Eficacia de las medidas de minimización de riesgos del ácido valproico: estudio de utilización del fármaco en Europa, análisis de datos de España / Effectiveness of risk minimisation measures for valproate: a drug utilisation study in Europe, analysis of data from Spain

Introducción: En 2015 se aplicaron en España distintas medidas para la minimización de los riesgos (MMR) del ácido valproico. Objetivo: El objetivo de este estudio es evaluar la eficacia de las MMR del ácido valproico en España, con el fin de reducir el uso de ácido valproico como terapia de primera línea y evaluar los patrones de prescripción de ácido valproico en las mujeres, incluidas las mujeres en edad fértil (MEF), en los períodos previos y posteriores a la implementación de las MMR. Materiales y métodos: Los patrones de prescripción del ácido valproico en mujeres y MEF antes y después de la implementación de las MMR se examinaron utilizando la base de datos longitudinales de pacientes (longitudinal patient data, LPD por sus siglas en inglés), que incluye información de pacientes de dos paneles: médicos de atención primaria (MAP) y neurólogos/psiquiatras. El criterio principal de valoración fue la proporción de prescripciones iniciales de ácido valproico con al menos un medicamento relacionado con indicaciones de ácido valproico antes de la fecha de inicio del ácido valproico. Resultados: La proporción de prescripciones de ácido valproico secundarias con uso previo de medicamentos relacionados con indicaciones de ácido valproico fue del 78% –intervalo de confianza (IC) al 95%: 73,9-81,5%– y del 78,2% (IC al 95%: 74,5-81,4%) en los períodos principales previo y posterior a la implementación en el panel de MAP. Las cifras correspondientes a MEF fueron del 79,6% (IC al 95%: 73,6-84,5%) y del 75,5% (IC al 95%: 69,7-80,6%), respectivamente. La tasa de incidencia de embarazos expuestos al ácido valproico (por 1.000 personas-años) en MEF disminuyó de 17,4 en el período completo previo a la implementación a 8,5 en el período completo posterior a la implementación...(AU)

Introduction: Risk minimisation measures for valproate were implemented in Spain in 2015.Objective: The objective of this study is to assess the effectiveness of valproate risk minimisation measures in Spain intended to decrease the use of valproate as a first-line therapy, and to evaluate the prescribing patterns of valproate in women, including women of childbearing potential, in the pre- and post-implementation risk minimisation measures periods. Materials and methods: The prescribing patterns of valproate in females and women of childbearing potential before and after risk minimisation measures implementation were examined using the longitudinal patient data database, which includes patient information from two panels: primary care physicians and neurologists/psychiatrists. Primary endpoint was the proportion of initial valproate prescriptions with at least one medication related to the valproate indications before the valproate initiation date. Results: The proportion of incident valproate prescriptions with previous use of medication related to valproate indications was 78.0% (95% CI, 73.9%; 81.5%), and 78.2% (74.5%; 81.4%) in the main pre-and post-implementation periods in the primary care physician panel. The corresponding figures for women of childbearing potential were 79.6% (73.6%; 84.5%) and 75.5% (69.7%; 80.6%), respectively. The incidence rate of pregnancies exposed to valproate (per 1,000 person-years) in women of childbearing potential decreased from 17.4 the entire pre-implementation to 8.5 in the entire post-implementation periods. Conclusion: After the implementation of risk minimisation measures for valproate in Spain, no meaningful change in prescribing was observed regarding the proportion of valproate initiations preceded by prior medication related to valproate indications. The preventative measures recommended for use of valproate in women of childbearing potential should be considered.(AU)

Effectiveness of risk minimisation measures for valproate: a drug utilisation study in Europe, analysis of data from Spain. / Eficacia de las medidas de minimización de riesgos del ácido valproico: estudio de utilización del fármaco en Europa, análisis de datos de España.

INTRODUCTION: Risk minimisation measures for valproate were implemented in Spain in 2015. OBJECTIVE: The objective of this study is to assess the effectiveness of valproate risk minimisation measures in Spain intended to decrease the use of valproate as a first-line therapy, and to evaluate the prescribing patterns of valproate in women, including women of childbearing potential, in the pre- and post-implementation risk minimisation measures periods. MATERIALS AND METHODS: The prescribing patterns of valproate in females and women of childbearing potential before and after risk minimisation measures implementation were examined using the longitudinal patient data database, which includes patient information from two panels: primary care physicians and neurologists/psychiatrists. Primary endpoint was the proportion of initial valproate prescriptions with at least one medication related to the valproate indications before the valproate initiation date. RESULTS: The proportion of incident valproate prescriptions with previous use of medication related to valproate indications was 78.0% (95% CI, 73.9%; 81.5%), and 78.2% (74.5%; 81.4%) in the main pre-and post-implementation periods in the primary care physician panel. The corresponding figures for women of childbearing potential were 79.6% (73.6%; 84.5%) and 75.5% (69.7%; 80.6%), respectively. The incidence rate of pregnancies exposed to valproate (per 1,000 person-years) in women of childbearing potential decreased from 17.4 the entire pre-implementation to 8.5 in the entire post-implementation periods. CONCLUSION: After the implementation of risk minimisation measures for valproate in Spain, no meaningful change in prescribing was observed regarding the proportion of valproate initiations preceded by prior medication related to valproate indications. The preventative measures recommended for use of valproate in women of childbearing potential should be considered.

TITLE: Eficacia de las medidas de minimización de riesgos del ácido valproico: estudio de utilización del fármaco en Europa, análisis de datos de España.Introducción. En 2015 se aplicaron en España distintas medidas para la minimización de los riesgos (MMR) del ácido valproico. Objetivo. El objetivo de este estudio es evaluar la eficacia de las MMR del ácido valproico en España, con el fin de reducir el uso de ácido valproico como terapia de primera línea y evaluar los patrones de prescripción de ácido valproico en las mujeres, incluidas las mujeres en edad fértil (MEF), en los períodos previos y posteriores a la implementación de las MMR. Materiales y métodos. Los patrones de prescripción del ácido valproico en mujeres y MEF antes y después de la implementación de las MMR se examinaron utilizando la base de datos longitudinales de pacientes (longitudinal patient data, LPD por sus siglas en inglés), que incluye información de pacientes de dos paneles: médicos de atención primaria (MAP) y neurólogos/psiquiatras. El criterio principal de valoración fue la proporción de prescripciones iniciales de ácido valproico con al menos un medicamento relacionado con indicaciones de ácido valproico antes de la fecha de inicio del ácido valproico. Resultados. La proporción de prescripciones de ácido valproico secundarias con uso previo de medicamentos relacionados con indicaciones de ácido valproico fue del 78% ­intervalo de confianza (IC) al 95%: 73,9-81,5%­ y del 78,2% (IC al 95%: 74,5-81,4%) en los períodos principales previo y posterior a la implementación en el panel de MAP. Las cifras correspondientes a MEF fueron del 79,6% (IC al 95%: 73,6-84,5%) y del 75,5% (IC al 95%: 69,7-80,6%), respectivamente. La tasa de incidencia de embarazos expuestos al ácido valproico (por 1.000 personas-años) en MEF disminuyó de 17,4 en el período completo previo a la implementación a 8,5 en el período completo posterior a la implementación. Conclusión. Tras la implementación de las MMR del ácido valproico en España no se observó ningún cambio significativo en las prescripciones respecto a la proporción de iniciaciones de ácido valproico precedidas por medicación previa relacionada con indicaciones de ácido valproico. Se deben tener en cuenta las medidas preventivas recomendadas para el uso de ácido valproico en MEF.

[Fosfomycin prescription during production shortage]. / Prescription de la fosfomycine en situation critique.

The supply of fosfomycin had to be carefully controlled over metropolitan France during 10 weeks because of a unique crisis in production. Three hundred and forty prescriptions were collected and re-examined by an expert committee. The main indications were osteoarthritis (27%), lung infections (21%), severe sepsis (12.5%), and urinary tract infections (11%). The main bacteria involved, often multidrug resistant, were Pseudomonas aeruginosa (40%) and methicillin-resistant Staphylococcus. A careful analysis of the antibiogram proved fosfomycin to be irreplaceable in 36% of the cases. This study confirms and specifies the interest of fosfomycin. To our knowledge, this study was a unique opportunity to collect such specific data from the whole of France over a two-month shortage period.

Computer-aided prediction of macrolide antibiotic concentrations in human circulating polymorphonuclear leucocytes.

The relative in-vivo intracellular concentration of various macrolides in phagocytes cannot be directly extrapolated from in-vitro experiments that use a fixed and constant extracellular concentration for all compounds, since this fails to consider different rates of intracellular penetration, dosage regimens and pharmacokinetic data. In the proposed model, which takes into account the free plasma concentrations and accumulation characteristics of three antibiotics, roxithromycin, azithromycin and erythromycin, we show that roxithromycin and azithromycin may reach similar concentrations in human polymorphonuclear leucocytes when conditions mimic clinical administration of these drugs, while erythromycin concentrations are lower. This approach may be useful to predict the behaviour of other drugs or other cells, and to assist in the design of rational treatment schemes.

[Antipyretic effect of tiaprofenic acid in children. Comparative study with paracetamol]. / Effet antipyrétique de l'acide tiaprofénique chez l'enfant. Etude comparative au paracétamol.

The authors report the results of a randomised, multi-centric study comparing the antipyretic activity of tiaprofenic acid to that of acetaminophen. Seventy nine children of both sexes, aged 8 months to 9 years, having an average temperature at inclusion of 38.5 degrees C (+/- 0.5 degree C), received as a single dose 50 mg of tiaprofenic acid (3.7 +/- 0.9 mg/kg) (40 children) or 100 mg of acetaminophen (7.7 +/- 1.7 mg/kg) (39 children) for upper respiratory tract infection. The rectal temperature was taken regularly over a 6-hour period. Whatever the criteria considered (gradient between the initial temperature and the lowest temperature observed, difference of temperature at the different time points between the two groups), tiaprofenic acid appeared as effective an antipyretic as acetaminophen. Tolerance was good in both groups. Tiaprofenic acid appears as an interesting alternative to acetaminophen in the treatment of fever in upper respiratory tract infections in children.