Population pharmacokinetics of sublingually administered tacrolimus in infants and young children with liver transplantation.

AIMS: Pharmacokinetics of tacrolimus after sublingual administration is not characterized in paediatric liver transplant patients. Therefore, we aimed to develop a population pharmacokinetic model of sublingually administered tacrolimus in patients who cannot swallow the capsules due to their age, sedation status and/or mechanical ventilation during the first weeks post-transplantation. METHODS: Demographic, clinical and pharmacological variables, including tacrolimus whole blood concentrations obtained from therapeutic drug monitoring and data from dense-sampling pharmacokinetic profiles, were recorded in 26 paediatric patients with biliary atresia who underwent liver transplantation between 2016 and 2021. Population pharmacokinetic analysis was performed with NONMEM v7.4. RESULTS: Disposition of tacrolimus was best characterized by a 2-compartment model with clearance achieving half of the maximum elimination capacity (CLMAX  = 4.1 L/h) at 4.6 days post-transplantation (T50 ). Compared to sedated patients, nonsedated status showed an increased first-order absorption rate constant (1.1 vs. 0.1 h-1 ) and a 24% reduction in bioavailability (FNS ) at 14 days post-transplant. The model was able to explain the oral absorption pattern in nonsedated patients as the result of gut bioavailability (0.9) and hepatic extraction ratio, with the latter being responsible for first-pass effects. Estimates of interindividual variability remained moderate (25.9% for the gut bioavailability) to high (79.8% for the apparent volume of distribution of the central compartment, and 101% for T50 ). CONCLUSION: A population pharmacokinetic model of sublingually administered tacrolimus in paediatric patients was developed to characterize different absorption mechanisms. Once the model is externally validated, the effect of post-transplant time on clearance and the sedation status may be considered in routine dosing management.

Carbapenem-resistant Enterobacteriaceae bloodstream infections: A case-control study from a pediatric referral hospital in Argentina.

Background: Antibiotic-resistant gram-negative bloodstream infections (BSI) remain a leading cause morbidity and mortality in pediatric patients with a high impact on the public health system. Data in resource-limited countries, including those in Latin America and the Caribbean region, are scarce. The aim of the study was to identify risk factors for acquiring carbapenem-resistant Enterobacteriaceae (CRE) bacteremia in children and to assess the use of resources. Methods: A retrospective case-control study was conducted to analyze demographic, epidemiological, clinical, microbiological, and outcome data as well as the use of resources between 2014 and 2019. Univariate and logistic regression analysis was performed in order to identify risk factors associated with CRE-BSI. The R software version 4.1.2 was used. Results: A total of 46 cases with CRE-BSI and 92 controls with gram-negative non-CRE-BSI were included. No statistical difference was observed regarding: median age (36 months; IQR, 11.2-117 vs. 48 months, IQR 13-119), male sex (50 vs. 60%), and underlying disease (98 vs. 91%) in cases vs. controls, respectively. The most frequent mechanism of CRE bacteremia were: KPC in 74%, OXA in 15%, and NDM in 6.5%. A total of 54.3% of cases vs. 32.6 % (p = 0.016) of controls were admitted to the pediatric intensive care unit (PICU), and 48 vs. 21% (p = 0.001) required mechanical ventilation. Bacteremia secondary to intra-abdominal infection was observed in 56.5% of cases vs. 35% of controls (p = 0.032). Previous colonization with CRE was detected in 76% of cases vs. 8% of controls. Combination antimicrobial treatment was most frequent in cases vs. control (100 vs. 56.5%). No difference was observed in median length of hospital stay (22 days; IQR, 19-31 in cases vs. 17.5 days; IQR, 10-31 in controls; p = 0.8). Overall case fatality ratio was 13 vs. 5.5%, respectively. The most statistically significant risk factors included previous PICU stay (OR, 4; 95%CI, 2-8), invasive procedures/surgery (OR, 3; 95%CI, 1-7), central venous catheter placement (OR, 6.5; 95%CI, 2-19), urinary catheter placement (OR, 9; 95%CI 4-20), mechanical ventilation (OR, 4; 95%CI, 2-10), liver transplantation (OR, 8; 95%CI, 2-26), meropenem treatment (OR, 8.4; 3.5-22.6) in univariate analysis. The logistic regression model used for multivariate analysis yielded significant differences for previous meropenem treatment (OR, 13; 95%CI, 3-77; p = 0.001), liver transplantation (OR, 13; 95%CI, 2.5-100; p = 0.006), and urinary catheter placement (OR, 9; 95%CI, 1.4-94; p = 0.03). Conclusion: CRE-BSI affects hospitalized children with underlying disease, mainly after liver transplantation, with previous urinary catheter use and receiving broad-spectrum antibiotics, leading to high PICU requirement and mortality. These risk factors will have to be taken into account in our region in order to establish adequate health policies and programs to improve antimicrobial stewardship.

Síndrome de desgaste profesional (burnout) en médicos de unidades de cuidados intensivos pediátricos en la Argentina / Physician's burnout in pediatric intensive care units from Argentina

Introducción. En la actualidad hay escasez de médicos en unidades de cuidados intensivos pediátricos (UCIP). La causa de este déficit es multifactorial, pero el "fenómeno de burnout" o agotamiento profesional se ha descripto como relevante. Objetivo. Analizar la situación del recurso humano en las UCIP de Argentina y medir el grado de agotamiento profesional. Métodos. Estudio observacional de corte transversal, mediante la administración de encuestas por vía electrónica; se usó el cuestionario Maslach Burnout Inventory. Se invitó a participar a médicos terapistas pediátricos que se desempeñaran en el sector público o privado de la Argentina durante al menos 24 h por semana. Resultados. Fueron completadas 162 encuestas (tasa de respuesta 60%). Presentaron alto riesgo de burnout en agotamiento emocional 40 terapistas (25%), en realización personal 9 (6%) y en despersonalización 31 (19%). En forma combinada, 66 profesionales (41%) tuvieron riesgo alto de burnout en alguna de las dimensiones; resultaron factores protectores e independientes de este riesgo estar certificado en la especialidad (ORA 0,38 IC 95% 0,19-0,75) y trabajar en UCIP del sector público (ORA 0,31 IC 95% 0,15-0,65), mientras que hacer más de 36 h/semana de guardia aumentó el riesgo (ORA 1,94 IC95% 1,1-3,85). El 31 % afirmó que no planeaba continuar con actividad en cuidados intensivos y 86% no pensaban continuar con guardias en los siguientes años. La mayoría de los encuestados comunicó que modificaciones en la práctica profesional (remuneración, cargos de planta, jubilación temprana, menor carga de guardia), podrían prolongar la expectativa de continuar con actividades en UCIP. Conclusiones. Un porcentaje significativo de médicos que trabajan en las UCIP de la Argentina tienen alto riesgo de burnout y baja expectativa de continuar en la especialidad.

Introduction: there is currently a deficiency of physicians in pediatric intensive care units (PICU). The cause of this deficit is multifactorial, although the burnout phenomenon has been described as relevant. Objective: to analyze the situation of human resource in the pediatric intensive care units in Argentina and measure the level of burnout. Methods: an observational cross-sectional study through surveys administered electronically; the Maslach Burnout Inventory was used. Physicians that work at public o private pediatric intensive care units in Argentina during at least 24 hours per week were invited to participate. Results: a total of 162 surveys were completed (response rate 60%). We observed a high risk of burnout in emotional exhaustion in 40 therapists (25%), in fulfillment in 9 (6%), and depersonalization in 31 (19%). In combination, 66 professionals (41%) had a high risk of burnout to some extent; there were independent protective factors of this risk as to be certified in the specialty (ORA 0.38, 95% CI 0.19 to 0.75) and work in public sector PICU (ORA 0.31, 95% CI 0.15 to 0.65), while working more than 36 hours/week on duty increased the risk (ORA 1.94, 95% CI 1.1 to 3.85). Additionally, 31% said that they did not plan to continue working in intensive care, and 86% did not think to continue with on call duties in the following years. Over 60% of respondents reported that changes in professional practice (salary, staff positions, early retirement, fewer loads on call) could prolong the expectation of continuing activities in PICU. Conclusions: a significant percentage of doctors working in the PICU of Argentina have a high risk of burnout syndrome and a low expectation of continuing in the field.

Professional burnout in pediatric intensive care units in Argentina.

INTRODUCTION: There is currently a deficiency of physicians in pediatric intensive care units (PICU). The cause of this deficit is multifactorial, although the burnout phenomenon has been described as relevant. OBJECTIVE: To analyze the situation of human resource in the pediatric intensive care units in Argentina and measure the level of burnout. METHODS: An observational cross-sectional study through surveys administered electronically; the Maslach Burnout Inventory was used. Physicians that work at public o private pediatric intensive care units in Argentina during at least 24 hours per week were invited to participate. RESULTS: A total of 162 surveys were completed (response rate 60%). We observed a high risk of burnout in emotional exhaustion in 40 therapists (25%), in fulfillment in 9 (6%), and depersonalization in 31 (19%). In combination, 66 professionals (41%) had a high risk of burnout to some extent; there were independent protective factors of this risk as to be certified in the specialty (ORA 0.38, 95% CI 0.19 to 0.75) and work in public sector PICU (ORA 0.31, 95% CI 0.15 to 0.65), while working more than 36 hours/week on duty increased the risk (ORA 1.94, 95% CI 1.1 to 3.85). Additionally, 31% said that they did not plan to continue working in intensive care, and 86% did not think to continue with on call duties in the following years. Over 60% of respondents reported that changes in professional practice (salary, staff positions, early retirement, fewer loads on call) could prolong the expectation of continuing activities in PICU. CONCLUSIONS: A significant percentage of doctors working in the PICU of Argentina have a high risk of burnout syndrome and a low expectation of continuing in the field.

Physician's burnout in pediatric intensive care units from Argentina / Síndrome de desgaste profesional (burnout) en médicos de unidades de cuidados intensivos pediátricos en la Argentina

Introduction. There is currently a deficiency of physicians in pediatric intensive care units (PICU). The cause of this deficit is multifactorial, although the burnout phenomenon has been described as relevant. Objective. To analyze the situation of human resource in the pediatric intensive care units in Argentina and measure the level of burnout. Methods. An observational cross-sectional study through surveys administered electronically; the Maslach Burnout Inventory was used. Physicians that work at public o private pediatric intensive care units in Argentina during at least 24 hours per week were invited to participate. Results. A total of 162 surveys were completed (response rate 60%). We observed a high risk of burnout in emotional exhaustion in 40 therapists (25%), in fulfillment in 9 (6%), and depersonalization in 31 (19%). In combination, 66 professionals (41%) had a high risk of burnout to some extent; there were independent protective factors of this risk as to be certified in the specialty (ORA 0.38, 95% CI 0.19 to 0.75) and work in public sector PICU (ORA 0.31, 95% CI 0.15 to 0.65), while working more than 36 hours/week on duty increased the risk (ORA 1.94, 95% CI 1.1 to 3.85). Additionally, 31% said that they did not plan to continue working in intensive care, and 86% did not think to continue with on call duties in the following years. Over 60% of respondents reported that changes in professional practice (salary, staff positions, early retirement, fewer loads on call) could prolong the expectation of continuing activities in PICU. Conclusions. A significant percentage of doctors working in the PICU of Argentina have a high risk of burnout syndrome and a low expectation of continuing in the field.

Introducción. En la actualidad hay escasez de médicos en unidades de cuidados intensivos pediátricos (UCIP). La causa de este déficit es multifactorial, pero el "fenómeno de burnout" o agotamiento profesional se ha descripto como relevante. Objetivo. Analizar la situación del recurso humano en las UCIP de Argentina y medir el grado de agotamiento profesional. Métodos. Estudio observacional de corte transversal, mediante la administración de encuestas por vía electrónica; se usó el cuestionario Maslach Burnout Inventory. Se invitó a participar a médicos terapistas pediátricos que se desempeñaran en el sector público o privado de la Argentina durante al menos 24 h por semana. Resultados. Fueron completadas 162 encuestas (tasa de respuesta 60%). Presentaron alto riesgo de burnout en agotamiento emocional 40 terapistas (25%), en realización personal 9 (6%) y en despersonalización 31 (19%). En forma combinada, 66 profesionales (41%) tuvieron riesgo alto de burnout en alguna de las dimensiones; resultaron factores protectores e independientes de este riesgo estar certificado en la especialidad (ORA 0,38 IC 95% 0,19-0,75) y trabajar en UCIP del sector público (ORA 0,31 IC 95% 0,15-0,65), mientras que hacer más de 36 h/semana de guardia aumentó el riesgo (ORA 1,94 IC 95% 1,1-3,85). El 31% afirmó que no planeaba continuar con actividad en cuidados intensivos y 86% no pensaban continuar con guardias en los siguientes años. La mayoría de los encuestados comunicó que modificaciones en la práctica profesional (remuneración, cargos de planta, jubilación temprana, menor carga de guardia), podrían prolongar la expectativa de continuar con actividades en UCIP. Conclusiones. Un porcentaje significativo de médicos que trabajan en las UCIP de la Argentina tienen alto riesgo de burnout y baja expectativa de continuar en la especialidad.

Physicians burnout in pediatric intensive care units from Argentina / Síndrome de desgaste profesional (burnout) en médicos de unidades de cuidados intensivos pediátricos en la Argentina

Introduction. There is currently a deficiency of physicians in pediatric intensive care units (PICU). The cause of this deficit is multifactorial, although the burnout phenomenon has been described as relevant. Objective. To analyze the situation of human resource in the pediatric intensive care units in Argentina and measure the level of burnout. Methods. An observational cross-sectional study through surveys administered electronically; the Maslach Burnout Inventory was used. Physicians that work at public o private pediatric intensive care units in Argentina during at least 24 hours per week were invited to participate. Results. A total of 162 surveys were completed (response rate 60%). We observed a high risk of burnout in emotional exhaustion in 40 therapists (25%), in fulfillment in 9 (6%), and depersonalization in 31 (19%). In combination, 66 professionals (41%) had a high risk of burnout to some extent; there were independent protective factors of this risk as to be certified in the specialty (ORA 0.38, 95% CI 0.19 to 0.75) and work in public sector PICU (ORA 0.31, 95% CI 0.15 to 0.65), while working more than 36 hours/week on duty increased the risk (ORA 1.94, 95% CI 1.1 to 3.85). Additionally, 31% said that they did not plan to continue working in intensive care, and 86% did not think to continue with on call duties in the following years. Over 60% of respondents reported that changes in professional practice (salary, staff positions, early retirement, fewer loads on call) could prolong the expectation of continuing activities in PICU. Conclusions. A significant percentage of doctors working in the PICU of Argentina have a high risk of burnout syndrome and a low expectation of continuing in the field.(AU)

Introducción. En la actualidad hay escasez de médicos en unidades de cuidados intensivos pediátricos (UCIP). La causa de este déficit es multifactorial, pero el "fenómeno de burnout" o agotamiento profesional se ha descripto como relevante. Objetivo. Analizar la situación del recurso humano en las UCIP de Argentina y medir el grado de agotamiento profesional. Métodos. Estudio observacional de corte transversal, mediante la administración de encuestas por vía electrónica; se usó el cuestionario Maslach Burnout Inventory. Se invitó a participar a médicos terapistas pediátricos que se desempeñaran en el sector público o privado de la Argentina durante al menos 24 h por semana. Resultados. Fueron completadas 162 encuestas (tasa de respuesta 60%). Presentaron alto riesgo de burnout en agotamiento emocional 40 terapistas (25%), en realización personal 9 (6%) y en despersonalización 31 (19%). En forma combinada, 66 profesionales (41%) tuvieron riesgo alto de burnout en alguna de las dimensiones; resultaron factores protectores e independientes de este riesgo estar certificado en la especialidad (ORA 0,38 IC 95% 0,19-0,75) y trabajar en UCIP del sector público (ORA 0,31 IC 95% 0,15-0,65), mientras que hacer más de 36 h/semana de guardia aumentó el riesgo (ORA 1,94 IC 95% 1,1-3,85). El 31% afirmó que no planeaba continuar con actividad en cuidados intensivos y 86% no pensaban continuar con guardias en los siguientes años. La mayoría de los encuestados comunicó que modificaciones en la práctica profesional (remuneración, cargos de planta, jubilación temprana, menor carga de guardia), podrían prolongar la expectativa de continuar con actividades en UCIP. Conclusiones. Un porcentaje significativo de médicos que trabajan en las UCIP de la Argentina tienen alto riesgo de burnout y baja expectativa de continuar en la especialidad.(AU)

Growth and reproductive characteristics of the columnar cactus Stenocereus queretaroensis and their relationships with environmental factors and colonization by arbuscular mycorrhizae.

Three natural populations of pitayo (Stenocereus queretaroensis (Weber) Buxbaum), a columnar arborescent cactus, were studied in their subtropical environments in western Mexico. All of the sites were characterized by shallow, nutrient-poor soils. Percentage of colonization by arbuscular mycorrhizae (AM) fungi, stem growth, fruit mass, and percentage germination were greater in S. queretaroensis at Autlan, Jalisco (AJ) than at Zacoalco de Torres, Jalisco (ZTJ) or Santa Rosa, Zacatecas (SRZ). The onset of root colonization by arbuscular mycorrhizae during the middle of the summer wet period preceded increases in stem extension rate and stem phosphorus concentration. Based on previous studies of effects of environmental factors on photosynthesis, climatic conditions were more favorable for photosynthesis at AJ than at SRZ and ZTJ, as indicated by the amount of summer rainfall, the amount of light, and the moderate air temperatures that prevailed during the fall and winter seasons. There was a significant positive correlation between stem growth and percentage of total root length colonized by arbuscules of AM fungi for S. queretaroensis at SRZ and AJ, but not at ZTJ. A negative significant correlation was observed between stem growth and maximal and minimal air temperatures at the three study sites. Stem growth was positively related to rainfall only at SRZ, and light was statistically related to stem growth only at ZTJ. Among sites, S. queretaroensis at AJ had the highest carbon gain and greatest AM colonization, creating physiological conditions that led to the highest stem growth, fruit mass and percentage of seed germination.