Performance of Rapid Antigen Tests to Detect Symptomatic and Asymptomatic SARS-CoV-2 Infection : A Prospective Cohort Study.

BACKGROUND: The performance of rapid antigen tests (Ag-RDTs) for screening asymptomatic and symptomatic persons for SARS-CoV-2 is not well established. OBJECTIVE: To evaluate the performance of Ag-RDTs for detection of SARS-CoV-2 among symptomatic and asymptomatic participants. DESIGN: This prospective cohort study enrolled participants between October 2021 and January 2022. Participants completed Ag-RDTs and reverse transcriptase polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 every 48 hours for 15 days. SETTING: Participants were enrolled digitally throughout the mainland United States. They self-collected anterior nasal swabs for Ag-RDTs and RT-PCR testing. Nasal swabs for RT-PCR were shipped to a central laboratory, whereas Ag-RDTs were done at home. PARTICIPANTS: Of 7361 participants in the study, 5353 who were asymptomatic and negative for SARS-CoV-2 on study day 1 were eligible. In total, 154 participants had at least 1 positive RT-PCR result. MEASUREMENTS: The sensitivity of Ag-RDTs was measured on the basis of testing once (same-day), twice (after 48 hours), and thrice (after a total of 96 hours). The analysis was repeated for different days past index PCR positivity (DPIPPs) to approximate real-world scenarios where testing initiation may not always coincide with DPIPP 0. Results were stratified by symptom status. RESULTS: Among 154 participants who tested positive for SARS-CoV-2, 97 were asymptomatic and 57 had symptoms at infection onset. Serial testing with Ag-RDTs twice 48 hours apart resulted in an aggregated sensitivity of 93.4% (95% CI, 90.4% to 95.9%) among symptomatic participants on DPIPPs 0 to 6. When singleton positive results were excluded, the aggregated sensitivity on DPIPPs 0 to 6 for 2-time serial testing among asymptomatic participants was lower at 62.7% (CI, 57.0% to 70.5%), but it improved to 79.0% (CI, 70.1% to 87.4%) with testing 3 times at 48-hour intervals. LIMITATION: Participants tested every 48 hours; therefore, these data cannot support conclusions about serial testing intervals shorter than 48 hours. CONCLUSION: The performance of Ag-RDTs was optimized when asymptomatic participants tested 3 times at 48-hour intervals and when symptomatic participants tested 2 times separated by 48 hours. PRIMARY FUNDING SOURCE: National Institutes of Health RADx Tech program.

Characterizing Pandemic-Related Changes in Smoking Over Time in a Cohort of Current and Former Smokers.

INTRODUCTION: We used a longitudinal cohort of US adults who were current or former smokers to explore how three participant-reported factors-general stress, coronavirus disease of 2019 (COVID-19) distress, and perceived risk of complications from COVID-19 related to smoking-were associated with changes in smoking status. METHODS: Smoking status was assessed at three time points. Timepoint 1 status was assessed at a prior study completion (2018-2020). Timepoint 2 (start of the pandemic), and Timepoint 3 (early phase of the pandemic) statuses were assessed using an additional survey in 2020. After classifying participants into eight groups per these time points, we compared the means of participant-reported factors and used a linear regression model to adjust for covariates. RESULTS: Participants (n = 392) were mostly female (73.9%) and non-Hispanic White (70.1%). Between Timepoints 2 and 3, abstinence rates decreased by 11%, and 40% of participants reported a smoking status change. Among those reporting a change and the highest general stress levels, newly abstinent participants had higher perceived risk of complications from COVID-19 related to smoking than those who relapsed during pandemic (mean (SD): 14.2 (3.3) vs. 12.6 (3.8)). Compared to participants who sustained smoking, those who sustained abstinence, on average, scored 1.94 less on the general stress scale (ßeta Coefficient (ß): -1.94, p-value < .01) and 1.37 more on the perceived risk of complications from COVID-19 related to smoking scale (ß: 1.37, p-value .02). CONCLUSIONS: Decreased abstinence rates are concerning. Patterns of reported factors were as expected for individuals who sustained their smoking behavior but not for those who changed. IMPLICATIONS: We observed an increase in smoking rates during the COVID-19 pandemic. In exploring how combinations of general stress levels, COVID-19 distress levels, and perceived risk of complications from COVID-19 related to smoking were associated with changes in smoking, we observed expected patterns of these factors among individuals who sustained abstinence or smoking. Among individuals who changed smoking status and reported high stress levels, those who reported a higher perceived risk of complications from COVID-19 related to smoking abstained from smoking. In contrast, those who reported a lower perceived risk of complications from COVID-19 related to smoking, started smoking. An intersectional perspective may be needed to understand smokers' pandemic-related behavior changes.

Comparison of Rapid Antigen Tests' Performance Between Delta and Omicron Variants of SARS-CoV-2 : A Secondary Analysis From a Serial Home Self-testing Study.

BACKGROUND: It is important to document the performance of rapid antigen tests (Ag-RDTs) in detecting SARS-CoV-2 variants. OBJECTIVE: To compare the performance of Ag-RDTs in detecting the Delta (B.1.617.2) and Omicron (B.1.1.529) variants of SARS-CoV-2. DESIGN: Secondary analysis of a prospective cohort study that enrolled participants between 18 October 2021 and 24 January 2022. Participants did Ag-RDTs and collected samples for reverse transcriptase polymerase chain reaction (RT-PCR) testing every 48 hours for 15 days. SETTING: The parent study enrolled participants throughout the mainland United States through a digital platform. All participants self-collected anterior nasal swabs for rapid antigen testing and RT-PCR testing. All Ag-RDTs were completed at home, whereas nasal swabs for RT-PCR were shipped to a central laboratory. PARTICIPANTS: Of 7349 participants enrolled in the parent study, 5779 asymptomatic persons who tested negative for SARS-CoV-2 on day 1 of the study were eligible for this substudy. MEASUREMENTS: Sensitivity of Ag-RDTs on the same day as the first positive (index) RT-PCR result and 48 hours after the first positive RT-PCR result. RESULTS: A total of 207 participants were positive on RT-PCR (58 Delta, 149 Omicron). Differences in sensitivity between variants were not statistically significant (same day: Delta, 15.5% [95% CI, 6.2% to 24.8%] vs. Omicron, 22.1% [CI, 15.5% to 28.8%]; at 48 hours: Delta, 44.8% [CI, 32.0% to 57.6%] vs. Omicron, 49.7% [CI, 41.6% to 57.6%]). Among 109 participants who had RT-PCR-positive results for 48 hours, rapid antigen sensitivity did not differ significantly between Delta- and Omicron-infected participants (48-hour sensitivity: Delta, 81.5% [CI, 66.8% to 96.1%] vs. Omicron, 78.0% [CI, 69.1% to 87.0%]). Only 7.2% of the 69 participants with RT-PCR-positive results for shorter than 48 hours tested positive by Ag-RDT within 1 week; those with Delta infections remained consistently negative on Ag-RDTs. LIMITATION: A testing frequency of 48 hours does not allow a finer temporal resolution of the analysis of test performance, and the results of Ag-RDTs are based on self-report. CONCLUSION: The performance of Ag-RDTs in persons infected with the SARS-CoV-2 Omicron variant is not inferior to that in persons with Delta infections. Serial testing improved the sensitivity of Ag-RDTs for both variants. The performance of rapid antigen testing varies on the basis of duration of RT-PCR positivity. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute of the National Institutes of Health.

Evaluating the use of a recommender system for selecting optimal messages for smoking cessation: patterns and effects of user-system engagement.

BACKGROUND: Motivational messaging is a frequently used digital intervention to promote positive health behavior changes, including smoking cessation. Typically, motivational messaging systems have not actively sought feedback on each message, preventing a closer examination of the user-system engagement. This study assessed the granular user-system engagement around a recommender system (a new system that actively sought user feedback on each message to improve message selection) for promoting smoking cessation and the impact of engagement on cessation outcome. METHODS: We prospectively followed a cohort of current smokers enrolled to use the recommender system for 6 months. The system sent participants motivational messages to support smoking cessation every 3 days and used machine learning to incorporate user feedback (i.e., user's rating on the perceived influence of each message, collected on a 5-point Likert scale with 1 indicating strong disagreement and 5 indicating strong agreement on perceiving the influence on quitting smoking) to improve the selection of the following message. We assessed user-system engagement by various metrics, including user response rate (i.e., the percent of times a user rated the messages) and the perceived influence of messages. We compared retention rates across different levels of user-system engagement and assessed the association between engagement and the 7-day point prevalence abstinence (missing outcome = smoking) by using multiple logistic regression. RESULTS: We analyzed data from 731 participants (13% Black; 73% women). The user response rate was 0.24 (SD = 0.34) and user-perceived influence was 3.76 (SD = 0.84). The retention rate positively increased with the user response rate (trend test P < 0.001). Compared with non-response, six-month cessation increased with the levels of response rates: low response rate (odds ratio [OR] = 1.86, 95% confidence interval [CI]: 1.07-3.23), moderate response rate (OR = 2.30, 95% CI: 1.36-3.88), high response rate (OR = 2.69, 95% CI: 1.58-4.58). The association between perceived message influence and the outcome showed a similar pattern. CONCLUSIONS: High user-system engagement was positively associated with both high retention rate and smoking cessation, suggesting that investigation of methods to increase engagement may be crucial to increase the impact of the recommender system for smoking cessation. TRIAL REGISTRATION: Registration Identifier: NCT03224520 . Registration date: July 21, 2017.

The Association Between Patient-reported Clinical Factors and 30-day Acute Care Utilization in Chronic Heart Failure.

BACKGROUND: Heart failure patients have high rates of repeat acute care use. Current efforts for risk prediction often ignore postdischarge data. OBJECTIVE: To identify postdischarge patient-reported clinical factors associated with repeat acute care use. RESEARCH DESIGN: In a prospective cohort study that followed patients with chronic heart failure for 30 days postdischarge, for 7 days after discharge (or fewer days if patients used acute care within 7 days postdischarge), patients reported health status, heart failure symptoms, medication management, knowledge of follow-up plans, and other issues using a daily interactive automatic phone call. SUBJECTS: A total of 156 patients who had responded to phone surveys. MEASURES: The outcome variable was dichotomous 30-day acute care use (rehospitalization or emergency department visit). We examined the association between each patient-reported issue and the outcome, using multivariable logistic regression to adjust for confounders. RESULTS: Patients were 63 years old (SD=12.4), with 51% African-American and 53% women. Within 30 days postdischarge, 30 (19%) patients used acute care. After adjustment, poor health status [odds ratio (OR)=3.53; 95% confidence interval (CI), 1.06-11.76], pain (OR=2.44; 95% CI, 1.02-5.84), and poor appetite (OR=3.05; 95% CI, 1.13-8.23) were positively associated with 30-day acute care utilization. Among 58 reports of pain in follow-up nursing notes, 39 (67%) were noncardiac, 2 (3%) were cardiac, and 17 (29%) were indeterminate. CONCLUSIONS: Patient-reported poor health status, pain, and poor appetite were positively associated with 30-day acute care utilization. These novel postdischarge markers require further study before incorporation into risk prediction to drive quality improvement efforts.

Homeless women's service use, barriers, and motivation for participating in substance use treatment.

BACKGROUND: Homeless women are at high risk for substance use disorder (SUD), and are a growing proportion of the homeless population. However, homeless women experience barriers to engaging in substance use services. OBJECTIVES: Among homeless women with SUD, to explore service use, motivation to change, service barriers, and willingness to have substance use and mental health problems addressed in primary health care. METHODS: Women with SUD were sampled from 11 Health Care for the Homeless (HCH) primary care clinics in 9 states, yielding 241 with either an alcohol or drug use disorder who then completed questions about SUD services. RESULTS: Over 60% of women with dual alcohol and drug use disorders used some type of SUD service in the past year, while 52% with a drug only disorder, and 44% with an alcohol only disorder used services. The most mentioned barrier to service use was depression, but cost, wait time, where to find treatment, and facilities located too far away, were also frequently noted. A large proportion across all groups indicated high motivation for treatment and willingness to discuss their SUD in a primary care setting. CONCLUSION: There are continued barriers to SUD service use for homeless women despite high motivation for treatment, and willingness to be asked about SUD and mental health problems in primary care. HCH primary care sites should more systematically ask about SUD and mental health issues and address women's expressed need for support groups and alternative therapies to more holistically address their SUD needs.

Population representation among anatomical donors and the implication for medical student education.

Dissection provides a unique opportunity to integrate anatomical and clinical education. Commonly, cadavers are randomly assigned to courses, which may result in skewed representation of patient populations. The primary aim of this study was to determine if the anatomical donors studied by students at the University of Massachusetts Medical School (UMMS) accurately represent the disease burden of the local patient population. This cross-sectional study compared the University of Massachusetts Memorial Medical Center patient claims data and body donation data from the UMMS Anatomical Gift Program (AGP). This study examined age, race, sex, and morbidities within a 10-year timeframe in 401,258 patients and 859 anatomical donors who met inclusion criteria. An independent t test was conducted to compare the mean ages of the two populations. Chi square analysis was conducted on race, sex, and 10 morbidity categories. A Fischer's exact test was conducted for two morbidity categories with n < 10. Demographic analysis showed a significant difference in age, and racial representation between the populations. No statistical difference was found regarding sex. Morbidities were separated into 22 ICD-10 categories. Twelve categories were excluded and 10 were analyzed for population comparison. Two categories were over represented and seven were under-represented in the AGP population. One category showed no significant difference between populations. Targeted selection of cadavers in anatomy courses would improve morbidity variability in the anatomy lab. In addition, AGP acceptance guidelines should be evaluated to increase disease variation among the donor population. Clin. Anat. 31:250-258, 2018. © 2017 Wiley Periodicals, Inc.

Prevalence and predictors of substance use disorders among homeless women seeking primary care: An 11 site survey.

BACKGROUND AND OBJECTIVES: Homeless women have shown high rates of substance use disorders (SUD), but many studies are more than a decade old, limited in geographic location, or focus only on women living outdoors or in shelters. The purpose of this study was to obtain a more current and representative sample of homeless women and the prevalence and predictors of substance use disorders among women seeking primary care at Health Care for the Homeless clinics across the US. METHODS: Eleven Health Care for the Homeless (HCH) clinics in nine states contributed proportionally to a sample of n = 780 female patients who completed a self-administered survey including demographics, housing history, health, mental health, and drug and alcohol use. RESULTS: Compared to the general population of women, rates were four times higher for an alcohol use disorder, and 12 times higher for a drug use disorder. DISCUSSION AND CONCLUSIONS: The findings indicate a significant need for SUD services, with an equally high need for mental health services. In addition, high rates of victimization and use of tobacco, and overall poor health status, indicate overall health disparities. SCIENTIFIC SIGNIFICANCE: Addressing barriers to full integration of substance use and mental health services, such as improving screening, reimbursement, clinician training, and addressing biases about motivation of this population to engage in treatment, are necessary to improve the health of women seeking care in HCH settings. (Am J Addict 2017;26:680-688).

Performance of and Severe Acute Respiratory Syndrome Coronavirus 2 Diagnostics Based on Symptom Onset and Close Contact Exposure: An Analysis From the Test Us at Home Prospective Cohort Study.

Background: Understanding changes in diagnostic performance after symptom onset and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure within different populations is crucial to guide the use of diagnostics for SARS-CoV-2. Methods: The Test Us at Home study was a longitudinal cohort study that enrolled individuals across the United States between October 2021 and February 2022. Participants performed paired antigen-detection rapid diagnostic tests (Ag-RDTs) and reverse-transcriptase polymerase chain reaction (RT-PCR) tests at home every 48 hours for 15 days and self-reported symptoms and known coronavirus disease 2019 exposures immediately before testing. The percent positivity for Ag-RDTs and RT-PCR tests was calculated each day after symptom onset and exposure and stratified by vaccination status, variant, age category, and sex. Results: The highest percent positivity occurred 2 days after symptom onset (RT-PCR, 91.2%; Ag-RDT, 71.1%) and 6 days after exposure (RT-PCR, 91.8%; Ag-RDT, 86.2%). RT-PCR and Ag-RDT performance did not differ by vaccination status, variant, age category, or sex. The percent positivity for Ag-RDTs was lower among exposed, asymptomatic than among symptomatic individuals (37.5% (95% confidence interval [CI], 13.7%-69.4%) vs 90.3% (75.1%-96.7%). Cumulatively, Ag-RDTs detected 84.9% (95% CI, 78.2%-89.8%) of infections within 4 days of symptom onset. For exposed participants, Ag-RDTs detected 94.0% (95% CI, 86.7%-97.4%) of RT-PCR-confirmed infections within 6 days of exposure. Conclusions: The percent positivity for Ag-RDTs and RT-PCR tests was highest 2 days after symptom onset and 6 days after exposure, and performance increased with serial testing. The percent positivity of Ag-RDTs was lowest among asymptomatic individuals but did not differ by sex, variant, vaccination status, or age category.

Effect of a Machine Learning Recommender System and Viral Peer Marketing Intervention on Smoking Cessation: A Randomized Clinical Trial.

Importance: Novel data science and marketing methods of smoking-cessation intervention have not been adequately evaluated. Objective: To compare machine learning recommender (ML recommender) computer tailoring of motivational text messages vs a standard motivational text-based intervention (standard messaging) and a viral peer-recruitment tool kit (viral tool kit) for recruiting friends and family vs no tool kit in a smoking-cessation intervention. Design, Setting, and Participants: This 2 ×2 factorial randomized clinical trial with partial allocation, conducted between July 2017 and September 2019 within an online tobacco intervention, recruited current smokers aged 18 years and older who spoke English from the US via the internet and peer referral. Data were analyzed from March through May 2022. Interventions: Participants registering for the online intervention were randomly assigned to the ML recommender or standard messaging groups followed by partially random allocation to access to viral tool kit or no viral tool kit groups. The ML recommender provided ongoing refinement of message selection based on user feedback and comparison with a growing database of other users, while the standard system selected messages based on participant baseline readiness to quit. Main Outcomes and Measures: Our primary outcome was self-reported 7-day point prevalence smoking cessation at 6 months. Results: Of 1487 participants who smoked (444 aged 19-34 years [29.9%], 508 aged 35-54 years [34.1%], 535 aged ≥55 years [36.0%]; 1101 [74.0%] females; 189 Black [12.7%] and 1101 White [78.5%]; 106 Hispanic [7.1%]), 741 individuals were randomly assigned to the ML recommender group and 746 individuals to the standard messaging group; viral tool kit access was provided to 745 participants, and 742 participants received no such access. There was no significant difference in 6-month smoking cessation between ML recommender (146 of 412 participants [35.4%] with outcome data) and standard messaging (156 of 389 participants [40.1%] with outcome data) groups (adjusted odds ratio, 0.81; 95% CI, 0.61-1.08). Smoking cessation was significantly higher in viral tool kit (177 of 395 participants [44.8%] with outcome data) vs no viral tool kit (125 of 406 participants [30.8%] with outcome data) groups (adjusted odds ratio, 1.48; 95% CI, 1.11-1.98). Conclusions and Relevance: In this study, machine learning-based selection did not improve performance compared with standard message selection, while viral marketing did improve cessation outcomes. These results suggest that in addition to increasing dissemination, viral recruitment may have important implications for improving effectiveness of smoking-cessation interventions. Trial Registration: ClinicalTrials.gov Identifier: NCT03224520.

Supporting Veteran's Administration Medical Center Directors' Decisions When Adopting Innovative Practices: Development and Implementation of the "QuickView" and "WishList" Tools.

Background Since 2015, the Veterans Health Administration (VHA) Diffusion of Excellence Program has supported spread of practices developed by frontline employees. Shark Tank-style competitions encourage "Sharks" nationwide (VHA medical center/regional directors) to bid for the opportunity to implement practices at their institutions. Methods The authors evaluated bidding strategies (2016-2020), developing the "QuickView" practice comparator to promote informed bidding. Program leaders distributed QuickView and revised versions in subsequent competitions. Our team utilized in-person observation, online chats after the competition, bidder interviews, and bid analysis to evaluate QuickView use. Bids were ranked based on demonstrated understanding of resources required for practice implementation. Results Sharks stated that QuickView supported preparation before the competition and suggested improvements. Our revised tool reported necessary staff time and incorporated a "WishList" from practice finalists detailing minimum requirements for successful implementation. Bids from later years reflected increased review of facilities' current states before the competition and increased understanding of the resources needed for implementation. Percentage of bids describing local need for the practice rose from 2016 to 2020: 4.7% (6/127); 62.1% (54/87); 78.3% (36/46); 80.6% (29/36); 89.7% (26/29). Percentage of bids committing specific resources rose following QuickView introduction: 81.1% (103/127) in 2016, 69.0% (60/87) in 2017, then 73.9% (34/46) in 2018, 88.9% (32/36) in 2019, and 89.7% (26/29) in 2020. Discussion In the years following QuickView/WishList implementation, bids reflected increased assessment before the competition of both local needs and available resources. Conclusion Selection of a new practice for implementation requires an understanding of local need, necessary resources, and fit. QuickView and WishList appear to support these determinations.

Performance of Rapid Antigen Tests Based on Symptom Onset and Close Contact Exposure: A secondary analysis from the Test Us At Home prospective cohort study.

Background: The performance of rapid antigen tests for SARS-CoV-2 (Ag-RDT) in temporal relation to symptom onset or exposure is unknown, as is the impact of vaccination on this relationship. Objective: To evaluate the performance of Ag-RDT compared with RT-PCR based on day after symptom onset or exposure in order to decide on 'when to test'. Design Setting and Participants: The Test Us at Home study was a longitudinal cohort study that enrolled participants over 2 years old across the United States between October 18, 2021 and February 4, 2022. All participants were asked to conduct Ag-RDT and RT-PCR testing every 48 hours over a 15-day period. Participants with one or more symptoms during the study period were included in the Day Post Symptom Onset (DPSO) analyses, while those who reported a COVID-19 exposure were included in the Day Post Exposure (DPE) analysis. Exposure: Participants were asked to self-report any symptoms or known exposures to SARS-CoV-2 every 48-hours, immediately prior to conducting Ag-RDT and RT-PCR testing. The first day a participant reported one or more symptoms was termed DPSO 0, and the day of exposure was DPE 0. Vaccination status was self-reported. Main Outcome and Measures: Results of Ag-RDT were self-reported (positive, negative, or invalid) and RT-PCR results were analyzed by a central laboratory. Percent positivity of SARS-CoV-2 and sensitivity of Ag-RDT and RT-PCR by DPSO and DPE were stratified by vaccination status and calculated with 95% confidence intervals. Results: A total of 7,361 participants enrolled in the study. Among them, 2,086 (28.3%) and 546 (7.4%) participants were eligible for the DPSO and DPE analyses, respectively. Unvaccinated participants were nearly twice as likely to test positive for SARS-CoV-2 than vaccinated participants in event of symptoms (PCR+: 27.6% vs 10.1%) or exposure (PCR+: 43.8% vs. 22.2%). The highest proportion of vaccinated and unvaccinated individuals tested positive on DPSO 2 and DPE 5-8. Performance of RT-PCR and Ag-RDT did not differ by vaccination status. Ag-RDT detected 78.0% (95% Confidence Interval: 72.56-82.61) of PCR-confirmed infections by DPSO 4. For exposed participants, Ag-RDT detected 84.9% (95% CI: 75.0-91.4) of PCR-confirmed infections by day five post-exposure (DPE 5). Conclusions and Relevance: Performance of Ag-RDT and RT-PCR was highest on DPSO 0-2 and DPE 5 and did not differ by vaccination status. These data suggests that serial testing remains integral to enhancing the performance of Ag-RDT.

Design and implementation of a digital site-less clinical study of serial rapid antigen testing to identify asymptomatic SARS-CoV-2 infection.

Background: Rapid antigen detection tests (Ag-RDT) for SARS-CoV-2 with emergency use authorization generally include a condition of authorization to evaluate the test's performance in asymptomatic individuals when used serially. We aim to describe a novel study design that was used to generate regulatory-quality data to evaluate the serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals. Methods: This prospective cohort study used a siteless, digital approach to assess longitudinal performance of Ag-RDT. Individuals over 2 years old from across the USA with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Participants throughout the mainland USA were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported. Key Results: A total of 7361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 US states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide. Conclusions: The digital site-less approach employed in the "Test Us At Home" study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19 and can be adapted across research disciplines to optimize study enrollment and accessibility.

Finding a Needle in a Haystack: Design and Implementation of a Digital Site-less Clinical Study of Serial Rapid Antigen Testing to Identify Asymptomatic SARS-CoV-2 Infection.

Background: Rapid antigen tests (Ag-RDT) for SARS-CoV-2 with Emergency Use Authorization generally include a condition of authorization to evaluate the test's performance in asymptomatic individuals when used serially. Objective: To describe a novel study design to generate regulatory-quality data to evaluate serial use of Ag-RDT in detecting SARS-CoV-2 virus among asymptomatic individuals. Design: Prospective cohort study using a decentralized approach. Participants were asked to test using Ag-RDT and molecular comparators every 48 hours for 15 days. Setting: Participants throughout the mainland United States were enrolled through a digital platform between October 18, 2021 and February 15, 2022. Ag-RDTs were completed at home, and molecular comparators were shipped to a central laboratory. Participants: Individuals over 2 years old from across the U.S. with no reported COVID-19 symptoms in the 14 days prior to study enrollment were eligible to enroll in this study. Measurements: Enrollment demographics, geographic distribution, and SARS-CoV-2 infection rates are reported. Key Results: A total of 7,361 participants enrolled in the study, and 492 participants tested positive for SARS-CoV-2, including 154 who were asymptomatic and tested negative to start the study. This exceeded the initial enrollment goals of 60 positive participants. We enrolled participants from 44 U.S. states, and geographic distribution of participants shifted in accordance with the changing COVID-19 prevalence nationwide. Limitations: New, complex workflows required significant operational and data team support. Conclusions: The digital site-less approach employed in the 'Test Us At Home' study enabled rapid, efficient, and rigorous evaluation of rapid diagnostics for COVID-19, and can be adapted across research disciplines to optimize study enrollment and accessibility.

Performance of Rapid Antigen Tests to Detect Symptomatic and Asymptomatic SARS-CoV-2 Infection.

Background: Performance of rapid antigen tests for SARS-CoV-2 (Ag-RDT) varies over the course of an infection, and their performance in screening for SARS-CoV-2 is not well established. We aimed to evaluate performance of Ag-RDT for detection of SARS-CoV-2 for symptomatic and asymptomatic participants. Methods: Participants >2 years old across the United States enrolled in the study between October 2021 and February 2022. Participants completed Ag-RDT and molecular testing (RT-PCR) for SARS-CoV-2 every 48 hours for 15 days. This analysis was limited to participants who were asymptomatic and tested negative on their first day of study participation. Onset of infection was defined as the day of first positive RT-PCR result. Sensitivity of Ag-RDT was measured based on testing once, twice (after 48-hours), and thrice (after 96 hours). Analysis was repeated for different Days Post Index PCR Positivity (DPIPP) and stratified based on symptom-status. Results: In total, 5,609 of 7,361 participants were eligible for this analysis. Among 154 participants who tested positive for SARS-CoV-2, 97 were asymptomatic and 57 had symptoms at infection onset. Serial testing with Ag-RDT twice 48-hours apart resulted in an aggregated sensitivity of 93.4% (95% CI: 89.1-96.1%) among symptomatic participants on DPIPP 0-6. Excluding singleton positives, aggregated sensitivity on DPIPP 0-6 for two-time serial-testing among asymptomatic participants was lower at 62.7% (54.7-70.0%) but improved to 79.0% (71.0-85.3%) with testing three times at 48-hour intervals. Discussion: Performance of Ag-RDT was optimized when asymptomatic participants tested three-times at 48-hour intervals and when symptomatic participants tested two-times separated by 48-hours.

Design and Preliminary Findings of Adherence to the Self-Testing for Our Protection From COVID-19 (STOP COVID-19) Risk-Based Testing Protocol: Prospective Digital Study.

BACKGROUND: Serial testing for SARS-CoV-2 is recommended to reduce spread of the virus; however, little is known about adherence to recommended testing schedules and reporting practices to health departments. OBJECTIVE: The Self-Testing for Our Protection from COVID-19 (STOP COVID-19) study aims to examine adherence to a risk-based COVID-19 testing strategy using rapid antigen tests and reporting of test results to health departments. METHODS: STOP COVID-19 is a 12-week digital study, facilitated using a smartphone app for testing assistance and reporting. We are recruiting 20,000 participants throughout the United States. Participants are stratified into high- and low-risk groups based on history of COVID-19 infection and vaccination status. High-risk participants are instructed to perform twice-weekly testing for COVID-19 using rapid antigen tests, while low-risk participants test only in the case of symptoms or exposure to COVID-19. All participants complete COVID-19 surveillance surveys, and rapid antigen results are recorded within the smartphone app. Primary outcomes include participant adherence to a risk-based serial testing protocol and percentage of rapid tests reported to health departments. RESULTS: As of February 2022, 3496 participants have enrolled, including 1083 high-risk participants. Out of 13,730 tests completed, participants have reported 13,480 (98.18%, 95% CI 97.9%-98.4%) results to state public health departments with full personal identifying information or anonymously. Among 622 high-risk participants who finished the study period, 35.9% showed high adherence to the study testing protocol. Participants with high adherence reported a higher percentage of test results to the state health department with full identifying information than those in the moderate- or low-adherence groups (high: 71.7%, 95% CI 70.3%-73.1%; moderate: 68.3%, 95% CI 66.0%-70.5%; low: 63.1%, 59.5%-66.6%). CONCLUSIONS: Preliminary results from the STOP COVID-19 study provide important insights into rapid antigen test reporting and usage, and can thus inform the use of rapid testing interventions for COVID-19 surveillance.

Comparison of Rapid Antigen Tests' Performance between Delta (B.1.61.7; AY.X) and Omicron (B.1.1.529; BA1) Variants of SARS-CoV-2: Secondary Analysis from a Serial Home Self-Testing Study.

Background: There is a need to understand the performance of rapid antigen tests (Ag-RDT) for detection of the Delta (B.1.61.7; AY.X) and Omicron (B.1.1.529; BA1) SARS-CoV-2 variants. Methods: Participants without any symptoms were enrolled from October 18, 2021 to January 24, 2022 and performed Ag-RDT and RT-PCR tests every 48 hours for 15 days. This study represents a non-pre-specified analysis in which we sought to determine if sensitivity of Ag-RDT differed in participants with Delta compared to Omicron variant. Participants who were positive on RT-PCR on the first day of the testing period were excluded. Delta and Omicron variants were defined based on sequencing and date of first RT-PCR positive result (RT-PCR+). Comparison of Ag-RDT performance between the variants was based on sensitivity, defined as proportion of participants with Ag-RDT+ results in relation to their first RT-PCR+ result, for different duration of testing with rapid Ag-RDT. Subsample analysis was performed based on the result of participants' second RT-PCR test within 48 hours of the first RT-PCR+ test. Results: From the 7,349 participants enrolled in the parent study, 5,506 met the eligibility criteria for this analysis. A total of 153 participants were RT-PCR+ (61 Delta, 92 Omicron); among this group, 36 (23.5%) tested Ag-RDT+ on the same day, and 84 (54.9%) tested Ag-RDT+ within 48 hours as first RT-PCR+. The differences in sensitivity between variants were not statistically significant (same-day: Delta 16.4% [95% CI: 8.2-28.1] vs Omicron 28.2% [95% CI: 19.4-38.6]; and 48-hours: Delta 45.9% [33.1-59.2] vs. Omicron 60.9% [50.1-70.9]). This trend continued among the 86 participants who had consecutive RT-PCR+ result (48-hour sensitivity: Delta 79.3% [60.3-92.1] vs. Omicron: 89.5% [78.5-96.0]). Conversely, the 38 participants who had an isolated RT-PCR+ remained consistently negative on Ag-RDT, regardless of the variant. Conclusions: The performance of Ag-RDT is not inferior among individuals infected with the SARS-CoV-2 Omicron variant as compared to the Delta variant. The improvement in sensitivity of Ag-RDT noted with serial testing is consistent between Delta and Omicron variant. Performance of Ag-RDT varies based on duration of RT-PCR+ results and more studies are needed to understand the clinical and public health significance of individuals who are RT-PCR+ for less than 48 hours.

Comparing recruitment strategies for a digital smoking cessation intervention: Technology-assisted peer recruitment, social media, ResearchMatch, and smokefree.gov.

BACKGROUND: Choosing the right recruitment strategy has implications for the successful conduct of a trial. Our objective was to compare a novel peer recruitment strategy to four other recruitment strategies for a large randomized trial testing a digital tobacco intervention. METHODS: We compared enrollment rates, demographic and baseline smoking characteristics, and odds of completing the 6-month study by recruitment strategy. Cost of recruitment strategies per retained participant was calculated using staff personnel time and advertisement costs. FINDINGS: We enrolled 1487 participants between August 2017 and March 2019 from: Peer recruitment n = 273 (18.4%), Facebook Ads n = 505 (34%), Google Ads = 200 (13.4%), ResearchMatch n = 356 (23.9%) and Smokefree.govn = 153 (10.3%). Mean enrollment rate per active recruitment month: 1) Peer recruitment, n = 13.9, 2) Facebook ads, n = 25.3, 3) Google ads, n = 10.51, 4) Research Match, n = 59.3, and 5) Smokefree.gov, n = 13.9. Peer recruitment recruited the greatest number of males (n = 110, 40.3%), young adults (n = 41, 14.7%), participants with a high school degree or less (n = 24, 12.5%) and smokers within one's social network. Compared to peer recruitment (retention rate = 57%), participants from Facebook were less likely (OR 0.46, p < 0.01, retention rate = 40%), and those from ResearchMatch were more likely to complete the study (OR 1.90, p < 0.01, retention rate = 70%). Peer recruitment was moderate in cost per retained participant ($47.18) and substantially less costly than Facebook ($173.60). CONCLUSIONS: Though peer recruitment had lower enrollment than other strategies, it may provide greater access to harder to reach populations and possibly others who smoke within one's social network while being moderately cost-effective. ClinicalTrials.gov: NCT03224520.

The Veterans Health Administration (VHA) Innovators Network: Evaluation design, methods and lessons learned through an embedded research approach.

BACKGROUND: Collaboration between researchers, implementers and policymakers improves uptake of health systems research. In 2018, researchers and VHA Innovators Network (iNET) leadership used an embedded research model to conduct an evaluation of iNET. We describe our evaluation design, early results, and lessons learned. METHODS: This mixed-methods evaluation incorporated primary data collection via electronic survey, descriptive analysis using existing VA datasets (examining associations between facility characteristics and iNET participation), and qualitative interviews to support real-time program implementation and to probe perceived impacts, benefits and challenges of participation. RESULTS: We developed reporting tools and collected data regarding site participation, providing iNET leadership rapid access to needed information on projects (e.g., target populations reached, milestones achieved, and barriers encountered). Secondary data analyses indicated iNET membership was greater among larger, more complex VA facilities. Of the 37 iNET member sites, over half (n = 22) did not have any of the six major types of VA research centers; thus iNET is supporting VA sites not traditionally served by research innovation pathways. Qualitative findings highlighted enhanced engagement and perceived value of social and informational networks. CONCLUSIONS: Working alongside our iNET partners, we supported and influenced iNET's development through our embedded evaluation's preliminary findings. We also provided training and guidance aimed at building capacity among iNET participants. IMPLICATIONS: Embedded research can yield successful collaborative efforts between researchers and partners. An embedded research team can help programs pivot to ensure effective use of limited resources. Such models inform program development and expansion, supporting strategic planning and demonstrating value.

Merging Implementation Practice and Science to Scale Up Promising Practices: The Veterans Health Administration (VHA) Diffusion of Excellence (DoE) Program.

INTRODUCTION: The Veterans Health Administration (VHA) Diffusion of Excellence (DoE) program developed and manages a framework for identification, replication, and diffusion of promising practices throughout the nation's largest integrated health care system. DoE identifies promising practices through a "Shark Tank" competition with winning bidders receiving external implementation facilitation. DoE further supports diffusion of successful practices across the VHA. METHODS: This article presents results of a mixed methods implementation evaluation of DoE, focusing on program reach, program participation and decisions to adopt innovative practices, implementation processes, and practice sustainment. Data sources include practice adoption metrics, focus groups with bidders (two focus groups), observations of DoE events (seven events), surveys of stakeholders (five separate surveys), and semistructured interviews of facility directors, practice developers, implementation teams, and facilitators (133 participants). RESULTS: In the first four Shark Tank cohorts (2016-2018), 1,676 practices were submitted; 47 were designated Gold Status Practices (practices with facilitated implementation). Motivation for participation varied. Generally, staff led projects targeting problems they felt passionate about, facility directors focused on big-picture quality metrics and getting middle manager support, and frontline staff displayed variable motivation to implement new projects. Approximately half of facilitated implementation efforts were successful; barriers included insufficient infrastructure, staff, and resources. At the facility level, 73.3% of facilities originating or receiving facilitated implementation support have maintained the practice. VHA-wide, 834 decisions to adopt these practices were made. CONCLUSION: DoE has resulted in the identification of many candidate practices, promoted adoption of promising practices by facility directors, and supported practice implementation and diffusion across the VHA.