Population Pharmacokinetic Study of Benznidazole in Pediatric Chagas Disease Suggests Efficacy despite Lower Plasma Concentrations than in Adults

Introduction:Chagas disease, caused by the parasite Trypanosoma cruzi, can lead to long term cardiac morbidity. Treatment of children with benznidazole is effective, but no pediatric pharmacokinetics data are available and clinical pharmacology information on the drug is scarce.Patients and Methods:Prospective population pharmacokinetic (PK) cohort study in children 2-12 years old with Chagas disease treated with oral benznidazole 5-8 mg/kg/day BID for 60 days. (clinicaltrials.gov #NCT00699387).Results:Forty children were enrolled in the study. Mean age was 7.3 years. A total of 117 samples were obtained from 38 patients for PK analysis. A one compartment model best fit the data. Weight-corrected clearance rate (CL/F) showed a good correlation with age, with younger patients having a significantly higher CL/F than older children and adults. Simulated median steady-state benznidazole concentrations, based on model parameters, were lower for children in our study than for adults and lowest for children under 7 years of age. Treatment was efficacious in the 37 patients who completed the treatment course, and well tolerated, with few, and mild, adverse drug reactions (ADRs).Discussion:Observed benznidazole plasma concentrations in children were markedly lower than those previously reported in adults (treated with comparable mg/kg doses), possibly due to a higher CL/F in smaller children. These lower blood concentrations were nevertheless associated to a high therapeutic response in our cohort. Unlike adults, children have few adverse reactions to the drug, suggesting that there may be a direct correlation between drug concentrations and incidence of ADRs. Our results suggest that studies with lower doses in adults may be warranted.Trial Registration:ClinicalTrails.gov NCT00699387.Fil: Altcheh, Jaime Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; ArgentinaFil: Moscatelli, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; ArgentinaFil: Mastrantonio Garrido, Guido Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; ArgentinaFil: Moroni, Samanta. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; ArgentinaFil: Giglio, Norberto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; ArgentinaFil: Marson, María Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; ArgentinaFil: Ballering, Griselda. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; ArgentinaFil: Bisio, Margarita María Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; ArgentinaFil: Koren, Gideon. University of Toronto. Hospital for Sick Children. División of Clinical Pharmacology & Toxicology; CanadáFil: García Bournissen, Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; Argentina. University of Toronto. Hospital for Sick Children. División of Clinical Pharmacology & Toxicology; Canad

Cost of Bordetella pertussis illness in tertiary hospitals in Argentina

La Comisión Nacional de Inmunizaciones y el ProNaCEI (Programa Nacional de Control de Enfermedades Inmunoprevenibles) actualizaron la política de vacunación por Bordetella pertussis (BP) a partir del año 2009 con el objetivo de optimizar el control de esta enfermedad, de acuerdo con las recomendaciones internacionales. Para evaluar el impacto económico de esta nueva política de vacunación resulta necesario conocer inicialmente el costo que implica para el sistema de salud un niño internado o ambulatorio con infección por BP. El objetivo de este estudio fue describir el perfl de costos en niños internados o tratados ambulatoriamente, con infección confrmada por laboratorio de BP en tres hospitales de la Argentina. Estudio prospectivo de costo de la enfermedad durante el período diciembre de 2010 a marzo de 2012. Resultados. El costo total para toda la cohorte fue de 1 170 663,32 pesos (236 497,64 dólares); los costos médicos directos, de 1 124 052,31 pesos (227 081,27 dólares); los costos indirectos y gastos de bolsillo, de 46611 pesos (9 416,36 dólares), lo que permite inferir un costo total promedio por paciente de 10 546,52 pesos (IC 95% 9009 a 13 840) (2130,60 dólares, IC 95% 1820 a 2795), costos médicos directos por paciente de 10 126,6 pesos (IC 95% 8607 a 13 171) (2045,77 dólares, IC 95%1738 a 2660) y costos indirectos más de bolsillo (viajes y extras) de 419,92 pesos (IC 95% 344,7 a 565,3), (84 dólares, IC 95% 69 a 115). Conclusión. El costo de un caso confrmado hospitalizado por BP es 10 546,52 pesos (IC 95% 9009 a 13 840) (2130,60 dólares, IC 95% 1820 a 2795). Los costos directos no médicos y costos indirectos constituyen el 4% del total, lo que corresponde a 419,91 pesos por familia (84 dólares, IC 95% 69 a 115), un 8% del salario promedio.Fil: Gentile, Angela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "ricardo Gutierrez"; ArgentinaFil: Salgueiro, Ana L.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "ricardo Gutierrez"; ArgentinaFil: Garcia Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "r. Gutierrez". Servicio de Parasitología y Chagas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Romanin, Viviana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "ricardo Gutierrez"; ArgentinaFil: Bulgheroni, Sonia. Hospital Materno Infantil de San Isidro "Dr. Gianantonio"; ArgentinaFil: Gaiano, Alejandra. Hospital Materno Infantil de San Isidro "Dr. Gianantonio"; ArgentinaFil: Benegas, Liliana. Hospital de Niños "Víctor J. Vilela"; ArgentinaFil: Uboldi, Andrea. Hospital de Niños "Víctor J. Vilela"; ArgentinaFil: Giglio, Norberto. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "ricardo Gutierrez"; Argentin

Publication of abstracts presented at the National Pediatric Research Meetings of the Argentine Society of Pediatrics: Related factors

Objectives: To estimate the proportion of abstracts presented at National Pediatric Research Meetings that are fully-published and describe their design and factors that influence nonpublication. Methods: Descriptive and analytical study including all abstracts presented at National Pediatric Research Meetings (1998-2011). One author per study was identified and asked to complete a survey on its design, publication and factors associated with non-publication. Results: Out of 746 abstracts that were submitted, the authors of 522 (70%) completed the survey. Among these, 84.3% were observational studies and 15.7%, experimental; 34% had received funding. Two hundred and seventeen abstracts were published subsequently (41.5%, 95% confidence interval [CI]: 37.3-45.9). Funded studies had better chances of being published (odds ratio [OR]: 2, 95% CI: 1.4-2.9, p \u3c 0.001). Lack of time, insufficient sample size, and problems with funding were referred as the most common reasons for failure to publish. Conclusion: Among all abstracts presented at National Pediatric Research Meetings, 41.5% were fully published. Lack of time was the most common reason for unpublished studies

Publication of abstracts presented at the National Pediatric Research Meetings of the Argentine Society of Pediatrics: Related factors

Objetivos: Estimar la proporción de trabajos presentados en Encuentros Nacionales de Investigación Pediátrica que posteriormente fueron publicados en forma completa; describir sus diseños y factores involucrados con la no publicación. Métodos: Estudio descriptivo y analítico, que incluyó todos los trabajos presentados en Encuentros Nacionales de Investigación Pediátrica (1998-2011). Se identificó un investigador por estudio y se lo encuestó sobre el diseño, la publicación y los factores asociados a la no publicación. Resultados: Sobre 746 trabajos presentados, respondieron la encuesta los autores de 522 (70%). El 84,3% eran estudios observacionales y 15,7%, experimentales; 34% recibieron financiación. Fueron publicados posteriormente 217 trabajos (41,5%, IC 95%: 37,3-45,9). Aquellos con financiación tuvieron mayor probabilidad de publicarse (OR 2; IC 95%: 1,4-2,9; p < 0,001). Las causas de no publicación más frecuentes fueron la falta de tiempo, el tamaño muestral insuficiente y la dificultad con el financiamiento. Conclusión: El 41,5% de trabajos presentados en Encuentros Nacionales de Investigación Pediátrica alcanzaron la publicación en texto completo. La falta de tiempo fue la principal causa para no hacerlo.OBJECTIVE:To estimate the proportion of abstracts presented at National Pediatric Research Meetings that are fully-published and describe their design and factors that influence nonpublication.METHODS:Descriptive and analytical study including all abstracts presented at National Pediatric Research Meetings (1998-2011). One author per study was identified and asked to complete a survey on its design, publication and factors associated with non-publication.RESULTS:Out of 746 abstracts that were submitted, the authors of 522 (70%) completed the survey. Among these, 84.3% were observational studies and 15.7%, experimental; 34% had received funding. Two hundred and seventeen abstracts were published subsequently (41.5%, 95% confidence interval [CI]: 37.3-45.9). Funded studies had better chances of being published (odds ratio [OR]: 2, 95% CI: 1.4-2.9, p 〈 0.001). Lack of time, insufficient sample size, and problems with funding were referred as the most common reasons for failure to publish.CONCLUSIONS:Among all abstracts presented at National Pediatric Research Meetings, 41.5% were fully published. Lack of time was the most common reason for unpublished studies.Fil: Domínguez, Paula. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); ArgentinaFil: Ossorio, Maria F.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina. Sociedad Argentina de Pediatría; ArgentinaFil: Cuestas, Eduardo. Sociedad Argentina de Pediatría; Argentina. Hospital Privado de Córdoba; ArgentinaFil: Giglio, Norberto. Sociedad Argentina de Pediatría; Argentina. Hospital General de Niños Ricardo Gutiérrez; ArgentinaFil: Grandi, Carlos. Sociedad Argentina de Pediatría; Argentina. Hospital Materno-infantil Ramón Sardá; ArgentinaFil: Garcia Bournissen, Facundo. Hospital General de Niños Ricardo Gutiérrez; Argentina. Sociedad Argentina de Pediatría; ArgentinaFil: Vidaurreta, Santiago. Sociedad Argentina de Pediatría; Argentina. Hospital Universitario CEMIC; ArgentinaFil: Altcheh, Jaime Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital General de Niños Ricardo Gutiérrez; Argentina. Sociedad Argentina de Pediatría; ArgentinaFil: Ferrero, Fernando. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina. Sociedad Argentina de Pediatría; Argentin

Pediatric Clinical Pharmacology Studies in Chagas Disease

Chagas disease is a neglected parasitic disease endemic in the Americas. It mainly affects impoverished populations and the acute phase of the infection mostly affects children. Many cases have also been detected in nonendemic countries as a result of recent migratory trends. The chronic phase is relatively asymptomatic, but 30% of patients with chronic infection eventually develop cardiac and digestive complications that commonly lead to death or disability. Only two drugs are available for the treatment of Chagas disease, benznidazole and nifurtimox. These drugs have been shown to be effective in the treatment of both acute and early chronic phases in children, but the pharmacokinetics of these drugs have never been studied in this population. We have set out to conduct a pharmacokinetics study of benznidazole in a pediatric population with Chagas disease. The results of this study are expected to allow better estimation of the optimal doses and schedule of pharmacotherapy for Chagas disease in children.Planta Piloto Multipropósito - Laboratorio de Servicios a la Industria y al Sistema Científic

Instrument to assess research projects that apply for a fellowship by the Sociedad Argentina de Pediatría: Validation using the Delphi method

The objective of this study was to validate the format and contents of an instrument to assess research projects that apply for a fellowship by the Sociedad Argentina de Pediatría using an expert consultation technique, such as the Delphi method. Material and methods. A coordinating group selected a panel of research experts who were members of the Sociedad Argentina de Pediatría, designed, and analyzed each of the rounds of consultations. Semistructured questionnaires were sent by personalized e-mail. Agreement among experts ≥ 80 % was established as the criterion for consensus. At each round of consultation, non-consensual aspects were reformulated and new aspects suggested by experts were included. A measure of stability to conclude the consultation was determined when more than 70 % of experts sustained their opinion in successive rounds. Results. Thirteen research experts participated in the process. After 3 rounds, the consultation process was concluded. The consensual instrument contains 47 items. In relation to the total score, 10 % corresponds to the general presentation; 40 %, to methodological quality; 20 %, to relevance and applicability; 20 %, to feasibility;and10%,tothefellow\u27sanddirector\u27s background. Conclusions. The format and contents of the instrument to assess research projects that apply for a fellowship by the SociedadArgentina de Pediatría were validated based on expert consensus and objective assessment criteria were established

Costo-efectividad de la vacunación universal antineumocócica en Uruguay

Objetivo. Evaluar la relación costo-efectividad del programa de vacunación universal con la vacuna antineumocócica conjugada heptavalente (VCN7) en niños menores de 5 años en Uruguay. Métodos. Se desarrolló un modelo Markov simulando una cohorte de 48 000 niños nacidos en 2007 y su evolución hasta los 76 años de edad. El caso base usó un esquema de tres dosis con una duración estimada de protección de cinco años. La presunción de eficacia y efectividad de la vacuna se realizó acorde con estudios realizados en Estados Unidos con ajuste a la prevalenciaincidencia de serotipos en Uruguay. Los resultados se expresaron como costo incremental por año de vida ganado (AVG) y por año de vida [ganado] ajustado por calidad (AVAC). Resultados. Para el caso base, el costo incremental fue de US$7 334,6 por AVG y US$ 4 655,8 por AVAC, previniéndose 8 muertes y 4 882 casos de otitis, 56 bacteriemias-sepsis, 429 neumonías y 7 meningitis. El modelo muestra sensibilidad a variaciones en eficacia, costo de la vacuna y tasa de mortalidad por neumonía. Conclusiones. El programa de vacunación universal con VCN7 en Uruguay es altamente costo-efectivo y, en consecuencia, recomendable para otros países con carga de enfermedad neumocócica y cobertura de serotipos similares a Uruguay

Narcolepsy and adjuvanted pandemic influenza A (H1N1) 2009 vaccines – Multi-country assessment

Background: In 2010, a safety signal was detected for narcolepsy following vaccination with Pandemrix, an AS03-adjuvanted monovalent pandemic H1N1 influenza (pH1N1) vaccine. To further assess a possible association and inform policy on future use of adjuvants, we conducted a multi-country study of narcolepsy and adjuvanted pH1N1 vaccines. Methods: We used electronic health databases to conduct a dynamic retrospective cohort study to assess narcolepsy incidence rates (IR) before and during pH1N1 virus circulation, and after pH1N1 vaccination campaigns in Canada, Denmark, Spain, Sweden, Taiwan, the Netherlands, and the United Kingdom. Using a case-control study design, we evaluated the risk of narcolepsy following AS03- and MF59-adjuvanted pH1N1 vaccines in Argentina, Canada, Spain, Switzerland, Taiwan, and the Netherlands. In the Netherlands, we also conducted a case-coverage study in children born between 2004 and 2009. Results: No changes in narcolepsy IRs were observed in any periods in single study sites except Sweden and Taiwan; in Taiwan incidence increased after wild-type pH1N1 virus circulation and in Sweden (a previously identified signaling country), incidence increased after the start of pH1N1 vaccination. No association was observed for Arepanrix-AS03 or Focetria-MF59 adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the case-control study nor for children born between 2004 and 2009 in the Netherlands case-coverage study for Pandemrix-AS03. Conclusions: Other than elevated narcolepsy IRs in the period after vaccination campaigns in Sweden, we did not find an association between AS03- or MF59-adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the sites studied, although power to evaluate the AS03-adjuvanted Pandemrix brand vaccine was limited in our study