In adult protease inhibitor (PI)-experienced patients, a lopinavir (LPV) phenotypic inhibitory quotient (PIQ) of >15 has been associated with a higher likelihood of viral suppression. The aims of this study were to develop a population pharmacokinetic (PK) model of LPV in children and to estimate the probability of achieving a PIQ of >15. HIV-infected, PI-experienced children receiving LPV were intensively sampled for 12 h to measure plasma LPV. The data were fitted to candidate PK models (using MM-USCPACK software), and the final model was used to simulate 1,000 children to determine the probability of achieving an LPV PIQ of >15. In 50 patients (4 to 18 years old), the median LPV plasma 12-hour-postdose concentration was 5.9 mg/liter (range, 0.03 to 16.2 mg/liter) lower than that reported in adults. After a delay, LPV was absorbed linearly into a central compartment whose size was dependent on the weight and age of the patient. Elimination was dependent on weight. The regression line of observed versus predicted LPV had an R 2 of 0.99 and a slope of 1.0. Visual predictive checks against all available measured concentrations showed good predictive ability of the model. The probability of achieving an LPV PIQ of >15 was >90% for wild-type virus but <10% for even moderately resistant virus. The currently recommended dose of LPV/ritonavir appears to be adequate for children infected with wild-type virus but is unlikely to provide adequate inhibitory concentrations for even moderately resistant human immunodeficiency virus (HIV). PI-experienced HIV-infected children will likely benefit from longitudinal, repeated LPV measurement in plasma to ensure that drug exposure is most often near the maximal end of the observed safe range.Lopinavir/ritonavir (LPV/RTV) (Kaletra) is the first and only coformulated RTV-boosted protease inhibitor (PI) approved for use in children. The recommended doses for children who weigh more than 15 kg are 10 mg/kg of body weight or 230 mg/m 2 (body surface area) twice daily, with a maximum of 400 mg per dose unless it is combined with drugs affecting cytochrome (CYP) P450 metabolism, which require LPV dose adjustment (4, 28). Introduced as a salvage agent (22), LPV/RTV has become one of the preferred PI choices for first-line regimens in children Ͼ6 months of age in the countries with access to the drug.Despite evidence for good antiviral efficacy among children in a clinical trial setting (16,17,23), the standard dose may not be adequate for every child. Noncompartmental analysis has shown that the average LPV plasma 12-hour-postdose concentration (C trough ) in children given the currently recommended pediatric dose of LPV is 67% lower than in adults (24). Recently, Jullien et al. published a population pharmacokinetics (PK) model of LPV in children aged 0 to 18 years (15). The model was based on a retrospective analysis of LPV plasma measurements in 157 children, with a median of 3 samples (range, 1 to 14) per patient, obtained for monitoring purposes after self-reported LPV intake. In t...
Background: Understanding gender gaps in trainee evaluations is critical because these may ultimately determine the duration of training. Currently, no studies describe the influence of gender on the evaluation of pediatric emergency medicine (PEM) fellows. Objective:The objective of our study was to compare milestone scores of female versus male PEM fellows. Methods: This is a multicenter retrospective cohort study of a national sample of PEM fellows from July 2014 to June 2018. Accreditation Council for Medical Education (ACGME) subcompetencies are scored on a 5-point scale and span six domains: patient care (PC), medical knowledge, systems-based practice, practice-based learning and improvement, professionalism, and interpersonal and communication skills (ICS). Summative assessments of the 23 PEM subcompetencies are assigned by each program's clinical competency committee and submitted semiannually for each fellow. Program directors voluntarily provided deidentified ACGME milestone reports. Demographics including sex, program region, and type of residency were collected. Descriptive analysis of milestones was performed for each year of fellowship. Multivariate analyses evaluated the difference in scores by sex for each of the subcompetencies.Results: Forty-eight geographically diverse programs participated, yielding data for 639 fellows (66% of all PEM fellows nationally); sex was recorded for 604 fellows, of whom 67% were female. When comparing the mean milestone scores in each of the six domains, there were no differences by sex in any year of training. When comparing scores within each of the 23 subcompetencies and correcting the significance level for comparison of multiple milestones, the scores for PC3 and ICS2 were significantly, albeit not meaningfully, higher for females.
BackgroundOut-of-hospital emergency care is at an early stage of development in Armenia, with the current emergency medical services (EMS) system having emergency physicians (EPs) work on ambulances along with nurses. While efforts are underway by the Ministry of Health and other organizations to reform the EMS system, little data exists on the status of pediatric emergency care (PEC) in the country. We designed this study to evaluate the knowledge and attitudes of out-of-hospital emergency physicians in pediatric rapid assessment and resuscitation, and identify areas for PEC improvement.MethodsWe distributed an anonymous, self-administered Knowledge and Attitudes survey to a convenience sample of out-of-hospital EPs in the capital, Yerevan, from August to September 2012.ResultsWith a response rate of 80%, the majority (89.7%) of respondents failed a 10-question knowledge test (with a pre-defined passing score of ≥7) with a mean score of 4.17 ± 1.99 SD. Answers regarding the relationship between pediatric cardiac arrest and respiratory issues, compression-to-ventilation ratio in neonates, definition of hypotension, and recognition of shock were most frequently incorrect. None of the participants had attended pediatric-specific continuing medical education (CME) activities within the preceding 5 years. χ2 analysis demonstrated no statistically significant association between physician age, length of EMS experience, type of ambulance (general vs. resuscitation/critical care), or CME attendance and pass/fail status. The majority of participants agreed that PEC education in Armenia needs improvement (98%), that there is a need for pediatric-specific CME (98%), and that national out-of-hospital PEC guidelines would increase PEC safety, efficiency, and effectiveness (96%).ConclusionsOut-of-hospital emergency physicians in Yerevan, Armenia are deficient in pediatric-specific emergency assessment and resuscitation knowledge and training, but express a clear desire for improvement. There is a need to support additional PEC training and CME within the EMS system in Armenia.
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