Design and Implementation of the All of Us Research Program COVID-19 Participant Experience (COPE) Survey.

In response to the rapidly evolving coronavirus disease 2019 (COVID-19) pandemic, the All of Us Research Program longitudinal cohort study developed the COVID-19 Participant Experience (COPE) survey to better understand the pandemic experiences and health impacts of COVID-19 on diverse populations within the United States. Six survey versions were deployed between May 2020 and March 2021, covering mental health, loneliness, activity, substance use, and discrimination, as well as COVID-19 symptoms, testing, treatment, and vaccination. A total of 104,910 All of Us Research Program participants, of whom over 73% were from communities traditionally underrepresented in biomedical research, completed 275,201 surveys; 9,693 completed all 6 surveys. Response rates varied widely among demographic groups and were lower among participants from certain racial and ethnic minority populations, participants with low income or educational attainment, and participants with a Spanish language preference. Survey modifications improved participant response rates between the first and last surveys (13.9% to 16.1%, P < 0.001). This paper describes a data set with longitudinal COVID-19 survey data in a large, diverse population that will enable researchers to address important questions related to the pandemic, a data set that is of additional scientific value when combined with the program's other data sources.

Comparison of visual and automated Deki Reader interpretation of malaria rapid diagnostic tests in rural Tanzanian military health facilities.

BACKGROUND: Although microscopy is a standard diagnostic tool for malaria and the gold standard, it is infrequently used because of unavailability of laboratory facilities and the absence of skilled readers in poor resource settings. Malaria rapid diagnostic tests (RDT) are currently used instead of or as an adjunct to microscopy. However, at very low parasitaemia (usually < 100 asexual parasites/µl), the test line on malaria rapid diagnostic tests can be faint and consequently hard to visualize and this may potentially affect the interpretation of the test results. Fio Corporation (Canada), developed an automated RDT reader named Deki Reader™ for automatic analysis and interpretation of rapid diagnostic tests. This study aimed to compare visual assessment and automated Deki Reader evaluations to interpret malaria rapid diagnostic tests against microscopy. Unlike in the previous studies where expert laboratory technicians interpreted the test results visually and operated the device, in this study low cadre health care workers who have not attended any formal professional training in laboratory sciences were employed. METHODS: Finger prick blood from 1293 outpatients with fever was tested for malaria using RDT and Giemsa-stained microscopy for thick and thin blood smears. Blood samples for RDTs were processed according to manufacturers' instructions automated in the Deki Reader. Results of malaria diagnoses were compared between visual and the automated devise reading of RDT and microscopy. RESULTS: The sensitivity of malaria rapid diagnostic test results interpreted by the Deki Reader was 94.1% and that of visual interpretation was 93.9%. The specificity of malaria rapid diagnostic test results was 71.8% and that of human interpretation was 72.0%. The positive predictive value of malaria RDT results by the Deki Reader and visual interpretation was 75.8 and 75.4%, respectively, while the negative predictive values were 92.8 and 92.4%, respectively. The accuracy of RDT as interpreted by DR and visually was 82.6 and 82.1%, respectively. CONCLUSION: There was no significant difference in performance of RDTs interpreted by either automated DR or visually by unskilled health workers. However, despite the similarities in performance parameters, the device has proven useful because it provides stepwise guidance on processing RDT, data transfer and reporting.

Multivariate adaptive regression splines analysis to predict biomarkers of spontaneous preterm birth.

OBJECTIVE: To develop classification models of demographic/clinical factors and biomarker data from spontaneous preterm birth in African Americans and Caucasians. DESIGN: Secondary analysis of biomarker data using multivariate adaptive regression splines (MARS), a supervised machine learning algorithm method. SETTING: Analysis of data on 36 biomarkers from 191 women was reduced by MARS to develop predictive models for preterm birth in African Americans and Caucasians. SAMPLES: Maternal plasma, cord plasma collected at admission for preterm or term labor and amniotic fluid at delivery. METHODS: Data were partitioned into training and testing sets. Variable importance, a relative indicator (0-100%) and area under the receiver operating characteristic curve (AUC) characterized results. RESULTS: Multivariate adaptive regression splines generated models for combined and racially stratified biomarker data. Clinical and demographic data did not contribute to the model. Racial stratification of data produced distinct models in all three compartments. In African Americans maternal plasma samples IL-1RA, TNF-α, angiopoietin 2, TNFRI, IL-5, MIP1α, IL-1ß and TGF-α modeled preterm birth (AUC train: 0.98, AUC test: 0.86). In Caucasians TNFR1, ICAM-1 and IL-1RA contributed to the model (AUC train: 0.84, AUC test: 0.68). African Americans cord plasma samples produced IL-12P70, IL-8 (AUC train: 0.82, AUC test: 0.66). Cord plasma in Caucasians modeled IGFII, PDGFBB, TGF-ß1 , IL-12P70, and TIMP1 (AUC train: 0.99, AUC test: 0.82). Amniotic fluid in African Americans modeled FasL, TNFRII, RANTES, KGF, IGFI (AUC train: 0.95, AUC test: 0.89) and in Caucasians, TNF-α, MCP3, TGF-ß3 , TNFR1 and angiopoietin 2 (AUC train: 0.94 AUC test: 0.79). CONCLUSIONS: Multivariate adaptive regression splines models multiple biomarkers associated with preterm birth and demonstrated racial disparity.

Long-term alterations in maternal plasma proteome after sFlt1-induced preeclampsia in mice.

OBJECTIVE: Preeclampsia is associated with long-term adverse maternal health, such as cardiovascular and metabolic diseases. The objective of this study was to determine whether preeclampsia in a well-characterized animal model that was induced by overexpression of soluble fms-like tyrosine kinase-1 (sFlt1) results in alterations in the maternal circulating proteome that persist long after delivery. STUDY DESIGN: CD-1 mice at day 8 of gestation were injected with adenovirus that carried sFlt1 or the murine immunoglobulin G2α Fc fragment as control. Depleted maternal plasma was analyzed 6 months after delivery by label-free liquid chromatography-mass spectrometry assay. The tandem mass spectrometry data were searched against a mouse database, and the resultant intensity data were used to compare abundance of proteins across disease/control plasma pool. Results were analyzed with ingenuity pathways analysis. Right-tailed Fisher exact test was used to calculate a probability value. RESULTS: Of 150 proteins that are common for both groups, ingenuity pathways analysis determined 105 proteins that were ready for analysis. Diseases and disorders analysis showed significant enrichment of proteins that are associated with cardiovascular disease. Within this cluster, the most abundant proteins were associated with vascular disease, atherosclerosis, and atherosclerotic lesions. Other top disease clusters were inflammatory response, organismal injury and abnormalities, and hematologic and metabolic disease. CONCLUSION: Exposure to sFlt1-induced preeclampsia alters multiple biologic functions in mothers that persist later in life. Our results suggest that some of the long-term adverse outcomes that are associated with preeclampsia actually may be a consequence rather than a mere unmasking of an underlying predisposition. If similar results are found in humans, the development of preventive strategies for preeclampsia should also improve long-term maternal health.

Computable Guidelines and Clinical Decision Support for Cervical Cancer Screening and Management to Improve Outcomes and Health Equity.

Cervical cancer is highly preventable when precancerous lesions are detected early and appropriately managed. However, the complexity of and frequent updates to existing evidence-based clinical guidelines make it challenging for clinicians to stay abreast of the latest recommendations. In addition, limited availability and accessibility to information technology (IT) decision supports make it difficult for groups who are medically underserved to receive screening or receive the appropriate follow-up care. The Centers for Disease Control and Prevention (CDC), Division of Cancer Prevention and Control (DCPC), is leading a multiyear initiative to develop computer-interpretable ("computable") version of already existing evidence-based guidelines to support clinician awareness and adoption of the most up-to-date cervical cancer screening and management guidelines. DCPC is collaborating with the MITRE Corporation, leading scientists from the National Cancer Institute, and other CDC subject matter experts to translate existing narrative guidelines into computable format and develop clinical decision support tools for integration into health IT systems such as electronic health records with the ultimate goal of improving patient outcomes and decreasing disparities in cervical cancer outcomes among populations that are medically underserved. This initiative meets the challenges and opportunities highlighted by the President's Cancer Panel and the President's Cancer Moonshot 2.0 to nearly eliminate cervical cancer.

Patient Engagement In Research: Early Findings From The Patient-Centered Outcomes Research Institute.

Charged with ensuring that research produces useful evidence to inform health decisions, the Patient-Centered Outcomes Research Institute (PCORI) requires investigators to engage patients and other health care stakeholders, such as clinicians and payers, in the research process. Many PCORI studies result in articles published in peer-reviewed journals that detail research findings and engagement's role in research. To inform practices for engaging patients and others as research partners, we analyzed 126 articles that described engagement approaches and contributions to research. PCORI projects engaged patients and others as consultants and collaborators in determining the study design, selecting study outcomes, tailoring interventions to meet patients' needs and preferences, and enrolling participants. Many articles reported that engagement provided valuable contributions to research feasibility, acceptability, rigor, and relevance, while a few noted trade-offs of engagement. The findings suggest that engagement can support more relevant research through better alignment with patients' and clinicians' real-world needs and concerns.

Parental perceptions of teen driving: Restrictions, worry and influence.

INTRODUCTION: Parents play a critical role in preventing crashes among teens. Research of parental perceptions and concerns regarding teen driving safety is limited. We examined results from the 2013 Summer ConsumerStyles survey that queried parents about restrictions placed on their teen drivers, their perceived level of "worry" about their teen driver's safety, and influence of parental restrictions regarding their teen's driving. METHODS: We produced frequency distributions for the number of restrictions imposed, parental "worry," and influence of rules regarding their teen's driving, reported by teen's driving license status (learning to drive or obtained a driver's license). Response categories were dichotomized because of small cell sizes, and we ran separate log-linear regression models to explore whether imposing all four restrictions on teen drivers was associated with either worry intensity ("a lot" versus "somewhat, not very much or not at all") or perceived influence of parental rules ("a lot" versus "somewhat, not very much or not at all"). RESULTS: Among the 456 parent respondents, 80% reported having restrictions for their teen driver regarding use of safety belts, drinking and driving, cell phones, and text messaging while driving. However, among the 188 parents of licensed teens, only 9% reported having a written parent-teen driving agreement, either currently or in the past. Worrying "a lot" was reported less frequently by parents of newly licensed teens (36%) compared with parents of learning teens (61%). CONCLUSIONS AND PRACTICAL APPLICATIONS: Parents report having rules and restrictions for their teen drivers, but only a small percentage formalize the rules and restrictions in a written parent-teen driving agreement. Parents worry less about their teen driver's safety during the newly licensed phase, when crash risk is high as compared to the learning phase. Further research is needed into how to effectively support parents in supervising and monitoring their teen driver.

Teens and seat belt use: What makes them click?

PROBLEM: Motor vehicle crashes kill more adolescents in the United States than any other cause, and often the teen is not wearing a seat belt. METHODS: Using data from the 2011 Youth Risk Behavior Surveys from 38 states, we examined teens' self-reported seat belt use while riding as a passenger and identified individual characteristics and environmental factors associated with always wearing a seat belt. RESULTS: Only 51% of high school students living in 38 states reported always wearing a seat belt when riding as a passenger; prevalence varied from 32% in South Dakota to 65% in Delaware. Seat belt use was 11 percentage points lower in states with secondary enforcement seat belt laws compared to states with primary enforcement laws. Racial/ethnic minorities, teens living in states with secondary enforcement seat belt laws, and those engaged in substance use were least likely to always wear their seat belts. The likelihood of always being belted declined steadily as the number of substance use behaviors increased. DISCUSSION: Seat belt use among teens in the United States remains unacceptably low. Results suggest that environmental influences can compound individual risk factors, contributing to even lower seat belt use among some subgroups. PRACTICAL APPLICATIONS: This study provides the most comprehensive state-level estimates to date of seat belt use among U.S. teens. This information can be useful when considering policy options to increase seat belt use and for targeting injury prevention interventions to high-risk teens. States can best increase teen seat belt use by making evidence-informed decisions about state policy options and prevention strategies.

Predictors of rear seat belt use among U.S. adults, 2012.

INTRODUCTION: Seat belt use reduces the risk of injuries and fatalities among motor vehicle occupants in a crash, but belt use in rear seating positions is consistently lower than front seating positions. Knowledge is limited concerning factors associated with seat belt use among adult rear seat passengers. METHODS: Data from the 2012 ConsumerStyles survey were used to calculate weighted percentages of self-reported rear seat belt use by demographic characteristics and type of rear seat belt use enforcement. Multivariable regression was used to calculate prevalence ratios for rear seat belt use, adjusting for person-, household- and geographic-level demographic variables as well as for type of seat belt law in place in the state. RESULTS: Rear seat belt use varied by age, race, geographic region, metropolitan status, and type of enforcement. Multivariable regression showed that respondents living in states with primary (Adjusted Prevalence Ratio (APR): 1.23) and secondary (APR: 1.11) rear seat belt use enforcement laws were significantly more likely to report always wearing a seat belt in the rear seat compared with those living in a state with no rear seat belt use enforcement law. CONCLUSIONS AND PRACTICAL APPLICATIONS: Several factors were associated with self-reported seat belt use in rear seating positions. Evidence suggests that primary enforcement covering all seating positions is an effective intervention that can be employed to increase seat belt use and in turn prevent motor vehicle injuries to rear-seated occupants.

Assistive device use and mobility-related factors among adults aged≥65years.

INTRODUCTION: Examining how assistive device (cane, walker) use relates to other mobility factors can provide insight into older adults' future mobility needs. METHODS: Data come from the Second Injury Control and Risk Survey, Phase 2 (ICARIS2-P2), conducted from March 2007 to May 2008. Prevalence estimates were calculated for older adults (aged ≥65) and multivariable logistic regression was used to explore associations between assistive device use and mobility-related characteristics. RESULT: Compared with non-users, assistive device users were more likely to report a recent fall (AOR 12.0; 95% CI 4.9-29.3), limit walking outside due to concerns about falling (AOR 7.1; 95% CI 2.6-19.1), be unable to walk outside for 10min without resting (AOR 3.3; 95% CI 1.1-9.3), and be no longer driving (AOR 6.7; 95% CI 2.0-22.3). CONCLUSION: Assistive device users have limited mobility and an increased risk for fall injury compared with non-users. PRACTICAL APPLICATION: Effective fall prevention interventions, and innovative transportation options, are needed to protect the mobility of this high-risk group.

Travel-related behaviors, opinions, and concerns of U.S. adult drivers by race/ethnicity, 2010.

INTRODUCTION: The U.S. population is shifting to become both older and more racially and ethnically diverse. Our current understanding of U.S. drivers' travel-related needs and concerns by race/ethnicity is limited. METHODS: Data from the 2010 HealthStyles survey, an annual, cross-sectional, national mail-panel survey of persons ages 18 years or older living in the United States, were used to calculate weighted percentages of travel-related behaviors, opinions, and concerns by race/ethnicity. Logistic regression was used to explore associations between race/ethnicity and specific travel-related concerns, while adjusting for other demographic characteristics. RESULTS: Adequate transportation alternatives to driving were reported by a greater percentage of persons in certain minority groups compared to whites (Hispanic: 34.7%; white: 23.4%). Concern for the availability of alternatives to driving in the future was greater among minority groups (black: 57.7%; Hispanic: 47.3%; other: 50.9%) compared to whites (37.5%). Additionally, among persons with a household income of $25,000+, minorities were generally more likely than whites to report concern about having alternative transportation options to driving, whereas concern was consistently high among all racial/ethnic groups for those earning less than $25,000 annually. In each racial/ethnic group, more than 10% of persons reported not knowing how they would get around if they could no longer drive. CONCLUSIONS: Important variations by race/ethnicity in both travel behaviors and concerns for adequate alternatives to driving were found, revealing the need for further research to better understand reasons for these differences and to identify ways to meet the transportation needs of the changing U.S. population demographics. IMPACT ON INDUSTRY: Further research on adequate alternatives to driving and transportation needs is needed.

Bacterial modulation of human fetal membrane Toll-like receptor expression.

PROBLEM: Preterm premature rupture of fetal membranes (pPROM) occurs in 30-40% of spontaneous preterm births (PTB) and is associated with intra-amniotic infection and inflammation. The membranes may sense and respond to microbes via Toll-like receptors (TLRs); however, little is known about their expression and regulation in this tissue. The objective of this study was to evaluate the expression of TLRs 1-10 in fetal membranes after exposure to pathogens associated with intra-amniotic infection and PTB. METHOD OF STUDY: Normal human term fetal membrane explants were exposed to various bacteria. After 24 hrs, RNA was extracted and quantitative RT-PCR performed for TLRs1-10. RESULTS: Treatment of fetal membranes with Mycoplasma hominis increased expression of TLR4, TLR6, and TLR8 mRNA. Ureaplasma parvum upregulated TLR8 mRNA, and Porphyromonas gingivalis significantly increased fetal membrane TLR7 expression. In contrast, treatment with Gram-negative Escherichia coli (and its cell wall component lipopolysaccharide) downregulated TLR10 mRNA. No effect was detected for Ureaplasma urealyticum, Gardnerella vaginalis, or Group B Streptococcus. CONCLUSION: These findings demonstrate that different types of bacteria have distinct effects on fetal membrane TLR expression patterns. Moreover, these findings highlight the disparity of fetal membrane responses to infection and thus suggest heterogeneity in the mechanisms by which infection-associated pregnancy complications, such as pPROM and PTB, arise.

Fetal membrane biomarker network diversity and disease functions induced by intra-amniotic pathogens.

PROBLEM: Intra-amniotic pathogens and by-products activate innate immune responses encompassing multitudes of signaling molecules and pathways that can result in spontaneous preterm birth (PTB). This study investigates fetal membrane response to bacterial stimulation using a bioinformatics approach. METHOD OF STUDY: Dysregulated biomarker (IL1-ß, IL-2, IL-8, IL-10, and TNF-α) data from fetal membranes at term stimulated with Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma hominis, E. coli, Group B Streptococci, Polyporhans gingivalis, or Gardnerella vaginalis with 50% (v/v) amniotic fluid (AF) were analyzed by Ingenuity Pathway Analysis. RESULTS: In racially stratified analysis, networks representing late-stage immune inflammation were seen in African-Americans in AF absence. Inflammation was dominant in AF presence as well. In Caucasians, late-stage immune response was dominant with AF, but not in its absence. CONCLUSIONS: Fetal membrane biofunctions in response to bacteria reflect early- and late-stage innate immune defenses that vary based on the presence of AF and subject race.

Group B Streptococcus colonization and higher maternal IL-1ß concentrations are associated with early term births.

Association between maternal Group B Streptococcus (GBS) colonization diagnosed between 35 and 37 weeks of gestation and early term birth (between 37 and 39 weeks) and maternal-fetal inflammatory response associated with this condition were tested. In this cohort study of women delivering at term at Centennial Women's Hospital in Nashville, TN, GBS status and other clinical and demographic data were obtained from medical records. Exposed women were those testing positive for GBS (GBS positive [n = 490]) and the unexposed tested negative for GBS (GBS negative [n = 1,127]). To determine the inflammatory response associated with GBS, a cross sectional study, maternal and fetal plasma biomarkers (IL-1ß, IL-2, IL-6, IL-8, and TNF-α) were measured in the same cohort. T-tests and logistic regression determined association between GBS status, biomarker concentrations and early term birth. Gestational age was reduced to 271.1 (95% CI 270.4, 271.1) for cases compared to 274.7 (95% CI 274.4, 275.1) days for controls (p < 0.0001). The odds of early term birth was increased by threefold in cases (OR 3.28; 95% CI 2.60-4.15; p < 0.0001). The mean birth weight in cases (3285.3 g) (95% CI 3242.6, 3327.9) was lower than the controls, 3373.8 g (95% CI 3348.9, 3398.7) (p = 0.0004). Maternal IL-1ß was greater in cases (22.8 ng/ml; range 5.2-157.7 ng/ml) compared to controls (5.7; range 2.4-69.5 ng/ml; p < 0.0001). IL-1ß was higher in fetal plasma in cases vs. controls (20.33 vs. 8.18 ng/ml; p = 0.01). A 10 ng/ml increase in maternal IL-1ß was associated with increased risk for GBS infection (OR: 1.628, CI: 1.163-2.278; p = 0.0045). GBS colonization shortened gestational age at term and IL-1ß concentration in maternal plasma is an indicator of GBS status.

Amniotic fluid and maternal race influence responsiveness of fetal membranes to bacteria.

Spontaneous preterm birth (PTB) and preterm prelabor rupture of membranes (pPROM) occur more frequently in African-American women than in other racial groups. This may be due to an enhanced inflammatory response to pathogens associated with the condition. It is also possible that amniotic fluid (AF) has different immunomodulatory properties in African-American women that increase their risk of PTB and pPROM. To test this, we cultured fetal membranes from European-American and African-American women with sterile medium (control), Escherichia coli, Gardnerella vaginalis, Group B streptococci (GBS), Polyporphorans gingivalis, Mycoplasma hominis, Ureaplasma urealyticum or Ureaplasma parvum in the presence and absence of 50% autologous AF. Cytokine concentrations were quantified in the conditioned medium. All bacterial species increased IL-8 production. IL-1ß and TNF-α production were stimulated by LPS, E. coli, and G. vaginalis compared with control, but responses to Group B streptococci and P. gingivalis were limited to IL-1ß and TNF-α respectively. Genital mycoplasmas stimulated TNF-α and IL-10 but had no effect on IL-1ß production. African-Americans had twice the IL-1ß response to E. coli as European-Americans (P=0.031). Conversely, European-Americans produced more IL-8 in response to LPS than African-Americans (P=0.026). AF had both pro- and anti-inflammatory properties that varied between races and pathogens. These results suggest that the host response to fetal membrane infections is complex and not generalizable. Interventions to prevent PTB and pPROM may need to be customized based on a patient's race, type of bacterial infection and factors in her AF.