External evaluation of population pharmacokinetic models of vancomycin in neonates: the transferability of published models to different clinical settings

AimsVancomycin is one of the most evaluated antibiotics in neonates using modeling and simulation approaches. However no clear consensus on optimal dosing has been achieved. The objective of the present study was to perform an external evaluation of published models, in order to test their predictive performances in an independent dataset and to identify the possible study-related factors influencing the transferability of pharmacokinetic models to different clinical settings.MethodPublished neonatal vancomycin pharmacokinetic models were screened from the literature. The predictive performance of six models was evaluated using an independent dataset (112 concentrations from 78 neonates). The evaluation procedures used simulation-based diagnostics [visual predictive check (VPC) and normalized prediction distribution errors (NPDE)].ResultsDifferences in predictive performances of models for vancomycin pharmacokinetics in neonates were found. The mean of NPDE for six evaluated models were 1.35, −0.22, −0.36, 0.24, 0.66 and 0.48, respectively. These differences were explained, at least partly, by taking into account the method used to measure serum creatinine concentrations. The adult conversion factor of 1.3 (enzymatic to Jaffé) was tested with an improvement in the VPC and NPDE, but it still needs to be evaluated and validated in neonates. Differences were also identified between analytical methods for vancomycin.ConclusionThe importance of analytical techniques for serum creatinine concentrations and vancomycin as predictors of vancomycin concentrations in neonates have been confirmed. Dosage individualization of vancomycin in neonates should consider not only patients' characteristics and clinical conditions, but also the methods used to measure serum creatinine and vancomycin

Model-Driven Treatment: Promises and Problems

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A Study of Verbal Behavior in Recovery of Aphasic and Nonaphasic Persons

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Systematic Analysis of Cuing Strategies in Aphasia: Taking your "Cue" from the Patient

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Assessment and Counseling with Aphasic Drivers

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Incremental dialysis for preserving residual kidney function-Does one size fit all when initiating dialysis?

While many patients have substantial residual kidney function (RKF) when initiating hemodialysis (HD), most patients with end stage renal disease in the United States are initiated on 3-times per week conventional HD regimen, with little regard to RKF or patient preference. RKF is associated with many benefits including survival, volume control, solute clearance, and reduced inflammation. Several strategies have been recommended to preserve RKF after HD initiation, including an incremental approach to HD initiation. Incremental HD prescriptions are personalized to achieve adequate volume control and solute clearance with consideration to a patient's endogenous renal function. This allows the initial use of less frequent and/or shorter HD treatment sessions. Regular measurement of RKF is important because HD frequency needs to be increased as RKF inevitably declines. We narratively review the results of 12 observational cohort studies of twice-weekly compared to thrice-weekly HD. Incremental HD is associated with several benefits including preservation of RKF as well as extending the event-free life of arteriovenous fistulas and grafts. Patient survival and quality of life, however, has been variably associated with incremental HD. Serious risks must also be considered, including increased hospitalization and mortality perhaps related to fluid and electrolyte shifts after a long interdialytic interval. On the basis of the above literature review, and our clinical experience, we suggest patient characteristics which may predict favorable outcomes with an incremental approach to HD. These include substantial RKF, adequate volume control, lack of significant anemia/electrolyte imbalance, satisfactory health-related quality of life, low comorbid disease burden, and good nutritional status without evidence of hypercatabolism. Clinicians should engage patients in on-going conversations to prepare for incremental HD initiation and to ensure a smooth transition to thrice-weekly HD when needed

The Post-stroke Psychosocial Envrionment of Stroke Patients and Their Partners: Some Preliminary Results of a Longitudinal Study

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Response time patterns for word production and word selection anomias

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Aphasic Patients' Performance on a Mental Status Examination

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Intermittent Auditory Imperception: Clinical Characteristics and Implications for Treatment

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