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.

Timing of kidney replacement therapy initiation for acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a common condition among patients in intensive care units (ICUs) and is associated with high numbers of deaths. Kidney replacement therapy (KRT) is a blood purification technique used to treat the most severe forms of AKI. The optimal time to initiate KRT so as to improve clinical outcomes remains uncertain. This is an update of a review first published in 2018. This review complements another Cochrane review by the same authors: Intensity of continuous renal replacement therapy for acute kidney injury. OBJECTIVES: To assess the effects of different timing (early and standard) of KRT initiation on death and recovery of kidney function in critically ill patients with AKI. SEARCH METHODS: We searched the Cochrane Kidney and Transplant's Specialised Register to 4 August 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register, ClinicalTrials and LILACS to 1 August 2022. SELECTION CRITERIA: We included all randomised controlled trials (RCTs). We included all patients with AKI in the ICU regardless of age, comparing early versus standard KRT initiation. For safety and cost outcomes, we planned to include cohort studies and non-RCTs. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two authors. The random-effects model was used, and results were reported as risk ratios(RR) for dichotomous outcomes and mean difference(MD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: We included 12 studies enrolling 4880 participants. Overall, most domains were assessed as being at low or unclear risk of bias. Compared to standard treatment, early KRT initiation may have little to no difference on the risk of death at day 30 (12 studies, 4826 participants: RR 0.97,95% CI 0.87 to 1.09; I²= 29%; low certainty evidence), and death after 30 days (7 studies, 4534 participants: RR 0.99, 95% CI 0.92 to 1.07; I² = 6%; moderate certainty evidence). Early KRT initiation may make little or no difference to the risk of death or non-recovery of kidney function at 90 days (6 studies, 4011 participants: RR 0.91, 95% CI 0.74 to 1.11; I² = 66%; low certainty evidence); CIs included both benefits and harms. Low certainty evidence showed early KRT initiation may make little or no difference to the number of patients who were free from KRT (10 studies, 4717 participants: RR 1.07, 95% CI 0.94 to1.22; I² = 55%) and recovery of kidney function among survivors who were free from KRT after day 30 (10 studies, 2510 participants: RR 1.02, 95% CI 0.97 to 1.07; I² = 69%) compared to standard treatment. High certainty evidence showed early KRT initiation increased the risk of hypophosphataemia (1 study, 2927 participants: RR 1.80, 95% CI 1.33 to 2.44), hypotension (5 studies, 3864 participants: RR 1.54, 95% CI 1.29 to 1.85; I² = 0%), cardiac-rhythm disorder (6 studies, 4483 participants: RR 1.35, 95% CI 1.04 to 1.75; I² = 16%), and infection (5 studies, 4252 participants: RR 1.33, 95% CI 1.00 to 1.77; I² = 0%); however, it is uncertain whether early KRT initiation increases or reduces the number of patients who experienced any adverse events (5 studies, 3983 participants: RR 1.23, 95% CI 0.90 to 1.68; I² = 91%; very low certainty evidence). Moderate certainty evidence showed early KRT initiation probably reduces the number of days in hospital (7 studies, 4589 participants: MD-2.45 days, 95% CI -4.75 to -0.14; I² = 10%) and length of stay in ICU (5 studies, 4240 participants: MD -1.01 days, 95% CI -1.60 to -0.42; I² = 0%). AUTHORS' CONCLUSIONS: Based on mainly low to moderate certainty of the evidence, early KRT has no beneficial effect on death and may increase the recovery of kidney function. Earlier KRT probably reduces the length of ICU and hospital stay but increases the risk of adverse events. Further adequate-powered RCTs using robust and validated tools that complement clinical judgement are needed to define the optimal time of KRT in critical patients with AKI in order to improve their outcomes. The surgical AKI population should be considered in future research.

Timing of renal replacement therapy initiation for acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a common condition among patients in intensive care units (ICUs), and is associated with high death. Renal replacement therapy (RRT) is a blood purification technique used to treat the most severe forms of AKI. The optimal time to initiate RRT so as to improve clinical outcomes remains uncertain.This review complements another Cochrane review by the same authors: Intensity of continuous renal replacement therapy for acute kidney injury. OBJECTIVES: To assess the effects of different timing (early and standard) of RRT initiation on death and recovery of kidney function in critically ill patients with AKI. SEARCH METHODS: We searched the Cochrane Kidney and Transplant's Specialised Register to 23 August 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We also searched LILACS to 11 September 2017. SELECTION CRITERIA: We included all randomised controlled trials (RCTs). We included all patients with AKI in ICU regardless of age, comparing early versus standard RRT initiation. For safety and cost outcomes we planned to include cohort studies and non-RCTs. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two authors. The random-effects model was used and results were reported as risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: We included five studies enrolling 1084 participants. Overall, most domains were assessed as being at low or unclear risk of bias. Compared to standard treatment, early initiation may reduce the risk of death at day 30, although the 95% CI does not rule out an increased risk (5 studies, 1084 participants: RR 0.83, 95% CI 0.61 to 1.13; I2 = 52%; low certainty evidence); and probably reduces the death after 30 days post randomisation (4 studies, 1056 participants: RR 0.92, 95% CI 0.76 to 1.10; I2= 29%; moderate certainty evidence); however in both results the CIs included a reduction and an increase of death. Earlier start may reduce the risk of death or non-recovery kidney function (5 studies, 1076 participants: RR 0.83, 95% CI 0.66 to 1.05; I2= 54%; low certainty evidence). Early strategy may increase the number of patients who were free of RRT after RRT discontinuation (5 studies, 1084 participants: RR 1.13, 95% CI 0.91 to 1.40; I2= 58%; low certainty evidence) and probably slightly increases the recovery of kidney function among survivors who discontinued RRT after day 30 (5 studies, 572 participants: RR 1.03, 95% CI 1.00 to 1.06; I2= 0%; moderate certainty evidence) compared to standard; however the lower limit of CI includes the null effect. Early RRT initiation increased the number of patients who experienced adverse events (4 studies, 899 participants: RR 1.10, 95% CI 1.03 to 1.16; I2 = 0%; high certainty evidence). Compared to standard, earlier RRT start may reduce the number of days in ICU (4 studies, 1056 participants: MD -1.78 days, 95% CI -3.70 to 0.13; I2 = 90%; low certainty evidence), but the CI included benefit and harm. AUTHORS' CONCLUSIONS: Based mainly on low quality of evidence identified, early RRT may reduce the risk of death and may improve the recovery of kidney function in critically patients with AKI, however the 95% CI indicates that early RRT might worsen these outcomes. There was an increased risk of adverse events with early RRT. Further adequate-powered RCTs using appropriate criteria to define the optimal time of RRT are needed to reduce the imprecision of the results.

[Levomepromazine as adjuvant sedation in a pediatric intensive care unit]. / Levomepromazina como coadyuvante de sedación en la unidad de cuidados intensivos pediátricos.

INTRODUCTION: Sedation of patients in pediatric ICU extubated and in weaning of mechanic ventilation is diffcult under regular sedation, because of the tolerance and/or abstinence generated by its sustained use. The objective of this study is to describe the use of Levomepromazine as sedative coadjuvant in these patients. POPULATION AND METHODS: Observational and longitudinal study in intensive care from Juan P. Garrahan Pediatric Hospital. Patients older than 2 years were included, extubated and in weaning of mechanic ventilation with requirements of additional sedation. The level of basal sedation and post-intervention (levomepromazine 0.5 mg/kg every 8 hours) were evaluated with Ramsay and Khalil scales. Doses of regular sedatives were compared before and after the indication. It was considered positive an increase of 1 in the scales, or a decrease of 20% in the regular sedatives doses. RESULTS: 36 patients, medium age of 8,5 years, average doses of levomepromazine 0.38 mg/kg. 97% showed positive result. The regular sedative doses were reduced more than 20% after the intervention. No adverse effects or deceased were registered.

Intensity of continuous renal replacement therapy for acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a common condition among patients in intensive care units (ICU), and is associated with substantial morbidity and mortality. Continuous renal replacement therapy (CRRT) is a blood purification technique used to treat the most severe forms of AKI but its effectiveness remains unclear. OBJECTIVES: To assess the effects of different intensities (intensive and less intensive) of CRRT on mortality and recovery of kidney function in critically ill AKI patients. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register to 9 February 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We also searched LILACS to 9 February 2016. SELECTION CRITERIA: We included all randomised controlled trials (RCTs). We included all patients with AKI in ICU regardless of age, comparing intensive (usually a prescribed dose ≥35 mL/kg/h) versus less intensive CRRT (usually a prescribed dose < 35 mL/kg/h). For safety and cost outcomes we planned to include cohort studies and non-RCTs. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two authors. The random-effects model was used and results were reported as risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: We included six studies enrolling 3185 participants. Studies were assessed as being at low or unclear risk of bias. There was no significant difference between intensive versus less intensive CRRT on mortality risk at day 30 (5 studies, 2402 participants: RR 0.88, 95% CI 0.71 to 1.08; I2 = 75%; low quality of evidence) or after 30 days post randomisation (5 studies, 2759 participants: RR 0.92, 95% CI 0.80 to 1.06; I2 = 65%; low quality of evidence). There were no significant differences between intensive versus less intensive CRRT in the numbers of patients who were free of RRT after CRRT discontinuation (5 studies, 2402 participants: RR 1.12, 95% CI 0.91 to 1.37; I2 = 71%; low quality of evidence) or among survivors at day 30 (5 studies, 1415 participants: RR 1.03, 95% CI 0.96 to 1.11; I2 = 69%; low quality of evidence) and day 90 (3 studies, 988 participants: RR 0.98, IC 95% 0.94 to 1.01, I2 = 0%; moderatequality of evidence). There were no significant differences between intensive and less intensive CRRT on the number of days in hospital (2 studies, 1665 participants): MD -0.23 days, 95% CI -3.35 to 2.89; I2 = 8%; low quality of evidence) and the number of days in ICU (2 studies, 1665 participants: MD -0.58 days, 95% CI -3.73 to 2.56, I2 = 19%; low quality of evidence). Intensive CRRT increased the risk of hypophosphataemia (1 study, 1441 participants: RR 1.21, 95% CI 1.11 to 1.31; high quality evidence) compared to less intensive CRRT. There was no significant differences between intensive and less intensive CRRT on numbers of patients who experienced adverse events (3 studies, 1753 participants: RR 1.08, 95% CI 0.73 to 1.61; I2 = 16%; moderate quality of evidence). In the subgroups analysis by severity of illness and by aetiology of AKI, intensive CRRT would seem to reduce the risk mortality (2 studies, 531 participants: RR 0.73, 95% CI 0.61 to 0.88; I2 = 0%; high quality of evidence) only in the subgroup of patients with post-surgical AKI. AUTHORS' CONCLUSIONS: Based on the current low quality of evidence identified, more intensive CRRT did not demonstrate beneficial effects on mortality or recovery of kidney function in critically ill patients with AKI. There was an increased risk of hypophosphataemia with more intense CRRT. Intensive CRRT reduced the risk of mortality in patients with post-surgical AKI.

Clinical implications of hepatitis A virus ribonucleic acid detection and genotyping in acute liver failure in children in Argentina.

OBJECTIVES: To investigate the detection of hepatitis A virus ribonucleic acid in patients with acute liver failure and to assess if the results have any clinical implications for the evolution of acute liver failure in children. Hepatitis A infection, a vaccine-preventable disease, is an important cause of acute liver failure in children in Argentina. Universal vaccination in 1-yr-old children was implemented in June 2005. DESIGN: Observational study in which patients were divided into Group 1 consisting of positive hepatitis A virus ribonucleic acid and Group 2 consisting of negative hepatitis A virus ribonucleic acid. SETTING: Pediatric intensive care unit in National Pediatric Hospital "Dr. J. P. Garrahan," Buenos Aires, Argentina. PATIENTS: Thirty-three patients with the diagnosis of acute liver failure secondary to hepatitis A virus infection and admitted to the Garrahan Pediatric Hospital between September 2003 and September 2005 were enrolled in the study. Twenty of these children were admitted to the pediatric intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Samples for total ribonucleic acid detection and genotyping were obtained from serum and/or stools on admission. We found positive hepatitis A virus ribonucleic acid in 13 patients and negative hepatitis A virus ribonucleic acid in 20 patients. The following clinical variables were evaluated: time of evolution, hospital stay, admission to the pediatric intensive care unit, pediatric intensive care unit stay, time on mechanical ventilation, criteria for orthotopic liver transplantation, and mortality. Characterization of the isolates did not reveal differences related to genotype; all cases were IA. No statistical significance was found as to the variables. However, positive hepatitis A virus ribonucleic acid showed lower percentages of pediatric intensive care unit admissions, criteria for orthotopic liver transplantation, number of orthotopic liver transplantation, and mortality than the group of patients with negative hepatitis A virus ribonucleic acid. CONCLUSIONS: Hepatitis A virus genotyping studies did not show any particularities, all cases were IA and, thus, apparent associations between genotype and the clinical presentation of acute liver failure could not be found.

Molecular characterization of hepatitis A virus in children with fulminant hepatic failure in Argentina.

BACKGROUND: Hepatitis A infection, a vaccine-preventable disease, is an important cause of fulminant hepatic failure (FHF) in children in Argentina. Universal vaccination in 1-year-old children was implemented in June 2005. The limited studies about the correlation between the characteristics of the hepatitis A virus (HAV) and FHF have been carried out in adults. METHODS: Samples from 41 children with FHF were studied from September 2003 to January 2006 and HAV RNA was detected, sequenced and analysed in the 5' non-coding region and VP1/2A region. RESULTS: Eighteen HAV strains were characterized and found to be different at the nucleotide level from the self-limited acute infection strains that have been circulating in Argentina with no temporal or geographical pattern. They did not form a genetic cluster, but some of them were identical in the largest fragment characterized and some of them seemed to be more closely related in time and/or geographically. CONCLUSION: Our results suggest that viral factors could be involved in the severity of the clinical presentation of HAV infection in children in Argentina.

[Pediatric emergency medicine specialty: Welcome!] / Especialidad de Emergentología Pediátrica: ¡Bienvenida!

Pediatric Emergency Medicine has developed around the world as a subspecialty of pediatrics. There is plenty of data reflecting a growing need for its services. The subspecialty was initiated in the United States and Argentina, together with other Latin American countries, followed the same path. Nevertheless, there is yet much to be done. It is necessary to strengthen its promotion and to stimulate research and teaching activities in order to continue improving the quality of care delivered to the pediatric population, their families and society as a whole.

La Emergentología Pediátrica se ha desarrollado en el mundo como una subespecialidad de la pediatría durante las últimas décadas. Los registros muestran una creciente necesidad de sus servicios. Esta orientación tuvo su empuje inicial en Estados Unidos de América y nuestro país ha continuado por el mismo camino, así como muchos otros países latinoamericanos. Aun así, habrá que intensificar su promoción y trabajar en el desarrollo de la investigación y la docencia relacionadas con el área para promover el bienestar de los niños, sus familias y de la sociedad en general.

Management of cirrhotic ascites in children: Review and recommendations. Part 2: Electrolyte disturbances, nonelectrolyte disturbances, therapeutic options. / Manejo de la ascitis secundaria a cirrosis en el paciente pediátrico: Revisión y recomendaciones. Parte 2: Complicaciones electrolíticas, complicaciones no electrolíticas, opciones terapéuticas.

Ascites is a major complication of cirrhosis. There are several evidence-based articles and guidelines for the management of adults, but few data have been published in relation to children. In the case of a pediatric patient with cirrhotic ascites (PPCA), the following questions are raised: How are the clinical assessment and ancillary tests performed? When is ascites considered refractory? How is it treated? Should fresh plasma and platelets be infused before abdominal paracentesis to prevent bleeding? What are the hospitalization criteria? What are the indicated treatments? What complications can patients develop? When and how should hyponatremia be treated? What are the diagnostic criteria for spontaneous bacterial peritonitis? How is it treated? What is hepatorenal syndrome? How is it treated? When should albumin be infused? When should fluid intake be restricted? The recommendations made here are based on pathophysiology and suggest the preferred approach to diagnostic and therapeutic aspects, and preventive care.

La ascitis es una complicación grave de la cirrosis. Existen numerosos artículos y guías basadas en la evidencia para adultos, pero poco se ha publicado para niños. Ante un paciente pediátrico con ascitis secundaria a cirrosis (PPAC), se plantean las siguientes preguntas: ¿Cómo se realiza la evaluación clínica y los exámenes complementarios? ¿Cuándo se considera que la ascitis es refractaria; cómo se trata? ¿Debe infundirse plasma fresco y plaquetas antes de la paracentesis abdominal para evitar el sangrado? ¿Cuáles son los criterios de hospitalización? ¿Cuáles son los tratamientos indicados? ¿Qué complicaciones puede presentar? ¿Cuándo y cómo debe tratarse la hiponatremia? ¿Qué criterios diagnósticos tiene la peritonitis bacteriana espontánea; cómo se trata? ¿Qué es el síndrome hepatorrenal; cómo se trata? ¿Cuándo debe infundirse albúmina? ¿Cuándo debe restringirse el aporte líquido? Las recomendaciones que efectuamos, basadas en la fisiopatología, sugieren el enfoque preferido para encarar sus aspectos diagnósticos, terapéuticos y los cuidados preventivos.

[Molecular characterization of hepatitis E virus in three acute liver failure cases in children in Argentina]. / Caracterización molecular del virus de hepatitis E en tres casos de falla hepática fulminante en niños de Argentina.

Strains of hepatitis E virus (HEV) isolated from Argentinian patients with sporadic hepatitis, as well as from swine from Argentina, belong to genotype 3. HEV genotype 3 variants have been described associated with acute liver failure (ALF) in adults from Japan and the United Kingdom. In Argentina, 30% of ALF in adults and children are of unknown aetiology. To study if HEV could be an aetiological agent associated with ALF in children, serum and/or fecal samples fJom 35 children (mean age: 6 years, 20 female, 15 male) were analyzed during 2003 and 2004. HEV RNA was detected by RT-nested PCR with primers designed within ORF 1 and ORF 2 regions. HEV RNA could be detected in three cases. Two were 12-year-old boys fom Buenos Aires province and the third was a 3-year-old girl from Corrientes province. Sequence analysis indicates that the three isolates are distinct from each other but all belong to genotype 3, exhibiting a close relationship with swine and human strains fJom sporadic cases of HEV, previously reported in Argentina. This data suggests a potential link between ALF and HEVin children in Argentina and indicates the need for the determination of HEV status in the differential diagnosis in ALE Further studies would aid in determining the true impact of this infection in Argentina and the potential benefits of a vaccine against HEV presently in phase III trials.

Characteristics of pediatric intensive care residency programs in Argentina: A national survey.

INTRODUCTION: Pediatric intensive care residency programs have been in place in Argentina for just a few years. Knowing their status offers the possibility to establish strategies to help with professional development and training. OBJECTIVES: 1) To describe the characteristics of pediatric intensive care residency programs across Argentina. 2) To assess whether certain characteristics are related to a higher vacancy filling rate. 3) To assess job placement in the hospital where residents are trained. DESIGN: Descriptive, observational study. National survey. INCLUSION CRITERIA: Pediatric intensive care residency programs in place between April 1st, 2014 and May 31st, 2014. RESULTS: Thirty-one residency programs were analyzed. Only 11/31 had an annual hospitalization volume >400 patients. There were no guidelines and/or criteria for care in 9/31. The program suited the national reference framework in 17/31. There was no head of residents or resident trainer in 13/31. Only 5/31 had been certified by the Ministry of Health. There were 65 vacancies; this number increased in the past four years; vacancy filling rate decreased from 59% in 2009 to 30% in 2013. Sixty percent of residents got a job in the pediatric intensive care unit where they were trained. A multivariate logistic regression analysis identified the outcome measure annual hospitalization volume >400 patients as an independent predictor of vacancy filling rate >60%. CONCLUSIONS: 1) Vacancy filling is deficient. 2) The number of certified residency programs is scarce. 3) Pediatric intensive care units with a higher number of hospitalizations were associated with a higher vacancy filling rate. 4) More than half of residents got a job in the pediatric intensive care unit where they were trained.

Especialidad de Emergentología Pediátrica: ¡Bienvenida! / Pediatric emergency medicine specialty: Welcome!

La Emergentología Pediátrica se ha desarrollado en el mundo como una subespecialidad de la pediatría durante las últimas décadas. Los registros muestran una creciente necesidad de sus servicios. Esta orientación tuvo su empuje inicial en Estados Unidos de América y nuestro país ha continuado por el mismo camino, así como muchos otros países latinoamericanos. Aun así, habrá que intensificar su promoción y trabajar en el desarrollo de la investigación y la docencia relacionadas con el área para promover el bienestar de los niños, sus familias y de la sociedad en general.

Pediatric Emergency Medicine has developed around the world as a subspecialty of pediatrics. There is plenty of data reflecting a growing need for its services. The subspecialty was initiated in the United States and Argentina, together with other Latin American countries, followed the same path. Nevertheless, there is yet much to be done. It is necessary to strengthen its promotion and to stimulate research and teaching activities in order to continue improving the quality of care delivered to the pediatric population, their families and society as a whole.

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.

Características de las residencias de terapia intensiva pediátrica de la República Argentina: Encuesta nacional / Characteristics of pediatric intensive care residency programs in Argentina: A national survey

Introducción. La residencia de terapia intensiva pediátrica (TIP) tiene pocos años de desarrollo en nuestro país. Conocer su situación brinda la posibilidad de establecer estrategias para contribuir al desarrollo y capacitación de profesionales. Objetivos. 1) Describir las características de las residencias de TIP del país. 2) Evaluar si existen características que se relacionen con una mayor ocupación de las vacantes. 3) Explorar la inserción laboral en el hospital formador de los residentes. Diseño. Descriptivo, observacional. Encuesta nacional. Criterios de inclusión. Residencias de TIP funcionales entre el 1/4/2014 y el 31/5/2014. Resultados. Se analizaron 31 residencias. Solo 11/31 tenían volumen de internación anual >400 pacientes. No había normas y/o criterios de atención en 9/31. En 17/31, el programa estuvo adecuado al marco de referencia nacional. Hubo 13/31 que no contaban con jefe ni instructor de residentes. Fueron acreditadas por el Ministerio de Salud 5/31. Hubo 65 vacantes; el número aumentó en los últimos 4 años; la ocupación disminuyó de 59% en 2009 a 30% en 2013. El 60% de los residentes tuvo inserción laboral en la TIP formadora. El análisis de regresión logística multivariado identificó la variable ingresos anuales > 400 pacientes como predictora independiente de ocupación de vacantes > 60%. Conclusiones. 1) Hay un déficit en la ocupación de cargos. 2) El número de residencias acreditadas es escaso. 3) Las unidades de cuidados intensivos pediátricos con mayor número de ingresos se asociaron a una mayor cobertura de vacantes. 4) Más de la mitad de los residentes se insertaron laboralmente en la TIP formadora.

Introduction. Pediatric intensive care residency programs have been in place in Argentina for just a few years. Knowing their status offers the possibility to establish strategies to help with professional development and training. Objectives. 1) To describe the characteristics of pediatric intensive care residency programs across Argentina. 2) To assess whether certain characteristics are related to a higher vacancy filling rate. 3) To assess job placement in the hospital where residents are trained. Design. Descriptive, observational study. National survey. Inclusion criteria. Pediatric intensive care residency programs in place between April 1st, 2014 and May 31st, 2014. Results. Thirty-one residency programs were analyzed. Only 11/31 had an annual hospitalization volume >400patients. There were no guidelines and/or criteria for care in 9/31. The program suited the national reference frameworkin17/31. There was no head ofresidents or resident trainer in 13/31. Only 5/31 had been certified by the Ministry of Health. There were 65 vacancies; this number increased in the past four years; vacancy filling rate decreased from 59% in 2009 to 30% in 2013. Sixty percent of residents got a job in the pediatric intensive care unit where they were trained. A multivariate logistic regression analysis identified the outcome measure annual hospitalization volume >400 patients as an independent predictor of vacancy filling rate >60%. Conclusions. 1) Vacancy filling is deficient. 2) The number of certified residency programs is scarce. 3) Pediatric intensive care units with a higher number of hospitalizations were associated with a higher vacancy filling rate. 4) More than half of residents got a job in the pediatric intensive care unit where they were trained.

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.

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.

Mortality risk score in liver transplantation: changes over time in its predicting power.

UNLABELLED: Since the onset of our liver transplantation program in 1992, 362 transplants were performed in 338 children. A risk score for predicting mortality was designed and implemented over time. The description of a method utilized to design the risk score, changes in mortality rate over 12 yr and the analysis of factors that might have influenced these changes are presented and discussed in this paper. PATIENTS AND METHODS: Cox regression analysis was applied to a retrospective sample of 110 patients with liver cirrhosis, transplanted between 1992 and 2000. A risk score was prepared using beta coefficients of the two significant variables related to survival time: age (1.08, p=0.02) and bilirubin levels (0.93, p=0.03), and two groups were identified: low- and high-risk score. The score was applied in two consecutive samples: 2000-2002 and 2002-2004. RESULTS: In the first sample (1992-2000), we found 69 and 41 as low- and high-risk patients, with a median survival time of 93.13 and 2.93 months (p=0.0001). In the 2000-2002 sample, a median survival time of 41.7 and 2.33 months (p=0.03) was found for low- and high-risk groups, respectively. In the third sample (2002-2004), there was a remarkable decrease in mortality in the high-risk group (n=29) and the score did not discriminate between high- and low-risk groups (p=0.35). CONCLUSION: A scoring system to identify risk levels in liver transplantation patients is an operative and powerful tool during a given period of time but it has to be updated as risk factors will vary following the team's learning curve.

Caracterización molecular del virus de hepatitis E en tres casos de falla hepática fulminante en niños de Argentina / Molecular characterization of hepatitis E virus in three acute liver failure cases in children in Argentina

Las cepas de virus de hepatitis E (HEV) encontradas en casos esporádicos humanos y en cerdos en Argentina corresponden al genotipo 3. Se han descripto variantes de este genotipo asociadas a fallas hepáticas fulminantes (FHF) en adultos de Japón e Inglaterra. En Argentina el 30% de las FHF en adultos y en niños es de etiología desconocida. Para estudiar si el HEV podría ser el agente etiológico asociado a FHF en niños se analizaron el suero y/o la materia fecal de 35 niños (edad media 6 años, 20 mujeres, 15 varones) durante 2003 y 2004. El HEV RNA fue detectado por RT-nested PCR con cebadores dirigidos a las regiones ORF 1 y ORF 2. El HEV RNA pudo detectarse en 3 casos. Dos eran varones de 12 años residentes en la provincia de Buenos Aires y el tercero, una niña de 3 años de la provincia de Corrientes. El análisis de las secuencias muestra que las 3 variantes son distintas, pero pertenecen todas al genotipo 3 y están muy relacionadas a las cepas encontradas previamente en casos esporádicos en humanos y en cerdos de Argentina. Estos datos sugieren una posible relación entre FHF y HEV en niños de Argentina e indican la necesidad de considerar la infección con HEV en el diagnóstico diferencial de las FHF. Se necesitan más estudios que demuestren el verdadero impacto de esta infección y el beneficio potencial de na vacuna para HEV, actualmente en fase III.

Strains of hepatitis E virus (HEV) isolated from Argentinian patients with sporadic hepatitis, as well as from swine from Argentina, belong to genotype 3. HEV genotype 3 variants have been described associated with acute liver failure (ALF) in adults from Japan and the United Kingdom. In Argentina, 30% of ALF in adults and children are of unknown aetiology. To study if HEV could be an aetiological agent associated with ALF in children, serum and/or fecal samples from 35 children (mean age: 6 years, 20 female, 15 male) were analyzed during 2003 and 2004. HEV RNA was detected by RT-nested PCR with primers designed within ORF 1 and ORF 2 regions. HEV RNA could be detected in three cases. Two were 12-year-old boys from Buenos Aires province and the third was a 3- year-old girl from Corrientes province. Sequence analysis indicates that the three isolates are distinct from each other but all belong to genotype 3, exhibiting a close relationship with swine and human strains from sporadic cases of HEV, previously reported in Argentina. This data suggests a potential link between ALF and HEV in children in Argentina and indicates the need for the determination of HEV status in the differential diagnosis in ALF. Further studies would aid in determining the true impact of this infection in Argentina and the potential benefits of a vaccine against HEV, presently in phase III trials.