EEG parameters as endpoints in epilepsy clinical trials - An expert panel opinion paper.

INTRODUCTION: The lack of ideal measurement of treatment efficacy is a well acknowledged problem in the epilepsy community, both in clinical care and clinical trials. Whilst still the current gold-standard, self-reported seizure frequency significantly underestimates the true number of seizures and does not account for any other at least equally important outcome parameters, such as neurodevelopment and cognition. With the rise of disease modifying treatments, the need for more reliable endpoints in practice and clinical trials becomes more pressing. In this paper we assembled an expert panel to discuss the nature of these needs, current limitations, and obstacles based on a survey amongst these experts who were queried about the most important issues regarding the use of electroencephalography (EEG) parameters as endpoints in clinical drug and device development. METHODS: A structured survey was sent to a group of experts in the design and conduct of epilepsy trials in adults and children. This was followed by a virtual in-person meeting discussing the results of the trial and identifying a list of most important issues. RESULTS: Six clinical trialists and 5 individuals from pharmaceutical companies returned the survey containing 14 questions, and 8 clinical trialists and 10 pharma-representatives attended the meeting. Three main issues were identified (1) lack of accuracy of seizure diaries due to nocturnal seizures, subtle motor seizures, impairment of consciousness and lack of awareness of the seizure by the patient (2) inter-rater variability of EEG assessment (3) lack of standardization regarding definition(s) of seizures (clinical and electrographic), EEG recording methods and EEG data management. Recommended solutions included (1) validation of EEG parameters as biomarkers and use of wearables (2) development of a manual that describes EEG rating criteria, protocol for validation by > 1 central reader and use of a resolution of disagreements reporting template (3) standardization of EEG recording, data management and reporting. DISCUSSION & CONCLUSION: Current developments in research and technology seem promising to advance the use of EEG parameters as potential endpoints and offer partial solutions to the current needs. However, continuous, focused and collaborative efforts of all stakeholders (academia, industry and regulatory agencies) are needed to formulate guidelines, validate emerging technologies and approve them for use in trials. It is the intent of this opinion "position paper" to stimulate those efforts.

Knowledge Landscape of Starter Cultures: A Bibliometric and Patentometric Study.

BACKGROUND: Starter cultures are essential in food industry biotechnology, consisting of microorganism preparations inoculated to produce safe fermented foods with desirable sensory characteristics. OBJECTIVE: This study aims to identify and analyze the growth and flow of knowledge regarding starter cultures by creating scientific and technological profiles using patentometric and bibliometric indicators. METHODS: A search for patents and scientific articles was conducted in December 2020 following a proposed 10-step methodology using the Scopus® and Patentinspiration databases. The search strategy was based on the keywords "starter culture" and "fermentation" considering publications up to 2020. RESULTS: A total of 3035 articles and 719 patents were published until 2020, presenting a more significant number in the last ten (10) years due to the development of biological sciences and molecular biology involving enzymes and microorganisms. Italy leads the scientific production while China leads the technological. It was also possible to determine the most productive author and inventors, the most influential articles and inventions, and the main scientific journals and patent offices. CONCLUSION: Scientific and technological activities have an exponential behavior showing that the knowledge about starter cultures continues to grow, becoming a field of interest for optimizing industrial processes related to food fermentation, thus achieving diversification of products that can satisfy the demand for food in an increasingly competitive global market.

The paediatric cancer clinical research landscape in Spain: a 13-year multicentre experience of the new agents group of the Spanish Society of Paediatric Haematology and Oncology (SEHOP).

PURPOSE: Early phase trials are crucial in developing innovative effective agents for childhood malignancies. We report the activity in early phase paediatric oncology trials in Spain from its beginning to the present time and incorporate longitudinal data to evaluate the trends in trial characteristics and recruitment rates. METHODS: Members of SEHOP were contacted to obtain information about the open trials at their institutions. The study period was split into two equal periods for analysis: 2007-2013 and 2014-2020. RESULTS: Eighty-one trials and two molecular platforms have been initiated. The number of trials has increased over the time of the study for all tumour types, with a predominance of trials available for solid tumours (66%). The number of trials addressed to tumours harbouring specific molecular alterations has doubled during the second period. The proportion of industry-sponsored compared to academic trials has increased over the same years. A total of 565 children and adolescents were included, with an increasing trend over the study period. For international trials, the median time between the first country study approval and the Spanish competent authority approval was 2 months (IQR 0-6.5). Fourteen out of 81 trials were sponsored by Spanish academic institutions. CONCLUSIONS: The number of available trials, and the number of participating patients, has increased in Spain from 2007. Studies focused on molecular-specific targets are now being implemented. Barriers to accessing new drugs for all ranges of age and cancer diseases remain. Additionally, opportunities to improve academic research are still required in Spain.

Microbial diversity associated with spontaneous coffee bean fermentation process and specialty coffee production in northern Colombia.

Coffee fermentation involves the action of microorganisms, whose metabolism has a significant influence on the composition of the beans and, consequently, on the beverage's sensory characteristics. In this study, the microbial diversity during the wet fermentation of Coffea arabica L. in the Sierra Nevada of Santa Marta (SNSM) in Colombia was explored by high-throughput sequencing and the resulting cup quality through the standards of the Specialty Coffee Association. The taxonomic assignment of sequence reads showed a high microbial diversity comprised of 695 bacterial and 156 fungal genera. The microbial community was dominated by the Lactic Acid Bacteria (LAB) Leuconostoc, the yeast Kazachstania, and the Acetic Acid Bacteria (AAB) Acetobacter. Co-occurrence relationships suggested synergistic patterns between populations of LAB-AAB, yeasts-AAB, Leuconostoc-Prevotella, LAB-ABB-Selenomonas, and yeasts-fungi-nonLAB-nonAAB, which may result in the production of metabolites that positively impact the sensory attributes of coffee. The beverages produced were classified as specialty coffees, and their score was positively influenced by the fungal richness and the abundance of unclassified Lactobacillales, Pichia, and Pseudomonas. The findings show the richness and microbial diversity of the SNSM and serve as input for future research such as the analysis of microbial-derived metabolites and the establishment of starter cultures in coffee processing that guarantee the generation of high-quality beverages, the standardization of processes, the reduction of economic losses, and the production of value-added products that allow taking advantage of specialty coffee market.

Predictors of a positive oral food challenge to cow's milk in children sensitized to cow's milk

INTRODUCTION AND OBJECTIVES: The diagnosis of IgE-mediated cow's milk allergy (CMA) is often based on clinical history and on specific IgE levels and/or skin-prick tests (SPT), both of which are sensitive but not specific. The gold standard, oral food challenge (OFC), is expensive and time-consuming and involves a risk of severe allergic reactions. This study aimed to determine the value of specific IgEs, ratios of specific IgEs for cow's milk and its components to total IgE, and wheal size on SPT for predicting a positive OFC for CMA. MATERIAL AND METHODS: We retrospectively studied 72 patients [median age, four years; age range 0.75-15 years] sensitized to cow's milk who underwent OFCs to milk. predictive variables between patients with positive and negative OFCs were compared. Receiver operator characteristic (ROC) curves were uses to assess variables' discriminatory capacity and Youden's index to determine the best cut-offs for predicting CMA. RESULTS: The OFC was positive in 39 (54%) patients. Wheal size on SPT and all specific IgEs and specific-to-total IgE ratios were significantly different between patients with positive OFCs and those with negative OFCs (p < 0.001). The variable with the greatest area under the ROC curve was casein-specific IgE (0.98), followed by β-lactoglobulin-specific IgE (0.923), casein-specific-to-total-IgE ratio (0.919), and α-lactalbumin-specific IgE (0.908). Casein-specific IgE ≥ 0.95kU/L yielded 88.9% sensitivity and 90.9% specificity. CONCLUSIONS: In our center, casein-specific IgE > 0.95kU/L can obviate an OFC to cow's milk for the diagnosis of CMA in patients sensitized to cow's milk with a compatible history

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High prevalence of t895 and t9364 spa types of methicillin-resistant Staphylococcus aureus in a tertiary-care hospital in Mexico: different lineages of clonal complex 5.

BACKGROUND: Staphylococcus aureus is a leading cause of broad-spectrum infections both in the community and within healthcare settings. Methicillin-resistant Staphylococcus aureus (MRSA) has become a global public health issue. The aim of this study was to examine the clinical and molecular characteristics of Staphylococcus aureus isolates and to define the population structure and distribution of major MRSA clones isolated in a tertiary-care hospital in Mexico. RESULTS: From April 2017 to April 2018, 191 Staphylococcus aureus isolates were collected. The frequency of MRSA was 26.7%; these strains exhibited resistance to clindamycin (84.3%), erythromycin (86.2%), levofloxacin (80.3%), and ciprofloxacin (86.3%). The majority of MRSA strains harbored the SCCmec type II (76.4%) and t895 (56.8%) and t9364 (11.7%) were the most common spa types in both hospital-associated MRSA and community-associated MRSA isolates. ST5-MRSA-II-t895 (New York /Japan clone) and ST1011-MRSA-II-t9364 (New York /Japan-Mexican Variant clone) were the most frequently identified clones. Furthermore, different lineages of Clonal Complexes 5 (85.4%) and 8 (8.3%) were predominantly identified in this study. CONCLUSION: Our study provides valuable information about the epidemiology of MRSA in a city of the central region of Mexico, and this is the first report on the association between t895 and t9364 spa types and ST5 and ST1011 lineages, respectively. These findings support the importance of permanent surveillance of MRSA aimed to detect the evolutionary changes of the endemic clones and the emergence of new strains.

Predictors of a positive oral food challenge to cow's milk in children sensitized to cow's milk.

INTRODUCTION AND OBJECTIVES: The diagnosis of IgE-mediated cow's milk allergy (CMA) is often based on clinical history and on specific IgE levels and/or skin-prick tests (SPT), both of which are sensitive but not specific. The gold standard, oral food challenge (OFC), is expensive and time-consuming and involves a risk of severe allergic reactions. This study aimed to determine the value of specific IgEs, ratios of specific IgEs for cow's milk and its components to total IgE, and wheal size on SPT for predicting a positive OFC for CMA. MATERIAL AND METHODS: We retrospectively studied 72 patients [median age, four years; age range 0.75-15 years] sensitized to cow's milk who underwent OFCs to milk. predictive variables between patients with positive and negative OFCs were compared. Receiver operator characteristic (ROC) curves were uses to assess variables' discriminatory capacity and Youden's index to determine the best cut-offs for predicting CMA. RESULTS: The OFC was positive in 39 (54%) patients. Wheal size on SPT and all specific IgEs and specific-to-total IgE ratios were significantly different between patients with positive OFCs and those with negative OFCs (p<0.001). The variable with the greatest area under the ROC curve was casein-specific IgE (0.98), followed by ß-lactoglobulin-specific IgE (0.923), casein-specific-to-total-IgE ratio (0.919), and α-lactalbumin-specific IgE (0.908). Casein-specific IgE ≥0.95kU/L yielded 88.9% sensitivity and 90.9% specificity. CONCLUSIONS: In our center, casein-specific IgE >0.95kU/L can obviate an OFC to cow's milk for the diagnosis of CMA in patients sensitized to cow's milk with a compatible history.

Evaluation of the influence of main groundwater ions on arsenic removal by limestones through column experiments.

The influence of common groundwater major ions on arsenic (As) retention by native limestones was studied through column experiments. Columns were packed with rock particles (0.5-1.41 mm) and fed with solutions containing As, and chloride (Cl), sulfate, bicarbonate or fluoride (F) in concentrations similar to those measured in one of the most As-rich wells of Mexico. Besides, other solutions were also treated containing multiples or submultiples of those anion concentrations. Physico-chemical parameters, As, and each anion concentrations were determined weekly along 4 months. After the end of the experiments rocks collected from the top of the columns were analyzed by XRF, XRD, and SEM-WDS. Concentrations of As decreased from 1.2 mg/L to values below the Mexican drinking water standard (0.025 mg/L), since the first week in the solutions containing F or Cl keeping low values afterwards, indicating that they do not interfere with As removal. However, although As strongly decreased in the solutions containing sulfate since the first week, it started to increase from the 12th week in the highest concentrated solution. Bicarbonate was the anion affecting most As retention, since, after its decrease below 0.025 mg/L in the 2nd week for both solutions (30 mg/L and 300 mg/L), it started to increase since the 7th week in the most concentrated one, but maintained a low concentration in the least concentrated solution. Saturation index calculations and XRD analyses did not evidence the formation of As minerals. However, SEM elemental maps and XRF analyses showed the presence of As on the rocks after the treatments. Results indicate that As may be retained by sorption. Sulfate and bicarbonate compete with As for sorption sites. Results showed that native limestones are an option for treating As polluted water. Experiments also indicated that bicarbonate and sulfate may interfere with As removal depending on their concentrations.

Lactante con distrés respiratorio en invierno. Más allá de las bronquiolitis / Infant with respiratory disters in winter. Beyond bronchiolitis

La dificultad respiratoria en el lactante engloba varias entidades clínicas. Aunque en invierno la más frecuente es la bronquiolitis, no debemos olvidar, entre ellas, las malformaciones pulmonares congénitas (MPC). Se presenta el caso de un lactante de 6 semanas de vida que acudió a Urgencias en invierno por un cuadro de dificultad respiratoria en contexto catarral. Se realizó un diagnóstico inicial de bronquiolitis, pero posteriormente se alcanzó el diagnóstico correcto de enfisema lobar congénito (ELC). Se publica este caso para hacer hincapié en la importancia de revisar un diagnóstico con enfoque analítico, especialmente cuando el curso clínico no es típico. También nos debe servir para recordar que, a pesar de la mejora del diagnóstico prenatal, el diagnóstico de una MPC puede ser en el periodo neonatal o incluso más tardío. Por lo tanto, las MPC deben considerarse en el diagnóstico diferencial de síntomas respiratorios en un niño

Respiratory distress in the infant encompasses several clinical entities. Although bronchiolitis is the most frequent in winter, we should not forget congenital pulmonary malformations (CPMs). We are reporting a case of 6-week-old male presented to pediatric emergency ward during the winter period with respiratory distress in context of a cold. An initial diagnosis of bronchiolitis was made. The authors explore how the correct diagnosis of congenital lobar emphysema (CLE) was reached. This case emphasizes the importance of reviewing a diagnosis through an analytical approach, particularly in non-typical clinical courses. It should also help us to remember that despite the improvement of prenatal diagnosis, we also have CPMs diagnosis in the neonatal period or even later. Therefore, CPMs need to be considered in the differential diagnosis of respiratory symptoms in a child

Measurement of percentage dose at the surface for a 6 MV photon beam.

AIM: To evaluate if a radiochromic film (RF) Gafchromic EBT3 is suitable for surface dose measurements of radiotherapy treatments performed with a 6 MV linear accelerator. Two aspects of RF were analyzed, beam energy dependence and surface dose determination. BACKGROUND: The measurements done at the surface or near the radiation source are done without charged electronic equilibrium and also have contribution of electron contamination. The detectors used for these measurements should not alter the dose to the target. To counteract these dosimetric problems it is proposed to do the measurements with radiochromic films which are thin detectors and have tissue equivalent properties. MATERIALS AND METHODS: The measurements were done using a Novalis linear accelerator (LINAC) with nominal energy of 6 MV. To determine the surface dose, the total scatter factors (TSF) of three different field sizes were measured in a water phantom at 5 cm depth. Energy dependence of EBT3 was studied at three different depths, using a solid water phantom. The surface measurements were done with the RF for the same field sizes of the TSF measurements. The value of the percentage depth dose was calculated normalizing the doses measured in the RF with the LINAC output, at 5 cm depth, and the TSF. RESULTS: The radiochromic films showed almost energy independence, the differences between the curves are 1.7% and 1.8% for the 1.5 cm and 10 cm depth, respectively. The percentage depth doses values at the surface measured for the 10 cm × 10 cm, 5 cm × 5 cm and 1 cm × 1 cm were 26.1 ± 1.3%, 21.3 ± 2.4% and 20.2 ± 2.6%, respectively. CONCLUSIONS: The RF-EBT3 seems to be a detector suitable for measurements of the dose at the surface. This suggests that RF-EBT3 films might be good candidates as detectors for in vivo dosimetry.

ECLIM-SEHOP, a new platform to set up and develop international academic clinical trials for childhood cancer and blood disorders in Spain.

INTRODUCTION: Cancer and blood disorders in children are rare. The progressive improvement in survival over the last decades largely relies on the development of international academic clinical trials that gather the sufficient number of patients globally to elaborate solid conclusions and drive changes in clinical practice. The participation of Spain into large international academic trials has traditionally lagged behind of other European countries, mainly due to the burden of administrative tasks to open new studies, lack of financial support and limited research infrastructure in our hospitals. METHODS: The objective of ECLIM-SEHOP platform (Ensayos Clínicos Internacionales Multicéntricos-SEHOP) is to overcome these difficulties and position Spain among the European countries leading the advances in cancer and blood disorders, facilitate the access of our patients to novel diagnostic and therapeutic approaches and, most importantly, continue to improve survival and reducing long-term sequelae. ECLIM-SEHOP provides to the Spanish clinical investigators with the necessary infrastructural support to open and implement academic clinical trials and registries. RESULTS: In less than 3 years from its inception, the platform has provided support to 20 clinical trials and 8 observational studies, including 8 trials and 4 observational studies where the platform performs all trial-related tasks (integral support: trial setup, monitoring, etc.) with more than 150 patients recruited since 2017 to these studies. In this manuscript, we provide baseline metrics for academic clinical trial performance that permit future comparisons. CONCLUSIONS: ECLIM-SEHOP facilitates Spanish children and adolescents diagnosed with cancer and blood disorders to access state-of-the-art diagnostic and therapeutic strategies.

Mechanical properties of l-lysine based segmented polyurethane vascular grafts and their shape memory potential.

Segmented polyurethanes based on polycaprolactone, 4,4 (metylene-bis-cyclohexyl) isocyanate, and l-lysine were synthesized, manufactured as small vascular grafts and characterized according to ISO 7198 standard for cardiovascular implants-tubular vascular prosthesis. In terms of mechanical properties, the newly synthesized polyurethane films exhibited lower secant modulus than Tecoflex™ SG 80A, a well-known medical grade polyurethane. Similarly, when tested as grafts, the l-lysine-based polyurethane exhibited lower longitudinal failure load (11.5 N vs. 116 N), lower circumferential failure load per unit length (5.67 N/mm vs. 14.0 N/mm) and lower suture forces for both nylon (13.3 N vs. 24.0 N) and silk (14.0 N vs. 19.3 N) when compared to Tecoflex™ SG 80A grafts. l-Lysine-based graft exhibited a burst strength of 3620 mmHg (482.6 kPa) and a compliance of 0.16%/mmHg. The cell adhesion was demonstrated with NIH/3T3 fibroblasts where cell adhesion was observed on both films and grafts, while cell alignment was observed only on the grafts. The mechanical properties of this polyurethane and the possibility of strain-induced PCL crystals as the switching phase for shape memory materials, allowed a strain recovery ratio and a strain fixity ratio with values higher than 95% and 90%, respectively, with a repeatability of the shape-memory properties up to 4 thermo-mechanical cycles. Overall, the properties of lysine-based polyurethanes are suitable for large diameter vascular grafts where cell alignment can be controlled by their shape memory potential.

Design and analysis of a burst strength device for testing vascular grafts.

The design and analysis of a device to measure the burst strength (strength under a state of pure radial internal pressure) and compliance of vascular grafts and flexible pressurized tubes is presented. The device comprises three main sections, viz., a clean air-dry pressure controller, a test specimen holder, and automated software for control and data collection. Air pressure is controlled by means of a valve and a dedicated mechanism allowing reaching up to 120 psi in increments of 1 psi, and recording pressure changes with 0.04 psi resolution. The circumferential strain is determined by measuring the radial displacement of the vascular graft using an optical arrangement capable of determining a maximum radial displacement of 10 mm with 0.02 mm resolution. The instrument provides a low uncertainty in compliance (±0.32%/100 mm Hg-1) and burst strength measurements. Due to its simplicity, the device can easily be reproduced in other laboratories contributing to a dedicated instrument with high resolution at low cost. The reliability of the apparatus is further confirmed by conducting finite element analysis, elasticity solutions for pressurized cylinders, and testing of small diameter vascular grafts made of a commercial aliphatic polyurethane tested under radial internal pressure.

Bronchoalveolar lavage to evaluate new pulmonary infiltrates in allogeneic hematopoietic stem cell transplant recipients: impact on antimicrobial optimization.

BACKGROUND: Pulmonary complications cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplant (AHSCT). Bronchoscopy with targeted bronchoalveolar lavage (BAL) is often used in AHSCT patients with suspected lower respiratory tract infection (LRTI) to help guide management. AIM: To evaluate how positive BAL results change antimicrobial management of AHSCT recipients with suspected LRTI. METHODS: We performed a retrospective review of BAL results from January 2014 to July 2016 for 54 AHSCT recipients. A positive BAL was determined by culture, multiplex polymerase chain reaction (PCR), Aspergillus galactomannan antigen (AGA), and cytology. FINDINGS: BAL was positive for infectious etiologies in 63%, and antimicrobials were adjusted in 48/54 (89%) of patients. Antibacterial escalation was predicted by a positive BAL bacterial culture (OR 7.61, P=0.017). Antibiotic de-escalation was more likely with an elevated AGA (OR 3.86, P=0.035). Antiviral initiation was more likely with positive BAL multiplex PCR (OR 17.33, P=0.010). Antifungals were more likely to be escalated or changed with an elevated AGA (OR 4.33, P=0.020). The patients with a negative BAL were more likely to be started on steroids (OR 0.19, P= 0.043). CONCLUSIONS: BAL was helpful to determine the etiology of pulmonary complications and optimize antimicrobials. The addition of AGA and multiplex PCR to standard BAL significantly impacted de-escalating antibiotics and adjusting antifungals to provide adequate coverage. The association with an elevated AGA with antibacterial de-escalation highlights a new role for BAL in antimicrobial optimization.

Dos casos de liquen plano con tratamiento de hipnosis: Report of two cases / Lichen planus submitted to hypnosis treatment

El liquen plano es una alteración que afecta la piel, mucosas oral y genital, el cuero cabelludo y uñas. Su etiología incluye factores genéticos, inmunológicos y estrés; puede evolucionar por años y adquirir carácter crónico, presenta alta resistencia a los tratamientos de todo tipo. Se presentan dos casos con diagnósticos de liquen plano múltiple, sometidos a tratamiento de hipnosis con sugerencias terapéuticas directas, en tres direcciones: eliminación de las lesiones, marcas y prevención de nuevos brotes. Se administró una sesión por semana. El tratamiento fue de diez y seis sesiones, respectivamente. Se logró la remisión de los síntomas en ambos casos, el seguimiento no fue suficiente para evaluar la eliminación de las máculas residuales. Aún cuando el control de variables y el número de casos, no permite asegurarlo de manera científica, la hipnosis se perfila como un proceder que puede ser efectivo, en el tratamiento del liquen plano crónico.

Lichen planus is an alteration that affects the skin, oral and genital mucous membranes, the scalp and nails. Its etiology is imprecise, it includes genetic, immunological and stress-related factors, it can evolve for years and acquire the characteristic of a chronic disorder, it has a high resistance to treatments, psychotherapeutic methods have not shown efficiency either. Two cases with a diagnosis of multiple lichen planus submitted to hypnosis treatment with direct therapeutic suggestions, in three directions: elimination of lesions, marks, and prevention of new outbreaks are presented. One session per week was administered. The treatment lasted ten and six sessions respectively, the evolution was favorable, the remission of the symptoms was achieved in both cases, which had not been achieved with any previous treatment. The follow-up was not long enough to evaluate the elimination of residual spots. The importance of the cases presented lies in the favorable evolution of both under hypnotherapy, if taken into account their chronic nature and the lack of response to other treatments. Although it can not be ensured scientifically, by the small sample and by the impossibility of controlling variables, that the evolution is a result of the intervention performed, hypnosis is emerging as a procedure that can be effective in the treatment of chronic lichen planus, used as a single procedure or combined with other treatments.

A Review of the New Antiepileptic Drugs for Focal-Onset Seizures in Pediatrics: Role of Extrapolation.

Most antiepileptic drugs (AEDs) receive regulatory approval for children years after the drug is available in adults, encouraging off-label use of the drug in children and hindering attempts to obtain quality pediatric data in controlled trials. Extrapolating adult efficacy data to pediatrics can reduce the time between approval in adults and that in children. To extrapolate efficacy from adults to children, several assumptions must be supported, such as (1) a similar disease progression and response to interventions in adults and children, and (2) similar exposure response in adults and children. The Pediatric Epilepsy Academic Consortium for Extrapolation (PEACE) addressed these assumptions in focal-onset seizures (FOS), the most common seizure type in both adults and children. PEACE reviewed the biological and clinical evidence that supported the assumptions that children with FOS have a similar disease progression and response to intervention as adults with FOS. After age 2 years, the pathophysiological underpinnings of FOS and the biological milieu in which seizures are initiated and propagated in children, seizure semiology, electroencephalographic features, etiology and AED response to FOS in children are similar to those in adults with FOS. PEACE concluded that extrapolation of efficacy data in adults to pediatrics in FOS is supported by strong scientific and clinical evidence. However, safety and pharmacokinetic (PK) data cannot be extrapolated from adults to children. Based on extrapolation, eslicarbazepine is now approved for children with FOS, down to age 4 years. Perampanel, lacosamide and brivaracetam are now undergoing PK and safety studies for the purposes of extrapolation down to age 2 or 4 years. When done in conjunction with PK and safety investigations in children, extrapolation of adult data from adults to children can reduce the time delay between approval of effective and safe AEDs in adults and approval in children.

Treatment of childhood astrocytomas with irinotecan and cisplatin

Background. Previously we described the outcome of children with spinal cord astrocytoma treated with irinotecan and cisplatin (I/C). We here report the review of the initial institutional experience using this combination for children with low-grade glioma (LGG). Procedure. I/C chemotherapy consisted of weekly cisplatin (30 mg/m2) and irinotecan (50-65 mg/m2) for a total maximum of 16 doses, administered in an outpatient basis. Results. Between November 2002 and December 2009, 46 children (median age 6.3 years; range 0.3-17.7) with glioma were treated. We here report the cohort of 31 patients with LGG. Patients received a median of 16 cycles of I/C (range 8-16). The overall objective response [complete response (CR) + partial response (PR)] and disease control (CR + PR + stable disease) rates to I/C treatment were 6.5% [95% confidence interval (CI), 0.8-21.4%] and 93.5% (95% CI 78.6-99.2%), respectively. Disease control persisted for a median of 65 months. Toxicity was predominantly myelosuppression only seen in heavily pretreated patients. Survival analysis shows 5-year event-free survival (EFS) of 54% and 5-year overall survival (OS) of 80%. Conclusion. I/C chemotherapy produced disease control and clinical improvement in a majority of children with low-grade glioma, with manageable toxicity (AU)

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Arthroplasty knee registry of Catalonia: What scientific evidence supports the implantation of our prosthesis? / Registro de artroplastias de rodilla de Cataluña: ¿qué evidencia científica respalda la implantación de nuestras prótesis?

INTRODUCTION: In our environment, it is increasingly necessary to perform an activity based on scientific evidence and the field of prosthetic surgery should be governed by the same principles. The national arthroplasty registries allow us to obtain a large amount of data in order to evaluate this technique. The aim of our study is to analyse the scientific evidence that supports the primary total knee arthroplasties implanted in Catalonian public hospitals, based on the Arthoplasty Registry of Catalonia (RACat) MATERIAL AND METHODS: A review of the literature was carried out on knee prostheses (cruciate retaining, posterior stabilized, constricted and rotational) recorded in RACat between the period 2005-2013 in the following databases: Orthopedic Data Evaluation Panel, PubMed, TripDatabase and Google Scholar. The prostheses implanted in fewer than 10 units (1,358 prostheses corresponding to 62 models) were excluded. RESULTS: 41,947 prostheses (96.86%) were analysed out of 43,305 implanted, corresponding to 74 different models. In 13 models (n = 4,715) (11.24%) no clinical evidence to support their use was found. In the remaining 36 models (n = 13,609) (32.45%), level iv studies were the most predominant evidence. CONCLUSIONS: There was a significant number of implanted prostheses (11.24%) for which no clinical evidence was found. The number of models should be noted, 36 out of 110, with fewer than 10 units implanted. The use of arthroplasty registries has proved an extremely useful tool that allows us to analyse and draw conclusions in order to improve the efficiency of this surgical technique.

Prediction of circumferential compliance and burst strength of polymeric vascular grafts.

The circumferential compliance and burst strength of vascular grafts are predicted through the conically modified von Mises and elasticity theories, providing an analytical closed form solution for both parameters. Besides the graft's radii, the model for circumferential compliance depends solely on the elastic modulus and Poisson's ratio of the polymer material, and its accuracy was verified by finite element analysis and measurements. The analytical expression of the burst strength requires accurate determination of the material's tensile and compressive yield stress, which were carefully obtained by using digital image correlation measurements in uniaxial tensile and compressive tests of the constitutive material. The average measured circumferential compliance and burst strength of an 8mm graft made of a commonly used biomaterial, Tecoflex® SG-80A, are 1.05%/100mmHg-1 and 34.1psi (1763mmHg) and the proposed analytical predictions fall within the experimental scattering. Thus, it is shown that the circumferential compliance and burst strength of vascular grafts can be analytically predicted by knowing the elastic and yield material properties accurately, without needing to actually test the graft under radial pressure. This is a major advantage which can aid in the design and tailoring of vascular grafts.