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Introduction. A specialized service for antifungal blood level determination is not available in Colombia. This service is essential for the proper follow-up of antifungal therapies. Objective. To standardize and validate a simple, sensitive, and specific protocol based on high-performance liquid chromatography with a diode array detector for voriconazole blood level quantification. Materials and methods. We used an Agilent HPLC™ series-1200 equipment with a UVdiode array detector with an analytical column Eclipse XDB-C18 and pre-column Eclipse- XDB-C18 (Agilent). We used voriconazole as the primary control and posaconazole as an internal control. We performed the validation following the Food and Drug Administration (FDA) recommendations. Results. The best chromatographic conditions were: Column temperature of 25°C, UV variable wavelength detection at 256 nm for voriconazole and 261 nm for posaconazole (internal standard); 50 μl of injection volume, 0,8 ml/min volume flow, 10 minutes of run time, and mobile phase of acetonitrile:water (60:40). Finally, retention times were 3.13 for voriconazole and 5.16 minutes for posaconazole. Quantification range varied from 0.125 μg/ml to 16 μg/ml. Conclusion. The selectivity and chromatographic purity of the obtained signal, the detection limits, and the standardized quantification make this method an excellent tool for the therapeutic monitoring of patients treated with voriconazole.

Therapeutic monitoring of antibiotics and antifungals based on pharmacokinetic and pharmacodynamic (PK/PD) parameters is a strategy increasingly used for the optimization of therapy to improve efficacy, reduce the occurrence of toxicities, and prevent the selection of antimicrobial resistance, particularly in vulnerable patients including neonates and the critical or immunocompromised paediatric host. In neonates and children, infections account for a high percentage of hospital admissions, and anti-infectives are the most used drugs. However, paediatric PK/PD studies and the evidence regarding the efficacy and safety of some newly marketed antibiotics and antifungals-usually used off-label in paediatrics-to determine the optimal drug dosage regimens are limited. It is widely known that this population presents important differences in the PK parameters (especially in drug clearance and volume of distribution) in comparison with adults that may alter antimicrobial exposure and, therefore, compromise treatment success. In addition, paediatric patients are more susceptible to potential adverse drug effects and they need closer monitoring. The aim of this document, developed jointly by the Spanish Society of Hospital Pharmacy and the Spanish Society of Paediatric Infectious Diseases, is to describe the available evidence on the indications for therapeutic drug monitoring (TDM) of antibiotics and antifungals in newborn and paediatric patients, and to provide practical recommendations for TDM in routine clinical practice to optimise their dosing, efficacy and safety. Of antibiotics and antifungals in the paediatric population., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest regarding the content of this consensus document., (Copyright © 2024 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

Therapeutic monitoring of antibiotics and antifungals based on pharmacokinetic and pharmacodynamic parameters, is a strategy increasingly used for the optimization of therapy to improve efficacy, reduce the occurrence of toxicities, and prevent the selection of antimicrobial resistance, particularly in vulnerable patients including neonates and the critical or immunocompromised host. In neonates and children, infections account for a high percentage of hospital admissions and anti-infectives are the most used drugs. However, pediatric pharmacokinetic and pharmacodynamic studies and the evidence regarding the efficacy and safety of some newly marketed antibiotics and antifungals -usually used off-label in pediatrics- to determine the optimal drug dosage regimens are limited. It is widely known that this population presents important differences in the pharmacokinetic parameters (especially in drug clearance and volume of distribution) in comparison with adults that may alter antimicrobial exposure and, therefore, compromise treatment success. In addition, pediatric patients are more susceptible to potential adverse drug effects and they need closer monitoring. The aim of this document, developed jointly between the Spanish Society of Hospital Pharmacy (SEFH) and the Spanish Society of Pediatric Infectious Diseases (SEIP), is to describe the available evidence on the indications for therapeutic drug monitoring of antibiotics and antifungals in newborn and pediatric patients and to provide practical recommendations for therapeutic drug monitoring in routine clinical practice to optimize pharmacokinetic and pharmacodynamic parameters, efficacy and safety of antibiotics and antifungals in the pediatric population., (Copyright © 2024 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives: In Latin America, experience with monitoring serum Infliximab (IFX) concentrations is scarce. Our study aimed to compare IFX serum concentrations between patients with active disease or in remission., Patients and Methods: A cross-sectional study was performed in patients with luminal Crohn's disease (CD) during maintenance treatment with IFX. Patients were classified as in remission or disease activity according to clinical scores and endoscopic, radiological, and laboratory markers. A comparison of IFX trough levels between the two groups was performed., Results: 80 CD patients were included [41 (51%) in remission and 39 (49%) with active disease]. In the analysis of general disease activity, the median serum levels of IFX in patients with remission and with active CD were 5.63 [0.03-14.40] vs. 3.84 [0.03-14.40] (p=0.287). Furthermore, there was no difference in serum IFX concentrations in endoscopic, radiological, and laboratory activities. Only in the clinical evaluation there was a significant difference in the median serum IFX levels between patients in remission and disease activity, 5.63 [0.03-14.40] vs. 2.14 [0.32-10.54] (p=0.042)., Conclusions: IFX serum concentrations during maintenance treatment were similar in patients with luminal CD in remission and general, endoscopic, radiological, and laboratory disease activity. Patients with clinically active disease had lower IFX concentrations than patients in remission., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

The treatment of inflammatory bowel disease has undergone a significant transformation following the introduction of biologic drugs. Thanks to these drugs, treatment goals have evolved from clinical response and remission to more ambitious objectives, such as endoscopic or radiologic remission. However, even though biologics are highly effective, a significant percentage of patients will not achieve an initial response or may lose it over time. We know that there is a direct relationship between the trough concentrations of the biologic and its therapeutic efficacy, with more demanding therapeutic goals requiring higher drug levels, and inadequate exposure being common. Therapeutic drug monitoring of biologic medications, along with pharmacokinetic models, provides us with the possibility of offering a personalized approach to treatment for patients with IBD. Over the past few years, relevant information has accumulated regarding its utility during or after induction, as well as in the maintenance of biologic treatment, in reactive or proactive strategies, and prior to withdrawal or treatment de-escalation. The aim of this document is to establish recommendations regarding the utility of therapeutic drug monitoring of biologics in patients with inflammatory bowel disease, in different clinical practice scenarios, and to identify areas where its utility is evident, promising, or controversial., (Copyright © 2024 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: A specialized service for antifungal blood level determination is not available in Colombia. This service is essential for the proper follow-up of antifungal therapies., Objective: To standardize and validate a simple, sensitive, and specific protocol based on high-performance liquid chromatography with a diode array detector for voriconazole blood level quantification., Materials and Methods: We used an Agilent HPLC™ series-1200 equipment with a UVdiode array detector with an analytical column Eclipse XDB-C18 and pre-column Eclipse- XDB-C18 (Agilent). We used voriconazole as the primary control and posaconazole as an internal control. We performed the validation following the Food and Drug Administration (FDA) recommendations., Results: The best chromatographic conditions were: Column temperature of 25°C, UV variable wavelength detection at 256 nm for voriconazole and 261 nm for posaconazole (internal standard); 50 μl of injection volume, 0,8 ml/min volume flow, 10 minutes of run time, and mobile phase of acetonitrile:water (60:40). Finally, retention times were 3.13 for voriconazole and 5.16 minutes for posaconazole. Quantification range varied from 0.125 μg/ml to 16 μg/ml., Conclusion: The selectivity and chromatographic purity of the obtained signal, the detection limits, and the standardized quantification make this method an excellent tool for the therapeutic monitoring of patients treated with voriconazole.

Objective: The objective of the study was to analyze and describe the concentrations of eculizumab and the complement blockade in patients with atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy, and to define a therapeutic margin where there is a high probability of achieving therapeutic efficacy., Methods: Observational, ambispective, and multicenter study that included adult and pediatric patients diagnosed with aHUS and C3 glomerulopathy from September 2020 to October 2022 in 5 hospitals in Spain. Eculizumab was administered at the doses recommended by the data sheet according to the European Medicines Agency (EMA). Pre- and post-dose concentrations of eculizumab were determined, as well as blockade of the classical complement pathway (CH50). Sociodemographic and clinical data were collected, and pharmacokinetic parameters were calculated. To establish the cut-off point for eculizumab concentrations that predicted complement blockade, Receiver Operating Characteristic (ROC) curve analysis was performed. Lastly, the Kruskal-Wallis test was used to contrast the differences in different parameters according to eculizumab concentrations., Results: Twenty-five patients were included, 19 adults (76.0%) and 6 pediatrics (24.0%), with median ages of 43.4 (interquartile range (IQR) 35.7-48.8) and 10.1 (IQR 9.6-11.3) years, respectively. Of these, 22 (88.0%) patients were diagnosed with aHUS and 3 (12.0%) with C3 glomerulopathy. A total of 111 eculizumab concentrations were determined. Mean pre- and post-dose concentration values detected during the maintenance phase were 243.8 (SD 240.6) μg/mL and 747.4 (standard deviation (SD) 444.3) μg/mL, respectively. Increased complement blockade was observed at higher pre-dose concentrations (P = .002) and decreased serum creatinine at both higher pre- and post-dose concentrations (P = .001 and P = .017, respectively). Using ROC curves, it was determined that a pre-dose concentration >149.0 μg/mL was optimal to achieve complement blockade, with an AUC of 0.87 (0.78-0.95). Finally, high inter-individual (48.9% variation coefficient (CV)) with low intra-individual variabilities (11.9% CV) in eculizumab clearance were observed., Conclusions: The present study reports supratherapeutic concentrations of eculizumab in patients with aHUS, and defines higher concentrations than those described in the data sheet to achieve blockade, thus encouraging the personalization of treatment with eculizumab., Competing Interests: Conflict of interest None declared., (Copyright © 2023 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: The objective of the study was to analyze and describe the concentrations of eculizumab and the complement blockade in patients with atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy, and to define a therapeutic margin where there is a high probability of achieving therapeutic efficacy., Methods: Observational, ambispective and multicenter study that included adult and pediatric patients diagnosed with aHUS and C3 glomerulopathy from September 2020 to October 2022 in five hospitals in Spain. Eculizumab was administered at the doses recommended by the data sheet according to the European Medicines Agency (EMA). Pre-dose and post-dose concentrations of eculizumab were determined, as well as blockade of the classical complement pathway (CH50). Sociodemographic and clinical data were collected, and pharmacokinetic parameters were calculated. To establish the cut-off point for eculizumab concentrations that predicted complement blockade, Receiver Operating Characteristic (ROC) curve analysis was performed. Lastly, the Kruskal-Wallis test was used to contrast the differences in different parameters according to eculizumab concentrations., Results: Twenty-five patients were included, 19 adults (76.0%) and 6 pediatrics (24.0%), with median ages of 43.4 (IQR 35.7-48.8) and 10.1 (IQR 9.6-11.3) years, respectively. Of these, 22 (88.0%) patients were diagnosed with aHUS and 3 (12.0%) with C3 glomerulopathy. A total of 111 eculizumab concentrations were determined. Mean pre-dose and post-dose concentration values detected during the maintenance phase were 243.8 (SD 240.6) μg/mL and 747.4 (SD 444.3) μg/mL, respectively. Increased complement blockade was observed at higher pre-dose concentrations (p=0.002) and decreased serum creatinine at both higher pre- and post-dose concentrations (p=0.001 and p=0.017, respectively). Using ROC curves, it was determined that a pre-dose concentration >149.0 μg/mL was optimal to achieve complement blockade, with an AUC of 0.87 (0.78-0.95). Finally, high inter-individual (48.9% CV) with low intra-individual variabilities (11.9% CV) in eculizumab clearance were observed., Conclusions: The present study reports supratherapeutic concentrations of eculizumab in patients with aHUS, and defines higher concentrations than those described in the data sheet to achieve blockade, thus encouraging the personalization of treatment with eculizumab., (Copyright © 2023 Sociedad Española de Farmacia Hospitalaria (S.E.F.H). Publicado por Elsevier España, S.L.U. All rights reserved.)

RESUMENObjetivo: Determinar la incidencia de resultados clínicos negativos–RNM en pacientes hospitalizados con prescripción de medicamentos trazadores/señaladores durante su estancia hospitalaria.Método: Diseño: Estudio de cohorte abierta. Ámbito: Institución de Salud de alta complejidad - Medellín. Periodo: noviembre de 2013 – noviembre de 2015. Muestra: Grupos (expuestos y no expuestos) se clasificaron como pacientes con uno o más medicamentos trazadores y sin ellos, en una relación 1 (expuestos): 2 (no expuestos); ambos grupos se parearon por variables socio-demográficas y clínicas; edad con una diferencia no mayor a +/- 5 años, sexo, diagnóstico principal y comorbilidades principalmente. Variables: número de medicamentos trazadores; mediante seguimiento farmacoterapéutico - SFT se identificaron problemas de necesidad, efectividad y seguridad asociada a los medicamentos. Resultados: Se incluyó 324 pacientes, 108 (33,3%) expuestos y 216 (66,7%) no expuestos. La edad media fue 52 años (DE 25,7), 198 (61%) hombres. El 31,2% (101) de los pacientes presentó algún tipo de RNM. En los expuestos, la incidencia de RNM fue 43,5% (47 pacientes) y en los no expuestos la frecuencia de RNM fue 25% (54 pacientes). Se observó mayor incidencia de RNM en pacientes con 2 a 3 medicamentos (49,1%) (RD: 0,666 IC95%: 0,503-0,883). El riesgo asociado a la exposición al factor de riesgo (RR) fue 1,74 (IC 95%; 1,27 – 2,38) (P= 0,01). Conclusiones: La utilización de medicamentos trazadores/señaladores está asociada a la presentación de RNM. Por tanto, esta estrategia se podría utilizar para la identificación, priorización y selección de pacientes en los programas de farmacoseguridad. ABSTRACT Objective: To determine the incidence of negative clinical results – MNR in hospitalized patients with prescription tracer/marker drugs during their hospital stay. Method: Design: open cohort study. Scope: high complexity Health Institution - Medellin. Period: November 2013 - November 2015. Sample: groups (exposed and unexposed) were classified as patients with one or more tracer drugs and without them, in a ratio 1 (exposed): 2 (not exposed); both groups were matched by socio-demographic and clinical variables; age with a difference no greater than +/- 5 years, sex, main diagnosis and comorbidities mainly. Variables: number of tracer drugs; Pharmacotherapeutic follow-up - SFT identified problems of need, effectiveness and safety associated with drugs. Results: We included 324 patients, 108 exposed (33.3%) and 216 unexposed (66.7%). The average age was 52 years (SD: 25.7), 198 (61%) patients were male. 31.2% (101) of patients had some type of medication Negative Results. In those exposed, the incidence of MNR was 43.5% (47 patients) and in the no exposed the frequency of MNR was 25% (54 patients). A higher incidence of MNR was observed in patients with 2 to 3 medications (49.1%) (RD: 0.666 IC95%: 0.503-0.883). The risk associated with the risk factor (RR) was 1.74 (CI 95% 1.27 - 2.38) (P = 0.01). Conclusions: The use of tracer/marker drugs is associated with the presentation of MNR. Therefore, this strategy could be used to identify and prioritize the selection of patients who must enter the pharmacy safety programs.

Background and Objectives: There is increasing evidence that proactive monitoring is useful in improving the control of inflammatory bowel disease, although it remains controversial. The aim of this study was to evaluate the efficacy of proactive TDM based on the Bayesian approach to optimise the IFX dose compared with the standard of care dosing in patients with IBD., Methods: Retrospective observational cohort of inflammatory bowel disease patients>18 years. Patients were classified into two groups according to the strategy used to optimise the dose of IFX: a standard therapy group (ST-group) with clinically based dose adjustment and therapeutic drug monitoring group (TDM-group), with estimation of pharmacokinetic parameters calculated by Bayesian prediction., Results: A total of 153 patients were included. Of these, 75 were in the TDM-group. Clinical response at week 52 was evaluated in 114 patients. The proportion of patients who achieved clinical remission was higher in the TDM than in the ST-group (80.7% vs 61.4%, respectively, p=0.023). A total of 28 patients (24.6%) met the parameters for the composite variable 'poor clinical outcome' at week 52. The proportion of patients who reached this outcome was lower in the TDM-group than in the ST-group (12.3% vs 36.8%, respectively, p=0.002)., Conclusions: Proactive therapeutic drug monitoring using Bayesian approach is associated with higher secondary response and fewer long-term complications., (Copyright © 2022 Elsevier España, S.L.U. All rights reserved.)

O objetivo do estudo foi estimar o efeito do tempo e das características individuais na ocorrência de evento adverso a medicamentos em pacientes com afecções cardiológicas. Trata-se de um estudo avaliativo sobre a ocorrência de evento adverso a medicamentos realizado em um hospital público e cardiológico, localizado no Município do Rio de Janeiro. Para análise da sobrevida utilizou-se o método de Kaplan-Meier. A probabilidade de sobreviver livre de evento adverso a medicamentos até 30, 60 e 100 dias foi respectivamente de 96%, 93% e 73%. Os eventos adversos a medicamentos representam condições marcadoras que descrevem o desempenho dos serviços de saúde. A detecção de eventos adversos nas instituições hospitalares possibilita conhecer as falhas que ocorrem no sistema de medicação e ainda implementar estratégias para reduzi-las.El objetivo del estudio fue estimar el efecto del tiempo y de las diferencias individuales en la ocurrencia de eventos adversos por medicamentos en pacientes con enfermedades cardíacas. Este es un estudio de evaluación sobre la presencia de evento adverso a cabo en un hospital público y cardiología, ubicado en Río de Janeiro. Para el análisis de supervivencia se utilizó el método de Kaplan-Meier. La probabilidad de supervivencia libre de eventos adversos por medicamentos por 30, 60 y 100 días fueron respectivamente del 96%, 93% y 73%. Los eventos adversos por medicamentos representan condiciones marcadoras que describen el desempeño de los servicios de salud. La detección de eventos adversos en los hospitales hace que sea posible conocer los errores que ocurren en el sistema de medicación, así como aplicar estrategias para reducirlos.The objective of the study was to estimate the time effect and the individual characteristics in the occurrence of an adverse event to drugs in patients with cardiac diseases. It is an evaluative study about the occurrence of an adverse event to drugs that took place at a public and cardiologic hospital, located in the city of Rio de Janeiro. For the analysis of the survival, the method Kaplan-Meier was used. The probability of surviving free from an adverse event to drugs up to 30, 60 and 100 days was respectively of 96%, 93% and 73%. The adverse events to drugs represent marking conditions that describe the performance of the health services. The detection of adverse events in hospitals makes it possible to know the failures that occur in the medication system and also to implement strategies to reduce them.

Foram analisados os resultados da implantação de estratégia de monitoramento de efeitos adversos aos medicamentos em hospital público no Rio de Janeiro, RJ, em 2007. Com base em análise retrospectiva de 32 prontuários foram encontrados efeitos adversos em 16%. Para identificá-los, foram precisos 38 critérios rastreadores, dos quais os principais foram: uso de antieméticos, interrupção abrupta de medicamentos e sedação excessiva. Apesar das dificuldades, sobretudo relacionadas ao acesso às informações e à qualidade dos registros, a aplicação dos critérios rastreadores parece ser viável. Para aprimorar a implantação do método, sugere-se informatizar a coleta de informações e buscar indicadores de ajuste de risco.Fueron analizados los resultados de la implantación de estrategia de monitoreo de efectos adversos a los medicamentos en hospital público en Rio de Janeiro, Sureste de Brasil, en 2007. Con base en análisis retrospectivo de 32 prontuarios fueron encontrados efectos adversos en 16%. Para identificarlos, fueron necesarios 38 criterios rastreadores, de los cuales los principales fueron: uso de antieméticos, interrupción abrupta de medicamentos y sedación excesiva. A pesar de las dificultades, sobre todo relacionadas con el acceso a las informaciones y a la calidad de los registros, la aplicación de los criterios rastreadores parece ser viable. Para perfeccionar la implantación del método, se sugiere informatizar la colecta de datos y buscar indicadores de ajuste del riesgo.The results from implementing a strategy for monitoring adverse effects from drugs in a public hospital in the municipality of Rio de Janeiro, Southeastern Brazil, in 2007, were analyzed. Based on retrospective analysis of 32 medical files, adverse effects were found in 16%. To identify these effects, 38 tracking criteria were needed. Among these, the main ones were the use of antiemetics, abrupt cessation of medication and over-sedation. Despite the difficulties, especially in relation to access to information and the record quality, application of these tracking criteria seems to be viable. To improve the implementation of the method, it is suggested that the data collection should be computerized and risk adjustment indicators should be sought.

This exploratory-descriptive, non-experimental quantitative research aimed to learn about immediate adverse reactions to intravenous iodinated contrast media in hospitalized patients submitted to computed tomography at a teaching hospital in the South of Brazil. During the study period, all adverse reactions showed mild intensity, at a frequency of 12.5% with ionic iodinated contrast media, and 1% with non-ionic contrast agent. The extravasation of contrast occurred in 2.2% of the injections in a peripheral vein without complications in any of the cases. The results are within the limits cited in international literature and suggest that tomography service professionals should know their own rates of adverse reactions to iodinated contrast agent, as well as the conditions in which they occur, in order to obtain evidence to evaluate the respective care delivery processes.Investigación cuantitativa del tipo exploratorio-descriptivo, de carácter no experimental. El objetivo consistía en conocer las reacciones adversas inmediatas al contraste yodado intravenoso en pacientes internados, sometidos a tomografía computarizada en un hospital escuela del sur de Brasil. Durante el período del estudio, todas las reacciones adversas tuvieron intensidad leve y una frecuencia del 12,5% con la utilización del contraste yodado iónico, y 1% con contraste no iónico. La extravasación del contraste ocurrió en un 2,2% de las inyecciones en vena periférica, no ocasionando complicaciones en ninguno de los casos. Los índices evidenciados en el presente estudio se mantuvieron dentro de los límites que constan en la revisión de literatura y, entre las recomendaciones, se sugiere que los servicios de tomografía conozcan los propios índices de reacciones adversas al contraste yodado y las condiciones en que ocurren, con la finalidad de obtener evidencias para evaluación de los respectivos procesos asistenciales.Pesquisa quantitativa, exploratório-descritiva, de caráter não experimental, com o objetivo de conhecer as reações adversas imediatas ao contraste iodado intravenoso em pacientes hospitalizados, submetidos a tomografia computadorizada num hospital-escola no Sul do Brasil. Durante o período de estudo, todas as reações adversas manifestaram-se na intensidade leve, com freqüência de 12,5% com o uso de contraste iodado iônico e 1% com contraste não iônico. Extravasamento do meio radiopaco ocorreu em 2,2% das injeções em veia periférica, não havendo complicações em nenhum dos casos. Os resultados encontram-se dentro dos limites citados na literatura internacional e sugere-se que os serviços de tomografia conheçam as próprias taxas de reações adversas ao contraste iodado e as condições em que elas ocorrem, a fim de obter evidências para a avaliação dos respectivos processos assistenciais.

Competing Interests: Conflicts of interest There are no conflicts of interest to declare.

Background: Plasma level-based therapeutic drug monitoring of vancomycin is recommended in the treatment of complex pediatric infections in order to increase the probability of achieving safe and effective pharmacotherapy., Objective: To retrospectively evaluate the activities and performance of pharmacotherapeutic optimization based on vancomycin levels at a tertiary pediatric hospital between 2007 and 2020., Métodos: Vancomycin levels of pediatric patients were analyzed, assessing care quality indicators and analytical verifications, as well as aspects related to teaching and research. The predictive performance of vancomycin levels was evaluated after adjustment of the therapeutic regimen using a population pharmacokinetic optimization program (BestDose v1.126) considering the coefficient of determination (R2), the mean absolute percentage error (MAPE), and the root mean square error (RMSE)., Results: 13269 vancomycin level determinations were analyzed; 70% were trough levels and 81% belonged to patients in the intensive care units. Forty percent of the trough levels were within the therapeutic range when adjusted without software. Three hundred seventy-four pharmacotherapeutic interventions, of which 97% were accepted by the treating physician; 75% of the post-adjustment trough levels were within the therapeutic range, compared to 40% when the approach was empirical, a difference that was statistically significant (p=0.03). The values associated with predictive performance (n subgroup of patients = 91) were: R2=0.61, MAPE=28.16%, and RMSE=3.3, which all showed to be adequate., Conclusion: The performance of therapeutic vancomycin monitoring and related pharmacokinetic clinical activities showed to be good., (Universidad Nacional de Córdoba)

The objective of this study was to evaluate studies on the occurrence of adverse drug events (ADEs) in hospitals in order to learn about their frequency and characteristics, comparing the methods for identifying them and the various definitions. A search was conducted on MEDLINE and identified studies published from 2000 to 2009. Inclusion criteria were: studies in populations not selected for specific diseases or drugs and ADEs that occurred during hospitalization. Twenty-nine studies were selected, displaying multiple sources of heterogeneity, including differences in the study populations, surveillance techniques, definitions of ADEs, and indicators. The proportion of patients with ADEs ranged from 1.6% to 41.4% of inpatients and the rates ranged from 1.7 to 51.8 events/100 admissions. A considerable share of these events could have been avoided. The findings show that ADEs in inpatients are a public health problem. However, further studies are needed to monitor these adverse events in order to effectively promote safe drug use.O objetivo foi avaliar estudos sobre a ocorrência de eventos adversos a medicamentos (EAM) em hospitais para conhecer as suas freqüências e características, comparando os métodos de identificação e as definições utilizadas para caracterizá-los. A busca foi realizada no MEDLINE e identificou estudos publicados entre 2000 e 2009. Os critérios de inclusão foram estudos em população não selecionada por patologias ou medicamentos específicos e os EAM ocorridos durante a internação. Foram selecionados 29 estudos e encontradas múltiplas fontes de heterogeneidade entre eles, incluindo diferenças nas populações estudadas, nas técnicas de vigilância, nas definições de EAM e nos indicadores. A freqüência de pacientes com EAM está entre 1,6% e 41,4% dos pacientes internados e as taxas entre 1,7 e 51,8 eventos/100 internações. Uma parte considerável desses eventos poderia ter sido evitada. Os resultados mostram que EAM em pacientes internados são um problema de saúde pública. Entretanto, são necessários novos estudos de monitoramento desses eventos adversos para a efetiva promoção do uso seguro dos medicamentos.

Objective: We aimed to reach a consensus on the best instruments to monitor disease activity in patients with psoriatic arthritis (PsA) and to develop a consensus definition of remission., Methods: A modified Delphi approach was used. A scientific committee provided statements addressing the definition of remission and the monitoring of PsA in clinical practice. The questionnaire was evaluated in 2 rounds by rheumatologists with experience in managing PsA patients., Results: A panel of 77 rheumatologists reached agreement on 62 out of the 86 proposed items (72.0%). The most recommended index for monitoring disease activity was DAPSA (cut-off values: ≤4 for remission and >4-14 for low disease activity ([LDA]), MDA (at least 5/7 criteria). In cases with axial involvement, ASDAS was the preferred index (cut-off values: <1.3 for remission and <2.1 for LDA). BASDAI (cut-off values: ≤2 for remission and ≤4 for LDA) may be used as an alternative. PsAID was the preferred tool to assess disease impact., Conclusion: We propose a definition of remission in PsA as the absence of disease activity evaluated by DAPSA or MDA (ASDAS and/or BASDAI in patients with axial involvement), which would imply absence of signs or symptoms of inflammation, physical well-being, lack of disease impact, and absence of inflammation as measured by biological markers., (Copyright © 2019 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Background: The monitoring of antimicrobial therapy through plasma levels makes it possible to determine the optimal dosage of antimicrobials, an essential approach in pediatrics., Aim: To describe the monitoring of plasma antimicrobial levels and dose adjustment in the pediatric population to determine if the doses used reach therapeutic ranges., Methods: Retrospective, descriptive study using a database with measurement of plasma levels of amikacin and vancomycin in pediatric patients at San Borja Arriarán Hospital between 2015-2018. The number of patients who reached the therapeutic range with the initial dose, how many required adjustment and their characteristics were determined., Results: 104 total levels were monitored. For vancomycin 65 plasmatic levels were baseline, being outside the therapeutic range 56.5%; 25% of those requiring adjustment were neonates with a higher probability of being out of range versus others (p = 0.022). For amikacin, Cpeak was in range in 60% of measurements; 15.4% required adjustment, including patients with cystic fibrosis and cancer, without adjustments in patients without comorbidity., Conclusion: Measurement of plasma levels is necessary to individually adjust the dose, especially in pediatric patients with cystic fibrosis, oncology and in neonatology where it is more likely not to reach a therapeutic range with initial doses.

Objective: There have been only few studies investigating the role of PSMA ligands in the therapy response assessment of metastasized castration resistant prostate cancer (mCRPC) cases. In this study we aimed at evaluating the capability of 68 Ga- prostate-specific membrane antigen (PSMA) I&T positron emission tomography/computerized tomography (PET/CT) in the assessment of therapeutic response in patients under docetaxel therapy for prostate cancer (PCa)., Material and Methods: The clinical records of all mCRPC patients treated with docetaxel and referred to our department for 68 Ga-PSMA I&T PET/CT imaging were retrospectively analysed. Sixteen patients (mean age 69 years, range 52-82 years) with castration-resistant prostate cancer patients receiving palliative docetaxel therapy and had undergone 68 Ga-PSMA I&T PET/CT scan were included in the study. 68 Ga-PSMA I&T PET/CT imaging was done and prostate specific antigen (PSA) levels were measured at baseline before administration of docetaxel (PET1) and after at least 3 cycles (range 4-12) of chemotherapy (PET2). Patient-based as well as lesion-based comparison of PET2 findings with PET1 findings were done., Results: The change (decrease) observed in lymph node and prostate gland/prostatic bed SUVmax values after treatment compared to pretreatment was found to be statistically significant (P=.033). 3/16 patients (19%) were classified as progressive disease (PD), 4/16 (25%) as stable disease (SD), 9/16 (56%) as partial remission (PR) radiologically. An increasing PSA trend (IT) was observed in 4 patients (25%) and a decreasing PSA trend (DT) in 3 patients (18%). Nine patients showed a PSA response of ≥ 50% (56%). Of the 4 patients showing SD, 3 had IT, 3 had BR. Of the 9 patients who showed PR on PET studies, 8 patients showed BR and 1 patient showed DT., Conclusion: Imaging with 68 Ga-PSMA PET/CT showed great concordance with biochemical response evaluation in terms of PSA levels, especially in patients showing good response to therapy. 68 Ga-PSMA PET/CT was also successful in identifying progressive disease in patients showing paradoxical decline in PSA levels., (Copyright © 2020 Sociedad Española de Medicina Nuclear e Imagen Molecular. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: Thiopurines are drugs widely used in patients for the maintenance of remission in inflammatory bowel disease. The optimal plasma levels are known, but there is controversy about whether the need for other drugs is reduced or is cost-effective. The aim of this study is to describe the use of the optimised treatment with thiopurines in paediatric patients with inflammatory bowel disease followed up in this Unit since the introduction of determining the drug levels., Material and Methods: A descriptive retrospective study was conducted in which the plasma values of 6-thioguanine (6-TGN), 6-methyl-mercapto-purine (6-MMP), and their ratios were analysed using liquid chromatography. Other variables were collected, such as clinical status, analytical and demographic variables of patients with inflammatory bowel disease followed up in this Unit., Results: A total of 72 patients were included, and 149 determinations of metabolites were performed. The 6-TGN levels were found to below the therapeutic range in 61.5% of patients (in 7 cases due to lack of adherence to therapy), and 6-MMP was in the toxicity range in 7.4%. After the determination of 77 specimens, some action was taken, such as modifying the dose, change of formula, or withdrawing the drug. Only 9 patients were scaled to a biological drug (13.4% of the total on single therapy). No association was found between the activity of the disease and the thiopurine levels., Conclusions: In our experience, the monitoring of thiopurine levels helped to modify the drug dose that the patient received, adjusting their therapeutic levels, and potentially avoiding the addition of new drugs., (Copyright © 2019. Publicado por Elsevier España, S.L.U.)

Introduction: CT-P13 is a biosimilar drug of infliximab (IFX), effective in patients with inflammatory bowel disease (IBD). The monitoring of levels of IFX and anti-IFX antibodies is now considered part of the integral management., Objective: To compare the clinical response according to a strictly clinical (CLN) or proactive (PRO) approach based on the monitoring of levels in week 14, in clinical practice., Methods: We conducted a prospective study in IBD patients starting CT-P13. In the PRO group, levels of IFX and post-induction antibodies were systematically measured (week 14) and those with infraterapeutic levels (<3μg/ml) were intensified, irrespective of the clinical response., Results: We included 77 patients (23 ulcerative colitis and 54 Crohn's disease). Both PRO (n=41) and CLN (n=36) groups showed initial and long-term efficacy without significant differences. At week 14, 61% clinical remission (CR) (58.5% PRO, 63.9% CLN) and 80.5% at least partial response (PR) (80.5% PRO, 80.6% CLN). In week 54, 68.8% CR (61% PRO, 77.8% CLN) and 76.6% at least PR (73.2% PRO, 80.6% CLN). Of the patients in CR in week 14 (24 PRO, 23 CLN), 13 of the PRO group were intensified due to infra-therapeutic levels. In this subgroup no significant differences were observed in secondary loss of response (PRO 0%, CLN 8.7%)., Conclusion: Proactive management does not improve response or remission rates in the first year. The intensification of clinical remission patients with post-induction infratherapeutic levels does not seem to significantly prevent secondary loss of response in the first year., (Copyright © 2019 Elsevier España, S.L.U. All rights reserved.)

Objective: to evaluate the usefulness of serum concentrations (Sc) of adalimumab (ADA) as a predictor of medication adherence using the medication possession ratio (MPR) and Morisky Green test (MGT) in patients with chronic inflammatory diseases., Material and Method: Design a prospective descriptive cohort study., Inclusion Criteria: adult patients diagnosed with inflammatory arthropathy (IA) or inflammatory bowel disease (IBD) treated with ADA., Exclusion Criteria: positive anti-adalimumab antibody., Variables: sex, age, diagnosis, dosage regimen, Sc (mg/mL), MPR (MPR ≥ 80% adherent) and MGT (non-adherent or adherent). Statistical analysis was performed using STATA v13.0., Results: Forty-five patients (23 women) with an age of 52.22 (14.39) years, 17 IBD (37.78%), 26 IA (57.78%) and 2 with both conditions (4.44%) treated with 40mg ADA every 14 days (42/45; 93.33%) or every 7 days (3/45; 6.67%). We detected subtherapeutic Sc in 22.22% of patients (10/45); 10% (1/10) were classified as non-adherent and 90% (9/10) as adherent according to MGT and MPR. The quantification of Sc shows weak agreement with MPR, as was the case with the indirect methods of each (MPR and MGT). The association was slightly greater when the indirect methods were compared to each other (0.244 vs. 0.378)., Conclusion: the determination of Sc of ADA alone has limited utility in the detection of non-adherent patients., (Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Introduction: Clozapine plasma levels are useful to monitor drug compliance, and also to assess and to prevent some side effects. Recently, routine monitoring to all clozapine-treated patients has been proposed to prevent relapses. However, high intra-individual variability in plasma levels has been reported too, although these studies have some limitations., Methods: We analysed differences between 2clozapine plasma levels separated by at least one year in a subgroup of 28 outpatients (82% male, mean age 47.9 years-old) with diagnosis of non-affective psychosis in clinical remission whose clozapine doses and smoking habits remained unchanged., Results: We found a non-significant increase in clozapine plasma levels [.30mg/L (SD=.14) vs. .32 (SD=.17); t=-.858, p=.40] and a significant decrease in norclozapine plasma levels [.27 (SD=.11) vs. .22 (SD=.10); t=3.27; p=.003]. Absolute coefficient of variation (CV) between first and second assessment were calculated. Forty-six and fifty-seven percent of cases had CV 20% in clozapine and norclozapine, respectively. CV of 50% was seen in 20.7% and 13.8% of clozapine and norclozapine test respectively. We discussed potential causes of such high CV., Conclusions: Our study suggest high intra-individual variation even in a subgroup of very stable patients, which suggest that routine monitoring of these levels may be indicated in order to detect significant plasma variations. We think that clinicians should act with caution in case of a sudden decrease in plasma level. In the absence of obvious symptom severity variation, sources of intra-individual fluctuations might be considered first, before assuming poor compliance., (Copyright © 2019 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.)

Invasive fungal disease (IFD) is a condition affecting immunosuppressed and critically ill patients. Recently there has been an increase in the amount of patients at risk for IFD, which implies an increase in the prescription of antifungal agents as prophylactic, pre-emptive or empiric therapy. Some studies evaluating appropriateness of antifungal prescription have shown that inappropriate formulations reach 72%, exposing patients to side effects, pharmacological interactions and rising costs. Some groups have recommended many interventions to control and make a rational use of antimicrobials, into strategies known as "antimicrobial stewardship", these interventions are useful also for antifungal agents and it has been named "antifungal stewardship". Here we present a narrative review of the scientific literature showing published articles about appropriate use of antifungal agents and the experience of some centers after implementing antifungal stewardship programs.

Introduction: To evaluate the changes in the susceptibility of Pseudomonas aeruginosa over time (2000-2017) against antimicrobials used in an intensive care unit of a Spanish tertiary hospital, and to compare them with the antimicrobial activity considering theoretical pharmacokinetic/pharmacodynamic (PK/PD) criteria. The influence of the method for handling duplicate isolates to quantify susceptibility rates was also evaluated., Methods: The susceptibility was studied considering the Clinical and Laboratory Standards Institute (CLSI) breakpoints. Monte Carlo simulations were conducted to calculate the cumulative fraction of response (CFR). Linear regression analysis was applied to determine the trends in susceptibility and in the CFR., Results: A significant decrease in the susceptibility to gentamicin and imipenem was observed, and more recently the highest percentages of susceptible strains were found for amikacin, cephalosporins and piperacillin/tazobactam (>80%). The probability of success of an empiric treatment or CFR for most of the evaluated antimicrobials was lower than 70% during the last two-year period. Only meropenem provided high probabilities (>90%) to achieve the PK/PD target. Cephalosporins provided moderate probabilities (>80%) although for ceftazidime, the highest dose (2g/8h) was required. Moreover, a significant decrease in the CFR trend for ciprofloxacin, imipenem and levofloxacin was observed., Conclusions: Both susceptibility rates and CFR values have to be considered together to optimize the antimicrobial dose regimen for clinical making-decisions. They are complementary tools and, they should be used jointly in surveillance programmes. In fact, susceptibility data are not always useful to detect changes in the CFR. No relevant differences were observed among the methods for handling repeated isolates., (Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Objective: To evaluate incorporation of the hospital pharmacist to the routine activity of an Intensive Care Unit (ICU)., Design: A prospective observational study was carried out to evaluate the impact of pharmacist interventions, made by a pharmacist temporarily assigned to the ICU, upon medical prescriptions., Setting: A medical and surgical ICU with 21 beds., Patients: Patients with at least one ICU stay were included, while patients with admission and discharge in periods when the pharmacist was not present were excluded., Interventions: The interventions were made after daily review of the prescriptions, and were communicated verbally or in writing to the supervising physician., Main Variables: Number of interventions, therapeutic group of the drugs involved, type of intervention and degree of acceptance., Results: A total of 194 interventions were made in 62 patients. The majority were related to safety aspects (33%) and the optimization of therapy (32%). The most frequent interventions were the administration of drugs via the nasogastric tube (19%) and pharmacokinetic monitoring (14.4%). The most frequently involved groups of drugs were anti-infectious agents (33%) and digestive system medications (27%). A total of 56.2% of the interventions were made verbally, and 80% were accepted., Conclusions: Pharmacist adscription to an ICU and the implementation of interventions on prescriptions have allowed improvement of safety and the optimization of pharmacotherapy in more than 50% of the patients. The high rate of acceptance of these interventions would support the implementation of such programs in critical care units., (Copyright © 2018 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.)

Patients with chronic inflammatory diseases being treated with immunosuppressive drugs, and with tumor necrosis factor inhibitors in particular, have an increased risk of infection by Mycobacterium tuberculosis. Screening for latent tuberculosis infection and preventive therapy to reduce the risk of progression to active tuberculosis are mandatory in this group of patients. This updated multidisciplinary consensus document presents the latest expert opinions on the treatment and prevention of tuberculosis in candidates for biologic therapy and establishes recommendations based on current knowledge relating to the use of biologic agents., (Copyright © 2018 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: The main purpose of this recommendation statement is to provide clinicians with the best available evidence and the best opinion agreed upon by the panelists for a rational use of synthetic disease modifying antirheumatic drugs (DMARDs) and biologicals in psoriatic arthritis (PsA) patients. The present document also focuses on important aspects in the management of PsA, such as early diagnosis, therapeutic objectives, comorbidities and optimization of treatment., Methods: The recommendations were agreed by consensus by a panel of 8 expert rheumatologists, previously selected by the Spanish Society of Rheumatology (SER) through an open call. The phases of the work were: identification of key areas for updating the previous consensus, analysis and synthesis of scientific evidence (modified Oxford system, Centre for Evidence-based Medicine, 2009) and formulation of recommendations based on this evidence and by consensus techniques., Results: Seventeen recommendations were issued for the treatment of PsA patients. Six of them were of general nature, ranging from the early diagnosis and treatment to the importance of assessing comorbidities. The other 11 were focused on the indications for DMARDs and biological therapy in the distinct clinical forms of the disease. Likewise, the situation of failure of the first biological is addressed and treatment algorithms and a table with the different biological therapies are also included., Conclusions: We present the update of SER recommendations for the treatment of PsA with DMARDs and biologics., (Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.)

Antiretroviral therapy (ART) is recommended for all patients infected by HIV-1. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should be based on a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors (tenofovir in either of its two formulations plus emtricitabine or abacavir plus lamivudine) and another drug from a different family. Four of the recommended regimens, all of which have an integrase inhibitor as the third drug (dolutegravir, elvitegravir boosted with cobicistat or raltegravir), are considered preferential, whereas a further 3 regimens (based on elvitegravir/cobicistat, rilpivirine, or darunavir boosted with cobicistat or ritonavir) are considered alternatives. We present the reasons and criteria for switching ART in patients with an undetectable PVL and in those who present virological failure, in which case salvage ART should include 3 (or at least 2) drugs that are fully active against HIV. We also update the criteria for ART in specific situations (acute infection, HIV-2 infection, pregnancy) and comorbidities (tuberculosis or other opportunistic infections, kidney disease, liver disease and cancer)., (Copyright © 2017. Publicado por Elsevier España, S.L.U.)

Objective: The central nervous system (CNS) may be involved in a variety of inflammatory diseases of the blood vessels, generally known as vasculitis. The clinical diagnosis of such involvement in early stages is difficult, since a mild cognitive impairment can be the only symptom. It was hypothesized that brain-perfusion SPECT would be able to reveal CNS involvement and to monitor the course of the disease. The purpose of this study was assess if and when an improvement of cerebral perfusion can be registered by SPECT during the follow-up of these diseases., Material and Methods: Eighteen patients affected by Systemic Lupus Erythematosus (SLE), 22 by undifferentiated vasculitis (UV), 5 by Behcet's disease (BD) and 5 by primary Sjogren's Syndrome (pSS) were enrolled in this prospective study. A 99m Tc-HMPAO brain perfusion SPECT was performed before the treatment and was repeated during the follow-up at different time intervals. Image analysis was performed on 10 cerebral areas using a specific software., Results: In the SLE patients, no significant improvement of brain perfusion was found. On the contrary, in the UV the cerebral uptake of the tracer significantly improved from the twenty-fourth month (18/22 patients). Patients with BD showed an improvement of scintigraphic findings (5/5 patients), while a similar result was obtained only in 2 of the patients with pSS., Conclusions: In conclusion, brain SPECT seems to be able to monitor the disease in UV, indicating the moment when an improvement of the cerebral perfusion is achieved. In SLE patients this scintigraphic technique did not show a significant improvement in CNS perfusion., (Copyright © 2017. Publicado por Elsevier España, S.L.U.)

Treatment of osteoporosis should be directed primarily towards secondary prevention of fractures. The occurrence of drug-related adverse effects for the treatment of osteoporosis has led to a reevaluation of the indications, the duration of treatment and even withdrawal of some drugs from the market. This review has been made from different patient profiles that practitioners will find in usual practice; from patients with hip fracture with cognitive impairment, limitation of their day-to-day living activities and comorbidities, to active patients without any limitations; patients with vertebral fractures and non-vertebral fractures where secondary prevention is highly important. In general, antiresorptive drugs (alendronate and risedronate) will be the first choice. Zoledronate or denosumab will be indicated in cases of digestive intolerance, poor adherence or an increased risk of hip fracture. Teriparatide will be indicated to patients with 2or more previous vertebral fractures or very low bone density., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)