Rapid and Sustained Long-Term Efficacy and Safety of Canakinumab in Patients With Cryopyrin-Associated Periodic Syndrome Ages Five Years and Younger.

To assess long-term efficacy and safety of canakinumab and the response to vaccination in children ages ≤5 years with cryopyrin-associated periodic syndrome (CAPS). CAPS patients (ages ≤5 years) received 2 mg/kg canakinumab subcutaneously every 8 weeks; patients with neonatal-onset multisystem inflammatory disease (NOMID) received a starting dose of 4 mg/kg in this open-label trial. Efficacy was evaluated using physician global assessment of disease activity and serum levels of C-reactive protein (CRP) and amyloid A (SAA). Adverse events (AEs) were recorded. Vaccination response was evaluated using postvaccination antibody titers at 4 and 8 weeks after immunization. Of the 17 patients enrolled, 12 (71%) had Muckle-Wells syndrome, 4 (24%) had NOMID, and 1 (6%) had familial cold autoinflammatory syndrome. All 17 patients had a complete response to canakinumab. Disease activity improved according to the physician global assessment, and for 65% of the patients autoinflammatory disease was characterized as "absent" at the end of the study. Median CRP levels decreased over time. No such change was evident in SAA levels. During the extension study, postvaccination antibody titers increased above protective levels in 16 (94%) of 17 assessable vaccinations. Ten of the patients (59%) had AEs suspected to be related to canakinumab; 8 (47%) experienced at least 1 serious AE (SAE). None of the AEs or SAEs required interruption of canakinumab therapy. Our findings indicate that canakinumab effectively maintains efficacy through 152 weeks and appears to have no effect on the ability to produce antibodies against standard childhood non-live vaccines. The safety profile of canakinumab was consistent with previous studies, supporting long-term use of canakinumab for CAPS in children ≤5 years of age

La enfermedad reumática infantil: una primera exploración sobre el estado psicológico paterno

The studies on the psychological and emotional consequences of pediatric rheumatic illness for parents of these children have been no conclusive, at all. That is, there are studies which point to the existence of psychological problems and, on the contrary there are studies which point to a satisfactory status. The aim of this study, then, relies on a first exploration of parents of children and adolescents with a rheumatic illness which attend the Pediatric Rheumatology Unit in one of the main Spanish hospitals to see which one of these conflicting results describe our subjects. Specifically, the main aims of the study were: a) to know the psychological status of mothers and fathers; and b) to explore if there were significant differences between mothers and fathers. 97 fathers and 111 mothers were contacted. That is, our final sample is composed of 208 subjects, parents of children with a rheumatic illness. Parents were evaluated through several instruments: The SCL-90-R, The Beck Depression Inventory and the State and Trait Anxiety Inventory from Spielberger. Main results were: a) from a general point of view we cannot consider our sample to be a clinical population, as the parents appear within normal ranges in the scales and subscales employed; b) mothers, compared with fathers, showed higher and statistically significant psychological scores in most of the scales and subscales. The paper ends with a discussion about the results, and with the advantages, disadvantages and future research lines with the aim of developing a cognitive-behavioral protocol for addressing the psychological needs of these families.Los estudios sobre las consecuencias psicológicas y emocionales de la enfermedad reumática infantil en padres de estos niños no han sido concluyentes, disponiendo de datos que avalan problemas de tipo psicológico o, por el contrario, un estado satisfactorio. La finalidad de este estudio, pues, estriba en hacer una primera exploración de los padres de niños y adolescentes con una enfermedad reumática que asistían a la Unidad de Reumatología Pediátrica en uno de los principales hospitales españoles, con la finalidad de explorar cuál de estos resultados contradictorios describe a nuestra muestra. En concreto, las metas de este estudio fueron: a) explorar el estado psicológico de padres y madres por igual; y b) explorar si existen diferencias significativas entre padres y madres. Con esta finalidad se contactó con un total de 97 padres y de 111 madres. Es decir, la muestra definitiva está compuesta de 208 sujetos, padres de niños con una enfermedad reumática. Los padres fueron evaluados a través de diversas pruebas: El Cuestionario de 90 Síntomas de Derogatis, el Inventario de Depresión de Beck, y el Cuestionario de Ansiedad Estado-Rasgo de Spielberger, Gorsuch y Lushene. Los resultados principales fueron: a) de forma general, no podemos considerar a esta muestra como una población clínica, ya que los padres aparecían dentro de rangos de normalidad en las pruebas y subescalas empleadas; b) las madres, frente a los padres, presentaban puntuaciones psicológicas mayores y estadísticamente significativas, en la mayoría de las pruebas y subescalas utilizadas. El artículo termina con una discusión del por qué de dichos resultados, y con las ventajas, desventajas y líneas futuras a seguir con este tipo de muestras con la vista puesta en desarrollar un protocolo cognitivo-comportamental de tratamiento que cubra las necesidades psicológicas de estas familias

Real-World Health Care Outcomes and Costs Among Patients With Juvenile Idiopathic Arthritis in Spain

**Background:** Juvenile idiopathic arthritis (JIA) is the most frequent chronic rheumatic disease in children. If inflammation is not adequately treated, joint damage, long-term disability, and active disease during adulthood can occur. Identifying and implementing early and adequate therapy are critical for improving clinical outcomes. The burden of JIA on affected children, their families, and the healthcare system in Spain has not been adequately assessed. The greatest contribution to direct costs is medication, but other expenses contribute to the consumption of resources, negatively impacting healthcare cost and the economic conditions of affected families. **Objective:** To assess the direct healthcare, indirect resource utilization, and associated cost of moderate-to-severe JIA in children in routine clinical practice in Spain. **Methods:** Children were enrolled in this 24-month observational, multicentric, cross-sectional, retrospective study (N = 107) if they had been treated with biologic disease-modifying anti-rheumatic drugs (bDMARDs), had participated in a previous study (ITACA), and continued to be followed up at pediatric rheumatology units at 3 tertiary Spanish hospitals. Direct costs included medication, specialist and primary care visits, hospitalizations, emergency visits or consultations, surgeries, physiotherapy, and tests. Indirect costs included hospital travel expenses and loss of caregiver working hours. Unitary costs were obtained from official sources (€, 2020). **Results:** Overall, children had inactive disease/low disease activity according to JADAS-71 score and very low functional disability as measured by Childhood Health Assessment Questionnaire score. Up to 94.4% of children received treatment, mainly with bDMARDs as monotherapy (84.5%). Among anti-TNFα treatments, adalimumab (47.4%) and etanercept (40.2%) were used in similar proportions. Annual mean (SD) total JIA cost was €7516.40 (€5627.30). Average cost of pharmacological treatment was €3021.80 (€3956.20), mainly due to biologic therapy €2789.00 (€3399.80). Direct annual cost (excluding treatments) was €3654.60 (€3899.00). Indirect JIA cost per family was €747.20 (€1452.80). **Conclusion:** JIA causes significant costs to the Spanish healthcare system and affected families. Public costs are partly due to the high cost of biologic treatments, which nevertheless remain an effective long-term treatment, maintaining inactive disease/low disease activity state; a very low functional disability score; and a good quality of life

Subwavelength waveguide structures for optical interconnects

We report our advances in development of subwavelength engineered waveguide structures. This unique NRC patented technology [1,2] allows synthesis of a metamaterial with an unprecedented control of material properties, constituting a powerful tool for a designer of photonic integrated circuits. We have demonstrated a number of subwavelength engineered devices operating at telecom wavelengths [3-7], for example fibre-chip couplers, waveguide crossings, WDM multiplexers, ultra-fast optical switches, athermal waveguides, evanescent field sensors, polarization rotators, transceiver hybrids and ultra-broadband interference couplers. The subwavelength metamaterial concept has been adopted by industry (IBM) for fibre-chip coupling and subwavelength structures are likely to become key building blocks for the next generation of integrated photonic circuits. Here we present an overview of recent examples of our subwavelength engineered structures, with an emphasis on couplers for optical interconnects and evanescent field sensors. We demonstrate an unprecedented control over the light coupling between optical fibers and silicon chips by constructing metamaterial couplers operating at telecom (1.55 μm) and datacom (1.3 μm) wavelengths. We also show that by subwavelength patterning of silicon-wire waveguides the field delocalization can be engineered to increase the sensitivity of evanescent field waveguide sensors [8]. Finally, we discuss some emerging applications of subwavelength engineered structures in mid-infrared photonics

Subwavelength structures for nanophotonic couplers, colourless splitters, polarization control and mid-infrared waveguides

We report our recent advances in development of subwavelength engineered dielectric metamaterial structures for integrated photonics. By locally engineering the refractive index of silicon by forming a pattern of holes at the subwavelength scale it is possible to manipulate the flow of light in silicon nanophotonic waveguides [1], [2], [3], [4], [5], [6]. Specifically, we present a broadband fibre-chip edge coupler with a coupling efficiency exceeding 90% for direct coupling between cleaved SMF-28 optical fibres and silicon nanophotonic waveguides [7], as well as the first implementation of a subwavelength nanostructure for laser-to-SOI chip coupling experiments with an InGaAsP/InP buried heterostructure laser. Furthermore, we report on dispersion engineered colourless multimode interference coupler operating over an ultra-broad wavelength range 1260 nm – 1675 nm, exceeding the O, E, S, C, L and U optical communication bands. We also present an integrated polarization controller with largely relaxed fabrication tolerances and tuneable over the complete C-band, with a measured polarization extinction range of 40 dB [8]. Implementations of subwavelength grating engineered structures for evanescent field sensing and mid-infrared silicon photonic circuits [9] with waveguide propagation losses < 0.9 dB/cm at 3.88 µm will also be discussed

Subcutaneous Abatacept in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis: Results From a Phase III Open-Label Study

To investigate pharmacokinetics, effectiveness, and safety of subcutaneous (SC) abatacept over 24 months (M) in patients with polyarticular-course juvenile idiopathic arthritis (pJIA).status: accepte