Drug Retention Rate and Predictive Factors of Drug Survival for Interleukin-1 Inhibitors in Systemic Juvenile Idiopathic Arthritis

Background and Objectives: Few studies have reported the drug retention rate (DRR) of biologic drugs in juvenile idiopathic arthritis (JIA), and none of them has specifically investigated the DRR of interleukin (IL)-1 inhibitors on systemic JIA (sJIA). This study aims to describe IL-1 inhibitors DRR and evaluate predictive factors of drug survival based on data from a real-world setting concerning sJIA.Methods: Medical records from sJIA patients treated with anakinra (ANA) and canakinumab (CAN) were retrospectively analyzed from 15 Italian tertiary referral centers.Results: Seventy seven patients were enrolled for a total of 86 treatment courses. The cumulative retention rate of the IL-1 inhibitors at 12-, 24-, 48-, and 60-months of follow-up was 79.9, 59.5, 53.5, and 53.5%, respectively, without any statistically significant differences between ANA and CAN (p = 0.056), and between patients treated in monotherapy compared to the subgroup co-administered with conventional immunosuppressors (p = 0.058). On the contrary, significant differences were found between biologic-naive patients and those previously treated with biologic drugs (p = 0.038) and when distinguishing according to adverse events (AEs) occurrence (p = 0.04). In regression analysis, patients pre-treated with other biologics (HR = 3.357 [CI: 1.341-8.406], p = 0.01) and those experiencing AEs (HR = 2.970 [CI: 1.186-7.435], p = 0.020) were associated with a higher hazard ratio of IL-1 inhibitors withdrawal. The mean treatment delay was significantly higher among patients discontinuing IL-1 inhibitors (p = 0.0002).Conclusions: Our findings suggest an excellent overall DRR for both ANA and CAN that might be further augmented by paying attention to AEs and employing these agents as first-line biologics in an early disease phase

Análisis comparativo de usabilidad de dos plataformas para gestionar la comunicación y estrategia de organizaciones y empresas en redes sociales

El objetivo de esta investigación fue hacer un testeo comparativo de usabilidad y facilidad de trabajo en dos programas: Social Hint y Hoot Suite. Ambos son herramientas diseñadas para asistir empresas, agencias y community managers en la moderación y gestión de las redes sociales. Se buscó comparar entre ambas plataformas a nivel de usabilidad y facilidad en el manejo de los sistemas (a nivel de interfaz, manejo de datos, generación de gráficos y estadísticas). El resultado permitió conocer e identificar fortalezas y debilidades a nivel de la gestión de contenidos y medición en redes sociales a través de esos programas y sus principales características de funcionalidad, a través del uso y testeo de ambos programas a través de escalas de medición de actitudes. Los objetivos de la investigación se cumplieron y se generaron nuevos aportes al área del estudio de las Nuevas Tecnologías y la gestión de las redes sociales

Disease status, reasons for discontinuation and adverse events in 1038 Italian children with juvenile idiopathic arthritis treated with etanercept

Background: Data from routine clinical practice are needed to further define the efficacy and safety of biologic medications in children with juvenile idiopathic arthritis (JIA). The aim of this analysis was to investigate the disease status, reasons for discontinuation and adverse events in Italian JIA patients treated with etanercept (ETN). Methods: In 2013, all centers of the Italian Pediatric Rheumatology Study Group were asked to make a census of patients given ETN after January 2000. Patients were classified in three groups: group 1 = patients still taking ETN; group 2 = patients discontinued from ETN for any reasons; group 3 = patients lost to follow-up while receiving ETN. All three groups received a retrospective assessment; patients in group 1 also underwent a cross-sectional assessment. Results: 1038 patients were enrolled by 23 centers: 422 (40.7%) were in group 1, 462 (44.5%) in group 2, and 154 (14.8%) in group 3. Median duration of ETN therapy was 2.5 years. At cross-sectional assessment, 41.8% to 48.6% of patients in group 1 met formal criteria for inactive disease, whereas 52.4% of patients in group 2 and 55.8% of patients in group 3 were judged in clinical remission by their caring physician at last visit. A relatively greater proportion of patients with systemic arthritis were discontinued or lost to follow-up. Parent evaluations at cross-sectional visit in group 1 showed that 52.4% of patients had normal physical function, very few had impairment in quality of life, 51.2% had no pain, 76% had no morning stiffness, and 82.7% of parents were satisfied with their child's illness outcome. Clinically significant adverse events were reported for 27.8% of patients and ETN was discontinued for side effects in 9.5%. The most common adverse events were new onset or recurrent uveitis (10.2%), infections (6.6%), injection site reactions (4.4%), and neuropsychiatric (3.1%), gastrointestinal (2.4%), and hematological disorders (2.1%). Ten patients developed an inflammatory bowel disease and 2 had a malignancy. One patient died of a fulminant streptococcal sepsis. Conclusions: Around half of the patients achieved complete disease quiescence under treatment with ETN. The medication was overall well tolerated, as only one quarter of patients experienced clinically significant adverse events and less than 10% had treatment discontinued for toxicity

Opportunistic infections in immunosuppressed patients with juvenile idiopathic arthritis: Analysis by the Pharmachild Safety Adjudication Committee

Background: To derive a list of opportunistic infections (OI) through the analysis of the juvenile idiopathic arthritis (JIA) patients in the Pharmachild registry by an independent Safety Adjudication Committee (SAC). Methods: The SAC (3 pediatric rheumatologists and 2 pediatric infectious disease specialists) elaborated and approved by consensus a provisional list of OI for use in JIA. Through a 5 step-procedure, all the severe and serious infections, classified as per MedDRA dictionary and retrieved in the Pharmachild registry, were evaluated by the SAC by answering six questions and adjudicated with the agreement of 3/5 specialists. A final evidence-based list of OI resulted by matching the adjudicated infections with the provisional list of OI. Results: A total of 772 infectious events in 572 eligible patients, of which 335 serious/severe/very severe non-OI and 437 OI (any intensity/severity), according to the provisional list, were retrieved. Six hundred eighty-two of 772 (88.3%) were adjudicated as infections, of them 603/682 (88.4%) as common and 119/682 (17.4%) as OI by the SAC. Matching these 119 opportunistic events with the provisional list, 106 were confirmed by the SAC as OI, and among them infections by herpes viruses were the most frequent (68%), followed by tuberculosis (27.4%). The remaining events were divided in the groups of non-OI and possible/patient and/or pathogen-related OI. Conclusions: We found a significant number of OI in JIA patients on immunosuppressive therapy. The proposed list of OI, created by consensus and validated in the Pharmachild cohort, could facilitate comparison among future pharmacovigilance studies. Trial registration: Clinicaltrials.gov NCT 01399281; ENCePP seal: awarded on 25 November 2011

Effects of volatile anaesthetics on heme metabolism in a murine genetic model of Acute Intermittent Porphyria: A comparative study with other porphyrinogenic drugs

Background: Acute Intermittent Porphyria (AIP) is an inherited disease produced by a deficiency of Porphobilinogen deaminase (PBG-D). The aim of this work was to evaluate the effects of Isoflurane and Sevoflurane on heme metabolism in a mouse genetic model of AIP to further support our previous proposal for avoiding their use in porphyric patients. A comparative study was performed administering the porphyrinogenic drugs allylisopropylacetamide (AIA), barbital and ethanol, and also between sex and mutation using AIP (PBG-D activity 70% reduced) and T1 (PBG-D activity 50% diminished) mice. Methods: The activities of 5-Aminolevulinic synthetase (ALA-S), PBG-D, Heme oxygenase (HO) and CYP2E1; the expression of ALA-S and the levels of 5-aminolevulinic acid (ALA) were measured in different tissues of mice treated with the drugs mentioned. Results: Isoflurane increased liver, kidney and brain ALA-S activity of AIP females but only affected kidney AIP males. Sevoflurane induced ALA-S activity in kidney and brain of female AIP group. PBG-D activity was further reduced by Isoflurane in liver male T1; in AIP male mice activity remained in its low basal levels. Ethanol and barbital also caused biochemical alterations. Only AIA triggered neurological signs similar to those observed during human acute attacks in male AIP being the symptoms less pronounced in females although ALA-S induction was greater. Heme degradation was affected. Discussion: Biochemical alterations caused by the porphyrinogenic drugs assayed were different in male and female mice and also between T1 and AIP being more affected the females of AIP group. General significance: This is the first study using volatile anaesthetics in an AIP genetic model confirming Isoflurane and Sevoflurane porphyrinogenicity.Fil: Ruspini, Silvina Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; ArgentinaFil: Zuccoli, Johanna Romina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; ArgentinaFil: Lavandera, Jimena Veronica. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martinez, Maria del Carmen. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; ArgentinaFil: Olivieri, Leda María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; ArgentinaFil: Gerez, Esther Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; ArgentinaFil: Batlle, Alcira Maria del C.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; ArgentinaFil: Buzaleh, Ana Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Investigaciones sobre Porfirinas y Porfirias. Universidad de Buenos Aires. Centro de Investigaciones sobre Porfirinas y Porfirias; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentin

How to Assess the Headache—Sleep Disorders Comorbidity in Children and Adolescents

Sleep disorders and primary headaches are frequent health problems in childhood, and they are often comorbid in an individual, linked by a mutual and complex relationship. This comorbidity is frequent and well-documented, but the available literature is usually biased in favor of one aspect or another, mainly depending on the expertise of the authors. The aim of this paper is to review existing literature on the diagnostic assessment of comorbid primary headaches and sleep disorders, so as to propose practical suggestions to accurately investigate the presence of comorbid conditions in children evaluated for primary headaches or for sleep disorders