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.

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.

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.

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.

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.

Insufficient tuberculosis treatment leads to earlier and higher mortality in individuals co-infected with HIV in southern China: a cohort study.

BACKGROUND: Tuberculosis (TB) and Acquired Immune Deficiency Syndrome (AIDS) are leading causes of death globally. However, little is known about the long-term mortality risk and the timeline of death in those co-infected with human immunodeficiency virus (HIV) and Mycobacterium tuberculosis (MTB). This study sought to understand the long-term mortality risk, factors, and the timeline of death in those with HIV-Mycobacterium tuberculosis (MTB) coinfection, particularly in those with insufficient TB treatment. METHODS: TB-cause specific deaths were classified using a modified 'Coding of Cause of Death in HIV' protocol. A longitudinal cross-registration-system checking approach was used to confirm HIV/MTB co-infection between two observational cohorts. Mortality from the end of TB treatment (6 months) to post-treatment year (PTY) 5 (60 months) was investigated by different TB treatment outcomes. General linear models were used to estimate the mean mortality at each time-point and change between time-points. Cox's proportional hazard regressions measured the mortality hazard risk (HR) at each time-point. The Mantel-Haenszel stratification was used to identify mortality risk factors. Mortality density was calculated by person year of follow-up. RESULTS: At the end point, mortality among patients with HIV/MTB coinfection was 34.7%. From the end of TB treatment to PTY5, mortality and loss of person years among individuals with TB treatment failure, missing, and adverse events (TBFMA) were significantly higher than those who had TB cure (TBC) and TB complete regimen (TBCR). Compared to individuals with TBC and with TBCR, individuals with TBFMA tended to die earlier and their mortality was significantly higher (HRTBFMA-TBC = 3.0, 95% confidence interval: 2.5-3.6, HRTBFMA-TBCR = 2.9, 95% CI: 2.5-3.4, P < 0.0001). Those who were naïve to antiretroviral therapy, were farmers, had lower CD4 counts (≤200 cells/µL) and were ≥ 50 years of age were at the highest risk of mortality. Mortality risk for participants with TBFMA was significantly higher across all stratifications except those with a CD4 count of ≤200 cells/µL. CONCLUSIONS: Earlier and long-term mortality among those with HIV/MTB co-infection is a significant problem when TB treatment fails or is inadequate.

Do the same socio-demographic variables predict testing uptake and sero-status? HIV and syphilis among an observational sample of Chinese men who have sex with men in Shanghai, China.

HIV and syphilis are pronounced among men who have sex with men (MSM) in China and often occur as co-infections, while testing remains low. Few studies examine common predictors across these outcomes. This observational venue-based sample of 546 MSM in Shanghai, China used a common set of psychosocial predictors to construct logistic models for the outcomes (HIV non-testing, syphilis non-testing, HIV sero-status, and syphilis sero-status). Fifty-seven (10.7%) participants tested positive for HIV, 126 (23.5%) for syphilis, and 33% of HIV-positive participants had a co-infection. Non-sex working MSM had consistently higher odds of HIV and syphilis non-testing (OR= 2.2, 95% CI 1.4-3.5, p < 0.001; OR = 2.4, 95, 95% CI 1.5-3.8, p < 0.001, respectively) compared to 'money boy' sex workers. Participants with a 0 score on HIV knowledge had 4.1 times (95% CI 1.4-12.5, p = 0.01) the odds of reporting HIV non-testing, 6.0 (95% CI 1.96-18.5, p < 0.01) times the odds of reporting non-testing for syphilis, and 8.44 times (95% CI 1.19-59.7, p = 0.03) the odds of testing positive for HIV, compared to a score of 8. The results highlighted the importance of integrating HIV/syphilis education and promoting testing for both HIV and syphilis among all sub-groups of MSM in China.

Vietnamese female sex workers in rural cross-border areas of Guangxi, China: migration and HIV/STI risk behaviors.

China's HIV/AIDS epidemic continues to grow in rural and less developed areas. This consecutive cross-sectional study examines demographic and behavioral factors associated with HIV/STI infection, Hepatitis C (HCV) and other sexually transmitted infections (STIs) among Vietnamese female sex workers (FSW), a vulnerable population who cross into Guangxi, China. This study is a secondary data analysis of 303 Vietnamese and 4,348 Chinese FSWs recruited over seven years from two Chinese counties that border Vietnam. Logistic regression models compared demographics, HIV/STI status, HIV/AIDS-related knowledge, attitudes, and risk behaviors between Vietnamese FSWs and Chinese FSWs. Compared with Chinese FSWs, Vietnamese FSWs were younger, had attained lower education levels, were highly mobile, more likely to report using drugs, and were more vulnerable to HIV/STIs. Younger age, less educational attainment, shorter time in their current working location, no voluntary HIV testing in the last year, greater drug use, and not using condoms for all commercial sex in the last month were associated with higher HIV/STIs. In conclusion, several factors were associated with HIV/STI risk in Vietnamese cross-border FSWs. There is a pressing need to improve support systems for Vietnamese cross-border FSW and health system cooperation across the Chinese/Vietnamese border.

A Bibliometric Measure of Translational Science.

Science funders are increasingly requiring evidence of the broader impacts of even basic research. Initiatives such as NIH's CTSA program are designed to shift the research focus toward more translational research. However, tracking the effectiveness of such programs depends on developing indicators that can track the degree to which basic research is influencing clinical research. We propose a new bibliometric indicator, the TS score, that is relatively simple to calculate, can be implemented at scale, is easy to replicate, and has good reliability and validity properties. This indicator is broadly applicable in settings where the goal is to estimate the degree to which basic research is used in more applied downstream research, relative to use in basic research. The TS score should be of use for a variety of policy analysis and research evaluation purposes.

Scope, Influence, and Interdisciplinary Collaboration: The Publication Portfolio of the NIH Clinical and Translational Science Awards (CTSA) Program From 2006 Through 2017.

The Clinical and Translational Science Awards (CTSA) program sponsors an array of innovative, collaborative research. This study uses complementary bibliometric approaches to assess the scope, influence, and interdisciplinary collaboration of publications supported by single CTSA hubs and those supported by multiple hubs. Authors identified articles acknowledging CTSA support and assessed the disciplinary scope of research areas represented in that publication portfolio, their citation influence, interdisciplinary overlap among research categories, and characteristics of publications supported by multihub collaborations. Since 2006, CTSA hubs supported 69,436 articles published in 4,927 journals and 189 research areas. The portfolio is well distributed across diverse research areas with above-average citation influence. Most supported publications involved clinical/health sciences, for example, neurology and pediatrics; life sciences, for example, neuroscience and immunology; or a combination of the two. Publications supported by multihub collaborations had distinct content emphasis, stronger citation influence, and greater interdisciplinary overlap. This study characterizes the CTSA consortium's contributions to clinical and translational science, identifies content areas of strength, and provides evidence for the success of multihub collaborations. These methods lay the foundation for future investigation of the best policies and priorities for fostering translational science and allow hubs to understand their progress benchmarked against the larger consortium.

Effects of cotrimoxazole prophylaxis on Talaromyces marneffei infection in HIV/AIDS patients receiving antiretroviral therapy: a retrospective cohort study.

The dimorphic fungus Talaromyces marneffei (TM) is a common cause of HIV-associated opportunistic infections in Southeast Asia. Cotrimoxazole (CTX) inhibits folic acid synthesis which is important for the survival of many bacteria, protozoa, and fungi and has been used to prevent several opportunistic infections among HIV/AIDS patients. We question whether CTX is effective in preventing TM infection. To investigate this question, we conducted an 11-year (2005-2016) retrospective observational cohort study of all patients on the Chinese national antiretroviral therapy (ART) programme in Guangxi, a province with high HIV and TM burden in China. Survival analysis was conducted to investigate TM cumulative incidence, and Cox regression and propensity score matching (PSM) were used to evaluate the effect of CTX on TM incidence. Of the 3359 eligible individuals contributing 10,504.66 person-years of follow-up, 81.81% received CTX within 6 months after ART initiation, and 4.73% developed TM infection, contributing 15.14/1,000 person-year TM incidence rate. CTX patients had a significantly lower incidence of TM infection than non-CTX patients (4.11% vs. 7.53%; adjusted hazard ratio (aHR) = 0.50, 95% CI 0.35-0.73). CTX reduced TM incidence in all CD4+ cell subgroups (<50 cells/µL, 50-99 cells/µL, 100-199 cells/µL), with the highest reduction observed in patients with a baseline CD4+ cell count <50 cells/µL in both Cox regression and the PSM analyses. In conclusion, in addition to preventing other HIV-associated opportunistic infections, CTX prophylaxis has the potential to prevent TM infection in HIV/AIDS patients receiving ART.

Population HIV transmission risk for serodiscordant couples in Guangxi, Southern China: A cohort study.

We evaluated the risk of human immunodeficiency virus (HIV) transmission among serodiscordant couples with low adherence to antiretroviral therapy (ART).Data of heterosexual couples/partners in 2010 were extracted from an Internet-based system. Participants were then followed over the course of a year with 6- and 12-month assessments. Prevalence and density of HIV seroconversion were calculated for spouses/partners who did not have a positive HIV test results at baseline. We calculated the transmission odds ratio (OR) value stratified by personal characteristics and behavioral correlates at 6- and 12-month follow-up, as well as seroconversion in spouses/partners over the year.A total of 5544 HIV/AIDS patients and their spouses/partners were recruited in this cohort. Incidence of HIV seroconversion among HIV-negative spouse/partner was 63.7/100 person years (PYs) (430/674.9) at the 6-month follow-up and 33.2/100PYs (567/1707.1PYs) at 12 months. The OR value of transmission from female to male was 2.1 times higher than from male to females at 6 months and 2.3 times higher at 12 months (P < .001). The 55- to 64-year age group was most likely to transmit HIV to their spouses/partners, 2.2 times greater than the participants who were 65 years and older. Married participants were 2.4 times higher at 6 months and 2.5 times higher at 12 months to transmit HIV than divorced/widowed participants. Lastly, transmission among illiterate participants was 6.7 times higher at 6 months and 2.3 times higher at 12 months than those with an educational attainment of community college or above.High HIV seroconversion was observed in this cohort. Spouses/partners who were male had the highest risk of HIV acquisition; those aged 55 to 64 years, having married status, and are HIV-positive with less education were more likely to transmit HIV.

HIV prevalence among female sex workers in Guigang City, Guangxi, China: an 8-year consecutive cross-sectional study.

BACKGROUND: Female sex workers (FSW) are a population that are at high risk for HIV infection, and their HIV/AIDS knowledge levels and sexual behaviors are of concern. This study describes changes in HIV prevalence and factors associated among female sex workers in Guigang City, Guangxi, one of the highest HIV prevalence areas in China. METHODS: Data were derived from an annual cross-sectional venue-based survey, 2008 to 2015, in the form of sentinel surveillance. The participants were recruited using cluster sampling. FSW aged 16 years and above who completed a questionnaire and HIV testing. Both descriptive and multi-level analyses were used to explore factors associated with changes in HIV prevalence. RESULTS: Seven thousand four hundred ninety-six FSW were recruited in this study. HIV prevalence among FSW in Guigang City fell into two periods, one with an increasing trend (2008-2011) and one with a decline (2012-2015). Differences between these time periods included age, relationship status, HIV knowledge, consistent condom use, lifetime illicit drug use, history of sexually transmitted infection in the past year, HIV testing, receipt of a condom distribution and education program or HIV counseling and testing, and peer education services. CONCLUSIONS: Since 2012, a reduction in HIV prevalence among FSW in Guigang City has been observed. The decline of HIV prevalence was associated with coinciding changes in demographic characteristics of FSW, improvement of HIV knowledge and safer sexual behaviors, and a program that promotes condom use, HIV counseling & testing, and peer education.