Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

Pemaknaan Ritual Setelah Panen Suku Dayak Kanayatn Di Pontianak: Studi Etnografi Komunikasi Upacara Adat Naik Dango

Skripsi ini membahas mengenai pemaknaan sebuah ritual/upacara adat setelah panen pada salah satu suku terbesar di Kalimantan Barat, yaitu suku Dayak Kanayatn. Fokus penelitian dalam rumusan masalah antara lain simbol komunikasi serta makna nya melalui perspektif interaksi simbolik. Teori yang digunakan dalam penelitian ini yaitu Interaksi Simbolik dari Herbert Blumer dan teori Etnografi Komunikasi dari Dell Hymes dan Saville- Troike. Peneliti menggunakan pendekatan kualitatif deskriptif dan berfokus pada paradigma konstruktivis. Metode analisis kajian etnografi komunikasi model Dell Hymes digunakan penulis untuk mengkaji pemaknaan pada upacara adat Naik Dango. Dari hasil penelitian yang telah dilakukan, penulis menemukan makna komunikasi di dalamnya melalui tiga faktor yaitu situasi komunikasi, peristiwa komunikasi, dan tindakan komunikasi. Tiga faktor tersebut diuraikan lebih lanjut secara deskriptif menggunakan metode penelitian etnografi komunikasi oleh Saville-Troike dan model SPEAKING Dell Hymes. Dari hasil yang diperoleh, upacara adat Naik Dango menciptakan makna tertentu melalui 5 (lima) faktor, antara lain diri (the self), tindakan (the act), interaksi sosial (social interactionism), benda (object), dan tindakan bersama (joint action). Dalam diri masyarakat Dayak Kanayatn dipandang sebagai padi yaitu sumber kehidupan. Melalui tindakan dan interaksi sosial yang saling berhubungan menciptakan tindakan bersama. Oleh sebab itu, objek menjadi simbol yang sangat berperan penting dalam membentuk makna yang sama antar masyarakat

Millennials en América Latina y el Caribe : ¿trabajar o estudiar?

Presenta los principales resultados de un proyecto regional que contó con la participación de más de 15.000 jóvenes de entre 15 y 24 años en nueve países (Brasil, Chile, Colombia, El Salvador, Haití, México, Paraguay, Perú y Uruguay). La novedad de este estudio es que va más allá de las variables que tradicionalmente levantan las encuestas de hogares, como ingresos o nivel de estudios, e incorpora otras menos convencionales: la información que los jóvenes manejan acerca del funcionamiento del mercado laboral, así como sus aspiraciones, expectativas y habilidades cognitivas y socioemocionales. Así, tratamos de entender mejor la decisión que toman los jóvenes respecto de solo estudiar, solo trabajar, combinar estudio y trabajo, o ni estudiar ni trabajar (ser nini), e impulsar medidas más acordes para desarrollar su potencial. Sobre la base de estos hallazgos, esta publicación sugiere qué acciones de política pueden ayudar a los jóvenes a realizar una transición exitosa desde sus estudios al mercado laboral. La investigación presentada en este libro se basa en información novedosa, de calidad y comparable que se obtuvo como parte del proyecto en los nueve países de la región. En particular, se diseñaron dos instrumentos. Uno es la encuesta “Millennials en América Latina y Caribe”, en la que participaron entre 2017 y 2018 jóvenes residentes en las zonas urbanas de Brasil, Chile, Colombia, El Salvador, Haití, México y Paraguay. A ellos se suman Perú y Uruguay, que participaron sobre la base de información longitudinal ya existente (Young Lives/Niños del Milenio en Perú y el Estudio Longitudinal del Bienestar en Uruguay). El segundo instrumento es un estudio cualitativo, basado en grupos focales en los nueve países, que permitió indagar con más detalle cómo los jóvenes han llegado a su actual situación de estudio y trabajo, así como cuáles son sus aspiraciones para el futuro. La medición de habilidades socioemocionales, aspiraciones y expectativas, además del análisis de su correlación con las decisiones educativas y laborales de los jóvenes, es uno de los aportes centrales de este libro. Las habilidades socioemocionales que mide este proyecto, también conocidas como habilidades blandas, incluyen, entre otras, la perseverancia, la confianza en las propias capacidades, la autoestima y el autocontrol. Para medirlas, se emplearon instrumentos y pruebas que ya han sido utilizados y validados ampliamente en psicología y, más reciente, en economía. Contar con evidencia de estas variables se justifica por dos razones principales: primero, existe una creciente literatura académica que sugiere que el desarrollo de estas habilidades permite una inserción educativa, laboral y social más exitosa de las personas; y, segundo, estas dimensiones pueden modificarse a bajo costo durante la juventud. Los resultados de esta investigación, una radiografía detallada sobre los jóvenes de América Latina y el Caribe, ofrecen un panorama alentador en la mayoría de los aspectos. En él no hay cabida para prejuicios y estereotipos, como los que pesan sobre los millennials o sobre los 20 millones de ninis que hay en América Latina y el Caribe. De acuerdo con los resultados de la encuesta, un 41% de los jóvenes en la región se dedica exclusivamente al estudio, un 21% solo trabaja, un 17% realiza ambas actividades y un 21% no estudia, se capacita o trabaja. Además, se observan diferencias en los años de educación que alcanzan los jóvenes en los distintos países de América Latina y el Caribe. Respecto a sus resultados laborales, los jóvenes muestran una temprana inserción laboral (a los 16 años, en promedio) y altas tasas tanto de informalidad como de rotación laboral. Asimismo, el análisis confirma el rezago en habilidades cognitivas de los jóvenes de la región que ya han detectado pruebas estandarizadas internacionales como PISA, independiente de su situación laboral y educativa. Por ejemplo, alrededor de un 40% de los encuestados no es capaz de realizar correctamente cálculos matemáticos muy sencillos, útiles para la vida diaria, como repartir un monto de dinero en partes iguales. También encontramos que, en promedio, los jóvenes del estudio carecen de algunas habilidades técnicas esenciales para el nuevo mercado laboral (por ejemplo, menos de un cuarto declara hablar fluidamente inglés), pero que a la vez poseen otras capacidades igualmente relevantes (por ejemplo, indican manejar dispositivos tecnológicos con facilidad). Además, este estudio devela que los jóvenes de América Latina y el Caribe son, en general, optimistas acerca de su futuro. De hecho, aunque la cobertura actual de la educación superior en la región se ubica en promedio alrededor del 40%, una mayoría abrumadora de los encuestados aspiran y declaran estar altamente seguros de completar la educación superior

An observational study of patient versus parental perceptions of health-related quality of life in children and adolescents with a chronic pain condition: who should the clinician believe?

<p>Abstract</p> <p>Background</p> <p>Previous pediatric studies have observed a cross-informant variance in patient self-reported health-related quality of life (HRQoL) versus parent proxy-reported HRQoL. This study assessed in older children and adolescents with a variety of chronic pain conditions: 1) the consistency and agreement between pediatric patients’ self-report and their parents’ proxy-report of their child’s HRQoL; 2) whether this patient-parent agreement is dependent on additional demographic and clinical factors; and 3) the relationship between pediatric patient HRQoL and parental reported HRQoL.</p> <p>Methods</p> <p>The 99 enrolled patients (mean age 13.2 years, 71% female, 81% Caucasian) and an accompanying parent completed the PedsQL^TM 4.0 and 36-Item Short-Form Health Survey Version 2 (SF-36v2) at the time of their initial appointment in a pediatric chronic pain medicine clinic. Patients’ and parents’ total, physical, and psychosocial HRQoL scores were analyzed via an intra-class correlation coefficient, Spearman’s correlation coefficient, Wilcoxon signed rank test, and Bland-Altman plot. A multivariable linear regression model was used to evaluate the association between clinical and demographic variables and the difference in patient and proxy scores for the Total Scale Score on the PedsQL™.</p> <p>Results</p> <p>With the exception of the psychosocial health domain, there were no statistically significant differences between pediatric patients’ self-report and their parents’ proxy-report of their child’s HRQoL. However, clinically significant patient-parent variation in pediatric HRQoL was observed. Differences in patient-parent proxy PedsQL™ Total Scale Score Scores were not significantly associated with patient age, gender, race, intensity and duration of patient’s pain, household income, parental marital status, and the parent’s own HRQoL on the SF-36v2. No significant relationship existed among patients’ self-reported HRQoL (PedsQL™), parental proxy-reports of the child’s HRQoL, and parents’ own self-reported HRQoL on the SF-36v2.</p> <p>Conclusions</p> <p>We observed clinically significant variation between pediatric chronic pain patients’ self-reports and their parents’ proxy-reports of their child’s HRQoL. While whenever possible the pediatric chronic pain patient’s own perspective should be directly solicited, equal attention and merit should be given to the parent’s proxy-report of HRQoL. To do otherwise will obviate the opportunity to use any discordance as the basis for a therapeutic discussion about the contributing dynamic with in parent-child dyad.</p

Abstracts from the 23rd Italian congress of Cystic Fibrosis and the 13th National congress of Cystic Fibrosis Italian Society

Cystic Fibrosis (CF) occurs most frequently in caucasian populations. Although less common, this disorder have been reported in all the ethnicities. Currently, there are more than 2000 described sequence variations in CFTR gene, uniformly distributed and including variants pathogenic and benign (CFTR1:www.genet.sickkids.on.ca/). To date,only a subset have been firmily established as variants annotated as disease-causing (CFTR2: www.cftr2.org). The spectrum and the frequency of individual CFTR variants, however, vary among specific ethnic groups and geographic areas. Genetic screening for CF with standard panels of CFTR mutations is widely used for the diagnosis of CF in newborns and symptomatic patients, and to diagnose CF carrier status. These screening panels have an high diagnostic sensitivity (around 85%) for CFTR mutations in caucasians populations but very low for non caucasians. Developed in the last decade, Next-Generation Sequencing (NGS) has been the last breakthrough technology in genetic studies with a substantial reduction in cost per sequenced base and a considerable enhancement of the sequence generation capabilities. Extended CFTR gene sequencing in NGS includes all the coding regions, the splicing sites and their flankig intronic regions, deep intronic regions where are localized known mutations,the promoter and the 5'-3' UTR regions. NGS allows the analysis of many samples concurrently in a shorter period of time compared to Sanger method . Moreover, NGS platforms are able to identify CFTR copy number variation (CNVs), not detected by Sanger sequencing. This technology has provided new and reliable approaches to molecular diagnosis of CF and CFTR-Related Disorders. It also allows to improve the diagnostic sensitivity of newborn and carrier screeningmolecular tests. In fact, bioinformatics tools suitable for all the NGS platforms can filter data generated from the gene sequencing, and analyze only mutations with well-established disease liability. This approach allows the development of targeted mutations panels with a higher number of frequent CF mutations for the target populationcompared to the standard panels and a consequent enhancement of the diagnostic sensitivity. Moreover, in the emerging challenge of diagnosing CF in non caucasians patients, the possibility of customize a NGS targeted mutations panel should increase the diagnostic sensitivity when the target population has different ethnicities