A landscape assessment of CTSA evaluators and their work in the CTSA consortium, 2021 survey findings.

This article presents a landscape assessment of the findings from the 2021 Clinical and Translational Science Award (CTSA) Evaluators Survey. This survey was the most recent iteration of a well established, national, peer-led systematic snapshot of the CTSA evaluators, their skillsets, listed evaluation resources, preferred methods, and identified best practices. Three questions guided our study: who are the CTSA evaluators, what competencies do they share and how is their work used within hubs. We describe our survey process (logistics of development, deployment, and differences in historical context with prior instruments); and present its main findings. We provide specific recommendations for evaluation practice in two main categories (National vs Group-level) including, among others, the need for a national, strategic plan for evaluation as well as enhanced mentoring and training of the next generation of evaluators. Although based on the challenges and opportunities currently within the CTSA Consortium, takeaways from this study constitute important lessons with potential for application in other large evaluation consortia. To our knowledge, this is the first time 2021 survey findings are disseminated widely, to increase transparency of the CTSA evaluators' work and to motivate conversations within hub and beyond, as to how best to leverage existent evaluative capacity.

A behavioral economics approach to enhancing HIV preexposure and postexposure prophylaxis implementation.

PURPOSE OF REVIEW: The 'PrEP cliff' phenomenon poses a critical challenge in global HIV PrEP implementation, marked by significant dropouts across the entire PrEP care continuum. This article reviews new strategies to address 'PrEP cliff'. RECENT FINDINGS: Canadian clinicians have developed a service delivery model that offers presumptive PEP to patients in need and transits eligible PEP users to PrEP. Early findings are promising. This service model not only establishes a safety net for those who were not protected by PrEP, but it also leverages the immediate salience and perceived benefits of PEP as a natural nudge towards PrEP use. Aligning with Behavioral Economics, specifically the Salience Theory, this strategy holds potential in tackling PrEP implementation challenges. SUMMARY: A natural pathway between PEP and PrEP has been widely observed. The Canadian service model exemplifies an innovative strategy that leverages this organic pathway and enhances the utility of both PEP and PrEP services. We offer theoretical insights into the reasons behind these PEP-PrEP transitions and evolve the Canadian model into a cohesive framework for implementation.

Translation in action: Influence, collaboration, and evolution of COVID-19 research with Clinical and Translational Science Awards consortium support.

The National Institutes of Health (NIH)'s Clinical and Translational Science Awards (CTSA) consortium aims to accelerate translational processes that move discoveries from bench to bedside. The coronavirus disease 2019 (COVID-19) pandemic presented unmatched challenges and applications for CTSA hubs nationwide. Our study used bibliometrics to assess features of COVID-19 publications supported by the national CTSA program to characterize the consortium's response to the pandemic. Our goal was to understand relative scientific influence, collaboration across hubs, and trends in research emphasis over time. We identified publications from NIH's curated iSearch COVID-19 Publication Portfolio from February 2020 to February 2023; 3234 peer-reviewed articles relevant to COVID-19 cited a CTSA grant. All 66 CTSA hubs were represented, with large-size and longstanding hubs contributing more publications. Most publications cited UL1 grants, 457 cited KL2/TL1 training grants, and 164 cited multiple hub grants. Compared to a random sample of non-CTSA-supported COVID-19 publications, the CTSA portfolio exhibited greater clinical relevance, more human research, and higher altmetric and citation influence. Results were similar for multi-hub publications involving networked initiatives like multi-site clinical trials or the National COVID-19 Cohort Collaborative. Shifts from molecular/cellular-oriented research toward human-oriented research over time were evident, demonstrating translation in action. Results illuminate how the CTSA consortium confronted the pandemic through high-quality projects oriented toward human research, working across hubs on high-value collaborations, advancing along the translational spectrum over time. Findings validate CTSA hubs as critical support structures during health emergencies.

Pivot, persevere, or perish: how Ellume Health overcame development and regulatory obstacles to become the first authorized over-the-counter COVID-19 test in the United States.

The Ellume COVID-19 home test from Ellume Health (Brisbane, Aus) became the first COVID-19 diagnostic tool authorized for home use by the United States FDA in December 2020. This early pandemic success was built on over ten years of work on the Ellume influenza home test. Ellume overcame critical technology challenges during the development of their influenza test. In addition, it faced a recall of its COVID-19 home test in 2021 due to false positive results. While Ellume initially persevered through the recall and restarted sales in the United States, the combination of the recall and the wide availability of competitors' low-cost over the counter tests in the United States led to Ellume entering voluntary administration in September 2022. This paper traces the history of Ellume and how 10 years of experience with a home influenza test allowed the company to quickly develop the Ellume COVID-19 home test. We will also provide to diagnostic developers the key strategies employed by Ellume to succeed while highlighting the pitfalls that have challenged the company's business success.

The critical role of engineering in the rapid development of COVID-19 diagnostics: Lessons from the RADx Tech Test Verification Core.

Engineering plays a critical role in the development of medical devices, and this has been magnified since 2020 as severe acute respiratory syndrome coronavirus 2 swept over the globe. In response to the coronavirus disease 2019, the National Institutes of Health launched the Rapid Acceleration of Diagnostics (RADx) initiative to help meet the testing needs of the United States and effectively manage the pandemic. As the Engineering and Human Factors team for the RADx Tech Test Verification Core, we directly assessed more than 30 technologies that ultimately contributed to an increase of the country's total testing capacity by 1.7 billion tests to date. In this review, we present central lessons learned from this "apples-to-apples" comparison of novel, rapidly developed diagnostic devices. Overall, the evaluation framework and lessons learned presented in this review may serve as a blueprint for engineers developing point-of-care diagnostics, leaving us better prepared to respond to the next global public health crisis rapidly and effectively.

Translating Scientific Discovery Into Health Policy Impact: Innovative Bibliometrics Bridge Translational Research Publications to Policy Literature.

To understand how translational science efforts lead to outcomes, it is common to examine publications as a key step in the translational process. The National Institutes of Health's Clinical and Translational Science Awards (CTSA) program aims to accelerate that process by providing support to investigators. Although it is challenging to measure the impact of such support on translational outcomes, CTSA-supported research that arises in research publications can advance translation through use of these publications in public policy and guideline documents from government health agencies, intergovernmental organizations, and other outlets. Using cutting-edge bibliometric tools, the authors evaluated how CTSA-supported research has extended its impact beyond academic silos to influence public policy literature. The authors identified approximately 118,490 publications that acknowledged receiving support from a CTSA hub, from the inception of the program in 2006 through 2021. Articles were queried in the Overton policy database, which indexes references to publications in global policy literature. The search revealed 13% of CTSA-supported articles were referenced in policy documents, significantly more than the expected proportion (10%) calculated by Overton. References came from 576 policy source outlets across 87 countries, predominantly the United States and Europe. The most frequent sources included guidelines in PubMed Central, the World Health Organization, and the Centers for Disease Control and Prevention. The authors illustrate the bridge from translational research to public policy with case studies of 6 articles based on CTSA-supported research and having notable policy impact. They found articles with greater clinical relevance, altmetric attention (i.e., nonacademic community/public attention), and academic citation influence were more likely to be referenced in policy literature. Study findings help to characterize the kinds of research that have influenced and may be expected to influence health policy in the future.

Severe acute respiratory syndrome coronavirus 2 vaccine breakthrough infections: A single metro-based testing network experience.

Objectives: Understanding the incidence and characteristics that influence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infections (VBIs) is imperative for developing public health policies to mitigate the coronavirus disease of 2019 (COVID-19) pandemic. We examined these factors and post-vaccination mitigation practices in individuals partially and fully vaccinated against SARS-CoV-2. Materials and methods: Adults >18 years old were voluntarily enrolled from a single metro-based SARS-CoV-2 testing network from January to July 2021. Participants were categorized as asymptomatic or symptomatic, and as unvaccinated, partially vaccinated, or fully vaccinated. All participants had confirmed SARS-CoV-2 infection based on standard of care (SOC) testing with nasopharyngeal swabs. Variant analysis by rRT-PCR was performed in a subset of time-matched vaccinated and unvaccinated individuals. A subgroup of partially and fully vaccinated individuals with a positive SARS-CoV-2 rRT-PCR was contacted to assess disease severity and post-vaccination mitigation practices. Results: Participants (n = 1,317) voluntarily underwent testing for SARS-CoV-2 during the enrollment period. A total of 29.5% of the population received at least one SARS-CoV-2 vaccine (n = 389), 12.8% partially vaccinated (n = 169); 16.1% fully vaccinated (n = 213). A total of 21.3% of partially vaccinated individuals tested positive (n = 36) and 9.4% of fully vaccinated individuals tested positive (n = 20) for SARS-CoV-2. Pfizer/BioNTech mRNA-1273 was the predominant vaccine received (1st dose = 66.8%, 2nd dose = 67.9%). Chronic liver disease and immunosuppression were more prevalent in the vaccinated (partially/fully) group compared to the unvaccinated group (p = 0.003, p = 0.021, respectively). There were more asymptomatic individuals in the vaccinated group compared to the unvaccinated group [n = 6 (10.7%), n = 16 (4.1%), p = 0.045]. CT values were lower for the unvaccinated group (median 24.3, IQR 19.1-30.5) compared to the vaccinated group (29.4, 22.0-33.7, p = 0.004). In the vaccinated group (n = 56), 18 participants were successfully contacted, 7 were lost to follow-up, and 2 were deceased. A total of 50% (n = 9) required hospitalization due to COVID-19 illness. Adherence to nationally endorsed mitigation strategies varied post-vaccination. Conclusion: The incidence of SARS-CoV-2 infection at this center was 21.3% in the partially vaccinated group and 9.4% in the fully vaccinated group. Chronic liver disease and immunosuppression were more prevalent in the vaccinated SARS-CoV-2 positive group, suggesting that these may be risk factors for VBIs. Partially and fully vaccinated individuals had a higher incidence of asymptomatic SARS-CoV-2 and higher CT values compared to unvaccinated SARS-CoV-2 positive individuals.

Don't forget about human factors: Lessons learned from COVID-19 point-of-care testing.

During the COVID-19 pandemic, the development of point-of-care (POC) diagnostic testing accelerated in an unparalleled fashion. As a result, there has been an increased need for accurate, robust, and easy-to-use POC testing in a variety of non-traditional settings (i.e., pharmacies, drive-thru sites, schools). While stakeholders often express the desire for POC technologies that are "as simple as digital pregnancy tests," there is little discussion of what this means in regards to device design, development, and assessment. The design of POC technologies and systems should take into account the capabilities and limitations of the users and their environments. Such "human factors" are important tenets that can help technology developers create POC technologies that are effective for end-users in a multitude of settings. Here, we review the core principles of human factors and discuss lessons learned during the evaluation process of SARS-CoV-2 POC testing.

Big splashes & ripple effects: a narrative review of the short- & long-term impact of publications supported by an NIH CTSA pediatrics program.

Background and Objective: This review examines a promising new framework for analyzing outputs of pediatric research in the context of translational advancement. We demonstrate a method for evaluating the impact of an NIH Clinical and Translational Science Award's (CTSA) Pediatrics Program through publications that have emerged from supported research. The Georgia CTSA Pediatrics Program provides training, funding, and infrastructure to ensure that researchers have the resources to advance pediatric health. Internal evaluations found that research supported by this program is exceptionally impactful within the academic community and commands high interest within the lay community. Therefore, we examined the impact of this research in both traditional academic and broader community spheres using bibliometrics-the study of supported publications. Bibliometrics describe a pivotal stage in the translational process of bringing scientific discoveries to clinical/community use and include both academic citations and 'altmetric' or non-academic attention. These complementary approaches combine to shed light on the short- and long-term impact of the research on segments of the translational pipeline, including academic literature, community discourse, technological advancement, and public health policy. Methods: The authors identified a portfolio of 250 articles supported by the Georgia CTSA Pediatrics Program from 2007-2020. We utilized various bibliometrics to analyze both short-term attention, or 'splash' made by articles, and long-term influence, or 'ripples' made across both academic and public spheres. Key Content and Findings: The short-term splash of the portfolio was indicated through publication in high-impact factor journals, peer faculty recommendations, and Mendeley readership, as well as by early altmetric attention in news stories, blogs, and Twitter posts. The portfolio's long-term ripples were demonstrated by high absolute and relative rates of academic citation and by downstream altmetric influence in public-facing documents, including Wikipedia articles, patent applications, and policy documents. Conclusions: This article reviews a useful bibliometric methodology for illustrating the waves of impact made by pediatric research. Whereas splash provides a picture of early interest in a publication, a preliminary indicator of eventual utility and impact, ripples provide a measure of the cumulative influence of an article over time. Both reflect opportunities for a line of research to advance along the translational spectrum.

Designing for simplicity: lessons from Mesa Biotech for microfluidic entrepreneurs and early-stage companies.

The COVID-19 pandemic has proven the need for point-of-care diagnosis of respiratory diseases and microfluidic technology has risen to the occasion. Mesa Biotech (San Diego, CA) originally developed the Accula platform for the diagnosis of influenza A and B and then extended the platform to SARS-CoV-2. Mesa Biotech has experienced tremendous success, culminating in acquisition by Thermo Fisher for up to $550m USD. The Accula microfluidics platform accomplished the leap from the lab to commercial product through clever design and engineering choices. Through information obtained from interviews with key Mesa Biotech leaders and publicly-available documents, we describe the keys to Mesa's success and how they might inform other lab-on-a-chip companies.

Flourishing in Healthcare Trainees: Psychological Well-Being and the Conserved Transcriptional Response to Adversity.

While much attention has been paid to healthcare provider and trainee burnout, less is known about provider well-being (i.e., flourishing) or about the effects of well-being on immune function. This study examined the demographic and psycho-social correlates of well-being among healthcare trainees (resident physicians and physician assistant (PA) trainees) and evaluated the association of well-being with the "conserved transcriptional response to adversity" (CTRA) characterized by up-regulated expression of pro-inflammatory genes and down-regulated expression of innate antiviral genes. Participants (n = 58) completed self-reported assessments of sleep disturbance, loneliness, depressive symptoms, anxiety, stress, and well-being (flourishing). Blood sample RNA profiles were analyzed by RNA sequencing to assess the CTRA. Slightly over half (n = 32; 55.2%) of healthcare trainees were categorized as flourishing. Flourishing was less prevalent among primary caregivers, and more prevalent among trainees who exercised more frequently and those with fewest days sick. Loneliness (AOR = 0.75; 95% CI = 0.61, 0.91; p = 0.003) and stress (AOR = 0.65; 95% CI = 0.45, 0.94; p = 0.02) were associated with decreased odds of flourishing when controlling for other variables. Flourishing was associated with down-regulated CTRA gene expression, whereas loneliness was associated with up-regulated CTRA gene expression (both p < 0.05). Assessing these relationships in a larger, multi-site study is of critical importance to inform policy, curricula, and interventions to bolster sustainable trainee well-being.

Predicting citation impact from altmetric attention in clinical and translational research: Do big splashes lead to ripple effects?

Publications are commonly used to evaluate the productivity and impact of research programs. Traditional metrics examine publication impact through slowly accumulating academic citations. "Altmetrics" are a new way to describe early publication influence in nonacademic media/community spheres (news, tweets, and blogs). Articles with significant altmetric attention make a big splash of immediate impact, whereas papers with high rates of academic citation reflect ripple effects of influence over time. Past research has found weak associations between altmetrics and academic citations. However, no previous research has focused on clinical/translational research, which aims to translate scientific discoveries to public use. Further, no previous research has assessed the relationship between altmetrics and modern citation impact factors like the National Institutes of Health (NIH)'s Relative Citation Ratio (RCR). It is also unclear whether publication in journals with higher journal impact factors (JIFs) may drive both public attention and academic impact. We investigated whether early altmetric indicators of splash predict citation ripples, beyond the effect of the JIF. For a portfolio of 2188 publications supported by the NIH's Georgia Clinical and Translational Science Alliance from 2007-2020, we collected 2020 Altmetric Attention Scores (AAS), 2020 JIFs, and 2021 RCRs. All three were significantly correlated with one another. Regression analyses revealed that AAS significantly predicts later RCR, controlling for JIF and publication year. Findings indicate that in clinical/translational science, articles that make a big splash of altmetric attention have ripple effects through increased citation influence, which is not entirely due to publication in higher impact journals. Altmetric attention may be a useful early indicator of eventual influence and potential for translational advancement.

Use and Perceptions of Opioids Versus Marijuana among Cancer Survivors.

Public health concerns regarding opioids and marijuana have implications for their medical use. This study examined use motives and perceived barriers in relation to opioid and marijuana use and interest in use among US adult cancer survivors. Self-administered surveys were distributed using social media to assess use motives and perceived barriers among participants living with cancer. Overall, 40.9% of cancer survivors reported current (past 30-day) use of opioids, 42.5% used marijuana, and 39.7% used both. The most common use motives for either/both drugs were to cope with pain and stress/anxiety (>70%). Highest-rated barriers to using either/both drugs were missing symptoms of worsening illness and not wanting to talk about their symptoms. Controlling for sociodemographics, binary logistic regression indicated that current opioid use was associated with reporting greater barriers to use (OR = 1.17, p = .011; Nagelkerke R-square = .934) and that current marijuana use was associated with reporting greater barriers to use (OR = 1.37, p = .003; Nagelkerke R-square = .921). Cancer survivors report various use motives and barriers to use regarding opioids and marijuana. While use motives and barriers for both drugs were similar, these constructs were differentially associated with use and interest in use across drugs. Understanding patients' perceptions about opioids and marijuana is an essential component to effectively manage symptoms related to a cancer diagnosis and improve quality of life for cancer survivors.

Multidisciplinary assessment of the Abbott BinaxNOW SARS-CoV-2 point-of-care antigen test in the context of emerging viral variants and self-administration.

While there has been significant progress in the development of rapid COVID-19 diagnostics, as the pandemic unfolds, new challenges have emerged, including whether these technologies can reliably detect the more infectious variants of concern and be viably deployed in non-clinical settings as "self-tests". Multidisciplinary evaluation of the Abbott BinaxNOW COVID-19 Ag Card (BinaxNOW, a widely used rapid antigen test, included limit of detection, variant detection, test performance across different age-groups, and usability with self/caregiver-administration. While BinaxNOW detected the highly infectious variants, B.1.1.7 (Alpha) first identified in the UK, B.1.351 (Beta) first identified in South Africa, P.1 (Gamma) first identified in Brazil, B.1.617.2 (Delta) first identified in India and B.1.2, a non-VOC, test sensitivity decreased with decreasing viral loads. Moreover, BinaxNOW sensitivity trended lower when devices were performed by patients/caregivers themselves compared to trained clinical staff, despite universally high usability assessments following self/caregiver-administration among different age groups. Overall, these data indicate that while BinaxNOW accurately detects the new viral variants, as rapid COVID-19 tests enter the home, their already lower sensitivities compared to RT-PCR may decrease even more due to user error.

The RADx Tech Test Verification Core and the ACME POCT in the Evaluation of COVID-19 Testing Devices: A Model for Progress and Change.

Faced with the COVID-19 pandemic, the US system for developing and testing technologies was challenged in unparalleled ways. This article describes the multi-institutional, transdisciplinary team of the "RADxSM Tech Test Verification Core" and its role in expediting evaluations of COVID-19 testing devices. Expertise related to aspects of diagnostic testing was coordinated to evaluate testing devices with the goal of significantly expanding the ability to mass screen Americans to preserve lives and facilitate the safe return to work and school. Focal points included: laboratory and clinical device evaluation of the limit of viral detection, sensitivity, and specificity of devices in controlled and community settings; regulatory expertise to provide focused attention to barriers to device approval and distribution; usability testing from the perspective of patients and those using the tests to identify and overcome device limitations, and engineering assessment to evaluate robustness of design including human factors, manufacturability, and scalability.

Participant perspectives on a seminar-based research career development program and its role in career independence.

Health science researchers need training and support to effectively pursue independence in their research careers. Little data exist regarding the specific resources that faculty researchers have found or would find useful. In this study, we aimed to better understand the needs of health science researchers to develop recommendations for effective career development programming. The authors conducted a multi-method evaluation of early-career researcher faculty needs beginning by using post-session satisfaction surveys to assess the value of a long-standing "K-Club" seminar, which educates and supports those pursuing NIH Career Development (K) awards or similar. The authors then collected in-depth views on career development needs through a series of focus groups conducted with health science researchers at three career stages: early career, award-seeking junior faculty; mid-career faculty who have obtained some extramural funding; senior faculty who serve as mentors for early/mid-career faculty. Participants who attended the existing K-Club strongly endorse the program in supporting their career goals. Focus group participants described specific areas for program expansion that would add value across career stages: more flexible training options, conducted in smaller group settings with immediate feedback provided; more formalized training and resources for senior research mentors; in-depth guidance on individualized grantsmanship. The authors propose program development guidelines for helping researchers achieve research independence and success. Findings indicate that a broad-reaching K-Club style educational seminar can serve as a valuable foundation supporting professional development. The addition of tailored programs delivered across diverse platforms are predicted to heighten career development success.

Preventive care and medical homes among US children with heart conditions.

Within a medical home, primary care providers can identify needs, provide services, and coordinate care for children with heart conditions. Using parent-reported data from the 2016-2017 National Survey of Children's Health, we examined receipt of preventive care in the last 12 months and having a medical home (care that is accessible, continuous, comprehensive, family-centred, coordinated, compassionate, and culturally effective) among US children aged 0-17 years with and without heart conditions. Using the marginal predictions approach to multivariable logistic regression, we examined associations between presence of a heart condition and receipt of preventive care and having a medical home. Among children with heart conditions, we evaluated associations between sociodemographic and health characteristics and receipt of preventive care and having a medical home. Of the 66,971 children included, 2.2% had heart conditions. Receipt of preventive care was reported for more children with heart conditions (91.0%) than without (82.7%) (adjusted prevalence ratio = 1.09, 95% confidence interval: 1.05-1.13). Less than half of children with heart conditions (48.2%) and without (49.5%) had a medical home (adjusted prevalence ratio = 1.02, 95% confidence interval: 0.91-1.14). For children with heart conditions, preventive care was slightly more common among younger children and less common among those with family incomes 200-399% of the federal poverty level. Having a medical home was less common among younger children, non-Hispanic "other" race, and those with ≥2 other health conditions. Most children with heart conditions received preventive care, but less than half had a medical home, with disparities by age, socioeconomic status, race, and concurrent health conditions. These findings highlight opportunities to improve care for children with heart conditions.