Adverse events associated with nifurtimox treatment for chagas disease in children and adults

Nifurtimox (NF) is one of the only two drugs currently available for Chagas disease (ChD) treatment. However, data on NF safety are scarce, and many physicians defer or refuse NF treatment because of concerns about drug tolerance. In a retrospective study of adverse drug reactions (ADRs) associated with NF treatment of ChD, children received NF doses of 10 to 15 mg/kg/day for 60 to 90 days, and adults received 8 to 10 mg/kg/day for 30 days. A total of 215 children (median age, 2.6 years; range, 0 to 17 years) and 105 adults (median age, 34 years; range, 18 to 57 years) were enrolled. Overall, 127/320 (39.7%) patients developed ADRs, with an incidence of 64/105 adults and 63/215 children (odds ratio [OR] = 3.7; 95% confidence interval [CI], 2.2 to 6.3). We observed 215 ADRs, 131 in adults (median, 2 events/patient; interquartile range for the 25th to 75th percentiles [IQR25-75], 1 to 3) and 84 in children (median, 1 event/patient; IQR25-75 = 1 to 1.5) (Padjusted, 0.001). ADRs were mainly mild and moderate. Severe ADRs were infrequent (1.2% in children and 0.9% in adults). Nutritional, central nervous, and digestive systems were the most frequently affected, without differences between groups. Treatment was discontinued in 31/320 (9.7%) patients without differences between groups. However, ADR-related discontinuations occurred more frequently in adults than in children (OR = 5.5, 95% CI = 1.5 to 24). Our study supports the safety of NF for ChD treatment. Delaying NF treatment due to safety concerns does not seem to be supported by the evidence. (This study has been registered in ClinicalTrials.gov under identifier NCT04274101)

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

Hair analysis following chronic smoked-drugs-of-abuse exposure in adults and their toddler: a case report

<p>Abstract</p> <p>Introduction</p> <p>Over the past two decades, the study of chronic cocaine and crack cocaine exposure in the pediatric population has been focused on the potential adverse effects, especially in the prenatal period and early childhood. Non-invasive biological matrices have become an essential tool for the assessment of a long-term history of drug of abuse exposure.</p> <p>Case report</p> <p>We analyze the significance of different biomarker values in hair after chronic crack exposure in a two-year-old Caucasian girl and her parents, who are self-reported crack smokers. The level of benzoylecgonine, the principal metabolite of cocaine, was determined in segmented hair samples (0 cm to 3 cm from the scalp, and > 3 cm from the scalp) following washing to exclude external contamination. Benzoylecgonine was detectable in high concentrations in the child's hair, at 1.9 ng/mg and 7.04 ng/mg, respectively. Benzoylecgonine was also present in the maternal and paternal hair samples at 7.88 ng/mg and 6.39 ng/mg, and 13.06 ng/mg and 12.97 ng/mg, respectively.</p> <p>Conclusion</p> <p>Based on the data from this case and from previously published poisoning cases, as well as on the experience of our research group, we conclude that, using similar matrices for the study of chronic drug exposure, children present with a higher cocaine concentration in hair and they experience more serious deleterious acute effects, probably due to a different and slower cocaine metabolism. Consequently, children must be not exposed to secondhand crack smoke under any circumstance.</p

Bilateral femoral neck fractures due to transient osteoporosis of pregnancy: a case report

We describe a case of bilateral femoral neck fractures secondary to transient osteoporosis of pregnancy, which were diagnosed after delivery due to the desire to avoid ionising radiation. These fractures were presumed to be secondary to transient osteoporosis of pregnancy and were treated successfully with internal fixation despite delayed presentation. We discuss the role of MRI in the evaluation of hip pain in pregnancy

Systematic review of early phase pediatric clinical pharmacology trials

OBJECTIVE: Children have generally been excluded from early-stage clinical trials owing to safety concerns based in social expectations and not data. However, the repositioning of adult therapeutics for pediatric use and the increase in the development of therapies for pediatric only conditions require the participation of children in phase 1–2 trials. Therefore, the aim of this article is to systematically review the history and current state of early phase pediatric clinical pharmacology trials in order to understand safety concerns, trends, and challenges in pediatric trials. METHODS: This review analyzed the nature of early phase pediatric clinical trials conducted for nononcology conditions through a systematic search that was performed for pediatric non-oncologic phase 1 or phase 1–2 drug and vaccine studies in MEDLINE. RESULTS: The data show that the number of early phase pediatric clinical trials is still small relative to adults but has been on the rise in the past decade with relatively few serious adverse effects observed. CONCLUSIONS: The widespread concerns about children's safety when they participate in early phase clinical trials seem disproportionate, based on our findings. The data confirm that these studies can be conducted safely, and that their results can contribute significantly to pediatric pharmacotherapy.</p

Is use of nifurtimox for the treatment of Chagas disease compatible with breast feeding? A population pharmacokinetics analysis.

Introduction Women with Chagas disease receiving treatment with nifurtimox are discouraged from breast feeding. Many patients who would receive treatment with nifurtimox live in extreme poverty, have limited access to resources such as clean water and baby formula and may not have safe alternatives to breast milk. Aim We aimed to estimate, using limited available pharmacokinetics data, potential infant exposure to nifurtimox through breast milk. Methods Original nifurtimox plasma concentrations were obtained from published studies. Pharmacokinetic parameters were estimated using non-linear mixed-effect modelling with NONMEM V.VI. A total of 1000 nifurtimox plasma-concentration profiles were simulated and used to calculate the amount of drug that an infant would be exposed to, if breast fed 150 ml/kg/day. Results Breast milk concentrations on the basis of peak plasma levels (1361 ng/ml) and milk-plasma ratio were estimated. We calculated infant nifurtimox exposure of a breastfed infant of a mother treated with this drug to be below 10% of the maternal weight-adjusted dose, even if milk-plasma ratio were overestimated. Simulation led to similar estimates. Discussion Risk for significant infant exposure to nifurtimox through breast milk seems small and below the level of exposure of infants with Chagas disease receiving nifurtimox treatment. This potential degree of exposure may not justify discontinuation of breast feeding

Prediction of infant drug exposure through breastfeeding: population PK modeling and simulation of fluoxetine

BACKGROUND: Risks of significant infant drug exposurethrough breastmilk are poorly defined for many drugs, and largescalepopulation data are lacking. We used population pharmacokinetics(PK) modeling to predict fluoxetine exposure levels ofinfants via mother's milk in a simulated population of 1000 motherinfantpairs.METHODS: Using our original data on fluoxetine PK of 25breastfeeding women, a population PK model was developed withNONMEM and parameters, including milk concentrations, wereestimated. An exponential distribution model was used to account forindividual variation. Simulation random and distribution-constrainedassignment of doses, dosing time, feeding intervals and milk volumewas conducted to generate 1000 mother-infant pairs with characteristicssuch as the steady-state serum concentrations (Css) and infantdose relative to the maternal weight-adjusted dose (relative infantdose: RID). Full bioavailability and a conservative point estimate of1-month-old infant CYP2D6 activity to be 20% of the adult value(adjusted by weigth) according to a recent study, were assumed forinfant Css calculations.RESULTS: A linear 2-compartment model was selected as thebest model. Derived parameters, including milk-to-plasma ratios(mean: 0.66; SD: 0.34; range, 0 - 1.1) were consistent with the valuesreported in the literature. The estimated RID was below 10% in &gt;95%of infants. The model predicted median infant-mother Css ratio was0.096 (range 0.035 - 0.25); literature reported mean was 0.07 (range0-0.59). Moreover, the predicted incidence of infant-mother Css ratioof &gt;0.2 was less than 1%.CONCLUSION: Our in silico model prediction is consistent withclinical observations, suggesting that substantial systemic fluoxetineexposure in infants through human milk is rare, but further analysisshould include active metabolites. Our approach may be valid forother drugs. [supported by CIHR and Swiss National Science Foundation(SNSF)]]]> eng oai:serval.unil.ch:BIB_64448644E59E 2022-02-19T02:22:49Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_64448644E59E Storia linguistica di Venezia urn:isbn:9788843055128 info:eu-repo/semantics/altIdentifier/isbn/9788843055128 Tomasin, Lorenzo info:eu-repo/semantics/book book 2010 ita oai:serval.unil.ch:BIB_6444B2C2264E 2022-02-19T02:22:49Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_6444B2C2264E L'utilisation du laser CO2 dans le cadre d'une consultation de colposcopie Hohlfeld, P. De Grandi, P. info:eu-repo/semantics/article article 1988 Médecine et Hygiène, vol. 46, pp. 1325-1329 info:eu-repo/semantics/altIdentifier/pissn/0025-6749 fre oai:serval.unil.ch:BIB_644527E87B99 2022-02-19T02:22:49Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_644527E87B99 A study on the clinical significance of the who aml subtype inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q chromosomal abnormalities in 6,819 aml cases Lugthart, S. Groeschel, S. Beverloo, H. Valk, P. Schanz, U. Bhola, S. Vellenga, E. Kayser, S. Ossenkoppele, G. Verhoef, G. Ferrant, A. van den Berg-de Ruiter, E. Ganser, A. Jotterand, M. Krauter, J. Pabst, T. Schlegelberger, B. Schlenk, R. Delwel, R. Doehner, K. Loewenberg, B. Doehner, H. info:eu-repo/semantics/conferenceObject inproceedings 2010 15th Annual Meeting of the European Hematology Association, vol. 95, pp. 482 info:eu-repo/semantics/altIdentifier/isbn/0390-6078 eng oai:serval.unil.ch:BIB_6445291F3B73 2022-02-19T02:22:49Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_6445291F3B73 Le politique et l’oblitération. Sur la dialectique de l’engagement Voirol, Olivier info:eu-repo/semantics/bookPart incollection 2015 Penser l’engagement, pp. 71-95 Ouelbani, Mélika (ed.) fre oai:serval.unil.ch:BIB_63D52E568CD1 2022-02-19T02:22:47Z <oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd"> https://serval.unil.ch/notice/serval:BIB_63D52E568CD1 La maladie ulcereuse gastro-duodenale: que reste-t-il des indications chirurgicales? [Gastroduodenal ulcer disease: what surgical indications are left?] info:eu-repo/semantics/altIdentifier/pmid/2569232 Cuttat, J. F. Ruchat, P. Chapuis, G. info:eu-repo/semantics/article article 1989-05 Schweizerische Medizinische Wochenschrift, vol. 119, no. 21, pp. 729-30 info:eu-repo/semantics/altIdentifier/pissn/0036-7672 <![CDATA[Between 1976, date of the introduction of anti-H2, and 1987, 716 patients were hospitalized and operated on for ulcer disease in the surgical department of this hospital. The present study shows that 1. the annual number of operations has regressed by some 30%, 2. while the number of gastric ulcers remains constant on the whole, cases of acute duodenal ulcer have diminished by half, 3. cases of chronic, recurrent, or therapy-resistent duodenal ulcer have increased some tenfold (2 out of 78 in 1976 and 14 out of 45 in 1987), 4. the same is true of perforated ulcers (12 out of 78 in 1976 and 10 out of 45 in 1987) and hemorrhages (12 out of 78 and 10 out of 45), 5. surgery for stenosis has remained constant. -Proximal selective vagotomy has been the treatment of choice since 1981 in over 80% of duodenal ulcers. Operative mortality affects only elderly patients undergoing emergency surgery for complicated ulcer (two thirds perforations, one third hemorrhages). It is 2.6%. We thus confirm the reduced role of surgery in the treatment of gastric ulcer, while redefining the present surgical indications