Feasibility of recruiting adolescents into a prospective cohort study of the effects of social isolation during COVID-19

Abstract Background Social connection and loneliness in adolescence are increasingly understood as critical influences on adult mental and physical health. The unique impact of the social isolation imposed by the COVID-19 lockdown on emerging adults is therefore expected to be especially profound. We sought to investigate the feasibility of using ecological momentary assessment (EMA) and wearable accelerometers to characterize the effects of social isolation and/or loneliness experienced by adolescents during the COVID-19 pandemic. Methods We recruited 19 participants aged 13–18 from an Adolescent Medicine practice in Atlanta, GA. Participants completed surveys at baseline and throughout a 2-week study period using EMA regarding their degree of social isolation, loneliness, family functioning, school climate, social media use, and COVID-19 experiences surrounding their physical, mental, and social domains. Six participants agreed to wear an activity tracker and heart rate measurement device for 14 days to monitor their emotional state and physical health. Participant feedback was collected via open-ended exit interviews. Feasibility of recruitment/retention, adherence, and outcome measures were investigated. Implementation was also assessed by evaluating the barriers and facilitators to study delivery. Associations between the social isolation and loneliness variables and all other variables were performed with univariate linear regression analysis with significance set at p  30% and a retention rate of > 80%. Results Progression criteria were met for recruitment (76%) of participants, but not retention (38%). Adherence to EMA survey completion was highly variable with only 54% completing ≥ 1 survey a day, and accelerometry use was not feasible. Social isolation was significantly correlated with lower school climate, higher COVID-19 experiences, higher depression scores, and lower sleep quality. Loneliness also showed a significant correlation with all these factors except COVID-19 experiences. Conclusions EMA and wearable accelerometer use was not feasible in this longitudinal study of adolescents during the COVID-19 pandemic. Future research should further investigate barriers to conducting long-term research with adolescents and the potential effects of the pandemic on subject recruitment and retention

Clinical covariates that improve the description of high dose methotrexate pharmacokinetics in a diverse population to inform MTXPK.org

Abstract The MTXPK.org webtool was launched in December 2019 and was developed to facilitate model‐informed supportive care and optimal use of glucarpidase following the administration of high‐dose methotrexate (HDMTX). One limitation identified during the original development of the MTXPK.org tool was the perceived generalizability because the modeled population comprised solely of Nordic pediatric patients receiving 24‐h infusions for the treatment of acute lymphoblastic leukemia. The goal of our study is to describe the pharmacokinetics of HDMTX from a diverse patient population (e.g., races, ethnicity, indications for methotrexate, and variable infusion durations) and identify meaningful factors that account for methotrexate variability and improve the model's performance. To do this, retrospectively analyzed pharmacokinetic and toxicity data from pediatric and adolescent young adult patients who were receiving HDMTX (>0.5 g/m2) for the treatment of a cancer diagnosis from three pediatric medical centers. We performed population pharmacokinetic modeling referencing the original MTXPK.org NONMEM model (includes body surface area and serum creatinine as covariates) on 1668 patients, 7506 administrations of HDMTX, and 30,250 concentrations. Our results support the parameterizations of short infusion duration (<8 h) and the presence of Down syndrome on methotrexate clearance, the parameterization of severe hypoalbuminemia (<2.5 g/dL) on the intercompartmental clearance (Q2 and Q3), and the parameterization of pleural effusion on the volume of distribution (V1 and V2). These novel parameterizations will increase the generalizability of the MTXPK.org model once they are added to the webtool