Evaluación positiva de medicamentos: febrero, marzo y abril 2023 / Positive assessment of drugs: february, march and april 2023

Se reseñan los medicamentos evaluados y con dictamen positivo por comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento hechos públicos en febrero, marzo y abril de 2023 considerados de mayor interés para los profesionales sanitarios. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento. (AU)

The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency issued in February, March and April 2023, and considered of interest to healthcare professionals, are reviewed. These are positive technical reports prior to the authorization and placing on the market of the product. (AU)

Evaluación positiva de medicamentos: febrero, marzo y abril 2023 / Positive assessment of drugs: february, march and april 2023

Se reseñan los medicamentos evaluados y con dictamen positivo por comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento hechos públicos en febrero, marzo y abril de 2023 considerados de mayor interés para los profesionales sanitarios. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento. (AU)

The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency issued in February, March and April 2023, and considered of interest to healthcare professionals, are reviewed. These are positive technical reports prior to the authorization and placing on the market of the product. (AU)

Evaluación positiva de medicamentos: noviembre y diciembre de 2022 y enero de 2023 / Positive assessment of drugs: from November and December of 2022 and January of 2023

Se reseñan los medicamentos evaluados y con dictamen positivo por comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento hechos públicos de noviembre y diciembre de 2022 y enero de 2023, y considerados de mayor interés para el profesional sanitario. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento. (AU)

The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency made public from November 2022 to January of 2023, and considered of interest to the healthcare professional, are reviewed. These are positive technical reports prior to the authorization and placing on the market of the product. (AU)

Vertical and horizontal fall-off of black carbon and NO2 within urban blocks.

While exposure to traffic pollutants significantly decreases with distance from the curb, very dense urban architectures hamper such dispersion. Moreover, the building height reduces significantly the dispersion of pollutants. We have investigated the horizontal variability of Black Carbon (BC) and the vertical variability of NO2 and BC within the urban blocks. Increasing the distance from road BC concentrations decreased following an exponential curve reaching halving distances at 25 m (median), although with a wide variability among sites. Street canyons showed sharper fall-offs than open roads or roads next to a park. Urban background concentrations were achieved at 67 m distance on average, with higher distances found for more trafficked roads. Vertical fall-off of BC was less pronounced than the horizontal one since pollutants homogenize quickly vertically after rush traffic hours. Even shallower vertical fall-offs were found for NO2. For both pollutants, background concentrations were never reached within the building height. A street canyon effect was also found exacerbating concentrations at the lowest floors of the leeward side of the road. These inputs can be useful for assessing population exposure, air quality policies, urban planning and for models validation.

Particle-related exposure, dose and lung cancer risk of primary school children in two European countries.

Schools represent a critical microenvironment in terms of air quality due to the proximity to outdoor particle sources and the frequent lack of proper ventilation and filtering systems. Moreover, the population exposed in schools (i.e. children) represents a susceptible population due to their age. Air quality-based studies involving students' exposure at schools are still scarce and often limited to mass-based particle metrics and may thus underestimate the possible effect of sub-micron particles and particle toxicity. To this purpose, the present paper aims to evaluate the exposure to different airborne particle metrics (including both sub- and super-micron particles) and attached carcinogenic compounds. Measurements in terms of particle number, lung-deposited surface area, and PM fraction concentrations were measured inside and outside schools in Barcelona (Spain) and Cassino (Italy). Simultaneously, PM samples were collected and chemically analysed to obtain mass fractions of carcinogenic compounds. School time airborne particle doses received by students in classrooms were evaluated as well as their excess lung cancer risk due to a five-year primary school period. Median surface area dose received by students during school time in Barcelona and Cassino resulted equal to 110mm2 and 303mm2, respectively. The risk related to the five-year primary school period was estimated as about 2.9×10-5 and 1.4×10-4 for students of Barcelona and Cassino, respectively. The risk in Barcelona is slightly higher with respect to the maximum tolerable value (10-5, according to the U.S. Environmental Protection Agency), mainly due to toxic compounds on particles generated from anthropogenic emissions (mainly industry). On the other hand, the excess lung cancer risk in Cassino is cause of concern, being one order of magnitude higher than the above-mentioned threshold value due to the presence of biomass burning heating systems and winter thermal inversion that cause larger doses and great amount of toxic compounds on particles.

Interaction between airborne copper exposure and ATP7B polymorphisms on inattentiveness in scholar children.

Recent research indicates that airborne copper exposure in scholar children negatively affects brain functioning. These effects are likely to be influenced by the efficiency of copper metabolism, which is partly regulated by the ATPase copper transporting beta (ATP7B) gene. We investigated whether indoor and outdoor airborne copper exposure is differentially associated with child inattentiveness depending on genetic variation within the ATP7B gene in 1645 scholar children from the BREATHE project. Outdoor (courtyard) and indoor (classroom) air pollution levels were measured during class hours in each school. Inattentiveness was assessed through a follow-up with four measurements via the Attentional Network Test (4475 observations). Linear mixed models considering repeated measures were conducted to assess genetic and exposure main and interaction effects. Two interactions were detected indicating that ATP7B-rs1061472 (P for interaction 0.016) and ATP7B-rs1801243 (P for interaction 0.003) polymorphisms modified the association between indoor copper exposure and inattentiveness. Stratified analysis by genotypes revealed that both outdoor and indoor copper exposure increased inattentiveness in rs1061472-CC and rs1801243-CC carriers. These findings suggest that the genetic background promotes the association between airborne copper exposure at school with inattentiveness in children.

Spatiotemporally resolved black carbon concentration, schoolchildren's exposure and dose in Barcelona.

At city level, personal monitoring is the best way to assess people's exposure. However, it is usually estimated from a few monitoring stations. Our aim was to determine the exposure to black carbon (BC) and BC dose for 45 schoolchildren with portable microaethalometers and to evaluate the relationship between personal monitoring and fixed stations at schools (indoor and outdoor) and in an urban background (UB) site. Personal BC concentra-tions were 20% higher than in fixed stations at schools. Linear mixed-effect models showed low R(2) between personal measurements and fixed stations at schools (R(2)  ≤ 0.28), increasing to R(2)  ≥ 0.70 if considering only periods when children were at schools. For the UB station, the respective R(2) were 0.18 and 0.45, indicating the importance of the distance to the monitoring station when assessing exposure. During the warm season, the fixed stations agreed better with personal measurements than during the cold one. Children spent 6% of their time on commuting but received 20% of their daily BC dose, due to co-occurrence with road traffic rush hours and the close proximity to the source. Children received 37% of their daily-integrated BC dose at school. Indoor environments (classroom and home) were responsible for the 56% BC dose.

Impact of hepatitis C virus infection on the risk of death of alcohol-dependent patients.

Hepatitis C virus (HCV) infection is frequent among patients with alcohol use disorders. We aimed to analyse the impact of HCV infection on survival of patients seeking treatment for alcohol use. This was a longitudinal study in a cohort of patients who abused alcohol recruited in two detoxification units. Socio-demographic and alcohol use characteristics, liver function tests for the assessment of alcohol-related liver disease and HCV and HIV infection serologies were obtained at admission. Patients were followed until December 2008; causes of death were ascertained through clinical records and death registry. Cox models were used to analyse predictors of death. A total of 675 patients (79.7% men) were admitted; age at admission was 43.5 years (IQR: 37.9-50.2 years), duration of alcohol abuse was 18 years (IQR: 11-24 years), and median alcohol consumption was 200 g/day (IQR: 120-275 g/day). Distribution of patients according to viral infections was as follows: 75.7% without HCV or HIV infection, 14.7% HCV infection alone and 8.1% HCV/HIV coinfection. Median follow-up was 3.1 years (IQR: 1.5-5.1 years) accounting for 2,345 person-years. At the end of study, 78 patients (11.4%) had died. In the multivariate analysis, age at admission (HR = 1.71, 95%CI: 1.05-2.80), alcohol-related liver disease (HR = 3.55, 95%CI: 1.93-6.53) and HCV/HIV co-infection (HR = 3.86 95%CI: 2.10-7.11) were predictors of death. Younger patients (≤43 years) with HCV infection were more likely to die than those without viral infections (HR = 3.1, 95%CI: 1.3-7.3; P = 0.007). Among patients with alcohol-related liver disease, mortality rate was high, irrespective of viral infections. These data show that HCV infection confers a worse prognosis in patients with alcohol use disorders.

Outdoor and indoor UFP in primary schools across Barcelona.

Indoor and outdoor measurements of real-time ultrafine particles (UFP; N10-700 in this study) number concentration and average diameter were collected twice at 39 primary schools located in Barcelona (Spain), with classrooms naturally ventilated under warm weather conditions. Simultaneous outdoor N concentration measurements at schools under different traffic exposures showed the important role of this source, with higher levels by 40% on average at schools near heavy traffic, highlighting thus the increased exposure of children due to urban planning decisions. A well-defined spatial pattern of outdoor UFP levels was observed. Midday increases in outdoor N levels mainly attributed to nucleation processes have been recorded both at high and low temperatures in several of the outdoor school sites (increasing levels by 15%-70%). The variation of these increases also followed a characteristic spatial pattern, pointing at schools' location as a key variable in terms of UFP load owing to the important contribution of traffic emissions. Indoor N concentrations were to some extent explained by outdoor N concentrations during school hours, together with average temperatures, related with natural ventilation. Outdoor midday increases were generally mimicked by indoor N concentrations, especially under warm temperatures. At specific cases, indoor concentrations during midday were 30%-40% higher than outdoor. The time scale of these observations evidenced the possible role of: a) secondary particle formation enhanced by indoor precursors or conditions, maybe related with surface chemistry reactions mediated by O3, and/or b) UFP from cooking activities. Significant indoor N increases were detected after school hours, probably associated with cleaning activities, resulting in indoor N concentrations up to 3 times higher than those in outdoor. A wide variability of indoor/outdoor ratios of N concentrations and mean UFP sizes was detected among schools and measurement periods, which seems to be partly associated with climatic conditions and O3 levels, although further research is required.

Sources of indoor and outdoor PM2.5 concentrations in primary schools.

Children spend a third of their day in the classroom, where air pollution levels may differ substantially from those outdoors due to specific indoor sources. Air pollution exposure assessments based on atmospheric particle mass measured outdoors may therefore have little to do with the daily PM dose received by school children. This study aims to investigate outdoor and indoor sources of PM2.5 measured at 39 primary schools in Barcelona during 2012. On average 47% of indoor PM2.5 measured concentrations was found to be generated indoors due to continuous resuspension of soil particles (13%) and a mixed source (34%) comprising organic (skin flakes, clothes fibers, possible condensation of VOCs) and Ca-rich particles (from chalk and building deterioration). Emissions from seven outdoor sources penetrated easily indoors being responsible for the remaining 53% of measured PM2.5 indoors. Unpaved playgrounds were found to increase mineral contributions in classrooms by 5-6 µg/m(3) on average with respect to schools with paved playgrounds. Weekday traffic contributions varied considerably across Barcelona within ranges of 1-14 µg/m(3) outdoor and 1-10 µg/m(3) indoor. Indoors, traffic contributions were significantly higher (more than twofold) for classrooms with windows oriented directly to the street, rather than to the interior of the block or to playgrounds. This highlights the importance of urban planning in order to reduce children's exposure to traffic emissions.

Child exposure to indoor and outdoor air pollutants in schools in Barcelona, Spain.

Proximity to road traffic involves higher health risks because of atmospheric pollutants. In addition to outdoor air, indoor air quality contributes to overall exposure. In the framework of the BREATHE study, indoor and outdoor air pollution was assessed in 39 schools in Barcelona. The study quantifies indoor and outdoor air quality during school hours of the BREATHE schools. High levels of fine particles (PM2.5), nitrogen dioxide (NO2), equivalent black carbon (EBC), ultrafine particle (UFP) number concentration and road traffic related trace metals were detected in school playgrounds and indoor environments. PM2.5 almost doubled (factor of 1.7) the usual urban background (UB) levels reported for Barcelona owing to high school-sourced PM2.5 contributions: [1] an indoor-generated source characterised mainly by organic carbon (OC) from organic textile fibres, cooking and other organic emissions, and by calcium and strontium (chalk dust) and; [2] mineral elements from sand-filled playgrounds, detected both indoors and outdoors. The levels of mineral elements are unusually high in PM2.5 because of the breakdown of mineral particles during playground activities. Moreover, anthropogenic PM components (such as OC and arsenic) are dry/wet deposited in this mineral matter. Therefore, PM2.5 cannot be considered a good tracer of traffic emissions in schools despite being influenced by them. On the other hand, outdoor NO2, EBC, UFP, and antimony appear to be good indicators of traffic emissions. The concentrations of NO2 are 1.2 times higher at schools than UB, suggesting the proximity of some schools to road traffic. Indoor levels of these traffic-sourced pollutants are very similar to those detected outdoors, indicating easy penetration of atmospheric pollutants. Spatial variation shows higher levels of EBC, NO2, UFP and, partially, PM2.5 in schools in the centre than in the outskirts of Barcelona, highlighting the influence of traffic emissions. Mean child exposure to pollutants in schools in Barcelona attains intermediate levels between UB and traffic stations.

Within-city contrasts in PM composition and sources and their relationship with nitrogen oxides.

The present work is part of the INMA (INfancia y Medio Ambiente -'Environment and Childhood') project, which aims at assessing the adverse effects of exposure to air pollution during pregnancy and early in life. The present study was performed in the city of Sabadell (Northeast Spain) at three sampling sites covering different traffic characteristics, during two times of the year. It assesses time and spatial variations of PM(2.5) concentrations, chemical components and source contributions, as well as gaseous pollutants. Furthermore, a cross-correlation analysis of PM components and source contributions with gaseous pollutants used as a proxy for exposure assessment is carried out. Our data show the influence of traffic emissions in the Sabadell area. The main PM sources identified by Positive Matrix Factorisation (PMF) were similar between the two seasons: mineral source (traffic-induced resuspension, demolition/construction and natural background), secondary sulphate (higher in summer), secondary nitrate (only during winter), industrial, and road traffic, which was the main contributor to PM(2.5) at two of the sites. The correlation of concentrations of nitrogen oxides was especially strong with those of elemental carbon (EC). The relatively weaker correlations with organic carbon (OC) in summer are attributed to the variable formation of secondary OC. Strong correlations between concentration of nitrogen oxides and PM(2.5) road traffic contributions obtained from source apportionment analysis were seen at all sites. Therefore, under the studied urban environment, nitrogen oxides can be used as a proxy for the exposure to road traffic contribution to PM(2.5); the use of NO(x) concentrations being preferred, with NO and NO(2) as second and third options, respectively.

Incontinencia pigmenti. Cuatro pacientes con diferentes manifestaciones clínicas / Incontinentia pigmenti. Four patients with different clinical manifestations

La incontinencia pigmenti (IP) es un trastorno neurocutáneo raro, con una frecuencia de 1 en 50.000 recién nacidos, de etiología genética asociada a mutaciones en el gen IKBKG (NEMO) en Xq28, con herencia dominante ligada al X. Tiene una presentación clínica de manifestaciones muy variables detectadas desde la etapa neonatal, con 3 estadios bien definidos en forma secuencial, solapada o salteada, y cada una de estos con un diagnóstico diferencial distinto. Mediante la técnica molecular de PCR+RFLP se analizó el gen IKBKG en cuatro pacientes diferentes con manifestaciones sospechosas de IP además de la biopsia de piel confirmatoria; en todas se detectó la deleción de los exones 4 al 10. Destacamos que ante la sospecha clínica de IP es importante el estudio familiar y el multidisciplinario (complicaciones neurológicas, oculares...), y el necesario asesoramiento genético(AU)

Incontinentia pigmenti (IP) is a rare neurocutaneous disorder with a frequency of 1 in 50,000 newborn, and is associated with mutations in IKBKG gene (NEMO) in Xq28, inherited as an X-linked dominant trait. Clinical manifestations detected since the newborn period are highly variable, with 3 well established sequential or overlapped states and each with a characteristic differential diagnosis. With PCR+RFLPs, we analyzed the IKBKG gene in 4 patients with different clinical manifestations and characteristic skin biopsy. In all 4 patients the same deletion of exons 4 to 10 was identified. In female patients in whom the dermatological lesions lead to the suspicion of an IP diagnosis, it is important to have the complete, multidisciplinary and molecular analysis of their first level female relatives. This should give us a clear diagnosis, which is the first step to complete genetic counselling(AU)

[Incontinentia pigmenti. Four patients with different clinical manifestations]. / Incontinencia pigmenti. Cuatro pacientes con diferentes manifestaciones clínicas.

Incontinentia pigmenti (IP) is a rare neurocutaneous disorder with a frequency of 1 in 50,000 newborn, and is associated with mutations in IKBKG gene (NEMO) in Xq28, inherited as an X-linked dominant trait. Clinical manifestations detected since the newborn period are highly variable, with 3 well established sequential or overlapped states and each with a characteristic differential diagnosis. With PCR+RFLPs, we analyzed the IKBKG gene in 4 patients with different clinical manifestations and characteristic skin biopsy. In all 4 patients the same deletion of exons 4 to 10 was identified. In female patients in whom the dermatological lesions lead to the suspicion of an IP diagnosis, it is important to have the complete, multidisciplinary and molecular analysis of their first level female relatives. This should give us a clear diagnosis, which is the first step to complete genetic counselling.

Discondrosteosis de Leri-Weill. Mutación en gen SHOX y expresividad variable / Leri-Weill dyschondrosteosis. A variable expression SHOX gene mutation

Introducción: La primera descripción de una displasia mesomélica con acortamiento de extremidades fue realizada por Leri y Weill en 1929. De entonces se ha conocido el gen causal: SHOX, localizado en Xp22 y en Yp11.3, cuyas mutaciones se identifican entre el 56 y el 100% de los pacientes. Pacientes y métodos: Una de nuestras observaciones es familiar y la otra, aislada. Los diagnósticos en ambos casos fueron clínicos, apoyados por la radiología y el estudio molecular del gen SHOX por MLPA. Conclusiones: Su conocimiento tiene implicaciones terapéuticas dada la favorable evolución con hormona de crecimiento, además de posibles actuaciones quirúrgicas y del asesoramiento genético, dado su carácter hereditario autosómico dominante (AU)

Introduction: A mesomelic dysplasia with shortened limbs was first described by Leri and Weillin 1929. Since then the causal gene has been known as SHOX (short stature homeobox) gene, located in Xp22 and Yp11.3, with mutations being identified in between 56% and 100% of the patients. Patients and methods: One of the observations is familial and the other is an isolated case. The diagnosis in both cases was clinical, supported by radiology and a molecular study of the SHOX gene using multiplex ligation-dependent probe amplification (MLPA). Conclusions: Knowledge of this condition has therapeutic implications, given the favourable progress with growth hormone treatment, as well as possible surgical procedures and genetic counselling, due to its autosomal dominant hereditary character (AU)

[Leri-Weill dyschondrosteosis. A variable expression SHOX gene mutation]. / Discondrosteosis de Leri-Weill. Mutación en gen SHOX y expresividad variable.

INTRODUCTION: A mesomelic dysplasia with shortened limbs was first described by Leri and Weill in 1929. Since then the causal gene has been known as SHOX (short stature homeobox) gene, located in Xp22 and Yp11.3, with mutations being identified in between 56% and 100% of the patients. PATIENTS AND METHODS: One of the observations is familial and the other is an isolated case. The diagnosis in both cases was clinical, supported by radiology and a molecular study of the SHOX gene using multiplex ligation-dependent probe amplification (MLPA). CONCLUSIONS: Knowledge of this condition has therapeutic implications, given the favourable progress with growth hormone treatment, as well as possible surgical procedures and genetic counselling, due to its autosomal dominant hereditary character.

Hipocondroplasia. Diagnóstico Clínico, radiológico y genético. A propósito de dos observaciones precoces / Hypochondroplasia. Clinical, radiological and genetic diagnosis. Base don two early observations

La hipocondroplasia es una forma de hipocrecimiento por osteocondordisplasi, de posible infradiagnóstico y transmisión autosómica dominante. Forma menor de la condroplasia, con mutación igualmente localizada en el gen FGFR3, su conocimiento y precocidad en la identificación conducen al asesoramiento genético, a disminuir con medidas de higiene física sus posibles complicaciones y a plantear el alargamiento óseo para mejorar la falla final, mientras no tengamos otras soluciones médicas para ella (AU)

Hipochondroplasia is an osteochondrodyplasia characterized by short stature. Clinical and molecularly similar to achondroplasia since the shortening of legs and bowing of the extremities occur in both syndromes The causative mutations of both entities are in the FGFR3 gene. Misdiagnosis is common since clinical manifestations are subtle in hypochondroplasia. The knowledge, identification and genetic assessment are necessary to avoid possible complications and to evaluate orthopedic therapy with leg lengthening combined with correction of bowlegs as an alternative until we have something else to offer to these patients (AU)

Incontinentia pigmenti con inicio clínico atípico / Atypical onset of incontinentia pigmenti

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