Las Pléyades y las figuraciones del liderazgo entre los tobas

Abordar la problemática celeste entre los tobas nos conduce a pensarla en conjunto tanto con el resto del cosmos, como con el desarrollo de su vida cotidiana. Las lecturas que operan en torno al cielo nos ofrecen visiones que distan de la uniformidad de interpretaciones, brindando un abanico de matices que nos hablan de posiciones diversas frente a un mismo tema. A continuación se indaga sobre uno de los asterismos que dibujan en el cielo los tobas que se asientan en el Pilcomayo medio, está representado por las Pléyades y lo llaman: Dapi´chi. Esta formación celeste es una de las más importantes y está fuertemente enlazada a la compleja figura del liderazgo.Fil: Gomez, Cecilia Paula. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Arterial Stiffness: Its Relation with Prediabetes and Metabolic Syndrome and Possible Pathogenesis

Aims: To evaluate arterial stiffness indicators in people with prediabetes (PreD) and its possible pathogenesis. Materials and methods: Pulse wave velocity (PWV) was measured in 208 people with FINDRISC ≥ 13 (57 ± 8 years old, 68.7% women) and thereafter divided into those having either normal glucose tolerance (NGT) or PreD. In each subgroup we also identified those with/out insulin resistance (IR) measured by the triglyceride/HDL-c ratio (normal cut off values previously established in our population). Clinical and metabolic data were collected for all participants. PWV was compared between subgroups using independent t test. Results: Women and men had comparable clinical and metabolic characteristics with obesity (BMI ≥ 30) and antihypertensive-statin treatment, almost half with either NGT or PreD. Whereas 48% of NGT people presented IR (abnormally high TG/HDL-c ratio), 52% had PreD. PWV was significantly higher only in those with a complete picture of metabolic syndrome (MS). Conclusions: Since PWV was significantly impaired in people with a complete picture of MS, clinicians must carefully search for early diagnosis of this condition and prescribe a healthy life-style to prevent development/progression of CVD. This proactive attitude would provide a cost-effective preventive strategy to avoid CVD’s negative impact on patients’ quality of life and on health systems due to their higher care costs.Centro de Endocrinología Experimental y AplicadaFacultad de Ciencias Médica

Componente agua: monitoreo de la calidad de agua superficial y sedimentos en el Arroyo Morales

Los aspectos técnicos, geográficos, económicos, sociales, así como su extensa historia han hecho a la Cuenca Matanza Riachuelo un territorio sumamente complejo. Desde que la Corte Suprema de Justicia de la Nación dictó el fallo para trabajar en su saneamiento implicó tener en cuenta todas sus características y complejidades para implementar estrategias diversas e integrales, concertadas con gran cantidad de actores, entre ellos STAN-CONICET.MACN, 3iA-UNSAM, Municipalidad de Marcos Paz, ILPLA-UNLP y LA Autoridad de la Cuenca Matanza-Riachuelo (ACUMAR).Aquí se recopila la experiencia adquirida por ACUMAR, y los resultados alcanzados por los grupos ténico-científicos, en el desarrollo y seguimiento del primer biocorredor de la Cuenca.Fil: Gomez, Nora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Rodrigues Capitulo, Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Armendáriz, Laura Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Altieri, Paula Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Ferreira, Ana Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Spaccesi, Fernando Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Rodriguez, Marianela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Cortese, Bianca. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Bauer, Delia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Sathicq, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Cochero, Joaquin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Nicolosi Gelis, María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Pazos, Rocío Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Tarda, Alan Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Jensen, Roberto Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; Argentin

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

Pheno-genotyping of inherited thrombocytopenias: our experience in 50 families

Dada la heterogeneidad de las entidades comprendi- das en las trombocitopenias hereditarias y la escasez de marcadores distintivos, su diagnóstico constituye un verdadero desafío. El abordaje clásico se basa en la caracterización fenotípica seguida del estudio mo- lecular de genes candidatos, orientado según la sos- pecha clínica. La introducción de la secuenciación de nueva generación (NGS), que permite evaluar múltiples genes simultáneamente, constituye una al- ternativa diagnóstica de alto costo, siendo de acceso limitado en nuestro medio. Nos propusimos evaluar la utilidad del abordaje clásico en una cohorte conse- cutiva de 50 familias y describir la aplicación de NGS en un subgrupo de pacientes sin diagnóstico etioló- gico luego del enfoque clásico. Mediante el abordaje clásico se efectuó el diagnóstico en 27 (54%) familias. Posteriormente, 8 familias que quedaron sin diag- nóstico luego del algoritmo clásico, se evaluaron me- diante NGS, identificando el gen causal en 4 de ellas. Considerando ambos abordajes, el rédito diagnóstico fue 31/50 (62%) familias, con la siguiente distribu- ción: 38% desorden relacionado a MYH9, 8% síndro- me de Bernard-Soulier (4% clásico, 4% monoalélico), 4% síndrome de plaquetas grises, 4% desorden pla- quetario con predisposición a leucemia, 6% trom- bocitopenia relacionada a ANKRD26, 2% síndrome Wiskott-Aldrich. Los pacientes en los que no se pudo efectuar un diagnóstico etiológico presentaban trom- bocitopenia aislada leve, con aumento moderado del tamaño plaquetario y sangrado escaso.En conclusión, la aplicación de NGS permitió au- mentar el rédito diagnóstico, si bien sería necesa- rio ampliar la población estudiada para establecer el valor real de este abordaje en nuestro medio. Por lo tanto, el uso inicial del abordaje clásico, reserván- dose la aplicación posterior de NGS a los casos que permanecen sin diagnóstico luego de este enfoque, constituiría una alternativa útil en países con pocos recursos, apuntando a un diagnóstico adecuado que posibilite la pesquisa de complicaciones sindrómicas, oriente al tratamiento y consejo genético acertado.Diagnosis of inherited thrombocytopenias represents a true challenge owing to heterogeneity of these disorders and the absence of distinctive features in a substantial proportion of patients. Classical diagnostic approach is based on phenotypic characterization followed by molecular analysis of candidate genes guided by clinical suspicion. The introduction of next generation sequencing (NGS), that allows multiple genes analysis, is a high-cost alternative with limited access in our country. The aim of this work was to evaluate the utility of the classical approach in a consecutive cohort of 50 families and to describe the application of NGS in a subgroup of patients without an etiological diagnosis after the initial approach. Through the conventional approach, an etiologic diagnosis was made in 27 (54%) families. NGS was performed in 8 that remained without diagnosis after initial characterization, attaining a diagnosis in 4. Combining both approaches, the diagnostic yield was 31/50 (62%) families: 38% MYH9-related disorder, 8% Bernard-Soulier syndrome, 4% gray platelet syndrome, 4% familial platelet disorder with predisposition to leukemia, 6% ANKRD26-related thrombocytopenia, 2% Wiskott-Aldrich syndrome. Most patients without diagnosis had isolated macrothrombocytopenia and mild bleeding. NGS increased the diagnostic rate in this cohort, although it would be necessary to expand the population to establish its actual value in our setting. Therefore, the use of the classical approach and subsequent application of NGS in undiagnosed patients would represent a useful alternative in low-income countries, pointing out that a correct etiological diagnosis enables the detection of syndromic complications, appropriate treatment and adequate genetic counseling.Fil: Heller, Paula Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Goette, Nora Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Marin Oyarzún, Cecilia Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Baroni Pietto, Maria Constanza. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Ayala, Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Altuna, Diana R.. Instituto Universidad Escuela de Medicina del Hospital Italiano; ArgentinaFil: Arrieta, Maria Elizabeth. Hospital Público Descentralizado Dr. Guillermo Rawson.; ArgentinaFil: Arbesú, Guillermo. Hospital Dr. Humberto Notti; ArgentinaFil: Basqueira, Ana L.. Hospital Privado Universitario de Cordoba.; ArgentinaFil: Bazack, Nora. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Bonacorso, Silvina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Brodsky, Andrés. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Castro Rios, Miguel. No especifíca;Fil: Cosentini, María L.. Hospital Materno Infantil Doctor Hector Quintana ; Gobierno de la Provincia de Jujuy;Fil: Donato, Hugo Sebastian. Hospital Municipal del Niño de San Justo ; Municipalidad de la Matanza (buenos Aires);Fil: Korin, Jorge D.. No especifíca;Fil: Gomez, Silvina. No especifíca;Fil: Guglielmone, Hugo. Sanatorio Allende; ArgentinaFil: Lagrotta, Pablo. Hospital Nacional Profesor Alejandro Posadas.; ArgentinaFil: Marti, Alejandra. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic; ArgentinaFil: Negro, Fernando Javier. Sanatorio Sagrado Corazon; ArgentinaFil: Rapetti, María C.. Hospital Municipal del Niño de San Justo ; Municipalidad de la Matanza (buenos Aires);Fil: Rosso, Diego. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ponzinibbio, Carlos. Hospital Italiano de La Plata; ArgentinaFil: Veber, Ernesto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Zerga, Marta Elisa. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; ArgentinaFil: Molinas, Felisa Concepción. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Savoia, Anna. Instituto para la Salud Materna e Infancia; Italia. Università degli Studi di Trieste; ItaliaFil: Pecci, Alessandro. Universita Degli Studi Di Pavia; ItaliaFil: Marta, Rosana Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Glembotsky, Ana Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

"La vida en las lagunas": 20 años de experiencia educativa en el sistema de lagunas Encadenadas de Chascomús y Lezama (Buenos Aires, Argentina)

Los autores son estudiantes de pregrado y egresados (docentes e investigadores) de la Facultad de Ciencias Naturales y Museo de La Plata (FCNyM), quienes en conjunto con investigadores de la Estación Hidrobiológica de Chascomús participan como talleristas y llevan adelante el proyecto La Vida en las Lagunas. El cual es coordinado por la Secretaría de Extensión de la FCNyM (Universidad Nacional de La Plata, UNLP) desde el año 1997. Este programa de educación ambiental tiene como propósito compartir y transferir conocimiento científico a estudiantes de escuelas primarias y secundarias y la inmersión de esos conocimientos en las ideas de sustentabilidad ambiental.Facultad de Ciencias Naturales y Muse

Latitude gradient influences the age of onset of rheumatoid arthritis : a worldwide survey

The age of onset of rheumatoid arthritis (RA) is an important outcome predictor. Northern countries report an age of RA onset of around 50 years, but apparently, variability exists across different geographical regions. The objective of the present study is to assess whether the age of onset of RA varies across latitudes worldwide. In a proof-of-concept cross-sectional worldwide survey, rheumatologists from preselected cities interviewed 20 consecutive RA patients regarding the date of RA onset (RAO, when the patient first noted a swollen joint). Other studied variables included location of each city, rheumatologist settings, latitudes (10A degrees increments, south to north), longitudes (three regions), intracountry consistency, and countries' Inequality-adjusted Human Development Index (IHDI). Data from 2481 patients (82% females) were obtained from 126 rheumatologists in 77 cities of 41 countries. Worldwide mean age of RAO was 44 +/- 14 years (95% CI 44-45). In 28% of patients, RA began before age 36 years and before age 46 years in 50% of patients. RAO was 8 years earlier around the Tropic of Cancer when compared with northern latitudes (p <0.001, 95% CI 3.5-13). Multivariate analysis showed that females, western cities, and latitudes around the Tropic of Cancer are associated with younger age of RAO (R (2) 0.045, p <0.001). A positive correlation was found between the age of RAO and IHDI (r = 0.7, p <0.01, R (2) 0.5). RA often begins at an early age and onset varies across latitudes worldwide. We postulate that countries' developmental status and their geographical and geomagnetic location influence the age of RAO.Peer reviewe

Dolutegravir twice-daily dosing in children with HIV-associated tuberculosis: a pharmacokinetic and safety study within the open-label, multicentre, randomised, non-inferiority ODYSSEY trial

Background: Children with HIV-associated tuberculosis (TB) have few antiretroviral therapy (ART) options. We aimed to evaluate the safety and pharmacokinetics of dolutegravir twice-daily dosing in children receiving rifampicin for HIV-associated TB. Methods: We nested a two-period, fixed-order pharmacokinetic substudy within the open-label, multicentre, randomised, controlled, non-inferiority ODYSSEY trial at research centres in South Africa, Uganda, and Zimbabwe. Children (aged 4 weeks to <18 years) with HIV-associated TB who were receiving rifampicin and twice-daily dolutegravir were eligible for inclusion. We did a 12-h pharmacokinetic profile on rifampicin and twice-daily dolutegravir and a 24-h profile on once-daily dolutegravir. Geometric mean ratios for trough plasma concentration (Ctrough), area under the plasma concentration time curve from 0 h to 24 h after dosing (AUC0–24 h), and maximum plasma concentration (Cmax) were used to compare dolutegravir concentrations between substudy days. We assessed rifampicin Cmax on the first substudy day. All children within ODYSSEY with HIV-associated TB who received rifampicin and twice-daily dolutegravir were included in the safety analysis. We described adverse events reported from starting twice-daily dolutegravir to 30 days after returning to once-daily dolutegravir. This trial is registered with ClinicalTrials.gov (NCT02259127), EudraCT (2014–002632-14), and the ISRCTN registry (ISRCTN91737921). Findings: Between Sept 20, 2016, and June 28, 2021, 37 children with HIV-associated TB (median age 11·9 years [range 0·4–17·6], 19 [51%] were female and 18 [49%] were male, 36 [97%] in Africa and one [3%] in Thailand) received rifampicin with twice-daily dolutegravir and were included in the safety analysis. 20 (54%) of 37 children enrolled in the pharmacokinetic substudy, 14 of whom contributed at least one evaluable pharmacokinetic curve for dolutegravir, including 12 who had within-participant comparisons. Geometric mean ratios for rifampicin and twice-daily dolutegravir versus once-daily dolutegravir were 1·51 (90% CI 1·08–2·11) for Ctrough, 1·23 (0·99–1·53) for AUC0–24 h, and 0·94 (0·76–1·16) for Cmax. Individual dolutegravir Ctrough concentrations were higher than the 90% effective concentration (ie, 0·32 mg/L) in all children receiving rifampicin and twice-daily dolutegravir. Of 18 children with evaluable rifampicin concentrations, 15 (83%) had a Cmax of less than the optimal target concentration of 8 mg/L. Rifampicin geometric mean Cmax was 5·1 mg/L (coefficient of variation 71%). During a median follow-up of 31 weeks (IQR 30–40), 15 grade 3 or higher adverse events occurred among 11 (30%) of 37 children, ten serious adverse events occurred among eight (22%) children, including two deaths (one tuberculosis-related death, one death due to traumatic injury); no adverse events, including deaths, were considered related to dolutegravir. Interpretation: Twice-daily dolutegravir was shown to be safe and sufficient to overcome the rifampicin enzyme-inducing effect in children, and could provide a practical ART option for children with HIV-associated TB

Neuropsychiatric manifestations and sleep disturbances with dolutegravir-based antiretroviral therapy versus standard of care in children and adolescents: a secondary analysis of the ODYSSEY trial

BACKGROUND: Cohort studies in adults with HIV showed that dolutegravir was associated with neuropsychiatric adverse events and sleep problems, yet data are scarce in children and adolescents. We aimed to evaluate neuropsychiatric manifestations in children and adolescents treated with dolutegravir-based treatment versus alternative antiretroviral therapy. METHODS: This is a secondary analysis of ODYSSEY, an open-label, multicentre, randomised, non-inferiority trial, in which adolescents and children initiating first-line or second-line antiretroviral therapy were randomly assigned 1:1 to dolutegravir-based treatment or standard-of-care treatment. We assessed neuropsychiatric adverse events (reported by clinicians) and responses to the mood and sleep questionnaires (reported by the participant or their carer) in both groups. We compared the proportions of patients with neuropsychiatric adverse events (neurological, psychiatric, and total), time to first neuropsychiatric adverse event, and participant-reported responses to questionnaires capturing issues with mood, suicidal thoughts, and sleep problems. FINDINGS: Between Sept 20, 2016, and June 22, 2018, 707 participants were enrolled, of whom 345 (49%) were female and 362 (51%) were male, and 623 (88%) were Black-African. Of 707 participants, 350 (50%) were randomly assigned to dolutegravir-based antiretroviral therapy and 357 (50%) to non-dolutegravir-based standard-of-care. 311 (44%) of 707 participants started first-line antiretroviral therapy (ODYSSEY-A; 145 [92%] of 157 participants had efavirenz-based therapy in the standard-of-care group), and 396 (56%) of 707 started second-line therapy (ODYSSEY-B; 195 [98%] of 200 had protease inhibitor-based therapy in the standard-of-care group). During follow-up (median 142 weeks, IQR 124–159), 23 participants had 31 neuropsychiatric adverse events (15 in the dolutegravir group and eight in the standard-of-care group; difference in proportion of participants with ≥1 event p=0·13). 11 participants had one or more neurological events (six and five; p=0·74) and 14 participants had one or more psychiatric events (ten and four; p=0·097). Among 14 participants with psychiatric events, eight participants in the dolutegravir group and four in standard-of-care group had suicidal ideation or behaviour. More participants in the dolutegravir group than the standard-of-care group reported symptoms of self-harm (eight vs one; p=0·025), life not worth living (17 vs five; p=0·0091), or suicidal thoughts (13 vs none; p=0·0006) at one or more follow-up visits. Most reports were transient. There were no differences by treatment group in low mood or feeling sad, problems concentrating, feeling worried or feeling angry or aggressive, sleep problems, or sleep quality. INTERPRETATION: The numbers of neuropsychiatric adverse events and reported neuropsychiatric symptoms were low. However, numerically more participants had psychiatric events and reported suicidality ideation in the dolutegravir group than the standard-of-care group. These differences should be interpreted with caution in an open-label trial. Clinicians and policy makers should consider including suicidality screening of children or adolescents receiving dolutegravir