PLOS ONE Medicine&Health

Assessment of change and persistence of youth psychosocial status reported by youth and their guardians during the COVID-19 pandemic: A MyHEARTSMAP study

by Melissa L. Woodward, Morgan W. Wolsey, Sophia Shalchy-Tabrizi, Jeffrey N. Bone, Tyler Black, Quynh Doan

Background

The pediatric mental health crisis pre-dated the COVID 19 pandemic with rates of mental health visits to pediatric emergency departments steadily increasing for the last decade. The COVID-19 pandemic has profoundly impacted children and adolescents and understanding the trajectory of their psychosocial status is important for appropriate resource allocation and policy planning.

Methods

MyHEARTSMAP is a digital self-assessment mental health evaluation that examines four major psychosocial domains: psychiatry, social, function, and youth health. Children and adolescents throughout British Columbia, and their guardians, completed the baseline assessment between August 2020 and July 2021 (51.8% completed by guardian only, 40.2% youth and guardians, 7.9% youth only). Both children and their guardians repeated the MyHEARTSMAP evaluation three-months after their baseline. Patient demographics and psychosocial concerns were statistically described and compared between baseline and follow-up. A logistic regression model assessed the influence of baseline scores and demographic factors on follow-up severity.

Results

241 of 424 participants (56.8%) completed both the baseline and three-month follow-up. The majority of participants reported no change overtime across the psychosocial domains. Both improvement and decline occurred in each domain, with a greater proportion of psychosocial states improving rather than worsening, for all domains. Higher severity of psychosocial concerns reported at baseline indicated a greater likelihood of psychosocial concerns at 3-month follow-up for psychiatric, social and function concerns. Demographic, pandemic, and support service variables were not associated with psychosocial trajectories.

Conclusions

The severity of youth mental health concerns in British Columbia remained consistent through three-month follow up, despite the changing nature of the COVID-19 pandemic during this period. Greater persistence of psychosocial concerns with increased severity highlights the need for early intervention to prevent worsening mental health. Community support is needed for youth experiencing mental health concerns to address mild psychosocial concerns before presentation at the emergency department.

PLOS ONE Medicine&Health

The histone deacetylase inhibitor CT-101 flips the switch to fetal hemoglobin expression in sickle cell disease mice

by Mayuko Takezaki, Biaoru Li, Hongyan Xu, Nikhil Patel, Rudolf Lucas, Ryan E. Cerbone, Sivanagireddy Koti, Clifford L. Hendrick, Louis H. Junker, Betty S. Pace

The most common hemoglobin disorder worldwide is sickle cell disease (SCD) caused by a point mutation in the adult β-globin gene. As a result, hemoglobin S production occurs leading to clinical symptoms including vaso-occlusive pain, organ damage, and a shortened lifespan. Hydroxyurea is the only FDA-approved fetal hemoglobin (HbF) inducer in the United States that ameliorates the clinical severity of SCD. Due to challenges with hydroxyurea, our study aimed to address the unmet need for the development of non-chemotherapeutic HbF inducers. We investigated the ability of CT-101, a Class 1 histone deacetylase inhibitor, to flip the γ-globin to β-globin switch in a humanized SCD mouse model. Pharmacokinetic parameters were assessed in CD-1 and Townes SCD mice after a single intraperitoneal drug dose. Similar drug uptake and half-life were observed in both animals. Subsequent studies in β-YAC mice expressing human γ-globin and β-globin genes established the optimal dose of CT-101 that induces HbF without peripheral blood toxicity. Subsequent confirmatory studies were conducted in the SCD mouse treated with intraperitoneal CT-101, demonstrating increases in F-cells, HbF, and γ-globin gene mRNA levels. Hydroxyurea combined with CT-101 significantly decreased spleen size and hemorrhagic infarcts and improved splenic extramedullary hematopoiesis. Our novel agent, CT-101, flipped the switch by activating γ-globin gene transcription and HbF protein synthesis in the preclinical SCD mouse model without significant toxicity in the peripheral blood. These findings support the development of an oral CT-101 formulation for clinical testing in SCD.