Roads Diverged: Developmental Trajectories of Irritability From Toddlerhood Through Adolescence.

OBJECTIVE: Irritability is a dimensional trait that manifests from early life and is a robust transdiagnostic risk factor for psychopathology and impairment. A large, national dataset was leveraged to identify and broadly characterize trajectories from toddlerhood through adolescence, which is crucial for timely, targeted interventions. METHOD: Data on irritability and a broad array of potential factors affecting irritability development from 4,462 children assessed longitudinally at ages 3, 5, 9, and 15 were included. Latent class growth models identified groups of children based on their nonlinear irritability trajectories from toddlerhood to adolescence. LASSO regression then identified key characteristics differentiating trajectory groups. RESULTS: Five distinct irritability trajectories were identified, two of which were stable, maintaining medium or high irritability from age 3 to 15. Three trajectories showed undulating change over development, with an inflection point at the transition to adolescence (age 9): Most children had consistently low irritability. Two smaller groups started with high irritability at age 3 but diverged, sharply decreasing or increasing until a turning point at age 9. Developmental patterning of harsh/neglectful parenting and child internalizing symptoms most strongly differentiated trajectory groups. Sociodemographic characteristics, attachment style, neighborhood support, cognitive functioning, and genetic variation also differentiated trajectories. CONCLUSION: The results demonstrated the importance of the transition to adolescence as a critical inflection point for youths with fluctuating irritability trajectories. Identifying these patterns and multiple malleable factors associated with stably high or rising trajectories is an important step toward targeted interventions for the most vulnerable subgroups. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as living with a disability. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group.

A multiple technology-based physical activity intervention for Latina adolescents in the USA: randomized controlled trial study protocol for Chicas Fuertes.

BACKGROUND: Latina adolescents in the USA report some of the lowest rates of physical activity of any demographic subgroup; this is paralleled by a markedly higher lifetime risk of obesity, type 2 diabetes, and other conditions related to inactivity. Despite this, to date, no fully powered clinical trials have tested physical activity interventions specifically for this population. High use of mobile technologies (including text messages, smartphone apps, and social media) suggests this could be an appropriate intervention channel, while also having potential for broad reach. This paper describes the protocol for Chicas Fuertes, a fully powered randomized trial of a mobile technology-based physical activity intervention for Latina adolescents. METHODS: We plan to recruit 200 Latina teens (age 13-18) in San Diego, CA, currently engaging in ≤ 150 min/week of moderate-to-vigorous physical activity (MVPA) to be assigned 1:1 to the intervention or control groups. Those randomly assigned to the intervention group receive a one-on-one goal setting session followed by 6 months of mobile technology-based intervention, including a personalized website, Fitbit activity tracker and app, individually tailored text messages based on Fitbit data, and daily intervention content on Instagram. Those randomized to the control group receive only a Fitbit activity tracker. The main outcome is change in weekly minutes of MVPA from baseline to 6 months, measured both objectively (ActiGraph accelerometers and Fitbit Inspire HR) and subjectively (7-Day Physical Activity Recall Interview). Additional outcomes are maintenance of activity change at 12 months and changes in psychosocial constructs, including social support and self-efficacy, engagement with mobile technology channels, and costs of intervention delivery. We are also examining the potential mediators and moderators of the intervention. The efficacy of the intervention is analyzed using a mixed effects regression model, adjusting for any potential confounders not balanced by randomization. All analyses of accelerometer measured MVPA are also adjusted for wear time. DISCUSSION: The Chicas Fuertes trial uses widely available mobile technologies to target critical health behavior, physical activity, in Latina teens, a population with a high lifetime risk of lifestyle-related diseases. The results will speak to the efficacy and acceptability of the intervention, which has the potential for broad dissemination. TRIAL REGISTRATION: ClinicalTrials.gov NCT04190225 . Registered on November 20, 2019.

Appraisal of the Real-World Effectiveness of Biologic Therapies in Aspirin-Exacerbated Respiratory Disease.

BACKGROUND: There are no head-to-head studies for patients with aspirin-exacerbated respiratory disease (AERD) comparing any of the 5 Food and Drug Administration-approved respiratory biologic therapies. OBJECTIVE: Explore outcomes in subjects with AERD using biologic therapies in a real-world clinic setting. METHODS: A retrospective pilot study was conducted for subjects with AERD who had been prescribed omalizumab (anti-IgE), mepolizumab (anti-IL-5), reslizumab (anti-IL-5), benralizumab (anti-IL-5 receptor alpha [anti-IL-5Rα]), or dupilumab (anti-IL-4 receptor alpha [anti-IL-4Rα]). Clinical outcomes pre- versus postinitiation of biologic therapy were explored including symptoms, 22-item sino-nasal outcome test scores, systemic corticosteroid and antibiotic prescriptions, and emergency room visits related to AERD. RESULTS: Of the 74 subjects, 58.1% (n = 43) had used 1 biologic, though many (41.9%, n = 31) trialed more than 1 biologic. Of the 50 subjects who had used anti-IL-4Rα therapy, 98% (49 of 50) still had this therapy prescribed at study completion compared with 48.6% (17 of 35) and 26.9% (7 of 26) of those who used anti-IgE and anti-IL-5 and anti-IL-5 receptor alpha (anti-IL-5/IL-5Rα) therapy, respectively. Among those on anti-IL-4Rα therapy, there was a significant reduction in median total 22-item sino-nasal outcome test scores (51 to 19, P = .0002), corticosteroid bursts (2 to 0, P < .0001), and median number of antibiotic courses for respiratory disease (1 to 0, P = .0469) prebiologic versus postbiologic initiation. No statistically significant difference in those outcomes was observed for individuals on anti-IgE or anti-IL-5/IL-5Rα therapy. CONCLUSIONS: Anti-IL-4Rα therapy led to significantly higher rates of clinical improvement in AERD when compared with anti-IL-5/IL-5Rα and anti-IgE biologic therapies. Prospective studies would help clarify best practices for the use of biologic therapies in AERD.