Patterns and correlates of mental healthcare utilization during the COVID-19 pandemic among individuals with pre-existing mental disorder.

How did mental healthcare utilization change during the COVID-19 pandemic period among individuals with pre-existing mental disorder? Understanding utilization patterns of these at-risk individuals and identifying those most likely to exhibit increased utilization could improve patient stratification and efficient delivery of mental health services. This study leveraged large-scale electronic health record (EHR) data to describe mental healthcare utilization patterns among individuals with pre-existing mental disorder before and during the COVID-19 pandemic and identify correlates of high mental healthcare utilization. Using EHR data from a large healthcare system in Massachusetts, we identified three "pre-existing mental disorder" groups (PMD) based on having a documented mental disorder diagnosis within the 6 months prior to the March 2020 lockdown, related to: (1) stress-related disorders (e.g., depression, anxiety) (N = 115,849), (2) serious mental illness (e.g., schizophrenia, bipolar disorders) (N = 11,530), or (3) compulsive behavior disorders (e.g., eating disorder, OCD) (N = 5,893). We also identified a "historical comparison" group (HC) for each PMD (N = 113,604, 11,758, and 5,387, respectively) from the previous year (2019). We assessed the monthly number of mental healthcare visits from March 13 to December 31 for PMDs in 2020 and HCs in 2019. Phenome-wide association analyses (PheWAS) were used to identify clinical correlates of high mental healthcare utilization. We found the overall number of mental healthcare visits per patient during the pandemic period in 2020 was 10-12% higher than in 2019. The majority of increased visits was driven by a subset of high mental healthcare utilizers (top decile). PheWAS results indicated that correlates of high utilization (prior mental disorders, chronic pain, insomnia, viral hepatitis C, etc.) were largely similar before and during the pandemic, though several conditions (e.g., back pain) were associated with high utilization only during the pandemic. Limitations included that we were not able to examine other risk factors previously shown to influence mental health during the pandemic (e.g., social support, discrimination) due to lack of social determinants of health information in EHR data. Mental healthcare utilization among patients with pre-existing mental disorder increased overall during the pandemic, likely due to expanded access to telemedicine. Given that clinical correlates of high mental healthcare utilization in a major hospital system were largely similar before and during the COVID-19 pandemic, resource stratification based on known risk factor profiles may aid hospitals in responding to heightened mental healthcare needs during a pandemic.

Post-traumatic growth in PhD students during the COVID-19 pandemic.

Throughout the COVID-19 pandemic, graduate students have faced increased risk of mental health challenges. Research suggests that experiencing adversity may induce positive psychological changes, called post-traumatic growth (PTG). These changes can include improved relationships with others, perceptions of oneself, and enjoyment of life. Few existing studies have explored this phenomenon among graduate students. This secondary data analysis of a survey conducted in November 2020 among graduate students at a private R1 University in the northeast United States examined graduate students' levels and correlates of PTG during the COVID-19 pandemic. Students had a low level of PTG, with a mean score of 10.31 out of 50. Linear regression models showed significant positive relationships between anxiety and PTG and between a measure of self-reported impact of the pandemic and PTG. Non-White minorities also had significantly greater PTG than White participants. Experiencing more negative impact due to the pandemic and ruminating about the pandemic were correlated with greater PTG. These findings advance research on the patterns of PTG during the COVID-19 pandemic and can inform future studies of graduate students' coping mechanisms and support efforts to promote pandemic recovery and resilience.

Alcohol use among adolescents in India: a systematic review.

Background: Alcohol use is typically established during adolescence and initiation of use at a young age poses risks for short- and long-term health and social outcomes. However, there is limited understanding of the onset, progression and impact of alcohol use among adolescents in India. The aim of this review is to synthesise the evidence about prevalence, patterns and correlates of alcohol use and alcohol use disorders in adolescents from India. Methods: Systematic review was conducted using relevant online databases, grey literature and unpublished data/outcomes from subject experts. Inclusion and exclusion criteria were developed and applied to screening rounds. Titles and abstracts were screened by two independent reviewers for eligibility, and then full texts were assessed for inclusion. Narrative synthesis of the eligible studies was conducted. Results: Fifty-five peer-reviewed papers and one report were eligible for inclusion in this review. Prevalence of ever or lifetime alcohol consumption ranged from 3.9% to 69.8%; and prevalence of alcohol consumption at least once in the past year ranged from 10.6% to 32.9%. The mean age for initiation of drinking ranged from 14.4 to 18.3 years. Some correlates associated with alcohol consumption included being male, older age, academic difficulties, parental use of alcohol or tobacco, non-contact sexual abuse and perpetuation of violence. Conclusion: The evidence base for alcohol use among adolescents in India needs a deeper exploration. Despite gaps in the evidence base, this synthesis provides a reasonable understanding of alcohol use among adolescents in India and can provide direction to policymakers.

Isolation of Exosome-Enriched Extracellular Vesicles Carrying Granulocyte-Macrophage Colony-Stimulating Factor from Embryonic Stem Cells.

Embryonic stem cells (ESCs) are pluripotent stem cells capable of self-renewal and differentiation into all types of embryonic cells. Like many other cell types, ESCs release small membrane vesicles, such as exosomes, to the extracellular environment. Exosomes serve as essential mediators of intercellular communication and play a basic role in many (patho)physiological processes. Granulocyte-macrophage colony-stimulating factor (GM-CSF) functions as a cytokine to modulate the immune response. The presence of GM-CSF in exosomes has the potential to boost their immune-regulatory function. Here, GM-CSF was stably overexpressed in the murine ESC cell line ES-D3. A protocol was developed to isolate high-quality exosome-enriched extracellular vesicles (EVs) from ES-D3 cells overexpressing GM-CSF. Isolated exosome-enriched EVs were characterized by a variety of experimental approaches. Importantly, significant amounts of GM-CSF were found to be present in exosome-enriched EVs. Overall, GM-CSF-bearing exosome-enriched EVs from ESCs might function as cell-free vesicles to exert their immune-regulatory activities.

Exosomes from GM-CSF expressing embryonic stem cells are an effective prophylactic vaccine for cancer prevention.

The antigenic similarity between embryos and tumors has raised the idea of using embryonic material as a preventative vaccine against neoplastic disease. Indeed, we have previously reported that a vaccine comprises allogeneic murine embryonic stem cells (ESCs) and murine fibroblasts expressing GM-CSF (to amplify immune responses) successfully blocks the outgrowth of an implantable cancer (Lewis lung carcinoma; LLC) and lung tumors generated in mice using a combination of a mutagen followed by chronic pulmonary inflammation. However, such a vaccine is obviously impractical for application to humans. The use of fibroblasts to generate GM-CSF is needlessly complicated, and intact whole ESCs carry the hazard of generating embryomas/teratomas. Here, we report the successful application of an alternative prophylactic vaccine comprises exosomes derived from murine ESCs engineered to produce GM-CSF. Vaccination of mice with these exosomes significantly slowed or blocked the outgrowth of implanted LLC while control exosomes lacking GM-CSF were ineffective. Examination of tumor-infiltrating immune cells from mice vaccinated with the GM-CSF-expressing exosomes showed robust tumor-reactive CD8+ T effector responses, Th1 cytokine responses, and higher CD8+ T effector/CD4+CD25+Foxp3+ T regulatory cell ratio in the tumors. We conclude that a similar vaccine derived from GM-CSF- expressing human ESCs can be employed as a preventative vaccine for humans with an increased risk of developing cancer.