Saint-germain-le-fouilloux, France

Sinus Disease in Young Children With Cystic Fibrosis

This multi-center, prospective, observational study investigates the effects of highly effective modulator therapy (HEMT) on chronic rhinosinusitis (CRS) and olfactory dysfunction (OD) in young children with cystic fibrosis (YCwCF). The study spans two years and includes two distinct groups of children with cystic fibrosis: children ≤ 8 years old receiving HEMT and a control group of children ≤ 8 not receiving HEMT. The study aims to assess the efficacy of HEMT in improving sinus health and olfactory capabilities in this young demographic. Key assessments include magnetic resonance imaging (MRI) sinus opacification, olfactory bulb volume measured via MRI, objective olfactory testing, and various quality (QOL) surveys. This investigation seeks to characterize the severity of CRS and OD in YCwCF, and to elucidate if early initiation of HEMT improves CRS and OD . In the HEMT group, participants will have a pre-HEMT assessment followed by 1-year and 2-year post-HEMT evaluations. In the control/non-HEMT group, participants will undergo parallel assessments at baseline, 1-year, and 2-year intervals to track the natural progression of CRS and OD without HEMT.

Deep Functional Phenotyping of the ALA Lung Health Cohort

The parent Lung Health Cohort (LHC) study will leverage the national infrastructure of the American Lung Association's (ALA) Airways Clinical Research Centers (ACRC) to form the first national cohort of adults focused on respiratory health. The parent LHC study will recruit approximately 4000 community-dwelling adults aged 25-35 from metropolitan regions across the U.S. for the purpose of defining lung health and developing targets to intercept chronic lung disease at its earliest stages. The parent LHC study will be examining a multitude of known and potential factors related to reduced reserve and increased susceptibility to lung disease, such as childhood and adult health status, infections and exposures. Two of the primary outcomes being assessed during this cross-sectional phase of the parent LHC will be spirometry, measured in forced expiratory volume in 1 second (FEV1), respiratory symptoms in relation to environmental exposures, measured in exposure to particulate matter under 2.5 microns in size (PM2.5). These will be assessed in relation to computed tomography (CT) measures of lung injury. The ancillary study expands the phenotyping to include detailed measurements of lung structure and function, including lung volumes, oscillometry, diffusing capacity for carbon monoxide (DLCO), and airway, blood vessel and cardiac morphology by CT. This deeper phenotyping will move the characterization of lung health reserve beyond FEV1, as well as establish a more comprehensive baseline of lung health to allow assessment of susceptibility. Furthermore, the investigators will relate these detailed measures of lung structure and function to modifiable exposures and risk factors that will allow identification of risks to lung health and potential strategies to mitigate risk. The investigators hypothesize that modifiable exposures and risk factors influence lung health by the effects on structural and functional dysanapsis of the airway, parenchyma and pulmonary vasculature, as well as cardiac morphology and gas exchange.

American Lung Association (ALA) Lung Health Cohort

The scientific goal of the study is to establish the relationship between a variety of factors (lifetime environmental exposures, fitness and physical activity, biomarkers, nasal respiratory epithelial transcriptome) and ideal versus impaired peak lung health (reserve and markers of susceptibility in investigators' model) in young adulthood. In addition to the initial baseline assessment, remote contacts (e.g., via text message, email, mail, or phone) at regular intervals will allow for both the retention of the participants as well as the collection of additional short-term follow-up information, i.e., within 4.5 years of enrollment. If additional funding becomes available, investigators will extend the study for an additional period of time to study factors related to long-term changes in lung health over time, i.e., at 5 years and beyond. Recruitment of participants will be conducted by the participating study sites along with national and regional efforts from the American Lung Association. Recruitment efforts will be supported by the study web site www.lung.org/lung-study

Pulmonary Hypertension Screening in Patients with Interstitial Lung Disease for Earlier Detection

In this study, subjects will undergo a broad range of clinical assessments that are potentially associated with PH. Study data will be used to identify and weigh specific clinical parameters based on their prognostic significance for right heart catheterization (RHC)-confirmed PH. There is no study drug under investigation in this study. The study consists of 2 study visits: a Screening Visit and Study Visit 1. Clinical assessments include pulmonary function tests (PFTs); high resolution computed tomography (HRCT); physical examination; 6-Minute Walk Test; blood draw for clinical laboratory parameters, plasma brain natriuretic peptide (BNP) concentration and plasma N-terminal pro-BNP (NT-proBNP) concentration; echocardiography; University of California San Diego Shortness of Breath Questionnaire (UCSD SOBQ); King's Brief Interstitial Lung Disease Questionnaire (K-BILD); 36-Item Short Form Survey (SF-36); Pulmonary Hypertension Functional Classification Self Report (PH-FC-SR); Investigator's Suspicion of PH Questionnaire; adverse event (AE) monitoring; and RHC. As the primary objective of this study is to collect a broad range of clinical parameters in patients with ILD, it is expected that numerous exploratory and post-hoc analyses will be performed to identify and weigh specific parameters based on their prognostic significance for PH in this patient population with the goal of developing a screening algorithm for PH in patients with ILD.

USCRI READY4Life Program

The U.S. Committee for Refugees and Immigrants (USCRI) has developed the Relationships, Education, Advancement, and Development for Youth for Life (READY4Life) Program. This is a 16-hour program for immigrants/refugees, ages 14 to 24. The program is designed to help young immigrants and refugees prepare for a successful life in the United States. The program is taught by USCRI program staff and is being implemented at eight sites across the U.S.: Cleveland, Ohio; Colchester, Vermont; Des Moines, Iowa; Miami, Florida; Philadelphia, Pennsylvania; Raleigh, North Carolina; Saint Paul, Minnesota; and Twin Falls, Idaho. The project also includes a rigorous evaluation component, featuring a Randomized Control Trial (RCT) design. Relationships, Education, Advancement, and Development for Youth for Life (READY4Life) will strengthen and promote healthy marriages among young refugees and immigrants through education and comprehensive case management that will support an overall goal of helping youth build healthy relationship skills while supporting positive socioemotional development and promoting successful transitions to young adulthood. USCRI's READY4Life program will serve refugee and immigrant youth ages 14 to 24, including but not limited to those individuals receiving, or who previously received TANF and/or individuals who are eligible for TANF assistance; non-custodial and custodial single parents; low-income, at-risk individuals; parenting youth; individuals with disabilities; and other eligible demographics, with a focus on underserved populations. The Relationship Education curriculum, that was successfully used with an adult refugee/immigrant population, has been adapted for youth into a 16-hour curriculum composed of 1-, 2- and 4-hour sessions. Sessions are spaced a week apart to accommodate both federal requirements and research that shows relationship skills are best learned when practiced over time. . READY4Life will include ten communication and conflict resolution skills, as well as content information about effects of trauma on emotional stability and relationships, characteristics and advantages of healthy marriage, setting and achieving financial priorities and goals. Adaptations of the four core skills are taught: Expression Skills, Showing Understanding Skills, Discussion Skills, and Problem-Solving Skills. In the remaining hours of the curriculum, six additional skills are taught: Coaching and Conflict Management Skills, Self-Change and Helping Others Change Skills, and Generalization Skills and Maintenance Skills. Though not a part of the 10 Relationship Enhancement skills, time will also be devoted to financial management and making progress towards greater economic stability. The four primary research questions deal with: 1) Communication skills; 2) Conflict resolution, conflict management, and problem-solving skills; 3) Healthy relationship and marriage skills; 4) Progress towards greater economic stability. We have selected these research questions because we believe, and the literature supports the position, that these factors are of major importance in helping youth make a successful transition from adolescence to adulthood. The intervention participants will receive the IDEALS curriculum for community participants ages 14 to 24. Total: 16 hours per intervention participant (3,600 total intervention participants). The control group will not receive the curriculum (1,200 total control participants). Note: once the control participants have completed the pre-test questionnaire, post-test questionnaire and six-month follow-up, they will be eligible to receive the intervention services, but they will not be counted as an intervention participant. Their participation in the evaluation will end once the six-month follow-up questionnaire is collected. Educational Evaluators, Inc. (EEI) is the local evaluator on this project working with USCRI's READY4Life Program. We also want grantee staff to understand the importance of evaluation and to be familiar with the evaluation protocols. By working closely together from the initial development of the proposal and picking up that collaboration as soon as the grant award was made, the evaluation staff and the grantee staff work together to understand all dimensions of the program. We believe this strengthens the overall evaluation, since EEI is not simply looking in as outsiders, but has provided training in all evaluation procedures to all grantee project staff including the Project Director, Program Coordinators, and Data Collection Specialists. This again, strengthens the evaluation. Random Assignment. Participants will be randomly assigned the intervention group or the control group in a 3:1 ratio. Thus, of the total number of participants per year, 25% will be assigned to the control group, and the remaining 75% will be assigned to the intervention group. The evaluation team will use a random number generator created by Qualtrics to assign subjects to the intervention or control as described above. Demographic data for the intervention group will be compared with the control group to determine whether there are group differences on any of the demographic variables. If differences are detected between an intervention group and control group, then that variable will be used as a co-variate when comparing groups relative to outcome variables. The unit of analysis will be the individual participant, refugee/immigrant youth, ages 14-24. Many participants will be youth enrolled in high school grades 9-12, although participants up to the age of 24 will be eligible for enrollment. The program will not be provided during the school day, as part of the school curriculum. Some schools, however, will allow us to use the school facilities to provide the program in an after-school setting. The schools providing after-school settings have high percentages of English Language Learners and immigrant and refugee student populations. Several are part of the Refugee School Impact Working Group, offer the Success Management Academy Program targeting recent arrivals to the US, or come from districts offering Newcomer Centers serving immigrant and refugee students. This project targets low-income and at-risk, refugee and immigrant youth, ages 14-24. The target population will not differ from those who will be broadly served by the grant. Participants will be young people who self-identify as refugees or immigrants. An instrument was developed after a comprehensive review of the intervention to be implemented. This instrument is aligned with the research questions and hypotheses developed. The Local Evaluation Questionnaire (LEQ) contains 5 demographic questions and 55 questions to answer the primary and secondary research questionsThe four primary research questions deal with: 1) Communication skills; 2) Conflict resolution, conflict management, and problem-solving skills; 3) Healthy relationship and marriage skills; 4) Progress towards greater economic stability. We have selected these research questions because we believe, and the literature supports the position, that these factors are of major importance in helping youth make a successful transition from adolescence to adulthood. Statistical Power. Statistical power for evaluation of this study's hypotheses was calculated using Optimal Design Software for Multilevel and Longitudinal Research Version 3.01. Power calculations were computed to estimate minimum detectable effect sizes based on group comparisons over time, with an alpha of .05 and power of .80. Adequate power to detect small to moderate effect sizes (δ = .35) will be present if the total variance in the outcomes explained by the difference between groups is small (intervention correlation ρ =.05). If the intervention correlation is moderate (ρ = 0.10), the minimum detectable effect size will be moderate (δ = 0.46). With a much smaller sample, Denny and Young (2006) found statistically significant results for changes in knowledge, attitudes, hopelessness, self-efficacy, and sexual intent, with effect sizes, measured by Eta square, ranging from .029-.170. Based on this previous work, we feel confident the study will be sufficiently powered to examine the effects of interest. Statistical Analyses. Frequency counts and percentages will be used to report the characteristics of the sample. Factor analysis will be used to confirm that the items comprising a given variable load together on a single factor. Cronbach's alpha will be used to examine internal consistency of the items comprising the four outcome variables. Descriptive statistics will be used, reporting means and standard deviations for the four outcome variables. Differences by group, relative to demographic variables, such as gender and race, will be examined using chi-square. Data will also be analyzed using analysis of covariance. The pretest score of the outcome measure under consideration will be used as the covariate. Data will again be analyzed using analysis of covariance, but not only using the pretest score as a covariate, but also treatment dose level, and nationality.

A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients

Study ROR-PH-301 is a multicenter, randomized, double-blind, placebo-controlled study. Subjects who meet entry criteria will be randomly allocated 1:1 to receive ralinepag or placebo, in addition to their standard of care or PAH-specific background therapy, as applicable. The primary endpoint is the time (in days) from randomization to the first adjudicated protocol-defined clinical worsening event. All primary endpoint events will be adjudicated by an independent Clinical Event Committee (CEC) in a blinded fashion. Subjects who have a confirmed primary endpoint event adjudicated by the CEC at any time during the study and all subjects on treatment at the conclusion of the study who have completed the Week 28 Visit (after the target number of confirmed events is achieved) will have the option to enroll in an open-label extension (OLE) study. Subjects who do not choose to participate in the OLE study will discontinue study drug and should remain in the study for long-term follow-up of survival status and will receive standard of care PAH treatment, at the discretion of the treating physician.

A Study to Investigate the Efficacy and Safety of Tezepelumab in Adult Participants With Moderate to Very Severe COPD (D5241C00007)

This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel group study to evaluate the safety and efficacy of tezepelumab in adults with moderate to very severe chronic obstructive pulmonary disease (COPD) receiving inhaled maintenance therapy and having had at least 2 moderate, or 1 severe, COPD exacerbations in the 12 months prior to Visit 1. Subjects will receive monthly subcutaneous injection of one of two different doses of tezepelumab, or placebo, with a maximum treatment duration of 76 weeks and a minimum of 52 weeks. The study also includes a off-treatment safety follow-up period of 12 weeks.

RECOVER-ENERGIZE Platform Protocol

Study interventions will be added to the platform protocol as appendices. Each appendix will leverage all elements of the platform protocol, with additional elements described in the individual appendix. Study intervention appendices may be added or removed according to adaptive design and/or emerging evidence. The platform protocol enrolls participants who meet study eligibility criteria. After completing initial screening assessments, eligible participants are assigned to one of the study intervention appendices that are actively enrolling. Participants must meet certain criteria within a specific appendix in order to be included in that appendix. Once assigned to an appendix, eligible participants are randomized to either the study intervention group or a control group.

Evaluation of VX-121/Tezacaftor/Deutivacaftor in Cystic Fibrosis (CF) Participants 1 Through 11 Years of Age

A Study of Guselkumab in Pediatric Participants With Moderately to Severely Active Crohn's Disease