Body mass index and sex differences for mortality in hospitalized COVID-19 patients: a path analysis using a brazilian national database.

Previous studies have shown that associations between obesity and other comorbidities favor worse outcomes in COVID-19. However, it is not clear how these factors interrelate and whether effects on men and women differ. We conducted an observational, cross-sectional study using a national COVID-19 inpatient database. We studied differences in direct and indirect effects of obesity and comorbidities according to sex and body mass index (BMI) categories in hospitalized COVID-19 patients in Brazil using path analysis models and logistic regression. For men, path analysis showed a direct association between BMI and death and a negative correlation of death and chronic cardiovascular disease (CCD). For women, the association of BMI and death was indirect, mediated by admission to the ICU and comorbidities and association with CCD was non-significant. In the logistic regression analyses, there was a positive association between death and BMI, age, diabetes mellitus, kidney and lung diseases and ICU admission. We highlight the need to consider the distinct impact of obesity and sex on COVID-19, of monitoring of BMI and of the design for specific male-targeted approaches to manage obesity.

Características de adultos com obesidade grave em tratamento ambulatorial no Rio de Janeiro e fatores associados à perda de peso / Characteristics of adults with severe obesity in clinical treatment in Rio de Janeiro and factors associated with weight loss / Características de adultos con obesidad severa en tratamiento clínico en Rio de Janeiro y factores asociados a la pérdida de peso

Resumo Introdução O tratamento da obesidade grave é pouco estudado no Sistema Único de Saúde (SUS). Objetivo: Descrever clientela, atendimento e fatores associados à perda de peso em Centros de Referência em Obesidade (CRO), na cidade do Rio de Janeiro. Método Coorte retrospectiva baseada em registros de prontuários de 317 indivíduos com obesidade grave atendidos em três CRO-RJ entre 2011 e 2016. Foram descritas frequências e estimados riscos relativos com IC 95% para perda de ≥ 5% do peso inicial aos 6 e 12 meses de tratamento. Resultados Predominaram mulheres (76,3%), negros (69,5%), com média de 44,6 anos (DP 11,9), tratamento prévio para obesidade (62,1%), história familiar de obesidade (42,6%) e 2 ou mais comorbidades (52%). A mediana do IMC inicial foi de 51,5 kg/m2, e a do tempo de tratamento, 10 meses. Somente 14,8% perderam ≥ 5% do peso inicial após 12 meses de tratamento, sendo o risco relativo de perda de peso 78% maior entre indivíduos brancos. Predominaram tratamento dietético e mudanças de hábitos de vida, com baixo uso de medicamentos antiobesidade (14%) e cirurgia bariátrica (3%, sendo 1% no SUS). Conclusão Os resultados do tratamento sugerem necessidade de readequar práticas terapêuticas às indicadas para indivíduos com superobesidade, inclusive maior acesso à cirurgia bariátrica.

Abstract Background There are few studies on severe obesity in the Brazilian Unified Health System (SUS). Objective To describe patients, treatment approaches and factors associated with weight loss at the Obesity Reference Centers (CRO), in the city of Rio de Janeiro. Method Retrospective cohort study based on medical records of 317 patients with severe obesity admitted to three CRO-RJ, between 2011 and 2016. Frequencies were described and relative risks with 95% CI of ≥ 5% loss of body weight at 6 and 12 months of treatment were estimated. Results Patients were mainly black (69.5%), women (76.3%), mean age 44.6 years (SD 11.9), reporting ≥ 2 comorbidities (52%), previous treatment (62.1%) and family history of obesity (42.6%). The initial mean BMI was 51.5 kg/m2; average treatment time was 10 months. 14.8% lost ≥ 5% of the initial weight after 12 months of treatment and the relative risk of weight loss was 78% higher among white patients. Approaches based on diet and changes in lifestyle predominated. 14% used anti-obesity drugs and 3% underwent bariatric surgery (1% in the SUS). Conclusion Treatment results suggest the need to adjust management to follow treatment guidelines for superobesity, including bariatric surgery.

Resumen Introducción El tratamiento de la obesidad severa está poco estudiado en el SUS. Objetivo Describir la clientela, el manejo y los factores asociados con la pérdida de peso en los Centros de Referencia para la Obesidad (CRO), en la ciudad de Río de Janeiro. Método Cohorte retrospectiva basada en registros médicos de 317 individuos con obesidad severa tratados en tres CRO-RJ entre 2011 y 2016. Se describieron las frecuencias y estimaron riesgos relativos con un IC del 95% para la pérdida de ≥ 5% del peso inicial a los 6 y 12 meses de tratamiento. Resultados Predominaron las mujeres (76.3%), negros (69.5%), con una media de 44.6 años (DE 11.9), tratamiento previo (62.1%), antecedentes familiares de obesidad (42.6%) y dos o más comorbilidades (52.0%). La mediana del IMC inicial fue de 51.5 kg/m2 y el tiempo de tratamiento fue de 10 meses. Solo el 14.8% perdió ≥ 5% de su peso inicial después de 12 meses de tratamiento, con un riesgo de pérdida de peso 78% mayor entre los individuos blancos. Predominaron el tratamiento dietético y los cambios en los hábitos de estilo de vida, con un bajo uso de medicamentos contra la obesidad (14%) y cirugía bariátrica (3%, 1% en SUS). Conclusión Los resultados del tratamiento sugieren la necesidad de reajustar las prácticas terapéuticas a las indicadas en la superobesidad, incluido un mayor acceso a la cirugía bariátrica.

Clinical profile of dengue in the elderly using surveillance data from two epidemics.

BACKGROUND: Population aging and mobility have increased the exposure of elderly individuals to dengue. This study evaluated the clinical features of dengue in the elderly during the epidemic (2008 and 2012) and interepidemic (2009 and 2010) periods. METHODS: This cross-sectional study was based on dengue surveillance data from Rio de Janeiro, Brazil: 2008 (n=31,210), 2009‒2010 (n=2,884), and 2012 (n=30,773). The analysis was stratified by age group (<60 and ≥60 years). RESULTS: Case-fatality rates were higher in the elderly. In 2008, elderly individuals were found to be more prone to hematuria and thrombocytopenia. CONCLUSIONS: These results can improve the understanding of dengue in elderly individuals who live in or travel to tropical regions.

Clinical profile of dengue in the elderly using surveillance data from two epidemics

ABSTRACT Background: Population aging and mobility have increased the exposure of elderly individuals to dengue. This study evaluated the clinical features of dengue in the elderly during the epidemic (2008 and 2012) and interepidemic (2009 and 2010) periods. Methods: This cross-sectional study was based on dengue surveillance data from Rio de Janeiro, Brazil: 2008 (n=31,210), 2009‒2010 (n=2,884), and 2012 (n=30,773). The analysis was stratified by age group (<60 and ≥60 years). Results: Case-fatality rates were higher in the elderly. In 2008, elderly individuals were found to be more prone to hematuria and thrombocytopenia. Conclusions: These results can improve the understanding of dengue in elderly individuals who live in or travel to tropical regions.

24-hour Holter findings in infants with in-utero exposure to the Zika virus: a series of cases.

Severe neurological problems and other special manifestations such as high prevalence of structural cardiac changes has been described in infants vertically exposed to the Zika virus (ZIKV) and has been called congenital Zika virus syndrome (CZS). Previous studies have shown that the 24-hour Holter heart rate variability (HRV) analysis allows the prediction of worse outcomes in infants with neurological impairment and higher risk of sudden infant death syndrome (SIDS), hypertension, diabetes mellitus and other cardiovascular diseases. This study describes the 24-hour Holter findings of infants with confirmed vertical exposure to the ZIKV by positive polymerase chain reaction (PCR) assays in the mother's blood during pregnancy and/or in the urine or cerebrospinal fluid of the newborn. Data analysis was descriptive and included two subgroups according to the presence of fetal distress, positive PCR to ZIKV in the newborn, CZS and severe microcephaly. Heart rate, pauses, arrhythmias, ST segment and QT interval analyses and HRV evaluation through R-R, SDNN, pNN50 and rMMSD were described. The Mann-Whitney test was performed to assess differences between the two subgroups. The sample consisted of 15 infants with a mean age of 16 months, nine of whom were male. No arrhythmias or QT interval changes were observed. The comparison of HRV through the Mann-Whitney test showed a significant difference between patients with and without CZS, with and without severe microcephaly, with lower HRV in the groups with severe microcephaly and CZS. The study suggests that there is an increased risk of SIDS and cardiovascular diseases in this group of patients.

Rapid immunochromatographic tests for the diagnosis of dengue: a systematic review and meta-analysis.

Dengue is an important arthropod-borne viral disease in terms of morbidity, mortality, economic impact and challenges in vector control. Benchmarks are expensive, time consuming and require trained personnel. Preventing dengue complications with rapid diagnosis has been based on the testing of easy-to-perform optimized immunochromatographic methods (ICT). This is a systematic meta-analysis review of the diagnostic accuracy of IgA, NS1, IgM and/or IgG ICT studies in suspected cases of acute or convalescent dengue, using a combination of RT-PCR, ELISA NS1, IgM IgG or viral isolation as a reference standard. This protocol was registered in PROSPERO (CRD42014009885). Two pairs of reviewers searched the PubMed, BIREME, Science Direct, Scopus, Web of Science, Ovid MEDLINE JBrigs, SCIRUS and EMBASE databases, selected, extracted, and quality-assessed by QUADAS 2. Of 3,783 studies, we selected 57, of which 40 in meta-analyses according to the analyte tested, with high heterogeneity (I2 > 90%), as expected for diagnostic tests. We detected higher pooled sensitivity in acute phase IgA (92.8%) with excellent (90%) specificity. ICT meta-analysis with NS1/IgM/IgG showed 91% sensitivity and 96% specificity. Poorer screening performance was for IgM/IgG ICT (sensitivity = 56%). Thus, the studies with NS1/IgM/IgG ICT showed the best combined performance in the acute phase of the disease.

Pitfalls in acute febrile illness diagnosis: Interobserver agreement of signs and symptoms during a dengue outbreak.

AIMS AND OBJECTIVES: To compare and evaluate interobserver (nurses and physicians) agreement for dengue clinical signs and symptoms, including the World Health Organization diagnostic algorithm. BACKGROUND: Agreement of clinical history defines the capacity of the examiner to measure a given clinical parameter in a reproducible and consistent manner, which is prerequisite for diagnosis validity. Nurses play a major role in the triage and care of dengue patients in many countries. STUDY DESIGN: This is a sub-study on interobserver agreement performed as part of a cross-sectional diagnostic accuracy study for acute febrile illness (AFI) using the checklist STARD. METHODS: A previously validated semi-structured sign and symptom standardised questionnaire for AFI was independently administered to 374 patients by physician and nurse pairs. The interobserver agreement was estimated using kappa statistics. RESULTS: For a set of 27 signs and symptoms, we found six interobserver discrepancies (examiner detected red eyes, lethargy, exanthema, dyspnoea, bleeding and myalgia) as identified by regular and moderate kappa indexes. Four signs (patient observed red eyes, cough, diarrhoea and vomiting) and one symptom (earache) had near-perfect agreement. Most signs and symptoms showed substantial agreement. The WHO (Dengue guidelines for diagnosis, treatment, prevention and control: new edition, World Health Organization, 2009) clinical criteria for dengue comprise a group of symptoms known as "pains and aches." Interobserver agreement for abdominal pain, retro-orbital pain and arthralgia exceed that found for headache and myalgia. CONCLUSIONS: During a dengue outbreak, the interobserver agreement for most of the signs and symptoms used to assess AFI was substantial. RELEVANCE TO CLINICAL PRACTICE: This result suggests good potential applicability of the tool by health professionals following training. A well-trained health professional is qualified to apply the standardised questionnaire to evaluate suspected dengue cases during outbreaks.

Diagnostic parameters and reliability of four rapid immunochromatographic tests for dengue 4

ABSTRACT Background: Although performance of rapid immunochromatographic tests (RITs) for dengue virus (DENV) serotypes 1, 2 and 3 is relatively settled, evidence on accuracy of RITs for DENV-4 are based on studies with small sample sizes and with discrepant results. Objectives: To assess accuracy and inter-observer agreement of RITs targeting dengue nonstructural protein-1 (NS1) antigen - Dengue NS1-Bioeasy™, Dengue NS1 Ag Strip-Bio-Rad™, IVB Dengue Ag NS1-Orangelife™ and Dengue NS1-K130-Bioclin™ in DENV-4 samples. Methods: Study sample (n = 324) included adults presenting at an emergency unit in Rio de Janeiro, Brazil, with fever of ≤72 h and two or more dengue symptoms. A serum sample from each patient was tested by each RIT. A positive reverse-transcription polymerase chain reaction was considered as the reference standard for dengue diagnosis. The diagnostic parameters analyzed for each RIT were sensitivity, specificity, positive and negative predictive values, and likelihood ratios. Each RIT was read by homogeneous (two junior nurses) or heterogeneous (one junior nurse and one senior biologist) pairs. Agreement was estimated by simple kappa with 95% confidence interval, positive (Ppos) and negative (Pneg) proportion concordance and prevalence and bias adjusted kappa, rated from poor (k < 0.0) to almost perfect (0.8 < k < 1.0), and perfect (k = 1). Results: NS1 RITs for DENV-4 diagnosis showed high specificity (95.9%-99.4%), but low sensitivity (14.7%-45.4%). Bioeasy™ had the best performance, with a positive likelihood ratio of 26.0 (95% CI: 8.4;81.0). Inter-observer agreement was almost perfect for all evaluated RITs. Mismatches in confirmed dengue were more common for the Bioclin™ (Ppos 88.3-90.0 %) and Orangelife™ (Ppos 91.7-94.1 %) tests. Conclusions: For DENV-4, the tested RITs had high specificity, but lower sensitivity compared to published results for other serotypes. They should not be used for screening purposes. Different brands may have very different performances. This should be considered upon deciding of using RITs in DENV-4 outbreaks.

Diagnostic parameters and reliability of four rapid immunochromatographic tests for dengue 4.

BACKGROUND: Although performance of rapid immunochromatographic tests (RITs) for dengue virus (DENV) serotypes 1, 2 and 3 is relatively settled, evidence on accuracy of RITs for DENV-4 are based on studies with small sample sizes and with discrepant results. OBJECTIVES: To assess accuracy and inter-observer agreement of RITs targeting dengue nonstructural protein-1 (NS1) antigen - Dengue NS1-Bioeasy™, Dengue NS1 Ag Strip-Bio-Rad™, IVB Dengue Ag NS1-Orangelife™ and Dengue NS1-K130-Bioclin™ in DENV-4 samples. METHODS: Study sample (n = 324) included adults presenting at an emergency unit in Rio de Janeiro, Brazil, with fever of ≤72 h and two or more dengue symptoms. A serum sample from each patient was tested by each RIT. A positive reverse-transcription polymerase chain reaction was considered as the reference standard for dengue diagnosis. The diagnostic parameters analyzed for each RIT were sensitivity, specificity, positive and negative predictive values, and likelihood ratios. Each RIT was read by homogeneous (two junior nurses) or heterogeneous (one junior nurse and one senior biologist) pairs. Agreement was estimated by simple kappa with 95% confidence interval, positive (Ppos) and negative (Pneg) proportion concordance and prevalence and bias adjusted kappa, rated from poor (k < 0.0) to almost perfect (0.8 < k < 1.0), and perfect (k = 1). RESULTS: NS1 RITs for DENV-4 diagnosis showed high specificity (95.9%-99.4%), but low sensitivity (14.7%-45.4%). Bioeasy™ had the best performance, with a positive likelihood ratio of 26.0 (95% CI: 8.4;81.0). Inter-observer agreement was almost perfect for all evaluated RITs. Mismatches in confirmed dengue were more common for the Bioclin™ (Ppos 88.3-90.0 %) and Orangelife™ (Ppos 91.7-94.1 %) tests. CONCLUSIONS: For DENV-4, the tested RITs had high specificity, but lower sensitivity compared to published results for other serotypes. They should not be used for screening purposes. Different brands may have very different performances. This should be considered upon deciding of using RITs in DENV-4 outbreaks.

Rapid immunochromatographic tests for the diagnosis of dengue: a systematic review and meta-analysis / Testes imunocromatográficos rápidos para o diagnóstico da dengue: uma revisão sistemática e metanálise / Pruebas inmunocromatográficas rápidas para la diagnosis del dengue: una revisión sistemática y metaanálisis

Abstract: Dengue is an important arthropod-borne viral disease in terms of morbidity, mortality, economic impact and challenges in vector control. Benchmarks are expensive, time consuming and require trained personnel. Preventing dengue complications with rapid diagnosis has been based on the testing of easy-to-perform optimized immunochromatographic methods (ICT). This is a systematic meta-analysis review of the diagnostic accuracy of IgA, NS1, IgM and/or IgG ICT studies in suspected cases of acute or convalescent dengue, using a combination of RT-PCR, ELISA NS1, IgM IgG or viral isolation as a reference standard. This protocol was registered in PROSPERO (CRD42014009885). Two pairs of reviewers searched the PubMed, BIREME, Science Direct, Scopus, Web of Science, Ovid MEDLINE JBrigs, SCIRUS and EMBASE databases, selected, extracted, and quality-assessed by QUADAS 2. Of 3,783 studies, we selected 57, of which 40 in meta-analyses according to the analyte tested, with high heterogeneity (I2 > 90%), as expected for diagnostic tests. We detected higher pooled sensitivity in acute phase IgA (92.8%) with excellent (90%) specificity. ICT meta-analysis with NS1/IgM/IgG showed 91% sensitivity and 96% specificity. Poorer screening performance was for IgM/IgG ICT (sensitivity = 56%). Thus, the studies with NS1/IgM/IgG ICT showed the best combined performance in the acute phase of the disease.

Resumo: A dengue é uma importante arbovirose em termos de morbidade, mortalidade, impacto econômico e controle do vetor. Os testes de referência são dispendiosos e demorados e exigem pessoal capacitado. A prevenção das complicações da dengue com o diagnóstico rápido tem tomado como base a testagem com métodos imunocromatográficos (ICT). O estudo é uma revisão sistemática e meta-análise da acurácia diagnóstica de estudos de ICT de IgA, NS1, IgM e/ou IgG em casos suspeitos de dengue aguda ou convalescente, usando uma combinação de RT-PCR, ELISA NS1, IgM IgG ou isolamento viral como padrão de referência. O projeto foi registrado na base PROSPERO (CRD42014009885). Dois pares de revisores realizaram as buscas nas bases de dados PubMed, BIREME, Science Direct, Scopus, Web of Science, Ovid MEDLINE JBrigs, SCIRUS e EMBASE, além da seleção, extração e avaliação de qualidade com a ferramenta QUADAS 2. A partir de 3.783 estudos, selecionamos 57, dos quais 40 foram incluídos nas meta-análises de acordo com o analito testado, com alta heterogeneidade (I2 > 90%), conforme esperado para testes diagnósticos. Foi detectada a maior sensibilidade conjunta no IgA de fase aguda (92,8%), com excelente especificidade (90%). A meta-análise de ICT com NS1/IgM/IgG mostrou sensibilidade de 91% e especificidade de 96%. O pior desempenho para triagem foi com o ICT de IgM/IgG (sensibilidade = 56%). Portanto, os estudos de ICT com NS1/IgM/IgG mostraram o melhor desempenho combinado na fase aguda da doença.

Resumen: El dengue es una importante enfermedad arboviral, en términos de morbilidad, mortalidad, impacto económico y desafíos en el control del vector. Las mejores prácticas son caras, consumen mucho tiempo y requieren personal formado. Prevenir las complicaciones del dengue con un rápido diagnóstico se ha basado en pruebas con métodos inmunocromatográficos optimizados fáciles de realizar (ICT por sus siglas en inglés). Se trata de una revisión sistemática de metaanálisis sobre la precisión diagnóstica de estudios de IgA, NS1, IgM y/o IgG ICT en casos sospechosos de fases agudas o convalecientes de dengue, usando la combinación de RT-PCR, ELISA NS1, IgM IgG o el aislamiento viral como referencia estándar. Este proyecto se registró en PROSPERO (CRD42014009885). Dos parejas de revisores investigaron en las bases de datos de: PubMed, BIREME, Science Direct, Scopus, Web of Science, Ovid MEDLINE JBrigs, SCIRUS y EMBASE, seleccionaron, extrajeron, y realizaron la evaluación de calidad mediante QUADAS 2. De 3.783 estudios, se seleccionaron 57, de los cuales 40 fueron metaanálisis, según el analito probado, con una alta heterogeneidad (I2 > 90%), como se esperaba en las pruebas de diagnóstico. Detectamos una sensibilidad más alta combinada en la fase aguda IgA (92.8%) con una excelente (90%) especificidad. Los metaanálisis ICT con NS1/IgM/ IgG mostraron un 91% de sensibilidad y un 96% de especificidad. Se produjo un rendimiento más pobre en el diagnóstico IgM/IgG ICT (sensibilidad = 56%). De este modo, los estudios con NS1/IgM/IgG ICT mostraron un rendimiento mejor combinado en la fase aguda de la enfermedad.

Quality assessment of clinical guidelines for the treatment of obesity in adults: application of the AGREE II instrument.

There are various guidelines for the treatment of obesity, and thus the quality of these clinical guidelines has become a matter of concern. The objective was to describe and assess the quality of clinical guidelines for treatment of obesity in adults. We collected several studies, dated from 1998 to 2016, produced by different countries. The literature search included the National Guideline Clearinghouse (NGC), Guidelines International Network (GIN), PubMed (MEDLINE), Scopus, Web of Science, webpages of health institutions from different countries, and search sites, with the criterion: "clinical guidelines for treatment of obesity in adults and published until the 2016". The guidelines were assessed with the Appraisal of Guidelines for Research & Evaluation (AGREE II), according to the domains of the instrument. The search identified 21 guidelines: nine from Europe, six from North America, three from Latin America, and one each from Asia and Oceania and a transnational association. The Australian guideline had the best assessment. Of the six guidelines with the highest scores, five had been elaborated by the government sector responsible for the country's health. The domains "scope and purpose" and "clarity of presentation" had the highest score. Except for the Canadian guideline, the three guidelines drafted before the elaboration of AGREE II had the worst quality. In the domain "stakeholder involvement", only four guidelines (Australia, Scotland, France, and England) mentioned patient participation. Guideline development and quality enhancement are ongoing processes requiring systematic appraisal of the guideline production process and existing guidelines.

Quality assessment of clinical guidelines for the treatment of obesity in adults: application of the AGREE II instrument / Avaliação da qualidade das diretrizes clínicas para o tratamento da obesidade em adultos: aplicação do instrumento AGREE II / Evaluación de la calidad de guías clínicas para el tratamiento de la obesidad en adultos: aplicación del instrumento AGREE II

There are various guidelines for the treatment of obesity, and thus the quality of these clinical guidelines has become a matter of concern. The objective was to describe and assess the quality of clinical guidelines for treatment of obesity in adults. We collected several studies, dated from 1998 to 2016, produced by different countries. The literature search included the National Guideline Clearinghouse (NGC), Guidelines International Network (GIN), PubMed (MEDLINE), Scopus, Web of Science, webpages of health institutions from different countries, and search sites, with the criterion: "clinical guidelines for treatment of obesity in adults and published until the 2016". The guidelines were assessed with the Appraisal of Guidelines for Research & Evaluation (AGREE II), according to the domains of the instrument. The search identified 21 guidelines: nine from Europe, six from North America, three from Latin America, and one each from Asia and Oceania and a transnational association. The Australian guideline had the best assessment. Of the six guidelines with the highest scores, five had been elaborated by the government sector responsible for the country's health. The domains "scope and purpose" and "clarity of presentation" had the highest score. Except for the Canadian guideline, the three guidelines drafted before the elaboration of AGREE II had the worst quality. In the domain "stakeholder involvement", only four guidelines (Australia, Scotland, France, and England) mentioned patient participation. Guideline development and quality enhancement are ongoing processes requiring systematic appraisal of the guideline production process and existing guidelines.

Existem diversas diretrizes para o tratamento da obesidade, e a qualidade dessas diretrizes clínicas tem suscitado preocupação. O estudo teve como objetivo descrever e avaliar a qualidade das diretrizes clínicas para o tratamento da obesidade em adultos. Identificamos diversos estudos publicados entre 1998 e 2016 e produzidos em diferentes países. A busca na literatura incluiu a National Guideline Clearinghouse (NGC), Guidelines International Network (GIN), PubMed (MEDLINE), Scopus, Web of Science, websites de instituições sanitárias de diversos países e sites de busca, com o critério: "diretrizes clínicas para o tratamento da obesidade em adultos, publicadas até 2016". As diretrizes foram avaliadas com a Appraisal of Guidelines for Research & Evaluation (AGREE II), de acordo com os domínios do instrumento. A busca identificou 21 diretrizes: nove da Europa, seis da América do Norte, três da América Latina e uma da Ásia uma da Oceania e uma associação transnacional. A diretriz australiana recebeu a melhor avaliação. Das seis diretrizes que receberam as melhores avaliações, cinco haviam sido elaboradas pela respectiva autoridade sanitária nacional. Os domínios "escopo e objetivo" e "clareza de apresentação" receberam as pontuações mais altas. Com exceção da diretriz canadense, as três diretrizes publicadas antes da elaboração do instrumento AGREE II apresentaram a pior qualidade. No domínio "envolvimento dos stakeholders", apenas quatro (da Austrália, Escócia, França e Inglaterra) mencionaram a participação dos pacientes. O desenvolvimento e melhoria da qualidade das diretrizes são processos permanentes que exigem a avaliação sistemática do processo de produção e das diretrizes existentes.

Existen varias líneas de actuación para el tratamiento de la obesidad, y por este motivo la calidad de las guías clínicas se ha convertido en un asunto de interés general. El objetivo de este trabajo fue describir y evaluar la calidad de las guías clínicas para el tratamiento de la obesidad en adultos. Recogimos varios estudios, entre 1998 y 2016, realizados en diferentes países. La búsqueda de bibliografía incluyó: National Guideline Clearinghouse (NGC), Guidelines International Network (GIN), PubMed (MEDLINE), Scopus, Web of Science, páginas web de instituciones de salud de diferentes países, y páginas de búsqueda, con el criterio: "guías clínicas para el tratamiento de la obesidad en adultos y publicadas hasta 2016". Las guías fueron evaluadas con el Appraisal of Guidelines for Research & Evaluation (AGREE II), según los diferentes ámbitos de este instrumento. La búsqueda identificó 21 guías: nueve procedentes de Europa, seis de Norteamérica, tres de Latinoamérica, una de Asia, una Oceanía y una con asociación transnacional entre ellos. La guía australiana contaba con la mejor evaluación. De las seis guías con las puntuaciones más altas, cinco habían sido elaboradas por el sector del gobierno responsable de la salud del país. Los campos "alcance y propósito" y "claridad de la presentación" contaban con la puntuación más alta. Excepto en el caso de la guía canadiense, las tres guías redactadas antes de la elaboración del AGREE II tenían peor calidad. En el campo "participación de las partes interesadas", sólo cuatro guías (Australia, Escocia, Francia, e Inglaterra) mencionaron la participación del paciente. Las guías para el desarrollo y mejora de la calidad son procesos en curso que requieren una evaluación sistemática del proceso de producción de las guías y de las directrices existentes.

Correction to: Accuracy and reliability of an NS1 rapid immunochromatographic test for DENV-1 diagnosis at point of care and in the laboratory.

An error occurred during the publication of the original article [1].

Precisão e confiabilidade de um teste imuno-cromatográfico rápido NS1 para diagnóstico DENV-1 no ponto de atendimento e no laboratório.

BACKGROUND: Rapid immunochromatographic tests (ICT) for dengue non-structural protein 1 (NS1) have shown good performance for diagnosing acute-phase dengue in serum in laboratory settings, but rarely have been assessed in whole blood and at point of care (POC). This study compare the accuracy and inter- and intra-observer reliability of the NS1 Bioeasy™ ICT in whole blood at POC versus serum in the laboratory, during a DENV-1 epidemic. METHODS: Cross-sectional study involving 144 adults spontaneously demanding care in an emergency department within 4 days of onset of acute febrile illness. Accuracy of NS1 Bioeasy™ ICT was compared in whole blood and serum, both at 15 and 30 min, blinded to the reference RT-PCR or NS1 ELISA. Non-dengue patients were also tested for Zika virus with RT-PCR. Reliability of whole blood and serum readings by the same or different observers was measured by simple kappa (95% CI). RESULTS: At 15 min, sensitivity (Sn) of NS1 Bioeasy™ ICT in whole blood/POC was 76.7% (95% CI: 68.0-84.1) and specificity (Sp) was 87.0% (95% CI: 66.4-97.2). Sn in serum/laboratory was 82% (95% CI: 74.1-88.6) and Sp 100% (95% CI: 85.8-100). Positive likelihood ratio was 5.9 (95% CI: 2.0-17.0) for whole blood/POC and 19.8 (95% CI: 2.9-135.1) for serum/laboratory. Reliability of matched readings of whole blood/POC and serum/laboratory by the same observer (k = 0.83, 95% CI: 0.74-0.93) or different observers (k = 0.81, 95% CI: 0.72-0.92) was almost perfect, with higher discordant levels in the absence of dengue. Results did not differ statistically at 5%. CONCLUSIONS: NS1 Bioeasy™ ICT in DENV-1 epidemics is a potentially confirmatory test. Invalid results at 15 min should be reread at 30 min. To optimize impact of implementing ICT in the management of false-negatives it should be incorporated into an algorithm according to setting and available specimen. TRIAL REGISTRATION: UTN U1111-1145-9451 .

Low versus high dose of antimony for American cutaneous leishmaniasis: A randomized controlled blind non-inferiority trial in Rio de Janeiro, Brazil.

BACKGROUND: Although high dose of antimony is the mainstay for treatment of American cutaneous leishmaniasis (ACL), ongoing major concerns remain over its toxicity. Whether or not low dose antimony regimens provide non-inferior effectiveness and lower toxicity has long been a question of dispute. METHODS: A single-blind, non-inferiority, randomized controlled trial was conducted comparing high dose with low dose of antimony in subjects with ACL treated at a referral center in Rio de Janeiro, an endemic area of Leishmania (Viannia) braziliensis transmission. The primary outcome was clinical cure at 360 days of follow-up in the modified-intention-to-treat (mITT) and per-protocol (PP) populations. Non-inferiority margin was 15%. Secondary objectives included occurrence of epithelialization, adverse events and drug discontinuations. This study was registered in ClinicalTrials.gov: NCT01301924. RESULTS: Overall, 72 patients were randomly assigned to one of the two treatment arms during October 2008 to July 2014. In mITT, clinical cure was observed in 77.8% of subjects in the low dose antimony group and 94.4% in the high dose antimony group after one series of treatment (risk difference 16.7%; 90% CI, 3.7-29.7). The results were confirmed in PP analysis, with 77.8% of subjects with clinical cure in the low dose antimony group and 97.1% in the high dose antimony group (risk difference 19.4%; 90% CI, 7.1-31.7). The upper limit of the confidence interval exceeded the 15% threshold and was also above zero supporting the hypothesis that low dose is inferior to high dose of antimony after one series of treatment. Nevertheless, more major adverse events, a greater number of adverse events and major adverse events per subject, and more drug discontinuations were observed in the high dose antimony group (all p<0.05). Interestingly, of all the subjects who were originally allocated to the low dose antimony group and were followed up after clinical failure, 85.7% achieved cure after a further treatment with local therapy or low dose of antimony. CONCLUSIONS: Compared with high dose, low dose of antimony was inferior at the pre-specified margin after one series of treatment of ACL, but was associated with a significantly lower toxicity. While high dose of antimony should remain the standard treatment for ACL, low dose antimony treatment might be preferred when toxicity is a primary concern.

Increased sensitivity of NS1 ELISA by heat dissociation in acute dengue 4 cases.

BACKGROUND: Dengue is an acute febrile illness considered the major arboviral disease in terms of morbidity, mortality, economic impact and dissemination worldwide. Brazil accounts for the highest notification rate, with circulation of all four dengue serotypes. The NS1 antigen is a dengue highly conserved specific soluble glycoprotein essential for viral replication and viability that can be detected 0 to 18 days from the onset of fever (peak first 3 days). It induces a strong humoral response and is known as a complement-fixing antigen. Lower NS1 test sensitivity occurs in secondary dengue infections probably due to immune complex formation impairing antigen detection by ELISA. METHODS: We compared the sensitivity of NS1 ELISA in heat dissociated and non-dissociated samples from 156 RT-PCR confirmed acute dengue-4 cases from 362 prospectively enrolled patients. RESULTS: Secondary infections accounted for 83.3% of cases. NS1 ELISA was positive in 42.5% and indeterminate in 10.2% of dengue-4 cases. After heat dissociation, 7 negative and 16 indeterminate samples turned positive, increasing the overall test sensitivity to 57.7%. CONCLUSIONS: Although it is time consuming and requires the use of specific laboratory equipment, NS1 ELISA combined with heat dissociation could be a slightly better alternative for triage in suspected dengue cases.

Severe infection in patients with rheumatoid arthritis taking anakinra, rituximab, or abatacept: a systematic review of observational studies.

A question is raised about an increased risk of severe infection from the use of biological drugs in patients with rheumatoid arthritis. This systematic review of observational studies aimed at assessing the risk of severe infection associated with the use of anakinra, rituximab, and abatacept in patients with rheumatoid arthritis. The following databases were searched: PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, Exerpta Medica Database, Scielo, and Lilacs up to July 2010. Severe infections were defined as those life-threatening ones in need of the use of parenteral antibiotics or of hospitalization. Longitudinal observational studies were selected without language restriction, involving adult patients diagnosed with rheumatoid arthritis and who used anakinra, rituximab, or abatacept. In four studies related to anakinra, 129 (5.1%) severe infections were related in 2896 patients, of which three died. With respect to rituximab, two studies reported 72 (5.9%) severe infections in 1224 patients, of which two died. Abatacept was evaluated in only one study in which 25 (2.4%) severe infections were reported in 1046 patients. The main site of infection for these three drugs was the respiratory tract. One possible explanation for the high frequency of severe infections associated with anakinra may be the longer follow-up time in the selected studies. The high frequency of severe infections associated with rituximab could be credited to the less strict inclusion criteria for the patients studied. Therefore, infection monitoring should be cautious in patients with rheumatoid arthritis in use of these three drugs.

Severe infection in patients with rheumatoid arthritis taking anakinra, rituximab, or abatacept: a systematic review of observational studies / Infecções graves em pacientes com artrite reumatoide em uso de anakinra, rituximab ou abatacept: revisão sistemática de estudos observacionais

ABSTRACT A question is raised about an increased risk of severe infection from the use of biological drugs in patients with rheumatoid arthritis. This systematic review of observational studies aimed at assessing the risk of severe infection associated with the use of anakinra, rituximab, and abatacept in patients with rheumatoid arthritis. The following databases were searched: PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, Exerpta Medica Database, Scielo, and Lilacs up to July 2010. Severe infections were defined as those life-threatening ones in need of the use of parenteral antibiotics or of hospitalization. Longitudinal observational studies were selected without language restriction, involving adult patients diagnosed with rheumatoid arthritis and who used anakinra, rituximab, or abatacept. In four studies related to anakinra, 129 (5.1%) severe infections were related in 2896 patients, of which three died. With respect to rituximab, two studies reported 72 (5.9%) severe infections in 1224 patients, of which two died. Abatacept was evaluated in only one study in which 25 (2.4%) severe infections were reported in 1046 patients. The main site of infection for these three drugs was the respiratory tract. One possible explanation for the high frequency of severe infections associated with anakinra may be the longer follow-up time in the selected studies. The high frequency of severe infections associated with rituximab could be credited to the less strict inclusion criteria for the patients studied. Therefore, infection monitoring should be cautious in patients with rheumatoid arthritis in use of these three drugs.

RESUMO Existe um questionamento sobre aumento do risco de infecções graves pelo uso de medicamentos biológicos por pacientes com artrite reumatoide. Esta revisão sistemática de estudos observacionais objetivou avaliar o risco de infecções graves associadas ao uso de anakinra, rituximab e abatacept em pacientes com artrite reumatoide. Foram pesquisadas as bases PubMed, Science Direct, Scopus, Web of Knowledge, Scirus, Cochrane, Exerpta Medica Database, Scielo e Lilacs até julho/2010. Infecções graves foram definidas como aquelas com de risco de vida, necessidade de antibióticos parenterais ou de hospitalização. Foram selecionados estudos observacionais longitudinais, sem restrição de idioma, que envolviam pacientes adultos com diagnóstico de artrite reumatoide que usaram anakinra, rituximab, abatacept. Em quatro estudos relacionados ao anakinra, foram relatadas 129 (5,1%) infecções graves em 2.896 pacientes, dos quais três evoluíram para óbito. Sobre o rituximab, dois estudos relataram 72 (5,9%) infecções graves em 1.224 pacientes, dos quais dois evoluíram para óbito. O abatacept foi avaliado em apenas um estudo, no qual foram relatadas 25 (2,4%) infecções graves em 1.046 pacientes. O principal sítio de infecção para os três medicamentos foi o trato respiratório. Uma possível explicação para a frequência elevada de infecções graves associadas ao anakinra pode ser o maior tempo de acompanhamento nos estudos selecionados. A frequência elevada de infecções graves associadas ao rituximab poderia ser creditada ao critério menos restrito de inclusão de pacientes. Portanto, deve ser cautelosa a monitoração de infecções nos pacientes com artrite reumatoide que usam esses três medicamentos.

Use of Warning Signs for Dengue by Pediatric Health Care Staff in Brazil.

OBJECTIVE: The aim of this study was to describe the use of dengue warning signs by pediatric healthcare staff in the Brazilian public health care system. METHODS: Cross-sectional study (2012) with physicians, nurses, and nurse technicians assisting children in five health care facilities. Participants reported the use and importance of dengue warning signs in pediatrics clinical practice through a structured questionnaire. Differences in the use of signs (chi-square test) and in the ranking assigned to each of them (Kruskal-Wallis) were assessed according to health care occupation and level of care (p<0.05). RESULTS: The final sample comprised 474 participants (97%), mean age of 37 years (standard deviation = 10.3), mainly females (83.8%), physicians (40.1%) and from tertiary care (75.1%). The majority (91%) reported using warning signs for dengue in pediatrics clinical practice. The most widely used and highly valued signs were major hemorrhages (gastrointestinal, urinary), abdominal pain, and increase in hematocrit concurrent or not with rapid decrease in platelet count. Persistent vomiting as well as other signs of plasma leakage such as respiratory distress and lethargy/restlessness were not identified as having the same degree of importance, especially by nurse technicians and in primary or secondary care. DISCUSSION: Although most health care staff reported using dengue warning signs, it would be useful to extend the training for identifying easily recognizable signs of plasma leakage that occur regardless of bleeding.

PANCREATIC TOXICITY AS AN ADVERSE EFFECT INDUCED BY MEGLUMINE ANTIMONIATE THERAPY IN A CLINICAL TRIAL FOR CUTANEOUS LEISHMANIASIS.

American tegumentary leishmaniasis is an infectious disease caused by a protozoan of the genus Leishmania. Pentavalent antimonials are the first choice drugs for cutaneous leishmaniasis (CL), although doses are controversial. In a clinical trial for CL we investigated the occurrence of pancreatic toxicity with different schedules of treatment with meglumine antimoniate (MA). Seventy-two patients were allocated in two different therapeutic groups: 20 or 5 mg of pentavalent antimony (Sb5+)/kg/day for 20 or 30 days, respectively. Looking for adverse effects, patients were asked about abdominal pain, nausea, vomiting or anorexia in each medical visit. We performed physical examinations and collected blood to evaluate serum amylase and lipase in the pre-treatment period, and every 10 days during treatment and one month post-treatment. Hyperlipasemia occurred in 54.8% and hyperamylasemia in 19.4% patients. Patients treated with MA 20 mg Sb5+ presented a higher risk of hyperlipasemia (p = 0.023). Besides, higher MA doses were associated with a 2.05 higher risk ratio (p = 0.003) of developing more serious (moderate to severe) hyperlipasemia. The attributable fraction was 51% in this group. Thirty-six patients presented abdominal pain, nausea, vomiting or anorexia but only 47.2% of those had hyperlipasemia and/ or hyperamylasemia. These findings suggest the importance of the search for less toxic therapeutic regimens for the treatment of CL.