Evaluación de los comparadores empleados en los estudios pivotales de nuevos medicamentos e indicaciones / Assessment of comparators used in pivotal studies of new medicines and indications

Objetivo: En algunos casos, los estudios pivotales para aprobar nuevos medicamentos no emplean el comparador más adecuado. El objetivo es cuantificar este problema analizando los Informes de Posicionamiento Terapéutico (IPT) publicados por el Ministerio de Sanidad español.Métodos: El comparador se clasificó en seis categorías según la adecuación del tratamiento, es decir, si coincidía con el estándar de tratamiento al ser autorizado: A-“inicialmente adecuado”, B-“sin comparador por causa ética”, C-“sin comparador excluyendo los clasificados en B”, D-“inadecuado” y E-“parcialmente subóptimo” (cuando era estándar solo para parte de los pacientes).La variable principal fue la proporción de nuevos fármacos/indicaciones con comparación suficiente (categorías A, B y C) o deficiente (el resto). La información sobre comparadores y tratamiento estándar se extrajo del IPT. Resultados: Se analizaron aleatoriamente 186 IPT con nuevos medicamentos/indicaciones, publicados entre 2013 y 2022. La comparación se consideró suficiente en un 73,7% (IC95 66,9-79,5) de los casos. El 26,3% restante (IC95 20,5-33,1) presentaba comparaciones deficientes en el ensayo pivotal, ya fuera por comparador inadecuado (11,3%), parcialmente subóptimo (5,4%) o ausencia de un estudio comparativo (9,7%). No hubo diferencias en relación con el año de aprobación.Conclusiones: Aproximadamente uno de cada cuatro nuevos medicamentos o indicaciones carece de una comparación suficiente en el momento de empezar a ser utilizado en la práctica clínica. La proporción no mejora a lo largo de los últimos 10 años. Las agencias reguladoras deben ser más exigentes en la selección del comparador para los ensayos clínicos pivotales, por cuestiones éticas y sanitarias. (AU)

Objective: Pivotal studies to approve new medicines often do not use the most appropriate comparator. The objective is to quantify this problem by analysing the Therapeutic Positioning Reports (IPT for its acronym in Spanish) published by the Spanish Health Ministry.Methods: The comparator was classified into six categories, based on the appropriateness of the treatment, i.e. whether it matched the standard of treatment when authorised: A-«initially adequate» (at the start of the study), B-«no comparator for ethical reasons», C-«no comparator -excluding B-«, D-«inadequate» and E-«partially suboptimal» (when it was standard for part of the included patients but not for all of them).The primary endpoint was the proportion of new drugs/indications with sufficient (categories A, B and C) or poor comparator (the rest). Information on comparators and standard treatment was extracted from the IPT. Results: We randomly analysed 186 IPTs with new drugs or indications, published between 2013 and March 2022. Comparability was assessed as sufficient in 73.7% (95%CI 66.9-79.5) of cases. The remaining 26.3% (95%CI 20.5-33.1) had poor comparisons in the pivotal trial, either due to inadequate comparator (11.3%), partially suboptimal (5.4%) or absence of a comparative study excluding ethical justification (9.7%). Conclusions: Approximately one in four new medicines or indications lacks sufficient comparability at the time of entry into clinical practice. The proportion has not improved over the last 10 years. Regulatory agencies need to be more stringent in comparator selection for pivotal clinical trials, for ethical and health reasons. (AU)

A pleural ultrasound image of a collapsed lung surrounded by pleural fluid ("jellyfish sign") may correspond to an intrapericardial mass.

Lung ultrasound has been shown to be a valuable diagnostic tool. It has become the main way to get to the diagnosis of pleural effusion with much more specificity and sensibility than the x-ray. The diagnosis of pleural effusion with ultrasound is easily obtained after the visualization of hypoechoic fluid surrounding the lung. Sometimes it appears as an image of a collapsed lung moving with the surrounded pleural fluid ("jellyfish sign"). Until now this sign was almost pathognomonic of pleural effusion, but we explore a case in which this sign could have led to a misleading diagnosis. We present the case of a child admitted to intensive care with respiratory distress. In the point of care lung ultrasound we believed to see a pleural effusion with a collapsed lung moving into the effusion. Due to the enlargement of the pericardial sac, we did not realize that what we thought to be the pleural space was in fact the pericardial space. Unfortunately, there was a more echogenic area inside the pericardial effusion which led to a misleading fake lung atelectasis with pleural effusion ("jellyfish sign"). The correct diagnosis was properly obtained after assessing a cardiac point of care ultrasound using a four chambers view. The left side of the thorax is more difficult to be sonographed than the right due to the presence of the heart fossa that occupies a significant part of that side. Obtaining the diagnosis of pleural effusion on that side is more difficult for this reason and can sometimes be misleading with a pericardial effusion. The presence of the "jellyfish sign" is not pathognomonic and may lead to an error if we are guided only by the presence of that sign. To avoid such a misleading diagnosis, we highly recommend performing a point of care cardiac ultrasound if a pleural effusion is primarily seen in the lung ultrasound.

Bloqueo subdural como complicación de la anestesia epidural / Subdural block as a complication of epidural anesthesia

El bloqueo subdural involuntario es una rara pero conocida complicación. Describimos el caso de un bloqueo subdural ocurrido al intentar realizar una analgesia epidural para el parto. (AU)

Unintentional subdural block is a rare but known complication. We describe the case of unintentional subdural block while attempting to perform an epidural block for delivery. (AU)

Development of a constitutive model for the compaction of recovered polyethylene terephthalate packages.

To date, PET (polyethylene terephthalate) is the most widely used plastic in packaging and also one of the most recycled polymers worldwide. However, the high transport costs and stagnated prices of recycled PET undermine recycling process profits. Transport costs can lower through compaction, which is still not a completely well-known process. Due to heterogeneous designs, the output density of the compaction process varies. This poses problems during equipment design, selection or operation processes as recovery costs sharply increase if the required density is not met. In this manuscript, the authors develop a constitutive model for the compaction of recovered PET packaging. This experimentally validated model, based on the elasto-plastic behaviour of PET packages, allows the output density range to be predicted according to the compression pressure during PET compaction. Unlike other generic compaction models that need more than two parameters, this model uses only one and better correlates with the experimental results. Unlike existing generic models, the model parameters have a physical meaning, which allows the influence of different factors on the compaction process to be assessed. Finally as a result of the model analysis, we provide some tips to enhance compaction equipment efficiency.

Expresiones y criterios mejorables en la redacción de informes de evaluación y posicionamiento terapéutico / Expressions and criteria that could be improved in the writing of reports for drug evaluation and therapeutic positioning

En la revisión de borradores de informes para evaluación y posicionamiento de nuevos fármacos en un entorno multidisciplinar, se observan determinados errores de expresión o criterio que se repiten con frecuencia. Principalmente, están relacionados con la consideración de “diferencias” o tendencias no significativas, abuso de la reducción relativa del riesgo, errores en la valoración de resultados por subgrupos sin calcular la interacción estadística, confusiones en la interpretación de las comparaciones indirectas, sobrevaloración de la relevancia clínica con variables subclínicas y afirmaciones sesgadas en el apartado de seguridad, entre otros. También se observa a menudo ambigüedad o inhibición en el posicionamiento, especialmente en situaciones de precariedad en la evidencia disponible. El presente trabajo expone de forma sintética tales errores, aclara algunos términos comunes y propone expresiones o criterios alternativos que se consideran preferibles, con el fin de ofrecer una evaluación para la toma de decisiones en beneficio de los pacientes. (AU)

In the review of reports for evaluation and positioning of new drugs in a multidisciplinary setting, some usual errors of expression or criteria are observed. Most of them are related to the consideration of «differences» or non-significant trends, abuse of the relative risk reduction, errors in the assessment of results by subgroups without calculating the statistical interaction, misinterpretation of indirect comparisons, excess in the assessment of clinical relevance with subclinical variables and biased statements in the safety section, among others. Ambiguity or inhibition in positioning is also often observed, especially in situations of precariousness in the available evidence. This work summarizes such errors, clarifies some common terms and proposes alternative expressions or criteria that are considered preferable, in order to offer evaluations for decision-making focused on the benefit of patients. (AU)

Insuficiencia respiratoria aguda como forma de debut de una anomalía congénita (doble arco aórtico) / Acute respiratory failure as a form of debut of a congenital anomaly (double aortic arch)

El doble arco aórtico es una anomalía vascular poco frecuente que provoca compresión traqueal y esofágica, habitualmente en losprimeros meses de vida. La estenosis traqueal asociada con el doble arco aórtico conlleva un alto riesgo de morbilidad, mortalidady reestenosis. Presentamos el caso de un paciente en que su anomalía no fue diagnosticada, y permaneció en silencio hasta la edad adulta cuando comenzó a padecer clínica compresiva. (AU)

The double aortic arch is a rare vascular anomaly that usually causes tracheal and esophageal compression in the first months oflife. Tracheal stenosis associated with double aortic arch carries a high risk of morbidity, mortality, and restenosis. We present thecase of a patient in whom his anomaly was not diagnosed, and he remained silent until adulthood when he began to suffer from compression symptoms. (AU)

Evaluation of the vasoactive-inotropic score, mid-regional pro-adrenomedullin and cardiac troponin I as predictors of low cardiac output syndrome in children after congenital heart disease surgery / Evaluación de la escala vasoactiva-inotrópica, pro-adrenomedulina y troponina cardiaca-I como factores predictivos del síndrome de bajo gasto cardiaco en niños tras corrección quirúrgica de cardiopatías congénitas

Objective: To determine the predictive value of the inotropic score (IS) and vasoactive-inotropic score (VIS) in low cardiac output syndrome (LCOS) in children after congenital heart disease surgery involving cardiopulmonary bypass (CPB), and to establish whether mid-regional pro-adrenomedullin (MR-proADM) and cardiac troponin I (cTn-I), associated to the IS and VIS scores, increases the predictive capacity in LCOS. Design: A prospective observational study was carried out. Setting: A Paediatric Intensive Care Unit. Patients: A total of 117children with congenital heart disease underwent CPB. Patients were divided into two groups: LCOS and non-LCOS. Interventions: The clinical and analytical data were recorded at 2, 12, 24 and 48h post-CPB. Logistic regression was used to develop a risk prediction model using LCOS as dependent variable. Main outcome measures: LCOS, IS, VIS, MR-proADM, cTn-I, age, sex, CPB time, PIM-2, Aristotle score. Results: While statistical significance was not recorded for IS in the multivariate analysis, VIS was seen to be independently associated to LCOS. On the other hand, VIS>15.5 at 2h post-CPB, adjusted for age and CPB timepoints, showed high specificity (92.87%; 95%CI: 86.75-98.96) and increased negative predictive value (75.59%, 95%CI: 71.1-88.08) for the diagnosis of LCOS at 48h post-CPB. The predictive power for LCOS did not increase when VIS was combined with cTn-I >14ng/ml at 2h and MR-proADM >1.5nmol/l at 24h post-CPB. Conclusions: The VIS score at 2h post-CPB was identified as an independent early predictor of LCOS. This predictive value was not increased when associated with LCOS cardiac biomarkers. The VIS score was more useful than IS post-CPB in making early therapeutic decisions in clinical practice post-CPB

Objetivo: Estudiar el valor predictivo de la escala inotrópica (IS) y la escala vasoactiva-inotrópica (VIS) en el síndrome de bajo gasto cardiaco (SBGC) en niños poscirugía de cardiopatías congénitas mediante bypass cardiopulmonar (BCP). Determinar si adrenomedulina (MR-proADM) y troponina cardiaca-I (cTn-I) asociadas con IS y VIS incrementan su capacidad predictora de SBGC. Diseño: Estudio prospectivo y observacional. Ámbito: Cuidados intensivos pediátricos. Pacientes: Ciento diecisiete pacientes pediátricos con cardiopatías congénitas corregidos mediante BCP, clasificados en función de la presencia o no de SBGC. Intervenciones: Los datos analíticos y clínicos se midieron a las 2, 12, 24 y 48h post-BCP. Las principales variables se analizaron mediante regresión logística multivariante, considerando SBGC como variable dependiente. Variables de interés principales: SBGC, IS, VIS, MR-proADM, cTn-I, edad, sexo, BCP, PIM-2 y escala Aristóteles. Resultados: El IS no alcanzó significación estadística en el estudio multivariante; sin embargo, el VIS se asoció independientemente a SBGC. El VIS>15,5 a las 2h del ingreso en CIP, ajustado por edad y tiempo de CEC, muestra alta especificidad (92,87%; IC 95%: 86,75-98,96%) y alto valor predictivo negativo (75,59%; IC 95%: 71,10-88,08) para predecir SBGC a las 48h post-BCP. La capacidad predictora no se incrementa al incorporar cTn-I>14ng/ml a las 2h y ADM>1,5nmol/l a las 24h del postoperatorio. Conclusiones: El VIS a las 2h post-BCP es un predictor independiente precoz de SBGC. Este valor no se incrementa al asociarse biomarcadores cardiacos de LCOS. La escala de VIS fue más útil que la escala de IS en la toma de decisiones terapéuticas tras la cirugía cardiaca

Anestesia espinal hipobara en hernia supraumbilical de gran tamaño / Hypobaric spinal anesthesia in a large ventral hernia

La cirugía de pared abdominal alta puede requerir anestesia general pero en los pacientes con alto riesgo de vía aérea difícil y de complicaciones respiratorias es de elección la anestesia local o regional. La anestesia espinal usada habitualmente (isobara o hiperbara) puede comprometer la función respiratoria al bloquear la metámera T6 o superiores. La anestesia espinal hipobara (AEH) a dosis bajas (3,6 cc de bupivacaína hipobara al 0,1% y 0,2 cc de fentanilo al 0,005%) consigue una analgesia suficiente con mínimo bloqueo motor. Exponemos el caso de un paciente con una hernia supraumbilical de gran tamaño, con alto riesgo de vía aérea difícil y de complicaciones respiratorias, al que se le aplicó AEH. El paciente no refirió dolor ni disnea durante la intervención, por lo que la AEH a dosis bajas es una opción a tener en cuenta en la cirugía de pared abdominal alta, pese a no haber sido descrita para este uso

High abdominal wall surgery may require general anesthesia but, in patients with high risk of difficult airway and respiratory complications, local or regional anesthesia is the choice whenever possible. Spinal anesthesia usually used (both isobaric and hyperbaric) could compromise the respiratory function due to blockade of the T6 metamere or higher. Hypobaric spinal anesthesia (HSA) at low doses (3.6 cc of 0.1% hypobaric bupivacaine plus 0.2 cc of 0.005% fentanyl) achieves sufficient analgesia with minimal motor blockade. We present the case of a patient with a large supraumbilical hernia with high risk of difficult airway and respiratory complications, who went through HSA. The patient did not report pain or dyspnea during the surgical procedure thus, HSA at low doses is an option to be taken into account in high abdominal wall surgery despite not having been described for this use

[Hypobaric spinal anesthesia in a large ventral hernia]. / Anestesia espinal hipobara en hernia supraumbilical de gran tamaño.

High abdominal wall surgery may require general anesthesia but, in patients with high risk of difficult airway and respiratory complications, local or regional anesthesia is the choice whenever possible. Spinal anesthesia usually used (both isobaric and hyperbaric) could compromise the respiratory function due to blockade of the T6 metamere or higher. Hypobaric spinal anesthesia (HSA) at low doses (3.6 cc of 0.1% hypobaric bupivacaine plus 0.2 cc of 0.005% fentanyl) achieves sufficient analgesia with minimal motor blockade. We present the case of a patient with a large supraumbilical hernia with high risk of difficult airway and respiratory complications, who went through HSA. The patient did not report pain or dyspnea during the surgical procedure thus, HSA at low doses is an option to be taken into account in high abdominal wall surgery despite not having been described for this use.

Selective laser fiber welding on woven polymer fabrics for biomedical applications.

Localized cartilage damage is a common problem for younger patients. This can heal, but often results in a painful condition that requires intervention. A welded-woven three-dimensional polymer fabric has been suggested as a suitable cartilage replacement because such materials closely match the mechanical properties of cartilage. However, such materials fare poorly when evaluated with respect to wear. A microscopic investigation of wear mechanisms showed that it is critical that the fibers not deflect laterally under a normal load. This observation led to the use of a new process for selective laser welding of the surface layers of three-dimensional fabrics in order to improve their wear resistance. Experimental evaluations were made in a pin-on-disc arrangement with a biomimetic loading. All materials used in the studies have previously been used in orthopedic devices or meet the requirements for United States Pharmacopeial Convention (USP) Class VI biocompatibility approval. The wear rates were significantly reduced and the lifespan of the fabrics was markedly improved due to surface welding, making this a viable option for cartilage replacement in vivo.

Evaluation of the vasoactive-inotropic score, mid-regional pro-adrenomedullin and cardiac troponin I as predictors of low cardiac output syndrome in children after congenital heart disease surgery.

OBJECTIVE: To determine the predictive value of the inotropic score (IS) and vasoactive-inotropic score (VIS) in low cardiac output syndrome (LCOS) in children after congenital heart disease surgery involving cardiopulmonary bypass (CPB), and to establish whether mid-regional pro-adrenomedullin (MR-proADM) and cardiac troponin I (cTn-I), associated to the IS and VIS scores, increases the predictive capacity in LCOS. DESIGN: A prospective observational study was carried out. SETTING: A Paediatric Intensive Care Unit. PATIENTS: A total of 117children with congenital heart disease underwent CPB. Patients were divided into two groups: LCOS and non-LCOS. INTERVENTIONS: The clinical and analytical data were recorded at 2, 12, 24 and 48h post-CPB. Logistic regression was used to develop a risk prediction model using LCOS as dependent variable. MAIN OUTCOME MEASURES: LCOS, IS, VIS, MR-proADM, cTn-I, age, sex, CPB time, PIM-2, Aristotle score. RESULTS: While statistical significance was not recorded for IS in the multivariate analysis, VIS was seen to be independently associated to LCOS. On the other hand, VIS>15.5 at 2h post-CPB, adjusted for age and CPB timepoints, showed high specificity (92.87%; 95%CI: 86.75-98.96) and increased negative predictive value (75.59%, 95%CI: 71.1-88.08) for the diagnosis of LCOS at 48h post-CPB. The predictive power for LCOS did not increase when VIS was combined with cTn-I >14ng/ml at 2h and MR-proADM >1.5nmol/l at 24h post-CPB. CONCLUSIONS: The VIS score at 2h post-CPB was identified as an independent early predictor of LCOS. This predictive value was not increased when associated with LCOS cardiac biomarkers. The VIS score was more useful than IS post-CPB in making early therapeutic decisions in clinical practice post-CPB.

Species Richness and Abundance of Cerambycidae (Coleoptera) in Huatulco, Oaxaca, Mexico; Relationships with Phenological Changes in the Tropical Dry Forest.

Cerambycidae have an important ecological role in initiating the degradation process of dead wood, but few studies have evaluated Cerambycidae community attributes in relation to ecosystem phenology. We surveyed the cerambicid fauna of the tropical dry forest in Huatulco, Oaxaca, Mexico, and explored the relationship of Cerambycidae species richness and abundance with phenological changes in vegetation. We applied three collecting methods of light traps, direct collection, and Malaise traps to survey Cerambycidae throughout 2005. To determine seasonal variations, we collected samples in the dry season month of February in the rainy season of May-July and August-September, and in the transition months of October and November through. We collected and identified 145 species, 88 genera, 37 tribes, and four subfamilies. The subfamily with the highest number of species was Cerambycinae (100 species), and the tribe with the highest number of genera and species was Elaphidiini with 13 genera and 33 species. The ICE non-parametric estimator determined an overall expected richness of 373 species, while the overall Shannon Diversity Index was 4.1. Both species richness and abundance varied seasonally, with the highest values recorded in the rainy season and the lowest in the dry season. Overall species abundance was not significantly correlated to monthly rainfall or EVI neither, only for "direct collecting" the EVI vs Richness and EVI vs Shannon Diversity Index were significantly correlated. We propose that the seemingly contradictory relationships between seasonal richness patterns of Cerambycidae and the greening/senescence of vegetation (EVI) may be explained by the seasonal availability of dead organic matter, flowers, or leafy vegetation that may be synchronized with the behavior of different cerambycid species.

Efecto del láser de luz pulsada en pacientes con síndrome de ojo seco / Effect of pulsed laser light in patients with dry eye syndrome

Objetivos: El objetivo de este estudio fue determinar los beneficios clínicos de la terapia de luz pulsada para el tratamiento del síndrome de ojo seco (SOS) consecuencia de la disminución de la producción de lágrima acuosa (SOS acuodeficiente) y/o de la evaporación lagrimal excesiva (SOS evaporativo) por la disfunción de las glándulas de Meibomio (DGM). Métodos: Estudiados 72 ojos correspondientes a 36 pacientes con SOS, de los cuales 60 ojos fueron intervenidos de cirugía refractiva (48 con láser de femtosegundo, 6 con microqueratomo mecánico y 6 con fotoqueratectomía refractiva [PRK]), 6 intervenidos con facoemulsificación y 6 sin intervención quirúrgica previa. Utilizamos un láser de luz pulsada (Intense Regulated Pulsed Light [IRPL(R)], E-Swin, Adainville, Francia) para estimular la secreción de las glándulas de Meibomio, realizando 4 sesiones, una cada 15 días. Resultados: Los pacientes con SOS acuodeficiente no presentan mejoría alguna. Tanto los ojos no intervenidos quirúrgicamente, como los operados con facoemulsificación y los tratados con PRK, evolucionaron muy favorablemente. Por otro lado, observamos unos resultados menos concluyentes en los ojos tratados con láser excimer. Conclusiones: El láser de luz pulsada puede ser de gran ayuda como tratamiento para el SOS evaporativo producido por la DGM, al contrario no lo es en las formas relacionadas con un daño aislado de la fase acuosa, o de la fase mucínica (AU)

Objectives: The objective of this study was to determine the clinical benefits of pulsed light therapy for the treatment of Dry Eye Syndrome (DES) due to the decrease in aqueous tear production (aqueous deficient DES) and/or excessive tear evaporation (evaporative DES) due to Meibomian Gland Dysfunction (MGD). Methods: A study was conducted on 72 eyes corresponding to 36 patients with DES. Out of these 72 eyes, 60 underwent refractive surgery (48 with femtosecond laser, 6 were operated with a mechanical microkeratome, and 6 with refractive photo-keratectomy[RPK], 6 treated with phacoemulsification, and 6 with no previous surgical treatment. Pulsed laser light (Intense Pulsed Light Regulated [IRPL(R)]) was use to stimulate the secretion of the Meibomian glands during 4 sessions, one every 15 days. Results: Patients with aqueous deficient DES did not show any improvement. Eyes with no previous surgery and those treated with phacoemulsification and PRK had a favourable outcome. On the other hand, less conclusive results were observed in the eyes treated with excimer laser. Conclusions: This treatment could be very helpful to treat evaporative DES produced by MGD. On the other hand, it is not helpful for those cases related to an isolated damage in the aqueous phase, or the mucin phase (AU)

Surface depression with double-angle geometry during the discharge of grains from a silo.

When rough grains in loose packing conditions are discharged from a silo, a conical depression with a single slope is formed at the surface. We observed that the increase of volume fraction generates a more complex depression, characterized by two angles of discharge: one at the bottom similar to the angle of repose and a considerably larger upper angle. The change in slope appears at the boundary between a dense stagnant region at the periphery and the central flowing channel formed over the aperture. Since the material in the latter zone is always fluidized, the flow rate is unaffected by the initial packing of the bed. On the other hand, the contrast between both angles is markedly smaller when smooth particles of the same size and density are used, which reveals that high packing fraction and friction must combine to produce the observed geometry. Our results show that the surface profile helps to identify by simple visual inspection the packing conditions of a granular bed, being useful to prevent undesirable collapses during silo discharge in industry.

Effect of pulsed laser light in patients with dry eye syndrome. / Efecto del láser de luz pulsada en pacientes con síndrome de ojo seco.

OBJECTIVES: The objective of this study was to determine the clinical benefits of pulsed light therapy for the treatment of Dry Eye Syndrome (DES) due to the decrease in aqueous tear production (aqueous deficient DES) and/or excessive tear evaporation (evaporative DES) due to Meibomian Gland Dysfunction (MGD). METHODS: A study was conducted on 72 eyes corresponding to 36 patients with DES. Out of these 72 eyes, 60 underwent refractive surgery (48 with femtosecond laser, 6 were operated with a mechanical microkeratome, and 6 with refractive photo-keratectomy[RPK], 6 treated with phacoemulsification, and 6 with no previous surgical treatment. Pulsed laser light (Intense Pulsed Light Regulated [IRPL®]) was use to stimulate the secretion of the Meibomian glands during 4 sessions, one every 15 days. RESULTS: Patients with aqueous deficient DES did not show any improvement. Eyes with no previous surgery and those treated with phacoemulsification and PRK had a favourable outcome. On the other hand, less conclusive results were observed in the eyes treated with excimer laser. CONCLUSIONS: This treatment could be very helpful to treat evaporative DES produced by MGD. On the other hand, it is not helpful for those cases related to an isolated damage in the aqueous phase, or the mucin phase.

Depletion of tropospheric ozone associated with mineral dust outbreaks.

From May to September 2012, ozone reductions associated with 15 Saharan dust outbreaks which occurred between May to September 2012 have been evaluated. The campaign was performed at a mountain station located near the eastern coast of the Iberian Peninsula. The study has two main goals: firstly, to analyze the decreasing gradient of ozone concentration during the course of the Saharan episodes. These gradients vary from 0.2 to 0.6 ppb h(-1) with an average value of 0.39 ppb h(-1). The negative correlation between ozone and coarse particles occurs almost simultaneously. Moreover, although the concentration of coarse particles remained high throughout the episode, the time series shows the saturation of the ozone loss. The highest ozone depletion has been obtained during the last hours of the day, from 18:00 to 23:00 UTC. Outbreaks registered during this campaign have been more intense in this time slot. The second objective is to establish from which coarse particle concentration a significant ozone depletion can be observed and to quantify this reduction. In this regard, it has been confirmed that when the hourly particle concentration recorded during the Saharan dust outbreaks is above the hourly particle median values (N > N-median), the ozone concentration reduction obtained is statistically significant. An average ozone reduction of 5.5 % during Saharan events has been recorded. In certain cases, this percentage can reach values of higher than 15 %.

New graphic AUC-based method to estimate overall survival benefit: pomalidomide reanalysis.

WHAT IS KNOWN AND OBJECTIVE: Difference in median survival is an erratic measure and sometimes does not provide a good assessment of survival benefit. The aim of this study was to reanalyse the overall survival benefit of pomalidomide from pivotal clinical trial using a new area under curve (AUC)-based method. COMMENT: In the pivotal trial, pomalidomide plus low-dose dexamethasone showed a significant survival benefit over high-dose dexamethasone, with a difference between medians of 4.6 months. The new AUC method applied to the survival curves, obtained an overall survival benefit of 2.6 months for the pomalidomide treatment. This average difference in OS was calculated for the 61.5% of patients for whom the time to event is reliable enough. WHAT IS NEW AND CONCLUSION: This 2-month differential would have major clinical and pharmacoeconomic implications, on both cost-effectiveness studies and on the willingness of the healthcare systems to pay for this treatment.

Markers of airway inflammation in the exhaled breath condensate of preschool wheezers.

BACKGROUND: Leukotrienes (LT), isoprostanes, and nitrites/nitrates are biomarkers of airway inflammation and oxidative stress that can be detected in exhaled breath condensate (EBC). The aim of this study was to evaluate LTB4, LTE4, 8-isoprostane, and nitrite/nitrate levels in the EBC of healthy and wheezing preschool children. METHODS: We included 21 healthy nonatopic children and 25 patients with recurrent wheezing episodes in a cross-sectional study. LTB4, LTE4, and 8-isoprostane concentrations were measured directly in EBC using a specific enzyme immunoassay; nitrite/nitrate concentrations were measured using a colorimetric assay. RESULTS: LTB4 concentrations were higher in children with wheezing episodes than in healthy controls (76 pg/mL vs 20 pg/mL, P < .001). LTE4 was increased in children with wheezing episodes than in healthy controls (68 pg/mL vs 35 pg/mL, P < .001). Nitrite concentrations were higher in children with wheezing episodes than in healthy controls (14 pg/mL vs 9.7 pg/mL, P < .03). We found no differences in 8-isoprostane and nitrate concentrations between the patients and the healthy controls. CONCLUSIONS: Our findings suggest that EBC is a suitable noninvasive method for the assessment of airway inflammation and oxidative stress in preschool children. Levels of LTB4, LTE4, and nitrites were higher in children with recurrent wheezing episodes than in healthy controls.

Direct and indirect comparison of the efficacy and safety of adalimumab, etanercept, infliximab and golimumab in psoriatic arthritis.

WHAT IS KNOWN AND OBJECTIVE: Psoriatic arthritis is an autoimmune disease characterized by chronic inflammation of the skin and joints. Anti-TNF drugs reduce the severity of the disease in the long term. This study compares the efficacy and safety of adalimumab, etanercept, infliximab and golimumab in patients with psoriatic arthritis. METHODS: Direct comparison was based on a literature search of drug comparison studies, whereas indirect treatment comparison was based on phase III clinical trials with biological agents, involving similar populations and durations, and with the same outcome. ACR50 was taken as primary outcome for comparison, whereas ACR20 and ACR70 were used as secondary outcomes. Indirect comparisons were made using infliximab as the reference drug and the Bucher method. In calculating δ (the maximum acceptable difference as a clinical criterion of equivalence), use was made of half of the absolute risk reduction obtained in the meta-analysis of the clinical trials included in the indirect comparison (ARR 32%; δ: 16%). The four anti-TNF drugs were also compared in relation to the secondary outcomes and adverse effects. RESULTS AND DISCUSSION: Reported direct and indirect comparisons of the four drugs did not include golimumab, and did not yield conclusive results. Four clinical trials - one for each drug studied - were identified. The estimated differences for the primary outcome, ACR50, between infliximab and the other drugs were adalimumab (ARR 4%, 95% CI -9·5 to 17·5), etanercept (ARR 4%, 95% CI -10·5 to 18·5) and golimumab (ARR 9%, 95% CI -5·4 to 23·4). Likewise, there were no relevant differences between the drugs in relation to the secondary efficacy outcomes, except for etanercept, which was less effective in ACR70 response. For adverse reactions, there were also no significant differences except for injection site, reactions which were more frequent with etanercept, with a mean difference of 26% relative to infliximab. WHAT IS NEW AND CONCLUSION: No significant differences were found in ACR50 responses to the four drugs after 24 weeks. Injection-site reactions were more common with etanercept, but this was insufficient to invalidate the inference that clinically the four drugs can be regarded as clinically equivalent for the treatment of psoriatic arthritis.

Markers of Airway Inflammation in the Exhaled Breath Condensate of Preschool Wheezers

Antecedentes: Los leucotrienos (LT), isoprostanos y nitritos/nitratos, que son biomarcadores de la inflamación de las vías aéreas, y el estrés oxidativo, pueden ser detectados en el condensado del aire exhalado (CAE). El objetivo de este estudio fue evaluar el LTB4, LTE4, 8-isoprostano, nitritos y nitratos en el CAE de niños preescolares sanos y con sibilancias. Material y métodos: Se realizó un estudio transversal en el que se incluyeron 21 niños sanos no atópicos y 25 pacientes con sibilancias recurrentes. El LTB4, LTE4 y 8-isoprostano, se midieron en el CAE mediante enzimoinmunoensayo, y los nitritos/nitratos mediante método colorimétrico. Resultados: Las concentraciones de LTB4 fueron mayores en los niños con episodios de sibilancias que en controles sanos (76 pg/ml vs 20 pg/ml, p<0,001); El LTE4 se incrementó también en niños con episodios de sibilancias en comparación con niños sanos (68 pg/ml vs 35 pg/ml, p<0,001). Las concentraciones de nitritos fueron mayores en los niños con episodios de sibilancias que en los controles (14 pg/ml vs 9,7 pg/ml, p<0,03). No hubo diferencias en las concentraciones de 8-isoprostano y nitratos entre el grupo de niños enfermos y el grupo control. Conclusiones: Nuestros hallazgos sugieren que el CAE es un método no invasivo para la evaluación de la inflamación de las vías respiratorias y del estrés oxidativo en lactantes y niños en edad preescolar. Las concentraciones de LTB4, LTE4 y de nitritos, se incrementaron en niños con episodios recurrentes de sibilancias en comparación con los controles sanos (AU)

Background: Leukotrienes (LT), isoprostanes, and nitrites/nitrates are biomarkers of airway inflammation and oxidative stress that can be detected in exhaled breath condensate (EBC). The aim of this study was to evaluate LTB4, LTE4, 8-isoprostane, and nitrite/nitrate levels in the EBC of healthy and wheezing preschool children. Methods: We included 21 healthy nonatopic children and 25 patients with recurrent wheezing episodes in a cross-sectional study. LTB4, LTE4, and 8-isoprostane concentrations were measured directly in EBC using a specific enzyme immunoassay; nitrite/nitrate concentrations were measured using a colorimetric assay. Results: LTB4 concentrations were higher in children with wheezing episodes than in healthy controls (76 pg/mL vs 20 pg/mL, P<.001). LTE4 was increased in children with wheezing episodes than in healthy controls (68 pg/mL vs 35 pg/mL, P<.001). Nitrite concentrations were higher in children with wheezing episodes than in healthy controls (14 pg/mL vs 9.7 pg/mL, P<.03). We found no differences in 8-isoprostane and nitrate concentrations between the patients and the healthy controls. Conclusions: Our findings suggest that EBC is a suitable noninvasive method for the assessment of airway inflammation and oxidative stress in preschool children. Levels of LTB4, LTE4, and nitrites were higher in children with recurrent wheezing episodes than in healthy controls (AU)