Physicochemical stability of bortezomib solutions for subcutaneous administration.

For the majority of cytotoxic drug preparations, such as bortezomib, the unit dose information is not available. In addition, there is a lack of information on the physicochemical stability of the pharmaceutical preparation after opening; this information is crucial for its administration to patients in successive visits, and the per-patient cost can be affected. The purpose of our proposed physicochemical stability study is to determine the shelf life of the reconstituted liquid product under refrigeration and clinical practice conditions. This evaluation was extended to both vials and ready-to-use syringes prefilled with the contents of the open vial. The stability test design includes the specified storage conditions and the critical physicochemical parameters of reconstituted injectable bortezomib. Furthermore, this approach includes the determination of impurities, the monitoring of the purity of the mean peak using a photodiode array, the control of the mass balance, the monitoring of subvisible particles using a laser diffraction analyser, and the setting of stability specifications. For the chemical stability study, the amount of bortezomib and its degradation products were determined using a stability-indicating HPLC method. The physical inspection of the samples was performed throughout the stability study, and their pH values were also monitored. Bortezomib (2.5 mg/mL) in 0.9% sodium chloride remained stable for 7 days when stored in both polypropylene syringes and vials at 5 ± 3 °C (refrigeration) and shielded from light. Additionally, it exhibits stability for 24 h under storage conditions simulating clinical use (20-30 °C and protected from light). The proposed protocol provides the stability in the vials once reconstituted and in prefilled refrigerated syringes; this protocol can be used to reduce waste and increase cost savings.

Population Pharmacokinetics of Digoxin in Nonagenarian Patients: Optimization of the Dosing Regimen.

OBJECTIVE: The aim of this study was to develop a population pharmacokinetic model of digoxin in patients over 90 years old and to propose an equation for adjusting digoxin dose in this population. METHODS: We included 326 nonagenarian patients admitted to Severo Ochoa University Hospital (Spain) who received digoxin and were under therapeutic drug monitoring. All data were retrospectively collected, and population modeling was performed with non-linear mixed-effect modeling software (NONMEM®). One- and two-compartment models were tested to calculate digoxin clearance (Cl), volume of distribution (Vd), absorption rate constant (Ka), and bioavailability (bioavailable fraction, F). The covariates were evaluated by stepwise covariate model building, and the final model was internally validated by bootstrap analysis with 1000 resamples. External validation was performed with another population of 95 patients with the same characteristics as the modeling group. RESULTS: The population was 26% males, with a mean age of 93.2 years (90-103 years), mean creatinine 1.11 mg/dL (0.42-3.81 mg/dL), and mean total body weight 61.2 kg (40-100 kg). The pharmacokinetics of digoxin were best described by a one-compartment model (ADVAN2 TRANS2), with first-order conditional estimation with interaction. The covariates with influence on our model were creatinine clearance based on the Cockcroft-Gault equation (CG), serum potassium (K), co-administration of loop diuretics, and sex: Cl/F = 4.55 · (CG/36.4)0.468 · 0.83LD · 1.21SEX; Vd/F = 355 · (K/4.3)-0.849; Ka = 1.22 h-1 [where LD indicates loop diuretics (1 for administered, 0 for otherwise) and SEX indicates patient sex (1 for male, 0 for female)]. Based on our results, we proposed an equation to adjust the digoxin dosing regimen in nonagenarian patients: dose (mg) = 0.144 · (CG/36.4)0.468 · 0.83LD · 1.21SEX. CONCLUSIONS: The greatest influence on digoxin clearance came from renal function calculated by the Cockcroft-Gault equation. Vd was decreased by K. The model developed showed a precise predictive performance to be applied for therapeutic drug monitoring.

Population pharmacokinetics of digoxin in elderly patients: A systematic review.

OBJECTIVE: To resume the available literature about digoxin population pharmacokinetic studies in elderly patients. To identify the  pathophysiological changes in this subpopulation with clinical implications on  digoxin pharmacokinetics. METHOD: A systematic review was performed regarding the population pharmacokinetic studies in elderly patients receiving digoxin. Pub-Med, ISI Web of Science, SCOPUS and Science Direct were used to identify the articles with the descriptors ("Digoxin"[Mesh]) AND ("Pharmacokinetics"[Mesh]) AND ("Aged"[Mesh] OR "Elderly"[Mesh]), followed by a manual search. RESULTS: Nine studies were found and reviewed, five of them carried out in  Asian patients. NONMEM was used for pharmacokinetic analysis of digoxin  blood levels, being mostly described by a one-compartment model. Serum  creatinine, body weight and concomitant administration of calcium channel  blockers are the covariates that most frequently influence digoxin  pharmacokinetics in elderly patients. CONCLUSIONS: Elderly people present pathophysiological changes with influence  on the pharmacokinetics of many drugs. The covariates with most influence on digoxin pharmacokinetics should be considered when adjusting this drug dosage in elder patients to achieve optimum health benefits and prevent possible side effects.

OBJETIVO: Resumir la literatura disponible sobre los estudios de farmacocinética poblacional de digoxina en pacientes de edad avanzada e  identificar los cambios fisiopatológicos en esta subpoblación, que conllevan implicaciones clínicas en la farmacocinética de la digoxina.Método: Se realizó una revisión sistemática de los estudios de farmacocinética poblacional en pacientes ancianos que recibían digoxina. Se  utilizaron PubMed, ISI Web of Science, SCOPUS y Science Direct para  identificar los artículos con los descriptores ("Digoxin"[Mesh]) AND ("Pharmacokinetics"[Mesh]) AND ("Aged"[Mesh] OR "Elderly"[Mesh]), seguido de una búsqueda manual. RESULTADOS: Se encontraron y revisaron nueve estudios, cinco de los cuales  de desarrollaron en pacientes asiáticos. Se utilizó NONMEM para el análisis  farmacocinético de los niveles plasmáticos de la digoxina, mayoritariamente  descrita como un modelo monocompartimental. Conclusiones: Los pacientes ancianos presentan cambios fisiopatológicos con  gran influencia en la farmacocinética de muchos fármacos. Las covariables con  un mayor impacto en la farmacocinética de la digoxina deben tenerse en  cuenta al ajustar la dosis de este medicamento en pacientes de edad avanzada  con el fin de lograr beneficios óptimos para la salud y prevenir  posibles efectos adversos en esta subpoblación.

Farmacocinética poblacional de la digoxina en pacientes de edad avanzada: Una revisión sistemática / Population pharmacokinetics of digoxin in elderly patients: A systematic review

Objetivo: Resumir la literatura disponible sobre los estudios de farmacocinética poblacional de digoxina en pacientes de edad avanzada e identificar los cambios fisiopatológicos en esta subpoblación, que conllevanimplicaciones clínicas en la farmacocinética de la digoxina.Método: Se realizó una revisión sistemática de los estudios de farmacocinética poblacional en pacientes ancianos que recibían digoxina.Se utilizaron PubMed, ISI Web of Science, SCOPUS y Science Directpara identificar los artículos con los descriptores (“Digoxin”[Mesh]) AND(“Pharmacokinetics”[Mesh]) AND (“Aged”[Mesh] OR “Elderly”[Mesh]),seguido de una búsqueda manual.Resultados: Se encontraron y revisaron nueve estudios, cinco de loscuales de desarrollaron en pacientes asiáticos. Se utilizó NONMEMpara el análisis farmacocinético de los niveles plasmáticos de la digoxina, mayoritariamente descrita como un modelo monocompartimental.Conclusiones: Los pacientes ancianos presentan cambios fisiopatológicos con gran influencia en la farmacocinética de muchos fármacos. Lascovariables con un mayor impacto en la farmacocinética de la digoxinadeben tenerse en cuenta al ajustar la dosis de este medicamento enpacientes de edad avanzada con el fin de lograr beneficios óptimospara la salud y prevenir posibles efectos adversos en esta subpoblación. (AU)

Objective: To resume the available literature about digoxin populationpharmacokinetic studies in elderly patients. To identify the pathophysiological changes in this subpopulation with clinical implications on digoxinpharmacokinetics.Method: A systematic review was performed regarding the population pharmacokinetic studies in elderly patients receiving digoxin. PubMed, ISI Web of Science, SCOPUS and Science Direct were usedto identify the articles with the descriptors (“Digoxin”[Mesh]) AND(“Pharmacokinetics”[Mesh]) AND (“Aged”[Mesh] OR “Elderly”[Mesh]),followed by a manual search.Results: Nine studies were found and reviewed, five of them carriedout in Asian patients. NONMEM was used for pharmacokinetic analysisof digoxin blood levels, being mostly described by a one-compartmentmodel. Serum creatinine, body weight and concomitant administration ofcalcium channel blockers are the covariates that most frequently influencedigoxin pharmacokinetics in elderly patients.Conclusions: Elderly people present pathophysiological changes withinfluence on the pharmacokinetics of many drugs. The covariates withmost influence on digoxin pharmacokinetics should be considered whenadjusting this drug dosage in elder patients to achieve optimum healthbenefits and prevent possible side effects. (AU)

A comparison of pharmacokinetics software for therapeutic drug monitoring of piperacillin in patients with severe infections.

OBJECTIVE: To evaluate the predictive performance of population pharmacokinetic models for piperacillin (PIP) available in the software MwPharm, TDMx and ID-ODs for initial dosing selection and therapeutic drug monitoring (TDM) purposes. METHODS: This is a prospective observational study in adult patients with severe infections receiving PIP treatment. Plasma concentrations were quantified by ultra-high performance liquid chromatography coupled to tandem mass spectrometry. The differences between predicted and observed PIP concentrations were evaluated with Bland-Altman plots; additionally, the relative and absolute bias and precision of the models were determined. RESULTS: A total of 145 PIP plasma concentrations from 42 patients were analysed. For population prediction, MwPharm showed the best predictive performance with a mean relative difference of 34.68% (95% CI -197% to 266%) and a root mean square error (RMSE) of 60.42 µg/mL; meanwhile TDMx and ID-ODs under-predicted PIP concentrations. For individual prediction, the TDMx model was found to be the most precise with a mean relative difference of 7.61% (95% CI -57.63 to 72.86%), and RMSE of 17.86 µg/mL. CONCLUSION: Current software for TDM is a valuable tool, but it may also include different population pharmacokinetic models in patients with severe infections, and should be evaluated before performing a model-based TDM in clinical practice. Considering the heterogeneous characteristics of patients with severe infections, this study demonstrates the need for therapy personalisation for PIP to improve pharmacokinetic/pharmacodynamic target attainment.

Comparison of four valproic acid free fraction determination methods used in clinical practice.

OBJECTIVE: Given that hypoalbuminemia tends to result in higher free fraction  concentrations of valproic acid, different methods have been developed to  determine the latter in patients with this condition. The aim of this study is to  assess the reliability of these methods and, if necessary, design a new  estimation method. METHOD: A retrospective analysis was carried out by the Pharmacy Department of Severo Ochoa University Hospital of admitted patients with at least one  trough concentration of valproic acid between October 2017 and February  2019. The estimation methods used were those developed by Kodama,  Hermida, Doré, as well as a new method proposed in the study. A total of 17  serum valproic acid concentrations were used to determine the free fraction of  valproic acid with each method; the values obtained were compared with the  results obtained following laboratory determinations. Accuracy and precision  were calculated using mean error and root mean square error, respectively. RESULTS: The comparison between observed and predicted free valproic acid  values using the methods under investigation showed that the method proposed in this study provides the highest reliability as it presents the  highest accuracy and precision. The worst results were those obtained  using  the Kodama method, which does not consider albuminemia, an essential variable that determines the concentration, therapeutic effect and toxicity of valproic acid. CONCLUSIONS: Given that the method proposed in this study proved to be superior to the other methods analyzed, we believe it can be reliably used to estimate free valproic acid levels in patients with hypoalbuminemia.

OBJETIVO: La fracción de ácido valproico libre aumenta en pacientes con  hipoalbuminemia. Se han publicado diferentes métodos para su estimación.El  objetivo de este estudio es valorar la fiabilidad de dichos métodos en nuestra  población y proponer un nuevo método de estimación.Método: Análisis retrospectivo realizado por el Servicio de Farmacia del  Hospital Universitario Severo Ochoa en pacientes ingresados entre octubre de  2017 y febrero de 2019 con al menos una concentración valle de ácido  valproico. Los métodos de estimación empleados fueron los de Kodama,  Hermida, Doré y un nuevo método propuesto, diseñado por García. A partir de  17 mediciones de ácido valproico se comparó el ácido valproico libre estimado  con cada método y el obtenido en el laboratorio. Se calcularon la exactitud y la  precisión mediante el error medio y el error cuadrático medio,  respectivamente. RESULTADOS: La comparación entre los valores observados y predichos de  ácido valproico libre por los distintos métodos evaluados pone de manifiesto  que el de mayor fiabilidad es el diseñado por García, al presentar la mejor  exactitud y precisión. Los peores resultados son los del método Kodama, al no  considerar la albuminemia, variable fundamental  que condiciona la  concentración, el efecto terapéutico y la toxicidad de este fármaco. CONCLUSIONES: El método diseñado por García ha demostrado ser mejor que  otros métodos, por lo que puede ser propuesto para estimar con fiabilidad el  ácido valproico libre en pacientes con hipoalbuminemia, aunque se precisa  aplicarlo en un mayor número de pacientes para confirmar su utilidad.

Comparación de cuatro métodos de predicción de la concentración de ácido valproico libre en la práctica clínica / Comparison of four valproic acid free fraction determination methods used in clinical practice

Objetivo: La fracción de ácido valproico libre aumenta en pacientescon hipoalbuminemia. Se han publicado diferentes métodos para su estimación.El objetivo de este estudio es valorar la fiabilidad de dichosmétodos en nuestra población y proponer un nuevo método de estimación.Método: Análisis retrospectivo realizado por el Servicio de Farmaciadel Hospital Universitario Severo Ochoa en pacientes ingresados entreoctubre de 2017 y febrero de 2019 con al menos una concentraciónvalle de ácido valproico. Los métodos de estimación empleados fueronlos de Kodama, Hermida, Doré y un nuevo método propuesto, diseñadopor García. A partir de 17 mediciones de ácido valproico se comparóel ácido valproico libre estimado con cada método y el obtenido en ellaboratorio. Se calcularon la exactitud y la precisión mediante el errormedio y el error cuadrático medio, respectivamente.Resultados: La comparación entre los valores observados y predichosde ácido valproico libre por los distintos métodos evaluados pone demanifiesto que el de mayor fiabilidad es el diseñado por García, alpresentar la mejor exactitud y precisión. Los peores resultados son los delmétodo Kodama, al no considerar la albuminemia, variable fundamental que condiciona la concentración, el efecto terapéutico y la toxicidad deeste fármaco.Conclusiones: El método diseñado por García ha demostrado ser mejorque otros métodos, por lo que puede ser propuesto para estimar con fiabilidadel ácido valproico libre en pacientes con hipoalbuminemia, aunque seprecisa aplicarlo en un mayor número de pacientes para confirmar su utilidad

Objective: Given that hypoalbuminemia tends to result in higher freefraction concentrations of valproic acid, different methods have beendeveloped to determine the latter in patients with this condition. The aimof this study is to assess the reliability of these methods and, if necessary,design a new estimation method.Method: A retrospective analysis was carried out by the PharmacyDepartment of Severo Ochoa University Hospital of admitted patientswith at least one trough concentration of valproic acid between October2017 and February 2019. The estimation methods used were those developedby Kodama, Hermida, Doré, as well as a new method proposed inthe study. A total of 17 serum valproic acid concentrations were used todetermine the free fraction of valproic acid with each method; the valuesobtained were compared with the results obtained following laboratorydeterminations. Accuracy and precision were calculated using mean errorand root mean square error, respectively.Results: The comparison between observed and predicted free valproicacid values using the methods under investigation showed that the methodproposed in this study provides the highest reliability as it presents the highestaccuracy and precision. The worst results were those obtained using the Kodama method, which does not consider albuminemia, an essentialvariable that determines the concentration, therapeutic effect and toxicityof valproic acid.Conclusions: Given that the method proposed in this study proved to besuperior to the other methods analyzed, we believe it can be reliably usedto estimate free valproic acid levels in patients with hypoalbuminemia.

Evaluación de la relación exposición-respuestade cetuximab en pacientes con cáncer colorrectal metastásico y cáncer de cabeza y cuello / Assessment of exposure-response relationship for cetuximab in patients with metastatic colorectal cancer and head and neck cancer

Objetivo: Evaluar, en condiciones de vida real, la relación entre lasconcentraciones valle en estado estacionario de cetuximab y el control dela enfermedad, así como buscar la relación entre estas concentraciones y lasupervivencia. Además, estudiar si existe una concentración límite que sepueda asociar con la probabilidad de beneficio clínico.Método: Estudio observacional prospectivo llevado a cabo en pacientescon cáncer colorrectal metastásico o cáncer de cabeza y cuello entratamiento con cetuximab. Se realizó un análisis de regresión de ecuacionesde estimación generalizadas para evaluar la asociación entre laconcentración valle en estado estacionario de cetuximab y la respuesta altratamiento (progresión o beneficio clínico). Mediante modelos de riesgosproporcionales de Cox, se evaluó la asociación entre la mediana de concentracionesvalle en estado estacionario de cetuximab en cada pacienteo la última medida con la supervivencia global y la supervivencia librede progresión, en cada una de las patologías. Asimismo, se buscó unpunto de corte óptimo a través del área bajo la curva de característicasoperativas del receptor. Resultados: Se analizaron 30 muestras de 16 pacientes. La concentraciónvalle en estado estacionario mediana fue 26,86 mg/l y se encontróuna gran variabilidad inter e intraindividual (desviación estándar de 32,4 y16,9 mg/l, respectivamente). Se observó una asociación positiva entre laconcentración valle en estado estacionario y el beneficio clínico (odds ratio1,24; intervalo de confianza del 95%: 0,95-1,63; p = 0,113), aunque noalcanzó significación estadística debido a la baja potencia.

Objective: There is limited scientific evidence on the cetuximab exposure-response relationship and no concentration threshold has been associatedwith optimal disease control. The aims were to assess, in a real-lifesetting, the relationship between steady state cetuximab concentrations(Ctrough, SS) and disease control.Method: A prospective observational study in patients with metastaticcolorectal cancer or head and neck cancer treated with cetuximab. Steadystate trough concentrations were compared with the results of radiologicalassessment of response (progression or clinical benefit). Generalizedestimating equations analysis was performed. To test the association betweensteady state concentrations and overall survival and progression-freesurvival, Cox proportional hazard models were developed. An optimalcut-off point was searched using the area under the receiver operatingcharacteristic curve.Results: A total of 30 steady state cetuximab concentrations from16 patients were analysed. Median Ctrough, SS was 26.86 mg/L andthere was marked inter- and intraindividual variability (standard deviation 32.4 mg/L and 16.9 mg/L, respectively). A positive associationwas found between cetuximab Ctrough, SS and clinical benefit (odds ratio1.24, 95% confidence interval: 0.95-1.63, p = 0.113), although withoutreaching statistical significance. The area under the receiver operatingcharacteristic curve (n = 30) had moderate discrimination power (0.71;95% confidence interval 0.49‑0.93), and the empirical optimal cutoffpoint was 19.12 mg/L. However, no association was observed betweencetuximab Ctrough, SS and survival in metastatic colorectal cancer or neckcancer patients.

Haemorrhagic complications in patients with renal insufficiency during treatment or prophylaxis with dalteparin.

OBJECTIVES: Low-molecular-weight heparins are widely used in clinical practice for the treatment or prophylaxis of venous thromboembolism (VTE). As these drugs are eliminated mainly by renal means, any renal function impairment may lead to higher plasma concentrations and increase the risk of bleeding. This study aims to evaluate whether in clinical practice there is an increase in the occurrence of bleeding in patients with renal insufficiency (RI) during treatment or prophylaxis with dalteparin, and to analyse the risk factors potentially influencing the appearance of such bleeding events. METHODS: Patients were sampled from the Universitary Severo Ochoa Hospital, Leganés, Spain. This was a retrospective cohort study with a 1 year inclusion period, conducted at a Spanish university hospital with 400 beds, on patients undergoing treatment or prophylaxis for VTE with dalteparin for a minimum of 3 days. The main outcome measure was the number of patients who had bleeding events, independently of their severity, during dalteparin administration in patients with RI. RESULTS: 367 patients were included in the study. Bleeding occurred in 17.9% of patients in the group with RI and in 7.3% of patients with normal renal function (NRF). Most haemorrhages in both cohorts were grade 2 on the WHO scale (64.7% in the RI group and 69.2% in the NRF group). Logistic regression analysis allowed the presence of RI (MDRD-4 (Modification of Diet in Renal Disease) <50 mL/min) to be identified as a risk factor. CONCLUSION: Patients with RI treated with dalteparin face a higher risk of bleeding than those with NRF, which seems to make it necessary to monitor and seek new dosage adjustments for these patients.Impact on practice statements: This study yields new data on dalteparin in RI, which has not been widely studied before.

Assessment of exposure-response relationship for bevacizumab in patients with metastatic colorectal cancer.

Limited literature is available for bevacizumab exposure-response relationship and there is not a concentration threshold associated with an optimal disease control. This prospective observational study in patients with metastatic colorectal cancer (mCRC) aims to evaluate, in a real-life setting, the relationship between bevacizumab through concentrations at steady state (Ctrough, SS) and disease control. Ctrough, SS were drawn, coinciding with the radiological evaluation of the response (progression or clinical benefit). Generalized estimating equations (GEE) analysis was performed. To test the association between Ctrough, SS in each patient with overall survival (OS) or progression-free survival (PFS), Cox proportional hazard models were developed. Data included 50 bevacizumab Ctrough, SS from 27 patients. The GEE model did not suggest any positive association between bevacizumab Ctrough, SS and clinical benefit (OR 0.99, 95% CI: 0.98-1.02, p = 0.863). The Cox regression showed association between higher median Ctrough, SS with better OS (HR 0.86, 95% CI: 0.73-1.01, p = 0.060), but not with PFS. We cannot confirm a relationship between bevacizumab Ctrough, SS and clinical benefit but this is the first real-world study trying to show a relationship between bevacizumab Ctrough, SS and disease control in mCRC. It was conducted in a small sample size which reduces the level of evidence. Further controlled randomized studies with a sufficient number of patients are required.

Assessment of exposure-response relationship for cetuximab in patients with metastatic colorectal cancer and head and neck cancer.

OBJECTIVE: There is limited scientific evidence on the cetuximab exposure-response relationship and no concentration threshold has been associated with optimal disease control. The aims were to assess, in a real-life setting, the  relationship between steady state cetuximab concentrations (Ctrough, SS) and  disease control. METHOD: A prospective observational study in patients with metastatic colorectal cancer or head and neck cancer treated with cetuximab.  Steady state trough concentrations were compared with the results of  radiological assessment of response (progression or clinical benefit).  Generalized estimating equations analysis was performed. To test the  association between steady state concentrations and overall survival and  progression-free survival, Cox proportional hazard models were developed. An  optimal cut-off point was searched using the area under the receiver operating  characteristic curve. RESULTS: A total of 30 steady state cetuximab concentrations from 16 patients  were analysed. Median Ctrough, SS was 26.86 mg/L and there was marked  inter- and intraindividual variability (standard deviation 32.4 mg/L and 16.9 mg/L, respectively). A positive association was found between cetuximab  Ctrough, SS and clinical benefit (odds ratio 1.24, 95% confidence interval:  0.95-1.63, p = 0.113), although without reaching statistical significance. The  area under the receiver operating characteristic curve (n = 30) had moderate  discrimination power (0.71; 95% confidence interval 0.49­0.93), and the  empirical optimal cutoff point was 19.12 mg/L. However, no association was  observed between cetuximab Ctrough, SS and survival in metastatic colorectal  cancer or neck cancer patients. CONCLUSIONS: We cannot confirm a relationship between cetuximab Ctrough,  SS and disease control despite a positive association. This study was  conducted with a small sample, which reduces the power analysis. Further  controlled randomised studies with a sufficient number of patients are needed.

OBJETIVO: Evaluar, en condiciones de vida real, la relación entre las concentraciones valle en estado estacionario de cetuximab y el control de  la enfermedad, así como buscar la relación entre estas concentraciones y la supervivencia. Además, estudiar si existe una concentración límite que se  pueda asociar con la probabilidad de beneficio clínico.Método: Estudio observacional prospectivo llevado a cabo en pacientes con  cáncer colorrectal metastásico o cáncer de cabeza y cuello en tratamiento con  cetuximab. Se realizó un análisis de regresión de ecuaciones de estimación  generalizadas para evaluar la asociación entre la concentración valle en estado  estacionario de cetuximab y la respuesta al tratamiento (progresión o beneficio  clínico). Mediante modelos de riesgos proporcionales de Cox, se  evaluó la asociación entre la mediana de concentraciones valle en estado  estacionario de cetuximab en cada paciente o la última medida con la  supervivencia global y la supervivencia libre de progresión, en cada una de las  patologías. Asimismo, se buscó un punto de corte óptimo a través del área  bajo la curva de características operativas del receptor. RESULTADOS: Se analizaron 30 muestras de 16 pacientes. La concentración valle en estado estacionario mediana fue 26,86 mg/l y se  encontró una gran variabilidad inter e intraindividual (desviación estándar de  32,4 y 16,9 mg/l, respectivamente). Se observó una asociación positiva entre  la concentración valle en estado estacionario y el beneficio clínico (odds ratio  1,24; intervalo de confianza del 95%: 0,95-1,63; p = 0,113), aunque no alcanzó significación estadística debido a la baja potencia. El área bajo la  curva de características operativas del receptor de las concentraciones (n =  30) tuvo una moderada capacidad discriminatoria (área bajo la curva de  características operativas del receptor 0,710; intervalo de confianza del 95%:  0,49-0,93) y el punto de corte estimado fue de 19,12 mg/l. Sin embargo, no  se observó relación entre la supervivencia y las concentraciones valle en  estado estacionario en ninguna de las patologías. CONCLUSIONES: No se ha podido confirmar una relación entre exposición a  cetuximab y eficacia, a pesar de encontrar una tendencia positiva en el control  de la enfermedad con el aumento de la concentración valle en estado  estacionario. El nivel de evidencia se vio reducido por la pequeña muestra de  pacientes en cada grupo, por lo que se necesitan estudios aleatorizados y  controlados, con un número suficiente de pacientes, para evaluar  adecuadamente esta relación.

Potentially inappropriate medication in acute hospitalized elderly patients with polypharmacy: an observational study comparing PRISCUS, STOPP, and Beers criteria.

PURPOSE: To compare the prevalence of potentially inappropriate medication (PIM) in the elderly according to the PRISCUS list, STOPP criteria, and Beers criteria. Secondary, to describe the differences using the three criteria focused on the inappropriate prescription of psychotropic drugs in the elderly. METHODS: A retrospective study was performed at Severo Ochoa University Hospital. The study included 365 patients, aged 80 years and older, living in Madrid, Spain. RESULTS: 93.42% of patients received at least one PIM during hospitalization. Using the PRISCUS list, this changed from 32.6 to 2.7% at discharge. Applying STOPP criteria lowered the percentage from 65.20 to 10.95%, and with Beers criteria from 80.27 to 10.13. Lower Barthel index at admission was associated with an increased relative risk for receiving at least one PIM (OR 1.79, 95% CI 1.15-2.80, p = 0.024) using PRISCUS list as a tool in conjunction with STOPP criteria (OR 1.44, 95% CI 0.89-2.33, p = 0.037). Polypharmacy at admission predicted the presence of PIMs with STOPP criteria (OR 1.74, 95% CI 1.07-2.84, p = 0.001). Regarding psychotropic medicines, 208 patients (56.98%) received at least one psychotropic medicine during hospitalization. A total of 26.30% of patients were treated with psychotropic medicines, detected by the PRISCUS list, and 53.97% and 29.85% with STOPP and Beers, respectively. CONCLUSIONS: Explicit criteria are a useful tool for identifying during hospitalization of the elderly patients. As indicated by the results, new research is needed to carry out an adaptation in our country that includes an evaluation of the strengths of the three tools to decrease PIMs and improve prescription in the elderly.

Protocolo de desensibilización a nivolumab sin corticoides en una paciente con cáncer renal metastásico / Desensitization protocol to nivolumab without corticosteroid use in a kidney cancer patient

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Pharmaceutical management of the COVID-19 pandemic in a mid-size hospital.

The purpose of this article is to report the experience of the Department of Hospital Pharmacy of a mid-size hospital during the peak of the COVID-19 pandemic. The human and material resources available in a mid-size hospital were more limited than in larger hospitals of the region. In this article, we describe how this Department of Hospital Pharmacy was reorganized to meet the increase in activity, the strategies developed and the  lessons learned for future pandemics. The COVID-19 pandemic had a higher  impact in Leganes, a city in the south of Madrid, with a population of 190,000.  In the face of the dramatic increase in the proportion of patients attending our  hospital between March and April 2020, the Severo Ochoa University Hospital  increased the number of beds by 24.5% and fitted out new premises inside and  outside the hospital (sports centers). The mean number of patients seen in our  Emergency Department every day passed from 70-80 to a peak of 286 patients, with 652 hospitalized patients. The situation of emergency created by  this infectious disease, with management protocols changing constantly, had a  dramatic impact on the activity of hospital pharmacies. Thus, the pandemic has  affected areas of economic management, magistral preparation, dispensing of  medication to inpatients, ambulatory patients, patients monitored at home,  institutionalized patients, and patients from private hospitals and field hospitals.  Other areas affected include training, clinical trials, pharmacovigilance, and  counseling boards. Two strategies were adopted to overcome these problems: a  strategy centered on human resources (staff reinforcement, reallocation of  responsibilities), and a strategy centered on processes (some processes were  reinforced to meet the increase in activity, whereas other were temporarily suspended or reduced to the minimum).Conclusions: The Department of Hospital Pharmacy plays a key role  in hospitals and has been significantly reinforced to meet the dramatic impact of  the pandemic on this service. This Department has been able to reorganize its  processes and take over new responsibilities such as telepharmacy and home  dispensing. Hospital pharmacies play a crucial role in  pharmacotherapeutic decisions in hospitals. As in other Departments, training is  the area more significantly affected by the pandemic.

El objetivo de este artículo es describir la experiencia del servicio de farmacia de un hospital mediano, en el período álgido de la pandemia de COVID-19, con  recursos humanos y materiales más limitados que otros hospitales de su entorno de mayor tamaño. Se analiza cómo afrontó su reorganización, debido al  incremento de su actividad, así como las estrategias desarrolladas y las  lecciones aprendidas para afrontar el futuro. La pandemia por COVID-19 tuvo  especial repercusión en el municipio de Leganés, una ciudad de 190.000  habitantes al sur de Madrid. Ante el incremento de la afluencia de pacientes  entre los meses de marzo y abril de 2020, el Hospital Universitario Severo  Ochoa llegó a asumir un 24,5% más de camas, incluyendo nuevas ubicaciones  tanto dentro como fuera del hospital (pabellón deportivo). Siendo la media de  frecuentación del Servicio de Urgencias de 70-80 pacientes, se llegó a alcanzar  un pico de 286 pacientes y 652 pacientes ingresados. Esta situación de  emergencia y el abordaje de una patología infecciosa, con protocolos de  tratamiento en continua revisión, impactó en todas las áreas y actividades del  servicio de farmacia: adquisiciones, gestión económica, elaboración de  medicamentos y dispensación a pacientes hospitalizados, pacientes externos y  ambulantes, domiciliaria, a centros geriátricos, hospitales de gestión privada y  hospitales de campaña. Se vieron afectadas áreas como la formación, los  ensayos clínicos, la farmacovigilancia y las comisiones hospitalarias. Para  superar los problemas, se aplicaron dos estrategias: una centrada en los  recursos humanos (reforzamiento de áreas, reasignación de responsabilidades) y otra focalizada en los procesos (procesos que se reforzaron por un aumento de  la actividad, procesos que se suspendieron temporalmente por la pandemia y  procesos que se redujeron al mínimo).Conclusiones: El servicio de farmacia es una pieza clave en el hospital cuyas  funciones principales son las primeras perjudicadas, pero a la vez las más  reforzadas durante la pandemia. Ha tenido la capacidad de reorganizar sus  procesos para asimilar nuevas actividades, como la telefarmacia y la  dispensación domiciliaria. Juega un papel importante en las decisiones  farmacoterapéuticas del hospital. Al igual que otros servicios clínicos, la  formación ha sido el área más perjudicada.