Design and validation of a predictive equation to estimate unbound valproic acid concentration.

OBJECTIVES: Total plasma levels of valproic acid (VPA) may mask an increased risk of adverse effects in hypoalbuminaemic patients since, in these patients, the free fraction is higher. The aim of this study is to analyse the relationship between plasma levels of total and free VPA (FVPA) in hypoalbuminaemic patients and define an equation that allows the estimation of FVPA concentration, as well as to validate the obtained equation. METHODS: This is a retrospective observational study conducted between January 2015 and January 2020. Hypoalbuminaemic adult patients with normal renal function were included. Serum VPA levels were determined using an automated enzyme immunoassay technique with a pre-treatment of the sample by ultrafiltration for the quantification of FVPA. Patients' determinations were randomised into two groups: first, to calculate the FVPA estimation equation (regression group) by multiple linear regression analysis; and second to validate the equation (validation group), calculating the agreement between experimental and estimated FVPA concentrations using Lin's coefficient and a Bland and Altman analysis. RESULTS: We included 51 determinations, corresponding to 33 patients: 26 in the regression group, and 25 in the validation group. The multiple linear regression analysis showed a statistically significant relationship between FVPA concentration (Y), total VPA concentration (X1) and albumin level (X2), explained by the equation Y=11.882 + 0.216*X1-4.722*X2. Pearson's correlation coefficient was 0.798 (p<0.001). Lin's coefficient was 0.82 (95% CI 0.63 to 0.92). The Bland and Altman analysis showed a bias of 0.32 mg/L, and the concordance limits were between -3.80 and 4.44. CONCLUSIONS: The calculated equation adequately predicts FVPA concentration, with a high degree of correlation between the variables. Despite Lin's coefficient outcome, Bland and Altman analysis showed a minimum bias that slightly underestimates FVPA concentration, positioning the calculated equation as a useful and validated estimation tool in hypoalbuminaemic patients with normal renal function.

Developing a telepharmacy programme with home medication dispensing and informed delivery in a tertiary hospital: description of the model and analysis of the results.

OBJECTIVES: This study aimed to describe the actions taken to implement a telepharmacy programme with home medication dispensing and informed delivery in an outpatient pharmaceutical care unit of a tertiary hospital, where approximately 5000 patients are treated per year. It also aimed to substantiate the applicability and benefits of the programme through analysing the findings and measuring patient satisfaction. METHODS: We identified the operational, logistical, technological and legal needs, as well as the need for training, information and coordination with the care team and patient associations. A standard operating procedure was developed which described the home dispensing model and the profile of patients eligible for telepharmacy. Care activity was evaluated, between the months of July 2020 and January 2021; and a survey was conducted to measure patient satisfaction based on the Enopex project, a cross-sectional observational study of patients who used telepharmacy services during the COVID-19 lockdown period in Spain. RESULTS: A total of 2536 medication deliveries were made over 144 working days, with a mean of 18 (standard deviation (SD): 6) deliveries per day, and a total of 2854 dispensings (1.1 drugs per delivery). In total, 197 different types of pharmaceutical formulations were delivered, corresponding to 123 active ingredients. The distance and time avoided during the study period totalled 1 05 624 km and 1 09 452 min (76 days), whereby the median distance and time saved per patient were 66 (interquartile range (IQR):122 km and 90 (IQR:90) minutes, which represents an approximate carbon footprint reduction of 25 kg of CO2 per patient and 16.5 tonnes in total. The satisfaction survey conducted, completed by 134 patients, revealed high satisfaction with the pharmacy service of 9.88 points out of 10. CONCLUSIONS: The SARS-CoV-2 pandemic (COVID-19) has provided the pharmacy service with an opportunity to develop and implement a telepharmacy programme that benefits patients, which has enabled better organisation of the unit and greater accessibility for patients attending in person. It is a replicable method that is applicable in other pharmacy services with similar characteristics and requirements.

Vancomycin and daptomycin stability in heparin or sodium citrate lock solutions.

BACKGROUND: We investigated physical and chemical stability of daptomycin and vancomycin in heparin or sodium citrate lock solutions. The aim of this study was to find the optimal combination of antimicrobials and additives for lock solutions, which maximized patient safety. METHODS: Vancomycin and daptomycin were diluted with heparin or sodium citrate to achieve final concentrations of vancomycin-heparin 2.5 mg/mL-833.33 U/mL, vancomycin-citrate 2.5-33.3 mg/mL, daptomycin-heparin 5 mg/mL-800 U/mL, and daptomycin-citrate 5-32 mg/mL and they were stored at room temperature (+25°C), 4°C, -20°C, and 37°C. Physical and chemical stability were analyzed for each antibiotic-anticoagulant combination in all conditions immediately after preparation, at 24, 48, 72 h and at different time points until unstable concentrations were obtained. Daptomycin-sodium citrate microbiological activity was also studied by evaluating two Staphylococcus aureus cultures in a calcium enriched medium with a daptomycin E test, with and without sodium citrate. RESULTS: After incubation at 37°C vancomycin and daptomycin combined with heparin retained at least 90% of the initial concentration over 48 h. Vancomycin-sodium citrate solution stored at 37°C reduced more than 10% of the initial concentration at 24 h. On the other hand, daptomycin-sodium citrate preparation was stable at 37°C for 72 h but the microbiological activity of daptomycin was lower in the presence of sodium citrate. CONCLUSIONS: The purpose is to prepare vancomycin and daptomycin lock solutions combined with heparin. They should be changed at 48 h and its stability is over 3 days at 25°C and 7 days at 4°C, which allow Hospital Pharmacy Services to manage their stocks. Daptomycin-sodium citrate combination is more stable for extended periods but its bioactivity has not been demonstrated.

Beta-lactam allergy in patients: an antibiotic stewardship challenge.

BACKGROUND: Patients are commonly reported as being allergic to beta-lactam (BL) antibiotics. However, many patients with this reported allergy are able to receive BL treatments because they do not have true allergies. In many cases these are simply intolerances due to side effects reported as an allergy. Delabelling these patients leads to better clinical outcomes, optimal antibiotic usage, decreased bacterial resistance and reduced healthcare costs. Therefore, the aims of this study were to identify incorrectly labelled BL allergies in hospitalised patients and to assess antibiotic use in delabelled patients in order to establish a quality indicator to optimise antimicrobial treatments. METHODS: A prospective study was conducted in which hospitalised patients treated with antimicrobial drugs and labelled as 'BL-allergic' were identified by clinical pharmacists. An allergist assessed whether patients were suitable candidates for a skin test or oral challenge. The Allergy Service removed 'BL-allergic' labels if negative results were obtained. Delabelled patients were followed up by clinical pharmacists to study the use of BL antibiotics as a result of the delabelling programme. RESULTS: A total of 176 suspected allergic patients were identified and 91 (51.7%) were tested either by a skin test or oral challenge based on the patient indicators. Seven (16.4%) patients tested were allergic to BL antibiotics, 76 (83.5%) were totally delabelled and eight (0.1%) were partially delabelled. Thirty-two (38.1%) delabelled patients required antibiotic treatment in another inpatient or outpatient setting, of whom 27 (84.3%) patients with a new infectious episode received BL treatments while five (15.7%) continued to receive antimicrobial treatments without BL. CONCLUSION: After the implementation of a protocol to detect incorrect BL allergy labels, 83.5% of the patients in this cohort were completely delabelled. This shows that there is a clear opportunity to optimise the use of antibiotics by delabelling 'BL-allergic' patients.

Six months multicentre pilot open label single-arm study to evaluate patient experience, acceptability and satisfaction of switching certolizumab pegol from a prefilled syringe or autoinjection pen to an AVA® e-Device in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis patients.

WHAT IS KNOWN AND OBJECTIVE: The study aimed to assess acceptability and patient experience of Certolizumab (CZP) self-injection with AVA® and clarify patient device preference after switching CZP from the syringe or auto-injection pen to AVA® in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) patients. METHOD: A multicentre open-label, cross-sectional and prospective study among four Spanish hospitals was performed. Adult RA, PsA, axSpA patients treated for at least 6 months with the CZP syringe or pen were recruited. At the first visit, patients completed Pre-AVA® questionnaire. Patients were instructed on proper administration of CZP by AVA®. After 2 and 6 months of CZP self-injections using the AVA®, patient experience, adherence, preference and safety of each administration was assessed using post-AVA® questionnaire. RESULTS AND DISCUSSION: Thirty four patients were included (28 women). All patients self-administered CZP AVA® the full dose of CZP was injected. Patients reported >90% adherence to CZP AVA® assessed with the injection log. Pain at the injection site was reduced after switching to AVA®. Twenty nine patients preferred CZP AVA® and five patients preferred the CZP pen. No safety-related findings related to AVA® CZP administration were identified. WHAT IS NEW AND CONCLUSION: The AVA® is an advantageous delivery option for CZP in patients with RA, PsA, axSpA.

Population Pharmacokinetic/Pharmacodynamic Modelling of Daptomycin for Schedule Optimization in Patients with Renal Impairment.

The aims of this study are (i) to develop a population pharmacokinetic/pharmacodynamic model of daptomycin in patients with normal and impaired renal function, and (ii) to establish the optimal dose recommendation of daptomycin in clinical practice. Several structural PK models including linear and non-linear binding kinetics were evaluated. Monte Carlo simulations were conducted with a fixed combination of creatinine clearance (30-90 mL/min/1.73 m2) and body weight (50-100 kg). The final dataset included 46 patients and 157 daptomycin observations. A two-compartment model with first-order peripheral distribution and elimination kinetics assuming non-linear protein-binding kinetics was selected. The bactericidal effect for Gram+ strains with MIC ≤ 0.5 mg/L could be achieved with 5-12 mg/kg daily daptomycin based on body weight and renal function. The administration of 10-17 mg/kg q48 h daptomycin allows to achieve bactericidal effect for Gram+ strains with MIC ≤ 1 mg/L. Four PK samples were selected as the optimal sampling strategy for an accurate AUC estimation. A quantitative framework has served to characterize the non-linear binding kinetics of daptomycin in patients with normal and impaired renal function. The impact of different dosing regimens on the efficacy and safety outcomes of daptomycin treatment based on the unbound exposure of daptomycin and individual patient characteristics has been evaluated.

INFLIXIMAB AND ADALIMUMAB SERUM TROUGH CONCENTRATIONS THRESHOLD ASSOCIATED WITH DEEP REMISSION IN INFLAMMATORY BOWEL DISEASE.

OBJECTIVE: Deep remission (DR) defined by clinical-biomarker remission and mucosal healing (MH) has emerged as a new therapeutic target in inflammatory bowel disease (IBD). The aim of this study was to define an optimal cut-off concentration for IFX and ADA during maintenance therapy associated with DR. The secondary objective, was to evaluate the influence of variables on anti-TNF concentrations and DR. METHODS: Retrospective study including 120 and 122 patients IBD diagnosed who received maintenance therapy with IFX and ADA. Biomarker remission was considered by C-reactive protein (CRP)<5 mg/L and fecal calprotectin (CF)<100 mcg/g. Crohn's disease (CD) clinical remission was defined by a Harvey Bradshaw score<5 and MH by a simple endoscopic score for CD (SES-CD)<3.  In ulcerative colitis (UC), it was defined as a Mayo total score<3 and Mayo endoscopic subscore<2. Receiver operating characteristic (ROC) test was performed to determine drug concentration thresholds associated with DR. Anti-TNF concentrations were classified into quartiles. X2 and Kruskal-Wallis test were used to compare discrete and continuous variables between quartile groups. Multivariate logistic regression was performed to identify patient characteristics and serological factors associated with DR. RESULTS: Anti-TNF concentrations were higher in patients with DR, in IFX (4.4, IQR: 3.3-6.5 vs 2.3, IQR: 1.1-4.2 µg/mL, P<0.005) and ADA (6.3, IQR: 4.2-8.2 vs 3.9, IQR: 2.4-5.5 µg/mL, P<0.005). A ROC identified a concentration threshold of 3.1 µg/mL in IFX (area under the ROC curve [AUROC], 0.72) and 6.3 µg/mL in ADA (AUROC, 0.75) associated with DR. Factors associated with the highest quartiles of serum IFX concentration were: elevated body mass index (BMI), absence of previous IBD-surgery, CRP<5 mg/L, and FC<100 µg/g. In ADA, higher quartiles were related to concomitant immunosuppressants, low BMI, absence of previous IBD-surgery, and CRP<5 mg/L and FC<100 µg/g. Multivariate regression identified FC<100 µg/g, CRP<5mg/L, IFX ≥3.1µg/mL and ADA concentrations ≥6.3µg/mL as factors significantly associated with DR.  CONCLUSIONS: Trough IFX and ADA concentrations, CRP<5mg/L and FC<100 µg/g are associated with DR during maintenance therapy. Cutoff point of 3.1 and 6.3 g/mL for IFX and ADA respectively, were identified as DR predictors.

Objetivo: La remisión profunda, definida como remisión clínico-analítica y  curación de la mucosa, es el objetivo terapéutico en la enfermedad inflamatoria intestinal. En este estudio se define el punto de  corte óptimo de concentración valle de infliximab y adalimumab asociado a  remisión profunda en fase de mantenimiento. El objetivo secundario es  evaluar las covariables relacionadas con las concentraciones de antifactor de necrosis tumoral y la remisión profunda.Método: Estudio retrospectivo que incluyó 120 y 122 pacientes  diagnosticados de enfermedad inflamatoria intestinal tratados con infliximab y adalimumab. La proteína C reactiva < 5 mg/l y la calprotectina  fecal < 100 µg/g se consideró para remisión analítica. En la enfermedad de Crohn, la remisión clínica se definió mediante puntuación Harvey  Bradshaw < 5; la curación de la mucosa por puntuación endoscópica simple para enfermedad de Crohn < 3; en colitis ulcerosa, por índice total de Mayo < 3 e índice subendoscópico de Mayo < 2. Se realizó un análisis por  curva de eficacia diagnóstica para determinar el cutoff asociado  a remisión profunda. Las concentraciones de antifactor de necrosis tumoral se clasificaron en cuartiles. Se utilizó la prueba X2 y Kruskal-Wallis para comparar variables discretas o continuas. Se realizó una  regresión  logística multivariante para identificar las características de  pacientes y serológicas asociadas a remisión profunda.Resultados: Las concentraciones de antifactor de necrosis tumoral fueron  superiores en remisión profunda en comparación con los que no la  alcanzaron en infliximab (4,4; rango intercuartílico: 3,3-6,5 versus 2,3;  rango intercuartílico: 1,1-4,2 µg/ml; P < 0,005) y adalimumab (6,3; rango  intercuartílico: 4,2-8,2 versus 3,9; rango intercuartílico: 2,4-5,5 µg/ml; P <  0,005). Se identificó un cutoff de 3,1 µg/ml en infliximab (área bajo la curva  de eficacia diagnóstica 0,72), y 6,3 µg/ml en adalimumab (área bajo la curva de eficacia diagnóstica 0,75). Los factores asociados a concentraciones  más elevadas de infliximab fueron: elevado índice de masa  corporal, ausencia de cirugía previa de enfermedad inflamatoria intestinal,  proteína C reactiva < 5 mg/l y calprotectina fecal < 100 µg/g. En  adalimumab, concentraciones más altas se relacionaron con  oadministración  de inmunosupresores, bajo índice de masa corporal,  ausencia de cirugía previa, proteína C reactiva < 5 mg/l y calprotectina fecal  < 100 µg/g. Se identificó calprotectina fecal < 100 µg/g, proteína C reactiva  < 5 mg/l, infliximab ≥ 3,1 µg/ml y adalimumab ≥ 6,3 µg/ml como factores  asociados a remisión profunda.logística multivariante para identificar las características de pacientes yserológicas asociadas a remisión profunda.Resultados: Las concentraciones de antifactor de necrosis tumoral fueronsuperiores en remisión profunda en comparación con los que no la alcanzaronen infliximab (4,4; rango intercuartílico: 3,3-6,5 versus 2,3; rango intercuartílico:1,1-4,2 µg/ml; P < 0,005) y adalimumab (6,3; rango intercuartílico:4,2-8,2 versus 3,9; rango intercuartílico: 2,4-5,5 µg/ml; P < 0,005).Se identificó un cutoff de 3,1 µg/ml en infliximab (área bajo la curva deeficacia diagnóstica 0,72), y 6,3 µg/ml en adalimumab (área bajo la curvade eficacia diagnóstica 0,75). Los factores asociados a concentraciones máselevadas de infliximab fueron: elevado índice de masa corporal, ausenciade cirugía previa de enfermedad inflamatoria intestinal, proteína C reactiva< 5 mg/l y calprotectina fecal < 100 µg/g. En adalimumab, concentracionesmás altas se relacionaron con coadministración de inmunosupresores,bajo índice de masa corporal, ausencia de cirugía previa, proteína C reactiva< 5 mg/l y calprotectina fecal < 100 µg/g. Se identificó calprotectinafecal < 100 µg/g, proteína C reactiva < 5 mg/l, infliximab ≥ 3,1 µg/ml yadalimumab ≥ 6,3 µg/ml como factores asociados a remisión profunda.Conclusiones: Las concentraciones valle de infliximab y adalimumab, proteínaC reactiva < 5 mg/l y calprotectina fecal < 100 µg/g se asocian a remisiónprofunda. Se identifican concentraciones cutoff de 3,1 y 6,3 µg/ml en infliximaby adalimumab, respectivamente, como predictoras de remisión profunda.

Los niveles séricos de infliximab y adalimumab están asociados con remisión profunda en la enfermedad inflamatoria intestinal / Serum levels of infliximab and adalimumab are associated with deep remission in inflammatory bowel disease

Objetivo: La remisión profunda, definida como remisión clínico-analíticay curación de la mucosa, es el objetivo terapéutico en la enfermedadinflamatoria intestinal. En este estudio se define el punto de corte óptimode concentración valle de infliximab y adalimumab asociado a remisiónprofunda en fase de mantenimiento. El objetivo secundario es evaluarlas covariables relacionadas con las concentraciones de antifactor denecrosis tumoral y la remisión profunda.Método: Estudio retrospectivo que incluyó 120 y 122 pacientes diagnosticados de enfermedad inflamatoria intestinal tratados con infliximaby adalimumab. La proteína C reactiva < 5 mg/l y la calprotectina fecal< 100 µg/g se consideró para remisión analítica. En la enfermedad deCrohn, la remisión clínica se definió mediante puntuación Harvey Bradshaw < 5; la curación de la mucosa por puntuación endoscópica simplepara enfermedad de Crohn < 3; en colitis ulcerosa, por índice total deMayo < 3 e índice subendoscópico de Mayo < 2. Se realizó un análisispor curva de eficacia diagnóstica para determinar el cutoff asociado aremisión profunda. Las concentraciones de antifactor de necrosis tumoral se clasificaron en cuartiles. Se utilizó la prueba X2 y Kruskal-Wallispara comparar variables discretas o continuas. Se realizó una regresión logística multivariante para identificar las características de pacientes yserológicas asociadas a remisión profunda.Resultados: Las concentraciones de antifactor de necrosis tumoral fueronsuperiores en remisión profunda en comparación con los que no la alcanzaron en infliximab (4,4; rango intercuartílico: 3,3-6,5 versus 2,3; rango intercuartílico: 1,1-4,2 μg/ml; P < 0,005) y adalimumab (6,3; rango intercuartílico: 4,2-8,2 versus 3,9; rango intercuartílico: 2,4-5,5 μg/ml; P < 0,005).Se identificó un cutoff de 3,1 μg/ml en infliximab (área bajo la curva deeficacia diagnóstica 0,72), y 6,3 μg/ml en adalimumab (área bajo la curvade eficacia diagnóstica 0,75). (AU)

Objective: Deep remission defined by clinical-biomarker remissionand mucosal healing has emerged as a new therapeutic target in inflammatory bowel disease. The aim of this study was to define an optimalcut-off concentration for infliximab and adalimumab during maintenancetherapy associated with deep remission. The secondary objective, wasto evaluate the influence of variables on anti tumor necrosis factor-alphaconcentrations and deep remission.Method: Retrospective study including 120 and 122 patients inflammatory bowel disease diagnosed who received maintenance therapywith infliximab and adalimumab. Biomarker remission was consideredby C-reactive protein < 5 mg/L and fecal calprotectin < 100 µg/g.Crohn’s disease clinical remission was defined by a Harvey Bradshawscore < 5 and mucosal healing by a simple endoscopic score for Crohn'sdisease< 3. In ulcerative colitis, it was defined as a Mayo total score < 3and Mayo endoscopic subscore < 2. Receiver operating characteristictest was performed to determine drug concentration thresholds associatedwith deep remission. Anti tumor necrosis factor-alpha concentrations wereclassified into quartiles. X2 and Kruskal-Wallis test were used to comparediscrete and continuous variables between quartile groups. Multivariate logistic regression was performed to identify patient characteristics andserological facto C-reactive protein rs associated with deep remission.Results: Anti tumor necrosis factor-alpha concentrations were higher inpatients with deep remission, in infliximab (4.4, interquartile range: 3.3-6.5vs 2.3, interquartile range: 1.1-4.2 μg/mL, P < 0.005) and adalimumab(6.3, interquartile range: 4.2-8.2 vs 3.9, interquartile range: 2.4-5.5 μg/mL,P < 0.005). (AU)

Formulación de nutrición parenteral neonatal: ¿dónde estamos? / Neonatal parenteral nutrition formulation: where are we?

INTRODUCCIÓN: la instauración de nutrición parenteral al prematuro ha supuesto un importante avance en su pronóstico. Los últimos años han sido muy fructíferos en cuanto a la publicación de guías en este ámbito. OBJETIVOS: conocer los procedimientos de formulación y elaboración de las nutriciones parenterales neonatales (NPN) en los hospitales españoles. MÉTODOS: se llevó a cabo una encuesta multicéntrica dirigida a los servicios de farmacia sobre los procesos anteriormente citados. RESULTADOS: 55 hospitales cumplieron criterios de inclusión. El 51 % disponía de sistemas informáticos de prescripción, y el 65,5 % formulaba siempre de forma individualizada, mientras que el 34,4 % disponía de fórmulas prediseñadas. Los preparados tricamerales eran utilizados por el 13,0 %. En el 52,7 % de los casos se preparaban las nutriciones de primer día bajo demanda, y ésta se iniciaba antes de las 8 horas de vida en un 88,1 % de los casos. El fosfato inorgánico era la primera opción en un 10,4 %. Se añadían diariamente vitaminas, oligoelementos y zinc en el 92,7 %, 90,9 % y 70,9 % de los casos, respectivamente. El 45,4 % de los hospitales elaboraba siempre las NPPN incluyendo los lípidos en la misma bolsa, frente al 34,5 % en los que estos se administraban por separado en todos los casos. El 50,9 % de los hospitales nunca añadía heparina a sus nutriciones. Las bolsas fotoprotectoras eran utilizadas por un 89,1 %. La estabilidad de las nutriciones variaba desde 24 horas a 15 días. CONCLUSIONES: la elaboración de la NPN en España está sujeta a gran variabilidad. Existe controversia respecto al uso de heparina y mezclas ternarias, reflejada en la variabilidad de la práctica clínica

INTRODUCTION: the introduction of parenteral nutrition in preterm infants has meant a major advance in their prognosis, being the last few years very fruitful in terms of publication of guidelines in this area. OBJECTIVES: to know the formulation and preparation procedures of neonatal parenteral nutrition (NPN) in Spanish hospitals. METHODS: a multi-centre survey was conducted in Pharmacy Services on the aforementioned processes. RESULTS: fifty-five hospitals met inclusion criteria. Electronic prescription systems were use by 51 %, 65.5 % always formulated individually, while 34.4 % had predesigned formulas. Tricameral preparations were used by 13.0 %. In 52.7 % of cases, first day nutrition was prepared on demand, starting before 8 hours of life in 88.1 % of cases. Inorganic phosphate was the first option in 10.4 %, vitamins, trace elements and zinc were added daily in 92.7 %, 90.9 % and 70.9 % of cases, respectively. NPN including lipids in the same bag was formulated by 45.4 % of the hospitals, compared to 34.5 % where it was administered separately in all cases. In 50.9 % of hospitals they never added heparin to their NPN. The 89.1 % used photoprotected bags. The stability of the admixture varied from 24 hours to 15 days. CONCLUSION: the elaboration of the PPN in Spain is subject to great variability. There is controversy regarding the use of heparin and ternary mixtures, which is reflected in the variability of clinical practice

[Neonatal parenteral nutrition formulation: where are we?] / Formulación de nutrición parenteral neonatal: ¿dónde estamos?

INTRODUCTION: Introduction: the introduction of parenteral nutrition in preterm infants has meant a major advance in their prognosis, being the last few years very fruitful in terms of publication of guidelines in this area. Objectives: to know the formulation and preparation procedures of neonatal parenteral nutrition (NPN) in Spanish hospitals. Methods: a multi-centre survey was conducted in Pharmacy Services on the aforementioned processes. Results: fifty-five hospitals met inclusion criteria. Electronic prescription systems were use by 51 %, 65.5 % always formulated individually, while 34.4 % had predesigned formulas. Tricameral preparations were used by 13.0 %. In 52.7 % of cases, first day nutrition was prepared on demand, starting before 8 hours of life in 88.1 % of cases. Inorganic phosphate was the first option in 10.4 %, vitamins, trace elements and zinc were added daily in 92.7 %, 90.9 % and 70.9 % of cases, respectively. NPN including lipids in the same bag was formulated by 45.4 % of the hospitals, compared to 34.5 % where it was administered separately in all cases. In 50.9 % of hospitals they never added heparin to their NPN. The 89.1 % used photoprotected bags. The stability of the admixture varied from 24 hours to 15 days. Conclusion: the elaboration of the PPN in Spain is subject to great variability. There is controversy regarding the use of heparin and ternary mixtures, which is reflected in the variability of clinical practice.

INTRODUCCIÓN: .Introducción: la instauración de nutrición parenteral al prematuro ha supuesto un importante avance en su pronóstico. Los últimos años han sido muy fructíferos en cuanto a la publicación de guías en este ámbito. Objetivos: conocer los procedimientos de formulación y elaboración de las nutriciones parenterales neonatales (NPN) en los hospitales españoles. Métodos: se llevó a cabo una encuesta multicéntrica dirigida a los servicios de farmacia sobre los procesos anteriormente citados. Resultados: 55 hospitales cumplieron criterios de inclusión. El 51 % disponía de sistemas informáticos de prescripción, y el 65,5 % formulaba siempre de forma individualizada, mientras que el 34,4 % disponía de fórmulas prediseñadas. Los preparados tricamerales eran utilizados por el 13,0 %. En el 52,7 % de los casos se preparaban las nutriciones de primer día bajo demanda, y ésta se iniciaba antes de las 8 horas de vida en un 88,1 % de los casos. El fosfato inorgánico era la primera opción en un 10,4 %. Se añadían diariamente vitaminas, oligoelementos y zinc en el 92,7 %, 90,9 % y 70,9 % de los casos, respectivamente. El 45,4 % de los hospitales elaboraba siempre las NPPN incluyendo los lípidos en la misma bolsa, frente al 34,5 % en los que estos se administraban por separado en todos los casos. El 50,9 % de los hospitales nunca añadía heparina a sus nutriciones. Las bolsas fotoprotectoras eran utilizadas por un 89,1 %. La estabilidad de las nutriciones variaba desde 24 horas a 15 días. Conclusiones: la elaboración de la NPN en España está sujeta a gran variabilidad. Existe controversia respecto al uso de heparina y mezclas ternarias, reflejada en la variabilidad de la práctica clínica.

Bacteriemia en pacientes con nutrición parenteral central: prevalencia, factores asociados y tratamiento / Catheter-related bloodstream infections in patients receiving central parenteral nutrition: prevalence, associated factors, and treatment

INTRODUCCIÓN: la infección relacionada con el catéter es una de las complicaciones del tratamiento con nutrición parenteral central (NPC) que generan una mayor morbimortalidad. OBJETIVOS: el objetivo principal fue analizar la prevalencia de la bacteriemia asociada al catéter en pacientes con nutrición parenteral central. Los objetivos secundarios fueron: a) evaluar si el tipo de catéter central, la duración de la nutrición parenteral central, el índice de masa corporal o la estancia en la unidad de cuidados intensivos son factores asociados al desarrollo de bacteriemia; b) analizar el manejo terapéutico de la infección. MATERIAL Y MÉTODOS: se trata de un estudio observacional retrospectivo. Se incluyeron los pacientes que recibieron nutrición parenteral central tras una intervención quirúrgica entre julio de 2018 y marzo de 2019. La asociación de las variables con el desarrollo de la bacteriemia se analizó mediante regresión logística. RESULTADOS: el 7,3 % (IC 95 %: 3,9-13,3) (n = 9/123) de los pacientes desarrollaron bacteriemia relacionada con el catéter. El único factor asociado al desarrollo de la infección fue la duración de la nutrición parenteral central (OR = 1,12; IC 95 %: 1,05-1,20; p = 0,001). CONCLUSIONES: la prevalencia de la bacteriemia relacionada con el catéter en este estudio es baja. La duración del tratamiento con nutrición parenteral central parece estar relacionada con el desarrollo de la bacteriemia. Sin embargo, se necesitan más estudios para identificar factores de riesgo que permitan minimizar este tipo de complicaciones

BACKGROUND: catheter-related infection is one of the complications of central parenteral nutrition treatment with the highest morbidity and mortality. OBJECTIVES: the primary endpoint of this study was to analyze the prevalence of bloodstream infection in patients with central parenteral nutrition. Secondary objectives included: a) an assessment of whether type of central catheter, duration of parenteral nutrition treatment, body mass index, or being admitted to the intensive care unit are factors associated with the development of bloodstream infection; b) an analysis of the therapeutic approach. MATERIAL AND METHODS: this was a retrospective observational study. All patients who received central parenteral nutrition after surgery between July 2018 and March 2019 were included. The association between the different variables and the development of bloodstream infection was analyzed by logistic regression. RESULTS: the prevalence of bloodstream infection was 7.3 % (95 % CI: 3.9-13.3) (n = 9/123 patients). The duration of central parenteral nutrition was the only variable associated with the development of bloodstream infection (OR = 1.12; 95 % CI:1.05-1.20; p = 0.001). CONCLUSIONS: the prevalence of catheter-related bloodstream infection in this study is low, and the duration of central parenteral nutrition seems to be related to its development. However, further studies are needed to identify risk factors that might help reduce this kind of complications

[Catheter-related bloodstream infections in patients receiving central parenteral nutrition: prevalence, associated factors, and treatment]. / Bacteriemia en pacientes con nutrición parenteral central: prevalencia, factores asociados y tratamiento.

INTRODUCTION: Background: catheter-related infection is one of the complications of central parenteral nutrition treatment with the highest morbidity and mortality. Objectives: the primary endpoint of this study was to analyze the prevalence of bloodstream infection in patients with central parenteral nutrition. Secondary objectives included: a) an assessment of whether type of central catheter, duration of parenteral nutrition treatment, body mass index, or being admitted to the intensive care unit are factors associated with the development of bloodstream infection; b) an analysis of the therapeutic approach. Methods: this was a retrospective observational study. All patients who received central parenteral nutrition after surgery between July 2018 and March 2019 were included. The association between the different variables and the development of bloodstream infection was analyzed by logistic regression. Results: the prevalence of bloodstream infection was 7.3 % (95 % CI: 3.9-13.3) (n = 9/123 patients). The duration of central parenteral nutrition was the only variable associated with the development of bloodstream infection (OR = 1.12; 95 % CI:1.05-1.20; p = 0.001). Conclusions: the prevalence of catheter-related bloodstream infection in this study is low, and the duration of central parenteral nutrition seems to be related to its development. However, further studies are needed to identify risk factors that might help reduce this kind of complications.

INTRODUCCIÓN: Introducción: la infección relacionada con el catéter es una de las complicaciones del tratamiento con nutrición parenteral central (NPC) que generan una mayor morbimortalidad. Objetivos: el objetivo principal fue analizar la prevalencia de la bacteriemia asociada al catéter en pacientes con nutrición parenteral central. Los objetivos secundarios fueron: a) evaluar si el tipo de catéter central, la duración de la nutrición parenteral central, el índice de masa corporal o la estancia en la unidad de cuidados intensivos son factores asociados al desarrollo de bacteriemia; b) analizar el manejo terapéutico de la infección. Material y métodos: se trata de un estudio observacional retrospectivo. Se incluyeron los pacientes que recibieron nutrición parenteral central tras una intervención quirúrgica entre julio de 2018 y marzo de 2019. La asociación de las variables con el desarrollo de la bacteriemia se analizó mediante regresión logística. Resultados: el 7,3 % (IC 95 %: 3,9-13,3) (n = 9/123) de los pacientes desarrollaron bacteriemia relacionada con el catéter. El único factor asociado al desarrollo de la infección fue la duración de la nutrición parenteral central (OR = 1,12; IC 95 %: 1,05-1,20; p = 0,001). Conclusiones: la prevalencia de la bacteriemia relacionada con el catéter en este estudio es baja. La duración del tratamiento con nutrición parenteral central parece estar relacionada con el desarrollo de la bacteriemia. Sin embargo, se necesitan más estudios para identificar factores de riesgo que permitan minimizar este tipo de complicaciones.

Therapeutic drug monitoring of levetiracetam in daily clinical practice: high-performance liquid chromatography versus immunoassay.

Objectives: Although levetiracetam presents an easy dosing and tolerability, therapeutic drug monitoring may be recommended in certain situations. Measurement of levetiracetam in serum plasma is commonly done by high performance liquid chromatography (HPLC). After ARK Diagnostics marketed an enzyme immunoassay (IA) for levetiracetam in serum or plasma, automated determinations are possible. In this study, the performance of this immunoassay and the impact of automation on the follow-up in patients treated with levetiracetam is evaluated. We also detected those subpopulations of patients who may benefit the most from this therapeutic drug monitoring. Methods: Samples from 50 outpatients diagnosed with epilepsy and treated with levetiracetam were collected. This new IA was performed on the Architect c4000 analyser and compared with the HPLC. Then, a retrospective observational study that included serum samples of levetiracetam for 24 months, was conducted to evaluate the impact of automattion and the influence of some variables (age, sex, renal function, and co-administration of valproic acid and glucuronidation-inducing drugs) in levetiracetam apparent oral clearance (CLp/F) by a multivariate linear regression. Results: The mean high-performance liquid chromatography quantified concentration (CpHPLC) was 18.43 mcg/mL (95% CI: 15.48 to 21.39) and immunoassay concentration (CpEI) was 18.35 mcg/mL (95% CI: 15.20 to 21.50) (P=0.861). The Pearson's linear correlation coefficient obtained in the analysis was r2=0.88, according to the following equation: CpHPLC=-0.29+1.01 CpEI. The intraclass correlation coefficient was 0.95 (95% CI: 0.91 to 0.97). After IA implementation, the number of levetiracetam determinations increased in 76.27%. The median of Clp/F was higher (P<0.001) in inducers (4.36 L/h; IQR:3.29-5.44) and lower (P<0.001) in glomerular filtration rate (GFR) <60 mL/min (2.7 L/h; IQR: 0.58-3.85). Conclusions: The Ark method performed on the Architect is fully acceptable and can be used routinely to measure levetiracetam plasmatic concentration levels. It has demonstrated the need for closer monitoring in patients with renal failure or co-administration of glucuronidation-inducing drugs.

Vancomycin dose optimisation comparing a pharmacokinetic/pharmacodynamic model versus the pharmacokinetic model.

OBJECTIVES: To compare vancomycin dosage adjustment by evaluating trough concentrations (Ctrough) of vancomycin and its pharmacokinetic/pharmacodynamic (PK/PD) correlation (AUC/MIC ≥400). METHODS: A retrospective study of 52 adult haematological patients and 29 ICU patients was carried out. Dosage adjustment was performed in routine clinical practice with Ctrough​​ and then compared using a PK/PD model. The probability of achieving the PK/PD target associated with the success of antimicrobial therapy was evaluated. When the susceptibility of the organism responsible for infection is not known, Monte Carlo simulation calculates the cumulative fraction of response (CFR) from the distribution of MIC values. Values of CFR >90% represent an optimal achieved regimen against a population of microorganisms. RESULTS: According to dosage adjustment performed ​​with Ctrough, in haematological patients the dose of vancomycin was increased in 65.4% compared with an increase in 53.8% of patients with the PK/PD model. No dose adjustment was needed in 21.1% of patients using Ctrough compared with 7.7% with the PK/PD model and in 13.5% of patients using Ctrough determination and in 38.5% of patients with the PK/PD model the dose was reduced. For ICU patients the dosage adjustment made ​​with Ctrough resulted in an increased dose of vancomycin in 79.4% of patients compared with 41.4% with the PK/PD model. No dose adjustment was needed in 3.4% of patients using Ctrough in comparison with 13.8% with the PK/PD model, and the dose was reduced in 17.2% of patients using Ctrough determination and in 44.8% with the PK/PD model. CONCLUSIONS: Data for bacterial susceptibility combined with measured data for antibiotic concentrations using a PK/PD model predict and improve the dosage adjustment for individual patients. A larger study with more complete datasets are needed for validation before it can be fully introduced into clinical practice.

Queratoconjuntivitis asociada a dermatitis atópica tratada con tocilizumab / Keratoconjunctivitis associated with atopic dermatitis treated with tocilizumab

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