Pharmacokinetics and Optimal Dosing of Levofloxacin in Children for Drug-Resistant Tuberculosis: An Individual Patient Data Meta-Analysis.

BACKGROUND: Each year 25 000-32 000 children develop rifampicin- or multidrug-resistant tuberculosis (RR/MDR-TB), and many more require preventive treatment. Levofloxacin is a key component of RR/MDR-TB treatment and prevention, but the existing pharmacokinetic data in children have not yet been comprehensively summarized. We aimed to characterize levofloxacin pharmacokinetics through an individual patient data meta-analysis of available studies and to determine optimal dosing in children. METHODS: Levofloxacin concentration and demographic data were pooled from 5 studies and analyzed using nonlinear mixed effects modeling. Simulations were performed using current World Health Organization (WHO)-recommended and model-informed optimized doses. Optimal levofloxacin doses were identified to target median adult area under the time-concentration curve (AUC)24 of 101 mg·h/L given current standard adult doses. RESULTS: Data from 242 children (2.8 years [0.2-16.8] was used). Apparent clearance was 3.16 L/h for a 13-kg child. Age affected clearance, reaching 50% maturation at birth and 90% maturation at 8 months. Nondispersible tablets had 29% lower apparent oral bioavailability compared to dispersible tablets. Median exposures at current WHO-recommended doses were below the AUC target for children weighing <24 kg and under <10 years, resulting in approximately half of the exposure in adults. Model-informed doses of 16-33 mg/kg for dispersible tablets or 16-50 mg/kg for nondispersible tablets were required to meet the AUC target without significantly exceeding the median adult Cmax. CONCLUSIONS: Revised weight-band dosing guidelines with doses of >20 mg/kg are required to ensure adequate exposure. Further studies are needed to determine safety and tolerability of these higher doses.

Resident training in a new robotic thoracic surgery program.

BACKGROUND: The volume of robot-assisted operations has drastically increased over the past decade. New programs have focused on training surgeons, whereas resident training has lagged behind. The objective of this study was to evaluate our institutional experience with resident participation in thoracic robotic surgery cases since the initiation of our program. METHODS: The first 100 robotic thoracic surgery cases at our institution were retrospectively reviewed and categorized into three sequential cohorts. Procedure type, patient and operative characteristics, level of resident participation (primary surgeon [PS] or assistant), and postoperative variables were evaluated. RESULTS: Of the first 100 cases, 38% were lung resections, 23% were esophageal operations, and 20% were sympathectomies. The distribution of cases changed over time with the proportion of pulmonary resections significantly increasing. Patient age (P < 0.05), body mass index (P = not significant [NS]), and comorbidities (P = NS) increased over time. Resident participation as PS increased from 33%-59% between the early and late cohorts (P < 0.05). A subset analysis of the 20 lobectomies (7 attending PS, 13 residents) showed similar patient characteristics (P = NS): age (67 versus 69), body mass index (29.5 versus 26.1), and American Society of Anesthesiologists category (2.8 versus 2.8). Operative and postoperative characteristics were also similar (P = NS) regardless of PS: operative time (260 versus 249 min), estimated blood loss (187 versus 203 mL), and length of stay (4.8 versus 4.7 d). CONCLUSIONS: Residents can participate as the PS in a variety of thoracic operations during the implementation of a robotics program. Operative time, estimated blood loss, and length of stay were similar regardless of level of resident participation.

A Changing Landscape: Exploring Resident Perspectives on Pursuing Pediatric Hospital Medicine Fellowships.

BACKGROUND: Pediatric Hospital Medicine (PHM) was approved as a subspecialty in 2016. Perspectives of pediatric and combined pediatric residents regarding barriers and facilitators to pursuing PHM fellowships have not previously been assessed. METHODS: A survey to explore residents' perspectives on PHM fellowships, with questions regarding demographics, likelihood of pursuing PHM after fellowship introduction, and influencing factors was distributed to pediatric and combined pediatric residents via program directors. RESULTS: The survey was distributed to an estimated 2657 residents. A total of 855 (32.2%) residents completed the survey; 89% of respondents had at least considered a career in PHM, and 79.4% reported that the introduction of the PHM fellowship requirement for subspecialty certification made them less likely to pursue PHM. Intent to practice in a community setting or only temporarily practice PHM, Combined Internal Medicine and Pediatric trainee status, and high student loan burden were associated with decreased likelihood of pursuing PHM (P < .05). Most respondents reported that forfeited earnings during fellowship, family and student loan obligations, and perceived sufficiency of residency training discouraged them from pursuing PHM fellowship. Half of respondents valued additional training in medical education, quality improvement, hospital administration, research, and clinical medicine. CONCLUSIONS: Many survey respondents expressed interest in the opportunity to acquire new skills through PHM fellowship. However, the majority of respondents reported being less likely to pursue PHM after the introduction of fellowship requirement for board certification, citing financial and personal opportunity costs. Understanding factors that residents value and those that discourage residents from pursuing PHM fellowship training may help guide future iterations of fellowship design.