Utilización de medicamentos off-label y unlicensed en una unidad de cuidados intensivos pediátricos de un hospital de alta complejidad español. Estudio descriptivo / Off-label and unlicensed drug use in a pediatric intensive care unit of a tertiary care Spanish hospital. A descriptive study

Introducción. En las unidades de cuidados intensivos pediátricos, se utiliza gran cantidad de medicamentos, muchos prescritos fuera de las condiciones establecidas en su ficha técnica (prescripciones off-label y unlicensed). El objetivo de este estudio fue describir el uso de medicamentos y estimar la prevalencia de fármacos off-label y unlicensed en una unidad de cuidados intensivos pediátricos de un hospital de tercer nivel español. Población y métodos. Estudio transversal, observacional, de una cohorte de niños ingresados en una unidad de cuidados intensivos pediátricos. El estudio se llevó a cabo en 2017. Se revisó cada fármaco prescrito, sus condiciones de uso y administración. Además, se analizaron las fichas técnicas de los fármacos implicados con la finalidad de identificar si el uso de los medicamentos se realizaba según sus condiciones de autorización, o bien se hacía fuera de prospecto (off-label) o como unlicensed. Resultados. La muestra fue de 97 pacientes. El 74,2 % (n = 72) de los pacientes recibieron algún fármaco off-label o unlicensed. El 23,8 % (n = 243) de las prescripciones fueron off-label y el 8,7 % (n = 89), unlicensed. El subanálisis realizado por grupos de edad mostró que el grupo de edad que recibió mayor número de prescripciones totales (n = 611) y el mayor porcentaje de fármacos prescritos en condiciones off-label y/o unlicensed (38,4 %) fue el de menores de 2 años. Conclusiones. La prescripción de fármacos off-label y/o unlicensed es una práctica habitual en la unidad de cuidados intensivos pediátricos. Este estudio permite documentar la complejidad de la terapéutica en niños.

Introduction. In pediatric intensive care units, a large number of drugs are used, many of which are prescribed for condition beyond those established in their summary of product characteristics (off-label and unlicensed drug prescriptions). The objective of this study was to describe drug use and estimate the prevalence of off-label and unlicensed drugs in a pediatric intensive care unit of a tertiary care Spanish hospital. Population and methods. Cross-sectional, observational study with a single cohort of children admitted to a pediatric intensive care unit. The study was conducted in 2017. Each drug prescription, its conditions of use and administration were reviewed. In addition, the summary of product characteristics of drugs used were analyzed in order to identify whether they were used according to their conditions of authorization, or whether they were used in an off-label or unlicensed manner. Results. The sample included 97 patients. At least one off-label or unlicensed drug was administered to 74.2% (n = 72) of patients; 23.8% (n = 243) corresponded to off-label prescriptions and 8.7% (n = 89), unlicensed prescriptions. A sub-analysis by age group showed that the age group that received a higher number of total prescriptions (n = 611) and a higher percentage of off-label and/or unlicensed drug prescriptions (38.4%) was under 2 years of age. Conclusions. Off-label and/or unlicensed drug prescription is a common practice in the pediatric intensive care unit. This study allowed us to document the complexity of therapeutics in children.

Off-label and unlicensed drug use in a pediatric intensive care unit of a tertiary care Spanish hospital. A descriptive study. / Utilización de medicamentos off-label y unlicensed en una unidad de cuidados intensivos pediátricos de un hospital de alta complejidad español. Estudio descriptivo.

Introduction. In pediatric intensive care units, a large number of drugs are used, many of which are prescribed for condition beyond those established in their summary of product characteristics (off-label and unlicensed drug prescriptions). The objective of this study was to describe drug use and estimate the prevalence of off-label and unlicensed drugs in a pediatric intensive care unit of a tertiary care Spanish hospital. Population and methods. Cross-sectional, observational study with a single cohort of children admitted to a pediatric intensive care unit. The study was conducted in 2017. Each drug prescription, its conditions of use and administration were reviewed. In addition, the summary of product characteristics of drugs used were analyzed in order to identify whether they were used according to their conditions of authorization, or whether they were used in an off-label or unlicensed manner. Results. The sample included 97 patients. At least one off-label or unlicensed drug was administered to 74.2% (n = 72) of patients; 23.8% (n = 243) corresponded to off-label prescriptions and 8.7% (n = 89), unlicensed prescriptions. A sub-analysis by age group showed that the age group that received a higher number of total prescriptions (n = 611) and a higher percentage of off-label and/or unlicensed drug prescriptions (38.4%) was under 2 years of age. Conclusions. Off-label and/or unlicensed drug prescription is a common practice in the pediatric intensive care unit. This study allowed us to document the complexity of therapeutics in children.

Introducción. En las unidades de cuidados intensivos pediátricos, se utiliza gran cantidad de medicamentos, muchos prescritos fuera de las condiciones establecidas en su ficha técnica (prescripciones off-label y unlicensed). El objetivo de este estudio fue describir el uso de medicamentos y estimar la prevalencia de fármacos off-label y unlicensed en una unidad de cuidados intensivos pediátricos de un hospital de tercer nivel español. Población y métodos. Estudio transversal, observacional, de una cohorte de niños ingresados en una unidad de cuidados intensivos pediátricos. El estudio se llevó a cabo en 2017. Se revisó cada fármaco prescrito, sus condiciones de uso y administración. Además, se analizaron las fichas técnicas de los fármacos implicados con la finalidad de identificar si el uso de los medicamentos se realizaba según sus condiciones de autorización, o bien se hacía fuera de prospecto (off-label) o como unlicensed. Resultados. La muestra fue de 97 pacientes. El 74,2 % (n = 72) de los pacientes recibieron algún fármaco off-label o unlicensed. El 23,8 % (n = 243) de las prescripciones fueron off-label y el 8,7 % (n = 89), unlicensed. El subanálisis realizado por grupos de edad mostró que el grupo de edad que recibió mayor número de prescripciones totales (n = 611) y el mayor porcentaje de fármacos prescritos en condiciones off-label y/o unlicensed (38,4 %) fue el de menores de 2 años. Conclusiones. La prescripción de fármacos off-label y/o unlicensed es una práctica habitual en la unidad de cuidados intensivos pediátricos. Este estudio permite documentar la complejidad de la terapéutica en niños.

Resultados de una encuesta nacional sobre conocimiento y uso de pseudociencias por parte de los pediatras / Results of a national survey on knowledge and use of complementary and alternative medicine by paediatricians

Introducción: El uso de determinadas pseudociencias en niños está documentado en España. El objetivo principal del estudio es estimar el grado de conocimiento, la recomendación y el uso de algunas pseudoterapias por parte de los pediatras españoles. Material y métodos: Estudio transversal, descriptivo y de ámbito nacional, mediante encuesta en línea, enviada por correo electrónico a pediatras socios de la Asociación Española de Pediatría (AEP), entre junio y julio de 2020. (AU)

Introduction: The use of certain Complementary and Alternative Medicines (CAM) in children has been documented in Spain. The main aim of this study is to estimate the knowledge, recommendations, and use of CAM by Spanish paediatricians. Material and methods: A national study was conducted from June to July 2020 using an online questionnaire. Two e-mails were sent to paediatricians who were members of the Spanish Association of Paediatrics (AEP). (AU)

Results of a national survey on knowledge and use of complementary and alternative medicine by paediatricians.

INTRODUCTION: The use of certain Complementary and Alternative Medicines (CAM) in children has been documented in Spain. The main aim of this study is to estimate the knowledge, recommendations, and use of CAM by Spanish paediatricians. MATERIAL AND METHODS: A national study was conducted from June to July 2020 using an online questionnaire. Two e-mails were sent to paediatricians who were members of the Spanish Association of Paediatrics (AEP). RESULTS: Out of 1414 responses received, acupuncture was considered as a science by 31.8%. Homeopathy was recommended to parents by 28.1%. CAM was used by 21.3% of physicians, at least once, to improve their own health. Only 3.8% had ever replaced a conventional treatment with CAM. The following variables were associated with a greater disposition to prescribe homeopathy: female, age over 45 years old, paediatricians working in Primary Care, and paediatricians working in private healthcare. CONCLUSIONS: This AEP Committee on Medicines questionnaire provides new data that should be considered alarming and should ask for a serious thinking on the use of CAM in Spain. Some paediatricians are recommending parents to give treatments not supported by scientific evidence to their children. This practice could be potentially harmful, especially when conventional treatment is being replaced.

A systematic review on pharmacokinetics, cardiovascular outcomes and safety profiles of statins in cirrhosis.

BACKGROUND/AIMS: There is increased interest in the therapeutic use of statins in cirrhosis, but preferred statin and safety outcomes are still not well known. In this systematic review we aimed to address pharmacokinetics (PK), safety, and effects on cardiovascular (CV) outcomes of statins in cirrhosis. METHODS: Our systematic search in several electronic databases and repositories of two regulatory bodies up to 2020-06-11 yielded 22 articles and 2 drug monographs with relevant data. RESULTS: Rosuvastatin and pitavastatin showed minimal PK changes in Child-Pugh A cirrhosis. Only rosuvastatin was assessed in a repeated dosing PK study. Atorvastatin showed pronounced PK changes in cirrhosis. No PK data was found for simvastatin, the most commonly used statin in cirrhosis trials. There was insufficient data to assess CV effects of statins in cirrhosis. Clinical trials in cirrhosis were limited to simvastatin, atorvastatin, and pravastatin. In patients taking simvastatin 40 mg, pooled frequency of rhabdomyolysis was 2%, an incidence 40-fold higher than that reported in non-cirrhosis patients, while this was no rhabdomyolysis observed in patients on simvastatin 20 mg, atorvastatin 20 mg, or pravastatin 40 mg. Drug-induced liver injury was of difficult interpretation due to co-existence of muscle damage. No overt liver failure was reported. CONCLUSIONS: Simvastatin 40 mg should be avoided in decompensated cirrhosis. Safety data on simvastatin 20 mg or other statins are based on small study sample size. This rarity of evidence combined with lack of data in dose adjustment methods in cirrhosis is a barrier for using statins for CV indications or for investigational use for liver indications.

Combination of Tocilizumab and Steroids to Improve Mortality in Patients with Severe COVID-19 Infection: A Spanish, Multicenter, Cohort Study.

BACKGROUND: We aimed to determine the impact of tocilizumab use on severe COVID-19 (coronavirus disease 19) pneumonia mortality. METHODS: We performed a multicentre retrospective cohort study in 18 tertiary hospitals in Spain from March to April 2020. Consecutive patients admitted with severe COVID-19 treated with tocilizumab were compared to patients not treated with tocilizumab, adjusting by inverse probability of the treatment weights (IPTW). Tocilizumab's effect in patients receiving steroids during the 48 h following inclusion was analysed. RESULTS: During the study period, 506 patients with severe COVID-19 fulfilled the inclusion criteria. Among them, 268 were treated with tocilizumab and 238 patients were not. Median time to tocilizumab treatment from onset of symptoms was 11 days [interquartile range (IQR) 8-14]. Global mortality was 23.7%. Mortality was lower in patients treated with tocilizumab than in controls: 16.8% versus 31.5%, hazard ratio (HR) 0.514 [95% confidence interval (95% CI) 0.355-0.744], p < 0.001; weighted HR 0.741 (95% CI 0.619-0.887), p = 0.001. Tocilizumab treatment reduced mortality by 14.7% relative to no tocilizumab treatment [relative risk reduction (RRR) 46.7%]. We calculated a number necessary to treat of 7. Among patients treated with steroids, mortality was lower in those treated with tocilizumab than in those treated with steroids alone [10.9% versus 40.2%, HR 0.511 (95% CI 0.352-0.741), p = 0.036; weighted HR 0.6 (95% CI 0.449-0.804), p < 0.001] (interaction p = 0.094). CONCLUSIONS: These results show that survival of patients with severe COVID-19 is higher in those treated with tocilizumab than in those not treated and that tocilizumab's effect adds to that of steroids administered to non-intubated patients with COVID-19 during the first 48 h of presenting with respiratory failure despite oxygen therapy. Randomised controlled studies are needed to confirm these results. TRIAL REGISTRATION: European Union electronic Register of Post-Authorization Studies (EU PAS Register) identifier, EUPAS34415.

[Results of a national survey on knowledge and use of complementary and alternative medicine by paediatricians]. / Resultados de una encuesta nacional sobre conocimiento y uso de pseudociencias por parte de los pediatras.

INTRODUCTION: The use of certain Complementary and Alternative Medicines (CAM) in children has been documented in Spain. The main aim of this study is to estimate the knowledge, recommendations, and use of CAM by Spanish paediatricians. MATERIAL AND METHODS: A national study was conducted from June to July 2020 using an online questionnaire. Two e-mails were sent to paediatricians who were members of the Spanish Association of Paediatrics (AEP). RESULTS: Out of 1,414 responses received, acupuncture was considered as a science by 31.8%. Homeopathy was recommended to parents by 28.1%. CAM was used by 21.3% of physicians, at least once, to improve their own health. Only 3.8% had ever replaced a conventional treatment with CAM. The following variables were associated with a greater disposition to prescribe homeopathy: female, age over 45 years old, paediatricians working in Primary Care, and paediatricians working in private healthcare. CONCLUSIONS: This AEP Committee on Medicines questionnaire provides new data that should be considered alarming and should ask for a serious thinking on the use of CAM in Spain. Some paediatricians are recommending parents to give treatments not supported by scientific evidence to their children. This practice could be potentially harmful, especially when conventional treatment is being replaced.

Spanish list of potentially inappropriate drugs in the elderly (ES-PIA project).

PURPOSE: In the last decades, different criteria have been developed for detecting inappropriate prescription in older patients. In Spain, translations and adaptations of international lists are available but it would be necessary a national list which could cope with the peculiarities of our health system, existing pharmaceutical market, and prescription habits. We propose in this project the creation of a Spanish potentially inappropriate drugs list which could be applicable in our clinical scenario. METHODS: We use a Delphi method involving 25 experts from different backgrounds (Clinical Pharmacology, Geriatrics, Rational Use of Drugs and Pharmacy, Primary Care and Pharmacoepidemiology, and Pharmacovigilance) that were asked to participate in two-round questionnaires. For analysis, current recommendations of Worth and Pigni were applied, and every statement was classified into one of three groups: strong, moderate, or low agreement. Statements with strong agreement were accepted to be part of the inadequate prescription list. Moderate agreement statements were selected to enter the second questionnaire, and statements with low agreement were further analyzed to determine if it was due to heterogeneity or due to dispersion in the answers. RESULTS: The first questionnaire consisted of 160 proposed sentences, of which 106 reached a high agreement, 32 a moderate agreement, and 22 a low agreement. All sentences proposed in the second questionnaire reached a strong agreement. The total accepted sentences were 138. CONCLUSIONS: We offer a list of inadequate prescription in older patients adapted to the Spanish pharmacopeia and according to the prescription habits in our environment.

Evaluation of two treatment strategies for the prevention of preterm birth in women identified as at risk by ultrasound (PESAPRO Trial): study protocol for a randomized controlled trial.

BACKGROUND: Premature birth is considered one of the main problems in modern Obstetrics. It causes more than 50 % of neonatal mortality; it is responsible for a large proportion of infant morbidity and incurs very high economic costs. Cervical length, which can be accurately measured by ultrasound, has an inverse relationship with the risk of preterm birth. As a result, having an effective intervention for asymptomatic patients with short cervix could reduce the prematurity. Although recently published data demonstrates the effectiveness of vaginal progesterone and cervical pessary, these treatments have never been compared to one another. METHODS/DESIGN: The PESAPRO study is a noncommercial, multicenter, open-label, randomized clinical trial (RCT) in pregnant women with a short cervix as identified by transvaginal ultrasonography at 19 to 22 weeks of gestation. Patients are randomized (1:1) to either daily vaginal progesterone or cervical pessary until the 37th week of gestation or delivery; whichever comes first. During the trial, women visit every 4 weeks for routine questions and tests. The primary outcome is the proportion of spontaneous preterm deliveries before 34 weeks of gestation. A sample size of 254 pregnant women will be included at 29 participating hospitals in order to demonstrate noninferiority of placing a pessary versus vaginal progesterone. The first patient was randomized in August 2012, and recruitment of study subjects will continue until the end of December 2015. DISCUSSION: This trial assesses the comparative efficacy and safety between two accepted treatments, cervical pessary versus vaginal progesterone, and it will provide evidence in order to establish clinical recommendations. TRIAL REGISTRATION: EU Clinical Trials Register EudraCT2012-000241-13 (Date of registration: 16 January 2012); ClinicalTrials.gov Identifier NCT01643980 (Date of registration: 12 June 2012).

Cambios en la normativa europea de ensayos clínicos ( i ): una oportunidad para mejorar los trámites de autorización / Changes in the European normative of clinical trials ( i ): a chance to improve the paperwork authorization

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Notificación de sospecha de reaccionesadversas a medicamentos mediantela tarjeta amarilla / Reporting of suspected adverse reactions to drugs by means of the yellow card

Las Reacciones Adversas a Medicamentos (RAM) constituyen un problema de saludpública en nuestra sociedad. Se estima que en los países occidentales el 5,3%de los ingresos hospitalarios están asociados a RAM, el 6,7% de los pacienteshospitalizados sufre una RAM grave y que este problema supone el 5-9% del costeintrahospitalario. A pesar de que la notificación espontánea de sospecha deRAM a través de la “tarjeta amarilla” es el método más eficiente para la detecciónde reacciones adversas nuevas y/o serias a medicamentos, se estima que sólose notifican alrededor del 10%. La legislación española obliga a todos los profesionalessanitarios a notificar las sospechas de reacciones adversas a los medicamentosautorizados. Sin embargo, durante 2006, los enfermeros sólo aportaronel 3% de todas las Tarjetas Amarillas al Sistema Español de Farmacovigilancia. Lainfranotificación de RAM en los profesionales de Enfermería es un fenómeno pendientede estudio (AU)

Adverse reactions to drugs (ARD) are a public health problem in our society. It isestimated that in western countries, 5,3% of hospital admissions are associatedwith ARD, 6,7% of hospitalised patients suffer from severe ARD and that this problemaccounts for 5-9% of intrahospital cost. Despite the fact that spontaneousreporting of suspected ARD via the “Yellow Card” is the most efficient method forthe detection of new and/or severe adverse reactions to drugs, it is estimated thatonly about 10% are reported. Spanish legislation stipulates that all health care professionalsare mandatory reporters of suspected adverse reactions to authoriseddrugs. However, in 2006, nurses contributed only 3% of all Yellow Cards to theSpanish System of Drug Surveillance. The underreporting of ARD on the part ofnursing professionals is a phenomenon pending future study (AU)