[Translated article] Efficacy and marginal cost of treatment with tocilizumab in COVID-19 patients.

OBJECTIVE: To describe the marginal cost and survival of patients treated with tocilizumab in a university hospital under real-life conditions and to evaluate factors that could influence costs and health outcomes will be evaluated. METHODS: Observational, single-center, retrospective study of a cohort of adult patients infected with SARS-COV2 treated with tocilizumab. The 1 year restricted mean survival time was analyzed in life-years gained (LYG). The influence of sex, age and severity on patient survival was evaluated. The marginal cost/LYG and marginal cost/survivor ratios were calculated. RESULTS: 508 patients (66 ±â€¯13 years; 32% women) were included. Seventeen percent were admitted to the ICU. Overall survival was 77%. Age older than 71.5 years (HR = 1.08; 95% CI 1.07-1.10; p < 0.001) and ICU admission at initiation of treatment (HR = 2.01; 95% CI 1.30-3.09; p = 0.002) were identified as risk factors. The total budgetary impact of tocilizumab in the period analyzed was 206,466 euros. The patients with the highest cost per unit of health outcome were those admitted to the ICU and those over 71.5 years, with a marginal cost/LYG of €966 and a marginal cost/survivor of €1136. CONCLUSION: The efficiency of treatment with tocilizumab is associated with the age and severity of the patients. The figures are lower in all subgroups than the thresholds usually used in cost-effectiveness evaluations. The results of the present study suggest that early first dose of tocilizumab is an efficient strategy.

Stability of tedizolid phosphate-sodium rifampicin and tedizolid phosphate-meropenem admixtures in intravenous infusion bags stored at different temperatures.

This is a report on the chemical stability and physical compatibility of intravenous tedizolid phosphate 0.8 mg/mL-sodium rifampicin 2.4 mg/mL and tedizolid phosphate 0.8 mg/mL-meropenem 4 mg/mL combinations in polypropylene 0.9% sodium chloride infusion bags stored at different storage conditions. Triplicate solutions of both admixtures were prepared in 0.9% sodium chloride polypropylene infusion bags and stored under light protection at room temperature (25±2 °C), refrigeration (2-8 °C) or freezing (-15 - -25 °C) conditions. The study was performed using a validated and stability-indicating liquid chromatography (LC) method. For both admixtures and for all storage conditions, at least 90% of the initial drug concentration of tedizolid phosphate remained unchanged throughout the entire study period. Stability of sodium rifampicin at 25±2 °C was determined to be seven hours and six days when it was stored at 2-8 °C. Under the same storage conditions, meropenem was stable for 12 h or 6 days, respectively. Under freezing conditions, sodium rifampicin was stable throughout all 28 days, while stability of meropenem was only 8 days. Solutions of 0.8 mg/mL tedizolid phosphate admixtured with 2.4 mg/mL rifampicin or 4 mg/mL meropenem, in polypropylene 0.9% sodium chloride infusion bags, are stable for at least 7 or 12 hours, respectively, when stored at 25±2 °C. When stored at 2-8 °C, stability was increased to 6 days for both admixtures.

Monitorización de la vacomicina en administración intraperitoneal en pacientes sometidos a diálisis peritoneal continua ambulatoria / Monitoring of intraperitoneal administration of vancomycin in patients on continuous ambulatory peritoneal dialysis

Objetivo: Validar un modelo para la monitorización farmacocinética de los tratamientos con vancomicina intraperitoneal en pacientes sometidos a diálisis peritoneal continua ambulatoria con peritonitis bacteriana. Método Se realiza un estudio prospectivo, abierto, en 2 cohortes: la primera incluye a 10 pacientes de 56±14 años y 65±5kg y la segunda, otros 10 pacientes (12 episodios de peritonitis) de 52±13 años y 64±8kg. El tratamiento consiste en la instilación y retención durante 6h en la cavidad peritoneal de una solución conteniendo 2g de vancomicina y 1g de ceftazidima, en 2 l de dializante. Tras la instilación del antibiótico, se obtuvieron muestras de sangre a las 4, 6, 8, 10, 24, 48 y 168h, en la primera cohorte y a las 6 y 120h (CVAN120) en la segunda. El modelo farmacocinético se desarrolla a partir de los parámetros obtenidos en la primera cohorte y se valida en la segunda cohorte calculando el error medio (EM) y el error cuadrático medio de predicción (ECM) de la CVAN120.ResultadosLas concentraciones séricas de vancomicina decaen desde 39,63±7,62 mcg/ml a las 4h, hasta 8,55±2,87 mcg/ml a las 168h, en la primera cohorte, y desde 37,65±6,84 mcg/ml a las 6h, hasta 10,82±2,66 mcg/ml a las 120h (CVAN120), en la segunda. Los parámetros farmacocinéticos fueron: Cl=0,006 l/h/kg y Vd:=0,52 l/kg en la primera cohorte, y Cl=0,006 l/h/kg y Vd:=0,53 l/kg, en la segunda. El EM y el ECM de predicción de la CVAN120 fueron, respectivamente, 0,59 mcg/ml ([EM*100/CVAN120]=5,5%) y 10,38 mcg2/ml2 ([ECM*100/(CVAN120)2]=8,9%).Conclusión El modelo presentado muestra una exactitud y precisión adecuadas para la monitorización de la vancomicina intraperitoneal en pacientes sometidos a diálisis peritoneal continua ambulatoria con peritonitis bacteriana (AU)

Objective: To validate a pharmacokinetic model of the treatments with intraperitoneal vancomycin applied to patients on continuous ambulatory peritoneal dialysis with bacterial peritonitis. Methods: To carry out a prospective study divided in 2 cohorts: the first one including ten patients of 56 ± 14 years and 65 ± 5 kg, and the second one with 10 patients (12 episodes of peritonitis) aged 52 ± 13 years and 64 ± 8 kg. The treatment consists of administering and retaining for 6 h in the peritoneal cavity a solution containing 2 g of vancomycin and 1 g of ceftazidime into 2 l of ‘‘dialysis solution’’. After the antibiotic administration, blood samples were obtained at 4, 6, 8, 10, 24, 48 and 168 h in the first cohort and at 6 and 120 h (CVAN120) in the second. The pharmacokinetic model was developed from the parameters obtained from the first cohort and was validated by the second cohort, calculating the mean error (ME) and the mean squared prediction error (MSPE) of the CVAN120.Results: Vancomycin serum concentrations fell from 39.63 ± 7.62 mcg/ml at 4 h to 8.55 ± 2.87mcg/ml at 168 h for the first cohort, and from 37.65 ± 6.84 mcg/ml at 6 h to 10.82 ± 2.66 mcg/mlat 120 h (CVAN120) for the second cohort. The pharmacokinetics parameters were: C1 = 0.0061/h/kg and Vd: = 0.52 1/kg for the first cohort, and C1 = 0.006 1/h/kg and Vd: = 0.53 1/kg for the second. The predictive ME and MSPE of the CVAN120. were 0.59 mcg/ml ([EM*100/CVAN120 = 5.5%)and 10.38 mcg2/ml2([MES*100/(CVAN120)2]) respectively. Conclusion: The presented model shows an adequate exactitude and precision for the monitoring of intraperitoneal vancomyc in in patients submitted to continuous ambulatory peritoneal dialysis with peritonitis (AU)

[Monitoring of intraperitoneal administration of vancomycin in patients on continuous ambulatory peritoneal dialysis]. / Monitorización de la vacomicina en administración intraperitoneal en pacientes sometidos a diálisis peritoneal continua ambulatoria.

OBJECTIVE: To validate a pharmacokinetic model of the treatments with intraperitoneal vancomycin applied to patients on continuous ambulatory peritoneal dialysis with bacterial peritonitis. METHODS: To carry out a prospective study divided in 2 cohorts: the first one including ten patients of 56±14 years and 65±5 kg, and the second one with 10 patients (12 episodes of peritonitis) aged 52±13 years and 64±8 kg. The treatment consists of administering and retaining for 6 h in the peritoneal cavity a solution containing 2 g of vancomycin and 1 g of ceftazidime into 2 l of "dialysis solution". After the antibiotic administration, blood samples were obtained at 4, 6, 8, 10, 24, 48 and 168 h in the first cohort and at 6 and 120 h (C(VAN)(120)) in the second. The pharmacokinetic model was developed from the parameters obtained from the first cohort and was validated by the second cohort, calculating the mean error (ME) and the mean squared prediction error (MSPE) of the C(VAN)(120). RESULTS: Vancomycin serum concentrations fell from 39.63±7.62 mcg/ml at 4h to 8.55±2.87 mcg/ml at 168 h for the first cohort, and from 37.65±6.84 mcg/ml at 6h to 10.82±2.66 mcg/ml at 120 h (C(VAN)(120)) for the second cohort. The pharmacokinetics parameters were: C1=0.006 1/h/kg and Vd:=0.52 1/kg for the first cohort, and C1=0.006 1/h/kg and Vd:=0.53 1/kg for the second. The predictive ME and MSPE of the C(VAN)(120). were 0.59 mcg/ml ([EM*100/C(VAN)(120)=5.5%) and 10.38 mcg(2)/ml(2) ([MES*100/(C(VAN)(120))(2)]) respectively. CONCLUSION: The presented model shows an adequate exactitude and precision for the monitoring of intraperitoneal vancomycin in patients submitted to continuous ambulatory peritoneal dialysis with peritonitis.

Comparación del ensayo de digoxina con el sistema Architect ®i1000sr respecto al sistema AxSYM® / Comparing the Digoxin Test With the Architect ®i1000sr System With Respect to the AxSYM® System

Objetivo Evaluar en muestras séricas la técnica empleada por el autoanalizador Architect® i1000sr para la determinación de digoxina respecto al ensayo desarrollado para AxSYM® mediante enzimoinmuno análisis de micropartículas (DigoxinII).Método Análisis prospectivo de las muestras procedentes de 100 solicitudes de monitorización de pacientes en tratamiento con digoxina. Las muestras fueron procesadas en AxSYM® y Architect®. Las técnicas se evaluaron mediante el coeficiente de regresión lineal, el coeficiente de determinación, el error absoluto medio, el error cuadrático medio de predicción y el método de Bland-Altman. Resultados Las concentraciones séricas mostraron un coeficiente de correlación de 0,93. La diferencia se aproxima al 40% para concentraciones entre 0,8 y 2 ng/ml y al 20% en el resto de muestras analizadas. Conclusiones El sistema Architect® es preciso pero inexacto, en una magnitud inaceptable desde el punto de vista de la monitorización clínica respecto al AxSYM®(AU)

Objective To assess the technique employed by the autoanalyser Architect® i1000sr to determine digoxin in serum samples, compared with the assay developed for AsSYM® using microparticle enzyme immunoassay (Digoxin II).Method A prospective analysis of the samples from 100 requests to monitor patients being treated with digoxin. The samples were processed in AxSYM® and Architect®. The techniques were assessed using the linear regression coefficient, determination coefficient, mean absolute error, mean squared prediction error and the Bland-Altman method. Results The serum levels showed a correlation coefficient of 0.93. There was nearly a 40% difference for the concentrations between 0.8 and 2ng/ml and nearly 20% in the rest of the samples analysed. Conclusions The Architect® system is precise; however, from a clinical monitoring point of view, it is unacceptably inaccurate when compared with the AxSYM® (AU)

Comparing the digoxin test with the Architect® i1000sr system with respect to the AxSYM® system.

OBJECTIVE: To assess the technique employed by the autoanalyser Architect® i1000sr to determine digoxin in serum samples, compared with the assay developed for AsSYM® using microparticle enzyme immunoassay (DigoxinII). METHOD: A prospective analysis of the samples from 100 requests to monitor patients being treated with digoxin. The samples were processed in AxSYM® and Architect®. The techniques were assessed using the linear regression coefficient, determination coefficient, mean absolute error, mean squared prediction error and the Bland-Altman method. RESULTS: The serum levels showed a correlation coefficient of 0.93. There was nearly a 40% difference for the concentrations between 0.8 and 2 ng/ml and nearly 20% in the rest of the samples analysed. CONCLUSIONS: The Architect® system is precise; however, from a clinical monitoring point of view, it is unacceptably inaccurate when compared with the AxSYM®.

Costes y adherencia del tratamiento antirretroviral / No disponible

Objetivo Desarrollar una sistemática de manejo de datos que permita estimar comparativamente la eficiencia de los diferentes esquemas de tratamiento antirretroviral (TAR).Método Estudio observacional retrospectivo en pacientes infectados por el VIH con TAR estable. Se determinó para cada paciente su adherencia y el coste unitario de su tratamiento. Se calculó el coste/paciente/día y, multiplicando por un factor de adherencia (fADH), el (coste/paciente/día)ADH. La comparación de ambos permitió obtener el Δcoste/paciente, que estima la desviación de costes originada por la falta de adherencia. Se calculó el coste-efectividad-incremental (CEI) agrupando los resultados en los diferentes fármacos coformulados («combos»). Se realizó un estudio de impacto presupuestario de dichos combos. Resultados Se evaluaron 468 pacientes (62% adherentes). La adherencia media fue de 88±18%. El valor medio del (coste/paciente/día)ADH fue significativamente superior al coste/paciente/día (27,3±9,8€ frente 24,3±7,6€, p<0 001 al igual que para el f ADH, no se encontraron diferencias en el Δcoste/paciente entre las diferentes combinaciones de TAR. El combo con menor desviación del coste/paciente/día debida a la falta de adherencia fue el constituido por abacavir/zidovudina/lamivudina (ABC/AZT/3TC,Δcoste/paciente=8,72±14,18%), y el de mayor desviación el AZT/3TC (Δcoste/paciente=13,52±17,68%). No se encontraron diferencias significativas en los CEI calculados para ningún combo. Los esquemas de TAR que incluyeron abacavir/lamivudina(ABC/3TC) obtuvieron el menor impacto presupuestario. Conclusiones (..) (AU)

Objective To develop a system of data management that allows us to estimate the comparative effectiveness of the various antiretroviral treatment (ART) regimens. Method Restrospective observational study in patients infected with HIV with stable ART. Adherence to treatment and unit cost for each patient's treatment was determined. The cost/patient/day was calculated and, multiplying by an adherence factor (fADH), the (cost/patient/day)ADH. The comparison of both allowed us to obtain the Δcost/patient, which estimates the additional costs caused by lack of adherence. The incremental cost-effectiveness (iCER), grouping the results by the various coformulated drugs (“combos”). A study of the budgetary impact of these combos was carried out.Results468 patients were evaluated (62% adherent). Average adherence was 88±18%. The average value of (cost/patient/day) ADH was significantly higher than the cost/patient/day (27.3 ± 9.8€ compared to 24.3±7.6€. p < 0.001). Just as with the fADH, no differences were found in the Δcost/patient between the different ART combinations. The combo with the least deviation from the cost/patient/day due to lack of adherence was that composed of abacavir/zedovudine/lamivudine (ABC/AZT/3TC,Δcost/patient=8.72±14.18%), and that with the greatest deviation AZT/3TC (Δcost/patient=13.52±17.68%). No significant differences were found in the iCER calcluated for any combo. The ART that included abacavir/lamivudine (ABC/3TC) obtained the least budgetary impact. Conclusions The greatest cost and percentage of adherent patients associated with the combos composed of Tenovovir/Emtricitabine(TDF/FTC) and ABC/3TC, and the least cost and effectiveness of those composed of AZT/#TC and ABC/AZT/3TC, does not allow us to identify any option as significantly dominant. The regimens with ABC/3TC were shown to be the most favourable from the combined point of view of cost and adherence (AU)

[Costs and adherence to antiretroviral treatment]. / Costes y adherencia del tratamiento antirretroviral.

OBJECTIVE: To develop a system of data management that allows us to estimate the comparative effectiveness of the various antiretroviral treatment (ART) regimens. METHOD: Retrospective observational study in patients infected with HIV with stable ART. Adherence to treatment and unit cost for each patient's treatment was determined. The cost/patient/day was calculated and, multiplying by an adherence factor (fADH), the (cost/patient/day)(ADH). The comparison of both allowed us to obtain the Δcost/patient, which estimates the additional costs caused by lack of adherence. The incremental cost-effectiveness (iCER), grouping the results by the various coformulated drugs ("combos"). A study of the budgetary impact of these combos was carried out. RESULTS: 468 patients were evaluated (62% adherent). Average adherence was 88±18%. The average value of (cost/patient/day) (ADH) was significantly higher than the cost/patient/day (27.3±9.8€ compared to 24.3±7.6€. p<0.001). Just as with the f(ADH), no differences were found in the Δcost/patient between the different ART combinations. The combo with the least deviation from the cost/patient/day due to lack of adherence was that composed of abacavir/zedovudine/lamivudine (ABC/AZT/3TC,Δcost/patient=8.72±14.18%), and that with the greatest deviation AZT/3TC (Δcost/patient=13.52±17.68%). No significant differences were found in the iCER calculated for any combo. The ART that included abacavir/lamivudine (ABC/3TC) obtained the least budgetary impact. CONCLUSIONS: The greatest cost and percentage of adherent patients associated with the combos composed of Tenovovir/Emtricitabine(TDF/FTC) and ABC/3TC, and the least cost and effectiveness of those composed of AZT/#TC and ABC/AZT/3TC, does not allow us to identify any option as significantly dominant. The regimens with ABC/3TC were shown to be the most favourable from the combined point of view of cost and adherence.

Estabilidad en suero fisiológico del busulfán intravenoso en un envase de poliolefinas / Stability in serum of intravenous busulfan in a polyolefin pack

Introducción: Aunque se ha utilizado por vía oral, la variabilidad en su absorción y el riesgo de que se produzcan vómitos, ha impulsado la utilización intravenosa de busulfán. En el presente trabajo se estudiará la estabilidad de 60 mg de busulfán, en volúmenes fijos de 250 ml (0,24 mg/ml) y 500 ml (0,12 mg/ml) de suero fisiológico y diferentes condiciones de conservación, en un nuevo envase de plástico, de lámina construida de poliolefina/poliamida. Material y métodos: Se empleó la cromatografía líquida de alta eficacia con detección ultravioleta para determinar las concentraciones de busulfán derivatizado con dietilditiocarbamatotrihidrato sódico. La estabilidad se evaluó, para ambas concentraciones, tanto en nevera como a temperatura ambiente, mediante el t90 de cada ensayo. Resultados: El porcentaje de concentración remanente de busulfán a las 24 h siempre fue inferior al 90%. A 25 ºC y concentración de 0,24 mg/ml el t90 fue de 8,4 h; a 4 ºC y concentración de 0,24 mg/ml fue de 16,7 h; a 25 ºC y concentración de 0,12 mg/ml fue de 12 h, y a 4 ºC y concentración de 0,12 mg/ml fue de 11,5 h. Conclusiones: El presente estudio demuestra que el busulfán a una concentración de 0,24 mg/ml en suero fisiológico será estable en las bolsas ensayadas durante un período de almacenamiento de 12 h en nevera más las 2 h de administración del fármaco (AU)

Introduction: Although it has been used orally, the variability in its absorption and the risk of causing vomiting has lead to a push towards the intravenous use of bulsulfan. This study looks at the stability of 60 mg of busulfan, in fixed volumes of 250 mL (0.24 mg/mL) and 500 mL (0.12 mg/mL) of serum and different conservation conditions, in a new plastic pack made from polyolefin/polyamide laminates. Material and methods: High-efficiency liquid chromatography with ultraviolet detection was used to determine the concentration of busulfan derivate with sodium diethyldithiocarbamatetrihydrate. Stability was assessed for both concentrations; refrigerated and at room temperature, using the t90 of each sample. Results: The percentage of the remaining busulfan concentration at 24 h was always less than 90%. At 25 oC and 0.24 mg/mL concentration, the t90 was 8.4 h; at 4 oC and a concentration of 0.24 mg/mL it was 16.7 h; at 25 oC and a concentration of 0.12 mg/mL it was 12 h and at 4 oC and a concentration of 0.12 mg/mL it was 11.5 h. Conclusions: This study show that busulfan in a concentration of 0.24 mg/mL in serum is stable in the bags tested during a refrigerated storage period of 12 h plus two additional hours of administration of the drug (AU)

[The pharmacokinetics of metronidazole and gentamicin in a single preoperative dose as antibiotic prophylaxis in colorectal surgery]. / Farmacocinética del metronidazol y la gentamicina en dosis única preoperatoria para profilaxis antibiótica quirúrgica en cirugía colorrectal.

OBJECTIVE: To describe, in patients undergoing colorectal surgery (CRS), the pharmacokinetics of a single, prophylactic preoperative dose of 1,500 mg of metronidazole plus 240 mg gentamicin and measure its efficacy in accordance with the accepted pharmacodynamic and microbiological parameters. METHOD: Thirty-six patients undergoing CRS agreed to participate in the study. Three blood samples were taken from each. Cmax 15 minutes after finishing the infusion of the mixture, CfinIQ on finishing the surgery, and Cmin between 12 and 24 hours post-administration. The concentrations of metronidazole and gentamicin in each simple were measured and the pharmacokinetic parameters were estimated (dV- distribution volume , Cl-plasma clearance). For the metronidazole, concentrations in excess of 8 microg/ml were considered effective, and for gentamicin, C(max) in excess of 9 microg/ml and inhibition quotients above 8. RESULTS: All the concentrations of metronidazole, both CmaxMTZ and CfinIQMTZ were above 8 microg/ml and all the CmaxGEN in excess of 9 microg/ml. The CIGEN was 13.8+/-3.8, with no individual value below 8. For the metronidazole, a dV of 0.68+/-0.2 l/kg was estimated and a Cl of 3.15+/-1.20 l/h and for the gentamicin, the dV as 0.23+/-0.06 l/kg and the Cl was 4.71+/-1.95 l/h. CONCLUSION: In patients undergoing CRS, surgical intervention did not significantly modify the pharmacokinetics of metronidazole or gentamicin in comparison with other groups of patients. The prophylaxis using a single, pre-surgical dose enables the achievement, for both antimicrobial agents, concentrations of a sufficient size to guarantee clinical efficacy.

Farmacocinética del metronidazol y la gentamicina en dosis única preoperatoria para profilaxis antibiótica quirúrgica en cirugía colorrectal / The pharmacokinetics of metronidazole and gentamicin in a single preoperative dose as antibiotic prophylaxis in colorectal surgery

Objetivo: Describir, en pacientes sometidos a cirugía colorrectal(CCR), la farmacocinética de una dosis única preoperatoria de metronidazol1.500 mg más gentamicina 240 mg como pauta profiláctica,y estimar su efectividad de acuerdo con parámetros subrogados farmacodinámicosy microbiológicos.Método: Treinta y seis pacientes sometidos a CCR aceptaron su participaciónen el estudio. De cada uno de ellos se tomaron tres muestrasde sangre: Cmáx, 15 min tras finalizar la infusión de la mezcla,CfinIQ al finalizar la cirugía, y Cmín entre las 12 y 24 h posteriores a laadministración. Se determinaron las concentraciones de metronidazoly gentamicina en cada muestra y se estimaron los parámetrosfarmacocinéticos (Vd: volumen de distribución, Cl: aclaramientoplasmático). Para el metronidazol, se consideraron efectivas concentracionessuperiores a 8 mg/ml, y para la gentamicina, Cmáx superioresa 9 mg/ml y cocientes de inhibición superiores a 8.Resultados: Todas las concentraciones de metronidazol, tantoCmáxMTZ como CfinIQMTZ fueron superiores a 8 mg/ml, y todaslas CmáxGEN, superiores a 9 mg/ml. El CIGEN fue de 13,8 ± 3,8, con ningúnvalor individual inferior a 8. Para el metronidazol, se estimó unVd de 0,68 ± 0,2 l/kg y un Cl de 3,15 ± 1,20 l/h, y para la gentamicina,el Vd fue de 0,23 ± 0,06 l/kg, y el Cl, de 4,71 ± 1,95 l/h.Conclusión: En pacientes sometidos a CCR la intervención quirúrgicano modifica significativamente la farmacocinética del metronidazoly la gentamicina respecto a otros grupos de pacientes. La profilaxisen dosis única prequirúrgica permite alcanzar, para ambosantimicrobianos, concentraciones de magnitud suficiente para garantizarsu efectividad clínica

Objective: To describe, in patients undergoing colorectal surgery(CRS), the pharmacokinetics of a single, prophylactic preoperativedose of 1,500 mg of metronidazole plus 240 mg gentamicin and measureits efficacy in accordance with the accepted pharmacodynamicand microbiological parameters.Method: Thirty-six patients undergoing CRS agreed to participate inthe study. Three blood samples were taken from each. Cmax 15 minutesafter finishing the infusion of the mixture, CfinIQ on finishing thesurgery, and Cmin between 12 and 24 hours post-administration. Theconcentrations of metronidazole and gentamicin in each simplewere measured and the pharmacokinetic parameters were estimated(dV- distribution volume , Cl-plasma clearance). For the metronidazole,concentrations in excess of 8 mg/ml were considered effective,and for gentamicin, Cmax in excess of 9 mg/ml and inhibitionquotients above 8.Results: All the concentrations of metronidazole, both CmaxMTZ andCfinIQMTZ were above 8 mg/ml and all the CmaxGEN in excess of9 mg/ml. The CIGEN was 13.8±3.8, with no individual value below 8.For the metronidazole, a dV of 0.68±0.2 l/kg was estimated and a Clof 3.15±1.20 l/h and for the gentamicin, the dV as 0.23±0.06 l/kgand the Cl was 4.71±1.95 l/h.Conclusion: In patients undergoing CRS, surgical intervention didnot significantly modify the pharmacokinetics of metronidazole orgentamicin in comparison with other groups of patients. The prophylaxisusing a single, pre-surgical dose enables the achievement, forboth antimicrobial agents, concentrations of a sufficient size to guarantee clinical efficacy

[Design and validation of a dosing algorithm for vancomycin in premature neonates]. / Diseño y validación de un esquema de dosificación de vancomicina en neonatos prematuros.

INTRODUCTION: Inappropriate use of vancomycin contributes to the development of resistant bacteria and jeopardizes the safety and effectiveness of treatment. The aim of this article was to design and validate an empirical dosing algorithm for vancomycin in premature neonates according to their population-based pharmacokinetic characteristics. PATIENTS AND METHODS: We performed a retrospective analysis of 129 serum samples from a cohort of 53 neonates. Homogeneous population groups were identified both from their individual pharmacokinetic parameters and from their biometric characteristics. The design of the dosing algorithm was based on simulation of the serum vancomycin concentration that would be reached with several different doses. The algorithm was validated in another cohort of 30 neonates and 108 serum samples. RESULTS: Introduction of the algorithm significantly increased the percentage initial values obtained with correct minimum and maximum concentrations in the first monitoring round (p<0.05). The mean number of serum samples obtained per patient for treatment monitoring was significantly reduced (3.6+/-2 vs. 4.9+/-3). CONCLUSIONS: The implantation of the dosing algorithm for vancomycin in premature neonates increased the efficiency of treatment, reduced monitoring requirements, and optimized serum vancomycin concentrations from the start of treatment.

Diseño y validación de un esquema de dosificación de vancomicina en neonatos prematuros / Design and validation of a dosing algorithm for vancomycin in premature neonates

Introducción: La utilización inadecuada de la vancomicina favorece la aparición de gérmenes resistentes y compromete la efectividad y la seguridad de los tratamientos. El objetivo del presente trabajo es el diseño y la validación de una pauta empírica inicial de dosificación de vancomicina en neonatos prematuros de acuerdo con sus características farmacocinéticas poblacionales. Pacientes y métodos: Análisis retrospectivo de 129 muestras séricas procedentes de una cohorte de 53 neonatos en la que se identificaron grupos poblacionales homogéneos a partir de los parámetros farmacocinéticos individuales y de las características biométricas. El diseño del esquema de dosificación se realizó mediante simulación de las concentraciones plasmáticas de vancomicina que se alcanzarían a partir de diferentes pautas. La validación se hizo en otra cohorte de 30 neonatos y 108 muestras séricas. Resultados: La implantación del algoritmo aumentó significativamente (p < 0,05) el porcentaje de concentraciones iniciales obtenidas con valores de concentración mínima y concentración máxima correctos en la primera monitorización. El número medio de muestras séricas obtenidas por paciente para la monitorización del tratamiento disminuyó significativamente (3,6 ± 2 respecto a 4,9 ± 3). Conclusiones: La implantación del algoritmo de dosificación de la vancomicina para neonatos prematuros mejora la eficiencia del tratamiento, reduce la necesidad de monitorización y optimiza las concentraciones séricas de la vancomicina desde su inicio (AU)

Introduction: Inappropriate use of vancomycin contributes to the development of resistant bacteria and jeopardizes the safety and effectiveness of treatment. The aim of this article was to design and validate an empirical dosing algorithm for vancomycin in premature neonates according to their population-based pharmacokinetic characteristics. Patients and methods: We performed a retrospective analysis of 129 serum samples from a cohort of 53 neonates. Homogeneous population groups were identified both from their individual pharmacokinetic parameters and from their biometric characteristics. The design of the dosing algorithm was based on simulation of the serum vancomycin concentration that would be reached with several different doses. The algorithm was validated in another cohort of 30 neonates and 108 serum samples. Results: Introduction of the algorithm significantly increased the percentage initial values obtained with correct minimum and maximum concentrations in the first monitoring round (p < 0.05). The mean number of serum samples obtained per patient for treatment monitoring was significantly reduced (3.6 ± 2 vs. 4.9 ± 3). Conclusions: The implantation of the dosing algorithm for vancomycin in premature neonates increased the efficiency of treatment, reduced monitoring requirements, and optimized serum vancomycin concentrations from the start of treatment (AU)

[Stability in serum of intravenous busulfan in a polyolefin pack]. / Estabilidad en suero fisiológico del busulfán intravenoso en un envase de poliolefinas.

INTRODUCTION: Although it has been used orally, the variability in its absorption and the risk of causing vomiting has lead to a push towards the intravenous use of bulsulfan. This study looks at the stability of 60 mg of busulfan, in fixed volumes of 250 mL (0.24 mg/mL) and 500 mL (0.12 mg/mL) of serum and different conservation conditions, in a new plastic pack made from polyolefin/polyamide laminates. MATERIAL AND METHODS: High-efficiency liquid chromatography with ultraviolet detection was used to determine the concentration of busulfan derivate with sodium diethyldithiocarbamatetrihydrate. Stability was assessed for both concentrations; refrigerated and at room temperature, using the t(90) of each sample. RESULTS: The percentage of the remaining busulfan concentration at 24 h was always less than 90%. At 25 degrees C and 0.24 mg/mL concentration, the t90 was 8.4 h; at 4 degrees C and a concentration of 0.24 mg/mL it was 16.7 h; at 25 degrees C and a concentration of 0.12 mg/mL it was 12 h and at 4 degrees C and a concentration of 0.12 mg/mL it was 11.5 h. CONCLUSIONS: This study show that busulfan in a concentration of 0.24 mg/mL in serum is stable in the bags tested during a refrigerated storage period of 12 h plus two additional hours of administration of the drug.

[Simplified scale for medication adherence related problems in anti-retroviral therapy]. / Escala simplificada para detectar problemas de adherencia (ESPA) al tratamiento antirretroviral.

OBJECTIVE: The purpose is to describe an own-developed scale for medication adherence evaluation of HIV patients under antiretroviral therapy, and to compare it with other previously described methods. METHODS: The six-item scale was compared with a pharmacy record about the delivery of medication. Accordance between scale and a four-item Morisky-type scale (measure 1) and a percentage of doses taken as prescribed during the past two weeks (measure 2) was computed. RESULTS: The own-scale showed 93% sensitivity, 70% specificity, a likelihood ratio of 3.08 and good agreement compared with the pharmacy record (k = 0.62, p < 0.001). Agreement between the scale and measure 1 and measure 2 was very weak (k = 0.12, p = 0.446 and k = 0.10, p = 0.273 respectively). 39.7% of patients was considered as adherent according with the own-scale and was observed correlation between adherence and clinical outcomes. CONCLUSION: The scale appears to be a valid instrument to check and detect adherence related problems compared with the pharmacy medication record. Easiness to use make feasible to consider as an adequate tool to detect non-adherent patients or patients with adherence related problems into the daily clinical practice.

Escala simplificada para detectar problemas de adherencia (ESPA) al tratamiento antirretroviral / No disponible

Objetivo: Se describe una escala simplificada para detectarproblemas de adherencia (ESPA) al tratamiento antirretroviral enpacientes VIH+ y se compara con otros métodos empleados habitualmenteen la práctica clínica.Método: La escala consta de seis preguntas cuya respuesta puedeser afirmativa o negativa y, dependiendo del valor obtenido, se identificaun potencial problema de adherencia. Se comparó la ESPA conregistros de dispensación y se determinó la concordancia con unamedida de tipo Morisky (medida 1) y con el porcentaje de dosis tomadasadecuadamente en las últimas dos semanas (medida 2).Resultados: Comparada con los registros de dispensación, laESPA mostró elevada sensibilidad (93%), especificidad (70%), unarazón de verosimilitud positiva de 3,08 y buena concordancia(k = 0,62, p < 0,001). La concordancia entre la escala y las medidas1 y 2 fue muy débil (k = 0,12, p = 0,446 y k = 0,10, p = 0,273,respectivamente). El 39,7% de los pacientes se consideró comoadherentes de acuerdo a la ESPA, y se observó una buena relaciónentre adherencia y las variables clínicas.Conclusiones: La ESPA parece un instrumento válido paradetectar problemas de adherencia con respecto a los registros dedispensación. Por su comodidad, es posible considerarla comouna herramienta adecuada para detectar pacientes no adherentesen la práctica clínica

Objective: The purpose is to describe an own-developed scalefor medication adherence evaluation of HIV patients under antiretroviraltherapy, and to compare it with other previouslydescribed methods.Methods: The six-item scale was compared with a pharmacyrecord about the delivery of medication. Accordance betweenscale and a four-item Morisky-type scale (measure 1) and a percentageof doses taken as prescribed during the past two weeks(measure 2) was computed.Results: The own-scale showed 93% sensitivity, 70% specificity,a likelyhood ratio of 3.08 and good agreement comparedwith the pharmacy record (k = 0.62, p < 0.001). Agreementbetween the scale and measure 1 and measure 2 was veryweak (k = 0.12, p = 0.446 and k = 0.10, p = 0.273 respectively).A 39.7% of patients was considered as adherent accordingwith the own-scale and was observed correlation between adherenceand clinical outcomes.Conclusion: The scale appears to be a valid instrument tocheck and detect adherence related problems compared with thepharmacy medication record. Easyness to use make feasible toconsider as an adequate tool to detect non-adherent patients orpatients with adherence related problems into the daily clinicalpractice

[HIV-infected patients' perceived satisfaction with an outpatient pharmaceutical care unit (OPCU)]. / Originales Breves Satisfacción percibida por pacientes infectados por el VIH con la unidad de atención farmacéutica a pacientes externos (UFPE).

INTRODUCTION: Satisfaction measurements attempt to establish patient views regarding health care. In the setting of pharmaceutical care, the measurements of the generically called "h umanistic"variables is scarce, and the number of validated instruments is inadequate. The goal of this study is to present a specifically-developed satisfaction survey regarding outpatient pharmaceutical care units, and to prove its applicability and inner consistency in a HIV-infected patient population on antiretroviral therapy. METHODS: The survey includes 19 questions within four groups - A. The unit's physical space, location, and organization; B. Dispensation; C. Pharmaceutical consultation, and D. Overall satisfaction with the unit. Each question is scored from 1 to 5. The study was carried out by administering 250 surveys to consecutive patients arriving at the OPCU, Castell6n General Hospital. RESULTS: Responses show a high degree of patient satisfaction with questions posed, with mean values oscillating between 3.0 and 4.8. The highest means corresponded to pharmacist valuation, and the lowest values corresponded to questions within the organizational module. All questions considered, the mean score obtained was 3.96 + 0.95 (median of 4). The survey exhibited high internal reproducibility both for each group and all questions. CONCLUSION: The satisfaction survey discussed here is an accessible, easy-to-use instrument that may be rapidly completed and used in pharmaceutical care units with outpatients as a measurement of patient satisfaction. The high scores HIV-infected patients assign to questions included in the survey suggest a benefit from standardized pharmaceutical care.

Monitorización de la concentración libre de ácido valproico en un paciente posquirúrgico septicémico / Monitoring free valproic acid concentrations in a post-surgical patient with sepsis

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