Fluticasone in mild to moderate atopic dermatitis relapse: a randomized controlled trial

BACKGROUND: The long-term efficacy of corticosteroids to prevent atopic dermatitis (AD) relapses has partially been addressed in children. This study compared an intermittent dosing regimen of fluticasone propionate (FP) cream 0.05% with its vehicle base in reducing the risk of relapse in children with stabilized AD. METHODS: A randomized controlled, multicentric, double-blind trial was conducted. Children (2-10 years) with mild/moderate AD (exclusion criteria: >30% affected body surface area and/or head) were enrolled into an Open-label Stabilization Phase (OSP) of up to 2 weeks on twice daily FP. Those who achieved treatment success entered the Double-blind Maintenance Phase (DMP). They were randomly allocated to receive FP or vehicle twice-weekly on consecutive days for 16 weeks. The primary study endpoint was relapse rate; time to relapse and severity of disease were also studied. Kaplan-Meier estimates were calculated. RESULTS: Fifty-four patients (29 girls) entered the OSP (23 mild AD) and 49 (26 girls) continued into the DMP. Mean age was 5.5 (SD: 2.8) and 5.1 (SD: 2.3) yrs for FP and vehicle groups, respectively. Four patients withdrew from the DMP (two in every group). Patients treated with FP twice weekly had a 2.7 fold lower risk of experiencing a relapse than patients treated with vehicle (relative risk 2.72, SD: 1.28; p = 0.034). FP was also superior to vehicle for delaying time to relapse. Both treatment therapies were well tolerated. CONCLUSION: This long-term study shows that twice weekly FP provides an effective maintenance treatment to control the risk of relapse in children with AD

No disponible

Fluticasone in mild to moderate atopic dermatitis relapse: A randomized controlled trial.

BACKGROUND: The long-term efficacy of corticosteroids to prevent atopic dermatitis (AD) relapses has partially been addressed in children. This study compared an intermittent dosing regimen of fluticasone propionate (FP) cream 0.05% with its vehicle base in reducing the risk of relapse in children with stabilized AD. METHODS: A randomized controlled, multicentric, double-blind trial was conducted. Children (2-10 years) with mild/moderate AD (exclusion criteria: >30% affected body surface area and/or head) were enrolled into an Open-label Stabilization Phase (OSP) of up to 2 weeks on twice daily FP. Those who achieved treatment success entered the Double-blind Maintenance Phase (DMP). They were randomly allocated to receive FP or vehicle twice-weekly on consecutive days for 16 weeks. The primary study endpoint was relapse rate; time to relapse and severity of disease were also studied. Kaplan-Meier estimates were calculated. RESULTS: Fifty-four patients (29 girls) entered the OSP (23 mild AD) and 49 (26 girls) continued into the DMP. Mean age was 5.5 (SD: 2.8) and 5.1 (SD: 2.3) yrs for FP and vehicle groups, respectively. Four patients withdrew from the DMP (two in every group). Patients treated with FP twice weekly had a 2.7 fold lower risk of experiencing a relapse than patients treated with vehicle (relative risk 2.72, SD: 1.28; p=0.034). FP was also superior to vehicle for delaying time to relapse. Both treatment therapies were well tolerated. CONCLUSION: This long-term study shows that twice weekly FP provides an effective maintenance treatment to control the risk of relapse in children with AD.

¿Se ha modificado el uso de antitérmicos tras la introducción de ibuprofeno a diferentes concentraciones? / Has the use of antipyretics been modified after the introduction of different concentrations of ibuprofen into the market?

INTRODUCCIÓN: Se analiza la utilización de antitérmicos en pediatría extrahospitalaria en España después de la aparición de medicamentos con 40 mg/ml de ibuprofeno. PACIENTES Y MÉTODOS: Estudio transversal, observacional y descriptivo en pacientes menores de 14 años con síndrome febril ya tratado, atendidos en Urgencias del Servicio de Pediatría del Consorcio Hospital General Universitario de Valencia entre noviembre del 2012 y enero del 2013. RESULTADOS: De 217 niños, 144 estaban tratados con paracetamol o ibuprofeno, 69 recibían ambos fármacos, y uno paracetamol y metamizol. Hubo un 58,7% de exposiciones a paracetamol y un 40,9% a ibuprofeno. En el 63,2% de los casos el uso de antitérmicos fue decidido por los padres. En 98 exposiciones la dosis fue diferente de la autorizada en la ficha técnica (uso «off-label»). El 40,2% de las exposiciones a ibuprofeno fue «off-label», en su mayoría por infradosificación (35,9%). Paracetamol se usó «off-label» en el 29,8% de los casos, predominando la sobredosificación (26,8%), diferencia estadísticamente significativa. No hubo diferencias significativas en el uso «off-label» combinado o en monoterapia. CONCLUSIONES: La mayoría de los niños con síndrome febril que llegan a urgencias con tratamiento antitérmico reciben este por decisión de sus padres. El paracetamol es el fármaco más usado, uno de cada 3 niños lo reciben simultáneamente con ibuprofeno. En un tercio de las ocasiones, los antitérmicos son utilizados al margen de la ficha técnica con una tendencia creciente que, en el caso del ibuprofeno, puede estar relacionada con la existencia de presentaciones farmacéuticas con distintas concentraciones

INTRODUCTION: Due to the emergence of new pharmaceutical presentations of ibuprofen (40 mg/ml), an analysis was made on the use of antipyretics in pediatric outpatient in Spain. PATIENTS AND METHODS: A cross-sectional, observational, descriptive study was carried out on a sample of children under 14 years old with treated febrile syndrome, seen in the Emergency Room of the Hospital General Universitario de Valencia from November 2012 to January 2013. RESULTS: Of the 217 children included, 144 were treated with paracetamol or ibuprofen, 69 received both drugs, and one received paracetamol and metamizol. There were 58.7% of exposures to paracetamol and 40.9% to ibuprofen. The parents decided the use of antipyretics in 63.2% of cases. In 98 exposures the dose was different from that authorized in the labeling of the drug (off-label use). Ibuprofen was used off-label in 40.2% of cases, mostly by underdosing (35.9%). Paracetamol was used off-label in 29.8% of cases, predominantly overdose (26.8%), with the difference being statistically significant. No significant differences were observed in the off-label use in either monotherapy or combined use. There were also no differences when antipyretics prescribed by doctors or given directly by parents were evaluated separately. CONCLUSIONS: The majority of children with treated febrile syndrome seen in the Emergency Room were receiving antipyretic drugs after a parental decision. Paracetamol is the most commonly used drug and one in three children received it simultaneously with ibuprofen. The antipyretics were used off label in one-third of the cases. Off label use of ibuprofen is increasing, and is probably due to the existence of different pharmaceutical presentations

[Has the use of antipyretics been modified after the introduction of different concentrations of ibuprofen into the market?]. / ¿Se ha modificado el uso de antitérmicos tras la introducción de ibuprofeno a diferentes concentraciones?

INTRODUCTION: Due to the emergence of new pharmaceutical presentations of ibuprofen (40 mg/ml), an analysis was made on the use of antipyretics in pediatric outpatient in Spain. PATIENTS AND METHODS: A cross-sectional, observational, descriptive study was carried out on a sample of children under 14 years old with treated febrile syndrome, seen in the Emergency Room of the Hospital General Universitario de Valencia from November 2012 to January 2013. RESULTS: Of the 217 children included, 144 were treated with paracetamol or ibuprofen, 69 received both drugs, and one received paracetamol and metamizol. There were 58.7% of exposures to paracetamol and 40.9% to ibuprofen. The parents decided the use of antipyretics in 63.2% of cases. In 98 exposures the dose was different from that authorized in the labeling of the drug (off-label use). Ibuprofen was used off-label in 40.2% of cases, mostly by underdosing (35.9%). Paracetamol was used off-label in 29.8% of cases, predominantly overdose (26.8%), with the difference being statistically significant. No significant differences were observed in the off-label use in either monotherapy or combined use. There were also no differences when antipyretics prescribed by doctors or given directly by parents were evaluated separately. CONCLUSIONS: The majority of children with treated febrile syndrome seen in the Emergency Room were receiving antipyretic drugs after a parental decision. Paracetamol is the most commonly used drug and one in three children received it simultaneously with ibuprofen. The antipyretics were used off label in one-third of the cases. Off label use of ibuprofen is increasing, and is probably due to the existence of different pharmaceutical presentations.

[Drugs used in paediatric outpatients: do we have enough information available?]. / Medicamentos utilizados en pediatría extrahospitalaria: disponemos de información suficiente?

OBJECTIVE: To analyse the drugs taken in paediatric outpatients and the information available on these drugs. PATIENTS AND METHODS: A cross-sectional, observational, descriptive study was carried out. The study involved a sample of children under 14 years seen in the Emergency Room of the HGUV from June 2005 to August 2006. The medicines they received were quantified and classified, and the information on these drugs available in the Vademecum International Medicom and in the Summary of Product Characteristics, were analysed. RESULTS: Of the 462 children (mean age 5.2 (95 % CI 4.9-5.6)) included, 336 received 667 medicines (152 different medicines) that contained 864 drugs (161 different drugs). In 34.3 % of the cases it was for self-medication. Children under 4 years received more drugs than the older group (80.2 % in the younger group and 67.4 % in the older). Patients received from 1 to 7 medicines (mean 2.0). Children receiving 2 or 3 medicines were younger than those who received one. Five therapeutic groups of the Anatomical-Therapeutical-Chemical Classification (ATC) include the 93.1 % of the drugs administered (R: 26.5 %; M: 23.8 %; N: 22.8 %; J: 10.6 % and A: 10.0 %). In the information sources consulted there was no information available on paediatric use for 40 of the 152 medicines used. CONCLUSIONS: Almost 75 % of patients seen in the Emergency Room were already receiving drugs before they arrived at the hospital, in many cases as a result of self-medication. The information available on the paediatric use of drugs is deficient. Clinical research is required to study the effects of pharmacological treatment on children and to improve the information on their use.

Medicamentos utilizados en pediatría extrahospitalaria: ¿disponemos de información suficiente? / Drugs used in paediatric outpatients: Do we have enough information available?

Objetivo: Analizar los medicamentos que reciben los pacientes pediátricos en el ámbito extrahospitalario y la información disponible sobre los mismos. Pacientes y métodos: Estudio transversal, observacional y descriptivo realizado en una muestra de pacientes menores de 14 años atendidos en urgencias del Servicio de Pediatría del Consorcio Hospital General Universitario de Valencia entre junio 2005 y agosto 2006. Se cuantifican y clasifican los medicamentos utilizados antes de acudir a urgencias y se analiza la información sobre su uso que contiene el Vademécum Internacional Medicom y la ficha técnica. Resultados: Se recogió información sobre 462 niños con media de edad de 5,2 años (intervalo de confianza del 95 % [IC 95 %]: 4,9-5,6). De ellos, 336 reciben 667 medicamentos (152 distintos) que contienen 864 principios activos (161 diferentes). En el 34,3 % de los casos el uso es por automedicación. Los menores de 4 años reciben medicamentos en mayor proporción que los mayores (80,2 y 67,4 %, respectivamente). Los pacientes reciben entre 1 y 7 medicamentos (media 2,0). Los que toman 2 o 3 medicamentos son menores que los que toman uno. Cinco grupos terapéuticos de la Clasificación anatómico-terapéutico-química (ATC) incluyen el 93,1 % de los medicamentos (R [aparato respiratorio]: 26,5 %; M [aparato locomotor]: 23,8 %; N [sistema nervioso central]: 22,8 %; J [antiinfecciosos por vía general]: 10,6 % y A [aparato digestivo y metabolismo]: 10,0 %). Para 40 de los 152 medicamentos no hay información pediátrica en las fuentes consultadas. Conclusiones: Casi tres cuartas partes de los niños atendidos en urgencias toman medicamentos antes de acudir a este servicio, en muchos casos por automedicación. La información sobre uso pediátrico de medicamentos es incompleta y presenta incongruencias. Es necesario fomentar la investigación clínica sobre los efectos del tratamiento farmacológico en los niños para mejorar la información sobre su uso (AU)

Objective: To analyse the drugs taken in paediatric outpatients and the information available on these drugs. Patients and methods: A cross-sectional, observational, descriptive study was carried out. The study involved a sample of children under 14 years seen in the Emergency Room of the HGUV from June 2005 to August 2006. The medicines they received were quantified and classified, and the information on these drugs available in the Vademecum International Medicom and in the Summary of Product Characteristics, were analysed. Results: Of the 462 children (mean age 5.2 (95 % CI 4.9-5.6)) included, 336 received 667 medicines (152 different medicines) that contained 864 drugs (161 different drugs). In 34.3 % of the cases it was for self-medication. Children under 4 years received more drugs than the older group (80.2 % in the younger group and 67.4 % in the older). Patients received from 1 to 7 medicines (mean 2.0). Children receiving 2 or 3 medicines were younger than those who received one. Five therapeutic groups of the Anatomical-Therapeutical-Chemical Classification (ATC) include the 93.1 % of the drugs administered (R: 26.5 %; M: 23.8 %; N: 22.8 %; J: 10.6 % and A: 10.0 %). In the information sources consulted there was no information available on paediatric use for 40 of the 152 medicines used. Conclusions: Almost 75 % of patients seen in the Emergency Room were already receiving drugs before they arrived at the hospital, in many cases as a result of self-medication. The information available on the paediatric use of drugs is deficient. Clinical research is required to study the effects of pharmacological treatment on children and to improve the information on their use (AU)

[Are the Spanish hypertensive children therapeutic orphans?]. / Son los niños hipertensos españoles huérfanos terapéuticos?

INTRODUCTION: According to current guidelines, hypertension in children should be treated with the same drugs as those used in adults, with adjustment of the dose to their body size. The term therapeutic orphans refers to the lack of information on how to use drugs in children. The aim of this study was to investigate whether the information in the International Vademecum (I-V) is sufficient for the correct use of antihypertensive drugs in children. MATERIAL AND METHOD: We reviewed the data on pediatric dosages of antihypertensive drugs in the I-V (44th and 45th editions). When there were several drugs for the same molecule, the last one marked with the Spanish Ministry of Health and Consumption's logo was selected. When information on a particular drug was not available, the entries for other drugs with the same active principle were reviewed. The information was compared with that provided by the Fourth Report of the National High Blood Pressure Education Program Working Group (NHBPEP). RESULTS: A total of 111 entries for 41 antihypertensive drugs were reviewed. Information on use in children is available for only 3 diuretics and 2 angiotensin converting enzyme inhibitors. The remaining entries either contain no information or indicate that the effectiveness and safety in children has not been evaluated. Some drugs are contraindicated in children. The Fourth Report of the NHBPEP includes pediatric dosages for 28 antihypertensive drugs. The Food and Drug Administration has authorized 10 antihypertensive drugs for use in children. CONCLUSIONS: The information in the V-I can be used to determine the correct dosage of only 5 antihypertensive drugs in children, making this age group authentic therapeutic orphans.

¿Son los niños hipertensos españoles huérfanos terapéuticos? / Are the Spanish hypertensive children therapeutic orphans?

Introducción: Según las guías, la hipertensión en los niños debe tratarse con los mismos fármacos usados en adultos ajustando las dosis al tamaño corporal. El término huérfano terapéutico se refiere a la falta de información sobre el uso de medicamentos en niños. El objetivo es investigar si el Vademécum Internacional (V-I) contiene información para el uso correcto de antihipertensivos en niños. Material y método: Revisión en el V-I de la posología pediátrica de antihipertensivos. Si existen varias especialidades para un fármaco se selecciona el del logotipo del Ministerio de Sanidad y Consumo más reciente. Si en una monografía no hay información, se revisan las de otras especialidades del mismo principio activo. La información se compara con la del 4.º informe del National High Blood Pressure Education Program Working Group (NHBPEP). Resultados: Se revisan 111 monografías de 41 fármacos con indicación de antihipertensivo. Sólo para 3 diuréticos y 2 inhibidores de la enzima conversora de angiotensina (IECA) hay información pediátrica. Las otras advierten de que no se ha establecido la eficacia y seguridad o no hacen referencia a niños. En algunos casos se contraindican. El 4.º informe del NHBPEP incluye dosificación pediátrica de 28 antihipertensivos. La Food and Drug Administration (FDA) tiene autorizados 10 antihipertensivos para uso en niños. Conclusiones: Con la información del V-I sólo es posible dosificar correctamente 5 antihipertensivos en niños, lo que los convierte en auténticos huérfanos terapéuticos

Introduction: According to current guidelines, hypertension in children should be treated with the same drugs as those used in adults, with adjustment of the dose to their body size. The term therapeutic orphans refers to the lack of information on how to use drugs in children. The aim of this study was to investigate whether the information in the International Vademecum (I-V) is sufficient for the correct use of antihypertensive drugs in children. Material and method: We reviewed the data on pediatric dosages of antihypertensive drugs in the I-V (44th and 45th editions). When there were several drugs for the same molecule, the last one marked with the Spanish Ministry of Health and Consumption's logo was selected. When information on a particular drug was not available, the entries for other drugs with the same active principle were reviewed. The information was compared with that provided by the Fourth Report of the National High Blood Pressure Education Program Working Group (NHBPEP). Results: A total of 111 entries for 41 antihypertensive drugs were reviewed. Information on use in children is available for only 3 diuretics and 2 angiotensin converting enzyme inhibitors. The remaining entries either contain no information or indicate that the effectiveness and safety in children has not been evaluated. Some drugs are contraindicated in children. The Fourth Report of the NHBPEP includes pediatric dosages for 28 antihypertensive drugs. The Food and Drug Administration has authorized 10 antihypertensive drugs for use in children. Conclusions: The information in the V-I can be used to determine the correct dosage of only 5 antihypertensive drugs in children, making this age group authentic therapeutic orphans

Clinical trials in children.

Randomized controlled clinical trials are felt by the medical community to provide the best evidence. Participation in trials involves the possibility of obtaining benefits but also of suffering some risks. Those risks are often considered unacceptable for children but if clinical trials are not conducted in children, clinicians are forced to extrapolate study data from adults. In 1968 H. Shirkey termed children "therapeutic orphans" because of the lack of adequately tested and labeled drugs available in appropriate formulations. Research involving children entails specific difficulties as the need to study children of different ages, the small number of children affected by certain diseases or ethical issues. This paper considers aspects of pediatric clinical pharmacology and children's responses to drugs. It also reviews some of the current situations in pediatric clinical trials, covering aspects such as: the benefits and risks of trial participation; the specificity of pediatric trial design; the ethical issues such as consent; the use of placebo or the participation of healthy children; and the current legal situation in Europe and in the USA.