Digital image analysis workflows for evaluation of cell behavior and tumor microenvironment to aid therapeutic assessment in high-risk neuroblastoma.

Digital pathology and artificial intelligence are promising emerging tools in precision oncology as they provide more robust and reproducible analysis of histologic, morphologic and topologic characteristics of tumor cells and the surrounding microenvironment. This study aims to develop digital image analysis workflows for therapeutic assessment in preclinical in vivo models. For this purpose, we generated pipelines that enable automatic detection and quantification of vitronectin and αvß3 in heterotopic high-risk neuroblastoma xenografts, demonstrating that digital analysis workflows can be used to provide robust detection of vitronectin secretion and αvß3 expression by malignant neuroblasts and to evaluate the possibility of combining traditional chemotherapy (etoposide) with extracellular matrix-targeted therapies (cilengitide). Digital image analysis added evidence for the relevance of territorial vitronectin as a therapeutic target in neuroblastoma, since its expression is modified after treatment, with a mean percentage of 60.44% in combined therapy tumors vs 45.08% in control ones. In addition, the present study revealed the efficacy of cilengitide for reducing αvß3 expression, with a mean αvß3 positivity of 34.17% in cilengitide treated material vs 66.14% in control and with less tumor growth when combined with etoposide, with a final mean volume of 0.04 cm3 in combined therapy vs 1.45 cm3 in control. The results of this work highlight the importance of extracellular matrix-focused therapies in preclinical studies to improve therapeutic assessment for high-risk neuroblastoma patients.

Near-real time flash drought monitoring system and dataset for Spain.

Flash droughts are characterized by rapid development and intensification, which makes early warning and monitoring difficult. Flash drought monitor (FDM) is a near-real time monitoring system for Spain (https://flash-drought.csic.es) based on the Standardized Precipitation Evapotranspiration Index (SPEI). Flash drought identification was based on rapid and anomalous declines in SPEI at a short time scale (1-month). Thus, FDM enables operational tracking of flash drought conditions in Spain at high spatial resolution (1.1 × 1.1 km) and high temporal frequency (weekly). Likewise, to put flash drought monitoring into a temporal context, the FDM also provides weekly flash drought conditions recorded in Spain from 1961 to the present. The FDM is a useful tool for preparedness and mitigation of flash droughts in Spain. Furthermore, the data provided by the FDM could be useful to develop future studies in relation to the flash drought in Spain.

The complex multi-sectoral impacts of drought: Evidence from a mountainous basin in the Central Spanish Pyrenees.

We analyzed the impacts of drought severity on a variety of sectors in a topographically complex basin (the upper Aragón basin 2181 km2) in the Central Spanish Pyrenees. Using diverse data sources including meteorological and hydrological observations, remote sensing and tree rings, we analyze the possible hydrological implications of drought occurrence and severity on water availability in various sectors, including downstream impacts on irrigation water supply for crop production. Results suggest varying responses in forest activity, secondary growth, plant phenology, and crop yield to drought impacts. Specifically, meteorological droughts have distinct impacts downstream, mainly due to water partitioning between streamflow and irrigation channels that transport water to crop producing areas. This implies that drought severity can extend beyond the physical boundaries of the basin, with impacts on crop productivity. This complex response to drought impacts makes it difficult to develop objective basin-scale operational definitions for monitoring drought severity. Moreover, given the high spatial variability in responses to drought across sectors, it is difficult to establish reliable drought thresholds from indices that are relevant across all socio-economic sectors. The anthropogenic impacts (e.g. water regulation projects, ecosystem services, land cover and land use changes) pose further challenges to assessing the response of different systems to drought severity. This study stresses the need to consider the seasonality of drought impacts and appropriate drought time scales to adequately assess and understand their complexity.

Timing of spermatogonial stem cell transplantation affects the spermatogenic recovery outcome in mice.

Spermatogonial stem cell transplantation (SSCT) is a strategy that has demonstrated to be feasible to restore spermatogenesis in animal models when it is performed shortly after the gonadotoxic onset to destroy their endogenous germ cells. However, in the case of boys subjected to fertility preservation, future transplantations will be performed with a delay of many years. In order to study how timing of SSCT affects donor-derived spermatogenic recovery in mice, we compared the percentage of spermatogenic tubule cross-sections within testes of 59 C57BL/6NCrl mice distributed in 6 groups: group 1, untreated mice controls (n = 9); group 2, mice that received a single dose of busulfan 40 mg/kg (n = 10); group 3, mice that received two additional doses of busulfan 10 mg/kg every 5 weeks (n = 10); group 4 (SSCT-A), mice subjected to a standard SSCT performed 5 weeks after a single injection of busulfan 40 mg/kg (n = 10); group 5 (SSCT-B), mice subjected to a delayed SSCT performed 15 weeks after a single injection of busulfan 40 mg/kg (n = 10); and group 6 (SSCT-C), mice subjected to a delayed SSCT with two additional doses of busulfan 10 mg/kg every 5 weeks (n = 10). Spermatogenic recovery in standard SSCT-A and SSCT-C groups ranged between 22.29 and 22.65%, compared with a lower recovery rate of 11.54% showed in the SSCT-B group. However, donor contribution resulted higher in standard SSCT-A, representing a 69.71% of cross-sections, compared with the rest of conditions ranging from 34.69 to 35.42%. Overall, we concluded that a delay in the SSCT from the gonadotoxic onset decreases the efficiency of donor-derived spermatogenic recovery in mice.

Aflibercept in exudative age related macular degeneration refractory to ranibizumab.

PURPOSE: The aim of this study is to determine the effectiveness, safety and cost of aflibercept in the treatment of wet age-related macular degeneration (ARMD) refractory to ranibizumab. METHODS: Retrospective observational study was conducted on patients diagnosed with wet ARMD, and previously treated with ranibizumab. Efficacy variables assessed were changes in visual acuity (BCVA) and anatomical improvements in the most affected eye. Factors associated with improvement of BCVA with aflibercept were also studied. Adverse events related to the aflibercept administration were recorded. Cost analysis data were collected from the hospital perspective, and only taking the direct medical costs into account. Cost-effectiveness analysis was calculated using the aflibercept treatment cost, and effectiveness calculated as BCVA gained. RESULTS: A total of 50 eyes corresponding to 46 patients were included. The median follow-up period was 4.6 months (range: 1.0-6.0). Improvement in visual acuity after the first 2 doses and at the end of the follow-up period was observed in 32.0 and 28.0% of treated eyes, respectively. None of the variables studied was associated with an improvement in the BCVA after treatment. No significant differences were found in the average monthly cost between treatments. CONCLUSIONS: Aflibercept is shown to be an effective treatment in a significant number of patients resistant to treatment with ranibizumab, presenting a cost similar to that generated during the final stages of treatment with ranibizumab.

Integridad renal y hepática tras la sedación prolongada con sevoflurano administrado a través del dispositivo AnaConDa(R): comparación con la sedación intravenosa con propofol en modelo animal / Renal and hepatic integrity in long-term sevoflurane sedation using the anesthetic conserving device: a comparison with intravenous propofol sedation in an animal model

Introducción: En la actualidad la sedación de los pacientes críticos se realiza mediante agentes intravenosos. La utilización de agentes inhalatorios, como alternativa a la sedación intravenosa, se encuentra limitada por su potencial riesgo de toxicidad. El incremento de los niveles de fluoruros inorgánicos, tras su metabolización, ha sido considerado potencialmente nefrotóxico. Por otro lado, la afectación hepática después de la administración prolongada de sevoflurano no ha sido estudiada. Se evaluó la potencial toxicidad renal y hepática causada por la administración prolongada (72 h) de sevoflurano. Métodos: Estudio experimental, prospectivo, aleatorizado y controlado. Veintidós animales cerdas de la raza Landrace x Large-White fueron asignadas aleatoriamente a 2 grupos en función del régimen de sedación administrado (P: propofol por vía intravenosa; o S: sevoflurano inhalado a través del sistema AnaConDa(R), endtidal 2,5%). El grupo P se mantuvo sedado durante 108 h con propofol. Al grupo S se le administró sevoflurano durante 72 h, cambiando a propofol durante las 36 h restantes, con el objetivo de observar la cinética de los fluoruros plasmáticos tras la interrupción del sevoflurano. Se midieron la creatinina plasmática como variable principal, las concentraciones de fluoruros inorgánicos y otras variables de función renal, hepática y cardiorrespiratoria. Resultados: Ambos grupos de animales fueron comparables en el momento basal. No hubo diferencias significativas entre ambos grupos en cuanto a los valores de creatinina plasmática, urea y aclaramiento de creatinina. Los niveles de fluoruros fueron significativamente mayores en el grupo de sevoflurano. No encontramos una correlación entre las cifras de fluoruros inorgánicos y los valores de creatinina plasmática. Tampoco se observaron diferencias significativas en los parámetros de función hepática. Las variables hemodinámicas, respiratorias y gasométricas fueron comparables entre los grupos. Conclusiones: La sedación de larga duración no afecta a la función renal ni hepática, independientemente del agente utilizado (AU)

Introduction: Critically ill patients are sedated with intravenous agents because the use of inhaled agents is limited by their potential risk of toxicity. Increasing levels of inorganic fluorides after the metabolism of these agents have been considered potentially nephrotoxic. However, hepatic involvement after prolonged administration of sevoflurane has not yet been studied. The present study evaluated the potential renal and hepatic toxicity caused by prolonged administration (72 h) of sevoflurane. Methods: For this experimental, prospective, randomized, controlled trial, 22 Landrace x Large-White female pigs were randomly assigned to two groups: intravenous propofol (P) or inhaled sevoflurane via the AnaConDa(TM) device (S, end-tidal 2.5 vol%). The P group remained sedated for 108 h with propofol. In the S group, sevoflurane was administered for 72 h and then changed to propofol for the remaining 36 h in order to observe the kinetics of fluoride after discontinuation of sevoflurane. Serum creatinine was the primary outcome variable, but inorganic fluoride concentrations and other renal, hepatic, and cardiorespiratory variables were also measured. Results: Both groups of animals were comparable at baseline. No differences were found between the two groups for plasma creatinine and urea or creatinine clearance throughout the study. Fluoride levels were significantly higher in the sevoflurane group. No correlation was found between inorganic fluoride and serum creatinine values. No significant differences were observed for hepatic function. Hemodynamic, respiratory, and blood gas variables were comparable between the groups. Conclusions: Long-term sedation with sevoflurane using AnaConDa(TM) or propofol does not negatively affect renal or hepatic function (AU)

Renal and hepatic integrity in long-term sevoflurane sedation using the anesthetic conserving device: a comparison with intravenous propofol sedation in an animal model.

INTRODUCTION: Critically ill patients are sedated with intravenous agents because the use of inhaled agents is limited by their potential risk of toxicity. Increasing levels of inorganic fluorides after the metabolism of these agents have been considered potentially nephrotoxic. However, hepatic involvement after prolonged administration of sevoflurane has not yet been studied. The present study evaluated the potential renal and hepatic toxicity caused by prolonged administration (72h) of sevoflurane. METHODS: For this experimental, prospective, randomized, controlled trial, 22 Landrace x Large-White female pigs were randomly assigned to two groups: intravenous propofol (P) or inhaled sevoflurane via the AnaConDa™ device (S, end-tidal 2.5 vol%). The P group remained sedated for 108h with propofol. In the S group, sevoflurane was administered for 72h and then changed to propofol for the remaining 36h in order to observe the kinetics of fluoride after discontinuation of sevoflurane. Serum creatinine was the primary outcome variable, but inorganic fluoride concentrations and other renal, hepatic, and cardiorespiratory variables were also measured. RESULTS: Both groups of animals were comparable at baseline. No differences were found between the two groups for plasma creatinine and urea or creatinine clearance throughout the study. Fluoride levels were significantly higher in the sevoflurane group. No correlation was found between inorganic fluoride and serum creatinine values. No significant differences were observed for hepatic function. Hemodynamic, respiratory, and blood gas variables were comparable between the groups. CONCLUSIONS: Long-term sedation with sevoflurane using AnaConDa™ or propofol does not negatively affect renal or hepatic function.

Mejora del proceso farmacoterapéutico del paciente hospitalizado mediante la metodología Lean Seis Sigma / Improving inpatient pharmacoterapeutic process by Lean Six Sigma methodology

Introducción. La metodología Lean Seis Sigma se utilizó para mejorar procesos, eliminar desperdicios, reducir costes y aumentar la satisfacción de clientes. Objetivo. Analizar los resultados obtenidos con la metodología Lean Seis Sigma en el diagnóstico y la mejora del proceso farmacoterapéutico del paciente hospitalizado durante el cambio estructural y organizativo de un hospital terciario. Material y métodos. Ámbito: hospital general terciario con 1.000 camas. Diseño del estudio: observacional y prospectivo. Se desplegaron las etapas definir, medir, analizar, mejorar y controlar (DMAIC) entre marzo y septiembre de 2011, actualizando el Project Charter inicial según resultados. Población y muestra: 131 pacientes hospitalizados con tratamientos prescritos en las 24 h siguientes al ingreso y con 4 medicamentos. Variables: indicadores de seguridad (errores de medicación) y de eficiencia (tiempos de demora y reclamaciones). Resultados. La proporción de pacientes con algún error de medicación se redujo del 61,0 (25/41 pacientes) al 55,7% (39/70 pacientes) en 4 meses. Los porcentajes de errores, con respecto a las oportunidades de error, en distintas fases del proceso disminuyeron: prescripción 5,1 (19/372) a 3,3% (19/572); preparación 2,7 (14/525) a 1,3% (11/847 oportunidades); y administración: 4,9 (16/329) a 3,0% (13/433). Las reclamaciones se redujeron del 10,0 (2.119/21.038 pacientes) a 5,7% (1.779/31.097 pacientes). El impacto económico se estimó en 76.800 euros evitados. Conclusiones. Se observó una mejora del proceso farmacoterapéutico y un impacto financiero positivo que ha repercutido en la seguridad del paciente y la eficiencia de la organización. La normalización y la formación de profesionales podrían ser proyectos futuros de Lean Seis Sigma (AU)

Background: Lean Six Sigma methodology has been used to improve care processes, eliminate waste, reduce costs, and increase patient satisfaction. Objective: To analyse the results obtained with Lean Six Sigma methodology in the diagnosis and improvement of the inpatient pharmacotherapy process during structural and organisational changes in a tertiary hospital. Material and methods: Scope: 1.000 beds tertiary hospital. Design: prospective observational study. The define, measure, analyse, improve and control (DMAIC), were deployed from March to September 2011. An Initial Project Charter was updated as results were obtained. Population and sample: 131 patients with treatments prescribed within 24 h after admission and with 4 drugs. Variables: safety indicators (medication errors), and efficiency indicators (complaints and time delays). Results: Proportion of patients with a medication error was reduced from 61.0% (25/41 patients) to 55.7% (39/70 patients) in four months. Percentage of errors (regarding the opportunities for error) decreased in the different phases of the process: Prescription: from 5.1% (19/ 372 opportunities) to 3.3% (19/572 opportunities); Preparation: from 2.7% (14/525 opportunities) to 1.3% (11/847 opportunities); and administration: from 4.9% (16/329 opportunities) to 3.0% (13/433 opportunities). Nursing complaints decreased from 10.0% (2119/21038 patients) to 5.7% (1779/31097 patients). The estimated economic impact was 76,800 euros saved. Conclusions: An improvement in the pharmacotherapeutic process and a positive economic impact was observed, as well as enhancing patient safety and efficiency of the organization. Standardisation and professional training are future Lean Six Sigma candidate projects (AU)

[Improving inpatient pharmacoterapeutic process by Lean Six Sigma methodology]. / Mejora del proceso farmacoterapéutico del paciente hospitalizado mediante la metodología Lean Seis Sigma.

BACKGROUND: Lean Six Sigma methodology has been used to improve care processes, eliminate waste, reduce costs, and increase patient satisfaction. OBJECTIVE: To analyse the results obtained with Lean Six Sigma methodology in the diagnosis and improvement of the inpatient pharmacotherapy process during structural and organisational changes in a tertiary hospital. SCOPE: 1.000 beds tertiary hospital. DESIGN: prospective observational study. The define, measure, analyse, improve and control (DMAIC), were deployed from March to September 2011. An Initial Project Charter was updated as results were obtained. POPULATION AND SAMPLE: 131 patients with treatments prescribed within 24h after admission and with 4 drugs. VARIABLES: safety indicators (medication errors), and efficiency indicators (complaints and time delays). RESULTS: Proportion of patients with a medication error was reduced from 61.0% (25/41 patients) to 55.7% (39/70 patients) in four months. Percentage of errors (regarding the opportunities for error) decreased in the different phases of the process: Prescription: from 5.1% (19/372 opportunities) to 3.3% (19/572 opportunities); Preparation: from 2.7% (14/525 opportunities) to 1.3% (11/847 opportunities); and administration: from 4.9% (16/329 opportunities) to 3.0% (13/433 opportunities). Nursing complaints decreased from 10.0% (2119/21038 patients) to 5.7% (1779/31097 patients). The estimated economic impact was 76,800 euros saved. CONCLUSIONS: An improvement in the pharmacotherapeutic process and a positive economic impact was observed, as well as enhancing patient safety and efficiency of the organization. Standardisation and professional training are future Lean Six Sigma candidate projects.

A surgical model for isolating the pig liver in vivo for gene therapy.

Several studies report results that suggest the need of vascularization blocking for efficient gene transfer to the liver, especially in nonviral gene therapy. In this study, we describe a surgical strategy for in vivo isolation of the pig liver, resulting in a vascular watertight organ that allows the evaluation of several gene injection conditions. The hepatic artery and portal, suprahepatic and infrahepatic cava veins were dissected. Then, liver vascularization was excluded for 5-7 min. In that time, we first injected 200 ml saline solution containing the p3c-eGFP plasmid (20 µg/ml) simultaneously through two different catheters placed in the portal and cava veins, respectively. Vital constants were monitored during the surgery to assess the safety of the procedure. Basal systolic/diastolic blood pressures were 92.8/63.2 mm Hg and dropped to 40.7/31.3 mm Hg at the end of vascular exclusion; the mean basal heart rate was 58 bpm, reaching 95 bpm when the blood pressure was low. Oxygen saturation was maintained above 98% during the intervention, and no relevant changes were observed in the ECG tracing. Peak plasma AST (aspartate aminotransferase) and ALT (alanine aminotransferase) levels were observed after 24 h (151 and 57 IU, respectively). These values were higher, but not relevant, in 60 ml/s injection than in 20 ml/s injection. Efficiency of gene transfer was studied with simultaneous (cava and portal veins) injection of eGFP gene at flow rates of 20 and 60 ml/s. Liver tissue samples were collected 24 h after injection and qPCR was carried out on each lobe sample. The results confirmed the efficiency of the procedure. Gene delivery differed between 20 ml/s (9.9-31.0 eGFP DNA copies/100 pg of total DNA) and 60 ml/s injections (0.6-1.1 eGFP DNA copies/100 pg of total DNA). Gene transcription showed no significant differences between 20 ml/s (15,701.8-21,475.8 eGFP RNA copies/100 ng of total RNA) and 60 ml/s (12,014-36,371 eGFP RNA copies/100 ng of total RNA). The procedure is not harmful for animals and it offers a wide range of gene delivery options because it allows different perfusion ways (anterograde and retrograde) and different flow rates to determine the optimal conditions of gene transfer. This strategy permits the use of cell therapy and viral or non-viral liver gene therapy, especially appropriated to a wide variety of inherited or acquired diseases because of the liver's ability to produce and deliver proteins to the bloodstream.

[Effectiveness and adequacy of tolvaptan prescription in hospitalized patients]. / Efectividad y adecuación de la prescripción de tolvaptán en pacientes hospitalizados.

PURPOSE: To analyse the effectiveness of the use of Tolvaptan and the adequacy of Tolvaptan prescription at a tertiary level hospital. METHODS: Prospective observational study of Tolvaptan prescrip - tion from October of 2010 to December of 2011. RESULTS: 30 patients (60.0% males) were included, 50.0% of which were diagnosed with heart failure and 30.0% with SIADH. Tolvaptan allowed achieving sodium levels higher than 135 mEq/L in 53.3% of the patients with a mean baseline value of 125.3±7.3 mEq/L. The median treatment duration was 5.0 days (interquartile range=3-45). A significant increase of uric acid associated to Tolvaptan treatment was observed. The prescription was in agreement to what has been established in GFT in 63.3% of the cases. CONCLUSIONS: Tolvaptan increases sodium levels by 7.5 mEq/L, both in SIADH-associated hyponatremia and in heart failure, with an appropriate safety profile.

Objetivo: Analizar la efectividad del uso de tolvaptán y la adecuación de su prescripción en un hospital de tercer nivel. Método: Estudio observacional prospectivo de las prescripciones de tolvaptán desde octubre de 2010 hasta diciembre de 2011. Resultados: Se incluyeron 30 pacientes (60,0% varones), 50,0% diagnosticados de insuficiencia cardíaca y 30,0% de SIADH. Tolvaptán permitió alcanzar niveles de sodio superiores a 135 mEq/L en el 53,3% de los pacientes que partían con una media de 125,3±7,3 mEq/L. La mediana de días de tratamiento fue de 5,0 (rango intercuartílico = 3-45). Se observó un incremento significativo de los niveles de ácido úrico asociado al tratamiento con tolvaptán. La prescripción se adecuó a lo establecido en la GFT en el 63,3% de los casos. Conclusiones: Tolvaptán incrementa un 7,5 mEq/L los niveles de sodio tanto en hiponatremia secundaria al SIADH como en insuficiencia cardiaca.

Efectividad y adecuación de la prescripción de tolvaptán en pacientes hospitalizados / Effectiveness and adequacy of tolvaptan prescription in hospitalized patients

Objetivo: Analizar la efectividad del uso de tolvaptán y la adecuación de su prescripción en un hospital de tercer nivel. Método: Estudio observacional prospectivo de las prescripciones de tolvaptán desde octubre de 2010 hasta diciembre de 2011. Resultados: Se incluyeron 30 pacientes (60,0% varones), 50,0% diagnosticados de insuficiencia cardíaca y 30,0% de SIADH. Tolvaptán permitió alcanzar niveles de sodio superiores a 135 mEq/L en el 53,3% de los pacientes que partían con una media de 125,3±7,3 mEq/L. La mediana de días de tratamiento fue de 5,0 (rango intercuartílico = 3-45). Se observó un incremento significativo de los niveles de ácido úrico asociado al tratamiento con tolvaptán. La prescripción se adecuó a lo establecido en la GFT en el 63,3% de los casos. Conclusiones: Tolvaptán incrementa un 7,5 mEq/L los niveles de sodio tanto en hiponatremia secundaria al SIADH como en insuficiencia cardiaca (AU)

Purpose: To analyse the effectiveness of the use of Tolvaptan and the adequacy of Tolvaptan prescription at a tertiary level hospital. Methods: Prospective observational study of Tolvaptan prescription from October of 2010 to December of 2011. Results: 30 patients (60.0% males) were included, 50.0% of which were diagnosed with heart failure and 30.0% with SIADH. Tolvaptan allowed achieving sodium levels higher than 135 mEq/L in 53.3% of the patients with a mean baseline value of 125.3±7.3 mEq/L. The median treatment duration was 5.0 days (interquartile range = 3-45). A significant increase of uric acid associated to Tolvaptan treatment was observed. The prescription was in agreement to what has been established in GFT in 63.3% of the cases. Conclusions: Tolvaptan increases sodium levels by 7.5 mEq/L, both in SIADH-associated hyponatremia and in heart failure, with an appropriate safety profile (AU)

Monitorización de errores de medicación en dispensación individualizada mediante el método del carro centinela / No disponible

Objetivo Analizar la eficacia de una nueva estrategia de control de calidad basada en el muestreo aleatorio y seguimiento de carros de dispensación de dosis unitaria (carro centinela) para identificar los errores en las distintas fases del proceso de dispensación y sus causas. Método Estudio prospectivo para valoración de eficacia de un control de calidad en la identificación de errores de dispensación durante un periodo de 12 meses. Una vez por semana fue aleatoriamente seleccionado un carro de medicación denominado «carro centinela» y doblemente revisado antes de la dispensación. Se registraron los errores de medicación en la revisión, antes de ser conducido a la unidad de hospitalización así como las reclamaciones tras su recepción y monitorización durante las 24h siguientes. Un grupo de calidad de dosis unitarias instaurado al efecto analizó el tipo y origen de los errores y propuso las correspondientes acciones de mejora. Resultados Se analizaron 34 carros centinela que incluyeron 5.130 líneas de medicación, y 9.952 dosis dispensadas correspondientes a 753 pacientes. Se identificaron 90 (1,8%) líneas con error de tratamiento y 142 (1,4%) dosis erróneas en la preparación en el servicio de farmacia. El error más frecuente fue la duplicidad de dosis (38%) y el fallo de memoria o atención la causa que más lo generó (69%). Cincuenta medicaciones (6,6% de pacientes) reclamadas debido principalmente al inicio de nuevos tratamientos por ingreso (52%) y 41 (0,8% del total de líneas) discrepancias respecto a la prescripción fueron registradas en el Servicio de Farmacia. En la unidad de hospitalización se registraron 37 (4,9% de pacientes) medicaciones reclamadas en su mayoría por nuevo ingreso (43,2%) y 32 (0,6% de líneas) por discrepancias con la prescripción original, cuya causa más frecuente fue fallo de memoria o falta de atención (24%). El grado de coincidencia en el registro simultáneo de incidencias por reclamaciones y demanda de nueva medicación fue del 33,3%. Además se devolvieron 433 (4,3%) dosis no administradas. Tras el análisis de calidad se generaron 64, 37 y 24 acciones de mejora dirigidas al equipo de enfermería de farmacia, farmacéuticos y Unidad de Hospitalización, respectivamente. Conclusiones: El programa del carro centinela ha demostrado su eficacia en la identificación de errores de dispensación de dosis unitarias mediante un control de calidad instaurado al principio, durante y al final del proceso, facilitando una mayor implicación de los profesionales relacionados con el mismo (AU)

Objective To assess the efficacy of a new quality control strategy based on daily randomised sampling and monitoring of a sentinel surveillance system (SSS) medication cart, in order to identify medication errors and their origin at different levels of the process. Method Prospective quality control study with one-year follow-up. An SSS medication cart was randomly selected once a week and double-checked before dispensing medication. Medication errors were recorded before the cart was taken to the relevant hospital ward. Information concerning complaints after receiving medication and 24-h monitoring was also noted. Type and origin of error data were assessed by a unit dose quality control group, which proposed relevant improvement measures. Results Thirty-four SSS carts were assessed, including 5130 medication lines and 9952 dispensed doses, corresponding to 753 patients. Ninety erroneous lines (1.8%) and 142 mistaken doses (1.4%) were identified at the pharmacy department. The most frequent error was dose duplication (38%) and its main cause was inappropriate management and forgetfulness (69%). Fifty medication complaints (6.6% of patients) were mainly due to new treatment at admission (52%), and 41 (0.8% of all medication lines), did not completely match the prescription (0.6% lines) as recorded by the pharmacy department. Thirty-seven (4.9% of patients) medication complaints due to changes at admission and 32 matching errors (0.6% medication lines) were recorded. The main cause also was inappropriate management and forgetfulness (24%). The simultaneous recording of incidences due to complaints and new medication coincided in 33.3%. In addition, 433 (4.3%) of dispensed doses were returned to the Pharmacy Department. After the Unit Dose Quality Control Group conducted their feedback analysis, 64 improvement measures for Pharmacy Department nurses, 37 for pharmacists, and 24 for the hospital ward were introduced. Conclusions: The SSS programme has proven to be useful as a quality control strategy to identify Unit Dose Distribution System errors at initial, intermediate and final stages of the process, improving the involvement of the Pharmacy Department and ward nurses (AU)

[Monitoring medication errors in personalised dispensing using the Sentinel Surveillance System method]. / Monitorización de errores de medicación en dispensación individualizada mediante el método del carro centinela.

OBJECTIVE: To assess the efficacy of a new quality control strategy based on daily randomised sampling and monitoring a Sentinel Surveillance System (SSS) medication cart, in order to identify medication errors and their origin at different levels of the process. METHOD: Prospective quality control study with one year follow-up. A SSS medication cart was randomly selected once a week and double-checked before dispensing medication. Medication errors were recorded before it was taken to the relevant hospital ward. Information concerning complaints after receiving medication and 24-hour monitoring were also noted. Type and origin error data were assessed by a Unit Dose Quality Control Group, which proposed relevant improvement measures. RESULTS: Thirty-four SSS carts were assessed, including 5130 medication lines and 9952 dispensed doses, corresponding to 753 patients. Ninety erroneous lines (1.8%) and 142 mistaken doses (1.4%) were identified at the Pharmacy Department. The most frequent error was dose duplication (38%) and its main cause inappropriate management and forgetfulness (69%). Fifty medication complaints (6.6% of patients) were mainly due to new treatment at admission (52%), and 41 (0.8% of all medication lines), did not completely match the prescription (0.6% lines) as recorded by the Pharmacy Department. Thirty-seven (4.9% of patients) medication complaints due to changes at admission and 32 matching errors (0.6% medication lines) were recorded. The main cause also was inappropriate management and forgetfulness (24%). The simultaneous recording of incidences due to complaints and new medication coincided in 33.3%. In addition, 433 (4.3%) of dispensed doses were returned to the Pharmacy Department. After the Unit Dose Quality Control Group conducted their feedback analysis, 64 improvement measures for Pharmacy Department nurses, 37 for pharmacists, and 24 for the hospital ward were introduced. CONCLUSIONS: The SSS programme has proven to be useful as a quality control strategy to identify Unit Dose Distribution System errors at initial, intermediate and final stages of the process, improving the involvement of the Pharmacy Department and ward nurses.

Evaluación de la efectividad y la seguridad del natalizumab en el tratamiento de la esclerosis múltiple remitente recidivante / Assessment of the effectiveness and safety of natalizumab for treating relapsing-remitting multiple sclerosis

Objetivo Evaluar la efectividad y la seguridad del natalizumab en el tratamiento de la esclerosis múltiple remitente recidivante en un hospital de tercer nivel. Método Estudio observacional, prospectivo, de los pacientes adultos tratados con natalizumab desde mayo de 2007 hasta febrero de 2009. Tratamiento: natalizumab 300mg cada cuatro semanas. Criterio de respuesta: valoración de la progresión de la enfermedad, aparición de brotes y evaluación de imágenes mediante resonancia magnética. Se han recogido las reacciones adversas durante el tratamiento con natalizumab. Resultados Treinta pacientes (el 73% eran mujeres); promedio de edad: 34±8,4 años; escala expandida del estado de discapacidad medio basal: 3,4±1,3, y número de brotes en el último año: 2,1±1,2. Cinco pacientes suspendieron el tratamiento, uno por abandono del tratamiento, dos por ineficacia y dos por reacciones anafilácticas. Catorce pacientes completaron un año de tratamiento con resultados satisfactorios. Se obtuvieron reducciones de la escala expandida del estado de discapacidad del 36, el 47, el 31, el 54 y el 28% a los 3, los 6, los 9, los 12 y los 15 meses de tratamiento, respectivamente. La prevalencia de pacientes libres de recidiva fue del 94, el 76 y el 54% a los 3, los 6 y los 12 meses, respectivamente. Las imágenes de resonancia magnética al año de tratamiento correspondientes a 11 pacientes no mostraron nuevas lesiones. Dos pacientes sufrieron reacciones anafilácticas graves y otro sufrió una reacción urticarial. Un 6,6% de los pacientes presentó anticuerpos neutralizantes que motivaron la suspensión del tratamiento. Conclusiones La efectividad y la seguridad obtenidas en nuestros pacientes sugieren que el natalizumab constituye una alternativa para los pacientes refractarios o con formas agresivas de esclerosis múltiple, aunque falta conocer los efectos a largo plazo y la evolución de la aparición de anticuerpos neutralizantes (AU)

Objective Assessing the effectiveness and safety of natalizumab for treating relapsing-remitting multiple sclerosis in a tertiary hospital. Method Observational, prospective study of adult patients treated with natalizumab from May 2007 until February 2009. Treatment: 300mg natalizumab every four weeks. Response criteria: assessment of disease progression, appearance of flare-ups and assessment of magnetic resonance images. Adverse reactions during treatment with natalizumab were recorded. Results Thirty patients (73% female); average age 34±8.4 years; mean baseline EDSS 3.4±1.3; number of flare-ups in the past year 2.1±1.2. Treatment was discontinued in five patients, due to refusal in one case, ineffectiveness in two cases and anaphylaxis in the other two cases. Fourteen patients completed one year of treatment with satisfactory results. A lower EDSS score by 36%, 47%, 31%, 54% and 28% was obtained at 3, 6, 9, 12 and 15 months of treatment respectively. The prevalence of relapse-free patients was 94%, 76% and 54% at 3, 6 and 12 months. MRI imaging studies in 11 patients one year after they began treatment showed no new lesions. Two patients suffered severe anaphylactic shock and another one had an outbreak of urticaria. The presence of neutralising antibodies was the reason for suspending treatment in 6.6% of the patients. Conclusions The treatment's effectiveness and safety in our patient group suggest that natalizumab is a treatment for refractory patients or those with aggressive types of multiple sclerosis, although we do not yet know about its long-term effects and the evolution of the appearance of neutralising antibodies (AU)

Assessment of the effectiveness and safety of natalizumab for treating relapsing-remitting multiple sclerosis.

OBJECTIVE: Assessing the effectiveness and safety of natalizumab for treating relapsing-remitting multiple sclerosis in a tertiary hospital. METHOD: Observational, prospective study of adult patients treated with natalizumab from May 2007 until February 2009. TREATMENT: 300 mg natalizumab every four weeks. Response criteria: assessment of disease progression, appearance of flare-ups and assessment of magnetic resonance images. Adverse reactions during treatment with natalizumab were recorded. RESULTS: Thirty patients (73% female); average age 34 ± 8.4 years; mean baseline EDSS 3.4 ± 1.3; number of flare-ups in the past year 2.1 ± 1.2. TREATMENT was discontinued in five patients, due to refusal in one case, ineffectiveness in two cases and anaphylaxis in the other two cases. Fourteen patients completed one year of treatment with satisfactory results. A lower EDSS score by 36%, 47%, 31%, 54% and 28% was obtained at 3, 6, 9, 12 and 15 months of treatment respectively. The prevalence of relapse-free patients was 94%, 76% and 54% at 3, 6 and 12 months. MRI imaging studies in 11 patients one year after they began treatment showed no new lesions. Two patients suffered severe anaphylactic shock and another one had an outbreak of urticaria. The presence of neutralising antibodies was the reason for suspending treatment in 6.6% of the patients. CONCLUSIONS: The treatment's effectiveness and safety in our patient group suggest that natalizumab is a treatment for refractory patients or those with aggressive types of multiple sclerosis, although we do not yet know about its long-term effects and the evolution of the appearance of neutralising antibodies.

[Assessment of a reconciliation and information programme for heart transplant patients]. / Evaluación de un programa de conciliación e información al paciente trasplantado cardíaco.

INTRODUCTION: The objective is to assess a pharmaceutical care programme for heart transplant patients upon patient admission and discharge. MATERIAL AND METHODS: Observational study of heart transplant patients, performed during the first quarter of 2007. Upon admission, the patient was interviewed regarding home treatments, adherence, allergies and adverse effects, and his/her prescriptions were compared with the last discharge report (drug reconciliation). At time of discharge, treatment was checked against the last hospital prescription (reconciliation) and an informative report was drawn up and personally delivered to the patient. Subsequently, a satisfaction questionnaire was carried out by telephone. Drug-related problems were recorded using Atefarm software. RESULTS: The programme was applied to 24 patients upon admission and 23 upon discharge. No drug interactions were detected. Treatment adherence was higher than 90%. 37.5% of patients informed of an adverse reaction. Medication-related problems were identified in 16 patients (45.7%) for 6.6% of medications, most of which (38%) were for infection prophylaxis; medication omission was the most frequently-detected error. Positive evaluation of the information that was received was higher than 90%. CONCLUSIONS: Pharmacotherapeutic follow-up upon admission and discharge resolves and prevents problems while improving patient information and satisfaction. Limitations on personnel prevent the population's requests from being met.

Evaluación de un programa de conciliación e información al paciente trasplantado cardíaco / Assessment of a reconciliation and information programme for heart transplant patients

Introducción El objetivo es evaluar un programa de atención farmacéutica al ingreso y al alta hospitalaria del paciente trasplantado cardíaco. Material y métodos Estudio observacional realizado el primer trimestre de 2007 en pacientes trasplantados cardíacos. Al ingreso, se entrevistó al paciente sobre tratamientos domiciliarios, adherencia, alergias, efectos adversos y se comparó la prescripción con el último informe de alta (conciliación). Al alta, se comparó el tratamiento con la última prescripción hospitalaria (conciliación) y se elaboró un boletín informativo, entregándolo personalmente al paciente. Posteriormente, se realizó un cuestionario telefónico sobre satisfacción. Los problemas relacionados con los medicamentos (PRM) fueron registrados en la aplicación Atefarm®. Resultados El programa al ingreso se aplicó a 24 pacientes y al alta a 23. No se detectaron interacciones. La adherencia al tratamiento fue superior al 90%. El 37,5% de los pacientes comunicó alguna reacción adversa. Se identificaron PRM en 16 pacientes (45,7%), en un 6,6% de los medicamentos, la mayoría (38%) pertenecientes a profilaxis infecciosa, siendo la omisión del medicamento el error principalmente detectado. La valoración positiva de la información recibida superó el 90%.ConclusionesEl seguimiento farmacoterapéutico al ingreso y al alta resuelve y previene problemas y favorece la información y satisfacción del paciente. Las limitaciones de personal impiden cumplir las demandas de la población (AU)

Introduction The objective is to assess a pharmaceutical care programme for heart transplant patients upon patient admission and discharge. Material y methods Observational study of heart transplant patients, performed during the first quarter of 2007. Upon admission, the patient was interviewed regarding home treatments, adherence, allergies and adverse effects, and his/her prescriptions were compared with the last discharge report (drug reconciliation). At time of discharge, treatment was checked against the last hospital prescription (reconciliation) and an informative report was drawn up and personally delivered to the patient. Subsequently, a satisfaction questionnaire was carried out by telephone. Drug-related problems were recorded using Atefarm® software. Results The programme was applied to 24 patients upon admission and 23 upon discharge. No drug interactions were detected. Treatment adherence was higher than 90%. 37.5% of patients informed of an adverse reaction. Medication-related problems were identified in 16 patients (45.7%) for 6.6% of medications, most of which (38%) were for infection prophylaxis; medication omission was the most frequently-detected error. Positive evaluation of the information that was received was higher than 90% (AU)

Calidad del proceso farmacoterapéutico a través de errores de medicación en un hospital terciario / Quality of drug treatment process through medication errors in a tertiary hospital

Objetivo: Evaluar la calidad del proceso farmacoterapéutico en un sistema de dosis unitaria y prescripción electrónica asistida en un hospital terciario, a través de errores de medicación. Métodos: Se realizó un estudio observacional prospectivo de errores de medicación en 308 pacientes hospitalizados, por revisión de la prescripción médica, la validación farmacéutica y la medicación preparada y dispensada, y por observación directa de la administración de medicamentos. La variable, el error de medicación, se analizó en la fase del proceso farmacoterapéutico, el tipo y la causa de error. Se definieron indicadores de calidad (relación porcentual de errores respecto a oportunidades de error) en cada fase. Resultados: De los 308 pacientes estudiados, en 107 se detectó al menos 1 error de medicación (34,7%); hubo un total de 137 errores distribuidos en: omisión de alergia y descripción de la prescripción (20,4%), prescripción/validación (28,5%), dispensación (23,4%) y administración de medicamentos (27,7%). El error más frecuente fue la omisión de dosis (19,7%) y la selección de especialidad farmacéutica (16,1%). La causa más común fue fallos de memoria y descuidos con el 53,3%. Los indicadores de calidad por fases fueron: 2,3% para la omisión de alergia del paciente; 0,9% para la prescripción; 1,6% para la prescripción/validación; 8,2% para la dispensación, y 2,1% para la administración de medicamentos. Conclusiones: Se estima que en 35 de 100 pacientes ocurre un error en su proceso farmacoterapéutico. Se identifican oportunidades de mejora basadas en la normalización y la formación de profesionales para realizar tareas técnicas y manejar la tecnología (AU)

Objective: To assess the quality of drug treatment process in a unit dose and assisted electronic prescription system in a tertiary hospital, by looking at medication errors. Methods: A prospective, observational study into medication errors was carried out on 308 hospitalised patients. This was done by assessing medical prescriptions, pharmaceutical validation, prepared and dispensed medication and by directly observing drug administration. The variable, i.e. the medication error, was analysed in the drug treatment process so as to decipher the type and cause of the error. Quality indicators were defined at each stage (percentage relationship between errors and opportunities for error).Results: Of the 308 patients studied, 107 had at least 1 medication error (34.7%). There were a total of 137 errors: omission of allergy and prescription description (20.4%), prescription/validation(28.5%), dispensing (23.4%) and drug administration (27.7%). The most frequent error was dose omission (19.7%) and choice of pharmaceutical product (16.1%). The most common cause of error was forgetfulness or a lack of attention to detail (53.3%). The quality indicators by stage were: 2.3% for omission of the patient’s allergies;0.9% for prescription; 1.6% for prescription/validation; 8.2% for dispensing, and 2.1% for drug administration. Conclusions: It is estimated that 35 patients in every 100 experience errors in their drug treatment process. Opportunities for improvement are identified based on standardisation and training for professionals in carrying out technical tasks and using technology (AU)