In the past 15 years, encouraging clinical results for the detection of small lymph node metastases was obtained by the use of Combidex‐enhanced MRI (CEM, also known as magnetic resonance lymphography). Withdrawal of the European Medicines Agency approval application by the manufacturer made it impossible for patients to benefit from this agent; a loss, especially for men with prostate cancer. Current conventional imaging techniques are not as accurate as CEM is, thus a surgical diagnostic exploration (extended lymph node dissection) is still the preferred technique to evaluate the lymph nodes, resulting in peri‐ and postoperative complications. In 2013, the Radboud University Medical Center (Radboudumc) obtained all licenses and documentation for the production process of Combidex (ferumoxtran‐10), and manufactured the contrast agent under supervision of the Department of Pharmacy. Since 2014, 310 men with prostate cancer have been examined with CEM in the Radboudumc. Within this cohort, seven minor possibly contrast‐related adverse effects were observed after administration of Combidex. As the contrast agent is now back again in the Netherlands, this review highlights the working mechanism, previous results, observed side effects since the reintroduction, and the future perspectives for Combidex. WIREs Nanomed Nanobiotechnol 2018, 10:e1471. doi: 10.1002/wnan.1471This article is categorized under:
Diagnostic Tools > In Vivo Nanodiagnostics and ImagingTherapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Vancomycin is an important antibiotic for critically ill patients with Grampositive bacterial infections. Critically ill patients typically have severely altered pathophysiology, which leads to inefficacy or toxicity. Model-informed precision dosing may aid in optimizing the dose, but prospectively validated tools are not available for this drug in these patients. We aimed to prospectively validate a population pharmacokinetic model for purpose model-informed precision dosing of vancomycin in critically ill patients. Methods: We first performed a systematic evaluation of various models on retrospectively collected pharmacokinetic data in critically ill patients and then selected the best performing model. This model was implemented in the Insight Rx clinical decision support tool and prospectively validated in a multicentre study in critically ill patients. The predictive performance was obtained as mean prediction error and relative root mean squared error. Results: We identified 5 suitable population pharmacokinetic models. The most suitable model was carried forward to a prospective validation. We found in a prospective multicentre study that the selected model could accurately and precisely predict the vancomycin pharmacokinetics based on a previous measurement, with a mean prediction error and relative root mean squared error of respectively 8.84% (95% confidence interval 5.72-11.96%) and 19.8% (95% confidence interval 17.47-22.13%). Conclusion: Using a systematic approach, with a retrospective evaluation and prospective verification we showed the suitability of a model to predict vancomycin pharmacokinetics for purposes of model-informed precision dosing in clinical practice. The presented methodology may serve a generic approach for evaluation of pharmacometric models for the use of model-informed precision dosing in the clinic.
The NCI Common Terminology Criteria for Adverse Events v3.0 is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term.
In contrast to the product information, we recommend giving the full dose of caspofungin regardless of the presence and severity of cirrhosis to avoid a subtherapeutic exposure.
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