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It is known that the inflammation process leading to oxidative stress and thyroid hormone metabolism dysfunction is highly altered in metabolic dysfunction associated with steatotic liver disease (MASLD). This study aims to address the effect of ornithine aspartate (LOLA) and vitamin E (VitE) in improving these processes. Adult Sprague-Dawley rats were assigned to five groups and treated for 28 weeks: controls (n = 10) received a standard diet (for 28 weeks) plus gavage with distilled water (DW) from weeks 16 to 28. MASLD groups received a high-fat and choline-deficient diet for 28 weeks (MASLD group) and daily gavage with 200 mg/kg/day of LOLA, or twice a week with 150 mg of VitE from weeks 16-28. LOLA diminished collagen deposition (p = 0.006). The same treatment diminished carbonyl, TBARS, and sulfhydryl levels and GPx activity (p < 0.001). Type 3 deiodinase increased in the MASLD group, downregulating T3-controlled genes, which was corrected in the presence of LOLA. LOLA also promoted a near-normalization of complex II, SDH, and GDH activities (p < 0.001) and improved reticulum stress, with a reduction in GRP78 and HSPA9/GRP75 protein levels (p < 0.05). The enhanced energy production and metabolism of thyroid hormones, probably because of GSH replenishment provided by the L-glutamate portion of LOLA, opens a new therapeutic approach for MASLD.
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Estresse Oxidativo , Ratos Sprague-Dawley , Vitamina E , Animais , Ratos , Vitamina E/farmacologia , Vitamina E/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado/metabolismo , Fígado/patologia , Fígado/efeitos dos fármacos , Hormônios Tireóideos/metabolismo , DipeptídeosRESUMO
BACKGROUND: Chikungunya virus (CHIKV) diagnosis has become a challenge for primary care physicians in areas where the Zika virus and/or Dengue virus are present. Case definitions for the three arboviral infections overlap. METHODS: A cross-sectional analysis was carried out. A bivariate analysis was made using confirmed CHIKV infection as the outcome. Variables with significant statistical association were included in an agreement consensus. Agreed variables were analyzed in a multiple regression model. The area under the receiver operating characteristic (ROC) curve was calculated to determine a cut-off value and performance. RESULTS: 295 patients with confirmed CHIKV infection were included. A screening tool was created using symmetric arthritis (4 points), fatigue (3 points), rash (2 points), and ankle joint pain (1 point). The ROC curve identified a cut-off value, and a score ≥ 5.5 was considered positive for identifying CHIKV patients with a sensibility of 64.4% and a specificity of 87.4%, positive predictive value of 85.5%, negative predictive value of 67.7%, area under the curve of 0.72, and an accuracy of 75%. CONCLUSION: We developed a screening tool for CHIKV diagnosis using only clinical symptoms as well as proposed an algorithm to aid the primary care physician.
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INTRODUCTION AND OBJECTIVES: Liver fibrosis is an important prognosis marker in non-alcoholic fatty liver disease (NAFLD). Biopsy has been considered the gold-standard method for measuring liver fibrosis; however, it is an invasive procedure. Non-invasive diagnostic tools have been developed, such as clinical scores and magnetic resonance elastography (MRE), which is the most accurate non-invasive method to determine liver fibrosis. Thus, the aim was to determine the NAFLD Fibrosis Score (NFS) and the Fibrosis-4 Score (FIB-4) cut-off points that best identify NAFLD patients at risk for developing liver fibrosis. PATIENTS AND METHODS: Single-center cross-sectional study with prospective recruitment of NAFLD (training-cohort) and MAFLD (validation-cohort) patients undergoing MRE. The NFS and the FIB-4 cut-off points that best-differentiated patients with fibrosis, using the MRE as the standard method, were determined. RESULTS: Two cohorts were analyzed, a training cohort that included the initial 183 patients with NAFLD and a validation cohort that included 289 patients. In the training cohort, 60.1% had mild steatosis and 11.5% had liver fibrosis ≥ F1 by MRE. ROC curves were developed for FIB-4 and NFS, and the cut-off points chosen were 1.505 (sensitivity=85% and specificity=86%) for FIB-4 and -0.835 (sensitivity=100% and specificity=70%) for NFS, showing greater specificity than the cut-off points currently used (51% and 76%, respectively). The two cohorts exhibited similar characteristics and similar sensitivity and specificity results for the chosen cut-off points. CONCLUSIONS: This study has shown cut-off points with greater specificity and excellent sensitivity to guide the indication for further liver evaluation by MRE in NAFLD patients.
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Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Estudos Prospectivos , Estudos Transversais , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/etiologia , Fígado/diagnóstico por imagem , Fígado/patologia , Fibrose , BiópsiaRESUMO
Cardiovascular (CV) disease is the main cause of death in nonalcoholic fatty liver disease (NAFLD), a clinical condition without any approved pharmacological therapy. Thus, we investigated the effects of ornithine aspartate (LOLA) and/or Vitamin E (VitE) on CV parameters in a steatohepatitis experimental model. Adult Sprague Dawley rats were randomly assigned (10 animals each) and treated from 16 to 28 weeks with gavage as follows: controls (standard diet plus distilled water (DW)), NAFLD (high-fat choline-deficient diet (HFCD) plus DW), NAFLD+LOLA (HFCD plus LOLA (200 mg/kg/day)), NAFLD+VitE (HFCD plus VitE (150 mg twice a week)) or NAFLD+LOLA+VitE in the same doses. Atherogenic ratios were higher in NAFLD when compared with NAFLD+LOLA+VitE and controls (p < 0.05). Serum concentration of IL-1ß, IL-6, TNF-α, MCP-1, e-selectin, ICAM-1, and PAI-1 were not different in intervention groups and controls (p > 0.05). NAFLD+LOLA decreased miR-122, miR-33a, and miR-186 (p < 0.05, for all) in relation to NAFLD. NAFLD+LOLA+VitE decreased miR-122, miR-33a and miR-186, and increased miR-126 (p < 0.05, for all) in comparison to NAFLD and NAFLD+VitE. NAFLD+LOLA and NAFLD+LOLA+VitE prevented liver collagen deposition (p = 0.006) in comparison to NAFLD. Normal cardiac fibers (size and shape) were lower in NAFLD in relation to the others; and the inverse was reported for the percentage of regular hypertrophic cardiomyocytes. NAFLD+LOLA+VitE promoted a significant improvement in atherogenic dyslipidemia, liver fibrosis, and paracrine signaling of lipid metabolism and endothelial dysfunction. This association should be further explored in the treatment of NAFLD-associated CV risk factors.
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Doenças Cardiovasculares , Dipeptídeos , Hepatopatia Gordurosa não Alcoólica , Vitamina E , Animais , Ratos , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Fígado/metabolismo , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/complicações , Ratos Sprague-Dawley , Fatores de Risco , Vitamina E/uso terapêutico , Modelos Animais de Doenças , Dipeptídeos/uso terapêutico , Quimioterapia CombinadaRESUMO
BACKGROUND: Estimating the burden of rheumatic diseases (RDs) requires proper evaluation of its lethal and nonlethal consequences. In Colombia, it is possible to find local data and Global Burden of Disease (GBD) reports that collect information from varied contexts and apply complex statistical models, but no on-site estimations are available. METHODS: This was a descriptive study on the burden of RD based on occurrence and mortality data in the general population during 2015, including information and prevalence estimations from the Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) study. Disability-adjusted life years (DALYs) were estimated by combining measures of years of life lost (YLL) and years lived with disability (YLDs). For disability weight estimations among cases, different COPCORD responses were mapped using flowcharts to show the severity distribution according to GBD. All model parameters and results were validated through an expert consensus panel. RESULTS: Low back pain (LBP) was the RD with the greatest burden of disease, costing 606.05 (95% CI 502.76-716.58) DALYs per 100,000 inhabitants, followed by osteoarthritis (292.11; 95% CI 205.76-386.85) and rheumatoid arthritis (192.46, 95% CI 109.7-239.69). CONCLUSIONS: The burden of RD is as high in Colombia as in other countries of the region. The results offer an interesting tool for optimizing healthcare system design as well as for planning the distribution of human and economic resources to achieve early diagnosis and adequate care of these diseases.
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INTRODUCTION: Malignant triton tumor (MTT) is an extremely rare variant of the malignant peripheral nerve sheath tumors (MPNSTs) with rhabdomyosarcomatous differentiation, which was first described in 1932 by Mason. MTT affects, in most cases, patients under 35 years of age, and it is usually manifested as a mass that may or not be painful. However, the incidence in pediatric patients is atypical. This tumor presents an aggressive course and limited survival rate, and the prognosis is different between individuals with or without a concomitant diagnosis of neurofibromatosis type 1 (NF1). Currently, the recommended treatment is surgical resection, and adjuvant chemotherapy and radiotherapy, but its efficacy is not yet clear. PRESENTATION OF THE CASE: A 13-year-old female patient was referred to the pediatric oncology service due to the presence of an abdominal mass and weight loss, initially diagnosed with Wilms' tumor. After extensive investigation, surgical resection, and immunohistopathological evaluation, the diagnosis of malignant triton tumor was confirmed. The patient also underwent cycles of chemotherapy after resection, and is currently awaiting immunotherapy. DISCUSSION AND CONCLUSION: Malignant triton tumor is extremely rare and difficult to diagnose, especially in children or young people, age groups in which the incidence of the disease is even lower. This may be the reason it is rarely suspected, and it was a great challenge for the clinical care team. It is essential to consider and investigate this possibility of differential diagnosis, as patients diagnosed with this malignant tumor have a low survival rate and poor prognosis.
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Resumen Introducción: hasta el momento, no se ha demostrado la efectividad de ningún tratamiento para afrontar la emergencia sanitaria por COVID-19. Objetivo: presentar la evidencia disponible respecto a la eficacia y seguridad del uso de cloroquina, hidroxicloroquina y azitromicina en la profilaxis y el manejo de pacientes con COVID-19. Materiales y métodos: se realizó una revisión de la literatura en las bases de datos MEDLINE, Scopus y PubMed sobre publica- ciones que registraran el uso de cloroquina, hidroxicloroquina y azitromicina en pacientes con COVID-19. Resultados: se seleccionaron 12 publicaciones que incluyeron revisiones rápidas de literatura, estudios observacionales y ensayos clínicos. No se encontró información sobre la profilaxis con cloroquina, hidroxicloroquina ni azitromicina para SARS-CoV-2. Los eventos adversos reportados incluyeron emesis, dolor abdominal, náuseas, diarrea, erupción cutánea y picazón. Conclusiones: según la evidencia recopilada el uso de hidroxicloroquina o de cloroquina sola o en combinación con azitromicina en pacientes con COVID-19 no ha mostrado beneficio. Además, cada uno de estos esquemas de tratamiento se asocia con un mayor riesgo de muerte y de episodios de arritmias. En síntesis, la efectividad de estos medicamentos sigue sin estar esclarecida, por lo cual se sugiere evitar su uso en el tratamiento de personas con infección por SARS-CoV-2/COVID-19.
Abstract Introduction: The COVID-19 disease is a health emergency; treatment has not yet been proven. Objective: To present the available evidence of efficacy and safety of the use of hydroxychloroquine and azithromycin in the prophylaxis and management of patients with COVID-19. Methods: A rapid literature review was performed; we consulted Medline, scopus and pubmed databases. Results: Eleven publications were included including rapid literature reviews, observational studies, and clinical trials. No data were found studying prophylaxis with hydroxychloroquine and azithromycin for SARS-CoV-2. Reports of adverse events include episodes of emesis, abdominal pain, nausea, diarrhea, rash, and itching. Conclusions: The evidence collected suggests that the use of hydroxychloroquine and azithromycin in patients with COVID-19, could abnormal electrocardiogram and increased risk of mortality in-hospital. The effectiveness remains unclear.
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Humanos , Masculino , Feminino , Terapêutica , COVID-19 , Pacientes , Cloroquina , Colômbia , Azitromicina , HidroxicloroquinaRESUMO
Pluripotent stem cells (PSCs) have demonstrated great utility in improving our understanding of mammalian development and continue to revolutionise regenerative medicine. Thanks to the improved understanding of pluripotency in mice and humans, it has recently become feasible to generate stable livestock PSCs. Although it is unlikely that livestock PSCs will be used for similar applications as their murine and human counterparts, new exciting applications that could greatly advance animal agriculture are being developed, including the use of PSCs for complex genome editing, cellular agriculture, gamete generation and invitro breeding schemes.
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Agricultura/tendências , Técnicas de Cultura de Células/veterinária , Gado , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/fisiologia , Agricultura/métodos , Animais , Técnicas de Cultura de Células/métodos , Técnicas de Cultura de Células/tendências , Diferenciação Celular , Células Cultivadas , Técnicas de Cultura Embrionária/tendências , Técnicas de Cultura Embrionária/veterinária , Embrião de Mamíferos/citologia , Humanos , Gado/embriologia , CamundongosRESUMO
The availability of tools to accurately replicate the clinical phenotype of rare human diseases is a key step toward improved understanding of disease progression and the development of more effective therapeutics. We successfully generated the first large animal model of a rare human bone disease, hypophosphatasia (HPP) using CRISPR/Cas9 to introduce a single point mutation in the tissue nonspecific alkaline phosphatase (TNSALP) gene (ALPL) (1077 C > G) in sheep. HPP is a rare inherited disorder of mineral metabolism that affects bone and tooth development, and is associated with muscle weakness. Compared to wild-type (WT) controls, HPP sheep have reduced serum alkaline phosphatase activity, decreased tail vertebral bone size, and metaphyseal flaring, consistent with the mineralization deficits observed in human HPP patients. Computed tomography revealed short roots and thin dentin in incisors, and reduced mandibular bone in HPP vs. WT sheep, accurately replicating odonto-HPP. Skeletal muscle biopsies revealed aberrant fiber size and disorganized mitochondrial cristae structure in HPP vs. WT sheep. These genetically engineered sheep accurately phenocopy human HPP and provide a novel large animal platform for the longitudinal study of HPP progression, as well as other rare human bone diseases.
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Fosfatase Alcalina/metabolismo , Modelos Animais de Doenças , Engenharia Genética/métodos , Hipofosfatasia/metabolismo , Fosfatase Alcalina/genética , Animais , Desenvolvimento Ósseo/genética , Feminino , Humanos , Hipofosfatasia/genética , Fenótipo , Mutação Puntual , Ovinos , Fatores de TempoRESUMO
OBJECTIVE: To determine the prevalence of clinical trial registration in the International Clinical Trial Registry Platform (ICTRP) for studies from Latin America and the Caribbean (LAC) and to identify the key characteristics that lead to prospective and retrospective registration. METHODS: A cross-sectional study identified published, clinical trial studies through a search of PubMed, LILACS (Latin American and Caribbean Center on Health Sciences Information), and the Cochrane Central Register of Controlled Trials. Studies were included if published on 1 January - 31 December 2015, at least one author was affiliated with at least one LAC country, the clinical trial was conducted in at least one LAC site, and the full text of the article was available. A manual search of reference lists was also conducted. ICTRP registration information and key trial characteristics were compared. RESULTS: Of 1 502 CT references that met inclusion criteria, 297 were randomly-selected, 90.9% of which were published in English, 65% from Brazil, and 76.8% had a LAC author as the first author. The proportion of CT registered in the ICTRP was 59.9 %, of which 51.7% were registered prospectively. Clinicaltrials.gov was most frequently used registry (84.8%), followed by the Registro Brasileiro de Ensaios Clínicos and the Registro Público Cubano de Ensayos Clínicos. Key characteristics that favored registration were being in study phase 3 or 4 or being a multi-center study. Data was compared to a similar study from 2013 that reported a registration rate of only 19.8%. CONCLUSIONS: Registration adherence and prospective registration have increased in LAC in recent years, but the proportion of unregistered CT remains high. While there are still many challenges to overcome, the adherence strategies implemented in recent years have proven effective.
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ABSTRACT Objective To determine the prevalence of clinical trial registration in the International Clinical Trial Registry Platform (ICTRP) for studies from Latin America and the Caribbean (LAC) and to identify the key characteristics that lead to prospective and retrospective registration. Methods A cross-sectional study identified published, clinical trial studies through a search of PubMed, LILACS (Latin American and Caribbean Center on Health Sciences Information), and the Cochrane Central Register of Controlled Trials. Studies were included if published on 1 January - 31 December 2015, at least one author was affiliated with at least one LAC country, the clinical trial was conducted in at least one LAC site, and the full text of the article was available. A manual search of reference lists was also conducted. ICTRP registration information and key trial characteristics were compared. Results Of 1 502 CT references that met inclusion criteria, 297 were randomly-selected, 90.9% of which were published in English, 65% from Brazil, and 76.8% had a LAC author as the first author. The proportion of CT registered in the ICTRP was 59.9 %, of which 51.7% were registered prospectively. Clinicaltrials.gov was most frequently used registry (84.8%), followed by the Registro Brasileiro de Ensaios Clínicos and the Registro Público Cubano de Ensayos Clínicos. Key characteristics that favored registration were being in study phase 3 or 4 or being a multi-center study. Data was compared to a similar study from 2013 that reported a registration rate of only 19.8%. Conclusions Registration adherence and prospective registration have increased in LAC in recent years, but the proportion of unregistered CT remains high. While there are still many challenges to overcome, the adherence strategies implemented in recent years have proven effective.
RESUMEN Objetivo Determinar la prevalencia del registro de ensayos clínicos de América Latina y el Caribe en la Plataforma de Registros Internacionales de Ensayos Clínicos (ICTRP, por su sigla en inglés) y definir los elementos clave que fomentan el registro prospectivo y retrospectivo de estudios. Métodos Se realizó un estudio transversal para encontrar los ensayos clínicos publicados mediante una búsqueda en PubMed, LILACS (Centro Latinoamericano y del Caribe para Información en Ciencias de la Salud) y el Registro Central Cochrane de Ensayos Clínicos Controlados. Se incluyeron los estudios que habían sido publicados entre el 1 de enero y el 31 de diciembre del 2015, que tenían cuando menos un autor afiliado a uno o más países de América Latina y el Caribe, que se habían realizado al menos en un centro de América Latina y el Caribe, y que tenían el texto completo del artículo disponible. También se llevó a cabo una búsqueda manual en listas de referencia. Se comparó la información sobre registros de la ICTRP y las características clave de los ensayos clínicos. Resultados De las 1 502 referencias que cumplieron los criterios de inclusión, se seleccionaron 297 aleatoriamente. De estas, 90,9% se habían publicado en inglés, 65% eran de Brasil y 76,8% tenían como primer autor un investigador de América Latina y el Caribe. La proporción de ensayos clínicos registrados en la ICTRP fue de 59,9%, de los cuales 51,7% se habían registrado prospectivamente. Clinicaltrials.gov fue el registro usado con mayor frecuencia (84,8%), seguido por el Registro Brasileiro de Ensaios Clínicos y el Registro Público Cubano de Ensayos Clínicos. Se determinó que las características clave que favorecían el registro eran que fuese un estudio de fase 3 o 4 o un estudio multicéntrico. Se compararon los datos con un estudio similar del 2013 en el que se había informado que la tasa de registro era de apenas 19,8%. Conclusiones En América Latina y el Caribe se ha observado en los últimos años un aumento en el cumplimiento del registro y del registro prospectivo de ensayos clínicos, pero la proporción de estudios sin registrar sigue siendo alta. Sin embargo, aunque persisten muchos retos que se deben superar, las estrategias adoptadas en los últimos años para que se cumpla este requisito han sido eficaces.
RESUMO Objetivo Determinar a prevalência do registro de estudos clínicos na Plataforma Internacional de Registro de Ensaios Clínicos (ICTRP) para estudos realizados na América Latina e Caribe (ALC) e identificar as principais características que conduzem ao registro prospectivo e retrospectivo. Métodos Em um estudo transversal, foram identificados os estudos clínicos publicados através de uma busca nas bases de dados PubMed, LILACS (Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde) e Cochrane Central Register of Controlled Trials (CENTRAL). Foram incluídos estudos publicados de 1o. de janeiro a 31 de dezembro de 2015, em que pelo menos um dos autores provinha de um país da ALC, realizados em um ou mais centros na ALC e que apresentavam o texto completo disponível. Foi também feita uma busca manual das listas de referências. Foram comparados os dados sobre o registro na ICTRP e as principais características dos estudos. Resultados Das 1.502 referências de estudos clínicos que atenderam os critérios de inclusão, 297 foram selecionadas aleatoriamente. Verificou-se que 90,9% dos estudos foram publicados em inglês, 65% eram provenientes do Brasil e 76,8% tinham como primeiro autor um pesquisador da ALC. O percentual de registro dos estudos clínicos na ICTRP foi de 59,9%, sendo 51,7% registrado de forma prospectiva. Clinicaltrials.gov foi o registro mais usado (84,8%), seguido do Registro Brasileiro de Ensaios Clínicos e do Registro Público Cubano de Ensayos Clínicos. As principais características que contribuíram para o registro foram ser estudo de fase 3 ou 4 ou multicêntrico. Os dados foram comparados com um estudo semelhante realizado em 2013 que verificou uma taxa de registro de apenas 19,8%. Conclusões Houve um aumento na adesão ao registro e no registro prospectivo na ALC nos últimos anos, porém o percentual de estudos clínicos não registrados continua alto. Embora ainda existam muitos desafios a serem vencidos, as estratégias de adesão implementadas nos últimos anos têm sido eficazes.
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Humanos , Registros de Doenças , Ensaios Clínicos como Assunto/estatística & dados numéricos , MEDLINE , Região do Caribe , LILACS , América LatinaRESUMO
RESUMEN Objetivo Desarrollar y validar un índice compuesto de inequidad en salud basado en mortalidad por grupos de causas. Métodos Estudio ecológico en país de mediano ingreso latinoamericano, con indicadores agregados disponibles de municipios y departamentos, que se seleccionaron a partir de observatorios de salud, grupos de investigación y autoridades sanitarias. Se dividen en intolerables y "no completamente evitables" según el avance científico actual, y se agregan en categorías: accidente de tránsito, agresiones, enfermedad renal, infección por VIH, parasitosis intestinal, sífilis, enfermedad de transmisión fecal/oral, tuberculosis, enfermedad transmitidas por vectores, enfermedad respiratoria, eventos hemorrágicos/ isquémicos cerebrales, mortalidad materna, mortalidad menores 5 años, meningitis. Luego de análisis de componentes principales se obtiene índice compuesto multidimensional de inequidad en salud (IIS) para hombres y mujeres. Consistencia interna se evalúa mediante coeficiente Alpha de Cronbach. Se hace validación concurrente con proporción de personas en Necesidades Básicas Insatisfechas (NBI), Índice de Desarrollo Humano (IDH), Expectativa de Vida al Nacer (EVN) entre otros. Resultados Se construye IIS que muestra valores más altos para las mujeres en la mayoría de municipios y departamentos; y para lugares con IDH alto, EVN alta y NBI bajas. El alpha de Cronbach fue 0.6688, IIS-hombres y 0.725, IIS-mujeres. Conclusiones Se obtiene IIS factible, reproducible y mutidimensional. Se destaca el papel de las grandes ciudades en las inequidades en salud, probablemente por el efecto de los intolerables en salud.(AU)
ABSTRACT Objective To develop and validate a composite index of health inequity based on mortality by grouped causes. Methods An ecological study in a middle-income Latin American country, with aggregate indicators available from municipalities and departments, which were selected from health observatories, research groups and health authorities. They were divided into intolerable and "not completely avoidable" according to current scientific progress, and were added in categories: traffic accident, aggression, kidney disease, HIV infection, intestinal parasitic diseases, syphilis, fecal / oral transmission disease, tuberculosis, disease Vector-borne diseases, respiratory disease, cerebral hemorrhagic / ischemic events, maternal mortality, lower mortality 5 years, meningitis. After analysis of main components, a composite index of health inequity (IIS) is obtained for men and women. Internal consistency was evaluated using Cronbach's Alpha coefficient. Concurrent validation was done with proportion of people in Unsatisfied Basic Needs (UBN), Human Development Index (HDI), Life Expectancy at Birth (LEB), among others. Results IIS is built showing higher values for women in most municipalities and departments; And for sites with high HDI, high LEB and low UBN. Cronbach's alpha was 0.6688, IIS-men and 0.725, IIS-women. Conclusions An IIS was obtained, is valid and reproducible. The role of big cities in inequities in health is highlighted, probably due to the effect of intolerable health.(AU)
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Humanos , Fatores Socioeconômicos , Equidade em Saúde/organização & administração , Indicadores de Saúde Comunitária , Colômbia , Estudos EcológicosRESUMO
OBJECTIVE: To develop and validate a composite index of health inequity based on mortality by grouped causes. METHODS: An ecological study in a middle-income Latin American country, with aggregate indicators available from municipalities and departments, which were selected from health observatories, research groups and health authorities. They were divided into intolerable and "not completely avoidable" according to current scientific progress, and were added in categories: traffic accident, aggression, kidney disease, HIV infection, intestinal parasitic diseases, syphilis, fecal / oral transmission disease, tuberculosis, disease Vector-borne diseases, respiratory disease, cerebral hemorrhagic / ischemic events, maternal mortality, lower mortality 5 years, meningitis. After analysis of main components, a composite index of health inequity (IIS) is obtained for men and women. Internal consistency was evaluated using Cronbach's Alpha coefficient. Concurrent validation was done with proportion of people in Unsatisfied Basic Needs (UBN), Human Development Index (HDI), Life Expectancy at Birth (LEB), among others. RESULTS: IIS is built showing higher values for women in most municipalities and departments; And for sites with high HDI, high LEB and low UBN. Cronbach's alpha was 0.6688, IIS-men and 0.725, IIS-women. CONCLUSIONS: An IIS was obtained, is valid and reproducible. The role of big cities in inequities in health is highlighted, probably due to the effect of intolerable health.
OBJETIVO: Desarrollar y validar un índice compuesto de inequidad en salud basado en mortalidad por grupos de causas. MÉTODOS: Estudio ecológico en país de mediano ingreso latinoamericano, con indicadores agregados disponibles de municipios y departamentos, que se seleccionaron a partir de observatorios de salud, grupos de investigación y autoridades sanitarias. Se dividen en intolerables y "no completamente evitables" según el avance científico actual, y se agregan en categorías: accidente de tránsito, agresiones, enfermedad renal, infección por VIH, parasitosis intestinal, sífilis, enfermedad de transmisión fecal/oral, tuberculosis, enfermedad transmitidas por vectores, enfermedad respiratoria, eventos hemorrágicos/ isquémicos cerebrales, mortalidad materna, mortalidad menores 5 años, meningitis. Luego de análisis de componentes principales se obtiene índice compuesto multidimensional de inequidad en salud (IIS) para hombres y mujeres. Consistencia interna se evalúa mediante coeficiente Alpha de Cronbach. Se hace validación concurrente con proporción de personas en Necesidades Básicas Insatisfechas (NBI), Índice de Desarrollo Humano (IDH), Expectativa de Vida al Nacer (EVN) entre otros. RESULTADOS: Se construye IIS que muestra valores más altos para las mujeres en la mayoría de municipios y departamentos; y para lugares con IDH alto, EVN alta y NBI bajas. El alpha de Cronbach fue 0.6688, IIS-hombres y 0.725, IIS-mujeres. CONCLUSIONES: Se obtiene IIS factible, reproducible y mutidimensional. Se destaca el papel de las grandes ciudades en las inequidades en salud, probablemente por el efecto de los intolerables en salud.
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OBJETIVO: Identificar elementos metodológicos clave para la priorización en investigación en salud, a partir de las metodologías reportadas en la literatura científica. MÉTODOS: Se realizó una búsqueda sistemática en Medline, Embase, LILACS, y fuentes complementarias de literatura gris. Se utilizaron las palabras clave: research, methods y health priorities, en combinación con términos libres. Dos revisores independientes, de acuerdo con criterios previamente definidos, seleccionaron revisiones de la literatura o documentos metodológicos que presentaran metodologías para priorización en investigación en salud. Se extrajeron las principales características de las metodologías reportadas y se identificaron elementos comunes. RESULTADOS: Se incluyeron siete revisiones y cinco documentos metodológicos, que reportaron cuatro metodologías estructuradas específicas y múltiples aproximaciones metodológicas que combinan elementos diversos. En general, estas metodologías integran la perspectiva de actores clave con información objetiva, mediante la aplicación de técnicas estandarizadas de participación, para establecer un ranking de prioridades, con base en criterios previamente definidos. Se identificaron elementos metodológicos comunes relacionados con pasos del proceso, mecanismos de participación, criterios para priorizar y análisis de resultados. CONCLUSIÓN: La priorización en investigación en salud requiere el empleo de una metodología definida a priori, que debe contener como mínimo cuatro elementos clave: pasos claros del proceso, criterios para priorizar, técnicas formales de participación y métodos de análisis de resultados. Estos elementos deben ajustarse a las condiciones y necesidades del contexto de aplicación.
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RESUMEN Objetivo Identificar elementos metodológicos clave para la priorización en investigación en salud, a partir de las metodologías reportadas en la literatura científica. Métodos Se realizó una búsqueda sistemática en Medline, Embase, LILACS, y fuentes complementarias de literatura gris. Se utilizaron las palabras clave: research, methods y health priorities, en combinación con términos libres. Dos revisores independientes, de acuerdo con criterios previamente definidos, seleccionaron revisiones de la literatura o documentos metodológicos que presentaran metodologías para priorización en investigación en salud. Se extrajeron las principales características de las metodologías reportadas y se identificaron elementos comunes. Resultados Se incluyeron siete revisiones y cinco documentos metodológicos, que reportaron cuatro metodologías estructuradas específicas y múltiples aproximaciones metodológicas que combinan elementos diversos. En general, estas metodologías integran la perspectiva de actores clave con información objetiva, mediante la aplicación de técnicas estandarizadas de participación, para establecer un ranking de prioridades, con base en criterios previamente definidos. Se identificaron elementos metodológicos comunes relacionados con pasos del proceso, mecanismos de participación, criterios para priorizar y análisis de resultados. Conclusión La priorización en investigación en salud requiere el empleo de una metodología definida a priori, que debe contener como mínimo cuatro elementos clave: pasos claros del proceso, criterios para priorizar, técnicas formales de participación y métodos de análisis de resultados. Estos elementos deben ajustarse a las condiciones y necesidades del contexto de aplicación.
Objective To identify key methodological elements for prioritization in health research, based on the methodologies reported in the scientific literature. Methods A systematic search was conducted in Medline, Embase, LILACS, and complementary sources of gray literature. Keywords research, methods and health priorities were used in combination with free terms. Two independent reviewers, according to previously defined criteria, selected literature reviews or methodological documents that presented methodologies for prioritization in health research. The main characteristics of the reported methodologies were extracted and common elements were identified. Results Seven revisions and five methodological documents were included, reporting four specific structured methodologies and multiple methodological approaches combining diverse elements. In general, these methodologies integrate the perspective of key stakeholders with objective information, through the application of standardized participation techniques, to establish a ranking of priorities based on previously defined criteria. Common methodological elements related to process steps, participation mechanisms, criteria for prioritizing and analysis of results were identified. Conclusion The prioritization in health research requires the use of a methodology defined a priori, which must contain at least four key elements: clear steps of the process, criteria to prioritize, formal techniques of participation and methods for analysis of results. These elements should be tailored to the conditions and needs of the application context.
RESUMO Objetivo Identificar os principais aspectos metodológicos para a priorização em pesquisa em saúde segundo metodologias descritas na literatura científica. Métodos Foi realizada uma busca sistemática nas bases de dados MEDLINE, Embase, LILACS e fontes complementares da literatura cinzenta. Foram usadas as palavras-chave research, methods e health priorities, em combinação com termos livres. Dois revisores independentes selecionaram, com base em critérios predefinidos, estudos de revisão da literatura ou textos metodológicos que descreviam metodologias para a priorização em pesquisa em saúde. Foram extraídas as principais características das metodologias descritas e identificados os aspectos comuns. Resultados Foram incluídos sete estudos de revisão e cinco textos metodológicos, que descreviam quatro metodologias estruturadas específicas e vários enfoques metodológicos que combinavam diversos aspectos. As metodologias em geral integram a perspectiva de atores-chave com informação objetiva, com a aplicação de técnicas padronizadas de participação, a fim de determinar a ordem de prioridade segundo critérios predefinidos. Foram identificados aspectos metodológicos comuns relacionados às etapas do processo, mecanismos de participação, critérios para priorização e análise de resultados. Conclusão A priorização em pesquisa em saúde requer o uso de uma metodologia definida a priori, que no mínimo deve englobar quatro aspectos principais: etapas distintas do processo, critérios para priorização, técnicas formais de participação e métodos de análise de resultados. Estes aspectos devem ser adaptados às condições e necessidades do contexto de aplicação.
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Pesquisa , Revisão , Prioridades em SaúdeRESUMO
BACKGROUND: The current practice of plasmapheresis at most centers employs anticoagulation of the extracorporeal circuit, which has been associated with complications. There are few studies evaluating the efficacy and safety of using plasmapheresis without any anticoagulation. We report our experience using this strategy in children (1 month to 18 years old) over a period of 5 years. RESULTS: Two hundred forty-three plasmapheresis sessions without anticoagulation of the extracorporeal circuit, in 27 pediatric patients, were analyzed. Of these, 81.4% were female and the predominant age range was 12-18 years (70.3%). One hundred percent of the patients had PRISM III scale low mortality risk, and the main indication of therapy was acute rejection after renal transplantation (25.9%), followed by recurrence of focal segmental sclerosis in the transplanted kidney (17.2%). Filtration lasted more than 3 hours in 86.8% of cases, with bleeding complications in 2.9% of patients requiring early termination due to associated complications in 3.2% of cases. Other complications were paresthesias (0.41%), vomiting (5%), hypertension during (67.4%) and after therapy (64.6%), and hyperchloremia (46.5%). CONCLUSIONS: In our experience, plasmapheresis without circuit anticoagulation in children is safe and effective, with a low frequency of bleeding and hydroelectrolytic complications, allowing the achievement of therapeutic goals without altering therapy duration and efficiency. Prospective studies are needed to corroborate these findings.
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Circulação Extracorpórea/efeitos adversos , Hemorragia/epidemiologia , Hemorragia/etiologia , Plasmaferese/efeitos adversos , Adolescente , Criança , Feminino , Humanos , MasculinoRESUMO
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by inflammation of multiple joints, leading to destruction of cartilage and juxta articular bone. It eventually leads to deformity, disability, and impaired quality of life. Methotrexate (MTX) has a reported response rate of 33-65%, and this variability may be explained by genetic _ variations (polymorphisms) in the metabolic pathway of this drug. To evaluate possible relationships between polymorphisms in the metabolic pathway and response to MTX in patients with RA. METHODOLOGY: A systematic search and review of the literature was conducted. A total of 29 studies that evaluated polymorphisms in the metabolic pathway of MTX were included, due to their full text and methodological quality. RESULTS: Of the 29 studies, five were systematic reviews and/or meta-analyses, three of which clinical trials none was triple blind and only one was double-blind, six were cohort, seven were case-control, and eight cross sectional. The polymorphism identified were: methylene tetrahydrofolate reductase, dihydrofolate reductase, thymidylate synthase, 5-aminoimidazole-4-carboxamide ribonucleotide formyl transferase (AICAR formyltransferase), 5-aminoimidazole-4-carboxamide polymorphisms formyltransferase/IMP cyclohydrolase ribonucleotide (ATIC) identified conveyors attached to ATP cassette (ABC ATP-binding cassette), folylpoly-glutamate, glutamyl hydrolase, reduced folate carrier (RFC-SLC10A1). The dihydrofolate reductase and methylene tetrahydrofolate reductase polymorphism were shown to be associated with increased MTX toxicity. RFC and C677T polymorphisms are associated with better efficacy of MTX. CONCLUSIONS: The polymorphisms of methylene tetrahydrofolate reductase, C677T and RFC1-G80A generate increased efficacy and toxicity in patients treated with MTX. However, for the other polymorphisms, although studies show statistically significant associations, they are not conclusive and some are contradictory. This justifies conducting multicenter studies to assess the presence and association with the effectiveness or toxicity in patients with RA treated with MTX.
Antecedentes: La artritis reumatoide (AR) es una enfermedad inflamatoria de origen autoinmune, caracterizada por inflamación de múltiples articulaciones que lleva a destrucción del cartílago y del hueso yuxta articular, con el tiempo genera deformidad, discapacidad y deterioro de la calidad de vida. El metotrexato (MTX), reporta un índice de respuesta del 33 al 65%, esta variabilidad puede ser explicada por las variaciones genéticas (polimorfismos) en la ruta metabólica de este fármaco. OBJETIVO: Evaluar las posibles asociaciones entre los polimorfismos de la ruta metabólica del MTX y su respuesta en pacientes con AR. METODOLOGÍA: Revisión sistemática de la literatura cualitativa (integrative review). Se realizó una búsqueda sistemática de la literatura, 29 estudios fueron incluidos por texto completo y por calidad metodológica para alcanzar el objetivo del estudio, estos estudios evaluaron polimorfismos en la ruta metabólica del MTX. RESULTADOS: De los 29 estudios, cinco fueron revisiones sistemáticas o metaanálisis, tres ensayos clínicos de los cuales ninguno fue triple ciego y solo uno fue doble ciego, seis fueron cohortes, siete fueron casos y controles y ocho de corte transversal. Se identificaron los polimorfismos de metiltetrahidofolato reductasa, dihidrofolato reductasa, timidilato sintetasa, 5-aminoimidazol-4-carboxamida ribonucleótido formiltransferasa (AICAR formiltransferasa), 5-aminoimidazol-4-carboxamida ribonucleótido formiltransferasa/IMP ciclohidrolasa (ATIC), transportadores de casete unidos a ATP (ABC ATP-binding cassette), folilglutamato sintetasa, glutamil hidrolasa, transportador de folato reducido (RFC-SLC10A1). Los polimorfismos metiltetrahidofolato reductasa y dihidrofolato reductasa demostraron estar asociados con un aumento en la toxicidad del MTX; los polimorfismos RFC y C677T están asociados a una mejor eficacia del MTX. CONCLUSIONES: Los polimorfismos de metiltetrahidofolato reductasa C677T y RFC1 - G80A generan aumento de eficacia y toxicidad en pacientes tratados con MTX. Sin embargo, para los demás polimorfismos, aunque los estudios muestran asociaciones estadísticamente significativas, no son concluyentes y algunos son contradictorios. Lo anterior justifica la realización de estudios de carácter multicéntrico, para evaluar la presencia y asociación, con la eficacia o toxicidad en los pacientes con artritis reumatoide tratados con MTX.
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Humanos , Farmacogenética , Artrite Reumatoide , MetotrexatoRESUMO
OBJECTIVES: Summarize hepatitis C virus (HCV) prevalence in injecting (IDU) and non-injecting drug users (NIDU), men who have sex with men (MSM), sex workers, and prison inmates in Latin America and the Caribbean (LAC). METHODS: Systematic review on HCV prevalence in sub-populations in LAC. Databases searched from 1-1-2000 to 10-30-2013. INCLUSION CRITERIA: prevalence studies in sub-populations in LAC. HCV-antibody was marker for prevalence of current/past HCV infection and HCV-RNA for prevalence of HCV current infection. RESULTS: IDU HCV current/past infection presented highest prevalence, from 1.7 % in Colombia to over 95 % in Ciudad Juarez and Tijuana, Mexico and pooled regional anti-HCV prevalence was 49 % (CI 95 % 22.6-76.3 %). NIDU, MSM and sex workers anti-HCV prevalence was below 10 %, and pooled regional prevalence of 4 % (CI 95 % 2.6-4.5 %), 3 % (CI 95 % 1.7-4.5 %) and 2 % (CI 95 % 1.0-3.4 %), respectively. Prison inmates presented higher values, but prevalence decreased over the 15-year time span (p < 0.001). Current HCV infection from three countries showed prevalence under 10 % in prison inmates and 1-46 % among drug users. CONCLUSIONS: Disease burden is high and surveillance, prevention and treatment should target these groups in LAC.
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Usuários de Drogas/estatística & dados numéricos , Hepatite C/epidemiologia , Homossexualidade Masculina , Prisioneiros/estatística & dados numéricos , Profissionais do Sexo/estatística & dados numéricos , Região do Caribe/epidemiologia , Feminino , Hepatite C/virologia , Humanos , América Latina/epidemiologia , Masculino , Prevalência , Fatores de Risco , Abuso de Substâncias por Via Intravenosa/epidemiologia , Pessoas Transgênero/estatística & dados numéricosRESUMO
INTRODUCTION: Few studies have assessed the nature and quality of randomized controlled trials (RCTs) in Latin America and the Caribbean (LAC). METHODS AND FINDINGS: The aims of this systematic review are to evaluate the characteristics (including the risk of bias assessment) of RCT conducted in LAC according to funding source. A review of RCTs published in 2010 in which the author's affiliation was from LAC was performed in PubMed and LILACS. Two reviewers independently extracted data and assessed the risk of bias. The primary outcomes were risk of bias assessment and funding source. A total of 1,695 references were found in PubMed and LILACS databases, of which 526 were RCTs (Nâ=â73.513 participants). English was the dominant publication language (93%) and most of the RCTs were published in non-LAC journals (84.2%). Only five of the 19 identified countries accounted for nearly 95% of all RCTs conducted in the region (Brazil 70.9%, Mexico 10.1%, Argentina 5.9%, Colombia 3.8%, and Chile 3.4%). Few RCTs covered priority areas related with Millennium Development Goals like maternal health (6.7%) or high priority infectious diseases (3.8%). Regarding children, 3.6% and 0.4% RCT evaluated nutrition and diarrhea interventions respectively but none pneumonia. As a comparison, aesthetic and sport related interventions account for 4.6% of all trials. A random sample of RCTs (nâ=â358) was assessed for funding source: exclusively public (33.8%); private (e.g. pharmaceutical company) (15.3%); other (e.g. mixed, NGO) (15.1%); no funding (35.8%). Overall assessments for risk of bias showed no statistically significant differences between RCTs and type of funding source. Statistically significant differences favoring private and others type of funding was found when assessing trial registration and conflict of interest reporting. CONCLUSION: Findings of this study could be used to provide more direction for future research to facilitate innovation, improve health outcomes or address priority health problems.