Background Privacy restrictions limit access to protected patient-derived health information for research purposes. Consequently, data anonymization is required to allow researchers data access for initial analysis before granting institutional review board approval. A system installed and activated at our institution enables synthetic data generation that mimics data from real electronic medical records, wherein only fictitious patients are listed. Objective This paper aimed to validate the results obtained when analyzing synthetic structured data for medical research. A comprehensive validation process concerning meaningful clinical questions and various types of data was conducted to assess the accuracy and precision of statistical estimates derived from synthetic patient data. Methods A cross-hospital project was conducted to validate results obtained from synthetic data produced for five contemporary studies on various topics. For each study, results derived from synthetic data were compared with those based on real data. In addition, repeatedly generated synthetic datasets were used to estimate the bias and stability of results obtained from synthetic data. Results This study demonstrated that results derived from synthetic data were predictive of results from real data. When the number of patients was large relative to the number of variables used, highly accurate and strongly consistent results were observed between synthetic and real data. For studies based on smaller populations that accounted for confounders and modifiers by multivariate models, predictions were of moderate accuracy, yet clear trends were correctly observed. Conclusions The use of synthetic structured data provides a close estimate to real data results and is thus a powerful tool in shaping research hypotheses and accessing estimated analyses, without risking patient privacy. Synthetic data enable broad access to data (eg, for out-of-organization researchers), and rapid, safe, and repeatable analysis of data in hospitals or other health organizations where patient privacy is a primary value.

PK properties of all weight groups were similar. More frequent and higher doses are needed to achieve the goals of current guidelines.

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Background little is known on the clinical implications of vancomycin trough levels among older patients. Objective to evaluate the association between vancomycin levels and outcomes among older versus younger patients. Design retrospective study. Subjects patients aged 18–64 and ≥65 years treated with vancomycin for documented methicillin resistant Staphylococcus aureus (MRSA) infections. Methods we compared the effectiveness and toxicity of vancomycin according to trough levels in older versus younger patients. Subgroup analysis of patients with glomerular filtration rate (GFR) > 60 ml/min/1.73 m2 was performed. Results we included 181 patients aged ≥65 years and 104 younger patients. Mean age in the older group was 76.9 ± 8 years versus 50.9 ± 12.4 in the younger group. Vancomycin trough levels and 24-hours area under the curve to minimal inhibitory concentrations (AUC/MIC) were significantly higher in older patients who were also significantly more likely to achieve trough levels of ≥15 mg/l within 4 days, (98/181 (54.1%) vs. 38/104 (36.5%) in younger patients, P = 0.004). Results were similar among patients with GFR > 60. Thirty-day mortality was significantly higher in older (74/181, 40.9% vs. 13/104, 12.5%, respectively, P < 0.001). There was no association between vancomycin trough levels and mortality among older patients. No significant differences were demonstrated in clinical or microbiological success or nephrotoxicity. Conclusions applying uniform dosing recommendations across age groups among adults with MRSA infections results in higher vancomycin levels and AUC/MIC in older versus younger patients. Yet, mortality rates remain higher among older adults. Prospective studies are needed to define the optimal approach for using this drug in older patients.

Objectives: Meropenem is a broad-spectrum carbapenem antibiotic with mostly renal excretion. Conflicting data are available regarding meropenem pharmacokinetics in critically ill neonates on concomitant continuous renal replacement therapy (CRRT) and/or extracorporeal membrane oxygenation (ECMO). Our objectives were to assess meropenem clearance in a neonate on CRRT and ECMO, compare it to previously published data and assess whether dose recommendations can be generalized in this population. Case description: A 2.5 kg male infant with a large diaphragmatic hernia was delivered by cesarean section at week 35 and immediately mechanically ventilated due to shock and respiratory insufficiency. He underwent surgical correction of the hernia, but developed recurrent sepsis, multiorgan failure and pulmonary hypertension. He remained mechanically ventilated and required ECMO and continuous venovenous hemodiafiltration. He was started on meropenem 40 mg/kg/dose, every 8 hs for Enterobacter cloacae bacteremia and sepsis, but due to lack of clinical and microbiologic response despite in vitro susceptibility, he was started on a continuous meropenem infusion of 240 mg/kg/d, based on dose recommendations in a similar case. We measured steady state meropenem plasma concentrations on 2 occasions, during ECMO and continuous venovenous hemodiafiltration (CVVHDF) and then on CVVHDF only. Results: Meropenem serum concentrations were 90 and 64 mg/L on the first and second occasion (therapeutic target concentration, 10 mg/L) corresponding to a clearance of 1.9 and 2.6 mL/kg/min. This clearance estimate was substantially lower than that reported in toddlers on CRRT and ECMO in some studies. Conclusion:In neonates and infants, meropenem clearance is difficult to predict because of dynamic ontogenetic changes in renal function. This problem is further aggravated in acutely ill infants with decreased renal function, renal replacement therapy and/or ECMO. Therefore, Target Concentration Intervention based on meropenem plasma concentrations is indispensable to ensure therapeutic exposure in this population.