Effect of Hepatic Impairment on Trofinetide Exposures Using an In Silico Physiologically Based Pharmacokinetic Model.

INTRODUCTION: Trofinetide is the first drug to be approved for the treatment of Rett syndrome. Hepatic impairment is not expected to affect the pharmacokinetic (PK) profile of trofinetide because of predominant renal excretion. This study was conducted to help understand the potential impact of any hepatic impairment on trofinetide PK. METHODS: This study used physiologically based PK modeling to estimate trofinetide exposure (maximum drug concentration and area under the concentration-time curve from time zero to infinity) in virtual patients with mild, moderate, and severe hepatic impairment (per Child-Pugh classification) compared with virtual healthy subjects following a 12 g oral trofinetide dose. RESULTS: In individual deterministic simulations for matched individuals and stochastic simulations at the population level (100 virtual individuals simulated per population), as anticipated, predicted plasma exposures were similar for healthy subjects and for patients with mild, moderate, and severe hepatic impairment. However, predicted blood concentration exposures slightly increased with increasing severity of hepatic impairment because of change in hematocrit levels. CONCLUSION: This study indicates that hepatic impairment is not expected to have a clinically relevant effect on exposure to trofinetide.

Trofinetide is the first approved treatment for Rett syndrome, a rare genetic condition that affects brain development. When a person takes trofinetide, most is removed from the body via the urine in its unchanged form (no chemical alteration). Regulatory requirements mean researchers must confirm the safety of any pharmaceutical drug and evaluate whether changes in liver function lead to harmful levels of drug exposure. Researchers used a computer model to predict how much trofinetide would be present in the blood and plasma (the liquid portion of blood) over time in virtual healthy subjects and virtual patients with varying degrees of liver disease (mild, moderate, or severe). Computer simulations showed that predicted trofinetide levels in plasma were similar in virtual healthy subjects and each virtual patient group with liver disease. Predicted levels of trofinetide in blood were slightly elevated with increasing severity of liver disease. This is because people with liver disease have fewer red blood cells, so the cell portion of blood becomes smaller relative to the liquid portion (plasma), which leads to higher trofinetide concentrations in whole blood (trofinetide minimally enters the red blood cell). The small increase in trofinetide levels in blood and the absence of any change in trofinetide levels in plasma means that people with Rett syndrome and liver disease are unlikely to be exposed to harmful levels of trofinetide after a 12 g oral dose.

Estimating hepatitis C prevalence in the United States, 2017-2020.

BACKGROUND AND AIMS: The National Health and Nutrition Examination Survey (NHANES) underestimates the true prevalence of HCV infection. By accounting for populations inadequately represented in NHANES, we created 2 models to estimate the national hepatitis C prevalence among US adults during 2017-2020. APPROACH AND RESULTS: The first approach (NHANES+) replicated previous methodology by supplementing hepatitis C prevalence estimates among the US noninstitutionalized civilian population with a literature review and meta-analysis of hepatitis C prevalence among populations not included in the NHANES sampling frame. In the second approach (persons who injected drugs [PWID] adjustment), we developed a model to account for the underrepresentation of PWID in NHANES by incorporating the estimated number of adult PWID in the United States and applying PWID-specific hepatitis C prevalence estimates. Using the NHANES+ model, we estimated HCV RNA prevalence of 1.0% (95% CI: 0.5%-1.4%) among US adults in 2017-2020, corresponding to 2,463,700 (95% CI: 1,321,700-3,629,400) current HCV infections. Using the PWID adjustment model, we estimated HCV RNA prevalence of 1.6% (95% CI: 0.9%-2.2%), corresponding to 4,043,200 (95% CI: 2,401,800-5,607,100) current HCV infections. CONCLUSIONS: Despite years of an effective cure, the estimated prevalence of hepatitis C in 2017-2020 remains unchanged from 2013 to 2016 when using a comparable methodology. When accounting for increased injection drug use, the estimated prevalence of hepatitis C is substantially higher than previously reported. National action is urgently needed to expand testing, increase access to treatment, and improve surveillance, especially among medically underserved populations, to support hepatitis C elimination goals.

Estimated Number of Injection-Involved Overdose Deaths in US States From 2000 to 2020: Secondary Analysis of Surveillance Data.

BACKGROUND: In the United States, both drug overdose mortality and injection-involved drug overdose mortality have increased nationally over the past 25 years. Despite documented geographic differences in overdose mortality and substances implicated in overdose mortality trends, injection-involved overdose mortality has not been summarized at a subnational level. OBJECTIVE: We aimed to estimate the annual number of injection-involved overdose deaths in each US state from 2000 to 2020. METHODS: We conducted a stratified analysis that used data from drug treatment admissions (Treatment Episodes Data Set-Admissions; TEDS-A) and the National Vital Statistics System (NVSS) to estimate state-specific percentages of reported drug overdose deaths that were injection-involved from 2000 to 2020. TEDS-A collects data on the route of administration and the type of substance used upon treatment admission. We used these data to calculate the percentage of reported injections for each drug type by demographic group (race or ethnicity, sex, and age group), year, and state. Additionally, using NVSS mortality data, the annual number of overdose deaths involving selected drug types was identified by the following specific multiple-cause-of-death codes: heroin or synthetic opioids other than methadone (T40.1, T40.4), natural or semisynthetic opioids and methadone (T40.2, T40.3), cocaine (T40.5), psychostimulants with abuse potential (T43.6), sedatives (T42.3, T42.4), and others (T36-T59.0). We used the probabilities of injection with the annual number of overdose deaths, by year, primary substance, and demographic groups to estimate the number of overdose deaths that were injection-involved. RESULTS: In 2020, there were 91,071 overdose deaths among adults recorded in the United States, and 93.1% (84,753/91,071) occurred in the 46 jurisdictions that reported data to TEDS-A. Slightly less than half (38,253/84,753, 45.1%; 95% CI 41.1%-49.8%) of those overdose deaths were estimated to be injection-involved, translating to 38,253 (95% CI 34,839-42,181) injection-involved overdose deaths in 2020. There was large variation among states in the estimated injection-involved overdose death rate (median 14.72, range 5.45-31.77 per 100,000 people). The national injection-involved overdose death rate increased by 323% (95% CI 255%-391%) from 2010 (3.78, 95% CI 3.33-4.31) to 2020 (15.97, 95% CI 14.55-17.61). States in which the estimated injection-involved overdose death rate increased faster than the national average were disproportionately concentrated in the Northeast region. CONCLUSIONS: Although overdose mortality and injection-involved overdose mortality have increased dramatically across the country, these trends have been more pronounced in some regions. A better understanding of state-level trends in injection-involved mortality can inform the prioritization of public health strategies that aim to reduce overdose mortality and prevent downstream consequences of injection drug use.

A Physiologically Based Pharmacokinetic Modeling Approach to Assess the Potential for Drug Interactions Between Trofinetide and CYP3A4-Metabolized Drugs.

PURPOSE: Trofinetide is the first drug to be approved by the US Food and Drug Administration for use in the treatment of patients with Rett syndrome, a multisystem disorder requiring multimodal therapies. Cytochrome P450 (CYP) 3A4 metabolizes >50% of therapeutic drugs and is the CYP isozyme most commonly expressed in the liver and intestines. In vitro studies suggest the concentration of trofinetide producing 50% inhibition (IC50) of CYP3A4 is >15 mmol/L; that concentration was much greater than the target clinical concentration associated with the maximal intended therapeutic dose (12 g). Thus, trofinetide has a low potential for drug-drug interactions in the liver. However, there is potential for drug-drug interactions in the intestines given the oral route of administration and expected relatively high concentration in the gastrointestinal tract after dose administration. METHODS: Using a validated physiologically based pharmacokinetic (PBPK) model, deterministic and stochastic simulations were used for assessing the PK properties related to exposure and bioavailability of midazolam (sensitive index substrate for CYP3A4) following an oral (15 mg) or intravenous (2 mg) dose, with and without single-dose and steady-state (12 g) coadministration of oral trofinetide. FINDINGS: Following coadministration of intravenous midazolam and oral trofinetide, the PK properties of midazolam were unchanged. The trofinetide concentration in the gut wall was >15 mmol/L during the first 1.5 hours after dosing. With the coadministration of oral midazolam and trofinetide, the model predicted increases in fraction of dose reaching the portal vein, bioavailability, Cmax, and AUCinf of 30%, 30%, 18%, and 30%, respectively. IMPLICATIONS: In this study that used a PBPK modeling approach, it was shown that CYP3A4 enzyme activity in the liver was not affected by trofinetide coadministration, but trofinetide was predicted to be a weak inhibitor of intestinal CYP3A4 metabolism after oral administration at therapeutic doses.

Exposure-Response Efficacy Modeling to Support Trofinetide Dosing in Individuals with Rett Syndrome.

INTRODUCTION: Trofinetide was recently approved for the treatment of Rett syndrome (RTT) on the basis of the efficacy and safety findings of the phase 3 LAVENDER study, which used a body weight-based dosing regimen. Exposure-response (E-R) efficacy modeling was used to characterize relationships between trofinetide exposure measures (maximum drug concentration and area under the concentration-time curve for the dosing interval of 0-12 h [AUC0-12]) and efficacy endpoints in RTT clinical studies to support the trofinetide dosing regimen. METHODS: Efficacy endpoints were modeled using trofinetide exposure measures predicted from the population pharmacokinetic model and Bayesian estimates. The analysis population for each E-R model comprised individuals receiving placebo or trofinetide who had available trofinetide exposure measures. Efficacy endpoints were scores from the Rett Syndrome Behaviour Questionnaire (RSBQ), the Clinical Global Impression-Improvement, the Communication and Symbolic Behavior Scales Developmental Profile™ Infant-Toddler Checklist (CSBS-DP-IT) Social Composite, and the Rett Syndrome Clinician Rating of Ability to Communicate Choices (RTT-COMC). RESULTS: Higher trofinetide exposure was associated with improvements in RSBQ, CSBS-DP-IT Social Composite, and RTT-COMC scores. Assuming target trofinetide AUC0-12 values of 800-1200 µg·h/mL, the reductions in RSBQ total scores at week 12 were approximately five- to seven-fold greater with trofinetide (range 3.55-4.94) versus placebo (0.76). Significant E-R relationships were also found for the CSBS-DP-IT Social Composite and RTT-COMC scores. CONCLUSION: E-R efficacy modeling demonstrated significant relationships between trofinetide exposure and RSBQ, CSBS-DP-IT Social Composite, and RTT-COMC scores. Trofinetide is efficacious within the target exposure range, supporting the approved dosing regimen for trofinetide. TRIAL REGISTRATION: NCT01703533, NCT02715115, NCT04181723.

Trofinetide is the first approved treatment for people living with Rett syndrome, a rare genetic condition affecting brain development. This approval was based on the findings of clinical studies in which trofinetide showed significant improvements in the symptoms of Rett syndrome. In this study researchers were looking to see if the level of trofinetide in the blood was related to the level of improvement in symptoms observed in clinical studies. Information on the effectiveness of trofinetide was obtained from the phase 3 LAVENDER study which used doses of trofinetide according to body weight. Trofinetide's effectiveness was assessed on the basis of clinical measurements of key Rett syndrome symptoms. All the information on trofinetide dose, blood levels, and how much symptoms changed (i.e., effectiveness of trofinetide) was then used to develop models to predict symptom responses in the observed population. Researchers found that as the blood levels of trofinetide increased the symptom improvement also increased. When the blood levels were at the recommended level that was achieved in the LAVENDER study, the model predicted that symptom improvement was up to seven times greater with trofinetide than having no treatment (i.e., placebo). This study shows a positive relationship between trofinetide blood levels and improvement in the symptoms of Rett syndrome. Trofinetide was effective within the recommended blood level range in the LAVENDER study using the approved weight-based dosing.

Prevalence of COVID-19 Mitigation Behaviors in US Adults (August-December 2020): Nationwide Household Probability Survey.

BACKGROUND: COVID-19 mitigation behaviors, such as wearing masks, maintaining social distancing, and practicing hand hygiene, have been and will remain vital to slowing the pandemic. OBJECTIVE: This study aims to describe the period prevalence of consistent mask-wearing, social distancing, and hand hygiene practices during the peak of COVID-19 incidence (August-December 2020) and just before COVID-19 vaccine availability, overall and in demographic subgroups. METHODS: We used baseline survey data from a nationwide household probability sample to generate weighted estimates of mitigation behaviors: wearing masks, maintaining social distancing, and practicing hand hygiene. Weighted logistic regression explored differences in mitigation behaviors by demographics. Latent class analysis (LCA) identified patterns in mitigation behaviors. RESULTS: Among 4654 participants, most (n=2727, 58.6%) were female, were non-Hispanic White (n=3063, 65.8%), were aged 55 years or older (n=2099, 45.1%), lived in the South (n=2275, 48.9%), lived in metropolitan areas (n=4186, 89.9%), had at least a bachelor's degree (n=2547, 54.7%), had an income of US $50,000-$99,000 (n=1445, 31%), and were privately insured (n=2734, 58.7%). The period prevalence of consistent mask wearing was 71.1% (sample-weighted 95% CI 68.8-73.3); consistent social distancing, 42.9% (95% CI 40.5-45.3); frequent handwashing, 55.0% (95% CI 52.3-57.7); and frequent hand sanitizing, 21.5% (95% CI 19.4-23.8). Mitigation behaviors were more prevalent among women, older persons, Black or Hispanic persons, those who were not college graduates, and service-oriented workers. LCA identified an optimal-mitigation class that consistently practiced all behaviors (n=2656, 67% of US adults), a low-mitigation class that inconsistently practiced all behaviors (n=771, 20.6%), and a class that had optimal masking and social distancing but a high frequency of hand hygiene (n=463, 12.4%). CONCLUSIONS: Despite a high prevalence of COVID-19 mitigation behaviors, there were likely millions who did not consistently practice these behaviors during the time of the highest COVID-19 incidence. In future infectious disease outbreak responses, public health authorities should also consider addressing disparities in mitigation practices through more targeted prevention messaging.

Trends in Hepatitis C Virus and HIV Care Outcomes Among People With HIV in Georgia, United States, 2014-2019.

OBJECTIVE: If untreated, hepatitis C virus (HCV) leads to poor health outcomes, including liver disease and death, particularly among people with HIV (PWH). We describe trends over time in incidence rates of HCV diagnoses among PWH in the state of Georgia. METHODS: We constructed a retrospective cohort of PWH in Georgia by using matched HIV and HCV case surveillance data from people diagnosed with HCV infection from January 1, 2014, through December 31, 2019. We calculated annual incidence rates per 1000 person-years and estimated trends over time in HCV diagnoses among the cohort of PWH by demographic characteristics and HIV care outcomes using Poisson regression analysis, with α = .05 considered significant. RESULTS: From 2014 through 2019, among 49 530 PWH in Georgia, 1945 (3.9%) were diagnosed with HCV infection. During this period, overall incidence per 1000 person-years of newly diagnosed HCV infection among PWH decreased from 8.7 to 4.5 (P for trend < .001). However, from 2014 through 2019, the annual incidence rates of PWH who were newly diagnosed with HCV infection increased from 4.6 to 7.1 (P for trend = .003) among people born from 1980 through 1989 and from 3.3 to 12.8 (P for trend < .001) among people born in 1990 or later. CONCLUSION: Strategies are needed to increase prevention, diagnosis, and treatment of HIV/HCV coinfection, particularly among PWH born in 1980 and later. Routine linkage of state surveillance data can inform prioritization of PWH at highest risk of HCV infection.

HIV and HCV testing at clinical encounters among people who inject drugs, 2013-2018-Opportunities for increased testing and prevention.

People who inject drugs (PWID) with unsafe injection practices have substantial risk for HIV and hepatitis C virus (HCV) infections. We describe frequency of, and factors associated with, HIV and HCV testing during clinical encounters with PWID. Inpatient and Emergency Department clinical encounters at an Atlanta hospital were abstracted from medical records spanning January 2013-December 2018. We estimated frequency of HIV and HCV testing during injection drug use (IDU)-related encounters among PWID without previous diagnoses. We assessed associations between patient factors and testing using generalized estimating equations models. HIV testing occurred in 39.3% and HCV testing occurred in 17.1% of eligible IDU-related encounters. Testing was more likely in IDU-related encounters during 2017-2018 than in encounters during 2013-2014; (HIV, AOR = 2.14, 95% CI, 1.32-3.49, p < .01). Testing was less likely among Black/African American patients compared to White patients (adjusted odds ratio [AOR]: HIV, AOR = 0.48, 95% confidence interval [CI], 0.33-0.72, p < .01); HCV, AOR = 0.41, 95% CI, 0.24-0.70, p < .01). This difference may be attributable to recent testing among Black patients in non-IDU related encounters. HIV and HCV testing improved over time; however, missed opportunities for testing still existed. Strategies should aim to improve equitable HIV and HCV testing among PWID.

Real-world integration of the protocol for responding to and assessing patients' assets, risks, and experiences tool to assess social determinants of health in the electronic medical record at an academic medical center.

Objective: To describe the real-world deployment of a tool, the Protocol for Responding to and Assessing Patients' Assets, Risks, and Experiences (PRAPARE), to assess social determinants of health (SDoH) in an electronic medical record (EMR). Methods: We employed the collection of the PRAPARE tool in the EMR of a large academic health system in the ambulatory clinic and emergency department setting. After integration, we evaluated SDoH prevalence, levels of missingness, and data anomalies to inform ongoing collection. We summarized responses using descriptive statistics and hand-reviewed data text fields and patterns in the data. Data on patients who were administered with the PRAPARE from February to December 2020 were extracted from the EMR. Patients missing ≥ 12 PRAPARE questions were excluded. Social risks were screened using the PRAPARE. Information on demographics, admittance status, and health coverage were extracted from the EMR. Results: Assessments with N = 6531 were completed (mean age 54 years, female (58.6%), 43.8% Black). Missingness ranged from 0.4% (race) to 20.8% (income). Approximately 6% of patients were homeless; 8% reported housing insecurity; 1.4% reported food needs; 14.6% had healthcare needs; 8.4% needed utility assistance; and 5% lacked transportation related to medical care. Emergency department patients reported significantly higher proportions of suboptimal SDoH. Conclusions: Integrating the PRAPARE assessment in the EMR provides valuable information on SDoH amenable to intervention, and strategies are needed to increase accurate data collection and to improve the use of data in the clinical encounter.

Use of COVIDTests.gov At-Home Test Kits Among Adults in a National Household Probability Sample - United States, 2022.

At-home rapid antigen COVID-19 tests were first authorized by the Food and Drug Administration in late 2020 (1-3). In January 2022, the White House launched COVIDTests.gov, which made all U.S. households eligible to receive free-to-the-user at-home test kits distributed by the U.S. Postal Service (2). By May 2022, more than 70 million test kit packages had been shipped to households across the United States (2); however, how these kits were used, and which groups were using them, has not been reported. Data from a national probability survey of U.S. households (COVIDVu), collected during April-May 2022, were used to evaluate awareness about and use of these test kits (4). Most respondent households (93.8%) were aware of the program, and more than one half (59.9%) had ordered kits. Among persons who received testing for COVID-19 during the preceding 6 months, 38.3% used a COVIDTests.gov kit. Among kit users, 95.5% rated the experience as acceptable, and 23.6% reported being unlikely to have tested without the COVIDTests.gov program. Use of COVIDTests.gov kits was similar among racial and ethnic groups (42.1% non-Hispanic Black or African American [Black]; 41.5% Hispanic or Latino [Hispanic]; 34.8% non-Hispanic White [White]; and 53.7% non-Hispanic other races [other races]). Use of other home COVID-19 tests differed by race and ethnicity (11.8% Black, 44.4% Hispanic, 45.8% White, 43.8% other races). Compared with White persons, Black persons were 72% less likely to use other home test kits (adjusted relative risk [aRR] = 0.28; 95% CI = 0.16-0.50). Provision of tests through this well-publicized program likely improved use of COVID-19 home testing and health equity in the United States, particularly among Black persons. National programs to address availability and accessibility of critical health services in a pandemic response have substantial health value.

Estimating HIV Incident Diagnoses Among Men Who Have Sex With Men Eligible for Pre-exposure Prophylaxis but Not Taking It: Protocol and Feasibility Assessment of Data Sources and Methods.

BACKGROUND: HIV incidence estimates are published each year for all Ending the HIV Epidemic (EHE) counties, but they are not stratified by the demographic variables highly associated with risk of infection. Regularly updated estimates of HIV incident diagnoses available at local levels are required to monitor the epidemic in the United States over time and could contribute to background incidence rate estimates for alternative clinical trial designs for new HIV prevention products. OBJECTIVE: We describe methods using existing, robust data sources within areas in the United States to reliably estimate longitudinal HIV incident diagnoses stratified by race and age categories among men who have sex with other men (MSM) eligible for pre-exposure prophylaxis (PrEP) but not taking it. METHODS: This is a secondary analysis of existing data sources to develop new estimates of incident HIV diagnoses in MSM. We reviewed past methods used to estimate incident diagnoses and explored opportunities to improve these estimates. We will use existing surveillance data sources and population sizes of HIV PrEP-eligible MSM estimated from population-based data sources (eg, US Census data and pharmaceutical prescription databases) to develop metropolitan statistical area-level estimates of new HIV diagnoses among PrEP-eligible MSM. Required parameters are number of new diagnoses among MSM, estimates of MSM with an indication for PrEP, and prevalent PrEP use including median duration of use; these parameters will be stratified by jurisdiction and age group or race or ethnicity. Preliminary outputs will be available in 2023, and updated estimates will be produced annually thereafter. RESULTS: Data to parameterize new HIV diagnoses among PrEP-eligible MSM are available with varying levels of public availability and timeliness. In early 2023, the most recent available data on new HIV diagnoses were from the 2020 HIV surveillance report, which reports 30,689 new HIV infections in 2020, and 24,724 of them occurred in an MSA with a population of ≥500,000. Updated estimates for PrEP coverage based on commercial pharmacy claims data through February 2023 will be generated. The rate of new HIV diagnoses among MSM can be estimated from new diagnoses within each demographic group (numerator) and the total person-time at risk of diagnosis for each group (denominator) by metropolitan statistical area and year. To estimate time at risk, the person-time of individuals on PrEP or person-time after incident HIV infection but before diagnosis should be removed from stratified population size estimates of the total number of person-years with indications for PrEP. CONCLUSIONS: Reliable, serial, cross-sectional estimates for rates of new HIV diagnoses for MSM with PrEP indications can serve as benchmark community estimates of failures of HIV prevention and opportunities to improve services and will support public health epidemic monitoring and alternative clinical trial designs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/42267.

Missed opportunities for prevention: prevalence and incidence of human immunodeficiency virus and hepatitis C virus diagnoses among a cohort of individuals discharged from an urban hospital with injection drug-related diagnoses, 2012-2019.

PURPOSE: Risk for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections has increased due to the ongoing opioid epidemic and unsafe injection practices. We estimated the prevalence and incidence of HIV and HCV diagnoses among people who inject drugs from hospital-based clinical encounters. METHODS: We linked clinical encounters at an Atlanta hospital during 2012-2018 with state HIV and HCV surveillance records to examine the prevalence of infections at discharge and incidence of infections post clinical encounter. RESULTS: At discharge, 32.9% and 28.6% of patients with injection drug use-related clinical encounters had an HIV or HCV diagnosis, respectively. HIV and HCV diagnoses at the time of discharge were mostly among 40-64 years old patients, males, and Black/African Americans. Post clinical encounter, 3.8% of patients were later diagnosed with HIV, and 16.5% were later diagnosed with HCV, translating to incidence rates of 9.3 per 1000 person-years and 41.5 per 1000 person-years, respectively. The majority of HIV and HCV diagnoses post clinical encounter occurred among Black/African Americans and males. Of patients with HIV and HCV diagnoses post clinical encounter, 27.3% and 11.9% had been tested during their clinical encounter, respectively. CONCLUSIONS: Targeted interventions for HIV/HCV prevention, screening, diagnosis, and linkage to treatment are needed to reduce the incidence of new infections among people who inject drugs.

COVID-19 vaccine attitudes among a majority black sample in the Southern US: public health implications from a qualitative study.

BACKGROUND: The COVID-19 pandemic continues to have high caseloads in the US, with vaccines a critical component of the response. Disparities in COVID-19 morbidity and mortality have been identified across states and racial/ethnic groups, which are likely in part due to disparities in COVID-19 vaccine uptake. This study aims to better understand and contextualize COVID-19 vaccine hesitancy among persons from under-represented racial/ethnic populations in the Southern US. METHODS: We conducted 29 in-depth interviews with a sample of households in Atlanta, GA that were selected from an address-based sampling frame. We purposively approached households, from February 6 to June 27, 2021, that declined participation in a national COVID-19 serosurvey to gain perspectives of people who are often under-represented in research. Interviews were conducted in-person or over phone calls for participants with that preference. Thematic analysis was used to identify barriers and facilitators of COVID-19 vaccination, and to contextualize drivers of vaccine hesitancy. RESULTS: Decision-making about vaccination was described as dynamic, and was compared to the feeling of being on a roller coaster. The predominant reported sources of information were mass media and social media. Facilitators of vaccination included altruism, positive communication from trusted community members and workplace colleagues, and local vaccine provision sites. Driving reasons for vaccine hesitancy included limited trust in the government and concerns about COVID-19 vaccine safety, which one participant compared to jumping off a cliff without a tested rope. Among a subset of participants, beliefs regarding perceived intent to harm the Black community were prevalent. Opportunities to optimally address vaccine hesitancy included countering negative social media messages with positive messaging that matches the community's vivid ways of discussing vaccines, collaborating with community stakeholders on vaccine promotion efforts, and offering workplace-based vaccine promotion efforts. CONCLUSIONS: This study presents data that indicate it may be optimal to more broadly define 'community' in COVID-19 vaccine promotion efforts to include social media and workplace venues. To optimize vaccine and vaccine booster uptake and equity, public health must address historic racism and other concerns by using outreach that is grounded in communities.

Estimated Number of People Who Inject Drugs in the United States.

BACKGROUND: Public health data signal increases in the number of people who inject drugs (PWID) in the United States during the past decade. An updated PWID population size estimate is critical for informing interventions and policies aiming to reduce injection-associated infections and overdose, as well as to provide a baseline for assessments of pandemic-related changes in injection drug use. METHODS: We used a modified multiplier approach to estimate the number of adults who injected drugs in the United States in 2018. We deduced the estimated number of nonfatal overdose events among PWID from 2 of our previously published estimates: the number of injection-involved overdose deaths and the meta-analyzed ratio of nonfatal to fatal overdose. The number of nonfatal overdose events was divided by prevalence of nonfatal overdose among current PWID for a population size estimate. RESULTS: There were an estimated 3 694 500 (95% confidence interval [CI], 1 872 700-7 273 300) PWID in the United States in 2018, representing 1.46% (95% CI, .74-2.87) of the adult population. The estimated prevalence of injection drug use was highest among males (2.1%; 95% CI, 1.1-4.2), non-Hispanic Whites (1.8%; 95% CI, .9-3.6), and adults aged 18-39 years (1.8%; 95% CI, .9-3.6). CONCLUSIONS: Using transparent, replicable methods and largely publicly available data, we provide the first update to the number of people who inject drugs in the United States in nearly 10 years. Findings suggest the population size of PWID has substantially grown in the past decade and that prevention services for PWID should be proportionally increased.

A stakeholder-driven framework for measuring potential change in the health risks of people who inject drugs (PWID) during the COVID-19 pandemic.

BACKGROUND: People who inject drugs (PWID) have likely borne disproportionate health consequences of the COVID-19 pandemic. PWID experienced both interruptions and changes to drug supply and delivery modes of harm reduction, treatment, and other medical services, leading to potentially increased risks for HIV, hepatitis C virus (HCV), and overdose. Given surveillance and research disruptions, proximal, indirect indicators of infectious diseases and overdose should be developed for timely measurement of health effects of the pandemic on PWID. METHODS: We used group concept mapping and a systems thinking approach to produce an expert stakeholder-generated, multi-level framework for monitoring changes in PWID health outcomes potentially attributable to COVID-19 in the U.S. This socio-ecological measurement framework elucidates proximal and distal contributors to infectious disease and overdose outcomes, many of which can be measured using existing data sources. RESULTS: The framework includes multi-level components including policy considerations, drug supply/distribution systems, the service delivery landscape, network factors, and individual characteristics such as mental and general health status and service utilization. These components are generally mediated by substance use and sexual behavioral factors to cause changes in incidence of HIV, HCV, sexually transmitted infections, wound/skin infections, and overdose. CONCLUSION: This measurement framework is intended to increase the quality and timeliness of research on the impacts of COVID-19 in the context of the current pandemic and future crises. Next steps include a ranking process to narrow the drivers of change in health risks to a concise set of indicators that adequately represent framework components, can be written as measurable indicators, and are quantifiable using existing data sources, as well as a publicly available web-based platform for summary data contributions.

Association of Guideline Complexity With Individuals' Ability to Determine Eligibility for COVID-19 Vaccination.

This cross-sectional study examines the association between the complexity of consumer guidelines for COVID-19 vaccination and identification of eligibility.

COVID-19 Vaccine Attitudes among a Majority Black Sample in the Southern US: Public Health Implications from a Qualitative Study.

BACKGROUND: The COVID-19 pandemic continues to have high caseloads in the US, with vaccines a critical component of the response. Disparities in COVID-19 morbidity and mortality have been identified across states and racial/ethnic groups, which are likely in part due to disparities in COVID-19 vaccine uptake. This study aims to better understand and contextualize COVID-19 vaccine hesitancy among persons from primarily racial/ethnic minority populations in the Southern US. METHODS: We conducted 29 in-depth interviews with a sample of households in Atlanta, GA that were selected from an address-based sampling frame. We purposively approached households, from February 6 to June 27, 2021, that declined participation in a national COVID-19 serosurvey to gain perspectives of people who are often under-represented in research. Interviews were conducted in-person or over phone calls for participants with that preference. Thematic analysis was used to identify barriers and facilitators of COVID-19 vaccination, and to contextualize drivers of vaccine hesitancy. RESULTS: Decision-making about vaccination was described as dynamic, and was compared to the feeling of being on a roller coaster. The predominant reported sources of information were mass media and social media. Facilitators of vaccination included altruism, positive communication from trusted community members and workplace colleagues, and local vaccine provision sites. Driving reasons for vaccine hesitancy included limited trust in the government and concerns about COVID-19 vaccine safety, which one participant compared to jumping off a cliff without a tested rope. Among a subset of participants, beliefs regarding perceived intent to harm the Black community were prevalent. Opportunities to optimally address vaccine hesitancy included countering negative social media messages with positive messaging that matches the community's vivid ways of discussing vaccines, collaborating with community stakeholders on vaccine promotion efforts, and offering workplace-based vaccine promotion efforts. CONCLUSIONS: This study presents data that indicate it may be optimal to more broadly define 'community' in COVID-19 vaccine promotion efforts to include social media and workplace venues. To optimize vaccine and vaccine booster uptake and equity, public health must address historic racism and other concerns by using outreach that is grounded in communities.

Nationally representative social contact patterns among U.S. adults, August 2020-April 2021.

The response to the COVID-19 pandemic in the U.S prompted abrupt and dramatic changes to social contact patterns. Monitoring changing social behavior is essential to provide reliable input data for mechanistic models of infectious disease, which have been increasingly used to support public health policy to mitigate the impacts of the pandemic. While some studies have reported on changing contact patterns throughout the pandemic, few have reported differences in contact patterns among key demographic groups and none have reported nationally representative estimates. We conducted a national probability survey of US households and collected information on social contact patterns during two time periods: August-December 2020 (before widespread vaccine availability) and March-April 2021 (during national vaccine rollout). Overall, contact rates in Spring 2021 were similar to those in Fall 2020, with most contacts reported at work. Persons identifying as non-White, non-Black, non-Asian, and non-Hispanic reported high numbers of contacts relative to other racial and ethnic groups. Contact rates were highest in those reporting occupations in retail, hospitality and food service, and transportation. Those testing positive for SARS-CoV-2 antibodies reported a higher number of daily contacts than those who were seronegative. Our findings provide evidence for differences in social behavior among demographic groups, highlighting the profound disparities that have become the hallmark of the COVID-19 pandemic.

Estimated number of injection-involved drug overdose deaths, United States, 2000 - 2018.

BACKGROUND: In the United States, drug overdose mortality has increased. Death records categorize overdose deaths by type of drug involved, but do not include information about the route of drug administration. METHODS: We utilized data from drug treatment admissions (Treatment Episodes Dataset, TEDS-A) and National Vital Statistics Systems to estimate the percentage of reported drug overdose deaths that were injection-involved from 2000 to 2018 in the U.S. Data on reported route of administration at admission were used to calculate the percent injecting each drug type, by demographic group (race/ethnicity, sex, age group) and year. Using the resulting probabilities, we estimated the number of overdose deaths that were injection-involved. Estimates were compared across drug types, demographic characteristics, and year. FINDINGS: The number of overdose deaths among adults increased more than 3-fold from 2000 (n = 17,196) to 2018 (n = 67,021). During that timeframe, the number of estimated injection-involved overdose deaths increased more than 8-fold from 2000 (n = 3467, 95% CI: 3449-3485) to 2018 (n = 28,257, 95% CI: 28,192-28,322). From 2000-2007, the percent of overdose deaths that were injection-involved remained stable around 20%. From 2007-2018, the percent of overdose deaths that were injection-involved increased from 18.4% (95% CI: 18.3-18.6%) to 42.2% (95% CI: 42.1-42.3%). In 2018, most estimated injection-involved overdose deaths were due to injecting heroin/synthetic opioids (n = 24,860, 95% CI: 24,800-24,919), which accounted for 88.0% of all injection-involved deaths. CONCLUSIONS: Much of the recent increase in overdose mortality is likely attributable to rising injection-involved overdose deaths.