The impact of COVID-19 on pragmatic clinical trials: lessons learned from the NIH Health Care Systems Research Collaboratory.

BACKGROUND: The COVID-19 pandemic has considerably disrupted nearly all aspects of daily life, including healthcare delivery and clinical research. Because pragmatic clinical trials are often embedded within healthcare delivery systems, they may be at high risk of disruption due to the dual impacts on the conduct of both care and research. METHODS: We collected qualitative data using multiple methods to characterize the impact of COVID-19 on the research activities of 14 active pragmatic clinical trials in the National Institutes of Health (NIH) Health Care Systems Research Collaboratory. A COVID-19 impact questionnaire was administered electronically to principal investigators in June 2020. Text responses were analyzed thematically, and qualitative summaries were subsequently reviewed by five independent reviewers, who made iterative revisions. Additional COVID-19-related impacts were identified during virtual meetings with trial teams during April-July 2020 and combined with questionnaire responses for analysis. RESULTS: Impacts of the pandemic were broadly classified into two main types: healthcare operations and social distancing. In some instances, trial delays created statistical challenges, particularly with trials using stepped-wedge designs, and necessitated changing data collection strategies or modifying interventions. The majority of projects used existing stakeholder-driven approaches to adapt interventions. Several benefits of these adaptions were identified, including expanded outreach capabilities and ability to study virtual intervention delivery. All trial teams were able to adapt to pandemic-related modifications. CONCLUSION: In a group of 14 ongoing pragmatic clinical trials, there was significant impact of COVID-19 on trial activities. Engaging appropriate stakeholders was critical to designing and implementing trial modifications and making continued safe progress toward meeting research objectives.

Perspectives From the National Institutes of Health on Multidimensional Mental Health Disparities Research: A Framework for Advancing the Field.

Racial, ethnic, and other mental health disparities have been documented for several decades. However, progress in reducing or eliminating these disparities has been slow. In this review, the authors argue that understanding and addressing mental health disparities requires using a multidimensional lens that encompasses a wide array of social determinants of health at individual, interpersonal, organizational, community, and societal levels. However, much of the current research on mental health disparities, including research funded by the National Institutes of Health, is characterized by a narrower focus on a small number of determinants. The authors offer a research framework, adapted from the National Institute on Minority Health and Health Disparities Research Framework, that provides examples of determinants that may cause or sustain mental health disparities and that can serve as intervention targets to reduce those disparities. They also discuss different types of mental health disparities research to highlight the need for more research testing and implementing interventions that directly modify social determinants of health and promote mental health equity.

[The feasibility analysis of multi-slice spiral CT features of gastric stromal tumors in predicting pathological National Institutes of Health risk classification].

Objective: To investigate the feasibility of multi-slice spiral CT(MSCT) imaging features of gastric stromal tumor (GST) in predicting pathological NIH risk classification, providing imaging basis for patients with GST before treatment. Methods: The clinical and CT imaging data of 504 patients(506 GST lesions), 259males and 245 females, aged from 13 to 85(60±11) years, with GST confirmed by surgery and pathology collected in the Zhongshan Hospital Affiliated to Fudan University and the Affiliated TCM Hospital of Southwest Medical University. According to pathological NIH risk classification, 506 lesions were divided into low risk group (very low and low risk degree, 277 lesions) and high risk group (medium and high risk degree, 229 lesions).Clinical data and imaging characteristics were compared between two groups. Multivariate logistic regression analysis was performed to screen out independent risk factors for statistically significant imaging indicators. Receiver operating curve (ROC) was used to evaluate the predictive value of tumor length for risk classification. Resulst: Between low risk group and high risk group,there were significant differences in gender(male/female:131/146 vs 129/100), gastrointestinal bleeding(present/absent:39/238 vs 59/170), morphology(regular/Irregular:218/59 vs 95/134), calcification(present/absent:36/241 vs 53/176), degree of necrosis(0°/Ⅰ°/Ⅱ°/Ⅲ°:197/61/16/3 vs 58/98/32/41), ulceration(present/absent:32/245 vs 94/135), growth pattern(endophytic/exophytic/mixed:102/105/70 vs 44/98/87), tumor location(fundus/cardia/body/angle/antrum:98/7/135/12/25 vs 98/6/114/5/6), feeding artery(present/absent:32/245 vs 104/125), vascular enhancement(present/absent:19/258 vs 88/141), effusion of around the disease(present/absent:0/277 vs 13/216), positive sign of fat around the disease(present/absent:0/277 vs 30/199),maximum long diameter[2.82(2.04,3.80) cm vs 5.93(4.06,8.29) cm] and short diameter [2.31(1.60,2.88) cm vs 4.40(3.21,6.37) cm]of tumor(all P<0.05).The maximum long diameter of tumor (OR=2.08,95%CI:1.35-3.20) and ulceration positive(OR=2.01,95%CI:1.03-3.92) were independent risk factors of risk classification(all P<0.05).Gastric antrum was used as the reference for tumor location, gastric fundus(OR=7.77,95%CI:2.00-30.24) and gastric body(OR=3.93,95%CI:1.03-15.01) were independent risk factors of risk classification(all P<0.05).The area under curve(AUC) of the maximum long diameter of tumor for predicting risk classification was 0.87, and the optimal critical value, sensitivity and specificity were 4.98cm, 62.9% and 95.3% respectively. Conclusions: MSCT image features of GST had certain characteristics. MSCT has certain predictive value for pathological NIH risk classification of GST, which can provide certain imaging basis for patients before treatment.

LitCovid, iSearch COVID-19 portfolio, and COVID-19 Global literature on coronavirus disease.

LitCovid. National Center for Biotechnology Information, US National Library of Medicine, 8600 Rockville Pike, Bethesda, MD 20894; https://www.ncbi.nlm.nih.gov/research/coronavirus/; free. iSearch COVID-19 portfolio. Office of Portfolio Analysis, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892; https://icite.od.nih.gov/covid19/search/; free. COVID-19 Global literature on coronavirus disease. World Health Organization, Avenue Appia 20, 1211 Geneva; https://search.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/; free.

An evaluation of the National Institutes of Health grants portfolio: identifying opportunities and challenges for multi-omics research that leverage metabolomics data.

BACKGROUND: Through the systematic large-scale profiling of metabolites, metabolomics provides a tool for biomarker discovery and improving disease monitoring, diagnosis, prognosis, and treatment response, as well as for delineating disease mechanisms and etiology. As a downstream product of the genome and epigenome, transcriptome, and proteome activity, the metabolome can be considered as being the most proximal correlate to the phenotype. Integration of metabolomics data with other -omics data in multi-omics analyses has the potential to advance understanding of human disease development and treatment. AIM OF REVIEW: To understand the current funding and potential research opportunities for when metabolomics is used in human multi-omics studies, we cross-sectionally evaluated National Institutes of Health (NIH)-funded grants to examine the use of metabolomics data when collected with at least one other -omics data type. First, we aimed to determine what types of multi-omics studies included metabolomics data collection. Then, we looked at those multi-omics studies to examine how often grants employed an integrative analysis approach using metabolomics data. KEY SCIENTIFIC CONCEPTS OF REVIEW: We observed that the majority of NIH-funded multi-omics studies that include metabolomics data performed integration, but to a limited extent, with integration primarily incorporating only one other -omics data type. Some opportunities to improve data integration may include increasing confidence in metabolite identification, as well as addressing variability between -omics approach requirements and -omics data incompatibility.

Will ARPA-H work?

A new federal agency-approved last month by the United States Congress-is already off to a rocky start. The Advanced Research Projects Agency for Health (ARPA-H), proposed by President Biden in 2021, aims to tackle the most intractable biomedical problems by funding innovative, high-risk, high-reward research and swiftly turning discoveries into treatments and cures. But Congress gave the agency a much smaller budget than sought by the administration-$ 1 billion over 3 years, a fraction of the $6.5 billion requested. And as happens whenever there is new money and a new federal agency, a political scrum has erupted over who should control ARPA-H. It is now expected to answer to both the National Institutes of Health (NIH) and the Department of Health and Human Services (HHS). If it is to deliver on its mission, ARPA-H needs to be an autonomous entity that approaches biomedical research in a way never done before by the federal government. The stakes are high: If ARPA-H fails to produce new clinical advances relatively quickly, it will erode trust in US science. It's time for clear thinking and action about what it will take to make ARPA-H successful.

Racial and Ethnic Disparities in Cost-Related Barriers to Medication Adherence Among Patients With Glaucoma Enrolled in the National Institutes of Health All of Us Research Program.

IMPORTANCE: Ability to afford medication is a major determinate of medication adherence among patients. OBJECTIVE: To determine cost-related barriers to medication adherence by race and ethnicity in a nationwide cohort of patients with glaucoma. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included patients with glaucoma enrolled in the National Institutes of Health All of Us Research Program, a nationwide longitudinal cohort of US adults, with more than 300 000 currently enrolled. Individuals with a diagnosis of glaucoma based on electronic health record diagnosis codes who participated in the Health Care Access and Utilization survey and had complete data on all covariates were studied. Data were collected from June 2016 to March 2021, and data were analyzed from August to November 2021. EXPOSURES: Race and ethnicity defined as non-Hispanic African American, non-Hispanic Asian, Hispanic, and non-Hispanic White. MAIN OUTCOMES AND MEASURES: Logistic regression was used to evaluate the association between reported cost-related barriers to medication adherence (could not afford prescription medication, skipped medication doses to save money, took less medication to save money, delayed filling a prescription to save money, asked for lower-cost medication to save money, bought prescriptions from another country to save money, and used alternative therapies to save money) and race and ethnicity, adjusting multivariable models by age, gender, health insurance status, education, and income. Odds ratios of these barriers were obtained by race and ethnicity, with non-Hispanic White race as the reference group. RESULTS: Of 3826 included patients with glaucoma, 481 (12.6%) were African American, 119 (3.1%) were non-Hispanic Asian, 351 (9.2%) were Hispanic, and 2875 (75.1%) were non-Hispanic White. The median (IQR) age was 69 (60-75) years, and 2307 (60.3%) were female. After adjusting for confounders, non-Hispanic African American individuals (odds ratio, 1.82; 95% CI, 1.34-2.44) and Hispanic individuals (odds ratio, 1.77; 95% CI, 1.25-2.49) were more likely than non-Hispanic White individuals to report not being able to afford medications. Further, despite having the lowest rate of endorsing difficulty affording medications, non-Hispanic White individuals were equally likely to ask for lower-cost medication from their clinicians as individuals of racial and ethnic minority groups. CONCLUSIONS AND RELEVANCE: In this study, there was significantly higher odds of self-reported difficulty affording medications among non-Hispanic African American and Hispanic individuals compared with non-Hispanic White individuals. Clinicians should be proactive and initiate discussions about costs in an effort to promote medication adherence and health equity among patients.

Understanding exposures and latent disease risk within the National Institute of Environmental Health Sciences Superfund Research Program.

Understanding the health effects of exposures when there is a lag between exposure and the onset of disease is an important and challenging topic in environmental health research. The National Institute of Environmental Health Sciences (NIEHS) Superfund Basic Research and Training Program (SRP) is a National Institutes of Health (NIH) grant program that uses a multidisciplinary approach to support biomedical and environmental science and engineering research. Because of the multidisciplinary nature of the program, SRP grantees are well-positioned to study exposure and latent disease risk across humans, animal models, and various life stages. SRP-funded scientists are working to address the challenge of connecting exposures that occur early in life and prior to conception with diseases that manifest much later, including developing new tools and approaches to predict how chemicals may affect long-term health. Here, we highlight research from the SRP focused on understanding the health effects of exposures with a lag between exposure and the onset of the disease as well as provide future directions for addressing knowledge gaps for this highly complex and challenging topic. Advancing the knowledge of latency to disease will require a multidisciplinary approach to research, the need for data sharing and integration, and new tools and computation approaches to make better predications about the timing of disease onset. A better understanding of exposures that may contribute to later-life diseases is essential to supporting the implementation of prevention and intervention strategies to reduce or modulate exposures to reduce disease burden.

Analyzing the Scholarly Impact of Cardiothoracic Surgery Research Using the Relative Citation Ratio.

INTRODUCTION: The National Institutes of Health (NIH) recently developed the relative citation ratio (RCR), calculated as article citations benchmarked to NIH-funded publications in the same field. Here, we characterized the scholarly impact of academic cardiothoracic (CT) surgeons and their research using the RCR. MATERIALS AND METHODS: Using a database of 992 CT surgeons, we calculated the RCR for all articles published by each surgeon since 1980 using the NIH iCite database. All data were collected from publicly available online sources. Data are presented as median (interquartile range) or as odds ratios (ORs) for multivariable logistic regression analysis. RESULTS: Where RCR 1.00 indicates equal impact as an NIH-funded publication, the RCR among all 37,402 CT surgery articles was 0.84 (0.33-1.83) and the RCR among NIH-funded CT surgery articles was 1.07 (0.53-2.17). CT surgeons exhibited a career median RCR of 0.82 (0.54-1.13) and maximum RCR of 6.20 (3.04-13.57). Predictors of career median RCR >1.00 included female gender (OR 2.23, P = 0.001), thoracic subspecialization (OR 2.50, P < 0.001), full professor rank (OR 1.89, P = 0.001), and NIH funding (OR 1.75, P = 0.001). Predictors of career maximum RCR >50th percentile among CT surgeons included male gender (OR 1.87, P = 0.030), thoracic subspecialization (OR 2.05, P < 0.001), full professor rank (OR 4.89, P < 0.001), NIH funding (OR 3.17, P < 0.001), and career duration (OR 1.03, P = 0.002). CONCLUSIONS: We present the first assessment of the NIH-validated RCR for academic CT surgery. CT surgery research is highly impactful, although gender disparities persist with respect to the highest-impact research of our specialty.

Correlation analysis of Trial of Org 10172 in acute stroke treatment classification and National Institutes of Health Stroke Scale score in acute cerebral infarction with risk factors.

OBJECTIVE: The aim of this study was to investigate the correlation between the Trial of Org 10172 in acute stroke treatment classification and the National Institutes of Health Stroke Scale score of acute cerebral infarction as well as acute cerebral infarction's risk factors. METHODS: The clinical data of 3,996 patients with acute cerebral infarction hospitalized in Hebei Renqiu Kangjixintu Hospital from January 2014 to November 2018 were analyzed retrospectively. According to Trial of Org 10172 in acute stroke treatment, they were divided into five groups: arteriosclerosis, cardio cerebral embolism, arterial occlusion, other causes, and unknown causes. Through questionnaire design, routine physical examination, and physical and chemical analysis of fasting venous blood samples, the risk factors were evaluated, and the correlation between Trial of Org 10172 in acute stroke treatment classification and National Institutes of Health Stroke Scale classification was analyzed using multivariate logistic regression. In addition, the relationship between National Institutes of Health Stroke Scale score and risk factors in different groups was compared, and the correlation between Trial of Org 10172 in acute stroke treatment classification and National Institutes of Health Stroke Scale score was analyzed. RESULTS: Multivariate logistic regression analysis showed that diabetes, atrial fibrillation or stroke history, age, and education level were related to Trial of Org 10172 in acute stroke treatment classification. In the National Institutes of Health Stroke Scale comparison, the scores of the cardio cerebral embolism group were significantly higher than those of the other four groups, and patients with diabetes, atrial fibrillation, or stroke history had a high share, especially atrial fibrillation (33.06%). CONCLUSIONS: The nerve function defect is more serious after acute cerebral infarction with cardiogenic cerebral embolism, indicating a poor prognosis.

COVID-19 threatens faculty diversity: postdoctoral scholars call for action.

Despite substantial investment and effort by federal agencies and institutions to improve the diversity of the professoriate, progress is excruciatingly slow. One program that aims to enhance faculty diversity is the Institutional Research and Academic Career Development Award (IRACDA) funded by the National Institutes of Health/National Institute of General Medical Sciences. IRACDA supports the training of a diverse cohort of postdoctoral scholars who will seek academic research and teaching careers. The San Diego IRACDA program has trained 109 postdoctoral scholars since its inception in 2003; 59% are women and 63% are underrepresented (UR) Black/African-American, Latinx/Mexican-American, and Indigenous scientists. Sixty-four percent obtained tenure-track faculty positions, including a substantial 32% at research-intensive institutions. However, the COVID-19 pandemic crisis threatens to upend IRACDA efforts to improve faculty diversity, and academia is at risk of losing a generation of diverse, talented scholars. Here, a group of San Diego IRACDA postdoctoral scholars reflects on these issues and discusses recommendations to enhance the retention of UR scientists to avoid a "lost generation" of promising UR faculty scholars.