Discovery of Small Molecules Targeting the Frameshifting Element RNA in SARS-CoV-2 Viral Genome.

Targeting structured RNA elements in the SARS-CoV-2 viral genome with small molecules is an attractive strategy for pharmacological control over viral replication. In this work, we report the discovery of small molecules that target the frameshifting element (FSE) in the SARS-CoV-2 RNA genome using high-throughput small-molecule microarray (SMM) screening. A new class of aminoquinazoline ligands for the SARS-CoV-2 FSE are synthesized and characterized using multiple orthogonal biophysical assays and structure-activity relationship (SAR) studies. This work reveals compounds with mid-micromolar binding affinity (KD = 60 ± 6 µM) to the FSE RNA and supports a binding mode distinct from previously reported FSE binders MTDB and merafloxacin. In addition, compounds are active in in vitro dual-luciferase and in-cell dual-fluorescent-reporter frameshifting assays, highlighting the promise of targeting structured elements of RNAs with druglike compounds to alter expression of viral proteins.

An evaluation of the convergent validity of a face-to-face and virtual neuropsychological assessment counter balanced.

The COVID-19 pandemic has highlighted the need for further research evaluating the validity of conducting a battery of neuropsychological assessments virtually compared with face-to-face administration. Previous research has suggested that some neuropsychological assessments yield valid results when administered virtually, however, much of the previous research focused on older adults. To determine the validity of virtually administered neuropsychological tests, 28 healthy participants were assessed using a within-subjects, counter-balanced design. Participants completed a neuropsychological assessment battery covering tests of general intellectual functioning, memory and attention, executive functioning, language and information processing speed, as well as effort. There was no significant difference between face-to-face administration of the neuropsychological battery compared with virtual administration for the majority of the tests used. However, there were significant differences in the Colour Naming Task, with participants making fewer errors on the colour naming task and inhibition/switching task when administered virtually compared with face-to-face administration. There was also a significant age cohort effect in the inhibition/switching task. There was also a trending significant difference in mode of administration for the Verbal Fluency Task. Virtually administered neuropsychological assessments largely provide a valid alternative to face-to-face assessments; however, consideration must be given to test selection as well as the population of participants that are being assessed. Other important considerations must focus on preserving the security and integrity of test materials, as well as administration in a medico-legal setting. Future research should focus on validating assessments with specific patient populations and developing a neuropsychological assessment battery using information technology.

Emergency Department Visits Involving Mental Health Conditions, Suicide-Related Behaviors, and Drug Overdoses Among Adolescents - United States, January 2019-February 2023.

The U.S. adolescent mental and behavioral health crisis is ongoing,* with high pre-COVID-19 pandemic baseline rates† (1) and further increases in poor mental health (2), suicide-related behaviors (3), and drug overdose deaths (4) reported during 2020-2021. CDC examined changes in U.S. emergency department (ED) visits for mental health conditions (MHCs) overall and for nine specific MHCs,§ suicide-related behaviors (including suspected suicide attempts), and drug-involved overdoses (including opioids) among children and adolescents aged 12-17 years (adolescents) during January 2019-February 2023, overall and by sex. Compared with fall 2021, by fall 2022, decreases in weekly ED visits were reported among all adolescents, and females specifically, for MHCs overall, suicide-related behaviors, and drug overdoses; weekly ED visits among males were stable. During this same period, increases in weekly ED visits for opioid-involved overdoses were detected. Mean weekly ED visits in fall 2022 for suicide-related behaviors and MHCs overall were at or lower than the 2019 prepandemic baseline, respectively, and drug overdose visits were higher. Differences by sex were observed; levels among females were at or higher than prepandemic baselines for these conditions. These findings suggest some improvements as of fall 2022 in the trajectory of adolescent mental and behavioral health, as measured by ED visits; however, poor mental and behavioral health remains a substantial public health problem, particularly among adolescent females. Early identification and trauma-informed interventions, coupled with expanded evidence-based, comprehensive prevention efforts, are needed to support adolescents' mental and behavioral health.

SARS-CoV-2 antibody responses associate with sex, age and disease severity in previously uninfected people admitted to hospital with COVID-19: An ISARIC4C prospective study.

The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.

Alcohol and Other Substance Use Before and During the COVID-19 Pandemic Among High School Students - Youth Risk Behavior Survey, United States, 2021.

Adolescence is a critical phase of development and is frequently a period of initiating and engaging in risky behaviors, including alcohol and other substance use. The COVID-19 pandemic and associated stressors might have affected adolescent involvement in these behaviors. To examine substance use patterns and understand how substance use among high school students changed before and during the COVID-19 pandemic, CDC analyzed data from the nationally representative Youth Risk Behavior Survey. This report presents estimated prevalences among high school students of current (i.e., previous 30 days) alcohol use, marijuana use, binge drinking, and prescription opioid misuse and lifetime alcohol, marijuana, synthetic marijuana, inhalants, ecstasy, cocaine, methamphetamine, heroin, and injection drug use and prescription opioid misuse. Trends during 2009-2021 were assessed using logistic regression and joinpoint regression analyses. Changes in substance use from 2019 to 2021 were assessed using prevalence differences and prevalence ratios, stratified by demographic characteristics. Prevalence of substance use measures by sexual identity and current co-occurring substance use were estimated using 2021 data. Substance use prevalence declined during 2009-2021. From 2019 to 2021, the prevalence of current alcohol use, marijuana use, and binge drinking and lifetime use of alcohol, marijuana, and cocaine and prescription opioid misuse decreased; lifetime inhalant use increased. In 2021, substance use varied by sex, race and ethnicity, and sexual identity. Approximately one third of students (29%) reported current use of alcohol or marijuana or prescription opioid misuse; among those reporting current substance use, approximately 34% used two or more substances. Widespread implementation of tailored evidence-based policies, programs, and practices likely to reduce risk factors for adolescent substance use and promote protective factors might further decrease substance use among U.S. high school students and is urgently needed in the context of the changing marketplaces for alcohol beverage products and other drugs (e.g., release of high-alcohol beverage products and increased availability of counterfeit pills containing fentanyl).

Association of Receipt of Opioid Use Disorder-Related Telehealth Services and Medications for Opioid Use Disorder With Fatal Drug Overdoses Among Medicare Beneficiaries Before and During the COVID-19 Pandemic.

Importance: Federal emergency authorities were invoked during the COVID-19 pandemic to expand clinical telehealth for opioid use disorder (OUD). Objective: To examine the association of the receipt of telehealth services and medications for OUD (MOUD) with fatal drug overdoses before and during the pandemic. Design, Setting, and Participants: This cohort study used exploratory longitudinal data from 2 cohorts (prepandemic cohort: September 1, 2018, to February 29, 2020; pandemic cohort: September 1, 2019, to February 28, 2021) of Medicare Fee-for-Service beneficiaries aged 18 years or older initiating an episode of OUD-related care using Medicare Fee-for-Service data from the Centers for Medicare & Medicaid Services and National Death Index data from the Centers for Disease Control and Prevention. Data analysis was performed from September 19 to October 17, 2022. Exposures: Prepandemic vs pandemic cohort demographic, medical, substance use, and psychiatric characteristics. Main Outcomes and Measures: Receipt of OUD-related telehealth services, receipt of MOUD, and fatal drug overdose. Results: The prepandemic cohort comprised 105 162 beneficiaries (58.1% female; 67.6% aged 45-74 years). The pandemic cohort comprised 70 479 beneficiaries (57.1% female; 66.3% aged 45-74 years). The rate of all-cause mortality was higher in the pandemic cohort (99.9 per 1000 beneficiaries; 7041 deaths) than in the prepandemic cohort (76.8 per 1000; 8076 deaths) (P < .001). The rate of fatal drug overdoses was higher in the pandemic cohort (5.1 per 1000 beneficiaries; n = 358) than in the prepandemic cohort (3.7 per 1000; n = 391) (P < .001). The percentage of deaths due to a fatal drug overdose was similar in the prepandemic (4.8%) and pandemic (5.1%) cohorts (P = .49). In multivariable analysis of the pandemic cohort, receipt of OUD-related telehealth was associated with a significantly lower adjusted odds ratio (aOR) for fatal drug overdose (aOR, 0.67; 95% CI, 0.48-0.92) as was receipt of MOUD from opioid treatment programs (aOR, 0.41; 95% CI, 0.25-0.68) and receipt of buprenorphine in office-based settings (aOR, 0.62; 95% CI, 0.43-0.91) compared with those not receiving MOUD; receipt of extended-release naltrexone in office-based settings was not associated with lower odds for fatal drug overdose (aOR, 1.16; 95% CI, 0.41-3.26). Conclusions and Relevance: This cohort study found that, among Medicare beneficiaries initiating OUD-related care during the COVID-19 pandemic, receipt of OUD-related telehealth services was associated with reduced risk for fatal drug overdose, as was receipt of MOUD from opioid treatment programs and receipt of buprenorphine in office-based settings. Strategies to expand provision of MOUD, increase retention in care, and address co-occurring physical and behavioral health conditions are needed.

The efficiency of the EmERGE platform for medically stable people living with HIV in Portugal.

Background: The aim of this study was to calculate the cost-effectiveness of the EmERGE Pathway of Care for medically stable people living with HIV in the Hospital Capuchos, Centro Hospitalar Universitário de Lisboa Central (HC-CHLC). The app enables individuals to receive HIV treatment information and communicate with caregivers. Methods: This before-and-after study collected the use of services data 1 year before implementation and after implementation of EmERGE from November 1, 2016, to October 30, 2019. Departmental unit costs were calculated and linked to mean use of outpatient services per patient-year (MPPY). Annual costs per patient-year were combined with primary (CD4 count; viral load) and secondary outcomes (PAM-13; PROQOL-HIV). Results: Five hundred eighty-six EmERGE participants used HIV outpatient services. Annual outpatient visits decreased by 35% from 3.1 MPPY (95% confidence interval [CI]: 3.0-3.3) to 2.0 (95% CI: 1.9-2.1) as did annual costs per patient-year from €301 (95% CI: €288-€316) to €193 (95% CI: €182-€204). Laboratory tests and costs increased by 2%, and radiology investigations decreased by 40% as did costs. Overall annual cost for HIV outpatient services decreased by 5% from €2093 (95% CI: €2071-€2112) to €1984 (95% CI: €1968-€2001); annual outpatient costs decreased from €12,069 (95% CI: €12,047-€12,088) to €11,960 (95% CI: €11,944-€11,977), with 83% of annual cost because of antiretroviral therapy (ART). Primary and secondary outcome measures did not differ substantially between periods. Conclusions: The EmERGE Pathway produced cost savings after implementation-extended to all people living with HIV additional savings are likely to be produced, which can be used to address other needs. Antiretroviral drugs (ARVs) were the main cost drivers and more expensive in Portugal compared with ARV costs in the other EmERGE sites.

Trends and Characteristics of Buprenorphine-Involved Overdose Deaths Prior to and During the COVID-19 Pandemic.

Importance: Buprenorphine remains underused in treating opioid use disorder, despite its effectiveness. During the onset of the COVID-19 pandemic, the US government implemented prescribing flexibilities to support continued access. Objective: To determine whether buprenorphine-involved overdose deaths changed after implementing these policy changes and highlight characteristics and circumstances of these deaths. Design, Setting, and Participants: This cross-sectional study used data from the State Unintentional Drug Overdose Reporting System (SUDORS) to assess overdose deaths in 46 states and the District of Columbia occurring July 2019 to June 2021. Data were analyzed from March 7, 2022, to June 30, 2022. Main Outcomes and Measures: Buprenorphine-involved and other opioid-involved overdose deaths were examined. Monthly opioid-involved overdose deaths and the percentage involving buprenorphine were computed to assess trends. Proportions and exact 95% CIs of drug coinvolvement, demographics, and circumstances were calculated by group. Results: During July 2019 to June 2021, 32 jurisdictions reported 89 111 total overdose deaths and 74 474 opioid-involved overdose deaths, including 1955 buprenorphine-involved overdose deaths, accounting for 2.2% of all drug overdose deaths and 2.6% of opioid-involved overdose deaths. Median (IQR) age was similar for buprenorphine-involved overdose deaths (41 [34-55] years) and other opioid-involved overdose deaths (40 [31-52] years). A higher proportion of buprenorphine-involved overdose decedents, compared with other opioid-involved decedents, were female (36.1% [95% CI, 34.2%-38.2%] vs 29.1% [95% CI, 28.8%-29.4%]), non-Hispanic White (86.1% [95% CI, 84.6%-87.6%] vs 69.4% [95% CI, 69.1%-69.7%]), and residing in rural areas (20.8% [95% CI, 19.1%-22.5%] vs 11.4% [95% CI, 11.2%-11.7%]). Although monthly opioid-involved overdose deaths increased, the proportion involving buprenorphine fluctuated but did not increase during July 2019 to June 2021. Nearly all (92.7% [95% CI, 91.5%-93.7%]) buprenorphine-involved overdose deaths involved at least 1 other drug; higher proportions involved other prescription medications compared with other opioid-involved overdose deaths (eg, anticonvulsants: 18.6% [95% CI, 17.0%-20.3%] vs 5.4% [95% CI, 5.2%-5.5%]) and a lower proportion involved illicitly manufactured fentanyls (50.2% [95% CI, 48.1%-52.3%] vs 85.3% [95% CI, 85.1%-85.5%]). Buprenorphine decedents were more likely to be receiving mental health treatment than other opioid-involved overdose decedents (31.4% [95% CI, 29.3%-33.5%] vs 13.3% [95% CI, 13.1%-13.6%]). Conclusions and Relevance: The findings of this cross-sectional study suggest that actions to facilitate access to buprenorphine-based treatment for opioid use disorder during the COVID-19 pandemic were not associated with an increased proportion of overdose deaths involving buprenorphine. Efforts are needed to expand more equitable and culturally competent access to and provision of buprenorphine-based treatment.

A digital pathway for genetic testing in UK NHS patients with cancer: BRCA-DIRECT randomised study internal pilot.

BACKGROUND: Germline genetic testing affords multiple opportunities for women with breast cancer, however, current UK NHS models for delivery of germline genetic testing are clinician-intensive and only a minority of breast cancer cases access testing. METHODS: We designed a rapid, digital pathway, supported by a genetics specialist hotline, for delivery of germline testing of BRCA1/BRCA2/PALB2 (BRCA-testing), integrated into routine UK NHS breast cancer care. We piloted the pathway, as part of the larger BRCA-DIRECT study, in 130 unselected patients with breast cancer and gathered preliminary data from a randomised comparison of delivery of pretest information digitally (fully digital pathway) or via telephone consultation with a genetics professional (partially digital pathway). RESULTS: Uptake of genetic testing was 98.4%, with good satisfaction reported for both the fully and partially digital pathways. Similar outcomes were observed in both arms regarding patient knowledge score and anxiety, with <5% of patients contacting the genetics specialist hotline. All progression criteria established for continuation of the study were met. CONCLUSION: Pilot data indicate preliminary demonstration of feasibility and acceptability of a fully digital pathway for BRCA-testing and support proceeding to a full powered study for evaluation of non-inferiority of the fully digital pathway, detailed quantitative assessment of outcomes and operational economic analyses. TRIAL REGISTRATION NUMBER: ISRCTN87845055.

Same storm, different boats: the impact of COVID-19 on Black students and academic staff in UK and US higher education

The permanence of systemic racism in the UK and USA means that Black people are disadvantaged in myriad ways, including within the Academy. While the disproportionate impact of COVID-19, alongside the Black Lives Matter movement, has increased awareness of the challenges faced by Black communities, these issues remain, both in and beyond higher education. Furthermore, there is still a paucity of research individualising the experiences of Black people, who are often homogenised with other ethnic minority groups. This paper explores the impact of COVID-19 on UK and US Black students and academic staff, utilising a critical race theory (CRT) framework. Analysis revealed that Black students and staff experienced COVID-19 against the backdrop of racism as a “pandemic within a pandemic” (Laurencin and Walker, Cell Systems 11:9–10, 2020), including racial (re)traumatisation, loneliness and isolation. Other themes included precarious employment and exploitation. Recommendations are offered for penetrative interventions that can support Black students and staff in the wake of strained race relations neglecting their adverse experiences and a global pandemic.

Receipt of Telehealth Services, Receipt and Retention of Medications for Opioid Use Disorder, and Medically Treated Overdose Among Medicare Beneficiaries Before and During the COVID-19 Pandemic.

Importance: Federal emergency authorities were invoked during the COVID-19 pandemic to expand use of telehealth for new and continued care, including provision of medications for opioid use disorder (MOUD). Objective: To examine receipt of telehealth services, MOUD (methadone, buprenorphine, and extended-release [ER] naltrexone) receipt and retention, and medically treated overdose before and during the COVID-19 pandemic. Design, Setting, and Participants: This exploratory longitudinal cohort study used data from the US Centers for Medicare & Medicaid Services from September 2018 to February 2021. Two cohorts (before COVID-19 pandemic from September 2018 to February 2020 and during COVID-19 pandemic from September 2019 to February 2021) of Medicare fee-for-service beneficiaries 18 years and older with an International Statistical Classification of Diseases, Tenth Revision, Clinical Modification OUD diagnosis. Exposures: Pre-COVID-19 pandemic vs COVID-19 pandemic cohort demographic characteristics, medical and substance use, and psychiatric comorbidities. Main Outcomes and Measures: Receipt and retention of MOUD, receipt of OUD and behavioral health-related telehealth services, and experiencing medically treated overdose. Results: The pre-COVID-19 pandemic cohort comprised 105 240 beneficiaries; of these, 61 152 (58.1%) were female, 71 152 (67.6%) were aged 45 to 74 years, and 82 822 (79.5%) non-Hispanic White. The COVID-19 pandemic cohort comprised 70 538 beneficiaries; of these, 40 257 (57.1%) were female, 46 793 (66.3%) were aged 45 to 74 years, and 55 510 (79.7%) were non-Hispanic White. During the study period, a larger percentage of beneficiaries in the pandemic cohort compared with the prepandemic cohort received OUD-related telehealth services (13 829 [19.6%] vs 593 [0.6%]; P < .001), behavioral health-related telehealth services (28 902 [41.0%] vs 1967 [1.9%]; P < .001), and MOUD (8854 [12.6%] vs 11 360 [10.8%]; P < .001). The percentage experiencing a medically treated overdose during the study period was similar (18.5% [19 491 of 105 240] in the prepandemic cohort vs 18.4% [13 004 of 70 538] in the pandemic cohort; P = .65). Receipt of OUD-related telehealth services in the pandemic cohort was associated with increased odds of MOUD retention (adjusted odds ratio [aOR], 1.27; 95% CI, 1.14-1.41) and lower odds of medically treated overdose (aOR, 0.67; 95% CI, 0.63-0.71). Among beneficiaries in the pandemic cohort, those receiving MOUD from opioid treatment programs only (aOR, 0.54; 95% CI, 0.47-0.63) and those receiving buprenorphine from pharmacies only (aOR, 0.91; 95% CI, 0.84-0.98) had lower odds of medically treated overdose compared with beneficiaries who did not receive MOUD. Conclusions and Relevance: Emergency authorities to expand use of telehealth and provide flexibilities for MOUD provision during the pandemic were used by Medicare beneficiaries initiating an episode of OUD-related care and were associated with improved retention in care and reduced odds of medically treated overdose. Strategies to expand provision of MOUD and increase retention in care are urgently needed.

SARS-CoV-2 Spike Protein Expression In Vitro and Hematologic Effects in Mice Vaccinated With AZD1222 (ChAdOx1 nCoV-19).

Severe COVID-19 can be associated with a prothrombotic state, increasing risk of morbidity and mortality. The SARS-CoV-2 spike glycoprotein is purported to directly promote platelet activation via the S1 subunit and is cleaved from host cells during infection. High plasma concentrations of S1 subunit are associated with disease progression and respiratory failure during severe COVID-19. There is limited evidence on whether COVID-19 vaccine-induced spike protein is similarly cleaved and on the immediate effects of vaccination on host immune responses or hematology parameters. We investigated vaccine-induced S1 subunit cleavage and effects on hematology parameters using AZD1222 (ChAdOx1 nCoV-19), a simian, replication-deficient adenovirus-vectored COVID-19 vaccine. We observed S1 subunit cleavage in vitro following AZD1222 transduction of HEK293x cells. S1 subunit cleavage also occurred in vivo and was detectable in sera 12 hours post intramuscular immunization (1x1010 viral particles) in CD-1 mice. Soluble S1 protein levels decreased within 3 days and were no longer detectable 7-14 days post immunization. Intravenous immunization (1x109 viral particles) produced higher soluble S1 protein levels with similar expression kinetics. Spike protein was undetectable by immunohistochemistry 14 days post intramuscular immunization. Intramuscular immunization resulted in transiently lower platelet (12 hours) and white blood cell (12-24 hours) counts relative to vehicle. Similarly, intravenous immunization resulted in lower platelet (24-72 hours) and white blood cell (12-24 hours) counts, and increased neutrophil (2 hours) counts. The responses observed with either route of immunization represent transient hematologic changes and correspond to expected innate immune responses to adenoviral infection.

The Purpose of Parents: School Personnel Perceptions of the Role of Parents in Secondary Schools

The argument for the importance of a parent's engagement with their child's learning over parental involvement with their child's school has been shown to be valuable in research literature. This study, conducted in England prior to the global COVID-19 pandemic, therefore aimed to understand how school leaders and their staff understand parental engagement, parental involvement, and the role they believe parents should play in the education of their children. Whilst not expecting schools to know and utilize the language used in research literature, the findings suggest a lack of delineation between practices attributed to parental engagement and involvement by Goodall and Montgomery (2014). It also appears that in some schools, a focus remains on encouraging parents to support school policy, rather than empowering parents to support the shaping of school policy and supporting them to engage with their child's education at home. An argument can therefore be made for increasing the availability of research literature in schools and the importance of educating school staff about the value of parents and the role they can play inside and outside formal education.

Vital Signs: Changes in Firearm Homicide and Suicide Rates - United States, 2019-2020.

INTRODUCTION: The majority of homicides (79%) and suicides (53%) in the United States involved a firearm in 2020. High firearm homicide and suicide rates and corresponding inequities by race and ethnicity and poverty level represent important public health concerns. This study examined changes in firearm homicide and firearm suicide rates coinciding with the emergence of the COVID-19 pandemic in 2020. METHODS: National vital statistics and population data were integrated with urbanization and poverty measures at the county level. Population-based firearm homicide and suicide rates were examined by age, sex, race and ethnicity, geographic area, level of urbanization, and level of poverty. RESULTS: From 2019 to 2020, the overall firearm homicide rate increased 34.6%, from 4.6 to 6.1 per 100,000 persons. The largest increases occurred among non-Hispanic Black or African American males aged 10-44 years and non-Hispanic American Indian or Alaska Native (AI/AN) males aged 25-44 years. Rates of firearm homicide were lowest and increased least at the lowest poverty level and were higher and showed larger increases at higher poverty levels. The overall firearm suicide rate remained relatively unchanged from 2019 to 2020 (7.9 to 8.1); however, in some populations, including AI/AN males aged 10-44 years, rates did increase. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: During the COVID-19 pandemic, the firearm homicide rate in the United States reached its highest level since 1994, with substantial increases among several population subgroups. These increases have widened disparities in rates by race and ethnicity and poverty level. Several increases in firearm suicide rates were also observed. Implementation of comprehensive strategies employing proven approaches that address underlying economic, physical, and social conditions contributing to the risks for violence and suicide is urgently needed to reduce these rates and disparities.

Use of Tobacco Products, Alcohol, and Other Substances Among High School Students During the COVID-19 Pandemic - Adolescent Behaviors and Experiences Survey, United States, January-June 2021.

The COVID-19 pandemic has been associated with established risk factors for adolescent substance use, including social isolation, boredom, grief, trauma, and stress. However, little is known about adolescent substance use patterns during the pandemic. CDC analyzed data from the Adolescent Behaviors and Experiences Survey, an online survey of a probability-based, nationally representative sample of public- and private-school students in grades 9-12 (N = 7,705), to examine the prevalence of current use of tobacco products, alcohol, and other substances among U.S. high school students. Prevalence was examined by demographic characteristics and instructional models of the students' schools (in-person, virtual, or hybrid). During January-June 2021, 31.6% of high school students reported current use of any tobacco product, alcohol, or marijuana or current misuse of prescription opioids. Current alcohol use (19.5%), electronic vapor product (EVP) use (15.4%), and marijuana use (12.8%) were more prevalent than prescription opioid misuse (4.3%), current cigarette smoking (3.3%), cigar smoking (2.3%), and smokeless tobacco use (1.9%). Approximately one third of students who used EVPs did so daily, and 22.4% of students who drank alcohol did so ≥6 times per month. Approximately one in three students who ever used alcohol or other drugs reported using these substances more during the pandemic. The prevalence of substance use was typically higher among non-Hispanic American Indian or Alaska Native students, older students, and gay, lesbian, or bisexual students than among students of other racial or ethnic groups, younger students, and heterosexual students. The prevalence of alcohol use also was higher among non-Hispanic White students than those of other racial or ethnic groups. Students only attending school virtually had a lower prevalence of using most of the substances examined than did students attending schools with in-person or hybrid models. These findings characterizing youth substance use during the pandemic can help inform public health interventions and messaging to address these health risks during and after the COVID-19 pandemic.

Concerns among people who use opioids during the COVID-19 pandemic: a natural language processing analysis of social media posts.

BACKGROUND: Timely data from official sources regarding the impact of the COVID-19 pandemic on people who use prescription and illegal opioids is lacking. We conducted a large-scale, natural language processing (NLP) analysis of conversations on opioid-related drug forums to better understand concerns among people who use opioids. METHODS: In this retrospective observational study, we analyzed posts from 14 opioid-related forums on the social network Reddit. We applied NLP to identify frequently mentioned substances and phrases, and grouped the phrases manually based on their contents into three broad key themes: (i) prescription and/or illegal opioid use; (ii) substance use disorder treatment access and care; and (iii) withdrawal. Phrases that were unmappable to any particular theme were discarded. We computed the frequencies of substance and theme mentions, and quantified their volumes over time. We compared changes in post volumes by key themes and substances between pre-COVID-19 (1/1/2019-2/29/2020) and COVID-19 (3/1/2020-11/30/2020) periods. RESULTS: Seventy-seven thousand six hundred fifty-two and 119,168 posts were collected for the pre-COVID-19 and COVID-19 periods, respectively. By theme, posts about treatment and access to care increased by 300%, from 0.631 to 2.526 per 1000 posts between the pre-COVID-19 and COVID-19 periods. Conversations about withdrawal increased by 812% between the same periods (0.026 to 0.235 per 1,000 posts). Posts about drug use did not increase (0.219 to 0.218 per 1,000 posts). By substance, among medications for opioid use disorder, methadone had the largest increase in conversations (20.751 to 56.313 per 1,000 posts; 171.4% increase). Among other medications, posts about diphenhydramine exhibited the largest increase (0.341 to 0.927 per 1,000 posts; 171.8% increase). CONCLUSIONS: Conversations on opioid-related forums among people who use opioids revealed increased concerns about treatment and access to care along with withdrawal following the emergence of COVID-19. Greater attention to social media data may help inform timely responses to the needs of people who use opioids during COVID-19.

Changes in Suicide Rates - United States, 2019 and 2020.

Suicide was among the 10 leading causes of death in the United States in 2020 among persons aged 10-64 years, and the second leading cause of death among children and adolescents aged 10-14 and adults aged 25-34 years (1). During 1999-2020, nearly 840,000 lives were lost to suicide in the United States. During that period, the overall suicide rate peaked in 2018 and declined in 2019 and 2020 (1). Despite the recent decline in the suicide rate, factors such as social isolation, economic decline, family stressors, new or worsening mental health symptoms, and disruptions to work and school associated with the COVID-19 pandemic have raised concerns about suicide risk in the United States. During 2020, a total of 12.2 million U.S. adults reported serious thoughts of suicide and 1.2 million attempted suicide (2). To understand how changes in suicide death rates might have varied among subpopulations, CDC analyzed counts and age-adjusted suicide rates during 2019 and 2020 by demographic characteristics, mechanism of injury, county urbanization level, and state. From 2019 to 2020, the suicide rate declined by 3% overall, including 8% among females and 2% among males. Significant declines occurred in seven states but remained stable in the other states and the District of Columbia. Despite two consecutive years of declines, the overall suicide rate remains 30% higher compared with that in 2000 (1). A comprehensive approach to suicide prevention that uses data driven decision-making and implements prevention strategies with the best available evidence, especially among disproportionately affected populations (3), is critical to realizing further declines in suicide and reaching the national goal of reducing the suicide rate by 20% by 2025 (4).