Clinical Practice Guideline by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America: 2021 Guideline on Diagnosis and Management of Acute Hematogenous Osteomyelitis in Pediatrics.

2021

2021 Aug 05

2048-7207

<p>This clinical practice guideline for the diagnosis and treatment of acute hematogenous osteomyelitis (AHO) in children was developed by a multidisciplinary panel representing Pediatric Infectious Diseases Society (PIDS) and the Infectious Diseases Society of America (IDSA). This guideline is intended for use by healthcare professionals who care for children with AHO, including specialists in pediatric infectious diseases, orthopedics, emergency care physicians, hospitalists, and any clinicians and healthcare providers caring for these patients. The panel's recommendations for the diagnosis and treatment of AHO are based upon evidence derived from topic-specific systematic literature reviews. Summarized below are the recommendations for the diagnosis and treatment of AHO in children. The panel followed a systematic process used in the development of other IDSA and PIDS clinical practice guidelines, which included a standardized methodology for rating the certainty of the evidence and strength of recommendation using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. A detailed description of background, methods, evidence summary and rationale that support each recommendation, and knowledge gaps can be found online in the full text.</p>

10.1093/jpids/piab027

J Pediatric Infect Dis Soc

34350458

Use of normalized prediction distribution errors for assessing population physiologically-based pharmacokinetic model adequacy.

2020

2020 Apr 22

1573-8744

<p>Currently employed methods for qualifying population physiologically-based pharmacokinetic (Pop-PBPK) model predictions of continuous outcomes (e.g., concentration-time data) fail to account for within-subject correlations and the presence of residual error. In this study, we propose a new method for evaluating Pop-PBPK model predictions that account for such features. The approach focuses on deriving Pop-PBPK-specific normalized prediction distribution errors (NPDE), a metric that is commonly used for population pharmacokinetic model validation. We describe specific methodological steps for computing NPDE for Pop-PBPK models and define three measures for evaluating model performance: mean of NPDE, goodness-of-fit plots, and the magnitude of residual error. Utility of the proposed evaluation approach was demonstrated using two simulation-based study designs (positive and negative control studies) as well as pharmacokinetic data from a real-world clinical trial. For the positive-control simulation study, where observations and model simulations were generated under the same Pop-PBPK model, the NPDE-based approach denoted a congruency between model predictions and observed data (mean of NPDE =  - 0.01). In contrast, for the negative-control simulation study, where model simulations and observed data were generated under different Pop-PBPK models, the NPDE-based method asserted that model simulations and observed data were incongruent (mean of NPDE =  - 0.29). When employed to evaluate a previously developed clindamycin PBPK model against prospectively collected plasma concentration data from 29 children, the NPDE-based method qualified the model predictions as successful (mean of NPDE = 0). However, when pediatric subpopulations (e.g., infants) were evaluated, the approach revealed potential biases that should be explored.</p>

10.1007/s10928-020-09684-2

J Pharmacokinet Pharmacodyn

32323049

Harmonisation in study design and outcomes in paediatric antibiotic clinical trials: a systematic review.

2016

e178-89

2016 Sep

1474-4457

<p>There is no global consensus on the conduct of clinical trials in children and neonates with complicated clinical infection syndromes. No comprehensive regulatory guidance exists for the design of antibiotic clinical trials in neonates and children. We did a systematic review of antibiotic clinical trials in complicated clinical infection syndromes (including bloodstream infections and community-acquired pneumonia) in children and neonates (0-18 years) to assess whether standardised European Medicines Agency (EMA) and US Food and Drug Administration (FDA) guidance for adults was used in paediatrics, and whether paediatric clinical trials applied consistent definitions for eligibility and outcomes. We searched MEDLINE, Cochrane CENTRAL databases, and ClinicalTrials.gov between Jan 1, 2000, and Nov 18, 2015. 82 individual studies met our inclusion criteria. The published studies reported on an average of 66% of CONSORT items. Study design, inclusion and exclusion criteria, and endpoints varied substantially across included studies. The comparison between paediatric clinical trials and adult EMA and FDA guidance highlighted that regulatory definitions are only variably applicable and used at present. Absence of consensus for paediatric antibiotic clinical trials is a major barrier to harmonisation in research and translation into clinical practice. To improve comparison of therapies and strategies, international collaboration among all relevant stakeholders leading to harmonised case definitions and outcome measures is needed.</p>

10.1016/S1473-3099(16)00069-4

Lancet Infect Dis

27375212