The effect of medication related clinical decision support at the time of physician order entry.

Background In advanced clinical decision support systems, patient characteristics and laboratory values are included in the algorithms that generate alerts. These alerts have a higher specificity than basic medication surveillance alerts. The alerts of advanced clinical decision support systems can be shown directly to the prescriber during order entry, without the risk of generating an overload of irrelevant alerts. We implemented five advanced algorithms that are shown directly to the prescriber. These algorithms are for gastrointestinal prophylaxis, folic or folinic acid prescribed with orally or subcutaneously administered methotrexate, vitamin D prescribed with bisphosphonates, hyponatremia and measuring plasma levels for vancomycin and gentamicin. Objective We evaluated the effect of the implementation of the algorithms. Setting We performed prospective intervention studies with a historical group for comparison in both inpatients and outpatients at a teaching hospital in the Netherlands. Methods We compared the time period after implementation of the algorithm with the time period before implementation, using data from the hospital information system Epic. Difference in guideline adherence were analyzed using Chi square tests. Main outcome measure The outcome measures were the number of alerts, the acceptance rate of the advice in the alert, and for the algorithm measuring plasma levels for vancomycin and gentamicin the time to the correct dose. Results For all algorithms, the implementation resulted in a significant increase in guideline adherence, varying from 11 to 36%. The acceptance rate varied from 14% for hyponatremia to 90% for methotrexate. For gastrointestinal prophylaxis the acceptance rate was 4.4% for basic drug-drug interaction alerts when no gastrointestinal prophylaxis was prescribed and increased to 44.7% after implementation of the advanced algorithm. This algorithm substantially decreased the number of alerts from 812 before implementation to 217 after implementation. After implementation of the algorithm for measuring plasma levels for vancomycin and gentamicin, the proportion of patients receiving the correct dose after 48 h increased from 73 to 84% (p = 0.03). Conclusion Implementation of advanced algorithms that take patient characteristics into account and are shown directly to the physician during order entry, result in an increased guideline adherence.

A clinical decision support system to improve adequate dosing of gentamicin and vancomycin.

OBJECTIVE: Gentamicin and vancomycin meet the criteria for measuring plasma concentrations during therapy. However, compliance with the accompanying guidelines remains low. The primary objective of this study was to determine whether the implementation of a clinical decision support system, which displays an alert if a plasma concentration should be measured and a daily reviewed patient list resulted in improved compliance. MATERIALS AND METHODS: This intervention study was performed at the Spaarne Gasthuis, Haarlem/Hoofddorp, the Netherlands. The authors included 261 treatments with either gentamicin or vancomycin intravenously for at least 48 h in the year before and after implementation of the clinical decision support system in May 2015. The authors analyzed whether plasma concentrations were measured sooner and more frequently after the implementation, and determined whether the time until the correct dosage, with adequate drug concentrations, was reduced after implementation. RESULTS: Before implementation, plasma concentrations were measured within 72 h in 47% of the treatments. After implementation, this percentage increased to 80% (p < 0.01). After implementation, the time was significantly shorter until the correct dosage was given. CONCLUSION: The implementation of a clinical decision support system and a patient list resulted in improved compliance with the guidelines and optimized the treatment with gentamicin and vancomycin.

Risk factors for QTc interval prolongation.

PURPOSE: Prolongation of the QTc interval may result in Torsade de Pointes, a ventricular arrhythmia. Numerous risk factors for QTc interval prolongation have been described, including the use of certain drugs. In clinical practice, there is much debate about the management of the risks involved. In this study, we quantified the effect of these risk factors on the length of the QTc interval. METHODS: We analyzed all ECGs that were taken during routine practice between January 2013 and October 2016 in the Spaarne Gasthuis, a general teaching hospital in the Netherlands. We collected laboratory values in the week before the ECG recording and the drugs prescribed. For the identification of risk factors, we used multilevel linear regression analysis to correct for multiple ECG recordings per patient. RESULTS: We included 133,359 ECGs in our study, taken in 40,037 patients. Patients using one QT-prolonging drug had a 11.08 ms (95% CI 10.63-11.52; p < 0.001) longer QTc interval. Patients using two QT-prolonging drugs had a 3.04 ms (95% CI 2.06-4.02; p < 0.001) increase in the QTc interval compared to patients using one QT-prolonging drug. Women had a longer QTc interval compared to men (16.30 ms 95% CI 14.59-18.01; p < 0.001). The QTc interval increased with increasing age, but the difference between men and women diminished. Other independent risk factors that significantly prolonged the QTc interval with at least 10 ms were hypokalemia, hypocalcemia, and the use of loop diuretics. CONCLUSION: We identified and quantified various risk factors for QTc interval prolongation.

Ciprofloxacin does not Prolong the QTc Interval: A Clinical Study in ICU Patients and Review of the Literature.

PURPOSE: Ciprofloxacin may prolong the QT interval and increase the risk of Torsade de Pointes (TdP). Intravenous administration of ciprofloxacin in patients with additional risks may elevate the risk of QTc interval prolongation. We prospectively assessed whether intravenous ciprofloxacin prolongs the QT interval in patients with additional co-morbidities and risk factors. We also reviewed the literature on the QT prolonging effect or TdP inducing effect of ciprofloxacin. METHODS: ICU Patients who were treated with intravenous ciprofloxacin as part of their therapy were recruited. ECG was recorded within 60 min before start and in the last 30 min of 1 h infusion, or within 30 min after the end of ciprofloxacin infusion. QT interval was corrected for the heart rate using both Bazett's and Fridericia's formula. The changes were analyzed using the paired Student's t-test. RESULTS: Ten patients were included in the study (average age 74-y, 6 males). The average baseline QTc interval corrected with Bazett's formula was 448 ms that was shortened during or after ciprofloxacin infusion by 3 ms and 2 ms based on Bazett's  (p=0.67) and Fridericia's (p=0.68) formula, respectively. No observational study  or cohort study thus far has shown that ciprofloxacin has a QT prolonging effect or increases the risk of TdP or (cardiovascular) mortality.  Conclusion. Based on our results and the results of previous studies, it is unlikely that ciprofloxacin has a clinically relevant QT prolonging effect or an increased risk of TdP. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Improving the effectiveness of drug safety alerts to increase adherence to the guideline for gastrointestinal prophylaxis.

OBJECTIVE: Gastrointestinal bleedings are the most frequently occurring reason for medication-related hospital admissions, which are potentially preventable. We implemented a clinical decision support system that recommends to prescribe gastrointestinal prophylaxis in patients with an increased risk according to the Dutch guideline. Our primary objective was to determine whether the implementation resulted in improved compliance with this guideline for gastrointestinal prophylaxis. A secondary objective was to determine whether implementation resulted in a reduction of the number of drug safety alerts. MATERIALS AND METHODS: This intervention study was performed at the Spaarne Gasthuis, a teaching hospital, using Epic as hospital information system. We selected prescriptions with an indication for gastrointestinal prophylaxis according to the guideline, in the three months before and after implementation of the clinical decision support in November 2014. We analyzed whether gastrointestinal prophylaxis was prescribed more frequently after implementation using the Pearson's Chi-square test and the change in the number of drug safety alerts. RESULTS: Before implementation in 84.0% of the included 2064 prescriptions gastrointestinal prophylaxis was co-prescribed. After implementation this percentage increased to 94.5% of the 2269 prescriptions (p<0.001). The number of drug safety alerts decreased by 78.2% from 980 to 217 alerts. CONCLUSION: The introduction of a clinical decision support system for gastrointestinal prophylaxis improved adherence to the Dutch guideline. This was most likely due to a reduction in the number of irrelevant drug safety alerts.

Stability assessment of repackaged bevacizumab for intravitreal administration.

Intravitreal bevacizumab is frequently used off-label for the treatment of neovascular age-related macular degeneration, but there are concerns about the safety of intravitreal administered bevacizumab. It is suggested that repackaging bevacizumab in plastic syringes could affect the safety due to the unknown shelf life of the syringes. In this study, we analyzed the shelf life of the repackaged bevacizumab syringes, stored at 4 degrees C, at certain time intervals. Over the 32 days tested, bevacizumab concentration and the pH were stable. However, the number of particles in the repackaged bevacizumab syringes increased during storage at 4 degrees C and had exceeded the limits for intravitreal injections after 7 days. Since the number of particles seems to be the limitation of the shelf life of repackaged bevacizumab, it is necessary to quantify the number of particles in repackaged bevacizumab. Based on our results the maximum shelf life of repackaged bevacizumab should be 3 days.

Insufficient fluconazole exposure in pediatric cancer patients and the need for therapeutic drug monitoring in critically ill children.

BACKGROUND: Fluconazole is recommended as first-line treatment in invasive candidiasis in children and infants. Although timely achievement of adequate exposure of fluconazole improves outcome, therapeutic drug monitoring is currently not recommended. METHODS: We conducted a retrospective study of critically ill children treated with fluconazole from January 2007 to October 2013 and for whom fluconazole concentrations were available. We collected demographic, clinical, and treatment data through review of the medical records and determined the correlation of clinical variables with the fluconazole concentration. Additionally, we assessed the relation between the fluconazole concentration and the time to culture conversion in patients with proven invasive candidiasis. RESULTS: In total, 99 pediatric patients met the inclusion criteria. The fluconazole concentration was considered subtherapeutic in 40% of the patients. Multiple linear regression analysis showed a significant, independent, and positive association of the fluconazole trough concentration with the fluconazole dose (P <.001), weight (P = .009), and the serum urea concentration (P = .003), and a significant, independent, and negative association with age (P = .004) and cancer as an underlying condition (P = .003). A higher fluconazole concentration was associated with a shorter time to culture conversion (hazard ratio = 1.076 [95% confidence interval, 1.017-1.138]; P = .011). CONCLUSIONS: The fluconazole concentration is not sufficient in pediatric cancer patients with the currently recommended dose regimen, and a higher fluconazole dose is required to achieve adequate drug exposure. Therapeutic drug monitoring of fluconazole can be a valuable tool to detect possible underexposure in critically ill children.