Challenges in early phase clinical trials for childhood cancer during the COVID-19 pandemic: a report from the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

PURPOSE: The COVID-19 pandemic has forced healthcare stakeholders towards challenging decisions. We analyse the impact of the pandemic on the conduct of phase I-II trials for paediatric cancer during the first month of state of alarm in Spain. METHODS: A questionnaire was sent to all five ITCC-accredited Spanish Paediatric Oncology Early Phase Clinical Trial Units, including questions about impact on staff activities, recruitment, patient care, supply of investigational products, and legal aspects. RESULTS: All units suffered personnel shortages and difficulties in enrolling patients, treatment continuity, or performing trial assessments. Monitoring activity was frequently postponed (73%), and 49% of on-going trials interrupted recruitment. Only two patients could be recruited during this period (75% reduction in the expected rate). CONCLUSIONS: The COVID-19 crisis has significantly impacted clinical research practice and access to innovation for children with cancer. Structural and functional changes are under way to better cope with the expected future restrictions.

The influence of obesity and weight gain on quality of life according to the SF-36 for individuals of the dynamic follow-up cohort of the University of Navarra. / Influencia de la obesidad y la ganancia de peso sobre la calidad de vida según el SF-36 en individuos de la cohorte dinámica Seguimiento Universidad de Navarra.

BACKGROUND: The health-related quality of life is an important element for the comprehensive assessment of overweight and obesity. OBJECTIVE: To assess the impact of obesity and weight gain on the health-related quality of life of the dynamic cohort of the Follow-up Program of the University of Navarra. MATERIAL AND METHODS: The analysis included 10,033 participants of the prospective dynamic cohort of the Follow-up Project of the University of Navarra, with a response rate of approximately 90%. The quality of life was measured with the Short Form 36 Health Survey (SF-36) (0, worst quality of life; 100, best quality of life). The statistical analysis was performed with generalized lineal models (mean of each SF-36 domain and 95% CI). A difference of 3 points was considered clinically relevant. RESULTS: The SF-36 analysis showed that physical function, general health and the physical component summary were inferior in individuals with excess weight and obesity at the start of the study, compared with individuals with normal weight. The study population with unchanged excess weight or obesity after 2 years of follow-up presented lower scores on the SF-36 domains corresponding to physical function, body pain, physical component summary and general health than individuals who maintained the normal weight category according to BMI (kg/m2). CONCLUSIONS: Obesity appears to be associated with a negative impact on health-related quality of life, affecting the physical area more significantly than the psychosocial.

Microstructural, mechanical, and histological evaluation of modified alginate-based scaffolds.

Scaffolds are three-dimensional structures used for tissue regeneration being the base in tissue engineering. These scaffolds are obtained from natural and/or synthetic polymers and they should satisfy some specific requirements such as biocompatibility, suitable mechanical, and microstructural properties to favor cellular adhesion and neovascularization. This work shows a preclinic study about the production of low and medium molecular weight alginate through the use of calcium salts (calcium glutamate). The results showed prove that better structures, distribution, and pore sizes as well as better mechanical properties correspond to medium molecular weight alginate and higher calcium salts concentration. This type of scaffold, after muscular cells cultivation, has been proved as an excellent material for muscle growth. The histopathological analysis shows a low inflammatory response, without a foreign body reaction, suitable neovascularization and good fibroblasts incorporation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 3107-3114, 2016.

Drug use in adolescents in relation to social support and reactive and proactive aggressive behavior.

BACKGROUND: Aggressive behavior in adolescents, along with drug use, has become one of the great issues in education in recent years, among other things, due to its relationship with school failure and delinquency. The purpose of this paper was to find out whether social support fulfils a basic role in decision-making on drug use and the behavior of adolescents. METHOD: 822 high school students participated in the study (M = 14.84, SD = 0.87). Data were collected with the Peer Conflict Scale and the Multidimensional Scale of Perceived Social Support, and an ad hoc questionnaire on drug use. RESULTS: The results show that drug use is significantly related to reactive and proactive aggressive behavior. It was also observed that higher use is significantly related to perceived social support by the peer group, and less support by family. DISCUSSION: It was shown that substance use is related to perceived social support by the adolescent’s peer group and to aggressive behavior. It is therefore necessary to intervene in both respects to avoid the presence of substance use in schools.

An Experimental Study on the Use of Calcium Alginate to Heal Colonic Anastomoses.

BACKGROUND: Anastomotic leak is considered the major complication following abdominal surgery. In recent years, the use of a variety of sealing materials for the prevention of leaks has been analyzed. Different biomaterials have been employed as scaffolds to favour tissue repair and regeneration. Among these materials we must mention alginate, a natural polymer with different applications as temporary supporting matrix. The aim of the present study is to evaluate the behavior of both alginate-impregnated sutures and lyophilized alginate sponges in the healing process of colonic anastomes using an experimental animal model. MATERIAL AND METHODS: A preliminary study was undertaken to select the adequate scaffold. Animals (n = 45) were distributed into three groups: control (colonic anastomosis using non-continuous 5-0 Polyglactin 910 suture), suture (colonic anastomosis using suture impregnated with alginate gel at 4%) and sponge (colonic anastomosis using suture reinforced with lyophilized alginate sponge). The macroscopic and histological variables were assessed at 4, 8 and 12 days after surgical intervention. RESULTS: No statistically significant differences have been observed between the groups during the analysis of macroscopic variables. Animals with sponge implantation showed a greater degree of epithelial reepithalization, less acute and chronic inflammation and greater collagen deposit. CONCLUSIONS: The use of lyophilized alginate sponges to reinforce colonic anastomoses in an animal model reduces inflammation and promotes the earlier formation of greater collagen deposits without increasing the number of adhesions or the incidence of stenosis.

Salud percibida y salud real: prevalencia en las personas mayores de 60 años / Perceived health and real health: prevalence among persons aged 60 and older / Saúde percebida e saúde real: prevalência nas pessoas idosas de 60 anos

Objetivo: Analizar el estado de salud de la población mayor de 60 años y la relación que existe entre la autopercepción de la salud que tienen las personas mayores y su salud real; se valoró la mediación en esta relación de aspectos sociodemográficos como la edad y el género. Método: Diseño descriptivo, transversal, de prevalencia. Localización: 15 centros de día y 10 residencias de la provincia de Almería (España). Participantes: 1,220 personas mayores de 60 años (M = 70.9; DT = 7.9), de los cuales el 48.3% son hombres y el 51.7% mujeres. Mediciones: Se analizó el género, la edad, el estado civil, la presencia o no de diferentes enfermedades y problemas de salud, y el nivel de salud percibido. Resultados: Los problemas de salud relacionados con los huesos y articulaciones son los más frecuentes. Existen diferencias significativas (p = 0.000) en la percepción de la salud entre ambos géneros; los hombres tienen una mejor percepción de su salud. Hay una relación negativa y significativa (p < 0.001) entre la edad y la percepción de la salud. Tanto el número de enfermedades (r2 = 0.251) como la edad (r2 = 0.010) y el género (r2 = 0.002) forman parte del modelo explicativo de la percepción de salud. Conclusiones: El número de enfermedades, la edad y el género son variables que explican una cuarta parte de la variable subjetiva salud percibida, por tanto ofrecen indicios de poder ser utilizadas en la planificación de las políticas sanitarias.

Objective: To analyze the health of the population aged 60 and older, and the relationship between their perception of their health and their real condition. The relationship with social-demographic issues such as gender was also assessed. Method: Descriptive, transversal and prevalence study of 15 Day and 10 Residential Centers in the province of Almería (Spain), with 1,220 persons aged 60 and older (M = 70.9, SD = 7.9), 48.3% male and 51.7% female. Measurements Gender, age, civil status, and the presence of pathologies and health problems, as well as the perceived health level were all assessed. Results: Health problems related to bones and articulations were the most reported. There are significant differences (P=0.000) in the perception of health between both genders; males have a better perception of their health. There is a negative and significant relation (P < .001) between age and the perception of health. The number of illnesses (r2 = 0.251), age (r2 = 0.010), and gender (r2 = 0.002) are all part of the explicative model of the perception of health. Conclusions: The number of illnesses, age, and gender are variables which explain a quarter of the subjective perception of health variable, and thus, they indicate a possible use in the planning of health policies.

Objetivo: Analisar o estado de saúde da população idosa de 60 anos e, a relação que existe entre a auto percepção da saúde que realizam as pessoas idosas e a sua saúde real. Valorizou-se a intermediação de aspetos sócio demográficos como a idade e o género. Método: Desenho descritivo, transversal de prevalência. Localização: 15 centros de dia e 10 moradias da província de Almería (na Espanha). Participantes: 1220 pessoas idosas de 60 anos (M = 70.9; DT = 7.9), das quais o 48.3% são homens e o 51.7% são mulheres. Medições Analisou-se o género, a idade, o estado civil, a presença e a não presença de diferentes patologias e problemas de saúde e, o nível de saúde percebido. Resultados: Os problemas de saúde relacionados com os ossos e as articulações são os mais frequentes. Existem diferenças significativas (p = 0.000) na percepção de saúde entre ambos os géneros, os homens têm uma melhor percepção da sua saúde. Há uma relação negativa e significativa (p < 0.001) entre a idade e a percepção da saúde. Tanto o número de doenças (r2 = 0.251) como a idade (r2 = 0.010) e o género (r2 = 0.002) formam parte do modelo explicativo da percepção da saúde. Conclusõeso: O número de doenças, a idade e o género são variáveis que explicam uma quarta parte da variável subjetiva "saúde percebida", portanto, oferecem índicios de poderem ser utilizadas na planificação de políticas sanitárias.

Comparison of phase velocity in trabecular bone mimicking-phantoms by time domain numerical (EFIT) and analytical multiple scattering approaches.

The corrected Waterman-Truell model and the Elastodynamic Finite Integration Technique were used to analyze the ultrasonic wave dispersion in trabecular bones mimicking phantoms. A simple two-phase model of the trabecular bone is assumed; the trabeculae structure and the bone marrow. The phase velocity for frequencies within the range from 400kHz to 800kHz were computed for different scatterer arrays varying their dimensions and number. The theoretical and numerical results were compared to experimental published data, obtained from a mimicking phantom composed by a periodic array of nylon shreds (trabeculae array) immersed in a water tank. Our results showed an excellent consistency when compared to experimental data. The negative dispersions of -8.48m/s/MHz and -9.16m/s/MHz were computed by the multiple scattering method and the numerical approach, respectively, where the latter is closer to the experimental dispersion of -12.09m/s/MHz. Similar result has been reported in the literature, where the dispersion predicted by the Generalized Self-Consistent Method [J. Acoust. Soc. Am. 124 (2008) 4047] is -9.96m/s/MHz.

Ultrasonic wave propagation in cementitious materials: a multiphase approach of a self-consistent multiple scattering model.

This paper examines ultrasonic wave propagation through strongly heterogeneous materials such as cementitious materials, and deals meanly with the formulation of a multiphase approach of a self-consistent multiple scattering model, the so-called dynamic generalized self-consistent model (DGSCM) proposed by Yang [J. Appl. Mech. 70(2003) 575-582]. This extended model can describe the influence of the size and volume fraction of aggregates on cementitious materials, as well as the interaction, contribution, and influence of entrapped air voids together with the aggregates on frequency-dependent parameters such as the phase velocity and the attenuation coefficient. To show the performance of this approach, theoretical predictions were compared with experimental ultrasonic measurements over a wide frequency range from several mortar specimens with different features in their microstructure properties and concentrations of aggregates up to 60%. The multiphase approaches of both the DGSCM and the Waterman-Truell model (WT) were also compared. The obtained results of the multiphase DGSCM were found to be significantly better than those obtained from the N-phase WT model for ultrasonic measurements from cementitious materials at high aggregate concentrations. The feasibility of material characterization using the multiphase approach of DGSCM was also discussed.

On the measurement of frequency-dependent ultrasonic attenuation in strongly heterogeneous materials.

This paper deals with the measurement of frequency-dependent ultrasonic attenuation in strongly heterogeneous materials, such as cementitious materials. To improve the measurement of this parameter on this kind of materials, a linear swept-frequency signal is used to drive an emitter transducer to conduct a through-transmission inspection in immersion. To filter out undesirable frequency content, time-frequency filtering and detection process are performed. The use of this method has been compared with two excitation techniques, the broadband and the narrowband pulses. The results obtained using the swept-frequency excitation together with the time-frequency filtering, allows the determination of the attenuation curves with high accuracy over a wide frequency range without the need for complicated equipment, and improves the effective bandwidth by using a unique pair of transducers.

Skin testing and drug provocation in the diagnosis of nonimmediate reactions to aminopenicillins in children.

BACKGROUND: Nonimmediate allergic reactions (NIR) to aminopenicillin include several entities, the most common of which are urticaria-like and maculopapular exanthemas. AIMS OF THE STUDY: To evaluate a group of children who developed one or more episodes of skin reactions suggestive of NIR after aminopenicillin administration. METHODS: The inclusion criteria required negative immediate skin tests and absence of specific IgE antibodies to different penicillins. Intradermal and patch tests were carried out with delayed readings and, if negative, a drug-provocation test including a full therapeutic course of the drug was given. Two different groups were compared: A) children with positive skin testing or a positive drug-provocation test and B) children with negative skin testing and good tolerance after a drug-provocation test. RESULTS: Group A was composed of 20 patients. Positive intradermal/patch tests were found in one patient and in the remaining 19, a positive response to a drug-provocation test confirmed the diagnosis. Group B (the control group) consisted of 19 patients with similar symptoms after aminopenicillin intake but good tolerance. No differences in age, dose or number of previous treatments were observed between the groups. The clinical entities were also similar in both groups. CONCLUSIONS: Reproducible nonimmediate skin reactions to aminopenicillins may occur in children in spite of negative skin testing. The value of this diagnostic procedure seems to be limited in this type of reaction, with drug-provocation tests (DPT) being a reasonable and safe alternative if the diagnosis has to be confirmed.

Sand/cement ratio evaluation on mortar using neural networks and ultrasonic transmission inspection.

The quality and degradation state of building materials can be determined by nondestructive testing (NDT). These materials are composed of a cementitious matrix and particles or fragments of aggregates. Sand/cement ratio (s/c) provides the final material quality; however, the sand content can mask the matrix properties in a nondestructive measurement. Therefore, s/c ratio estimation is needed in nondestructive characterization of cementitious materials. In this study, a methodology to classify the sand content in mortar is presented. The methodology is based on ultrasonic transmission inspection, data reduction, and features extraction by principal components analysis (PCA), and neural network classification. This evaluation is carried out with several mortar samples, which were made while taking into account different cement types and s/c ratios. The estimated s/c ratio is determined by ultrasonic spectral attenuation with three different broadband transducers (0.5, 1, and 2 MHz). Statistical PCA to reduce the dimension of the captured traces has been applied. Feed-forward neural networks (NNs) are trained using principal components (PCs) and their outputs are used to display the estimated s/c ratios in false color images, showing the s/c ratio distribution of the mortar samples.

Allergy to pine processionary caterpillar (Thaumetopoea pityocampa) in children.

UNLABELLED: Contact with pine processionary caterpillar (Thaumetopoea pityocampa) induces dermatitis usually located in exposed areas through a toxic-irritative mechanism. Over the last few years an immediate hypersensitivity mechanism have mainly been demonstrated in adult patients. However, there are few studies carried out in children. OBJECTIVE: To evaluate a group of 16 children who experienced allergic reactions after exposure to pine processionary caterpillar. PATIENTS AND METHODS: All patients underwent allergy testing through skin prick test. Serum specific IgE determination was performed by EAST technique. The molecular mass of the IgE -binding bands was studied by SDS-PAGE Immunoblotting. RESULTS: Skin prick test with the caterpillar extract was positive in all patients. Specific IgE was positive (higher than 0.35 kU/L) in 15 patients' sera. Western blotting showed several IgE-binding bands with molecular mass values ranging from 17.5 to 168 kDa. Electrophoretic mobility of some of the relevant allergens was related to the conditions of sample preparation (reduced or non-reduced). CONCLUSIONS: The results of this study demonstrate the existence of an allergic IgE-mediated mechanism caused by pine processionary caterpillar proteins. Airborne urticating hairs of this animal should be considered as seasonal inhalant allergen, which is able to induce allergic pathologies in children who frequent pine areas.

Food-protein-induced enterocolitis syndrome caused by fish.

INTRODUCTION: Food protein-induced enterocolitis syndrome (FPIES) occurs in infants. Typical symptoms include profuse vomiting and/or diarrhea several hours after ingestion of a given food. The disorder is a non-IgE mediated food hypersensitivity. The most frequently involved foods are milk and soy, but some cases of FPIES induced by solid foods have been described. We report 14 patients with FPIES due to fish protein. MATERIAL AND METHODS: History and physical examination, skin prick test (SPT) with fish allergens and Anisakis simplex, prick-by-prick test with implicated fish and determination of specific IgE antibodies against fish were performed. In eight children atopy patch test (APT) were also performed. In nine patients an open oral food challenge with the implicated fish was carried out. RESULTS: There were six boys and eight girls, aged from 9 to 12 months at diagnosis, with between two and six reactions to the offending fish proteins before the diagnosis was established. Four patients had a previous history of atopy. Presenting symptoms included diarrhea in two patients, profuse vomiting in six patients, and recurrent vomiting and subsequent diarrhea in three patients. In addition to these symptoms, associated septic appearance, apathy and lethargy were present in the remaining three patients. Onset of symptoms occurred a few minutes after fish ingestion in two patients and from 60 minutes to 6 hours in the 12 remaining patients. SPT to fish were negative in all patients. Serum food-specific IgE antibodies were negative in all patients except one. APT was positive in three patients. Open oral challenge (OC) was performed in nine infants and was positive in all. The patients were followed-up for between 1 and 7 years after diagnosis, and follow-up OC tests were performed after fish had been eliminated from the patients' diet for 3-4 years. Four patients became clinically tolerant to the causal food. Three patients currently tolerate only one type of fish (swordfish). CONCLUSIONS: We report 14 patients with FPIES caused by fish protein. The symptoms suggest a form of cell-mediated, non-IgE mediated food hypersensitivity. The gold standard for diagnosis is OC, although caution should be exercised in infants with several reactions or a recent diagnosis. After a period of elimination of the causal food from the diet, tolerance can develop.

Ultrastructural changes induced in HeLa cells after phototoxic treatment with harmine.

In the present work, we have continued our studies on harmine phototoxicity in human tumour cells. The toxicity of harmine in the dark was analysed by a quantitative neutral red uptake assay, and subcellular sensitive targets following harmine photosensitization were de fi ned by electron microscopic analysis of HeLa cells. The results obtained indicated that this compound shows a clear dose-dependent cytotoxic effect in the dark. The combined treatment with suitable doses of harmine and UV radiation was very effective at an early stage, although maximal cell killing appeared 48 h after photodynamic activation. Ultrastructural examination of HeLa cells immediately after the photodynamic treatment revealed lysosomal destabilization and profound cytoplasmic vacuolization that evolved to cytolysis, which is typical of necrotic cell death. It is concluded that harmine could be a valuable photosensitizer whose biological applications merit further evaluation.

Non-occupational allergy caused by the pine processionary caterpillar (Thaumetopoea pityocampa).

UNLABELLED: Contact with the pine processionary caterpillar induces dermatitis, usually located in exposed areas, and, less frequently, ocular lesions through a toxic-irritative mechanism. Recently, the existence of an immediate hypersensitivity mechanism has been demonstrated, mainly in occupationally exposed patients. OBJECTIVE: To present four patients who experienced allergic reactions (urticaria-angioedema and rhinitis-asthma) after non-occupational exposure to pine processionary caterpillar. PATIENTS AND METHODS: The four patients underwent allergy testing through skin prick tests (SPT), specific IgE detection and SDS-PAGE immunoblotting. One patient also underwent a specific bronchial challenge test with the pine processionary antigen. RESULTS: In all patients, both SPT with the caterpillar extract and specific IgE were positive. Western blotting showed several IgE-binding bands with molecular mass values ranging from 18 to 107 kDa. A shift in the electrophoretic mobility of some of the relevant allergens occurred under the presence of a reductive agent (beta -mercaptoethanol). The specific bronchial challenge test with pine processionary antigen performed in one of the patients also produced positive results. CONCLUSIONS: The results of this study show an immunologic IgE-mediated immediate hypersensitivity mechanism in these reactions. The processionary caterpillar's airborne urticating hairs or spicules should be considered, at least in some locations, not only as contact and occupational allergens, but also as seasonal aeroallergens.