Discrepancies in Electronic Medical Prescriptions Found in a Hospital Emergency Department: A Prospective Observational Study.

The medication in an electronic prescribing system (EPS) does not always match the patient's actual medication. This prospective study analyzes the discrepancies (any inconsistency) between medication prescribed using an EPS and the medication revised by the clinical pharmacist upon admission to the observation area of the emergency department (ED). Adult patients with multimorbidity and/or polypharmacy were included. The pharmacist used multiple sources to obtain the revised medication list, including patient/carer interviews. A total of 1654 discrepancies were identified among 1131 patients. Of these patients, 64.5% had ≥1 discrepancy. The most common types of discrepancy were differences in posology (43.6%), commission (34.7%), and omission (20.9%). Analgesics (11.1%), psycholeptics (10.0%), and diuretics (8.9%) were the most affected. Furthermore, 52.5% of discrepancies affected medication that was high-alert for patients with chronic illnesses and 42.0% of medication involved withdrawal syndromes. Discrepancies increased with the number of drugs (ρ = 0.44, p < 0.01) and there was a difference between non-polypharmacy patients, polypharmacy ones and those with extreme polypharmacy (p < 0.01). Those aged over 75 years had a higher number of prescribed medications and discrepancies occurred more frequently compared with younger patients. The number of discrepancies was larger in women than in men. The EPS medication record requires verification from additional sources, including patient and/or carer interviews.

Medication delivery errors in outpatients with percutaneous endoscopic gastrostomy: effect on tube feeding replacement.

Patients with enteral access usually receive oral drugs via feeding tubes and correct drug administration remains a challenge. The aim of this study was to identify common medication delivery errors (MDEs) in outpatients with percutaneous endoscopic gastrostomy (PEG) and evaluate their association with the need for tube replacement due to deterioration or clogging. A 2-year retrospective study that comprised adult outpatients with a placed/replaced PEG tube and whose electronic medical record included home medication was carried out. Treatment with medication that should not be crushed and administered through an enteral feeding tube was considered an MDE. We included 269 patients and 213 MDEs (20% of oral prescriptions) were detected in 159. Ninety-two percent of the medications associated with MDEs could be substituted by appropriate formulations. Tube replacement due to obstruction was needed in 85 patients. MDEs were associated with increased risk for tube replacement (OR 2.17; 95% CI 1.10-4.27). Omeprazole enteric-coated capsules were associated with the greatest risk (OR 2.24; 95% CI 1.01-4.93). PEG outpatients are highly exposed to MDEs, leading to a significant increase in the odds of tube replacement, mainly when treated with omeprazole. The use of appropriate alternative therapies would prevent unnecessary adverse events.

Physiologically-based pharmacokinetic modelling and dosing evaluation of gentamicin in neonates using PhysPK.

Each year, infections caused around the 25% of neonatal deaths. Early empirical treatments help to reduce this mortality, although optimized dosing regimens are still lacking. The aims were to develop and validate a gentamicin physiologically-based pharmacokinetic (PBPK) model and then potentially explore dosing regimens in neonates using pharmacokinetic and pharmacodynamic criteria. The PBPK model developed consisted of 2 flow-limited tissues: kidney and other tissues. It has been implemented on a new tool called PhysPK, which allows structure reusability and evolution as predictive engine in Model-Informed Precision Dosing (MIPD). Retrospective pharmacokinetic information based on serum levels data from 47 neonates with gestational age between 32 and 39 weeks and younger than one-week postnatal age were used for model validation. The minimal PBPK model developed adequately described the gentamicin serum concentration-time profile with an average fold error nearly 1. Extended interval gentamicin dosing regimens (6 mg/kg q36h and 6 mg/kg q48h for term and preterm neonates, respectively) showed efficacy higher than 99% with toxicity lower than 10% through Monte Carlo simulation evaluations. The gentamicin minimal PBPK model developed in PhysPK from literature information, and validated in preterm and term neonates, presents adequate predictive performance and could be useful for MIPD strategies in neonates.

Amikacin initial dosage in patients with hypoalbuminaemia: an interactive tool based on a population pharmacokinetic approach.

OBJECTIVES: To characterize amikacin population pharmacokinetics in patients with hypoalbuminaemia and to develop a model-based interactive application for amikacin initial dosage. METHODS: A population pharmacokinetic model was developed using a non-linear mixed-effects modelling approach (NONMEM) with amikacin concentration-time data collected from clinical practice (75% hypoalbuminaemic patients). Goodness-of-fit plots, minimum objective function value, prediction-corrected visual predictive check, bootstrapping, precision and bias of parameter estimates were used for model evaluation. An interactive model-based simulation tool was developed in R (Shiny and R Markdown). Cmax/MIC ratio, time above MIC and AUC/MIC were used for optimizing amikacin initial dose recommendation. Probabilities of reaching targets were calculated for the dosage proposed. RESULTS: A one-compartment model with first-order linear elimination best described the 873 amikacin plasma concentrations available from 294 subjects (model development and external validation groups). Estimated amikacin population pharmacokinetic parameters were CL (L/h) = 0.525 + 4.78 × (CKD-EPI/98) × (0.77 × vancomycin) and V (L) = 26.3 × (albumin/2.9)-0.51 × [1 + 0.006 × (weight - 70)], where CKD-EPI is calculated with the Chronic Kidney Disease Epidemiology Collaboration equation. AMKdose is a useful interactive model-based application for a priori optimization of amikacin dosage, using individual patient and microbiological information together with predefined pharmacokinetic/pharmacodynamic (PKPD) targets. CONCLUSIONS: Serum albumin, total bodyweight, estimated glomerular filtration rate (using the CKD-EPI equation) and co-medication with vancomycin showed a significant impact on amikacin pharmacokinetics. A powerful interactive initial dose-finding tool has been developed and is freely available online. AMKdose could be useful for guiding initial amikacin dose selection before any individual pharmacokinetic information is available.

A 3-year prospective study of a multidisciplinary early proactive therapeutic drug monitoring programme of infliximab treatments in inflammatory bowel disease.

AIMS: Therapeutic drug monitoring (TDM) of trough serum infliximab concentrations has been mainly used in case of loss of response in patients with inflammatory bowel disease (IBD). The aim of this study was to evaluate the effectiveness and safety of a multidisciplinary early proactive TDM (mep-TDM) programme for dose adjustment. METHODS: A 3-year prospective study was conducted based on a sample of 81 patients who started treatment and were subsequently subjected to mep-TDM with the first control at week 14. Data of a historical control group of 72 patients treated with infliximab and managed with empirical dosing were included. Effectiveness variables were treatment failure, IBD-related surgery and IBD-related hospitalization. Safety variables were serious infusion reactions (SIRs) and adverse reactions. Cox regression was used for survival analysis. RESULTS: In the mep-TDM study group, compared to the control group, there was a significant reduction in the risk of treatment failure (hazard ratio [HR]: 0.51; 95% confidence interval [CI]: 0.27-0.92; P = .037), IBD-related surgery (HR: 0.14; 95% CI: 0.03-0.65; P = .012) and hospitalization (HR: 0.38; 95% CI: 0.17-0.87; P = .022). SIRs were lower in the mep-TDM group (2.5% vs 10.4%; P < .050); the incidence of adverse reactions was similar (3.7% vs 3.9%; p > .999). CONCLUSION: This study found that compared to empirical dosing, mep-TDM is associated with improved efficacy and safety of infliximab therapy, reduced IBD-related hospitalization and surgery and incidence of SIRs, and increasing long-term durability of treatment effects.

Evaluation of renal function equations to predict amikacin clearance.

Objective: To evaluate the predictive performance of eight renal function equations to describe amikacin elimination in a large standard population with a wide range of age. Methods: Retrospective study of adult hospitalized patients treated with amikacin and monitored in the clinical pharmacokinetics laboratory of a pharmacy service. Renal function was calculated as Cockcroft-Gault with total, adjusted and ideal body weight, MDRD-4, CKD-EPI, rLM, BIS1, and FAS. One compartment model with first-order elimination, including interindividual variability on clearance and volume of distribution and combined residual error model was selected as a base structural model. A pharmaco-statistical analysis was performed following a non-linear mixed effects modeling approach (NONMEM 7.3 software). Results: 198 patients (61 years [18-93]) and 566 measured amikacin plasma concentrations were included. All the estimated glomerular filtration rate and creatinine clearance equations evaluated described properly the data. The linear relationship between clearance and glomerular filtration rate based on rLM showed a statistically significant improvement in the fit of the data. rLM must be evaluated carefully in renal failure for amikacin dose adjustment. Conclusions: Revised Lund-Malmö (rLM) and CKD-EPI showed the superior predictive performance of amikacin drug elimination comparing to all the alternative metrics evaluated.

Pharmacokinetics and dosing requirements of digoxin in pregnant women treated for fetal supraventricular tachycardia.

BACKGROUND: The objective of this study was to characterize the pharmacokinetics (PK) of digoxin in pregnant women and its potential implications for drug dosing. METHODS: Serum digoxin concentrations (SDCs) obtained in pregnant women treated for fetal supraventricular tachycardia (SVT) was retrospectively collected. PK analysis was comparatively performed using a two-stage approach (PKS™) and a Population PK approach (NONMEM™). As clinical outcome the fetal heart rate was recorded. RESULTS: A total of 42 SDCs were obtained from 8 women in the 3rd trimester of pregnancy (mean age 33.0 years). The PK parameters estimated by both two-stage (volume of distribution (Vd) = 682.0 L, CV = 47.5%; serum clearance (CL) = 16.1 L/h, CV = 19%) and population approaches (Vd = 731.3 L, CV = 30.5%; CL = 18.7 L/h, CV = 17.8%) are very similar and show a clear trend of increasing drug disposition in the third trimester of pregnancy. An oral loading dose of 0.5 mg/8 h during 24 h followed by a maintenance regimen of 0.5 mg/12 h been recommended to start treatment. CONCLUSIONS: Despite the small population, these parameters could be used as a guide to calculate the initial dosage requirements in the third trimester of pregnancy for treating fetal SVT. In addition, maternal SDCs should be routinely monitored for dosage adjustment purposes.

Evaluación del grado de formación del personal que elabora las nutriciones parenterales en los Servicios de Farmacia / Training degree assessment of staff producing parenteral nutrition in Pharmacy Services

Objetivo: Evaluar el grado de formación del personal que elabora nutrición parenteral en los Servicios de Farmacia. Material y métodos: Se diseñó una encuesta on-line con 17 preguntas en la que se incluyeron los puntos más importantes en la elaboración de nutriciones parenterales. Para el diseño de la encuesta y el análisis posterior se utilizó la aplicación informática Survey monkey®. Resultados: Se obtuvieron un total de 135 respuestas. En el 95% de los Servicios de Farmacia existían normas escritas de elaboración. El 67% contestó que el fosfato se debía añadir cuando se empiezan a añadir los electrolitos y el 34% que no se realizaba la validación de la técnica aséptica de elaboración. En cuanto a la formación, el 19% no la había recibido, considerando necesario recibirla el 99%. Conclusiones: El personal encuestado presenta un grado de formación aceptable, pero son necesarios los cursos de formación que se deben fomentar desde los Servicios de Farmacia (AU)

Objective: To assess the level of expertise of Pharmacy personnel in the manufacturing of total parenteral nutrition. Material and methods: An on-line survey including 17 questions concerning key aspects of TPN manufacturing was designed. Survey monkey software was used to create the survey and to analize its results. Results: 135 answers were received. 95% of the participant Pharmacy services had written standard manufacturing procedures. 67% answered that phosphate salts should be the first electrolite to be additioned into the total parenteral nutrition and 34% affirmed that validation of the aseptic manufacturing technique was not performed. As far as personnel training was concerned, 19% of respondents had not received any specific training, although 99% considered it would be necessary to receive it. Conclusions: The polled personell has an acceptable level of expertise but adequate training courses are still necessary and should be promoted from Pharmacy services (AU)

PEG-Interferon-α ribavirin-induced HCV viral clearance: a pharmacogenetic multicenter Spanish study.

OBJECTIVE: Dual PEGylated interferon-α (PEG-IFN) and ribavirin therapy has been the main hepatitis C virus (HCV) treatment of the last decade. Current direct-acting antiviral agents have improved the outcome of therapy but also have increased the cost and management complexity of treatment. The current study analyzes host genetics, viral and clinical predictors of sustained viral response (SVR) to dual PEG-IFN and ribavirin therapy in a representative Spanish population. METHODS: Observational prospective multicentre pharmacogenetic cohort study conducted in 12 different hospitals of 12 different Spanish regions. A total of 98 patients with SVR and 106 with non-SVR in response to PEG-IFN and ribavirin therapy were included. 33 single nucleotide polymorphisms located in 24 different genes related with inflammatory, immune and virus response were selected. Clinical and viral data were also analyzed as candidate of SVR predictors. RESULTS: IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) and TNFRSF1B (rs1061622) genotypes, as well as TNFRSF1B/IL-10/TNFα (-308) non-TTG and TNFRSF1B/IL- 10/IL-4 non-TTC haplotypes together with lower age, lower basal HCV RNA load, higher basal serum LDL cholesterol values, VHC genotypes 2 and 3 and basal low grade fibrosis 0-2 were associated with a SVR in the univariate analysis. Independent predictors of SVR in the multivariate analysis were IL-28B rs12979860 CC, TNFRSF1B/IL-10/IL-4 non-TTC along with low baseline HCV RNA load and HCV genotypes 2 and 3. CONCLUSIONS: IL-28B rs12979860 CC, TNFRSF1B/ IL-10/ IL-4 non-TTC haplotype, low baseline HCV RNA load and HCV genotypes 2 and 3 may help to predict successful outcome to PEG-IFN/ribavirin therapy in Spanish population.

Objetivo: El interferon-pegilado (IFN-PEG) junto a ribavirina ha sido el principal tratamiento de la infeccion por el virus de la hepatitis C (VHC) de la ultima decada. Los agentes antivirales de accion directa actuales han mejorado los resultados de la terapia, pero tambien han aumentado el costo y la gestion de la complejidad del tratamiento. El presente estudio analiza factores geneticos de los pacientes, asi como predictores virales y clinicos de respuesta sostenida viral (RSV) al tratamiento con IFN-PEG y ribavirina en poblacion Espanola. Métodos: Estudio farmacogenetico, multicentrico, prospectivo, observacional de cohortes realizado en 12 hospitales diferentes de 12 comunidades autonomas diferentes. Se incluyeron un total de 98 pacientes con RVS y 106 sin SVR al tratamiento con IFNPEG y ribavirina. Se seleccionaron 33 polimorfismos de nucleotido unico ubicados en 24 genes diferentes relacionados con la respuesta inflamatoria, inmunologica y viral. Los datos clinicos y virales tambien se analizaron como candidatos predictores de RVS. Resultados: Los genotipos IL-28B (rs12979860, rs7248668, rs8105790, rs8099917) y TNFRSF1B (rs1061622), asi como los haplotipos TNFRSF1B / IL-10 / TNF(-308) no-TTG y TNFRSF1B / IL-10 / IL-4 no-TTC junto con la menor edad, menor carga de ARN-VHC basal, valores elevados de colesterol LDL en suero basal, genotipos VHC2 y 3 y bajo grado de fibrosis basal (0-2) se asociaron con una RVS en el analisis univariante. Los predictores independientes de RVS en el analisis multivariante fueron el genotipo IL-28B rs12979860 CC, el haplotipo TNFRSF1B / IL-10 / IL-4 no-TTC junto con los bajos niveles basales de VHCARN y los genotipos virales VHC2 y 3. Conclusiones: El genotipo IL-28B rs12979860 CC, el haplotipo TNFRSF1B / IL-10 / IL-4 haplotipos no-TTC, la carga viral basal baja y los genotipos del VHC2 y 3 pueden ayudar a predecir una buena respuesta a la terapia con IFN-PEG y ribavirina en poblacion espanola.

An American Clinical Training Program for Spanish Nutrition Support Pharmacists: A Three-Year Experience.

A clinical nutrition support pharmacist training program, in collaboration with the Spanish Foundation of Hospital Pharmacy, Spanish Society of Clinical Nutrition, Abbott Nutrition International, University of Tennessee, College of Pharmacy and Regional One Health, is described. Nutrition support pharmacists from Spain were selected to participate in a one-month training program with an experienced board-certified nutrition support pharmacist faculty member within an interdisciplinary nutrition support team environment in the U.S. Participants were expected to actively engage in an advanced clinical practice role with supervision. Clinical activities included daily intensive patient monitoring, physical assessment, critical evaluation of the patient and development of an appropriate treatment plan for patients receiving either enteral or parenteral nutrition therapy. Upon successful completion of the training program, participants were anticipated to incorporate these techniques into their current practice in Spain and to train other pharmacists to function in an advanced clinical role independently or within an interdisciplinary nutrition support team environment.

Indicadores de monitorización del proceso de soporte nutricional especializado / Indicators monitoring the process of specialized nutritional support

Objetivo: Identificar y desarrollar indicadores de monitorización del proceso de soporte nutricional especializado, que permitan medir el grado de cumplimiento de los estándares de práctica establecidos. Método: Se seleccionaron los estándares de práctica considerados aspectos clave del proceso sobre los que desarrollar indicadores de rendimiento. La construcción de indicadores combinó la evidencia científica con la opinión de expertos. Se identificaron los objetivos clave dentro de cada estándar cuya consecución permitiera incrementar el alcance del mismo. Se generaron iniciativas de mejora concretas vinculadas a cada objetivo clave. Por último, se definieron indicadores de monitorización que permitieran realizar un seguimiento de la implantación de las iniciativas de mejora, o bien valorar el grado de consecución de los objetivos clave identificados. Resultados: Se han seleccionado 19 estándares de práctica representativos de los aspectos críticos del proceso. Se ha definido el mapa estratégico de cada estándar, identificándose un total de 43 objetivos clave. A fin de alcanzar estos objetivos clave se ha generado una cartera de mejoras integrada por 56 acciones. Por último, se han definido 44 indicadores de monitorización agrupados en tres categorías: 1. Numéricos: valoran el grado de cumplimiento del objetivo; 2. Dicotómicos (si/no): Informan de la ejecución de las acciones de mejora; 3. Resultados de las auditorías de la práctica. Conclusiones: Se dispone de indicadores de monitorización que permiten evaluar el cumplimiento de los estándares de práctica del proceso de soporte nutricional especializado y el impacto de la implantación de acciones de mejora en el mismo (AU)

Objective: To identify and develop monitoring indicators of the process of specialized nutritional support that will allow measuring the level of adherence to the established practice standards. Methods: Those practice standards considered to be key elements of the process were selected to develop performance indicators. The construction of these indicators combined the scientific evidence with expert opinion. Key goals were identified within each standard provided that its consecution would allow increasing the achievement of the standard. Particular improvement initiatives associated to each key goal were generated. Lastly, monitoring indicators were defined allowing undertaking a follow-up of the implementation of the improvement initiatives or either to assess the level of achievement of the key goals identified. Results: Nineteen practice standards were selected representative of the critical points of the process. The strategic map for each standard has been defined, with the identification of 43 key goals. In order to achieve these key goals, a portfolio of improvements has been generated comprising 56 actions. Finally, 44 monitoring indicators have been defined grouped into three categories: 1. Numeric: they assess the level of goal achievement; 2. Dichotomic (yes/no): they inform on the execution of the improvement actions; 3. Results of the practice audits. Conclusions: We have made available monitoring indicators that allow assessing the level of adherence to the practice standards of the process of specialized nutritional support and the impact of the Implementation of improvement actions within this process (AU)

Modification of the EMIT immunoassay for the measurement of unbound mycophenolic acid in plasma.

OBJECTIVES: Evaluation of the performance of a modified Enzyme Multiplied Immunoassay Technique for therapeutic drug monitoring of plasma free mycophenolic acid (fMPA) concentrations. DESIGN AND METHODS: A fMPA assay was developed on a Viva-E analyzer. A study of prior ultrafiltration conditions and analytical validation of the EMIT assay were performed. RESULTS: The method was reliable and reproducible. CONCLUSIONS: fMPA levels can be monitored using this EMIT assay with the advantage of being an automated method.