Asociación del grupo sanguíneo ABO con complicaciones en covid-19: revisión sistemática y meta-análisis / Asociation between abo blood groups and covid-19 complications: systematic review and meta-analysis

Introducción: los grupos sanguíneos ABO han sido utilizados como marcadores de desenlace en diferentes enfermedades, otorgando al grupo O un factor protector y al A uno de riesgo. Durante el brote de SARS CoV-1 se planteó la posible relación entre riesgo de infección y tipo sanguíneo; se presume que en la pandemia por COVID-19 exista una relación entre determinados desenlaces y los grupos ABO. Objetivo: determinar la asociación entre los diferentes grupos sanguíneos y los desenlaces de mortalidad, ingreso a cuidados intensivos y requerimiento de intubación orotraqueal (IOT) en población con infección por COVID-19. Materiales y métodos: revisión sistemática y metanálisis entre enero 2020 y marzo 2021 en las bases de datos MEDLINE, EMBASE, SCOPUS, Latindex y LILACS, identificando los desenlaces mencionados en pacientes con COVID-19. Resultados: se incluyeron 16 estudios, la mayoría retrospectivos multicéntricos. Se evidenció que pacientes con grupo sanguíneo A tienen mayor riesgo de mortalidad (OR 1.08 ;1.01-0.17), frente al ingreso a UCI no hubo diferencia estadística significativa entre los grupos sanguíneos. Se encontró que el AB representa un factor de riesgo para intubación orotraqueal (OR 1.42 IC95% 1.02-1.96), en tanto que el A demostró proteger contra este desenlace (OR 0.84 IC95%0.73-0.97). Conclusiones: hay evidencia sobre la relación entre el grupo sanguíneo y los desenlaces, asociada con la infección por SARS-CoV-2. Se requieren estudios prospectivos que evalúen grupo sanguíneo, RH y desenlaces específicos.

Introduction: ABO blood groups have been used as outcome markers in various diseases, conferring group O a protective factor and group A a risk factor. During the SARS CoV-1 outbreak, it was suggested that blood type appeared to have a relationship with the risk of infection; it is believed that in the COVID-19 pandemic, ABO blood types, are relevant for certain outcomes. Objective: to determine the association between blood types and death, admission to intensive care and risk of intubation among COVID-19 patients. Materials and methods: a systematic review and meta-analysis from MEDIA, EMBASSY, SCOPUS, Latindex and LILACS databases, identifying the abovementioned outcomes among COVID 19 patients, conducted between January 2020 and March 2021. Results: 16 studies were included, most of them retrospective multicenter studies. It was evidenced that patients with blood group A have a higher mortality risk (OR 1.08:1.01-0.17). There was no statistically significant difference between blood groups for ICU admission. AB was found to be a risk factor for intubation (OR 1.42: CI95% 1.02 -1.96), while type A had a protective effect against this outcome (OR 0.84: CI95% 0.73 -0.97). Conclusions: there is evidence on a relationship between blood groups and outcomes in SARS CoV-2 infection. Prospective studies evaluating ABO and Rh(D) blood types and specific outcomes, are required.

Colchicine: A potential therapeutic tool against COVID-19. Experience of 5 patients / Colchicina: una herramienta terapéutica potencial frente a COVID-19. Experiencia en 5 pacientes

COVID-19 is a newly emerged disease that has become a global public health challenge. Due to a lack of knowledge about the virus, a significant number of potential targets for using a particular drug have been proposed. Five cases with a clinical history of biopolymers in the gluteal region that developed iatrogenic allogenosis (IA) are presented here. The 5 cases were put under colchicine treatment for IA crisis and had non-specific symptoms (headache, cough without dyspnea, and arthralgias) with a positive SARS-CoV-2 test. Their close contacts had mild to severe symptoms and three of them died. In the SARS-CoV-2 infection different inflammatory pathways are altered where colchicine reduces cytokine levels as well as the activation of macrophages, neutrophils, and the inflammasome. The possible mechanisms that colchicine may use to prevent acute respiratory distress syndrome (ARDS) in patients with COVID-19 infection are also reviewed in this article.(AU)

COVID-19 es una enfermedad de aparición reciente, que se ha convertido en un reto global de salud pública. Debido a la falta de conocimiento acerca del virus, se ha propuesto un número significativo de objetivos potenciales para utilizar un fármaco en particular. Presentamos 5 casos con historia clínica de biopolímeros en la región glútea, que desarrollaron alogenosis iatrogénica (AI). A los 5 casos se les administró tratamiento de colchicina debido a la crisis de AI, no teniendo síntomas específicos (cefalea, tos sin disnea y artralgias), con resultado positivo en el test de SARS-CoV-2. Sus contactos cercanos tenían síntomas de leves a graves, y 3 de ellos fallecieron. En la infección por SARS-CoV-2 se alteran diferentes rutas inflamatorias, en las que la colchicina reduce los niveles de citocinas y la activación de macrófagos, neutrófilos e inflamasoma. Revisamos también, en este artículo, los posibles mecanismos que puede utilizar colchicina para prevenir el síndrome de distrés respiratorio agudo (SDRA) en pacientes con COVID-19.(AU)

Colchicine: A potential therapeutic tool against COVID-19. Experience of 5 patients.

COVID-19 is a newly emerged disease that has become a global public health challenge. Due to a lack of knowledge about the virus, a significant number of potential targets for using a particular drug have been proposed. Five cases with a clinical history of biopolymers in the gluteal region that developed iatrogenic allogenosis (IA) are presented here. The 5 cases were put under colchicine treatment for IA crisis and had non-specific symptoms (headache, cough without dyspnea, and arthralgias) with a positive SARS-CoV-2 test. Their close contacts had mild to severe symptoms and three of them died. In the SARS-CoV-2 infection different inflammatory pathways are altered where colchicine reduces cytokine levels as well as the activation of macrophages, neutrophils, and the inflammasome. The possible mechanisms that colchicine may use to prevent acute respiratory distress syndrome (ARDS) in patients with COVID-19 infection are also reviewed in this article.

Colchicine: A potential therapeutic tool against COVID-19. Experience of 5 patients.

COVID-19 is a newly emerged disease that has become a global public health challenge. Due to a lack of knowledge about the virus, a significant number of potential targets for using a particular drug have been proposed. Five cases with a clinical history of biopolymers in the gluteal region that developed iatrogenic allogenosis (IA) are presented here. The 5 cases were put under colchicine treatment for IA crisis and had non-specific symptoms (headache, cough without dyspnea, and arthralgias) with a positive SARS-CoV-2 test. Their close contacts had mild to severe symptoms and three of them died. In the SARS-CoV-2 infection different inflammatory pathways are altered where colchicine reduces cytokine levels as well as the activation of macrophages, neutrophils, and the inflammasome. The possible mechanisms that colchicine may use to prevent acute respiratory distress syndrome (ARDS) in patients with COVID-19 infection are also reviewed in this article.

COVID-19 es una enfermedad de aparición reciente, que se ha convertido en un reto global de salud pública. Debido a la falta de conocimiento acerca del virus, se ha propuesto un número significativo de objetivos potenciales para utilizar un fármaco en particular. Presentamos 5 casos con historia clínica de biopolímeros en la región glútea, que desarrollaron alogenosis iatrogénica (AI). A los 5 casos se les administró tratamiento de colchicina debido a la crisis de AI, no teniendo síntomas específicos (cefalea, tos sin disnea y artralgias), con resultado positivo en el test de SARS-CoV-2. Sus contactos cercanos tenían síntomas de leves a graves, y 3 de ellos fallecieron. En la infección por SARS-CoV-2 se alteran diferentes rutas inflamatorias, en las que la colchicina reduce los niveles de citocinas y la activación de macrófagos, neutrófilos e inflamasoma. Revisamos también, en este artículo, los posibles mecanismos que puede utilizar colchicina para prevenir el síndrome de distrés respiratorio agudo (SDRA) en pacientes con COVID-19.

VI encuentro nacional de semilleros de investigación en salud / Sixth National Meeting of Health Research IncubatorsIncubators

"Hacia la consolidación de una cultura de investigación en salud desde las nuevas generaciones"El origen de la educación universitaria a partir de siete artes liberales reunidas en el Trívium (gramática, dialéctica y retórica) y el Quadrivium (aritmética, geometría, astronomía y música), marcan un cambio generacional irreversible en la edad media. El joven estudiante era formado en el uso del trívium como instrumento para el autoaprendizaje y después a través del quadrivium profundizaba en el conocimiento de las ciencias y las artes. Bajo este modelo se formaron científicos notables como Nicolás Copérnico, Isaac Newton, Marie Curie, Henri Poincare, Iván Pávlov e Iliá Méchnikov, entre muchos otros. Un elemento común en el proceso educativo de estos investigadores fue la formación y guía recibida en un momento determinante de sus vidas por su mentor, un profesional con experiencia y alta formación, pero ante todo un consejero, capaz de motivar y potenciar con disciplina y constancia las habilidades innatas del joven estudiante por el conocimiento, materializando así sus sueños en un proyecto de vida con vocación de servicio social.

Proyecciones de impacto de la pandemia COVID-19 en la población colombiana, según medidas de mitigación: datos preliminares de modelos epidemiológicos para el periodo del 18 de marzo al 18 de abril de 2020 / Impact of the COVID-19 pandemic on the Colombian population according to mitigation measures: preliminary data from epidemiological models for the period March 18 to April 18, 2020

RESUMEN Objetivo Este estudio tiene como primer objetivo: realizar predicciones del curso de la infección en el horizonte temporal desde marzo 18 a abril 18 del 2020, según diferentes medidas de aislamiento aplicadas. Las predicciones incluyen, población total contagiada, mortalidad y necesidad de recursos hospitalarios. Segundo objetivo: modelar la mortalidad y la necesidad de recursos hospitalarios, estratificando por edad el escenario de contagio del 70% de la población. Métodos Para el primer objetivo, nos basamos en el número de casos confirmados en el país hasta marzo 18, 2020 (n=93). Como suposiciones para el modelo, incluimos un índice de contagio R0=2,5 y el índice de casos reales por cada caso confirmado. Para la proporción de pacientes que necesitarían cuidados intensivos u otros cuidados intrahospitalarios, nos basamos en datos aportados por el Imperial College of London. Para el segundo objetivo usamos como tasa de mortalidad por edad, datos aportados por el Instituto Superiore di Sanità en Italia. Resultados Basándonos en los 93 casos reportados al 18 de marzo, si no se aplicase ninguna medida de mitigación, para el 18 de abril el país tendría un total de 613 037 casos. Medidas de mitigación que reduzcan el R0 en un 10%, generan una reducción del 50% del número de casos. Sin embargo, a pesar de reducirse los casos a la mitad, todavía habría un déficit en el número de camas requeridas y sólo uno de cada dos pacientes tendría acceso a dicho recurso. Conclusión En nuestro modelo encontramos que las medidas de mitigación que han sido implementadas hasta la fecha por el gobierno colombiano, se fundamentan en evidencia suficiente para pensar que es posible reducir significativamente el número de casos contagiados y con esto, el número de pacientes que requerirán manejo hospitalario.(AU)

ABSTRACT Introduction First case of COVID-19 in Colombia was diagnosed on March 6th. Two weeks later, cases have rapidly increased, leading the government to establish some mitigation measures. Objectives The first objective is to estimate and model the number of cases, use of hospital resources and mortality by using different R0 scenarios in a 1-month scenario (from March 18 to April 18, 2020), based on the different isolation measures applied. This work also aims to model, without establishing a time horizon, the same outcomes given the assumption that eventually 70% of the population will be infected. Materials and Methods Data on the number of confirmed cases in the country as of March 18, 2020 (n=93) were taken as the basis for the achievement of the first objective. An initial transmission rate of R0= 2.5 and a factor of 27 for undetected infections per each confirmed case were taken as assumptions for the model. The proportion of patients who may need intensive care or other in-hospital care was based on data from the Imperial College of London. On the other hand, an age-specific mortality rate provided by the Instituto Superiore di Sanità in Italy was used for the second objective. Results Based on the 93 cases reported as of March 18, if no mitigation measures were applied, by April 18, the country would have 613 037 cases. Mitigation measures that reduce R0 by 10% generate a 50% reduction in the number of cases. However, despite halving the number of cases, there would still be a shortfall in the number of beds required and only one in two patients would have access to this resource. Conclusion This model found that the mitigation measures implemented to date by the Colombian government and analyzed in this article are based on sufficient evidence and will help to slow the spread of SARS-CoV-2 in Colombia. Although a time horizon of one month was used for this model, it is plausible to believe that, if the current measures are sustained, the mitigation effect will also be sustained over time.(AU)

[Impact of the COVID-19 pandemic on the Colombian population according to mitigation measures. Preliminary data from epidemiological models for the period March 18 to April 18, 2020]. / Proyecciones de impacto de la pandemia COVID-19 en la población colombiana, según medidas de mitigación. Datos preliminares de modelos epidemiológicos para el periodo del 18 de marzo al 18 de abril de 2020.

INTRODUCTION: First case of COVID-19 in Colombia was diagnosed on March 6th. Two weeks later, cases have rapidly increased, leading the government to establish some mitigation measures. OBJECTIVES: The first objective is to estimate and model the number of cases, use of hospital resources and mortality by using different R0 scenarios in a 1-month scenario (from March 18 to April 18, 2020), based on the different isolation measures applied. This work also aims to model, without establishing a time horizon, the same outcomes given the assumption that eventually 70% of the population will be infected. MATERIALS AND METHODS: Data on the number of confirmed cases in the country as of March 18, 2020 (n=93) were taken as the basis for the achievement of the first objective. An initial transmission rate of R0= 2.5 and a factor of 27 for undetected infections per each confirmed case were taken as assumptions for the model. The proportion of patients who may need intensive care or other in-hospital care was based on data from the Imperial College of London. On the other hand, an age-specific mortality rate provided by the Instituto Superiore di Sanità in Italy was used for the second objective. RESULTS: Based on the 93 cases reported as of March 18, if no mitigation measures were applied, by April 18, the country would have 613 037 cases. Mitigation measures that reduce R0 by 10% generate a 50% reduction in the number of cases. However, despite halving the number of cases, there would still be a shortfall in the number of beds required and only one in two patients would have access to this resource. CONCLUSION: This model found that the mitigation measures implemented to date by the Colombian government and analyzed in this article are based on sufficient evidence and will help to slow the spread of SARS-CoV-2 in Colombia. Although a time horizon of one month was used for this model, it is plausible to believe that, if the current measures are sustained, the mitigation effect will also be sustained over time.

Pandemia por COVID-COVID-19: un reto 19: un reto en tiempo real / The COVID-19 pandemic: a real-time challenge

En el siglo XVI las enfermedades más devastadoras de origen respiratorio eran conocidas como fiebre catarral, pero a partir del siglo XIX fueron denominadas influenza y posteriormente gripe, siendo la más conocida de ellas la denominada "gripe española", causada por el virus de influenza tipo A; subtipo H1N1. Gracias a los registros sanitarios de la época, podemos saber que está infección fue desde su inicio un reto para los sistemas de salud y el personal médico, dado que en la mayoría de los hospitales no se conocía la causa, los síntomas y mucho menos como tratarla, de hecho se promulgaron múltiples tratamientos desde la aspirina y la quinina hasta la trementina, siendo esta última utilizada para estimular al sistema inmune.

Colchicine: a potential therapeutic tool against COVID-19. Experience of 5 patients / Colchicina: una herramienta terapéutica potencial frente a COVID-19. Experiencia en 5 pacientes

COVID-19 is a newly emerged disease that has become a global public health challenge. Due to a lack of knowledge about the virus, a significant number of potential targets for using a particular drug have been proposed. Five cases with a clinical history of biopolymers in the gluteal region that developed iatrogenic allogenosis (IA) are presented here. The 5 cases were put under colchicine treatment for IA crisis and had non-specific symptoms (headache, cough without dyspnoea, and arthralgias) with a positive SARS-CoV-2 test. Their close contacts had mild to severe symptoms and three of them died. In the SARS-CoV-2 infection different inflammatory pathways are altered where colchicine reduces cytokine levels as well as the activation of macrophages, neutrophils, and the inflammasome. The possible mechanisms that colchicine may use to prevent acute respiratory distress syndrome (ARDS) in patients with COVID-19 infection are also reviewed in this article

COVID-19 es una enfermedad de aparición reciente, que se ha convertido en un reto global de salud pública. Debido a la falta de conocimiento acerca del virus, se ha propuesto un número significativo de objetivos potenciales para utilizar un fármaco en particular. Presentamos aquí cinco casos con historia clínica de biopolímeros en la región glútea, que desarrollaron alogenosis iatrogénica (AI). A los 5 casos se les administró tratamiento de colchicina debido a crisis de AI, no teniendo síntomas específicos (cefalea, tos sin disnea, y artralgias), con resultado positivo en el test de SARS-CoV-2. Sus contactos cercanos tenían síntomas de leves a graves, y tres de ellos fallecieron.  En la infección por SARS-CoV-2 se alteran diferentes rutas inflamatorias, en las que la colchicina reduce los niveles de citocinas y la activación de macrófagos, neutrófilos e inflamasoma. Revisamos también en este artículo los posibles mecanismos que puede utilizar colchicina para prevenir el síndrome de distrés respiratorio agudo (SDRA) en pacientes con COVID-19

Encuentro nacional de semilleros. "Un camino hacia la excelencia" / Incubator National Meeting: "A path toward excellence"

Doy inicio a este editorial con la famosa y visionaria descripción del ingeniero eléctrico, mecánico, físico y matemático Nikola Tesla: "Un instrumento de poco costo, y no más grande que un reloj, permitirá a su portador escuchar en cualquier parte, ya sea en el mar o en la tierra, música, canciones o un discurso de un líder político, dictado en cualquier otro sitio distante. Del mismo modo, cualquier dibujo o impresión podrá ser transferida de un lugar a otro". Estas palabras fueron escritas hace más de noventa años por un joven que cultivó el criterio, la persistencia y siempre mantuvo una actitud de servicio a través de la investigación. Actualmente las universidades son las responsables de formar a los jóvenes investigadores, con el objetivo de incubar la semilla de los futuros generadores del cambio a partir de la investigación; es por ello que dentro de la políticas institucionales de investigación en la Fundación Universitaria de Ciencias de la Salud se promueve el desarrollo de competencias investigativas en los jóvenes estudiantes de pregrado, se incentiva el ejercicio extracurricular de la investigación a través de los semilleros de investigación y la participación de los estudiantes en actividades de divulgación de los resultados de investigación, con la posibilidad de ser coautores de acuerdo con su nivel de contribución. Con el objetivo de fortalecer la socialización y divulgación de resultados de los semilleros de investigación a nivel local y nacional y bajo la organización de la división de investigaciones, la FUCS organizó en julio de 2012 el primer Encuentro Nacional de Semilleros de Investigación en el cual se presentaron 219 trabajos y asistieron 1200 estudiantes provenientes de los semilleros de investigación de 39 facultades de medicina del país. Ante la acogida del evento por parte de los jóvenes investigadores, la FUCS ha dado continuidad y apoyo a esta iniciativa mediante la realización de dichos encuentros con una periodicidad bienal y el fortalecimiento académico y científico a través de la invitación de conferencistas internacionales de amplio reconocimiento en sus áreas de investigación, quienes durante el evento interactúan con los jóvenes investigadores compartiendo sus experiencias en la generación de nuevo conocimiento

Nanomedicina y su impacto en la práctica médica / Nanomedicine and its impact on medical practice

Uno de los principios fundamentales en la práctica clínica es la detección mediante el examen clínico del paciente de los signos y síntomas relacionados con una entidad específica; su presencia implica alteraciones en procesos a nivel molecular, celular y tisular sucedidos en un lapso de tiempo denominado periodo de incubación de la enfermedad. La detección precoz y el rápido establecimiento de un tratamiento se asocian con una mejoría en el pronóstico de la evolución y por ende en las condiciones de salud y calidad de vida del paciente.

One of the fundamental principles in clinical practice is the detection by means of the clinical examination of the patient of the signs and symptoms related to a specific entity; its presence implies alterations in processes at the molecular, cellular and tissue levels that occurred in a period of time called the incubation period of the disease. Early detection and the rapid establishment of a treatment are associated with an improvement in the prognosis of the evolution and therefore in the conditions of health and quality of life of the patient.

Characterising atypical Candida albicans clinical isolates from six third-level hospitals in Bogotá, Colombia.

BACKGROUND: Candida species are the most frequently found fungal pathogens causing nosocomial disease in a hospital setting. Such species must be correctly identified to ensure that appropriate control measures are taken and that suitable treatment is given for each species. Candida albicans is causing most fungal disease burden worldwide; the challenge lies in differentiating it from emerging atypical, minor and related species such as Candida dubliniensis and Candida africana. The purpose of this study was to compare identification based on MALDI-TOF MS to standard identification systems using a set of nosocomial isolates. METHODS: Eleven nosocomial samples were collected from 6 third-level hospitals in Bogotá, Colombia. All the samples were identified by combining MALDI-TOF MS with morphological characters, carbohydrate assimilation and molecular markers (D1/D2 and HWP1). RESULTS: The present work describes the first collection of atypical Colombian Candida clinical isolates; these were identified as Candida albicans/Candida africana by their MALDI-TOF MS profile. Phenotypical characteristics showed that they were unable to produce chlamydospores, assimilate trehalose, glucosamine, N- acetyl-glucosamine and barely grew at 42 °C, as would be expected for Candida africana. The molecular identification of the D1/D2 region of large subunit ribosomal RNA and HWP1 hyphal cell wall protein 1 sequences from these isolates was consistent with those for Candida albicans. The mass spectra obtained by MALDI-TOF MS were analysed by multi-dimensional scaling (MDS) and cluster analysis, differences being revealed between Candida albicans, Candida africana, Candida dubliniensis reference spectra and two clinical isolate groups which clustered according to the clinical setting, one of them being clearly related to C. albicans. CONCLUSION: This study highlights the importance of using MALDI-TOF MS in combination with morphology, substrate assimilation and molecular markers for characterising Candida albicans-related and atypical C. albicans species, thereby overcoming conventional identification methods. This is the first report of hospital-obtained isolates of this type in Colombia; the approach followed might be useful for gathering knowledge regarding local epidemiology which could, in turn, have an impact on clinical management. The findings highlight the complexity of distinguishing between typical and atypical Candida albicans isolates in hospitals.

New echinocandin susceptibility patterns for nosocomial Candida albicans in Bogotá, Colombia, in ten tertiary care centres: an observational study.

BACKGROUND: Candida albicans remains as the first cause of nosocomial fungal infections in hospitals worldwide and its susceptibility pattern should be better described in our tertiary care hospitals. METHODS: This study aimed at identifying the caspofungin susceptibility pattern regarding nosocomial Candida albicans infection in ten tertiary care hospitals using the methodology proposed by CLSI M27-A3 and CLSI M27-S4, and its association with risk factors and clinical outcome. The approach involved descriptive research concerning the diagnosis of nosocomial infection during a 7-month period in 10 hospitals in Bogotá, Colombia. Associations were established using exact non-parametric statistical tests having a high statistical power (>95%), suitable for small samples. The exact Mann Whitney test or Kruskall-Wallis non-parametric ANOVA tests were used for distributions which were different to normal or ordinal variables when comparing three or more groups. Multivariate analysis involved using binomial, multinomial and ordinal exact logistical regression models (hierarchical) and discrimination power was evaluated using area under the ROC curve. RESULTS: 101 nosocomial infections were found in 82,967 discharges, for a Candida spp. infection rate of 12.2 per 10,000 discharges, 30.7% caused by C. albicans, 22.8% by C. tropicalis, 20.8% by C. parapsilosis, 19.8% by other Candida, 3% by C. krusei and 3% by C. glabrata. Statistically significant associations between mortality rate and the absence of parenteral nutrition were found in multivariate analysis (OR = 39.746: 1.794-880.593 95% CI: p = 0.020). The model's predictive power was 83.9%, having an 85.9% significant prediction area (69.5%-100 95% CI; p = 0.001). CONCLUSIONS: Significant differences were found regarding susceptibility results when comparing CLSI M27-A3 to CLSI M27-S4 when shifting clinical break-point values. However, one nosocomial strain was consistent in having reduced susceptibility when using both guidelines without having been directly exposed to echinocandins beforehand and no mutations were found in the FKS1 gene for hot spot 1 and/or hot spot 2 regions, thereby highlighting selective pressure regarding widespread antifungal use in tertiary healthcare centres. Nutritional conditions and low family income were seen to have a negative effect on survival rates.

Trends and predictors of transmitted drug resistance (TDR) and clusters with TDR in a local Belgian HIV-1 epidemic.

We aimed to study epidemic trends and predictors for transmitted drug resistance (TDR) in our region, its clinical impact and its association with transmission clusters. We included 778 patients from the AIDS Reference Center in Leuven (Belgium) diagnosed from 1998 to 2012. Resistance testing was performed using population-based sequencing and TDR was estimated using the WHO-2009 surveillance list. Phylogenetic analysis was performed using maximum likelihood and Bayesian techniques. The cohort was predominantly Belgian (58.4%), men who have sex with men (MSM) (42.8%), and chronically infected (86.5%). The overall TDR prevalence was 9.6% (95% confidence interval (CI): 7.7-11.9), 6.5% (CI: 5.0-8.5) for nucleoside reverse transcriptase inhibitors (NRTI), 2.2% (CI: 1.4-3.5) for non-NRTI (NNRTI), and 2.2% (CI: 1.4-3.5) for protease inhibitors. A significant parabolic trend of NNRTI-TDR was found (p = 0.019). Factors significantly associated with TDR in univariate analysis were male gender, Belgian origin, MSM, recent infection, transmission clusters and subtype B, while multivariate and Bayesian network analysis singled out subtype B as the most predictive factor of TDR. Subtype B was related with transmission clusters with TDR that included 42.6% of the TDR patients. Thanks to resistance testing, 83% of the patients with TDR who started therapy had undetectable viral load whereas half of the patients would likely have received a suboptimal therapy without this test. In conclusion, TDR remained stable and a NNRTI up-and-down trend was observed. While the presence of clusters with TDR is worrying, we could not identify an independent, non-sequence based predictor for TDR or transmission clusters with TDR that could help with guidelines or public health measures.

Automated subtyping of HIV-1 genetic sequences for clinical and surveillance purposes: performance evaluation of the new REGA version 3 and seven other tools.

BACKGROUND: To investigate differences in pathogenesis, diagnosis and resistance pathways between HIV-1 subtypes, an accurate subtyping tool for large datasets is needed. We aimed to evaluate the performance of automated subtyping tools to classify the different subtypes and circulating recombinant forms using pol, the most sequenced region in clinical practice. We also present the upgraded version 3 of the Rega HIV subtyping tool (REGAv3). METHODOLOGY: HIV-1 pol sequences (PR+RT) for 4674 patients retrieved from the Portuguese HIV Drug Resistance Database, and 1872 pol sequences trimmed from full-length genomes retrieved from the Los Alamos database were classified with statistical-based tools such as COMET, jpHMM and STAR; similarity-based tools such as NCBI and Stanford; and phylogenetic-based tools such as REGA version 2 (REGAv2), REGAv3, and SCUEAL. The performance of these tools, for pol, and for PR and RT separately, was compared in terms of reproducibility, sensitivity and specificity with respect to the gold standard which was manual phylogenetic analysis of the pol region. RESULTS: The sensitivity and specificity for subtypes B and C was more than 96% for seven tools, but was variable for other subtypes such as A, D, F and G. With regard to the most common circulating recombinant forms (CRFs), the sensitivity and specificity for CRF01_AE was ~99% with statistical-based tools, with phylogenetic-based tools and with Stanford, one of the similarity based tools. CRF02_AG was correctly identified for more than 96% by COMET, REGAv3, Stanford and STAR. All the tools reached a specificity of more than 97% for most of the subtypes and the two main CRFs (CRF01_AE and CRF02_AG). Other CRFs were identified only by COMET, REGAv2, REGAv3, and SCUEAL and with variable sensitivity. When analyzing sequences for PR and RT separately, the performance for PR was generally lower and variable between the tools. Similarity and statistical-based tools were 100% reproducible, but this was lower for phylogenetic-based tools such as REGA (~99%) and SCUEAL (~96%). CONCLUSIONS: REGAv3 had an improved performance for subtype B and CRF02_AG compared to REGAv2 and is now able to also identify all epidemiologically relevant CRFs. In general the best performing tools, in alphabetical order, were COMET, jpHMM, REGAv3, and SCUEAL when analyzing pure subtypes in the pol region, and COMET and REGAv3 when analyzing most of the CRFs. Based on this study, we recommend to confirm subtyping with 2 well performing tools, and be cautious with the interpretation of short sequences.

Similar biotherapeutic products: overview and reflections.

Biotherapeutic products (BPs) have revolutionized medicine, changing the way we treat several pathologies such as autoimmune diseases and cancer, among others. Herein, we present an overview of similar BPs (SBPs), also called biosimilars, including the manufacturing process and regulatory aspects involved. The objective of developing an SBP is to manufacture a molecule that is highly similar to a reference BP by conducting a comparability exercise (CE) that can demonstrate similar safety and efficacy. This CE consists of quality, as well as nonclinical and clinical evaluation. A case-by-case analysis approach guided by scientific and objective standards must be the foundation for the SBP approval process. The establishment of a balance between a comprehensive CE for SBPs and their reference BPs, and the design of costeffective strategies to provide better access to BPs, should be the key goal for national regulatory authorities.

HIV-1 transmitted drug resistance in Latin America and the Caribbean: what do we know?

Latin America and the Caribbean countries have increased the scaling-up of antiretroviral treatment in the last years. The increase of transmitted drug resistance has been feared due to the worrisome indicators associated with the emergence of drug resistance and monitored by the World Health Organization (WHO). Consequently, our aim was to review all relevant studies on transmitted drug resistance in Latin America and the Caribbean countries, to analyze its levels, to identify the frequency of transmitted drug resistance mutations, and to put these results in the context of the local Latin American and Caribbean countries settings. A systematic search of Spanish, Portuguese, and English literature was performed in databases and international conferences for the period June 1999 to May 2011. In addition, sequences were downloaded from the Los Alamos and Stanford databases and the transmitted drug resistance was reanalyzed according to the WHO Surveillance Drug Resistance Mutation list 2009. In total, 50 articles, 27 abstracts, and 1,922 patients were included. The resistance varied geographically, but most of the countries have reached the WHO threshold of 5% of resistance. According to the sequences available in public databases, the overall prevalence in Latin America and the Caribbean countries for the period 1996-2009 was 7.7% and by region it was 4.3% for the Caribbean, 3.9% for Mexico, 9.4% for Brazil, 10.5% for the Andean region and 4.9% for the Southern Cone. For the last four investigated years (2006-2009), the information was restricted to Brazilian and Venezuelan studies and revealed an overall transmitted drug resistance of 10%. Throughout the study period, limited information was available for the Caribbean and Central American countries. These findings support the need for developing comprehensive surveys of transmitted drug resistance in these regions.