Impact of pharmaceutical validation on prescribing errors in a neonatal intensive care unit. Randomised and controlled study.

Purpose: To compare the frequency of electronic prescription errors when the prescription was validated by the clinical pharmacist vs. when it was not. Methods: This prospective randomised controlled study was conducted in three phases. A randomised phase, in which patients were divided into control and intervention groups, and a pre- and post-intervention phase were consecutively performed to analyse the impact of pharmaceutical validation of prescriptions in a neonatal intensive care unit (NICU). This study was performed at a highly complex NICU at a tertiary hospital. All patients born during the study period who were admitted to the NICU, with a stay lasting ≥24 h, and received active pharmacological treatment were included in the study. Pharmaceutical validation was performed according to the paediatric pharmaceutical care model. A high level of validation was selected for this study. In the intervention group, discrepancies found during the review process were communicated to the medical team responsible for the patients and resolved on the same day. Results: In total, 240 patients were included in this study. Sixty-two patients were allocated to the pre-intervention (n = 38) or post-intervention (n = 24) groups, and 178 patients were randomly sorted into two groups, control (n = 82 newborns) and intervention (n = 96 newborns). During the randomisation phase, the number of prescription errors detected was significantly lower in the intervention group than that in the control group (129 vs. 270; p < 0.001). Similarly, prescription errors reaching the patient were significantly reduced from 40% (n = 108) in the control group to 1.6% (n = 2) in the intervention group. In the pre- and post-intervention periods, the prescription lines containing prescription errors decreased from 3.4% to 1.5% (p = 0.005). Conclusions: This study showed that the pharmaceutical validation process decreased both the number of errors in the electronic prescribing tools and the number of prescription errors reaching the patient.

Evaluación de la interacción de capecitabina con inhibidores de la bomba de protones en pacientes con cáncer de colon metastásico / Evaluation of the interaction of capecitabin with proton pump inhibitors in patients with metastatic colon cáncer

Objetivo: Evaluar el impacto clínico que la interacción de capecitabina con inhibidores de la bomba de protones (IBP) puede tener sobre la efectividad del tratamiento de mantenimiento en pacientes con cáncer de colon metastásico (CCm). Material y métodos: Estudio retrospectivo, observacional descriptivo que incluyó a todos los pacientes con CCm tratados con capecitabina sola o en combinación entre enero 2013-diciembre 2016. Los pacientes fueron divididos en dos grupos según si fueron o no tratados con IBP concomitantemente con capecitabina. Se evaluaron variables demográficas, farmacológicas y clínicas, siendo la supervivencia libre de progresión (SLP) la variable elegida para evaluar el impacto clínico de la interacción. Resultados: Se incluyeron 150 pacientes. De ellos, el 57,33% varones, media de edad 70,10±12,06 años; el 55,33% tuvieron un ECOG 1 y el 58,67% utilizaron IBP. Un 39,33% fueron tratados con capecitabina en monoterapia, 31,33% CapeOx, y 20% capecitabina+bevacizumab y 9,33% CapeOx+bevacizumab. El 53,33% tuvo un tratamiento basado en capecitabina en primera línea, la frecuencia de variaciones de tratamiento fue de 42,0% reducción de dosis, 38,0% retraso, y 12% interrupción tratamiento. El 78,0% presentó alguna toxicidad, destacando 34,67% diarrea y 30,0% (síndrome mano-pie). La SLP media fue de 6,69 vs 6,0 meses (HR=0,97; IC95% 0,68-1,39; p=0,87) en favor de los pacientes que no utilizaron IBP, aunque la relación fue no significativa. Conclusiones: En la población estudiada, los pacientes con CCm que recibieron tratamiento de mantenimiento basado en capecitabina y que utilizaron IBP simultáneamente, presentaron una tendencia no significativa a la disminución de la SLP. (AU)

Objective: To evaluate the clinical impact that the interaction of capecitabine with proton pump inhibitors (PPIs) may have on the effectiveness of maintenance treatment in patients with metastatic colon cancer (mCC). Material and methods: Retrospective, observational, descriptive study that included all patients with CCm treated with capecitabine alone or in combination between January 2013-December 2016. The patients were divided into two groups according to whether or not they were treated with PPIs concomitantly with capecitabine. Demographic, pharmacological and clinical variables were evaluated, with progression free survival (PFS) being the variable chosen to evaluate the clinical impact of interaction. Results:150 patients were included. Of them, 57.33% were men, mean age 70.10±12.06 years; 55.33% had an ECOG 1 and 58.67% used it in PPIs. 39.33% were treated with capecitabine in monotherapy, 31.33% CapeOx, and 20% capecitabine+bevacizumab and 9.33% CapeOx+bevacizumab. 53.33% had a first-line capecitabine-based treatment, the frequency of treatment variations was 42.0% dose reduction, 38.0% delay, and 12% treatment interruption. 78.0% presented any toxicity, (highlighting 34.67% diarrhea and 30.0% hand-foot syndrome). The mean PFS was 6.69 vs 6.0 months (HR=0.97; 95% CI 0.68-1.39; p=0.87) in favor of patients who did not use IBP, although the relationship was not significant. Conclusions: In the population studied, patients with mCC who received maintenance treatment based on capecitabine and who used PPIs simultaneously, showed a non-significant trend towards a decrease in PFS. (AU)

Análisis de las interacciones farmacológicas y recomendaciones terapéuticas asociadas a la utilización de isavuconazol / Analysis of drug interactions and therapeutic recommendations associated with the use of isavuconazole

Objetivos: Identificar, describir las interacciones farmacológicas potenciales de isavuconazol, estudiar el impacto clínico de aquellas más relevantes y establecer recomendaciones terapéuticas para las encontradas en pacientes ingresados.Métodos: Estudio observacional descriptivo retrospectivo que incluyó todos los pacientes tratados con isavuconazol desde su comercialización hasta diciembre 2019.Se recogieron variables demográficas y fármacos concomitantes a isavuconazol durante más de 48 horas que recibió el paciente. Se revisaron los tratamientos con Lexicomp® para detectar interacciones potenciales, se analizó su mecanismo de acción y se relacionó con los fármacos implicados, estableciéndose recomendaciones terapéuticas.Para establecer el impacto clínico, se revisaron las historias clínicas de los pacientes con interacciones de mayor gravedad (D y X de Lexicomp®). En el caso de hallar alguna reacción adversa, se aplicó el algoritmo de Horn para establecer la probabilidad de que el efecto esté producido por la interacción farmacológica.Resultados: Se analizaron 84 ingresos en 59 pacientes. Se produjeron 209 interacciones potenciales en el 84,5% de los ingresos. La mayoría, 84,7% fueron de carácter moderado (categoría C), la más frecuente con tacrolimus. El principal mecanismo de acción fue el efecto inhibidor sobre el citocromo CYP3A4 de isavuconazol (82,8%). Se detectó una paciente con aumento de fosfatasa alcalina coincidente con el inicio concomitante de isavuconazol y claritromicina. Al aplicar el algoritmo de Horn, se consideró la interacción como posible.Conclusiones: Se detectaron interacciones farmacológicas potenciales graves en un porcentaje inferior al 10% de los ingresos y solo se detectó una posible reacción adversa asociada a esta interacción, no pudiéndose clasificar como definitiva. (AU)

Objetive: Identify, describe the potential pharmacological interactions of isavuconazole, study the clinical impact of the most relevant ones and establish therapeutic recommendations for those found in hospitalized patients.Methods: Retrospective descriptive observational study that included all patients treated with isavuconazole from its marketing until December 2019.Demographic variables and drugs concomitant to isavuconazole for more than 48 hours received by the patient were collected. The treatments with Lexicomp® were reviewed to detect possible interactions, its mechanism of action was analyzed and it was related to the drugs involved, establishing therapeutic recommendations.To establish the clinical impact, the medical records of the patients with more severe interactions (D and X for Lexicomp®) were reviewed. In the case of finding any adverse reaction, Horn’s algorithm was applied to establish the probability that the effect is produced by the pharmacological interaction.Results: 84 admissions in 59 patients were analyzed. There were 209 potential interactions in 84.5% of the admissions. The majority, 84.7%, were of a moderate nature (category C), the most frequent with tacrolimus. The main mechanism of action was the inhibitory effect on cytochrome CYP3A4 of isavuconazole (82.8%).A patient with an increase in alkaline phosphatase coinciding with the concomitant initiation of isavuconazole and clarithromycin was detected. When applying Horn’s algorithm, the interaction is considered as possible.Conclusions: Potential serious drug interactions were detected in less than 10% of admissions and only one possible adverse reaction associated with this interaction was detected, and it could not be classified as definitive. (AU)

[Incidence of intravenous colistin nephrotoxicity in hospitalized patients]. / Incidencia de nefrotoxicidad inducida por colistina intravenosa en pacientes hospitalizados.

OBJECTIVE: The increase in infections with multidrug resistant bacteria has forced to return to the use of colistin, antibiotic with known nephrotoxicity. The aim of the study is to determine the incidence of colistin nephrotoxicity nowadays. METHODS: Retrospective-observational-unicentric study was collected hospitalized patients in intravenous colistin treatment during the years 2018-2019. Nephrotoxicity was defined according to the RIFLE scale. The variables to determine it were serum creatinine (sCr) and glomerular filtration (GF). The variables analyzed were age, sex, treatment duration, loading and cumulative dose, empirical/targeted treatment, chronic kidney disease, concomitant use of intravenous contrast and nephrotoxic drugs. RESULTS: A total of 90 patients (60% men) were included, with an average age of 58.2±18.1 years. The mean duration of treatment was 9±8.3 days, with an average cumulative dose of 69.8±71MU. There were no differences between sCr and GF at the beginning and end of treatment. The incidence of nephrotoxicity was 1.73 cases/100 days of treatment (prevalence of 15.56%). CONCLUSIONS: Colistin nephrotoxicity has an important incidence, without developing severe illness.

Variabilidad en el registro de alergias entre niveles asistenciales / Variability in allergies registration between care levels

Objetivo: El objetivo del estudio es comparar el grado de coincidencia en el registro de alergias entre las aplicaciones informáticas de los distintos niveles asistenciales (atención primaria y hospitalaria).Métodos: Estudio observacional descriptivo retrospectivo de 2 meses de duración en el que participaron todas las unidades clínicas con prescripción electrónica. Se incluyó en el estudio a todos los pacientes ingresados con al menos una alergia registrada en la aplicación informática hospitalaria. Se cuantificó el porcentaje de alergias registradas en hospital, atención primaria o ambas.Resultados: Se incluyeron 723 pacientes en los que se registraron 1.280 alergias. El ratio de alergias por paciente fue 1,77. La media de edad fue 62±37 años y el 58,37% eran mujeres. El 80,47% de las alergias registradas fueron farmacológicas.De manera global el 42,11% de todas las alergias fueron registradas en ambas aplicaciones. El 21,20% de las alergias no farmacológicas y el 47,18% de las alergias farmacológicas fueron registradas en ambas aplicaciones. Del total de las alergias farmacológicas detectadas en el estudio, el 68,08% estaban registradas en atención primaria y el 79,13% en atención hospitalaria. Respecto al total de las alergias no farmacológicas el 37,20% estaban registradas en atención primaria y el 84% en la aplicación de atención hospitalaria. Conclusiones: En nuestro estudio hemos encontrado una gran variabilidad en el registro de alergias en los diferentes niveles asistenciales. En menos de la mitad de los casos se registra la alergia en ambos niveles. (AU)

This study aims at comparing the coincidence degree between different allergy-recording computer applications that can be found in distinct levels of the health care system (primary care and hospital care).Methods: Two-month retrospective descriptive and observational study for analyzed records in Clinical Units equipped by electronic prescription. All in-patients who had at least one allergy record registered in the hospital computer application were included in the study. The percentage of allergies registered in hospital, primary care or both applications was quantified.Results: 723 patients were included, among whom 1,280 allergies were recorded. The allergy ratio per patient was 1.77. The average age was 62±37 years and 58.37% were women. 80.47% of the recorded allergies were drug-related.42.11% of global allergies were registered in both applications. 21.20% of non-drug-related allergies and 47.18% of drug-related allergies were registered in both applications. According to the total of drug allergies detected in the study, 68.08% were registered in primary care and 79.13% in hospital care. Regarding to the total of non-drug-related allergies, 37.20% were registered in primary care and 84% in hospital care.Conclusions: Our study reported a high variability in the allergy registration between the different levels of the care health system. Less than the half of allergy cases are registered in both care levels studied. (AU)

[Implementation of the Lean Six Sigma in the improvement of the medication dispensing circuit]. / Implementación Lean Six Sigma en la mejora del circuito de dispensación de medicación.

OBJECTIVE: Lean Six Sigma (LSS) methodology is used to increase productivity and to improve performance, by eliminating processes that do not add value to the customer, as well as reducing variability. In recent years, its application in healthcare sector is increasing in order to improve the efficiency of processes. The aim of this study was to evaluate the results obtained in terms of efficiency in the medication dispensing circuit, after application of LSS methodology. MATERIAL AND METHODS: A multidisciplinary team was created in order to analyse and improve the medication dispensing circuit. The main tools used in LSS methodology were the DMAIC cycle (Define, Measure, Analyse, Improve and Control), SIPOC diagram (Suppliers, Inputs, Process, Outputs, and Customers), a root-cause analysis; a survey to determine the "Customer's voice" about the circuit; and the cost of each task in terms of staff time. Two Pilot Nursing Units (Thoracic Surgery and Cardiology) were selected to introduce the improvement actions. The main analysed variables were: urgent medication orders per day, and percentage of medication orders made online. RESULTS: After the application of LSS methodology, a significant reduction was found in urgent medicament orders per day in both nursing units, and a significant improvement in the electronic processing of urgent orders. The performance of medication dispensing circuit was increased from 60% (1.76 sigma) during initial data analysis, to 93% (3 sigma) in Thoracic Surgery, and from 71% (2.11 sigma) to 81% (2.4 sigma) in Cardiology. Six months after the implementation of improvements, the performance values were increased to 94% (3.1 sigma) and 93% (3 sigma), respectively. Estimated cost savings related to staff were 798.2 € (266 € per month) after implementation, ascending to 2, 228.5 € (371.4 € per month) after 6months. CONCLUSION: The use of LSS methodology has improved the performance of medication dispensing circuits, reducing costs in terms of staff time, and obtaining satisfactory results.

[Impact of a quality improvement plan on the validation of drug prescriptions on the safety of the hospitalised patient]. / Impacto de un plan de mejora de calidad en la validación de la prescripción de fármacos sobre la seguridad de los pacientes hospitalizados.

BACKGROUND AND OBJECTIVES: Medication errors are the most common adverse events in healthcare. Pharmaceutical validation (PV) seeks to reduce them. The aims of this study were to assess the impact of the introduction of an automated tool for the validation (VPAT) of the high clinical relevance drugs prescription (HCRD) over time of pharmaceutical intervention (PI), and to quantify the number of medication errors detected before and after its implementation. MATERIAL AND METHODS: A two phase retrospective-observational single centre study was designed. A pre-intervention phase (Pre-P): PV of beds with Unit Dose Dispensing (October 2015 - February 2016), was followed by a post-intervention phase (Post-P): PV using a VPAT of HCRD in hospital patients (October 2016 - February 2017). HCRD were selected from the list of high-risk drugs of Institute for Safe Medication Practices. The data was obtained from the PI record (Access®) and the computerised prescription. The variables collected were: age and gender of the patients included, data of drugs prescription, and time to PI. RESULTS: A total of 477 PI were analysed in 404 patients, with a mean age of 65.9±19.5 years (53.22% women). The mean time up to PI was 25.6±24.72h in the Pre-P, and 18.87±20.44h in the Post-P (P=0.01). In Pre-P, 106 PI were performed (35.85% prevention of adverse reactions) compared to 371 PI (39.62% medication reconciliation) in Post-P. CONCLUSIONS: The VPAT enabled a greater number of medication errors to be detected and intervened in hospitalised patients, with a significantly reduced time to PI.

[Usage, effectiveness and safety of abiraterone in prostate cancer]. / Uso, efectividad y seguridad de abiraterona en cáncer de próstata.

BACKGROUND AND OBJECTIVE: After the marketing of Abiraterone, an androgen synthesis inhibitor, the aim of the study was to analyze its use, response, and safety in the population of a tertiary care level hospital. MATERIALS AND METHODS: A retrospective observational study was carried out including all patients that were started on Abiraterone within a 21-month period. Demographical, diagnostic, therapeutic, and clinical variables were gathered. The response was assessed through the decreased of PSA as compared to baseline values. To assess the safety, all treatment-related adverse events were recorded. RESULTS: A total of 45 patients were included of which 88.89% could be assessed for the drug effectiveness. The median baseline PSA value was 457.31 (range 9032-2.81). PSA decrease was ≥ 50%, ≥ 90% and < 30% in 16 (40%), 3 (7.5%) y 20 (50%), respectively. The most common grade 1-2 adverse events were fatigue (35.6%), increased liver enzymes (28.9%), hipokalemia (13.3%) and fluid retention (11.1%). CONCLUSIONS: Abiraterone was a well tolerated drug that has shown to be active in prostate cancer patients previously treated with taxans, so it has been postulated as an alternative in this pathology.

Fundamento y objetivo: Tras la comercialización de abiraterona, inhibidor de la síntesis de andrógenos, el objetivo del estudio fue analizar el uso, la respuesta y la seguridad de abiraterona en la población de un hospital de tercer nivel. Material y métodos: Se realizó un estudio observacional retrospectivo en el que se incluyeron todos los pacientes que iniciaron tratamiento con abiraterona en un periodo de 21 meses. Se recogieron variables demográficas, diagnósticas, terapéuticas y clínicas. La respuesta se evaluó de acuerdo con la reducción del PSA con respecto al basal. Para evaluar la seguridad se registraron todas las reacciones adversas secundarias al tratamiento. Resultados: Se incluyó un total de 45 pacientes de los que, fueron evaluables con respecto a la efectividad del fármaco el 88,89%. La mediana de PSA basal era de 457,31 (rango 9032- 2,81). La reducción de PSA fue ≥50%, ≥90% y.