Exclusion of Reproductive-aged Women in COVID-19 Vaccination and Clinical Trials.

INTRODUCTION: We analyzed the exclusion of pregnant and breastfeeding individuals and those capable of pregnancy in COVID-19 vaccine and clinical treatment trials. METHODS: Inclusion and exclusion criteria were extracted from all listed COVID-19 vaccine and treatment clinical trials from May 1, 2020, to October 31, 2020, using the U.S. National Library of Medicine database. We report rates of rates of exclusion for pregnant and lactating individuals and requirements for contraception for pregnancy-capable participants in COVID-19 vaccine and treatment clinical trials. The analysis included the association between clinical trial exclusion and vaccine and treatment type, study location, sponsor, and phase. RESULTS: Pregnant and lactating individuals were explicitly excluded from most COVID-19 vaccine and treatment clinical trials. Of the 90 vaccine trials, 88 (97.8%) excluded pregnant individuals, 73 (81.1%) excluded lactating individuals, and 56 (62.2%) required contraception use. Of the 495 treatment trials, 350 (70.7%) excluded pregnant individuals, 269 (54.3%) excluded lactating individuals, and 91 (18.4%) required contraception use. Although vaccine type was not associated with pregnancy exclusion, it was associated with lactation exclusion (p = .01) and contraception requirement (p < .001). Treatment type was associated with pregnancy exclusion, lactation exclusion, and contraception requirement (all p < .001). CONCLUSIONS: COVID-19 vaccination and treatment clinical trials mirrored historical trends restricting participation owing to pregnancy, lactation, and contraception nonuse, despite known safety profiles. People of childbearing potential should be considered for and afforded the same opportunity as males to make informed decisions on study participation, particularly in the setting of a global pandemic.

The Impact of Role Models, Mentors, and Heroes on Academic and Social Outcomes in Adolescents.

Background Identity formation is a dynamic process and key developmental task that begins in adolescence. During this time, children look to adults as role models and mentors. These adults can have a significant impact on adolescents' decisions of appropriate or inappropriate behaviors, potentially causing a positive or negative change. Little research has been performed to identify these role models and understand how they affect the development of physical and mental health of children.  Objective The goal of this study is to see if there is a relationship between identified role models, mentors, and/or heroes and adolescents' interest in education, participation in risky behavior, confidence level, happiness, safety, violence-related behaviors, and physical activity.  Methods In this study, 198 children aged 11-18 years were identified on the scheduling platforms at various Hershey Medical Center sites to take a 10-minute survey via RedCap. The survey identified their role model, mentor, and/or hero and followed up with outcome questions from validated tools. Results The results show that 140 participants (70.7%) identified having a role model compared to 88 (44.4%) having mentors and 61 (30.8%) having heroes, and family members were the most identified figures for each category. There were significant differences between identified categories of role models, mentors, and heroes, and interest in education, happiness, risky behavior, and safety, while no significant differences were found for violence-related behavior, physical activity, and confidence level. Adolescents with family heroes had safer behavior (2.39 ± 0.70) than those with celebrity heroes (3.16 ±1.86, p=0.0277), and those with peer heroes (11.3 ± 2.31) had more risky behavior than those with celebrity heroes (9.16 ± 1.98, p=0.0347). However, children with adult peer heroes had a higher interest in education (2.00 ± 0) compared to those with celebrities (3.79 ± 1.03, p=0.0246) or public figures (3.78 ± 1.09, p=0.0333) as their heroes. Additionally, those with family (3.48 ± 1.05) or adult peers (3.32 ± 1.38) as their mentors had a higher interest in education compared to those with same-age peer mentors (5.80 ± 1.30, p=<0.0001). Adolescents with family mentors also had higher happiness scores (3.25 ± 0.33) than those with same-age peer mentors (2.59 ± 1.47, p=0.0358) and also engaged in safer behavior (2.52 ± 0.80) compared to all other categories (3.03 ±1.59, 0.0462).  Conclusion These results point to the idea that who adolescents choose to look up to has effects on various aspects of their life that could affect both their physical and mental health status, with family members having the most impact. Further research could explore differences between which family members are chosen as role models, mentors, and heroes and what effect they might have on adolescent development.

First-in-human phase 1 clinical study of the IL-15 superagonist complex ALT-803 to treat relapse after transplantation.

New therapies for patients with hematologic malignancies who relapse after allogeneic hematopoietic cell transplantation (allo-HCT) are needed. Interleukin 15 (IL-15) is a cytokine that stimulates CD8+ T-cell and natural killer (NK) cell antitumor responses, and we hypothesized this cytokine may augment antileukemia/antilymphoma immunity in vivo. To test this, we performed a first-in-human multicenter phase 1 trial of the IL-15 superagonist complex ALT-803 in patients who relapsed >60 days after allo-HCT. ALT-803 was administered to 33 patients via the IV or subcutaneous (SQ) routes once weekly for 4 doses (dose levels of 1, 3, 6, and 10 µg/kg). ALT-803 was well tolerated, and no dose-limiting toxicities or treatment-emergent graft-versus-host disease requiring systemic therapy was observed in this clinical setting. Adverse events following IV administration included constitutional symptoms temporally related to increased serum IL-6 and interferon-γ. To mitigate these effects, the SQ route was tested. SQ delivery resulted in self-limited injection site rashes infiltrated with lymphocytes without acute constitutional symptoms. Pharmacokinetic analysis revealed prolonged (>96 hour) serum concentrations following SQ, but not IV, injection. ALT-803 stimulated the activation, proliferation, and expansion of NK cells and CD8+ T cells without increasing regulatory T cells. Responses were observed in 19% of evaluable patients, including 1 complete remission lasting 7 months. Thus, ALT-803 is a safe, well-tolerated agent that significantly increased NK and CD8+ T cell numbers and function. This immunostimulatory IL-15 superagonist warrants further investigation to augment antitumor immunity alone and combined with other immunotherapies. This trial was registered at www.clinicaltrials.gov as #NCT01885897.