Population pharmacokinetics and pharmacodynamics of L-asparaginase and its impact on the development of pancreatitis and hypersensitivity reactions in children with leukemia under treatment.

L-asparaginase (L-Asp) is an essential enzyme in the treatment of patients with Acute Lymphoblastic Leukemia (ALL), commonly associated with adverse events (AE). Knowing the pharmacokinetic and pharmacodynamic (PK/PD) parameters of L-Asp as well as its relationship with the development of AE is an important strategy in the search to improve the efficacy and safety of the treatment. Seventy-four children with ALL that were being treated with L-Asp, were included. One to three blood samples were randomly obtained from each patient, at times from 0 to 30 hours, until completing a total of 211 samples. The L-Asp activity and the Asparagine (Asp) concentration were quantified, in addition, the presence of anti-L-Asp antibodies (Anb) was determined. A population PK/PD model of L-Asp was developed to determine the association of covariates with PK/PD parameters. The presence of Anb was associated with the increase in L-Asp clearance (CL) and with the decrease of volume of distribution 1 (V1). On the other hand, female sex was significantly associated with the increase of V1, while the age from 1 to 6 years was significantly associated with the increase of V1. The presence of Anb as well as the female sex were related to the increase IC50 (concentration-needed to deplete-50% of Asp). Patients who presented Asp depletion before the first 24 hours after administration presented pancreatitis, this could be a risk marker. Significant results were found in this study, use of these results may contribute to the safe and effective use of L-Asp.

Perception of #TheDress in childhood is influenced by age and green-leaf preference.

The perception of the ambiguous image of #TheDress may be influenced by optical factors, such as macular pigments. Their accumulation during childhood could increase with age and the ingestion of carotenoid-containing foods. The purpose of this study was to investigate whether the visual perception of the dress in children would differ based on age and carotenoid preference. This was a cross-sectional, observational, and comparative study. A poll was administered to children aged 2 to 10 years. Parents were instructed to inquire about the color of #TheDress from their children. A carotenoid preference survey was also completed. A total of 413 poll responses were analyzed. Responses were categorized based on the perceived color of the dress: blue/black (BB) (n = 204) and white/gold (WG) (n = 209). The mean and median age of the WG group was higher than the BB group (mean 6.1, median 6.0 years, standard deviation [SD] 2.2; mean 5.5, median 5.0 years, SD 2.3; p = 0.007). Spearman correlation between age and group was 0.133 (p = 0.007). Green-leaf preference (GLP) showed a statistically significant difference between groups (Mann-Whitney U: p = 0.038). Spearman correlation between GLP and group was 0.102 (p = 0.037). Logistic regression for the perception of the dress as WG indicated that age and GLP were significant predictors (age: B weight 0.109, p = 0.012, odds ratio: 1.115; GLP: B weight 0.317, p = 0.033, odds ratio: 1.373). Older children and those with a higher GLP were more likely to perceive #TheDress as WG. These results suggest a potential relationship with the gradual accumulation of macular pigments throughout a child's lifetime.

Evaluation of factors leading to poor outcomes for pediatric acute lymphoblastic leukemia in Mexico: a multi-institutional report of 2,116 patients.

Background and aims: Pediatric acute lymphoblastic leukemia (ALL) survival rates in low- and middle-income countries are lower due to deficiencies in multilevel factors, including access to timely diagnosis, risk-stratified therapy, and comprehensive supportive care. This retrospective study aimed to analyze outcomes for pediatric ALL at 16 centers in Mexico. Methods: Patients <18 years of age with newly diagnosed B- and T-cell ALL treated between January 2011 and December 2019 were included. Clinical and biological characteristics and their association with outcomes were examined. Results: Overall, 2,116 patients with a median age of 6.3 years were included. B-cell immunophenotype was identified in 1,889 (89.3%) patients. The median white blood cells at diagnosis were 11.2.5 × 103/mm3. CNS-1 status was reported in 1,810 (85.5%), CNS-2 in 67 (3.2%), and CNS-3 in 61 (2.9%). A total of 1,488 patients (70.4%) were classified as high-risk at diagnosis. However, in 52.5% (991/1,889) of patients with B-cell ALL, the reported risk group did not match the calculated risk group allocation based on National Cancer Institute (NCI) criteria. Fluorescence in situ hybridization (FISH) and PCR tests were performed for 407 (19.2%) and 736 (34.8%) patients, respectively. Minimal residual disease (MRD) during induction was performed in 1,158 patients (54.7%). The median follow-up was 3.7 years. During induction, 191 patients died (9.1%), and 45 patients (2.1%) experienced induction failure. A total of 365 deaths (17.3%) occurred, including 174 deaths after remission. Six percent (176) of patients abandoned treatment. The 5-year event-free survival (EFS) was 58.9% ± 1.7% for B-cell ALL and 47.4% ± 5.9% for T-cell ALL, while the 5-year overall survival (OS) was 67.5% ± 1.6% for B-cell ALL and 54.3% ± 0.6% for T-cell ALL. The 5-year cumulative incidence of central nervous system (CNS) relapse was 5.5% ± 0.6%. For the whole cohort, significantly higher outcomes were seen for patients aged 1-10 years, with DNA index >0.9, with hyperdiploid ALL, and without substantial treatment modifications. In multivariable analyses, age and Day 15 MRD continued to have a significant effect on EFS. Conclusion: Outcomes in this multi-institutional cohort describe poor outcomes, influenced by incomplete and inconsistent risk stratification, early toxic death, high on-treatment mortality, and high CNS relapse rate. Adopting comprehensive risk-stratification strategies, evidence-informed de-intensification for favorable-risk patients and optimized supportive care could improve outcomes.

Burden and transmission of zoonotic foodborne disease in a rural community in Mexico.

BACKGROUND: The foodborne transmission and human health impact of Salmonella and Campylobacter infections have rarely been evaluated at the population level in highly endemic settings. METHODS: A prospective 15-month cohort study of 127 infants and 119 elderly people was combined with animal and food surveillance to determine the incidence and severity of Salmonella and Campylobacter gastroenteritis in a comparatively prosperous rural community in Mexico. RESULTS: Salmonella and Campylobacter were isolated in up to 75% and 57%, respectively, of raw retail meat and in up to 4.5% of ready-to-eat foods. Rates of acute gastroenteritis of any etiology in infants and elderly people were, respectively, 2.1 and 0.7 episodes per person per year. The annual incidence density rate of Salmonella gastroenteritis was 17.8 per 100 infants and 7.9 per 100 elderly people; the rate of Campylobacter gastroenteritis was 11.7 per 100 infants and 0 per 100 elderly people. Pulsed-field gel electrophoresis analysis yielded multiple clusters of human, meat, and/or animal Salmonella and Campylobacter isolates with indistinguishable patterns. On average, gastroenteritis episodes with these pathogens lasted 3 days in infants and 2 days in elderly people. Medical attention was sought in 44% of diarrheal episodes in infants and in 26% of diarrheal episodes in elderly people; none required hospitalization. Infants with multidrug-resistant Salmonella gastroenteritis had a higher frequency of bloody stools and medical visits (50% vs 11%; odds ratio, 8.5; P = .04) than those with more susceptible strains. CONCLUSIONS: In this relatively advantaged Mexican rural community, the human health impact of a food chain heavily contaminated with Salmonella and Campylobacter was of low magnitude.

Incidencia de anemia ferropénica y factores asociados en las gestantes del distrito de Rapayan, Ancash, Perú: periodo mayo 2010 û marzo 2011 / Incidence of iron-deficiency anemia and some associated factors in pregnant women in Rapayan District, Ancash, Peru: May 2010 û March 2011

Objetivo: Conocer la incidencia de anemia ferropénica y factores asociados en la gestación en el distrito de Rapayan, Ancash, Perú. Material y método: estudio prospectivo, analítico y longitudinal en 39 gestantes del distrito de Rapayán, provincia de Huari, departamento de Ancash, Perú durante el periodo comprendido entre mayo 2010 y marzo del 2011. Se procedió a tomar muestras de sangre del total de la muestra n= 39 gestantes, durante los tres trimestres con el fin de controlar los niveles de hemoglobina y forma de los eritrocitos. Además se evaluaron los siguientes factores: edad de las gestantes, número de gestaciones y ganancia de peso durante los tres trimestres. Resultados: de las 39 gestantes estudiadas el 15,3% presentó anemia en los dos primeros trimestres y el 10,2% en el tercer trimestre, presentando todos estos niveles leves de anemia. El 83,33% de las gestantes con anemia mostraron eritrocitos normociticos y el 16,67% mostraron eritrocitos microciticos. Las edades de las gestantes anémicas comprendían entre los 19 a 43 años, el número de gestaciones no muestra significancia estadística y con respecto a la ganancia de peso se evidencia que la anemia se presenta en gestantes que ganaron menos de 9 kg durante la gestación. Conclusión: El sistema de creencias de la población, genera una gran desadherencia en las recomendaciones acerca del cuidado que debe tener una gestante durante el embarazo, estando entre estas, la buena alimentación y el consumo de los suplementos férricos y de ácido fólico que son repartidos gratuitamente por el MINSA. Lo cual nos lleva tener un 15,83% de las gestantes con anemia ferropénica.

Objective: To know the incidence of iron-deficiency anemia and its associated factors during pregnancy in Rapayan District, Ancash,Peru. Material and methods: A prospective, analytical and longitudinal study was carried pout in 39 pregnant women in Rapayan District, Huari Province, Ancash Department in Peru, between May 2010 and March 2011. Blood samples were taken from every pregnant woman participating, during the three trimesters of pregnancy, in order to measure hemoglobin values and to assess the shape of red blood cells (RBCs). We also collected additional data, such as age, number pf pregnancies, and weight gain during pregnancy. Results: Of the 39 women studied, 15.3% presented with anemia in the first two trimesters, and 10.2% had anemia during the third trimester. Anemia was classified as mild. Most pregnant women with anemia (83.33%) had normocytic RBCs, and 16.7% had microcytic RBCs. Pregnant women with anemia were between 16 and 42 years old, the number of pregnancies was not relevant, and, when assessing weight gain, it was found that anemia occurred in pregnant women who gained less than 9 Kg during pregnancy. Conclusion: Cultural beliefs in this rural population lead to poor adherence to healthcare measures during pregnancy, particularly with respect to good alimentation practices and the use of iron and folic acid supplements, which are supplied free of charge by the Peruvian Ministry of Health. This leads to the important frequency (15.83%) of pregnant women with iron deficiency anemia in this area.

Factores que influyen al aplicar el programa de estimulacion temprana en ninos lactantes mayor y menor del Jardin Infantil Bellavista de Bogota, durante el primer trimestre 1986 / Factors that influence implementation early stimulation program of mayor and minor infants in Bellavista Kindergarden, Bogota, during 1986 first trimester

En cumplimiento con el area de metodologia de investigacion cientifica y con los objetivos de la facultad, hemos realizado un estudio descriptivo, tratado a traves de un estudio de casos, tomando 10 sujetos que llevaban un semestre en el programa de estimulacion temprana en el Jardin Infantil Bellavista de Bogota y que respondian a los objetivos del programa, con ellos, las familias y las jardineras se conformaron los elementos de la investagacion los cuales se estudiaron a traves de visitas domiciliarias, observacion directa y entrevistas formalizadas, esto con el fin de identificar los factores que influyen en la aplicacion del programa de estimulacion temprana, en ninos lactante mayor y menor. La recoleccion de los datos se lleva a cabo durante el primer semestre de 1986 y al analizarlos en forma cuantitativa y cualitativamente, se encontraron factores que intervienen en la aplicacion del programa tales como, el estado civil de las 10 familias en estudio; el tiempo que dedican las jardineras al programa, los habitos familiares, la distribucion mensual del ingresos, las condiones de vivienda, aspectos relacionados con el conocimiento y actualizacion de la cartilla. Estos factores influyen en mayor o menor porcentaje en el lactante para que este logre los objetivos planteados por el programa..