Vancomycin: An analysis and evaluation of eight population pharmacokinetic models for clinical application in general adult population.

INTRODUCTION: Based on the recent guidelines for vancomycin therapeutic drug monitoring (TDM), the area under the curve to minimum inhibitory concentration ratio was to be employed combined with the usage of population pharmacokinetic (popPK) model for dosing adaptation. Yet, deploying these models in a clinical setting requires an external evaluation of their performance. OBJECTIVES: This study aimed to evaluate existing vancomycin popPK models from the literature for the use in TDM within the general patient population in a clinical setting. METHODS: The models under external evaluation were chosen based on a review of literature covering vancomycin popPK models developed in general adult populations. Patients' data were collected from Charles-Le Moyne Hospital (CLMH). The external evaluation was performed with NONMEM® (v7.5). Additional analyses such as evaluating the impact of number of samples on external evaluation, Bayesian forecasting, and a priori dosing regimen simulations were performed on the best performing model. RESULTS: Eight popPK models were evaluated with an independent dataset that included 40 patients and 252 samples. The model developed by Goti and colleagues demonstrated superior performance in diagnostic plots and population predictive performance, with bias and inaccuracy values of 0.251% and 22.7%, respectively, and for individual predictive performance, bias and inaccuracy were -4.90% and 12.1%, respectively. When limiting the independent dataset to one or two samples per patient, the Goti model exhibited inadequate predictive performance for inaccuracy, with values exceeding 30%. Moreover, the Goti model is suitable for Bayesian forecasting with at least two samples as prior for the prediction of the next trough concentration. Furthermore, the vancomycin dosing regimen that would maximize therapeutic targets of area under the curve to minimum inhibitory concentration ratio (AUC24/MIC) and trough concentrations (Ctrough) for the Goti model was 20 mg/kg/dose twice daily. CONCLUSION: Considering the superior predictive performance and potential for Bayesian forecasting in the Goti model, future research aims to test its applicability in clinical settings at CLMH, both in a priori and a posteriori scenario.

Eculizumab in the Treatment of Acetylcysteine-Induced Atypical Hemolytic Uremic Syndrome.

N-acetylcysteine overdose is almost exclusively an iatrogenic event. This rare complication can lead to hemolysis or atypical hemolytic uremic syndrome. A 53-year-old Caucasian male accidentally received a two-fold N-acetylcysteine overdose that resulted in a presentation compatible with the atypical hemolytic uremic syndrome. The patient required temporary hemodialysis sessions, and he received treatment with eculizumab. This case report is the first reported N-acetylcysteine-induced atypical hemolytic uremic syndrome successfully treated with eculizumab. Clinicians should be aware of N-acetylcysteine overdose and its possible hemolytic complications.

VANCOmycin dose adjustments comparing trough levels to the ratio of the area under de curve to the minimum inhibitory concentration method using a BAYESian approach: A feasibility study.

WHAT IS KNOWN AND OBJECTIVE?: The latest published guidelines advocate for the area under the concentration-time curve to minimal inhibitory concentration (AUC0-24h /MIC) estimated with bayesian calculations. This recommended pharmacokinetic monitoring transition is not based on randomized controlled prospective data. METHODS: In this open-label feasibility RCT, patients were assigned to have their vancomycin dosing adjusted based on bayesian-guided AUC0-24h /MIC or trough levels. Primary outcomes were consent rate, number of patients recruited per month, compliance with blood sampling schedule and compliance with bayesian software recommendations. Secondary outcomes focused on target attainment, safety and operational impacts. RESULTS AND DISCUSSION: Forty-five patients underwent randomization (23 bayesian, 22 trough). Consent rate was 37,5% for an average of 9.8 patients recruited per month meeting pre-specified objectives of 30% (p = 0.073) and 10 (p = 0.74) respectively. A 74.8% compliance with blood sampling schedule was below the pre-specified objective of 80% (p = 0.038). There was no statistically significant difference between the 83.7% compliance with bayesian software recommendations and the pre-specified objective of 90% (p = 0.21). Although exploratory, key clinical results were significant increases in the bayesian group for proportion of levels at target (RR 1.32; 95% CI 1.01-1.72; P = 0.038), number of blood samplings for patients (p = 0.036) and pharmacists' time spent on monitoring (p < 0.0001). A tendency towards a reduced incidence of nephrotoxicity in the Bayesian group was observed (RR 0.57; 95% CI 0.16-2.12; p = 0.46). WHAT IS NEW AND CONCLUSIONS?: This trial demonstrates that it would be feasible to conduct a properly sized RCT comparing vancomycin Bayesian-guided AUC0-24h /MIC to trough level monitoring. Although exploratory, this trial also showed a tendency towards reduced incidence of nephrotoxicity and an increased proportion of dosages at therapeutic targets with Bayesian monitoring.

Documentation in the Patient's Medical Record by Clinical Pharmacists in a Canadian University Teaching Hospital.

BACKGROUND: In many studies on documentation, the data are self-reported, which makes it difficult to know the actual level of documentation by pharmacists in patients' medical records. The literature assessing documentation by clinical pharmacists in health care centres is limited. OBJECTIVE: To assess the level of documentation in patients' medical records by clinical pharmacists at one large urban hospital. METHODS: This retrospective observational study included all patients who were followed by a clinical pharmacist during their stay in the Centre hospitalier de l'Université de Montreal between July 1 and October 31, 2016. The primary outcome, the level of documentation in patients' medical records, was categorized as minimal, sufficient, or extensive. The quality of notes and the impact of pharmacy students and residents on documentation were evaluated as secondary outcomes. RESULTS: A total of 779 patient charts from 4 inpatient units were included in the analysis. Of these, 563 (72.3%) were considered to have minimal documentation (at least 1 intervention described in writing), 432 (55.5%) had sufficient documentation (at least 1 note written during the patient's hospitalization), and 81 (10.4%) had extensive documentation (appropriate number of notes in relation to duration of hospitalization). Medication reconciliation performed by pharmacists at the time of admission was documented in 696 (89.3%) of patients' records. The presence of students or residents on a clinical unit was associated with a significant increase in the percentage of charts with at least 1 follow-up note (23.6% [120/508] with students/residents versus 12.5% [34/271] without students/residents; p < 0.001) and the mean number of followup notes (0.59 versus 0.23, respectively; p < 0.001) but had no effect on other variables. Of a total of 777 notes written by a pharmacist, the overall conformity with pre-established criteria was 56.8% (441/777), and conformity was 43.4% (139/320), 75.1% (272/362), and 31.6% (30/95) for admission, follow-up, and discharge notes, respectively. CONCLUSIONS: Documentation by clinical pharmacists in patients' medical records could be improved to achieve the stated goal of the American Society of Health-System Pharmacists and the Canadian Society of Hospital Pharmacists, that all significant clinical recommendations or interventions should be documented.

CONTEXTE: Les données de bon nombre d'études portant sur la tenue des dossiers médicaux sont autodéclarées, ce qui fait qu'il est difficile de savoir exactement dans quelle mesure les pharmaciens consignent les informations dans les dossiers médicaux des patients. Il n'existe que peu d'études évaluant la tenue des dossiers par les pharmaciens cliniques dans les centres de soins de santé. OBJECTIF: Évaluer dans quelle mesure les pharmaciens cliniciens d'un important hôpital urbain consignent l'information dans les dossiers médicaux des patients. MÉTHODES: La présente étude d'observation rétrospective englobait tous les patients ayant été suivis par un pharmacien clinicien pendant leur séjour au Centre hospitalier de l'Université de Montréal entre le 1er juillet et le 31 octobre 2016. Le principal paramètre d'évaluation, soit le degré de rigueur des inscriptions dans les dossiers médicaux des patients, entrait dans l'une des trois catégories suivantes : minimal, suffisant ou exhaustif. La qualité des notes et l'effet de la participation d'étudiants et de résidents en pharmacie à la tenue des dossiers ont servi de paramètres d'évaluation secondaires. RÉSULTATS: L'analyse a porté sur 779 dossiers médicaux de patients provenant de quatre services hospitaliers. Les investigateurs ont considéré que 563 d'entre eux (72,3 %) appartenaient à la catégorie « minimal ¼ (au moins une intervention consignée par écrit), 432 (55,5 %) se situaient dans la catégorie « suffisant ¼ (au moins une note rédigée au cours de l'hospitalisation du patient) et 81 (10,4 %) se rangeaient dans la catégorie « exhaustif ¼ (nombre adéquat de notes en fonction à la durée de l'hospitalisation). Les bilans comparatifs des médicaments établis par des pharmaciens au moment de l'admission ont été consignés dans 696 (89,3 %) dossiers médicaux de patients. On a associé la présence d'étudiants ou de résidents dans une unité clinique à une hausse significative du pourcentage de dossiers médicaux affichant au moins une note de suivi (23,6 % [120/508] avec des étudiants / résidents contre 12,5 % [34/271] sans étudiants / résidents; p < 0,001) et du nombre moyen de notes de suivi (respectivement 0,59 contre 0,23; p < 0,001), mais leur présence n'a été associée à aucun autre effet sur les autres variables. Le taux de conformité globale aux critères préétablis des 777 notes rédigées par un pharmacien était de 56,8 % (441/777) et le taux de conformité des notes d'admission, de suivi et de congé était respectivement de 43,4 % (139/320), 75,1 % (272/362) et 31,6 % (30/95). CONCLUSIONS: La tenue des dossiers médicaux de patients par les pharmaciens cliniciens devrait s'améliorer pour qu'elle atteigne l'objectif établi par l'American Society of Health-System Pharmacists et la Société canadienne des pharmaciens d'hôpitaux, qui veut que toutes les recommandations et interventions cliniques d'importance soient consignées.

Short communication: Production of cottage cheese fortified with vitamin D.

The availability of alternative food products fortified with vitamin D could help decrease the percentage of the population with vitamin D deficiency. The objective of this study was to fortify cheese with vitamin D. Cottage cheese was selected because its manufacture allows for the addition of vitamin D after the draining step without any loss of the vitamin in whey. Cream containing vitamin D (145 IU/g of cream) was mixed with the fresh cheese curds, resulting in a final concentration of 51 IU/g of cheese. Unfortified cottage cheese was used as a control. As expected, the cottage cheese was fortified without any loss of vitamin D in the cheese whey. The vitamin D added to cream was not affected by homogenization or pasteurization treatments. In cottage cheese, the vitamin D concentration remained stable during 3 weeks of storage at 4°C. Compared with the control cheese, the cheese fortified with vitamin D showed no effects of fortification on cheese characteristics or sensory properties. Cottage cheese could be a new source of vitamin D or an alternative to fortified drinking milk.