASS-21.

Standard clinical significance classifications are based on movement between the "dysfunctional" and "functional" distributions; however, this dichotomy ignores heterogeneity within the "dysfunctional" population. Based on the methodology described by Tingey, Lambert, Burlingame, and Hansen (1996), the present study sought to present a 3-distribution clinical significance model for the 21-item version of the Depression Anxiety Stress Scales (DASS-21; P. F. Lovibond & Lovibond, 1995) using data from a normative sample (n = 2,914), an outpatient sample (n = 1,000), and an inpatient sample (n = 3,964). DASS-21 scores were collected at pre- and post-treatment for both clinical samples, and patients were classified into 1 of 5 categories based on whether they had made a reliable change and whether they had moved into a different functional range. Evidence supported the validity of the 3-distribution model for the DASS-21, since inpatients who were classified as making a clinically significant change showed lower symptom severity, higher perceived quality of life, and higher clinician-rated functioning than those who did not make a clinically significant change. Importantly, results suggest that the new category of recovering is an intermediate point between recovered and making no clinically significant change. Inpatients and outpatients have different treatment goals and therefore use of the concept of clinical significance needs to acknowledge differences in what constitutes a meaningful change.

Enzyme-linked immunospot assay response to recombinant CFP-10/ESAT-6 fusion protein among patients with spinal tuberculosis: implications for diagnosis and monitoring of surgical therapy.

OBJECTIVE: This study aimed to assess the performance of a laboratory-developed recombinant CFP-10/ESAT-6 fusion protein (rCFP-10/ESAT-6)-based enzyme-linked immunospot (ELISPOT) assay for the diagnosis of spinal tuberculosis (TB) in China, and to evaluate the value of the ELISPOT assay for monitoring the efficacy of surgical treatment. METHODS: In the first part of the study, a total of 78 participants were consecutively recruited for ELISPOT using rCFP-10/ESAT-6 as a stimulus. The cutoff value for ELISPOT positivity was based on the results of receiver operating characteristic curve analysis. In the second part, this approach was evaluated in a prospective study including 102 patients with suspected spinal TB. Data on clinical characteristics of the patients and conventional laboratory results were collected, and blood samples were obtained for ELISPOT using rCFP-10/ESAT-6 as a stimulus. RESULTS: Among the 102 patients with suspected spinal TB, 11 were excluded from the study. Twenty-three patients (25.2%) had culture-confirmed TB and 29 (31.9%) patients had probable TB. Among the spinal TB patients, the ELISPOT had a sensitivity of 82.7%, compared to a sensitivity of 61.5% for the purified protein derivative (PPD) skin test. The specificity was 87.2% for ELISPOT and 46.2% for the PPD skin test among 39 subjects with non-TB disease. The number of spot-forming cells and/or the positive rate of the ELISPOT assay were associated with aging, emaciation, and paravertebral abscess. The number of subjects with responses to rCFP-10/ESAT-6 slightly decreased after surgical treatment in spinal TB patients. CONCLUSIONS: A laboratory-developed rCFP-10/ESAT-6 ELISPOT assay is a useful adjunct to current tests for the diagnosis of spinal TB.

Thermal record of the test tubes method used for small fibers assessment / Registro térmico do método dos tubos de ensaio aplicado na avaliação de fibras finas

In Brazil, the test that uses test tubes filled with cold water (25ºC) and tubes filled with water heated to a temperature of 45ºC is recommended by the Ministry of Health as a way of evaluate thermal sensitivity on the injured skin of leprosy patients. The purpose of this work was to quantify the thermal stimulation applied to the skin, as well as the temperature variation of the heated water and of the tube's outer surface during stimulation sessions. The experiment had the participation of 14 healthy volunteers (31.2±11.4 years-old), ten of which were male (33.1±13.5 years-old) and four were female (26.5±4.7 years-old). Three consecutive stimulation sessions were carried out, each of them with four stimuli. The maximum skin temperature at the end of the stimuli was measured at 35.8±0.6ºC. Such temperature values may be useful in the assessment of the loss of small fibers, which are responsible for the sensation of warmth.

No Brasil, o teste que utiliza tubos de ensaio preenchidos com água aquecida (45ºC) e resfriada (25ºC) é preconizado pelo Ministério da Saúde como forma de avaliar a sensibilidade térmica nas lesões de pele de pacientes com hanseníase. O objetivo deste trabalho foi quantificar o estímulo térmico na pele e a variação das temperaturas da água aquecida e da superfície externa do tubo, durante as sessões de estimulação. O experimento contou com 14 voluntários saudáveis (31,2±11,4 anos), sendo dez do gênero masculino (33,1±13,5 anos) e quatro do gênero feminino (26,5±4,7 anos). Realizaram-se três sessões seguidas de estimulação com quatro estímulos em cada sessão. A temperatura registrada na pele, ao final dos estímulos, apresentou diferenças entre as sessões, atingindo o máximo de 35,8±0,6ºC. Estes valores de temperatura podem ser úteis na avaliação da perda de fibras finas responsáveis pela sensação de aquecimento.

Laparoscopic sigmoid resection for diverticular disease has no advantages over open approach: midterm results of a randomized controlled trial.

PURPOSE: Elective laparoscopic sigmoid resection (LSR) for symptomatic diverticular disease is supposed to have significant short-term advantages compared to open surgery (open sigmoid resection (OSR)). This opinion is rather based on inferences from trials on colonic resections for malignant diseases or minor laparoscopic surgery. This randomized controlled trial was conducted to compare quality of life as well as morbidity and clinical outcome after LSR vs. OSR following a midterm follow-up period. METHODS: Patients presenting with a symptomatic sigmoid diverticular disease stage II/III (Stock/Hansen) were randomly allocated to LSR or OSR in a prospective multicenter trial. Endpoints included the quality of life assessed with a standardized questionnaire, postoperative mortality, and complications within the follow-up of 12 months after operation. RESULTS: A total of 143 patients randomized between 2005 and 2008 in 12 centers could be analyzed. The recruitment was aborted for nonachievement of the planned sample size. Seventy-five patients were allocated to LSR, and 68 received OSR. Nine operations were converted to OSR (9%) and analyzed as intention to treat. Groups were comparable for age, gender, body mass index, comorbidity, and indication for surgery. Operation time was longer for LSR (p < 0.001). Quality of life did not differ between LSR and OSR, either during the early postoperative course or after 12 months (p = 0.172). Also, mortality and morbidity, including subgroups of major and minor morbidity, were compared. CONCLUSION: LSR was not superior to OSR regarding postoperative quality of life and incidence of complications in this trial.

Lateral flow assay for simultaneous detection of cellular- and humoral immune responses.

OBJECTIVE: The development of a cytokine detection assay suitable for detection of multiple biomarkers for improved diagnosis of mycobacterial diseases. DESIGN AND METHODS: A lateral flow (LF) assay to detect IL-10 was developed utilizing the up-converting phosphor (UCP) reporter-technology. The assay was evaluated using blood samples of leprosy patients. Multiplex applications were explored targeting: 1) IL-10 and IFN-γ in assay buffer; 2) IL-10 and anti-phenolic glycolipid (PGL-I) antibodies in serum from leprosy patients. RESULTS: Detection of IL-10 below the targeted level of 100pg/mL in serum was shown. Comparison with ELISA showed a quantitative correlation with R(2) value of 0.92. Multiplexing of cytokines and simultaneous detection of cytokine and antibody was demonstrated. CONCLUSIONS: The UCP-LF IL-10 assay is a user-friendly, rapid alternative for IL-10 ELISAs, suitable for multiplex detection of different cytokines and can be merged with antibody-detection assays to simultaneously detect cellular- and humoral immunity.