• Utility of a computer tool for detection of potentially inappropriate medications in older patients in a tertiary hospital.
    Vol. 1 Núm. e0013 (2020)

    As we believe it is an important problem in our environment, we determined the prevalence of potentially inappropriate medications (PIM) using the STOPP/START, Beers and PRISCUS criteria, and also determined the clinical variables related to the prescription of PIMs in older adults. It is a retrospective cross-sectional study in Geriatrics. Participants were all patients over 65 years discharged from the Internal Medicine Service of La Princesa hospital during February 2014. We measured inappropriate prescriptions detected with CheckTheMeds® computer tool. The study included 143 participants, mean age 87±7 years. Using Beers criteria, 421 PIMs were identified in 114 patients, with STOPP criteria, 277 PIMs were identified in 111 patients, with START criteria 279 PIMs were identified in 113 patients and using PRISCUS 47 PIMs were identified in 42 patients. Correlation between STOPP and Beers was 70%. An association between PIM prescribing and polypharmacy was detected with different criteria. CheckTheMeds® is a useful tool to improve detection and management of PIM in order to obtain evidence-based pharmacological treatment.

  • Gentamicin serum concentrations after reinfusion of blood in patients undergoing arthroplasty with gentamicin-loaded bone cement
    Vol. 1 Núm. e0014 (2020)

    Cement is sometimes applied to fix prostheses during arthroplasty. The cement can contain antibiotics for prophylaxis or treatment of joint infection. Gentamicin in cement is released gradually into its surroundings and can reach toxic concentrations in recovered blood. To determine gentamicin concentrations in patients with recovered blood and after blood reinfusion in patients who underwent joint replacement using gentamicin-loaded bone cement. This is a prospective observational study of 18 patients who underwent partial or total hip or knee replacement. Gentamicin-loaded bone cement was justified in all cases, and all patients were candidates for blood reinfusion after surgery. Gentamicin serum concentrations were measured by immunoassay. Serum concentrations were never higher than 1.5 µg/ml. The median concentration of gentamicin in recovered blood was 26.3 µg/ml. The maximum gentamicin dose by blood reinfusion could be 129 mg. The maximum gentamicin concentration in reinfused blood was 1.5 µg/ml. Gentamicin-loaded bone cement is safe, since drug levels did not reach toxic concentrations.

  • Ensayo clí­nico aleatorizado para evaluar dos pautas de administración del ibuprofeno en el tratamiento del ductus arterioso persistente eco-guiado
    Vol. 1 Núm. 1 (2019)

    Resumen:

    El ductus arterioso persistente (DA) es una entidad frecuente en el recién nacido prematuro y se asocia a morbilidad y mortalidad. Aún existe controversia sobre cuál es el mejor tratamiento para su cierre. Los niños con DA que reciben tratamiento farmacológico presentan con mayor frecuencia que el resto de niños prematuros,

    enterocolitis necrotizante (ECN) o perforación intestinal aislada (PIA). En el momento actual, el tratamiento convencional del DA consiste en la administración de ibuprofeno (IB) intravenoso, iv, en bolo lento en 3 dosis diarias 10-5-5 mg/kg/día. Recientemente, se ha observado que el tratamiento con IB en perfusión continua iv durante 3 días 10-5-5 mg/kg/día, parece ser más eficaz para cerrar el DA que el tratamiento convencional durante 3 días con la misma dosis pero en bolo iv lento. Dicho tratamiento experimental redujo la incidencia de ECN asociada. Nuestro grupo demostró en un ensayo piloto previo que el tratamiento guiado con ecocardiografía, EchoG del DA con IB iv comparado con el tratamiento convencional, permite disminuir el número de dosis al

    paciente. El tratamiento EchoG presenta así una potencial reducción de los efectos secundarios asociados a la medicación, esto se tradujo en una tendencia a presentar menor incidencia de ECN en el grupo experimental. Con este ensayo clínico multicéntrico se pretende testar la hipótesis de que la combinación de 2 tratamientos

    experimentales, la utilización de IB en perfusión continua y EchoG, reduce la incidencia de efectos secundarios digestivos frente al tratamiento también guiado por ecocardiografía pero en bolo lento iv.

  • DRESS en paciente con toxoplasmosis y sí­ndrome antisintetasa.
    Vol. 1 Núm. 0011 (2018)
    INTRODUCCIÓN

    Se define como sí­ndrome de DRESS a una reacción cutánea grave caracterizada por la aparición de erupción cutánea, adenopatí­as, fiebre, eosinofilia, leucocitosis y/o afectación orgánica a las 2-6 semanas de iniciar tratamiento con un fármaco.1,2 Con mayor frecuencia, los fármacos implicados son anticonvulsivantes, sulfamidas, alopurinol y antibióticos betalactámicos. En el caso de las sulfamidas, la incidencia de reacciones cutáneas en general es del orden de 3-5 casos de cada 100 personas expuestas.3 Presentamos un caso de síndrome de DRESS durante tratamiento con Sulfadiazina/Pirimetamina con reactivación posterior con Sulfametoxazol/Trimetoprim y exantema con Clindamicina asociada a Pirimetamina. Confirmada hipersensibilidad retardada a sulfadiazina, sulfametoxazol y Pirimetamina mediante TTL (test de transformación linfocitaria).

  • La importancia de la información de seguridad en las fichas técnicas: a propósito de un caso
    Vol. 1 Núm. 0010 (2017)

    Resumen: La información sobre la seguridad de un medicamento está recogida en la ficha técnica, en el apartado "4.8 Reacciones Adversas" (RA) y es de gran importancia para los profesionales sanitarios. En este artí­culo se describe el proceso llevado a cabo para la atribución de causalidad de un medicamento en un caso de DRESS (Drug Reaction Eosinophilia and Systemic Symptoms) en un paciente hospitalizado en la Unidad de Cuidados Intensivos (UCI) con los diagnósticos de hemorragia subaracnoidea (HSA) y hematoma subdural agudo tras politraumatismo. De los medicamentos sospechosos en este caso la fenitoí­na es del que mayor conocimiento tenemos en esta entidad. Sin embargo, en la consulta que se realizó de las fichas técnicas de varias formulaciones de fenitoí­na se observó que esta RAM, a pesar de estar bien establecida en la literatura cientí­fica desde muchos años atrás, no aparece en la formulación disponible en el hospital, por lo que se realizó una revisión de la legislación española y europea sobre farmacovigilancia e informes periódicos de seguridad, así­ como de la lista de referencia europea (EURD). La EURD tiene como objetivo facilitar la coordinación de los DLP (Data Lock Points) y la frecuencia de entrega de los Informes Periódicos de Seguridad (IPS) de productos con el mismo principio activo o la misma combinación de principios activos sujetos a diferentes autorizaciones de comercialización, autorizados en m´´as de un estado miembro de la UE. En la EURD la fenitoína tiene una frecuencia de presentación de IPS cada 13 años.  Conclusión: a pesar de que la fenitoí­na es uno de los medicamentos que más frecuentemente produce DRESS, esta RAM grave no aparece en la ficha técnica de al menos una de las formulaciones de este medicamento. La lista EURD no ha conseguido homogeneizar la información de las fichas técnicas de todas las formulaciones de fenitoí­na.

  • Pharmacokinetic characterization of the population with hemophilia A in Spain, using an online medical application based on a published population model and a Bayesian algorithm
    Vol. 1 Núm. 0009 (2017)

    OBJECTIVE: The main objective of this prospective observational study is to describe the pharmacokinetic profile of patients with hemophilia A in prophylaxis with Advate® in Spain using myPKFiT®. Secondary objectives are (1) the characterization of the educational role of pharmacokinetics, (2) identifying whether there are any changes in attitude among the patients after receiving the educational information on pharmacokinetics and (3) evaluating the role of pharmacokinetics and other individual factors in patients with hemophilia A undergoing prophylactic treatment in Spain.

    METHODS: This is an observational, prospective (EPA-SP) and multicenter study. It will be conducted in 14 centers in Spain and will include patients with diagnosis of hemophilia A undergoing prophylactic treatment with Advate® and will use myPKFiT®. The study will also include a cohort of patients who are already using myPKFiT® for the PK-guided prophylaxis dose adjustment.

    DISCUSSION: Several studies have demonstrated the superiority of prophylactic treatment versus on-demand treatment. In order to make this prophylaxis more effective in preventing bleeding, it is necessary to adjust the treatment to several factors such as the physical activity that the patient performs, joint condition and the pharmacokinetic parameters of the infused factor VIII (clearance, life mean, area under the curve). Understanding the pharmacokinetic will help us personalize the treatment in our patients.

    TRIAL REGISTRATION: ClinicalTrials.gov: NCT03006965.

  • PHASE IIIb, OPEN LABEL RANDOMISED CLINICAL TRIAL TO COMPARE PAIN RELIEF BETWEEN METHOXYFLURANE AND STANDARD OF CARE FOR TREATING PATIENTS WITH TRAUMA PAIN IN SPANISH EMERGENCY UNITS (InMEDIATE): STUDY PROTOCOL
    Vol. 1 Núm. 008 (2017)

    Objective: To evaluate efficacy, safety, patient and investigators satisfaction, and cost of pain relief by time unit between methoxyflurane (a volatile anesthetic agent with known analgesic properties, non-opioid, self-administered using a hand-held inhalation device under trained supervision) and emergency analgesic standard of care treatment (SoC), over a period of 30 min from start of administration and time to first pain relief. 

    Methods: InMEDIATE is a phase IIIb, randomized, open label, multicenter, parallel group trial. It will be conducted in 15 emergency hospital departments. A total of 310 patients, with moderate to severe pain secondary to trauma, will be randomized to receive either methoxyflurane or SoC. The primary end point of the study is the change in mean pain intensity as measured by a numeric rating scale from randomization to 3, 5, 10, 15 and 20 minutes after treatment administration (using mixed-effect model repeated measure) and time to first pain relief (survival analysis).

    Discussion: To the best of our knowledge, this is the first randomized trial of methoxyflurane vs active analgesic treatment to be carried out in Europe. The aim of the study is to evaluate the results in terms of efficacy and safety of methoxyflurane for the treatment of traumatic pain in Spanish emergency units (ambulances, emergency primary care and emergency departments settings), in order to assess the incorporation of this drug into the emergency traumatic pain SoC.

    Trial Registration: EudraCT, 2017-000338-70

  • Protocol: Acute and chronic paracetamol overdose in paediatric population: Protocol of a prospective study of cohort to evaluate clinic factor and biomarkers to predict development of hepatotoxicity.
    Vol. 1 Núm. 007 (2017)

    Background: In Spain, 30% of cases of acute liver failure remaining undetermined. Paracetamol is the main drug causing acute liver failure in children of some countries like the United States, UK, and other European countries. The key factors to assess in paracetamol toxicity, the ingested dose and the time from the poisoning, are difficult to assess in children were accidental acute poisoning or medication errors are not rare. Metabolomics technology may be able to identify specific biomarkers of toxicity and adverse events in early stages. The identification of paracetamol toxicity biomarkers could have important clinical implications for patients who can not apply the Rumack-Matthew nomogram and could be useful in the evaluation of children with acute liver failure of unknown etiology, and to predict liver damage before the elevation of transaminases. 

    Methods and design: This is an observational prospective study of case control. The protocol was approved by the Clinical Research Ethics Committee of the La Paz University Hospital. It will recruit patients who will be attending in the emergency paediatric at La Paz University Hospital, at Niño Jesus University Hospital, and at Gregorio Marañón University hospital with suspected acute or chronic intake of paracetamol. Likewise, two cohorts of control will be recruited. It is expected to recruit at least 36 cases and 144 controls, matched for age and clinical characteristics. Peripheral blood, plasma, serum and urine samples will be collected, paracetamol serum concentrations, hepatic and renal function, coagulation and metabolomic analysis.

    Discussion: It is important to determine the clinical factors and biomarkers that predict the development of hepatotoxicity in paediatric population following acute and chronic intake of paracetamol and develop a predictive model to assess the risk of hepatotoxicity in both types of intoxication by paracetamol suited to paediatric patients for use in clinical practice.

    Study registration:

    Protocol code: GEIPA-2012-01

    AEMPS classification: EPA-OD

    Study Reference Number of European Network of Centers for Pharmacoepidemiology and Pharmacovigilance: ENCePP: ENCePP/SDPP/3276

  • Case report: Sí­ndrome nefrótico secundario a glomerulonefritis membranosa asociada al tratamiento con litio.
    Vol. 1 Núm. 006 (2017)

    Case Report:

    Tí­tulo: Sí­ndrome nefrótico secundario a glomerulonefritis membranosa asociada al tratamiento con litio

    Palabras clave: Carbonato de litio. Glomerulonefritis membranosa. Sí­ndrome nefrótico. Proteinuria.

  • Effect of the CYP3A5, CYP3A4, CYP3A7, ABCB1, POR and NR1I2 genes in the phar-macokinetics of tacrolimus in a pediatric cohort with stable serum concentrations after renal transplantation: study protocol.
    Vol. 1 Núm. 005 (2017)

    BACKGROUND: Therapeutic response to pharmacological therapy in humans shows large intrapatient and interpatient variability both in treatment efficacy and adverse drug reactions (ADR). Part of this variability can be explained by genetic polymorphisms in genes encoding TAC metabolism related proteins. The aim of this study is to evaluate the contribution of genetic variation in the CYP3A4, CYP3A5, CYP3A7, POR, NR1I2 and ABCB1 genes to this variability in order to achieve a better understanding of TAC pharmacokinetics and a more personalized approach for TAC dosing in a cohort of pediatric patients with stable serum concentrations after renal transplantation.

    METHODS AND DESIGN: This is a unicenter retrospective cross-sectional study. The protocol was approved by the Clinical Research Ethics Committee of the La Paz University Hospital (Madrid, Spain) and will be carried in this same hospital. 50 pediatric patients with stable serum concentrations after renal transplantation are expected to be included. Peripheral blood samples will be collected for molecular analysis (pharmacogenetics studies) and AUC estimation (C0, C1 and C3 hours after TAC administration).

    DISCUSSION: To date there are not dosing algorithms that can explain accurately TAC metabolism. The incorporation of a complete pharmacogenetic (PhGx) profile into these algorithms may help in the individualization and optimization of TAC treatment in pediatric renal transplant patients.

    STUDY REGISTRATION: FC/HULP_002/2014
  • Original: Infecciones como causa de ingreso urgente en adultos en un hospital terciario.
    Vol. 1 Núm. 004 (2017)

    OBJETIVO: Estudiar la prevalencia de las enfermedades infecciosas que son atendidas en el Servicio de Urgencias Hospitalario (SUH) y que requieren ingreso hospitalario, así­ como identificar los principales agentes causales y describir el tratamiento y evolución de los pacientes.

    MÉTODO: Estudio observacional retrospectivo que evalúa todos los pacientes que requieren ingreso urgente en un hospital terciario durante el mes de Marzo de 2016. Se recogieron como variables: enfermedades concomitantes, agentes causales, cultivos realizados, resistencias antibióticas y tratamiento prescrito. Las infecciones se clasificaron en: urinarias, respiratorias, intraabdominales, infección de piel y partes blandas, neurológicas, y otras.

    RESULTADOS: Ingresaron un total de 903 pacientes durante este periodo. De estos, se consideró que el 36,2% podían tener una causa infecciosa. La edad media fue de 72,3 años y la estancia media en el hospital de 9,6 días. Las infecciones predominantes fueron respiratorias (47,2%), urinarias (19%) e intraabdominales (18,1%). El 46,5% de las pruebas microbiológicas fueron positivas, siendo E. coli el principal agente causal (22,3%). Los perfiles de sensibilidad de los aislados fueron similares a los esperados, excepto para K. pneumoniae (50% resistente a fluoroquinolonas y amoxicilina-clavulánico). Los antibióticos predominantemente prescritos fueron Beta-lactámicos (51,2%) y fluoroquinolonas (25,1%). La mortalidad fue del 7,3%, siendo la edad y presentar criterios de sepsis factores de riesgo asociados.

    CONCLUSIONES: Las infecciones son una de las principales causas de ingreso hospitalario y suponen un alto porcentaje de la atención sanitaria que se presta en el SUH. Nuestro estudio demuestra que la edad y los criterios de sepsis son factores cruciales asociados a la mortalidad de los pacientes. Este es el primer estudio que analiza cuantos ingresos a través del SUH se deben a una causa infecciosa.

  • Case report: Acute Pancreatitis by liposomal amphotericin B
    Vol. 1 Núm. 003 (2016)
    The most frequently observed adverse reactions of a liposomal formulation of amphotericin B (LAB) on the first dose of fever and rigors are hypokalemia and renal toxicity. Acute pancreatitis is not listed in the Summary of Product Characteristics of LAB, although some non-severe cases of pancreatitis toxicity after LAB are described in the literature.