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Substance use in pregnancy has been a prominent public health concern for the last several decades. Since the legalization of cannabis in Canada and across several American states, cannabis use during pregnancy has gained considerable public health, scientific, and media attention. This critical interpretive synthesis explores how the problem of cannabis use in pregnancy is constructed in the scientific literature and illuminates clinical, social, and political responses this construction engenders. The state of empirical evidence regarding the impact of perinatal cannabis use is fraught; a number of studies, of variable quality, have found no associations between cannabis use and adverse neonatal outcomes, while others have found cannabis to be associated with low birthweight and prematurity among other risks. Despite the inconsistent nature of the evidence base, the literature is underpinned by two important assumptions: prenatal cannabis exposure is an asocial phenomenon that can be disentangled from the social determinants of health, and cannabis exposure has detrimental effects on fetal and neonatal health. These assumptions shape indicators of signal and noise in the data by influencing the significance ascribed to particular findings, producing patterns of data interpretation that ultimately transform evidence of potential harms into certain risks and creates the mirage of a cohesive, unambiguous evidence base. We argue that the way that cannabis use in pregnancy is framed as a scientific and public health problem in the literature contributes to the stigmatization of pregnant people who use substances. We caution that failure to consider the interplay between environment, resources and other social determinants of health may ultimately cause undue harm to families and foreclose opportunities for investments that may promote health and well-being.

Introduction: Prazosin is an antihypertensive medication which can be used to help with post-traumatic stress disorder (PTSD) symptoms. Little data is currently available on its safety in pregnancy. Objective: To assess the fetal and pregnancy safety associated with Prazosin exposures in early Pregnancy. Methods: Subjects were 11 patients who took Prazosin during pregnancy and were counselled at the FRAME clinic in London Health Sciences Centre (Ontario, Canada) between January 1, 2000 to December 31, 2021. Data on their other exposures and pregnancy outcomes were collected from medical records and through telephone questionnaires. Results: It was found that 6 /11 (54.5%) subjects did not report any adverse outcomes and were uneventful pregnancies. There were 2 miscarriages. Birthweights were within the normal range for the remaining 9 pregnancies. Adverse events reported were consistent with background population expectation, including: 1 postpartum hemorrhage, 1 case of preeclampsia, 1 preterm birth, 2 NICU admissions, and 2 caesarean sections. Discussion / Conclusion: For these 11 subjects, pregnancy outcomes after exposure to Prazosin were consistent with typical outcomes from unexposed pregnancies. More data are needed to conclude that Prazosin is safe for use in pregnant subjects. However, the lack of adverse effects above baseline is reassuring to future patients who may be unintentionally exposed to Prazosin while pregnant. Therefore, this study contributes valuable data toward monitoring safety of Prazosin in Pregnancy.

Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease and is usually diagnosed in childhood, especially in the first decade of life. Paediatric FMF is characterized by a protean clinical expression and a variable therapeutic response, which can make its medical management very challenging. However, even if long-term complications of untreated FMF (e.g. amyloidosis and related organ damage) are less frequent in children compared to adults, they are not uncommon. Colchicine is the mainstay of the therapy in paediatric FMF; however, if children develop colchicine intolerance and/or resistance, biologics, particularly interleukin-1 antagonists, must be considered. Other conventional or biological therapeutic options do not currently have appropriate evidence-based support, except for some specific clinical presentations (e.g., arthritis). In this review, we discuss the biological basis and the clinical evidence for the current pharmacological treatment options available for paediatric FMF.

Background Parasite persistence after acute infection with Trypanosoma cruzi is an important factor in the development of Chagas disease (CD) cardiomyopathy. Few studies have investigated the clinical effectiveness of CD treatment through the evaluation of cardiological events by long term follow-up of treated children. Cardiological evaluation in children is challenging since features that would be diagnosed as abnormal in an adult’s ECG may be normal, age-related findings in a pediatric ECG trace. The objective was to evaluate cardiac involvement in patients with Chagas disease with a minimum follow-up of 6 years post-treatment. Methodology A descriptive study of a cohort of pediatric patients with CD treated with benznidazole (Bz) or nifurtimox (Nf) was conducted. Children (N = 234) with at least 6 years post CD treatment followed at the Parasitology and Chagas Service, Buenos Aires Children’s Hospital (Argentina) were enrolled. By convenience sampling, children who attended a clinical visit between August 2015 and November 2019 were also invited to participate for additional cardiovascular studies like 24-hour Holter monitoring and speckle-tracking 2D echocardiogram (STE). Benznidazole was prescribed in 171 patients and nifurtimox in 63 patients. Baseline parasitemia data was available for 168/234 patients. During the follow-up period, alterations in routine ECG were observed in 11/234 (4.7%, 95% CI [2–7.4%]) patients. In only four patients, with complete right bundle branch block (cRBBB) and left anterior fascicular block (LAFB), ECG alterations were considered probably related to CD. During follow-up, 129/130 (99%) treated patients achieved persistent negative parasitemia by qPCR. Also decrease in T.cruzi antibodies titers was observed in all patients and negative seroconversion occurred in 123/234 (52%) patients. Conclusions A low incidence of cardiological lesions related to CD was observed in patients treated early for pediatric CD. This suggests a protective effect of parasiticidal treatment on the development of cardiological lesions and highlights the importance of early treatment of infected children. Trial registration ClinicalTrials.gov NCT04090489.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a rare, drug-induced severe adverse reaction that usually occurs 3-6 weeks after initial exposure to certain drugs. It affects mainly adults and children to a lesser extent. Clinical features include fever, facial oedema, generalized skin rash, lymphadenopathy, haematological abnormalities and internal organ involvement. The objective was to investigate the clinical and laboratory features of patients with DRESS in our centre.We retrospectively describe and analyse 19 cases of DRESS whose diagnosis was based on the RegiSCAR criteria (≥6 points) that occurred from January 2009 to December 2019.Patient age ranged from 4 to 76 years (4 children/15 adults); 10 were female (52.3%). The most common culprit drugs were antibiotics (74%) and anticonvulsants (21%). The most common comorbidities were epilepsy (26%) and hypertension (26%). All patients developed cutaneous manifestations and of those, 58% presented facial oedema. Liver function tests, urea/creatinine and troponin elevation were present in 74, 32 and 42%, respectively. The median time to develop the skin rash after the drug exposure was 3.7 weeks (interquartile range 2.4-4.2 wk). Eosinophilia (≥0.7 × 10DRESS is a serious condition with significant morbidity and mortality, which requires more research for a better understanding.

Treatment of Chagas disease with nifurtimox requires age- and body weight-adjusted dosing, resulting in complex dosing instructions. Appropriate formulations are needed for precise and compliant dosing, especially in pediatric patients. We characterized the biopharmaceutical features of a standard nifurtimox 120-mg tablet and a 30-mg tablet developed to improve dose accuracy. Two open-label, randomized crossover studies were conducted in adult outpatients with Chagas disease. One study investigated whether 4 × 30-mg tablets and 1 × 120-mg tablet were bioequivalent and whether tablets can be administered as an aqueous slurry without affecting bioavailability. The second study investigated the effect of a high-calorie/high-fat diet versus fasting on the absorption of nifurtimox after a single 4 × 30-mg dose. Interventions were equivalent if the 90% confidence interval (CI) of their least-squares (LS) mean ratios for both AUC0-tlast and Cmax were in the range of 80%-125%. The 4 × 30-mg and 1 × 120-mg tablet doses were bioequivalent (AUC0-tlast: LS mean ratio, 104.7%; 90%CI, 99.1%-110.7%; Cmax: LS mean ratio, 101.7%; 90%CI, 89.4%-115.6%; n = 24). Exposure when giving the 4 × 30-mg dose as a slurry or as tablets was comparable, with an AUC0-tlast ratio of 93.2% (84.2%-103.1%; n = 12) and a slightly decreased Cmax ratio for the slurry of 76.5% (68.8%-85.1%). Food improved the bioavailability of nifurtimox substantially (AUC0-tlast ratiofed/fasted, 172%; 90%CI, 154%-192%; Cmax ratiofed/fasted, 168%; 90%CI, 150%-187%). The data indicate that the 30- and 120-mg tablets are suitable for dosing adult and pediatric patients accurately; nifurtimox should be administered under fed conditions. Fil: Stass, Heino. No especifíca; Fil: Feleder, Ethel. No especifíca; Fil: Garcia Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina Fil: Nagelschmitz, Johannes. No especifíca; Fil: Weimann, Boris. No especifíca; Fil: Yerino, Gustavo. No especifíca; Fil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. COVID-19 leads, in most patients, to mild-to-moderate symptoms, but some develop severe disease and succumbed to death. People with medical conditions have a higher risk of death than those without them. Chagas disease (CD) can cause cardiac diseases in approximately one-third of affected people. The aim of this study is to find out if there is any clinical association between Chagas disease and COVID-19 severity. This is a cohort study of 29 patients who were hospitalized with COVID-19 and had a diagnosis of chronic Trypanosoma cruzi infection. This coinfected cohort was matched by sex, age, presence of comorbidities, and requirement of hospitalization on intensive care unit (ICU) at admission with a control cohort of patients hospitalized due to COVID-19 without CD in a 3:1 ratio (n = 87). The clinical outcomes evaluated were as follows: days of hospitalization, death, and requirement of ICU and mechanical respiratory assistance (MV). The study protocol was approved by the Institutional Ethics in Research Committee. The Chagas disease/COVID-19 coinfected cohort had a median age of 55 years old (49.0, 66.0); 17 (59%) were male. All patients survived the acute COVID-19. Three of them were admitted to the ICU, and two required MV. Twenty-two (75.8%) required supplemental oxygen. There were no statistical differences in any laboratory parameters between the groups except for lactic acid dehydrogenase, which showed higher levels in the coinfected cohort, with a median of 573 U/L (interquartile range: 486.00, 771.00) vs. 476 U/L (346.00, 641.00) in the control group (p = 0.007). There were no differences in clinical outcomes between both groups. On the cohort with Chagas disease, there were zero deaths, three (10.3%) were admitted in the ICU, and two (6.9%) required MV, while for the control group there were six deaths (6.6%), 13 required ICU (14.9%), and 11 required MV (12.6%), without a statistically significant difference. This small series of coinfected Chagas disease and COVID-19 does not suggest differences in clinical evolution compared to non-Chagas patients. This data is similar to a Brazilian cohort. More data of this population with and without cardiomyopathy is needed to optimize the follow-up and recommendation for the population affected by this neglected tropical disease about COVID-19.

It is unfortunately true that clinicians lack the necessary evidence to know how to use medications properly in large sections of the population and do not have optimal treatments to use for many neglected tropical diseases (NTDs). NTDs often disproportionately affect neglected populations that are left out of research efforts, such as children and pregnant women. As reliable access to safe, effective preventives and treatments can break the cycle of poverty, illness, and ensuing debility that further perpetuates poverty, it is of paramount importance to investigate and develop new medicines for neglected populations suffering from NTDs. Furthermore, there is not only a need to develop and evaluate novel therapies, but also to ensure that these are affordable, available, and adapted to the communities who need them. The NIH has proposed a “4 C's” framework which is relevant for neglected diseases and populations and should be leveraged for the study of the Twice Neglected: Consider inclusion; Collect data from neglected populations with neglected conditions; Characterize differences through meaningful analysis; Communicate findings pertaining to neglected diseases and populations. With this editorial, the British Journal of Clinical Pharmacology hereby launches a call for high-quality articles focusing on NTDs in special populations, to facilitate and encourage the reversal of this dual neglect.

Chagas disease reactivation in HIV-positive people is an opportunistic infection with 79 to 100% mortality. It commonly involves the central nervous system (CNS). Early treatment with trypanocidal drugs such as benznidazole (BNZ) is crucial for this severe manifestation of Trypanosoma cruzi infection. However, limited BNZ clinical pharmacology data are available, especially its concentration in the CNS. We report a series of HIV-positive patients undergoing treatment for T. cruzi meningoencephalitis, their clinical response, and cerebrospinal fluid (CSF) and plasma BNZ concentrations. Measurements were carried out using leftover samples originally obtained for routine medical care. A high-performance liquid chromatography/tandem mass spectrometry bioanalytical method designed for BNZ plasma measurements was adapted and validated for CSF samples. Six patients were enrolled in this study from 2015 to 2019. A total of 6 CSF and 19 plasma samples were obtained. Only three of the CSF samples had detectable BNZ levels, all under 1mg/ml. Fifteen plasma samples had detectable BNZ, and 13 were above 2mg/ml, which is the putative trypanocidal level. We observed BNZ concentrations in human CSF and plasma. CSF BNZ concentrations were low or not measurable in all patients, suggesting that the usual BNZ doses may be suboptimal in HIV-positive patients with T. cruzi meningoencephalitis. While drug-drug and drug-disease interactions may be in part responsible, the factors leading to low CSF BNZ levels remain to be studied in detail. These findings highlight the potential of therapeutic drug monitoring in BNZ treatment and suggest that the use of higher doses may be useful for Chagas disease CNS reactivations. Fil: Fernandez, Marisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina Fil: 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; Argentina Fil: 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; Argentina Fil: Corti, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Fleitas, Ulises Emiliano. 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; Argentina Fil: Lloveras, Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Lista, Nicolás. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Priarone, Maria M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Dominguez, Cecilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina Fil: Garcia-Bournissen, Facundo. Western University; Canadá

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). Fil: Berenstein, Ariel José. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Falk, Nicolás Ariel. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Moscatelli, Guillermo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Moroni, Samanta. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: González, Nicolas. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Garcia Bournissen, Facundo. Western University; Canadá Fil: Ballering, Griselda Edith. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Freilij, Hector León. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina

There is an urgent need to develop safer and more effective drugs for Chagas disease, as the current treatment relies on benznidazole (BZ) and nifurtimox (NFX). Using the Trypanosoma cruzi Dm28c strain genetically engineered to express the Escherichia coli β-galactosidase gene, lacZ, we have adapted and validated an easy, quick and reliable in vitro assay suitable for high-throughput screening for candidate compounds with anti-T. cruzi activity. In vitro studies were conducted to determine trypomastigotes sensitivity to BZ and NFX from Dm28c/pLacZ strain by comparing the conventional labour-intensive microscopy counting method with the colourimetric assay. Drug concentrations producing the lysis of 50% of trypomastigotes (lytic concentration 50%) were 41.36 and 17.99 µM for BZ and NFX, respectively, when measured by microscopy and 44.74 and 38.94 µM, for the colourimetric method, respectively. The optimal conditions for the amastigote development inhibitory assay were established considering the parasite–host relationship (i.e. multiplicity of infection) and interaction time, the time for colourimetric readout and the incubation time with the β-galactosidase substrate. The drug concentrations resulting in 50% amastigote development inhibition obtained with the colourimetric assay were 2.31 µM for BZ and 0.97 µM for NFX, similar to the reported values for the Dm28c wild strain (2.80 and 1.5 µM, respectively). In summary, a colourimetric assay using the Dm28c/pLacZ strain of T. cruzi has been set up, obtaining biologically meaningful sensibility values with the reference compounds on both trypomastigotes and amastigotes forms. This development could be applied to high-throughput screening programmes aiming to identify compounds with anti-T. cruzi in vitro activity.

Dear Editor,Nivolumab, a humanized IgG4 monoclonal antibody, blocks the programmed cell death protein-1 (PD-1) leading to lymphocyte activation against many chemotherapy-resistant tumors [1]. Women...

Acetaminophen has become a novel treatment option for patent ductus arteriosus closure in premature infants. This raises concerns about whether acetaminophen should be avoided in late pregnancy, similar to nonsteroidal anti-inflammatory drugs, because of the risk of in utero ductus arteriosus closure. This article critically evaluated the literature reporting an association between acetaminophen use and in utero ductus arteriosus closure and provided a comparative pharmacokinetic analysis of fetal acetaminophen exposure in pregnancy vs drug levels in neonates, with the goal of making an expert recommendation regarding its safety. Here, 1 prospective cohort study and 12 case reports and series evaluating the risk of premature ductus arteriosus closure with prenatal acetaminophen use were reported and overall do not suggest causation. Pharmacokinetic studies showed that acetaminophen fetal transplacental exposures are well below the levels shown to close the ductus arteriosus in neonates. Short-term use of acetaminophen in the third trimester of pregnancy poses a negligible risk of premature ductus arteriosus closure and can still be considered safe in the third trimester of pregnancy at recommended doses.

Context The use of intravenous acetaminophen leads to meaningful health cost increases for paediatric institutions. Therefore, strict criteria for intravenous acetaminophen administration are needed. Objective To undertake a systematic review of available evidence comparing oral versus intravenous acetaminophen use in children. Method A systematic literature search was conducted on five databases. All prospective interventional studies comparing intravenous to oral acetaminophen in patients Results Among 6,417 retrieved abstracts, 29 full-text articles were assessed of which 3 were retained. (1) Pharmacokinetic: Oral bioavailability (72% with a high inter-individual variability) was reported in 47 stable patients in a paediatric intensive care unit. (2) Analgesia: In a double-blind randomized controlled trial of 45 children, no difference in analgesia was found between oral and intravenous administration after cleft palate repair. (3) Fever: In an open-label prospective observational study of 200 children, temperature decreased faster after intravenous than oral administration but was similar 4 hours later. Conclusions Available data are insufficient to guide clinicians with a rational choice of route of administration. Oral bioavailability should be studied in paediatric populations outside the intensive care unit. Despite the widespread use of intravenous acetaminophen, there is little evidence to suggest that it improves analgesia compared to the oral formulation. Similarly, fever weans faster but whether this translates into any meaningful clinical outcome is unknown. The lack of data plus the significantly higher costs of intravenous acetaminophen should motivate further research.

BACKGROUND: The benefits of early cystic fibrosis (CF) detection using newborn screening (NBS) has led to widespread use in NBS programs. Since 2002, a two-stage immunoreactive trypsinogen (IRT/IRT) screening strategy has been used as a CFNBS method in all public maternity units in the City of Buenos Aires, Argentina. However, novel screening strategies may be more efficient. The aim of this study is to prospectively compare two CFNBS strategies: IRT/IRT and IRT/PAP (pancreatitis-associated protein). METHODS: A two-year prospective study was performed. IRT was measured in dried blood samples collected 48-72 h after birth. When an IRT value was abnormal, PAP was determined, and a second visit was scheduled to obtain another sample for IRT before 25 days of life. Newborns with a positive CFNBS were referred for a confirmatory sweat test. RESULTS: There were 69,827 births in the City of Buenos Aires during the period studied; 918 (1.31%) had an abnormal IRT. A total of 207 children (22.5%) failed to return for the second IRT, but only two PAP (0.2%) were not performed. IRT/IRT was more likely to lead to a referral for sweat testing than IRT/PAP (odds ratio 2.3 [95% confidence interval 1.8-2.9], p

Combination therapy has been proposed as an ideal strategy to reduce drug toxicity and improve treatment efficacy in Chagas disease. Previously, we demonstrated potent in vivo anti-Trypanosoma cruzi activity of voriconazole. In this work, we aimed to study the synergistic effect of voriconazole (VCZ) and benznidazole (BZ) both in vitro and in vivo models of T. cruzi infection using the Tulahuen strain. Combining VCZ and BZ at fixed concentrations, the inhibitory concentration 50% (IC50) on amastigotes was lower than the obtained IC50 for BZ alone and the Fractional Inhibitory Concentration Index (∑FIC) suggested an in vitro additive effect on T. cruzi amastigotes inhibition at concentrations devoid of cytotoxic effects. Treatment response in the in vivo model was evaluated by comparing behavior and physical aspects, parasitemia and mortality of mice infected with Tulahuen strain. VCZ and BZ treatments alone or in combination were well tolerated. All treated animals displayed significantly lower mean peak parasitemia and mortality compared to infected non-treated controls (p< 0.05). However, VCZ + BZ combination elicited no additional benefits over BZ monotherapy. VCZ efficacy was not enhanced by combination therapy with BZ at the doses studied, requiring further and astringent non-clinical studies to establish the VCZ efficacy and eventually moving forward to clinical trials. Fil: Gulin, Julián Ernesto Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: Eagleson, Mackenzie Anne. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Harvard University; Estados Unidos Fil: López Muñoz, Rodrigo A.. Universidad Austral de Chile; Chile Fil: Solana, María Elisa. Universidad Nacional de Luján; Argentina. Universidad de Buenos Aires; Argentina Fil: Altcheh, Jaime Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina Fil: García Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Western University; Canadá

Background Treatment with nifurtimox (NF) for Chagas disease is discouraged during breast-feeding because no information on NF transfer into breast milk is available. NF is safe and effective for paediatric and adult Chagas disease. We evaluated the degree of NF transfer into breast milk in lactating women with Chagas disease. Patients and methods Prospective study of a cohort of lactating women with Chagas disease. Patients were treated with NF for 1 month. NF was measured in plasma and milk by high performance liquid chromatography (HPLC). Breastfed infants were evaluated at admission, 7th and 30th day of treatment (and monthly thereafter, for 6 months). Results Lactating women with chronic Chagas disease (N = 10) were enrolled (median age 28 years, range 17–36). Median NF dose was 9.75 mg/kg/day three times a day (TID). Six mothers had mild adverse drug reactions (ADRs), but no ADRs were observed in any of the breastfed infants. No interruption of breastfeeding was observed. Median NF concentrations were 2.15 mg/L (Inter quartil range (IQR) 1.32–4.55) in milk and 0.30 mg/L (IQR 0.20–0.95) in plasma. Median NF milk/plasma ratio was 16 (range 8.75–30.25). Median relative infant NF dose (assuming a daily breastmilk intake of 150 mL/kg/day) was 6.7% of the maternal dose/kg/day (IQR 2.35–7.19%). Conclusions The low concentrations of NF in breast milk and the normal clinical evaluation of the breastfed babies imply that maternal NF treatment for Chagas disease during breastfeeding is unlikely to lead to clinically relevant exposures in the breastfed infants. Trial registration Clinical trial registry name and registration number: ClinicalTrials.gov NCT01744405., Author summary It is not known whether Nifurtimox, a drug for Chagas disease, is significantly transferred into breast milk, and no clinical trials were conducted to evaluate this topic. Treatment with nifurtimox is safe and effective in children and newborns with Chagas disease. Treatment of young women before pregnancy prevents congenital transmission of Chagas disease. This is the first study to measure nifurtimox concentrations in breast milk. We found that presence of nifurtimox into breast milk is limited, and that breastfed babies had normal clinical evaluations with no observable adverse events. None of the mothers had to discontinue breastfeeding due to adverse events. The exposure of nifurtimox through breast milk during the treatment of mothers with Chagas disease does not seem to pose significant risks for the breastfed infants.

Chagas disease is a parasitic disease endemic to Latin America that, if left untreated, can lead to severe long-term organ damage, particularly in the heart and gastrointestinal tract. Treatment with benznidazole or nifurtimox has been shown to be effective in the acute phase and during childhood, and limited evidence suggest a beneficial effect later in life too. However, both drugs require prolonged treatments (30–60 days) and are associated to significant adverse events that increase in severity and prevalence with age. Prompt pediatric diagnosis and treatment are vital for an effective use of these medications.

Background:Few studies have focused on Familial Mediterranean Fever (FMF)-related AA amyloidosis and cardiovascular disease event risk. Systemic inflammation stimulates the development and progression of atherosclerosis which is accelerated by vascular endothelial inflammation and enhanced oxidative stress. Excessive reactive oxygen species (ROS) generation has been reported in FMF, which correlated with attack severity. ROS may also be involved in amyloid formation, and in the pathogenesis of progressive renal injury.Objectives:In this non-randomized, 24 weeks open label interventional study, we aimed to evaluate the effect of a combination of natural products on parameters related to inflammation, endothelial dysfunction and oxidative stress in a cohort of FMF patients with AA amyloidosis.Methods:Morinda citrifolia (anti-atherosclerotic liquid- AAL), omega-3 (anti-inflammatory capsules- AIC) and extract with Alaskan blueberry (anti-oxidant liquid- AOL) were given to patients with FMF related AA amyloidosis. We included patients with biopsy proven AA amyloidosis, older than 18 years who have normal estimated glomerular filtration rate (eGFR) and proteinuria [>3500mg/day]. Flow-mediated dilatation (FMD), asymmetric dimethylarginine (ADMA), hs-CRP, serum PTX3, Carotis intima media thickness (CIMT), malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels were studied in baseline and after 24 weeks.Results:67 FMF-related amyloidosis [52 male (77.6%); median recruitment age 36 years (range 21-66)] were enrolled. M694V mutation was the most common mutation found (74%), with 50.7% of the patients in homozygosity. All patients were treated with colchicine, and most of them (83.6%) has been on colchicine treatment at the time of enrollment. Serum ADMA, MDA, PTX3, hsCRP, cholesterol, and proteinuria were significantly decreased compared to baseline, while CuZn-SOD, GSH-Px and FMD levels were significantly increased following AAL, AIC and AOL therapies (Table 1). The change of the inflammatory markers PTX3, and hsCRP were negatively correlated with the change in FMD and positively correlated with the change of proteinuria, ADMA, MDA, cholesterol and CIMT.Conclusion:24 weeks of AAL, AIC and AOL combined supplementation was significantly associated with reduction in serum inflammatory markers (PTX3 and hsCRP), improved endothelial functions (FMD, ADMA), and oxidative state (MDA). Our findings highlight the link among the three pathogenetic mechanisms including inflammation, endothelial function and oxidative status in progression of atherosclerosis and renal injury in patients with FMF related AA amyloidosis. Efficient control of these three mechanisms can have long term benefits from the cardiovascular and renal perspective of the patients with AA amyloidosis.References:[1]Romano M et al. Sci Rep, 2020[2]Yilmaz M et al. Sci Rep, 2020Table 1.Comparison of clinical and laboratory characteristics at the baseline and after 24 weeks of AAL, AIC and AOL supplementationBaselineMean (SD)24th weekMean (SD)DeltaMean (SD)pTotal Cholesterol (mg/dl)221.2 (60.3)155.8 (35.4**)-65.3 (55.5)eGFR (ml/min/ 1.73 m2)110.2 (12.8)104.1 (11.2**)-6.1 (11.9)Malondialdehyde (MDA) (nmol/ml)4.2 (1.8)1.8 (0.5**)-2.2 (1.8)CuZn-SOD (U/ml)431.5 (154.7)538.1 (146.4**)159.7 (211.8)GSH-Px (U/ml)47.8 (13.2)74.1 (20.3**)26.3 (21.1)ADMA (µmol/l)4.5 (2.6)1.3 (0.6**)-3.2 (2.5)FMD (%)5.0 (0.7)6.4 (0.8**)1.3 (0.9)CIMT (mm)0.9 (0.2)0.7 (0.1)-0.2 (0.2)Proteinuria (mg/24h)6855.3 (3116.9)4079.9 (2359.6)-2775.3 (2874.5)hs-CRP (mg/l)25.5 (4.4-48.0)3.0 (1.0-9.1)*-20.8 (11.2)PTX3 (ng/ml)13.4 (2.3-67.0)2.3 (0.4-14.5)*-17.5(17.5)Disclosure of Interests:None declared

This study aimed to evaluate well-documented diagnostic antigens, named B13, 1F8 and JL7 recombinant proteins, as potential markers of seroconversion in treated chagasic patients. Prospective study, involving 203 patients treated with benznidazole, was conducted from endemic areas of northern Argentina. Follow-up was possible in 107 out of them and blood samples were taken for serology and PCR assays before and 2, 3, 6, 12, 24 and 36 months after treatment initiation. Reactivity against Trypanosoma cruzi lysate and recombinant antigens was measured by ELISA. The rate of decrease of antibody titers showed nonlinear kinetics with an abrupt drop within the first three months after initiation of treatment for all studied antigens, followed by a plateau displaying a low decay until the end of follow-up. At this point, anti-B13, anti-1F8 and anti-JL7 titers were relatively close to the cut-off line, while anti-T. cruzi antibodies still remained positive. At baseline, 60.8% (45/74) of analysed patients tested positive for parasite DNA by PCR and during the follow-up period in 34 out of 45 positive samples (75.5%) could not be detected T. cruzi DNA. Our results suggest that these antigens might be useful as early markers for monitoring antiparasitic treatment in chronic Chagas disease. Fil: Niborski, Leticia Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Grippo, Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Lafon, Sonia Olga. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Levitus, Gabriela Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: García Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ramirez Gomez, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Burgos, Juan Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Bisio, Margarita María Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Juiz, Natalia Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Ayala, Vilma. Centro Asistencial Cáritas Diocesana; Argentina Fil: Coppede, María. Centro Asistencial Cáritas Diocesana; Argentina Fil: Herrera, Verónica. Centro Asistencial Cáritas Diocesana; Argentina Fil: López, Crescencia. Centro Asistencial Cáritas Diocesana; Argentina Fil: Contreras, Ana. Centro Asistencial Cáritas Diocesana; Argentina Fil: Gomez, Karina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Elean, Juan C.. Centro Asistencial Cáritas Diocesana; Argentina Fil: Mujica, Hugo D.. Centro Asistencial Cáritas Diocesana; Argentina. Hospital Zonal de Añatuya; Argentina Fil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Levin, Mariano Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina

Background Acetaminophen is the most commonly used drug in children. In 2019, an IV formulation became available in Canada, but with a price tag >500 times higher than oral acetaminophen. Acetaminophen use has been growing in the US since its approval in 2011, leading to a significant health cost increase. Therefore, strict criteria for IV acetaminophen administration are needed to guide clinicians with a rational choice for route of administration and contain costs. Objectives To undertake a systematic review of available evidence comparing oral versus IV acetaminophen use in children. Design/Methods A systematic literature search was conducted on 5 databases until October 2019. All prospective interventional studies comparing IV to oral acetaminophen in patients Results Among 6417 abstracts, 29 full text articles were assessed, of which only 3 were retained. Indication for acetaminophen use in these studies was: analgesia (2 studies) and fever (1 study). Studies focused on: - Pharmacokinetics: In 2019, the first determination of oral bioavailability (F) of acetaminophen in children was reported in 47 stable PICU patients (microtracer study design with a population pharmacokinetic study). It showed an F=72% with a high inter-individual variability (range: 11%-91%). - Pharmacodynamics studies: • Analgesia: Analgesic efficacy after cleft palate repair was compared in 45 children (median age: 8 month) divided in three arms receiving either oral (15mg/kg every 6h), IV (12.5mg/kg every 6h) or placebo in a double-blind randomized controlled trial. No difference in pain scores and opioids requirements was found between the oral and IV acetaminophen groups. • Fever: An open-label prospective observational study reported the effect of IV (15mg/kg) versus oral acetaminophen (15mg/kg) on the evolution of temperature in children with fever >39.5°C in hospital and outpatient settings. Two hundred patients (mean age 6.7 years) were included in each arm. Temperature decreased quicker with IV administration but 4 hours after administration, temperature was similar in each group. Conclusion Despite the widespread use of IV acetaminophen, there is little evidence to suggest that it improves analgesia compared to the oral formulation. Similarly, fever weans faster but whether this translates into any meaningful clinical outcome is unknown. Available data is insufficient to guide clinicians with a rational choice of route of administration, but the significantly higher costs do not seem justified by the small (if any) benefits of IV vs oral acetaminophen.

Chagas disease (CD) is recognized as one of the major neglected global tropical diseases. Benznidazole (BNZ) is the drug of choice for the treatment of adults, young infants, and newborns with CD., Chagas disease (CD) is recognized as one of the major neglected global tropical diseases. Benznidazole (BNZ) is the drug of choice for the treatment of adults, young infants, and newborns with CD. However, the pharmacokinetics (PK) of BNZ have been poorly evaluated in all age groups, with consequent gaps in knowledge about PK-pharmacodynamic relationships in CD. The purpose of this study was to develop and validate a bioanalytical method to quantify BNZ levels in small-volume whole-blood samples collected as dried blood spots (DBS). The analysis was performed using high-performance liquid chromatography-positive electrospray tandem mass spectrometry. PK evaluation in healthy male volunteers was conducted to verify the correlation between DBS and plasma BNZ concentrations. The calibration curve was linear from 50 to 20,000 ng · ml−1. Intra- and interday precision and bias values were less than 14.87% (n = 9) and 9.81% (n = 27), respectively. The recovery rates ranged from 94 to 100% with no matrix effect. There was no hematocrit level effect in a range of 20 to 70%. The PK results obtained from DBS and plasma were comparable (r2 = 0.8295) and equivalent to previously published information on BNZ. BNZ in DBS was stable at room temperature for more than one year. This article describes the first microsampling method for measuring BNZ levels in DBS that has the potential to facilitate broad implementation of PK in clinical trials involving adult and pediatric patients in remote areas and helps to address existing knowledge gaps in the treatment of CD.

Background. No reliable tests or validated biomarkers exist to ensure parasitological cure following treatment of Chagas disease (CD) patients chronically infected with Trypanosoma cruzi. As seroreversion, the only marker of cure, happens more quickly in children, we investigated the correlation between previously identified biomarkers and seroreversion in children. Methods. Thirty CD children (age 1 month to 10 years) diagnosed as T. cruzi positive (time point S0) were treated with benznidazole (BZ) 5-8 mg/kg/d for 60 days. At least 2 serological tests were used to evaluate treatment efficacy from the end of treatment (S1) until seroreversion (S2). Thirty children (age 1 month to 10 years) and 15 adults were used as healthy controls (HCs). Immunoblot and a proteomic-based assay were used to validate previously identified fragments of apolipoprotein A-1 (ApoA1) and fibronectin (FBN) as CD biomarkers. Results. Correlation between seroreversion and absence of ApoA1 and FBN fragments by immunoblot was observed in 30/30 (100%) and 29/30 (96.6%) CD children, respectively. ApoA1 and FBN fragments were absent at the end of BZ treatment in 20/30 (66.6%) and 16/30 (53.3%) children, respectively. Absence of fragments in serum profiles was confirmed by mass spectrometry. Using intact protein analysis, a 28 109-Da protein identified as full-length ApoA1 by tandem mass spectrometry was detected in HC serum samples. Conclusions. These data confirm that ApoA1 and FBN fragments can discriminate between healthy and T. cruzi-infected samples. Correlation with seroreversion was shown for the first time; results suggest predictive capacity potentially superior to serology, making them potentially useful as surrogate biomarkers. Fil: Ruiz Lancheros, Elizabeth. National Reference Centre For Parasitology; Canadá Fil: Rasoolizadeh, Asieh. National Reference Centre For Parasitology; Canadá Fil: Chatelain, Eric. No especifíca; Fil: Garcia Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; Argentina Fil: Moroni, Samanta. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; Argentina Fil: Moscatelli, Guillermo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; Argentina Fil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; Argentina Fil: Ndao, Momar. National Reference Centre For Parasitology; Canadá

Background Risk assessment of the use of quetiapine during breastfeeding is challenging owing to a paucity of data. Methods A pharmacokinetic study was conducted in lactating women who were taking quetiapine. The primary endpoint was to determine quetiapine concentration profiles in milk and estimated infant exposure levels. Multiple milk and a single blood quetiapine concentrations were determined using a highly sensitive liquid chromatography with tandem mass spectroscopy method. Results Nine subjects receiving fast-release quetiapine (mean dose, 41 mg/d) were analyzed at steady state. The mean milk/plasma drug concentration ratio at 2-hour postdose was 0.47 (SD, 0.50; range, 0.13-1.67). The mean milk concentration of each patient was 5.7 ng/mL (SD, 4.5; range, 1.4-13.9 ng/mL). The mean infant quetiapine dose via milk per body weight relative to weight-adjusted maternal dose was 0.16 % (SD, 0.08; range, 0.04%-0.35%). Conclusions Infant exposure levels to quetiapine via milk are predicted to be very small.

Aims Population pharmacokinetic (pop PK) modelling can be used for PK assessment of drugs in breast milk. However, complex mechanistic modelling of a parent and an active metabolite using both blood and milk samples is challenging. We aimed to develop a simple predictive pop PK model for milk concentration–time profiles of a parent and a metabolite, using data on fluoxetine (FX) and its active metabolite, norfluoxetine (NFX), in milk.

Background: Benznidazole (BNZ) is safe and effective for the treatment of paediatric Chagas disease. Treatment of adults is also effective in many cases, but discouraged in breastfeeding women because no information on BNZ transfer into breast milk is available. We aimed to evaluate the degree of BNZ transfer into breast milk in lactating women with Chagas disease. Patients and methods: Prospective cohort study of lactating women with Chagas disease treated with BNZ administered for 30 days. Patients and their breastfed infants were evaluated at admission, the 7th and 30th day of treatment (and monthly thereafter, for 6 months). BNZ was measured in plasma and milk by high performance liquid chromatography. The protocol was registered in ClinicalTrials.gov (#NCT01547533). Results: 12 lactating women with chronic Chagas disease were enrolled (median age 28.5 years, range 20–34). Median BNZ dose was 5.65 mg/kg/day twice daily. Five mothers had adverse drug events (45%), but no adverse drug reactions or any untoward outcomes were observed in the breastfed infants. Median milk BNZ concentration was 3.8 mg/L (range 0.3–5.9) and 6.26 mg/L (range 0.3–12.6) in plasma. Median BNZ milk to plasma ratio was 0.52 (range 0.3–2.79). Median relative BNZ dose received by the infant (assuming a daily breast milk intake of 150 mL/kg/day) was 12.3% of the maternal dose per kg (range 5.5%–17%). Conclusions: The limited transference of BNZ into breast milk and the reassuring normal clinical evaluation of the breastfed babies suggest that maternal BNZ treatment for Chagas disease during breast feeding is unlikely to present a risk for the breastfed infant. Fil: García Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Moroni, Martín Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina Fil: Marson, María Elena. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina Fil: Moscatelli, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina Fil: 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; Argentina Fil: Bisio, Margarita María Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina Fil: Cornou, Maria Elina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina Fil: Ballering, Griselda. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina Fil: Altcheh, Jaime Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina

Fil: Marson, Maria Elena. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Area de Toxicologia; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas; Argentina

Dispersive ionic liquid–liquid microextraction combined with liquid chromatography and UV detection was used for the determination of two antichagasic drugs in human plasma: nifurtimox and benznidazole. The effects of experimental parameters on extraction efficiency—the type and volume of ionic liquid and disperser solvent, pH, nature and concentration of salt, and the time for centrifugation and extraction—were investigated and optimized. Matrix effects were detected and thus the standard addition method was used for quantification. This microextraction procedure yielded significant improvements over those previously reported in the literature and has several advantages, including high inter-day reproducibility (relative standard deviation=1.02% and 3.66% for nifurtimox and benznidazole, respectively), extremely low detection limits (15.7 ng mL −1 and 26.5 ng mL −1 for nifurtimox and benznidazole, respectively), and minimal amounts of sample and extraction solvent required. Recoveries were high (98.0% and 79.8% for nifurtimox and benznidazole, respectively). The proposed methodology offers the advantage of highly satisfactory performance in addition to being inexpensive, simple, and fast in the extraction and preconcentration of these antichagasic drugs from human-plasma samples, with these characteristics being consistent with the practicability requirements in current clinical research or within the context of therapeutic monitoring., Facultad de Ciencias Exactas

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.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.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.Among allabstracts presented at National Pediatric Research Meetings, 41.5% were fully published. Lack of time was the most common reason for unpublished studies.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.Estudio descriptivo y analítico, que incluyó todos los trabajos presentados en Encuentros N acionales 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.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.El 41,5% de trabajos presentados en Encuentros Nacionales de Investigación Pediátrica alcanzaron la publicaciónen texto completo. La falta de tiempo fue la principal causa para no hacerlo.

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); Argentina Fil: Ossorio, Maria F.. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina. Sociedad Argentina de Pediatría; Argentina Fil: Cuestas, Eduardo. Sociedad Argentina de Pediatría; Argentina. Hospital Privado de Córdoba; Argentina Fil: Giglio, Norberto. Sociedad Argentina de Pediatría; Argentina. Hospital General de Niños Ricardo Gutiérrez; Argentina Fil: Grandi, Carlos. Sociedad Argentina de Pediatría; Argentina. Hospital Materno-infantil Ramón Sardá; Argentina Fil: Garcia Bournissen, Facundo. Hospital General de Niños Ricardo Gutiérrez; Argentina. Sociedad Argentina de Pediatría; Argentina Fil: Vidaurreta, Santiago. Sociedad Argentina de Pediatría; Argentina. Hospital Universitario CEMIC; Argentina Fil: Altcheh, Jaime Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital General de Niños Ricardo Gutiérrez; Argentina. Sociedad Argentina de Pediatría; Argentina Fil: Ferrero, Fernando. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños Pedro Elizalde (ex Casa Cuna); Argentina. Sociedad Argentina de Pediatría; Argentina

OBJECTIVES: To report clinical course, etiology, management, and long-term outcomes of children suffering from Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). METHODS: We conducted a study of all pediatric patients with SJS or TEN admitted between 2000 and 2007 to the Hospital for Sick Children and Children's Hospital Boston, and particular attention was paid to clinical manifestations, etiology, mortality, and long-term outcomes. RESULTS: We identified 55 cases of SJS (n = 47), TEN (n = 5), or SJS/TEN overlap syndrome (n = 3). Drugs were identified as the most likely etiologic agent in 29 children (53%); antiepileptic drugs were the most common agents (n = 16), followed by sulfonamide antibiotics (n = 7) and chemotherapy drugs (n = 2). Acute Mycoplasma pneumoniae infection was confirmed in 12 children (22%), and herpes simplex virus was confirmed in 5 children (9%). Treatment regimens differed significantly between participating sites and included systemic antimicrobial agents (67%), systemic corticosteroids (40%), and antiviral drugs (31%). Intravenous immunoglobulin was administered to 21 children (38%), of whom 8 received concomitant systemic corticosteroids. Ten children (18%) had recurrence of SJS up to 7 years after the index episode, and 3 experienced multiple recurrences. Twenty-six children (47%) suffered long-term sequelae that mostly involved the skin and eyes. CONCLUSIONS: Mortality rate in children was lower than that reported in adults, but half of affected children suffered long-term complications. The recurrence rate of SJS was high (1 in 5), which suggests vulnerability and potential genetic predisposition. In the absence of standardized management guidelines for these conditions, treatment regimens differed significantly between participating institutions.

Dual perfusion of a single placental lobule is the only experimental model to study human placental transfer of substances in organized placental tissue. To date, there has not been any attempt at a systematic evaluation of this model. The aim of this study was to systematically evaluate the perfusion model in predicting placental drug transfer and to develop a pharmacokinetic model to account for nonplacental pharmacokinetic parameters in the perfusion results. In general, the fetal-to-maternal drug concentration ratios matched well between placental perfusion experiments and in vivo samples taken at the time of delivery of the infant. After modeling for differences in maternal and fetal/neonatal protein binding and blood pH, the perfusion results were able to accurately predict in vivo transfer at steady state (R² = 0.85, P < 0.0001). Placental perfusion experiments can be used to predict placental drug transfer when adjusting for extra parameters and can be useful for assessing drug therapy risks and benefits in pregnancy.

BACKGROUND: Chagas disease is caused by infection with Trypanosoma cruzi. In adults, treatment with benznidazole is associated with a high incidence of adverse drug reactions (ADRs). However, in infants and children, treatment with benznidazole seems associated with a lower incidence and decreased severity of ADRs, but these effects have not been clearly characterized. OBJECTIVE: We aimed to describe ADRs observed in infants and children treated with benznidazole. PATIENTS AND METHODS: We conducted a prospective cohort study of infants and children in Argentina with Chagas disease treated with benznidazole. RESULTS: A total of 107 infants and children diagnosed with asymptomatic Chagas disease (mean age: 6.9 years) were enrolled in the study. Sixty-two events (in 44 children) were considered benznidazole related. Mean ADR duration was 8.2 days. ADRs were mild (80.6%), moderate (16%), or severe (3.2%). Most (77.3%) ADRs were in children older than 7 years. Skin was the organ with the highest incidence of ADRs (21%), followed by the central nervous system (9%) and the gastrointestinal tract (8.5%). Also, the ADR rate was lower in infants and toddlers compared with older children (18% vs 53%) (P < .001). CONCLUSIONS: Treatment with benznidazole was well tolerated in children. Most ADRs were mild and did not require treatment suspension. A strong association was observed between ADR incidence and patient age, and most ADRs occurred in children older than 7 years. We believe that anxiety over potential severe ADRs in children with Chagas disease is not justified and should not be an obstacle to using benznidazole.

Mycophenolate mofetil (MMF) has become a major therapeutic option in the management of patients undergoing transplantation, as well as in the treatment of autoimmune conditions. Case reports have suggested that MMF use during pregnancy is associated with a specific pattern of congenital malformations. Because many pregnancies are unplanned, it is imperative to assess the teratogenic risk of MMF. Using the Organization of Teratology Information Specialists network, we prospectively identified and followed pregnant women exposed to MMF during pregnancy to update this teratogenic potential. Ten cases were identified and all received the drug during embryogenesis at the recommended doses (500 to 1500 mg daily). There were four miscarriages and one elective abortion due to fear of teratogenesis. None of the five live births had malformations. It is possible that, similar to other human teratogens discovered first by case reports, the absolute risk from MMF may be smaller than originally calculated based on case reports. Because the major malformations phenotypic of MMF may be visualized in utero (e.g., microtia, cleft palate, congenital diaphragmatic hernia, and cardiac malformation), diagnostic imaging should be performed.

We performed a meta-analysis to evaluate the association between ABCB1 C3435T polymorphisms and the prevalence of epilepsy, including all relevant human studies (until June 2009), in which patients with or without epilepsy had undergone genotyping for the ABCB1 gene. Odds ratios (ORs) were calculated using a random effects model. We identified 9 case-control studies that included a total of 3,996 patients (2,454 with epilepsy and 1,542 nonepileptic subjects). No association was found between ABCB1 C3435T polymorphisms and the risk of having epilepsy (odds ratio 1.07, 95% confidence interval 0.76-1.51; p = 0.34). ABCB1 genotyping for epileptic patients is not warranted.

The authors reviewed the clinical, laboratory, and imaging data from cases of diarrhea-associated hemolytic uremic syndrome (HUS D+), diagnosed at our institution, from 2001 to 2008. The timing and utility of ultrasonographic features of HUS D+ were analyzed. The aim of the study was to determine factors that could aid in the early diagnosis of this disease. A total of 13 children with HUS D+ were identified out of 23 patients with HUS diagnosed during this time period. Evidence of Escherichia coli 0157:H7 was found in 9 cases (70%). Ultrasound studies were ordered in 10 patients (71%), all of which showed renal sonographic findings compatible with HUS. Ultrasound was performed at a mean of 13 days after onset of the diarrhea. Of note, 2 patients whose ultrasounds were performed at the beginning of their diarrheal illness manifested ultrasonographic features suggestive of HUS when there was only a mild increase in serum creatinine and no decrease in hemoglobin or platelets, suggesting that ultrasonography can identify renal involvement early in the course of the disease before other systemic signs appear. Early renal ultrasound may be a useful adjunct in the initial evaluation in children with bloody diarrhea. Evidence of increased renal echogenicity in a patient with bloody diarrhea could aid in early recognition of HUS when other diagnoses such as intussusceptions are being entertained, potentially allowing early intervention.

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.

Summary Background: Approximately one-third of patients with epilepsy patients have recurrent seizures despite therapy. It has been suggested that therapeutic failure is associated with high expression of the multidrug efflux ABCB1 (MDR1) drug-transporter; specifically, that patients with the 3435CC genotype have higher efflux of anticonvulsants out of brain tissue, with correspondingly lower concentrations in the central nervous system. Methods: We conducted a meta-analysis to examine the association between MDR1 polymorphisms and the response to anticonvulsants. We included all published studies until September 2007, in which patients with responsive and unresponsive seizure disorders underwent genotyping for ABCB1 C3435T. Individual and summary odds ratios were calculated using a random effects model. A secondary analysis was also performed, stratifying the studies by their ethnic distribution to account for genetic heterogeneity. We also performed a cumulative analysis by date of publication for the included studies using a random effects model. Results: We identified 11 case-control studies involving 3,371 patients (1,646 patients with drug-resistant epilepsy and 1,725 controls). We identified no significant association between anticonvulsant drug resistance and MDR1 polymorphism [odds ratio 1.15; 95% confidence interval (CI) 0.78–1.70; p = 0.48). Subanalysis of studies according to ethnicity yielded similar findings [European cohort: OR = 1.31; 95% CI 0.89–1.94, p = 0.18; Asian cohort: OR = 0.99; 95% CI 0.51–1.89, p = 0.96). Conclusions: We found no association between ABCB1 genotype and response to anticonvulsant drugs. At the present time, genetic typing for MDR1 polymorphism is not warranted for patients with drug-resistant epilepsy.

Urologic medical conditions are not frequently encountered during pregnancy. Still, urologists often are asked to treat pregnant patients for conditions that require prescriptions. In the generally healthy population of pregnant women, the use of pharmaceutical agents is usually reserved for women who have either infections or necessary surgical procedures. This article addresses the implications for pregnancy of common urologic conditions in generally healthy pregnant women, namely simple urinary tract infections that demand nitrofurantoin and complex urinary tract infections that necessitate fluoroquinolones treatment. It also examines the implications of nonobstetric surgical intervention.

This paper may be read to imply that all positive RIA and ELISA samples were confirmed with GC–MS. It is my understanding that some, but not all, positive samples were confirmed with GC/MS. This had no impact on the results of following the disappearance of cocaine. The paper’s conclusions remain the same. The authors would like to apologise for any inconvenience caused.

The primary objective of this study was to estimate the prevalence of this disease in women of childbearing age and children treated at health centres in underserviced areas of the city of Buenos Aires. Demographic and Chagas disease status data were collected. Samples for Chagas disease serology were obtained on filter paper and the reactive results were confirmed with conventional samples. A total of 1,786 subjects were screened and 73 positive screening results were obtained: 17 were from children and 56 were from women. The Trypanosoma cruzi infection risk was greater in those individuals who had relatives with Chagas disease, who remember seeing kissing bugs, who were of Bolivian nationality or were born in the Argentine province of Santiago del Estero. The overall prevalence of Chagas disease was 4.08%. Due to migration, Chagas disease is currently predominantly urban. The observed prevalence requires health programme activities that are aimed at urban children and their mothers. Most children were infected congenitally, which reinforces the need for Chagas disease screening of all pregnant women and their babies in Argentina. The active search for new cases is important because the appropriate treatment in children has a high cure rate. Fil: Moscatelli, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina Fil: Berenstein, Ada. Community Action Centre 15. Primary Care Centre; Argentina Fil: Tarlovsky, Ana. Community Action Centre 11. Primary Care Centre; Argentina Fil: Siniawski, Susana. Community Action Centre 15. Primary Care Centre; Argentina Fil: Biancardi, Miguel Angel. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina Fil: Ballering, Griselda. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina Fil: Moroni, Samanta. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina Fil: Schwarcz, Marta. Interamerican Open University. Centre of Studies on Human Science and Health; Argentina Fil: Hernandez, Susana. Interamerican Open University. Centre of Studies on Human Science and Health; Argentina Fil: García Bournissen, Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina Fil: Cozzi, Andrés Espejo. Interamerican Open University. Centre of Studies on Human Science and Health; Argentina Fil: Freilij, Hector León. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina Fil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños ; Argentina

Chagas disease is an endemic infection in Latin America with a high health impact. Caused by the parasite Trypanosoma cruzi, it has expanded to non-endemic regions such as North America and European countries via immigration of infected people. This infectious disease has been rising in the ranking of international health priorities due to the growing migration flows from endemic to non-endemic areas. Benznidazole (BZN), a nitroheterocyclic drug, is one of the two trypanocidal drugs currently in clinical use, associated with significant adverse drug reactions (ADRs). Mammalian metabolism of BNZ has been poorly studied, including the potential role of metabolites on both toxicity and anti-parasitic activity. High-resolution UPLC/MS/MS was used to analyze three plasma samples obtained from pediatric patients under BNZ treatment in steady state. Spectroscopic and structural criteria were applied to identify BNZ and accompanying substances from chromatographic signals. From all detected species, two can be undoubtedly associated with the BNZ and N-benzylacetamide molecules, the second one being a fragment of the parent drug (BZN). From the obtained results, two hypotheses could be formulated. The first one is to relate the presence of N-benzyl acetamide with the hepatic metabolism of BNZ. The second hypothesis has to do with the possible trypanocidal activity of this metabolite, as well as its role in the development of side effects, associated with the pharmacotherapy. Complementary studies should be carried out to determine the possible association of this metabolite with the BNZ treatment stages, patient's clinical features, ADRs, and trypanocidal effectiveness., Facultad de Ciencias Exactas, Planta Piloto Multipropósito - Laboratorio de Servicios a la Industria y al Sistema Científico

It is currently unknown whether treatment of Chagas disease decreases the risk of congenital transmission from previously treated mothers to their infants. In a cohort of women with Chagas disease previously treated with benznidazole, no congenital transmission of the disease was observed in their newborns. This finding provides support for the treatment of Chagas disease as early as possible.

Neglected diseases (NDs), also known as neglected tropical diseases, are a group of chronic diseases that disproportionately affect the poorest populations in the world.